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Sample records for hcv-related lymphoproliferative disorders

  1. Impact of Immunogenetic IL28B Polymorphism on Natural Outcome of HCV Infection

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    Valli De Re

    2014-01-01

    Full Text Available With the aim of investigating whether interleukin 28B gene (IL28B rs1297860 polymorphism is associated with different hepatitis C (HCV infection statuses, we compared IL28B allelic distribution in an Italian case series of 1050 patients with chronic infection and different outcomes, 47 individuals who spontaneously cleared HCV, and 178 blood donors. Furthermore, we compared IL28B variants among 3882 Caucasian patients with chronic infection, 397 with spontaneous clearance, and 1366 blood donors reported in PubMed. Overall data confirmed a relation between IL28B C allele and HCV spontaneous clearance. Furthermore, we found that IL28B T allele had a weak relation with chronic HCV progression to hepatocellular carcinoma. Study findings are in accordance with the hepatocellular carcinogenic model where IL28B TT genotype, by promoting a persistent chronic hepatitis which leads to both hepatocyte injury and chronic inflammation, could facilitate HCC development. Conversely, patients with lymphoproliferative disorders had not any significantly different IL28B rs1297860 allelic distribution than those with chronic HCV, but, like all chronic HCV-related diseases, they showed a lower CC frequency than patients who spontaneously cleared HCV. Study results confirmed the model of persistent HCV infection as a risk factor for the pathogenesis of both liver and lymphoproliferative disorders.

  2. Posttransplant Lymphoproliferative Disorder in a Patient with Worsening Ascites after Liver Transplantation

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    Harsh D. Patel

    2017-01-01

    Full Text Available Posttransplant lymphoproliferative disorder (PTLD is a spectrum of diseases that involves abnormal lymphoid and/or plasmacytic proliferation in patients with solid organ or hematopoietic cell transplantation. It is a condition with a low incidence of 3.5–4.3% in liver transplant (LT recipients. This case involves a 63-year-old male with history of LT for chronic HCV induced cirrhosis who presented with abdominal distension related to worsening ascites. Cytological ascitic fluid analysis revealed EBV (+ malignant cells without a malignant focal point on imaging. Diagnosis of monomorphic PTLD with primary effusion lymphoma-like morphology and immunophenotype was established. This case highlights the complexity in diagnosis, different diagnostic modalities, and rare clinical presentations of PTLD.

  3. HCV Infection and B-Cell Lymphomagenesis

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    Masahiko Ito

    2011-01-01

    Full Text Available Hepatitis C virus (HCV has been recognized as a major cause of chronic liver diseases worldwide. It has been suggested that HCV infects not only hepatocytes but also mononuclear lymphocytes including B cells that express the CD81 molecule, a putative HCV receptor. HCV infection of B cells is the likely cause of B-cell dysregulation disorders such as mixed cryoglobulinemia, rheumatoid factor production, and B-cell lymphoproliferative disorders that may evolve into non-Hodgkin's lymphoma (NHL. Epidemiological data indicate an association between HCV chronic infection and the occurrence of B-cell NHL, suggesting that chronic HCV infection is associated at least in part with B-cell lymphomagenesis. In this paper, we aim to provide an overview of recent literature, including our own, to elucidate a possible role of HCV chronic infection in B-cell lymphomagenesis.

  4. Cutaneous lymphoproliferative disorder complicating infectious mononucleosis in an immunosuppressed patient.

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    Owen, Cindy England; Callen, Jeffrey P; Bahrami, Soon

    2011-01-01

    Infectious mononucleosis is the syndrome produced by primary infection with Epstein-Barr virus during adolescence or early adulthood. In immunosuppressed individuals, depressed T-cell function allows the Epstein-Barr virus-driven B-cell proliferation to continue unabated, potentially leading to a lymphoproliferative disorder. A 15-year-old girl with a history of ulcerative colitis treated with 6-mercaptopurine and mesalamine presented with the acute onset of a rapidly enlarging, ulcerative nodule on her left lower eyelid 4 weeks following recovery from infectious mononucleosis. The biopsy revealed an Epstein-Barr virus-positive lymphoproliferative disorder. Systemic disease was absent. Following discontinuation of 6-mercaptopurine, the patient was treated with two courses of intravenous cyclophosphamide. The lesion resolved completely and she remains disease free at 14 months following diagnosis. We report a solitary cutaneous lesion of an immunosuppression-related lymphoproliferative disorder (IR-LPD) occurring as a complication of infectious mononucleosis, and review the pathogenesis and reported cases of Epstein-Barr virus-related immunosuppression-related lymphoproliferative disorder arising in the setting of inflammatory bowel disease. It is important for dermatologists and dermatopathologists to be aware of the occurrence of IR-LPD in patients being treated for inflammatory conditions, including inflammatory bowel disease. Given the role of primary infection with Epstein-Barr virus in the development of IR-LPD, consideration may be given to assessing Epstein-Barr virus status prior to initiating immunosuppressive therapy in young patients. © 2010 Wiley Periodicals, Inc.

  5. Relative adrenal insufficiency in post-transplant lymphoproliferative disorder.

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    Cinclair R

    2003-01-01

    Full Text Available Post-transplant lymphoproliferative disorder is treated with rapid decrement of immunosuppressive therapy. This cannot be achieved with ease in patients on long-term glucocorticoid therapy, as chronically suppressed adrenal glands may not be capable of mounting adequate response to stress. A 52-year-old Caucasian male presented with fever, orthostatic hypotension, lymphadenopathy and hyponatraemia. Serum cortisol levels were within normal levels with a sub optimal response to stimulation by ACTH. Hyponatraemia and orthostasis responded poorly to fluid restriction, saline and salt repletion but corrected after increasing the steroid dose. The normal baseline cortisol levels represented a stimulated adrenal gland, however, the ACTH stimulation had inadequate response. This sub optimal stimulation and a good response to increased steroids suggest the presence of relative or occult adrenal insufficiency. Relative adrenal insufficiency must be considered in patients who have received prolonged glucocorticoid therapy and have symptoms such as hypotension and/or hyponatraemia.

  6. The radiographic findings of lymphoproliferative disorders of the lung

    International Nuclear Information System (INIS)

    Song Wei; Li Liping; Yan Hongzhen

    2002-01-01

    Objective: To study the radiographic findings of lymphoproliferative disorders of the lung. Methods: Twenty-five patients with lymphoproliferative disorders of the lung were examined by X-ray film, tomography, and CT. Results: Multiple and mediastinal lymphadenopathy were observed in 2 patients with pulmonary pseudolymphoma. Multiple nodules or masses were observed in 4 patients with pulmonary lymphomatoid granulomatosis. Hilar and mediastinal lymphadenopathy was observed in each patient with angioimmunoblastic lymphadenopathy, 2 patients had multiple nodules or masses, 8 patients had single or multiple patchy infiltrations, 10 had diffuse interstitial infiltrations. 3 patients with Castlemen' disease had a mass in the mediastinum, and another patient had mediastinal lymphadenopathy. Conclusion: Radiographic findings of lymphoproliferative disorders of the lung are varied, and the final diagnosis relies on pathology

  7. Granulomatous Lymphoproliferative Disorders: Granulomatous Slack Skin and Lymphomatoid Granulomatosis.

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    Gangar, Pamela; Venkatarajan, Sangeetha

    2015-07-01

    Granulomatous cutaneous T-cell lymphomas (CTCL) and lymphomatoid granulomatosis are considered granulomatous lymphoproliferative disorders. The most common types of granulomatous CTCL are granulomatous mycosis fungoides and granulomatous slack skin. Lymphomatoid granulomatosis is a rare Epstein-Barr virus driven lymphoproliferative disorder. This article reviews the etiopathogenesis, clinical presentation, systemic associations, and management of both granulomatous slack skin syndrome and lymphomatoid granulomatosis. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. Molecular Signatures of Hepatitis C Virus (HCV-Induced Type II Mixed Cryoglobulinemia (MCII

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    Roberto Burioni

    2012-11-01

    Full Text Available The role of hepatitis C virus (HCV infection in the induction of type II mixed cryoglobulinemia (MCII and the possible establishment of related lymphoproliferative disorders, such as B-cell non-Hodgkin lymphoma (B-NHL, is well ascertained. However, the molecular pathways involved and the factors predisposing to the development of these HCV-related extrahepatic complications deserve further consideration and clarification. To date, several host- and virus-related factors have been implicated in the progression to MCII, such as the virus-induced expansion of selected subsets of B-cell clones expressing discrete immunoglobulin variable (IgV gene subfamilies, the involvement of complement factors and the specific role of some HCV proteins. In this review, we will analyze the host and viral factors taking part in the development of MCII in order to give a general outlook of the molecular mechanisms implicated.

  9. Hepatitis C Virus-Related Lymphomagenesis in a Mouse Model

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    Tsukiyama-Kohara, Kyoko; Sekiguchi, Satoshi; Kasama, Yuri; Salem, Nagla Elwy; Machida, Keigo; Kohara, Michinori

    2011-01-01

    B cell non-Hodgkin lymphoma is a typical extrahepatic manifestation frequently associated with hepatitis C virus (HCV) infection. The mechanism by which HCV infection leads to lymphoproliferative disorder remains unclear. Our group established HCV transgenic mice that expressed the full HCV genome in B cells (RzCD19Cre mice). We observed a 25.0% incidence of diffuse large B cell non-Hodgkin lymphomas (22.2% in male and 29.6% in female mice) within 600 days of birth. Interestingly, RzCD19Cre mice with substantially elevated serum-soluble interleukin-2 receptor α-subunit (sIL-2Rα) levels (>1000 pg/mL) developed B cell lymphomas. Another mouse model of lymphoproliferative disorder was established by persistent expression of HCV structural proteins through disruption of interferon regulatory factor-1 (irf-1_/_/CN2 mice). Irf-1_/_/CN2 mice showed extremely high incidences of lymphomas and lymphoproliferative disorders. Moreover, these mice showed increased levels of interleukin (IL)-2, IL-10, and Bcl-2 as well as increased Bcl-2 expression, which promoted oncogenic transformation of lymphocytes. PMID:22084693

  10. Consequences of extrahepatic manifestations of hepatitis C viral infection (HCV

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    Agnieszka Pawełczyk

    2016-04-01

    Full Text Available The hepatitis C virus (HCV is a primarily hepatotropic virus. However, numerous extrahepatic symptoms are observed in patients chronically infected with HCV, e.g. cryoglobulinemia, lymphoproliferative disorders, kidney diseases, disturbances of the central and peripheral nervous system, thyroid gland, pancreas, lymph nodes and pituitary gland, that develop at various times after the infection. Complex mechanisms underlie these processes, both molecular, related to direct effects of the virus on cells or tissues and indirect mechanisms, resulting from the response of the immune system to infection (via cytokines or oxidative stress, and from the antiviral treatment used. Understanding these mechanisms may contribute to the definition of new prognostic factors, important for the early diagnosis of the infection, which in turn may improve treatment efficacy.This paper is a review of the incidence of selected extrahepatic manifestations of HCV infection and their underlying pathogenetic mechanisms and risk factors.

  11. Cerebral Post-Transplant Lymphoproliferative Disorder Occurring after Renal Transplantation: A Case Report

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    Suh, Jang Ho; Byun, Woo Mok; Kim, Hong Chul; Hwang, Min Su [Dept. of Radiology, Yeungnam University College of Medicine, Daegu (Korea, Republic of)

    2012-04-15

    Post-transplant lymphoproliferative disorder (PTLD) is a complication of organ transplantation and immunosuppression. A 36-year-old woman with a history of renal transplantation visited the hospital complaining of headache and on pathology was diagnosed with cerebral PTLD manifesting as multiple rim enhanced masses in both hemispheres. We report here a case of post-transplant lymphoproliferative disorder involving the cerebrum occurring after renal transplantation, and describe the MRI findings for this patient

  12. Cerebral Post-Transplant Lymphoproliferative Disorder Occurring after Renal Transplantation: A Case Report

    International Nuclear Information System (INIS)

    Suh, Jang Ho; Byun, Woo Mok; Kim, Hong Chul; Hwang, Min Su

    2012-01-01

    Post-transplant lymphoproliferative disorder (PTLD) is a complication of organ transplantation and immunosuppression. A 36-year-old woman with a history of renal transplantation visited the hospital complaining of headache and on pathology was diagnosed with cerebral PTLD manifesting as multiple rim enhanced masses in both hemispheres. We report here a case of post-transplant lymphoproliferative disorder involving the cerebrum occurring after renal transplantation, and describe the MRI findings for this patient

  13. Pulmonary lymphoproliferative disorders with affinity to lymphoma: a clinicopathoradiologic study of 16 cases

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    Fernandez Cruz, J.; Gonzalez Garcia, A.; Escobar Casas, P.; Gomez Benitez, S.; Gonzalez Guirao, M.A.; Borderas, F.

    1993-01-01

    Pulmonary lymphoproliferative disorders include plasma cell granuloma, Castleman's disease, pseudolymphoma, lymphocytic interstitial pneumonia, angioimmunoblastic lymphadenopathy and lymphomatoid granulomatosis. We carried out a retrospective study for the purpose of analysing the clinical and radiological findings of 16 cases of pulmonary lymphoproliferative disorders seen during the decade 1980-1990. The cases comprised 8 lymphocytic interstitial pneumonia, 5 lymphomatoid granulomatosis, 2 plasma cell granuloma and 1 angioimmunoblastic lymphadenopathy. Owing to the overlap and low specificity of the radiological patterns in these processes, histopathological examination is required. In view of the frequent evolution of pulmonary lymphoproliferative disorders to malignant lymphoma (4 cases, 1 of lymphocytic interstitial pneumonia and 3 of lymphomatoid granulomatosis, in our series) we provide a description of the radiological changes that occur during this process. (orig.)

  14. Favorable outcome of Epstein-Barr virus-associated B-cell lymphoproliferative disorder complicated by immunoglobulin G4-related disease treated with rituximab-based therapy: a case report.

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    Ueda, Koki; Ikeda, Kazuhiko; Ogawa, Kazuei; Sukegawa, Masumi; Sano, Takahiro; Kimura, Satoshi; Suzuki, Osamu; Hashimoto, Yuko; Takeishi, Yasuchika

    2016-08-24

    After acute infection of Epstein-Barr virus, Epstein-Barr virus-infected B cells survive but usually do not show clonal proliferation. However, Epstein-Barr virus-infected B cells occasionally acquire a proliferative capacity that provokes clonal lymphoproliferative disorders. We herein present a case with Epstein-Barr virus-infected CD30+ B cell and immunoglobulin G4+ plasmacytoid cell proliferation in the lymph nodes, suggesting a pathological and clinical interaction between Epstein-Barr virus-associated B-cell lymphoproliferative disorders and immunoglobulin G4-related disease. Immunoglobulin G4-related disease has been recognized as a benign disease with proliferation of IgG4-related disease+ plasmacytoid cells. Several studies have recently reported the coexistence of immunoglobulin G4-related disease+ plasmacytoid cells with Epstein-Barr virus-infected B cells in lymph nodes in some immunoglobulin G4-related disease cases. However, the pathogenic role of the clonal proliferation of Epstein-Barr virus-infected B cells in immunoglobulin G4-related disease, as well as the treatments for patients with both Epstein-Barr virus-infected B cells and immunoglobulin G4-related disease, have never been discussed. A 50-year-old Japanese man was referred to us for persistent fatigue and lymphadenopathy. His blood examination showed elevated IgG4, and detected high levels of Epstein-Barr virus DNA. A lymph node biopsy revealed IgG4+ plasmacytoid cells and infiltration of large lymphoid cells, which were positive for CD20, CD30, Epstein-Barr virus-related late membrane protein 1, and Epstein-Barr virus-encoded RNA, and were negative for IgG4. Based on the diagnosis of both Epstein-Barr virus-associated B-cell lymphoproliferative disorder and IgG4-related disease, the patient received eight cycles of rituximab combined with cyclophosphamide and prednisolone, which resulted in the complete disappearance of lymphadenopathy. Moreover, his serum IgG4 level was significantly

  15. Characterization of primary cutaneous CD8+/CD30+ lymphoproliferative disorders.

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    Martires, Kathryn J; Ra, Seong; Abdulla, Farah; Cassarino, David S

    2015-11-01

    CD30 primary cutaneous lymphoproliferative diseases include both lymphomatoid papulosis (LyP) and primary cutaneous anaplastic large cell lymphoma (PCALCL). The neoplastic cell of most primary CD30 lymphoproliferative disorders is CD4 positive. The terminology LyP "type D" has been used to describe a growing number of cases of LyP with a predominantly CD8 infiltrate. PCALCL with a CD8 phenotype has also been described, which presents a particularly difficult diagnostic and management challenge, given the difficulty in distinguishing it histologically from other cytotoxic lymphomas such as primary cutaneous aggressive epidermotropic CD8 cytotoxic T-cell lymphoma and CD8 gamma/delta and natural killer/T-cell lymphoma. We report 7 additional cases of these rare cutaneous CD8/CD30 lymphoproliferative disorders. We also present a unique case of CD8/CD30 LyP with histologic similarities to LyP type B. In all 7 of our cases of CD8 LyP and CD8 anaplastic large cell lymphoma, we found focal to diffuse MUM-1 positivity. We propose that MUM-1 may represent an adjunctive marker for CD8 lymphoproliferative disease. Finally, we review the current literature on cases of CD8 LyP and PCALCL. For the 106 cases examined, we found similar clinical and histologic features to those reported for traditional CD4CD30 LyP and PCALCL.

  16. A typical aspects of intrathoracic posttransplantation lymphoproliferative disorders

    International Nuclear Information System (INIS)

    Beigelman, C.; Leblond, V.; Suberbielle, C.; Lenoir, S.; Dorent, R.; Grenier, P.

    1995-01-01

    Posttransplant lymphoproliferative disorders (PTLD), developing after immunosuppressive therapy in human organ-graft recipients, are, for the most part, Epstein-Barr virus-induced. The earlier the diagnosis is made, the greater the potential for reversibility. The chest radiographs and CT scans of 10 patients with thoracic locations of PTLD were reviewed. Mediastinal and hilar adenopathy, pulmonary nodules, and pleural thickening or effusion were encountered. The incidence of partial resolution with clinical remission appears to be noteworthy, and in all likelihood is related to the extensive necrosis that is frequently seen. Slow regression, transitory deterioration in one case, and localization only on the graft side in two cases, were observed. These morphological and evolutionary peculiarities must be known in order to optimize the diagnosis, and thus the prognosis, of these very original disorders. (orig.)

  17. Mutlifocal osseous posttransplantation lymphoproliferative disorder: case report

    International Nuclear Information System (INIS)

    Lo, Ryan; Michalicek, Zachary; Lazarus, Martin

    2015-01-01

    Posttransplant lymphoproliferative disorder (PTLD) is a known complication of organ transplantation, but musculoskeletal involvement of PTLD remains very rare. We present a case of recurrent PTLD of the bone in a heart transplant patient that was misdiagnosed as gout for several years. There are only a few cases of osseous PTLD in the literature, and we hope to better characterize its imaging findings on multiple imaging modalities. (orig.)

  18. Mutlifocal osseous posttransplantation lymphoproliferative disorder: case report

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    Lo, Ryan [University of Chicago, Department of Radiology, Chicago, IL (United States); Michalicek, Zachary [Northshore University Healthsystems, Department of Pathology, Evanston, IL (United States); Lazarus, Martin [Northshore University Healthsystems, Department of Radiology, Evanston, IL (United States)

    2015-02-14

    Posttransplant lymphoproliferative disorder (PTLD) is a known complication of organ transplantation, but musculoskeletal involvement of PTLD remains very rare. We present a case of recurrent PTLD of the bone in a heart transplant patient that was misdiagnosed as gout for several years. There are only a few cases of osseous PTLD in the literature, and we hope to better characterize its imaging findings on multiple imaging modalities. (orig.)

  19. Post-kidney transplant large bowel lymphoproliferative disorder

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    Neeraj Singh

    2014-01-01

    Full Text Available Epstein-Barr virus (EBV-associated post-transplant lymphoproliferative disorder (PTLD is a serious complication of organ transplantation. The gastrointestinal (GI tract is a common site involved, but non-specific signs and symptoms often delay the diagnosis. We report a case of EBV-associated GI-PTLD in a 68-year-old kidney transplant patient who received the kidney ten months earlier. He presented with chronic diarrhea and developed massive pneumo-peritoneum secondary to multiple colonic perforations.

  20. IgG4-related disease in autoimmune lymphoproliferative syndrome.

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    van de Ven, Annick A J M; Seidl, Maximilian; Drendel, Vanessa; Schmitt-Graeff, Annette; Voll, Reinhard E; Rensing-Ehl, Anne; Speckmann, Carsten; Ehl, Stephan; Warnatz, Klaus; Kollert, Florian

    2017-07-01

    A patient with autoimmune lymphoproliferative disorder (ALPS) developed IgG4-related disease. In retrospect, he had high levels of serum IgG4 for several years prior to presenting with IgG4-related pancreatitis. These high IgG4 levels were masked by hypergammaglobulinemia, a common feature of ALPS. We next screened 18 ALPS patients; four of them displayed increased levels of IgG4. Hence, IgG4-related disease should be considered in ALPS patients, especially in those manifesting lymphocytic organ infiltration or excessive hypergammaglobulinaemia. Screening of IgG4-related disease patients for ALPS-associated mutations would provide further information on whether this disease could be a late-onset atypical presentation of ALPS. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Treatment of Primary Cutaneous CD4 Small/Medium T cell Lymphoproliferative Disorder with Intralesional Triamcinolone Acetonide.

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    2018-02-15

    12. REPORT TYPE 02/15/2018 Poster 4. TITLE AND SUBTITLE Treatment of Primary Cutaneous CD4+ Small/Medium T- cell Lymphoproliferative Disorder with...cutaneous CD4+ small/medium T- cell lymphoproliferative disorder (LPD) is a generally indolent cutaneous T- cell proliferation. Most cases follow a benign...lmmunohistochemistry showed diffuse CD3+ CD4+ T- cells without CD30, TIA1 or CD10. A subset of medium to large cells expressed BCL-6. Small subsets of B- cells and CDB

  2. Native kidney posttransplant lymphoproliferative disorder in a renal transplant recipient.

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    Chandra, Abhilash; Kaul, Anupama; Aggarwal, Vinita; Srivastava, Divya

    2017-01-01

    Compared with the general population, cancer risk in kidney transplant recipients is much higher. In the present study, we report a patient who was diagnosed with posttransplant lymphoproliferative disorder (PTLD) and had a fulminant course, dying within few days of diagnosis. This case report highlights the importance of timely detection and treatment of PTLD as it is associated with high mortality rate.

  3. Native kidney posttransplant lymphoproliferative disorder in a renal transplant recipient

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    Abhilash Chandra; Anupama Kaul; Vinita Aggarwal; Divya Srivastava

    2017-01-01

    Compared with the general population, cancer risk in kidney transplant recipients is much higher. In the present study, we report a patient who was diagnosed with posttransplant lymphoproliferative disorder (PTLD) and had a fulminant course, dying within few days of diagnosis. This case report highlights the importance of timely detection and treatment of PTLD as it is associated with high mortality rate.

  4. Development of an Epstein-Barr virus-associated lymphoproliferative disorder in a patient treated with azacitidine for chronic myelomonocytic leukaemia.

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    Menter, T; Schlageter, M; Bastian, L; Haberthür, R; Rätz Bravo, A E; Tzankov, A

    2014-03-01

    Some chemotherapeutic agents can cause iatrogenic lymphoproliferative disorders. In analogy to what has been observed with other nucleoside analogues such as cladribine and fludarabine, we document the first case of an Epstein-Barr virus-positive, iatrogenic immunodeficiency-associated, lymphoproliferative disease, formally resembling polymorphic post-transplant lymphoproliferative disease in a patient treated with azacitidine (Vidaza) for chronic myelomonocytic leukaemia (CMML). A 78-year-old female patient was diagnosed with CMML in January 2012, and treatment with azacitidine was initiated, which lasted for five cycles from February until June 2012. The patient was hospitalized in June 2012 under the suspicion of pneumonia. Transformation of the CMML was suspected at that time too. During hospitalization, a generalized enlargement of the lymph nodes and the spleen was noticed. The patient rapidly deteriorated and finally died of respiratory insufficiency. At autopsy, an Epstein-Barr virus-associated lymphoproliferative disorder, resembling polymorphic post-transplant lymphoproliferative disease with involvement of the lymph nodes, the spleen and the lung and causing necrotizing pneumonia, was diagnosed. Diagnostic criteria for diffuse large B-cell lymphoma or infectious mononucleosis-like lymphoproliferative disease were not met. This is the first documented case of an azacitidine-associated lymphoproliferative disease, raising awareness for possible not yet known side effects of this drug, which should be kept in mind by oncologists and pathologists. Copyright © 2013 John Wiley & Sons, Ltd.

  5. Native kidney posttransplant lymphoproliferative disorder in a renal transplant recipient

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    Abhilash Chandra

    2017-01-01

    Full Text Available Compared with the general population, cancer risk in kidney transplant recipients is much higher. In the present study, we report a patient who was diagnosed with posttransplant lymphoproliferative disorder (PTLD and had a fulminant course, dying within few days of diagnosis. This case report highlights the importance of timely detection and treatment of PTLD as it is associated with high mortality rate.

  6. Notch signalling in primary cutaneous CD30+ lymphoproliferative disorders: a new therapeutic approach?

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    Kamstrup, M R; Biskup, E; Gniadecki, R

    2010-01-01

    The oncogenic potential of deregulated Notch signalling has been described in several haematopoietic malignancies. We have previously reported an increased expression of Notch1 in primary cutaneous CD30+ lymphoproliferative disorders, lymphomatoid papulosis and primary cutaneous anaplastic large...

  7. Interleukin-10 and posttransplant lymphoproliferative disorder after kidney transplantation

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    Birkeland, S.A.; Bendtzen, K.; Moller, B.

    1999-01-01

    Background. Posttransplant lymphoproliferative disorder (PTLD) is a life-threatening complication of transplantation, which comprises a morphologically and clinically heterogeneous spectrum of B-lymphocyte diseases. Risk factors include primary or reactivated Epstein-Barr virus (EBV) infection...... to the development of PTLD in three kidney transplanted patients. The study now includes nine patients that could be followed before and/or after the occurrence of lymphoma, Methods. Nine patients with lymphomas (eight PTLDs and one Hodgkin's disease) were diagnosed among 268 consecutive renal transplantations (1990...

  8. Mapping the x-linked lymphoproliferative syndrome

    International Nuclear Information System (INIS)

    Skare, J.C.; Milunsky, A.; Byron, K.S.; Sullivan, J.L.

    1987-01-01

    The X-linked lymphoproliferative syndrome is triggered by Epstein-Barr virus infection and results in fatal mononucleosis, immunodeficiency, and lymphoproliferative disorders. This study shows that the mutation responsible for X-linked lymphoproliferative syndrome is genetically linked to a restriction fragment length polymorphism detected with the DXS42 probe (from Xq24-q27). The most likely recombination frequency between the loci is 4%, and the associated logarithm of the odds is 5.26. Haplotype analysis using flanking restriction fragment length polymorphism markers indicates that the locus for X-linked lymphoproliferative syndrome is distal to probe DXS42 but proximal to probe DXS99 (from Xq26-q27). It is now possible to predict which members of a family with X-linked lymphoproliferative syndrome are carrier females and to diagnose the syndrome prenatally

  9. Mapping the x-linked lymphoproliferative syndrome

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    Skare, J.C.; Milunsky, A.; Byron, K.S.; Sullivan, J.L.

    1987-04-01

    The X-linked lymphoproliferative syndrome is triggered by Epstein-Barr virus infection and results in fatal mononucleosis, immunodeficiency, and lymphoproliferative disorders. This study shows that the mutation responsible for X-linked lymphoproliferative syndrome is genetically linked to a restriction fragment length polymorphism detected with the DXS42 probe (from Xq24-q27). The most likely recombination frequency between the loci is 4%, and the associated logarithm of the odds is 5.26. Haplotype analysis using flanking restriction fragment length polymorphism markers indicates that the locus for X-linked lymphoproliferative syndrome is distal to probe DXS42 but proximal to probe DXS99 (from Xq26-q27). It is now possible to predict which members of a family with X-linked lymphoproliferative syndrome are carrier females and to diagnose the syndrome prenatally.

  10. Possible Association of Multicentric Castleman's Disease with Autoimmune Lymphoproliferative Syndrome

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    Hiroyuki Minemura

    2018-04-01

    Full Text Available Multicentric Castleman's disease (MCD is lymphoproliferative disorder characterized by systemic inflammatory symptoms such as fever and weight loss. Human herpes virus-8 (HHV-8 is thought to be a causable pathogen in all HIV-positive and some HIV-negative MCD patients. Furthermore, the term idiopathic MCD (iMCD was recently proposed to represent a group of HIV-negative and HHV-8-negative patients with unknown etiologies. Although the international diagnostic criteria for iMCD require exclusion of infection-related disorders, autoimmune/autoinflammatory diseases and malignant/lymphoproliferative disorders to make an iMCD diagnosis, the relationships and differences between these disorders and MCD have not yet been clarified. We recently reported the first case of MCD with autoimmune lymphoproliferative syndrome (ALPS. Although ALPS was included in the iMCD exclusion criteria as an autoimmune/autoinflammatory disease according to the international diagnostic criteria, there is a lack of evidence on the association between MCD and ALPS. In this study, we review the recent understanding of MCD and discuss the possible association between MCD with ALPS.

  11. The splenomegaly of myeloproliferative and lymphoproliferative disorders: splenic cellularity and vascularity

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    Zhang, B (Capital Hospital, Peking University Medical College, Beijing (China)); Lewis, S.M. (Department of Haematology, Royal Postgraduate Medical School, London (UK))

    1989-01-01

    Employing radionuclide scanning, the volume of the spleen, its red cell pool and plasma pool have been measured in vivo, and the relative proportions of cellularity and vascularity of the spleen have been calcualted in 51 patients with myeloproliferactive and lymphoproliferative disorders. In primary proliferative polycythaemia (polycythaemia vera), the increase of spleen size was attributed mainly to the increase of splenic vascularity; in myelofibrosis and in hairy cell leukaemia, the increase of spleen size was associated with increase in both splenic vascularity and cellularity, whilst in size was associated with increase in both splenic vascularity and cellularity, whilst in CGL and CLL the increase was attributed more to cellularity than to vascularity. (author).

  12. Impaired cytokine production and suppressed lymphocyte proliferation activity in HCV-infected cocaine and heroin ("speedball") users.

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    Ríos-Olivares, Eddy; Vilá, Luis M; Reyes, Juan C; Rodríguez, José W; Colón, J Héctor M; Pagán, Nat O; Marrero, Amalia; Ríos-Orraca, Zilka M; Boukli, Nawal M; Shapshak, Paul; Robles, Rafaela R

    2006-12-01

    HCV-infected "speedball" users (n = 30) were selected from an original cohort of 400 intravenous drug users for cytokine analysis. Cytokine concentrations (TNF-alpha, IL-1beta, IL-6, IFN-gamma, IL-2, IL-4, IL-10 and IL-12) were determined in plasma and peripheral blood mononuclear cells (PBMC) cultures derived ex vivo from these patients. In addition, lymphocyte proliferation was measured in 49 HCV-positive "speedball" users. TNF-alpha, IL-6, IFN-gamma, IL-2, IL-4, IL-10, IL-12 cytokines and not IL-1beta were significantly increased in plasma from HCV-positive "speedball" users compared with healthy controls. Except for IL-10, all other cytokines measured were augmented in phytohemagglutinin-stimulated PBMC cultures from HCV-positive "speedball" users. Likewise, overproduction of cytokines TNF-alpha, IL-1beta, IL-6 and IFN-gamma, was consistently detected when PBMC cultures from HCV-positive "speedball" users were stimulated with a biological response modifier. However, HCV-infected "speedball" users showed significant reduction in lymphoproliferative activity. Compared with healthy subjects, there was a consistent overproduction of both TH1 and TH2 type cytokines in the plasma and PBMC's of HCV-infected "speedball" users. Furthermore, there was a persistent reduction of lymphoproliferative activity in this group. These immunologic abnormalities, coupled with the range of response between the two TH-types in HCV-infected "speedball" users, suggest impairment in the regulatory mechanism of the TH1-TH2 system.

  13. Post-transplant lymphoproliferative disorders.

    Science.gov (United States)

    Singavi, Arun K; Harrington, Alexandra M; Fenske, Timothy S

    2015-01-01

    Post-transplant lymphoproliferative disorders (PTLD) are a serious complication after solid organ or allogeneic hematopoietic stem cell transplantation and include a range of diseases from benign proliferations to malignant lymphomas. Risk factors for developing PTLD include Epstein-Barr virus (EBV) infection, recipient age, transplanted organ, type of immunosuppression, and genetics. Uncontrolled proliferation of EBV-infected B cells is implicated in EBV-positive PTLD, whereas the pathogenesis of EBV-negative PTLD may be similar to non-Hodgkin's lymphoma in the general population. The World Health Organization (WHO) classifies PTLD into four categories: early lesions, polymorphic PTLD, monomorphic PTLD, and classical Hodgkin's lymphoma (cHL). Treatment is aimed at cure of PTLD, while maintaining transplanted organ function. However, there are no established guidelines for the treatment of PTLD. Immune suppression reduction (ISR) is the first line of treatment in most cases, with more recent data suggesting early use of rituximab. In more aggressive forms of PTLD, upfront chemotherapy may offer a better and more durable response. Sequential therapy using rituximab followed by chemotherapy has demonstrated promising results and may establish a standard of care. Novel therapies including anti-viral agents, adoptive immunotherapy, and monoclonal antibodies targeting cytokines require further study in the prevention and treatment of PTLD.

  14. Risk factors for Epstein-Barr virus-related post-transplant lymphoproliferative disease after allogeneic hematopoietic stem cell transplantation.

    Science.gov (United States)

    Uhlin, Michael; Wikell, Helena; Sundin, Mikael; Blennow, Ola; Maeurer, Markus; Ringden, Olle; Winiarski, Jacek; Ljungman, Per; Remberger, Mats; Mattsson, Jonas

    2014-02-01

    Allogeneic hematopoietic stem cell transplantation is a successful treatment for hematologic malignancies and a variety of genetic and metabolic disorders. In the period following stem cell transplantation, the immune-compromised milieu allows opportunistic pathogens to thrive. Epstein-Barr virus-associated post-transplant lymphoproliferative disease can be a life-threatening complication for transplanted patients because of suppressed T-cell-mediated immunity. We analyzed possible risk factors associated with post-transplant lymphoproliferative disease in a cohort of over 1,000 patients. The incidence of post-transplant lymphoproliferative disease was 4%. Significant risk factors identified by multivariate analysis were: human leukocyte antigen-mismatch (PEpstein-Barr virus mismatch recipient-/donor+ (Pdisease grade II to IV (P=0.006), pre-transplant splenectomy (P=0.008) and infusion of mesenchymal stromal cells (P=0.015). The risk of post-transplant lymphoproliferative disease has increased in more recent years, from less than 2% before 1998 to more than 6% after 2011. Additionally, we show that long-term survival of patients with post-transplant lymphoproliferative disease is poor despite initial successful treatment. The 3-year survival rate among the 40 patients with post-transplant lymphoproliferative disease was 20% as opposed to 62% among patients without post-transplant lymphoproliferative disease (Pdisease after transplantation in need of pre-emptive measures.

  15. Epstein-Barr Virus-associated lymphoproliferative disorders: experimental and clinical developments

    Science.gov (United States)

    Geng, Lingyun; Wang, Xin

    2015-01-01

    Epstein-Barr Virus (EBV), the first human virus related to oncogenesis, was initially identified in a Burkitt lymphoma cell line in 1964. EBV infects over 90% of the world’s population. Most infected people maintain an asymptomatic but persistent EBV infection lifelong. However, in some individuals, EBV infection has been involved in the development of cancer and autoimmune disease. Nowadays, oncogenic potential of EBV has been intensively studied in a wide range of human neoplasms, including Hodgkin’s lymphoma (HL), non-Hodgkin’s lymphoma (NHL), nasopharyngeal carcinoma (NPC), gastric carcinoma (GC), etc. EBV encodes a series of viral protein and miRNAs, promoting its persistent infection and the transformation of EBV-infected cells. Although the exact role of EBV in the oncogenesis remains to be clarified, novel diagnostic and targeted therapeutic approaches are encouraging for the management of EBV-related malignancies. This review mainly focuses on the experimental and clinical advances of EBV-associated lymphoproliferative disorders. PMID:26628948

  16. Treatment of post-transplantation lymphoproliferative disorders after kidney transplant with rituximab and conversion to m-TOR inhibitor.

    Science.gov (United States)

    Nieto-Rios, John Fredy; Gómez de Los Ríos, Sandra Milena; Serna-Higuita, Lina María; Ocampo-Kohn, Catalina; Aristizabal-Alzate, Arbey; Gálvez-Cárdenas, Kenny Mauricio; Zuluaga-Valencia, Gustavo Adolfo

    2016-12-30

    Post-transplantation lymphoproliferative disorders are serious complications of organ transplantation which treatment is not yet standardized. To describe the clinical response, overall and graft survival of patients in our center with this complication after kidney transplantation, which received rituximab as part of their treatment as well as conversion to m-TOR. Retrospective study, which included patients, diagnosed with post-transplant lymphoproliferative disorders after kidney transplantation from January 2011 to July 2014. Eight cases were found with a wide spectrum of clinical presentations. Most had monomorphic histology, 85% were associated with Epstein-Barr virus, 25% of patients had tumor involvement of the renal graft, and 12.5% ​​had primary central nervous system lymphoma. All patients were managed with reduction of immunosuppression, conversion to m-TOR (except one who lost the graft at diagnosis) and rituximab-based therapy. The overall response rate was 87.5% (62.5% complete response, 25% partial response). Survival was 87.5% with a median follow-up of 34 months. An additional patient lost the graft, with chronic nephropathy already known. All the remaining patients had stable renal function. There are no standardized treatment regimens for lymphoproliferative disorders after kidney transplantation, but these patients can be managed successfully with reduction of immunosuppression, conversion to m-TOR and rituximab-based schemes.

  17. Post-transplant Lymphoproliferative Disorder Arising from Renal Allograft Parenchyma: A Case Report

    Energy Technology Data Exchange (ETDEWEB)

    Park, Byung Kwan; Kim, Chan Kyo; Kwon, Ghee Young [Samsung Medical Center, Sungkyunkwan University College of Medicine, Seoul (Korea, Republic of)

    2010-06-15

    Post-transplant lymphoproliferative disorder (PTLD) is a rare but serious complication that occurs in patients undergoing kidney transplantation. PTLD usually manifests as a renal hilar mass comprised of histologically B-lymphocytes. We report our experience of managing a patient with PTLD arising from renal parenchyma. Ultrasonographic and MR imaging features of this unusual PTLD suggested differentiated renal cell carcinoma arising from the renal allograft

  18. Two rare cases of Epstein-Barr virus-associated lymphoproliferative disorders in inflammatory bowel disease patients on thiopurines and other immunosuppressive medications.

    Science.gov (United States)

    Subramaniam, K; Cherian, M; Jain, S; Latimer, M; Corbett, M; D'Rozario, J; Pavli, P

    2013-12-01

    The setting of chronic immunosuppression in inflammatory bowel disease (IBD) may promote the proliferation of Epstein-Barr virus-positive neoplastic clones. We report two rare cases of Epstein-Barr virus-associated lymphoproliferative disorder in IBD patients: one resembled lymphomatoid granulomatosis, and the other was a lymphoma resembling Hodgkin lymphoma. There are currently no guidelines for the prevention of lymphoproliferative disorder in IBD patients on immunosuppressive therapy. © 2013 The Authors; Internal Medicine Journal © 2013 Royal Australasian College of Physicians.

  19. Patogenetic correction of anemia with erythropoiesis-stimulating agents in lymphoproliferative disorders (literature review

    Directory of Open Access Journals (Sweden)

    N. A. Romanenko

    2014-07-01

    Full Text Available Literature review of anemia pathogenesis in patients with lymphatic system malignancies is presented. Advantages and disadvanta ges of eritropoiesis-stimulating preparations (ESP used for anemia correction are shown. Efficacy of anemia treatment with ESP in various types of lymphoproliferative disorders (LPD is presented. Prognostic factors that predict positive response on ESP in LPD pati ents and reduce treatment cost are identified.

  20. Patogenetic correction of anemia with erythropoiesis-stimulating agents in lymphoproliferative disorders (literature review

    Directory of Open Access Journals (Sweden)

    N. A. Romanenko

    2011-01-01

    Full Text Available Literature review of anemia pathogenesis in patients with lymphatic system malignancies is presented. Advantages and disadvanta ges of eritropoiesis-stimulating preparations (ESP used for anemia correction are shown. Efficacy of anemia treatment with ESP in various types of lymphoproliferative disorders (LPD is presented. Prognostic factors that predict positive response on ESP in LPD pati ents and reduce treatment cost are identified.

  1. Occurrence and prognostic relevance of CD30 expression in post-transplant lymphoproliferative disorders

    DEFF Research Database (Denmark)

    Vase, Maja Ølholm; Maksten, Eva Futtrup; Bendix, Knud

    2015-01-01

    Post-transplant lymphoproliferative disorders (PTLDs) are potentiallyfatal, often Epstein-Barr virus (EBV)-driven neoplasias developing in immunocompromised hosts. Initial treatment usually consists of a reduction in immunosuppressive therapy and/or rituximab with or without chemotherapy. However...... favorable outcome. For diffuse large B-cell lymphoma (DLBCL)-type PTLD this was regardless of EBV status, and remained significant in multivariate analysis. Cell-of-origin had no independent prognostic value in our series of DLBCL PTLD....

  2. Treatment response in HCV related chronic hepatitis

    International Nuclear Information System (INIS)

    Hussain, A.B.; Hussain, T.; Hussain, S.; Masood, A.; Kazmi, Y.; Tariq, W.Z.; Karamat, K.A.

    2004-01-01

    Objective: To evaluate the virological response to treatment with interferon and ribavirin in-patients with hepatitis C related liver disease. Material and Methods: Two hundred seventy-nine patients were included in the study. These patients had taken interferon and ribavirin treatment for HCV related chronic hepatitis, and were referred to AFIP for HCV RNA testing by polymerase chain reaction (PCR) between January 2002 and September 2002. Out of 279 cases, 229 had taken the treatment for 06 or 12 months and were tested for end-of-treatment response (ETR). Fifty patients had completed there treatment regimens of 6 or 12 months treatment, at least 24 weeks before their PCR test and were having follow-up testing for sustained viral response (SVR). The sera of these patients were tested for HCV RNA by PCR, using a commercial kit of Amplicor (Roche) for qualitative detection of HCV RNA. Results: Out of 229 cases tested for end-of-treatment response, 198 (86.5%) had no detectable HCV RNA (responders) and 31 (13.50%) were PCR positive (non-responders). Thirty-eight out of 50 cases, tested for a sustained viral response, had a negative result for HCV PCR thus showing sustained response rate of 76%. Conclusion: The viral remission/response to interferon and ribavirin combination therapy in our patients was better than that quoted in other regions. (author)

  3. Hepatitis C virus infection in nephrology patients.

    Science.gov (United States)

    Rostaing, Lionel; Izopet, Jacques; Kamar, Nassim

    2013-10-01

    Hepatitis C virus (HCV) infection leads to chronic liver disease, but also to extra-hepatic manifestations. Directory of Open Access Journals (DOAJ), Google Scholar, Pubmed (NLM), LISTA (EBSCO) and Web of Science have been searched. Herein, we provide an overview of renal diseases related to HCV and their therapies, as well as the treatment options available for HCV (+)/RNA (+) dialysis patients. We will not mention, however, HCV infection-related complications in the post-kidney transplantation setting. Extra-hepatic manifestations of HCV infection include mixed cryoglobulinemia, lymphoproliferative disorders, and renal disease. HCV infection has been reported in association with distinct histological patterns of glomerulonephritis in native kidneys.

  4. Psychiatric and substance use disorders in HIV/hepatitis C virus (HCV)-coinfected patients: does HCV clearance matter? [Agence Nationale de Recherche sur le SIDA et les Hépatites Virales (ANRS) HEPAVIH CO13 cohort].

    Science.gov (United States)

    Michel, L; Lions, C; Winnock, M; Lang, J-P; Loko, M-A; Rosenthal, E; Marchou, B; Valantin, M-A; Morlat, P; Roux, P; Sogni, P; Spire, B; Poizot-Martin, I; Lacombe, K; Lascoux-Combe, C; Duvivier, C; Neau, D; Dabis, F; Salmon-Ceron, D; Carrieri, M P

    2016-11-01

    The objective of this nested study was to assess the prevalence of psychiatric disorders in a sample of HIV/hepatitis C virus (HCV)-coinfected patients according to their HCV status. The nested cross-sectional study, untitled HEPAVIH-Psy survey, was performed in a subset of HIV/HCV-coinfected patients enrolled in the French Agence Nationale de Recherche sur le SIDA et les Hépatites Virales (ANRS) CO13 HEPAVIH cohort. Psychiatric disorders were screened for using the Mini International Neuropsychiatric Interview (MINI 5.0.0). Among the 286 patients enrolled in the study, 68 (24%) had never received HCV treatment, 87 (30%) were treatment nonresponders, 44 (15%) were currently being treated and 87 (30%) had a sustained virological response (SVR). Of the 286 patients enrolled, 121 patients (42%) screened positive for a psychiatric disorder other than suicidality and alcohol/drug abuse/dependence, 40 (14%) screened positive for alcohol abuse/dependence, 50 (18%) screened positive for drug abuse/dependence, 50 (17.5%) were receiving an antidepressant treatment and 69 (24%) were receiving an anxiolytic. Patients with an SVR did not significantly differ from the other groups in terms of psychiatric disorders. Patients receiving HCV treatment screened positive less often for an anxiety disorder. The highest rate of drug dependence/abuse was among HCV treatment-naïve patients. Psychiatric disorders were frequent in HIV/HCV-coinfected patients and their rates were comparable between groups, even for patients achieving an SVR. Our results emphasize the need for continuous assessment and care of coinfected patients, even after HCV clearance. Drug addiction remains an obstacle to access to HCV treatment. Despite the recent advent and continued development of directly acting antiviral agents (DAAs), it is still crucial to offer screening and comprehensive care for psychiatric and addictive disorders. © 2016 British HIV Association.

  5. Epstein-Barr virus in inflammatory bowel disease: the spectrum of intestinal lymphoproliferative disorders.

    Science.gov (United States)

    Nissen, Loes H C; Nagtegaal, Iris D; de Jong, Dirk J; Kievit, Wietske; Derikx, Lauranne A A P; Groenen, Patricia J T A; van Krieken, J Han J M; Hoentjen, Frank

    2015-05-01

    Inflammatory bowel disease (IBD) patients on thiopurine therapy are at increased risk of Epstein-Barr virus (EBV)-associated lymphomas. This virus is frequently detected in the intestinal mucosa of IBD patients and may cause a wide spectrum of lymphoproliferations similar to post-transplantation lymphoproliferative disorders (PTLDs). We aimed to assess whether histological aberrations aid in predicting EBV presence and to correlate histological assessment and EBV load with disease outcome in IBD. We included all IBD patients from our centre who underwent EBV testing of intestinal biopsies between January 2004 and October 2013. All biopsies were classified according to the WHO PTLD classification and the EBV load was scored per high-power field (HPF). Clinical data were collected from patient charts. Reported clinical outcomes included colectomy, need for chemotherapy and mortality. Our cohort included 58 patients: 28 were EBV-positive and 30 EBV-negative. An atypical infiltrate was seen more frequently in EBV-positive than in EBV-negative patients (57.1 versus 3.3%; p < 0.001). A high EBV load occurred more frequently in EBV-positive patients undergoing colectomy than in EBV-positive patients without colectomy (50.0 versus 10.0%; p = 0.048). Monomorphic lymphoproliferative disorders, including two overt lymphomas, were present in 10 patients. Reduction of immunosuppression resulted in histological normalization and loss of EBV expression in seven of eight non-lymphoma patients. The presence of atypical infiltrate in the intestinal mucosa of IBD patients warrants EBV testing. Reduction of immunosuppression is an effective strategy to achieve morphological normalization and loss of EBV. Lymphoproliferation related to IBD appears to have less aggressive clinical behaviour than PTLDs. Copyright © 2015 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  6. Long-term follow-up of kidney transplant patients with posttransplant lymphoproliferative disorder

    DEFF Research Database (Denmark)

    Birkeland, S A; Hamilton-Dutoit, Stephen Jacques; Bendtzen, K

    2003-01-01

    Posttransplant lymphoproliferative disorder (PTLD) can be resolved in many transplant patients by the reduction or cessation of immunosuppression, after which many grafts continue to function as the result of a form of operational tolerance. When graft function deteriorates, retransplantation may...... be an option. Cytokines such as interleukin (IL)-10 and IL-18 may play a role in PTLD tolerance induction and tumor regression. We report long-term follow-up on the duration of graft tolerance and the course of retransplantation in a series of patients who underwent kidney transplantation and demonstrated PTLD...

  7. Efficacy of Low-Dose Protocol in Follow-Up of Lymphoproliferative Disorders - Preliminary Results

    International Nuclear Information System (INIS)

    Popic-Ramac, J.; Brnic, Z.; Klasic, B.; Hebrang, A.; Knezevic, Z.

    2011-01-01

    Most medically-related radiation is caused by diagnostic examinations, in particular by computed tomography (CT). The purpose of this research is to reduce radiation doses faced by the population frequently exposed to such procedures-those with lymphoproliferative disorders. The research was conducted comparing radiation-exposition doses received by the radiosensitive organs (thyroid, lens, breast and gonad) using the standard thoracic CT protocol with the radiation received using the low-dose protocol, while maintaining display quality. The standard-dose thoracic protocol implies 120 kV and 150 mAs. The low-dose protocol was conducted on the same device using 120 kV and 30 mAs. We confirmed the hypothesis that the use of the low-dose thoracic CT protocol leads to a reduction in radiation dose without compromising display quality. It is further expected that a reduction in doses will reduce the risk of radiation-related mutations. (author)

  8. CD30+ lymphoproliferative disorder with spindle-cell morphology.

    Science.gov (United States)

    Martires, Kathryn J; Cohen, Brandon E; Cassarino, David S

    2016-11-01

    Lymphomatoid papulosis (LyP) is classified as a CD30+ primary cutaneous lymphoproliferative disease. The phenotypic variability along the spectrum of CD30+ lymphoproliferative diseases is highlighted by the distinct histologic subtypes of LyP types A, B, C, and the more recently described types D, E, and F. We report the case of an elderly woman with a clinical presentation and histopathologic findings consistent with LyP, whose atypical CD30+ infiltrate uniquely demonstrated a spindle-cell morphology. To our knowledge, this is the first reported case of LyP characterized by CD30+ spindle-shaped cells, and may represent a new and distinct histologic variant of LyP. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  9. Response to rituximab-based therapy and risk factor analysis in epstein barr virus-related lymphoproliferative disorder after hematopoietic stem cell transplant in children and adults: a study from the Infectious Diseases Working Party of the European Group for Blood and Marrow Transplantation.

    NARCIS (Netherlands)

    Styczynski, J.; Gil, L.; Tridello, G.; Ljungman, P.; Donnelly, J.P.; Velden, W. van der; Omar, H.; Martino, R.; Halkes, C.; Faraci, M.; Theunissen, K.; Kalwak, K.; Hubacek, P.; Sica, S.; Nozzoli, C.; Fagioli, F.; Matthes, S.; Diaz, M.A.; Migliavacca, M.; Balduzzi, A.; Tomaszewska, A.; amara Rde, L. C; Biezen, A. van; Hoek, J. van den; Iacobelli, S.; Einsele, H.; Cesaro, S.

    2013-01-01

    BACKGROUND: The objective of this analysis was to investigate prognostic factors that influence the outcome of Epstein-Barr virus (EBV)-related posttransplant lymphoproliferative disorder (PTLD) after a rituximab-based treatment in the allogeneic hematopoietic stem cell transplant (HSCT) setting.

  10. Small intestinal involvement by lymphoproliferative disorders post-renal transplantation: A report from the post-transplant lymphoproliferative disorder international survey

    Directory of Open Access Journals (Sweden)

    Hossein Khedmat

    2013-01-01

    Full Text Available In this study, data on post-renal transplant lymphoproliferative disorders (PTLD collected from the existing literature were pooled and analyzed to compare the characteristics, predictors and prognosis of small intestinal PTLDs. We performed a comprehensive search for the available data by Pubmed and Google scholar search engines for reports on this subject. Data from 18 previously published studies, comprising 120 renal allograft recipients, were included in the analysis. Renal transplant recipients with intestinal PTLD were significantly less likely to have Hogkin′s and Hogkin′s-like lesions (P = 0.044 and to be younger at the time of transplan-tation (P = 0.07. Except for Hodgkin′s-like lesions, histopathological evaluations elsewhere were comparable between the group with PTLD in the small intestine and age- and sex-matched renal transplant recipients with PTLD in other sites. The overall mortality was relatively higher in the control group (P = 0.09. When death only due to PTLD was used as the outcome, a trend toward better outcome was seen for the intestinal PTLD group compared with the other localizations (P = 0.1. The 1- and 5-year survival rates for intestinal PTLD patients were 57% and 37%, respectively, compared with 54% and 21%, respectively, for the control group. According to our findings based on analysis of international data, renal transplant patients with small intestinal PTLD are more likely to be of younger age but less frequently represent Hodgkin′s and Hodgkin′s-like lesions. They also have better patient survival compared with transplant recipients with PTLD in other locations. Further multi-center prospective studies are needed to confirm our results.

  11. Endobronchial Epstein-Barr Virus Associated Post-transplant Lymphoproliferative Disorder in Hematopoietic Stem Cell Transplantation

    Directory of Open Access Journals (Sweden)

    S. Feuillet

    2009-01-01

    Full Text Available The Epstein-Barr virus (EBV associated Post-Transplant Lymphoproliferative Disorders (PTLD are increasingly recognized as a fatal complication of hematological stem cell transplantation (HSCT. Thoracic involvement, that may be isolated or part of a disseminated disease, usually encompasses pulmonary nodules or masses and mediastinal lymph node enlargement. The current case study presents 2 patients who underwent HSCT, one allogenic and the other autologous, who developed an exceptional endobronchial EBV related PTLD. The first patient had a fleshy white endobronchial mass resulting in a right upper lobe atelectasis and the second had an extensive necrotising mucosa from trachea to both basal bronchi without any significant change of lung parenchyma on the CT scan. In both cases, the diagnosis was made by bronchial biopsies. Physicians should be aware of an endobronchial pattern of EBV associated PTLD after HSCT to permit quick diagnosis and therapeutic intervention.

  12. Notch-deficient skin induces a lethal systemic B-lymphoproliferative disorder by secreting TSLP, a sentinel for epidermal integrity.

    Directory of Open Access Journals (Sweden)

    Shadmehr Demehri

    2008-05-01

    Full Text Available Epidermal keratinocytes form a highly organized stratified epithelium and sustain a competent barrier function together with dermal and hematopoietic cells. The Notch signaling pathway is a critical regulator of epidermal integrity. Here, we show that keratinocyte-specific deletion of total Notch signaling triggered a severe systemic B-lymphoproliferative disorder, causing death. RBP-j is the DNA binding partner of Notch, but both RBP-j-dependent and independent Notch signaling were necessary for proper epidermal differentiation and lipid deposition. Loss of both pathways caused a persistent defect in skin differentiation/barrier formation. In response, high levels of thymic stromal lymphopoietin (TSLP were released into systemic circulation by Notch-deficient keratinocytes that failed to differentiate, starting in utero. Exposure to high TSLP levels during neonatal hematopoiesis resulted in drastic expansion of peripheral pre- and immature B-lymphocytes, causing B-lymphoproliferative disorder associated with major organ infiltration and subsequent death, a previously unappreciated systemic effect of TSLP. These observations demonstrate that local skin perturbations can drive a lethal systemic disease and have important implications for a wide range of humoral and autoimmune diseases with skin manifestations.

  13. Transfusion Related Hepatitis C Virus (HCV) Infection in Sickle Cell ...

    African Journals Online (AJOL)

    Rev Olaleye

    ABSTRACT: This study aimed to determine retrospectively, the prevalence of hepatitis C virus infection in relation to a background history of blood transfusion; through anti HCV antibody screening test, amongst adult sickle cell disease patients. Anti HCV antibody was tested for in the serum of 92 consecutively selected ...

  14. Advances in Understanding the Pathogenesis of Epstein-Barr Virus-Associated Lymphoproliferative Disorders.

    Science.gov (United States)

    Yang, Xi; Nishida, Naonori; Zhao, Xiaodong; Kanegane, Hirokazu

    2015-10-01

    Epstein-Barr virus (EBV) was discovered 50 years ago from an african Burkitt lymphoma cell line. EBV-associated lymphoproliferative disorders (LPDs) are life- threatening diseases, especially in children. In this article, we review EBV-associated LPDs, especially in the area of primary immunodeficiency disease (PID). We searched PubMed for publications with key words including EBV infection, lymphoma, LPDs and PID, and selected the manuscripts written in English that we judged to be relevant to the topic of this review.On the basis of the data in the literature, we grouped the EBV-associated LPDs into four categories: nonmalignant disease, malignant disease, acquired immunodeficiency disease and PID. Each category has its own risk factor for LPD development. EBV-associated LPD is a complex disease, creating new challenges for diagnosis and treatment.

  15. LYMPHOPROLIFERATIVE SYNDROMES ASSOCIATED WITH HUMAN HERPESVIRUS-6A AND HUMAN HERPESVIRUS-6B

    Directory of Open Access Journals (Sweden)

    Eva Eliassen

    2018-05-01

    Full Text Available Human herpesvirus 6A and 6B (HHV-6A and HHV-6B have been noted since their discovery for their T-lymphotropism. Although it has proven difficult to determine the extent to which HHV-6A and HHV-6B are involved in the pathogenesis of many diseases, evidence suggests that primary infection and reactivation of both viruses may induce or contribute to the progression of several lymphoproliferative disorders, ranging from benign to malignant and including infectious mononucleosis-like illness, drug induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms (DIHS/DRESS, and nodular sclerosis Hodgkin’s lymphoma. Herein, we discuss the conditions associated with the lymphoproliferative capacity of HHV-6, as well as the potential mechanisms behind them. Continued exploration on this topic may add to our understanding of the interactions between HHV-6 and the immune system and may open the doors to more accurate diagnosis and treatment of certain lymphoproliferative disorders.

  16. Detection of bcl-2 translocation in patients with chronic hepatitis C and its possible relation to antiviral therapy: preliminary study

    International Nuclear Information System (INIS)

    Ibrahim, N.S.; Hanna, M.O.F.; Farid, R.J.; Zayed, N.A.; Hunter, S.S.; Esmat, J.

    2007-01-01

    It has been suggested that t(14; 18) translocation of bcl-2 to the immunoglobulin heavy chain (IgH) locus may contribute to the pathogenesis of lymphoproliferative disorders (LPD) related to hepatitis C virus (HCV) infection. The present study aimed to assess the prevalence of bcl-2 translocation in Egyptian chronic HCV patients and to investigate the effect of combination antiviral therapy of interferon a and ribavirin on t(14;18). Fifty five chronic HCV patients were studied for the prevalence of t(l4; 18). These patients were classified into 2 groups, 33 non treated HCV patients and 22 treated HCV patients with antiviral therapy as well as control group of age and sex matched individuals. The bcl-2/IgH rearrangement was detected in peripheral blood mononuclear cells (PBMCs) by nested polymerase chain reaction. All patients have undergone HCV viral determination by real time PCR. Bcl-2/IgH translocation was detected in 21 (38.2%) of all 55 chronically infected HCV patients. Considering all patients with chronic HCV-infection, bcl-2 rearrangement was slightly more frequent in the non treated group than in those who underwent treatment with interferon plus ribavirin but the difference was not statistically significant, although treated patients showed biochemical and virologic response at the end of 6 months of antiviral therapy. In conclusion, t(l4;18) in PBMCs is a frequent finding in chronic HCV infection

  17. Associations among Epstein-Barr virus subtypes, human leukocyte antigen class I alleles, and the development of posttransplantation lymphoproliferative disorder in bone marrow transplant recipients

    NARCIS (Netherlands)

    Görzer, Irene; Puchhammer-Stöckl, Elisabeth; van Esser, Joost W J; Niesters, Hubert G M; Cornelissen, Jan J

    2007-01-01

    The association between Epstein-Barr virus subtype, human leukocyte antigen class I alleles, and the development of posttransplantation lymphoproliferative disorder was examined in a group of 25 bone marrow transplant recipients. A highly statistically significant correlation was observed between

  18. Outpatient management of steroid-induced hyperglycaemia and steroid-induced diabetes in people with lymphoproliferative disorders treated with intermittent high dose steroids

    Directory of Open Access Journals (Sweden)

    Jennifer Vidler

    2017-09-01

    Eighty-three people were diagnosed with a lymphoproliferative disorder, of whom 6 had known Type 2 diabetes. Fifty-three people without known diabetes were screened by HbA1c and random venous plasma glucose. All patients (n = 34 subsequently prescribed HDS checked capillary blood glucose (CBG pre-breakfast and pre-evening meal. Treatment algorithms used initiation and/or dose titration of gliclazide or human NPH insulin, aiming for pre-meal CBG 5–11 mmol/l. Type 2 diabetes was identified in 4/53 people screened (7.5%. Of 34 people treated with HDS, 17 (44% developed SIH/SID. All 7 people with Type 2 diabetes developed SIH and 3 required insulin. Of 27 people without known diabetes, 8 (30% developed SID and 1 required insulin. Pre-treatment HbA1c was higher in people who developed SID compared to those that did not (p = 0.002. This is the first report of a SID/SIH detection and treatment protocol for use in people with lymphoproliferative disorders receiving intermittent HDS, demonstrating its feasibility and safety.

  19. Mitochondrial Dysfunctions and Altered Metals Homeostasis: New Weapons to Counteract HCV-Related Oxidative Stress

    Directory of Open Access Journals (Sweden)

    Mario Arciello

    2013-01-01

    Full Text Available The hepatitis C virus (HCV infection produces several pathological effects in host organism through a wide number of molecular/metabolic pathways. Today it is worldwide accepted that oxidative stress actively participates in HCV pathology, even if the antioxidant therapies adopted until now were scarcely effective. HCV causes oxidative stress by a variety of processes, such as activation of prooxidant enzymes, weakening of antioxidant defenses, organelle damage, and metals unbalance. A focal point, in HCV-related oxidative stress onset, is the mitochondrial failure. These organelles, known to be the “power plants” of cells, have a central role in energy production, metabolism, and metals homeostasis, mainly copper and iron. Furthermore, mitochondria are direct viral targets, because many HCV proteins associate with them. They are the main intracellular free radicals producers and targets. Mitochondrial dysfunctions play a key role in the metal imbalance. This event, today overlooked, is involved in oxidative stress exacerbation and may play a role in HCV life cycle. In this review, we summarize the role of mitochondria and metals in HCV-related oxidative stress, highlighting the need to consider their deregulation in the HCV-related liver damage and in the antiviral management of patients.

  20. HLA associations and risk of posttransplant lymphoproliferative disorder in Danish population-based cohort

    DEFF Research Database (Denmark)

    Vase, Maja Ølholm; Maksten, Eva Futtrup; Strandhave, Charlotte

    2015-01-01

    Background: Posttransplant lymphoproliferative disorder (PTLD) is a feared complication to organ transplantation, associated with substantial morbidity and inferior survival. Risk factors for PTLD include T cell–depleting induction therapy and primary infection or reactivation of Epstein-Barr virus....... Possible associations between certain HLA types and the risk of developing PTLD have been reported by other investigators; however, results are conflicting. Methods: We conducted a retrospective, population-based study on 4295 Danish solid organ transplant patients from the Scandiatransplant database...... can be clinically useful after transplantation in personalized monitoring schemes. Given the strong linkage disequilibrium in the HLA region, the associations must be interpreted carefully. The large size, virtually complete ascertainment of cases and no loss to follow-up remain important strengths...

  1. EXPRESSION OF A NEW A3 ANTIGEN IN THE CELLS OF PATIENTS WITH VARIOUS LYMPHOPROLIFERATIVE DISEASES

    Directory of Open Access Journals (Sweden)

    N. L. Deineko

    2014-01-01

    Full Text Available We have conducted a study of a novel monoclonal A3 antibody raised by means of hybridoma biotechnology. The study was performed with malignant cells of the patients with various lymphoproliferative disorders, and persons with nonmalignant diseases, as compared with intact lymphocytes from healthy people,using a method of immunocytochemical staining and indirect immunofluorescence technique. It was found that in cases of lymphoproliferative diseases with low proliferation rates, as based on the numbers of Ki-67 positive cells, as well as in non-malignant blood diseases, the A3 antigen was localized in nucleoli, and it was visualized as focal fluorescence. In malignant lymphoproliferative diseases with high proliferation indexes, the number of brightly fluorescent foci is observed, with formation of necklace-like structures within the nucleolar structures. The obtained data point to a diagnostic significance of A3 Mab in assessment of cellular proliferative rates in patients with various lymphoproliferative diseases. It was established that, in contrast to Ki-67, the proliferation stage could be determined for each cell, according to the number of fuorescent foci in nucleoli. This specific property of the A3 antigen points to its significance for diagnostics and malignancy staging of lymphoproliferative disorders.

  2. Extrahepatic Manifestations and Autoantibodies in Patients with Hepatitis C Virus Infection

    Directory of Open Access Journals (Sweden)

    Takashi Himoto

    2012-01-01

    Full Text Available Patients with chronic hepatitis C virus (HCV infection frequently have many extrahepatic manifestations, as persistent HCV infection often triggers lymphoproliferative disorders and metabolic abnormalities. These manifestations primarily include autoimmune disorders such as cryoglobulinemia, Sjögren’s syndrome, and autoimmune thyroid disorders. It has been well established that chronic HCV infection plays important roles in the production of non-organ-specific autoantibodies, including antinuclear antibodies and smooth muscle antibodies, and organ-specific autoantibodies such as thyroid autoantibodies. However, the clinical significance of autoantibodies associated with the extrahepatic manifestations caused by HCV infection has not been fully recognized. In this paper, we mainly focus on the relationship between extrahepatic manifestations and the emergence of autoantibodies in patients with HCV infection and discuss the clinical relevance of the autoantibodies in the extrahepatic disorders.

  3. Orbital benign and malignant lymphoproliferative disorders: Differentiation using semi-quantitative and quantitative analysis of dynamic contrast-enhanced magnetic resonance imaging

    International Nuclear Information System (INIS)

    Hu, Hao; Xu, Xiao-Quan; Liu, Hu; Hong, Xun-Ning; Shi, Hai-Bin; Wu, Fei-Yun

    2017-01-01

    Objectives: To assess the value of dynamic contrast-enhanced MR imaging (DCE-MRI) in differentiating benign from malignant orbital lymphoproliferative disorders (OLPDs). Methods: Thirty-nine patients with orbital lymphoproliferative disorders (21 malignant and 18 benign) underwent DCE-MRI scan for pre-treatment evaluation from March 2013 to December 2015. Both semi-quantitative (TTP, AUC, Slope max ) and quantitative (K trans , k ep , v e ) parameters were calculated, and compared between two groups. Receiver operating characteristic (ROC) curve analyses were used to determine the diagnostic value of each significant parameter. Results: Malignant OLPDs showed significantly higher k ep , lower v e , and lower AUC than benign OLPDs, while no significant differences were found on K trans , TTP and Slope max . ROC analyses indicated that v e exhibited the best diagnostic performance in predicting malignant OLPDs (cutoff value, 0.211; area under the curve, 0.896; sensitivity, 76.2%; specificity, 94.9%), followed by k ep (cutoff value, 0.853; area under the curve, 0.839; sensitivity, 85.7%; specificity, 89.9%). Conclusion: DCE-MRI and specially its derived quantitative parameters of k ep and v e are promising metrics for differentiating malignant from benign OLPDs.

  4. Chemoimmunotherapy and withdrawal of immunosupression for monomorphic post-transplant lymphoproliferative disorders

    Science.gov (United States)

    Podoltsev, Nikolai; Zhang, Bingnan; Yao, Xiaopan; Bustillo, Ivan; Deng, Yanhong; Cooper, Dennis L.

    2013-01-01

    Introduction Monomorphic post-transplant lymphoproliferative disorders (PTLD) are the most aggressive type of PTLD occurring after solid organ transplantation (SOT). Current guidelines for treatment suggest a stepwise approach that includes a reduction of immunosuppression (RIS) with or without rituximab, followed by chemotherapy if there is no response. Nevertheless, recommendations regarding the extent and duration of RIS are non-standardized and RIS as an initial strategy may be associated with an unacceptably high frequency of graft loss and disease progression. Patients and Methods We reviewed the outcome of a combination program of aggressive chemo-immunotherapy and complete withdrawal of immunosuppression in treating 22 patients with monomorphic PTLD between January 1995 and August 2012. Results 12 of 22 patients (55%) received CHOP-R every 2 weeks (dose dense CHOP-R) and 10 patients received other doxorubicin-based regimens. There was no treatment related mortality (TRM). Complete response (CR) was seen in 91% of patients. Median overall survival was 9.61 years with 95% CI (5.21-10.74). Median progression free survival (PFS) was 5.39 years with 95% CI (2.10-10.74). The graft-rejection rate was 18% with 95% CI (0.03-0.34). Conclusion We conclude that the use of aggressive chemo-immunotherapy in combination with withdrawal of immunosuppression approach yields excellent results and should be prospectively studied in a multi-institutional setting. PMID:24035715

  5. Insulin-resistance HCV infection-related affects vascular stiffness in normotensives.

    Science.gov (United States)

    Perticone, Maria; Maio, Raffaele; Tassone, Eliezer Joseph; Tripepi, Giovanni; Di Cello, Serena; Miceli, Sofia; Caroleo, Benedetto; Sciacqua, Angela; Licata, Anna; Sesti, Giorgio; Perticone, Francesco

    2015-01-01

    BACKGROUND AND AIMS. Arterial stiffness evaluated as pulse wave velocity, is an early marker of vascular damage and an independent predictor for cardiovascular events. We investigated if the insulin resistance/hyperinsulinemia chronic hepatitis C virus infection-related could influence arterial stiffness. METHODS. We enrolled 260 outpatients matched for age, body mass index, gender, ethnicity: 52 with never-treated uncomplicated chronic hepatitis C virus infection (HCV(+)), 104 never-treated hypertensives (HT) and 104 healthy subjects (NT). Pulse wave velocity was evaluated by a validated system employing high-fidelity applanation tonometry. We also measured: fasting plasma glucose and insulin, total, LDL- and HDL-cholesterol, triglyceride, creatinine, e-GFR-EPI, HOMA, quantitative HCV-RNA. RESULTS. HCV(+) patients with respect to NT had an increased pulse wave velocity (7.9 ± 2.1 vs 6.4 ± 2.1 m/s; P direct correlation between HOMA and pulse wave velocity in HCV(+) patients, similar to that observed in hypertensives. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  6. Post-transplant lymphoproliferative disorder in the pelvis successfully treated with consolidative radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Habibeh, Omar; Elsayad, Khaled; Kriz, Jan; Haverkamp, Uwe; Eich, Hans Theodor [University Hospital of Muenster, Department of Radiation Oncology, Muenster (Germany)

    2017-01-15

    Post-transplant lymphoproliferative disorders (PTLDs) are aggressive malignancies which represent one of the major post-transplant complications. However, treatment options vary significantly and localized disease may be curatively treated with radiotherapy (RT) or surgery. We report a case of recurrent rectal PTLD, which was successfully treated by chemoimmunotherapy followed by RT. We describe a patient who developed a rectal lymphoproliferative lesion 11 years after kidney transplant, which was successfully treated with consolidative RT using 25.4 Gy sequential to chemoimmunotherapy (R-CHOP). RT was well tolerated and the patient showed no signs of grade 3 or 4 toxicity. This patient is free of recurrence 52 months after RT, with an overall survival of 62 months since diagnosis. Conventionally fractionated moderate-dose RT appears to be a tolerable and effective treatment option for localized PTLD if a sufficient systemic treatment cannot be applied. (orig.) [German] Posttransplantationslymphoproliferative Erkrankungen (PTLDs) sind eine haeufige Komplikation nach einer Organtransplantation. Nichtdestotrotz unterscheiden sich die Behandlungsmoeglichkeiten signifikant und vor allem lokalisierte Stadien koennen kurativ entweder mit Strahlentherapie (RT) und/oder Operation behandelt werden. Wir berichten ueber einen Fall einer rezidivierten rektalen PTLD, die erfolgreich mit einer Chemoimmuntherapie mit anschliessender RT behandelt wurde. Wir beschreiben einen Patienten der 11 Jahre nach einer Nierentransplantation eine PTLD entwickelte. Diese wurde erfolgreich mit konsolidierender RT (25,4 Gy) im Anschluss an eine Chemoimmuntherapie (R-CHOP) behandelt. Die RT wurde komplikationslos vertragen und es zeigten sich keine Nebenwirkungen. Das rezidivfreie Ueberleben betrug zum Zeitpunkt der letzten Nachsorgeuntersuchung 52 Monate mit einer Gesamtueberlebenszeit von 62 Monaten seit der Diagnose. Die konventionelle fraktionierte moderat dosierte RT scheint eine gut

  7. Fine-needle aspiration biopsy of lymphoproliferative disorders--interpretations based on morphologic criteria alone: results from the College of American Pathologists Interlaboratory Comparison Program in Nongynecologic Cytopathology.

    Science.gov (United States)

    Young, Nancy A; Moriarty, Ann T; Haja, Jennifer C; Wilbur, David C

    2006-12-01

    Diagnosis of lymphoproliferative disorders is one of the most challenging tasks faced by the cytologist. The initial cytomorphologic evaluation of lymphoproliferative lesions directs the choice of ancillary studies that ultimately lead to a diagnosis based on the World Health Organization classification system using a composite of clinical, morphologic, immunophenotypic, and molecular features. To evaluate the ability of participating laboratories in the College of American Pathologists Interlaboratory Comparison Program in Non-Gynecologic Cytopathology to appropriately categorize lymphoproliferative lesions based solely on cytomorphologic criteria. Laboratory responses for lymph node aspirates were examined. All responses were based on review of glass slides without ancillary immunologic or molecular data available. The benchmarking data provided for each specific diagnosis were analyzed, with a focus on the performance for evaluation of lymphoproliferative lesions. Based on morphology alone, responses for lymph node aspirates in the Non-Gynecologic Cytopathology program were correct to the exact reference diagnosis for 87.1% of Hodgkin lymphoma. Non-Hodgkin lymphoma was identified in 69.5% of the large cell non-Hodgkin lymphoma cases, of which 66.8% were correctly classified as large cell type. Non-Hodgkin lymphoma was identified in 68.1% of non-Hodgkin lymphoma, other than large cell cases, and of these, 94.7% were identified as other than large cell type. The spectrum of specific responses was consistent for lymphoproliferative lesions, with a reasonable differential diagnosis based on cytomorphology alone, which, in practice, facilitates the appropriate choice of immunophenotypic markers and other ancillary studies.

  8. Orbital benign and malignant lymphoproliferative disorders: Differentiation using semi-quantitative and quantitative analysis of dynamic contrast-enhanced magnetic resonance imaging

    Energy Technology Data Exchange (ETDEWEB)

    Hu, Hao; Xu, Xiao-Quan [Department of Radiology, First Affiliated Hospital of Nanjing Medical University, Nanjing (China); Liu, Hu [Department of Ophthalmology, First Affiliated Hospital of Nanjing Medical University, Nanjing (China); Hong, Xun-Ning; Shi, Hai-Bin [Department of Radiology, First Affiliated Hospital of Nanjing Medical University, Nanjing (China); Wu, Fei-Yun, E-mail: wfydd_njmu@163.com [Department of Radiology, First Affiliated Hospital of Nanjing Medical University, Nanjing (China)

    2017-03-15

    Objectives: To assess the value of dynamic contrast-enhanced MR imaging (DCE-MRI) in differentiating benign from malignant orbital lymphoproliferative disorders (OLPDs). Methods: Thirty-nine patients with orbital lymphoproliferative disorders (21 malignant and 18 benign) underwent DCE-MRI scan for pre-treatment evaluation from March 2013 to December 2015. Both semi-quantitative (TTP, AUC, Slope{sub max}) and quantitative (K{sup trans}, k{sub ep}, v{sub e}) parameters were calculated, and compared between two groups. Receiver operating characteristic (ROC) curve analyses were used to determine the diagnostic value of each significant parameter. Results: Malignant OLPDs showed significantly higher k{sub ep}, lower v{sub e}, and lower AUC than benign OLPDs, while no significant differences were found on K{sup trans}, TTP and Slope{sub max}. ROC analyses indicated that v{sub e} exhibited the best diagnostic performance in predicting malignant OLPDs (cutoff value, 0.211; area under the curve, 0.896; sensitivity, 76.2%; specificity, 94.9%), followed by k{sub ep} (cutoff value, 0.853; area under the curve, 0.839; sensitivity, 85.7%; specificity, 89.9%). Conclusion: DCE-MRI and specially its derived quantitative parameters of k{sub ep} and v{sub e} are promising metrics for differentiating malignant from benign OLPDs.

  9. Management of post-transplant lymphoproliferative disorder in adult solid organ transplant recipients - BCSH and BTS Guidelines.

    Science.gov (United States)

    Parker, Anne; Bowles, Kristin; Bradley, J Andrew; Emery, Vincent; Featherstone, Carrie; Gupte, Girish; Marcus, Robert; Parameshwar, Jayan; Ramsay, Alan; Newstead, Charles

    2010-06-01

    A joint working group established by the Haemato-oncology subgroup of the British Committee for Standards in Haematology (BCSH) and the British Transplantation Society (BTS) has reviewed the available literature and made recommendations for the diagnosis and management of post-transplant lymphoproliferative disorder in adult recipients of solid organ transplants. This review details the therapeutic options recommended including reduction in immunosuppression (RIS), transplant organ resection, radiotherapy and chemotherapy. Effective therapy should be instituted before progressive disease results in declining performance status and multi-organ dysfunction. The goal of treatment should be a durable complete remission with retention of transplanted organ function with minimal toxicity.

  10. A 5-year old male with “leukemic form” of disseminated post-transplant lymphoproliferative disorder

    Directory of Open Access Journals (Sweden)

    Saadiya Haque

    2010-03-01

    Full Text Available Post-transplant lymphoproliferative disorder (PTLD represents an abnormal lymphoid proliferation that occurs in recipients of solid organ or bone marrow allograft. It includes a diverse group of diseases ranging from polymorphic B-cell hyperplasia to frank malignant lymphoma. Clinical presentation is variable, ranging from asymptomatic to generalized lymphadenopathy, mononucleosis-like syndrome, nodal or extranodal tumors (usually gastrointestinal tract, systemic lymphomatous involvement, and rare (less than 1% of cases fulminant disseminated disease. PTLD is more common in children than in adults. Younger patients usually present with mononucleosis-like symptoms. We present an unusual case of a 5-year old male who developed a widely disseminated leukemic form of PTLD, involving lymph nodes, tonsils, multiple organs, bone marrow, cerebrospinal fluid, and peripheral blood.

  11. Hairy B-cell lymphoproliferative disorder and its differential diagnosis: a case with long-term follow-up

    Directory of Open Access Journals (Sweden)

    Kensuke Matsuda

    2017-09-01

    Full Text Available Hairy B-cell lymphoproliferative disorder (HBLD is one of chronic polyclonal B-cell lymphocytosis. We report a 47-year-old female Japanese patient diagnosed as having HBLD based on lymphocytosis with hairy cell appearance and characteristic phenotypes including CD11c+, and without B-cell monoclonalities. She was a non-smoker, and possessed HLA-DR4. She has been closely followed up without treatment and lymphoma development for over five years. Although this disease is quite rare and has been reported, to our knowledge, in only 13 Japanese cases, an accurate diagnosis, particularly differential diagnosis from persistent polyclonal B-cell lymphocytosis or hairy cell leukemia-Japanese variant is essential for the prevention of unnecessary treatments.

  12. Partial Least Squares Based Gene Expression Analysis in EBV- Positive and EBV-Negative Posttransplant Lymphoproliferative Disorders.

    Science.gov (United States)

    Wu, Sa; Zhang, Xin; Li, Zhi-Ming; Shi, Yan-Xia; Huang, Jia-Jia; Xia, Yi; Yang, Hang; Jiang, Wen-Qi

    2013-01-01

    Post-transplant lymphoproliferative disorder (PTLD) is a common complication of therapeutic immunosuppression after organ transplantation. Gene expression profile facilitates the identification of biological difference between Epstein-Barr virus (EBV) positive and negative PTLDs. Previous studies mainly implemented variance/regression analysis without considering unaccounted array specific factors. The aim of this study is to investigate the gene expression difference between EBV positive and negative PTLDs through partial least squares (PLS) based analysis. With a microarray data set from the Gene Expression Omnibus database, we performed PLS based analysis. We acquired 1188 differentially expressed genes. Pathway and Gene Ontology enrichment analysis identified significantly over-representation of dysregulated genes in immune response and cancer related biological processes. Network analysis identified three hub genes with degrees higher than 15, including CREBBP, ATXN1, and PML. Proteins encoded by CREBBP and PML have been reported to be interact with EBV before. Our findings shed light on expression distinction of EBV positive and negative PTLDs with the hope to offer theoretical support for future therapeutic study.

  13. HCV viraemia in anti-HCV-negative haemodialysis patients: Do we need HCV RNA detection test?

    Science.gov (United States)

    Papadopoulos, Nikolaos; Griveas, Ioannis; Sveroni, Eirini; Argiana, Vasiliki; Kalliaropoulos, Antonios; Martinez-Gonzalez, Beatriz; Deutsch, Melanie

    2018-03-01

    Hepatitis C virus (HCV) infection is still common among dialysis patients, but the natural history of HCV in this group is not completely understood. The KDIGO HCV guidelines of 2009 recommend that chronic haemodialysis patients be screened for HCV antibody upon admission to the dialysis clinic and every 6 months thereafter if susceptible to HCV infection. However, previous studies have shown the presence of HCV viraemia in anti-HCV-negative haemodialysis patients as up to 22%. To evaluate the presence of HCV viraemia, using HCV RNA detection, among anti-HCV-negative haemodialysis patients from a tertiary dialysis unit in Athens. We enrolled 41 anti-HCV-negative haemodialysis patients diagnosed with third-generation enzyme immunoassay. HCV viraemia was evaluated using a sensitive (cut-off: 12 IU/mL) reverse transcriptase polymerase chain reaction (COBAS AmpliPrep/TaqMan system) for HCV RNA. None of the 41 anti-HCV-negative haemodialysis patients were shown to be viraemic. Routine HCV RNA testing appears not to be necessary in anti-HCV-negative haemodialysis patients.

  14. Diagnosis of post-transplant lymphoproliferative disorder in solid organ transplant recipients - BCSH and BTS Guidelines.

    Science.gov (United States)

    Parker, Anne; Bowles, Kristin; Bradley, J Andrew; Emery, Vincent; Featherstone, Carrie; Gupte, Girish; Marcus, Robert; Parameshwar, Jayan; Ramsay, Alan; Newstead, Charles

    2010-06-01

    A joint working group established by the Haemato-oncology subgroup of the British Committee for Standards in Haematology (BCSH) and the British Transplantation Society (BTS) has reviewed the available literature and made recommendations for the diagnosis and management of post-transplant lymphoproliferative disorder (PTLD) in adult recipients of solid organ transplants. This review details the risk factors predisposing to development, initial features and diagnosis. It is important that the risk of developing PTLD is considered when using post transplant immunosuppression and that the appropriate investigations are carried out when there are suspicions of the diagnosis. These must include tissue for histology and computed tomography scan to assess the extent of disease. These recommendations have been made primarily for adult patients, there have been some comments made with regard to paediatric practice.

  15. Inhibition of HCV replication by oxysterol-binding protein-related protein 4 (ORP4 through interaction with HCV NS5B and alteration of lipid droplet formation.

    Directory of Open Access Journals (Sweden)

    In-Woo Park

    Full Text Available Hepatitis C virus (HCV RNA replication involves complex interactions among the 3'x RNA element within the HCV 3' untranslated region, viral and host proteins. However, many of the host proteins remain unknown. In this study, we devised an RNA affinity chromatography /2D/MASS proteomics strategy and identified nine putative 3' X-associated host proteins; among them is oxysterol-binding protein-related protein 4 (ORP4, a cytoplasmic receptor for oxysterols. We determined the relationship between ORP4 expression and HCV replication. A very low level of constitutive ORP4 expression was detected in hepatocytes. Ectopically expressed ORP4 was detected in the endoplasmic reticulum and inhibited luciferase reporter gene expression in HCV subgenomic replicon cells and HCV core expression in JFH-1-infected cells. Expression of ORP4S, an ORP4 variant that lacked the N-terminal pleckstrin-homology domain but contained the C-terminal oxysterol-binding domain also inhibited HCV replication, pointing to an important role of the oxysterol-binding domain in ORP4-mediated inhibition of HCV replication. ORP4 was found to associate with HCV NS5B and its expression led to inhibition of the NS5B activity. ORP4 expression had little effect on intracellular lipid synthesis and secretion, but it induced lipid droplet formation in the context of HCV replication. Taken together, these results demonstrate that ORP4 is a negative regulator of HCV replication, likely via interaction with HCV NS5B in the replication complex and regulation of intracellular lipid homeostasis. This work supports the important role of lipids and their metabolism in HCV replication and pathogenesis.

  16. HCV-related liver cancer in people with haemophilia

    NARCIS (Netherlands)

    Meijer, K.; Haagsma, E. B.

    . The topic of this monograph is liver cancer associated with chronic HCV infection. We start with some background information on chronic HCV infection and its long-term sequelae, one of which is liver cancer. The rest of the article is concerned with liver cancer or hepatocellular carcinoma (HCC).

  17. Epstein-Barr Virus-Positive Extranodal Marginal Zone Lymphoma of Bronchial-Associated Lymphoid Tissue in the Posttransplant Setting: An Immunodeficiency-Related (Posttransplant) Lymphoproliferative Disorder?

    Science.gov (United States)

    Cassidy, Daniel P; Vega, Francisco; Chapman, Jennifer R

    2017-12-20

    Posttransplant lymphoproliferative disorders (PTLDs) are a heterogeneous group of hematolymphoid proliferations arising in the context of chronic immunosuppression. The common and indolent B-cell lymphomas, including extranodal marginal zone lymphomas (ENMZLs) of mucosa-associated lymphoid tissue (MALT), are excluded from the category of PTLD in the current World Health Organization classification. We report a case of Epstein-Barr virus (EBV)-positive bronchial-associated lymphoid tissue (BALT) lymphoma involving the lungs of a transplant patient. Aside from history of cardiac transplant, young patient age, and EBV positivity, the histopathologic findings were indistinguishable from usual BALT lymphoma. We review the literature of ENMZL occurring in immunocompromised patients and present this case for consideration that this specific entity is a PTLD. We believe that additional studies might lend strength to the hypothesis that this particular group of EBV-positive, posttransplant ENMZLs merits classification and management as PTLDs. © American Society for Clinical Pathology, 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

  18. Genetics Home Reference: X-linked lymphoproliferative disease

    Science.gov (United States)

    ... my area? Other Names for This Condition Duncan disease Epstein-Barr virus-induced lymphoproliferative disease in males familial fatal ... the proapoptotic SAP function in X-linked lymphoproliferative disease aggravates Epstein-Barr virus (EBV) induced mononucleosis and promotes lymphoma development. ...

  19. Risk of Hematopoietic and Lymphoproliferative Malignancies among U. S. Radiologic Technologists

    International Nuclear Information System (INIS)

    Linet, M. S.; Fredman, D. M.; Mohan, A.; Morin Doody, M.; Ron, E.; Mabuchi, K.; Alexander, B. B.; Sigurdson, A.; Matanoski, G.; Hauptmann, M.

    2004-01-01

    To evaluate risks of hematopoietic and lymphoproliferative malignancies among medical workers exposed to protracted low-to-moderate-dose radiation exposures, a follow-up investigation was conducted in a nation wide cohort of U. S. radiologic technologists. eligible for this study were 71.894 technologists (78% female) certified for at least 2 years during 1926-82, who had responded to a baseline mail questionnaire during 1983-89, were cancer-free except for non-melanoma skin cancer at completion of the questionnaire, and completed a second questionnaire during 1994-98 or died through August 1998. There were 241 technologists with hematopoietic or lymphoproliferative malignancies, including 41 with leukemia subtypes associated with radiation exposures (specifically acute myeloid, acute lymphoid and chronic myeloid leukemias, hereafter designated radiogenic leukemias), 23 with chronic lymphocytic leukemia, 28 with multiple myeloma, 118 with non-Hodgkin lymphoma, and 31 with Hodgkin lymphoma. Of the 241 hematopoietic or lymphoproliferative malignancies identified among radiologic technologists, 85 percent were confirmed by medical records or death certificates, including 98 percent of radiogenic leukemia. Risks of the hematopoietic or lymphoproliferative malignancies were evaluated in relation to questionnaire-derived information on employment as a radiologic technologist, including procedures, work practices, and protective measures. cox proportional hazards regression analysis was used to compute relative risks and 95% confidence intervals, using age at diagnosis as the response, stratifying at baseline for birth cohort in 5-year intervals, and adjusting for potential confounding. Risks were not increased for any of the hematopoietic or lymphoproliferative neoplasms according to year first worked or total duration of years worked as radiologic technologist. For the combined radiogenic leukemias, risks rose significantly with an increasing number of years worked

  20. X-Linked Lymphoproliferative Disease Presenting as Pancytopenia in a 10-Month-Old Boy

    Directory of Open Access Journals (Sweden)

    S. Nicole Chadha

    2010-01-01

    Full Text Available X-linked lymphoproliferative disease, also known as Duncan's syndrome, is a rare genetic disorder that causes exaggerated immune responses to Epstein-Barr virus (EBV infection and often leads to death. Patient presentation varies but can include signs and symptoms typical of EBV, pancytopenia, and fulminant hepatitis.

  1. Desordem linfoproliferativa pós-transplante em paciente pediátrico Post-transplantation lymphoproliferative disorder in pediatric patient

    Directory of Open Access Journals (Sweden)

    Paulo Manuel Pêgo Fernandes

    2006-10-01

    Full Text Available Terapias de imunossupressão, a que pacientes transplantados devem ser submetidos, os expõe a um alto risco de desenvolver desordens linfoproliferativas pós-transplante (PTLD. Descrevemos o caso de uma criança submetida a transplante cardíaco aos sete meses de idade e que acabou desenvolvendo PTLD, aos nove anos, diagnosticada por meio de retirada de nódulo pulmonar.Immunosuppressive therapy for transplanted patients exposes them to a high risk of developing posttransplantation lymphoproliferative disorders (PTLD. We report the case of a child undergoing heart transplantation at seven months of age who developed PTLD at nine years of age, diagnosed by resection of a pulmonary nodule.

  2. Preventing acute rejection, Epstein-Barr virus infection, and posttransplant lymphoproliferative disorders after kidney transplantation: Use of aciclovir and mycophenolate mofetil in a steroid-free immunosuppressive protocol

    DEFF Research Database (Denmark)

    Birkeland, S.A.; Andersen, H.K.; Hamilton-Dutoit, Stephen Jacques

    1999-01-01

    Background: A widely held view is that any increase in the potency of an immunosuppressive agent will lead to an increase in infection and malignancy, such as life-threatening Epstein-Barr virus (EBV) induced posttransplant lymphoproliferative disorders (PTLD), We tested this paradigm by studying...... or reactivated EBV infection (PREBV) was correlated to acute rejection (treated with OKT3; Pdisease is included); (2) aciclovir protected against PREBV (P

  3. Oncogenic Notch signaling in T-cell and B-cell lymphoproliferative disorders.

    Science.gov (United States)

    Chiang, Mark Y; Radojcic, Vedran; Maillard, Ivan

    2016-07-01

    This article highlights recent discoveries about Notch activation and its oncogenic functions in lymphoid malignancies, and discusses the therapeutic potential of Notch inhibition. NOTCH mutations arise in a broad spectrum of lymphoid malignancies and are increasingly scrutinized as putative therapeutic targets. In T-cell acute lymphoblastic leukemia (T-ALL), NOTCH1 mutations affect the extracellular negative regulatory region and lead to constitutive Notch activation, although mutated receptors remain sensitive to Notch ligands. Other NOTCH1 mutations in T-ALL and NOTCH1/2 mutations in multiple B-cell malignancies truncate the C-terminal proline (P), glutamic acid (E), serine (S), threonine (T)-rich (PEST) domain, leading to decreased Notch degradation after ligand-mediated activation. Thus, targeting Notch ligand-receptor interactions could provide therapeutic benefits. In addition, we discuss recent reports on clinical testing of Notch inhibitors in T-ALL that influenced contemporary thinking on the challenges of targeting Notch in cancer. We review advances in the laboratory to address these challenges in regards to drug targets, the Notch-driven metabolome, and the sophisticated protein-protein interactions at Notch-dependent superenhancers that underlie oncogenic Notch functions. Notch signaling is a recurrent oncogenic pathway in multiple T- and B-cell lymphoproliferative disorders. Understanding the complexity and consequences of Notch activation is critical to define optimal therapeutic strategies targeting the Notch pathway.

  4. HCV knowledge among a sample of HCV positive Aboriginal Australians residing in New South Wales.

    Science.gov (United States)

    Wilson, Hannah; Brener, Loren; Jackson, L Clair; Saunders, Veronica; Johnson, Priscilla; Treloar, Carla

    2017-06-01

    Australian Aboriginal and Torres Strait Islanders are overrepresented in both the prevalence and incidence of the hepatitis C (HCV). HCV knowledge has been associated with a range of positive health behaviours. HCV knowledge has previously been investigated as a single construct; however examining different knowledge domains (i.e. transmission, risk of complications, testing and treatment) separately may be beneficial. This study investigated whether having greater HCV knowledge in different domains is associated with self-reported positive health behaviours. 203 Aboriginal people living with HCV completed a survey assessing HCV knowledge, testing and care, lifestyle changes since diagnosis and treatment intent. Respondents' knowledge was relatively high. Greater knowledge of risk of health complications was associated with undertaking more positive lifestyle changes since diagnosis. Respondents testing and treatment knowledge was significantly associated with incarceration, lifestyle changes since diagnosis and future treatment intentions. This study illustrates the importance of ensuring that knowledge is high across different HCV domains to optimise a range of positive health behaviours of Aboriginal people living with HCV. Future health promotion campaigns targeted at Aboriginal people living with HCV could benefit from broadening their focus from prevention to other domains such as testing and treatment.

  5. Correlates of HCV seropositivity among familial contacts of HCV positive patients

    Directory of Open Access Journals (Sweden)

    Matera Antonio

    2006-09-01

    Full Text Available Abstract Background Determinants of intrafamilial HCV transmission are still being debated. The aim of this study is to investigate the correlates of HCV seropositivity among familial contacts of HCV positive patients in Italy. Methods A cross-sectional study was conducted with 175 HCV positive patients (index cases, recruited from Policlinico Gemelli in Rome as well as other hospitals in Central Italy between 1995 and 2000 (40% female, mean age 57 ± 15.2 years, and 259 familial contacts. Differences in proportions of qualitative variables were tested with non-parametric tests (χ2, Yates correction, Fisher exact test, and a p value Results Seropositivity for HCV was found in 8.9% of the contacts. From the univariate analysis, risk factors significantly associated to HCV positivity in the contacts were: intravenous drug addiction (p = 0.004 and intercourse with drug addicts (p = 0.005. The only variables associated significantly and independently to HCV seropositivity in patients' contacts were intercourse with drug addicts (OR = 19.28; 95% CI: 2.01 – 184.94, the retirement status from work (OR = 3.76; 95% CI: 1.17 – 11.98, the time of the relationship (OR = 1.06; 95% CI: 1.00 – 1.11 and tattoos (OR = 7.68; 95% CI: 1.00 – 60.20. Conclusion The present study confirms that having intercourse with a drug addict is the most significant risk factor for intrafamilial HCV transmission. The association with retirement status from work could be related to both a long-term relationship with an index case and past exposure to common risk factors.

  6. Molecular Pathogenesis of B-Cell Posttransplant Lymphoproliferative Disorder: What Do We Know So Far?

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    J. Morscio

    2013-01-01

    Full Text Available Posttransplant lymphoproliferative disorder (PTLD is a potentially fatal disease that arises in 2%–10% of solid organ and hematopoietic stem cell transplants and is most frequently of B-cell origin. This very heterogeneous disorder ranges from benign lymphoproliferations to malignant lymphomas, and despite the clear association with Epstein-Barr Virus (EBV infection, its etiology is still obscure. Although a number of risk factors have been identified (EBV serostatus, graft type, and immunosuppressive regimen, it is currently not possible to predict which transplant patient will eventually develop PTLD. Genetic studies have linked translocations (involving C-MYC, IGH, BCL-2, various copy number variations, DNA mutations (PIM1, PAX5, C-MYC, RhoH/TTF, and polymorphisms in both the host (IFN-gamma, IL-10, TGF-beta, HLA and the EBV genome to B-cell PTLD development. Furthermore, the tumor microenvironment seems to play an important role in the course of disease representing a local niche that can allow antitumor immune responses even in an immunocompromised host. Taken together, B-cell PTLD pathogenesis is very complex due to the interplay of many different (patient-dependent factors and requires thorough molecular analysis for the development of novel tailored therapies. This review aims at giving a global overview of the currently known parameters that contribute to the development of B-cell PTLD.

  7. Primary and secondary cutaneous CD30(+) lymphoproliferative disorders: a report from the Dutch Cutaneous Lymphoma Group on the long-term follow-up data of 219 patients and guidelines for diagnosis and treatment

    NARCIS (Netherlands)

    Bekkenk, M. W.; Geelen, F. A.; van Voorst Vader, P. C.; Heule, F.; Geerts, M. L.; van Vloten, W. A.; Meijer, C. J.; Willemze, R.

    2000-01-01

    To evaluate our diagnostic and therapeutic guidelines, clinical and long-term follow-up data of 219 patients with primary or secondary cutaneous CD30(+) lymphoproliferative disorders were evaluated. The study group included 118 patients with lymphomatoid papulosis (LyP; group 1), 79 patients with

  8. Hodgkin's disease as unusual presentation of post-transplant lymphoproliferative disorder after autologous hematopoietic cell transplantation for malignant glioma

    Directory of Open Access Journals (Sweden)

    Scelsi Mario

    2005-08-01

    Full Text Available Abstract Background Post-transplant lymphoproliferative disorder (PTLD is a complication of solid organ and allogeneic hematopoietic stem cell transplantation (HSCT; following autologous HSCT only rare cases of PTLD have been reported. Here, a case of Hodgkin's disease (HD, as unusual presentation of PTLD after autologous HSCT for malignant glioma is described. Case presentation 60-years old man affected by cerebral anaplastic astrocytoma underwent subtotal neurosurgical excision and subsequent high-dose chemotherapy followed by autologous HSCT. During the post HSCT course, cranial irradiation and corticosteroids were administered as completion of therapeutic program. At day +105 after HSCT, the patient developed HD, nodular sclerosis type, with polymorphic HD-like skin infiltration. Conclusion The clinical and pathological findings were consistent with the diagnosis of PTLD.

  9. Molecular Signature in HCV-Positive Lymphomas

    Directory of Open Access Journals (Sweden)

    Valli De Re

    2012-01-01

    Full Text Available Hepatitis C virus (HCV is a positive, single-stranded RNA virus, which has been associated to different subtypes of B-cell non-Hodgkin lymphoma (B-NHL. Cumulative evidence suggests an HCV-related antigen driven process in the B-NHL development. The underlying molecular signature associated to HCV-related B-NHL has to date remained obscure. In this review, we discuss the recent developments in this field with a special mention to different sets of genes whose expression is associated with BCR coupled to Blys signaling which in turn was found to be linked to B-cell maturation stages and NF-κb transcription factor. Even if recent progress on HCV-B-NHL signature has been made, the precise relationship between HCV and lymphoma development and phenotype signature remain to be clarified.

  10. Systematic Epstein-Barr virus-positive T-cell lymphoproliferative disease presenting as a persistent fever and cough: a case report.

    Science.gov (United States)

    Ameli, Fereshteh; Ghafourian, Firouzeh; Masir, Noraidah

    2014-08-27

    Systemic Epstein-Barr virus-positive T-cell lymphoproliferative childhood disease is an extremely rare disorder and classically arises following primary acute or chronic active Epstein-Barr virus infection. It is characterized by clonal proliferation of Epstein-Barr virus-infected T-cells with an activated cytotoxic phenotype. This disease has a rapid clinical course and is more frequent in Asia and South America, with relatively few cases being reported in Western countries. The clinical and pathological features of the disease overlap with other conditions including infectious mononucleosis, chronic active Epstein-Barr virus infection, hemophagocytic lymphohistiocytosis and natural killer cell malignancies. We describe the rare case of systemic Epstein-Barr virus-positive T-cell lymphoproliferative childhood disease in a 16-year-old Malay boy. He presented with a six-month history of fever and cough, with pulmonary and mediastinal lymphadenopathy and severe pancytopenia. Medium- to large-sized, CD8+ and Epstein-Barr virus-encoded RNA-positive atypical lymphoid cells were present in the bone marrow aspirate. He subsequently developed fatal virus-associated hemophagocytic syndrome and died due to sepsis and multiorgan failure. Although systemic Epstein-Barr virus-positive T-cell lymphoproliferative childhood disease is a disorder which is rarely encountered in clinical practice, our case report underlines the importance of a comprehensive diagnostic approach in the management of this disease. A high level of awareness of the disease throughout the diagnosis process for young patients who present with systemic illness and hemophagocytic syndrome may be of great help for the clinical diagnosis of this disease.

  11. HCV-specific immune responses induced by CIGB-230 in combination with IFN-α plus ribavirin

    Science.gov (United States)

    Amador-Cañizares, Yalena; Martínez-Donato, Gillian; Álvarez-Lajonchere, Liz; Vasallo, Claudia; Dausá, Mariacarla; Aguilar-Noriega, Daylen; Valenzuela, Carmen; Raíces, Ivette; Dubuisson, Jean; Wychowski, Czeslaw; Cinza-Estévez, Zurina; Castellanos, Marlén; Núñez, Magdalys; Armas, Anny; González, Yaimé; Revé, Ismariley; Guerra, Ivis; Pérez Aguiar, Ángel; Dueñas-Carrera, Santiago

    2014-01-01

    AIM: To analyze hepatitis C virus (HCV)-specific immune responses in chronically infected patients under triple therapy with interferon-α (IFN-α) plus ribavirin and CIGB-230. METHODS: CIGB-230 was administered in different schedules with respect to IFN-α plus ribavirin therapy. Paired serum and peripheral blood mononuclear cells (PBMC) samples from baseline and end of treatment were analyzed. The HCV-specific humoral response was tested by enzyme-linked immunosorbent assay, neutralizing antibodies were evaluated by cell culture HCV neutralization assays, PBMC proliferation was assayed by carboxyfluorescein succinimidyl ester staining and IFN-γ secretion was assessed by enzyme-linked immunospot. Data on virological and histological response and their association with immune variables are also provided. RESULTS: From week 12 to week 48, all groups of patients showed a significant reduction in mean leukocyte counts. Statistically significant reductions in antibody titers were frequent, but only individuals immunized with CIGB-230 as early add-on treatment sustained the core-IgG response, and the neutralizing antibody response was enhanced only in patients receiving CIGB-230. Cell-mediated immune responses also tended to decline, but significant reductions in IFN-γ secretion and total absence of core-specific lymphoproliferation were exclusive of the control group. Only CIGB-230-immunized individuals showed de novo induced lymphoproliferative responses against the structural antigens. Importantly, it was demonstrated that the quality of the CIGB-230-induced immune response depended on the number of doses and timing of administration in relation to the antiviral therapy. Specifically, the administration of 6 doses of CIGB-230 as late add-on to therapy increased the neutralizing antibody activity and the de novo core-specific IFN-γ secretion, both of which were associated with the sustained virological response. CONCLUSION: CIGB-230, combined with IFN

  12. Extrahepatic manifestations associated with Chronic Hepatitis C Virus Infection

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    A. Flores-Chávez

    Full Text Available Summary Chronic hepatitis C virus (HCV infection has been associated with both organ-specific and systemic autoimmune diseases, with cryoglobulinemia being the most frequent associated disease. Experimental, virologic, and clinical evidence have demon-strated a close association between HCV infection and some systemic autoimmune diseases, especially Sjögren’s syndrome, but also rheumatoid arthritis and lupus. A higher prevalence of hematological processes has also been described in patients with HCV infection, including cytopenias and lymphoproliferative disorders (B-cell lymphoma. In addition, patients with chronic HCV infection have a higher frequency of other extrahepatic manifestations including endocrine, metabolic and cardiovascular disorders that may worse the prognosis of patients, along with neuropsychiatric manifestations and general symptoms that have a significant influence on the quality of life of the patient. Direct-acting antiviral therapies (DAAs that have recently begun to be used are providing the opportunity to effectively cure chronic HCV infection and reduce the burden of both hepatic and extrahepatic complications.

  13. A meta-analysis of potential relationship between Epstein-Barr-Encoded-RNA (EBER and onset time of post-transplant lymphoproliferative disorders

    Directory of Open Access Journals (Sweden)

    Hossein Khedmat

    2015-01-01

    Full Text Available Epstein-Barr virus (EBV encodes two non-polyadenylated RNAs termed EBV-encoded RNAs (EBERs. In this study, we tried to find series in which data of EBER and onset time of post-transplant lymphoproliferative disorder (PTLD for patients have been documented to conduct a meta-analysis. A comprehensive search of the literature was performed by Pubmed and Google scholar to find reports indicating test results for EBER and PTLD onset in transplant patients. PTLD was considered "early onset" when it develops within the first post-transplant year. Finally, 265 patients from 15 studies have been included in the meta-analysis. The overall meta-analysis also showed a significant relation between EBER test positivity and early-onset PTLD development [relative risk (RR: 1.36; 95% CI: 1.16-1.59; P <0.001]. The i2 index was 49.8%. Our study suggests that PTLD lesions with positive EBER test are more likely to develop within the early post-transplant period. Since early-onset PTLD is supposed to have better prognosis, having a positive EBER test might not be a bad news. However, for having a precise conclusion, prospective studies are needed to be conducted.

  14. Immune biomarker differences and changes comparing HCV mono-infected, HIV/HCV co-infected, and HCV spontaneously cleared patients.

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    Lauren E Kushner

    Full Text Available Immune biomarkers are implicated in HCV treatment response, fibrosis, and accelerated pathogenesis of comorbidities, though only D-dimer and C-reactive protein have been consistently studied. Few studies have evaluated HIV/HCV co-infection, and little longitudinal data exists describing a broader antiviral cytokine response.Fifty immune biomarkers were analyzed at baseline (BL and HCV end of treatment follow-up(FU time point using the Luminex 50-plex assay in plasma samples from 15 HCV-cleared, 24 HCV mono- and 49 HIV/HCV co-infected patients receiving antiretroviral treatment, who either did or did not receive pegylated-interferon/ribavirin HCV treatment. Biomarker levels were compared among spontaneous clearance patients, mono- and co-infected, untreated and HCV-treated, and sustained virologic responders (SVR and non-responders (NR at BL and FU using nonparametric analyses. A Bonferroni correction, adjusting for tests of 50 biomarkers, was used to reduce Type I error.Compared to HCV patients at BL, HIV/HCV patients had 22 significantly higher and 4 significantly lower biomarker levels, following correction for multiple testing. There were no significantly different BL levels when comparing SVR and NR in mono- or co-infected patients; however, FU levels changed considerably in co-infected patients, with seven becoming significantly higher and eight becoming significantly lower in SVR patients. Longitudinally between BL and FU, 13 markers significantly changed in co-infected SVR patients, while none significantly changed in co-infected NR patients. There were also no significant changes in longitudinal analyses of mono-infected patients achieving SVR or mono-infected and co-infected groups deferring treatment.Clear differences exist in pattern and quantity of plasma immune biomarkers among HCV mono-infected, HIV/HCV co-infected, and HCV-cleared patients; and with SVR in co-infected patients treated for HCV. Though >90% of patients were male and

  15. Epstein-Barr virus induced hemophagocytic lymphohistiocytosis in X-linked lymphoproliferative disease

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    Senthilkumar Sankararaman

    2014-01-01

    Full Text Available X-linked lymphoproliferative disease (XLP is a rare, often fatal genetic disorder characterized by extreme vulnerability to Epstein-Barr virus (EBV. EBV-induced hemophagocytic lymphohistiocytosis (HLH is a known presentation in XLP. In EBV-induced HLH in XLP, the brain imaging findings in the acute phase include a non specific pattern. In this report, we highlight the magnetic resonance imaging and magnetic resonance spectroscopy findings in a child with EBV induced HLH in XLP.

  16. Anti-soluble liver antigen (SLA) antibodies in chronic HCV infection.

    Science.gov (United States)

    Vitozzi, Susana; Lapierre, Pascal; Djilali-Saiah, Idriss; Marceau, Gabriel; Beland, Kathie; Alvarez, Fernando

    2004-05-01

    Hepatitis C infection is associated with autoimmune disorders, such as the production of autoantibodies. Anti-LKM1 and anti-LC1, immunomarkers of type 2 autoimmune hepatitis, have been previously associated with a HCV infection. Anti-Soluble-Liver-Antigen autoantibodies (SLA) are specifically associated with type 1 and type 2 autoimmune hepatitis and more closely related to patients who relapse after steroid therapy. The recent molecular cloning of the soluble liver antigen provides the opportunity to develop more specific tests for the detection of antibodies against it. The aim of this work is to characterize anti-soluble-liver autoantibodies in sera from patients chronically infected by HCV. A recombinant cDNA from activated Jurkat cells coding for the full length tRNP(Ser)Sec/SLA antigen was obtained. ELISA, Western Blot and immunoprecipitation tests were developed and used to search for linear and conformational epitopes recognized by anti-SLA antibodies in sera from patients chronically infected by HCV. Anti-soluble liver antigen antibodies were found in sera from 10.4% of HCV-infected patients. The prevalence was significantly increased to 27% when anti-LKM1 was also present. Most anti-SLA reactivity was directed against conformational epitopes on the antigen. The means titers by ELISA were lower than those obtained in type 2 AIH. The result of autoantibody isotyping showed a subclass restriction to IgG1 and also IgG4. This study shows the presence of anti-SLA antibodies in approximately 10% of HCV infected patients. The prevalence of SLA autoantibodies in HCV infected patients increases when LKM1 autoantibodies are also present. The relationship between the prevalence of this characteristic autoimmune hepatitis autoantibody and the implication of an autoimmune phenomenon in the liver injury of patients chronically infected by HCV needs further investigation.

  17. PML tumor suppressor protein is required for HCV production

    International Nuclear Information System (INIS)

    Kuroki, Misao; Ariumi, Yasuo; Hijikata, Makoto; Ikeda, Masanori; Dansako, Hiromichi; Wakita, Takaji; Shimotohno, Kunitada; Kato, Nobuyuki

    2013-01-01

    Highlights: ► PML tumor suppressor protein is required for HCV production. ► PML is dispensable for HCV RNA replication. ► HCV could not alter formation of PML-NBs. ► INI1 and DDX5, PML-related proteins, are involved in HCV life cycle. -- Abstract: PML tumor suppressor protein, which forms discrete nuclear structures termed PML-nuclear bodies, has been associated with several cellular functions, including cell proliferation, apoptosis and antiviral defense. Recently, it was reported that the HCV core protein colocalizes with PML in PML-NBs and abrogates the PML function through interaction with PML. However, role(s) of PML in HCV life cycle is unknown. To test whether or not PML affects HCV life cycle, we examined the level of secreted HCV core and the infectivity of HCV in the culture supernatants as well as the level of HCV RNA in HuH-7-derived RSc cells, in which HCV-JFH1 can infect and efficiently replicate, stably expressing short hairpin RNA targeted to PML. In this context, the level of secreted HCV core and the infectivity in the supernatants from PML knockdown cells was remarkably reduced, whereas the level of HCV RNA in the PML knockdown cells was not significantly affected in spite of very effective knockdown of PML. In fact, we showed that PML is unrelated to HCV RNA replication using the subgenomic HCV-JFH1 replicon RNA, JRN/3-5B. Furthermore, the infectivity of HCV-like particle in the culture supernatants was significantly reduced in PML knockdown JRN/3-5B cells expressing core to NS2 coding region of HCV-JFH1 genome using the trans-packaging system. Finally, we also demonstrated that INI1 and DDX5, the PML-related proteins, are involved in HCV production. Taken together, these findings suggest that PML is required for HCV production.

  18. HCV and HCC molecular epidemiology

    Directory of Open Access Journals (Sweden)

    Flor H. Pujol

    2007-02-01

    Full Text Available

    iHepatitis C virus (HCV is a member of the family Flaviviridae, responsible for the majority of the non-A non-B post-transfusion hepatitis before 1990. Around 170 millions persons in the world are thought to be infected with this virus. A high number of HCV-infected people develop cirrhosis and from these, a significant proportion progresses to hepatocellular carcinoma (HCC. Six HCV genotypes and a large number of subtypes in each genotype have been described. Infections with HCV genotype 1 are associated with the lowest therapeutic success. HCV genotypes 1, 2, and 3 have a worldwide distribution. HCV subtypes 1a and 1b are the most common genotypes in the United States and are also are predominant in Europe, while in Japan, subtype 1b is predominant. Although HCV subtypes 2a and 2b are relatively common in America, Europe, and Japan, subtype 2c is found commonly in northern Italy. HCV genotype 3a is frequent in intravenous drug abusers in Europe and the United States. HCV genotype 4 appears to be prevalent in Africa and the Middle East, and genotypes 5 and 6 seem to be confined to South Africa and Asia, respectively. HCC accounts for approximately 6% of all human cancers. Around 500,000 to 1 million cases occur annually worldwide, with HCC being the fifth common malignancy in men and the ninth in women. HCC is frequently a consequence of infection by HBV and HCV. The first line of evidences comes from epidemiologic studies. While HBV is the most frequent cause of HCC in many countries of Asia and South America, both HBV and HCV are found at similar frequencies, and eventually HCV at a higher frequency than HBV, among HCC patients in Europe, North America, and Japan. The cumulative appearance rate of HCC might be higher for HCV

  19. Lymphoproliferative disorders in non-AIDS associated Kaposi's ...

    African Journals Online (AJOL)

    The association of the non-AIDS-related, classic fonn of Kaposi's sarcoma (KS) with secondary malignancies, especially Iymphoproliferative disorders, has frequently been noted. However, in endemic: African-type KS, such an association has been reported only rarely. A review of 62 non-AIDS-related cases of KS treated ...

  20. Retention in buprenorphine treatment is associated with improved HCV care outcomes.

    Science.gov (United States)

    Norton, B L; Beitin, A; Glenn, M; DeLuca, J; Litwin, A H; Cunningham, C O

    2017-04-01

    Persons who inject drugs, most of whom are opioid dependent, comprise the majority of the HCV infected in the United States. As the national opioid epidemic unfolds, increasing numbers of people are entering the medical system to access treatment for opioid use disorder, specifically with buprenorphine. Yet little is known about HCV care in patients accessing buprenorphine-based opioid treatment. We sought to determine the HCV prevalence, cascade of care, and the association between patient characteristics and completion of HCV cascade of care milestones for patients initiating buprenorphine treatment. We reviewed electronic health records of all patients who initiated buprenorphine treatment at a primary-care clinic in the Bronx, NY between January 2009 and January 2014. Of the 390 patients who initiated buprenorphine treatment, 123 were confirmed to have chronic HCV infection. The only patient characteristic associated with achieving HCV care milestones was retention in opioid treatment. Patients retained (vs. not retained) in buprenorphine treatment were more likely to be referred for HCV specialty care (63.1% vs. 34.0%, p<0.01), achieve an HCV-specific evaluation (40.8% vs. 21.3%, p<0.05), be offered HCV treatment (22.4% vs. 8.5%, p<0.05), and initiate HCV treatment (9.2% vs. 6.4%, p=0.6). Given the current opioid epidemic in the US and the growing number of people receiving buprenorphine treatment, there is an unprecedented opportunity to access and treat persons with HCV, reducing HCV transmission, morbidity and mortality. Retention in opioid treatment may improve linkage and retention in HCV care; innovative models of care that integrate opioid drug treatment with HCV treatment are essential. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. PML tumor suppressor protein is required for HCV production

    Energy Technology Data Exchange (ETDEWEB)

    Kuroki, Misao [Department of Tumor Virology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1, Shikata-cho, Okayama 700-8558 (Japan); Research Fellow of the Japan Society for the Promotion of Science (Japan); Center for AIDS Research, Kumamoto University, Kumamoto 860-0811 (Japan); Ariumi, Yasuo, E-mail: ariumi@kumamoto-u.ac.jp [Department of Tumor Virology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1, Shikata-cho, Okayama 700-8558 (Japan); Center for AIDS Research, Kumamoto University, Kumamoto 860-0811 (Japan); Hijikata, Makoto [Department of Viral Oncology, Institute for Virus Research, Kyoto University, Kyoto 606-8507 (Japan); Ikeda, Masanori; Dansako, Hiromichi [Department of Tumor Virology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1, Shikata-cho, Okayama 700-8558 (Japan); Wakita, Takaji [Department of Virology II, National Institute of Infectious Diseases, Tokyo 162-8640 (Japan); Shimotohno, Kunitada [Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, Ichikawa, Chiba 272-8516 (Japan); Kato, Nobuyuki [Department of Tumor Virology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1, Shikata-cho, Okayama 700-8558 (Japan)

    2013-01-11

    Highlights: Black-Right-Pointing-Pointer PML tumor suppressor protein is required for HCV production. Black-Right-Pointing-Pointer PML is dispensable for HCV RNA replication. Black-Right-Pointing-Pointer HCV could not alter formation of PML-NBs. Black-Right-Pointing-Pointer INI1 and DDX5, PML-related proteins, are involved in HCV life cycle. -- Abstract: PML tumor suppressor protein, which forms discrete nuclear structures termed PML-nuclear bodies, has been associated with several cellular functions, including cell proliferation, apoptosis and antiviral defense. Recently, it was reported that the HCV core protein colocalizes with PML in PML-NBs and abrogates the PML function through interaction with PML. However, role(s) of PML in HCV life cycle is unknown. To test whether or not PML affects HCV life cycle, we examined the level of secreted HCV core and the infectivity of HCV in the culture supernatants as well as the level of HCV RNA in HuH-7-derived RSc cells, in which HCV-JFH1 can infect and efficiently replicate, stably expressing short hairpin RNA targeted to PML. In this context, the level of secreted HCV core and the infectivity in the supernatants from PML knockdown cells was remarkably reduced, whereas the level of HCV RNA in the PML knockdown cells was not significantly affected in spite of very effective knockdown of PML. In fact, we showed that PML is unrelated to HCV RNA replication using the subgenomic HCV-JFH1 replicon RNA, JRN/3-5B. Furthermore, the infectivity of HCV-like particle in the culture supernatants was significantly reduced in PML knockdown JRN/3-5B cells expressing core to NS2 coding region of HCV-JFH1 genome using the trans-packaging system. Finally, we also demonstrated that INI1 and DDX5, the PML-related proteins, are involved in HCV production. Taken together, these findings suggest that PML is required for HCV production.

  2. Posttransplant Lymphoproliferative Disorder After Clinical Islet Transplantation: Report of the First Two Cases.

    Science.gov (United States)

    Peters, A; Olateju, T; Deschenes, J; Shankarnarayan, S H; Chua, N; Shapiro, A M J; Senior, P

    2017-09-01

    We report the first two cases of posttransplant lymphoproliferative disorder (PTLD) in recipients of islet transplants worldwide. First, a 44-year-old recipient of three islet infusions developed PTLD 80 months after his initial transplantation, presenting with abdominal pain and diffuse terminal ileum thickening on imaging. He was treated with surgical excision, reduction of immunosuppression, and rituximab. Seven months later, he developed central nervous system PTLD, presenting with vertigo and diplopia; immunosuppression was discontinued, resulting in graft loss, and he was given high-dose methotrexate and underwent consolidative autologous stem cell transplantation. He remains in remission 37 months after the initial diagnosis. Second, a 58-year-old female recipient of two islet infusions developed PTLD 24 months after initial islet infusion, presenting with pancytopenia secondary to extensive bone marrow involvement. Immunosuppression was discontinued, resulting in graft loss, and she received rituximab and chemotherapy, achieving complete remission. Both patients were monomorphic B cell PTLD subtype by histology and negative for Epstein-Barr virus in tissue or blood. These cases document the first occurrences of this rare complication in islet transplantation, likely secondary to prolonged, intensive immunosuppression, and highlight the varying clinical manifestations of PTLD. Further studies are needed to determine incidence rate and risk factors in islet transplantation. © 2017 The American Society of Transplantation and the American Society of Transplant Surgeons.

  3. Hepatitis C virus (HCV) RNA profiles among chronic HIV/HCV-coinfected individuals in ESPRIT; spontaneous HCV RNA clearance observed in nine individuals.

    Science.gov (United States)

    Grint, D; Tedaldi, E; Peters, L; Mocroft, A; Edlin, B; Gallien, S; Klinker, H; Boesecke, C; Kokordelis, P; Rockstroh, J K

    2017-07-01

    Studies have shown that hepatitis C virus (HCV) RNA levels remain stable over time in HIV/HCV-coinfected individuals taking combination antiretroviral therapy (cART), while spontaneous clearance of HCV RNA during the persistent infection phase has been documented only rarely among those with the CC interleukin (IL)-28B genotype. This study describes HCV RNA profiles and factors associated with changes over time in HCV RNA levels in the ESPRIT study. HIV/HCV-coinfected individuals positive for HCV RNA were included in the study. Follow-up was counted from the first HCV RNA positive test and censored at the initiation of interferon-based treatment. HCV RNA and IL-28B measurements were performed in the same reference laboratory. Random effects mixed models were used to analyse changes over time in HCV RNA. A total of 312 ESPRIT patients were included in the study (151 in the arm receiving subcutaneous recombinant IL-2 and 161 in the control arm). Most of the patients were white (89%) and male (76%), and they had a median of 5 HCV RNA measurements per person [interquartile range (IQR) 3-6; range 1-9]. Median follow-up was 5 years (IQR: 2-6 years). At baseline, 96% of patients were taking cART and 93% had undetectable HIV RNA. Mean HCV RNA levels decreased by 13% per year over the study period [95% confidence interval (CI) 8-18%; P < 0.0001]. Baseline HCV RNA levels and the change over time in HCV RNA did not differ by randomization arm (P = 0.16 and P = 0.56, respectively). Nine individuals spontaneously cleared HCV RNA during follow-up [IL-28B genotypes: CC, five patients (56%); CT, four patients (44%)]. HCV RNA levels decreased over time in this population with well-controlled HIV infection. Spontaneous clearance of HCV RNA was documented in five individuals with IL-28B genotype CC and four with the CT genotype. © 2016 British HIV Association.

  4. HCV Specific IL-21 Producing T Cells but Not IL-17A Producing T Cells Are Associated with HCV Viral Control in HIV/HCV Coinfection.

    Directory of Open Access Journals (Sweden)

    Sonya A MacParland

    Full Text Available Decreased hepatitis C virus (HCV clearance, faster cirrhosis progression and higher HCV RNA levels are associated with Human Immunodeficiency virus (HIV coinfection. The CD4+ T helper cytokines interleukin (IL-21 and IL-17A are associated with virus control and inflammation, respectively, both important in HCV and HIV disease progression. Here, we examined how antigen-specific production of these cytokines during HCV mono and HIV/HCV coinfection was associated with HCV virus control.We measured HCV-specific IL-21 and IL-17A production by transwell cytokine secretion assay in PBMCs from monoinfected and coinfected individuals. Viral control was determined by plasma HCV RNA levels.In acutely infected individuals, those able to establish transient/complete HCV viral control tended to have stronger HCV-specific IL-21-production than non-controllers. HCV-specific IL-21 production also correlated with HCV viral decline in acute infection. Significantly stronger HCV-specific IL-21 production was detected in HAART-treated coinfected individuals. HCV-specific IL-17A production was not associated with lower plasma HCV RNA levels in acute or chronic HCV infection and responses were stronger in HIV coinfection. HCV-specific IL-21/ IL-17A responses did not correlate with microbial translocation or fibrosis. Exogenous IL-21 treatment of HCV-specific CD8+ T cells from monoinfected individuals enhanced their function although CD8+ T cells from coinfected individuals were somewhat refractory to the effects of IL-21.These data show that HCV-specific IL-21 and IL-17A-producing T cells are induced in HIV/HCV coinfection. In early HIV/HCV coinfection, IL-21 may contribute to viral control, and may represent a novel tool to enhance acute HCV clearance in HIV/HCV coinfected individuals.

  5. T-Cell lymphoproliferative disorder of hand-mirror cell morphology presenting in an eosinophilic loculated peritoneal effusion, with omental "caking"

    Directory of Open Access Journals (Sweden)

    Tufankjian Dearon

    2006-01-01

    Full Text Available Abstract Background Cells with "hand mirror" morphology have not, to the best of our knowledge, been described in a primary effusion sample. This paper describes a case of T-cell lymphoma with eosinophilia in a patient with suspected peritoneal carcinomatosis. Rarely, a T-cell lymphoproliferative process may mimic primary peritoneal carcinomatosis, clinically suggested by a presentation in CT imaging of omental caking with bilateral massive loculated effusions in a patient without lymphadenopathy or splenomegaly. Methods A 60 year old caucasian male presented with vague abdominal discomfort and increasing abdominal girth. Computed tomography showed a two centimeter thick omental cake and a small loculated effusion. The clinical presentation and imaging findings were most consistent with peritoneal carcinomatosis. Cytologic evaluation of the effusion was undertaken for diagnostic study. Results Rapid intraprocedural interpretation of the effusion sample showed a monomorphic population of cells with "hand-mirror" cell morphology exhibiting cytoplasmic extensions (uropodia with 3–5 course dark cytoplasmic granules and a rim of vacuolated cytoplasm capping the opposing "mirror head" side. These cells were seen within a background of mature eosinophils. Flow cytometric evaluation of the ascites fluid demonstrated an atypical T-cell population with the following immunophenotype: CD2-, CD3+, CD4-, CD5-, CD7-, CD8+, CD56+. T-cell receptor (TCR gene rearrangement was positive for clonal TCR-gamma gene rearrangement, supporting the diagnosis of a T-lymphoprolifereative disorder. Conclusion A T-cell lymphoproliferative process may present with "hand mirror" morphology in an effusion sample. These cells may show polar cytoplasmic vacuolization and 3–5 course granules within the "handle" of these unique cells. Cytoplasm shows peripheral constriction around the nucleus.

  6. Preventing acute rejection, Epstein-Barr virus infection, and posttransplant lymphoproliferative disorders after kidney transplantation: Use of aciclovir and mycophenolate mofetil in a steroid-free immunosuppressive protocol

    DEFF Research Database (Denmark)

    Birkeland, S.A.; Andersen, H.K.; Hamilton-Dutoit, Stephen Jacques

    1999-01-01

    Background: A widely held view is that any increase in the potency of an immunosuppressive agent will lead to an increase in infection and malignancy, such as life-threatening Epstein-Barr virus (EBV) induced posttransplant lymphoproliferative disorders (PTLD), We tested this paradigm by studying......; the effect of adding mofetil to a steroid-free protocol under cover of high-dose aciclovir prophylaxis on the number of acute rejections, EBV infections and PTLDs after kidney transplantation. Methods: EBV serology was performed in 267 consecutive renal transplantations (1990-1997), All were treated...

  7. EBV-Associated Lymphoproliferative Disorder and Hemophagocytic Lymphohistiocytosis in a Patient with Severe Celiac Disease

    Directory of Open Access Journals (Sweden)

    John Jacob Kinross-Wright

    2018-01-01

    Full Text Available Background. Epstein-Barr virus- (EBV- associated lymphoproliferative disease (LPD is a rare condition, usually occurring in immunocompromised patients. We report a case of EBV-associated LPD in a patient with severe celiac disease, the first report to describe this syndrome in a patient with this diagnosis. Case Summary. A 69-year-old Caucasian woman with recent diagnosis of celiac sprue presented to our hospital with persistent diarrhea, abdominal pain, weight loss, and fatigue despite adherence to gluten-free diet for a number of weeks prior to presentation. She underwent evaluation for occult malignancy and was found to have diffuse intra-abdominal mesenteric lymphadenopathy on CT scan. Biopsy of mesenteric nodes revealed an EBV positive, CD20 positive mixed lymphoproliferative process with T-cell predominance, but without a monoclonal cell population felt to be consistent with EBV-associated LPD. Bone marrow biopsy revealed hemophagocytic lymphohistiocytosis, complicating her course. She was treated with steroids and rituximab but continued to decline, eventually developing MSSA bacteremia and succumbing to her disease. Conclusion. To our knowledge, this is the first report of the constellation of celiac sprue, EBV-associated LPD, and hemophagocytic lymphohistiocytosis. Providers caring for patients with severe, uncontrolled celiac disease and adenopathy should consider EBV-associated LPD.

  8. HCV Virus and Lymphoid Neoplasms

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    Yutaka Tsutsumi

    2011-01-01

    Full Text Available Hepatitis C virus (HCV is one of the viruses known to cause hepatic cancer. HCV is also believed to be involved in malignant lymphoma. In this paper, we investigated characteristics of malignant lymphoma cases that were anti-HCV antibody (HCV-Ab positive. We were able to perform pathological examinations on 13 out of 14 HCV-positive cases. Of these, lymphoid tissues of 10 stained positive for HCV-Ab. There was no significant correlation between the degree of HCV staining and the rate of recurrence or resistance to treatment. However, there did appear to be a consistent decrease in the amount of HCV-RNA between pre- and posttreatment among HCV-Ab-positive cases; that is, treatment-resistant cases that exhibited resistance from the first treatment and recurrent cases more frequently had a higher HCV level at treatment termination compared to the pretreatment level. This suggests that the HCV virus either accelerates oncogenesis by direct interaction with B cells or indirectly affects lymphoma prognosis.

  9. The evaluation of Recombinant Immunoblot assay (RIBA and HCV-RNA test results in patients with low titer Anti-HCV positivity

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    Berrin Uzun

    2014-12-01

    Full Text Available Objectives: Laboratory diagnosis of hepatitis C virus (HCV infection is based on the detection of anti-HCV antibodies by enzyme immunoassay (EIA or chemiluminescence immunoassay (CIA techniques. However, a consensus related to the problem of low titer (Serum/Cut-off; S/C= 1.0 anti-HCV antibodies is still lacking. The study attempts to evaluate the clinical status of the patients with low titer anti-HCV antibodies detected by third generation anti-HCV tests during February 2013- May 2014 retrospectively. Methods: Serum samples were studied by Advia Centaur XP autoanalyser (Bayer-Siemens, Germany for anti-HCV, and line immunoassay (Inno-LIATM HCV Score, İnnogenetics, Belgium for anti-HCV confirmatory test, Cobas AmpliPre/Cobas AMPLICOR HCV Test (Roche diagnostics, Switzerland for HCV RNA. Results: A total of 55.631 serum samples were studied, and 55 of them were anti-HCV positive of which with low antibody levels (sample/cutoff [S/CO]. S/CO values ranged from 1.15 to 6.15. Seventeen (31% of patients who have low antibody levels were defined as positive and 2 (4% patients were intermittent and 36 (65% patients were negative with line immunoassay. HCV-RNA was not detected in any of the samples. Conclusions: It is thought that antibody positivity must be verified in cases of recurrent reactivity when considering the cost-effectiveness of molecular tests. In the study was concluded that the use of molecular tests would be appropriate diagnosis, and the effectiveness of treatment if necessary after evaluation of patients with biochemical analysis. J Clin Exp Invest 2014; 5 (4: 553-556

  10. Formal hepatitis C education enhances HCV care coordination, expedites HCV treatment and improves antiviral response.

    Science.gov (United States)

    Lubega, Samali; Agbim, Uchenna; Surjadi, Miranda; Mahoney, Megan; Khalili, Mandana

    2013-08-01

    Formal Hepatitis C virus (HCV) education improves HCV knowledge but the impact on treatment uptake and outcome is not well described. We aimed to evaluate the impact of formal HCV patient education on primary provider-specialist HCV comanagement and treatment. Primary care providers within the San Francisco safety-net health care system were surveyed and the records of HCV-infected patients before and after institution of a formal HCV education class by liver specialty (2006-2011) were reviewed retrospectively. Characteristics of 118 patients who received anti-HCV therapy were: mean age 51, 73% males and ~50% White and uninsured. The time to initiation of HCV treatment was shorter among those who received formal education (median 136 vs 284 days, P non-1 genotype (OR 6.17, 95% CI 2.3-12.7, P = 0.0003) and receipt of HCV education (OR 3.0, 95% CI 1.1-7.9, P = 0.03) were associated with sustained virologic treatment response. Among 94 provider respondents (response rate = 38%), mean age was 42, 62% were White, and 63% female. Most providers agreed that the HCV education class increased patients' HCV knowledge (70%), interest in HCV treatment (52%), and provider-patient communication (56%). A positive provider attitude (Coef 1.5, 95% CI 0.1-2.9 percent, P = 0.039) was independently associated with referral rate to education class. Formal HCV education expedites HCV therapy and improves virologic response rates. As primary care provider attitude plays a significant role in referral to HCV education class, improving provider knowledge will likely enhance access to HCV specialty services in the vulnerable population. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  11. Molecular signatures associated with HCV-induced hepatocellular carcinoma and liver metastasis.

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    Valeria De Giorgi

    Full Text Available Hepatocellular carcinomas (HCCs are a heterogeneous group of tumors that differ in risk factors and genetic alterations. In Italy, particularly Southern Italy, chronic hepatitis C virus (HCV infection represents the main cause of HCC. Using high-density oligoarrays, we identified consistent differences in gene-expression between HCC and normal liver tissue. Expression patterns in HCC were also readily distinguishable from those associated with liver metastases. To characterize molecular events relevant to hepatocarcinogenesis and identify biomarkers for early HCC detection, gene expression profiling of 71 liver biopsies from HCV-related primary HCC and corresponding HCV-positive non-HCC hepatic tissue, as well as gastrointestinal liver metastases paired with the apparently normal peri-tumoral liver tissue, were compared to 6 liver biopsies from healthy individuals. Characteristic gene signatures were identified when normal tissue was compared with HCV-related primary HCC, corresponding HCV-positive non-HCC as well as gastrointestinal liver metastases. Pathway analysis classified the cellular and biological functions of the genes differentially expressed as related to regulation of gene expression and post-translational modification in HCV-related primary HCC; cellular Growth and Proliferation, and Cell-To-Cell Signaling and Interaction in HCV-related non HCC samples; Cellular Growth and Proliferation and Cell Cycle in metastasis. Also characteristic gene signatures were identified of HCV-HCC progression for early HCC diagnosis.A diagnostic molecular signature complementing conventional pathologic assessment was identified.

  12. [Significance of non-organ-specific autoantibodies in HCV-related chronic hepatitis].

    Science.gov (United States)

    Guidi, Marcello; Muratori, Paolo; Granito, Alessandro; Muratori, Luigi; Pappas, Georgios; Bianchi, Francesco B

    2005-12-01

    The preliminary question regarding the clinical issue of the antiviral therapy in the HCV related chronic hepatitis patients is: is it mandatory the research for the autoantibodies in the eligible patients for the antiviral treatment? This issue is of particular interest at the light of the the reported cases of HCV positive patients with positivity for liver kidney microsome type 1 antibody who developed a hepatitic flare during the antiviral treatment. The data from literature about the efficacy and safety on the antiviral treatment in patients with autoantibodies are few and controversial, particularly if the ones regarding antiviral drugs and more recent treatment regimens are taking into account (peg-interferon, combined therapy of interferon and ribavirin). Large and prospective studies are needed for a thorough evaluation about the potential impact of autoantibodies reactivity on the therapeutic outcome. To date, it must be confirmed that a strict monitoring of hepatic parameters is to recommend during the whole treatment phase. This in the light of a potential appearance of significant flares of aminotransferases, particularly in subjects with anti LKM-1 autoantibodies, during interferon therapy.

  13. Comparison of a newly developed automated and quantitative hepatitis C virus (HCV) core antigen test with the HCV RNA assay for clinical usefulness in confirming anti-HCV results.

    Science.gov (United States)

    Kesli, Recep; Polat, Hakki; Terzi, Yuksel; Kurtoglu, Muhammet Guzel; Uyar, Yavuz

    2011-12-01

    Hepatitis C virus (HCV) is a global health care problem. Diagnosis of HCV infection is mainly based on the detection of anti-HCV antibodies as a screening test with serum samples. Recombinant immunoblot assays are used as supplemental tests and for the final detection and quantification of HCV RNA in confirmatory tests. In this study, we aimed to compare the HCV core antigen test with the HCV RNA assay for confirming anti-HCV results to determine whether the HCV core antigen test may be used as an alternative confirmatory test to the HCV RNA test and to assess the diagnostic values of the total HCV core antigen test by determining the diagnostic specificity and sensitivity rates compared with the HCV RNA test. Sera from a total of 212 treatment-naive patients were analyzed for anti-HCV and HCV core antigen both with the Abbott Architect test and with the molecular HCV RNA assay consisting of a reverse transcription-PCR method as a confirmatory test. The diagnostic sensitivity, specificity, and positive and negative predictive values of the HCV core antigen assay compared to the HCV RNA test were 96.3%, 100%, 100%, and 89.7%, respectively. The levels of HCV core antigen showed a good correlation with those from the HCV RNA quantification (r = 0.907). In conclusion, the Architect HCV antigen assay is highly specific, sensitive, reliable, easy to perform, reproducible, cost-effective, and applicable as a screening, supplemental, and preconfirmatory test for anti-HCV assays used in laboratory procedures for the diagnosis of hepatitis C virus infection.

  14. Isolated Post-Transplantation Lymphoproliferative Disease Involving the Breast and Axilla as Peripheral T-cell Lymphoma

    OpenAIRE

    Hwang, Ji-Young; Cha, Eun Suk; Lee, Jee Eun; Sung, Sun Hee

    2013-01-01

    Post-transplantation lymphoproliferative disorders (PTLDs) are a heterogeneous group of diseases that represent serious complications following immunosuppressive therapy for solid organ or hematopoietic-cell recipients. In contrast to B-cell PTLD, T-cell PTLD is less frequent and is not usually associated with Epstein Barr Virus infection. Moreover, to our knowledge, isolated T-cell PTLD involving the breast is extremely rare and this condition has never been reported previously in the litera...

  15. Liver Fibrosis in HCV Monoinfected and HIV/HCV Coinfected Patients: Dysregulation of Matrix Metalloproteinases (MMPs and Their Tissue Inhibitors TIMPs and Effect of HCV Protease Inhibitors

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    Tiziana Latronico

    2016-03-01

    Full Text Available An imbalance between matrix metalloproteinases (MMPs and tissue inhibitors of metalloproteinases (TIMPs may contribute to liver fibrosis in patients with hepatitis C (HCV infection. We measured the circulating levels of different MMPs and TIMPs in HCV monoinfected and HIV/HCV coinfected patients and evaluated the potential for anti-HCV therapy to modulate MMP and TIMP levels in HCV subjects. We analyzed 83 plasma samples from 16 HCV monoinfected patients undergoing dual or triple anti-HCV therapy, 15 HIV/HCV coinfected patients with undetectable HIV load, and 10 healthy donors (HD. Levels of MMP-1, MMP-2, MMP-3, MMP-8, MMP-9, MMP-10, TIMP-1, and TIMP-2 were measured by a SearchLight Multiplex Immunoassay Kit. MMP-2 and MMP-9 were the highest expressed MMPs among all the analyzed samples and their levels significantly increased in HCV monoinfected and HIV/HCV coinfected subjects compared to HD. TIMP-1 levels were significantly higher in HCV and HIV/HCV subjects compared to HD and were correlated with liver stiffness. These findings raise the possibility of using circulating TIMP-1 as a non-invasive marker of liver fibrosis in HCV infection. A longitudinal study demonstrated that MMP-9 levels significantly decreased (40% reduction from baseline in patients receiving dual as well as triple direct-acting antivirals (DAA anti-HCV therapy, which had no effect on MMP-2, TIMP-1, and TIMP-2. As the dysregulation of MMP-2 and MMP-9 may reflect inflammatory processes in the liver, the decrease of MMP-9 following HCV protease inhibitor treatment suggests a positive effect on the reduction of liver inflammation.

  16. Identification of the transcripts associated with spontaneous HCV clearance in individuals co-infected with HIV and HCV

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    Yue Chen

    2016-11-01

    Full Text Available Abstract Background Infection with human immunodeficiency virus (HIV influences the outcome and natural disease progression of hepatitis C virus (HCV infection. While the majority of HCV mono-infected and HCV/HIV co-infected subjects develop chronic HCV infection, 20–46% of mono- and co-infected subjects spontaneously clear HCV infection. The mechanism underlying viral clearance is not clearly understood. Analysis of differential cellular gene expression (mRNA between HIV-infected patients with persistent HCV infection or spontaneous clearance could provide a unique opportunity to decipher the mechanism of HCV clearance. Methods Plasma RNA from HIV/HCV co-infected subjects who cleared HCV and those who remained chronically infected with HCV was sequenced using Ion Torrent technology. The sequencing results were analyzed to identify transcripts that are associated with HCV clearance by measuring differential gene expression in HIV/HCV co-infected subjects who cleared HCV and those who remained chronically infected with HCV. Results We have identified plasma mRNA, the levels of which are significantly elevated (at least 5 fold, False Discovery Rate (FDR <0.05 before HCV infection in subjects who cleared HCV compared to those who remained chronically infected. Upon further analysis of these differentially expressed genes, before and after HCV infection, we found that before HCV infection 12 genes were uniquely upregulated in the clearance group compared to the chronically infected group. Importantly, a number of these 12 genes and their upstream regulators (such as CCL3, IL17D, LBP, SOCS3, NFKBIL1, IRF are associated with innate immune response functions. Conclusions These results suggest that subjects who spontaneously clear HCV may express these unique genes associated with innate immune functions.

  17. Posttransplantation lymphoproliferative disease involving the pituitary gland.

    Science.gov (United States)

    Meriden, Zina; Bullock, Grant C; Bagg, Adam; Bonatti, Hugo; Cousar, John B; Lopes, M Beatriz; Robbins, Mark K; Cathro, Helen P

    2010-11-01

    Posttransplantation lymphoproliferative disorders (PTLD) are heterogeneous lesions with variable morphology, immunophenotype, and molecular characteristics. Multiple distinct primary lesions can occur in PTLD, rarely with both B-cell and T-cell characteristics. Lesions can involve both grafted organs and other sites; however, PTLD involving the pituitary gland has not been previously reported. We describe a patient who developed Epstein-Barr virus-negative PTLD 13 years posttransplantation involving the terminal ileum and pituitary, which was simultaneously involved by a pituitary adenoma. Immunohistochemistry of the pituitary lesion showed expression of CD79a, CD3, and CD7 with clonal rearrangements of both T-cell receptor gamma chain (TRG@) and immunoglobulin heavy chain (IGH@) genes. The terminal ileal lesion was immunophenotypically and molecularly distinct. This is the first report of pituitary PTLD and illustrates the potentially complex nature of PTLD. Copyright © 2010 Elsevier Inc. All rights reserved.

  18. Clinical management of drug-drug interactions in HCV therapy: Challenges and solutions

    NARCIS (Netherlands)

    Burger, D.M.; Back, D.; Buggisch, P.; Buti, M.; Craxi, A.; Foster, G.; Klinker, H.; Larrey, D.; Nikitin, I.; Pol, S. van der; Puoti, M.; Romero-Gomez, M.; Wedemeyer, H.; Zeuzem, S.

    2013-01-01

    Hepatitis C virus (HCV) infected patients often take multiple co-medications to treat adverse events related to HCV therapy, or to manage other co-morbidities. Drug-drug interactions associated with this polypharmacy are relatively new to the field of HCV pharmacotherapy. With the advent of the

  19. Hepatitis C virus (HCV) RNA profiles among chronic HIV/HCV-coinfected individuals in ESPRIT; spontaneous HCV RNA clearance observed in nine individuals

    DEFF Research Database (Denmark)

    Grint, D; Tedaldi, Ellen; Peters, L

    2017-01-01

    OBJECTIVES: Studies have shown that hepatitis C virus (HCV) RNA levels remain stable over time in HIV/HCV-coinfected individuals taking combination antiretroviral therapy (cART), while spontaneous clearance of HCV RNA during the persistent infection phase has been documented only rarely among tho...

  20. Rise and fall of HCV-related hepatocellular carcinoma in Italy: a long-term survey from the ITA.LI.CA centres.

    Science.gov (United States)

    Cazzagon, Nora; Trevisani, Franco; Maddalo, Gemma; Giacomin, Anna; Vanin, Veronica; Pozzan, Caterina; Poggio, Paolo Del; Rapaccini, Gianludovico; Nolfo, Anna M Di; Benvegnù, Luisa; Zoli, Marco; Borzio, Franco; Giannini, Edoardo G; Caturelli, Eugenio; Chiaramonte, Maria; Foschi, Francesco G; Cabibbo, Giuseppe; Felder, Martina; Ciccarese, Francesca; Missale, Gabriele; Baroni, Gianluca Svegliati; Morisco, Filomena; Pecorelli, Anna; Farinati, Fabio

    2013-10-01

    Hepatitis C virus (HCV) is the leading aetiological factor of HCC in the western world where, overall, its incidence is increasing, despite data suggesting an initial drop in some areas. The aim of this study was to evaluate epidemiology, clinical features and survival of HCV-related HCC (HCV-HCC) in a wide time range in Italy. Multicentre retrospective study including 3695 patients prospectively recruited by the ITA.LI.CA group. Patients were classified into three subgroups according to aetiology (Group A[GA], pure HCV; Group B[GB], HCV + cofactors; and Group C[GC], non-HCV) and in 5 time cohorts (5 years each), according to the year of diagnosis. Age, gender, Child-Pugh score, modality of diagnosis, stage, presence of thrombosis/metastases, type of treatment and survival were analysed. A total of 1801 GA patients, 445 GB and 1333 GC were recruited. The number of GA patients peaked in the 1996-2000, gradually dropping thereafter (P < 0.0001), as observed for GB (P < 0.0001). Age at diagnosis increased (P < 0.0001), while percentage of patients diagnosed during surveillance and stage improved only in GA (P = 0.02 and P = 0.003 respectively). The survival significantly increased over time particularly in GA (median 37 months) and was longer in GA than in GB and GC (P < 0.0001). The prevalence of HCC-HCV is decreasing in Italy since 2001. HCV-HCC patients are older, more frequently diagnosed under surveillance and in an earlier stage. HCC survival improved in the last 15 years and is significantly higher in patients with HCV-HCC. We therefore expect a further drop in both incidence and mortality for HCV-HCC in the years to come. © 2013 John Wiley & Sons A/S.

  1. HCV-induced autophagosomes are generated via homotypic fusion of phagophores that mediate HCV RNA replication.

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    Linya Wang

    2017-09-01

    Full Text Available Hepatitis C virus (HCV induces autophagy to promote its replication, including its RNA replication, which can take place on double-membrane vesicles known as autophagosomes. However, how HCV induces the biogenesis of autophagosomes and how HCV RNA replication complex may be assembled on autophagosomes were largely unknown. During autophagy, crescent membrane structures known as phagophores first appear in the cytoplasm, which then progress to become autophagosomes. By conducting electron microscopy and in vitro membrane fusion assay, we found that phagophores induced by HCV underwent homotypic fusion to generate autophagosomes in a process dependent on the SNARE protein syntaxin 7 (STX7. Further analyses by live-cell imaging and fluorescence microscopy indicated that HCV-induced phagophores originated from the endoplasmic reticulum (ER. Interestingly, comparing with autophagy induced by nutrient starvation, the progression of phagophores to autophagosomes induced by HCV took significantly longer time, indicating fundamental differences in the biogenesis of autophagosomes induced by these two different stimuli. As the knockdown of STX7 to inhibit the formation of autophagosomes did not affect HCV RNA replication, and purified phagophores could mediate HCV RNA replication, the assembly of the HCV RNA replication complex on autophagosomes apparently took place during the formative stage of phagophores. These findings provided important information for understanding how HCV controlled and modified this important cellular pathway for its own replication.

  2. Hepatitis C among Egyptian Patients Referred for Bone Marrow Examination: Seroprevalence and Analysis of Hematological Findings

    Directory of Open Access Journals (Sweden)

    Somaia Mohammed Mousa

    2014-01-01

    Full Text Available Hepatitis C is a significant public health problem in Egypt where the highest prevalence (14.7% of hepatitis C virus (HCV exists. HCV prevalence is even higher among clinical populations and groups at risk of exposure to infection. Chronic HCV infection is associated with several hematological complications that may necessitate bone marrow (BM examination. The aim of this study is to estimate HCV prevalence among patients referred for BM examination and to explore hematological and BM findings among HCV positive patients. One hundred adult patients referred for BM examination were included in the study and screened for HCV antibodies. Patients’ clinical, hematological, and BM findings were recorded. The seroprevalence of HCV among patients referred for BM examination was 42%. The most common indication for BM examination among HCV positive patients was peripheral cytopenias (88.1%. The most common cytopenia detected was thrombocytopenia (85.7%. The most common diagnosis among HCV positive patients was hypersplenism (52.4% followed by B-lymphoproliferative disorders (19% and then immune thrombocytopenic purpura (11.9%. In conclusion, HCV prevalence among patients referred for BM examination is higher than that estimated in the general population. Patients with unexplained peripheral cytopenias should be tested for HCV.

  3. Apoptosis and clinical severity in patients with psoriasis and HCV infection

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    Sami A Gabr

    2014-01-01

    Full Text Available Background: It has been proposed that hepatitis C virus (HCV antigens are involved in the pathogenesis of psoriasis and may contribute to severity of the disease. Increased expression of the apoptosis-regulating proteins p53 and tTG and decreased levels of bcl-2 in the keratinocytes of the skin of psoriatic patients have been reported. Aim: This study aims to identify the serum levels of apoptosis-regulating proteins in patients with psoriasis and without HCV infection and to study the relation between clinical severity of psoriasis and the presence of HCV infection. Materials and Methods: Disease severity was assessed by psoriasis area severity index score (PASI of 90 patients with psoriasis grouped as mild (n = 30, moderate (n = 30 and severe (n = 30; 20 healthy individuals were used as controls. All groups were subjected for complete history taking, clinical examination, and tests for liver function and HCV infection. The serum levels of apoptosis related proteins: p53, tTG and bcl-2 were estimated by enzyme linked immune sorbent assay (ELISA. Results: There was a statistically significant (P < 0.001 correlation between clinical severity of psoriasis and presence of HCV antibodies and HCV-mRNA. In addition, significantly (P < 0.001 raised serum p53 and tTG, and reduced bcl-2 were observed among HCV-positive patients as compared to HCV-negative patients and control patients. Conclusion: These results conclude that clinical severity of psoriasis is affected by the presence of HCV antibodies and overexpression of apoptotic related proteins. In addition, altered serum levels of apoptosis-regulating proteins could be useful prognostic markers and therapeutic targets of psoriatic disease.

  4. The HCV and HIV coinfected patient: what have we learned about pathophysiology?

    Science.gov (United States)

    Talal, Andrew H; Canchis, P Wilfredo; Jacobson, Ira

    2002-02-01

    Hepatitis C virus (HCV) infection is an important problem in individuals who are also infected with HIV. HCV infection is very common in HIV-infected individuals, occurring in approximately one quarter to one third of this group, presumably as a consequence of shared routes of transmission related to virologic and pathogenic aspects of the viral infections. Although both are single-stranded RNA viruses and share similar epidemiologic properties, there are many important differences. Although the quantity of HIV RNA in plasma is an important prognostic determinant of HIV infection, this has not been shown with HCV. A direct relationship is apparent between HIV-related destruction of CD4 cells and the clinical consequences of the disease resulting from immunodeficiency. The pathogenesis of HCV, which occurs as a consequence of hepatic fibrosis, is much more complex. The hepatic stellate cell, the major producer of the extracellular matrix protein, is the main contributor to hepatic fibrosis, but the mechanism by which HCV induces hepatic fibrosis remains unclear. Treatment of HCV is increasingly important in HIV-infected patients due to improved HIV-associated morbidity and mortality and due to the frequency with which HCV occurs in patients with HIV-HCV coinfection. Timing of treatment initiation, management of side effects, and possible effects of anti-HCV therapy on HIV are among the issues that need consideration. Also, because several issues concerning HCV are unique to coinfected patients, further research is needed to determine optimal management of HCV in this setting.

  5. HCV-RNA quantification in liver bioptic samples and extrahepatic compartments, using the abbott RealTime HCV assay.

    Science.gov (United States)

    Antonucci, FrancescoPaolo; Cento, Valeria; Sorbo, Maria Chiara; Manuelli, Matteo Ciancio; Lenci, Ilaria; Sforza, Daniele; Di Carlo, Domenico; Milana, Martina; Manzia, Tommaso Maria; Angelico, Mario; Tisone, Giuseppe; Perno, Carlo Federico; Ceccherini-Silberstein, Francesca

    2017-08-01

    We evaluated the performance of a rapid method to quantify HCV-RNA in the hepatic and extrahepatic compartments, by using for the first time the Abbott RealTime HCV-assay. Non-tumoral (NT), tumoral (TT) liver samples, lymph nodes and ascitic fluid from patients undergoing orthotopic-liver-transplantation (N=18) or liver resection (N=4) were used for the HCV-RNA quantification; 5/22 patients were tested after or during direct acting antivirals (DAA) treatment. Total RNA and DNA quantification from tissue-biopsies allowed normalization of HCV-RNA concentrations in IU/μg of total RNA and IU/10 6 liver-cells, respectively. HCV-RNA was successfully quantified with high reliability in liver biopsies, lymph nodes and ascitic fluid samples. Among the 17 untreated patients, a positive and significant HCV-RNA correlation between serum and NT liver-samples was observed (Pearson: rho=0.544, p=0.024). Three DAA-treated patients were HCV-RNA "undetectable" in serum, but still "detectable" in all tested liver-tissues. Differently, only one DAA-treated patient, tested after sustained-virological-response, showed HCV-RNA "undetectability" in liver-tissue. HCV-RNA was successfully quantified with high reliability in liver bioptic samples and extrahepatic compartments, even when HCV-RNA was "undetectable" in serum. Abbott RealTime HCV-assay is a good diagnostic tool for HCV quantification in intra- and extra-hepatic compartments, whenever a bioptic sample is available. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Lymphoma and the control of B cell growth and differentiation.

    Science.gov (United States)

    Rui, Lixin; Goodnow, Christopher C

    2006-05-01

    It is now widely accepted that lymphomagenesis is a multistep transformation process. A number of genetic changes and environmental and infectious factors contributing to the development and malignant progression of B-cell lymphoproliferative disorders are well documented. Reciprocal chromosomal translocations involving the immunoglobulin loci are a hallmark of most mature B cell lymphomas and lead to dysregulated expression of proto-oncogenes (c-myc) important for cell proliferation or genes involved in cell cycle progression (cyclin D1), differentiation block (bcl-6, PAX5) and cell survival (bcl-2, NF-kappaB). In addition, genetic alterations that inactivate tumor suppressor genes (p53, p16) have been frequently detected in some lymphoma tissues. Many of these genes are normally regulated by signals from the B cell antigen receptor. The high prevalence of bacterial and viral infection in lymphoma patients supports the hypothesis that infectious agents may play a contributory role in the development and evolution of B cell lymphoproliferative disorders by either directly inducing polyclonal B cell hyperactivation (EBV, HCV), or providing a chronic antigenic stimulus (EBV, HCV, HBV, H. pylori), or mimicking B cell antigen receptor signaling (EBV, HCV, HHV8), although whether these are causative factors or they are secondary to genetic changes in lymphomagenesis remains to be defined. Stimulatory signals from reactive T cells, local cytokines and growth factors can also contribute, to some extent, to the progression of transformation. Modulation of B cell antigen receptor signaling therefore emerges as a potentially powerful strategy for controlling the growth of certain B cell lymphomas.

  7. Hepatitis C virus protects human B lymphocytes from Fas-mediated apoptosis via E2-CD81 engagement.

    Directory of Open Access Journals (Sweden)

    Zhihui Chen

    2011-04-01

    Full Text Available HCV infection is often associated with B-cell regulatory control disturbance and delayed appearance of neutralizing antibodies. CD81 is a cellular receptor for HCV and can bind to HCV envelope protein 2 (E2. CD81 also participates to form a B cell costimulatory complex. To investigate whether HCV influences B cell activation and immune function through E2 -CD81 engagement, here, human Burkitt's lymphoma cell line Raji cells and primary human B lymphocytes (PHB were treated with HCV E2 protein and cell culture produced HCV particles (HCVcc, and then the related cell phenotypes were assayed. The results showed that both E2 and HCVcc triggered phosphorylation of IκBα, enhanced the expression of anti-apoptosis Bcl-2 family proteins, and protected Raji cells and PHB cells from Fas-mediated death. In addition, both E2 protein and HCVcc increased the expression of costimulatory molecules CD80, CD86 and CD81 itself, and decreased the expression of complement receptor CD21. The effects were dependent on E2-CD81 interaction on the cell surface, since CD81-silenced Raji cells did not respond to both treatments; and an E2 mutant that lose the CD81 binding activity, could not trigger the responses of both Raji cells and PHB cells. The effects were not associated with HCV replication in cells, for HCV pseudoparticle (HCVpp and HCVcc failed to infect Raji cells. Hence, E2-CD81 engagement may contribute to HCV-associated B cell lymphoproliferative disorders and insufficient neutralizing antibody production.

  8. Spectrum of Epstein-Barr virus-related diseases. A pictorial review

    International Nuclear Information System (INIS)

    Maeda, Eriko; Akahane, Masaaki; Kiryu, Shigeru

    2009-01-01

    Epstein-Barr virus (EBV) prevails among more than 90% of the adult population worldwide. Most primary infections occur during young childhood and cause no or only nonspecific symptoms; then the virus becomes latent and resides in lymphocytes in the peripheral blood. Inactive latent EBV usually causes no serious consequences, but once it becomes active it can cause a wide spectrum of malignancies: epithelial tumors such as nasopharyngeal and gastric carcinomas; mesenchymal tumors such as follicular dendritic cell tumor/sarcoma; and lymphoid malignancies such as Burkitt lymphoma, lymphomatoid granulomatosis, pyothorax-associated lymphoma, immunodeficiency-associated lymphoproliferative disorders, extranodal natural killer (NK) cell/T-cell lymphoma, and Hodgkin's lymphoma. The purpose of this article is to describe the spectrum of EBV-related diseases and their key imaging findings. EBV-related lymphoproliferative disorders and lymphomas are especially common in immunocompromised patients. Awareness of their clinical settings and imaging spectrum contributes to early detection and early treatment of possibly life-threatening disorders. (author)

  9. Bone Marrow and Peripheral Blood Leptin Levels in Lymphoproliferative Diseases - Relation to the Bone Marrow Fat and Infiltration

    Czech Academy of Sciences Publication Activity Database

    Gaja, A.; Churý, Z.; Pecen, Ladislav; Fraňková, H.; Jandáková, H.; Hejlová, N.

    2000-01-01

    Roč. 47, č. 5 (2000), s. 307-312 ISSN 0028-2685 Institutional research plan: AV0Z1030915 Keywords : leptin * bone marrow fat * bone marrow infiltration * lymphoproliferative disease Subject RIV: BA - General Mathematics Impact factor: 0.579, year: 2000

  10. Health Beliefs and Co-morbidities Associated with Appointment-Keeping Behavior Among HCV and HIV/HCV Patients.

    Science.gov (United States)

    Pundhir, Pooja; North, Carol S; Fatunde, Oluwatomilade; Jain, Mamta K

    2016-02-01

    Appointment-keeping behavior is an important requisite for HCV linkage and treatment initiation. In this study we examine what impact hepatitis C (HCV) knowledge and attitudes has on appointment-keeping behavior among a cohort of HCV and HCV/HIV patients. Knowledge scores and attitude scales, obtained from a cross-sectional survey, were correlated with proportion of appointments kept 1 year prior to taking the survey. Independent risk factors for missing appointments were examined by multiple regression analysis. 292 HCV patients completed the survey, and 149 (51%) were co-infected with HIV. HCV patients kept 67.5 ± 17.4% of their total appointments and a similar proportion (67 ± 38.2) of Liver Clinic appointments, but they attended a higher proportion (73 ± 24.4) of Primary Care Clinic appointments. However, certain health beliefs, psychiatric illness, and HIV co-infection were independently associated with lower levels of appointment-keeping behavior. HCV knowledge was not associated with appointment-keeping behavior. Health beliefs, psychiatric illness, and HIV co-infection are associated with missing appointments, but no link between knowledge and appointment keeping behavior is apparent. In order to increase engagement into HCV care, HCV care coordination programs need to focus on addressing health beliefs and providing resources to those at highest risk for missing appointments.

  11. Prevalence and patterns of renal involvement in imaging of malignant lymphoproliferative diseases

    International Nuclear Information System (INIS)

    Bach, Andreas Gunter; Behrmann, Curd; Spielmann, Rolf Peter; Surov, Alexey; Holzhausen, Hans Jurgen; Katzer, Michaela; Arnold, Dirk

    2012-01-01

    Background: Renal involvement in patients with lymphoproliferative disease is an uncommon radiological finding. Purpose: To determine its prevalence and radiological appearances in a patient population. Material and Methods: All forms of lymphoproliferative disease (ICD: C81-C96) were considered. From January 2005 to January 2010, 668 consecutive patients with lymphoproliferative disease were identified with the help of the radiological database and patient records. Inclusion criteria were complete staging including appropriate CT scan and/or MRI. All stored images (initial staging and follow-up examinations) were reviewed. Results: Review of all stored images revealed renal infiltration in patients with non-Hodgkin lymphoma (11 of 364 = 3.0%; median age = 65 years, m:f = 6:5) but also multiple myeloma (2 of 162 = 1.2%; median age = 72 years; m:f = 1:1) and leukemia (5 of 101 4.9%; median age = 12 years; m:f = 2:3). There were no cases of renal infiltration in 41 patients with Hodgkin's disease. In total there were six patients with solitary lesions, five patients with diffuse renal enlargement, four patients with perirenal lesions, and two patients with direct invasion of the kidney. Conclusion: In leukemia the most common imaging pattern is diffuse enlargement. In the other subtypes of lymphoproliferative disease no specific correlation between typical CT patterns and subtype of lymphoproliferative disease can be found. The prevalence of renal involvement is in line with earlier studies. Contrary to earlier reports, multiple lesions were not found to be a common pattern

  12. Increased CD56(bright) NK cells in HIV-HCV co-infection and HCV mono-infection are associated with distinctive alterations of their phenotype.

    Science.gov (United States)

    Bhardwaj, Suvercha; Ahmad, Fareed; Wedemeyer, Heiner; Cornberg, Marcus; Schulze Zur Wiesch, Julian; van Lunzen, Jan; Sarin, Shiv K; Schmidt, Reinhold E; Meyer-Olson, Dirk

    2016-04-18

    HIV-HCV co-infection is associated with accelerated progression to hepatic fibrosis, cirrhosis and hepatocellular carcinoma than HCV mono-infection. The contribution of innate immunity during HIV-HCV co-infection has been a relatively under-investigated area. Natural killer (NK) cells are pivotal sentinels of innate immunity against viruses and tumour cells. In this study we evaluated the effect of HIV-HCV co-infection on peripheral blood NK cell subsets with emphasis on the phenotype of CD56(bright) NK cells. Sixty patients were included in the study; HIV mono-infected (n = 12), HCV mono-infected (n = 15), HCV-HIV co-infected (n = 21) and healthy controls (n = 16). PBMCs were isolated and immunophenotyping of NK cells was performed by flowcytometry. We observed an expansion of CD56(bright) NK cell subset in HIV-HCV co-infection as compared to healthy controls and HIV mono-infected group. All the infected groups had an upregulated expression of the activating receptor NKG2D on CD56(bright) NK cells in comparison to healthy controls while not differing amongst themselves. The expression of NKp46 in HIV-HCV co-infected group was significantly upregulated as compared to both HIV as well as HCV mono-infections while NKp30 expression in the HIV-HCV co-infected group significantly differed as compared to HIV mono-infection. The CD56(bright) NK cell subset was activated in HIV-HCV co-infection as assessed by the expression of CD69 as compared to healthy controls but was significantly downregulated in comparison to HIV mono-infection. CD95 expression on CD56(bright) NK cells followed the same pattern where there was an increased expression of CD95 in HIV mono-infection and HIV-HCV co-infection as compared to healthy controls. In contrast to CD69 expression, CD95 expression in HCV mono-infection was decreased when compared to HIV mono-infection and HIV-HCV co-infection. Finally, expression of CXCR3 on CD56(bright) NK cells was increased in HIV-HCV co-infection in comparison

  13. Packaging of HCV-RNA into lentiviral vector

    International Nuclear Information System (INIS)

    Caval, Vincent; Piver, Eric; Ivanyi-Nagy, Roland; Darlix, Jean-Luc; Pagès, Jean-Christophe

    2011-01-01

    Highlights: ► Description of HCV-RNA Core-D1 interactions. ► In vivo evaluation of the packaging of HCV genome. ► Determination of the role of the three basic sub-domains of D1. ► Heterologous system involving HIV-1 vector particles to mobilise HCV genome. ► Full length mobilisation of HCV genome and HCV-receptor-independent entry. -- Abstract: The advent of infectious molecular clones of Hepatitis C virus (HCV) has unlocked the understanding of HCV life cycle. However, packaging of the genomic RNA, which is crucial to generate infectious viral particles, remains poorly understood. Molecular interactions of the domain 1 (D1) of HCV Core protein and HCV RNA have been described in vitro. Since compaction of genetic information within HCV genome has hampered conventional mutational approach to study packaging in vivo, we developed a novel heterologous system to evaluate the interactions between HCV RNA and Core D1. For this, we took advantage of the recruitment of Vpr fusion-proteins into HIV-1 particles. By fusing HCV Core D1 to Vpr we were able to package and transfer a HCV subgenomic replicon into a HIV-1 based lentiviral vector. We next examined how deletion mutants of basic sub-domains of Core D1 influenced HCV RNA recruitment. The results emphasized the crucial role of the first and third basic regions of D1 in packaging. Interestingly, the system described here allowed us to mobilise full-length JFH1 genome in CD81 defective cells, which are normally refractory to HCV infection. This finding paves the way to an evaluation of the replication capability of HCV in various cell types.

  14. HIV/HCV Coinfection in Taiwan.

    Science.gov (United States)

    Hsu, Ching-Sheng; Kao, Jia-Horng

    2016-01-01

    Both human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infection are important global public health problems with shared transmission routes. Although HIV/HCV coinfection is not uncommon, the prevalence rates vary significantly across different studies and regions. In Taiwan, injection drug users have become the major contributors to the HIV/AIDS epidemic since 2005. Because the prevalence of HCV infection is high in injection drug users, this HIV epidemic is also associated with a significant increase of HIV/HCV coinfection in Taiwan. To control Taiwan's HIV epidemic, Taiwan Centers for Disease Control (CDC) launched a harm-reduction program in 2006. The HIV epidemic, the percentage attributed to injection drug users, and the prevalence of HIV/HCV coinfection gradually declined thereafter. In this article, we aimed to thoroughly examine the current literatures of HIV/HCV coinfection in Taiwan and hope to provide a better understanding of the needs for the management of this coinfection. We conducted a narrative review and searched for literature from PubMed, Ovid MEDLINE, and the Cochrane Library database untill August 2015. Studies relevant to the epidemiology and associated risk factors of HIV/HCV coinfection in Taiwan were examined and discussed.

  15. Drug treatment program patients' hepatitis C virus (HCV education needs and their use of available HCV education services

    Directory of Open Access Journals (Sweden)

    Osborne Andrew

    2007-03-01

    Full Text Available Abstract Background In spite of the disproportionate prevalence of hepatitis C virus (HCV infection among drug users, many remain uninformed or misinformed about the virus. Drug treatment programs are important sites of opportunity for providing HCV education to their patients, and many programs do, in fact, offer this education in a variety of formats. Little is known, however, about the level of HCV knowledge among drug treatment program patients, and the extent to which they utilize their programs' HCV education services. Methods Using data collected from patients (N = 280 in 14 U.S. drug treatment programs, we compared patients who reported that they never injected drugs (NIDUs with past or current drug injectors (IDUs concerning their knowledge about HCV, whether they used HCV education opportunities at their programs, and the facilitators and barriers to doing so. All of the programs were participating in a research project that was developing, implementing, and evaluating a staff training to provide HCV support to patients. Results Although IDUs scored higher on an HCV knowledge assessment than NIDUs, there were many gaps in HCV knowledge among both groups of patients. To address these knowledge gaps, all of the programs offered at least one form of HCV education: all offered 1:1 sessions with staff, 12 of the programs offered HCV education in a group format, and 11 of the programs offered this education through pamphlets/books. Only 60% of all of the participating patients used any of their programs' HCV education services, but those who did avail themselves of these HCV education opportunities generally assessed them positively. In all, many patients were unaware that HCV education was offered at their programs through individual sessions with staff, group meetings, and books/pamphlets, (42%, 49%, and 46% of the patients, respectively, and 22% were unaware that any HCV education opportunities existed. Conclusion Efforts especially need

  16. Packaging of HCV-RNA into lentiviral vector

    Energy Technology Data Exchange (ETDEWEB)

    Caval, Vincent [INSERM U966, Universite Francois Rabelais de Tours, Faculte de Medecine, 10 Bd. Tonnelle, 37000 Tours (France); Piver, Eric [INSERM U966, Universite Francois Rabelais de Tours, Faculte de Medecine, 10 Bd. Tonnelle, 37000 Tours (France); Service de Biochimie et Biologie Moleculaire, CHRU de Tours (France); Ivanyi-Nagy, Roland; Darlix, Jean-Luc [LaboRetro, ENS-Lyon INSERM, U758, 46 Allee d' Italie, 69364 Lyon (France); Pages, Jean-Christophe, E-mail: jean-christophe.pages@univ-tours.fr [INSERM U966, Universite Francois Rabelais de Tours, Faculte de Medecine, 10 Bd. Tonnelle, 37000 Tours (France); Service de Biochimie et Biologie Moleculaire, CHRU de Tours (France)

    2011-11-04

    Highlights: Black-Right-Pointing-Pointer Description of HCV-RNA Core-D1 interactions. Black-Right-Pointing-Pointer In vivo evaluation of the packaging of HCV genome. Black-Right-Pointing-Pointer Determination of the role of the three basic sub-domains of D1. Black-Right-Pointing-Pointer Heterologous system involving HIV-1 vector particles to mobilise HCV genome. Black-Right-Pointing-Pointer Full length mobilisation of HCV genome and HCV-receptor-independent entry. -- Abstract: The advent of infectious molecular clones of Hepatitis C virus (HCV) has unlocked the understanding of HCV life cycle. However, packaging of the genomic RNA, which is crucial to generate infectious viral particles, remains poorly understood. Molecular interactions of the domain 1 (D1) of HCV Core protein and HCV RNA have been described in vitro. Since compaction of genetic information within HCV genome has hampered conventional mutational approach to study packaging in vivo, we developed a novel heterologous system to evaluate the interactions between HCV RNA and Core D1. For this, we took advantage of the recruitment of Vpr fusion-proteins into HIV-1 particles. By fusing HCV Core D1 to Vpr we were able to package and transfer a HCV subgenomic replicon into a HIV-1 based lentiviral vector. We next examined how deletion mutants of basic sub-domains of Core D1 influenced HCV RNA recruitment. The results emphasized the crucial role of the first and third basic regions of D1 in packaging. Interestingly, the system described here allowed us to mobilise full-length JFH1 genome in CD81 defective cells, which are normally refractory to HCV infection. This finding paves the way to an evaluation of the replication capability of HCV in various cell types.

  17. Recurrent posttransplant lymphoproliferative disorder involving the larynx and trachea: case report and review of the literature.

    Science.gov (United States)

    Banks, Caroline A; Meier, Jeremy D; Stallworth, Christina R; White, David R

    2012-05-01

    Posttransplant lymphoproliferative disorder (PTLD) is a well-recognized complication of solid organ transplantation and commonly affects upper airway lymphoid tissue. Tracheal and laryngeal involvement in patients with PTLD, however, is rare. We present one such case. We report the case of a patient with recurrent PTLD involving the larynx and trachea and describe the presentation, evaluation, management, and outcome. An 11-year-old boy who underwent bilateral nephrectomy and renal transplantation as an infant was admitted to the hospital with chronic cough, fever, stridor, and dyspnea. His post-transplantation course was complicated by PTLD in cervical lymph nodes at 9 years of age that was successfully treated with chemotherapy. A computed tomographic scan during his present admission revealed supraglottic swelling, a distal tracheal mass, and paratracheal lymph node enlargement. The patient underwent laryngoscopy and bronchoscopy with biopsy specimens taken from the right laryngeal ventricle and distal trachea. Pathologic examination yielded a diagnosis of Epstein-Barr virus-positive PTLD. The patient was treated with chemotherapy, which resulted in resolution of the airway lesions, as seen on repeat bronchoscopy. This is the first report, to our knowledge, of recurrent PTLD involving simultaneous lesions in the larynx and the trachea. PTLD in the head and neck can present as lymphoid hypertrophy, airway obstruction, stridor, or cough. A high degree of clinical suspicion is essential for prompt diagnosis of this life-threatening complication.

  18. Maternal hepatitis C (HCV) infection and Anti-D immunoglobulin therapy: study testing antibodies, RNA and Genotype of HCV in Baghdad.

    Science.gov (United States)

    Al-Kubaisy, Waqar; Daud, Suzanna; Al-Kubaisi, Mustafa Waseem; Al-Kubaisi, Omar Waseem; Abdullah, Nik Nairan

    2018-04-30

    Hepatitis C virus (HCV) infection is a serious health problem. It is a major contributor to end-stage liver disease. Worldwide, 1-8% of all pregnant women were infected. Women with viral hepatitis may be at an increased risk of pregnancy complications. There are several obstetrics intervention acts as risk factors, which are specific to women pertaining the HCV infection; anti-D immunoglobulin (Ig) therapy may be one of them. Our objectives were to estimate the prevalence of HCV antibodies (anti-HCV), RNA, and genotype distribution among women with anti-D Ig therapy. A cross sectional study was conducted. A sample of 154 Rhesus negative (Rh - ve) pregnant women regardless of the anti-D Ig therapy was collected. Anti-HCV were tested using third generation enzyme immunoassay (EIA-3) and immunoblot assay (Lia Tek-111), subsequently. In addition, 89 serum samples were subjected to molecular analysis using RT-PCR and DNA enzyme immunoassay (DEIA) method for the detection of HCV-RNA and genotypes. Anti-HCV, and HCV-RNA seroprevalence were significantly higher (17.1, 35.5%) among women with anti-D Ig than their counter group (6.4, 13.16%), p = .038, .018, respectively. Significant direct positive dose response correlation (r = 0.78, p = .005) had been seen between number of anti-D Ig therapy and anti-HCV seropositive rate. Anti-D Ig therapy act as a risk factor (odds ratio (OR) = 3.01, 95%CI: 1.01-8.9) especially from the third dose onward. Women with anti-D Ig therapy were at higher risk (3.6 times more) of positive HCV-RNA (OR =3.6, 95%CI =1.19-10.837). Genotype HCV-1b showed higher prevalent (52.9%) among the recipients of anti-D Ig therapy while genotype HCV-3a (6.6%) was the lowest. Our study showed that Anti-D immunoglobulin therapy acts as a risk factor for acquiring HCV infection. Screening for HCV should be recommended for all recipients of anti-D Ig. Not only HCV antibodies but HCV-RNA detection being recommended for the diagnosis of HCV

  19. Hepatitis C Virus and Disrupted Interferon Signaling Promote Lymphoproliferation via Type II CD95 and Interleukins

    Science.gov (United States)

    MACHIDA, KEIGO; TSUKIYAMA-KOHARA, KYOKO; SEKIGUCH, SATOSHI; SEIKE, EIJI; TÓNE, SHIGENOBU; HAYASHI, YUKIKO; TOBITA, YOSHIMI; KASAMA, YURI; SHIMIZU, MASUMI; TAKAHASHI, HIDEMI; TAYA, CHYOJI; YONEKAWA, HIROMICHI; TANAKA, NOBUYUKI; KOHARA, MICHINORI

    2014-01-01

    BACKGROUND & AIMS The molecular mechanisms of lymphoproliferation associated with the disruption of interferon (IFN) signaling and chronic hepatitis C virus (HCV) infection are poorly understood. Lymphomas are extrahepatic manifestations of HCV infection; we sought to clarify the molecular mechanisms of these processes. METHODS We established interferon regulatory factor-1– null (irf-1−/−) mice with inducible and persistent expression of HCV structural proteins (irf-1/CN2 mice). All the mice (n = 900) were observed for at least 600 days after Cre/loxP switching. Histologic analyses, as well as analyses of lymphoproliferation, sensitivity to Fas-induced apoptosis, colony formation, and cytokine production, were performed. Proteins associated with these processes were also assessed. RESULTS Irf-1/CN2 mice had extremely high incidences of lymphomas and lymphoproliferative disorders and displayed increased mortality. Disruption of irf-1 reduced the sensitivity to Fas-induced apoptosis and decreased the levels of caspases-3/7 and caspase-9 messenger RNA species and enzymatic activities. Furthermore, the irf-1/CN2 mice showed decreased activation of caspases-3/7 and caspase-9 and increased levels of interleukin (IL)-2, IL-10, and Bcl-2, as well as increased Bcl-2 expression, which promoted oncogenic transformation of lymphocytes. IL-2 and IL-10 were induced by the HCV core protein in splenocytes. CONCLUSIONS Disruption of IFN signaling resulted in development of lymphoma, indicating that differential signaling occurs in lymphocytes compared with liver. This mouse model, in which HCV expression and disruption of IFN signaling synergize to promote lymphoproliferation, will be an important tool for the development of therapeutic agents that target the lymphoproliferative pathway. PMID:19362089

  20. High rate of hepatitis C virus (HCV) recurrence in HIV-infected individuals with spontaneous HCV RNA clearance

    DEFF Research Database (Denmark)

    Peters, L; Mocroft, A; Soriano, V

    2014-01-01

    OBJECTIVES: Following resolution of hepatitis C virus (HCV) infection, recurrence has been shown to occur in some persons with repeated exposure to HCV. We aimed to investigate the rate and factors associated with HCV RNA recurrence among HIV-1-infected patients with prior spontaneous HCV RNA cle......-up. Our findings underline the importance of maintaining focus on preventive measures to reduce IDU and sharing of contaminated needles. Clinicians should maintain a high degree of vigilance to identify patients with new HCV infection early....

  1. Central nervous system involvement in patients with HCV-related cryoglobulinemia: review and a case report

    Directory of Open Access Journals (Sweden)

    B. Canesi

    2011-09-01

    Full Text Available Introduction: Few well-documented cases of central nervous system involvement in patients with mixed cryoglobulinemia and/or HCV infection have been reported. We can distinguish between acute or subacute diffuse and focal lesions (transient ischemic attack-like syndromes and cerebrovascular accidents. Methods: A search of two electronic databases (Medline and EMBASE was conducted from the year of their inception (1966 for Medline and 1988 for EMBASE to September 2000. The search strategy employed entailed combining these terms: Cryoglobulinemia, Central Nervous System, Hepatitis C, chronic hepatitis. Cryoglobulinemia and Central Nervous System were also used as free test words. We analysed articles with case reports and the most frequent articles on the references list. Pathogenesis: The main pathophysiologic mechanism of cerebral involvement is ischemia (or rarely hemorrhage due to diffuse or segmental vasculitis of the small cerebral vessels. In these cases a brain MRI usually shows single or multiple increased T2 signals. Furthermore an occasional occlusive vasculopathy without vasculitis was documented histologically. In these patients ischemia could be started or enhanced by the engorgement of the microvasculature by clumps of red cells and by aggregates of cryoglobulins. In the same patients vasculitis and hemoreological abnormalities can affect the clinical picture of the cerebral involvement in mixed cryoglobulinemia. Finally, the detection of HCV in the lesions induces a hypothesis that, in some cases, CNS involvement could be directly related to chronic HCV infection, even in the absence of cryoglobulin production. Case report: We describe a 63 year-old woman with acute severe encephalopathy. Laboratory evaluation revealed a high positive test result for rheumatoid factor (3390 U/ml and hypocomplementemia (C4 less than 1.67 mg/dl. Protein immunofixation electrophoresis demonstrated 5% monoclonal proteins (IgM/k and IgG/k, 3

  2. Rheumatoid Case with HCV Infection

    OpenAIRE

    Bita Behnava; Seyed-Moayed Alavian

    2005-01-01

    Case Presentation:A 46-year-old woman referred to our center due to abnormality in aminotransferase level during check up. She had a history of blood transfusion 12 years ago. Anti-HCV Ab by ELISA method and HCV RNA by RT-PCR were positive. HCV RNA by Amplicor HCV monitor test counted 800,000 IU/ml and the genotype was 3a by Specific Primer-Targeted Region Core method. Laboratory evaluation revealed: Hb 11.9 mg/dl, WBC 5000 /ml, platelet count 190,000/ ml, ALT 70 IU/ml, AST 65 IU/ml, Alk phos...

  3. Hepatitis C virus (HCV genotype 1 subtype identification in new HCV drug development and future clinical practice.

    Directory of Open Access Journals (Sweden)

    Stéphane Chevaliez

    Full Text Available BACKGROUND: With the development of new specific inhibitors of hepatitis C virus (HCV enzymes and functions that may yield different antiviral responses and resistance profiles according to the HCV subtype, correct HCV genotype 1 subtype identification is mandatory in clinical trials for stratification and interpretation purposes and will likely become necessary in future clinical practice. The goal of this study was to identify the appropriate molecular tool(s for accurate HCV genotype 1 subtype determination. METHODOLOGY/PRINCIPAL FINDINGS: A large cohort of 500 treatment-naïve patients eligible for HCV drug trials and infected with either subtype 1a or 1b was studied. Methods based on the sole analysis of the 5' non-coding region (5'NCR by sequence analysis or reverse hybridization failed to correctly identify HCV subtype 1a in 22.8%-29.5% of cases, and HCV subtype 1b in 9.5%-8.7% of cases. Natural polymorphisms at positions 107, 204 and/or 243 were responsible for mis-subtyping with these methods. A real-time PCR method using genotype- and subtype-specific primers and probes located in both the 5'NCR and the NS5B-coding region failed to correctly identify HCV genotype 1 subtype in approximately 10% of cases. The second-generation line probe assay, a reverse hybridization assay that uses probes targeting both the 5'NCR and core-coding region, correctly identified HCV subtypes 1a and 1b in more than 99% of cases. CONCLUSIONS/SIGNIFICANCE: In the context of new HCV drug development, HCV genotyping methods based on the exclusive analysis of the 5'NCR should be avoided. The second-generation line probe assay is currently the best commercial assay for determination of HCV genotype 1 subtypes 1a and 1b in clinical trials and practice.

  4. Prevalence of mixed hepatitis C virus (HCV genotypes among recently diagnosed dialysis patients with HCV infection

    Directory of Open Access Journals (Sweden)

    Mohammed A Al Balwi

    2011-01-01

    Full Text Available Hepatitis C virus (HCV infection is considered a major health problem recognized globally. HCV is a major cause of chronic liver disease that may lead to cirrhosis and hepatocellular carcinoma. The aim of this study was to investigate the prevalence of multiple (mixed HCV genotypes in Saudi patients recently diagnosed with HCV infection and their association with various clinical risk factors. We examined a total of 1,292 newly diagnosed HCV-positive cases between January 2006 and July 2009 at the Molecular Pathology Laboratory, King Abdulaziz Medical City, Riyadh. The clinical and laboratory data of the study patients were collected. The HCV-RNA viral load and its genotyping were carried out with RT-PCR technology to assist in the follow-up and management of HCV-infected patients undergoing antiviral therapy. Twenty-two patients (1.7% were found to have mixed HCV genotypes; of them, mixed genotypes associated with genotype-4 were seen in 19 patients (86%, mixed genotypes associated with genotype-1 were found in 68.4%, with genotype-3 in 26.3% and with genotype-2 in 5.3%. Additionally, mixed genotypes associated with genotype-1 were seen in three cases (13.6%; they were associated with genotype-2 in two (66.7% and with genotype-5 in one patient (33.3%. In conclusion, the prevalence rate of mixed HCV genotypes in the cohort of the newly infected Saudi patients was 1.7%, with genotype-4 being the most frequent genotype encountered.

  5. An update on the management of hepatitis C virus-related arthritis.

    Science.gov (United States)

    Palazzi, Carlo; D'Amico, Emilio; D'Angelo, Salvatore; Gilio, Michele; Leccese, Pietro; Olivieri, Ignazio

    2014-10-01

    Hepatitis C virus (HCV)-related arthritis is an uncommon disease belonging to the autoimmune disorders due to the chronic stimulus exerted by the virus on the immune system. It shows two clinical subsets: a symmetrical polyarthritis resembling rheumatoid arthritis but less aggressive and an intermittent mono-oligoarthritis involving the lower limbs. We extensively review the current literature using the largest electronic databases (MEDLINE, EMBASE and COCHRANE) with regard to HCV-related arthritis (HCVrA) and studies focusing on the co-existence of HCV and other kinds of arthritides. The therapeutic approach to HCVrA remains largely empirical, because few studies have been published on this topic. Mainstream treatment based on the administration of hydroxychloroquine and low doses of corticosteroid is still largely preferred. Cyclosporine represents a useful alternative due to its antiviral properties. Anti-TNF agents are safe, but their hypothetic use appears excessive for a mild disorder such as HCVrA. IFN-α (and more recently pegylated IFN-α) when administered as a component of the combined (IFN-α + ribavirin) anti-HCV therapy can promote the appearance or the worsening of several autoimmune HCV-related disorders, including arthritis. New and forthcoming antiviral molecules will be used in the near future for a revolutionary IFN-free treatment.

  6. Hepatic HMOX1 expression positively correlates with Bach-1 and miR-122 in patients with HCV mono and HIV/HCV coinfection.

    Science.gov (United States)

    Jabłonowska, Elżbieta; Wójcik, Kamila; Szymańska, Bożena; Omulecka, Aleksandra; Cwiklińska, Hanna; Piekarska, Anna

    2014-01-01

    To analyze the expression of HMOX1 and miR-122 in liver biopsy samples obtained from HCV mono-and HIV/HCV co-infected patients in relation to selected clinical parameters, histological examination and IL-28B polymorphism as well as to determine whether HMOX1 expression is dependent on Bach-1. The study group consisted of 90 patients with CHC: 69 with HCV mono and 21 with HIV/HCV co-infection. RT-PCR was used in the analysis of HMOX1, Bach-1 and miR-122 expression in liver biopsy samples and in the assessment of IL-28B single-nucleotide polymorphism C/T (rs12979860) in the blood. Moreover in liver biopsy samples an analysis of HO-1 and Bach-1 protein level by Western Blot was performed. HCV mono-infected patients, with lower grading score (G600000 IU/mL) demonstrated higher expression of HMOX1. In patients with HIV/HCV co-infection, the expression of HMOX1 was lower in patients with lower lymphocyte CD4 count and higher HIV viral load. IL28B polymorphism did not affect the expression of either HMOX1 or miR-122. Higher HMOX1 expression correlated with higher expression of Bach-1 (Spearman's ρ = 0.586, p = 0.000001) and miR-122 (Spearman's ρ = 0.270, p = 0.014059). HMOX1 and miR-122 play an important role in the pathogenesis of CHC in HCV mono-and HIV/HCV co-infected patients. Reduced expression of HMOX1 in patients with HIV/HCV co-infection may indicate a worse prognosis in this group. Our results do not support the importance of Bach-1 in repression of HMOX1 in patients with chronic hepatitis C.

  7. Efficient infectious cell culture systems of the hepatitis C virus (HCV) prototype strains HCV-1 and H77

    DEFF Research Database (Denmark)

    Li, Yi-Ping; Ramirez, Santseharay; Mikkelsen, Lotte

    2015-01-01

    UNLABELLED: The first discovered and sequenced hepatitis C virus (HCV) genome and the first in vivo infectious HCV clones originated from the HCV prototype strains HCV-1 and H77, respectively, both widely used in research of this important human pathogen. In the present study, we developed...... efficiently after transfection and subsequent infection of naive Huh7.5 cells, reaching titers of 10(3.5) and 10(4.4) FFU/ml, respectively. IMPORTANCE: Hepatitis C virus (HCV) was discovered in 1989 with the cloning of the prototype strain HCV-1 genome. In 1997, two molecular clones of H77, the other HCV...... prototype strain, were shown to be infectious in chimpanzees, but not in vitro. HCV research was hampered by a lack of infectious cell culture systems, which became available only in 2005 with the discovery of JFH1 (genotype 2a), a genome that could establish infection in Huh7.5 cells. Recently, we...

  8. CD30-Positive T-Cell Lymphoproliferative Disease of the Oral Mucosa in Children: A Manifestation of Epstein-Barr Virus-Associated T-Lymphoproliferative Disorder.

    Science.gov (United States)

    Hong, Mineui; Ko, Young Hyeh

    2015-11-01

    Eosinophilic ulcer of the oral mucosa (EUOM) is a very rare, benign, self-limiting ulcerative lesion of the oral cavity of unknown pathogenesis, and belongs to the same spectrum of CD30(+) T-cell lymphoproliferative disease (LPD) of the oral mucosa. The etiology and pathogenesis of the disease are unknown. We report two cases in children who were initially diagnosed with EUOM and CD30(+) T-cell LPD, respectively. However, retrospective analysis revealed that a majority of infiltrated atypical T cells were positive for Epstein-Barr virus (EBV). The present cases suggest that the pathogenesis and etiology of EUOM or CD30(+) T-cell LPD occurring in children are different from those in adults. EUOM or CD30(+) T-cell LPD in children is a manifestation of EBV-positive T-cell LPD, and should therefore be distinguished from the disease in adults.

  9. Suppressed peripheral and placental blood lymphoproliferative responses in first pregnancies: relevance to malaria

    DEFF Research Database (Denmark)

    Rasheed, F N; Bulmer, J N; Dunn, D T

    1993-01-01

    protein derivative [PPD]) were examined in the peripheral and placental blood of 102 Gambian women at the time of delivery. The lymphoproliferative responses of placental cells were poor to all antigens compared with those of peripheral blood (Candida P PPD P ....003, and 190N P = 0.10). Reduced proliferative capacity of placental mononuclear cells may contribute to heavy parasite colonization of this organ. Proliferation to malarial and PPD but not Candida antigens was selectively suppressed in peripheral and placental blood of primiparae relative to multiparae (F32 P...... = 0.07, 190L P = 0.09, 190N P = 0.007, PPD P = 0.09). Autologous plasma contained factors that suppressed lymphoproliferative responses to the same series of antigens to which the primiparae responded poorly (F32 P PPD P = 0.03). Malarial antibody levels were...

  10. HCV IRES-mediated core expression in zebrafish.

    Directory of Open Access Journals (Sweden)

    Ye Zhao

    Full Text Available The lack of small animal models for hepatitis C virus has impeded the discovery and development of anti-HCV drugs. HCV-IRES plays an important role in HCV gene expression, and is an attractive target for antiviral therapy. In this study, we report a zebrafish model with a biscistron expression construct that can co-transcribe GFP and HCV-core genes by human hepatic lipase promoter and zebrafish liver fatty acid binding protein enhancer. HCV core translation was designed mediated by HCV-IRES sequence and gfp was by a canonical cap-dependent mechanism. Results of fluorescence image and in situ hybridization indicate that expression of HCV core and GFP is liver-specific; RT-PCR and Western blotting show that both core and gfp expression are elevated in a time-dependent manner for both transcription and translation. It means that the HCV-IRES exerted its role in this zebrafish model. Furthermore, the liver-pathological impact associated with HCV-infection was detected by examination of gene markers and some of them were elevated, such as adiponectin receptor, heparanase, TGF-β, PDGF-α, etc. The model was used to evaluate three clinical drugs, ribavirin, IFNα-2b and vitamin B12. The results show that vitamin B12 inhibited core expression in mRNA and protein levels in dose-dependent manner, but failed to impact gfp expression. Also VB12 down-regulated some gene transcriptions involved in fat liver, liver fibrosis and HCV-associated pathological process in the larvae. It reveals that HCV-IRES responds to vitamin B12 sensitively in the zebrafish model. Ribavirin did not disturb core expression, hinting that HCV-IRES is not a target site of ribavirin. IFNα-2b was not active, which maybe resulted from its degradation in vivo for the long time. These findings demonstrate the feasibility of the zebrafish model for screening of anti-HCV drugs targeting to HCV-IRES. The zebrafish system provides a novel evidence of using zebrafish as a HCV model organism.

  11. Modelling the impact of incarceration and prison-based hepatitis C virus (HCV) treatment on HCV transmission among people who inject drugs in Scotland.

    Science.gov (United States)

    Stone, Jack; Martin, Natasha K; Hickman, Matthew; Hutchinson, Sharon J; Aspinall, Esther; Taylor, Avril; Munro, Alison; Dunleavy, Karen; Peters, Erica; Bramley, Peter; Hayes, Peter C; Goldberg, David J; Vickerman, Peter

    2017-07-01

    People who inject drugs (PWID) experience high incarceration rates, and previous incarceration is associated with elevated hepatitis C virus (HCV) transmission risk. In Scotland, national survey data indicate lower HCV incidence in prison than the community (4.3 versus 7.3 per 100 person-years), but a 2.3-fold elevated transmission risk among recently released (prison-related prevention interventions, including scaling-up direct-acting antivirals (DAAs) in prison. Dynamic mathematical modelling of incarceration and HCV transmission, using approximate Bayesian computation for model calibration. Scotland, UK. A simulated population of PWID. Population-attributable fraction (PAF) of incarceration to HCV transmission among PWID. Decrease in HCV incidence and chronic prevalence due to current levels of prison opiate substitution therapy (OST; 57% coverage) and HCV treatment, as well as scaling-up DAAs in prison and/or preventing the elevated risk associated with prison release. Incarceration contributes 27.7% [PAF; 95% credible interval (CrI) -3.1 to 51.1%] of HCV transmission among PWID in Scotland. During the next 15 years, current HCV treatment rates (10.4/6.8 per 1000 incarcerated/community PWID annually), with existing prison OST, could reduce incidence and chronic prevalence among all PWID by a relative 10.7% (95% CrI = 8.4-13.3%) and 9.7% (95% CrI = 7.7-12.1%), respectively. Conversely, without prison OST, HCV incidence and chronic prevalence would decrease by 3.1% (95% CrI = -28.5 to 18.0%) and 4.7% (95% CrI = -11.3 to 14.5%). Additionally, preventing the heightened risk among recently released PWID could reduce incidence and chronic prevalence by 45.0% (95% CrI = 19.7-57.5%) and 33.3% (95% CrI = 15.6-43.6%) or scaling-up prison HCV treatments to 80% of chronic PWID prison entrants with sufficient sentences (>16 weeks) could reduce incidence and prevalence by 45.6% (95% CrI = 38.0-51.3%) and 45.5% (95% CrI = 39.3-51.0%), respectively

  12. Molecular epidemiology of HCV monoinfection and HIV/HCV coinfection in injection drug users in Liuzhou, Southern China.

    Directory of Open Access Journals (Sweden)

    Yi Tan

    Full Text Available BACKGROUND: Hepatitis C virus (HCV mono-infection and HCV/HIV (human immunodeficiency virus co-infection are growing problems in injection drug users (IDU. Their prevalence and genotypic patterns vary with geographic locations. Access to harm reduction measures is opening up opportunities for improving the HIV/HCV profiling of IDU in China, where IDUs account for a significant proportion of the two infections especially in the southern part of the country. METHODOLOGY/PRINCIPAL FINDINGS: A cross sectional study was conducted. Through the Liuzhou Methadone Clinic, a total of 117 injection drug users (IDUs were recruited from Guangxi, Southern China. A majority of the IDUs (96% were HCV antibody positive, of which 21% were HIV infected. Unlike HCV monoinfection, there was spatial heterogeneity in the distribution of HIV/HCV coinfection, the latter also characterized by a higher prevalence of needle-sharing. Phylogenetic analysis revealed that genotype 6a was predominant in the study population. There were shorter genetic distances among the 6a sequences compared to the other HCV subtypes-1a, 3a, and 3b. CONCLUSION/SIGNIFICANCE: The results suggested that HIV and HCV were introduced at around the same time to the IDU populations in Southern China, followed by their differential spread as determined by the biologic characteristics of the virus and the intensity of behavioural risk. This pattern is different from that in other South East Asian countries where HCV infections have probably predated HIV.

  13. Usefullness of IGH/TCR PCR studies in lymphoproliferative disorders with inconclusive clonality by flow cytometry.

    Science.gov (United States)

    Ribera, Jordi; Zamora, Lurdes; Juncà, Jordi; Rodríguez, Inés; Marcé, Silvia; Cabezón, Marta; Millá, Fuensanta

    2013-07-25

    In up to 5-15% of studies of lymphoproliferative disorders (LPD) flow cytometry (FCM) or immunomorphologic methods cannot discriminate malignant from reactive processes. The aim of this work was to determine the usefulness of PCR for solving these diagnostic uncertainties. We analyzed IGH and TCRγ genes by PCR in 106 samples with inconclusive FCM results. A clonal result was registered in 36/106 studies, with a LPD being confirmed in 27 (75%) of these cases. Specifically, 9/9 IGH clonal and 16/25 TCRγ clonal results were finally diagnosed with LPD. Additionally, 2 clonal TCRγ samples with suspicion of undefined LPD were finally diagnosed with T LPD. Although polyclonal results were obtained in 47 of the cases studied (38 IGH and 9 TCRγ), hematologic neoplasms were diagnosed in 4/38 IGH polyclonal and in 1/9 TCRγ polyclonal studies. There were also 14 PCR polyclonal results (4 IGH, 10 TCRγ), albeit non-conclusive. Of these, 2/4 were eventually diagnosed with B-cell lymphoma and 3/10 with T-cell LPD. In 8 IGH samples the results of PCR techniques were non-informative but in 3/8 cases a B lymphoma was finally confirmed. We concluded that PCR is a useful technique to identify LPD when FCM is inconclusive. A PCR clonal B result is indicative of malignancy but IGH polyclonal and non-conclusive results do not exclude lymphoid neoplasms. Interpretation of T-cell clonality should be based on all the available clinical and analytical data. © 2013 Clinical Cytometry Society. Copyright © 2013 Clinical Cytometry Society.

  14. Intrahepatic Vγ9Vδ2 T-cells from HCV-infected patients show an exhausted phenotype but can inhibit HCV replication.

    Science.gov (United States)

    Cimini, E; Bordoni, V; Sacchi, A; Visco-Comandini, U; Montalbano, M; Taibi, C; Casetti, R; Lalle, E; D'Offizi, G; Capobianchi, M R; Agrati, C

    2018-01-02

    Hepatitis C virus (HCV) persistence results from inefficiencies of both innate and adaptive immune responses to eradicate the infection. A functional impairment of circulating Vγ9Vδ2 T-cells was described but few data are available on Vγ9Vδ2 T-cells in the liver that, however, represents the battlefield in the HCV/host interaction. Aim of this work was to compare circulating and intrahepatic Vγ9Vδ2 T-cells in chronic HCV-infected patients (HCV pos ) and in HCV-negative (HCV neg ) subjects. Phenotypic and functional analysis was performed by flow cytometry. Anti-HCV activity was analyzed by using an in vitro autologous liver culture system. Independently from HCV infection, the liver was enriched of Vγ9Vδ2 T-cells expressing an effector/activated phenotype. In contrast, an enrichment of PD-1 expressing Vγ9Vδ2 T-cells was observed both in the peripheral blood and in the liver of HCV pos patients, probably due to a persistent antigenic stimulation. Moreover, a lower frequency of IFN-γ producing Vγ9Vδ2 T-cells was observed in the liver of HCV pos patients, suggesting a functional impairment in the cytokine production in HCV pos liver. Despite this hypo-responsiveness, intrahepatic Vγ9Vδ2 T-cells are able to exert an anti-HCV activity after specific stimulation. Altogether, our data show that HCV infection induced a dysregulation of intrahepatic Vγ9Vδ2 T cells that maintain their anti-HCV activity after specific stimulation. A study aimed to evaluate the mechanisms of the antiviral activity may be useful to identify new pathways able to improve Vγ9Vδ2 T-cells intrahepatic function during HCV infection. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Synthetic lipophilic antioxidant BO-653 suppresses HCV replication.

    Science.gov (United States)

    Yasui, Fumihiko; Sudoh, Masayuki; Arai, Masaaki; Kohara, Michinori

    2013-02-01

    The influence of the intracellular redox state on the hepatitis C virus (HCV) life cycle is poorly understood. This study demonstrated the anti-HCV activity of 2,3-dihydro-5-hydroxy-2,2-dipentyl-4,6-di-tert-butylbenzofuran (BO-653), a synthetic lipophilic antioxidant, and examined whether BO-653's antioxidant activity is integral to its anti-HCV activity. The anti-HCV activity of BO-653 was investigated in HuH-7 cells bearing an HCV subgenomic replicon (FLR3-1 cells) and in HuH-7 cells infected persistently with HCV (RMT-tri cells). BO-653 inhibition of HCV replication was also compared with that of several hydrophilic and lipophilic antioxidants. BO-653 suppressed HCV replication in FLR3-1 and RMT-tri cells in a concentration-dependent manner. The lipophilic antioxidants had stronger anti-HCV activities than the hydrophilic antioxidants, and BO-653 displayed the strongest anti-HCV activity of all the antioxidants examined. Therefore, the anti-HCV activity of BO-653 was examined in chimeric mice harboring human hepatocytes infected with HCV. The combination treatment of BO-653 and polyethylene glycol-conjugated interferon-α (PEG-IFN) decreased serum HCV RNA titer more than that seen with PEG-IFN alone. These findings suggest that both the lipophilic property and the antioxidant activity of BO-653 play an important role in the inhibition of HCV replication. Copyright © 2012 Wiley Periodicals, Inc.

  16. Performance comparison of new generation HCV core antigen test versus HCV RNA test in management of hepatitis C virus infection.

    Science.gov (United States)

    Çetiner, Salih; Çetin Duran, Alev; Kibar, Filiz; Yaman, Akgün

    2017-06-01

    The study has evaluated the performance of HCV core antigen (Cag) test by comparing HCV RNA PCR assay which is considered the gold standard for management of HCV infection. Totally, 132 samples sent for HCV RNA (real-time PCR) test were included in the study. Anti-HCV antibody test and HCV Cag test were performed by chemiluminescent enzyme immunoassay (CMEI). Anti-HCV test was positive in all samples. HCV RNA was detected in 112/132 (84.8%) samples, and HCV Cag in 105/132 (79.5%). The most common HCV genotype was genotype 1 (86%). Considering the HCV RNA test as gold standard; the sensitivity, specificity, positive predictive value, negative predictive value and accuracy of Cag test were found to be 93.75%, 100%, 100%, 74.07% and 94.69%, respectively, and paired test results were detected as highly concordant. A high level of correlation was seen between HCV RNA and Cag tests, however, the concordance between the two tests appeared to be disrupted at viral loads lower than 10 3 IU/mL. On the contrary, the correlation reached significance for the values higher than 10 3 IU/mL. Viral loads were in the 17-2500IU/mL range for the negative results for Cag test. Pearson's correlation coefficient revealed a considerably high correlation. The concordance between HCV RNA and Cag tests was disrupted under a viral load lower than 10 3 IU/mL. Therefore, it would be appropriate to consider cost effectiveness, advantages and limitations of the HCV RNA and Cag tests during the decision on which method to use for patient management. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Original Article: Investigation of Bcl-2 and PCNA in Hepatocellular Carcinoma: Relation to Chronic HCV

    International Nuclear Information System (INIS)

    ALENZI, F.Q.Ph.; ABBAS, M.Y.Ph.; HAMAD, A.M.; EL-SAEED, O.M.; EL-NASHAR, E.M.; AL-GHAMDI, S.S.; WYSE, R.K.H.; LOTFY, M.

    2010-01-01

    Bcl-2 family members can be functionally divided into anti-apoptotic and pro-apoptotic groups. The balance between these two groups may determine the fate of tumor cells. In hepatocellular carcinoma (HCC), this balance is often tilted towards the anti-apoptotic members in tumor cells, leading to resistance to cell death and rapid proliferation. Material and Methods: In the current study, we in-vestigated Bcl-2 and proliferating cell nuclear antigen (PCNA) immunohistochemically, using specific mono-clonal antibodies in liver tissues obtained from two patient groups. The first group included fifty patients infected with hepatitis C virus (HCV) without hepatocellular carcinoma, the other group included twenty five HCV-infected patients but with confirmed HCC. Serum Bcl-2 was assayed using enzyme immunoassay. Results: Results showed serum Bcl-2 was elevated in 82% versus 100% in HCC-free and HCC patients, respectively. Moreover, cytoplasmic staining of Bcl-2 was found in only 16% of chronic HCV patients without HCC, versus 8% in HCC patients. On the other hand, nuclear staining of PCNA was detected in 100% of HCC patients, but in none of the HCV patients without HCC. Conclusion: The results collectively suggest that in HCV-infected patients with and without HCC, apoptosis is dysregulated and proliferation activity perturbed. There may be prognostic and/or diagnostic potential in estimating Bcl-2 and PCNA proteins in these patient groups

  18. Glomerular diseases associated with HBV and HCV infection

    Directory of Open Access Journals (Sweden)

    Boriana Kiperova

    2014-03-01

    Full Text Available Hepatitis B and C viruses are human pathogens of major significance. Their extrahepatic manifestations are global health problem. HBV is a well-known cause of membranous nephropathy, membranoproliferative GN and IgA nephropathy, frequently in Asian populations. Polyarteritis nodosa is a rare, but serious systemic complication of chronic HBV. Immunosuppressive therapy in HBV-related GN is not recommended. Interferon alpha treatment produces sustained remission of porteinuria, often associated with clearance of HBeAg and/or HBsAg, however, it has many side effects. Compared to interferon, nucleos(tide analogues offer some advantages. These antiviral agents suppress HBV replication through their inhibitory effect on viral DNA polymerase. They have convenient administration and high tolerability. Lamivudine is well tolerated and safe in long-term studies, but the resistance of HBV is an escalating problem. The resistance to newer polymerase inhibitors Entecavir and Tenofovir is significantly lower. Hepatitis C virus causes cryoglobulinemia-mediated glomerulonephritis and other immune complex forms of GN. The renal manifestations are usually associated with long-lasting HCV infection. HCV glomerular disease is more frequent in adult males, and often leads to chronic renal insufficiency. The first line treatment in patients with mild to moderate clinical and histological kidney damage is the antiviral therapy with pegylated INF alpha and ribavirin. In case of severe HCV-associated cryoglobulinemic GN - nephrotic syndrome, nephritic syndrome and/or progressive renal failure, high activity score of glomerulonephritis on light microscopy, the initial treatment might consist of sequential administration of antiviral and immunosuppressive agents (corticosteroids, cyclophosphamide and plasma exchange, or rituximab. The treatment of HCV-related glomerular disease is still under debate and based on scant experimental evidence. Large randomized and controlled

  19. Frequency of anti-HCV, Hbsag and related risk factors in pregnant women at Nishtar Hospital, Multan

    International Nuclear Information System (INIS)

    Taseer, I.H.; Ishaq, F.; Hussain, L.; Safdar, S.; Mirbahar, A.M.; Faiz, S.A.

    2010-01-01

    Background: Viral hepatitis is a global issue. Among the hepatitis viruses hepatitis B and C are important in South Asia including Pakistan. There are various modes of transmission of these viruses. Vertical transmission is also gaining importance. Antepartum screening for HBV and HCV would help the infected women for appropriate antiviral therapy at appropriate time as well as for taking proper care of the newborns. The present study was designed to see the frequency of HBsAg and anti-HCV in pregnant women at Nishtar Hospital, Multan. Methods: This was a cross-sectional study carried out using non-probability purposive sampling technique. The period of the study was from June 2006 to August 2007. Five hundred (500) pregnant women attending outpatient department of Gynaecology and Obstetrics were included. Informed consent was taken. A specially designed proforma was filled in. Anti-HCV and HBsAg were tested by device method. Data were analyzed on SPSS-11. Results: Out of 500 pregnant women 35 (7.00%) were found to be anti-HCV positive and 23 (4.60%) were positive for HBsAg. Mean age was 26.7+-4.8 years. Majority of the patients 263 (52.60%) were in the age group 26-35 years. 138 (27.60%) women were nulliparous and 282 (56.40%) were para 1-4 and anti-HCV and HBsAg were common in this parity group. Only 80 (16.00%) women were para 5 or more. All anti-HCV and HBsAg positive women were house-wives. Most of them were belonging to rural areas having poor socio-economic status. Among 35 anti-HCV positive women, 20 (57.14%) had history of previous surgery, while 13 (37.14%) had history of multiple injections, 5 (14.28%) received blood transfusion, 4 (11.42%) had ear/nose piercing while tattooing was seen in only 2 (5.71%). Among 23 HBsAg positive women, 10 (43.47%) had history of previous surgery. History of multiple injections was present in 6 (26.08%) patients, 4 (17.39%) patients had history of blood transfusion, tattooing, ear/nose piercing, history of dental

  20. Stability of hepatitis C virus (HCV) RNA levels among interferon-naïve HIV/HCV-coinfected individuals treated with combination antiretroviral therapy

    DEFF Research Database (Denmark)

    Grint, D; Peters, L; Reekie, J

    2013-01-01

    Infection with hepatitis C virus (HCV) is a major cause of chronic liver disease. High HCV RNA levels have been associated with poor treatment response. This study aimed to examine the natural history of HCV RNA in chronically HCV/HIV-coinfected individuals.......Infection with hepatitis C virus (HCV) is a major cause of chronic liver disease. High HCV RNA levels have been associated with poor treatment response. This study aimed to examine the natural history of HCV RNA in chronically HCV/HIV-coinfected individuals....

  1. Addressing HCV infection in Europe: reported, estimated and undiagnosed cases

    DEFF Research Database (Denmark)

    Merkinaite, Simona; Lazarus, Jeff; Gore, Charles

    2008-01-01

    . At present, it is the most common cause of chronic liver disease and liver transplantation in a number of countries, with an estimated 250,000 people dying annually from HCV-related causes. Despite the magnitude of the problem, the virus does not receive adequate attention from either the general public...... or from health policy-makers. This study assesses HCV prevalence from both estimated totals and undiagnosed cases in selected European countries. Secondary sources were assessed and experts in 17 European countries were interviewed about HCV prevalence, reporting strategies and transmission. Available...

  2. Analytical characteristics and comparative evaluation of Aptima HCV quant Dx assay with the Abbott RealTime HCV assay and Roche COBAS AmpliPrep/COBAS TaqMan HCV quantitative test v2.0.

    Science.gov (United States)

    Worlock, A; Blair, D; Hunsicker, M; Le-Nguyen, T; Motta, C; Nguyen, C; Papachristou, E; Pham, J; Williams, A; Vi, M; Vinluan, B; Hatzakis, A

    2017-04-04

    The Aptima HCV Quant Dx assay (Aptima assay) is a fully automated quantitative assay on the Panther® system. This assay is intended for confirmation of diagnosis and monitoring of HCV RNA in plasma and serum specimens. The purpose of the testing described in this paper was to evaluate the performance of the Aptima assay. The analytical sensitivity, analytical specificity, precision, and linearity of the Aptima assay were assessed. The performance of the Aptima assay was compared to two commercially available HCV assays; the Abbott RealTime HCV assay (Abbott assay, Abbott Labs Illinois, USA) and the Roche COBAS Ampliprep/COBAS Taqman HCV Quantitative Test v2.0 (Roche Assay, Roche Molecular Systems, Pleasanton CA, USA). The 95% Lower Limit of Detection (LoD) of the assay was determined from dilutions of the 2nd HCV WHO International Standard (NIBSC 96/798 genotype 1) and HCV positive clinical specimens in HCV negative human plasma and serum. Probit analysis was performed to generate the 95% predicted detection limits. The Lower Limit of Quantitation (LLoQ) was established for each genotype by diluting clinical specimens and the 2nd HCV WHO International Standard (NIBSC 96/798 genotype 1) in HCV negative human plasma and serum. Specificity was determined using 200 fresh and 536 frozen HCV RNA negative clinical specimens including 370 plasma specimens and 366 serum specimens. Linearity for genotypes 1 to 6 was established by diluting armored RNA or HCV positive clinical specimens in HCV negative serum or plasma from 8.08 log IU/mL to below 1 log IU/mL. Precision was tested using a 10 member panel made by diluting HCV positive clinical specimens or spiking armored RNA into HCV negative plasma and serum. A method comparison was conducted against the Abbott assay using 1058 clinical specimens and against the Roche assay using 608 clinical specimens from HCV infected patients. In addition, agreement between the Roche assay and the Aptima assay using specimens with low

  3. Efficient infectious cell culture systems of the hepatitis C virus (HCV) prototype strains HCV-1 and H77.

    Science.gov (United States)

    Li, Yi-Ping; Ramirez, Santseharay; Mikkelsen, Lotte; Bukh, Jens

    2015-01-01

    The first discovered and sequenced hepatitis C virus (HCV) genome and the first in vivo infectious HCV clones originated from the HCV prototype strains HCV-1 and H77, respectively, both widely used in research of this important human pathogen. In the present study, we developed efficient infectious cell culture systems for these genotype 1a strains by using the HCV-1/SF9_A and H77C in vivo infectious clones. We initially adapted a genome with the HCV-1 5'UTR-NS5A (where UTR stands for untranslated region) and the JFH1 NS5B-3'UTR (5-5A recombinant), including the genotype 2a-derived mutations F1464L/A1672S/D2979G (LSG), to grow efficiently in Huh7.5 cells, thus identifying the E2 mutation S399F. The combination of LSG/S399F and reported TNcc(1a)-adaptive mutations A1226G/Q1773H/N1927T/Y2981F/F2994S promoted adaptation of the full-length HCV-1 clone. An HCV-1 recombinant with 17 mutations (HCV1cc) replicated efficiently in Huh7.5 cells and produced supernatant infectivity titers of 10(4.0) focus-forming units (FFU)/ml. Eight of these mutations were identified from passaged HCV-1 viruses, and the A970T/I1312V/C2419R/A2919T mutations were essential for infectious particle production. Using CD81-deficient Huh7 cells, we further demonstrated the importance of A970T/I1312V/A2919T or A970T/C2419R/A2919T for virus assembly and that the I1312V/C2419R combination played a major role in virus release. Using a similar approach, we found that NS5B mutation F2994R, identified here from culture-adapted full-length TN viruses and a common NS3 helicase mutation (S1368P) derived from viable H77C and HCV-1 5-5A recombinants, initiated replication and culture adaptation of H77C containing LSG and TNcc(1a)-adaptive mutations. An H77C recombinant harboring 19 mutations (H77Ccc) replicated and spread efficiently after transfection and subsequent infection of naive Huh7.5 cells, reaching titers of 10(3.5) and 10(4.4) FFU/ml, respectively. Hepatitis C virus (HCV) was discovered in 1989 with

  4. An animal model for human EBV-associated hemophagocytic syndrome: herpesvirus papio frequently induces fatal lymphoproliferative disorders with hemophagocytic syndrome in rabbits.

    Science.gov (United States)

    Hayashi, K; Ohara, N; Teramoto, N; Onoda, S; Chen, H L; Oka, T; Kondo, E; Yoshino, T; Takahashi, K; Yates, J; Akagi, T

    2001-04-01

    Epstein-Barr virus-associated hemophagocytic syndrome (EBV-AHS) is often associated with fatal infectious mononucleosis. However, the animal model for EBV-AHS has not been developed. We reported the first animal model for EBV-AHS using rabbits infected with EBV-related herpesvirus of baboon (HVP). Eleven of 13 (85%) rabbits inoculated intravenously with HVP-producing cells developed fatal lymphoproliferative disorders (LPD) between 22 and 105 days after inoculation. LPD was also accompanied by hemophagocytic syndrome (HPS) in nine of these 11 rabbits. The peroral spray of cell-free HVP induced the virus infection with increased anti-EBV-viral capsid antigen-IgG titers in three of five rabbits, and two of these three infected rabbits died of LPD with HPS. Autopsy revealed hepatosplenomegaly and swollen lymph nodes. Atypical lymphoid T cells expressing EBV-encoded small RNA-1 infiltrated diffusely in many organs, frequently involving the lymph nodes, spleen, and liver. Hemophagocytic histiocytosis was observed in the lymph nodes, spleen, bone marrow, and thymus. HVP-DNA was detected in the tissues and peripheral blood from the infected rabbits by polymerase chain reaction or Southern blot analysis. Reverse transcriptase-polymerase chain reaction revealed both HVP-EBNA1 and HVP-EBNA2 transcripts, suggesting latency type III infection. These data indicate that the high rate of rabbit LPD with HPS induction is caused by HVP. This system is useful for studying the pathogenesis, prevention, and treatment of human EBV-AHS.

  5. Epstein-Barr virus load in transplant patients: Early detection of post-transplant lymphoproliferative disorders.

    Science.gov (United States)

    Fellner, María Dolores; Durand, Karina A; Solernou, Veronica; Bosaleh, Andrea; Balbarrey, Ziomara; García de Dávila, María T; Rodríguez, Marcelo; Irazu, Lucía; Alonio, Lidia V; Picconi, María A

    2016-01-01

    High levels of circulating EBV load are used as a marker of post-transplant lymphoproliferative disorders (PTLD). There is no consensus regarding the threshold level indicative of an increase in peripheral EBV DNA. The aim of the study was to clinically validate a developed EBV quantification assay for early PTLD detection. Transversal study: paired peripheral blood mononuclear cells (PBMC), plasma and oropharyngeal lymphoid tissue (OLT) from children undergoing a solid organ transplant with (n=58) and without (n=47) PTLD. Retrospective follow-up: 71 paired PBMC and plasma from recipients with (n=6) and without (n=6) PTLD history. EBV load was determined by real-time PCR. The diagnostic ability to detect all PTLD (categories 1-4), advanced PTLD (categories 2-4) or neoplastic PTLD (categories 3 and 4) was estimated by analyzing the test performance at different cut-off values or with a load variation greater than 0.5log units. The higher diagnostic performance for identifying all, advanced or neoplastic PTLD, was achieved with cut-off values of 1.08; 1.60 and 2.47log EBVgEq/10(5) PBMC or 2.30; 2.60; 4.47loggEq/10(5) OLT cells, respectively. EBV DNA detection in plasma showed high specificity but low (all categories) or high (advanced/neoplastic categories) sensitivity for PTLD identification. Diagnostic performance was greater when: (1) a load variation in PBMC or plasma was identified; (2) combining the measure of EBV load in PBMC and plasma. The best diagnostic ability to identify early PTLD stages was achieved by monitoring EBV load in PBMC and plasma simultaneously; an algorithm was proposed. Copyright © 2016 Asociación Argentina de Microbiología. Publicado por Elsevier España, S.L.U. All rights reserved.

  6. HCV Transmission between serodiscordant couples through sexual route

    International Nuclear Information System (INIS)

    Khan, R.S.A.; Khalid, S.R.; Naseer, M.; Mirza, R.

    2014-01-01

    To determine the rate of transmission of HCV between n spouses through sexual route. Study Design: Descriptive study. Place and Duration of Study: This study was carried out at Military Hospital, Rawalpindi, Pakistan. It was conducted over a period of 4 years from June 2009 to June 2013. Patients and Methods: One hundred and sixty eight consecutive patients confirmed to have HCV infection by PCR for HCV RNA were enrolled in the study. Their spouses were also included in the study, and it was established through PCR for HCV RNA that the spouses were not suffering from HCV infection. All couples were inducted in the study within the first two months of starting the study. Therefore, the maximum and minimum follow-up time was 48 months and 46 months, respectively. The spouses were questioned for HCV risk factors and were tested for HCV antibodies six monthly. Once spouses were found to be anti-HCV positive, their HCV status was confirmed with PCR for HCV RNA. Results: Out of 168 patients, 90 (53.57%) were males and 78 (46.43%) were females. PCR for HCV RNA was found to be positive in 4 of 168 (2.38%) spouses. All the se 4 couples in whom HCV transmission was found had genotype 3a. Out of the 4 spouses who tested positive for HCV RNA PCR, 3 (75%) were females and 1 (25%) was male. So HCV infection was transmitted in 3 out of 90 (3.33 %) and 1 out of 78 (1.28%) female and male spouses, respectively. In PCR for HCV RNA positive and negative spouses, the duration of marriage was 202 +- 53 and 199 +- 49 weeks; and the number of total sexual intercourses was 171 +- 93 and 169 +- 89, respectively. Conclusion: HCV transmission among serodiscordant couples in our setup did occur. The overall rate of transmission was 2.38%. The rate of transmission from male to female (3.33%) was higher than female to male (1.28%). However, a large scale study conducted over a longer duration of time is needed to recommend protected sex in serodiscordant couples if either partner is suffering

  7. NAFLD and NASH in HCV Infection: Prevalence and Significance in Hepatic and Extrahepatic Manifestations

    Directory of Open Access Journals (Sweden)

    Luigi Elio Adinolfi

    2016-05-01

    Full Text Available The aim of this paper is to review and up to date the prevalence of hepatitis C virus (HCV-associated non-alcoholic fatty liver disease (NAFLD and non-alcoholic steatohepatitis (NASH and their significance in both accelerating progression of HCV-related liver disease and development of HCV-associated extrahepatic diseases. The reported mean prevalence of HCV-related NAFLD was 55%, whereas NASH was reported in 4%–10% of cases. HCV genotype 3 directly induces fatty liver deposition, namely “viral steatosis” and it is associated with the highest prevalence and degree of severity, whereas, HCV non-3 genotype infection showed lower prevalence of steatosis, which is associated with metabolic factors and insulin resistance. The host’s genetic background predisposes him or her to the development of steatosis. HCV’s impairment of lipid and glucose metabolism causes fatty liver accumulation; this seems to be a viral strategy to optimize its life cycle. Irrespective of insulin resistance, HCV-associated NAFLD, in a degree-dependent manner, contributes towards accelerating the liver fibrosis progression and development of hepatocellular carcinoma by inducing liver inflammation and oxidative stress. Furthermore, NAFLD is associated with the presence of metabolic syndrome, type 2 diabetes, and atherosclerosis. In addition, HCV-related “metabolic steatosis” impairs the response rate to interferon-based treatment, whereas it seems that “viral steatosis” may harm the response rate to new oral direct antiviral agents. In conclusion, a high prevalence of NAFLD occurs in HCV infections, which is, at least in part, induced by the virus, and that NAFLD significantly impacts progression of the liver disease, therapeutic response, and some extrahepatic diseases.

  8. Detection of HCV core antigen and its diagnostic significance

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    YANG Jie

    2013-02-01

    Full Text Available ObjectiveTo compare the abilities of the hepatitis C virus (HCV core antigen (cAg test and the HCV RNA assay for confirming anti-HCV presence in order to determine the clinical utility of the HCV-cAg as an alternative or confirmatory diagnostic tool. MethodsSerum samples collected from 158 patients diagnosed with HCV infection were subjected to the enzyme-linked immunosorbent assay-based HCV-cAg test. The optical density (OD measured values were used to calculate the ratio of specimen absorbance to the cutoff value (S/CO. Simultaneously, the serum samples were subjected to PCR-based nucleic acid amplification quantitative fluorescence detection of HCV RNA. ResultsNone of the serum samples had a S/CO value <1 for the HCV-cAg test (100% negative, but all of the samples had a S/CO value >5 (100% positive. The HCV-cAg test sensitivity was 87.05%, specificity was 76.67%, positive predictive value was 9653%, and negative predictive value was 44.23%. As the S/CO value gradually increased, the significantly higher positive coincident rate of the HCV RNA test decreased. The HCV RNA negative coincident rate was significantly higher than that of the HCV-cAg test. HCV-cAg S/CO values between 1 and 2 corresponded to an HCV RNA values between 1.0×103 copies/ml and 1.0×104 copies/ml. The highest S/CO value obtained was 1.992. ConclusionThe HCV-cAg test is comparable to the HCV RNA assay for diagnosing HCV infection.

  9. Composite cutaneous lymphoma (iatrogenic immunodeficiency-associated lymphoproliferative disorder) in a patient with rheumatoid arthritis treated with methotrexate: Staging and evaluation of response to therapy with "1'8F-FDG PET/CT

    International Nuclear Information System (INIS)

    Makis, William; Ciarallo, Anthony; Gonzalez-Verdecia, Milene; Wang, Beatrice; Probst, Stehan

    2017-01-01

    A 67 year old woman with a 10 year history of rheumatoid arthritis (RA) treated with methotrexate and prednisone, presented with a 2 year history of worsening multiple cutaneous plaques of variable appearance. Two distinct skin lesions were biopsied to reveal a composite cutaneous lymphoma, possibly caused by long term methotrexate therapy. An [18F] fluoro-2-deoxy-D-glucose ("1"8F-FDG) positron emission tomography/computed tomography (PET/CT) was performed to stage the malignancy, and was later repeated to evaluate response to chemotherapy, which guided subsequent management. We present the PET/CT imaging findings of this very rare iatrogenic (methotrexate induced) immunodeficiency-associated lymphoproliferative disorder

  10. The relationships between IFNL4 genotype, intrahepatic interferon-stimulated gene expression and interferon treatment response differs in HCV-1 compared with HCV-3.

    Science.gov (United States)

    Holmes, J A; Congiu, M; Bonanzinga, S; Sandhu, M K; Kia, Y H; Bell, S J; Nguyen, T; Iser, D M; Visvanathan, K; Sievert, W; Bowden, D S; Desmond, P V; Thompson, A J

    2015-08-01

    The biological mechanism underlying the association between IFNL4/IFNL3 polymorphism and peginterferon/ribavirin (PR) response in HCV-1 is thought to involve differential intrahepatic interferon-stimulated gene expression. HCV-3 is more sensitive to PR, but there are no studies of the association between IFNL4 polymorphism, PR treatment response and liver interferon-stimulated gene expression in HCV-3. We evaluated the association between IFNL4/IFNL3 genotypes, PR treatment outcomes and intrahepatic interferon-stimulated gene expression, according to HCV genotype. HCV-1 and HCV-3 patients who received PR therapy were identified. IFNL3 (rs12979860) and IFNL4 genotype (rs368234815) were determined. A second cohort with stored liver specimens was identified. Expression of ISGs was measured by rt-PCR. Two hundred and fifty-nine patients were identified: 55% HCV-1, 45% HCV-3. IFNL4 genotype frequency was TT/TT 44%, TT/ΔG 42% andΔG/ΔG 14%. Linkage disequilibrium with IFNL3 genotype was high (r(2) = 0.98). The association between IFNL4 genotype and PR response was attenuated in HCV-3 vs. HCV-1 (HCV-3: SVR 89% vs. 76% vs. 72% for TT/TT vs. TT/ΔG vs. ΔG/ΔG, P = 0.09; HCV-1: SVR: 82% vs. 29% vs. 24%, P < 0.001). Intrahepatic ISG expression was evaluated in 92 patients; 61% HCV-1. The association between IFNL4 genotype and liver ISG expression was significantly different for HCV-3 vs. HCV-1 (P-value for interaction = 0.046), with levels of interferon-stimulated gene expression being highest in HCV-1 patients who carried a poor-response IFNL4 genotype. The relationship between IFNL4 genotype and PR treatment response as well as intrahepatic interferon-stimulated gene expression differs between HCV-1 and HCV-3. These data suggest fundamental differences in host-virus interactions according to HCV genotype. © 2015 John Wiley & Sons Ltd.

  11. Post-Transplant Lymphoproliferative Disorder (PTLD) Manifesting in the Oral Cavity of a 13-Year-Old Liver Transplant Recipient (LTx).

    Science.gov (United States)

    Krasuska-Sławińska, Ewa; Minko-Chojnowska, Izabela; Pawłowska, Joanna; Dembowska-Bagińska, Bożenna; Pronicki, Maciej; Olczak-Kowalczyk, Dorota

    2015-08-18

    BACKGROUND Post-transplant lymphoproliferative disorder (PTLD) is a potential complication of solid organ or bone marrow transplants. The main PTLD risk factors are: the Epstein-Barr virus (EBV), transplant type, and use of immunosuppressants. It mainly consists of an uncontrolled growth of lymphocytes in transplant recipients under chronic immunosuppressive therapy. About 85% of PTLDs are EBV-containing B-cell proliferations; 14% are T-cell proliferations, of which only 40% contain EBV; and the remaining 1% is NK-cell or plasmocyte proliferations. PTLD may present various clinical manifestations, from non-specific mononucleosis-like syndrome to graft or other organ damage resulting from pathologic lymphocyte infiltration. PTLD may manifest in the oral cavity. CASE REPORT The objective of this study was to present the case of a 13-year-old female living-donor liver transplant recipient, resulting from biliary cirrhosis caused by congenital biliary atresia, with exophytic fibrous lesions on buccal mucosa and tongue. Exophytic and hyperplastic lesion of oral mucosa were removed and histopathological examination revealed polymorphic PTLD. The patient underwent 6 cycles of CHOP chemotherapy and all the oral lesions regressed completely. CONCLUSIONS All oral pathological lesions in organ transplant recipients need to be surgically removed and histopathologically examined because they present an increased risk of neoplastic transformations such as PTLD.

  12. Association of HCV Core Antigen Seropositivity with Long-Term Mortality in Patients on Regular Hemodialysis

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    Akihiko Kato

    2012-03-01

    Full Text Available Anti-hepatitis C virus (HCV antibody seropositivity is independently associated with poor prognosis in hemodialysis (HD patients. However, anti-HCV antibody cannot distinguish between patients with active infection and those who have recovered from infection. We therefore aimed in this study to examine the association of HCV core antigen (HCVcAg seropositivity with mortality in HD patients. We first measured serum HCVcAg using an immunoradiometric assay and anti-HCV antibody in 405 patients on regular HD, and followed them for 104 months. There were 82 patients (20.2% who had been positive for anti-HCV antibodies; 57 (69.5% of these were positive for HCVcAg. During the follow-up, 29 patients were excluded, so we tested the association of HCVcAg seropositivity with all-cause, cardiovascular (CV and non-CV mortalities in 376 patients. A total of 209 patients (55.6% had expired during the observational period, 92 out of them due to CV causes. After adjusting for comorbid parameters, HCVcAg was independently associated with overall mortality (HR 1.61, 95% CI 1.05–2.47, p < 0.05. HCV infection was significantly related to liver disease-related mortality. Past HCV infection also contributed to CV mortality (HR 2.63, 95% CI 1.27–5.45, p < 0.01. In contrast, anti-HCV antibody and HCVcAg seropositivities did not associate with infectious disease-related and cancer-related (expect for hepatocellular carcinoma mortality. It follows from these findings that HCVcAg serology is associated with all-cause and CV mortality in HD patients.

  13. High false-negative rate of anti-HCV among Egyptian patients on regular hemodialysis.

    Science.gov (United States)

    El-Sherif, Assem; Elbahrawy, Ashraf; Aboelfotoh, Atef; Abdelkarim, Magdy; Saied Mohammad, Abdel-Gawad; Abdallah, Abdallah Mahmoud; Mostafa, Sadek; Elmestikawy, Amr; Elwassief, Ahmed; Salah, Mohamed; Abdelbaseer, Mohamed Ali; Abdelwahab, Kouka Saadeldin

    2012-07-01

    Routine serological testing for hepatitis C virus (HCV) infection among hemodialysis (HD) patients is currently recommended. A dilemma existed on the value of serology because some investigators reported a high rate of false-negative serologic testing. In this study, we aimed to detect the false-negative rate of anti-HCV among Egyptian HD patients. Seventy-eight HD patients, negative for anti-HCV, anti-HIV, and hepatitis B surface antigen, were tested for HCV RNA by reverse transcriptase polymerase chain reaction (RT-PCR). In the next step, the viral load was quantified by real-time PCR in RT-PCR-positive patients. Risk factors for HCV infection, as well as clinical and biochemical indicators of liver disease, were compared between false-negative and true-negative anti-HCV HD patients. The frequency of false-negative anti-HCV was 17.9%. Frequency of blood transfusion, duration of HD, dialysis at multiple centers, and diabetes mellitus were not identified as risk factors for HCV infection. The frequency of false-negative results had a linear relation to the prevalence of HCV infection in the HD units. Timely identification of HCV within dialysis units is needed in order to lower the risk of HCV spread within the HD units. The high false-negative rate of anti-HCV among HD patients in our study justifies testing of a large scale of patients for precious assessment of effectiveness of nucleic acid amplification technology testing in screening HD patient. © 2012 The Authors. Hemodialysis International © 2012 International Society for Hemodialysis.

  14. Differential predictors of ART adherence among HIV-monoinfected versus HIV/HCV-coinfected individuals.

    Science.gov (United States)

    Shuper, Paul A; Joharchi, Narges; Irving, Hyacinth; Fletcher, David; Kovacs, Colin; Loutfy, Mona; Walmsley, Sharon L; Wong, David K H; Rehm, Jürgen

    2016-08-01

    Although adherence is an important key to the efficacy of antiretroviral therapy (ART), many people living with HIV (PLWH) fail to maintain optimal levels of ART adherence over time. PLWH with the added burden of Hepatitis C virus (HCV) coinfection possess unique challenges that potentially impact their motivation and ability to adhere to ART. The present investigation sought to (1) compare ART adherence levels among a sample of HIV/HCV-coinfected versus HIV-monoinfected patients, and (2) identify whether ART-related clinical and psychosocial correlates differ by HCV status. PLWH receiving ART (N = 215: 105 HIV/HCV-coinfected, 110 HIV-monoinfected) completed a comprehensive survey assessing ART adherence and its potential correlates. Medical chart extraction identified clinical factors, including liver enzymes. Results demonstrated that ART adherence did not differ by HCV status, with 83.7% of coinfected patients and 82.4% of monoinfected patients reporting optimal (i.e., ≥95%) adherence during a four-day recall period (p = .809). Multivariable logistic regression demonstrated that regardless of HCV status, optimal ART adherence was associated with experiencing fewer adherence-related behavioral skills barriers (AOR = 0.56; 95%CI = 0.43-0.73), lower likelihood of problematic drinking (AOR = 0.15; 95%CI = 0.04-0.67), and lower likelihood of methamphetamine use (AOR = 0.14; 95%CI = 0.03-0.69). However, among HIV/HCV-coinfected patients, optimal adherence was additionally associated with experiencing fewer ART adherence-related motivational barriers (AOR = 0.23; 95%CI = 0.08-0.62) and lower likelihood of depression (AOR = 0.06; 95%CI = 0.00-0.84). Findings suggest that although HIV/HCV-coinfected patients may face additional, distinct barriers to ART adherence, levels of adherence commensurate with those demonstrated by HIV-monoinfected patients might be achievable if these barriers are addressed.

  15. EBV AND HIV-RELATED LYMPHOMA

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    Michele Bibas

    2009-12-01

    Full Text Available HIV-associated lymphoproliferative disorders represent a heterogeneous group of diseases, arising in the presence of HIV-associated immunodeficiency. The overall prevalence of HIV-associated lymphoma is significantly higher compared to that of the general population and it continues to be relevant even after the wide availability of highly active antiretroviral therapy (HAART (1. Moreover, they still represent one of the most frequent cause of death in HIV-infected patients. Epstein–Barr virus (EBV, a γ-Herpesviruses, is involved in human lymphomagenesis, particularly in HIV immunocompromised patients. It has been largely implicated in the development of B-cell lymphoproliferative disorders as Burkitt lymphoma (BL, Hodgkin disease (HD, systemic non Hodgkin lymphoma (NHL, primary central nervous system lymphoma (PCNSL, nasopharyngeal carcinoma (NC. Virus-associated lymphomas are becoming of significant concern for the mortality of long-lived HIV immunocompromised patients, and therefore, research of advanced strategies for AIDS-related lymphomas is an important field in cancer chemotherapy. Detailed understanding of the EBV  lifecycle and related cancers at the molecular level is required for novel strategies of molecular-targeted cancer chemotherapy The linkage of HIV-related lymphoma with EBV infection of the tumor clone has several pathogenetic, prognostic and possibly therapeutic implications which are reviewed herein

  16. HCV Core Antigen Testing for Diagnosis of HCV Infection: A systematic review and meta-analysis

    Science.gov (United States)

    Freiman, J. Morgan; Tran, Trang M.; Schumacher, Samuel G; White, Laura F.; Ongarello, Stefano; Cohn, Jennifer; Easterbrook, Philippa J.; Linas, Benjamin P.; Denkinger, Claudia M.

    2017-01-01

    Background Diagnosis of chronic Hepatitis C Virus (HCV) infection requires both a positive HCV antibody screen and confirmatory nucleic acid test (NAT). HCV core antigen (HCVcAg) is a potential alternative to NAT. Purpose This systematic review evaluated the accuracy of diagnosis of active HCV infection among adults and children for five HCVcAg tests compared to NAT. Data Sources EMBASE, PubMed, Web of Science, Scopus, and Cochrane from 1990 through March 31, 2016. Study Selection Cohort, cross-sectional, and randomized controlled trials were included without language restriction Data Extraction Two independent reviewers extracted data and assessed quality using an adapted Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. Data Synthesis 44 studies evaluated 5 index tests. Studies for the ARCHITECT had the highest quality, while those for Ortho ELISA were the lowest. From bivariate analyses, the sensitivity and specificity with 95% CI were: ARCHITECT 93.4% (90.1, 96.4) and 98.8% (97.4, 99.5), Ortho ELISA 93.2% (81.6, 97.7) and 99.2% (87.9, 100), and Hunan Jynda 59.5% (46.0, 71.7) and 82.9% (58.6, 94.3). Insufficient data were available for a meta-analysis for Lumipulse and Lumispot. In three quantitative studies using ARCHITECT, HCVcAg correlated closely with HCV RNA above 3000 IU/mL. Limitations There was insufficient data on covariates such as HIV or HBV status for sub-group analyses. Few studies reported genotypes of isolates and there were scant data for genotypes 4, 5, and 6. Most studies were conducted in high resource settings within reference laboratories. Conclusions HCVcAg assays with signal amplification have high sensitivity, high specificity, and good correlation with HCV RNA above 3000 IU/mL. HCVcAg assays have the potential to replace NAT in high HCV prevalence settings. PMID:27322622

  17. HCV proteins and immunoglobulin variable gene (IgV) subfamilies in HCV-induced type II mixed cryoglobulinemia: a concurrent pathogenetic role.

    Science.gov (United States)

    Sautto, Giuseppe; Mancini, Nicasio; Solforosi, Laura; Diotti, Roberta A; Clementi, Massimo; Burioni, Roberto

    2012-01-01

    The association between hepatitis C virus (HCV) infection and type II mixed cryoglobulinemia (MCII) is well established, but the role played by distinct HCV proteins and by specific components of the anti-HCV humoral immune response remains to be clearly defined. It is widely accepted that HCV drives the expansion of few B-cell clones expressing a restricted pool of selected immunoglobulin variable (IgV) gene subfamilies frequently endowed with rheumatoid factor (RF) activity. Moreover, the same IgV subfamilies are frequently observed in HCV-transformed malignant B-cell clones occasionally complicating MCII. In this paper, we analyze both the humoral and viral counterparts at the basis of cryoglobulins production in HCV-induced MCII, with particular attention reserved to the single IgV subfamilies most frequently involved.

  18. Liver disease in adult transfusion-dependent beta-thalassaemic patients: investigating the role of iron overload and chronic HCV infection.

    Science.gov (United States)

    Kountouras, Dimitrios; Tsagarakis, Nikolaos J; Fatourou, Evangelia; Dalagiorgos, Efthimios; Chrysanthos, Nikolaos; Berdoussi, Helen; Vgontza, Niki; Karagiorga, Markissia; Lagiandreou, Athanasios; Kaligeros, Konstantinos; Voskaridou, Ersi; Roussou, Paraskevi; Diamanti-Kandarakis, Evanthia; Koskinas, John

    2013-03-01

    Iron overload and hepatitis-C virus (HCV) infection, have been implicated in the evolution of liver disease, in patients with transfusion-dependent beta-thalassaemia major (BTM). However, the impact of these factors in late stages of liver disease in adults with BTM, has not been extensively studied. To investigate serum indices of iron overload, HCV infection and liver disease, in a cohort of 211 adult Greek patients with BTM, in relation with the findings from liver biopsies. In this cross-sectional study, 211 patients with BTM were enrolled and studied, in relation with HCV infection, ferritin, transaminases, chelation treatment and antiviral treatment. Based on 109 patients biopsied, we correlated liver fibrosis, haemosiderosis and inflammation, with serum indices and HCV status Among all patients, 74.4% were anti-HCV positive (HCV+). Ferritin was positively correlated with transaminases and negatively correlated with age, while it was not significantly different among HCV+ and HCV- patients. Among the HCV+ patients, 55.4% reported antiviral treatment, while genotype 1 predominated. In a subfraction of 109 patients, in which liver biopsy was performed, 89% were HCV+ and 11% HCV-. Fibrosis was significantly correlated with age (P = 0.046), AST (P = 0.004), ALT (P = 0.044) and inflammation (P overload may be the critical determinant, since fibrosis is related to the minimal haemosiderosis, independently of HCV history. © 2012 John Wiley & Sons A/S.

  19. Isolated Post-Transplantation Lymphoproliferative Disease Involving the Breast and Axilla as Peripheral T-cell Lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Hwang, Ji-Young [Department of Radiology, Kangnam Sacred Heart Hospital, Hallym University College of Medicine, Seoul 150-950 (Korea, Republic of); Cha, Eun Suk; Lee, Jee Eun [Department of Radiology, Ewha Womans University School of Medicine, Seoul 158-710 (Korea, Republic of); Sung, Sun Hee [Department of Pathology, Ewha Womans University School of Medicine, Seoul 158-710 (Korea, Republic of)

    2013-07-01

    Post-transplantation lymphoproliferative disorders (PTLDs) are a heterogeneous group of diseases that represent serious complications following immunosuppressive therapy for solid organ or hematopoietic-cell recipients. In contrast to B-cell PTLD, T-cell PTLD is less frequent and is not usually associated with Epstein Barr Virus infection. Moreover, to our knowledge, isolated T-cell PTLD involving the breast is extremely rare and this condition has never been reported previously in the literature. Herein, we report a rare case of isolated T-cell PTLD of the breast that occurred after a patient had been treated for allogeneic peripheral blood stem cell transplantation due to acute myeloblastic leukemia.

  20. Isolated Post-Transplantation Lymphoproliferative Disease Involving the Breast and Axilla as Peripheral T-cell Lymphoma

    International Nuclear Information System (INIS)

    Hwang, Ji-Young; Cha, Eun Suk; Lee, Jee Eun; Sung, Sun Hee

    2013-01-01

    Post-transplantation lymphoproliferative disorders (PTLDs) are a heterogeneous group of diseases that represent serious complications following immunosuppressive therapy for solid organ or hematopoietic-cell recipients. In contrast to B-cell PTLD, T-cell PTLD is less frequent and is not usually associated with Epstein Barr Virus infection. Moreover, to our knowledge, isolated T-cell PTLD involving the breast is extremely rare and this condition has never been reported previously in the literature. Herein, we report a rare case of isolated T-cell PTLD of the breast that occurred after a patient had been treated for allogeneic peripheral blood stem cell transplantation due to acute myeloblastic leukemia

  1. Response to rituximab-based therapy and risk factor analysis in Epstein Barr Virus-related lymphoproliferative disorder after hematopoietic stem cell transplant in children and adults: a study from the Infectious Diseases Working Party of the European Group for Blood and Marrow Transplantation.

    Science.gov (United States)

    Styczynski, Jan; Gil, Lidia; Tridello, Gloria; Ljungman, Per; Donnelly, J Peter; van der Velden, Walter; Omar, Hamdy; Martino, Rodrigo; Halkes, Constantijn; Faraci, Maura; Theunissen, Koen; Kalwak, Krzysztof; Hubacek, Petr; Sica, Simona; Nozzoli, Chiara; Fagioli, Franca; Matthes, Susanne; Diaz, Miguel A; Migliavacca, Maddalena; Balduzzi, Adriana; Tomaszewska, Agnieszka; Camara, Rafael de la; van Biezen, Anja; Hoek, Jennifer; Iacobelli, Simona; Einsele, Hermann; Cesaro, Simone

    2013-09-01

     The objective of this analysis was to investigate prognostic factors that influence the outcome of Epstein-Barr virus (EBV)-related posttransplant lymphoproliferative disorder (PTLD) after a rituximab-based treatment in the allogeneic hematopoietic stem cell transplant (HSCT) setting.  A total of 4466 allogeneic HSCTs performed between 1999 and 2011 in 19 European Group for Blood and Marrow Transplantation centers were retrospectively analyzed for PTLD, either biopsy-proven or probable disease.  One hundred forty-four cases of PTLD were identified, indicating an overall EBV-related PTLD frequency of 3.22%, ranging from 1.16% for matched-family donor, 2.86% for mismatched family donor, 3.97% in matched unrelated donors, and 11.24% in mismatched unrelated donor recipients. In total, 69.4% patients survived PTLD. Multivariable analysis showed that a poor response of PTLD to rituximab was associated with an age ≥30 years, involvement of extralymphoid tissue, acute GVHD, and a lack of reduction of immunosuppression upon PTLD diagnosis. In the prognostic model, the PTLD mortality increased with the increasing number of factors: 0-1, 2, or 3 factors being associated with mortality of 7%, 37%, and 72%, respectively (P disease, and acute graft-vs-host disease predicted poor outcome.

  2. HBV And HCV Molecular Evolution

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    Flor H. Pujol

    2007-02-01

    hepatitis C virus (HCV. Six genotypes and a large number of subtypes in each genotype have been described for this member of the Flaviviridae family. Infections with HCV genotype 1 are associated with the lowest therapeutic success. HCV genotype 1b has also been more frequently associated with a more severe liver disease. However, this association seems to be due to the fact that individuals infected with this genotype have a longer mean duration of infection. HCV genotypes 1, 2, and 3 have a worldwide distribution and display an apidemic pattern of distribution. HCV subtypes 1a and 1b are the most common genotypes in the United States and are also are predominant in Europe, while in Japan, subtype 1b is predominant. Although HCV subtypes 2a and 2b are relatively common in America, Europe, and Japan, subtype 2c is found commonly in northern Italy. HCV genotype 3a is frequent in intravenous drug abusers in Europe and the United States. HCV genotype 4 appears to be prevalent in Africa and theMiddle East, and genotypes 5 and 6 seem to be confined to South Africa and Asia, respectively. These last genotypes display an endemic pattern of distribution. In addition, a change in the frequency of the prevailing genotypes has been described in several countries: in general, HCV genotype 1b is being displaced by genotypes 3a and/or 2. Coalescent studies have allowed to describe the epidemic pattern of dissemination of some HCV subtypes in specific countries, generally around 100 years ago. The origin of this virus is still an open question, but several studies traces it diversification only around 1,000 years ago.

    The replication of HCV is dependent on a RNA-polymerase RNA dependent which lacks proofreading activity, which confers to this virus a high rate of variability. This virus circulates as a quasispecies. This population dynamic inside a single strain confers to this virus the ability to

  3. Direct anti-HCV agents

    Directory of Open Access Journals (Sweden)

    Xingquan Zhang

    2016-01-01

    Full Text Available Unlike human immunodeficiency virus (HIV and hepatitis B virus (HBV, hepatitis C virus (HCV infection is a curable disease. Current direct antiviral agent (DAA targets are focused on HCV NS3/4A protein (protease, NS5B protein (polymerase and NS5A protein. The first generation of DAAs includes boceprevir and telaprevir, which are protease inhibitors and were approved for clinical use in 2011. The cure rate for genotype 1 patients increased from 45% to 70% when boceprevir or telaprevir was added to standard PEG-IFN/ribavirin. More effective and less toxic second generation DAAs supplanted these drugs by 2013. The second generation of DAAs includes sofosbuvir (Sovaldi, simeprevir (Olysio, and fixed combination medicines Harvoni and Viekira Pak. These drugs increase cure rates to over 90% without the need for interferon and effectively treat all HCV genotypes. With these drugs the “cure HCV” goal has become a reality. Concerns remain about drug resistance mutations and the high cost of these drugs. The investigation of new HCV drugs is progressing rapidly; fixed dose combination medicines in phase III clinical trials include Viekirax, asunaprevir+daclatasvir+beclabuvir, grazoprevir+elbasvir and others.

  4. Are RA patients from a non-endemic HCV population screened for HCV? A cross-sectional analysis of three different settings.

    Science.gov (United States)

    Skinner-Taylor, Cassandra Michelle; Erhard-Ramírez, Alejandro; Garza-Elizondo, Mario Alberto; Esquivel-Valerio, Jorge Antonio; Abud-Mendoza, Carlos; Martínez-Martínez, Marco Ulises; Vega-Morales, David; Arana-Guajardo, Ana

    In Mexico, other risk factors are associated with hepatitis C virus (HCV): prior heroin users, living alone, widower, and northern region residence. Rheumatoid arthritis (RA) patients are considered immunosuppressed and HCV testing is recommended before treatment. The aim of the study was to describe the characteristics of HCV testing in RA patients in three different medical care settings in a non-endemic area. A retrospective observational study was performed using medical records from 960 RA patients describing the indications for HCV testing. The test was performed in 28.6% and the HCV overall frequency was 0.36%. Population characteristics were not associated with an increased risk of HCV infection; therefore, anti-HCV positivity was low. The main reason for testing was before starting biological agents. Due to the low pre-test probability, testing for HCV infection should be personalized; i.e., according to disease prevalence in a particular geographical location and the individual risk factors. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

  5. HCV subtype characterization among injection drug users: implication for a crucial role of Zhenjiang in HCV transmission in China.

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    Chiyu Zhang

    Full Text Available BACKGROUND: HCV transmission is closely associated with drug-trafficking routes in China. However, the transmission route of HCV in Eastern China remains unclear. Here, we investigate the role of Zhenjiang city of Jiangsu province, an important transportation hub linking Shanghai with other regions of China, in HCV transmission. METHODOLOGY/PRINCIPAL FINDINGS: A total of 141 whole blood samples were collected from injection drug users (IDUs in Zhenjiang and then tested for HCV infection. Of them, 115 HCV positive plasmas were subjected to RNA extraction, RT-PCR amplification, and sequencing. The subtype characterization and the evolutionary origin of HCV strains circulating in Zhenjiang were determined using polygenetic or phylogeographic analyses. Seven HCV subtypes 1b, 2a, 3a, 3b, 6a, 6e and 6n were detected among Zhenjiang IDUs, showing a complex HCV epidemic. The most predominant subtypes were 3a (38% and 1b (26.8%. Among these subtypes, subtypes 3b, 6n and 6e originated from Southwestern China (i.e., Yunnan and/or Guangxi, subtypes 2a and 6a from Southern China (i.e., Guangdong, subtype 1b from Central (i.e., Henan and Northwestern (i.e., Xinjiang China, and subtype 3a from Southwestern (i.e., Yunnan and Northwestern (i.e., Xinjiang China. From Zhenjiang, subtypes 1b and 2a were further spread to Eastern (i.e., Shanghai and Northern (i.e., Beijing China, respectively. CONCLUSIONS/SIGNIFICANCE: The mixing of seven HCV subtypes in Zhenjiang from all quarters of China indicates that as an important middle station, Zhenjiang plays a crucial role in HCV transmission, just as it is important in population migration between other regions of China and Eastern China.

  6. Facial manifestations of Epstein-Barr virus-related lymphoproliferative disease in childhood acute lymphoblastic leukemia in remission: Two atypical presentations.

    Science.gov (United States)

    Lu, Benjamin Y; Kojima, Lisa; Huang, Mary S; Friedmann, Alison M; Ferry, Judith A; Weinstein, Howard J

    2016-11-01

    Epstein-Barr virus-related lymphoproliferative disease (EBV-LPD) rarely occurs in patients with acute lymphoblastic leukemia (ALL), who have not received hematopoietic transplantation. We describe EBV-LPD manifesting as facial lesions in two children with ALL in remission. One patient was a 16-year-old male with T-cell ALL with an EBV-positive angiocentric polymorphous lip lesion presenting as right-sided facial swelling. The other patient was a 12-year-old male with B-cell ALL with an EBV-positive polymorphous lymphoplasmacytic infiltrate presenting as bilateral dacryoadenitis. Neither patient had known primary immunodeficiencies. Both cases improved with immunosuppressant de-escalation. These cases suggest that immunosuppression induced by maintenance chemotherapy is sufficient to promote EBV-LPD. © 2016 Wiley Periodicals, Inc.

  7. Spontaneous viral clearance, viral load, and genotype distribution of hepatitis C virus (HCV) in HIV-infected patients with anti-HCV antibodies in Europe

    DEFF Research Database (Denmark)

    Soriano, Vincent; Mocroft, Amanda; Rockstroh, Juergen

    2008-01-01

    BACKGROUND: Variables influencing serum hepatitis C virus (HCV) RNA levels and genotype distribution in individuals with human immunodeficiency virus (HIV) infection are not well known, nor are factors determining spontaneous clearance after exposure to HCV in this population. METHODS: All HCV...... for hepatitis B surface antigen (HBsAg) were more likely to have spontaneously cleared HCV than were those negative for HBsAg (43% vs. 21%; aOR, 2.91 [95% CI, 1.94-4.38]). Of patients with HCV viremia, 786 (53%) carried HCV genotype 1, and 53 (4%), 440 (29%), and 217 (15%) carried HCV genotype 2, 3, and 4...

  8. HCV Proteins and Immunoglobulin Variable Gene (IgV Subfamilies in HCV-Induced Type II Mixed Cryoglobulinemia: A Concurrent Pathogenetic Role

    Directory of Open Access Journals (Sweden)

    Giuseppe Sautto

    2012-01-01

    Full Text Available The association between hepatitis C virus (HCV infection and type II mixed cryoglobulinemia (MCII is well established, but the role played by distinct HCV proteins and by specific components of the anti-HCV humoral immune response remains to be clearly defined. It is widely accepted that HCV drives the expansion of few B-cell clones expressing a restricted pool of selected immunoglobulin variable (IgV gene subfamilies frequently endowed with rheumatoid factor (RF activity. Moreover, the same IgV subfamilies are frequently observed in HCV-transformed malignant B-cell clones occasionally complicating MCII. In this paper, we analyze both the humoral and viral counterparts at the basis of cryoglobulins production in HCV-induced MCII, with particular attention reserved to the single IgV subfamilies most frequently involved.

  9. Cryoglobulinemia Vasculitis.

    Science.gov (United States)

    Cacoub, Patrice; Comarmond, Cloe; Domont, Fanny; Savey, Léa; Saadoun, David

    2015-09-01

    Cryoglobulinemic vasculitis (CryoVas) is a small-vessel vasculitis involving mainly the skin, the joints, the peripheral nervous system, and the kidneys. Type I CryoVas is single monoclonal immunoglobulins related to an underlying B-cell lymphoproliferative disorder. Type II and III cryoglobulins, often referred to as mixed cryoglobulinemia, consist of polyclonal immunoglobulin (Ig)G with or without monoclonal IgM with rheumatoid factor activity. Hepatitis C virus (HCV) infection represents the main cause of mixed CryoVas. The 10-year survival rates are 63%, 65%, and 87% in HCV-positive mixed CryoVas, HCV-negative mixed CryoVas, and type I CryoVas patients, respectively. In HCV-positive patients, baseline poor prognostic factors include the presence of severe liver fibrosis, and central nervous system, kidney, and heart involvement. Treatment with antivirals is associated with a good prognosis, whereas use of immunosuppressants (including corticosteroids) is associated with a poor outcome. In HCV-negative patients, pulmonary and gastrointestinal involvement, renal insufficiency, and age > 65 years are independently associated with death. Increased risk of lymphoma also should be underlined. Treatment of type I CryoVas is that of the hemopathy; specific treatment also includes plasma exchange, corticosteroids, rituximab, and ilomedine. In HCV-CryoVas with mild-to-moderate disease, an optimal antiviral treatment should be given. For HCV-CryoVas with severe vasculitis (ie, worsening of renal function, mononeuritis multiplex, extensive skin disease, intestinal ischemia…) control of disease with rituximab, with or without plasmapheresis, is required before initiation of antiviral therapy. Other immunosuppressants should be given only in case of refractory forms of CryoVas, frequently associated with underlying B-cell lymphoma. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. Early Gastric Post-Transplant Lymphoproliferative Disorder and H pylori Detection after Kidney Transplantation: A Case Report and Review of the Literature

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    CL Nash

    2000-01-01

    Full Text Available The incidence of post-transplantation lymphoproliferative disorder (PTLD in the adult renal transplant population ranges from 0.7% to 4%. The majority of cases involve a single site and arise, on average, seven months after transplantation. Histopathology usually reveals B-cell proliferative disease and has been standardized into its own classification. Treatment modalities consist of decreased immunosuppression, eradication of Epstein-Barr virus, surgical resection, systemic chemotherapy and monoclonal antibody therapy; however, mortality remains high, typically with a short survival time. In patients who have undergone renal transplantation, approximately 10% of those with PTLDs present with gastrointestinal symptomatology and disease. Reported sites include the stomach, and small and large bowel. Very few cases of Helicobacter pylori or mucosal-associated lymphoid tissue have been described in association with PTLD. In the era of cyclosporine immunosuppression, the incidence of PTLD affecting the gastrointestinal tract may be increasing in comparison with the incidence seen with the use of older immunosuppression regimens. A case of antral PTLD and H pylori infection occurring three months after renal transplantation is presented, and the natural history and management of gastric PTLD are reviewed.

  11. Effect of abacavir on sustained virologic response to HCV treatment in HIV/HCV co-infected patients, Cohere in Eurocoord

    DEFF Research Database (Denmark)

    Smit, Colette; Arends, Joop; Peters, Lars

    2015-01-01

    BACKGROUND: Contradicting results on the effect of abacavir (ABC) on hepatitis C virus (HCV) treatment responses in HIV/HCV co-infected patients have been reported. We evaluated the influence of ABC on the response to pegylated interferon (pegIFN) and ribavirin (RBV)-containing HCV treatment in H...

  12. Hepatitis C virus (HCV) induces formation of stress granules whose proteins regulate HCV RNA replication and virus assembly and egress.

    Science.gov (United States)

    Garaigorta, Urtzi; Heim, Markus H; Boyd, Bryan; Wieland, Stefan; Chisari, Francis V

    2012-10-01

    Stress granules (SGs) are cytoplasmic structures that are induced in response to environmental stress, including viral infections. Here we report that hepatitis C virus (HCV) triggers the appearance of SGs in a PKR- and interferon (IFN)-dependent manner. Moreover, we show an inverse correlation between the presence of stress granules and the induction of IFN-stimulated proteins, i.e., MxA and USP18, in HCV-infected cells despite high-level expression of the corresponding MxA and USP18 mRNAs, suggesting that interferon-stimulated gene translation is inhibited in stress granule-containing HCV-infected cells. Finally, in short hairpin RNA (shRNA) knockdown experiments, we found that the stress granule proteins T-cell-restricted intracellular antigen 1 (TIA-1), TIA1-related protein (TIAR), and RasGAP-SH3 domain binding protein 1 (G3BP1) are required for efficient HCV RNA and protein accumulation at early time points in the infection and that G3BP1 and TIA-1 are required for intracellular and extracellular infectious virus production late in the infection, suggesting that they are required for virus assembly. In contrast, TIAR downregulation decreases extracellular infectious virus titers with little effect on intracellular RNA content or infectivity late in the infection, suggesting that it is required for infectious particle release. Collectively, these results illustrate that HCV exploits the stress granule machinery at least two ways: by inducing the formation of SGs by triggering PKR phosphorylation, thereby downregulating the translation of antiviral interferon-stimulated genes, and by co-opting SG proteins for its replication, assembly, and egress.

  13. Impact of duration of therapy on side effect profile of anti-HCV ...

    African Journals Online (AJOL)

    Purpose: To evaluate the plausible risks and adverse effects related to the duration of therapy in hepatitis C (HCV) patients in Lahore, Pakistan. Method: A retrospective observational study involving 250 HCV patients who received combination therapy with ribavirin and interferon was conducted. The patients were ...

  14. Automated quantification of apoptosis in B-cell chronic lymphoproliferative disorders: a prognostic variable obtained with the Cell-Dyn Sapphire (Abbott) automated hematology analyzer.

    Science.gov (United States)

    Fumi, M; Martins, D; Pancione, Y; Sale, S; Rocco, V

    2014-12-01

    B-chronic lymphocytic leukemia CLL, a neoplastic clonal disorder with monomorphous small B lymphocytes with scanty cytoplasm and clumped chromatin, can be morphologically differentiated in typical and atypical forms with different prognosis: Smudge cells (Gumprecht's shadows) are one of the well-known features of the typical CLL and are much less inconsistent in other different types CLPD. Abbott Cell-Dyn Sapphire uses the fluorescence after staining with the DNA fluorochrome propidium iodide for the measurement of nucleated red blood cells (NRBCs) and nonviable cells (FL3+ cell fraction): We have studied the possible correlation between presence and number of morphologically identifiable smudge cells on smears and the percentage of nonviable cells produced by Cell-Dyn Sapphire. 305 blood samples from 224 patients with B-cell lymphoproliferative disorders and 40 healthy blood donors were analyzed by CBC performed by Cell-Dyn Sapphire, peripheral blood smear, and immunophenotype characterization. FL3+ fraction in CLPD directly correlated with the percentage of smudge cells and is significantly increased in patients with typical B-CLL. This phenomenon is much less evident in patients with atypical/mixed B-CLL and B-NHL. In small laboratories without FCM and cytogenetic, smudge cells%, can be utilized as a preliminary diagnostic and prognostic tool in differential diagnosis of CLPD. © 2014 John Wiley & Sons Ltd.

  15. Identification of Variants of Hepatitis C Virus (HCV Entry Factors in Patients Highly Exposed to HCV but Remaining Uninfected: An ANRS Case-Control Study.

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    Baptiste Fouquet

    Full Text Available Hepatitis C virus (HCV causes persistent infection in 75% of cases and is a major public health problem worldwide. More than 92% of intravenous drug users (IDU infected by human immunodeficiency virus type 1 (HIV-1 are seropositive for HCV, and it is conceivable that some HIV-1-infected IDU who remain uninfected by HCV may be genetically resistant.Here we conducted a case-control study to identify mutations in HCV entry coreceptors in HIV-infected IDU who remained uninfected by HCV. We recruited 138 patients, comprising 22 HIV+ HCV- case IDU and 116 HIV+ HCV+ control IDU. We focused on coreceptors in which point mutations are known to abolish HCV infectivity in vitro. Our previous study of the Claudin-1 gene revealed no specific variants in the same case population. Here we performed direct genomic sequencing of the Claudin-6, Claudin-9, Occludin and Scavenger receptor-B1 (SCARB1 gene coding regions. Most HIV+ HCV- IDU had no mutations in HCV coreceptors. However, two HIV+ HCV- patients harbored a total of four specific mutations/variants of HCV entry factors that were not found in the HIV+ HCV+ controls. One case patient harbored heterozygous variants of both Claudin-6 and Occludin, and the other case patient harbored two heterozygous variants of SCARB1. This suggests that HCV resistance might involve complex genetic events and factors other than coreceptors, a situation similar to that reported for HIV-1 resistance.

  16. POST-TRANSPLANT LYMPHOPROLIFERATIVE DISORDERS: ROLE OF VIRAL INFECTION, GENETIC LESIONS AND ANTIGEN STIMULATION IN THE PATHOGENESIS OF THE DISEASE

    Directory of Open Access Journals (Sweden)

    Daniela Capello

    2009-11-01

    Full Text Available Post-transplant lymphoproliferative disorders (PTLD are a life-threatening complication of solid organ transplantation or, more rarely, hematopoietic stem cell transplantation. The majority of PTLD is of B-cell origin and associated with Epstein–Barr virus (EBV infection. PTLD generally display involvement of extranodal sites, aggressive histology and aggressive clinical behavior. The molecular pathogenesis of PTLD involves infection by oncogenic viruses, namely Epstein-Barr virus, as well as genetic or epigenetic alterations of several cellular genes. At variance with lymphoma arising in immunocompetent hosts, whose genome is relatively stable, a fraction of PTLD are characterized by microsatellite instability as a consequence of defects in the DNA mismatch repair mechanism. Apart from microsatellite instability, molecular alterations of cellular genes recognized in PTLD include alterations of cMYC, BCL6, TP53, DNA hypermethylation, and aberrant somatic hypermutation of protooncogenes. The occurrence of IGV mutations in the overwhelming majority of PTLD documents that malignant transformation targets germinal centre (GC B-cells and their descendants both in EBV–positive and EBV–negative cases. Analysis of phenotypic markers of B-cell histogenesis, namely BCL6, MUM1 and CD138, allows further distinction of PTLD histogenetic categories. PTLD expressing the BCL6+/MUM1+/-/CD138- profile reflect B-cells actively experiencing the GC reaction, and comprise diffuse large B-cell lymphoma (DLBCL centroblastic and Burkitt lymphoma. PTLD expressing the BCL6-/MUM1+/CD138- phenotype putatively derive from B-cells that have concluded the GC reaction, and comprise the majority of polymorphic PTLD and a fraction of DLBCL immunoblastic. A third group of PTLD is reminiscent of post-GC and preterminally differentiated B-cells that show the BCL6-/MUM1+/CD138+ phenotype, and are morphologically represented by either polymorphic PTLD or DLBCL immunoblastic.

  17. [Comparison of eight screening tests for ant-HCV antibody].

    Science.gov (United States)

    Deguchi, Matsuo; Kagita, Masanori; Yamashita, Naoko; Nakano, Takasi; Tahara, Kazuko; Asari, Seishi; Iwatani, Yoshinori

    2002-09-01

    We compared eight HCV screening tests for detection of anti-HCV antibody; Ortho Quick Chaser HCV Ab (QC), Ortho HCV Ab ELISA III (ELISA), Ortho HVC Ab PA test III (PA), Lumipulse II Ortho HCV (LUMI), IMx HCV.DAINAPACKII (IMx), ARCHITECT HCV (ARCH), Immucheck.F-HCV C50 Ab (Immu), RANREAM HCV Ab Ex II (RAN). Sera from six hundred patients were examined by these eight screening tests. The positive rates of the eight screening tests were from 9.0% to 13.2%. Forty-five sera showed discrepant results between the eight screening tests, and about half of them showed weak positive reaction and/or false positive. Twenty-five of the forty-five sera were negative for ant-HCV antibody in the CHIRON RIBA III confirmatory test, and forty-four of them were negative for HCV-RNA in the PCR method. The agreement rates between the two reagents were from 95.5% to 99.2%, but were not always high between the two reagents that used similar antigen. The specificities and sensitivities evaluated by using the RIBA III confirmatory test were excellent in ELISA, LUMI, IMx, ARCH and Immu. Three BBI seroconversion panels were used to compare the positive readings in the initial stage of HCV infection by eight screening tests. ELISA and ARCH showed the earliest positive readings, and then IMx, LUMI = RAN, PA, QC and Immu in this order. These findings indicate that ELISA and ARCH were the most excellent in the sensitivity, specificity and early diagnosis of HCV infection. However, we must pay attention to the weak positive reaction in the screening tests, because there is a possibility of "false positive".

  18. Advances in the treatment of HIV/HCV coinfection in adults.

    Science.gov (United States)

    Schlabe, Stefan; Rockstroh, Jürgen K

    2018-01-01

    Direct-acting antivirals (DAA) have revolutionized the modern treatment of chronic hepatitis C (HCV). These highly efficacious, well-tolerated, all-oral HCV regimens allow cure of HCV in over 95% of HCV-monoinfected as well as HIV/HCV-coinfected patients with short treatment durations of 8-12 weeks. Areas covered: This review will address recent developments of DAA-therapy in HIV/HCV-coinfected patients in clinical trials and real life cohorts and evaluate remaining challenges, particularly resistance, drug-drug interactions, acute HCV infection and liver transplantation focusing on HIV/HCV-coinfected patients. Expert opinion: Indeed, all available data have shown that HIV/HCV-coinfection has no impact on HCV-treatment outcome. Management, indication of therapy and follow-up of HCV-infection are now the same for both patient populations. HIV/HCV-coinfected patients however, require careful evaluation of potential drug-drug-interactions between HCV drugs and HIV antiretroviral therapy, medication for substance abuse and other comedications. The few remaining gaps in DAA-therapy in particular treatment of cirrhotic treatment-experienced genotype 3 infections, decompensated cirrhosis, chronic kidney disease and patients with prior DAA treatment failure have mostly been overcome by the development of new HCV agents recently licensed. Clearly, the biggest challenge globally remains the access to treatment and the inclusion of all patient populations affected in particular people who inject drugs (PWID).

  19. Proteasome- and Ethanol-Dependent Regulation of HCV-Infection Pathogenesis

    Directory of Open Access Journals (Sweden)

    Natalia A. Osna

    2014-09-01

    Full Text Available This paper reviews the role of the catabolism of HCV and signaling proteins in HCV protection and the involvement of ethanol in HCV-proteasome interactions. HCV specifically infects hepatocytes, and intracellularly expressed HCV proteins generate oxidative stress, which is further exacerbated by heavy drinking. The proteasome is the principal proteolytic system in cells, and its activity is sensitive to the level of cellular oxidative stress. Not only host proteins, but some HCV proteins are degraded by the proteasome, which, in turn, controls HCV propagation and is crucial for the elimination of the virus. Ubiquitylation of HCV proteins usually leads to the prevention of HCV propagation, while accumulation of undegraded viral proteins in the nuclear compartment exacerbates infection pathogenesis. Proteasome activity also regulates both innate and adaptive immunity in HCV-infected cells. In addition, the proteasome/immunoproteasome is activated by interferons, which also induce “early” and “late” interferon-sensitive genes (ISGs with anti-viral properties. Cleaving viral proteins to peptides in professional immune antigen presenting cells and infected (“target” hepatocytes that express the MHC class I-antigenic peptide complex, the proteasome regulates the clearance of infected hepatocytes by the immune system. Alcohol exposure prevents peptide cleavage by generating metabolites that impair proteasome activity, thereby providing escape mechanisms that interfere with efficient viral clearance to promote the persistence of HCV-infection.

  20. Composite cutaneous lymphoma (iatrogenic immunodeficiency-associated lymphoproliferative disorder) in a patient with rheumatoid arthritis treated with methotrexate: Staging and evaluation of response to therapy with {sup 1}'8F-FDG PET/CT

    Energy Technology Data Exchange (ETDEWEB)

    Makis, William [Dept. of Diagnostic Imaging, CCI, Diagnostic Imaging, Edmonton (Canada); Ciarallo, Anthony; Gonzalez-Verdecia, Milene [MUHC Glen Site, Montreal (Canada); Wang, Beatrice [MUHC, Dermatology, Westmount (Canada); Probst, Stehan [MUHC Jewish General Hospital, Nuclear Medicine, Montreal (Canada)

    2017-09-15

    A 67 year old woman with a 10 year history of rheumatoid arthritis (RA) treated with methotrexate and prednisone, presented with a 2 year history of worsening multiple cutaneous plaques of variable appearance. Two distinct skin lesions were biopsied to reveal a composite cutaneous lymphoma, possibly caused by long term methotrexate therapy. An [18F] fluoro-2-deoxy-D-glucose ({sup 18}F-FDG) positron emission tomography/computed tomography (PET/CT) was performed to stage the malignancy, and was later repeated to evaluate response to chemotherapy, which guided subsequent management. We present the PET/CT imaging findings of this very rare iatrogenic (methotrexate induced) immunodeficiency-associated lymphoproliferative disorder.

  1. Waldenström's macroglobulinemia harbors a unique proteome where Ku70 is severely underexpressed as compared with other B-lymphoproliferative disorders

    International Nuclear Information System (INIS)

    Perrot, A; Pionneau, C; Azar, N; Baillou, C; Lemoine, F M; Leblond, V; Merle-Béral, H; Béné, M-C; Herbrecht, R; Bahram, S; Vallat, L

    2012-01-01

    Waldenström's macroglobulinemia (WM) is a clonal B-cell lymphoproliferative disorder (LPD) of post-germinal center nature. Despite the fact that the precise molecular pathway(s) leading to WM remain(s) to be elucidated, a hallmark of the disease is the absence of the immunoglobulin heavy chain class switch recombination. Using two-dimensional gel electrophoresis, we compared proteomic profiles of WM cells with that of other LPDs. We were able to demonstrate that WM constitutes a unique proteomic entity as compared with chronic lymphocytic leukemia and marginal zone lymphoma. Statistical comparisons of protein expression levels revealed that a few proteins are distinctly expressed in WM in comparison with other LPDs. In particular we observed a major downregulation of the double strand repair protein Ku70 (XRCC6); confirmed at both the protein and RNA levels in an independent cohort of patients. Hence, we define a distinctive proteomic profile for WM where the downregulation of Ku70—a component of the non homologous end-joining pathway—might be relevant in disease pathophysiology

  2. Multiple Introduction and Naturally Occuring Drug Resistance of HCV among HIV-Infected Intravenous Drug Users in Yunnan: An Origin of China's HIV/HCV Epidemics.

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    Min Chen

    Full Text Available The human immunodeficiency virus 1 (HIV-1 epidemic in China historically stemmed from intravenous drug users (IDUs in Yunnan. Due to a shared transmission route, hepatitis C virus (HCV/HIV-1 co-infection is common. Here, we investigated HCV genetic characteristics and baseline drug resistance among HIV-infected IDUs in Yunnan.Blood samples of 432 HIV-1/HCV co-infected IDUs were collected from January to June 2014 in six prefectures of Yunnan Province. Partial E1E2 and NS5B genes were sequenced. Phylogenetic, evolutionary and genotypic drug resistance analyses were performed.Among the 293 specimens successfully genotyped, seven subtypes were identified, including subtypes 3b (37.9%, 111/293, 3a (21.8%, 64/293, 6n (14.0%, 41/293, 1b (10.6%, 31/293, 1a (8.2%, 24/293, 6a (5.1%, 15/293 and 6u (2.4%, 7/293. The distribution of HCV subtypes was mostly related to geographic location. Subtypes 3b, 3a, and 6n were detected in all six prefectures, however, the other four subtypes were detected only in parts of the six prefectures. Phylogeographic analyses indicated that 6n, 1a and 6u originated in the western prefecture (Dehong and spread eastward and showed genetic relatedness with those detected in Burmese. However, 6a originated in the southeast prefectures (Honghe and Wenshan bordering Vietnam and was transmitted westward. These subtypes exhibited different evolutionary rates (between 4.35×10-4 and 2.38×10-3 substitutions site-1 year-1 and times of most recent common ancestor (tMRCA, between 1790.3 and 1994.6, suggesting that HCV was multiply introduced into Yunnan. Naturally occurring resistance-associated mutations (C316N, A421V, C445F, I482L, V494A, and V499A to NS5B polymerase inhibitors were detected in direct-acting antivirals (DAAs-naïve IDUs.This work reveals the temporal-spatial distribution of HCV subtypes and baseline HCV drug resistance among HIV-infected IDUs in Yunnan. The findings enhance our understanding of the characteristics and

  3. HCV-Induced Oxidative Stress: Battlefield-Winning Strategy

    Directory of Open Access Journals (Sweden)

    Khadija Rebbani

    2016-01-01

    Full Text Available About 150 million people worldwide are chronically infected with hepatitis C virus (HCV. The persistence of the infection is controlled by several mechanisms including the induction of oxidative stress. HCV relies on this strategy to redirect lipid metabolism machinery and escape immune response. The 3β-hydroxysterol Δ24-reductase (DHCR24 is one of the newly discovered host markers of oxidative stress. This protein, as HCV-induced oxidative stress responsive protein, may play a critical role in the pathogenesis of HCV chronic infection and associated liver diseases, when aberrantly expressed. The sustained expression of DHCR24 in response to HCV-induced oxidative stress results in suppression of nuclear p53 activity by blocking its acetylation and increasing its interaction with MDM2 in the cytoplasm leading to its degradation, which may induce hepatocarcinogenesis.

  4. Discovery of Cellular Proteins Required for the Early Steps of HCV Infection Using Integrative Genomics

    Science.gov (United States)

    Yang, Jae-Seong; Kwon, Oh Sung; Kim, Sanguk; Jang, Sung Key

    2013-01-01

    Successful viral infection requires intimate communication between virus and host cell, a process that absolutely requires various host proteins. However, current efforts to discover novel host proteins as therapeutic targets for viral infection are difficult. Here, we developed an integrative-genomics approach to predict human genes involved in the early steps of hepatitis C virus (HCV) infection. By integrating HCV and human protein associations, co-expression data, and tight junction-tetraspanin web specific networks, we identified host proteins required for the early steps in HCV infection. Moreover, we validated the roles of newly identified proteins in HCV infection by knocking down their expression using small interfering RNAs. Specifically, a novel host factor CD63 was shown to directly interact with HCV E2 protein. We further demonstrated that an antibody against CD63 blocked HCV infection, indicating that CD63 may serve as a new therapeutic target for HCV-related diseases. The candidate gene list provides a source for identification of new therapeutic targets. PMID:23593195

  5. Animal models for HCV and HBV studies

    Directory of Open Access Journals (Sweden)

    Isabelle Chemin

    2007-02-01

    Full Text Available

    The narrow host range of infection and lack of suitable tissue culture systems for the propagation of hepatitis B and C viruses are limitations that have prevented a more thorough understanding of persistent infection and the pathogenesis of chronic liver disease.

    Despite decades of intensive research and significant progresses in understanding of viral hepatitis, many basic questions and clinical problems still await to be resolved. For example, the HBV cellular receptor and related mechanisms of viral entry have not yet been identified. Little is also known about the function of certain non-structural viral products, such as the hepatitis B e antigen and the X protein, or about the role of excess hepadnavirus subviral particles circulating in the blood stream during infection. Furthermore, the molecular mechanisms involved in the development of hepatocellular carcinoma and the role of the immune system in determining the fate of infection are not fully understood.

    The reason for these drawbacks is essentially due to the lack of reliable cell-based in vitro infection systems and, most importantly, convenient animal models.

    This lack of knowledge has been partially overcome for hepatitis B virus (HBV, by the discovery and characterization of HBV-like viruses in wild animals while for hepatitis C virus (HCV, related flaviviruses have been used as surrogate systems.

    Other laboratories have developed transgenic mice that express virus gene products and/or support virus replication. Some HBV transgenic mouse models

  6. Performance characteristics of the ARCHITECT anti-HCV assay.

    Science.gov (United States)

    Jonas, Gesa; Pelzer, Claudia; Beckert, Christian; Hausmann, Michael; Kapprell, Hans-Peter

    2005-10-01

    The ARCHITECT Anti-HCV assay is a fully automated high throughput chemiluminescent microparticle immunoassay (CMIA) for the detection of antibodies to structural and nonstructural proteins of the hepatitis C virus (HCV). To further enhance the performance of this test, the assay was modified to improve the specificity for blood donor specimens. The specificity of the enhanced ARCHITECT Anti-HCV assay was evaluated by screening blood donor samples randomly collected from various German blood banks, as well as hospitalized patient samples derived from Germany and the US. Additionally, antibody sensitivity was determined on commercially available anti-HCV seroconversion panels and on a commercially available worldwide anti-HCV genotype performance panel. Apparent specificity of the modified ARCHITECT Anti-HCV assay in a blood donor population consisting of 3811 specimens was 99.92%, compared to 99.76% for the current on-market assay. Additionally, antibody sensitivity was determined on commercially available anti-HCV seroconversion panels. Seroconversion sensitivity equivalent to or better than the current on-market product was observed by testing 33 seroconversion panels. This study demonstrates that the modified version of the ARCHITECT Anti-HCV assay shows improved specificity for blood donor specimens compared to the current assay on market without compromising sensitivity. With the availability of the improved ARCHITECT Anti-HCV assay and the recent launch of the ARCHITECT HIV Ag/Ab Combo assay, the ARCHITECT system now offers a full hepatitis/retrovirus menu with excellent performance on a high throughput, random access, automated analyzer, ideally suited for blood screening and diagnostic applications.

  7. [Contribution of HCV core antigen testing in HCV diagnosis by test from the company Abbott Laboratories].

    Science.gov (United States)

    Trbusek, J

    2009-11-01

    Detection of HCV core antigen as direct marker of hepatitis C infection clearly improves diagnosis of this disease (especially reduction of window period) and brings broad clinical utilization. The company Abbott Laboratories offers fully automated laboratory test for measurement of HCV core antigen on ARCHITECT analyzers.

  8. Distribution of HCV genotypes among different exposure categories in Brazil

    Directory of Open Access Journals (Sweden)

    Oliveira M.L.A.

    1999-01-01

    Full Text Available Hepatitis C virus (HCV infection is widespread and responsible for more than 60% of chronic hepatitis cases. HCV presents a genetic variability which has led to viral classification into at least 6 genotypes and a series of subtypes. These variants present characteristic geographical distribution, but their association with different responses to treatment with interferon and severity of disease still remains controversial. The aim of this study was to investigate the patterns of distribution of HCV genotypes among different exposure categories in Brazil. Two hundred and fifty anti-HCV positive samples were submitted to HCV-RNA detection by RT-PCR and their genotype was determined by restriction fragment length polymorphism (RFLP analysis. In addition, the genotype/subtype of 60 samples was also determined by a reverse hybridization assay. HCV 1 was the most prevalent (72.0%, followed by type 3 (25.3%, HCV 2 (2.0% and HCV 4 (0.7%. The HCV genotype distribution varied among the different exposure categories, with HCV 1 being more frequent among blood donors, hemophiliacs and hemodialysis patients. A high frequency of HCV 3 was observed in cirrhotic patients, blood donors from the South of Brazil and injecting drug users (IDUs. The general distribution of the HCV genotype in Brazil is similar to that in other regions of the world.

  9. Model projections on the impact of HCV treatment in the prevention of HCV transmission among people who inject drugs in Europe

    DEFF Research Database (Denmark)

    Fraser, Hannah; Martin, Natasha K; Brummer-Korvenkontio, Henrikki

    2018-01-01

    BACKGROUND: Prevention of hepatitis C virus (HCV) transmission among people who inject drugs (PWID) is critical to eliminating HCV in Europe. We estimate impact of current and scaled-up HCV treatment with and without scaling-up opioid substitution therapy (OST) and needle and syringe programmes (...

  10. Hepatitis C infection in patients with hereditary bleeding disorders: epidemiology, natural history, and management.

    Science.gov (United States)

    Papadopoulos, Nikolaos; Argiana, Vasiliki; Deutsch, Melanie

    2018-01-01

    Hereditary bleeding disorders include a group of diseases with abnormalities of coagulation. Prior to 1990, infection with hepatitis C virus (HCV) was mainly transmitted via pooled plasma products as a treatment for hereditary bleeding disorders. Anti-HCV positivity in these patients may be as high as >70% in some areas, while some of them have also been coinfected with human immunodeficiency virus. Since about 20% of HCV-infected patients clear the infection naturally, chronic HCV infection represents a significant health problem in this group of patients. Mortality due to chronic HCV infection is estimated to be >10 times higher in patients with hemophilia than in the general population, and is mainly due to liver cirrhosis and hepatocellular carcinoma. The antiviral treatment of HCV in patients with hereditary bleeding disorders is not different from that of any other infected patients. Nevertheless, many patients with hereditary bleeding disorders have declined (Peg)interferon-based treatment because of side effects. In recent years, multiple orally administrated direct-acting antivirals (DAAs) have been approved for HCV treatment. Unfortunately, there is not much experience from treating these patients with DAA regimens, as major studies and real-life data did not include adequate numbers of patients with inherited hemorrhagic disorders. However, the available data indicate that DAAs have an excellent safety profile with a sustained virological response rate of >90%.

  11. Lymphoproliferative disorders in non-AIDS- associated Kaposi's ...

    African Journals Online (AJOL)

    proliferative disorders are mostly of B-cell origin and include non-Hodgkin's lymphoma, chronic lymphatic leukaemia and multiple .... Bone marrow trephine biopsy revealed ... transplants, patients with auto-immune diseases and patients with ...

  12. HCV viremia in clinical and biomedical perspective

    International Nuclear Information System (INIS)

    Hussain, A.B.; Tariq, W.Z.; Karamat, K.A.; Ghani, E.; Mushtaq, S.

    2000-01-01

    Sera of 172 patients from military / civil hospitals and general practitioners of Rawalpindi/Islamabad region and vicinity areas of northern Pakistan with anti-HCV IgG positive aerostats were tested at Armed Forces Institute of Pathology (AFIP), Rawalpindi, between July and November, 1997 for detection of HCV viremia by reverse transcriptases polymerase chain reaction (RT-PCR). Randomly selected 100 samples (40 viremia positive and 60 negative after PCR) were tested for serum alanine aminotransferase (ALT) levels. For each patient, information based upon clinical and laboratory findings was recorded on a performa to correlate the clinical and biochemical findings with the results of qualitative reverse transcriptase polymerase Chain Reaction (RT PCR) for HCV in Hepatitis C virus (HCV) infected patients. Of the total 172 HCV infected (Anti HCV Positive), 61(35.61%) patients were found to be viremic. Active infection was more frequent in the age of 30 years onwards. The past history of jaundice, surgical operation and chronic renal failure was more frequent with the viremia positive cases. Although, statistically insignificant, there was evidence of some association of diabetes mellitus with viremia ALT levels and its mean were higher in viremics, 27(73%) of 37 cases with a minimum three months history of interferon treatment for hepatitis C were found negative for viremia. (author)

  13. Anti-HCV effect of Lentinula edodes mycelia solid culture extracts and low-molecular-weight lignin.

    Science.gov (United States)

    Matsuhisa, Koji; Yamane, Seiji; Okamoto, Toru; Watari, Akihiro; Kondoh, Masuo; Matsuura, Yoshiharu; Yagi, Kiyohito

    2015-06-19

    Lentinula edodes mycelia solid culture extract (MSCE) contains several bioactive molecules, including some polyphenolic compounds, which exert immunomodulatory, antitumor, and hepatoprotective effects. In this study, we examined the anti-hepatitis C virus (HCV) activity of MSCE and low-molecular-weight lignin (LM-lignin), which is the active component responsible for the hepatoprotective effect of MSCE. Both MSCE and LM-lignin inhibited the entry of two HCV pseudovirus (HCVpv) types into Huh7.5.1 cells. LM-lignin inhibited HCVpv entry at a lower concentration than MSCE and inhibited the entry of HCV particles in cell culture (HCVcc). MSCE also inhibited HCV subgenome replication. LM-lignin had no effect on HCV replication, suggesting that MSCE contains additional active substances. We demonstrate here for the first time the anti-HCV effects of plant-derived LM-lignin and MSCE. The hepatoprotective effect of LM-lignin suggests that lignin derivatives, which can be produced in abundance from existing plant resources, may be effective in the treatment of HCV-related diseases. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Susceptibility to thyroid disorders in hepatitis C.

    Science.gov (United States)

    Muratori, Luigi; Bogdanos, Dimitrios P; Muratori, Paolo; Lenzi, Marco; Granito, Alessandro; Ma, Yun; Mieli-Vergani, Giorgina; Bianchi, Francesco B; Vergani, Diego

    2005-06-01

    Autoimmune thyroid disorders (AITDs) are reported, especially during interferon treatment, in chronic HCV infection, in which non-organ-specific autoantibodies (NOSAs) are common. We wondered whether seropositivity for NOSA is associated with susceptibility to AITDs. We evaluated thyroid function and antithyroglobulin and antithyroperoxidase antibodies in 348 Italian patients with chronic hepatitis C (34% NOSA-positive), 196 patients (33% NOSA-positive) of whom received interferon treatment. At baseline, thyroid disorders were significantly more frequent in liver/kidney microsomal antibody type 1 (LKM1)-positive patients (29% vs 9%, P LKM1-positive patients (50% vs 3%, P LKM1 positivity were predictors of AITD, but only the latter remained significant after logistic regression analysis. Cross-reactivity to all 7 linear epitopes encoding homologous amino acid sequences shared by the HCV polyprotein, CYP2D6 (the LKM1 autoantigen), and thyroperoxidase was detected in 86% LKM1-positive HCV patients with clinical thyroid disorders, but in none of the LKM1-positive or negative HCV patients without thyroid disease, and none of an HCV-negative control group comprising subjects with LKM1-positive autoimmune hepatitis or AITD without liver disease ( P LKM1 are susceptible to develop AITDs, in association with treatment. Molecular mimicry and epitope spreading are potential pathogenic mechanisms.

  15. Rituximab-Based Treatment, HCV Replication, and Hepatic Flares

    Directory of Open Access Journals (Sweden)

    Evangelista Sagnelli

    2012-01-01

    Full Text Available Rituximab, a chimeric mouse-human monoclonal antibody directed to the CD20 antigen expressed on pre-B lymphocytes and mature lymphocytes, causes a profound B-cell depletion. Due to its peculiar characteristics, this drug has been used to treat oncohaematological diseases, B cell-related autoimmune diseases, rheumatoid arthritis, and, more recently, HCV-associated mixed cryoglobulinaemic vasculitis. Rituximab-based treatment, however, may induce an increased replication of several viruses such as hepatitis B virus, cytomegalovirus, varicella-zoster virus, echovirus, and parvovirus B19. Recent data suggest that rituximab-based chemotherapy induces an increase in HCV expression in hepatic cells, which may become a target for a cell-mediated immune reaction after the withdrawal of treatment and the restoration of the immune control. Only a few small studies have investigated the occurrence of HCV reactivation and an associated hepatic flare in patients with oncohaematological diseases receiving R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone. These studies suggest that the hepatic flares are frequently asymptomatic, but life-threatening liver failure occurs in nearly 10% of cases.

  16. Rituximab-based treatment, HCV replication, and hepatic flares.

    Science.gov (United States)

    Sagnelli, Evangelista; Pisaturo, Mariantonietta; Sagnelli, Caterina; Coppola, Nicola

    2012-01-01

    Rituximab, a chimeric mouse-human monoclonal antibody directed to the CD20 antigen expressed on pre-B lymphocytes and mature lymphocytes, causes a profound B-cell depletion. Due to its peculiar characteristics, this drug has been used to treat oncohaematological diseases, B cell-related autoimmune diseases, rheumatoid arthritis, and, more recently, HCV-associated mixed cryoglobulinaemic vasculitis. Rituximab-based treatment, however, may induce an increased replication of several viruses such as hepatitis B virus, cytomegalovirus, varicella-zoster virus, echovirus, and parvovirus B19. Recent data suggest that rituximab-based chemotherapy induces an increase in HCV expression in hepatic cells, which may become a target for a cell-mediated immune reaction after the withdrawal of treatment and the restoration of the immune control. Only a few small studies have investigated the occurrence of HCV reactivation and an associated hepatic flare in patients with oncohaematological diseases receiving R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone). These studies suggest that the hepatic flares are frequently asymptomatic, but life-threatening liver failure occurs in nearly 10% of cases.

  17. The challenge of treating hepatitis C virus-associated cryoglobulinemic vasculitis in the era of anti-CD20 monoclonal antibodies and direct antiviral agents.

    Science.gov (United States)

    Roccatello, Dario; Sciascia, Savino; Rossi, Daniela; Solfietti, Laura; Fenoglio, Roberta; Menegatti, Elisa; Baldovino, Simone

    2017-06-20

    Mixed cryoglobulinemia syndrome (MC) is a systemic vasculitis involving kidneys, joints, skin, and peripheral nerves. While many autoimmune, lymphoproliferative, and neoplastic disorders have been associated with this disorder, hepatitis C virus (HCV) is known to be the etiologic agent in the majority of patients. Therefore, clinical research has focused on anti-viral drugs and, more recently, on the new, highly potent Direct-acting Antiviral Agents (DAAs). These drugs assure sustained virologic response (SVR) rates >90%. Nevertheless, data on their efficacy in patients with HCV-associated cryoglobulinemic vasculitis are disappointing, possibly due to the inability of the drugs to suppress the immune-mediated process once it has been triggered.Despite the potential risk of exacerbation of the infection, immunosuppression has traditionally been regarded as the first-line intervention in cryoglobulinemic vasculitis, especially if renal involvement is severe. Biologic agents have raised hopes for more manageable therapeutic approaches, and Rituximab (RTX), an anti CD20 monoclonal antibody, is the most widely used biologic drug. It has proved to be safer than conventional immunosuppressants, thus substantially changing the natural history of HCV-associated cryoglobulinemic vasculitis by providing long-term remission, especially with intensive regimens.The present review focuses on the new therapeutic opportunities offered by the combination of biological drugs, mainly Rituximab, with DAAs.

  18. Preliminary experience on the use of PET/CT in the management of pediatric post-transplant lymphoproliferative disorder.

    Science.gov (United States)

    Guerra-García, Pilar; Hirsch, Steffen; Levine, Daniel S; Taj, Mary M

    2017-12-01

    Post-transplant lymphoproliferative disorder (PTLD) is a well-known complication following prolonged immunosuppression. Contrary to other lymphomas, there is no standardized imaging approach to assess PTLD either at staging or for response to therapy. Positron emission tomography/computed tomography (PET/CT) is an imaging modality that has proven to be useful in lymphoma. However, there is still limited data concerning its use in pediatric PTLD. Our study evaluates the use of PET/CT in pediatric PTLD at our institution. To assess the role of PET/CT in pediatric PTLD, we reviewed the pediatric patients with PTLD who had undergone PET/CT at our institution between 2000 and 2016. Nine patients were identified. Six had PET/CT at diagnosis. All lesions seen on CT were identified with PET/CT. Fourteen PET/CTs were done during treatment. Eight PET/CTs were negative, including three where CT showed areas of uncertain significance. In these cases, PET/CT helped us to stop treatment and the patients remain in remission after a long follow-up (mean 74.3 months; range 12.4-180.9 months). PET/CT revealed additional disease in two cases, therefore treatment was intensified. Six biopsies and close follow-up was done to confirm PET/CT results. In one case, PET/CT did not identify central nervous system involvement demonstrated on magnetic resonance imaging. PET/CT may have an important role in the staging and follow-up of pediatric PTLD. In our cohort, PET/CT was helpful in staging and assessing treatment response and in clarifying equivocal findings on other imaging modalities. © 2017 Wiley Periodicals, Inc.

  19. Seroprevalence study of HCV among hospitalized intravenous drug users in Ahvaz, Iran (2001–2006

    Directory of Open Access Journals (Sweden)

    Seyed Mohammad Alavi

    Full Text Available Summary: Background and aims: Prevalence of hepatitis C virus (HCV in intravenous drug users (IDU varies in different areas according to socioeconomic and geographical circumstances. The present study was performed to determine seroprevalence of HCV in IDU individuals in Ahvaz, Iran. Materials and methods: 142 IDU patients were included in this retrospective study in Ahvaz southwest Iran from 2001 to 2006. Patients were placed in two groups determined by HCV Ab positive or negative status. Data were analyzed using SPSS for Windows (version 11.5; SPSS Inc., USA software. Results: Out of total 142 cases, 74 persons (52.11% had a positive HCV-Ab test according to the ELISA method. There was no difference in age, sex, level of education, residency and co-infection with HIV and hepatitis B virus between HCV-Ab positive (HAP and HCV-Ab negative (HAN groups (p > 0.05. HCV-Ab positivity was significantly related to imprisonment and duration spent in prison [OR: 3.22, 95% (CI 2.61–3.76, p < 0.0001]. Conclusion: Patients with IDU constitute a high-risk group for acquisition of HCV infection. Transmission of HCV via sharing syringe and needle as well as blood transfusion has been a significant source of hepatitis C infection for patients with intravenous drug addiction. Keywords: Intravenous drug user, Hepatitis C virus, Seroprevalence, Ahvaz

  20. Virological Mechanisms in the Coinfection between HIV and HCV

    Directory of Open Access Journals (Sweden)

    Maria Carla Liberto

    2015-01-01

    Full Text Available Due to shared transmission routes, coinfection with Hepatitis C Virus (HCV is common in patients infected by Human Immunodeficiency Virus (HIV. The immune-pathogenesis of liver disease in HIV/HCV coinfected patients is a multifactorial process. Several studies demonstrated that HIV worsens the course of HCV infection, increasing the risk of cirrhosis and hepatocellular carcinoma. Also, HCV might increase immunological defects due to HIV and risk of comorbidities. A specific cross-talk among HIV and HCV proteins in coinfected patients modulates the natural history, the immune responses, and the life cycle of both viruses. These effects are mediated by immune mechanisms and by a cross-talk between the two viruses which could interfere with host defense mechanisms. In this review, we focus on some virological/immunological mechanisms of the pathogenetic interactions between HIV and HCV in the human host.

  1. Autophagy in HCV Infection: Keeping Fat and Inflammation at Bay

    Directory of Open Access Journals (Sweden)

    Tiziana Vescovo

    2014-01-01

    Full Text Available Hepatitis C virus (HCV infection is one of the main causes of chronic liver disease. Viral persistence and pathogenesis rely mainly on the ability of HCV to deregulate specific host processes, including lipid metabolism and innate immunity. Recently, autophagy has emerged as a cellular pathway, playing a role in several aspects of HCV infection. This review summarizes current knowledge on the molecular mechanisms that link the HCV life cycle with autophagy machinery. In particular, we discuss the role of HCV/autophagy interaction in dysregulating inflammation and lipid homeostasis and its potential for translational applications in the treatment of HCV-infected patients.

  2. Hepatitis C virus infection, cryoglobulinemia, and peripheral neuropathy: a case report

    Directory of Open Access Journals (Sweden)

    Vigani A.G.

    2005-01-01

    Full Text Available Hepatitis C virus (HCV is essentially hepatotropic but its manifestations can extend beyond the liver. It can be associated with autoimmune diseases, such as mixed cryoglobulinemia, membranoproliferative glomerulonephritis, autoimmune thyroiditis, and lymphoproliferative disorders. The mechanisms that trigger these manifestations are not completely understood. We describe a 48-year-old man with chronic HCV infection (circulating HCV RNA and moderate hepatitis as indicated by liver biopsy, cryoglobulinemia, and sensory and motor peripheral neuropathy. The diagnosis of multineuropathy was confirmed by clinical examination and electromyographic tests. A nerve biopsy revealed an inflammatory infiltrate in the perineurial space and signs of demyelination and axonal degeneration. The patient had no improvement of neurological symptoms with the use of analgesics and neuro-modulators. He was then treated with interferon-alpha (3 million units subcutaneously, 3 times per week and ribavirin (500 mg orally, twice a day for 48 weeks. Six months after the end of therapy, the patient had sustained viral response (negative HCV RNA and remission of neurological symptoms, but cryoglobulins remained positive. A review of the literature on the pathogenesis and treatment of neurological manifestations associated with HCV infection is presented. This report underscores the need for a thorough evaluation of HCV-infected patients because of the possibility of extrahepatic manifestations. Antiviral treatment with interferon and ribavirin can be effective and should be considered in patients with neurological complications associated with HCV infection.

  3. Genetic variations of the NPC1L1 gene associated with hepatitis C virus (HCV) infection and biochemical characteristics of HCV patients in China.

    Science.gov (United States)

    Zhang, A-Mei; Zhang, Cheng-Lin; Song, Yuzhu; Zhao, Ping; Feng, Yue; Wang, Binghui; Li, Zheng; Liu, Li; Xia, Xueshan

    2016-12-01

    About 2% of the world population is infected with hepatitis C virus (HCV), a leading cause of hepatic cirrhosis and hepatocellular carcinoma. The Niemann-Pick C1-like 1 cholesterol absorption receptor (NPC1L1) was recently identified to be an important factor for HCV entry into host cells. Whether genetic variations of the NPC1L1 gene are associated with HCV infection is unknown. In this study, five single nucleotide polymorphisms (SNPs) of the NPC1L1 gene were analyzed in 261 HCV-infected individuals and 265 general controls from Yunnan Province, China. No significant differences were identified in genotypes or alleles of the SNPs between the two groups. After constructing haplotypes based on the five SNPs, a significant difference between HCV-infected individuals and general controls was shown for two haplotypes. Haplotype GCCTT appeared to be a protective factor and haplotype GCCCT was a risk factor for HCV-infected individuals. Genotypes of four SNPs correlated with biochemical characteristics of HCV-infected persons. Genotypes of SNPs rs799444 and rs2070607 were correlated with total bilirubin. Genotype TT of rs917098 was a risk factor for the gamma-glutamyltransferase level. Furthermore, HCV-infected individuals carrying genotype GG of rs41279633 showed statistically higher gamma-glutamyltransferase levels than HCV-infected persons with GT and TT. The results of this study identified the association between genetic susceptibility of the NPC1L1 gene and HCV infection, as well as biochemical characteristics of HCV-infected persons in Yunnan, China. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  4. Establishment and operation of a Good Manufacturing Practice-compliant allogeneic Epstein-Barr virus (EBV)-specific cytotoxic cell bank for the treatment of EBV-associated lymphoproliferative disease

    OpenAIRE

    Vickers, Mark A; Wilkie, Gwen M; Robinson, Nicolas; Rivera, Nadja; Haque, Tanzina; Crawford, Dorothy H; Barry, Jacqueline; Fraser, Neil; Turner, David M; Robertson, Victoria; Dyer, Phil; Flanagan, Peter; Newlands, Helen R; Campbell, John; Turner, Marc L

    2014-01-01

    Epstein-Barr virus (EBV) is associated with several malignancies, including post-transplant lymphoproliferative disorder (PTLD). Conventional treatments for PTLD are often successful, but risk organ rejection and cause significant side effects. EBV-specific cytotoxic T lymphocytes (CTLs) generated in vitro from peripheral blood lymphocytes provide an alternative treatment modality with few side effects, but autologous CTLs are difficult to use in clinical practice. Here we report the establis...

  5. HCV and HBV coexist in HBsAg-negative patients with HCV viremia; possibility of coinfection in these patients must be considered in HBV-high endemic area

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Dong Soon [Korea Cancer Center Hospital, Seoul (Korea, Republic of)

    1998-01-01

    Hepatocellular carcinoma (HCC) is one of the most common cancers and is highly associated with HBV infection in Korea. It has been suggested that HCV core protein may impair the polymerase activity of HBV in vitro, potentially lowering HBV titre in coinfected patients. The aim of this study was to confirm the coexistence of HBV viremia in HCV infected patients HCC who have apparent HBsAg seronegativity. The serological profiles of HBV and HCV in 616 patients with HCC were analysed and coinfection rate of HBV and HCV investigated. Sera were obtained from 16 patients who were both anti-HCV and HCV RNA positive but HbsAg negative, and tested for HBV BY PCR. As a control group, sera were obtained from 15 patients with HCC and 30 non-A abd non-B chronic hepatitis patients without HCC; both were anti-HCV, HCV-RNA, and HBsAg negative and tested for HBV PCR. Of 616 patients with HCC, 450 (73.1 %) had current HBV infection, 48 (7.8 %) had anti-HCV antibodies, and nine (1.5 %) had viral markers of both HCV abd HBV by serological profiles. Of 27 the patients with HCV viremia and HBsAg seronegativity, 14 (51.9 %) showed HBV viremia by PCR. In contrast, of the 75 patients in the control group who were both HCV PCR negative and HBsAg negative, five (11.1 %) showed HBV viremia by PCR. The PCR for HBV revealed coexistent HBV viremia in HCV viremia patients, despite HBsAg negativity by EIA. In HBV-endemic areas, the possibility of coinfection of HBV in HBsAg-negative patients with HCV viremia should be considered and molecular analysis for HBV-DNA performed. (author). 18 refs., 4 tabs.

  6. HCV and HBV coexist in HBsAg-negative patients with HCV viremia; possibility of coinfection in these patients must be considered in HBV-high endemic area

    International Nuclear Information System (INIS)

    Lee, Dong Soon

    1998-01-01

    Hepatocellular carcinoma (HCC) is one of the most common cancers and is highly associated with HBV infection in Korea. It has been suggested that HCV core protein may impair the polymerase activity of HBV in vitro, potentially lowering HBV titre in coinfected patients. The aim of this study was to confirm the coexistence of HBV viremia in HCV infected patients HCC who have apparent HBsAg seronegativity. The serological profiles of HBV and HCV in 616 patients with HCC were analysed and coinfection rate of HBV and HCV investigated. Sera were obtained from 16 patients who were both anti-HCV and HCV RNA positive but HbsAg negative, and tested for HBV BY PCR. As a control group, sera were obtained from 15 patients with HCC and 30 non-A abd non-B chronic hepatitis patients without HCC; both were anti-HCV, HCV-RNA, and HBsAg negative and tested for HBV PCR. Of 616 patients with HCC, 450 (73.1 %) had current HBV infection, 48 (7.8 %) had anti-HCV antibodies, and nine (1.5 %) had viral markers of both HCV abd HBV by serological profiles. Of 27 the patients with HCV viremia and HBsAg seronegativity, 14 (51.9 %) showed HBV viremia by PCR. In contrast, of the 75 patients in the control group who were both HCV PCR negative and HBsAg negative, five (11.1 %) showed HBV viremia by PCR. The PCR for HBV revealed coexistent HBV viremia in HCV viremia patients, despite HBsAg negativity by EIA. In HBV-endemic areas, the possibility of coinfection of HBV in HBsAg-negative patients with HCV viremia should be considered and molecular analysis for HBV-DNA performed. (author). 18 refs., 4 tabs

  7. Knowledge of HBV and HCV and individuals' attitudes toward HBV- and HCV-infected colleagues: a national cross-sectional study among a working population in Japan.

    Directory of Open Access Journals (Sweden)

    Hisashi Eguchi

    Full Text Available Prejudice and discrimination in the workplace regarding the risk of transmission of Hepatitis B virus (HBV and Hepatitis C virus (HCV are increased by excess concerns due to a lack of relevant knowledge. Education to increase knowledge about HBV and HCV and their prevention could be the first step to reduce prejudice and discrimination. This study aimed to determine the association between the level of knowledge and negative attitudes toward HBV- and HCV-infected colleagues among the Japanese working population. An online anonymous nationwide survey involving about 3,000 individuals was conducted in Japan. The questionnaire consisted of knowledge of HBV and HCV, and attitudes toward HBV- and HCV-infected colleagues in the workplace. Knowledge was divided into three categories: "ensuring daily activities not to be infected"; "risk of infection"; and "characteristics of HBV/HCV hepatitis", based on the result of factor analysis. Multiple logistic regression analysis was applied. A total of 3,129 persons responded to the survey: 36.0% reported they worried about the possibility of transmission of HBV and HCV from infected colleagues; 32.1% avoided contact with infected colleagues; and 23.7% had prejudiced opinions about HBV and HCV infection. The participants were classified into tertiles. A higher level of knowledge of HBV and HCV was significantly associated with these three negative attitudes (P for trend < 0.005. This study suggests that increasing knowledge may decrease individuals' negative attitudes towards HBV- and HCV-infected colleagues. Thus, we should promote increased knowledge of HBV and HCV in stages to reduce negative attitudes toward HBV- and HCV-infected colleagues.

  8. Constrained pattern of viral evolution in acute and early HCV infection limits viral plasticity.

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    Katja Pfafferott

    2011-02-01

    Full Text Available Cellular immune responses during acute Hepatitis C virus (HCV and HIV infection are a known correlate of infection outcome. Viral adaptation to these responses via mutation(s within CD8+ T-cell epitopes allows these viruses to subvert host immune control. This study examined HCV evolution in 21 HCV genotype 1-infected subjects to characterise the level of viral adaptation during acute and early HCV infection. Of the total mutations observed 25% were within described CD8+ T-cell epitopes or at viral adaptation sites. Most mutations were maintained into the chronic phase of HCV infection (75%. The lack of reversion of adaptations and high proportion of silent substitutions suggests that HCV has structural and functional limitations that constrain evolution. These results were compared to the pattern of viral evolution observed in 98 subjects during a similar phase in HIV infection from a previous study. In contrast to HCV, evolution during acute HIV infection is marked by high levels of amino acid change relative to silent substitutions, including a higher proportion of adaptations, likely reflecting strong and continued CD8+ T-cell pressure combined with greater plasticity of the virus. Understanding viral escape dynamics for these two viruses is important for effective T cell vaccine design.

  9. Potential geographic "hotspots" for drug-injection related transmission of HIV and HCV and for initiation into injecting drug use in New York City, 2011-2015, with implications for the current opioid epidemic in the US.

    Science.gov (United States)

    Des Jarlais, D C; Cooper, H L F; Arasteh, K; Feelemyer, J; McKnight, C; Ross, Z

    2018-01-01

    We identified potential geographic "hotspots" for drug-injecting transmission of HIV and hepatitis C virus (HCV) among persons who inject drugs (PWID) in New York City. The HIV epidemic among PWID is currently in an "end of the epidemic" stage, while HCV is in a continuing, high prevalence (> 50%) stage. We recruited 910 PWID entering Mount Sinai Beth Israel substance use treatment programs from 2011-2015. Structured interviews and HIV/ HCV testing were conducted. Residential ZIP codes were used as geographic units of analysis. Potential "hotspots" for HIV and HCV transmission were defined as 1) having relatively large numbers of PWID 2) having 2 or more HIV (or HCV) seropositive PWID reporting transmission risk-passing on used syringes to others, and 3) having 2 or more HIV (or HCV) seronegative PWID reporting acquisition risk-injecting with previously used needles/syringes. Hotspots for injecting drug use initiation were defined as ZIP codes with 5 or more persons who began injecting within the previous 6 years. Among PWID, 96% injected heroin, 81% male, 34% White, 15% African-American, 47% Latinx, mean age 40 (SD = 10), 7% HIV seropositive, 62% HCV seropositive. Participants resided in 234 ZIP codes. No ZIP codes were identified as potential hotspots due to small numbers of HIV seropositive PWID reporting transmission risk. Four ZIP codes were identified as potential hotspots for HCV transmission. 12 ZIP codes identified as hotspots for injecting drug use initiation. For HIV, the lack of potential hotspots is further validation of widespread effectiveness of efforts to reduce injecting-related HIV transmission. Injecting-related HIV transmission is likely to be a rare, random event. HCV prevention efforts should include focus on potential hotspots for transmission and on hotspots for initiation into injecting drug use. We consider application of methods for the current opioid epidemic in the US.

  10. Patient-to-patient transmission of hepatitis C virus (HCV) during colonoscopy diagnosis.

    Science.gov (United States)

    González-Candelas, Fernando; Guiral, Silvia; Carbó, Rosa; Valero, Ana; Vanaclocha, Hermelinda; González, Francisco; Bracho, Maria Alma

    2010-09-08

    No recognized risk factors can be identified in 10-40% of hepatitis C virus (HCV)-infected patients suggesting that the modes of transmission involved could be underestimated or unidentified. Invasive diagnostic procedures, such as endoscopy, have been considered as a potential HCV transmission route; although the actual extent of transmission in endoscopy procedures remains controversial. Most reported HCV outbreaks related to nosocomial acquisition have been attributed to unsafe injection practices and use of multi-dose vials. Only a few cases of likely patient-to-patient HCV transmission via a contaminated colonoscope have been reported to date. Nosocomial HCV infection may have important medical and legal implications and, therefore, possible transmission routes should be investigated. In this study, a case of nosocomial transmission of HCV from a common source to two patients who underwent colonoscopy in an endoscopy unit is reported. A retrospective epidemiological search after detection of index cases revealed several potentially infective procedures: sample blood collection, use of a peripheral catheter, anesthesia and colonoscopy procedures. The epidemiological investigation showed breaches in colonoscope reprocessing and deficiencies in the recording of valuable tracing data. Direct sequences from the NS5B region were obtained to determine the extent of the outbreak and cloned sequences from the E1-E2 region were used to establish the relationships among intrapatient viral populations. Phylogenetic analyses of individual sequences from viral populations infecting the three patients involved in the outbreak confirmed the patient pointed out by the epidemiological search as the source of the outbreak. Furthermore, the sequential order in which the patients underwent colonoscopy correlates with viral genetic variability estimates. Patient-to-patient transmission of HCV could be demonstrated although the precise route of transmission remained unclear. Viral

  11. Frequency of anti-HCV antibodies in patients with lichen planus

    International Nuclear Information System (INIS)

    Mahboob, A.; Haroon, T.S.; Iqbal, Z.; Butt, A.K.

    2003-01-01

    Objective: To determine the frequency of anti-HCV antibodies, identify risk factors associated with HCV infection and to screen asymptomatic carries in patients with lichen planus. Subjects and Methods: A total of 184 clinically diagnosed cased of lichen (LP) were selected for the study. Blood samples of all the patients were tested for anti hepatitis C virus antibodies (anti-HCV-Ab). Polymerase chain reaction for hepatitis C virus was done in patients with positive anti-HCV-Ab. Trancutaneous liver biopsy was performed in 7 patients with positive HCV-RNA. The histopathological results were evaluated using validated Metavir and Knodell scoring systems. Results: Out of 184 LP patients, 43 (23.4%) were anti-HCV antibodies positive. Females were predominantly affected and male to female ratio was 1:5.1. Maximum positively for anti-HCV was observed in age group 31-40 years (39.53%) followed by 41-50 years (25.58%). Eighty-one percent patients had history of dental treatment and 63% had received multiple injections for various ailments. Forty percent patients had family history of jaundice while 26% had jaundice in the past. Ten out of 16 anti-HCV antibody positive patients, checked for HCV-RNA, had high levels of virus in blood. Transcutaneous liver biopsy done in 7 patients revealed underlying liver disease at various stages. Four patients treated with alpha-interferon and ribazole therapy for liver disease, showed marked improvement in their skin disease. Conclusion: A high prevalence of HCV infection was detected in patients with lichen planus. Patients with lichen planus should be screened for HCV carrier state. (author)

  12. Limiting the access to direct-acting antivirals against HCV: an ethical dilemma.

    Science.gov (United States)

    Gentile, Ivan; Maraolo, Alberto E; Niola, Massimo; Graziano, Vincenzo; Borgia, Guglielmo; Paternoster, Mariano

    2016-11-01

    Hepatitis C virus (HCV) infection affects about 200 million people worldwide and represents a leading cause of liver-related mortality. Eradication of HCV infection, achieved mainly through direct-acting antivirals (DAA), results in a decrease of mortality and an improvement of quality of life. These drugs have a maximal efficacy and an optimal tolerability. However, their high cost precludes a universal access even in wealthy countries. Areas covered: This article deals with the policies adopted for the use of the new anti-HCV drugs, especially in Europe and most of all in Italy, supposedly the developed country with the highest HCV prevalence. The literature search was performed using Pubmed and Web of Science. Moreover, national regulatory institutional websites were consulted. Expert commentary: The current policy of limitation to the access of the DAA presents a series of ethical issues that makes it non-applicable. A 'treat-all' strategy should resolve all ethical dilemmas, by virtue of the wide benefits of anti-HCV treatment not only for the advanced stage of infection, but also for the initial stages. A reduction in price of the drugs is the actual condition to achieve such a change.

  13. [The velocity of HCV subtype 6a transmission in southwest China].

    Science.gov (United States)

    Hong, Guo-hu; Tan, Zhao-xia; Guo, Yan; Mao, Qing

    2011-07-01

    To estimate the velocity of HCV subtype 6a transmission in Southwest China. The HCV CE1 region from 61 patients infected with HCV genotype 6 were amplificated by RT-PCR and sequenced. The subtypes were identified, and the period of HCV 6a strains originated in southwest china was estimated by using molecular clock phylogenetic analysis. The velocity of HCV subtype 6a transmission in southwest China was estimated by BEAST v1.6.1 and Tracer v1.5 software theoretically. Most of HCV 6a strains distributed in Southwest China origine around the year 1968 and at last 4 epidemic strains existed. The earlier origine strains could be isolated both in intravenous drug users (IDU) and non-IDU patients. After 1997, the HCV 6a strains transmission in southwest China accelerated and the trend intensified in 2007. HCV 6a strains spread fastly both in IDU and non-IDU patients, which might be the main HCV subtype distributed in Southwest China in the future.

  14. Humanized-VHH Transbodies that Inhibit HCV Protease and Replication

    Directory of Open Access Journals (Sweden)

    Surasak Jittavisutthikul

    2015-04-01

    Full Text Available There is a need for safe and broadly effective anti-HCV agents that can cope with genetic multiplicity and mutations of the virus. In this study, humanized-camel VHHs to genotype 3a HCV serine protease were produced and were linked molecularly to a cell penetrating peptide, penetratin (PEN. Human hepatic (Huh7 cells transfected with the JFH-1 RNA of HCV genotype 2a and treated with the cell penetrable nanobodies (transbodies had a marked reduction of the HCV RNA intracellularly and in their culture fluids, less HCV foci inside the cells and less amounts of HCV core antigen in culture supernatants compared with the infected cells cultured in the medium alone. The PEN-VHH-treated-transfected cells also had up-regulation of the genes coding for the host innate immune response (TRIF, TRAF3, IRF3, IL-28B and IFN-β, indicating that the cell penetrable nanobodies rescued the host innate immune response from the HCV mediated-suppression. Computerized intermolecular docking revealed that the VHHs bound to residues of the protease catalytic triad, oxyanion loop and/or the NS3 N-terminal portion important for non-covalent binding of the NS4A protease cofactor protein. The so-produced transbodies have high potential for testing further as a candidate for safe, broadly effective and virus mutation tolerable anti-HCV agents.

  15. Minimal disease detection of B-cell lymphoproliferative disorders by flow cytometry: multidimensional cluster analysis.

    Science.gov (United States)

    Duque, Ricardo E

    2012-04-01

    Flow cytometric analysis of cell suspensions involves the sequential 'registration' of intrinsic and extrinsic parameters of thousands of cells in list mode files. Thus, it is almost irresistible to describe phenomena in numerical terms or by 'ratios' that have the appearance of 'accuracy' due to the presence of numbers obtained from thousands of cells. The concepts involved in the detection and characterization of B cell lymphoproliferative processes are revisited in this paper by identifying parameters that, when analyzed appropriately, are both necessary and sufficient. The neoplastic process (cluster) can be visualized easily because the parameters that distinguish it form a cluster in multidimensional space that is unique and distinguishable from neighboring clusters that are not of diagnostic interest but serve to provide a background. For B cell neoplasia it is operationally necessary to identify the multidimensional space occupied by a cluster whose kappa:lambda ratio is 100:0 or 0:100. Thus, the concept of kappa:lambda ratio is without meaning and would not detect B cell neoplasia in an unacceptably high number of cases.

  16. POST-TRANSPLANT LYMPHOPROLIFERATIVE DISORDERS: ROLE OF VIRAL INFECTION, GENETIC LESIONS AND ANTIGEN STIMULATION IN THE PATHOGENESIS OF THE DISEASE

    Directory of Open Access Journals (Sweden)

    Gianluca Gaidano

    2009-11-01

    Full Text Available

    Post-transplant lymphoproliferative disorders (PTLD are a life-threatening complication of solid organ transplantation or, more rarely, hematopoietic stem cell transplantation. The majority of PTLD is of B-cell origin and associated with Epstein–Barr virus (EBV infection. PTLD generally display involvement of extranodal sites, aggressive histology and aggressive clinical behavior. The molecular pathogenesis of PTLD involves infection by oncogenic viruses, namely Epstein-Barr virus, as well as genetic or epigenetic alterations of several cellular genes. At variance with lymphoma arising in immunocompetent hosts, whose genome is relatively stable, a fraction of PTLD are characterized by microsatellite instability as a consequence of defects in the DNA mismatch repair mechanism. Apart from microsatellite instability, molecular alterations of cellular genes recognized in PTLD include alterations of cMYC, BCL6, TP53, DNA hypermethylation, and aberrant somatic hypermutation of protooncogenes. The occurrence of IGV mutations in the overwhelming majority of PTLD documents that malignant transformation targets germinal centre (GC B-cells and their descendants both in EBV–positive and EBV–negative cases. Analysis of phenotypic markers of B-cell histogenesis, namely BCL6, MUM1 and CD138, allows further distinction of PTLD histogenetic categories. PTLD expressing the BCL6+/MUM1+/-/CD138- profile reflect B-cells actively experiencing the GC reaction, and comprise diffuse large B-cell lymphoma (DLBCL centroblastic and Burkitt lymphoma. PTLD expressing the BCL6-/MUM1+/CD138- phenotype putatively derive from B-cells that have concluded the GC reaction, and comprise the majority of polymorphic PTLD and a fraction of

  17. HBV-DNA in hemodialysis patients infected by HCV

    International Nuclear Information System (INIS)

    Arababadi, Mohammad Kazemi; Hassanshahi, Gholamhossein; Yousefi, Hassan

    2009-01-01

    End-stage renal disease patients on chronic hemodialysis (HD) patients are at risk for both hepatitis B virus (HBV) and hepatitis C virus (HCV) infection, and they may coexist. To determine the prevalence and clinical impact of HBV and HCV infection, we studied poly chain reaction (PCR) and reverse transcription (RT)-PCR on the blood samples of 90 HD patients in Kerman, Iran. ELISA test was used to detect anti-HBc, anti-HBs and HBs Ag. We found that 30 out of 90 (33.3%) patients were PCR-RT-PCR positive for HCV-RNA. No HBV-DNA (0%) was detected through the PCR study in both positive and negative HCV-RNA patient groups. Though none of the samples was HBsAg positive, 10 (33.3%) HCV-RNA positive patients were anti-HBc positive, and 12 (40.7%) were anti-HBs positive. We conclude that prevalence of hepatitis C infection is high in HD patients in our region, but not associated with active HBV infection. (author)

  18. HCV Co-infection is Associated with Metabolic Abnormalities among ...

    African Journals Online (AJOL)

    Table 3 shows results of simple linear regression of glucose and the cholesterol fractions against HCV co- infection status. HIV/HCV co infection predicted a statistically significant reduction in all the cholesterol containing fractions. No such relationship existed between the HCV co infection and glucose or triglycerides. The.

  19. School adolescents’ knowledge concerning hepatitis C virus (HCV

    Directory of Open Access Journals (Sweden)

    Lidia Sierpińska

    2017-01-01

    Full Text Available Introduction. Infection with hepatitis C virus (HCV is a serious clinical, epidemiological and social problem inPoland.    Objective. The objective of the study was recognition of knowledge concerning HCV infection among adolescents attending post-secondary schools. Material and method. The study was conducted in 2016, among 106 school adolescents attending two post-secondary schools inRadom, by means of a questionnaire designed by the author and a standardized questionnaire according to the Polish Group of HCV Experts. Statistical analysis was performed using the software Statistica 10.0. Results. The majority of adolescents (84.5% knew that HCV causes hepatitis C.  Boys more frequently than girls knew that the disease spreads by contact with infected blood (72.0% and 50.6%, respectively. Girls significantly more often than boys knew that approximately 700,000 people inPoland are infected with HCV (54.3% and 24.0%, respectively. According to 84.1% of respondents everyone is exposed to this infection.  Boys more often than girls (72.0% and 55.6% correctly provided examples of situations in which the infection may occur. The majority of adolescents (88.5% knew that the hepatitis C antibody (anti-HCV blood test indicates whether the person has an infection. A half of the examined adolescents (50.9% knew that there is currently no vaccine available to protect against hepatitis C, and that it is possible to cure the person infected with HCV. Conclusions. The level of adolescents’ knowledge concerning HCV infection varied according to the demographic and social factors. School adolescents should be provided incentives for prophylaxis of infection and participation in prophylactic programmes, in order to limit the risk of contracting hepatitis C.

  20. Alterations in microRNA expression profile in HCV-infected hepatoma cells: Involvement of miR-491 in regulation of HCV replication via the PI3 kinase/Akt pathway

    Energy Technology Data Exchange (ETDEWEB)

    Ishida, Hisashi; Tatsumi, Tomohide; Hosui, Atsushi; Nawa, Takatoshi; Kodama, Takahiro; Shimizu, Satoshi; Hikita, Hayato; Hiramatsu, Naoki; Kanto, Tatsuya [Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, 2-2, Yamadaoka, Suita 565-0871 (Japan); Hayashi, Norio [Kansai Rosai Hospital, 3-1-69, Inabaso, Amagasaki 660-8511 (Japan); Takehara, Tetsuo, E-mail: takehara@gh.med.osaka-u.ac.jp [Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, 2-2, Yamadaoka, Suita 565-0871 (Japan)

    2011-08-19

    Highlights: {yields} HCV infection upregulated miR-192, -194, -215, downregulated miR-320, -491. {yields} Transfection of miR-192, -215, and -491 enhanced HCV replication. {yields} Transfection of miR-491 inhibited Akt phosphorylation. {yields} Akt inhibition could be responsible for augmentation of HCV replication by miR-491. -- Abstract: The aim of this study was to investigate the role of microRNA (miRNA) on hepatitis C virus (HCV) replication in hepatoma cells. Using miRNA array analysis, miR-192/miR-215, miR-194, miR-320, and miR-491 were identified as miRNAs whose expression levels were altered by HCV infection. Among them, miR-192/miR-215 and miR-491 were capable of enhancing replication of the HCV replicon as well as HCV itself. HCV IRES activity or cell proliferation was not increased by forced expression of miR-192/miR-215 or miR-491. Investigation of signaling pathways revealed that miR-491 specifically suppressed the phosphoinositol-3 (PI3) kinase/Akt pathway. Under inhibition of PI3 kinase by LY294002, the suppressive effect of miR-491 on HCV replication was abolished, indicating that suppression of HCV replication by miR-491 was dependent on the PI3 kinase/Akt pathway. miRNAs altered by HCV infection would then affect HCV replication, which implies a complicated mechanism for regulating HCV replication. HCV-induced miRNA may be involved in changes in cellular properties including hepatocarcinogenesis.

  1. Acetaminophen-induced acute liver injury in HCV transgenic mice

    International Nuclear Information System (INIS)

    Uehara, Takeki; Kosyk, Oksana; Jeannot, Emmanuelle; Bradford, Blair U.; Tech, Katherine; Macdonald, Jeffrey M.; Boorman, Gary A.; Chatterjee, Saurabh; Mason, Ronald P.; Melnyk, Stepan B.; Tryndyak, Volodymyr P.; Pogribny, Igor P.; Rusyn, Ivan

    2013-01-01

    The exact etiology of clinical cases of acute liver failure is difficult to ascertain and it is likely that various co-morbidity factors play a role. For example, epidemiological evidence suggests that coexistent hepatitis C virus (HCV) infection increased the risk of acetaminophen-induced acute liver injury, and was associated with an increased risk of progression to acute liver failure. However, little is known about possible mechanisms of enhanced acetaminophen hepatotoxicity in HCV-infected subjects. In this study, we tested a hypothesis that HCV-Tg mice may be more susceptible to acetaminophen hepatotoxicity, and also evaluated the mechanisms of acetaminophen-induced liver damage in wild type and HCV-Tg mice expressing core, E1 and E2 proteins. Male mice were treated with a single dose of acetaminophen (300 or 500 mg/kg in fed animals; or 200 mg/kg in fasted animals; i.g.) and liver and serum endpoints were evaluated at 4 and 24 h after dosing. Our results suggest that in fed mice, liver toxicity in HCV-Tg mice is not markedly exaggerated as compared to the wild-type mice. In fasted mice, greater liver injury was observed in HCV-Tg mice. In fed mice dosed with 300 mg/kg acetaminophen, we observed that liver mitochondria in HCV-Tg mice exhibited signs of dysfunction showing the potential mechanism for increased susceptibility. -- Highlights: ► Acetaminophen-induced liver injury is a significant clinical challenge. ► HCV-infected subjects may be at higher risk for acetaminophen-induced liver injury. ► We used HCV transgenics to test if liver injury due to acetaminophen is exacerbated.

  2. Acetaminophen-induced acute liver injury in HCV transgenic mice

    Energy Technology Data Exchange (ETDEWEB)

    Uehara, Takeki; Kosyk, Oksana; Jeannot, Emmanuelle; Bradford, Blair U. [Department of Environmental Sciences and Engineering, University of North Carolina, Chapel Hill, NC 27599 (United States); Tech, Katherine; Macdonald, Jeffrey M. [Department of Biomedical Engineering, University of North Carolina, Chapel Hill, NC 27599 (United States); Boorman, Gary A. [Covance, Chantilly, VA 20151 (United States); Chatterjee, Saurabh; Mason, Ronald P. [Laboratory of Toxicology and Pharmacology, National Institute of Environmental Health Sciences, RTP, NC 27713 (United States); Melnyk, Stepan B. [Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR 72201 (United States); Tryndyak, Volodymyr P.; Pogribny, Igor P. [Division of Biochemical Toxicology, National Center for Toxicological Research, Jefferson, AR 72079 (United States); Rusyn, Ivan, E-mail: iir@unc.edu [Department of Environmental Sciences and Engineering, University of North Carolina, Chapel Hill, NC 27599 (United States)

    2013-01-15

    The exact etiology of clinical cases of acute liver failure is difficult to ascertain and it is likely that various co-morbidity factors play a role. For example, epidemiological evidence suggests that coexistent hepatitis C virus (HCV) infection increased the risk of acetaminophen-induced acute liver injury, and was associated with an increased risk of progression to acute liver failure. However, little is known about possible mechanisms of enhanced acetaminophen hepatotoxicity in HCV-infected subjects. In this study, we tested a hypothesis that HCV-Tg mice may be more susceptible to acetaminophen hepatotoxicity, and also evaluated the mechanisms of acetaminophen-induced liver damage in wild type and HCV-Tg mice expressing core, E1 and E2 proteins. Male mice were treated with a single dose of acetaminophen (300 or 500 mg/kg in fed animals; or 200 mg/kg in fasted animals; i.g.) and liver and serum endpoints were evaluated at 4 and 24 h after dosing. Our results suggest that in fed mice, liver toxicity in HCV-Tg mice is not markedly exaggerated as compared to the wild-type mice. In fasted mice, greater liver injury was observed in HCV-Tg mice. In fed mice dosed with 300 mg/kg acetaminophen, we observed that liver mitochondria in HCV-Tg mice exhibited signs of dysfunction showing the potential mechanism for increased susceptibility. -- Highlights: ► Acetaminophen-induced liver injury is a significant clinical challenge. ► HCV-infected subjects may be at higher risk for acetaminophen-induced liver injury. ► We used HCV transgenics to test if liver injury due to acetaminophen is exacerbated.

  3. Natural Polymorphisms Conferring Resistance to HCV Protease and Polymerase Inhibitors in Treatment-Naïve HIV/HCV Co-Infected Patients in China.

    Directory of Open Access Journals (Sweden)

    Kali Zhou

    Full Text Available The advent of direct-acting agents (DAAs has improved treatment of HCV in HIV co-infection, but may be limited by primary drug resistance. This study reports the prevalence of natural polymorphisms conferring resistance to NS3/4A protease inhibitors and NS5B polymerase inhibitors in treatment-naïve HIV/HCV co-infected individuals in China.Population based NS3/4A sequencing was completed for 778 treatment-naïve HIV/HCV co-infected patients from twelve provinces. NS3 sequences were amplified by nested PCR using in-house primers for genotypes 1-6. NS5B sequencing was completed for genotyping in 350 sequences. Resistance-associated variants (RAVs were identified in positions associated with HCV resistance.Overall, 72.8% (566/778 of all HCV sequences had at least one RAV associated with HCV NS3/4A protease inhibitor resistance. Variants were found in 3.6% (7/193 of genotype 1, 100% (23/23 of genotype 2, 100% (237/237 of genotype 3 and 92% (299/325 of genotype 6 sequences. The Q80K variant was present in 98.4% of genotype 6a sequences. High-level RAVs were rare, occurring in only 0.8% of patients. 93% (64/69 patients with genotype 1b also carried the C316N variant associated with NS5B low-level resistance.The low frequency of high-level RAVs associated with primary HCV DAA resistance among all genotypes in HIV/HCV co-infected patients is encouraging. Further phenotypic studies and clinical research are needed.

  4. Phenotypic characterization of lymphocytes in HCV/HIV co-infected patients.

    LENUS (Irish Health Repository)

    Roe, Barbara

    2009-02-01

    While hepatitis C virus (HCV)-specific immune responses are attenuated in HCV\\/HIV co-infected patients compared to those infected with HCV alone, the reasons for this remain unclear. In this study, the proportions of regulatory, naïve, and memory T cells, along with chemokine receptor expression, were measured in co-infected and mono-infected patients to determine if there is an alteration in the phenotypic profile of lymphocytes in these patients. HCV\\/HIV co-infected patients had increased proportions of CD4(+) naïve cells and decreased proportions of CD4(+) effector cells when compared to HCV mono-infected patients. The proportions of CD4(+) Tregs and CD4(+) CXCR3(+) T cells were also significantly lower in co-infected patients. A decrease in CD4(+) Tregs and subsequent loss of immunosuppressive function may contribute to the accelerated progression to liver disease in co-infected individuals. Dysregulation of immune responses following reduction in the proportions of CD4(+) CXCR3(+) Th-1 cells may contribute to the reduced functional capacity of HCV-specific immune responses in co-infected patients. The findings of this study provide new information on the T-cell immunophenotype in HCV\\/HIV co-infected patients when compared to those infected with HCV alone, and may provide insight into why cell-mediated immune responses are diminished during HCV infection.

  5. Genomic analysis reveals a potential role for cell cycle perturbation in HCV-mediated apoptosis of cultured hepatocytes.

    Directory of Open Access Journals (Sweden)

    Kathie-Anne Walters

    2009-01-01

    Full Text Available The mechanisms of liver injury associated with chronic HCV infection, as well as the individual roles of both viral and host factors, are not clearly defined. However, it is becoming increasingly clear that direct cytopathic effects, in addition to immune-mediated processes, play an important role in liver injury. Gene expression profiling during multiple time-points of acute HCV infection of cultured Huh-7.5 cells was performed to gain insight into the cellular mechanism of HCV-associated cytopathic effect. Maximal induction of cell-death-related genes and appearance of activated caspase-3 in HCV-infected cells coincided with peak viral replication, suggesting a link between viral load and apoptosis. Gene ontology analysis revealed that many of the cell-death genes function to induce apoptosis in response to cell cycle arrest. Labeling of dividing cells in culture followed by flow cytometry also demonstrated the presence of significantly fewer cells in S-phase in HCV-infected relative to mock cultures, suggesting HCV infection is associated with delayed cell cycle progression. Regulation of numerous genes involved in anti-oxidative stress response and TGF-beta1 signaling suggest these as possible causes of delayed cell cycle progression. Significantly, a subset of cell-death genes regulated during in vitro HCV infection was similarly regulated specifically in liver tissue from a cohort of HCV-infected liver transplant patients with rapidly progressive fibrosis. Collectively, these data suggest that HCV mediates direct cytopathic effects through deregulation of the cell cycle and that this process may contribute to liver disease progression. This in vitro system could be utilized to further define the cellular mechanism of this perturbation.

  6. Small molecule inhibitors of HCV replication from Pomegranate

    Science.gov (United States)

    Reddy, B. Uma; Mullick, Ranajoy; Kumar, Anuj; Sudha, Govindarajan; Srinivasan, Narayanaswamy; Das, Saumitra

    2014-06-01

    Hepatitis C virus (HCV) is the causative agent of end-stage liver disease. Recent advances in the last decade in anti HCV treatment strategies have dramatically increased the viral clearance rate. However, several limitations are still associated, which warrant a great need of novel, safe and selective drugs against HCV infection. Towards this objective, we explored highly potent and selective small molecule inhibitors, the ellagitannins, from the crude extract of Pomegranate (Punica granatum) fruit peel. The pure compounds, punicalagin, punicalin, and ellagic acid isolated from the extract specifically blocked the HCV NS3/4A protease activity in vitro. Structural analysis using computational approach also showed that ligand molecules interact with the catalytic and substrate binding residues of NS3/4A protease, leading to inhibition of the enzyme activity. Further, punicalagin and punicalin significantly reduced the HCV replication in cell culture system. More importantly, these compounds are well tolerated ex vivo and`no observed adverse effect level' (NOAEL) was established upto an acute dose of 5000 mg/kg in BALB/c mice. Additionally, pharmacokinetics study showed that the compounds are bioavailable. Taken together, our study provides a proof-of-concept approach for the potential use of antiviral and non-toxic principle ellagitannins from pomegranate in prevention and control of HCV induced complications.

  7. HCV RNA traffic and association with NS5A in living cells

    Energy Technology Data Exchange (ETDEWEB)

    Fiches, Guillaume N.; Eyre, Nicholas S.; Aloia, Amanda L.; Van Der Hoek, Kylie [Department of Molecular and Cellular Biology, Research Centre for Infectious Diseases, University of Adelaide, Adelaide and Centre for Cancer Biology, SA Pathology, Adelaide, SA (Australia); Betz-Stablein, Brigit; Luciani, Fabio [Systems Immunology, School of Medical Sciences, University of New South Wales, Sydney, NSW (Australia); Chopra, Abha [Institute for Immunology and infectious diseases (IIID), Murdoch University, Perth, WA (Australia); Beard, Michael R., E-mail: michael.beard@adelaide.edu.au [Department of Molecular and Cellular Biology, Research Centre for Infectious Diseases, University of Adelaide, Adelaide and Centre for Cancer Biology, SA Pathology, Adelaide, SA (Australia)

    2016-06-15

    The spatiotemporal dynamics of Hepatitis C Virus (HCV) RNA localisation are poorly understood. To address this we engineered HCV genomes harbouring MS2 bacteriophage RNA stem-loops within the 3′-untranslated region to allow tracking of HCV RNA via specific interaction with a MS2-Coat-mCherry fusion protein. Despite the impact of these insertions on viral fitness, live imaging revealed that replication of tagged-HCV genomes induced specific redistribution of the mCherry-tagged-MS2-Coat protein to motile and static foci. Further analysis showed that HCV RNA was associated with NS5A in both static and motile structures while a subset of motile NS5A structures was devoid of HCV RNA. Further investigation of viral RNA traffic with respect to lipid droplets (LDs) revealed HCV RNA-positive structures in close association with LDs. These studies provide new insights into the dynamics of HCV RNA traffic with NS5A and LDs and provide a platform for future investigations of HCV replication and assembly. - Highlights: • HCV can tolerate can bacteriophage MS2 stem-loop insertions within the 3′ UTR. • MS2 stem-loop containing HCV genomes allow for real-time imaging of HCV RNA. • HCV RNA is both static and motile and associates with NS5A and lipid droplets.

  8. HCV RNA traffic and association with NS5A in living cells

    International Nuclear Information System (INIS)

    Fiches, Guillaume N.; Eyre, Nicholas S.; Aloia, Amanda L.; Van Der Hoek, Kylie; Betz-Stablein, Brigit; Luciani, Fabio; Chopra, Abha; Beard, Michael R.

    2016-01-01

    The spatiotemporal dynamics of Hepatitis C Virus (HCV) RNA localisation are poorly understood. To address this we engineered HCV genomes harbouring MS2 bacteriophage RNA stem-loops within the 3′-untranslated region to allow tracking of HCV RNA via specific interaction with a MS2-Coat-mCherry fusion protein. Despite the impact of these insertions on viral fitness, live imaging revealed that replication of tagged-HCV genomes induced specific redistribution of the mCherry-tagged-MS2-Coat protein to motile and static foci. Further analysis showed that HCV RNA was associated with NS5A in both static and motile structures while a subset of motile NS5A structures was devoid of HCV RNA. Further investigation of viral RNA traffic with respect to lipid droplets (LDs) revealed HCV RNA-positive structures in close association with LDs. These studies provide new insights into the dynamics of HCV RNA traffic with NS5A and LDs and provide a platform for future investigations of HCV replication and assembly. - Highlights: • HCV can tolerate can bacteriophage MS2 stem-loop insertions within the 3′ UTR. • MS2 stem-loop containing HCV genomes allow for real-time imaging of HCV RNA. • HCV RNA is both static and motile and associates with NS5A and lipid droplets.

  9. Upper airway obstruction and pulmonary abnormalities due to lymphoproliferative disease following bone marrow transplantation in children

    Energy Technology Data Exchange (ETDEWEB)

    Fletcher, B.D. [Department of Diagnostic Imaging, St. Jude Children`s Research Hospital, 332 N. Lauderdale St., Memphis, TN 38105 (United States)]|[Departments of Radiology and Pediatrics, University of Tennessee, Memphis, Tennessee (United States); Heslop, H.E. [Department of Hematology/Oncology, St. Jude Children`s Research Hospital, Department of Pediatrics, University of Tennessee, Memphis, Tennessee (United States); Kaste, S.C. [Department of Diagnostic Imaging, St. Jude Children`s Research Hospital, Department of Radiology, University of Tennessee, Memphis, Tennessee (United States); Bodner, S. [Department of Pathology, St. Jude Children`s Research Hospital, Department of Pathology, University of Tennessee, Memphis, Tennessee (United States)

    1998-07-01

    We report three patients who developed severe supraglottic airway obstruction due to Epstein-Barr virus lymphoproliferative disease following allogeneic bone marrow transplantation. In addition to enlarged pharyngeal lymphoid tissue seen in all three patients, two had supraglottic airway narrowing and two developed pulmonary lymphoproliferative disease. They were treated with unmanipulated T cells or EBV-specific cytotoxic T lymphocytes. Life-threatening upper airway obstruction is a radiologically detectable complication of allogeneic bone marrow transplantation in children. (orig.) With 3 figs., 1 tab., 12 refs.

  10. The HCV Synthesis Project: Scope, methodology, and preliminary results

    Directory of Open Access Journals (Sweden)

    Scheinmann Roberta

    2008-09-01

    Full Text Available Abstract Background The hepatitis C virus (HCV is hyper-endemic in injecting drug users. There is also excess HCV among non-injection drug users who smoke, snort, or sniff heroin, cocaine, crack, or methamphetamine. Methods To summarize the research literature on HCV in drug users and identify gaps in knowledge, we conducted a synthesis of the relevant research carried out between 1989 and 2006. Using rigorous search methods, we identified and extracted data from published and unpublished reports of HCV among drug users. We designed a quality assurance system to ensure accuracy and consistency in all phases of the project. We also created a set of items to assess study design quality in each of the reports we included. Results We identified 629 reports containing HCV prevalence rates, incidence rates and/or genotype distribution among injecting or non-injecting drug user populations published between January 1989 and December 2006. The majority of reports were from Western Europe (41%, North America (26%, Asia (11% and Australia/New Zealand (10%. We also identified reports from Eastern Europe, South America, the Middle East, and the Caribbean. The number of publications reporting HCV rates in drug users increased dramatically between 1989 and 2006 to 27–52 reports per year after 1998. Conclusion The data collection and quality assurance phases of the HCV Synthesis Project have been completed. Recommendations for future research on HCV in drug users have come out of our data collection phase. Future research reports can enhance their contributions to our understanding of HCV etiology by clearly defining their drug user participants with respect to type of drug and route of administration. Further, the use of standard reporting methods for risk factors would enable data to be combined across a larger set of studies; this is especially important for HCV seroconversion studies which suffer from small sample sizes and low power to examine risk

  11. Seroprevalence of HBV, HCV & HIV co-infection and risk factors analysis in Tripoli-Libya.

    Directory of Open Access Journals (Sweden)

    Mohamed A Daw

    Full Text Available In 1998 Libya experienced a major outbreak of multiple blood borne viral hepatitis and HIV infections. Since then, no studies have been done on the epidemic features and risk factors of HBV, HCV, HIV and co-infection among the general population.A prospective study was carried out using a multi-centre clustering method to collect samples from the general population. The participants were interviewed, and relevant information was collected, including socio-demographic, ethnic, and geographic variables. This information was correlated with the risk factors involved in the transmission of HBV, HCV and HIV. Blood samples were collected and the sera were tested for HBsAg, anti-HCV and anti-HIV using enzyme immunoassay.A total of 9,170 participants from the nine districts of Tripoli were enrolled. The average prevalence of HBsAg was 3.7%, anti-HCV 0.9%, anti-HIV 0.15% and co-infection 0.02%. The prevalence varied from one district to another. HBV was more prevalent among those aged over 50 years and was associated with family history. Anti-HCV and anti-HIV were more prevalent among those aged 20-40 years. Intravenous drug use and blood transfusion were the main risk factors for HCV and HIV infection.HBV, HCV, HIV and co-infection are relatively common in Libya. High prevalence was associated with geographic, ethnic and socioeconomic variability within the community. HCV and HIV infections among the younger age groups are becoming an alarming issue. Regulations and health care education need to be implemented and longer term follow-up should be planned.

  12. Differences in HCV viral decline between low and standard-dose pegylated-interferon-alpha-2a with ribavirin in HIV/HCV genotype 3 patients.

    Directory of Open Access Journals (Sweden)

    Antonio Rivero-Juárez

    Full Text Available BACKGROUND: The aim of the study was to analyze the different impact of standard and low-dose Peg-IFN-α2a/RBV therapies on HCV viral decline in HIV/HCV genotype 3 co-infected patients during the first weeks of treatment. METHODS: Plasma HCV viral decline was analyzed between baseline and weeks 1, 2 and 4 in two groups of treatment-naïve HCV genotype 3 patients with HIV co-infection. The Standard Dose Group (SDG included patients who received Peg-IFN at 180 µg/per week with a weight-adjusted dose of ribavirin; Low-Dose Group (LDG patients received Peg-IFN at 135 µg/per week with 800 mg/day ribavirin. The effect of IL28B genotype on HCV viral decline was evaluated in both groups. HCV viral decline was analyzed using a multivariate linear regression model. RESULTS: One hundred and six patients were included: 48 patients in the SDG and 58 in the LDG. HCV viral decline for patients in the LDG was less than for those in the SDG (week 1:1.72±0.74 log(10 IU/mL versus 1.78±0.67 log(10 IU/mL, p = 0.827; week 2:2.3±0.89 log(10 IU/mL versus 3.01±1.02 log(10 IU/mL, p = 0.013; week 4:3.52±1.2 log(10 IU/mL versus 4.09±1.1 log(10 IU/mL, p = 0.005. The linear regression model identified the Peg-IFN/RBV dose as an independent factor for HCV viral decline at week 4. CONCLUSIONS: Our results showed that HCV viral decline was less for patients in the low-dose group compared to those receiving the standard dose. Until a randomized clinical trial is conducted, clinicians should be cautious about using lower doses of Peg-IFN/RBV in HIV/HCV genotype 3 co-infected patients.

  13. Lacrimal sac lymphoproliferative lesion: case report.

    Science.gov (United States)

    Coloma-González, I; Ruíz-García, L; Ceriotto, A; Corredor-Casas, S; Salcedo-Casillas, G

    2015-03-01

    The case is presented of a 51 year-old woman with a firm mass at the medial canthus of the right eye of five years onset. A low-grade lymphoproliferative lesion (reactive lymphoid hyperplasia) was diagnosed from an excisional biopsy Lacrimal sac tumors are rare, with a peak incidence in the fifth decade of life. The initial clinical features are epiphora and medial canthus swelling. As it mimics nasolacrimal duct obstruction, up to 40% of these tumors are misdiagnosed until undergoing surgery. Copyright © 2013 Sociedad Española de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.

  14. Anti-HCV activity of the Chinese medicinal fungus Cordyceps militaris.

    Science.gov (United States)

    Ueda, Youki; Mori, Kyoko; Satoh, Shinya; Dansako, Hiromichi; Ikeda, Masanori; Kato, Nobuyuki

    2014-05-02

    Persistent hepatitis C virus (HCV) infection causes chronic liver diseases and is a global health problem. Although the sustained virologic response rate in the treatment of genotype 1 using new triple therapy (pegylated-interferon, ribavirin, and telaprevir/boceprevir) has been improved by more than 70%, several severe side effects such as skin rash/ageusia and advanced anemia have become a problem. Under these circumstances, a new type of anti-HCV oral drug with few side effects is needed. Our recently developed HCV drug assay systems, including the HuH-7 cell line-derived OR6 and AH1R, and the Li23 cell line-derived ORL8 and ORL11, allow genome-length HCV RNAs (several strains of genotype 1b) encoding renilla luciferase to replicate efficiently. Using these systems as anti-HCV candidates, we have identified numerous existing medicines that can be used against HCV with few side effects, such as statins and teprenon. To obtain additional anti-HCV candidates, we evaluated a number of oral health supplements, and found that the capsule but not the liquid form of Cordyceps militaris (CM) (Ascomycotinanorth, North Chinese caterpillar fungus), which is used as a Chinese herbal medicine, exhibited moderate anti-HCV activity. In combination with interferon-α or ribavirin, CM exhibited an additive inhibitory effect. Among the main components of CM, cordycepin, but not ergosterol, contributed to the anti-HCV activity of CM. In consideration of all these results, we suggest that CM would be useful as an oral anti-HCV agent in combination with interferon-α and/or ribavirin. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. Imaging features of microvascular invasion in hepatocellular carcinoma developed after direct-acting antiviral therapy in HCV-related cirrhosis

    Energy Technology Data Exchange (ETDEWEB)

    Renzulli, Matteo; Brocchi, Stefano; Golfieri, Rita [Sant' Orsola-Malpighi Hospital, Department of Diagnostic Medicine and Prevention, Bologna (Italy); Buonfiglioli, Federica; Conti, Fabio; Verucchi, Gabriella; Andreone, Pietro [University of Bologna, Research Centre for the Study of Hepatitis, Department of Medical and Surgical Sciences DIMEC, Bologna (Italy); Serio, Ilaria [Sant' Orsola-Malpighi Hospital, Department of Digestive Diseases, Bologna (Italy); Foschi, Francesco Giuseppe [Ospedale di Faenza, Division of Internal Medicine, Faenza (Italy); Caraceni, Paolo; Mazzella, Giuseppe [University of Bologna, Department of Medical and Surgical Sciences (DIMEC), Bologna (Italy); Brillanti, Stefano [University of Bologna, Research Centre for the Study of Hepatitis, Department of Medical and Surgical Sciences DIMEC, Bologna (Italy); U.O. di Gastroenterologia, Bologna (Italy)

    2018-02-15

    To evaluate imaging features of microvascular invasion (MVI) in hepatocellular carcinoma (HCC) developed after direct-acting antiviral (DAA) therapy in HCV-related cirrhosis. Retrospective cohort study on 344 consecutive patients with HCV-related cirrhosis treated with DAA and followed for 48-74 weeks. Using established imaging criteria for MVI, HCC features were analysed and compared with those in nodules not occurring after DAA. After DAA, HCC developed in 29 patients (single nodule, 18 and multinodular, 11). Median interval between therapy end and HCC diagnosis was 82 days (0-318). Forty-one HCC nodules were detected (14 de novo, 27 recurrent): maximum diameter was 10-20 mm in 27, 20-50 mm in 13, and > 50 mm in 1. Imaging features of MVI were present in 29/41 nodules (70.7%, CI: 54-84), even in 17/29 nodules with 10-20 mm diameter (58.6%, CI: 39-76). MVI was present in only 17/51 HCC nodules that occurred before DAA treatment (33.3%, CI: 22-47) (p= 0.0007). MVI did not correlate with history of previous HCC. HCC occurs rapidly after DAA therapy, and aggressive features of MVI characterise most neoplastic nodules. Close imaging evaluations are needed after DAA in cirrhotic patients. (orig.)

  16. Detection of HCV genotypes using molecular and radio-isotopic methods

    International Nuclear Information System (INIS)

    Ahmad, N.; Baig, S.M.; Shah, W.A.; Khattak, K.F.; Khan, B.; Qureshi, J.A.

    2004-01-01

    Hepatitis C virus (HCV) accounts for most cases of acute and chronic non-A and non-B liver diseases. Persistent HCV infection may lead to liver cirrhosis and hepatocellular carcinoma. Six major HCV genotypes have been recognized. Infection with different genotypes results in different clinical pictures and responses to antiviral therapy. In the area of Faisalabad (Punjab province of Pakistan), the prevalence and molecular epidemiology of Hepatitis C virus infection had never been investigated before. In this study, we have made an attempt to determine the prevalence, distribution and clinical significance of HCV infection in 1100 suspected patients of liver disease by nested reverse transcriptase polymerase chain reaction (RTPCR) over a period of four years. HCV genotypes of isolates were determined by dot-blot hybridization with genotype specific radiolabeled probes in 337 subjects. The proportion of patients with HCV genotypes 1,2,3 and 4 were 37.38%, 1.86%, 16.16% and 0.29% respectively. Mixed infection of HCV genotype was detected in 120 (35.6%) patients, whereas 31 (9.1%) samples remained unclassified. This study revealed changing epidemiology of hepatitis C virus genotype 1 and 3 in the patients. Multiple infection of HCV genotype in the same patient may be of great clinical and pathological importance and interest. (author)

  17. Telaprevir for previously treated chronic HCV infection

    NARCIS (Netherlands)

    McHutchison, John G.; Manns, Michael P.; Muir, Andrew J.; Terrault, Norah A.; Jacobson, Ira M.; Afdhal, Nezam H.; Heathcote, E. Jenny; Zeuzem, Stefan; Reesink, Hendrik W.; Garg, Jyotsna; Bsharat, Mohammad; George, Shelley; Kauffman, Robert S.; Adda, Nathalie; Di Bisceglie, Adrian M.; Heathcote, E. J.; Kaita, K.; Ma, M.; Myers, R.; Sherman, M.; Yoshida, E.; Berg, T.; Manns, M. P.; Zeuzem, S.; de Knegt, R.; van Hoek, B.; Afdhal, N. H.; Arora, S.; Bernstein, D.; Cochran, J.; Di Bisceglie, A. M.; Dickson, R.; Dieterich, D. T.; Etzkorn, K.; Everson, G. T.; Faruqui, S.; Ghalib, R.; Gitlin, N.; Godofsky, E.; Gordon, S.; Hassanein, T.; Jacobson, I. M.; Kilby, A.; Kugelmas, M.; Kwo, P. Y.; Lawitz, E. S.; Lindsay, K.; Maillard, M.; Nelson, D. R.; Nyberg, L.

    2010-01-01

    Patients with genotype 1 hepatitis C virus (HCV) who do not have a sustained response to therapy with peginterferon alfa and ribavirin have a low likelihood of success with retreatment. We randomly assigned patients with HCV genotype 1 who had not had a sustained virologic response after

  18. Association of HCV with diabetes mellitus: an Egyptian case-control study

    Directory of Open Access Journals (Sweden)

    Esmat Gamal G

    2011-07-01

    Full Text Available Abstract Background The highest Hepatitis C Virus (HCV prevalence in the world occurs in Egypt. Several studies from different parts of the world have found that 13% to 33% of patients with chronic HCV have associated diabetes, mostly type II Diabetes Mellitus (DM. In Egypt the prevalence of DM is 25.4% among HCV patients. Therefore, it is important to identify the magnitude of the problem of diabetes in order to optimize the treatment of chronic hepatitis C. Methods The objective of this case-control study was to evaluate the prevalence of DM and other extrahepatic (EH manifestations among patients with different HCV morbidity stages including asymptomatic, chronic hepatic and cirrhotic patients. In this study, 289 HCV patients older than 18 were selected as cases. Also, 289 healthy controls were included. Laboratory investigations including Liver Function tests (LFT and blood glucose level were done. Also serological assays including cryoglobulin profile, rheumatoid factor, antinuclear antibody, HCV-PCR were performed. Results Out of 289 HCV cases, 40 (13.84% were diabetic. Out of 289 healthy controls, 12 (4.15% were diabetic. It was found that the diabetic HCV group mean age was [48.1 (± 9.2]. Males and urbanians represented 72.5% and 85% respectively. Lower level of education was manifested in 52.5% and 87.5% were married. In the nondiabetic HCV group mean age was [40.7 (± 10.4]. Males and urbanians represented 71.5% and 655% respectively. secondary and higher level of education was attained in 55.4% and 76.7% were married. Comparing between the diabetic HCV group and the non diabetic HCV group, age, residence and alcohol drinking were the only significant factors affecting the incidence of diabetes between the two groups. There was no significant difference regarding sonar findings although cirrhosis was more prevalent among diabetic HCV cases and the fibrosis score was higher in diabetic HCV patients than among the non diabetic HCV cases

  19. Prevalence of HCV Infections Among Hemodialysis Patients in Al ...

    African Journals Online (AJOL)

    1527 patients (11%) who were HCV free at the start of the study. By the end of the study, a total of 42.2% were found to be anti-HCV reactive. Conclusion: The study demonstrated high prevalence of anti-HCV in HD units in Al Gharbiyah Governorate. Similar studies must be conducted in all Egyptian governorates' HD units ...

  20. Kaposi's Sarcoma-Associated Herpesvirus-Related Solid Lymphoma Involving the Heart and Brain

    Directory of Open Access Journals (Sweden)

    Jason R. Andrews

    2011-01-01

    Full Text Available Since its discovery in 1994, Kaposi's sarcoma-associated herpesvirus (KSHV has been associated with lymphoproliferative disorders, particularly in patients infected with human immunodeficiency virus (HIV. The disorders most strongly linked to KSHV are multicentric Castleman's Disease (MCD, primary effusion lymphoma, and diffuse large B-cell lymphomas. We report an unusual case of KSHV-associated lymphoma in an HIV-infected patient manifesting with myocardial and central nervous system involvement. We discuss this case in the context of increasing array of KSHV-associated lymphomas. In the HIV-infected patient with a mass lesion, a history of cutaneous Kaposi's sarcoma and prolonged immunosuppression should alert clinicians as to the possibility of KSHV-associated lymphoproliferative disorders, in order to establish a timely diagnosis.

  1. Liver transplantation for HCV cirrhosis at Karolinska University Hospital Huddinge, Stockholm.

    Science.gov (United States)

    Gjertsen, H; Weiland, O; Oksanen, A; Söderdahl, G; Broomé, U; Ericzon, B-G

    2006-10-01

    Hepatitis C virus (HCV)-induced cirrhosis is the major indication for liver transplantation globally, and an increasing indication for liver transplantation in Sweden. We have retrospectively examined the 120 patients transplanted for HCV cirrhosis from 1987 through 2005, including 11 who received more than one graft. The 1-, 3-, and 5-year postoperative survivals for all patients transplanted for HCV with or without hepatocellular cancer (HCC) were 77%, 66%, and 53%, respectively. HCV patients without HCC had a 1-, 3-, and 5-year survivals of 78%, 73%, and 61%, compared with 84%, 79% and 74%, respectively, for patients transplanted with chronic liver diseases without cancer or HCV. The number of patients with HCV cirrhosis transplanted in our center is increasing. Compared with patients transplanted for other chronic liver diseases, we experienced inferior results among patients with HCV cirrhosis.

  2. The history of hepatitis C virus (HCV)

    DEFF Research Database (Denmark)

    Bukh, Jens

    2016-01-01

    The discovery of hepatitis C virus (HCV) in 1989 permitted basic research to unravel critical components of a complex life cycle for this important human pathogen. HCV is a highly divergent group of viruses classified in 7 major genotypes and a great number of subtypes, and circulating in infected...

  3. Molecular beacon probes-base multiplex NASBA Real-time for detection of HIV-1 and HCV.

    Science.gov (United States)

    Mohammadi-Yeganeh, S; Paryan, M; Mirab Samiee, S; Kia, V; Rezvan, H

    2012-06-01

    Developed in 1991, nucleic acid sequence-based amplification (NASBA) has been introduced as a rapid molecular diagnostic technique, where it has been shown to give quicker results than PCR, and it can also be more sensitive. This paper describes the development of a molecular beacon-based multiplex NASBA assay for simultaneous detection of HIV-1 and HCV in plasma samples. A well-conserved region in the HIV-1 pol gene and 5'-NCR of HCV genome were used for primers and molecular beacon design. The performance features of HCV/HIV-1 multiplex NASBA assay including analytical sensitivity and specificity, clinical sensitivity and clinical specificity were evaluated. The analysis of scalar concentrations of the samples indicated that the limit of quantification of the assay was beacon probes detected all HCV genotypes and all major variants of HIV-1. This method may represent a relatively inexpensive isothermal method for detection of HIV-1/HCV co-infection in monitoring of patients.

  4. Molecular Epidemiology of Hepatitis C Virus (HCV) in Kadun State ...

    African Journals Online (AJOL)

    Hepatitis C virus genotype 1b was found in the entire HCV RNA positive sample. Conclusions: The findings of 6.2% prevalence of HCV infection based on HCV RNA test confirmed that there is Hepatitis C virus in ... HOW TO USE AJOL.

  5. HOMA-AD in Assessing Insulin Resistance in Lean Noncirrhotic HCV Outpatients.

    Science.gov (United States)

    Michalczuk, Matheus Truccolo; Kappel, Camila Rippol; Birkhan, Oscar; Bragança, Ana Carolina; Alvares-da-Silva, Mário Reis

    2012-01-01

    Introduction. There is an association between HCV and insulin resistance (IR), which is currently assessed by HOMA-IR. There is evidence that HOMA-adiponectin (HOMA-AD) is more accurate, but its role in HCV patients is unknown. The purpose of this study was to evaluate IR in an HCV sample and controls, in order to compare the accuracy of HOMA-IR and HOMA-AD. Methods. Ninety-four HCV outpatients aged IR was estimated by HOMA-IR and HOMA-AD. Results. The groups were similar regarding sex and BMI, but the HCV patients were older. The median insulin level was higher in the HCV group (8.6 mU/mL (6.5-13.7) versus 6.5 (4.3-10.7), P = 0.004), as was median HOMA-IR (1.94 (1.51 to 3.48) versus 1.40 (1.02 to 2.36), P = 0.002) and the prevalence of IR (38.3% versus 10.3% (P = 0.009)). No differences were found in adiponectin levels (P = 0.294) and HOMA-AD (P = 0.393). Conclusion. IR is highly prevalent even in low-risk HCV outpatients. Adiponectin is not influenced by the presence of HCV. HOMA-AD does not seem to be useful in assessing IR in HCV patients.

  6. IFN-αα induced psoriatic arthritis and HCV-related liver cirrhosis. Therapeutic options and patient’s opinion

    Directory of Open Access Journals (Sweden)

    M. Piga

    2011-09-01

    Full Text Available Hepatitis C virus (HCV infection in the setting of Psoriatic Arthritis is an additional variable to be considered in the therapeutic approach to the disease because of the complications of an immunosuppressive treatment in the course of a chronic infection and the possible hepatotoxicity of many drugs conventionally used to treat psoriatic arthritis. The case reported explores the therapeutic options in a patient with IFN-α induced psoriatic arthritis, characterised by severe arthritis and psoriasis but also the concomitant presence of HCV chronic hepatitis, in light of the patient’s concerns

  7. An overview of HCV molecular biology, replication and immune responses

    Directory of Open Access Journals (Sweden)

    Nawaz Zafar

    2011-04-01

    Full Text Available Abstract Hepatitis C virus (HCV causes acute and chronic hepatitis which can eventually lead to permanent liver damage, hepatocellular carcinoma and death. Currently, there is no vaccine available for prevention of HCV infection due to high degree of strain variation. The current treatment of care, Pegylated interferon α in combination with ribavirin is costly, has significant side effects and fails to cure about half of all infections. In this review, we summarize molecular virology, replication and immune responses against HCV and discussed how HCV escape from adaptive and humoral immune responses. This advance knowledge will be helpful for development of vaccine against HCV and discovery of new medicines both from synthetic chemistry and natural sources.

  8. An OPTIMIZE study retrospective analysis for management of telaprevir-treated hepatitis C virus (HCV)-infected patients by use of the Abbott RealTime HCV RNA assay.

    Science.gov (United States)

    Sarrazin, Christoph; Dierynck, Inge; Cloherty, Gavin; Ghys, Anne; Janssen, Katrien; Luo, Donghan; Witek, James; Buti, Maria; Picchio, Gaston; De Meyer, Sandra

    2015-04-01

    Protease inhibitor (PI)-based response-guided triple therapies for hepatitis C virus (HCV) infection are still widely used. Noncirrhotic treatment-naive and prior relapser patients receiving telaprevir-based treatment are eligible for shorter, 24-week total therapy if HCV RNA is undetectable at both weeks 4 and 12. In this study, the concordance in HCV RNA assessments between the Roche High Pure System/Cobas TaqMan and Abbott RealTime HCV RNA assays and the impacts of different HCV RNA cutoffs on treatment outcome were evaluated. A total of 2,629 samples from 663 HCV genotype 1 patients receiving telaprevir/pegylated interferon/ribavirin in OPTIMIZE were analyzed using the High Pure System and reanalyzed using Abbott RealTime (limits of detection, 15.1 IU/ml versus 8.3 IU/ml; limits of quantification, 25 IU/ml versus 12 IU/ml, respectively). Overall, good concordance was observed between the assays. Using undetectable HCV RNA at week 4, 34% of the patients would be eligible for shorter treatment duration with Abbott RealTime versus 72% with the High Pure System. However, using Abbott RealTime, a similar proportion (74%) would be eligible. Of the patients receiving 24-week total therapy, 87% achieved a sustained virologic response with undetectable HCV RNA by the High Pure System or Abbott RealTime; however, 92% of the patients with undetectable HCV RNA by Abbott RealTime achieved a sustained virologic response. Using undetectable HCV RNA as the cutoff, the more sensitive Abbott RealTime assay would identify fewer patients eligible for shorter treatment than the High Pure System. Our data confirm the Abbott RealTime assay, to determine eligibility for shortened PI-based HCV treatment. (The study was registered with ClinicalTrials.gov under registration no. NCT01241760.). Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  9. Comorbidades entre dependência química, distimia, HIV e HCV: relato de caso Comorbidity between addiction, dysthymia, HIV and HCV: case report

    Directory of Open Access Journals (Sweden)

    Vanessa Fabiane Machado Gomes Marsden

    2009-01-01

    Full Text Available INTRODUÇÃO: A comorbidade entre dependência química e doenças infectocontagiosas é bem conhecida, assim como a relação entre transtornos de humor e uso de substâncias. Entretanto, o transtorno distímico nestes pacientes recebe pouca atenção. Em parte, isso se justifica porque a realização do diagnóstico de distimia é mais difícil do que de outros transtornos do humor em razão do tempo de abstinência (2 anos necessário para o diagnóstico, tendo em vista que toxicodependentes apresentam diversas recaídas durante o curso de suas vidas. As infecções pelos vírus HIV e HCV, frequentemente associadas ao consumo injetável de substâncias, contribuem para alterações do estado mental e o próprio tratamento pode causar diversas flutuações no humor. RELATO DE CASO: O paciente é um homem de 40 anos de idade que apresenta comorbidade entre dependência química (heroína e álcool e distimia, complicada por recaídas, consumo injetável e status sorológico positivo aos vírus HIV-1 e HCV. CONCLUSÃO: Pacientes dependentes químicos com comorbidades psiquiátricas e infectocontagiosas são desafiadores no que tange diagnóstico, tratamento e definição de abordagens terapêuticas para os diferentes problemas apresentados. Investigar e abordar adequadamente, entretanto, traz diversos benefícios na qualidade de vida do indivíduo afetado, assim como potenciais benefícios financeiros.BACKGROUND: Comorbidity between chemical dependence and infectious diseases is well known, as is the relationship between mood disorders and substance misuse. Nevertheless, dysthymia in these patients is not well explored. That is partly justified since the diagnoses of dysthymia is more difficult than other mood disorders due to the abstinence time (2 years required for the diagnoses, and since addiction patients present several relapses during the course of their lifetimes. HIV and HCV infections, frequently associated to intravenous (IV drug use

  10. The Association between Female Genital Cutting and Spousal HCV Infection in Egypt

    Directory of Open Access Journals (Sweden)

    Chris R. Kenyon

    2014-01-01

    Full Text Available Objective. To identify the risk factors for HCV infection within married couples in Egypt. Methods. In 2008 Egypt conducted its first nationally representative survey of HCV prevalence. 11126 of the 12780 individuals aged 15–59 year who were sampled agreed to participate and provided information via a questionnaire about demographic and behavioural characteristics and blood for HCV antibody and RNA analysis. We assessed the risk factors for HCV infection in a subsample of 5182 married individuals via multivariate logistic regression. Results. Overall HCV antibody prevalence in the married couples was 18.2% (95% CI, 16.8–19.6. HCV antibody prevalence was higher in the husbands (23.7% than the wives (12.1%; P<0.001. Having a spouse who was infected with HCV was an independent risk factor for HCV infection with odds ratios of 2.1 (95% CI, 1.6–2.9 and 2.2 (95% CI, 1.6–3.1 for women and men, respectively. Husbands whose wives had experienced female genital cutting (FGC had a higher prevalence of HCV and this relationship was driven by a strong association in urban areas. Amongst the women there was no association between FGC and HCV overall but in urban areas only women who had experienced FGC were HCV infected. Conclusions. This study provides additional evidence of the importance of intrafamilial transmission of HCV in Egypt.

  11. Seroprevalence of HBV, HCV & HIV Co-Infection and Risk Factors Analysis in Tripoli-Libya

    Science.gov (United States)

    Daw, Mohamed A.; Shabash, Amira; El-Bouzedi, Abdallah; Dau, Aghnya A.

    2014-01-01

    Background In 1998 Libya experienced a major outbreak of multiple blood borne viral hepatitis and HIV infections. Since then, no studies have been done on the epidemic features and risk factors of HBV, HCV, HIV and co-infection among the general population. Methods A prospective study was carried out using a multi-centre clustering method to collect samples from the general population. The participants were interviewed, and relevant information was collected, including socio-demographic, ethnic, and geographic variables. This information was correlated with the risk factors involved in the transmission of HBV, HCV and HIV. Blood samples were collected and the sera were tested for HBsAg, anti-HCV and anti-HIV using enzyme immunoassay. Results A total of 9,170 participants from the nine districts of Tripoli were enrolled. The average prevalence of HBsAg was 3.7%, anti-HCV 0.9%, anti-HIV 0.15% and co-infection 0.02%. The prevalence varied from one district to another. HBV was more prevalent among those aged over 50 years and was associated with family history. Anti-HCV and anti-HIV were more prevalent among those aged 20–40 years. Intravenous drug use and blood transfusion were the main risk factors for HCV and HIV infection. Conclusion HBV, HCV, HIV and co-infection are relatively common in Libya. High prevalence was associated with geographic, ethnic and socioeconomic variability within the community. HCV and HIV infections among the younger age groups are becoming an alarming issue. Regulations and health care education need to be implemented and longer term follow-up should be planned. PMID:24936655

  12. Anti-HCV antibody among newly diagnosed HIV patients in Ughelli ...

    African Journals Online (AJOL)

    Background: Human immunodeficiency virus (HIV) and hepatitis C virus (HCV) share common routes of infection and ... drug users (IDU)7. HCV occurrence among people living with HIV has long been reported. This is of great medical impor- tance as 80% HCV infection are ..... before transfusion or organ transplantation.

  13. High awareness of hepatitis C virus (HCV) but limited knowledge of HCV complications among HIV-positive and HIV-negative men who have sex with men

    NARCIS (Netherlands)

    Lambers, Femke A. E.; Prins, Maria; Davidovich, Udi; Stolte, Ineke G.

    2014-01-01

    Hepatitis C virus (HCV) has emerged as a sexually transmitted infection among HIV-positive men who have sex with men (MSM) in high-income countries. Little is reported about HCV awareness among MSM, although this is essential for developing targeted prevention strategies. We, therefore, studied HCV

  14. Changes in epidemiological patterns of HCV infection and their impact on liver disease over the last 20 years in Greece.

    Science.gov (United States)

    Savvas, S P; Koskinas, J; Sinani, C; Hadziyannis, A; Spanou, F; Hadziyannis, S J

    2005-09-01

    The aim of this study was to investigate the relative frequency of hepatitis C virus (HCV) genotypes in Greek patients with chronic infection as well as possible secular changes in their distribution in relation to modes of transmission, age and time at acquisition of the infection and other variables. We evaluated 434 unselected patients, 241 males and 193 females with a median age of 46.2 years (18-75), with chronic HCV infection presenting during the period 1996-2000. HCV infection was confirmed by the detection of HCV-RNA by polymerase chain reaction (PCR), while HCV genotyping was performed by the Inno-LiPA assay. Liver biopsies were evaluated according to Ishak's scoring system. Of 434 patients, 167 had a history of blood transfusion [post-transfusion hepatitis (PTH)], 80 were i.v. drug users and in 187 the route of infection remained unknown. The overall distribution of HCV genotypes 1, 2, 3 and 4 was 47, 8.3, 27 and 15.2%, respectively. Genotype 3 was common in younger adults and i.v. drug users, whereas genotype 1 predominated in older people and PTH patients (P duration of infection (P = 0.013). Our study revealed a change of HCV genotype distribution in the last 20 years among Greek patients with chronic HCV infection as a result of epidemiological changes in HCV transmission. The presence of cirrhosis was associated only with the duration of infection. These observations have impact both on prevention and treatment.

  15. The impact of HCV therapy in a high HIV-HCV prevalence population: A modeling study on people who inject drugs in Ho Chi Minh City, Vietnam.

    Directory of Open Access Journals (Sweden)

    Ruthie B Birger

    Full Text Available Human Immunodeficiency Virus (HIV and Hepatitis C Virus (HCV coinfection is a major global health problem especially among people who inject drugs (PWID, with significant clinical implications. Mathematical models have been used to great effect to shape HIV care, but few have been proposed for HIV/HCV.We constructed a deterministic compartmental ODE model that incorporated layers for HIV disease progression, HCV disease progression and PWID demography. Antiretroviral therapy (ART and Methadone Maintenance Therapy (MMT scale-ups were modeled as from 2016 and projected forward 10 years. HCV treatment roll-out was modeled beginning in 2026, after a variety of MMT scale-up scenarios, and projected forward 10 years.Our results indicate that scale-up of ART has a major impact on HIV though not on HCV burden. MMT scale-up has an impact on incidence of both infections. HCV treatment roll-out has a measurable impact on reductions of deaths, increasing multifold the mortality reductions afforded by just ART/MMT scale-ups.HCV treatment roll-out can have major and long-lasting effects on averting PWID deaths on top of those averted by ART/MMT scale-up. Efficient intervention scale-up of HCV alongside HIV interventions is critical in Vietnam.

  16. A new HCV genotype 6 subtype designated 6v was confirmed with three complete genome sequences.

    Science.gov (United States)

    Wang, Yizhong; Xia, Xueshan; Li, Chunhua; Maneekarn, Niwat; Xia, Wenjie; Zhao, Wenhua; Feng, Yue; Kung, Hsiang Fu; Fu, Yongshui; Lu, Ling

    2009-03-01

    Although hepatitis C virus (HCV) genotype 6 is classified into 21 subtypes, 6a-6u, new variants continue to be identified. To characterize the full-length genomes of three novel HCV genotype 6 variants: KMN02, KM046 and KM181. From sera of patients with HCV infection, the entire HCV genome was amplified by RT-PCR followed by direct DNA sequencing and phylogenetic analysis. The sera contained HCV genomes of 9461, 9429, and 9461nt in length, and each harboured a single ORF of 9051nt. The genomes showed 95.3-98.1% nucleotide similarity to each other and 72.2-75.4% similarity to 23 genotype 6 reference sequences, which represent subtypes 6a-6u and unassigned variants km41 and gz52557. Phylogenetic analyses demonstrated that they were genotype 6, but were subtypically distinct. Based on the current criteria of HCV classification, they were designed to represent a new subtype, 6v. Analysis of E1 and NS5B region partial sequences revealed two additional related variants, CMBD-14 and CMBD-86 that had been previously reported in northern Thailand and sequences dropped into Genbank. Three novel HCV genotype 6 variants were entirely sequenced and designated subtype 6v.

  17. Persistence of Circulating Hepatitis C Virus Antigens-Specific Immune Complexes in Patients with Resolved HCV Infection.

    Science.gov (United States)

    Hu, Ke-Qin; Cui, Wei

    2018-05-01

    Our recent study indicated the possible presence of detectable hepatitis C virus antigens (HCV-Ags) after denaturation of sera with resolved HCV (R-HCV) infection. The present study determined and characterized persistent HCV-Ags-specific immune complexes (ICs) in these patients. Sixty-eight sera with R-HCV and 34 with viremic HCV (V-HCV) infection were tested for free and IC-bound HCV-Ags using HCV-Ags enzyme immunoassay (EIA), the presence of HCV-Ags-specific ICs by immunoprecipitation and Western blot (IP-WB), HCV ICs containing HCV virions using IP and HCV RNA RT-PCR, and correlation of HCV ICs with clinical presentation in these patients. Using HCV-Ags EIA, we found 57.4% of sera with R-HCV infection were tested positive for bound, but not free HCV-Ags. Using pooled or individual anti-HCV E1/E2, cAg, NS3, NS4b, and/or NS5a to precipitate HCV-specific-Ags, we confirmed persistent HCV-Ags ICs specific to various HCV structural and non-structural proteins not only in V-HCV infection, but also in R-HCV infection. Using IP and HCV RNA PCR, we then confirmed the presence of HCV virions within circulating ICs in V-HCV, but not in R-HCV sera. Multivariable analysis indicated significant and independent associations of persistent circulating HCV-Ags-specific ICs with both age and the presence of cirrhosis in patients with R-HCV infection. Various HCV-Ag-specific ICs, but not virions, persist in 57.4% of patients who had spontaneous or treatment-induced HCV clearance for 6 months to 20 years. These findings enriched our knowledge on HCV pathogenesis and support further study on its long-term clinical relevance, such as extrahepatic manifestation, transfusion medicine, and hepatocarcinogenesis.

  18. HCV core protein induces hepatic lipid accumulation by activating SREBP1 and PPARγ

    International Nuclear Information System (INIS)

    Kim, Kook Hwan; Hong, Sung Pyo; Kim, KyeongJin; Park, Min Jung; Kim, Kwang Jin; Cheong, JaeHun

    2007-01-01

    Hepatic steatosis is a common feature in patients with chronic hepatitis C virus (HCV) infection. HCV core protein plays an important role in the development of hepatic steatosis in HCV infection. Because SREBP1 (sterol regulatory element binding protein 1) and PPARγ (peroxisome proliferators-activated receptor γ) are involved in the regulation of lipid metabolism of hepatocyte, we sought to determine whether HCV core protein may impair the expression and activity of SREBP1 and PPARγ. In this study, it was demonstrated that HCV core protein increases the gene expression of SREBP1 not only in Chang liver, Huh7, and HepG2 cells transiently transfected with HCV core protein expression plasmid, but also in Chang liver-core stable cells. Furthermore, HCV core protein enhanced the transcriptional activity of SREBP1. In addition, HCV core protein elevated PPARγ transcriptional activity. However, HCV core protein had no effect on PPARγ gene expression. Finally, we showed that HCV core protein stimulates the genes expression of lipogenic enzyme and fatty acid uptake associated protein. Therefore, our finding provides a new insight into the mechanism of hepatic steatosis by HCV infection

  19. Psychiatric disorders, HIV infection and HIV/hepatitis co-infection in the correctional setting.

    Science.gov (United States)

    Baillargeon, J G; Paar, D P; Wu, H; Giordano, T P; Murray, O; Raimer, B G; Avery, E N; Diamond, P M; Pulvino, J S

    2008-01-01

    Psychiatric disorders such as bipolar disorder, schizophrenia and depression have long been associated with risk behaviors for HIV, hepatitis C virus (HCV) and hepatitis B virus (HBV). The US prison population is reported to have elevated rates of HIV, hepatitis and most psychiatric disorders. This study examined the association of six major psychiatric disorders with HIV mono-infection, HIV/HCV co-infection and HIV/HBV co-infection in one of the nation's largest prison populations. The study population consisted of 370,511 Texas Department of Criminal Justice inmates who were incarcerated for any duration between January 1, 2003 and July 1, 2006. Information on medical conditions and sociodemographic factors was obtained from an institution-wide electronic medical information system. Offenders diagnosed with HIV mono-infection, HIV/HCV, HIV/HBV and all HIV combined exhibited elevated rates of major depression, bipolar disorder, schizophrenia, schizoaffective disorder, non-schizophrenic psychotic disorder and any psychiatric disorder. In comparison to offenders with HIV mono-infection, those with HIV/HCV co-infection had an elevated prevalence of any psychiatric disorder. This cross-sectional study's finding of positive associations between psychiatric disease and both HIV infection and hepatitis co-infection among Texas prison inmates holds both clinical and public health relevance. It will be important for future investigations to examine the extent to which psychiatric disorders serve as a barrier to medical care, communication with clinicians and adherence to prescribed medical regimens among both HIV-mono-infected and HIV/hepatitis-co-infected inmates.

  20. frequency and risk factors for chronic HCV infection: a community based study

    International Nuclear Information System (INIS)

    Tahir, M.; Mustafa, G.; Khan, M.B.

    2011-01-01

    It was a community based, cross-sectional study undertaken to assess the frequency of HCV infection and to find out the risk factors associated with its spread. Methods: Study was carried out from Oct 2004 to Mar 2005. One hundred and twenty five apparently healthy consecutive subjects not known to be infected with HBV or HCV, between the ages 13 and 60 years with equal sex distribution were selected from the population of the Village Mera Kalan near Rawalpindi. They were screened for Anti HCV antibodies using ELISA and interviewed in detail. Subjects found positive for Anti HCV Ab were tested for ALT (Alanine aminotransferase) levels and HCV RNA by PCR. Results: The frequency of HCV was found to be 53.6%. The most important risk factor associated with the transmission of HCV infection was unsafe injection therapy with contaminated equipment. Other risk factors include ear and nose piercing by unsterilized means in females and sharing of razors in males. Conclusion: The prevalence of HCV infection in our population is significantly higher than in the developed world. Public awareness programs should target the identified risk factors to prevent HCV transmission. (author)

  1. Prevention of Human Lymphoproliferative Tumor Formation in Ovarian Cancer Patient-Derived Xenografts

    Directory of Open Access Journals (Sweden)

    Kristina A. Butler

    2017-08-01

    Full Text Available Interest in preclinical drug development for ovarian cancer has stimulated development of patient-derived xenograft (PDX or tumorgraft models. However, the unintended formation of human lymphoma in severe combined immunodeficiency (SCID mice from Epstein-Barr virus (EBV–infected human lymphocytes can be problematic. In this study, we have characterized ovarian cancer PDXs which developed human lymphomas and explore methods to suppress lymphoproliferative growth. Fresh human ovarian tumors from 568 patients were transplanted intraperitoneally in SCID mice. A subset of PDX models demonstrated atypical patterns of dissemination with mediastinal masses, hepatosplenomegaly, and CD45-positive lymphoblastic atypia without ovarian tumor engraftment. Expression of human CD20 but not CD3 supported a B-cell lineage, and EBV genomes were detected in all lymphoproliferative tumors. Immunophenotyping confirmed monoclonal gene rearrangements consistent with B-cell lymphoma, and global gene expression patterns correlated well with other human lymphomas. The ability of rituximab, an anti-CD20 antibody, to suppress human lymphoproliferation from a patient's ovarian tumor in SCID mice and prevent growth of an established lymphoma led to a practice change with a goal to reduce the incidence of lymphomas. A single dose of rituximab during the primary tumor heterotransplantation process reduced the incidence of CD45-positive cells in subsequent PDX lines from 86.3% (n = 117 without rituximab to 5.6% (n = 160 with rituximab, and the lymphoma rate declined from 11.1% to 1.88%. Taken together, investigators utilizing PDX models for research should routinely monitor for lymphoproliferative tumors and consider implementing methods to suppress their growth.

  2. Current and future disease progression of the chronic HCV population in the United States.

    Science.gov (United States)

    Zalesak, Martin; Francis, Kevin; Gedeon, Alex; Gillis, John; Hvidsten, Kyle; Kidder, Phyllis; Li, Hong; Martyn, Derek; Orne, Leslie; Smith, Amanda; Kwong, Ann

    2013-01-01

    Chronic hepatitis C virus (HCV) infection can lead to advanced liver disease (AdvLD), including cirrhosis, decompensated cirrhosis, and liver cancer. The aim of this study was to determine recent historical rates of HCV patient progression to AdvLD and to project AdvLD prevalence through 2015. We first determined total 2008 US chronic HCV prevalence from the National Health and Nutrition Evaluation Surveys. Next, we examined disease progression and associated non-pharmacological costs of diagnosed chronic HCV-infected patients between 2007-2009 in the IMS LifeLink and CMS Medicare claims databases. A projection model was developed to estimate AdvLD population growth through 2015 in patients diagnosed and undiagnosed as of 2008, using the 2007-2009 progression rates to generate a "worst case" projection of the HCV-related AdvLD population (i.e., scenario where HCV treatment is the same in the forecasted period as it was before 2009). We found that the total diagnosed chronic HCV population grew from 983,000 to 1.19 million in 2007-2009, with patients born from 1945-1964 accounting for 75.0% of all patients, 83.7% of AdvLD patients, and 79.2% of costs in 2009, indicating that HCV is primarily a disease of the "baby boomer" population. Non-pharmacological costs grew from $7.22 billion to $8.63 billion, with the majority of growth derived from the 60,000 new patients that developed AdvLD in 2007-2009, 91.5% of whom were born between 1945 and 1964. The projection model estimated the total AdvLD population would grow from 195,000 in 2008 to 601,000 in 2015, with 73.5% of new AdvLD cases from patients undiagnosed as of 2008. AdvLD prevalence in patients diagnosed as of 2008 was projected to grow 6.5% annually to 303,000 patients in 2015. These findings suggest that strategies to diagnose and treat HCV-infected patients are urgently needed to increase the likelihood that progression is interrupted, particularly for patients born from 1945-1964.

  3. The design of drugs for HIV and HCV.

    Science.gov (United States)

    De Clercq, Erik

    2007-12-01

    Since the discovery of the human immunodeficiency virus (HIV) in 1983, dramatic progress has been made in the development of novel antiviral drugs. The HIV epidemic fuelled the development of new antiviral drug classes, which are now combined to provide highly active antiretroviral therapies. The need for the treatment of hepatitis C virus (HCV), which was discovered in 1989, has also provided considerable impetus for the development of new classes of antiviral drugs, and future treatment strategies for chronic HCV might involve combination regimens that are analogous to those currently used for HIV. By considering the drug targets in the different stages of the life cycle of these two viruses, this article presents aspects of the history, medicinal chemistry and mechanisms of action of approved and investigational drugs for HIV and HCV, and highlights general lessons learned from anti-HIV-drug design that could be applied to HCV.

  4. Quantitation of HCV RNA in liver of patients with chronic hepatitis C Quantificação do RNA-HCV no fígado de pacientes com hepatite C crônica

    Directory of Open Access Journals (Sweden)

    Ana de Lôurdes Candolo MARTINELLI

    2000-10-01

    Full Text Available Background/Aims - Liver HCV RNA has been quantitated in few studies and the feasibility and the role of this parameter in the evaluation of patients with chronic HCV hepatitis still warrant study. Our aim was to determine the concentrations of HCV RNA in the liver of chronic HCV patients and to correlate the results with serum viral load. We also studied the relation of levels of HCV RNA in the liver with serum aminotransferases levels and with the presence of cirrhosis. Methods - Twenty patients (14 males, aged 28 to 61 years were studied. Twelve were infected by HCV type 1, six by type 3 and one by type 5. Percutaneous liver biopsy samples were obtained from 14 patients, and the remainder from liver explant in patients undergoing OLT. Twelve had chronic hepatitis and eight cirrhosis. HCV RNA levels were determined by bDNA. Results - HCV RNA levels below the detection limit were found in one liver and in five serum samples. HCV RNA (mean ± SD was 2.1 x 10(8 ± 2.2 x 10(8Eq/gm in the liver and 94 x 10(5 ± 93 x 10(5Eq/mL in serum, with a significant correlation between these values (r = 0.89; P Introdução/Objetivos - Poucos estudos avaliam a quantificação do RNA-HCV no fígado, portanto a praticabilidade e a aplicação desse parâmetro na avaliação de pacientes com hepatite C crônica ainda não estão definidas. O objetivo foi determinar as concentrações do RNA-HCV no fígado de pacientes com infecção crônica pelo vírus C da hepatite e correlacionar os resultados com a carga viral do soro. Foram também estudadas a relação dos níveis de RNA-HCV no fígado com os de aminotransferases no soro e com a presença de cirrose. Métodos - Foram estudados 20 pacientes (14 homens, 28 a 61 anos. A genotipagem do vírus da hepatite C revelou: tipo 1 (12 pacientes, tipo 3 (6 pacientes , tipo 5 (1 paciente. Amostras de fígado foram obtidas por via percutânea em 14 pacientes e de explantes de fígado de pacientes submetidos a transplante em

  5. HLA antigens and post renal transplant lymphoproliferative disease : HLA-B matching is critical

    NARCIS (Netherlands)

    Bakker, N.A.; van Imhoff, G.W.; Verschuuren, E.A.M.; van Son, W.J.; van der Heide, J.J.H.; Lems, S.P.M.; Veeger, N.J.G.M.; Kluin, P.M.; Kluin-Nelemans, Hanneke; Hepkema, B.G.

    2005-01-01

    Although several risk factors for posttransplant lymphoproliferative disease (PTLD) after solid organ transplantation have been identified, the immunosuppressive regimen probably as most important one, their exact pathogenic role and relevance is still unclear. In hematopoietic stem cell

  6. Hepatic steatosis progresses faster in HIV mono-infected than HIV/HCV co-infected patients and is associated with liver fibrosis.

    Science.gov (United States)

    Pembroke, Thomas; Deschenes, Marc; Lebouché, Bertrand; Benmassaoud, Amine; Sewitch, Maida; Ghali, Peter; Wong, Philip; Halme, Alex; Vuille-Lessard, Elise; Pexos, Costa; Klein, Marina B; Sebastiani, Giada

    2017-10-01

    Hepatic steatosis (HS) seems common in patients infected with human immunodeficiency virus (HIV). However, the relative effect of HIV, as well as hepatitis C virus (HCV) in those co-infected, and the influence of HS on liver fibrosis progression are unclear. The LIVEr disease in HIV (LIVEHIV) is a Canadian prospective cohort study using transient elastography and associated controlled attenuation parameter (CAP) to screen for HS and liver fibrosis, in unselected HIV-infected adults. HS progression was defined as development of any grade HS (CAP ⩾248dB/m), or transition to severe HS (CAP >292dB/m), for those with any grade HS at baseline. Fibrosis progression was defined as development of significant liver fibrosis (liver stiffness measurement [LSM] >7.1kPa), or transition to cirrhosis (LSM >12.5kPa) for those with significant liver fibrosis at baseline. Cox regression analysis was used to assess predictors of HS and fibrosis progression. A prospective cohort study was conducted, which included 726 HIV-infected patients (22.7% HCV co-infected). Prevalence of any grade HS did not differ between HIV mono-infected and HIV/HCV co-infected patients (36.1% vs. 38.6%, respectively). 313 patients were followed for a median of 15.4 (interquartile range 8.5-23.0) months. The rate of HS progression was 37.8 (95% confidence interval [CI] 29.2-49.0) and 21.9 (95% CI 15.6-30.7) per 100 person-years in HIV mono-infection and HIV/HCV co-infection, respectively. HCV co-infection was an independent negative predictor of HS progression (adjusted hazard ratio [aHR] 0.50, 95% CI 0.28-0.89). HS predicted liver fibrosis progression in HIV mono-infection (aHR 4.18, 95% CI 1.21-14.5), but not in HIV/HCV co-infection. HS progresses faster and is associated with liver fibrosis progression in HIV mono-infection but not in HIV/HCV co-infection. Lay summary: Fatty liver is the most frequent liver disease in Western countries. People living with HIV seem at high risk of fatty liver due to

  7. Molecular Mechanisms of Liver Fibrosis in HIV/HCV Coinfection

    Directory of Open Access Journals (Sweden)

    Claudio M. Mastroianni

    2014-05-01

    Full Text Available Chronic hepatitis C virus (HCV infection is an important cause of morbidity and mortality in people coinfected with human immunodeficiency virus (HIV. Several studies have shown that HIV infection promotes accelerated HCV hepatic fibrosis progression, even with HIV replication under full antiretroviral control. The pathogenesis of accelerated hepatic fibrosis among HIV/HCV coinfected individuals is complex and multifactorial. The most relevant mechanisms involved include direct viral effects, immune/cytokine dysregulation, altered levels of matrix metalloproteinases and fibrosis biomarkers, increased oxidative stress and hepatocyte apoptosis, HIV-associated gut depletion of CD4 cells, and microbial translocation. In addition, metabolic alterations, heavy alcohol use, as well drug use, may have a potential role in liver disease progression. Understanding the pathophysiology and regulation of liver fibrosis in HIV/HCV co-infection may lead to the development of therapeutic strategies for the management of all patients with ongoing liver disease. In this review, we therefore discuss the evidence and potential molecular mechanisms involved in the accelerated liver fibrosis seen in patients coinfected with HIV and HCV.

  8. Prevalence and Incidence of HCV Infection among Prisoners in Central Brazil.

    Directory of Open Access Journals (Sweden)

    Marco Antonio Moreira Puga

    Full Text Available The aim of this multicenter, cross sectional study was to assess the prevalence, incidence and associated risk factors among incarcerated populations from twelve Brazilian prisons. The total of 3,368 individuals from twelve prisons was randomly recruited between March 2013 and March 2014. Participants were interviewed, and provided blood samples which were tested for antibodies to Hepatitis C (HCV ab. One year after the first investigation, a cohort study was conducted with 1,656 inmates who participated the cross sectional study. Positive samples were tested for the presence of HCV RNA. Out of 3,368 inmates, 520 (15.4% were females, and 2,848 (84.6% were males. The overall prevalence of HCV was 2.4% (95% CI: 1.9 to 2.9, with 0.6% (95% CI: 0.4 to 0.8 in females, and 2.7% (95% CI: 2.1 to 3.3 in males (p<0.01. HCV RNA was detected in 51/80 (63.7% samples. Among men prisoners, multivariate analysis of associated factors showed independent associations between HCV exposure and increasing age, inject drug use, length of incarceration, smoking hashish, sharing needle and syringe and HIV positivity. During the cohort study, 7/1,656 new cases of HCV infection were detected, and the incidence rate was 0.4/100 person-year. Once high frequency rates of specific HCV risk behaviors and new HCV infections have been identified inside prisons, effective interventions strategies such as screening, clinical evaluation and treatment to reduce the spread of HCV infection are essential.

  9. What Are Related Disorders?

    Science.gov (United States)

    ... The Marfan Foundation Marfan & Related Disorders What is Marfan Syndrome? What are Related Disorders? What are the Signs? ... Contact Us Donate Marfan & Related Disorders What is Marfan Syndrome? What are Related Disorders? What are the Signs? ...

  10. HCV core protein promotes hepatocyte proliferation and chemoresistance by inhibiting NR4A1

    Energy Technology Data Exchange (ETDEWEB)

    Tan, Yongsheng, E-mail: yongshengtanwhu@126.com; Li, Yan, E-mail: liyansd2@163.com

    2015-10-23

    This study investigated the effect of HCV core protein on the proliferation of hepatocytes and hepatocellular carcinoma cells (HCC), the influence of HCV core protein on HCC apoptosis induced by the chemotherapeutic agent cisplatin, and the mechanism through which HCV core protein acts as a potential oncoprotein in HCV-related HCC by measuring the levels of NR4A1 and Runt-related transcription factor 3 (RUNX3), which are associated with tumor suppression and chemotherapy resistance. In the present study, PcDNA3.1-core and RUNX3 siRNA were transfected into LO2 and HepG2 cells using Lipofectamine 2000. LO2-core, HepG2-core, LO2-RUNX3 {sup low} and control cells were treated with different concentrations of cisplatin for 72 h, and cell proliferation and apoptosis were assayed using the CellTiter 96{sup ®}Aqueous Non-Radioactive Cell Proliferation Assay Kit. Western blot and real time PCR analyses were used to detect NR4A1, RUNX3, smad7, Cyclin D1 and BAX. Confocal microscopy was used to determine the levels of NR4A1 in HepG2 and HepG2-core cells. The growth rate of HepG2-core cells was considerably greater than that of HepG2 cells. HCV core protein increased the expression of cyclin D1 and decreased the expressions of NR4A1 and RUNX3. In LO2 – RUNX3 {sup low}, the rate of cell proliferation and the level of cisplatin resistance were the same as in the LO2 -core. These results suggest that HCV core protein decreases the sensitivity of hepatocytes to cisplatin by inhibiting the expression of NR4A1 and promoting the expression of smad7, which negatively regulates the TGF-β pathway. This effect results in down regulation of RUNX3, a target of the TGF-β pathway. Taken together, these findings indicate that in hepatocytes, HCV core protein increases drug resistance and inhibits cell apoptosis by inhibiting the expressions of NR4A1 and RUNX3. - Highlights: • HCV core protein inhibits HepG2 cell sensitivity to cisplatin. • Core expression in HepG2 decreases

  11. HCV core protein promotes hepatocyte proliferation and chemoresistance by inhibiting NR4A1

    International Nuclear Information System (INIS)

    Tan, Yongsheng; Li, Yan

    2015-01-01

    This study investigated the effect of HCV core protein on the proliferation of hepatocytes and hepatocellular carcinoma cells (HCC), the influence of HCV core protein on HCC apoptosis induced by the chemotherapeutic agent cisplatin, and the mechanism through which HCV core protein acts as a potential oncoprotein in HCV-related HCC by measuring the levels of NR4A1 and Runt-related transcription factor 3 (RUNX3), which are associated with tumor suppression and chemotherapy resistance. In the present study, PcDNA3.1-core and RUNX3 siRNA were transfected into LO2 and HepG2 cells using Lipofectamine 2000. LO2-core, HepG2-core, LO2-RUNX3 "l"o"w and control cells were treated with different concentrations of cisplatin for 72 h, and cell proliferation and apoptosis were assayed using the CellTiter 96"®Aqueous Non-Radioactive Cell Proliferation Assay Kit. Western blot and real time PCR analyses were used to detect NR4A1, RUNX3, smad7, Cyclin D1 and BAX. Confocal microscopy was used to determine the levels of NR4A1 in HepG2 and HepG2-core cells. The growth rate of HepG2-core cells was considerably greater than that of HepG2 cells. HCV core protein increased the expression of cyclin D1 and decreased the expressions of NR4A1 and RUNX3. In LO2 – RUNX3 "l"o"w, the rate of cell proliferation and the level of cisplatin resistance were the same as in the LO2 -core. These results suggest that HCV core protein decreases the sensitivity of hepatocytes to cisplatin by inhibiting the expression of NR4A1 and promoting the expression of smad7, which negatively regulates the TGF-β pathway. This effect results in down regulation of RUNX3, a target of the TGF-β pathway. Taken together, these findings indicate that in hepatocytes, HCV core protein increases drug resistance and inhibits cell apoptosis by inhibiting the expressions of NR4A1 and RUNX3. - Highlights: • HCV core protein inhibits HepG2 cell sensitivity to cisplatin. • Core expression in HepG2 decreases expression of NR4A1

  12. Role of ribavirin in HCV treatment response: now and in the future.

    Science.gov (United States)

    Jain, Mamta K; Zoellner, Cindy

    2010-03-01

    Ribavirin is a broad spectrum antiviral agent that is used with pegylated IFN (Peg-IFN) for HCV treatment. Ribavirin does not significantly reduce HCV viral load when used alone but increases rates of sustained virologic response (SVR) when combined with Peg-IFN. HCV genotype 1 infected patients require higher doses of ribavirin administered for a longer duration of time versus HCV genotypes 2 and 3 patients who respond effectively to Peg-IFN with lower doses of ribavirin and shorter duration of therapy. Higher serum concentrations of ribavirin are associated with higher response rates but also higher rates of hemolytic anemia which is a dose limiting side effect. Alternatives to current therapy are under clinical evaluation. Systematic literature review of ribavirin use in HCV patients from 1995 to 2009 was conducted. To review the efficacy and safety of ribavirin in current HCV treatment and in new therapies in Phase III clinical trials. Ribavirin is a drug which is essential to produce higher SVR rates both with Peg-IFN and HCV protease inhibitors currently in Phase III clinical trials. Thus, ribavirin is and will remain an important drug to achieving higher SVR rates in HCV infected persons.

  13. A novel fibrosis index comprising a non-cholesterol sterol accurately predicts HCV-related liver cirrhosis.

    Directory of Open Access Journals (Sweden)

    Magdalena Ydreborg

    Full Text Available Diagnosis of liver cirrhosis is essential in the management of chronic hepatitis C virus (HCV infection. Liver biopsy is invasive and thus entails a risk of complications as well as a potential risk of sampling error. Therefore, non-invasive diagnostic tools are preferential. The aim of the present study was to create a model for accurate prediction of liver cirrhosis based on patient characteristics and biomarkers of liver fibrosis, including a panel of non-cholesterol sterols reflecting cholesterol synthesis and absorption and secretion. We evaluated variables with potential predictive significance for liver fibrosis in 278 patients originally included in a multicenter phase III treatment trial for chronic HCV infection. A stepwise multivariate logistic model selection was performed with liver cirrhosis, defined as Ishak fibrosis stage 5-6, as the outcome variable. A new index, referred to as Nordic Liver Index (NoLI in the paper, was based on the model: Log-odds (predicting cirrhosis = -12.17+ (age × 0.11 + (BMI (kg/m(2 × 0.23 + (D7-lathosterol (μg/100 mg cholesterol×(-0.013 + (Platelet count (x10(9/L × (-0.018 + (Prothrombin-INR × 3.69. The area under the ROC curve (AUROC for prediction of cirrhosis was 0.91 (95% CI 0.86-0.96. The index was validated in a separate cohort of 83 patients and the AUROC for this cohort was similar (0.90; 95% CI: 0.82-0.98. In conclusion, the new index may complement other methods in diagnosing cirrhosis in patients with chronic HCV infection.

  14. Seroprevalence of Anti-HCV Antibody in Patients with Chronic Kidney Disease before Starting Dialysis Therapy

    Directory of Open Access Journals (Sweden)

    Fareha Jesmin Rabbi

    2017-01-01

    Full Text Available Background: Hepatitis C virus (HCV infection and chronic kidney disease are common and potentially serious medical problems throughout the world. In recent years, it has become clear that these two conditions are linked in several important ways. Indeed, some forms of renal diseases are precipitated by HCV infection and patients with end-stage renal disease (ESRD are at increased risk for acquiring HCV infection. Patients with chronic kidney disease typically show an impaired immune response compared with healthy individuals and also other risk factors related with treatment and management. CKD patients ultimately undergo end stage renal therapy like dialysis for their treatment and survival. Risk factors for the infections are more in dialysis period than in predialytic stages. Like other developing countries CKD patients with HCV infection are very common in our country. For this reason the CKD patients should be properly diagnosed knowing the infection status before dialysis which would help both the patient and doctor to choose their proper treatment approach. Objective: This cross-sectional study was done to know the prevalence of HCV infection in the CKD patients before starting dialysis therapy. Materials and Methods: A total of 197 patients with chronic kidney disease stage five (CKD-V before starting dialysis therapy were included as subjects of this study. Among the CKD patients anti-HCV was detected to see prevalence of hepatitis C virus infection. The patients were also tested for HBsAg to assess co-infection. After collecting all the data of different test results analyses were done by SPSS version 15.0. Results: In this study 195 (99% patients were anti-HCV negative and only two patients (1% were found positive. Conclusion: HCV infection in CKD patients before dialysis should be taken into account so that HCV negative CKD patients would not get the infection during dialysis and standard screening procedures should be taken to

  15. Expression of chimeric HCV peptide in transgenic tobacco plants ...

    African Journals Online (AJOL)

    Expression of chimeric HCV peptide in transgenic tobacco plants infected with recombinant alfalfa mosaic virus for development of a plant-derived vaccine against HCV. AK El Attar, AM Shamloul, AA Shalaby, BY Riad, A Saad, HM Mazyad, JM Keith ...

  16. Active hepatitis C infection and HCV genotypes prevalent among the IDUs of Khyber Pakhtunkhwa

    Directory of Open Access Journals (Sweden)

    Uz Zaman Khaleeq

    2011-06-01

    Full Text Available Abstract Injection drug users (IDUs are considered as a high risk group to develop hepatitis C due to needle sharing. In this study we have examined 200 injection drug users from various regions of the Khyber Pakhtunkhwa province for the prevalence of active HCV infection and HCV genotypes by Immunochromatographic assays, RT-PCR and Type-specific PCR. Our results indicated that 24% of the IDUs were actively infected with HCV while anti HCV was detected among 31.5% cases. Prevalent HCV genotypes were HCV 2a, 3a, 4 and 1a. Majority of the IDUs were married and had attained primary or middle school education. 95% of the IDUs had a previous history of needle sharing. Our study indicates that the rate of active HCV infection among the IDUs is higher with comparatively more prevalence of the rarely found HCV types in KPK. The predominant mode of HCV transmission turned out to be needle sharing among the IDUs.

  17. Analytical and clinical performance of the Hologic Aptima HCV Quant Dx Assay for the quantification of HCV RNA in plasma samples

    DEFF Research Database (Denmark)

    Schønning, Kristian; Pedersen, Martin Schou; Johansen, Kim

    2017-01-01

    obtained from 13 patients undergoing treatment with DAAs. RESULTS: Deming regression of results from 187 plasma samples with HCV RNA >2 Log IU/mL indicated that the Aptima assay quantified higher than the CAPCTMv2 test for HCV RNA >4.9 Log IU/mL. The linearity of the Aptima assay was excellent across...

  18. Performance of ARCHITECT HCV core antigen test with specimens from US plasma donors and injecting drug users.

    Science.gov (United States)

    Mixson-Hayden, Tonya; Dawson, George J; Teshale, Eyasu; Le, Thao; Cheng, Kevin; Drobeniuc, Jan; Ward, John; Kamili, Saleem

    2015-05-01

    Hepatitis C virus (HCV) core antigen is a serological marker of current HCV infection. The aim of this study was mainly to evaluate the performance characteristics of the ARCHITECT HCV core antigen assay with specimens from US plasma donors and injecting drug users. A total of 551 serum and plasma samples with known anti-HCV and HCV RNA status were tested for HCV core antigen using the Abbott ARCHITECT HCV core antigen test. HCV core antigen was detectable in 100% of US plasma donor samples collected during the pre-seroconversion phase of infection (anti-HCV negative/HCV RNA positive). Overall sensitivity of the HCV core antigen assay was 88.9-94.3% in samples collected after seroconversion. The correlation between HCV core antigen and HCV RNA titers was 0.959. HCV core antigen testing may be reliably used to identify current HCV infection. Published by Elsevier B.V.

  19. 21 CFR 610.47 - Hepatitis C virus (HCV) “lookback” requirements.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 7 2010-04-01 2010-04-01 false Hepatitis C virus (HCV) âlookbackâ requirements... Disease Agents § 610.47 Hepatitis C virus (HCV) “lookback” requirements. (a) If you are an establishment... after a donor tests reactive for evidence of hepatitis C virus (HCV) infection when tested under § 610...

  20. PRO-C3-levels in patients with HIV/HCV-Co-infection reflect fibrosis stage and degree of portal hypertension

    DEFF Research Database (Denmark)

    Jansen, Christian; Leeming, Diana J; Mandorfer, Mattias

    2014-01-01

    BACKGROUND: Liver-related deaths represent the leading cause of mortality among patients with HIV/HCV-co-infection, and are mainly related to complications of fibrosis and portal hypertension. In this study, we aimed to evaluate the structural changes by the assessment of extracellular matrix (ECM......) derived degradation fragments in peripheral blood as biomarkers for fibrosis and portal hypertension in patients with HIV/HCV co-infection. METHODS: Fifty-eight patients (67% male, mean age: 36.5 years) with HIV/HCV-co-infection were included in the study. Hepatic venous pressure gradient (HVPG......4M and C5M levels were higher in patients with portal hypertension (HVPG>5 mmHg). CONCLUSION: PRO-C3 levels reflect liver injury, stage of liver fibrosis and degree of portal hypertension in HIV/HCV-co-infected patients. Furthermore, C4M and C5M were associated with increased portal pressure...

  1. Novel Electron Spin Resonance-Enzyme Immunosorbent Assay for Detecting Occult Hepatitis B Infection in HCV Chronic Liver Disease

    Directory of Open Access Journals (Sweden)

    Hala Badawi

    2017-11-01

    Full Text Available Background: Hepatitis B virus infection in patients who lack detectable hepatitis B surface antigen (HBsAg is called occult hepatitis B infection (OHB. The very low level of HBV genome may hamper its detection by molecular techniques. Recently, a highly sensitive EIA utilizing a novel modified electron spin resonance (ESR technique (modified ESR-EIA was developed to detect HBsAg by measuring stabilized nitroxide radicals. Aim: to detect occult HBV infection, using ESR-EIA among HCV-related chronic liver disease (CLD Egyptian patients who were seronegative for HBsAg by standard EIA. Methods: The study was conducted on two periods of time; in 1st period, 72 inpatients in Tropical Medicine Department of TBRI, were enrolled in the study. They were divided into two groups; 44 seropositive anti-HCV patients (Group I, 28 seronegative anti-HCV patients (Group II. Sera were subjected to virological assays for HBsAg, HBeAg, anti-HBc IgM, anti-HBc IgG, anti-HBs, anti-HCV and HCV RNA. We also examined serum HBV DNA by polymerase chain reaction (PCR technique and real-time detection polymerase chain reaction (RTD-PCR. In the 2nd period; modified ESR-EIA was applied on 32 TBRI inpatients, 23 in Tropical Medicine Department (Group I and 9 from hemodialysis unit (Group II with HCV-related CLD. Results: OHB was detected in 18.1% and 86.9% of our patients in 2002 and 2006 respectively. In phase 1, there was a higher detection rate among HCV patients in Group I (25% than Group II (7%, with higher prevalence (52.4% in patients with positive HCV RNA in Group I versus those with negative HCV viremia (8% in Group II. HBV DNA by either PCR or RTD-PCR was negative in all patients of both groups as the HBV viral load of the samples were below detectable level of the methods used; less than 100 copies/ml. None of 9 hemodialysis patients were positive for OHB. Conclusion: The newly developed quantitative ESR-EIA technique represents a great evolution for screening and

  2. T(14;18) is Not Associated with Mixed Cryoglobulinemia or with Clonal B Cell Expansion in Egyptian Patients with Hepatitis C Virus Infection

    International Nuclear Information System (INIS)

    ABBAS, O.M.; OMAR, N.A.; HASSAN, Z.K.

    2008-01-01

    Background/Aim: The mechanisms of B-cell lymphoproliferative disorders in chronic hepatitis C virus (Hv) infection are unclear. An increased prevalence of circulating monoclonal B-cells and t(14;18) has been reported. Geographic heterogeneity of prevalence of t(14;18) has been shown to exist. We investigated the prevalence of t(14;18) and B-cell clonality as possible mechanisms of lymphoma genesis in chronic HCV patients, in whom cryoglobulinemia status was previously detected. Methods: A cohort of 111 patients was studied, including 87 patients with chronic HCV disease (18 cryoglobulinemic and 69 non- cryoglobulinemic); 24 HCV negative, cryoglobulin negative patients with other nonimmune chronic liver diseases were enrolled as controls. The t(14;18) and IgH rearrangement (as a marker of B cell clonality) were detected by the polymerase chain reaction. Results: t(14;18) was detected in 27.6% of HCV patients and in none of the controls. Detection rates were comparable in both cryoglobulin-positive and negative groups (22.2% and 29%, respectively), p=0.769. IgH rearrangement was detected in 39.1% of HCV patients and in none of the controls. The cryo globulin-positive group showed significantly higher prevalence of IgH rearrangement compared to the cryoglobulin-negative group (61.1% and 33.3%, respectively), p=0.03, OR=3.13 and 95% CI=1.07-9.17. t(14;18) and monoclonal IgH rearrangement detection rates were not associated with each other, p=0.467. Conclusion: t(14;18) is uncommon in HCV-mixed cryogoblulinemia Egyptian patients; it does not seem to play a role in HCV-associated MC and lymphoma genesis in our geographical area. HCV may play a role in mixed cryogoblulinemia and lymphoma genesis, probably by inducing clonal B-cell expansions.

  3. Evaluation of the Abbott Real Time HCV genotype II assay for Hepatitis C virus genotyping.

    Science.gov (United States)

    Sariguzel, Fatma Mutlu; Berk, Elife; Gokahmetoglu, Selma; Ercal, Baris Derya; Celik, Ilhami

    2015-01-01

    The determination of HCV genotypes and subtypes is very important for the selection of antiviral therapy and epidemiological studies. The aim of this study was to evaluate the performance of Abbott Real Time HCV Genotype II assay in HCV genotyping of HCV infected patients in Kayseri, Turkey. One hundred patients with chronic hepatitis C admitted to our hospital were evaluated between June 2012 and December 2012, HCV RNA levels were determined by the COBAS® AmpliPrep/COBAS® TaqMan® 48 HCV test. HCV genotyping was investigated by the Abbott Real Time HCV Genotype II assay. With the exception of genotype 1, subtypes of HCV genotypes could not be determined by Abbott assay. Sequencing analysis was used as the reference method. Genotypes 1, 2, 3 and 4 were observed in 70, 4, 2 and 24 of the 100 patients, respectively, by two methods. The concordance between the two systems to determine HCV major genotypes was 100%. Of 70 patients with genotype 1, 66 showed infection with subtype 1b and 4 with subtype 1a by Abbott Real Time HCV Genotype II assay. Using sequence analysis, 61 showed infection with subtype 1b and 9 with subtype 1a. In determining of HCV genotype 1 subtypes, the difference between the two methods was not statistically significant (P>0.05). HCV genotype 4 and 3 samples were found to be subtype 4d and 3a, respectively, by sequence analysis. There were four patients with genotype 2. Sequence analysis revealed that two of these patients had type 2a and the other two had type 2b. The Abbott Real Time HCV Genotype II assay yielded results consistent with sequence analysis. However, further optimization of the Abbott Real Time HCV Genotype II assay for subtype identification of HCV is required.

  4. Utility of the Abbott RealTime HCV Genotype Plus RUO assay used in combination with the Abbott RealTime HCV Genotype II assay.

    Science.gov (United States)

    He, Chao; Germer, Jeffrey J; Ptacek, Elizabeth R; Bommersbach, Carl E; Mitchell, P Shawn; Yao, Joseph D C

    Hepatitis virus C (HCV) genotype (GT) determination and subtype (ST) differentiation (1a versus 1b) remain important for the selection of appropriate direct-acting antiviral (DAA) therapy. This study is a retrospective comparison of HCV GT and ST result distribution when using the Abbott RealTime HCV Genotype II assay (HCVGT II) alone and in combination with the Abbott RealTime HCV Genotype Plus RUO assay (HCVGT Plus) for routine testing of clinical serum specimens at a reference laboratory. HCVGT II results of specimens tested from June 2014 through January 2016 (period 1) were compared with combined results from HCVGT II and HCVGT Plus (HCVGT II/Plus) performed from January 2016 through January 2017 (period 2). A total of 44,127 and 25,361 specimens were tested during periods 1 and 2, respectively. Use of HCVGT II/Plus significantly reduced the frequency of GT 1 results without ST (0.4%) when compared to preliminary HCVGT II results during period 2 (5.3%; p < 0.01) and final HCVGT II results in period 1 (5.5%; p < 0.01). HCVGT II/Plus also resulted in GT 6 reactivity in 38 specimens with results of "HCV detected" (n = 17) or GT 1 (n = 21) following initial HCVGT II testing during period 2. When compared to the use of HCVGT II alone, HCVGT II/Plus significantly reduced the frequency of GT 1 without ST results observed in a large reference laboratory, while also enabling the identification of HCV GT 6. Copyright © 2018 Elsevier B.V. All rights reserved.

  5. Clonality assessment of lymphoproliferative lesions using the polymerase chain reaction: An analysis of two methods

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    Nikhil Moorchung

    2011-01-01

    Full Text Available Background: Lymphoid malignancies are a heterogeneous group of disorders which may be difficult to differentiate from reactive proliferations even after immunohistochemistry. Polymerase chain reaction (PCR is believed to be a good adjunct tool for diagnosis. Materials and Methods: We examined 24 cases of neoplastic and non-neoplastic lymphoproliferative lesions in this study and evaluated the PCR as an additional tool in the confirmation of the diagnosis. Two different PCR methodologies were evaluated. Results: In the evaluation of the T-cell PCR, it was seen that the correlation using both the commercial kits and the custom-synthesized primers was highly significant at a P value of 0.05. Conclusions: Both the methods showed an excellent concordance for T-cell γ gene rearrangements, However, the same was not seen in the B-cell receptor rearrangements. This may be because of the small sample size or the inability of consensus V primers to recognize complementary DNA sequences in all of the V segments.

  6. Undetectable hepatitis C virus RNA during syphilis infection in two HIV/HCV-co-infected patients

    DEFF Research Database (Denmark)

    Salado-Rasmussen, Kirsten; Knudsen, Andreas; Krarup, Henrik Bygum

    2014-01-01

    BACKGROUND: Treponema pallidum, the causative agent of syphilis, elicits a vigorous immune response in the infected host. This study sought to describe the impact of syphilis infection on hepatitis C virus (HCV) RNA levels in patients with HIV and chronic HCV infection. METHODS: Patients......-α), interferon gamma (IFN-γ), and IFN-γ-inducible protein 10 kDa (IP-10). RESULTS: Undetectable HCV RNA at the time of early latent syphilis infection was observed in 2 patients with HIV and chronic HCV infection. After treatment of the syphilis infection, HCV RNA levels increased again in patient 1, whereas...... patient 2 initiated HCV therapy and remained HCV RNA-negative. Available plasma samples obtained before and after the episode with undetectable HCV RNA were phylogenetically identical, making the possibility of spontaneous clearance and HCV reinfection less likely. The IL-10, TNF-α, and IP-10 levels...

  7. Cyclophilin B stimulates RNA synthesis by the HCV RNA dependent RNA polymerase

    OpenAIRE

    Heck, Julie A.; Meng, Xiao; Frick, David N.

    2009-01-01

    Cyclophilins are cellular peptidyl isomerases that have been implicated in regulating hepatitis C virus (HCV) replication. Cyclophilin B (CypB) is a target of cyclosporin A (CsA), an immunosuppressive drug recently shown to suppress HCV replication in cell culture. Watashi et al. recently demonstrated that CypB is important for efficient HCV replication, and proposed that it mediates the anti-HCV effects of CsA through an interaction with NS5B (Mol. Cell 19:111). We examined the effects of pu...

  8. Independent, parallel pathways to CXCL10 induction in HCV-infected hepatocytes.

    Science.gov (United States)

    Brownell, Jessica; Wagoner, Jessica; Lovelace, Erica S; Thirstrup, Derek; Mohar, Isaac; Smith, Wesley; Giugliano, Silvia; Li, Kui; Crispe, I Nicholas; Rosen, Hugo R; Polyak, Stephen J

    2013-10-01

    The pro-inflammatory chemokine CXCL10 is induced by HCV infection in vitro and in vivo, and is associated with outcome of IFN (interferon)-based therapy. We studied how hepatocyte sensing of early HCV infection via TLR3 (Toll-like receptor 3) and RIG-I (retinoic acid inducible gene I) led to expression of CXCL10. CXCL10, type I IFN, and type III IFN mRNAs and proteins were measured in PHH (primary human hepatocytes) and hepatocyte lines harboring functional or non-functional TLR3 and RIG-I pathways following HCV infection or exposure to receptor-specific stimuli. HuH7 human hepatoma cells expressing both TLR3 and RIG-I produced maximal CXCL10 during early HCV infection. Neutralization of type I and type III IFNs had no impact on virus-induced CXCL10 expression in TLR3+/RIG-I+ HuH7 cells, but reduced CXCL10 expression in PHH. PHH cultures were positive for monocyte, macrophage, and dendritic cell mRNAs. Immunodepletion of non-parenchymal cells (NPCs) eliminated marker expression in PHH cultures, which then showed no IFN requirement for CXCL10 induction during HCV infection. Immunofluorescence studies also revealed a positive correlation between intracellular HCV Core and CXCL10 protein expression (r(2) = 0.88, p ≤ 0.001). While CXCL10 induction in hepatocytes during the initial phase of HCV infection is independent of hepatocyte-derived type I and type III IFNs, NPC-derived IFNs contribute to CXCL10 induction during HCV infection in PHH cultures. Copyright © 2013 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  9. Systemic Epstein-Barr Virus-positive T-Cell Lymphoproliferative Disease of Childhood With Good Response to Steroid Therapy.

    Science.gov (United States)

    Kim, Do-Hoon; Kim, Myungshin; Kim, Yonggoo; Han, Kyungja; Han, Eunhee; Lee, Jae Wook; Chung, Nack-Gyun; Cho, Bin

    2017-11-01

    Systemic Epstein-Barr virus (EBV)-positive T-cell lymphoproliferative disease of childhood is a rare disease and has a very fulminant clinical course with high mortality. A 21-month-old female patient was referred to our hospital with a 1 week history of fever and was subsequently diagnosed with systemic Epstein-Barr virus-positive T-cell lymphoproliferative disease of childhood. After starting treatment with dexamethasone, she showed early defervescence and improvement of laboratory parameters, and has remained disease-free after stopping steroid treatment, although longer follow-up is necessary. Our report underscores the possibility that this disease entity may be heterogenous in terms of prognosis.

  10. Effect of hepatitis C treatment on CD4+ T-cell counts and the risk of death in HIV-HCV-coinfected patients

    DEFF Research Database (Denmark)

    Peters, Lars

    2012-01-01

    treatment. RESULTS: In total, 780/6,433 (12%) HIV-HCV-coinfected patients initiated HCV treatment (interferon [IFN] and ribavirin n=692, IFN alone n=88). CD4(+) T-cell counts decreased during the first 12 weeks of treatment (P... for comparing HCV-treated with -untreated individuals was 0.72 (95% CI 0.43, 1.21). The estimated hazard ratio for liver-related death was 0.57 (95% CI 0.21, 1.55). CONCLUSIONS: Despite its effect in reducing CD4(+) T-cell counts, the effect of HCV treatment on mortality was in the direction of benefit and our...

  11. Frequency of thyroid disorders during interferon and ribavirin therapy in chronic hepatitis C infection

    International Nuclear Information System (INIS)

    Masood, N.; Memon, A.; Memon, S.; Jaffri, M.

    2008-01-01

    The objective of this study was to assess the frequency of thyroid dysfunction in response to combination of interferon and ribavirin therapy in chronic hepatitis C (CHC) patients and HCV outcome. One hundred cases of CHC, proven by anti-HCV and HCV RNA-positive with baseline TSH, FT4 and FT3 within the normal reference range, who were treated with interferon alpha-2b (3 million unit subcutaneously three times per week) and oral ribavirin (1000-1200 mg per day) were included in this study. All patients were assessed for TSH, FT4, FT3 levels at 12 weeks and 24 weeks during therapy. Among the 100 patients, overt thyroid disease developed in 13 (13%) and sub-clinical thyroid disease in 5 (5%). Out of 13 patients of overt thyroid disorders, 11 (84.6%) had hypothyroidism and 02 (15.3%) hyperthyroidism. Four (80%) patients were of sub-clinical hypothyroidism and 01 (20%) patient was of sub-clinical hyperthyroidism. Overall, thyroid disorders developed in 18 (18%) both as overt and sub-clinical thyroid disorders. Ninety one (91%) patients became negative by HCV RNA. Treatment of HCV with IFN-alpha and ribavirin can be safely continued in patients with over and sub clinical hypothyroidism because thyroid disease responds well to treatment. (author)

  12. The management of HCV-infected pregnant women.

    Science.gov (United States)

    Valladares, Guillermo; Chacaltana, Alfonso; Sjogren, Maria H

    2010-01-01

    Hepatitis C is, at present, a worldwide health problem and is the most common cause of liver transplantation. Its prevalence in pregnant women is similar to that of the general population. In the absence of cirrhosis and portal hypertension, most HCV-infected pregnant women do not have obstetric complications. Screening of pregnant women that are asymptomatic and do not have risk factors is not cost effective. A high hepatitis C viral load reportedly increases vertical transmission and is higher in women who are coinfected with HIV or who are intravenous drug users. Prolonged rupture of the membrane for more than 6 h, amniocentesis, and perineal lacerations increase the potential risk of perinatal transmission. Although the hepatitis C virus can be transmitted intrapartum, prevention by caesarean delivery is not generally indicated. The HCV virus can be found in maternal milk; however, breast feeding is not contraindicated. In conclusion, there are no antiviral treatment recommendations for HCV-infected women during pregnancy, or guidelines for the prevention of vertical transmission.

  13. HCV infection among Saudi population: high prevalence of genotype 4 and increased viral clearance rate.

    Directory of Open Access Journals (Sweden)

    Ahmed S Abdel-Moneim

    Full Text Available HCV is a major etiological agent of liver disease with a high rate of chronic evolution. The virus possesses 6 genotypes with many subtypes. The rate of spontaneous clearance among HCV infected individuals denotes a genetic determinant factor. The current study was designed in order to estimate the rate of HCV infection and ratio of virus clearance among a group of infected patients in Saudi Arabia from 2008 to 2011. It was additionally designed to determine the genotypes of the HCV in persistently infected patients. HCV seroprevalence was conducted on a total of 15,323 individuals. Seropositive individuals were tested by Cobas AmpliPrep/Cobas TaqMan HCV assay to determine the ratio of persistently infected patients to those who showed spontaneous viral clearance. HCV genotyping on random samples from persistently infected patients were conducted based on the differences in the 5'untranslated region (5'UTR. Anti-HCV antibodies were detected in 7.3% of the totally examined sera. A high percentage of the HCV infected individuals experienced virus clearance (48.4%. HCV genotyping revealed the presence of genotypes 1 and 4, the latter represented 97.6% of the tested strains. Evidences of the widespread of the HCV genotype 4 and a high rate of HCV virus clearance were found in Saudi Arabia.

  14. Seroprevalence of Hepatitis C Virus (HCV) antibodies in pregnant ...

    African Journals Online (AJOL)

    Background: Hepatitis C virus (HCV) infection is a major public health concern. The aim of this study was to ascertain the seroprevalence and risk factors of HCV antibodies among pregnant women in Anyigba, Kogi State North Central Nigeria. Materials and methods:Blood samples (5mls) were collected from one hundred ...

  15. Spectrum and immunophenotyping of 653 patients with B-cell chronic lymphoproliferative disorders in China: A single-centre analysis.

    Science.gov (United States)

    Miao, Yi; Cao, Lei; Sun, Qian; Li, Xiao-Tong; Wang, Yan; Qiao, Chun; Wang, Li; Wang, Rong; Qiu, Hai-Rong; Xu, Wei; Li, Jian-Yong; Wu, Yu-Jie; Fan, Lei

    2018-02-01

    The incidence of B-cell chronic lymphoproliferative disorders (B-CLPDs) is significantly lower in China than that in western countries. There have been studies involving small cohorts with conflicting results regarding the spectrum of B-CLPDs in China, and the types and immunophenotyping of B-CLPDs in China remain largely unexplored. We conducted a retrospective analysis of 653 cases of B-CLPDs seen in our centre from 2011 to 2015. Four-colour flow cytometry was used to determine the expression of each immunological marker, and the diagnostic values of the immunological markers were also investigated. Chronic lymphocytic leukaemia (CLL) was the most common type of B-CLPD, which was consistent with that in west countries. However, the proportions of CLL (55.9%), follicular lymphoma (2.6%), and hairy cell leukaemia (0.2%) were lower, while the proportion of lymphoplasmacytic lymphoma/WaldenstrÖm macroglobulinaemia (5.4%) was higher in China, as compared with western countries. With respect to immunophenotypic characteristics, CD23 (31.7%) was more frequently expressed in mantle cell lymphoma (MCL) in our cohort than that in western countries. Immunophenotyping was useful in differentiating MCL from CLL or B-cell prolymphocytic leukaemia and lymphoplasmacytic lymphoma/WaldenstrÖm macroglobulinaemia from splenic marginal zone lymphoma. CD200 was of better diagnostic performance (accuracy: 94.6%) in differentiating CLL from MCL compared with CD23 (accuracy: 93.3%). Some cases of B-CPLDs, however, had no definite diagnoses, which were diagnosed as CD5 + B-CPLDs unclassified (7.7%) and CD5 - B-CPLDs unclassified (15.8%). This is the largest study that systematically explores the spectrum and immunophenotyping of B-CLPDs in Asia, confirming that spectrum of B-CLPDs in China was different from that in western countries. The immunophenotypic features of B-CLPDs were similar between China and western countries, although a few disparities exist. Cases with no definite

  16. EBV-associated post-transplantation B-cell lymphoproliferative disorder following allogenic stem cell transplantation for acute lymphoblastic leukaemia: tumor regression after reduction of immunosuppression - a case report

    Directory of Open Access Journals (Sweden)

    Niedobitek Gerald

    2010-03-01

    Full Text Available Abstract Epstein-Barr virus (EBV-associated B-cell post-transplantation lymphoproliferative disorder (PTLD is a severe complication following stem cell transplantation. This is believed to occur as a result of iatrogenic immunosuppression leading to a relaxation of T-cell control of EBV infection and thus allowing viral reactivation and proliferation of EBV-infected B-lymphocytes. In support of this notion, reduction of immunosuppressive therapy may lead to regression of PTLD. We present a case of an 18-year-old male developing a monomorphic B-cell PTLD 2 months after receiving an allogenic stem cell transplant for acute lymphoblastic leukemia. Reduction of immunosuppressive therapy led to regression of lymphadenopathy. Nevertheless, the patient died 3 months afterwards due to extensive graft-vs.-host-disease and sepsis. As a diagnostic lymph node biopsy was performed only after reduction of immunosuppressive therapy, we are able to study the histopathological changes characterizing PTLD regression. We observed extensive apoptosis of blast cells, accompanied by an abundant infiltrate comprising predominantly CD8-positive, Granzyme B-positive T-cells. This observation supports the idea that regression of PTLD is mediated by cytotoxic T-cells and is in keeping with the observation that T-cell depletion, represents a major risk factor for the development of PTLD.

  17. Interferon lambda: opportunities, risks, and uncertainties in the fight against HCV.

    Science.gov (United States)

    Laidlaw, Stephen M; Dustin, Lynn B

    2014-01-01

    Innate immunity is key to the fight against the daily onslaught from viruses that our bodies are subjected to. Essential to this response are the interferons (IFNs) that prime our cells to block viral pathogens. Recent evidence suggests that the Type III (λ) IFNs are intimately associated with the immune response to hepatitis C virus (HCV) infection. Genome-wide association studies have identified polymorphisms within the IFN-λ gene locus that correlate with response to IFNα-based antiviral therapy and with spontaneous clearance of HCV infection. The mechanisms for these correlations are incompletely understood. Restricted expression of the IFN-λ receptor, and the ability of IFN-λ to induce IFN-stimulated genes in HCV-infected cells, suggest potential roles for IFN-λ in HCV therapy even in this era of directly acting antivirals. This review summarizes our current understanding of the IFN-λ family and the role of λ IFNs in the natural history of HCV infection.

  18. Opposite Effects of Two Human ATG10 Isoforms on Replication of a HCV Sub-genomic Replicon Are Mediated via Regulating Autophagy Flux in Zebrafish

    Directory of Open Access Journals (Sweden)

    Yu-Chen Li

    2018-04-01

    Full Text Available Autophagy is a host mechanism for cellular homeostatic control. Intracellular stresses are symptoms of, and responses to, dysregulation of the physiological environment of the cell. Alternative gene transcription splicing is a mechanism potentially used by a host to respond to physiological or pathological challenges. Here, we aimed to confirm opposite effects of two isoforms of the human autophagy-related protein ATG10 on an HCV subgenomic replicon in zebrafish. A liver-specific HCV subreplicon model was established and exhibited several changes in gene expression typically induced by HCV infection, including overexpression of several HCV-dependent genes (argsyn, leugpcr, rasgbd, and scaf-2, as well as overexpression of several ER stress related genes (atf4, chop, atf6, and bip. Autophagy flux was blocked in the HCV model. Our results indicated that the replication of the HCV subreplicon was suppressed via a decrease in autophagosome formation caused by the autophagy inhibitor 3MA, but enhanced via dysfunction in the lysosomal degradation caused by another autophagy inhibitor CQ. Human ATG10, a canonical isoform in autophagy, facilitated the amplification of the HCV-subgenomic replicon via promoting autophagosome formation. ATG10S, a non-canonical short isoform of the ATG10 protein, promoted autophagy flux, leading to lysosomal degradation of the HCV-subgenomic replicon. Human ATG10S may therefore inhibit HCV replication, and may be an appropriate target for future antiviral drug screening.

  19. An update on the treatment options for HBV/HCV coinfection.

    Science.gov (United States)

    Sagnelli, Evangelista; Sagnelli, Caterina; Macera, Margherita; Pisaturo, Mariantonietta; Coppola, Nicola

    2017-11-01

    Despite the reciprocal inhibition exerted by HBV and HCV genomes, dual HBV/HCV infection is associated with more severe forms of liver disease and warrant effective treatment. Areas covered: A careful evaluation of disease progression to establish the predominance of one virus over another, concomitant HIV infection and comorbidities is essential to make the best therapy choices. In most virological conditions interferon (IFN)-based treatment has been replaced by a combination of different classes of second generation directly acting antivirals (DAAs), which offer better tolerability and HCV eradication in 95% of cases. Tenofovir or entecavir should be part of treatment for patients with active HBV production, for those coinfected with HIV and for those with cirrhosis. Expert opinion: DAAs have been successfully used to eradicate HCV infection in recent years, but the high cost may limit their use particularly in developing countries. Entecavir and tenofovir have been demonstrated to be effective for long-term inhibition of HBV replication. Careful monitoring of serum ALT and markers of HBV and HCV replication before and during treatment is essential for an early diagnosis and treatment of virus reactivation.

  20. Spillover effects of HIV testing policies: changes in HIV testing guidelines and HCV testing practices in drug treatment programs in the United States

    Directory of Open Access Journals (Sweden)

    Jemima A. Frimpong

    2016-07-01

    Full Text Available Abstract Background To examine the extent to which state adoption of the Centers for Disease Control and Prevention (CDC 2006 revisions to adult and adolescent HIV testing guidelines is associated with availability of other important prevention and medical services. We hypothesized that in states where the pretest counseling requirement for HIV testing was dropped from state legislation, substance use disorder treatment programs would have higher availability of HCV testing services than in states that had maintained this requirement. Methods We analyzed a nationally representative sample of 383 opioid treatment programs from the 2005 and 2011 National Drug Abuse Treatment System Survey (NDATSS. Data were collected from program directors and clinical supervisors through telephone surveys. Multivariate logistic regression models were used to measure associations between state adoption of CDC recommended guidelines for HIV pretest counseling and availability of HCV testing services. Results The effects of HIV testing legislative changes on HCV testing practices varied by type of opioid treatment program. In states that had removed the requirement for HIV pretest counseling, buprenorphine-only programs were more likely to offer HCV testing to their patients. The positive spillover effect of HIV pretest counseling policies, however, did not extend to methadone programs and did not translate into increased availability of on-site HCV testing in either program type. Conclusions Our findings highlight potential positive spillover effects of HIV testing policies on HCV testing practices. They also suggest that maximizing the benefits of HIV policies may require other initiatives, including resources and programmatic efforts that support systematic integration with other services and effective implementation.

  1. Hepatitis A virus infection suppresses hepatitis C virus replication and may lead to clearance of HCV.

    Science.gov (United States)

    Deterding, Katja; Tegtmeyer, Björn; Cornberg, Markus; Hadem, Johannes; Potthoff, Andrej; Böker, Klaus H W; Tillmann, Hans L; Manns, Michael P; Wedemeyer, Heiner

    2006-12-01

    The significance of hepatitis A virus (HAV) super-infection in patients with chronic hepatitis C had been a matter of debate. While some studies suggested an incidence of fulminant hepatitis A of up to 35%, this could not be confirmed by others. We identified 17 anti-HCV-positive patients with acute hepatitis A from a cohort of 3170 anti-HCV-positive patients recruited at a single center over a period of 12 years. Importantly, none of the anti-HCV-positive patients had a fulminant course of hepatitis A. HCV-RNA was detected by PCR in 84% of the anti-HCV-positive/anti-HAV-IgM-negative patients but only in 65% of anti-HCV-positive patients with acute hepatitis A (p=0.03), indicating suppression of HCV replication during hepatitis A. Previous HAV infection had no effect on HCV replication. After recovery from hepatitis A, an increased HCV replication could be demonstrated for 6 out of 9 patients with serial quantitative HCV-RNA values available while 2 patients remained HCV-RNA negative after clearance of HAV throughout follow-up of at least 2 years. HAV super-infection is associated with decreased HCV-RNA replication which may lead to recovery from HCV in some individuals. Fulminant hepatitis A is not frequent in patients with chronic hepatitis C recruited at a tertiary referral center.

  2. Association between depressive symptoms, CD4 count and HIV viral suppression among HIV-HCV co-infected people.

    Science.gov (United States)

    Aibibula, Wusiman; Cox, Joseph; Hamelin, Anne-Marie; Moodie, Erica E M; Anema, Aranka; Klein, Marina B; Brassard, Paul

    2018-05-01

    Depressive symptoms are associated with poor HIV viral control and immune recovery among people living with HIV. However, no prior studies assessed this association exclusively among people co-infected with HIV-hepatitis C virus (HCV). While people with HIV only and those with HIV-HCV co-infection share many characteristics, co-infected people may become more susceptible to the effects of depressive symptoms on health outcomes. We assessed this association exclusively among people co-infected with HIV-HCV in Canada using data from the Food Security & HIV-HCV Sub-Study (FS Sub-Study) of the Canadian Co-Infection Cohort (CCC). Stabilized inverse probability weighted marginal structural model was used to account for potential time-varying confounders. A total of 725 participants were enrolled between 2012 and 2015. At baseline, 52% of participants reported depressive symptoms, 75% had undetectable HIV viral load, and median CD4 count was 466 (IQR 300-665). People experiencing depressive symptoms had 1.32 times (95% CI: 1.07, 1.63) the risk of having detectable HIV viral load, but had comparable CD4 count to people who did not experience depressive symptoms (fold change of CD4 = 0.96, 95% CI: 0.91, 1.03). Presence of depressive symptoms is a risk factor for incomplete short-term HIV viral suppression among people co-infected with HIV-HCV. Therefore, depressive symptoms screening and related counseling may improve HIV related health outcomes and reduce HIV transmission.

  3. The association of syringe type and syringe cleaning with HCV infection among IDUs in Budapest, Hungary

    Science.gov (United States)

    Gyarmathy, V. Anna; Neaigus, Alan; Mitchell, Mary M.; Ujhelyi, Eszter

    2008-01-01

    We assessed whether syringe type, syringe cleaning and distributive syringe sharing were associated with self-reported and laboratory confirmed HCV infection among Hungarian IDUs. Injecting drug users (N=215) were recruited from non-treatment settings in Budapest, Hungary between October 2005 and December 2006. Multivariate logistic regression models identified correlates of self-report of being HCV infected and testing positive for HCV. While 37% tested positive for HCV, 14% of the total (39% of those who tested positive) self-reported being HCV infected. Using any two piece syringes was significantly associated with self-reported HCV infection, while distributive syringe sharing was not associated with self-report of being HCV infected. Engaging in receptive sharing of only one-piece syringes but always cleaning before reuse was not associated with testing HCV positive, while any receptive sharing of only one-piece syringes and not always cleaning before reuse was significantly associated with testing HCV positive. Sharing cookers and squirting drugs from one syringe into another syringe were not associated with testing HCV positive. The high percent of those HCV infected who did not know they were infected highlights the need to provide better access to confidential testing and counseling services. Counseling should emphasize secondary prevention of HCV among HCV infected IDUs. Our findings also indicate that syringe type and syringe cleaning practices may play a role in HCV transmission. Ethnographic research should identify the reasons why IDUs may use two-piece syringes and suggest means to reduce their use. Thorough cleaning of one-piece syringes when sterile syringes are unavailable may be an efficient way to reduce the risk of HCV infection. PMID:19058925

  4. Immunological disorders in chronic hepatitis C Egyptian patients.

    Science.gov (United States)

    Shaker, M K; Fahmy, H M

    1997-01-01

    It is known that hepatitis C virus (HCV) related to chronic liver disease may be associated with various immunological disorders, among these disorders are mixed cryoglobulinemia, serum antinuclear antibodies, antismooth muscle antibodies and liver/kidney microsomal antibody type 1 (LKM1). However, the actual prevalence and pathogenic role of these disorders in patients with chronic hepatitis C are unclear. It was our aim to estimate the prevalence of different autoimmune antibodies in cases of hepatitis C chronic liver disease and to assess if such changes have any clinical significance. A total of 30 chronic hepatitis C patients (22 males and 8 females) with a mean age of 43.5 +/- 6.7 years, all patients were ELISA II positive, HCV RNA PCR positive and HbsAg negative, with elevated ALT more than 2 folds of the normal, in addition to 20 healthy controls of matched age and sex were tested for rheumatoid factor, cryoglobulin, antinuclear antibody, antismooth muscle antibody, antimitochondrial antibody and LKM1. The rheumatoid factor was present in 18 (60%) of the HCV Ab +ve patients and in 1 (5%) of the controls (p 0.24), antinuclear antibody was positive in 4 (13.3%) of the patients and in 1 (5%) of the controls (p > 0.6), antismooth muscle antibody was positive in 1 (3.3%) of the patients and not detected in any of the controls, the antimitochondrial antibody and LKM1 were not detected in both the patients and the controls. In conclusion, we can see that chronic hepatitis C patients show prevalence of some autoimmune antibodies and their presence is not associated with any implication on the clinical presentation.

  5. New modalities in the treatment of HCV in pre and post - transplantation setting.

    Science.gov (United States)

    Araz, Filiz; Durand, Christine M; Gürakar, Ahmet

    2015-05-01

    End-stage liver disease and hepatocellular carcinoma (HCC) secondary to hepatitis C virus (HCV) infection are the leading indications for liver transplantation (LT) in developed countries. Recurrence of HCV following LT is universal if the recipient has detectable serum HCV RNA at the time of LT. Recurrent HCV has an accelerated course and is associated with poor long term patient and graft survival. Interferon (IFN)-based regimens have achieved low Sustained Virological Rates (SVR) in this setting and are associated with a high rate of adverse events, resulting in treatment discontinuation. With advances in understanding the HCV life cycle, drugs targeting specific steps, particularly inhibiting the NS3/4A protease, NS5B RNA dependent RNA polymerase and the NS5A protein, have been developed. Sofosbuvir (SOF), a nucleotide analogue inhibitor of NS5B polymerase was the first compound to enter the market. Combinations of SOF with new HCV antivirals from other classes have allowed for IFN-free regimens with low rates of adverse events and SVR rates >90%. With the availability of newer agents, the approach to the treatment of HCV infection during the pre-and post-liver transplantation period has changed. We will hereby review the current status of HCV treatment and discuss the potential future therapies in the transplant setting.

  6. 3D cultured immortalized human hepatocytes useful to develop drugs for blood-borne HCV

    International Nuclear Information System (INIS)

    Aly, Hussein Hassan; Shimotohno, Kunitada; Hijikata, Makoto

    2009-01-01

    Due to the high polymorphism of natural hepatitis C virus (HCV) variants, existing recombinant HCV replication models have failed to be effective in developing effective anti-HCV agents. In the current study, we describe an in vitro system that supports the infection and replication of natural HCV from patient blood using an immortalized primary human hepatocyte cell line cultured in a three-dimensional (3D) culture system. Comparison of the gene expression profile of cells cultured in the 3D system to those cultured in the existing 2D system demonstrated an up-regulation of several genes activated by peroxisome proliferator-activated receptor alpha (PPARα) signaling. Furthermore, using PPARα agonists and antagonists, we also analyzed the effect of PPARα signaling on the modulation of HCV replication using this system. The 3D in vitro system described in this study provides significant insight into the search for novel anti-HCV strategies that are specific to various strains of HCV.

  7. Sleep-related movement disorders.

    Science.gov (United States)

    Merlino, Giovanni; Gigli, Gian Luigi

    2012-06-01

    Several movement disorders may occur during nocturnal rest disrupting sleep. A part of these complaints is characterized by relatively simple, non-purposeful and usually stereotyped movements. The last version of the International Classification of Sleep Disorders includes these clinical conditions (i.e. restless legs syndrome, periodic limb movement disorder, sleep-related leg cramps, sleep-related bruxism and sleep-related rhythmic movement disorder) under the category entitled sleep-related movement disorders. Moreover, apparently physiological movements (e.g. alternating leg muscle activation and excessive hypnic fragmentary myoclonus) can show a high frequency and severity impairing sleep quality. Clinical and, in specific cases, neurophysiological assessments are required to detect the presence of nocturnal movement complaints. Patients reporting poor sleep due to these abnormal movements should undergo non-pharmacological or pharmacological treatments.

  8. Historical epidemiology of hepatitis C virus (HCV) in selected countries

    DEFF Research Database (Denmark)

    Bruggmann, P; Øvrehus, Anne Lindebo; Moreno, C

    2014-01-01

    Chronic infection with hepatitis C virus (HCV) is a leading indicator for liver disease. New treatment options are becoming available, and there is a need to characterize the epidemiology and disease burden of HCV. Data for prevalence, viremia, genotype, diagnosis and treatment were obtained...

  9. Hepatitis B virus reactivation after treatment for hepatitis C in hemodialysis patients with HBV/HCV coinfection

    Directory of Open Access Journals (Sweden)

    Raul Carlos Wahle

    2015-09-01

    Full Text Available In coinfected HBV/HCV patients, HBV replication is usually suppressed by HCV over the time. No study to date has evaluated the HBV viremia in long-term follow-up after HCV treatment in hemodialysis patients with HBV/HCV coinfection. This study aimed to assess the evolution of HBV viremia after HCV treatment in this special population. Ten hemodialysis patients with HBV/HCV coinfection with dominant HCV infection (HBV lower than 2000 IU/mL and significant fibrosis were treated with interferon-alpha 3 MU 3×/week for 12 months and could be followed for at least 36 months after HCV treatment. Six cases of HBV reactivation (60% during follow-up were observed and 5/6 had been successfully treated for HCV. Patients with HBV reactivation received anti-HBV therapy. Our preliminary findings indicate that treatment of hepatitis C in HBV/HCV coinfected hemodialysis patients may favor HBV reactivation. Thus, continued monitoring of HBV viremia must be recommended and prompt anti-HBV therapy should be implemented.

  10. Monocyte activation in HIV/HCV coinfection correlates with cognitive impairment.

    Directory of Open Access Journals (Sweden)

    Hans Rempel

    Full Text Available Coinfection with human immunodeficiency virus (HIV and hepatitis C virus (HCV challenges the immune system with two viruses that elicit distinct immune responses. Chronic immune activation is a hallmark of HIV infection and an accurate indicator of disease progression. Suppressing HIV viremia by antiretroviral therapy (ART effectively prolongs life and significantly improves immune function. HIV/HCV coinfected individuals have peripheral immune activation despite effective ART control of HIV viral load. Here we examined freshly isolated CD14 monocytes for gene expression using high-density cDNA microarrays and analyzed T cell subsets, CD4 and CD8, by flow cytometry to characterize immune activation in monoinfected HCV and HIV, and HIV-suppressed coinfected subjects. To determine the impact of coinfection on cognition, subjects were evaluated in 7 domains for neuropsychological performance, which were summarized as a global deficit score (GDS. Monocyte gene expression analysis in HIV-suppressed coinfected subjects identified 43 genes that were elevated greater than 2.5 fold. Correlative analysis of subjects' GDS and gene expression found eight genes with significance after adjusting for multiple comparisons. Correlative expression of six genes was confirmed by qPCR, five of which were categorized as type 1 IFN response genes. Global deficit scores were not related to plasma lipopolysaccharide levels. In the T cell compartment, coinfection significantly increased expression of activation markers CD38 and HLADR on both CD4 and CD8 T cells but did not correlate with GDS. These findings indicate that coinfection is associated with a type 1 IFN monocyte activation profile which was further found to correlate with cognitive impairment, even in subjects with controlled HIV infection. HIV-suppressed coinfected subjects with controlled HIV viral load experiencing immune activation could benefit significantly from successful anti-HCV therapy and may be

  11. Performance of the new Bayer VERSANT HCV RNA 3.0 assay for quantitation of hepatitis C virus RNA in plasma and serum: Conversion to international units and comparison with the Roche COBAS amplicor HCV monitor, version 2.0, assay

    NARCIS (Netherlands)

    Beld, Marcel; Sentjens, Roel; Rebers, Sjoerd; Weegink, Christine; Weel, Jan; Sol, Cees; Boom, René

    2002-01-01

    We have evaluated the VERSANT HCV RNA 3.0. Assay (HCV 3.0 bDNA assay) (Bayer Diagnostics, Berkeley, Calif.), which is an improved signal amplification procedure for the HCV 2.0 bDNA assay for the quantitation of hepatitis C virus (HCV) RNA in serum or plasma of HCV-infected individuals. The HCV 3.0

  12. Socioeconomic status in HCV infected patients – risk and prognosis

    DEFF Research Database (Denmark)

    Omland, Lars Haukali; Osler, Merete; Jepsen, Peter

    2013-01-01

    It is unknown whether socioeconomic status (SES) is a risk factor for hepatitis C virus (HCV) infection or a prognostic factor following infection.......It is unknown whether socioeconomic status (SES) is a risk factor for hepatitis C virus (HCV) infection or a prognostic factor following infection....

  13. Clearance of low levels of HCV viremia in the absence of a strong adaptive immune response

    Directory of Open Access Journals (Sweden)

    Manns Michael P

    2007-06-01

    Full Text Available Abstract Spontaneous clearance of hepatitis C virus (HCV has frequently been associated with the presence of HCV-specific cellular immunity. However, there had been also reports in chimpanzees demonstrating clearance of HCV-viremia in the absence of significant levels of detectable HCV-specific cellular immune responses. We here report seven asymptomatic acute hepatitis C cases with peak HCV-RNA levels between 300 and 100.000 copies/ml who all cleared HCV-RNA spontaneously. Patients were identified by a systematic screening of 1176 consecutive new incoming offenders in a German young offender institution. Four of the seven patients never developed anti-HCV antibodies and had normal ALT levels throughout follow-up. Transient weak HCV-specific CD4+ T cell responses were detectable in five individuals which did not differ in strength and breadth from age- and sex-matched patients with chronic hepatitis C and long-term recovered patients. In contrast, HCV-specific MHC-class-I-tetramer-positive cells were found in 3 of 4 HLA-A2-positive patients. Thus, these cases highlight that clearance of low levels of HCV viremia is possible in the absence of a strong adaptive immune response which might explain the low seroconversion rate after occupational exposure to HCV.

  14. Comparison of cobas HCV GT against Versant HCV Genotype 2.0 (LiPA) with confirmation by Sanger sequencing.

    Science.gov (United States)

    Yusrina, Falah; Chua, Cui Wen; Lee, Chun Kiat; Chiu, Lily; Png, Tracy Si-Yu; Khoo, Mui Joo; Yan, Gabriel; Lee, Guan Huei; Yan, Benedict; Lee, Hong Kai

    2018-05-01

    Correct identification of infecting hepatitis C virus (HCV) genotype is helpful for targeted antiviral therapy. Here, we compared the HCV genotyping performance of the cobas HCV GT assay against the Versant HCV Genotype 2.0 (LiPA) assay, using 97 archived serum samples. In the event of discrepant or indeterminate results produced by either assay, the core and NS5B regions were sequenced. Of the 97 samples tested by the cobas, 25 (26%) were deemed indeterminate. Sequencing analyses confirmed 21 (84%) of the 25 samples as genotype 6 viruses with either subtype 6m, 6n, 6v, 6xa, or unknown subtype. Of the 97 samples tested by the LiPA, thirteen (13%) were deemed indeterminate. Seven (7%) were assigned with genotype 1, with unavailable/inconclusive results from the core region of the LiPA. Notably, the 7 samples were later found to be either genotype 3 or 6 by sequencing analyses. Moreover, 1 sample by the LiPA was assigned as genotypes 4 (cobas: indeterminate) but were later found to be genotype 3 by sequencing analyses, highlighting its limitation in assigning the correct genotype. The cobas showed similar or slightly higher accuracy (100%; 95% CI 94-100%) compared to the LiPA (99%; 95% CI 92-100%). Twenty-six percent of the 97 samples tested by the cobas had indeterminate results, mainly due to its limitation in identifying genotype 6 other than subtypes 6a and 6b. This presents a significant assay limitation in Southeast Asia, where genotype 6 infection is highly prevalent. Copyright © 2018 Elsevier B.V. All rights reserved.

  15. Prevalence and presentation of hepatitis B and C virus (HBV and HCV) infection in Vietnamese Americans via serial community serologic testing.

    Science.gov (United States)

    Nguyen, Kelvin; Van Nguyen, Thai; Shen, Duke; Xia, Victor; Tran, Diep; Banh, Khanh; Ruan, Victor; Hu, Ke-Qin

    2015-02-01

    The prevalence of hepatitis B virus (HBV) infection is reportedly high in Vietnamese Americans (VAs), but most previous studies did not assess full HBV serology, and not the prevalence of HBV and hepatitis C virus (HCV) infection simultaneously. The aim of the study is to assess the prevalence of different HBV serologies and HCV infection in VAs. This study was based on the data collected by testing for Hepatitis B surface antigen (HBsAg), anti-hepatitis B core antibody (HBcAb IgG), anti-HBs antibody (HBsAb), and anti-HCV antibody (anti-HCV) in a series of community screening in VAs in Orange County, California. In 1,405 VA participants, the mean age was 51 (17-87) years, 45.1% were males; 68.2%, married; 97.2%, born in Vietnam. Most of the participants were non-US born with their primary language being non-English and with limited access to health care. Of the 1,405 cases, 124 (8.8%) were confirmed HBV infection by HBsAg+; 81 (5.8%), HCV infection by anti-HCV+; including four (0.3%) with HBV/HCV coinfection. Twelve percent of the participants with confirmed HBV infection thought they were previously tested negative, while 29.7% of the participants with confirmed HCV infection thought they were previously tested negative. In this cohort, 15.4% were HBsAg-/HBsAb-/HBcAb IgG-, i.e. being susceptible to HBV infection. In HCV infected participants, 65.4% were born between 1945 and 1965. This large serial survey and screening in the Vietnamese American community confirmed the rates of HBV and HCV infection to be as high as 8.8% and 5.8%, respectively. We have also identified factors related to HBV and HCV infection in this high-risk population.

  16. Application of 60Co γ-ray irradiated polystyrene microplate for anti-HCV ELISA

    International Nuclear Information System (INIS)

    Feng Bo; Zeng Hongyan; Tang Yufang; Wang Lu

    2005-01-01

    In order to explore the effect of 60 Co γ-ray irradiation on minor polypeptides absorption of polystyrene microplate, an indirect ELISA detection of anti-HCV was established, 60 Co γ-ray irradiated polystyrene microplates and the controls (without irradiation or UV-irradiated) were applied to absorb recombinant HCV antigens respectively. Cooperated with Bovine antihuman IgG labelled HRP, their related indices of sensitivity, specificity, homogeneity and stability were determinate. The results indicated that, optimum dose of the γ-ray irradiation is 8 kGy, and compared with the controls, detection sensitivity and homogeneity of the polystyrene microplate irradiated to 8 kGy could be improved markedly. (authors)

  17. Deregulated expression of HDAC9 in B cells promotes development of lymphoproliferative disease and lymphoma in mice

    Directory of Open Access Journals (Sweden)

    Veronica S. Gil

    2016-12-01

    Full Text Available Histone deacetylase 9 (HDAC9 is expressed in B cells, and its overexpression has been observed in B-lymphoproliferative disorders, including B-cell non-Hodgkin lymphoma (B-NHL. We examined HDAC9 protein expression and copy number alterations in primary B-NHL samples, identifying high HDAC9 expression among various lymphoma entities and HDAC9 copy number gains in 50% of diffuse large B-cell lymphoma (DLBCL. To study the role of HDAC9 in lymphomagenesis, we generated a genetically engineered mouse (GEM model that constitutively expressed an HDAC9 transgene throughout B-cell development under the control of the immunoglobulin heavy chain (IgH enhancer (Eμ. Here, we report that the Eμ-HDAC9 GEM model develops splenic marginal zone lymphoma and lymphoproliferative disease (LPD with progression towards aggressive DLBCL, with gene expression profiling supporting a germinal center cell origin, as is also seen in human B-NHL tumors. Analysis of Eμ-HDAC9 tumors suggested that HDAC9 might contribute to lymphomagenesis by altering pathways involved in growth and survival, as well as modulating BCL6 activity and p53 tumor suppressor function. Epigenetic modifications play an important role in the germinal center response, and deregulation of the B-cell epigenome as a consequence of mutations and other genomic aberrations are being increasingly recognized as important steps in the pathogenesis of a variety of B-cell lymphomas. A thorough mechanistic understanding of these alterations will inform the use of targeted therapies for these malignancies. These findings strongly suggest a role for HDAC9 in B-NHL and establish a novel GEM model for the study of lymphomagenesis and, potentially, preclinical testing of therapeutic approaches based on histone deacetylase inhibitors.

  18. Determination of Relative Frequency of HBS Ag, HCV and HIV Antibodies Serum Markers among Admitted Intravenous Drug Users in Infectious Disease Ward of Razi Hospital in Ahvaz, 2004-2005

    Directory of Open Access Journals (Sweden)

    Abdolrasool Nikkhooy

    2012-07-01

    Full Text Available Introduction: Intravenous drug users as a serious health problem in communities have economical and social effects as well as health and hygienic complications. Viral infections may be transmitted through drug injection by shared syringes among users. The aim of this study has been to determine the relative frequency of HBV, HCV and HIV infection’s markers as epidemiological data in Ahvaz. Materials & Methods: This retrospective cross sectional study was conducted on IV drug users (IVDUs who were admitted in infectious diseases ward of Razi Ahvaz Hospital in 2004-2005. The collected data of serum markers of these patients were coded, and statistical analyses were conducted. Results: 1890 patients were evaluated and 258 patients were IVDUs (14.6%. 154 patients (59.98% were tested for anti HCV-Ab of whom 65 patients were HCV-Ab positive (42.2%. 205 patients (79.45% were tested for anti HIV-Ab of whom 38 patients were HIV-Ab positive (18.53%. 67 patients (25.96% were tested for HBs-Ag of whom 15 patients were HBs-Ag positive (22.67%. 12 patients (4.65% were tested for anti HBc-Ab of whom 8 patients were HBc-Ab positive (66.66%. Conclusion: In this study, high infection rate relates to different causes such as increasing consumes of opium substances and recent differences in fumigated opium substances pattern toward injecting drug use in society level, which increases the prevalence of these infections, The present study determined some critical information about the prevalence of serum markers HBS Ag, HCV and HIV antibodies among intravenous drug users in southwestern of Iran.

  19. HIV and HCV prevalence among entrants to methadone maintenance treatment clinics in China: a systematic review and meta-analysis

    Directory of Open Access Journals (Sweden)

    Zhuang Xun

    2012-06-01

    Full Text Available Abstract Background Methadone maintenance treatment (MMT was implemented in China since 2004. It was initiated in 8 pilot clinics and subsequently expanded to 738 clinics by the end of 2011. Numerous individual research studies have been conducted to estimate HIV and HCV prevalence among MMT clients but an overview of the epidemics in relations to MMT remains unclear. The aim of this study is to estimate the magnitude and changing trends of HIV, HCV and HIV-HCV co-infections among entry clients to MMT clinics in China during 2004-2010. Methods Chinese and English databases of literature were searched for studies reporting HIV, HCV and co-infection prevalence among MMT clients in China from 2004 to 2010. The prevalence estimates were summarized through a systematic review and meta-analysis of published literatures. Results Ninety eligible articles were selected in this review (2 in English and 88 in Chinese. Nationally, pooled prevalence of HIV-HCV and HIV-HCV co-infection among MMT clients was 6.0% (95%CI: 4.7%-7.7%, 60.1% (95%CI: 52.8%-67.0% and 4.6% (95%CI: 2.9%-7.2%, respectively. No significant temporal trend was found in pooled prevalence estimates. Study location is the major contributor of heterogeneities of both HIV and HCV prevalence among drug users in MMT. Conclusions There was no significant temporal trend in HIV and HCV prevalence among clients in MMT during 2004–2010. Prevalence of HCV is markedly higher than prevalence of HIV among MMT clients. It is recommended that health educational programs in China promote the earlier initiation and wider coverage of MMT among injecting drug users (IDUs, especially HIV-infected IDUs.

  20. Hepatitis C virus genotyping of organ donor samples to aid in transplantation of HCV-positive organs.

    Science.gov (United States)

    Gentile, Caren; Van Deerlin, Vivianna M; Goldberg, David S; Reese, Peter P; Hasz, Richard D; Abt, Peter; Blumberg, Emily; Farooqi, Midhat S

    2018-02-01

    Given the availability of new highly efficacious anti-HCV therapies, some clinicians have advocated for wider use of kidneys from hepatitis C virus-positive (HCV+) donors, including transplanting them into HCV-negative recipients. As treatment regimens for HCV are commonly guided by genotype, pretransplant HCV genotyping of tissue donors would be beneficial. To our knowledge, donor HCV genotyping has never been reported. We retrieved archived frozen plasma samples for 17 previous organ donors through a local organ procurement organization. We performed HCV genotyping using the eSensor HCVg Direct Test (GenMark Diagnostics) and also by Sanger sequencing, for confirmation (Retrogen). In addition, viral loads were measured using the COBAS AmpliPrep/TaqMan system (Roche Diagnostics). We found that most of the samples (n = 14) were HCV Genotype 1a with the remainder being Genotype 2b (n = 1) or Genotype 3 (n = 2). All genotyping results were concordant with Sanger sequencing. The average HCV viral load in the sample group was ~ 1.6 million IU/mL (range: ~16 000 IU/mL to 7 million IU/mL). We demonstrate that viral RNA from organ donor plasma can be successfully genotyped for HCV. This ability suggests that transplantation of HCV+ kidneys into HCV-negative recipients, followed by genotype-guided antiviral therapy, could be feasible. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  1. Statin Utilization and Recommendations Among HIV- and HCV-infected Veterans: A Cohort Study.

    Science.gov (United States)

    Clement, Meredith E; Park, Lawrence P; Navar, Ann Marie; Okeke, Nwora Lance; Pencina, Michael J; Douglas, Pamela S; Naggie, Susanna

    2016-08-01

    Human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infections are associated with increased risk of cardiovascular disease (CVD). The potential impact of recently updated cholesterol guidelines on treatment of HIV- and HCV-infected veterans is unknown. We performed a retrospective cohort study to assess statin use and recommendations among 13 579 HIV-infected, 169 767 HCV-infected, and 6628 HIV/HCV-coinfected male veterans aged 40-75 years. Prior 2004 Adult Treatment Panel (ATP-III) guidelines were compared with current 2013 American College of Cardiology/American Heart Association (ACC/AHA) cholesterol guidelines and 2014 US Department of Veterans Affairs (VA)/US Department of Defense (DoD) joint clinical practice guidelines using laboratory, medication, and comorbidity data from the VA Clinical Case Registry from 2008 through 2010. Using risk criteria delineated by the ATP-III guidelines, 50.6% of HIV-infected, 45.9% of HCV-infected, and 33.8% of HIV/HCV-coinfected veterans had an indication for statin therapy. However, among those eligible, 22.7%, 30.5%, and 31.5%, respectively, were not receiving ATP-III recommended statin therapy. When current cholesterol guidelines were applied by VA/DoD and ACC/AHA criteria, increases in recommendations for statins were found in all groups (57.3% and 66.1% of HIV-infected, 64.4% and 73.7% of HCV-infected, 49.1% and 58.5% of HIV/HCV-coinfected veterans recommended). Statins were underutilized among veterans infected with HIV, HCV, and HIV/HCV according to previous ATP-III guidelines. Current VA/DoD and ACC/AHA guidelines substantially expand statin recommendations and widen the gap of statin underutilization in all groups. These gaps in care present an opportunity to improve CVD prevention efforts in these at-risk populations. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  2. Report: Study is about the prevalence of the HCV disease and survival of HCV patients with associated factors in the population of district Multan.

    Science.gov (United States)

    Tabassum, Hina; Amin, Muhammad; Amanullah, Muhammad; Tabassum, Sana

    2015-09-01

    To find out the significant factors associated with HCV disease and evaluate the impact of these factors on the survival pattern of HCV patients in district Multan. The study was conducted in Nishter Hospital of Multan district from 1st January 2011 to 1st October 2012. To see a significant difference between the survival rates of patients with associated factors, non-parametric Cox- proportional hazard model with their graphical results were used. All the patients above 11 years old of both sexes were included in the study. All those who were surviving with HCV disease were studied with their associated factors such as age, family history (FH) barber/parlor services, blood group (BG) types weight loss (WL), Gender and drug use were collected from Nishter Hospital Multan. Results indicated that age, blood group types and gender are the most significant factors in the patients who are surviving with HCV disease. It was also observed that survival rate of female patients is high as compare to male patients.

  3. Prevalence and characteristics of HIV/HBV and HIV/HCV coinfections in Tuscany

    Directory of Open Access Journals (Sweden)

    Monia Puglia

    2016-07-01

    Conclusions: We have observed less advanced disease in HIV and HCV-HIV patients compared with HBV–HIV coinfected patients. Moreover, our results show a higher prevalence of HIV/HCV among drug addicts and in the age-group 35–59, corresponding to those born in years considered most at risk for addiction. This study also confirms the finding of a less advanced HIV disease in HIV/HCV coinfected patients.

  4. CD4⁺ and CD8⁺ regulatory T cells (Tregs) are elevated and display an active phenotype in patients with chronic HCV mono-infection and HIV/HCV co-infection

    DEFF Research Database (Denmark)

    Hartling, H J; Gaardbo, J C; Ronit, A

    2012-01-01

    The aim of this study was to examine regulatory T cells (Tregs) in peripheral blood and liver tissue in patients with chronic hepatitis C virus (HCV) mono-infection and in patients with HIV/HCV co-infection. In a cross-sectional study were included 51 patients with chronic HCV infection, 24...... patients with HIV/HCV co-infection and 24 healthy individuals. CD4⁺ and CD8⁺ Tregs were determined using flow cytometry. Fibrosis was examined by transient elastography. Inflammation, fibrosis and Tregs were determined in liver biopsies from 12 patients. Increased frequency of CD4⁺ and CD8⁺ Tregs was found...... in HIV/HCV co-infected patients [median: 6.4% (IQR: 5.7-6.9) and 1.0% (0.7-1.2), respectively] compared to HCV mono-infected patients [5.6% (4.2-6.3), P = 0.01 and 0.5% (0.3-0.7), P

  5. HCV RNA in peripheral blood mononuclear cells (PBMCs) as a ...

    African Journals Online (AJOL)

    Abdel Fatah Fahmy Hanno

    2013-06-27

    Jun 27, 2013 ... tested positively for HCV RNA in PBMCs at the end of treatment had an overall significantly ... chronic hepatitis C, the history of previous use of antiviral medicine or .... Although hepatocytes are considered to be primary targets of. HCV, clinical .... 6. Yamagiwa S, Matsuda Y, Ichida T, Honda Y, Takamura M,.

  6. Occult HCV Infection (OCI) Diagnosis in Cirrhotic and Non-cirrhotic Naïve Patients by Intra-PBMC Nested Viral RNA PCR.

    Science.gov (United States)

    Abd Alla, Mohamed Darwish Ahmed; Elibiary, Saleh Ahmed; Wu, George Y; El-Awady, Mostafa Kamel

    2017-12-28

    Background and Aims: Occult HCV infections (OCIs) include IgG antibody seronegative cryptogenic (COCIs), as well as seropositive secondary naïve (SNOCIs) and experienced (SEOCIs) cases. We used peripheral-blood-mononuclear-cell (PBMC)-PCR to evaluate COCIs and SNOCIs prevalence, serum HCV spontaneous disappearance (SCSD) in naïve cirrhotics and non-cirrhotics, intra-PBMC HCV-RNA strands in relation to cirrhosis density in naïve non-viremia cases, and HCV-RNA seroconversion after 1 year of solitary naïve intra-PBMC infection. Methods: The anti-HCV IgG antibody-positive naïve-patients ( n = 785) were classified into viremic ( n = 673) and non-viremic [ n = 112, including non-cirrhotics ( n = 55) and cirrhotics ( n = 57)], and 62 controls without evidence of HCV-infection. Controls and post-HCV non-viremia cases ( n = 62+112 = 174) were submitted to hepatic Fibroscan-Elastography evaluation. All subjects ( n = 847) were screened for intra-PBMC HCV-RNA sense and antisense strands by nested-PCR. Results: Naïve-OCI cases (4.84%) that were diagnosed by PBMC-PCR significantly raised the total numbers of HCV-infection to 714 ( p = 0.01). The percent positivity of SNOCIs (34.82%) was significantly higher than for asymptomatic-COCIs (3.125%, p = 0.0001). Comparing PBMC-PCR with single-step-reverse-transcription (SRT)-PCR for identification of SCSD in naïve IgG antibody-positive non-viremia patients ( n = 112) revealed a decline in SCSD prevalence by PBMC-PCR (from 14.27% to 9.3%), regardless of presence of hepatic cirrhosis ( p = 0.03). SCSD was found to be higher by PBMC-PCR in non-cirrhotics compared to cirrhotics ( p = 0.0001), with an insignificant difference when using SRT-PCR ( p = 0.45). Intra-PBMC HCV-RNA infection was significantly more frequent in cirrhotics compared to both non-cirrhotics and controls ( p < 0.0005). An increased hepatic fibrosis density was recognized in intra-PBMC HCV-RNA infection with sense ( p = 0.0001) or antisense strand ( p = 0

  7. The effect of HCV Core protein on the expression of miR-150

    Directory of Open Access Journals (Sweden)

    Sayad Khanizadeh

    2016-09-01

    Full Text Available Background : Hepatitis C virus (HCV is considered as one of the major pathogenic agents of chronic liver diseases. Previous studies have shown that HCV proteins can interaction with gene regulatory networks such as microRNAs. The aim of this study was to investigate the effect of HCV core protein on the expression of miR-150 in a cell culture model. Materials and Methods: Plasmids expressing full HCV core protein was transfected into Huh7 cell lines while a GFP expressing plasmid employed as negative control. Subsequently, total RNA extracted and Real-Time PCR performed to measure the expression level of miR-150 expression. Moreover, trypan blue exclusion assay was performed to investigate the effect of core protein on cell viability. Results: The gene expression analysis of miR-150 in Huh7 cells showed that endogenous HCV core protein could significantly down regulation of miR-150 when compared to GFP control plasmid and normal cells (P<0.01. Beside, core protein induced no significant proliferative or cytotoxic effects on hepatic cells as determined by trypan blue exclusion assay (P<0.05. Conclusion: Our study suggests that HCV core protein can led to down regulation of miR-150 expression. This data revealed that HCV protein interactions with cell regulatory machinery may contribute to pathogenesis of chronic liver diseases.

  8. Utility of simultaneous assessment of bone marrow aspirates and trephine biopsy sections in various haematological disorders

    Directory of Open Access Journals (Sweden)

    Vandana Puri

    2018-01-01

    Conclusion: Bone marrow aspiration alone is sufficient for the diagnosis of megaloblastic anemia and most of the hematological malignancies. Bone marrow biopsy is more appropriate for detection of disorders with focal marrow involvement such as lymphoproliferative disorders, metastatic cancer, focal blast crisis in CML, granulomatous lesions, and hypoplastic marrow. However, it is strongly recommended that both should be reviewed simultaneously to ensure maximum diagnostic accuracy.

  9. Development of lymphoma in Autoimmune Lymphoproliferative Syndrome (ALPS) and its relationship to Fas gene mutations

    NARCIS (Netherlands)

    Poppema, Sibrand; Maggio, Ewerton; van den Berg, Anke

    Autoimmune Lymphoproliferative Syndrome (ALPS) is generally the result of a mutation in genes associated with apoptosis, like Fas, Fas ligand, Casp 8 and Casp 10. As a result, the normal homeostasis of T- and B-lymphocytes is disturbed and a proliferation of polyclonal T lymphocytes occurs. This

  10. [Chronic HCV hepatopathy and cryoglobulinemia. The associated clinical spectrum].

    Science.gov (United States)

    Pellicano, R; Leone, N; Maiocco, I A; Modena, V; Arena, V; Marietti, G; Puiatti, P; Palmas, F; Rizzetto, M; Ponzetto, A

    1999-01-01

    The hepatitis C infection (HCV) has numerous extrahepatic manifestations owing to the systemic nature of the infection itself. HCV infects the cells that carry a CD 81 receptor and show a marked tropism for hepatocytes, bone marrow staminal cells and circulating lymphomonocytes. One consequence of this tropism is the activation of B lymphocyte clones with the consequent production of autoantibodies and cryoglobulins. The secondary event is the formation of circulating immune complexes which, having precipitated at an intravascular level, may cause part of the extrahepatic manifestations associated with these infections. This retrospective study evaluated the manifestations correlated and/or associated with HCV hepatitis and mixed cryoglobulinaemia. This analysis showed that 75% of consecutively studied patients reveal clinically important extrahepatic manifestations. This underlines the "broad spectrum" action played by the hepatitis C virus in the host organism.

  11. Biological properties of purified recombinant HCV particles with an epitope-tagged envelope

    Energy Technology Data Exchange (ETDEWEB)

    Takahashi, Hitoshi; Akazawa, Daisuke [Department of Virology II, National Institute of Infectious Diseases, Tokyo (Japan); Toray Industries, Inc., Kanagawa (Japan); Kato, Takanobu; Date, Tomoko [Department of Virology II, National Institute of Infectious Diseases, Tokyo (Japan); Shirakura, Masayuki [Department of Virology II, National Institute of Infectious Diseases, Tokyo (Japan); Toray Industries, Inc., Kanagawa (Japan); Nakamura, Noriko; Mochizuki, Hidenori [Toray Industries, Inc., Kanagawa (Japan); Tanaka-Kaneko, Keiko; Sata, Tetsutaro [Department of Pathology, National Institute of Infectious Diseases, Tokyo (Japan); Tanaka, Yasuhito [Department of Clinical Molecular Informative Medicine, Nagoya City University Graduate School of Medicine, Nagoya (Japan); Mizokami, Masashi [Research Center for Hepatitis and Immunology, Kohnodai Hospital, International Medical Center of Japan, Chiba (Japan); Suzuki, Tetsuro [Department of Virology II, National Institute of Infectious Diseases, Tokyo (Japan); Wakita, Takaji, E-mail: wakita@nih.go.jp [Department of Virology II, National Institute of Infectious Diseases, Tokyo (Japan)

    2010-05-14

    To establish a simple system for purification of recombinant infectious hepatitis C virus (HCV) particles, we designed a chimeric J6/JFH-1 virus with a FLAG (FL)-epitope-tagged sequence at the N-terminal region of the E2 hypervariable region-1 (HVR1) gene (J6/JFH-1/1FL). We found that introduction of an adaptive mutation at the potential N-glycosylation site (E2N151K) leads to efficient production of the chimeric virus. This finding suggests the involvement of glycosylation at Asn within the envelope protein(s) in HCV morphogenesis. To further analyze the biological properties of the purified recombinant HCV particles, we developed a strategy for large-scale production and purification of recombinant J6/JFH-1/1FL/E2N151K. Infectious particles were purified from the culture medium of J6/JFH-1/1FL/E2N151K-infected Huh-7 cells using anti-FLAG affinity chromatography in combination with ultrafiltration. Electron microscopy of the purified particles using negative staining showed spherical particle structures with a diameter of 40-60 nm and spike-like projections. Purified HCV particle-immunization induced both an anti-E2 and an anti-FLAG antibody response in immunized mice. This strategy may contribute to future detailed analysis of HCV particle structure and to HCV vaccine development.

  12. Biological properties of purified recombinant HCV particles with an epitope-tagged envelope

    International Nuclear Information System (INIS)

    Takahashi, Hitoshi; Akazawa, Daisuke; Kato, Takanobu; Date, Tomoko; Shirakura, Masayuki; Nakamura, Noriko; Mochizuki, Hidenori; Tanaka-Kaneko, Keiko; Sata, Tetsutaro; Tanaka, Yasuhito; Mizokami, Masashi; Suzuki, Tetsuro; Wakita, Takaji

    2010-01-01

    To establish a simple system for purification of recombinant infectious hepatitis C virus (HCV) particles, we designed a chimeric J6/JFH-1 virus with a FLAG (FL)-epitope-tagged sequence at the N-terminal region of the E2 hypervariable region-1 (HVR1) gene (J6/JFH-1/1FL). We found that introduction of an adaptive mutation at the potential N-glycosylation site (E2N151K) leads to efficient production of the chimeric virus. This finding suggests the involvement of glycosylation at Asn within the envelope protein(s) in HCV morphogenesis. To further analyze the biological properties of the purified recombinant HCV particles, we developed a strategy for large-scale production and purification of recombinant J6/JFH-1/1FL/E2N151K. Infectious particles were purified from the culture medium of J6/JFH-1/1FL/E2N151K-infected Huh-7 cells using anti-FLAG affinity chromatography in combination with ultrafiltration. Electron microscopy of the purified particles using negative staining showed spherical particle structures with a diameter of 40-60 nm and spike-like projections. Purified HCV particle-immunization induced both an anti-E2 and an anti-FLAG antibody response in immunized mice. This strategy may contribute to future detailed analysis of HCV particle structure and to HCV vaccine development.

  13. High prevalence of human parvovirus 4 infection in HBV and HCV infected individuals in shanghai.

    Science.gov (United States)

    Yu, Xuelian; Zhang, Jing; Hong, Liang; Wang, Jiayu; Yuan, Zhengan; Zhang, Xi; Ghildyal, Reena

    2012-01-01

    Human parvovirus 4 (PARV4) has been detected in blood and diverse tissues samples from HIV/AIDS patients who are injecting drug users. Although B19 virus, the best characterized human parvovirus, has been shown to co-infect patients with hepatitis B or hepatitis C virus (HBV, HCV) infection, the association of PARV4 with HBV or HCV infections is still unknown.The aim of this study was to characterise the association of viruses belonging to PARV4 genotype 1 and 2 with chronic HBV and HCV infection in Shanghai.Serum samples of healthy controls, HCV infected subjects and HBV infected subjects were retrieved from Shanghai Center for Disease Control and Prevention (SCDC) Sample Bank. Parvovirus-specific nested-PCR was performed and results confirmed by sequencing. Sequences were compared with reference sequences obtained from Genbank to derive phylogeny trees.The frequency of parvovirus molecular detection was 16-22%, 33% and 41% in healthy controls, HCV infected and HBV infected subjects respectively, with PARV4 being the only parvovirus detected. HCV infected and HBV infected subjects had a significantly higher PARV4 prevalence than the healthy population. No statistical difference was found in PARV4 prevalence between HBV or HCV infected subjects. PARV4 sequence divergence within study groups was similar in healthy subjects, HBV or HCV infected subjects.Our data clearly demonstrate that PARV4 infection is strongly associated with HCV and HBV infection in Shanghai but may not cause increased disease severity.

  14. Circulating Interferon-λ3, Responsiveness to HBV Vaccination, and HBV/HCV Infections in Haemodialysis Patients

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    Alicja E. Grzegorzewska

    2017-01-01

    Full Text Available The IFN-λ3 gene (IFNL3 plays a role in HCV clearance. We investigated circulating IFN-λ3 and IFNL3 SNPs in haemodialysis patients who differed in their response to HBV vaccination and their HBV/HCV infection status. In 201 patients, plasma IFN-λ3 was determined using ELISA. IFNL3 SNPs (rs12979860, rs8099917 were genotyped using HRM analysis. Differences in IFN-λ3 levels were shown between responders and nonresponders to HBV vaccination and between HBsAg-positive patients and those who developed anti-HBs after infection and became HBsAg negative. HBV vaccine responders without HCV resolution revealed lower IFN-λ3 than noninfected responders. HBsAg/HCV RNA-positive subjects showed lower IFN-λ3 than patients positive only for HCV RNA or subjects who resolved both infections. Circulating IFN-λ3 correlated positively with anti-HBs and negatively with positive HCV RNA testing in the adjusted regression analyses. HBV vaccine nonresponders, HBsAg-positive patients, and subjects with replicating HCV composed a group with unfavourable outcomes. Responders to HBV vaccination, subjects who became HBsAg negative, and those who cleared HCV were analysed as having favourable outcomes. The latter showed higher IFN-λ3 but did not differ in distribution of IFNL3 SNPs compared with subjects with unfavourable outcomes. Higher IFN-λ3 concentrations are associated with response to HBV vaccination, self-limited HBV infection, and HCV resolution.

  15. Seroprevalence of HIV, HBV, HCV, and HTLV among Pregnant Women in Southwestern Nigeria.

    Science.gov (United States)

    Opaleye, Oluyinka Oladele; Igboama, Magdalene C; Ojo, Johnson Adeyemi; Odewale, Gbolabo

    2016-01-01

    Sexually transmitted infections (STIs) are major public health challenge especially in developing countries. This study was designed to determine the prevalence of Hepatitis B virus (HBV), Hepatitis C Virus (HCV), Human immunodeficiency virus (HIV), and Human T-cell lymphotropic Virus type I (HTLV-I) among pregnant women attending antenatal clinic, in Ladoke Akintola University Teaching Hospital, Osogbo, and South-Western Nigeria. One hundred and eighty two randomly selected pregnant women were screened for HBsAg, anti-HCV, anti-HIV and HTLV-1 IgM antibodies using commercially available ELISA kit. Of the 182 blood samples of pregnant women screened whose age ranged from 15-49 years, 13 (7.1%), 5 (2.7%), 9 (4.9%), and 44 (24.2%) were positive for HBsAg, anti-HCV, anti-HIV, and HTLV-1 IgM antibodies, respectively. The co-infection rate of 0.5% was obtained for HBV/HCV, HBV/HIV, HIV/HTLV-1, and HCV/HTLV-1 while 1.1% and 0% was recorded for HBV/HTLV-1 and HCV/HIV co-infections, respectively. Expected risk factors such as history of surgery, circumcision, tattooing and incision showed no significant association with any of the viral STIs (P > 0.05). This study shows that there is the need for a comprehensive screening of all pregnant women for HBsAg, anti-HCV, anti-HIV and HTLV-1 to prevent mother to child transmission of these viral infections and its attending consequences.

  16. Work-related voice disorder

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    Paulo Eduardo Przysiezny

    2015-04-01

    Full Text Available INTRODUCTION: Dysphonia is the main symptom of the disorders of oral communication. However, voice disorders also present with other symptoms such as difficulty in maintaining the voice (asthenia, vocal fatigue, variation in habitual vocal fundamental frequency, hoarseness, lack of vocal volume and projection, loss of vocal efficiency, and weakness when speaking. There are several proposals for the etiologic classification of dysphonia: functional, organofunctional, organic, and work-related voice disorder (WRVD.OBJECTIVE: To conduct a literature review on WRVD and on the current Brazilian labor legislation.METHODS: This was a review article with bibliographical research conducted on the PubMed and Bireme databases, using the terms "work-related voice disorder", "occupational dysphonia", "dysphonia and labor legislation", and a review of labor and social security relevant laws.CONCLUSION: WRVD is a situation that frequently is listed as a reason for work absenteeism, functional rehabilitation, or for prolonged absence from work. Currently, forensic physicians have no comparative parameters to help with the analysis of vocal disorders. In certain situations WRVD may cause, work disability. This disorder may be labor-related, or be an adjuvant factor to work-related diseases.

  17. Candidiasis and other oral mucosal lesions during and after interferon therapy for HCV-related chronic liver diseases.

    Science.gov (United States)

    Nagao, Yumiko; Hashimoto, Kouji; Sata, Michio

    2012-11-02

    Oral lichen planus (OLP) is seen frequently in patients with hepatitis C virus (HCV) infection. The aim of this study was to evaluate the occurrence of oral candidiasis, other mucosal lesions, and xerostomia during interferon (IFN) therapy for HCV infection. Of 124 patients with HCV-infected liver diseases treated with IFN therapy in our hospital, 14 (mean age 56.00 ± 12.94 years) who attended to receive administration of IFN once a week were identified and examined for Candida infection and other oral lesions and for the measurement of salivary flow. Serological assays also were carried out. Cultures of Candida from the tongue surfaces were positive in 7 (50.0%) of the 14 patients with HCV infection at least once during IFN therapy. C. albicans was the most common species isolated. The incidence of Candida during treatment with IFN did not increase above that before treatment. Additional oral mucosal lesions were observed in 50.0% (7/14) of patients: OLP in three (21.4%), angular cheilitis in three (21.4%) and recurrent aphthous stomatitis in one (7.1%). OLP occurred in one patient before treatment with IFN, in one during treatment and in one at the end of treatment. 85.7% of the oral lesions were treated with topical steroids. We compared the characteristics of the 7 patients in whom Candida was detected at least once during IFN therapy (group 1) and the 7 patients in whom Candida was not detected during IFN therapy (group 2). The prevalence of oral mucosal lesions (P=0.0075) and incidence of external use of steroids (P=0.0308) in group 1 were significantly higher than in group 2. The average body weight of group 1 decreased significantly compared to group 2 (P=0.0088). Salivary flow decreased in all subjects throughout the course of IFN treatment and returned at 6th months after the end of treatment. In group 1, the level of albumin at the beginning of the 6th month of IFN administration was lower than in group 2 (P=0.0550). According to multivariate analysis

  18. Dual-Routine HCV/HIV Testing: Seroprevalence and Linkage to Care in Four Community Health Centers in Philadelphia, Pennsylvania.

    Science.gov (United States)

    Coyle, Catelyn; Kwakwa, Helena

    2016-01-01

    Despite common risk factors, screening for hepatitis C virus (HCV) and HIV at the same time as part of routine medical care (dual-routine HCV/HIV testing) is not commonly implemented in the United States. This study examined improvements in feasibility of implementation, screening increase, and linkage to care when a dual-routine HCV/HIV testing model was integrated into routine primary care. National Nursing Centers Consortium implemented a dual-routine HCV/HIV testing model at four community health centers in Philadelphia, Pennsylvania, on September 1, 2013. Routine HCV and opt-out HIV testing replaced the routine HCV and opt-in HIV testing model through medical assistant-led, laboratory-based testing and electronic medical record modification to prompt, track, report, and facilitate reimbursement for tests performed on uninsured individuals. This study examined testing, seropositivity, and linkage-to-care comparison data for the nine months before (December 1, 2012-August 31, 2013) and after (September 1, 2013-May 31, 2014) implementation of the dual-routine HCV/HIV testing model. A total of 1,526 HCV and 1,731 HIV tests were performed before, and 1,888 HCV and 3,890 HIV tests were performed after dual-routine testing implementation, resulting in a 23.7% increase in HCV tests and a 124.7% increase in HIV tests. A total of 70 currently HCV-infected and four new HIV-seropositive patients vs. 101 HCV-infected and 13 new HIV-seropositive patients were identified during these two periods, representing increases of 44.3% for HCV antibody-positive and RNA-positive tests and 225.0% for HIV-positive tests. Linkage to care increased from 27 currently infected HCV--positive and one HIV-positive patient pre-dual-routine testing to 39 HCV--positive and nine HIV-positive patients post-dual-routine testing. The dual-routine HCV/HIV testing model shows that integrating dual-routine testing in a primary care setting is possible and leads to increased HCV and HIV screening

  19. HIV, HBV and HCV Coinfection Prevalence in Iran--A Systematic Review and Meta-Analysis.

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    Fahimeh Bagheri Amiri

    Full Text Available worldwide, hepatitis C and B virus infections (HCV and HCV, are the two most common coinfections with human immunodeficiency virus (HIV and has become a major threat to the survival of HIV-infected persons. The review aimed to estimate the prevalence of HIV, HBV, HCV, HIV/HCV and HIV/HBV and triple coinfections in different subpopulations in Iran.Following PRISMA guidelines, we conducted a systematic review and meta-analysis of reports on prevalence of HIV, HBV, HCV and HIV coinfections in different subpopulations in Iran. We systematically reviewed the literature to identify eligible studies from January 1996 to March 2012 in English or Persian/Farsi databases. We extracted the prevalence of HIV antibodies (diagnosed by Elisa confirmed with Western Blot test, HCV antibodies and HBsAg (with confirmatory laboratory test as the main primary outcome. We reported the prevalence of the three infections and coinfections as point and 95% confidence intervals.HIV prevalence varied from %0.00 (95% CI: 0.00-0.003 in the general population to %17.25 (95% CI: 2.94-31.57 in people who inject drugs (PWID. HBV prevalence ranged from % 0.00 (95% CI: 0.00-7.87 in health care workers to % 30.9 (95% CI: 27.88-33.92 in PWID. HCV prevalence ranged from %0.19 (95% CI: 0.00-0.66 in health care workers to %51.46 (95% CI: 34.30-68.62 in PWID. The coinfection of HIV/HBV and also HIV/HCV in the general population and in health care workers was zero, while the most common coinfections were HIV/HCV (10.95%, HIV/HBV (1.88% and triple infections (1.25% in PWID.We found that PWID are severely and disproportionately affected by HIV and the other two infections, HCV and HBV. Screenings of such coinfections need to be reinforced to prevent new infections and also reduce further transmission in their community and to others.

  20. Quantitative proteome analysis of plasma microparticles for the characterization of HCV-induced hepatic cirrhosis and hepatocellular carcinoma.

    Science.gov (United States)

    Taleb, Raghda Saad Zaghloul; Moez, Pacint; Younan, Doreen; Eisenacher, Martin; Tenbusch, Matthias; Sitek, Barbara; Bracht, Thilo

    2017-12-01

    Hepatocellular carcinoma (HCC) is the most common primary malignant liver tumor and a leading cause of cancer-related deaths worldwide. Cirrhosis induced by hepatitis-C virus (HCV) infection is the most critical risk factor for HCC. However, the mechanism of HCV-induced carcinogenesis is not fully understood. Plasma microparticles (PMP) contribute to numerous physiological and pathological processes and contain proteins whose composition correlates to the respective pathophysiological conditions. We analyzed PMP from 22 HCV-induced cirrhosis patients, 16 HCV-positive HCC patients with underlying cirrhosis and 18 healthy controls. PMP were isolated using ultracentrifugation and analyzed via label-free LC-MS/MS. We identified 840 protein groups and quantified 507 proteins. 159 proteins were found differentially abundant between the three experimental groups. PMP in both disease entities displayed remarkable differences in the proteome composition compared to healthy controls. Conversely, the proteome difference between both diseases was minimal. GO analysis revealed that PMP isolated from both diseases were significantly enriched in proteins involved in complement activation, while endopeptidase activity was downregulated exclusively in HCC patients. This study reports for the first time a quantitative proteome analysis for PMP from patients with HCV-induced cirrhosis and HCC. Data are available via ProteomeXchange with identifier PXD005777. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. New insights into HCV replication in original cells from Aedes mosquitoes.

    Science.gov (United States)

    Fallecker, Catherine; Caporossi, Alban; Rechoum, Yassine; Garzoni, Frederic; Larrat, Sylvie; François, Olivier; Fender, Pascal; Morand, Patrice; Berger, Imre; Petit, Marie-Anne; Drouet, Emmanuel

    2017-08-22

    The existing literature about HCV association with, and replication in mosquitoes is extremely poor. To fill this gap, we performed cellular investigations aimed at exploring (i) the capacity of HCV E1E2 glycoproteins to bind on Aedes mosquito cells and (ii) the ability of HCV serum particles (HCVsp) to replicate in these cell lines. First, we used purified E1E2 expressing baculovirus-derived HCV pseudo particles (bacHCVpp) so we could investigate their association with mosquito cell lines from Aedes aegypti (Aag-2) and Aedes albopictus (C6/36). We initiated a series of infections of both mosquito cells (Ae aegypti and Ae albopictus) with the HCVsp (Lat strain - genotype 3) and we observed the evolution dynamics of viral populations within cells over the course of infection via next-generation sequencing (NGS) experiments. Our binding assays revealed bacHCVpp an association with the mosquito cells, at comparable levels obtained with human hepatocytes (HepaRG cells) used as a control. In our infection experiments, the HCV RNA (+) were detectable by RT-PCR in the cells between 21 and 28 days post-infection (p.i.). In human hepatocytes HepaRG and Ae aegypti insect cells, NGS experiments revealed an increase of global viral diversity with a selection for a quasi-species, suggesting a structuration of the population with elimination of deleterious mutations. The evolutionary pattern in Ae albopictus insect cells is different (stability of viral diversity and polymorphism). These results demonstrate for the first time that natural HCV could really replicate within Aedes mosquitoes, a discovery which may have major consequences for public health as well as in vaccine development.

  2. Drug Abuse, HIV, and HCV in Asian Countries.

    Science.gov (United States)

    Hser, Yih-Ing; Liang, Di; Lan, Yu-Ching; Vicknasingam, Balasingam Kasinather; Chakrabarti, Amit

    2016-09-01

    Drug abuse and co-occurring infections are associated with significant morbidity and mortality. Asian countries are particularly vulnerable to the deleterious consequences of these risks/problems, as they have some of the highest rates of these diseases. This review describes drug abuse, HIV, and hepatitis C (HCV) in Asian countries. The most commonly used illicit drugs include opioids, amphetamine-type stimulants (ATS), cannabis, and ketamine. Among people who inject drugs, HIV rates range from 6.3 % in China to 19 % in Malaysia, and HCV ranges from 41 % in India and Taiwan to 74 % in Vietnam. In the face of the HIV epidemics, drug policies in these countries are slowly changing from the traditional punitive approach (e.g., incarcerating drug users or requiring registration as a drug user) to embrace public health approaches, including, for example, community-based treatment options as well as harm reduction approaches to reduce needle sharing and thus HIV transmission. HIV and HCV molecular epidemiology indicates limited geographic diffusion. While the HIV prevalence is declining in all five countries, use of new drugs (e.g., ATS, ketamine) continues to increase, as well as high-risk sexual behaviors associated with drug use-increasing the risk of sexual transmission of HIV, particularly among men who have sex with men. Screening, early intervention, and continued scaling up of therapeutic options (drug treatment and recovery support, ART, long-term HIV and HCV care for drug users) are critical for effective control or continued reduction of drug abuse and co-infections.

  3. Microarray analysis identifies a common set of cellular genes modulated by different HCV replicon clones

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    Gerosolimo Germano

    2008-06-01

    Full Text Available Abstract Background Hepatitis C virus (HCV RNA synthesis and protein expression affect cell homeostasis by modulation of gene expression. The impact of HCV replication on global cell transcription has not been fully evaluated. Thus, we analysed the expression profiles of different clones of human hepatoma-derived Huh-7 cells carrying a self-replicating HCV RNA which express all viral proteins (HCV replicon system. Results First, we compared the expression profile of HCV replicon clone 21-5 with both the Huh-7 parental cells and the 21-5 cured (21-5c cells. In these latter, the HCV RNA has been eliminated by IFN-α treatment. To confirm data, we also analyzed microarray results from both the 21-5 and two other HCV replicon clones, 22-6 and 21-7, compared to the Huh-7 cells. The study was carried out by using the Applied Biosystems (AB Human Genome Survey Microarray v1.0 which provides 31,700 probes that correspond to 27,868 human genes. Microarray analysis revealed a specific transcriptional program induced by HCV in replicon cells respect to both IFN-α-cured and Huh-7 cells. From the original datasets of differentially expressed genes, we selected by Venn diagrams a final list of 38 genes modulated by HCV in all clones. Most of the 38 genes have never been described before and showed high fold-change associated with significant p-value, strongly supporting data reliability. Classification of the 38 genes by Panther System identified functional categories that were significantly enriched in this gene set, such as histones and ribosomal proteins as well as extracellular matrix and intracellular protein traffic. The dataset also included new genes involved in lipid metabolism, extracellular matrix and cytoskeletal network, which may be critical for HCV replication and pathogenesis. Conclusion Our data provide a comprehensive analysis of alterations in gene expression induced by HCV replication and reveal modulation of new genes potentially useful

  4. Targeting endoplasmic reticulum and/or mitochondrial Ca2+ fluxes as therapeutic strategy for HCV infection

    Science.gov (United States)

    Scrima, Rosella; Piccoli, Claudia; Moradpour, Darius; Capitanio, Nazzareno

    2018-03-01

    Chronic hepatitis C is characterized by metabolic disorders and by a microenvironment in the liver dominated by oxidative stress, inflammation and regeneration processes that can in the long term lead to liver cirrhosis and hepatocellular carcinoma. Several lines of evidence suggest that mitochondrial dysfunctions play a central role in these processes. However, how these dysfunctions are induced by the virus and whether they play a role in disease progression and neoplastic transformation remains to be determined. Most in vitro studies performed so far have shown that several of the hepatitis C virus (HCV) proteins also localize to mitochondria, but the consequences of these interactions on mitochondrial functions remain contradictory and need to be confirmed in the context of productively replicating virus and physiologically relevant in vitro and in vivo model systems. In the past decade we have been proposing a temporal sequence of events in the HCV-infected cell whereby the primary alteration is localized at the mitochondria-associated ER membranes and causes release of Ca2+ from the ER, followed by uptake into mitochondria. This ensues successive mitochondrial dysfunction leading to the generation of reactive oxygen and nitrogen species and a progressive metabolic adaptive response consisting in decreased oxidative phosphorylation and enhanced aerobic glycolysis and lipogenesis. Here we resume the major results provided by our group in the context of HCV-mediated alterations of the cellular inter-compartmental calcium flux homeostasis and present new evidence suggesting targeting of ER and/or mitochondrial calcium transporters as a novel therapeutic strategy.

  5. Targeting Endoplasmic Reticulum and/or Mitochondrial Ca2+ Fluxes as Therapeutic Strategy for HCV Infection.

    Science.gov (United States)

    Scrima, Rosella; Piccoli, Claudia; Moradpour, Darius; Capitanio, Nazzareno

    2018-01-01

    Chronic hepatitis C is characterized by metabolic disorders and by a microenvironment in the liver dominated by oxidative stress, inflammation and regeneration processes that can in the long term lead to liver cirrhosis and hepatocellular carcinoma. Several lines of evidence suggest that mitochondrial dysfunctions play a central role in these processes. However, how these dysfunctions are induced by the virus and whether they play a role in disease progression and neoplastic transformation remains to be determined. Most in vitro studies performed so far have shown that several of the hepatitis C virus (HCV) proteins also localize to mitochondria, but the consequences of these interactions on mitochondrial functions remain contradictory and need to be confirmed in the context of productively replicating virus and physiologically relevant in vitro and in vivo model systems. In the past decade we have been proposing a temporal sequence of events in the HCV-infected cell whereby the primary alteration is localized at the mitochondria-associated ER membranes and causes release of Ca 2+ from the ER, followed by uptake into mitochondria. This ensues successive mitochondrial dysfunction leading to the generation of reactive oxygen and nitrogen species and a progressive metabolic adaptive response consisting in decreased oxidative phosphorylation and enhanced aerobic glycolysis and lipogenesis. Here we resume the major results provided by our group in the context of HCV-mediated alterations of the cellular inter-compartmental calcium flux homeostasis and present new evidence suggesting targeting of ER and/or mitochondrial calcium transporters as a novel therapeutic strategy.

  6. Cyclophilin B stimulates RNA synthesis by the HCV RNA dependent RNA polymerase.

    Science.gov (United States)

    Heck, Julie A; Meng, Xiao; Frick, David N

    2009-04-01

    Cyclophilins are cellular peptidyl isomerases that have been implicated in regulating hepatitis C virus (HCV) replication. Cyclophilin B (CypB) is a target of cyclosporin A (CsA), an immunosuppressive drug recently shown to suppress HCV replication in cell culture. Watashi et al. recently demonstrated that CypB is important for efficient HCV replication, and proposed that it mediates the anti-HCV effects of CsA through an interaction with NS5B [Watashi K, Ishii N, Hijikata M, Inoue D, Murata T, Miyanari Y, et al. Cyclophilin B is a functional regulator of hepatitis C virus RNA polymerase. Mol Cell 2005;19:111-22]. We examined the effects of purified CypB proteins on the enzymatic activity of NS5B. Recombinant CypB purified from insect cells directly stimulated NS5B-catalyzed RNA synthesis. CypB increased RNA synthesis by NS5B derived from genotype 1a, 1b, and 2a HCV strains. Stimulation appears to arise from an increase in productive RNA binding. NS5B residue Pro540, a previously proposed target of CypB peptidyl-prolyl isomerase activity, is not required for stimulation of RNA synthesis.

  7. Needlestick accident resulting in occupational transmission of HCV: Report of two cases

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    Eunice B Martin Chaves

    2016-01-01

    Full Text Available Occupational transmission of hepatitis C virus (HCV through needlestick injury is a serious problem worldwide. Occupational transmission of HCV is estimated at an average rate between 0,5% and 0,75%. There are factors associated with increased risk of transmission, such as deep injuries, procedures involving hollow-bore needle placement in the source patient’s vein or artery, and high HCV RNA titer in the source patient. We describe two cases of HCV seroconversion in nursing assistants after different risk needlestick injuries.   A transmissão ocupacional do vírus da hepatite C (VHC através de acidentes com material perfurocortante é um problema global. Essa transmissão é estimada, em média, entre 0,5% e 0,75%. Alguns fatores estão associados ao aumento do risco de transmissão, tais como lesões profundas, procedimentos que envolvam colocação da agulha em veia ou artéria, e altos títulos de HCV-RNA no paciente-fonte. Descrevemos dois casos de soroconversão ao VHC em auxiliares de enfermagem após acidentes com agulhas.

  8. Analysis of in vitro replicated human hepatitis C virus (HCV for the determination of genotypes and quasispecies

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    Chelyapov Nickolas

    2006-09-01

    Full Text Available Abstract Isolation and self-replication of infectious HCV has been a difficult task. However, this is needed for the purposes of developing rational drugs and for the analysis of the natural virus. Our recent report of an in vitro system for the isolation of human HCV from infected patients and their replication in tissue culture addresses this challenge. At California Institute of Molecular Medicine several isolates of HCV, called CIMM-HCV, were grown for over three years in cell culture. This is a report of the analysis of CIMM-HCV isolates for subtypes and quasispecies using a 269 bp segment of the 5'UTR. HCV RNA from three patients and eleven CIMM-HCV were analyzed for this purpose. All isolates were essentially identical. Isolates of HCV from one patient were serially transmitted into fresh cells up to eight times and the progeny viruses from each transmission were compared to each other and also to the primary isolates from the patient's serum. Some isolates were also transmitted to different cell types, while others were cultured continuously without retransmission for over three years. We noted minor sequence changes when HCV was cultured for extended periods of time. HCV in T-cells and non-committed lymphoid cells showed a few differences when compared to isolates obtained from immortalized B-cells. These viruses maintained close similarity despite repeated transmissions and passage of time. There were no subtypes or quasispecies noted in CIMM-HCV.

  9. Isolation and characterization of highly replicable hepatitis C virus genotype 1a strain HCV-RMT.

    Science.gov (United States)

    Arai, Masaaki; Tokunaga, Yuko; Takagi, Asako; Tobita, Yoshimi; Hirata, Yuichi; Ishida, Yuji; Tateno, Chise; Kohara, Michinori

    2013-01-01

    Multiple genotype 1a clones have been reported, including the very first hepatitis C virus (HCV) clone called H77. The replication ability of some of these clones has been confirmed in vitro and in vivo, although this ability is somehow compromised. We now report a newly isolated genotype 1a clone, designated HCV-RMT, which has the ability to replicate efficiently in patients, chimeric mice with humanized liver, and cultured cells. An authentic subgenomic replicon cell line was established from the HCV-RMT sequence with spontaneous introduction of three adaptive mutations, which were later confirmed to be responsible for efficient replication in HuH-7 cells as both subgenomic replicon RNA and viral genome RNA. Following transfection, the HCV-RMT RNA genome with three adaptive mutations was maintained for more than 2 months in HuH-7 cells. One clone selected from the transfected cells had a high copy number, and its supernatant could infect naïve HuH-7 cells. Direct injection of wild-type HCV-RMT RNA into the liver of chimeric mice with humanized liver resulted in vigorous replication, similar to inoculation with the parental patient's serum. A study of virus replication using HCV-RMT derivatives with various combinations of adaptive mutations revealed a clear inversely proportional relationship between in vitro and in vivo replication abilities. Thus, we suggest that HCV-RMT and its derivatives are important tools for HCV genotype 1a research and for determining the mechanism of HCV replication in vitro and in vivo.

  10. Isolation and characterization of highly replicable hepatitis C virus genotype 1a strain HCV-RMT.

    Directory of Open Access Journals (Sweden)

    Masaaki Arai

    Full Text Available Multiple genotype 1a clones have been reported, including the very first hepatitis C virus (HCV clone called H77. The replication ability of some of these clones has been confirmed in vitro and in vivo, although this ability is somehow compromised. We now report a newly isolated genotype 1a clone, designated HCV-RMT, which has the ability to replicate efficiently in patients, chimeric mice with humanized liver, and cultured cells. An authentic subgenomic replicon cell line was established from the HCV-RMT sequence with spontaneous introduction of three adaptive mutations, which were later confirmed to be responsible for efficient replication in HuH-7 cells as both subgenomic replicon RNA and viral genome RNA. Following transfection, the HCV-RMT RNA genome with three adaptive mutations was maintained for more than 2 months in HuH-7 cells. One clone selected from the transfected cells had a high copy number, and its supernatant could infect naïve HuH-7 cells. Direct injection of wild-type HCV-RMT RNA into the liver of chimeric mice with humanized liver resulted in vigorous replication, similar to inoculation with the parental patient's serum. A study of virus replication using HCV-RMT derivatives with various combinations of adaptive mutations revealed a clear inversely proportional relationship between in vitro and in vivo replication abilities. Thus, we suggest that HCV-RMT and its derivatives are important tools for HCV genotype 1a research and for determining the mechanism of HCV replication in vitro and in vivo.

  11. Point -of -care testing (POCT) in molecular diagnostics: Performance evaluation of GeneXpert HCV RNA test in diagnosing and monitoring of HCV infection.

    Science.gov (United States)

    Gupta, Ekta; Agarwala, Pragya; Kumar, Guresh; Maiwall, Rakhi; Sarin, Shiv Kumar

    2017-03-01

    Molecular testing at the point-of-care may turn out to be game changer for HCV diagnosis and treatment monitoring, through increased sensitivity, reduced turnaround time, and ease of performance. One such assay GeneXpert ® has recently been released. Comparative analysis between performances of GeneXpert ® and Abbott HCV-RNA was done. 174 HCV infected patients were recruited and, one time plasma samples from 154 patients and repeated samples from 20 patients, obtained at specific treatment time-points (0, 4, 12 and 24) weeks were serially re-tested on Xpert ® . Genotype 3 was the commonest, seen in 80 (66%) of the cases, genotype 1 in 34 (28.3%), genotype 4 in 4 (3.3%) and genotypes 2 and 5 in 1 (0.8%) each. Median HCV RNA load was 4.69 log 10 (range: 0-6.98log 10 ) IU/ml. Overall a very good correlation was seen between the two assays (R 2 =0.985), concordance of the results between the assays was seen in 138 samples (89.6%). High and low positive standards were tested ten times on Xpert ® to evaluate the precision and the coefficient of variation was 0.01 for HPC and 0.07 for the LPC. Monitoring of patients on two different regimes of treatment, pegylated interferon plus ribavirin and sofosbuvir plus ribavirin was done by both the systems at baseline, 4, 12 and 24 weeks. Perfect correlation between the assays in the course of therapy at different treatment time- point in genotypes 3 and 1 was seen. The study demonstrates excellent performance of the Xpert ® HCV assay in viral load assessment and in treatment course monitoring consistency. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. The mutator pathway is a feature of immunodeficiency-related lymphomas

    Science.gov (United States)

    Duval, Alex; Raphael, Martine; Brennetot, Caroline; Poirel, Helene; Buhard, Olivier; Aubry, Alban; Martin, Antoine; Krimi, Amor; Leblond, Veronique; Gabarre, Jean; Davi, Frederic; Charlotte, Frederic; Berger, Francoise; Gaidano, Gianluca; Capello, Daniela; Canioni, Danielle; Bordessoule, Dominique; Feuillard, Jean; Gaulard, Philippe; Delfau, Marie Helene; Ferlicot, Sophie; Eclache, Virginie; Prevot, Sophie; Guettier, Catherine; Lefevre, Pascale Cornillet; Adotti, Francoise; Hamelin, Richard

    2004-01-01

    The mutator phenotype caused by defects in the mismatch repair system is observed in a subset of solid neoplasms characterized by widespread microsatellite instability-high (MSI-H). It is known to be very rare in non-Hodgkin lymphomas (NHL), whereas mutator NHL is the most frequent tumor subtype in mismatch repair-deficient mice. By screening a series of 603 human NHL with specific markers of the mutator phenotype, we found here 12 MSI-H cases (12/603, 2%). Of interest, we demonstrated that this phenotype was specifically associated with immunodeficiency-related lymphomas (ID-RL), because it was observed in both posttransplant lymphoproliferative disorders (9/111, 8.1%) and HIV infection-related lymphomas (3/128, 2.3%) but not in a large series of NHL arising in the general population (0/364) (P < 0.0001). The MSI pathway is known to lead to the production of hundreds of abnormal protein neoantigens that are generated in MSI-H neoplasms by frameshift mutations of a number of genes containing coding microsatellite sequences. As expected, MSI-H ID-RL were found to harbor such genetic alterations in 12 target genes with a putative role in lymphomagenesis. The observation that the MSI-H phenotype was restricted to HIV infection-related lymphomas and posttransplant lymphoproliferative disorders suggests the existence of the highly immunogenic mutator pathway as a novel oncogenic process in lymphomagenesis whose role is favored when host immunosurveillance is reduced. Because MSI-H-positive cases were found to be either Epstein-Barr virus-positive or -negative, the mutator pathway should act synergistically or not with this other oncogenic factor, playing an important role in ID-RL. PMID:15047891

  13. Establishment and operation of a Good Manufacturing Practice-compliant allogeneic Epstein-Barr virus (EBV)-specific cytotoxic cell bank for the treatment of EBV-associated lymphoproliferative disease.

    Science.gov (United States)

    Vickers, Mark A; Wilkie, Gwen M; Robinson, Nicolas; Rivera, Nadja; Haque, Tanzina; Crawford, Dorothy H; Barry, Jacqueline; Fraser, Neil; Turner, David M; Robertson, Victoria; Dyer, Phil; Flanagan, Peter; Newlands, Helen R; Campbell, John; Turner, Marc L

    2014-11-01

    Epstein-Barr virus (EBV) is associated with several malignancies, including post-transplant lymphoproliferative disorder (PTLD). Conventional treatments for PTLD are often successful, but risk organ rejection and cause significant side effects. EBV-specific cytotoxic T lymphocytes (CTLs) generated in vitro from peripheral blood lymphocytes provide an alternative treatment modality with few side effects, but autologous CTLs are difficult to use in clinical practice. Here we report the establishment and operation of a bank of EBV-specific CTLs derived from 25 blood donors with human leucocyte antigen (HLA) types found at high frequency in European populations. Since licensure, there have been enquiries about 37 patients, who shared a median of three class I and two class II HLA types with these donors. Cells have been infused into ten patients with lymphoproliferative disease, eight of whom achieved complete remission. Neither patient with refractory disease was matched for HLA class II. Both cases of EBV-associated non-haematopoietic sarcoma receiving cells failed to achieve complete remission. Thirteen patients died before any cells could be issued, emphasizing that the bank should be contacted before patients become pre-terminal. Thus, this third party donor-derived EBV-specific CTL cell bank can supply most patients with appropriately matched cells and most recipients have good outcomes. © 2014 The Authors. British Journal of Haematology published by John Wiley & Sons Ltd.

  14. The Syndemic of Opioid Misuse, Overdose, HCV, and HIV: Structural-Level Causes and Interventions.

    Science.gov (United States)

    Perlman, David C; Jordan, Ashly E

    2018-04-01

    This article reviews the case for recognizing (1) the epidemics of opioid misuse, overdose, hepatitis C virus, and HIV as a syndemic and (2) the importance of examining and addressing structural factors in responses to this syndemic. We focus on the current syndemic in the US, but also consider data from other locations to highlight the issues existing and arising in various contexts. Advances in multi-level theory and statistical methods allow sound ecologic and multi-level analyses of the impact of structural factors on the syndemic. Studies of opioid misuse, overdoses, hepatitis C virus, and HIV demonstrate that area-level access to healthcare, medication-assisted treatment of opioid use disorders, sterile injection equipment, and overdose prevention with naloxone, as well as factors such as opioid marketing, income inequality, intensity of policing activities, and health care policies, are related to the prevalence of substance misuse, overdoses, infection risk, and morbidity. Structural variables can predict area-level vulnerability to the syndemic. The implementation of combined prevention and treatment interventions can control and reverse components of the syndemic. Recognizing and monitoring potent structural factors can facilitate the identification of areas at risk of vulnerability to the syndemic. Further, many structural factors are modifiable through intervention and policy to reduce structural vulnerability and create health-enabling environments. Evidence supports the immediate implementation of broader HCV and HIV testing and substance use screening, medication-assisted treatment, needle/syringe exchange programs, naloxone programs, increased population-level implementation of HCV treatment, and further attention to structural-level factors predicting, and contributing to, area-level vulnerability, such as degrees of opioid marketing, distribution, and prescribing.

  15. Genetic variants in IL-6 and IL-10 genes and susceptibility to hepatocellular carcinoma in HCV infected patients.

    Science.gov (United States)

    Sghaier, Ikram; Mouelhi, Leila; Rabia, Noor A; Alsaleh, Bano R; Ghazoueni, Ezzedine; Almawi, Wassim Y; Loueslati, Besma Yacoubi

    2017-01-01

    Hepatitis C virus (HCV) infection is the major cause of hepatocellular carcinoma (HCC), a common primary liver malignancy, and the third leading cause of cancer-related death. The HCC risk increases with the severity of liver inflammation, and the clinical course of HCV infection depends on a balance between pro- and anti-inflammatory cytokines. The former includes interleukin (IL)-6, while the latter includes IL-10. However, the exact pathogenic mechanisms underlying IL-6 and IL-10 effects remain unclear. The present study evaluated 174 chronic HCV Tunisian patients. Polymorphisms of IL-6 (rs1880242, rs1474847, rs2069840, rs1800797, rs1800796, rs2069845, rs2069827, rs1474348, rs1800795), and IL-10 (rs1800896, rs1800871, rs1800872, rs1554286, rs1878672, rs1518111) were determined by real-time PCR. Notable differences between chronic HCV-infected patients and HCC patients were observed for the three IL-10 SNPs; rs1800871 (-819T/C), rs1800872 (-592A/C), and rs1878672. Carriage of IL-6 rs1800796 G/G genotype, IL-6 rs1474358 C-allele, and IL-6 rs1800797 A-allele was more frequent in chronic HCV-infected patients than in HCC patients. On the other hand, IL-6 rs1474358 GG genotype had a favourable factor for HCC establishment. IL-10 and IL-6 SNPs markedly influence the clinical outcomes of HCV infection. These SNPs could be used as biomarkers for early detection and molecular therapy for preventing HCC, and prognostic factors for predicting the clinical outcomes of HCC. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. Impact of old Schistosomiasis infection on the use of transient elastography (Fibroscan) for staging of fibrosis in chronic HCV patients.

    Science.gov (United States)

    Ramzy, Iman; Elsharkawy, Aisha; Fouad, Rabab; Hafez, Hanan Abdel; El Raziky, Maissa; El Akel, Wafaa; El-Sayed, Mohammad; Khattab, Hany; Shehata, Mohamed; Elsharkawy, Marwa; Radwan, Amr; Esmat, Gamal

    2017-12-01

    In tropical regions, Hepatitis C virus (HCV) - Schistosomiasis coinfection remains one of the health problems. With the new era of HCV treatment and the variety of methods of assessment of liver fibrosis so we aimed to evaluate the effectiveness of FibroScan for staging hepatic fibrosis in HCV-Schistosomiasis coinfected patients. Three groups of patients were enrolled. Group 1: chronic HCV with out antischistosomal antibody (122 patients), Group 2: chronic HCV with positive antischistosomal antibodies and without periportal tract thickening (122 patients), Group 3: chronic HCV with positive antischistosomal antibodies and ultrasonographic picture of periportal tract thickening (108 patients). Routine laboratory workup, serum Antischistosomal antibody, and Schistosomal antigen in serum were performed. Ultrasound guided liver biopsy with histopathological examination; abdominal ultrasound and fibroscan examination were done for all patients. The agreement between results of liver biopsy and results of fibroscan in the staging of fibrosis was the best in group 1 (55.7%), Although the agreement was higher among those with no periportal tract thickening (70.7%) and the disagreement was higher among those with positive schistosomal serology (66.5%), yet this relation was not statistically significant. Multivariate logistic regression analysis showed that disagreement is significantly associated with older age, higher BMI (≥30), and increase in anti Schistosomal antibody titer. Fibroscan is a reliable, non-invasive tool for staging hepatic fibrosis among HCV-schistosomiasis co-infected patients with no effect of the induced periportal tract thickening on the readings. Only higher antischistosomal antibody titres may cause disagreement between liver biopsy and fibroscan. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Imaging findings in children with proliferative disorders following multivisceral transplantation

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    Hryhorczuk, Anastasia L. [Tufts Medical Center, Department of Radiology, Boston, MA (United States); Kim, Heung Bae [Boston Children' s Hospital, Department of Surgery, Boston, MA (United States); Harris, Marian H.; Vargas, Sara O. [Boston Children' s Hospital, Department of Pathology, Boston, MA (United States); Zurakowski, David [Boston Children' s Hospital, Department of Biostatistics, Boston, MA (United States); Lee, Edward Y. [Boston Children' s Hospital and Harvard Medical School, Departments of Radiology and Medicine, Boston, MA (United States)

    2015-08-15

    Multivisceral transplantation represents an important treatment option for children with intestinal failure. The attendant immunosuppression can lead to a spectrum of cellular proliferations including benign and malignant smooth muscle tumors and lymphoproliferative disorders, many related to cellular dysregulation from Epstein-Barr virus infection. The purpose of this study is to investigate the rates of post-transplantation proliferative disorders among children with multivisceral transplantation and to characterize the imaging and pathological features of these disorders. We identified all consecutive children who underwent multivisceral transplant from August 2004 to October 2011 with at least 27 months of clinical and imaging follow-up. We reviewed medical records to determine the underlying causes of the multivisceral transplant, age at transplantation, onset of neoplasm development, and outcome. Two pediatric radiologists reviewed all imaging studies independently and diagnosis of disease was made by consensus interpretation. Pathological specimens were reviewed for histopathological findings of post-transplantation neoplasm in this pediatric patient population. The study population consisted of 14 consecutive pediatric patients (7 boys and 7 girls; mean age 26 months, range 4-113 months). Of these 14 children, 4 (29%) developed histologically confirmed post-transplant neoplasms at a mean time of 2.4 years after multivisceral transplantation. Types of neoplasms included post-transplant lymphoproliferative disorder (PTLD) in three (21%) and Epstein-Barr-virus-associated smooth muscle tumor in two (14%). (One child developed both neoplasms following transplantation). Both children with smooth muscle tumor associated with Epstein-Barr virus presented with characteristic hypointense solid masses with peripheral rim enhancement on cross-sectional imaging studies. The mortality rate of children who developed post-transplant neoplasms was higher than that of those

  18. Imaging findings in children with proliferative disorders following multivisceral transplantation

    International Nuclear Information System (INIS)

    Hryhorczuk, Anastasia L.; Kim, Heung Bae; Harris, Marian H.; Vargas, Sara O.; Zurakowski, David; Lee, Edward Y.

    2015-01-01

    Multivisceral transplantation represents an important treatment option for children with intestinal failure. The attendant immunosuppression can lead to a spectrum of cellular proliferations including benign and malignant smooth muscle tumors and lymphoproliferative disorders, many related to cellular dysregulation from Epstein-Barr virus infection. The purpose of this study is to investigate the rates of post-transplantation proliferative disorders among children with multivisceral transplantation and to characterize the imaging and pathological features of these disorders. We identified all consecutive children who underwent multivisceral transplant from August 2004 to October 2011 with at least 27 months of clinical and imaging follow-up. We reviewed medical records to determine the underlying causes of the multivisceral transplant, age at transplantation, onset of neoplasm development, and outcome. Two pediatric radiologists reviewed all imaging studies independently and diagnosis of disease was made by consensus interpretation. Pathological specimens were reviewed for histopathological findings of post-transplantation neoplasm in this pediatric patient population. The study population consisted of 14 consecutive pediatric patients (7 boys and 7 girls; mean age 26 months, range 4-113 months). Of these 14 children, 4 (29%) developed histologically confirmed post-transplant neoplasms at a mean time of 2.4 years after multivisceral transplantation. Types of neoplasms included post-transplant lymphoproliferative disorder (PTLD) in three (21%) and Epstein-Barr-virus-associated smooth muscle tumor in two (14%). (One child developed both neoplasms following transplantation). Both children with smooth muscle tumor associated with Epstein-Barr virus presented with characteristic hypointense solid masses with peripheral rim enhancement on cross-sectional imaging studies. The mortality rate of children who developed post-transplant neoplasms was higher than that of those

  19. HCV core protein-induced down-regulation of microRNA-152 promoted aberrant proliferation by regulating Wnt1 in HepG2 cells.

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    Shifeng Huang

    Full Text Available Hepatitis C virus (HCV has been reported to regulate cellular microRNAs (miRNAs. The HCV core protein is considered to be a potential oncoprotein in HCV-related hepatocellular carcinoma (HCV-HCC, but HCV core-regulated miRNAs are largely unknown. Our preliminary experiments revealed significant down-regulation of microRNA-152 (miR-152 by HCV core protein in HepG2 cells. Through target gene prediction softwares, Wnt1 was predicted to be a potential target of miR-152. The present study was initiated to investigate whether miR-152 is aberrantly regulated by the HCV core protein, and involved in the regulation of the aberrant proliferation of HCV-HCC cells.MiR-152 levels were examined by stem-loop real-time RT-PCR (SLqRT-PCR. Cell proliferation was analyzed by MTT and colony formation assay. Cell cycle analysis was performed by flow cytometry. Luciferase reporter assay was conducted to confirm miRNA-target association. Wnt1 expression was determined by real-time qPCR and Western blotting.HCV core protein significantly suppressed miR-152 expression, and led to significant Wnt1 up-regulation with a concomitant aberrantly promoted proliferation. Moreover, we validated that miR-152 inhibition promoted, while miR-152 mimics inhibited cell proliferation. Using, qRT-PCR and western blot, Wnt1 was demonstrated to be regulated by miR-152. Luciferase activity assay showed that while miR-152 mimics significantly reduced the luciferase activity by 83.76% (P<0.0001, miR-152 inhibitor showed no effect on luciferase reporter. Most notably, salvage expression of miR-152 after Ad-HCV core infection for 24 h almost totally reversed the proliferation-promoting effect of the HCV core protein, and meanwhile, reduced the expression of both Wnt1 mRNA and protein to basal levels.These findings provide important evidence that the reduced miR-152 expression by HCV core protein can indirectly lose an inhibitory effect on Wnt1, which might, at least partially lead to cell

  20. Assessment of immunological changes in Epstein-Barr virus co-infection in Egyptian chronic HCV patients

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    Sahar Shoman

    2014-09-01

    Full Text Available Epstein-Barr virus (EBV plays a major role in liver pathology. Similar to other members of the herpesvirus family, EBV establishes a persistent infection in more than 90% of adults. The aim of this study was to evaluate the impact of EBV and chronic hepatitis C co-infection (HCV on biochemical and immunological responses in patients. The study was conducted in 62 patients and 33 apparently healthy controls. Patients were divided into three groups: group I, consisting of 31 patients with chronic hepatitis C infection (CHC, group II, consisting of eight patients with EBV infection and without HCV infection and group III, consisting of 23 patients with EBV and chronic HCV. The percentage of CD3+ cells, helper CD4+ cells and CD19+ B-cells was measured by flow cytometry. Human interferon-γ (IFN-γ and interleukin (IL-15 levels were measured by an ELISA. The levels of liver alanine aminotransferase and aspartate aminotransferase enzymes were higher in EBV/HCV patients compared to that in EBV and HCV mono-infected patients. EBV/HCV patients had significantly reduced percentages of CD3+ and CD4+ cells compared to EBV patients. Serum IFN-γ levels were significantly reduced in EBV/HCV patients (3.86 pg/mL compared to CHC patients (6.76 pg/mL and normal controls (4.69 pg/mL. A significant increase in serum IL-15 levels was observed in EBV/HCV patients (67.7 pg/mL compared to EBV patients (29.3 pg/mL. Taken together, these observations suggest that HCV and EBV co-infection can potentiate immune response dampening in patients.

  1. Neutralizing activities of caprine antibodies towards conserved regions of the HCV envelope glycoprotein E2

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    El-Shenawy Reem

    2011-08-01

    Full Text Available Abstract Anti HCV vaccine is not currently available and the present antiviral therapies fail to cure approximately half of the treated HCV patients. This study was designed to assess the immunogenic properties of genetically conserved peptides derived from the C-terminal region of HVR-1 and test their neutralizing activities in a step towards developing therapeutic and/or prophylactic immunogens against HCV infection. Antibodies were generated by vaccination of goats with synthetic peptides derived from HCV E2. Viral neutralizing capacity of the generated anti E2 antibodies was tested using in vitro assays. Goats immunized with E2 synthetic peptides termed p412 [a.a 412-419], p430 [a.a 430-447] and p517 [a.a 517-531] generated high titers of antibody responses 2 to 4.5 fold higher than comparable titers of antibodies to the same epitopes in chronic HCV patients. In post infection experiments of native HCV into cultured Huh7.5 cells anti p412 and anti p 517 were proven to be neutralizing to HCV genotype 4a from patients' sera (87.5% and 75% respectively. On the contrary anti p430 exhibited weak viral neutralization capacity on the same samples (31.25%. Furthermore Ab mixes containing anti p430 exhibited reduced viral neutralization properties. From these experiments one could predict that neutralization by Abs towards different E2-epitopes varies considerably and success in the enrichment of neutralization epitope-specific antibodies may be accompanied by favorable results in combating HCV infection. Also, E2 conserved peptides p517 and p412 represent potential components of a candidate peptide vaccine against HCV infection.

  2. The undiagnosed chronically-infected HCV population in France. Implications for expanded testing recommendations in 2014.

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    Cécile Brouard

    Full Text Available Recent HCV therapeutic advances make effective screening crucial for potential HCV eradication. To identify the target population for a possible population-based screening strategy to complement current risk-based testing in France, we aimed to estimate the number of adults with undiagnosed chronic HCV infection and age and gender distribution at two time points: 2004 and 2014.A model taking into account mortality, HCV incidence and diagnosis rates was applied to the 2004 national seroprevalence survey.In 2014, an estimated 74,102 individuals aged 18 to 80 were undiagnosed for chronic HCV infection (plausible interval: 64,920-83,283 compared with 100,868 [95%CI: 58,534-143,202] in 2004. Men aged 18-59 represented approximately half of the undiagnosed population in 2014. The proportion of undiagnosed individuals in 2004 (43% varied from 21.9% to 74.1% in the 1945-1965 and 1924-1944 birth cohorts. Consequently, age and gender distributions between the chronically-infected (diagnosed and undiagnosed and undiagnosed HCV populations were different, the 1945-1965 birth cohort representing 48.9% and 24.7%, respectively.Many individuals were still undiagnosed in 2014 despite a marked reduction with respect to 2004. The present work contributed to the 2014 recommendation of a new French complementary screening strategy, consisting in one-time simultaneous HCV, HBV and HIV testing in men aged 18-60. Further studies are needed to assess the cost-effectiveness and feasibility of such a strategy. We also demonstrated that data on the undiagnosed HCV population are crucial to help adapt testing strategies, as the features of the chronically-infected HCV population are very distinct.

  3. Cost-Effectiveness of HBV and HCV Screening Strategies – A Systematic Review of Existing Modelling Techniques

    Science.gov (United States)

    Geue, Claudia; Wu, Olivia; Xin, Yiqiao; Heggie, Robert; Hutchinson, Sharon; Martin, Natasha K.; Fenwick, Elisabeth; Goldberg, David

    2015-01-01

    Introduction Studies evaluating the cost-effectiveness of screening for Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) are generally heterogeneous in terms of risk groups, settings, screening intervention, outcomes and the economic modelling framework. It is therefore difficult to compare cost-effectiveness results between studies. This systematic review aims to summarise and critically assess existing economic models for HBV and HCV in order to identify the main methodological differences in modelling approaches. Methods A structured search strategy was developed and a systematic review carried out. A critical assessment of the decision-analytic models was carried out according to the guidelines and framework developed for assessment of decision-analytic models in Health Technology Assessment of health care interventions. Results The overall approach to analysing the cost-effectiveness of screening strategies was found to be broadly consistent for HBV and HCV. However, modelling parameters and related structure differed between models, producing different results. More recent publications performed better against a performance matrix, evaluating model components and methodology. Conclusion When assessing screening strategies for HBV and HCV infection, the focus should be on more recent studies, which applied the latest treatment regimes, test methods and had better and more complete data on which to base their models. In addition to parameter selection and associated assumptions, careful consideration of dynamic versus static modelling is recommended. Future research may want to focus on these methodological issues. In addition, the ability to evaluate screening strategies for multiple infectious diseases, (HCV and HIV at the same time) might prove important for decision makers. PMID:26689908

  4. Low prevalence of HCV infection with predominance of genotype 4 among HIV patients living in Libreville, Gabon.

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    Angélique Ndjoyi-Mbiguino

    Full Text Available Gabon is an endemic area for human immunodeficiency virus (HIV and hepatitis C virus (HCV and the risk of co-infection is high.Between November 2015 and April 2016, we conducted retrospective study on HCV infection among people living with HIV/AIDS (PLHA. A total of 491 PLHA were included in this study and tested for the presence of HCV infection. HIV viral loads were obtained using the Generic HIV viral Load® assay and the CD4+ T cells count was performed using BD FACSCount™ CD4 reagents. HCV screening was performed using the MP Diagnostics HCV ELISA 4.0 kit. HCV genotypes were determined by sequence analysis of NS5B and Core regions. The Mann-Whitney test was used to compare the groups. Chi-2 test and Fisher's Exact Test were used to compare prevalence.HCV seroprevalence was 2.9% (14/491, (95% confidence interval (CI:1.4-4.3%. The percentage of HCV viremic patients, defined by the detection of HCV RNA in plasma, was 57% (8/14, representing 1.6% of the total population. HCV seroprevalence and replicative infection were not statistically differ with gender. The percentage of co-infection increased with age. No correlation with CD4+ T cells count and HIV viral load level was registered in this study. Identified HCV strains were predominantly of genotype 4 (87.5% including 4k, 4e, 4g, 4p, 4f and 4c subtypes. Only one strain belonged to genotype 2 (subtype 2q. Analysis of the NS5B region did not reveal the presence of resistance-associated substitutions for sofosbuvir.A systematic screening of hepatitis C is therefore strongly recommended as well as genotyping of HCV strains in order to adapt treatments for the specific case of people living with HIV/AIDS in Central Africa.

  5. A study on the relationship of anti-HCV antibody and hepatitis C viremia in post-transfusion hepatitis

    International Nuclear Information System (INIS)

    Lee, Dong Soon

    1993-01-01

    The specimens of blood transfusion recipients who recieved the Anti-HCV antibody positive bloods were analyzed at irregular intervals by enzyme immunoassay to measure the anti-HCV antibody and reverse transcription PCR of hepatitis C virus to evaluate the viremic states. At the same time, the specimens of anti-HCV antibody positive healthy blood donors are analyzed by the reverse transcription PCR method. We analyzed the 9 cases of anti-HCV positive blood donors by reverse transcription PCR and no cases of positive HCV reverse transcription PCR is found. The 5 patients who recieved the anti-HCV positive blood by blood transfusion was followed at irregular interval. Of 5 blood recipients, Hepatitis C virus was detected in 2 patients (40%) and Anti-HCV antibody was detected in 2 patients (40%). We suppose that in contrast to disease group (Non A non B hepatitis), the possibility of viremia in the anti-HCV positive blood donors is significantly low and the character of those antibody may be convalescent antibody after hepatitis C resolution. (Author)

  6. A study on the relationship of anti-HCV antibody and hepatitis C viremia in post-transfusion hepatitis

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Dong Soon [Korea Cancer Center Hospital, Seoul (Korea, Republic of)

    1993-01-01

    The specimens of blood transfusion recipients who recieved the Anti-HCV antibody positive bloods were analyzed at irregular intervals by enzyme immunoassay to measure the anti-HCV antibody and reverse transcription PCR of hepatitis C virus to evaluate the viremic states. At the same time, the specimens of anti-HCV antibody positive healthy blood donors are analyzed by the reverse transcription PCR method. We analyzed the 9 cases of anti-HCV positive blood donors by reverse transcription PCR and no cases of positive HCV reverse transcription PCR is found. The 5 patients who recieved the anti-HCV positive blood by blood transfusion was followed at irregular interval. Of 5 blood recipients, Hepatitis C virus was detected in 2 patients (40%) and Anti-HCV antibody was detected in 2 patients (40%). We suppose that in contrast to disease group (Non A non B hepatitis), the possibility of viremia in the anti-HCV positive blood donors is significantly low and the character of those antibody may be convalescent antibody after hepatitis C resolution. (Author).

  7. CXCL10 Decreases GP73 Expression in Hepatoma Cells at the Early Stage of Hepatitis C Virus (HCV Infection

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    Yuan Liu

    2013-12-01

    Full Text Available Golgi protein 73 (GP73, which is up-regulated in hepatocellular carcinoma (HCC, has recently been identified as a novel serum marker for HCC diagnosis. Several reports also noted the increased levels of GP73 expression in chronic liver disease in patients with acute hepatitis of various etiologies, chronic Hepatitis C virus (HCV infection and alcoholic liver disease. The molecular mechanisms of GP73 expression in HCV related liver disease still need to be determined. In this study, we aimed to evaluate the effect of HCV infection on GP73 expression. GP73 was highly expressed in Huh7, Hep3B, 293T and HUVEC cells, and was low-expressed in HepG2 cells. HCV infection led to down-regulation of GP73 in Huh7 and HepG2/CD81 cells at the early stage of infection. CXCL10 decreased GP73 expression in Huh7 and HepG2 cells. Up-regulation of GP73 was noted in hepatocytes with cytopathic effect at advanced stage of HCV infection, and further research is needed to determine the unknown factors affecting GP73 expression. In conclusion, our study provided additional evidence for the roles of GP73 in liver disease.

  8. Correlation between HIV and HCV in Brazilian prisoners: evidence for parenteral transmission inside prison Correlação entre HIV e HCV em prisioneiros brasileiros: evidência de transmissão parenteral no encarceramento

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    MN Burattini

    2000-10-01

    Full Text Available OBJECTIVE: It is an accepted fact that confinement conditions increase the risk of some infections related to sexual and/or injecting drugs practices. Mathematical techniques were applied to estimate time-dependent incidence densities of HIV infection among inmates. METHODS: A total of 631 prisoners from a Brazilian prison with 4,900 inmates at that time were interviewed and their blood drawn. Risky behavior for HIV infection was analyzed, and serological tests for HIV, hepatitis C and syphilis were performed, intended as surrogates for parenteral and sexual HIV transmission, respectively. Mathematical techniques were used to estimate the incidence density ratio, as related to the time of imprisonment. RESULTS: Prevalence were: HIV -- 16%; HCV -- 34%; and syphilis -- 18%. The main risk behaviors related to HIV infection were HCV prevalence (OR=10.49 and the acknowledged use of injecting drugs (OR=3.36. Incidence density ratio derivation showed that the risk of acquiring HIV infection increases with the time of imprisonment, peaking around three years after incarceration. CONCLUSIONS: The correlation between HIV and HCV seroprevalence and the results of the mathematical analysis suggest that HIV transmission in this population is predominantly due to parenteral exposure by injecting drug, and that it increases with time of imprisonment.OBJETIVO: É um fato correntemente aceito que as condições de confinamento aumentam o risco de algumas infecções relacionadas às práticas sexuais e/ou ao uso de drogas injetáveis. Realizou-se estudo para estimar a densidade de incidência da infecção pelo HIV na população prisional com aplicação de técnicas matemáticas. MÉTODOS: Foram entrevistados em São Paulo, SP, 631 prisioneiros da maior prisão da América do Sul, que abrigava aproximadamente 4.900 presos na ocasião do estudo. Foi colhido sangue da população entrevistada, analisado o risco para a infecção pelo HIV e realizados testes

  9. Related Addictive Disorders.

    Science.gov (United States)

    Buck, Tina; Sales, Amos

    This paper provides an overview of addiction related to substance abuse. It provides basic information, prevalence, diagnostic criteria, assessment tools, and treatment issues for eating disorders, compulsive gambling, sex addictions, and work addictions. Eating disorders such as anorexia nervosa and bulimia nervosa, especially affect adolescents.…

  10. [Clinical benefit of HCV core antigen assay in patients receiving interferon and ribavirin combination therapy].

    Science.gov (United States)

    Higashimoto, Makiko; Takahashi, Masahiko; Jokyu, Ritsuko; Saito, Hidetsugu

    2006-02-01

    A highly sensitive second generation HCV core antigen assay has recently been developed. We compared viral disappearance and kinetics data between commercially available core antigen assays, Lumipulse Ortho HCV Ag, and a quantitative HCV RNA PCR assay, Cobas Amplicor HCV Monitor Test, Version 2 to estimate the predictive benefit of sustained viral response (SVR) and non-SVR in 59 patients treated with interferon and ribavirin combination therapy. We found a good correlation between HCV core Ag and HCV RNA level regardless of genotype. Although the sensitivity of the core antigen assay was lower than PCR, the dynamic range was broader than that of the PCR assay, so that we did not need to dilute the samples in 59 patients. We detected serial decline of core Ag levels in 24 hrs, 7 days and 14 days after interferon combination therapy. The decline of core antigen levels was significant in SVR patients compared to non-SVR as well as in genotype 2a, 2b patients compared to 1b. Core antigen-negative on day 1 could predict all 10 SVR patients (PPV = 100%), whereas RNA-negative could predict 22 SVR out of 25 on day 14 (PPV = 88.0%). None of the patients who had detectable serum core antigen on day 14 became SVR(NPV = 100%), although NPV was 91.2% on RNA negativity. An easy, simple, low cost new HCV core antigen detecting system seems to be useful for assessing and monitoring IFN treatment for HCV.

  11. Epstein-Barr Virus-Negative Post-Transplant Lymphoproliferative Diseases: Three Distinct Cases from a Single Center

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    Şule Mine Bakanay

    2014-03-01

    Full Text Available Three cases of Epstein-Barr virus (EBV-negative post-transplant lymphoproliferative disease that occurred 6 to 8 years after renal transplantation are reported. The patients respectively had gastric mucosa-associated lymphoid tissue lymphoma, gastric diffuse large B-cell lymphoma, and atypical Burkitt lymphoma. Absence of EBV in the tissue samples was demonstrated by both in situ hybridization for EBV early RNA and polymerase chain reaction for EBV DNA. Patients were treated with reduction in immunosuppression and combined chemotherapy plus an anti-CD20 monoclonal antibody, rituximab. Despite the reduction in immunosuppression, patients had stable renal functions without loss of graft functions. The patient with atypical Burkitt lymphoma had an abnormal karyotype, did not respond to treatment completely, and died due to disease progression. The other patients are still alive and in remission 5 and 3 years after diagnosis, respectively. EBV-negative post-transplant lymphoproliferative diseases are usually late-onset and are reported to have poor prognosis. Thus, reduction in immunosuppression is usually not sufficient for treatment and more aggressive approaches like rituximab with combined chemotherapy are required.

  12. HCV INFECTION THROUGH PERFORATING AND CUTTING MATERIAL AMONG CANDIDATES FOR BLOOD DONATION IN BELÉM, BRAZILIAN AMAZON

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    Rubenilson Caldas Valois

    2014-12-01

    Full Text Available This study evaluated epidemiological factors for HCV infection associated with sharing perforating and cutting instruments among candidates for blood donation (CBD in the city of Belém, Pará, Brazilian Amazon. Two definitions of HCV infection cases were used: anti-HCV positivity shown by EIA, and HCV-RNA detection by PCR. Infected and uninfected CBD completed a questionnaire about possible risk factors associated with sharing perforating and cutting instruments. The information was evaluated using simple and multiple logistic regressions. Between May and November 2010, 146 (1.1% persons with anti-HCV antibodies and 106 (0.8% with HCV-RNA were detected among 13,772 CBD in Belém. Risk factors associated with HCV infection based on the EIA (model 1 and PCR (model 2 results were: use of needles and syringes sterilized at home; shared use of razors at home, sharing of disposable razors in barbershops, beauty salons etc.; and sharing manicure and pedicure material. The models of HCV infection associated with sharing perforating and cutting instruments should be taken into account by local and regional health authorities and by those of other countries with similar cultural practices, in order to provide useful information to guide political and public strategies to control HCV transmission.

  13. Candidiasis and other oral mucosal lesions during and after interferon therapy for HCV-related chronic liver diseases

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    Nagao Yumiko

    2012-11-01

    Full Text Available Abstract Background Oral lichen planus (OLP is seen frequently in patients with hepatitis C virus (HCV infection. The aim of this study was to evaluate the occurrence of oral candidiasis, other mucosal lesions, and xerostomia during interferon (IFN therapy for HCV infection. Methods Of 124 patients with HCV-infected liver diseases treated with IFN therapy in our hospital, 14 (mean age 56.00 ± 12.94 years who attended to receive administration of IFN once a week were identified and examined for Candida infection and other oral lesions and for the measurement of salivary flow. Serological assays also were carried out. Results Cultures of Candida from the tongue surfaces were positive in 7 (50.0% of the 14 patients with HCV infection at least once during IFN therapy. C. albicans was the most common species isolated. The incidence of Candida during treatment with IFN did not increase above that before treatment. Additional oral mucosal lesions were observed in 50.0% (7/14 of patients: OLP in three (21.4%, angular cheilitis in three (21.4% and recurrent aphthous stomatitis in one (7.1%. OLP occurred in one patient before treatment with IFN, in one during treatment and in one at the end of treatment. 85.7% of the oral lesions were treated with topical steroids. We compared the characteristics of the 7 patients in whom Candida was detected at least once during IFN therapy (group 1 and the 7 patients in whom Candida was not detected during IFN therapy (group 2. The prevalence of oral mucosal lesions (P=0.0075 and incidence of external use of steroids (P=0.0308 in group 1 were significantly higher than in group 2. The average body weight of group 1 decreased significantly compared to group 2 (P=0.0088. Salivary flow decreased in all subjects throughout the course of IFN treatment and returned at 6th months after the end of treatment. In group 1, the level of albumin at the beginning of the 6th month of IFN administration was lower than in group 2 (P=0

  14. People with Multiple Tattoos and/or Piercings Are Not at Increased Risk for HBV or HCV in The Netherlands

    Science.gov (United States)

    Urbanus, Anouk T.; van den Hoek, Anneke; Boonstra, Albert; van Houdt, Robin; de Bruijn, Lotte J.; Heijman, Titia; Coutinho, Roel A.; Prins, Maria

    2011-01-01

    Background Although published results are inconsistent, it has been suggested that tattooing and piercing are risk factors for HBV and HCV infections. To examine whether tattooing and piercing do indeed increase the risk of infection, we conducted a study among people with multiple tattoos and/or piercings in the Netherlands who acquired their tattoos and piercings in the Netherlands and/or abroad. Methods Tattoo artists, piercers, and people with multiple tattoos and/or piercings were recruited at tattoo conventions, shops (N = 182), and a biannual survey at our STI-outpatient clinic (N = 252) in Amsterdam. Participants were interviewed and tested for anti-HBc and anti-HCV. Determinants of HBV and HCV infections were analysed using logistic regression analysis. Results The median number of tattoos and piercings was 5 (IQR 2–10) and 2 (IQR 2–4), respectively. Almost 40% acquired their tattoo of piercing abroad. In total, 18/434 (4.2%, 95%CI: 2.64%–6.46%) participants were anti-HBc positive and 1 was anti-HCV positive (0.2%, 95%CI: 0.01%–1.29%). Being anti-HBc positive was independently associated with older age (OR 1.68, 95%CI: 1.03–2.75 per 10 years older) and being born in an HBV-endemic country (OR 7.39, 95%CI: 2.77–19.7). Tattoo- and/or piercing-related variables, like having a tattoo or piercing in an HBV endemic country, surface percentage tattooed, number of tattoos and piercings etc., were not associated with either HBV or HCV. Conclusions We found no evidence for an increased HBV/HCV seroprevalence among persons with multiple tattoos and/or piercings, which might be due to the introduction of hygiene guidelines for tattoo and piercing shops in combination with the low observed prevalence of HBV/HCV in the general population. Tattoos and/or piercings, therefore, should not be considered risk factors for HBV/HCV in the Dutch population. These findings imply the importance of implementation of hygiene guidelines in other countries. PMID

  15. People with multiple tattoos and/or piercings are not at increased risk for HBV or HCV in The Netherlands.

    Science.gov (United States)

    Urbanus, Anouk T; van den Hoek, Anneke; Boonstra, Albert; van Houdt, Robin; de Bruijn, Lotte J; Heijman, Titia; Coutinho, Roel A; Prins, Maria

    2011-01-01

    Although published results are inconsistent, it has been suggested that tattooing and piercing are risk factors for HBV and HCV infections. To examine whether tattooing and piercing do indeed increase the risk of infection, we conducted a study among people with multiple tattoos and/or piercings in The Netherlands who acquired their tattoos and piercings in The Netherlands and/or abroad. Tattoo artists, piercers, and people with multiple tattoos and/or piercings were recruited at tattoo conventions, shops (N = 182), and a biannual survey at our STI-outpatient clinic (N = 252) in Amsterdam. Participants were interviewed and tested for anti-HBc and anti-HCV. Determinants of HBV and HCV infections were analysed using logistic regression analysis. The median number of tattoos and piercings was 5 (IQR 2-10) and 2 (IQR 2-4), respectively. Almost 40% acquired their tattoo of piercing abroad. In total, 18/434 (4.2%, 95%CI: 2.64%-6.46%) participants were anti-HBc positive and 1 was anti-HCV positive (0.2%, 95%CI: 0.01%-1.29%). Being anti-HBc positive was independently associated with older age (OR 1.68, 95%CI: 1.03-2.75 per 10 years older) and being born in an HBV-endemic country (OR 7.39, 95%CI: 2.77-19.7). Tattoo- and/or piercing-related variables, like having a tattoo or piercing in an HBV endemic country, surface percentage tattooed, number of tattoos and piercings etc., were not associated with either HBV or HCV. We found no evidence for an increased HBV/HCV seroprevalence among persons with multiple tattoos and/or piercings, which might be due to the introduction of hygiene guidelines for tattoo and piercing shops in combination with the low observed prevalence of HBV/HCV in the general population. Tattoos and/or piercings, therefore, should not be considered risk factors for HBV/HCV in the Dutch population. These findings imply the importance of implementation of hygiene guidelines in other countries.

  16. People with multiple tattoos and/or piercings are not at increased risk for HBV or HCV in The Netherlands.

    Directory of Open Access Journals (Sweden)

    Anouk T Urbanus

    Full Text Available BACKGROUND: Although published results are inconsistent, it has been suggested that tattooing and piercing are risk factors for HBV and HCV infections. To examine whether tattooing and piercing do indeed increase the risk of infection, we conducted a study among people with multiple tattoos and/or piercings in The Netherlands who acquired their tattoos and piercings in The Netherlands and/or abroad. METHODS: Tattoo artists, piercers, and people with multiple tattoos and/or piercings were recruited at tattoo conventions, shops (N = 182, and a biannual survey at our STI-outpatient clinic (N = 252 in Amsterdam. Participants were interviewed and tested for anti-HBc and anti-HCV. Determinants of HBV and HCV infections were analysed using logistic regression analysis. RESULTS: The median number of tattoos and piercings was 5 (IQR 2-10 and 2 (IQR 2-4, respectively. Almost 40% acquired their tattoo of piercing abroad. In total, 18/434 (4.2%, 95%CI: 2.64%-6.46% participants were anti-HBc positive and 1 was anti-HCV positive (0.2%, 95%CI: 0.01%-1.29%. Being anti-HBc positive was independently associated with older age (OR 1.68, 95%CI: 1.03-2.75 per 10 years older and being born in an HBV-endemic country (OR 7.39, 95%CI: 2.77-19.7. Tattoo- and/or piercing-related variables, like having a tattoo or piercing in an HBV endemic country, surface percentage tattooed, number of tattoos and piercings etc., were not associated with either HBV or HCV. CONCLUSIONS: We found no evidence for an increased HBV/HCV seroprevalence among persons with multiple tattoos and/or piercings, which might be due to the introduction of hygiene guidelines for tattoo and piercing shops in combination with the low observed prevalence of HBV/HCV in the general population. Tattoos and/or piercings, therefore, should not be considered risk factors for HBV/HCV in the Dutch population. These findings imply the importance of implementation of hygiene guidelines in other countries.

  17. Indeterminate RIBA results were associated with the absence of hepatitis C virus RNA (HCV-RNA) in blood donors

    OpenAIRE

    Pereira, Felicidade Mota; Zarife, Maria Alice Sant'ana; Reis, Eliana Almeida Gomes; G. Reis, Mitermayer

    2014-01-01

    Introduction: Hepatitis C virus (HCV) infection is diagnosed by the presence of antibodies and is supplemented by confirmatory testing methods, such as recombinant immunoblot assay (RIBA) and HCV-RNA detection. This study aimed to evaluate the efficacy of RIBA testing to diagnose HCV infection in blood donors positive for anti-HCV antibodies. Methods: A total of 102 subjects positive for anti-HCV determined by enzyme-linked immunosorbent assay (ELISA) at the Hematology and Hemotherapy Found...

  18. Arbidol: a broad-spectrum antiviral that inhibits acute and chronic HCV infection

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    Pécheur Eve-Isabelle

    2006-07-01

    Full Text Available Abstract Arbidol (ARB is an antiviral compound that was originally proven effective for treatment of influenza and several other respiratory viral infections. The broad spectrum of ARB anti-viral activity led us to evaluate its effect on hepatitis C virus (HCV infection and replication in cell culture. Long-term ARB treatment of Huh7 cells chronically replicating a genomic length genotype 1b replicon resulted in sustained reduction of viral RNA and protein expression, and eventually cured HCV infected cells. Pre-treatment of human hepatoma Huh7.5.1 cells with 15 μM ARB for 24 to 48 hours inhibited acute infection with JFH-1 virus by up to 1000-fold. The inhibitory effect of ARB on HCV was not due to generalized cytotoxicity, nor to augmentation of IFN antiviral signaling pathways, but involved impaired virus-mediated membrane fusion. ARB's affinity for membranes may inhibit several aspects of the HCV lifecycle that are membrane-dependent.

  19. Structure-based drug design of novel peptidomimetic cellulose derivatives as HCV-NS3 protease inhibitors.

    Science.gov (United States)

    Saleh, Noha A; Elshemey, Wael M

    2017-10-15

    Hepatitis C Virus (HCV) represents a global health threat not only due to the large number of reported worldwide HCV infections, but also due to the absence of a reliable vaccine for its prevention. HCV NS3 protease is one of the most important targets for drug design aiming at the deactivation of HCV. In the present work, molecular docking simulations are carried out for suggested novel NS3 protease inhibitors applied to the Egyptian genotype 4. These inhibitors are modifications of dimer cellulose by adding a hexa-peptide to the cellulose at one of the positions 2, 3, 6, 2', 3' or 6'. Results show that the inhibitor compound with the hexa-peptide at position 6 shows significantly higher simulation docking score with HCV NS3 protease active site. This is supported by low total energy value of docking system, formation of two H-bonds with HCV NS3 protease active site residues, high binding affinity and increased stability in the interaction system. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. HBV reactivation in patients with HCV/HBV cirrhosis on treatment with direct-acting antivirals.

    Science.gov (United States)

    Calvaruso, V; Ferraro, D; Licata, A; Bavetta, M G; Petta, S; Bronte, F; Colomba, G; Craxì, A; Di Marco, V

    2018-01-01

    Anecdotal reports suggest that patients with chronic hepatitis C virus (HCV) hepatitis and overt or occult hepatitis B virus (HBV) coinfection may reactivate HBV when HCV is suppressed or cleared by direct-acting antivirals (DAAs). We assessed the prevalence of overt or previous HBV coinfection and the risk of HBV reactivation in patients with HCV cirrhosis treated with DAAs. This was a retrospective cohort of 104 consecutive patients with HCV cirrhosis treated with DAAs. Serum HCV-RNA and HBV-DNA were tested at weeks 4, 8 and 12 of DAAs therapy and at week 12 of follow-up. At the start of DAAs, eight patients (7.7%) were HBsAg positive/HBeAg negative with undetectable HBV-DNA and low levels of quantitative HBsAg (four on nucleos(t)ide analogues [NUCs] and four inactive carriers), 37 patients (35.6%) had markers of previous HBV infection (25 anti-HBc positive, 12 anti-HBc/anti-HBs positive) and 59 (56.7%) had no evidence of HBV infection. Sixty-seven patients (64.4%) were HCV-RNA negative at week 4 and 98 (94.2%) achieved sustained virological response. All four HBsAg-positive patients treated with NUCs remained HBV-DNA negative, but three of four untreated patients showed an increase in HBV-DNA of 2-3 log without a biochemical flare and achieved HBV-DNA suppression when given NUCs. During or after DAAs, by conventional assay, HBV-DNA remained not detectable in all 37 anti-HBc-positive patients but in three of them (8.1%) HBV-DNA became detectable with a highly sensitive PCR. HBV reactivation is likely to occur in untreated HBV/HCV-coinfected cirrhotic patients when they undergo HCV treatment with DAAs. Pre-emptive therapy with NUCs should be considered in this setting. Anti-HBc-positive patients rarely reactivate HBV without clinical or virological outcomes. © 2017 John Wiley & Sons Ltd.

  1. Detection of hepatitis C virus (HCV among health care providers in an Egyptian university hospital: different diagnostic modalities

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    El-Sokkary RH

    2017-10-01

    Full Text Available Rehab H El-Sokkary,1 Rehab M Elsaid Tash,1 Takwa E Meawed,1 Omnia S El Seifi,2 Eman M Mortada2 1Medical Microbiology and Immunology Department, 2Community, Environmental and Occupational Medicine Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt Background: Hepatitis C virus (HCV infection has received much attention and is placed at the core of the infection control agenda. It is considered as a major public health problem in Egypt, where the highest prevalence of HCV exists. The great risk of exposure to infection of health care providers (HCPs has highlighted the urgent need for implementing an infection control program. Objective: The purpose of this study was to detect the prevalence of HCV infection among HCPs in Zagazig University Hospitals and to assess the performance of different diagnostic modalities.Methodology: Blood, polymerase chain reaction (PCR, enzyme-linked immunosorbent assay (ELISA, and saliva tests were performed in enrolled HCPs.Results: This study compared HCV diagnosis Hepanostika HCV Ultra ELISA as a screening test and PCR as gold standard test, which resulted in 40.6% positive results by ELISA compared to 34.8% by PCR (p<0.0001, while OraQuick HCV rapid antibody compared to PCR shows that 37.7% of the participants were positive by OraQuick HCV rapid antibody test. Application of standard precautions while dealing with blood has negative significant correlation with HCV infection (rs=–0.265, p=0.03.Conclusion: HCPs at Zagazig University Hospitals are at high risk for HCV infection. Lack of compliance and awareness of prevention and control of the infection are associated cofactors. Serum HCV-Ab detection by Hepanostika HCV Ultra ELISA and OraQuick HCV rapid antibody test are sensitive and specific serologic assays for diagnosis with correspondent results to that obtained by quantitative real-time PCR. Keywords: HCV, ROC curve, OraQuick HCV, infection control

  2. Post-transplant lymphoproliferative disease in liver transplant recipients

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    Mercedes Rubio-Manzanares-Dorado

    Full Text Available Introduction: Post-transplant lymphoproliferative syndrome (PTLD is a rare and potentially life-threatening complication after liver transplantation. The aim of this study was to analyze the clinicopathologic features related to PTLD in a single institution after liver transplantation. Methods: Observational study where we have retrospectively analyzed 851 cases who underwent liver transplantation. Ten cases have developed PTLD. Their clinical-pathological characteristics and the treatment received have been analyzed. Results: PTLD incidence was 1.2% (10/851. The mean time from liver transplantation to PTLD diagnosis was 36 months (range 1.2 to 144 months. PTLD localization was extranodal in all cases, the most frequent location being intestinal. Seven cases showed a monomorphic lymphoma which in all cases was differentiated B cell lymphomas. Fifty per cent of the series were seropositive for Epstein-Barr virus. Five patients were alive at the time of the review. Among these patients, we observed three cases of complete remission and two cases of disease stabilization. The death rate was higher in the first year after diagnosis of PTLD. Conclusion: PTLD is a rare complication after liver transplantation, but it may pose a threat to the life of a liver transplant recipient. It is essential to identify patients at risk, to establish an early diagnosis and treatment that can change the outcome of the disease.

  3. Determinazione quantitativa di HCV-RNA: valutazione comparativa dei saggi Abbott Real-Time e Versant bDNA v.3

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    Aldo Manzin

    2007-06-01

    Full Text Available Hepatitis C virus (HCV RNA measurement before, during and after antiviral therapy has become an essential tool in the management of interferon-based treatment of HCV-related infections. Conventional Polymerase Chain Reaction (PCR has been largely used to obtain quantitative data, but laborious, time-consuming post-PCR handling steps are required to gain valuable results. Real time (RT PCR now provides advantages over end-point (EP PCR due to its improved rapidity, sensitivity, reproducibility and the reduced risk of carry-over contamination, and has now proven itself to be valuable for the more precise monitoring of viral load kinetics and assessing antiviral response.The Abbott Real-Time HCV-RNA is a recently introduced assay for the automated processing of clinical samples and HCV-RNA quantitation: its basic technology relies on use of fluorescent linear probes (dynamic range using 0.5 ml as input target= 12-108 IU/mL and a hybridization/detection step at low temperature (35°C, which allows target mismatches to be tolerated. To determine the clinical application of the Abbott Real-Time assay and defining its correlation with the Bayer Versant bDNA v.3 assay, 68 consecutive samples from unselected HCV-infected patients were retrospectively analysed with RT and the results obtained using the two tests compared.A good correlation was found between RT-PCR and bDNA: 97% of samples tested had a result within a 0.5 log HCV IU/mL difference (bias=0.15 log, whereas 6 samples negative with bDNA gave positive results with Abbott RT (range, 1.89-3.07 log IU/mL and “in-house” qualitative RT-PCR assays.

  4. Indeterminate RIBA results were associated with the absence of hepatitis C virus RNA (HCV-RNA) in blood donors.

    Science.gov (United States)

    Pereira, Felicidade Mota; Zarife, Maria Alice Sant'ana; Reis, Eliana Almeida Gomes; G Reis, Mitermayer

    2014-01-01

    Hepatitis C virus (HCV) infection is diagnosed by the presence of antibodies and is supplemented by confirmatory testing methods, such as recombinant immunoblot assay (RIBA) and HCV-RNA detection. This study aimed to evaluate the efficacy of RIBA testing to diagnose HCV infection in blood donors positive for anti-HCV antibodies. A total of 102 subjects positive for anti-HCV determined by enzyme-linked immunosorbent assay (ELISA) at the Hematology and Hemotherapy Foundation of Bahia (HEMOBA) were later assessed with new samples using the Abbott Architect anti-HCV test (Abbott Diagnostics, Wiesbaden, Germany), the RIBA III test (Chiron RIBA HCV 3.0 SIA, Chiron Corp., Emeryville, CA, USA), the polymerase chain reaction (PCR; COBAS® AMPLICOR HCV Roche Diagnostics Corp., Indianapolis, IN, USA) and line probe assay (LiPA - Siemens, Tarrytown, NY, USA) genotyping for HCV diagnosis. Of these new samples, 38.2% (39/102) were positive, 57.8% (59/102) were negative and 3.9% (4/102) were indeterminate for anti-HCV; HCV-RNA was detected in 22.5% (23/102) of the samples. RIBA results were positive in 58.1% (25/43), negative in 9.3% (4/43) and indeterminate in 32.6% (14/43) of the samples. The prevailing genotypes were 1 (78.3%, 18/23), 3 (17.4%, 4/23) and 2 (4.3%, 1/23). All 14 samples with indeterminate RIBA results had undetectable viral loads (detection limit ≤50 IU/mL). Of these samples, 71.4% (10/14) were reevaluated six months later. Eighty percent (8/10) of these samples remained indeterminate by RIBA, and 20% (2/10) were negative. In this study, individuals with indeterminate RIBA results had no detectable HCV-RNA.

  5. Baseline HCV Antibody Prevalence and Risk Factors among Drug Users in China's National Methadone Maintenance Treatment Program.

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    Changhe Wang

    Full Text Available Hepatitis C virus (HCV is the most common viral infection among injecting drug users worldwide. We aimed to assess HCV antibody prevalence and associated risk factors among clients in the Chinese national methadone maintenance treatment (MMT program.Data from 296,209 clients who enrolled in the national MMT program between March 2004 and December 2012 were analyzed to assess HCV antibody prevalence, associated risk factors, and geographical distribution.Anti-HCV screening was positive for 54.6% of clients upon MMT entry between 2004 and 2012. HCV antibody prevalence at entry declined from 66.8% in 2005 to 45.9% in 2012. The most significant predictors of HCV seropositivity were injecting drug use (adjusted odds ratio [AOR]: 8.34, 95% confidence interval [CI]: 8.17-8.52, p<0.0001 and a history of drug use ≥9 years (AOR: 2.01, 95% CI: 1.96-2.06, p<0.0001. Being female, of Uyghur or Zhuang ethnicity, and unmarried were identified as demographic risk factors (all p-values<0.0001. Of the 28 provincial-level divisions included in the study, we found that 5 divisions had HCV antibody prevalence above 70% and 20 divisions above 50%. The HCV screening rate within 6 months after MMT entry greatly increased from 30.4% in 2004 to 93.1% in 2012.The current HCV antibody prevalence remains alarmingly high among MMT clients throughout most provincial-level divisions in China, particularly among injecting drug users and females. A comprehensive prevention strategy is needed to control the HCV epidemic among MMT clients in China.

  6. HIV and HCV coinfection: prevalence, associated factors and genotype characterization in the Midwest Region of Brazil.

    Science.gov (United States)

    Freitas, Solange Zacalusni; Teles, Sheila Araújo; Lorenzo, Paulo Cesar; Puga, Marco Antonio Moreira; Tanaka, Tayana Serpa Ortiz; Thomaz, Danilo Yamamoto; Martins, Regina Maria Bringel; Druzian, Angelita Fernandes; Lindenberg, Andréa Siqueira Campos; Torres, Marina Sawada; Pereira, Sérgio A; Villar, Livia Melo; Lampe, Elisabete; Motta-Castro, Ana Rita Coimbra

    2014-01-01

    A cross-sectional study on prevalence, associated factors and genotype distribution of HCV infection was conducted among 848 HIV-infected patients recruited at reference centers in the Midwest Region of Brazil. The prevalence rate of HIV-HCV coinfection was 6.9% (95% CI: 5.2 to 8.6). In multivariable analysis, increasing age, use of illicit drugs (injection and non-injection), a history of blood transfusion before 1994, and the absence of a steady partnership were significant independent associated factors for HIV-HCV coinfection. The phylogenetic analysis based on the NS5B region revealed the presence of two major circulating genotypes of HCV: genotypes 1 (58.3%) and 3 (41.7%). The prevalence of HIV-HCV coinfection was lower than those reported in studies conducted with HIV-infected patients in different regions of Brazil, due to the fact that illicit drug use is not a frequent mode of HIV transmission in this region of Brazil. Serologic screening of HIV-patients for HCV before initiating antiretroviral treatment, a comprehensive identification of associated factors, and the implementation of effective harm reduction programs are highly recommended to provide useful information for treatment and to prevent HCV coinfection in these patients.

  7. Characterization of skin blister fluids from children with Epstein-Barr virus-associated lymphoproliferative disease.

    Science.gov (United States)

    Wada, Taizo; Toma, Tomoko; Miyazawa, Hanae; Koizumi, Eiko; Shirahashi, Tetsujiro; Matsuda, Yusuke; Yachie, Akihiro

    2018-04-01

    Epstein-Barr virus (EBV)-associated T- or natural killer (NK)-cell lymphoproliferative disease (LPD) is a heterogeneous group of disorders characterized by chronic proliferation of EBV-infected lymphocytes. Patients may present with severe skin manifestations, including hypersensitivity to mosquito bites (HMB) and hydroa vacciniforme (HV)-like eruption, which are characterized by blister formation and necrotic ulceration. Skin biopsy specimens show inflammatory reactions comprising EBV-infected lymphocytes. However, blister fluids have not been fully assessed in patients with this disease. Blister fluids were collected from three patients with EBV-associated LPD: two with HMB and one with HV. Immunophenotyping of blister lymphocytes and measurement of tumor necrosis factor (TNF)-α in blister fluids were performed. The patients with HMB and HV exhibited markedly increased percentages of NK and γδ T cells, respectively, in both peripheral blood and blister fluids. These NK and γδ T cells strongly expressed the activation marker human leukocyte antigen-DR and were considered to be cellular targets of EBV infections. TNF-α was highly elevated in all blister fluids. Severe local skin reactions of EBV-associated LPD may be associated with infiltrating EBV-infected lymphocytes and a high TNF-α concentration in blister fluids. © 2018 Japanese Dermatological Association.

  8. Indeterminate RIBA results were associated with the absence of hepatitis C virus RNA (HCV-RNA in blood donors

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    Felicidade Mota Pereira

    2014-01-01

    Full Text Available Introduction: Hepatitis C virus (HCV infection is diagnosed by the presence of antibodies and is supplemented by confirmatory testing methods, such as recombinant immunoblot assay (RIBA and HCV-RNA detection. This study aimed to evaluate the efficacy of RIBA testing to diagnose HCV infection in blood donors positive for anti-HCV antibodies. Methods: A total of 102 subjects positive for anti-HCV determined by enzyme-linked immunosorbent assay (ELISA at the Hematology and Hemotherapy Foundation of Bahia (HEMOBA were later assessed with new samples using the Abbott Architect anti-HCV test (Abbott Diagnostics, Wiesbaden, Germany, the RIBA III test (Chiron RIBA HCV 3.0 SIA, Chiron Corp., Emeryville, CA, USA, the polymerase chain reaction (PCR; COBAS® AMPLICOR HCV Roche Diagnostics Corp., Indianapolis, IN, USA and line probe assay (LiPA - Siemens, Tarrytown, NY, USA genotyping for HCV diagnosis. Results: Of these new samples, 38.2% (39/102 were positive, 57.8% (59/102 were negative and 3.9% (4/102 were indeterminate for anti-HCV; HCV-RNA was detected in 22.5% (23/102 of the samples. RIBA results were positive in 58.1% (25/43, negative in 9.3% (4/43 and indeterminate in 32.6% (14/43 of the samples. The prevailing genotypes were 1 (78.3%, 18/23, 3 (17.4%, 4/23 and 2 (4.3%, 1/23. All 14 samples with indeterminate RIBA results had undetectable viral loads (detection limit ≤50 IU/mL. Of these samples, 71.4% (10/14 were reevaluated six months later. Eighty percent (8/10 of these samples remained indeterminate by RIBA, and 20% (2/10 were negative. Conclusions: In this study, individuals with indeterminate RIBA results had no detectable HCV-RNA.

  9. IMMUNOTHERAPY FOR EPSTEIN-BARR VIRUS-RELATED LYMPHOMAS

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    Alana Kennedy-Nasser

    2009-11-01

    Full Text Available Latent EBV infection is associated with several malignancies, including EBV post-transplant lymphoproliferative disorders (LPD, Hodgkin and non-Hodgkin lymphomas, nasopharyngeal carcinoma and Burkitt lymphoma. The range of expression of latent EBV antigens varies in these tumors, which influences how susceptible the tumors are to immunotherapeutic approaches. Tumors expressing type III latency, such as in LPD, express the widest array of EBV antigens making them the most susceptible to immunotherapy. Treatment strategies for EBV-related tumors include restoring normal cellular immunity by adoptive immunotherapy with EBV-specific T cells and targeting the malignant B cells with monoclonal antibodies. We review the current immunotherapies and future studies aimed at targeting EBV antigen expression in these tumors.

  10. Prevalence of anti HCV infection in patients with beta-thalassemia in Isfahan-Iran

    Directory of Open Access Journals (Sweden)

    Behrooz Ataei

    2012-01-01

    Conclusions: Our findings revealed that blood transfusion was the main risk factors for HCV infection among beta-thalassemic patients. Therefore, more blood donor screening programs and effective screening techniques are needed to prevent transmission of HCV infection among beta-thalassemic patients.

  11. Preclinical evaluation of multi antigenic HCV DNA vaccine for the prevention of Hepatitis C virus infection.

    Science.gov (United States)

    Lee, Hyojin; Jeong, Moonsup; Oh, Jooyeon; Cho, Youngran; Shen, Xuefei; Stone, John; Yan, Jian; Rothkopf, Zachary; Khan, Amir S; Cho, Byung Mun; Park, Young K; Weiner, David B; Son, Woo-Chan; Maslow, Joel N

    2017-03-07

    Direct-acting antiviral treatment for hepatitis C virus (HCV) infection is costly and does not protect from re-infection. For human and chimpanzees, recovery from acute HCV infection correlates with host CD4+ and CD8+ T cell responses. DNA plasmids targeting the HCV non-structural antigens NS3, NS4, and NS5, were previously reported to induce robust and sustained T cell responses in mice and primates. These plasmids were combined with a plasmid encoding cytokine IL-28B, together named as VGX-6150. The dose-dependent T cell response and safety of VGX-6150 administered intramuscularly and followed by electroporation was assessed in mice. Immune responses plateaued at 20 μg/dose with IL-28B demonstrating significant immunoadjuvant activity. Mice administered VGX-6150 at 40, 400, and 800 μg given either as a single injection or as 14 injections given bi-weekly over 26 weeks showed no vaccine related changes in any clinical parameter compared to placebo recipients. There was no evidence of VGX-6150 accumulation at the injection site or in any organ 1 month following the 14 th vaccination. Based on these studies, the approximate lethal dose (ALD) exceeds 800 μg/dose and the NOAEL was 800 μg/dose in mouse. In conclusion, VGX-6150 appears safe and a promising preventive vaccine candidate for HCV infection.

  12. [HCV and HBV seropositivity in university students of the State of Nuevo Leòn, Mexico].

    Science.gov (United States)

    Flores-Castañeda, M S; García-Méndez, B L; Tijerina-Menchaca, R

    1996-01-01

    Viral hepatitis is a contagious disease. Patients infected with hepatitis B virus (HBV) or hepatitis C virus (HCV), may be either chronically symptomatic or asymptomatic, and suffer cirrhosis and high risk of hepatic carcinoma. Asymptomatic carriers of HBV surface antigen (HBs-Ag) or with anti-HCV antibodies are potentially infectious, and therefore a risk to public health. This work seeks to establish the frequency of seropositivity for HBs-Ag and anti-HCV antibodies in a population of 774 newly accepted students of the Medical School of the Autonomous University of Nuevo Leon, whose average age was 18 years. Second generation ELISA test were used to screen for HBs-Ag and anti-HCV antibodies. HBs-Ag was confirmed by a neutralization test and anti-HCV antibodies were confirmed by a RIBA test. Three sera were positive for HBs-Ag by ELISA and only one serum (0.13% of analyzed samples) was confirmed by the neutralization technique. On the other hand 12 sera were positive for anti-HCV antibodies by ELISA, and eight of these were confirmed by RIBA (1.03% of the analyzed samples). Intensive reactivity bands were found in two sera, and weak reactivity bands were found in six sera. ELISA screening for anti-HCV antibodies showed 0.5% of false positives. This study shows that the frequency of anti-HCV antibodies is 7.95% times higher than that found for HBs-Ag. All seropositive patients were asymptomatic and potentially infective. This demonstrates the need to routinely screen for HBs-Ag and anti-HCV antibodies to establish the prevalence of these diseases in our area.

  13. Genotypes of HBV and HCV among HIV-1 co-infected individuals in ...

    African Journals Online (AJOL)

    Background: Hepatitis B and Hepatitis C viruses are the major causes of liver disease worldwide. Co-infections with HBV and HCV have turned out to be increasingly very common among people living with HIV, leading to a major public health concern. Objective: To determine HBV and HCV diversity among HIV infected ...

  14. RNA chaperoning and intrinsic disorder in the core proteins of Flaviviridae.

    Science.gov (United States)

    Ivanyi-Nagy, Roland; Lavergne, Jean-Pierre; Gabus, Caroline; Ficheux, Damien; Darlix, Jean-Luc

    2008-02-01

    RNA chaperone proteins are essential partners of RNA in living organisms and viruses. They are thought to assist in the correct folding and structural rearrangements of RNA molecules by resolving misfolded RNA species in an ATP-independent manner. RNA chaperoning is probably an entropy-driven process, mediated by the coupled binding and folding of intrinsically disordered protein regions and the kinetically trapped RNA. Previously, we have shown that the core protein of hepatitis C virus (HCV) is a potent RNA chaperone that can drive profound structural modifications of HCV RNA in vitro. We now examined the RNA chaperone activity and the disordered nature of core proteins from different Flaviviridae genera, namely that of HCV, GBV-B (GB virus B), WNV (West Nile virus) and BVDV (bovine viral diarrhoea virus). Despite low-sequence similarities, all four proteins demonstrated general nucleic acid annealing and RNA chaperone activities. Furthermore, heat resistance of core proteins, as well as far-UV circular dichroism spectroscopy suggested that a well-defined 3D protein structure is not necessary for core-induced RNA structural rearrangements. These data provide evidence that RNA chaperoning-possibly mediated by intrinsically disordered protein segments-is conserved in Flaviviridae core proteins. Thus, besides nucleocapsid formation, core proteins may function in RNA structural rearrangements taking place during virus replication.

  15. HIV AND HCV COINFECTION: PREVALENCE, ASSOCIATED FACTORS AND GENOTYPE CHARACTERIZATION IN THE MIDWEST REGION OF BRAZIL

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    Solange Zacalusni Freitas

    2014-12-01

    Full Text Available A cross-sectional study on prevalence, associated factors and genotype distribution of HCV infection was conducted among 848 HIV-infected patients recruited at reference centers in the Midwest Region of Brazil. The prevalence rate of HIV-HCV coinfection was 6.9% (95% CI: 5.2 to 8.6. In multivariable analysis, increasing age, use of illicit drugs (injection and non-injection, a history of blood transfusion before 1994, and the absence of a steady partnership were significant independent associated factors for HIV-HCV coinfection. The phylogenetic analysis based on the NS5B region revealed the presence of two major circulating genotypes of HCV: genotypes 1 (58.3% and 3 (41.7%. The prevalence of HIV-HCV coinfection was lower than those reported in studies conducted with HIV-infected patients in different regions of Brazil, due to the fact that illicit drug use is not a frequent mode of HIV transmission in this region of Brazil. Serologic screening of HIV-patients for HCV before initiating antiretroviral treatment, a comprehensive identification of associated factors, and the implementation of effective harm reduction programs are highly recommended to provide useful information for treatment and to prevent HCV coinfection in these patients.

  16. Serum Islet Cell Autoantibodies During Interferon α Treatment in Patients With HCV-Genotype 4 Chronic Hepatitis

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    Gamal Badra

    2006-01-01

    Full Text Available Chronic hepatitis C virus (HCV infection is a leading cause of end-stage liver disease worldwide and HCV genotype 4 (HCV4 is predominant in African and Middle Eastern countries. It is well established that interferon-α (IFNa treatment for HCV may trigger serum autoantibodies against pancreatic islet cells (ICA in a subgroup of patients. Available data on the incidence of ICA during IFNa therapy for chronic HCV4 infection are not conclusive. We investigated the appearance of ICA in 40 naïve Egyptian patients (38 males, 32 ± 6 years with histologically defined chronic HCV4 infection undergoing IFNa treatment at a dose of 9-million U/week for 24 weeks. Serum samples were collected at baseline and following IFNa therapy and ICA were detected using indirect immunofluorescence. Baseline evaluation indicated that 2/40 (5% patients had detectable serum ICA. After the completion of the treatment scheme, 12/38 (32% previously ICA negative patients became ICA positive; however, no patient developed impaired glucose tolerance (IGT or diabetes during follow-up. In conclusion, we submit that IFNa treatment for chronic hepatitis C (CHC may induce serum ICA in one-third of Egyptian patients with HCV4. These autoantibodies, however, do not lead to alterations in glucose metabolism.

  17. MLKL and FADD Are Critical for Suppressing Progressive Lymphoproliferative Disease and Activating the NLRP3 Inflammasome

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    Xixi Zhang

    2016-09-01

    Full Text Available MLKL, a key component downstream of RIPK3, is suggested to be a terminal executor of necroptosis. Genetic studies have revealed that Ripk3 ablation rescues embryonic lethality in Fadd- or Caspase-8-deficient mice. Given that RIPK3 has also been implicated in non-necroptotic pathways including apoptosis and inflammatory signaling, it remains unclear whether the lethality in Fadd−/− mice is indeed caused by necropotosis. Here, we show that genetic deletion of Mlkl rescues the developmental defect in Fadd-deficient mice and that Fadd−/−Mlkl−/− mice are viable and fertile. Mlkl−/−Fadd−/− mice display significantly accelerated lymphoproliferative disease characterized by lymphadenopathy and splenomegaly when compared to Ripk3−/− Fadd−/− mice. Mlkl−/−Fadd−/− bone-marrow-derived macrophages and dendritic cells have impaired NLRP3 inflammasome activation associated with defects in ASC speck formation and NF-κB-dependent NLRP3 transcription. Our findings reveal that MLKL and FADD play critical roles in preventing lymphoproliferative disease and activating the NLRP3 inflammasome.

  18. Transcriptional profiling of PBMCs unravels B cell mediated immunopathogenic imprints of HCV vasculitis.

    Science.gov (United States)

    Comstock, Emily; Kim, Cheol-Woo; Murphy, Alison; Emmanuel, Benjamin; Zhang, Xi; Sneller, Michael; Poonia, Bhawna; Kottilil, Shyamasundaran

    2017-01-01

    B cell depletion therapy using rituximab has been shown to be effective in achieving remission in patients with HCV-mixed cryoglobulinemic (MC) vasculitis. Previously, we have demonstrated abnormalities in peripheral immune cells involving neutrophils, chemotaxis, and innate immune activation among patients with HCV-MC vasculitis when compared to HCV patients without vasculitis. In this study, we evaluated the effect of B cell depletion therapy on transcriptional profiles of peripheral blood mononuclear cells before and after riruximab therapy, in order to unravel the pathogenic mechanism involved in HCV-MC vasculitis induced by abnormal B cell proliferation. DNA microarray analysis was performed using RNA from PBMCs from seven patients with HCV-MC vasculitis and seven normal volunteers. DNA was hybridized to Affymetrix U133A chips. After normalization, differentially expressed gene list with treatment was generated using partitional clustering. RT-PCR, flow cytometry, and enzyme immunoassay (EIA) was used to validate DNA microarray findings. Differentially expressed genes included B cells and non-B cell genes. Validation of genes using purified cell subsets demonstrated distinct effect of B cell depletion therapy on non-B cells, such as monocytes, T cells, and NK cells. Notably, B lymphocyte stimulator (BLyS) levels were persistently elevated in patients who subsequently relapsed. In conclusion, pathogenesis of HCV-MC vasculitis is mediated by abnormal proliferation of B cells, driven by BLyS, leading to significant effects on non-B cells in mediating symptomatology. Future therapeutics using a combination approach of B cell depletion and proliferation may be desired to achieve long-term remission.

  19. Variation of transaminases, HCV-RNA levels and Th1/Th2 cytokine production during the post-partum period in pregnant women with chronic hepatitis C.

    Directory of Open Access Journals (Sweden)

    Angeles Ruiz-Extremera

    Full Text Available This study analyses the evolution of liver disease in women with chronic hepatitis C during the third trimester of pregnancy and the post-partum period, as a natural model of immune modulation and reconstitution. Of the 122 mothers recruited to this study, 89 were HCV-RNA+ve/HIV-ve and 33 were HCV-RNA-ve/HIV-ve/HCVantibody+ve and all were tested during the third trimester of pregnancy, at delivery and post-delivery. The HCV-RNA+ve mothers were categorized as either Type-A (66%, with an increase in ALT levels in the post-partum period (>40 U/L; P<0.001 or as Type-B (34%, with no variation in ALT values. The Type-A mothers also presented a significant decrease in serum HCV-RNA levels in the post-delivery period (P<0.001 and this event was concomitant with an increase in Th1 cytokine levels (INFγ, P = 0.04; IL12, P = 0.01 and IL2, P = 0.01. On the other hand, the Type-B mothers and the HCV-RNA-ve women presented no variations in either of these parameters. However, they did present higher Th1 cytokine levels in the partum period (INFγ and IL2, P<0.05 than both the Type-A and the HCV-RNA-ve women. Cytokine levels at the moment of delivery do not constitute a risk factor associated with HCV vertical transmission. It is concluded that differences in the ALT and HCV-RNA values observed in HCV-RNA+ve women in the postpartum period might be due to different ratios of Th1 cytokine production. In the Type-B women, the high partum levels of Th1 cytokines and the absence of post-partum variation in ALT and HCV-RNA levels may be related to permanent Th1 cytokine stimulation.

  20. Seroprevalence of anti-HCV and hepatitis B surface antigen in HIV infected patients

    Directory of Open Access Journals (Sweden)

    Tankhiwale S

    2003-01-01

    Full Text Available Human immunodeficiency virus (HIV is known to influence the natural history of infections with certain hepatitis viruses and interactions between HIV and hepatitis viruses may potentiate HIV replication. There is high degree of epidemiological similarity between hepatitis B virus and HIV as regard to high-risk group and route of transmission. Transmission of hepatitis C virus (HCV through blood transfusion and intravenous drug abuse is well documented. Present study deals with the study of concurrent infection of HBV and HCV with HIV infection. In the study of 110 HIV seropositive patients, 34(30.4% were positive for HBV and 8(7.27% for HCV. The difference of concomitant infection was highly significant compared to controls. (p value < 0.0001. Heterosexual high risk behaviour was observed in 89(80.91% of 110 HIV positive patients, out of which 23(25.8% and 5(5.62% were HBsAg and anti-HCV positive respectively. History of transmission was unclear in remaining patients. Concomitant infection of HIV and HBV was found to be significantly more in the symptomatic group (40.68% compared to asymptomatic group (19.6%. As HIV infection is known to affect the natural history of both HBV and HCV infection, screening of their concurrent association is necessary.

  1. Comprehensive molecular diagnosis of Epstein-Barr virus-associated lymphoproliferative diseases using next-generation sequencing.

    Science.gov (United States)

    Ono, Shintaro; Nakayama, Manabu; Kanegane, Hirokazu; Hoshino, Akihiro; Shimodera, Saeko; Shibata, Hirofumi; Fujino, Hisanori; Fujino, Takahiro; Yunomae, Yuta; Okano, Tsubasa; Yamashita, Motoi; Yasumi, Takahiro; Izawa, Kazushi; Takagi, Masatoshi; Imai, Kohsuke; Zhang, Kejian; Marsh, Rebecca; Picard, Capucine; Latour, Sylvain; Ohara, Osamu; Morio, Tomohiro

    2018-05-18

    Epstein-Barr virus (EBV) is associated with several life-threatening diseases, such as lymphoproliferative disease (LPD), particularly in immunocompromised hosts. Some categories of primary immunodeficiency diseases (PIDs) including X-linked lymphoproliferative syndrome (XLP), are characterized by susceptibility and vulnerability to EBV infection. The number of genetically defined PIDs is rapidly increasing, and clinical genetic testing plays an important role in establishing a definitive diagnosis. Whole-exome sequencing is performed for diagnosing rare genetic diseases, but is both expensive and time-consuming. Low-cost, high-throughput gene analysis systems are thus necessary. We developed a comprehensive molecular diagnostic method using a two-step tailed polymerase chain reaction (PCR) and a next-generation sequencing (NGS) platform to detect mutations in 23 candidate genes responsible for XLP or XLP-like diseases. Samples from 19 patients suspected of having EBV-associated LPD were used in this comprehensive molecular diagnosis. Causative gene mutations (involving PRF1 and SH2D1A) were detected in two of the 19 patients studied. This comprehensive diagnosis method effectively detected mutations in all coding exons of 23 genes with sufficient read numbers for each amplicon. This comprehensive molecular diagnostic method using PCR and NGS provides a rapid, accurate, low-cost diagnosis for patients with XLP or XLP-like diseases.

  2. EFFECT OF HIV PREVENTION AND TREATMENT PROGRAM ON HIV AND HCV TRANSMISSION AND HIV MORTALITY AT AN INDONESIAN NARCOTIC PRISON.

    Science.gov (United States)

    Nelwan, Erni J; Indrati, Agnes K; Isa, Ahmad; Triani, Nurlita; Alam, Nisaa Nur; Herlan, Maria S; Husen, Wahid; Pohan, Herdiman T; Alisjahbana, Bachti; Meheus, Andre; Van Crevel, Reinout; van der Ven, Andre Jam

    2015-09-01

    Validated data regarding HIV-transmission in prisons in developing countries is scarce. We examined sexual and injecting drug use behavior and HIV and HCV transmission in an Indonesian narcotic prison during the implementation of an HIV prevention and treatment program during 2004-2007 when the Banceuy Narcotic Prison in Indonesia conducted an HIV transmission prevention program to provide 1) HIV education, 2) voluntary HIV testing and counseling, 3) condom supply, 4) prevention of rape and sexual violence, 5) antiretroviral treatment for HIV-positive prisoners and 6) methadone maintenance treatment. During a first survey that was conducted between 2007 and 2009, new prisoners entered Banceuy Narcotics Prison were voluntary tested for HIV and HCV-infection after written informed consent was obtained. Information regarding sexual and injecting risk behavior and physical status were also recorded at admission to the prison. Participants who tested negative for both HIV and HCV during the first survey were included in a second survey conducted during 2008-2011. During both surveys, data on mortality among HIV-seropositive patients were also recorded. All HIV-seropositive participants receive treatment for HIV. HIV/ AIDS-related deaths decreased: 43% in 2006, 18% in 2007, 9% in 2008 and 0% in 2009. No HIV and HCV seroconversion inside Banceuy Narcotic Prison were found after a median of 23 months imprisonment (maximum follow-up: 38 months). Total of 484.8 person-years observation was done. Participants reported HIV transmission risk-behavior in Banceuy Prison during the second survey was low. After implementation of HIV prevention and treatment program, no new HIV or HCV cases were detected and HIV-related mortality decreased.

  3. High incidence of Kaposi sarcoma-associated herpesvirus infection in HIV-related solid immunoblastic/plasmablastic diffuse large B-cell lymphoma

    NARCIS (Netherlands)

    Deloose, S. T. P.; Smit, L. A.; Pals, F. T.; Kersten, M.-J.; van Noesel, C. J. M.; Pals, S. T.

    2005-01-01

    Kaposi sarcoma-associated herpesvirus ( KSHV) is known to be associated with two distinct lymphoproliferative disorders: primary effusion lymphoma (PEL) and multicentric Castleman disease (MCD)/MCD-associated plasmablastic lymphoma. We here report a high incidence of KSHV infection in solid

  4. Correlations of folic acid, vitamin B12, homocysteine, and thrombopoietin to platelet count in HCV infection

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    Somayh S. Eissa

    2012-01-01

    Conclusion This study concluded that TCP in HCV-related chronic liver diseases is multifactorial and decreased FA is involved in its pathogenesis as an independent risk factor. Increased Hcy may cause TCP through platelet activation and endothelial dysfunction.

  5. The frequency of hypothyroidism and its relationship with HCV positivity in patients with thalassemia major in southern Iran.

    Science.gov (United States)

    Haghpanah, Sezaneh; Jelodari, Shohreh; Karamifar, Hammdollah; Saki, Forough; Rahimi, Rahil; De Sanctis, Vincenzo; Dehbozorgian, Javad; Karimi, Mehran

    2018-03-27

    Hypothyroidism is one the most complication due to iron overload in patients with β-thalassemia major (TM). On the other hand these patients are prone to Hepatitis C virus (HCV) infection that can cause  thyroid dysfunction by itself or as the side effect of treatment with interferon (INF) or IFN plus ribavirin. The aim of this study is to evaluate the association of hypothyroidism with HCV positivity and serum ferritin levels in patients with TM. In this cross-sectional study, 201 randomly selected patients with TM who were registered at the Thalassemia Clinic of a tertiary hospital in Shiraz, southern Iran were investigated. Thyroid function tests and serologic screening assays for HCV seropositivity (HCV Ab and HCV-RNA) were conducted for all patients. Frequency of hypothyroidism was 22.9% including 19.9% subclinical hypothyroidism, 2% primary overt hypothyroidism and 1% central hypothyroidism. Eighty six patients (42.8%) were HCV Ab positive and 60 patients (29.9%) were HCV RNA positive. No significant relationship was found between hypothyroidism and HCV positivity or receiving IFN-α (P>0.05). Hypothyroidism showed a borderline significant association with high serum ferritin levels in TM patients (P=0.055). Our results showed no significant association between hypothyroidism and HCV infection in TM patients. It seems that the main mechanism of hypothyroidism in our patients is iron overload; however, for better evaluation a larger multicenter study is recommended.  Also due to the importance of consequences of HCV infection, more careful pre-transfusional screening of blood should be considered in TM patients.

  6. Rates of sustained virological response 12 weeks after the scheduled end of direct-acting antiviral (DAA)-based hepatitis C virus (HCV) therapy from the National German HCV registry: does HIV coinfection impair the response to DAA combination therapy?

    Science.gov (United States)

    Bischoff, J; Mauss, S; Cordes, C; Lutz, T; Scholten, S; Moll, A; Jäger, H; Cornberg, M; Manns, M P; Baumgarten, A; Rockstroh, J K

    2018-04-01

    The European Association for the Study of the Liver (EASL) treatment recommendations for hepatitis C no longer discriminate between HIV/hepatitis C virus (HCV)-coinfected and HCV-monoinfected patients. However, recent data from Spain are questioning these recommendations on the basis of the findings of higher relapse rates and lower cure rates in HIV/HCV-infected subjects. The aim of our study was to compare HCV cure rates in monoinfected and coinfected patients from Germany. Data acquired from the Deutsches Hepatitis C-Registry were analysed. A total of 5657 HCV-monoinfected subjects and 488 HIV/HCV-coinfected patients were included in the study. Rates of sustained virological response 12 weeks after the scheduled end of therapy (SVR12) were collected in both subgroups and in cirrhotic and noncirrhotic patients. HIV/HCV-coinfected patients were more frequently male (84.6% vs. 56.4%, respectively; P  350 cells/μL in 63.1% of HIV-positive subjects and 88.7% were on antiretroviral therapy. SVR12 rates were 90.3% (5111 of 5657) in our HCV-monoinfected cohort and 91.2% (445 of 488) in our coinfected patients. Liver cirrhosis was confirmed in 1667 of 5657 (29.5%) monoinfected patients and 84 of 488 (17.2%; P < 0.001) coinfected patients. SVR12 rates did not differ between HCV-monoinfected and HIV/HCV-coinfected patients with liver cirrhosis (87.8% vs. 89.3%, respectively; P = 0.864). A treatment duration of 8 weeks did not reduce the percentage of patients with SVR12 in either subgroup (93.7% in both groups). We found high SVR12 rates in monoinfected as well as coinfected individuals. No differences were detected between the two subgroups regardless of whether there was accompanying liver cirrhosis or a shortened treatment duration. © 2018 British HIV Association.

  7. Recent advances in the risk factors, diagnosis and management of Epstein-Barr virus post-transplant lymphoproliferative disease.

    Science.gov (United States)

    Aguayo-Hiraldo, Paibel; Arasaratnam, Reuben; Rouce, Rayne H

    Fifty years after the first reports of Epstein-Barr virus (EBV)-associated endemic Burkitt's lymphoma, EBV has emerged as the third most prevalent oncogenic virus worldwide. EBV infection is associated with various malignancies including Hodgkin and non-Hodgkin lymphoma, NK/T-cell lymphoma and nasopharyngeal carcinoma. Despite the highly specific immunologic control in the immunocompetent host, EBV can cause severe complications in the immunocompromised host (namely, post-transplant lymphoproliferative disease). This is particularly a problem in patients with delayed immune reconstitution post-hematopoietic stem cell transplant or solid organ transplant. Despite advances in diagnostic techniques and treatment algorithms allowing earlier identification and treatment of patients at highest risk, mortality rates remain as high as 90% if not treated early. The cornerstones of treatment include reduction in immunosuppression and in vivo B cell depletion with an anti-CD20 monoclonal antibody. However, these treatment modalities are not always feasible due to graft rejection, emergence of graft vs. host disease, and toxicity. Newer treatment modalities include the use of adoptive T cell therapy, which has shown promising results in various EBV-related malignancies. In this article we will review recent advances in risk factors, diagnosis and management of EBV-associated malignancies, particularly post-transplant lymphoproliferative disease. We will also discuss new and innovative treatment options including adoptive T cell therapy as well as management of special situations such as chronic active EBV and EBV-associated hemophagocytic lymphohistiocytosis. Copyright © 2015 Hospital Infantil de México Federico Gómez. Publicado por Masson Doyma México S.A. All rights reserved.

  8. Prevalence of HCV infection and associated factors among illicit drug users in Breves, State of Pará, northern Brazil

    OpenAIRE

    Pacheco,Suzy Danielly Barbosa; Silva-Oliveira,Gláucia Caroline; Maradei-Pereira,Luciana Maria Cunha; Crescente,José Ângelo Barletta; Lemos,José Alexandre Rodrigues de; Oliveira-Filho,Aldemir Branco de

    2014-01-01

    Introduction: Illicit drug users (DUs) are vulnerable to hepatitis C virus (HCV) infection. The shared use of illicit drugs is the main method of HCV transmission. Methods: A cross-sectional study was conducted in Breves, in northern Brazil. We surveyed 187 DUs to determine the prevalence of and factors associated with HCV infection. Results: The prevalence of anti-HCV antibodies was 36.9%, and the prevalence of hepatitis C virus-ribonucleic acid (HCV-RNA) was 31%. Hepatitis C virus infec...

  9. Il controllo di qualità nell’impiego della PCR applicata alla determinazione qualitativa dell’HCV-RNA

    Directory of Open Access Journals (Sweden)

    Giuseppe Giuliani

    2004-03-01

    Full Text Available Detection of hepatitis C virus (HCV RNA in samples of plasma/serum has become an essential part of the diagnosis and management of HCV-infected patients. Qualitative HCV-RNA tests are used to identify acute HCV infections as well as chronic HCV carriers.In recent years,a variety of commercial and non commercial test systems have been developed for this purpose. Each of these methods is calibrate with proprietary standards and exhibits its own sensitivity (detection limit and specificity. Obviously, laboratories performing HCV-RNA test should report accurate and reliable results regardless of the type of assay used.Where commercial kit are used for part of or the complete analytical procedure, documented validation points already covered by the kit manufacturer can substitute for the validation by the user.Nevertheless, the performance of the kit with respect to its intended use has to be demonstrated by the user. One of the best ways to assess the performance of individual laboratories for validation of qualitative HCV-RNA test is determine: 1. Specificity. In order to validate the specificity of the analytical procedure, at least 100 HCV-RNA-negative plasma pools should be tested and shown to be non-reactive. 2. Positive cut-off point (detection limit/sensitivity.The positive cut-off point (as defined in the Ph Eur General Method 2. 6. 21 is the minimum number of the target sequences per volume sample which can be detected in 95% of test runs.A dilution series of a working reagent or reference material, which has been calibrated against the WHO HCV International Standard (96/790, should be tested on different days to examine variation between test runs.At least 3 independent dilution series should be tested with a sufficient number of replicates at each dilution to give a total number of 24 test results for each dilution to enable a statistical analysis of the results; 3. Robustness.To demonstrate robustness, at least 20 HCV-RNA negative plasma

  10. Stable replication of the EBNA1/OriP-mediated baculovirus vector and its application to anti-HCV gene therapy

    Directory of Open Access Journals (Sweden)

    Chang Myint OO

    2009-10-01

    Full Text Available Abstract Background Hepatitis C virus (HCV is one of the main causes of liver-related morbidity and mortality. Although combined interferon-α-ribavirin therapy is effective for about 50% of the patients with HCV, better therapies are needed and preventative vaccines have yet to be developed. Short-hairpin RNAs (shRNAs inhibit gene expression by RNA interference. The application of transient shRNA expression is limited, however, due to the inability of the shRNA to replicate in mammalian cells and its inefficient transduction. The duration of transgene (shRNA expression in mammalian cells can be significantly extended using baculovirus-based shRNA-expressing vectors that contain the latent viral protein Epstein-Barr nuclear antigen 1 (EBNA1 and the origin of latent viral DNA replication (OriP sequences. These recombinant vectors contain compatible promoters and are highly effective for infecting primary hepatocyte and hepatoma cell lines, making them very useful tools for studies of hepatitis B and hepatitis C viruses. Here, we report the use of these baculovirus-based vector-derived shRNAs to inhibit core-protein expression in full-length hepatitis C virus (HCV replicon cells. Results We constructed a long-term transgene shRNA expression vector that contains the EBV EBNA1 and OriP sequences. We also designed baculovirus vector-mediated shRNAs against the highly conserved core-protein region of HCV. HCV core protein expression was inhibited by the EBNA1/OriP baculovirus vector for at least 14 days, which was considerably longer than the 3 days of inhibition produced by the wild-type baculovirus vector. Conclusion These findings indicate that we successfully constructed a long-term transgene (shRNA expression vector (Ac-EP-shRNA452 using the EBNA1/OriP system, which was propagated in Escherichia coli and converted into mammalian cells. The potential anti-HCV activity of the long-term transgene (shRNA expression vector was evaluated with the view

  11. Prevalence of HCV infection and associated factors among illicit drug users in Breves, State of Pará, northern Brazil.

    Science.gov (United States)

    Pacheco, Suzy Danielly Barbosa; Silva-Oliveira, Gláucia Caroline; Maradei-Pereira, Luciana Maria Cunha; Crescente, José Ângelo Barletta; Lemos, José Alexandre Rodrigues de; Oliveira-Filho, Aldemir Branco de

    2014-01-01

    Illicit drug users (DUs) are vulnerable to hepatitis C virus (HCV) infection. The shared use of illicit drugs is the main method of HCV transmission. A cross-sectional study was conducted in Breves, in northern Brazil. We surveyed 187 DUs to determine the prevalence of and factors associated with HCV infection. The prevalence of anti-HCV antibodies was 36.9%, and the prevalence of hepatitis C virus-ribonucleic acid (HCV-RNA) was 31%. Hepatitis C virus infection was associated with tattoos, intravenous drug use, shared use of equipment for drug use, drug use for longer than 3 years, and daily drug use. Strategies for preventing and controlling HCV transmission should be implemented among DUs.

  12. dsRNA-Dependent Protein Kinase PKR and its Role in Stress, Signaling and HCV Infection

    Directory of Open Access Journals (Sweden)

    Eliane F. Meurs

    2012-10-01

    Full Text Available The double-stranded RNA-dependent protein kinase PKR plays multiple roles in cells, in response to different stress situations. As a member of the interferon (IFN‑Stimulated Genes, PKR was initially recognized as an actor in the antiviral action of IFN, due to its ability to control translation, through phosphorylation, of the alpha subunit of eukaryotic initiation factor 2 (eIF2a. As such, PKR participates in the generation of stress granules, or autophagy and a number of viruses have designed strategies to inhibit its action. However, PKR deficient mice resist most viral infections, indicating that PKR may play other roles in the cell other than just acting as an antiviral agent. Indeed, PKR regulates several signaling pathways, either as an adapter protein and/or using its kinase activity. Here we review the role of PKR as an eIF2a kinase, its participation in the regulation of the NF-kB, p38MAPK and insulin pathways, and we focus on its role during infection with the hepatitis C virus (HCV. PKR binds the HCV IRES RNA, cooperates with some functions of the HCV core protein and may represent a target for NS5A or E2. Novel data points out for a role of PKR as a pro-HCV agent, both as an adapter protein and as an eIF2a-kinase, and in cooperation with the di-ubiquitin-like protein ISG15. Developing pharmaceutical inhibitors of PKR may help in resolving some viral infections as well as stress-related damages.

  13. Cost effectiveness of screening strategies for early identification of HIV and HCV infection in injection drug users.

    Directory of Open Access Journals (Sweden)

    Lauren E Cipriano

    Full Text Available To estimate the cost, effectiveness, and cost effectiveness of HIV and HCV screening of injection drug users (IDUs in opioid replacement therapy (ORT.Dynamic compartmental model of HIV and HCV in a population of IDUs and non-IDUs for a representative U.S. urban center with 2.5 million adults (age 15-59.We considered strategies of screening individuals in ORT for HIV, HCV, or both infections by antibody or antibody and viral RNA testing. We evaluated one-time and repeat screening at intervals from annually to once every 3 months. We calculated the number of HIV and HCV infections, quality-adjusted life years (QALYs, costs, and incremental cost-effectiveness ratios (ICERs.Adding HIV and HCV viral RNA testing to antibody testing averts 14.8-30.3 HIV and 3.7-7.7 HCV infections in a screened population of 26,100 IDUs entering ORT over 20 years, depending on screening frequency. Screening for HIV antibodies every 6 months costs $30,700/QALY gained. Screening for HIV antibodies and viral RNA every 6 months has an ICER of $65,900/QALY gained. Strategies including HCV testing have ICERs exceeding $100,000/QALY gained unless awareness of HCV-infection status results in a substantial reduction in needle-sharing behavior.Although annual screening for antibodies to HIV and HCV is modestly cost effective compared to no screening, more frequent screening for HIV provides additional benefit at less cost. Screening individuals in ORT every 3-6 months for HIV infection using both antibody and viral RNA technologies and initiating ART for acute HIV infection appears cost effective.

  14. PROGRESSION OF LIVER FIBROSIS IN MONOINFECTED PATIENTS BY HEPATITIS C VIRUS AND COINFECTED BY HCV AND HUMAN IMMUNODEFICIENCY VIRUS

    Directory of Open Access Journals (Sweden)

    Cristiane Valle TOVO

    2013-03-01

    Full Text Available Context The progression of liver fibrosis in patients coinfected by hepatitis C virus and human immunodeficiency virus (HCV/HIV has been increasingly studied in the past decade. Studies made before the highly active antiretroviral therapy suggest that HIV can change the natural history of the HCV infection, leading to a faster progression of the liver fibrosis. Objective To evaluate and compare the fibrosis progression in two groups of patients (HCV/HIV coinfected and HCV monoinfected Methods Seventy patients HCV monoinfected and 26 patients HCV/HIV coinfected who had not undertaken HCV treatment and were submitted to serial percutaneous liver biopsies were retrospectively evaluated. There was no difference in the fibrosis progression between the two groups. Conclusion The fibrosis grade evolution was not worse in the coinfected patients. The immunosuppression absence and the shortest time period between the biopsies in the coinfected group are possible explanations.

  15. Exposure to low infective doses of HCV induces cellular immune responses without consistently detectable viremia or seroconversion in chimpanzees

    International Nuclear Information System (INIS)

    Shata, Mohamed Tarek; Tricoche, Nancy; Perkus, Marion; Tom, Darley; Brotman, Betsy; McCormack, Patricia; Pfahler, Wolfram; Lee, Dong-Hun; Tobler, Leslie H.; Busch, Michael; Prince, Alfred M.

    2003-01-01

    In hepatitis C virus (HCV) infection, there is accumulating data suggesting the presence of cellular immune responses to HCV in exposed but seemingly uninfected populations. Some studies have suggested cross-reactive antigens rather than prior HCV exposure as the main reason for the immune responses. In this study we address this question by analyzing the immune response of chimpanzees that have been sequentially exposed to increasing doses of HCV virions. The level of viremia, as well as the immune responses to HCV at different times after virus inoculation, were examined. Our data indicate that HCV infective doses as low as 1-10 RNA (+) virions induce detectable cellular immune responses in chimpanzees without consistently detectable viremia or persistent seroconversion. However, increasing the infective doses of HCV to 100 RNA (+) virions overcame the low-inoculum-induced immune response and produced high-level viremia followed by seroconversion

  16. Isolation as a strategy for controlling the transmission of hepatitis C virus (HCV) infection in haemodialysis units.

    Science.gov (United States)

    Bravo Zuñiga, Jessica I; Loza Munárriz, César; López-Alcalde, Jesús

    2016-08-11

    The hepatitis C virus (HCV) infection affects about 2% of the world's population and can cause chronic liver infection and persistent long-term sequelae such as cirrhosis and liver cancer.The prevalence of HCV infection among people on haemodialysis is often higher than the general population. The virus is easily transmitted parenterally, and blood transfusions have previously played a significant role in transmission; however, erythropoietin therapy has reduced the need for transfusions, and coupled with improved screening of donated blood, has significantly decreased transmission by transfusion. Although control of hospital-acquired infection has improved with the advent of biosafety measures, stopping HCV transmission in haemodialysis units remains challenging.Isolating people infected with HCV involves physical separation from others to limit direct or indirect transmission and includes a number of strategies during dialysis. The evidence for isolating people infected with HCV during haemodialysis is sparse with some inconsistencies. To evaluate the benefits and harms of isolation of HCV-infected patients during haemodialysis on the transmission of HCV to other patients. We searched the Cochrane Kidney and Transplant Specialised Register to 26 November 2015 through contact with the Information Specialist using search terms relevant to this review. We also searched the Latin American and Caribbean Health Sciences Literature Database (LILACS) (1982 to 2015), Web of Science Conference Proceedings Citation Index-Science (CPCI-S, 1990 to 2015), ProQuest Dissertations & Theses Database (1990 to 2015), and Open Grey (1990 to 2015). We included randomised controlled trials (RCTs), quasi-RCTs and cluster RCTs evaluating the clinical benefits and harms of isolating HCV-infected patients during haemodialysis on the transmission of HCV to other patients. We considered incidence of dialysis-acquired HCV infection, all-cause mortality, and adverse effects associated with

  17. EPSTEIN-BARR VIRUS RELATED LYMPHOPROLIFERATIONS AFTER STEM CELL TRANSPLANTATION

    Directory of Open Access Journals (Sweden)

    Patrizia Chiusolo

    2009-11-01

    Full Text Available

    Epstein-Barr virus related lymphoproliferative  disorders are a rare but potentially fatal complication of allogeneic stem cell transplantation with an incidence of 1-3% and  occurring within 6 months after transplantation.  The most relevant risk factors include the use of in vivo T-cell depletion with antithymocyte globulin, HLA disparities between donor and recipient, donor type,  splenectomy etc. The higher the numbers of risk factors the higher the risk of developing Epstein-Barr virus related lymphoproliferative  disorders. Monitoring EBV viremia after transplantation is of value and it should be applied to high risk patients since it allows pre-emptive therapy initiation  at specified threshold values   and early treatment. This strategy  might reduce mortality which was >80% prior to the implementation of anti-EBV therapy . Treatment of EBV-LPD after allogeneic SCT may consist of anti-B-cell therapy (rituximab, adoptive T-cell immunotherapy or both. Rituximab treatment should be considered the first treatment option, preferably guided by intensive monitoring of EBV DNA while reduction of immunosuppression should be carefully evaluated for the risk of graft versus host disease.

  18. Complete Remission of Methotrexate-Related Epstein-Barr-Virus-Associated Hodgkin-Like Lymphoma following Withdrawal of MTX Coupled with Clarithromycin Administration

    Directory of Open Access Journals (Sweden)

    Nobuo Takemori

    2012-01-01

    Full Text Available Patients with rheumatoid arthritis (RA are known to develop lymphoproliferative disorders (LPDs during the course of illness, particularly in cases treated with methotrexate (MTX for long periods. We describe a case of MTX-related Epstein-Barr-virus-(EBV- associated LPD resembling Hodgkin’s lymphoma (HL, in which a dramatic complete remission was achieved after withdrawal of MTX coupled with clarithromycin (CAM administration. Withdrawal of MTX coupled with CAM administration seemed to be effective for treating MTX-related EBV-associated LPDs. In particular, an immunomodulative effect of CAM might have been involved in achieving complete remission.

  19. Prevalence of HCV infection and associated factors among illicit drug users in Breves, State of Pará, northern Brazil

    Directory of Open Access Journals (Sweden)

    Suzy Danielly Barbosa Pacheco

    2014-06-01

    Full Text Available Introduction: Illicit drug users (DUs are vulnerable to hepatitis C virus (HCV infection. The shared use of illicit drugs is the main method of HCV transmission. Methods: A cross-sectional study was conducted in Breves, in northern Brazil. We surveyed 187 DUs to determine the prevalence of and factors associated with HCV infection. Results: The prevalence of anti-HCV antibodies was 36.9%, and the prevalence of hepatitis C virus-ribonucleic acid (HCV-RNA was 31%. Hepatitis C virus infection was associated with tattoos, intravenous drug use, shared use of equipment for drug use, drug use for longer than 3 years, and daily drug use. Conclusions: Strategies for preventing and controlling HCV transmission should be implemented among DUs.

  20. [Improvement of sensitivity in the second generation HCV core antigen assay by a novel concentration method using polyethylene glycol (PEG)].

    Science.gov (United States)

    Higashimoto, Makiko; Takahashi, Masahiko; Jokyu, Ritsuko; Syundou, Hiromi; Saito, Hidetsugu

    2007-11-01

    A HCV core antigen (Ag) detection assay system, Lumipulse Ortho HCV Ag has been developed and is commercially available in Japan with a lower detection level limit of 50 fmol/l, which is equivalent to 20 KIU/ml in PCR quantitative assay. HCV core Ag assay has an advantage of broader dynamic range compared with PCR assay, however the sensitivity is lower than PCR. We developed a novel HCV core Ag concentration method using polyethylene glycol (PEG), which can improve the sensitivity five times better than the original assay. The reproducibility was examined by consecutive five-time measurement of HCV patients serum, in which the results of HCV core Ag original and concentrated method were 56.8 +/- 8.1 fmol/l (mean +/- SD), CV 14.2% and 322.9 +/- 45.5 fmol/l CV 14.0%, respectively. The assay results of HCV negative samples in original HCV core Ag were all 0.1 fmol/l and the results were same even in the concentration method. The results of concentration method were 5.7 times higher than original assay, which was almost equal to theoretical rate as expected. The assay results of serially diluted samples were also as same as expected data in both original and concentration assay. We confirmed that the sensitivity of HCV core Ag concentration method had almost as same sensitivity as PCR high range assay in the competitive assay study using the serially monitored samples of five HCV patients during interferon therapy. A novel concentration method using PEG in HCV core Ag assay system seems to be useful for assessing and monitoring interferon treatment for HCV.

  1. Sex-specific effects of TLR9 promoter variants on spontaneous clearance of HCV infection.

    Science.gov (United States)

    Fischer, Janett; Weber, Alexander N R; Böhm, Stephan; Dickhöfer, Sabine; El Maadidi, Souhayla; Deichsel, Danilo; Knop, Viola; Klinker, Hartwig; Möller, Bernd; Rasenack, Jens; Wang, Lisa; Sharma, Manu; Hinrichsen, Holger; Spengler, Ulrich; Buggisch, Peter; Sarrazin, Christoph; Pawlita, Michael; Waterboer, Tim; Wiese, Manfred; Probst-Müller, Elsbeth; Malinverni, Raffaele; Bochud, Pierre-Yves; Gardiner, Clair; O'Farrelly, Cliona; Berg, Thomas

    2017-10-01

    As pathogen sensors, Toll-like receptors (TLR) play a role in the first defence line during HCV infection. However, the impact of the DNA sensor TLR9 on the natural course of HCV infection is unknown. To address this, TLR9 promoter polymorphisms (single nucleotide polymorphisms (SNPs)) rs187084 and rs5743836 were investigated for their effect on disease progression. Therefore, the TLR9 SNPs and the interferon lambda 4 ( IFNL4 ) rs12979860 were genotyped in chronically HCV type 1 infected (n=333), in patients who spontaneously cleared the infection (n=161), in the Swiss HCV cohort (n=1057) and the well-characterised German (n=305) and Irish (n=198) 'anti-D' cohorts. Functional analyses were done with promoter reporter constructs of human TLR9 in B cells and assessing TLR9 mRNA levels in whole blood of healthy volunteers. The TLR9 rs187084 C allele was associated with spontaneous virus clearance in women of the study cohort (OR=2.15 (95% CI 1.18 to 3.90) p=0.012), of the Swiss HCV cohort (OR=2.06 (95% CI 1.02 to 4.18) p=0.044) and in both 'anti-D' cohorts (German: OR=2.01 (95% CI 1.14 to 3.55) p=0.016; Irish: OR=1.93 (95% CI 1.10 to 3.68) p=0.047). Multivariate analysis in the combined study and Swiss HCV cohorts supported the results (OR=1.99 (95% CI 1.30 to 3.05) p=0.002). Functional analyses revealed higher transcriptional activities for both TLR9 variants and an association of the C allele of rs5743836 with allele-specific TLR9 mRNA regulation by oestrogens in women. TLR9 promoter SNPs are associated with the natural course of HCV infection and show higher transcriptional activities. Our results imply the DNA sensor TLR9 in natural immunity against the RNA virus, HCV. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  2. Structure of the hepatitis C virus IRES bound to the human 80S ribosome: remodeling of the HCV IRES.

    Science.gov (United States)

    Boehringer, Daniel; Thermann, Rolf; Ostareck-Lederer, Antje; Lewis, Joe D; Stark, Holger

    2005-11-01

    Initiation of translation of the hepatitis C virus (HCV) polyprotein is driven by an internal ribosome entry site (IRES) RNA that bypasses much of the eukaryotic translation initiation machinery. Here, single-particle electron cryomicroscopy has been used to study the mechanism of HCV IRES-mediated initiation. A HeLa in vitro translation system was used to assemble human IRES-80S ribosome complexes under near physiological conditions; these were stalled before elongation. Domain 2 of the HCV IRES is bound to the tRNA exit site, touching the L1 stalk of the 60S subunit, suggesting a mechanism for the removal of the HCV IRES in the progression to elongation. Domain 3 of the HCV IRES positions the initiation codon in the ribosomal mRNA binding cleft by binding helix 28 at the head of the 40S subunit. The comparison with the previously published binary 40S-HCV IRES complex reveals structural rearrangements in the two pseudoknot structures of the HCV IRES in translation initiation.

  3. Hepatitis C Virus (HCV) Registry Veterans in VHA Care in 2015, for the Nation, by VISN and by Station

    Data.gov (United States)

    Department of Veterans Affairs — This report describes the number of Hepatitis C Virus (HCV) registry Veterans in VHA care in 2015 based on serologic evidence of HCV infection status (HCV Positive)...

  4. Lack of correlation between immunologic markers and cell surface ultrastructure in the leukemic phase of lymphoproliferative diseases

    Energy Technology Data Exchange (ETDEWEB)

    Golomb, Harvey M.; Simon, Deberah

    1977-01-01

    In a prospective study of malignant cells from 13 patients with the leukemic phase of lymphoproliferative diseases, we wished to determine whether any correlation between the immunologic markers and the cell surface ultrastructure. Five patients had chronic lymphocytic leukemia, four had malignant lymphomas, poorly differentiated lymphocytic type, two had the Sezary syndrome, and one each had acute prolymphocytic leukemia and acute lymphocytic leukemia. Cell separation and isolation was done at room temperature for all specimens. Immunologic markers tested for were surface immunoglobins, a B-cell property, and E-rosettes, a T-cell property. Three patients had T-cell diseases, 6 had B-cell diseases, and 4 were classified as ''null.'' All but one patient had moderate to large numbers of microvilli on their malignant cells. The single exception had a typical B-cell form of chronic lymphocytic leukemia. There appears to be no correlation between immunologic markers and cell surface ultrastructure; therefore, SEM appears not to be valuable in the diagnosis or classification of immunologic sub-types of certain lymphoproliferative diseases.

  5. The effect of HIV infection and HCV viremia on inflammatory mediators and hepatic injury-The Women's Interagency HIV Study.

    Directory of Open Access Journals (Sweden)

    Sheila M Keating

    Full Text Available Hepatitis C virus infection induces inflammation and while it is believed that HIV co-infection enhances this response, HIV control may reduce inflammation and liver fibrosis in resolved or viremic HCV infection. Measurement of systemic biomarkers in co-infection could help define the mechanism of inflammation on fibrosis and determine if HIV control reduces liver pathology. A nested case-control study was performed to explore the relationship of systemic biomarkers of inflammation with liver fibrosis in HCV viremic and/or seropositive women with and without HIV infection. Serum cytokines, chemokines, growth factors and cell adhesion molecules were measured in HIV uninfected (HIV-, n = 18, ART-treated HIV-controlled (ARTc, n = 20, uncontrolled on anti-retroviral therapy (ARTuc, n = 21 and elite HIV controllers (Elite, n = 20. All were HCV seroreactive and had either resolved (HCV RNA-; <50IU/mL or had chronic HCV infection (HCV RNA+. In HCV and HIV groups, aspartate aminotransferase to platelet ratio (APRI was measured and compared to serum cytokines, chemokines, growth factors and cell adhesion molecules. APRI correlated with sVCAM, sICAM, IL-10, and IP-10 levels and inversely correlated with EGF, IL-17, TGF-α and MMP-9 levels. Collectively, all HCV RNA+ subjects had higher sVCAM, sICAM and IP-10 compared to HCV RNA-. In the ART-treated HCV RNA+ groups, TNF-α, GRO, IP-10, MCP-1 and MDC were higher than HIV-, Elite or both. In ARTuc, FGF-2, MPO, soluble E-selectin, MMP-9, IL-17, GM-CSF and TGF-α are lower than HIV-, Elite or both. Differential expression of soluble markers may reveal mechanisms of pathogenesis or possibly reduction of fibrosis in HCV/HIV co-infection.

  6. Hepatitis C virus (HCV): ever in reliable partnerships?

    African Journals Online (AJOL)

    GRACE

    2006-06-16

    Jun 16, 2006 ... hemophiliacs, multiple changes in HCV genotypes were observed in 58 % of the subjects, .... similar sources of transmission (Crockett and Keeffe,. 2005). .... tests 1 year apart. Longitudinal evaluation is also very important for ...

  7. EBV-Negative Monomorphic B-Cell Posttransplant Lymphoproliferative Disorder with Marked Morphologic Pleomorphism and Pathogenic Mutations in ASXL1, BCOR, CDKN2A, NF1, and TP53.

    Science.gov (United States)

    Bogusz, Agata M

    2017-01-01

    Posttransplant lymphoproliferative disorders (PTLDs) are a diverse group of lymphoid or plasmacytic proliferations frequently driven by Epstein-Barr virus (EBV). EBV-negative PTLDs appear to represent a distinct entity. This report describes an unusual case of a 33-year-old woman that developed a monomorphic EBV-negative PTLD consistent with diffuse large B-cell lymphoma (DLBCL) 13 years after heart-lung transplant. Histological examination revealed marked pleomorphism of the malignant cells including nodular areas reminiscent of classical Hodgkin lymphoma (cHL) with abundant large, bizarre Hodgkin-like cells. By immunostaining, the malignant cells were immunoreactive for CD45, CD20, CD79a, PAX5, BCL6, MUM1, and p53 and negative for CD15, CD30, latent membrane protein 1 (LMP1), and EBV-encoded RNA (EBER). Flow cytometry demonstrated lambda light chain restricted CD5 and CD10 negative B-cells. Fluorescence in situ hybridization studies (FISH) were negative for cMYC , BCL2, and BCL6 rearrangements but showed deletion of TP53 and monosomy of chromosome 17. Next-generation sequencing studies (NGS) revealed numerous genetic alterations including 6 pathogenic mutations in ASXL1, BCOR, CDKN2A, NF1, and TP53 (x2) genes and 30 variants of unknown significance (VOUS) in ABL1, ASXL1, ATM, BCOR, BCORL1, BRNIP3, CDH2, CDKN2A, DNMT3A, ETV6, EZH2, FBXW7, KIT, NF1, RUNX1, SETPB1, SF1, SMC1A, STAG2, TET2, TP53, and U2AF2.

  8. EBV-Negative Monomorphic B-Cell Posttransplant Lymphoproliferative Disorder with Marked Morphologic Pleomorphism and Pathogenic Mutations in ASXL1, BCOR, CDKN2A, NF1, and TP53

    Directory of Open Access Journals (Sweden)

    Agata M. Bogusz

    2017-01-01

    Full Text Available Posttransplant lymphoproliferative disorders (PTLDs are a diverse group of lymphoid or plasmacytic proliferations frequently driven by Epstein-Barr virus (EBV. EBV-negative PTLDs appear to represent a distinct entity. This report describes an unusual case of a 33-year-old woman that developed a monomorphic EBV-negative PTLD consistent with diffuse large B-cell lymphoma (DLBCL 13 years after heart-lung transplant. Histological examination revealed marked pleomorphism of the malignant cells including nodular areas reminiscent of classical Hodgkin lymphoma (cHL with abundant large, bizarre Hodgkin-like cells. By immunostaining, the malignant cells were immunoreactive for CD45, CD20, CD79a, PAX5, BCL6, MUM1, and p53 and negative for CD15, CD30, latent membrane protein 1 (LMP1, and EBV-encoded RNA (EBER. Flow cytometry demonstrated lambda light chain restricted CD5 and CD10 negative B-cells. Fluorescence in situ hybridization studies (FISH were negative for cMYC, BCL2, and BCL6 rearrangements but showed deletion of TP53 and monosomy of chromosome 17. Next-generation sequencing studies (NGS revealed numerous genetic alterations including 6 pathogenic mutations in ASXL1, BCOR, CDKN2A, NF1, and TP53(x2 genes and 30 variants of unknown significance (VOUS in ABL1, ASXL1, ATM, BCOR, BCORL1, BRNIP3, CDH2, CDKN2A, DNMT3A, ETV6, EZH2, FBXW7, KIT, NF1, RUNX1, SETPB1, SF1, SMC1A, STAG2, TET2, TP53, and U2AF2.

  9. High HCV seroprevalence and HIV drug use risk behaviors among injection drug users in Pakistan

    Directory of Open Access Journals (Sweden)

    Zafar Tariq

    2006-08-01

    Full Text Available Abstract Introduction HIV and HCV risk behaviors among injection drug users (IDUs in two urban areas in Pakistan were identified. Methods From May to June 2003, 351 IDUs recruited in harm-reduction drop-in centers operated by a national non-governmental organization in Lahore (Punjab province and Quetta (Balochistan province completed an interviewer-administered survey and were tested for HIV and HCV. Multivariable logistic regression identified correlates of seropositivity, stratifying by site. All study participants provided written, informed consent. Results All but two were male; median age was 35 and Discussion Despite no HIV cases, overall HCV prevalence was very high, signaling the potential for a future HIV epidemic among IDUs across Pakistan. Programs to increase needle exchange, drug treatment and HIV and HCV awareness should be implemented immediately.

  10. HBV Bypasses the Innate Immune Response and Does Not Protect HCV From Antiviral Activity of Interferon.

    Science.gov (United States)

    Mutz, Pascal; Metz, Philippe; Lempp, Florian A; Bender, Silke; Qu, Bingqian; Schöneweis, Katrin; Seitz, Stefan; Tu, Thomas; Restuccia, Agnese; Frankish, Jamie; Dächert, Christopher; Schusser, Benjamin; Koschny, Ronald; Polychronidis, Georgios; Schemmer, Peter; Hoffmann, Katrin; Baumert, Thomas F; Binder, Marco; Urban, Stephan; Bartenschlager, Ralf

    2018-05-01

    Hepatitis C virus (HCV) infection is sensitive to interferon (IFN)-based therapy, whereas hepatitis B virus (HBV) infection is not. It is unclear whether HBV escapes detection by the IFN-mediated immune response or actively suppresses it. Moreover, little is known on how HBV and HCV influence each other in coinfected cells. We investigated interactions between HBV and the IFN-mediated immune response using HepaRG cells and primary human hepatocytes (PHHs). We analyzed the effects of HBV on HCV replication, and vice versa, at the single-cell level. PHHs were isolated from liver resection tissues from HBV-, HCV-, and human immunodeficiency virus-negative patients. Differentiated HepaRG cells overexpressing the HBV receptor sodium taurocholate cotransporting polypeptide (dHepaRGNTCP) and PHHs were infected with HBV. Huh7.5 cells were transfected with circular HBV DNA genomes resembling viral covalently closed circular DNA (cccDNA), and subsequently infected with HCV; this served as a model of HBV and HCV coinfection. Cells were incubated with IFN inducers, or IFNs, and antiviral response and viral replication were analyzed by immune fluorescence, reverse-transcription quantitative polymerase chain reaction, enzyme-linked immunosorbent assays, and flow cytometry. HBV infection of dHepaRGNTCP cells and PHHs neither activated nor inhibited signaling via pattern recognition receptors. Incubation of dHepaRGNTCP cells and PHHs with IFN had little effect on HBV replication or levels of cccDNA. HBV infection of these cells did not inhibit JAK-STAT signaling or up-regulation of IFN-stimulated genes. In coinfected cells, HBV did not prevent IFN-induced suppression of HCV replication. In dHepaRGNTCP cells and PHHs, HBV evades the induction of IFN and IFN-induced antiviral effects. HBV infection does not rescue HCV from the IFN-mediated response. Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.

  11. Socioeconomic status in HCV infected patients – risk and prognosis

    Directory of Open Access Journals (Sweden)

    Oml

    2013-05-01

    Full Text Available Lars Haukali Omland,1 Merete Osler,2 Peter Jepsen,3,4 Henrik Krarup,5 Nina Weis,6 Peer Brehm Christensen,7 Casper Roed,1 Henrik Toft Sørensen,3 Niels Obel1 On behalf of the DANVIR Cohort Study1Department of Infectious Diseases, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark; 2Research Center for Prevention and Health, Copenhagen University Hospital, Glostrup Hospital, Glostrup, Denmark; 3Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark; 4Department of Medicine V (Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark; 5Department of Clinical Biochemistry, Aalborg Hospital, Aalborg, Denmark; 6Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre Hospital, Hvidovre, Denmark; 7Department of Infectious Diseases, Odense University Hospital, Odense, DenmarkBackground and aims: It is unknown whether socioeconomic status (SES is a risk factor for hepatitis C virus (HCV infection or a prognostic factor following infection.Methods: From Danish nationwide registries, we obtained information on three markers of SES: employment, income, and education. In a case control design, we examined HCV infected patients and controls; conditional logistic regression was employed to obtain odds ratios (ORs for HCV infection for each of the three SES markers, adjusting for the other two SES markers, comorbidity, and substance abuse. In a cohort design, we used Cox regression analysis to compute mortality rate ratios (MRRs for each of the three SES markers, adjusting for the other two SES markers, comorbidity level, age, substance abuse, and gender.Results: When compared to employed persons, ORs for HCV infection were 2.71 (95% confidence interval [CI]: 2.24–3.26 for disability pensioners and 2.24 (95% CI: 1.83–2.72 for the unemployed. When compared to persons with a high income, ORs were 1.64 (95% CI: 1.34–2.01 for low income persons and 1.19 (95% CI: 1.02–1.40 for

  12. HCV Core Protein Uses Multiple Mechanisms to Induce Oxidative Stress in Human Hepatoma Huh7 Cells

    Science.gov (United States)

    Ivanov, Alexander V.; Smirnova, Olga A.; Petrushanko, Irina Y.; Ivanova, Olga N.; Karpenko, Inna L.; Alekseeva, Ekaterina; Sominskaya, Irina; Makarov, Alexander A.; Bartosch, Birke; Kochetkov, Sergey N.; Isaguliants, Maria G.

    2015-01-01

    Hepatitis C virus (HCV) infection is accompanied by the induction of oxidative stress, mediated by several virus proteins, the most prominent being the nucleocapsid protein (HCV core). Here, using the truncated forms of HCV core, we have delineated several mechanisms by which it induces the oxidative stress. The N-terminal 36 amino acids of HCV core induced TGFβ1-dependent expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidases 1 and 4, both of which independently contributed to the production of reactive oxygen species (ROS). The same fragment also induced the expression of cyclo-oxygenase 2, which, however, made no input into ROS production. Amino acids 37–191 of HCV core up-regulated the transcription of a ROS generating enzyme cytochrome P450 2E1. Furthermore, the same fragment induced the expression of endoplasmic reticulum oxidoreductin 1α. The latter triggered efflux of Ca2+ from ER to mitochondria via mitochondrial Ca2+ uniporter, leading to generation of superoxide anions, and possibly also H2O2. Suppression of any of these pathways in cells expressing the full-length core protein led to a partial inhibition of ROS production. Thus, HCV core causes oxidative stress via several independent pathways, each mediated by a distinct region of the protein. PMID:26035647

  13. Kushenin induces the apoptosis of HCV-infected cells by blocking the PI3K-Akt-mTOR pathway via inhibiting NS5A

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Yi; Chen, Na; Liu, Xiaojing; Lin, Shumei [Department of Infectious Diseases, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi 710061 (China); Luo, Wenjuan, E-mail: wenjuanluoxa@163.com [School of Pharmacy, Xi’an Jiaotong University, Xi’an, Shaanxi 710061 (China); Liu, Min, E-mail: minliusx@163.com [Department of Infectious Diseases, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi 710061 (China)

    2016-07-01

    With the increased burden induced by HCV, there is an urgent need to develop better-tolerated agents with good safety. In this study, we evaluated the anti-HCV capability of kushenin, as well as the possible mechanism to Huh7.5-HCV cells. The results demonstrated that kushenin significantly inhibited the HCV-RNA level. Similarly, the expression of HCV-specific protein NS5A was also decreased. Molecular docking results displayed that kushenin bonded well to the active pockets of HCV NS5A, further confirming the effects of kushenin on HCV replication. Coimmunoprecipitation assay determined that kushenin suppressed the interaction between PI3K and NS5A in HCV-replicon cells. Furthermore, kushenin exerted an obviously induced function on HCV-replicon cells apoptosis by inhibiting PI3K-Akt-mTOR pathway, which could be ameliorated by the specific activator IGF-1 addition. Taken together, kushenin possesses the ability to inhibit HCV replication, and contributes to the increased apoptosis of HCV-infected cells by blocking the PI3K-Akt-mTOR pathway via inhibiting NS5A. Our results provide important evidence for a better understanding of the pathogenesis of HCV infection, and suggest that kushenin has the potential to treat HCV disease. - Highlights: • Kushenin inhibits HCV replication. • Kushenin bonds directly to NS5A protein. • Kushenin induces the apoptosis of HCV-infected cells. • kushenin suppresses the interaction between PI3K and NS5A. • Kushenin inhibits PI3K-Akt-mTOR pathway.

  14. Kushenin induces the apoptosis of HCV-infected cells by blocking the PI3K-Akt-mTOR pathway via inhibiting NS5A

    International Nuclear Information System (INIS)

    Zhou, Yi; Chen, Na; Liu, Xiaojing; Lin, Shumei; Luo, Wenjuan; Liu, Min

    2016-01-01

    With the increased burden induced by HCV, there is an urgent need to develop better-tolerated agents with good safety. In this study, we evaluated the anti-HCV capability of kushenin, as well as the possible mechanism to Huh7.5-HCV cells. The results demonstrated that kushenin significantly inhibited the HCV-RNA level. Similarly, the expression of HCV-specific protein NS5A was also decreased. Molecular docking results displayed that kushenin bonded well to the active pockets of HCV NS5A, further confirming the effects of kushenin on HCV replication. Coimmunoprecipitation assay determined that kushenin suppressed the interaction between PI3K and NS5A in HCV-replicon cells. Furthermore, kushenin exerted an obviously induced function on HCV-replicon cells apoptosis by inhibiting PI3K-Akt-mTOR pathway, which could be ameliorated by the specific activator IGF-1 addition. Taken together, kushenin possesses the ability to inhibit HCV replication, and contributes to the increased apoptosis of HCV-infected cells by blocking the PI3K-Akt-mTOR pathway via inhibiting NS5A. Our results provide important evidence for a better understanding of the pathogenesis of HCV infection, and suggest that kushenin has the potential to treat HCV disease. - Highlights: • Kushenin inhibits HCV replication. • Kushenin bonds directly to NS5A protein. • Kushenin induces the apoptosis of HCV-infected cells. • kushenin suppresses the interaction between PI3K and NS5A. • Kushenin inhibits PI3K-Akt-mTOR pathway.

  15. Assessing the impact of educational campaigns on controlling HCV among women in prison settings

    Science.gov (United States)

    Mushayabasa, S.; Bhunu, C. P.; Smith?, Robert J.

    2012-04-01

    Prior studies have shown that imprisonment is a major risk factor for hepatitis C infection, with the risk of infection directly proportional to the length of incarceration. Women are at least twice as likely as men to contract HCV as they have limited access to information, health services and safe intravenous drug injecting equipments. We develop a mathematical model to assess the impact of educational campaigns on controlling HCV among women in prison settings. Equilibria for the model are determined and their stability are examined. Population-level effects of increased educational campaigns to encourage safe injecting practices among women in prison are evaluated through numerical simulations. The results suggest that educating women prisoners about abstaining from intravenous drug misuse may significantly reduce HCV prevalence among women in prison settings. Targeted education campaigns, which are effective at stopping transmission of HCV more than 80% of the time, will be highly effective at controlling the disease among women in prisons.

  16. Comparison of liver fibrosis blood tests developed for HCV with new specific tests in HIV/HCV co-infection.

    Science.gov (United States)

    Calès, Paul; Halfon, Philippe; Batisse, Dominique; Carrat, Fabrice; Perré, Philippe; Penaranda, Guillaume; Guyader, Dominique; d'Alteroche, Louis; Fouchard-Hubert, Isabelle; Michelet, Christian; Veillon, Pascal; Lambert, Jérôme; Weiss, Laurence; Salmon, Dominique; Cacoub, Patrice

    2010-08-01

    We compared 5 non-specific and 2 specific blood tests for liver fibrosis in HCV/HIV co-infection. Four hundred and sixty-seven patients were included into derivation (n=183) or validation (n=284) populations. Within these populations, the diagnostic target, significant fibrosis (Metavir F > or = 2), was found in 66% and 72% of the patients, respectively. Two new fibrosis tests, FibroMeter HICV and HICV test, were constructed in the derivation population. Unadjusted AUROCs in the derivation population were: APRI: 0.716, Fib-4: 0.722, Fibrotest: 0.778, Hepascore: 0.779, FibroMeter: 0.783, HICV test: 0.822, FibroMeter HICV: 0.828. AUROCs adjusted on classification and distribution of fibrosis stages in a reference population showed similar values in both populations. FibroMeter, FibroMeter HICV and HICV test had the highest correct classification rates in F0/1 and F3/4 (which account for high predictive values): 77-79% vs. 70-72% in the other tests (p=0.002). Reliable individual diagnosis based on predictive values > or = 90% distinguished three test categories: poorly reliable: Fib-4 (2.4% of patients), APRI (8.9%); moderately reliable: Fibrotest (25.4%), FibroMeter (26.6%), Hepascore (30.2%); acceptably reliable: HICV test (40.2%), FibroMeter HICV (45.6%) (ptests). FibroMeter HICV classified all patients into four reliable diagnosis intervals ( or =F1, > or =F2) with an overall accuracy of 93% vs. 79% (pfibrosis. Tests designed for HCV infections are less effective in HIV/HCV infections. A specific test, like FibroMeter HICV, was the most interesting test for diagnostic accuracy, correct classification profile, and a reliable diagnosis. With reliable diagnosis intervals, liver biopsy can therefore be avoided in all patients. Copyright 2010 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  17. Quantitative Epstein-Barr virus (EBV) serology in lung transplant recipients with primary EBV infection and/or post-transplant lymphoproliferative disease.

    NARCIS (Netherlands)

    Verschuuren, E; van der Bij, W; Boer, W.; Timens, W.; Middeldorp, J.M.; The, T.H.

    2003-01-01

    The Epstein-Barr virus (EBV)-specific antibody response was studied in lung transplant patients to assess their value in the diagnosis and prognosis of post-transplant lymphoproliferative disease. Recently developed synthetic peptides representing Epstein-Barr nuclear antigen-1 (EBNA-1), diffuse

  18. Quantitative Epstein-Barr virus (EBV) serology in lung transplant recipients with primary EBV infection and/or post-transplant lymphoproliferative disease

    NARCIS (Netherlands)

    Verschuuren, E; van der Bij, W; de Boer, W; Timens, W; Middeldorp, J; The, TH

    The Epstein-Barr virus (EBV)-specific antibody response was studied in lung transplant patients to assess their value in the diagnosis and prognosis of post-transplant lymphoproliferative disease. Recently developed synthetic peptides representing Epstein-Barr nuclear antigen-1 (EBNA-1), diffuse

  19. Embolización de la arteria esplénica como tratamiento del hiperesplenismo en pacientes hemofílicos, HIV-1 y HCV seropositivos

    Directory of Open Access Journals (Sweden)

    M. E. Corti

    2003-06-01

    Full Text Available La trombocitopenia es una anomalía usual e importante en pacientes con coinfección por HIV-1/HCV. La esplenomegalia es un hallazgo frecuente en estos pacientes y, usualmente, causa hiperesplenismo y trombocitopenia. Analizamos los resultados clínicos de un método invasivo mínimo (embolización de la arteria esplénica para el tratamiento de la trombocitopenia secundaria al hiperesplenismo y refractaria a otras terapias en dos pacientes hemofílicos, infectados por el HIV-1 y con cirrosis causada por la infección crónica por HCV. Estos resultados sugieren que la embolización de la arteria esplénica es un método seguro, poco traumático y efectivo para el tratamiento de la esplenomegalia y el hiperesplenismo en pacientes con coinfección por HIV-1/HCV.Thrombocytopenia is an important and common hematological abnormality in patients with HIV-1/HCV coinfection. Splenomegaly is a frequent finding in these patients and usually causes hypersplenism and thrombocytopenia. We analyzed the clinical results of a minimal invasive treatment (splenic artery embolization for thrombocytopenia secondary to hypersplenism and refractory to other therapies in two hemophiliac patients, HIV seropositive and with cirrhosis due to chronic HCV infection. The results suggest that splenic artery embolization is a safe, relatively atraumatic and effective method for the treatment of splenomegaly and hypersplenism in selected patients with HIV-1/HCV coinfection.

  20. The Future of HCV Therapy: NS4B as an Antiviral Target

    Directory of Open Access Journals (Sweden)

    Hadas Dvory-Sobol

    2010-11-01

    Full Text Available Chronic hepatitis C virus (HCV infection is a major worldwide cause of liver disease, including cirrhosis and hepatocellular carcinoma. It is estimated that more than 170 million individuals are infected with HCV, with three to four million new cases each year. The current standard of care, combination treatment with interferon and ribavirin, eradicates the virus in only about 50% of chronically infected patients. Notably, neither of these drugs directly target HCV. Many new antiviral therapies that specifically target hepatitis C (e.g. NS3 protease or NS5B polymerase inhibitors are therefore in development, with a significant number having advanced into clinical trials. The nonstructural 4B (NS4B protein, is among the least characterized of the HCV structural and nonstructural proteins and has been subjected to few pharmacological studies. NS4B is an integral membrane protein with at least four predicted transmembrane (TM domains. A variety of functions have been postulated for NS4B, such as the ability to induce the membranous web replication platform, RNA binding and NTPase activity. This review summarizes potential targets within the nonstructural protein NS4B, with a focus on novel classes of NS4B inhibitors.

  1. HBV or HCV Coinfection in HIV-1-Infected Pregnant Women in France: Prevalence and Pregnancy Outcomes.

    Science.gov (United States)

    Benhammou, Valérie; Tubiana, Roland; Matheron, Sophie; Sellier, Pierre; Mandelbrot, Laurent; Chenadec, Jérôme Le; Marel, Emmanuelle; Khoshnood, Babak; Warszawski, Josiane

    2018-04-15

    Chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection is frequent in HIV-infected persons but their impact on pregnant HIV-infected women is understudied. We explored whether these coinfections are associated with adverse pregnancy outcomes and lower response to antiretroviral therapy (ART). Pregnancies in HIV-1-infected women included in the ANRS French Perinatal Cohort between 2005 and 2013 were analyzed if HBV and HCV infection statuses were available. Among 4236 women, the prevalence of HBV (HBs Ag+) and HCV (RNA+) were 6.2% (95% confidence interval: 5.4 to 6.8) and 1.7% (1.3 to 2.1), respectively. HCV coinfection was strongly associated with a history of drug use; HBV coinfection was 6 times more frequent in women born in Sub-Saharan Africa than in European France. Baseline HIV viral load, CD4 count, and HIV care during pregnancy were similar in coinfected and monoinfected HIV mothers, except that 90% of HBV/HIV women were receiving tenofovir and/or lamivudine or emtricitabine. HCV coinfection was significantly associated with cholestasis [adjusted odds ratio: 4.1 (1.5-10.8), P = 0.005], preterm delivery [3.0 (1.6-5.7), P HIV-infected women, chronic HBV infection, mostly treated using targeted ART, had no major impact on the course of pregnancy. By contrast, chronic HCV infection was associated with a higher risk of obstetrical complications and a poorer immune-virological response to ART. It is yet unknown whether cure of HCV infection before conception can limit these adverse outcomes.

  2. Sofosbuvir and Simeprevir Combination Therapy for HCV Genotype 1 Infection: Results of a Single-Center VA Experience

    Science.gov (United States)

    Hernandez, Maria Del Pilar; Vance, Evan; Gilinski, Dani; Youtseff, Helen; Toro, Maribel; Antoine, Marie; Jeffers, Lennox J.; Peyton, Adam

    2016-01-01

    Treatment of chronic hepatitis C virus (HCV) infection remains a priority in the veterans affairs (VA) health care system nationwide, as there is a high burden of liver disease due to HCV infection among US veterans. The combination of sofosbuvir and simeprevir was the first all-oral antiviral regimen used in clinical practice to treat veterans with HCV infection. In this study, we report a single-center experience showing both the feasibility and effectiveness of this all-oral combination to treat HCV genotype 1 infection. One hundred patients with HCV genotype 1 infection were treated between December 2013 and June 2014. Eighty-six patients were treated with sofosbuvir and simeprevir, with or without ribavirin, for 12 weeks; 12 patients were treated with sofosbuvir, pegylated interferon, and ribavirin for 12 weeks; and 2 patients were treated with sofosbuvir and ribavirin for 24 weeks. Overall, treatment was well tolerated and feasible, with compliance rates over 95% in patients treated with all-oral therapy. The sustained virologic response (SVR) rate for sofosbuvir and simeprevir (88.4%) was superior to the rate for sofosbuvir, pegylated interferon, and ribavirin (50.0%). Subgroup analysis showed diminished SVR rates in cirrhotic patients vs noncirrhotic patients. There were no significant differences in SVR when comparing treatment with or without ribavirin or among genotype subtypes. In conclusion, this study demonstrated excellent completion rates for all-oral treatment of veterans with chronic HCV infection. Additionally, treatment was highly effective, nearing a 90% cure rate. Thus, we recommend that the VA health care system continue to incorporate new HCV medications into its formulary so as to expand HCV treatment for US veterans. PMID:27917084

  3. Relative deprivation and disordered gambling in youths.

    Science.gov (United States)

    Elgar, Frank J; Canale, Natale; Wohl, Michael J A; Lenzi, Michela; Vieno, Alessio

    2018-03-07

    Previous research has found that area-level income inequality and individual-level relative deprivation both contribute to disordered gambling in adults. However, the socioeconomic factors that contribute to disordered gambling in youths and protective factors in their social environment have not been fully explored. This study examined the association between relative deprivation and youth disordered gambling and the potential moderating role of social support in this association. We used data on family material assets and self-reported symptoms of disordered gambling symptoms in 19 321 participants of the 2013/2014 Italian Health Behaviour in School-aged Children study. Relative deprivation was measured using the Yitzhaki index and classmates as a social reference group. Its association with disordered gambling was tested using multilevel negative binomial regression analyses. We also tested moderated effects of relative deprivation on disordered gambling by four sources of social support: families, peers, teachers and classmates. Relative deprivation related to a fourfold increase in the rate of disordered gambling symptoms (incidence rate ratio=4.18) after differences in absolute family wealth and other variables were statistically controlled. Symptoms were also more prevalent in males, first-generation immigrants and less supported youth. Peer support moderated the association between relative deprivation and symptoms, suggesting that high deprivation and low peer support have interactive links to disordered gambling. Relative deprivation among classmates relate to youth symptoms of disordered gambling. Youth who live in economically unequal settings and perceive a lack of social support may be at greatest risk. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  4. Epidemiological Profile and Risk Factors for Acquiring HBV and/or HCV in HIV-Infected Population Groups in Nepal.

    Science.gov (United States)

    Bhattarai, Manjula; Baniya, Jagat Bahadur; Aryal, Nirmal; Shrestha, Bimal; Rauniyar, Ramanuj; Adhikari, Anurag; Koirala, Pratik; Oli, Pardip Kumar; Pandit, Ram Deo; Stein, David A; Gupta, Birendra Prasad

    2018-01-01

    HBV and HCV infections are widespread among the HIV-infected individuals in Nepal. The goals of this study were to investigate the epidemiological profile and risk factors for acquiring HBV and/or HCV coinfection in disadvantaged HIV-positive population groups in Nepal. We conducted a retrospective study on blood samples from HIV-positive patients from the National Public Health Laboratory at Kathmandu to assay for HBsAg, HBeAg, and anti-HCV antibodies, HIV viral load, and CD4+ T cell count. Among 579 subjects, the prevalence of HIV-HBV, HIV-HCV, and HIV-HBV-HCV coinfections was 3.62%, 2.93%, and 0.34%, respectively. Multivariate regression analysis indicated that spouses of HIV-positive migrant labourers were at significant risk for coinfection with HBV infection, and an age of >40 years in HIV-infected individuals was identified as a significant risk factor for HCV coinfection. Overall our study indicates that disadvantaged population groups such as intravenous drug users, migrant workers and their spouses, female sex workers, and men who have sex with HIV-infected men are at a high and persistent risk of acquiring viral hepatitis. We conclude that Nepalese HIV patients should receive HBV and HCV diagnostic screening on a regular basis.

  5. Test of IL28B polymorphisms in chronic hepatitis C patients treated with PegIFN and ribavirin depends on HCV genotypes: results from a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Zhifang Jia

    Full Text Available Many studies have been published on the association between single nucleotide polymorphisms (SNP near the IL28B gene and response to the combined treatments of pegylated-interferon (PegIFN and ribavirin (RBV in chronic HCV-infected patients, but without identical conclusions. The aim of this study was to assess impact of the IL28B polymorphisms on the effect of HCV standard treatment using meta-analysis based method.Association studies between polymorphisms of rs12979860 or rs8099917 and response to PegIFN/RBV treatment in chronic HCV patients were retrieved from PubMed. Data of qualified studies on sustained virological response (SVR in different genotypes were extracted and analyzed using meta-analysis method in Stata 10 software.Thirty-four papers, containing 46 independent studies, were included in the analysis. In the HCV G1/4 patients without treatment history, individuals carrying rs12979860 CC genotype were more likely to achieve SVR (OR 3.97, 95%CI 3.29-4.80 compared to those carrying CT/TT genotypes. Similar results were observed in the HCV G1/4 patients with unsuccessful or unknown treatment history (OR 3.76, 95%CI 2.67-5.28 or in the patients co-infected with human immunodeficiency virus (OR 5.20, 95%CI 3.04-8.90. However, associations could not be observed in HCV G2/3 patients. For rs8099917, similar results were obtained for genotype TT compared to genotypes TG/GG, indicating that TT genotype was significantly associated with better treatment response in patients infected with genotype 1 or 4 HCV, but not genotype 2 or 3 HCV.Polymorphisms of rs12979860 and rs8099917 near IL28B only associate with the treatment response to PegIFN/RBV in patients infected with HCV genotype 1 or 4 but not with genotype 2 or 3, irrespective of the previous treatment history or HIV co-infected status. Therefore, identification of IL28B genotypes is necessary only in patients infected with relatively difficult-to-treat genotype 1 or 4 HCV.

  6. [Topiramate in substance-related and addictive disorders].

    Science.gov (United States)

    Cohen, Johan; Dervaux, Alain; Laqueille, Xavier

    2014-09-01

    Drug treatments used in substance use disorders are not effective in all patients. To assess the effectiveness of topiramate use in the treatment of substance use disorders. Medline database from January 1966 to December 2013, Cochrane database and clinicaltrials.gov. We used keywords topiramate, addiction, substance abuse, alcohol, tobacco, nicotine, cocaine, methamphetamine, opiate, heroin, benzodiazepine, cannabis, bulimia nervosa, binge eating disorder, gambling. All clinical trials were included. Animal trials, laboratory tests, reviews, answers to writers, case-reports, case series and publications unrelated to the topic were excluded. Twenty-eight articles investigating the efficacy of topiramate in substance use were included. In alcohol-related disorder, several trials and a meta-analysis showed a reduction of days of consumption. In a single-center trial on tobacco-related disorder, topiramate was not found effective in reducing the carbon monoxide expired. In cocaine-related disorder, one single-center trial showed a reduction of days of consumption and two single-center trials have found a trend in favour of topiramate. In alcohol and cocaine co-dependency, a single-center trial found a trend in favour of topiramate. In methamphetamine-related disorder, a multicenter trial found a trend in favour of topiramate. In bulimia nervosa, two single-center trials showed a reduction in binge eating and compensatory behaviours. In binge eating disorder, several trials showed a reduction of binge eating and weight. In gambling, one single-center trial did not show any significant results. There were no randomized controlled trials found in opioid-related disorder, benzodiazepines-related disorder, and cannabis-related disorder. Definition of abstinence and methods to assess the efficacy of topiramate differed between trials. The methodological quality of included trials was variable, especially with no double-blind procedure in eight trials. Topiramate showed

  7. High seroprevalence of HBV and HCV infection in HIV-infected adults in Kigali, Rwanda

    NARCIS (Netherlands)

    Rusine, John; Ondoa, Pascale; Asiimwe-Kateera, Brenda; Boer, Kimberly R.; Uwimana, Jean Marie; Mukabayire, Odette; Zaaijer, Hans; Mugabekazi, Julie; Reiss, Peter; van de Wijgert, Janneke H.

    2013-01-01

    Data on prevalence and incidence of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection in Rwanda are scarce. HBV status was assessed at baseline and Month 12, and anti-HCV antibodies at baseline, in a prospective cohort study of HIV-infected patients in Kigali, Rwanda: 104 men and 114

  8. Molecular epidemiology of HIV, HBV, HCV, and HTLV-1/2 in drug abuser inmates in central Javan prisons, Indonesia.

    Science.gov (United States)

    Prasetyo, Afiono Agung; Dirgahayu, Paramasari; Sari, Yulia; Hudiyono, Hudiyono; Kageyama, Seiji

    2013-06-15

    This study was conducted to determine the current molecular prevalence of human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), hepatitis D virus (HDV), and human T lymphotropic virus-1/2 (HTLV-1/2) circulating among drug abuser inmates incarcerated in prisons located in Central Java, Indonesia. Socio-epidemiological data and blood specimens were collected from 375 drug abuser inmates in four prisons. The blood samples were analyzed with serological and molecular testing for HIV, HBV, HCV, HDV, and HTLV-1/2. The seroprevalence of HIV, HBsAg, HCV, HDV, and HTLV-1/2 in drug abuser inmates was 4.8% (18/375), 3.2% (12/375), 34.1% (128/375), 0% (0/375), and 3.7% (14/375), respectively. No co-infections of HIV and HBV were found. Co-infections of HIV/HCV, HIV/HTLV-1/2, HBV/HCV, HBV/HTLV-1/2, and HCV/HTLV-1/2 were prevalent at rates of 4% (15/375), 1.3% (5/375), 1.1% (4/375), 0.3% (1/375), and 2.1% (8/375), respectively. The HIV/HCV co-infection rate was significantly higher in injection drug users (IDUs) compared to non-IDUs. Triple co-infection of HIV/HCV/HTLV-1/2 was found only in three IDUs (0.8%). HIV CRF01_AE was found to be circulating in the inmates. HBV genotype B3 predominated, followed by C1. Subtypes adw and adr were found. HCV genotype 1a predominated among HCV-infected inmates, followed by 1c, 3k, 3a, 4a, and 1b. All HTLV-1 isolates shared 100% homology with HTLV-1 isolated in Japan, while all of the HTLV-2 isolates were subtype 2a. Drug abuser inmates in prisons may offer a unique community to bridge prevention and control of human blood-borne virus infection to the general community.

  9. Transmission of HCV to a chimpanzee using virus particles produced in an RNA-transfected HepG2 cell culture.

    Science.gov (United States)

    Dash, S; Kalkeri, G; McClure, H M; Garry, R F; Clejan, S; Thung, S N; Murthy, K K

    2001-10-01

    It was demonstrated previously that HepG2 cells produce negative strand RNA and virus-like particles after transfection with RNA transcribed from a full-length hepatitis C virus (HCV) cDNA clone [Dash et al. (1997) American Journal of Pathology, 151:363-373]. To determine in vivo infectivity of these in vitro synthesized viral particles, a chimpanzee was inoculated intravenously with HCV derived from HepG2 cells. The infected chimpanzee was examined serially for elevation of liver enzymes, for the presence of HCV RNA in the serum by reverse transcription nested polymerase chain reaction (RT-PCR), anti-HCV antibodies in the serum, and inflammation in the liver. The chimpanzee developed elevated levels of liver enzymes after the second week, but the levels fluctuated over a 10-week period. HCV RNA was detected in the serum of the chimpanzee at the second, seventh and ninth weeks after inoculation, and remained positive up to 25 weeks. Liver biopsies at Weeks 18 and 19 revealed of mild inflammation. Nucleotide sequence analysis of HCV recovered from the infected chimpanzee at the second and ninth weeks showed 100% sequence homology with the clone used for transfection studies. Serum anti-HCV antibodies were not detected by EIA during the 25 weeks follow-up period. These results suggest that intravenous administration of the virus-like particles derived from RNA-transfected HepG2 cells are infectious, and therefore, the pMO9.6-T7 clone is an infectious clone. These results provide new information that in vitro synthesized HCV particles produced from full-length HCV clone can cause infection in a chimpanzee. This study will facilitate the use of innovative approaches to the study of assembly of HCV particles and mechanisms of virus infectivity in cell culture. Copyright 2001 Wiley-Liss, Inc.

  10. Depression in HIV and HCV co-infected patients: a systematic review and meta-analysis.

    Science.gov (United States)

    Fialho, Renata; Pereira, Marco; Rusted, Jennifer; Whale, Richard

    2017-10-01

    The aim of this study was to carry out a systematic review and meta-analysis of the differences in the prevalence of depression and presence of depressive symptoms between HIV/HCV co-infection, HIV mono-infection, and hepatitis C virus (HCV) mono-infection. A systematic electronic search of bibliographic databases was performed to locate articles published from the earliest available online until December 2014. Outcomes of depression were based on clinical interviews and validated self-reported measures of depression/depressive symptoms. Of the 188 records initially screened, 29 articles were included in the descriptive systematic review and six were included in the meta-analysis. The meta-analytic results indicated that, as measured by self-reported measures of depression, HIV/HCV co-infected patients were significantly more likely to report depressive symptoms than either HIV (SMD = .24, 95% CI: .03-.46, p = .02) or HCV mono-infected (SMD = .55, 95% CI: .17-.94, p = .005) patients. The variability of the results of the reviewed studies, largely dependent on the samples' characteristics and the methods of assessment of depression, suggests that a clear interpretation of how depression outcomes are affected by the presence of HIV/HCV co-infection is still needed. Failing to diagnose depression or to early screen depressive symptoms may have a significant impact on patients' overall functioning and compromise treatments' outcomes.

  11. The effect of HCV serological status on Doxorubicin based ...

    African Journals Online (AJOL)

    Karim Yousri Welaya

    2014-09-10

    Sep 10, 2014 ... Pretreatment evaluation included serological testing for HCV. FAC Adjuvant ... National Cancer Institute; IRB, Institutional Research Board; LVEF, ..... Mild Skin changes, including skin discoloration and nail changes, not ...

  12. PD-1 expression on peripheral CD8+ TEM/TEMRA subsets closely correlated with HCV viral load in chronic hepatitis C patients

    Directory of Open Access Journals (Sweden)

    Zhang Weidong

    2010-11-01

    Full Text Available Abstract Background Tight correlation between host circulating CD8+ T cell-mediated immune response and control of viral replication is classical characteristic of long-term HCV infection. CD8+ T cell maturation/activation markers are expected to be associated with viral replication and disease progression in chronic HCV infection. The aim of the present study was to explore novel markers on CD8+ T cells with ability to evaluate HCV viral replication and disease progression. Methods PBMCs were isolated from 37 chronic HCV-infected patients and 17 healthy controls. Distributed pattern of CD8+ T cells subsets and expression of PD-1, CD38, HLA-DR and CD127 were analyzed by flow cytometry. The correlation between expression of surface markers and HCV viral load or ALT was studied. Results Declined naïve and increased TEMRA CD8+ T subsets were found in HCV-infected individuals compared with healthy controls. Percentage and MFI of PD-1, CD38 and HLA-DR on all CD8+ T cell subsets were higher in HCV-infected patients than healthy controls. In contrast, CD127 expression on CD8+ TCM showed an opposite trend as PD-1, CD38 and HLA-DR did. In chronic HCV infection, MFI of PD-1 on CD8+ TEM (p Conclusion PD-1 level on peripheral CD8+ TEM/TEMRA was highly correlated with HCV viral load in chronic HCV-infected patients, which made PD-1 a novel indicator to evaluate HCV replication and disease progression in chronic hepatitis C patients.

  13. Comparison of seropositivity of HCV between oral lichen planus and healthy control group in Hamedan province (west of Iran

    Directory of Open Access Journals (Sweden)

    Ahmad Reza Mobaien

    2011-10-01

    Full Text Available Background: Lichen planus is an idiopathic inflammatory disease of the skin, nail, hair and mucous membranes. Oral lichen planus (LP is a chronic inflammatory condition that affects the oral mucous membranes with a variety of clinical presentations. Various etiologies include HCV suggested for LP, and the aim of this study was comparison of seropositivity of HCV in LP patients and control group. Methods: All oral LP patients that were referred to dermatology clinic of farshchian hospitalwere entered in the study. Five cc of clot blood was taken from each patient and tested for anti-HCVand when anti-HCV tested positive another 2cc clot bloodwas taken for HCV-Rt-PCR test. The results were analyzed with SPSS 16. Results: This prospective cross-sectional study was conducted on 30 oral lichen planus patients [males 13(43.3% females 17(56.7%] with mean ages of 46±13.7years and 60 healthy individual [males 26(43.3% females 34(56.7%]. There was no oral lichen planus patients who had anti-HCV positive whiles 2 males(3.3% of healthy group had anti-HCV positive which was confirmed by HCV-Rt-PCR. Conclusions: This study showed that there is no correlation between seropositivity of HCV and oral lichen planus in our patients in the west of Iran.

  14. Non-breathing-related sleep disorders following stroke.

    Science.gov (United States)

    Marquez-Romero, J M; Morales-Ramírez, M; Arauz, A

    2014-01-01

    It has been shown that sleep-related breathing disorders, especially sleep apnea, are very common in patients who have had a stroke, and that they also reduce the potential for neurological recovery. Nevertheless, other sleep disorders caused by stroke (excessive daytime sleepiness, insomnia, sleep related movement disorders) can also cause or increase stroke-related disability, and this fact is less commonly known. Studies with polysomnography have shown many abnormalities in sleep architecture during the acute phase of stroke; these abnormalities have a negative impact on the patient's quality of life although they tend to improve with time. This also happens with other sleep disorders occurring as the result of a stroke (insomnia, narcolepsy, restless legs syndrome, periodic limb movement disorder and REM sleep behavior disorder), which are nevertheless potentially treatable. In this article, we briefly review the physiopathology and epidemiology of the disorders listed above in order to raise awareness about the importance of these disorders and the effects they elicit in stroke patients. Sleep disorders that are not breathing-related have scarcely been studied in stroke patients despite the fact that almost all such disorders may present as a result of a cerebrovascular event. Copyright © 2012 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.

  15. Detection and quantification of serum or plasma HCV RNA: mini review of commercially available assays.

    Science.gov (United States)

    Le Guillou-Guillemette, Helene; Lunel-Fabiani, Francoise

    2009-01-01

    The treatment schedule (combination of compounds, doses, and duration) and the virological follow-up for management of antiviral treatment in patients chronically infected by HCV is now well standardized, but to ensure good monitoring of the treated patients, physicians need rapid, reproducible, and sensitive molecular virological tools with a wide range of detection and quantification of HCV RNA in blood samples. Several assays for detection and/or quantification of HCV RNA are currently commercially available. Here, all these assays are detailed, and a brief description of each step of the assay is provided. They are divided into two categories by method: those based on signal amplification and those based on target amplification. These two categories are then divided into qualitative, quantitative, and quantitative detection assays. The real-time reverse-transcription polymerase chain reaction (RT-PCR)-based assays are the most promising strategy in the HCV virological area.

  16. Assessing the Long-Term Impact of Treating Hepatitis C Virus (HCV-Infected People Who Inject Drugs in the UK and the Relationship between Treatment Uptake and Efficacy on Future Infections.

    Directory of Open Access Journals (Sweden)

    Hayley Bennett

    Full Text Available The prevalence of the hepatitis C virus (HCV remains high amongst people who inject drugs (PWID and accounts for the majority of newly acquired infections. This study aims to quantify the value of treatment amongst PWID with more efficacious treatments and at increased uptake rates, with respect to the avoidance of future infections and subsequent long-term complications of HCV.A dynamic HCV transmission and disease progression model was developed, incorporating acute and chronic infection and their long-term complications (decompensated cirrhosis, cancer, liver transplant and mortality, with the potential for HCV transmission to other PWID prior to successful treatment. The model was populated with prevalence and therapy data from a UK setting. Scenarios of current standard of care (SoC treatment efficacy and uptake were compared to anticipated sustained virologic response (SVR rates of 90-100% and increased uptake over varied horizons.SoC led to modest reductions in prevalence; >5% after 200 years. New treatments achieving 90% SVR could reduce prevalence below 5% within 60 years at current uptake rates or within 5 years if all patients are treated. Amongst 4,240 PWID, chronic HCV infections avoided as a result of increasing treatment uptake over the period 2015-2027 ranged from 20-580 and 34-912 with SoC and 90% SVR rates respectively. The reduction in downstream HCV infections due to increasing treatment uptake resulted in an approximate discounted gain of 300 life-years (from avoiding reduced life expectancy from HCV infection and a gain of 1,700 QALYs (from avoiding the disutility of HCV infection and related complications, with a projected £5.4 million cost saving.While improved SVR profiles led to reductions in modelled prevalence, increased treatment uptake was the key driver of future infections avoided. Increased treatment among PWID with new more efficacious therapies could significantly change the future dynamics, cost and health

  17. Receptor complementation and mutagenesis reveal SR-BI as an essential HCV entry factor and functionally imply its intra- and extra-cellular domains.

    Directory of Open Access Journals (Sweden)

    Marlène Dreux

    2009-02-01

    Full Text Available HCV entry into cells is a multi-step and slow process. It is believed that the initial capture of HCV particles by glycosaminoglycans and/or lipoprotein receptors is followed by coordinated interactions with the scavenger receptor class B type I (SR-BI, a major receptor of high-density lipoprotein (HDL, the CD81 tetraspanin, and the tight junction protein Claudin-1, ultimately leading to uptake and cellular penetration of HCV via low-pH endosomes. Several reports have indicated that HDL promotes HCV entry through interaction with SR-BI. This pathway remains largely elusive, although it was shown that HDL neither associates with HCV particles nor modulates HCV binding to SR-BI. In contrast to CD81 and Claudin-1, the importance of SR-BI has only been addressed indirectly because of lack of cells in which functional complementation assays with mutant receptors could be performed. Here we identified for the first time two cell types that supported HCVpp and HCVcc entry upon ectopic SR-BI expression. Remarkably, the undetectable expression of SR-BI in rat hepatoma cells allowed unambiguous investigation of human SR-BI functions during HCV entry. By expressing different SR-BI mutants in either cell line, our results revealed features of SR-BI intracellular domains that influence HCV infectivity without affecting receptor binding and stimulation of HCV entry induced by HDL/SR-BI interaction. Conversely, we identified positions of SR-BI ectodomain that, by altering HCV binding, inhibit entry. Finally, we characterized alternative ectodomain determinants that, by reducing SR-BI cholesterol uptake and efflux functions, abolish HDL-mediated infection-enhancement. Altogether, we demonstrate that SR-BI is an essential HCV entry factor. Moreover, our results highlight specific SR-BI determinants required during HCV entry and physiological lipid transfer functions hijacked by HCV to favor infection.

  18. Detection of HIV and HCV RNA in semen from Brazilian coinfected men using multiplex PCR before and after semen washing Detecção do RNA do HIV e HCV em sêmen de homens brasileiros, usando PCR multiplex antes e depois do "semen washing"

    Directory of Open Access Journals (Sweden)

    Cynthia Liliane Motta do Canto

    2006-08-01

    Full Text Available INTRODUCTION: Prolonged survival of patients under HAART has resulted in new demands for assisted reproductive technologies. HIV serodiscordant couples wish to make use of assisted reproduction techniques in order to avoid viral transmission to the partner or to the newborn. It is therefore essential to test the effectiveness of techniques aimed at reducing HIV and HCV loads in infected semen using molecular biology tests. METHODS: After seminal analysis, semen samples from 20 coinfected patients were submitted to cell fractioning and isolation of motile spermatozoa by density gradient centrifugation and swim-up. HIV and HCV RNA detection tests were performed with RNA obtained from sperm, seminal plasma and total semen. RESULTS: In pre-washing semen, HIV RNA was detected in 100% of total semen samples, whereas HCV RNA was concomitantly amplified in only one specimen. Neither HIV nor HCV were detected either in the swim-up or in the post-washing semen fractions. CONCLUSIONS: Reduction of HIV and/or HCV shedding in semen by density gradient centrifugation followed by swim-up is an efficient method. These findings lead us to believe that, although semen is rarely found to contain HCV, semen processing is highly beneficial for HIV/HCV coinfected individuals.O aumento da sobrevida dos pacientes que utilizam terapêutica antiretroviral altamente eficaz (HAART- Highly Active Antiretroviral Therapy trouxe uma nova demanda de casais sorodiscordantes que desejam filhos. Como esses casais não podem abandonar o uso de preservativos, torna-se indispensável tratar o sêmen infectado com técnicas laboratoriais eficazes que além de isolar os melhores espermatozóides, reduzam a carga viral do HIV e HCV a níveis indetectáveis. Para isso, são utilizadas técnicas de semen washing, associadas a testes ultra sensíveis de biologia molecular. Após análise seminal, sêmen de 20 pacientes co-infectados HIV-HCV foram submetidos a fracionamento celular e

  19. HBV or HCV coinfections and risk of myocardial infarction in HIV-infected individuals: the D:A:D Cohort Study

    DEFF Research Database (Denmark)

    Weber, Rainer; Sabin, Caroline; Reiss, Peter

    2010-01-01

    Data on a link between HCV or HBV infection and the development of cardiovascular disease among HIV-negative and HIV-positive individuals are conflicting. We sought to investigate the association between HBV or HCV infection and myocardial infarction in HIV-infected individuals.......Data on a link between HCV or HBV infection and the development of cardiovascular disease among HIV-negative and HIV-positive individuals are conflicting. We sought to investigate the association between HBV or HCV infection and myocardial infarction in HIV-infected individuals....

  20. No Evidence for JAK2(V617F) Mutation in Monoclonal B Cells in 2 Patients with Polycythaemia Vera and Concurrent Monoclonal B Cell Disorder

    NARCIS (Netherlands)

    Stijnis, C.; Kroes, W. G. M.; Balkassmi, S.; Marijt, E. W. A.; van Rossum, A. P.; Bakker, E.; Vlasveld, L. T.

    2012-01-01

    Occurrence of Philadelphia chromosome-negative myeloproliferative neoplasms (Ph- MPN) and lymphoproliferative disorders, like B cell chronic lymphocytic leukaemia (B-CLL), in the same patient is rare. JAK2(V617F) mutation was recently introduced as a powerful diagnostic tool for Ph- MPN. JAK2(V617F)

  1. International epidemiological studies on HIV, HCV and STI

    NARCIS (Netherlands)

    van der Helm, J.J.

    2014-01-01

    This thesis comprises international epidemiological studies on HIV, Hepatitis C (HCV) and sexually transmitted infections (STI) and the evaluation of STI diagnostic tests with the ultimate goal to decrease spread and disease burden of these infections. The main conclusions are: 1. Without the use of

  2. [Prevalence of sleep-related breathing disorders of inpatients with psychiatric disorders].

    Science.gov (United States)

    Behr, M; Acker, J; Cohrs, S; Deuschle, M; Danker-Hopfe, H; Göder, R; Norra, C; Richter, K; Riemann, D; Schilling, C; Weeß, H-G; Wetter, T C; Wollenburg, L M; Pollmächer, T

    2018-06-06

    Sleep-related breathing disorders seriously impair well-being and increase the risk for relevant somatic and psychiatric disorders. Moreover, risk factors for sleep-related breathing disorders are highly prevalent in psychiatric patients. The aim of this study was for the first time in Germany to study the prevalence of obstructive sleep apnea syndrome (OSAS) as the most common form of sleep-related breathing disorder in patients with psychiatric disorders. In 10 psychiatric hospitals in Germany and 1 hospital in Switzerland, a total of 249 inpatients underwent an 8‑channel sleep polygraphy to investigate the prevalence of sleep apnea in this group of patients. With a conspicuous screening result of 23.7% of the subjects, a high prevalence of sleep-related breathing disorders was found to occur among this group of patients. Male gender, higher age and high body mass index (BMI) were identified as positive risk factors for the detection of OSAS. The high prevalence indicates that sleep apnea is a common sleep disorder among psychiatric patients. Although OSAS can lead to substantial disorders of the mental state and when untreated is accompanied by serious somatic health problems, screening procedures are not part of the routine work-up in psychiatric hospitals; therefore, sleep apnea is presumably underdiagnosed in psychiatric patients. In view of the results of this and previous studies, this topic complex should be the subject of further research studies.

  3. [Sleep disorder and lifestyle-related disease].

    Science.gov (United States)

    Shibata, Rei; Murohara, Toyoaki

    2015-06-01

    Sleep disorder is associated with the lifestyle-related diseases including obesity, insulin resistance and atherosclerosis. Adipose tissue functions as an endocrine organ by producing bioactive secretory proteins, also known as adipokines, that can directly act on nearby or remote organs. Recently, the associations between these adipokines and sleep disorders such as obstructive sleep apnea have been reported. In this review, we focus on the relationship between sleep disorder and lifestyle-related diseases.

  4. Evaluation of the Ortho-Clinical Diagnostics Vitros ECi Anti-HCV test: comparison with three other methods.

    Science.gov (United States)

    Watterson, Jeannette M; Stallcup, Paulina; Escamilla, David; Chernay, Patrick; Reyes, Alfred; Trevino, Sylvia C

    2007-01-01

    After observing a high incidence of low positive hepatitis C virus (HCV) antibody screens by the Ortho-Clinical Vitros ECi test (Orthoclinical Diagnostics, Raritan, NJ), we compared results against those obtained using another chemiluminescent analyzer, as well as two U.S. Food and Drug Administration (FDA)-approved confirmatory methodologies. To ascertain the true anti-HCV status of samples deemed low-positive by the Ortho-Clinical Vitros ECi test, we tested samples using the ADVIA Centaur HCV screen test (Siemens Medical Solutions Diagnostics), the Chiron recombinant immunoblot assay (RIBA) test (Chiron Corp., Emeryville, CA), and the Roche COBAS Amplicor HCV qualitative test (Roche Diagnostics, Indianapolis, IN) in a series of studies. Of 94 specimens positive by Vitros ECi, 19% were observed to be negative by Centaur. A separate study of 91 samples with signal-to-cutoff (s/co) values less than 8.0 showed that all but one was negative for HCV ribonucleic acid (RNA). In comparison with RIBA, 100% (77) samples positive by the Vitros ECi test with s/co values less than 12.0 were negative or indeterminate by RIBA. A final study comparing all four methods side-by-side showed 63% disagreement by Centaur for Vitros ECi low-positive samples, 75% disagreement by RIBA, and 97% disagreement by polymerase chain reaction (PCR). In conclusion, the Ortho-Clinical Vitros ECi Anti-HCV test yields a high rate of false-positive results in the low s/co range in our patient population. (c) 2007 Wiley-Liss, Inc.

  5. HVR1-mediated antibody evasion of highly infectious in vivo adapted HCV in humanised mice

    DEFF Research Database (Denmark)

    Prentoe, Jannick; Verhoye, Lieven; Moctezuma, Rodrigo Velazquez

    2016-01-01

    Objective HCV is a major cause of chronic liver disease worldwide, but the role of neutralising antibodies (nAbs) in its natural history remains poorly defined. We analysed the in vivo role of hypervariable region 1 (HVR1) for HCV virion properties, including nAb susceptibility. Design Analysis o...

  6. Circulating sCD14 is associated with virological response to pegylated-interferon-alpha/ribavirin treatment in HIV/HCV co-infected patients.

    Directory of Open Access Journals (Sweden)

    Giulia Marchetti

    Full Text Available Microbial translocation (MT through the gut accounts for immune activation and CD4+ loss in HIV and may influence HCV disease progression in HIV/HCV co-infection. We asked whether increased MT and immune activation may hamper anti-HCV response in HIV/HCV patients.98 HIV/HCV patients who received pegylated-alpha-interferon (peg-INF-alpha/ribavirin were retrospectively analyzed. Baseline MT (lipopolysaccharide, LPS, host response to MT (sCD14, CD38+HLA-DR+CD4+/CD8+, HCV genotype, severity of liver disease were assessed according to Early Virological Response (EVR: HCV-RNA <50 IU/mL at week 12 of therapy or ≥2 log(10 reduction from baseline after 12 weeks of therapy and Sustained Virological Response (SVR: HCV-RNA <50 IU/mL 24 weeks after end of therapy. Mann-Whitney/Chi-square test and Pearson's correlation were used. Multivariable regression was performed to determine factors associated with EVR/SVR.71 patients displayed EVR; 41 SVR. Patients with HCV genotypes 1-4 and cirrhosis presented a trend to higher sCD14, compared to patients with genotypes 2-3 (p = 0.053 and no cirrhosis (p = 0.052. EVR and SVR patients showed lower levels of circulating sCD14 (p = 0.0001, p = 0.026, respectively, but similar T-cell activation compared to Non-EVR (Null Responders, NR and Non-SVR (N-SVR subjects. sCD14 resulted the main predictive factor of EVR (0.145 for each sCD14 unit more, 95%CI 0.031-0.688, p = 0.015. SVR was associated only with HCV genotypes 2-3 (AOR 0.022 for genotypes 1-4 vs 2-3, 95%CI 0.001-0.469, p = 0.014.In HIV/HCV patients sCD14 correlates with the severity of liver disease and predicts early response to peg-INF-alpha/ribavirin, suggesting MT-driven immune activation as pathway of HIV/HCV co-infection and response to therapy.

  7. Sustained virologic response following HCV eradication in two brothers with X-linked agammaglobulinaemia.

    LENUS (Irish Health Repository)

    Houlihan, Diarmaid D

    2009-08-21

    X-linked agammaglobulinaemia (XLA) is a humoral immunodeficiency syndrome characterized from childhood by the absence of circulating B lymphocytes, absent or reduced levels of serum immunoglobulin and recurrent bacterial infections. For many affected patients, regular treatment with immunoglobulin is life saving. Hepatitis C viral (HCV) infection acquired through contaminated blood products is widely described in this patient cohort. The natural history of HCV infection in patients with XLA tends to follow a more rapid and aggressive course compared to immunocompetent individuals. Furthermore, standard anti-viral therapy appears to be less efficacious in this patient cohort. Here we report the cases of two brothers with XLA who contracted HCV through contaminated blood products. They were treated with a six month course of Interferon alpha-2b and Ribavirin. We report a sustained virologic response five years after completing treatment.

  8. Frequency of HCV infection and its genotypes among patients attending a liver clinic and voluntary blood donors in a rural area of Pakistan

    International Nuclear Information System (INIS)

    Abbas, S.Z.; Ali, M.; Muhammad, A.H.; Shaw, S.; Abbas, S.Q.

    2009-01-01

    Objectives: To determine the frequency of Hepatitis C virus (HCV) infection and its genotypic distribution in a rural area of Sindh, Pakistan. Methodology: Retrospective study of patients attending the Free Liver Clinic (FLC), and investigated for detectable HCV antibodies (n=1638), and those screened for HCV infection prior to voluntary blood donation (n=804) at a teaching hospital, located in rural Sindh. All patients had HCV antibodies tested by ELISA. A total of 1022 patients, who tested 'reactive' to HCV antibodies, and who could financially afford to have HCV RNA tested by PCR, had their results analysed. A total of 200 patients also had their HCV genotyped and analysed. Results: Patients at FLC had a higher chance of being reactive for HCV antibodies, compared to voluntary blood donors (20% VS 14% - p = 0.004). HCV RNA was detectable in 904/1022 (88%) patients. Among type able genotypes, 125/166 (75%) had a single genotype, and 7 patients (4%) were infected with genotype 1, either alone (n=4) or in combination with 3a. Conclusions: One out of every five people tested in our FLC, and 14% of 'healthy' voluntary blood donors were seropositive for HCV antibodies. Genotype 1 is very rare in our region. (author)

  9. The Cedar Project: high incidence of HCV infections in a longitudinal study of young Aboriginal people who use drugs in two Canadian cities

    Directory of Open Access Journals (Sweden)

    Spittal Patricia M

    2012-08-01

    Full Text Available Abstract Background Factors associated with HCV incidence among young Aboriginal people in Canada are still not well understood. We sought to estimate time to HCV infection and the relative hazard of risk factors associated HCV infection among young Aboriginal people who use injection drugs in two Canadian cities. Methods The Cedar Project is a prospective cohort study involving young Aboriginal people in Vancouver and Prince George, British Columbia, who use illicit drugs. Participants’ venous blood samples were drawn and tested for HCV antibodies. Analysis was restricted to participants who use used injection drugs at enrolment or any of follow up visit. Cox proportional hazards regression was used to identify independent predictors of time to HCV seroconversion. Results In total, 45 out of 148 participants seroconverted over the study period. Incidence of HCV infection was 26.3 per 100 person-years (95% Confidence Interval [CI]: 16.3, 46.1 among participants who reported using injection drugs for two years or less, 14.4 per 100 person-years (95% CI: 7.7, 28.9 among participants who had been using injection drugs for between two and five years, and 5.1 per 100 person-years (95% CI: 2.6,10.9 among participants who had been using injection drugs for over five years. Independent associations with HCV seroconversion were involvement in sex work in the last six months (Adjusted Hazard Ratio (AHR: 1.59; 95% CI: 1.05, 2.42 compared to no involvement, having been using injection drugs for less than two years (AHR: 4.14; 95% CI: 1.91, 8.94 and for between two and five years (AHR: 2.12; 95%CI: 0.94, 4.77 compared to over five years, daily cocaine injection in the last six months (AHR: 2.47; 95% CI: 1.51, 4.05 compared to less than daily, and sharing intravenous needles in the last six months (AHR: 2.56; 95% CI: 1.47, 4.49 compared to not sharing. Conclusions This study contributes to the limited body of research addressing HCV infection among

  10. Calcitriol Inhibits HCV Infection via Blockade of Activation of PPAR and Interference with Endoplasmic Reticulum-Associated Degradation

    Directory of Open Access Journals (Sweden)

    Yu-Min Lin

    2018-01-01

    Full Text Available Vitamin D has been identified as an innate anti-hepatitis C virus (HCV agent but the possible mechanisms for this issue remain unclear. Here, we clarified the mechanisms of calcitriol-mediated inhibition of HCV infection. Calcitriol partially inhibited HCV infection, nitric oxide (NO release and lipid accumulation in Huh7.5 human hepatoma cells via the activation of vitamin D receptor (VDR. When cells were pretreated with the activators of peroxisome proliferator-activated receptor (PPAR-α (Wy14643 and -γ (Ly171883, the calcitriol-mediated HCV suppression was reversed. Otherwise, three individual stimulators of PPAR-α/β/γ blocked the activation of VDR. PPAR-β (linoleic acid reversed the inhibition of NO release, whereas PPAR-γ (Ly171883 reversed the inhibitions of NO release and lipid accumulation in the presence of calcitriol. The calcitriol-mediated viral suppression, inhibition of NO release and activation of VDR were partially blocked by an inhibitor of endoplasmic reticulum-associated degradation (ERAD, kifunensine. Furthermore, calcitriol blocked the HCV-induced expressions of apolipoprotein J and 78 kDa glucose-regulated protein, which was restored by pretreatment of kifunensine. These results indicated that the calcitriol-mediated HCV suppression was associated with the activation of VDR, interference with ERAD process, as well as blockades of PPAR, lipid accumulation and nitrative stress.

  11. Correlation between alanine aminotransferase level, HCV-RNA titer ...

    African Journals Online (AJOL)

    In contrast, an insignificant correlation was found between ALT level and grade of necroinflammation. In conclusion neither ALT level nor HCV viremia can reflect the histological liver change accurately. As a result, liver biopsy or other noninvasive procedures that measure liver stiffness (i.e., Fibroscan) remain essential for ...

  12. Mindfulness mediates the relation between disordered eating-related cognitions and psychological distress.

    Science.gov (United States)

    Masuda, Akihiko; Wendell, Johanna W

    2010-12-01

    The present study investigated whether mindfulness mediates the relation between disordered eating-related cognitions and negative psychological outcomes within a non-clinical college sample. Disordered eating-related cognitions were positively associated with general psychological ill-health and emotional distress in interpersonal contexts and inversely related to mindfulness. Mindfulness, which was also inversely related to general psychological ill-health and emotional distress, was found to partially mediate the relations between disordered eating-related cognitions and the two predicted variables. Copyright © 2010 Elsevier Ltd. All rights reserved.

  13. Detection of HCV-RNA by Reverse Transcription Polymerase Chain Reaction Using Biotinylated and Radioiodinated Primers

    International Nuclear Information System (INIS)

    Ryu, Jin Sook; Moon, Dae Hyuk; Cheon, Jun Hong; Chung, Yoon Young; Park, Hung Dong; Chung, Young Hwa; Lee, Young Sang

    1994-01-01

    This study was performed to evaluate the clinical applicability of the reverse transcription polymerase chain reaction (RT-PCR) kit of HCV-RNA using biotinylated and radioiodinated primers. Study subjects were 118 patients with positive anti-HCV. HCV-RNA in patients serum was extracted by guanidium thiocyanate method. After first amplification, the product was reamplified by primers labelled with biotin and I-125. The final amplification product was detected by counting the radioactivity after incubation in avidin coated tubes. In 51 samples, the test was repeated for evaluation of reproducibility. This new method was also compared with conventional RT-PCR methods in 34 samples from patients with chronic liver disease. The results were as follows, 1) HCV-RNA was positive in 85(97%)of 88 patients with chronic liver disease, and in 23 (73%) of 30 patients with normal liver function. 2) In comparison with conventional method, HCV-RNA was detected in 32(94%) of 34 patients with new method, whereas in 27(79% ) of the same group with conventional method 3) Repeated test with new method in 52 samples demonstrated 82% of concordant result. In conclusion, new method with biotinylated and radioiodinated primers was more sensitive than conventional method. However, great care must be taken for quality control because there were considerable interassay variation and possibility of false positivity and false negativity.

  14. Detection of HCV-RNA by Reverse Transcription Polymerase Chain Reaction Using Biotinylated and Radioiodinated Primers

    Energy Technology Data Exchange (ETDEWEB)

    Ryu, Jin Sook; Moon, Dae Hyuk; Cheon, Jun Hong; Chung, Yoon Young; Park, Hung Dong; Chung, Young Hwa; Lee, Young Sang [Asan Medical Center, University of Ulsan, Seoul (Korea, Republic of)

    1994-07-15

    This study was performed to evaluate the clinical applicability of the reverse transcription polymerase chain reaction (RT-PCR) kit of HCV-RNA using biotinylated and radioiodinated primers. Study subjects were 118 patients with positive anti-HCV. HCV-RNA in patients serum was extracted by guanidium thiocyanate method. After first amplification, the product was reamplified by primers labelled with biotin and I-125. The final amplification product was detected by counting the radioactivity after incubation in avidin coated tubes. In 51 samples, the test was repeated for evaluation of reproducibility. This new method was also compared with conventional RT-PCR methods in 34 samples from patients with chronic liver disease. The results were as follows, 1) HCV-RNA was positive in 85(97%)of 88 patients with chronic liver disease, and in 23 (73%) of 30 patients with normal liver function. 2) In comparison with conventional method, HCV-RNA was detected in 32(94%) of 34 patients with new method, whereas in 27(79% ) of the same group with conventional method 3) Repeated test with new method in 52 samples demonstrated 82% of concordant result. In conclusion, new method with biotinylated and radioiodinated primers was more sensitive than conventional method. However, great care must be taken for quality control because there were considerable interassay variation and possibility of false positivity and false negativity.

  15. Sub-optimal Testing and Awareness of HCV and HBV Among High Risk Individuals at an Underserved Safety-Net Hospital.

    Science.gov (United States)

    Wong, Robert J; Campbell, Brendan; Liu, Benny; Baden, Rachel; Bhuket, Taft

    2018-02-01

    Sub-optimal screening for chronic hepatitis C virus (HCV) and chronic hepatitis B virus (HBV) among high risk groups delays diagnosis and treatment. We aimed to evaluate overall rates of HCV and HBV screening and patient knowledge of their testing result. Adults age ≥18 years undergoing elective outpatient endoscopy at a large, urban safety-net hospital from July 2015 to July 2016 were prospectively evaluated to determine rates of HCV and HBV testing, the results of those completed tests, and patient knowledge of test results among high risk individuals (as determined by U.S. Preventative Services Task Force). Among 1125 patients (52.3% male, 70.4% foreign-born), 66.5% were high risk for chronic HCV; only 30.9% received prior testing. 14.7% had positive chronic HCV infection. Patients born in the 1945-1965 cohort were more likely to have received prior HCV testing compared to those born outside of this cohort (32.7 vs. 16.9%, p = 0.01). Among patients who received HCV screening, 29.3% were aware of test results. Overall, 61.6% were high risk for chronic HBV; only 25.1% received prior testing. 4.1% were positive for chronic HBV. Compared to Caucasians, Asians (19.0 vs. 44.4%, p HBV testing. Among patients who received prior HBV screening, 18.4% were aware of test results. Less than one-third of high risk patients received HCV and HBV screening among an ethnically diverse safety-net population. Equally low rates of patient knowledge of testing results were observed.

  16. Interferon lambda 4 (IFNL4 gene polymorphism is associated with spontaneous clearance of HCV in HIV-1 positive patients

    Directory of Open Access Journals (Sweden)

    Camila Fernanda da Silveira Alves

    Full Text Available Abstract Approximately one-third of the individuals infected with human immunodeficiency virus type 1 (HIV-1 are co-infected with hepatitis C virus (HCV. Co-infected patients have an increased risk for developing end-stage liver diseases. Variants upstream of the IFNL3 gene have been associated with spontaneous and treatment-induced clearance of HCV infection. Recently, a novel polymorphism was discovered, denoted IFNL4 ΔG > TT (rs368234815, which seems to be a better predictor of spontaneous clearance than the IFNL4 rs12979860 polymorphism. We aimed to determine the prevalence of the IFNL4 ΔG > TT variants and to evaluate the association with spontaneous clearance of HCV infection in Brazilian HIV-1 patients. The IFNL4 ΔG > TT genotypes were analyzed by polymerase chain reaction followed by restriction digestion in 138 HIV-1 positive patients who had an anti-HCV positive result. Spontaneous clearance of HCV was observed in 34 individuals (24.6%. IFNL4 genotype distribution was significantly different between individuals who had spontaneous clearance and chronic HCV patients (p=0.002. The probability of spontaneous clearance of HCV infection for patients with the IFNL4 TT/TT genotype was 3.6 times higher than for patients carrying the IFNL4 ΔG allele (OR=3.63, 95% CI:1.51-8.89, p=0.001. The IFNL4 ΔG > TT polymorphism seems to be better than IFNL4 rs12979860 to predict spontaneous clearance of the HCV in Brazilian HIV-1 positive patients.

  17. Direct-Acting Antivirals Improve Access to Care and Cure for Patients With HIV and Chronic HCV Infection.

    Science.gov (United States)

    Collins, Lauren F; Chan, Austin; Zheng, Jiayin; Chow, Shein-Chung; Wilder, Julius M; Muir, Andrew J; Naggie, Susanna

    2018-01-01

    Direct-acting antivirals (DAA) as curative therapy for hepatitis C virus (HCV) infection offer >95% sustained virologic response (SVR), including in patients with human immunodeficiency virus (HIV) infection. Despite improved safety and efficacy of HCV treatment, challenges remain, including drug-drug interactions between DAA and antiretroviral therapy (ART) and restrictions on access by payers. We performed a retrospective cohort study of all HIV/HCV co-infected and HCV mono-infected patients captured in care at our institution from 2011-2015, reflecting the DAA era, to determine treatment uptake and SVR, and to elucidate barriers to accessing DAA for co-infected patients. We identified 9290 patients with HCV mono-infection and 507 with HIV/HCV co-infection. Compared to mono-infected patients, co-infected patients were younger and more likely to be male and African-American. For both groups, treatment uptake improved from the DAA/pegylated interferon (PEGIFN)-ribavirin to IFN-free DAA era. One-third of co-infected patients in the IFN-free DAA era required ART switch and nearly all remained virologically suppressed after 6 months. We observed SVR >95% for most patient subgroups including those with co-infection, prior treatment-experience, and cirrhosis. Predictors of access to DAA for co-infected patients included Caucasian race, CD4 count ≥200 cells/mm 3 , HIV virologic suppression and cirrhosis. Time to approval of DAA was longest for patients insured by Medicaid, followed by private insurance and Medicare. DAA therapy has significantly improved access to HCV treatment and high SVR is independent of HIV status. However, in order to realize cure for all, barriers and disparities in access need to be urgently addressed.

  18. No correlation between PNPLA3 rs738409 genotype and fatty liver and hepatic cirrhosis in Japanese patients with HCV.

    Directory of Open Access Journals (Sweden)

    Masato Nakamura

    Full Text Available BACKGROUND: Hepatitis C virus (HCV infection is associated with the development of cirrhosis and hepatocellular carcinoma and is also related to fatty change of the liver. Variation in patatin-like phospholipase domain-containing 3 (PNPLA3 gene is associated with disease progression in nonalcoholic fatty liver disease (NAFLD. Recent reports have suggested that PNPLA3, IL28B and TLR4-associated single nucleotide polymorphisms (SNPs may have an impact on hepatic steatosis or fibrosis in patients with chronic HCV infection. METHODS AND FINDINGS: Four SNPs (PNPLA3 rs738409, TLR4 rs4986790, TLR4 rs4986791, IL28B rs8099917 were identified in Japanese patients infected with HCV. We examined the association between the distribution of these SNP alleles and fatty change of the liver or existence of hepatic cirrhosis diagnosed by ultrasonography, one of the widely accessible and easy-to-use methods. PNPLA3 rs738409 G-allele and IL28B rs 8099917 minor allele were found in 70.0% and 31.1%, respectively. These two TLR4 SNPs were uniform in Japanese. Fatty change of the liver developed independent of the abscence of hepatic cirrhosis on sonographic findings and younger age. Hepatic cirrhosis was associated with a higher aspartate aminotransferase/platelet ratio index (APRI, no fatty change of the liver, higher BMI and higher AFP levels. No association between PNPLA3 rs738409/IL28B rs8099917 genotypes and hepatic steatosis or liver fibrosis was observed. CONCLUSIONS: According to ultrasound examinations, no association between PNPLA3 rs738409 genotype and fatty change of the liver or hepatic cirrhosis was found in Japanese patients infected with HCV. Together, our results suggested that the mechanism of hepatic steatosis underlying HCV infection might differ from that of NAFLD and should be explored.

  19. Seropositivity of HBsAg, anti-HCV and anti-HIV in preoperative patients

    Directory of Open Access Journals (Sweden)

    Berrin Karaayak Uzun

    2014-12-01

    Full Text Available Objective: The infections caused by human immunodeficiency virus (HIV, hepatitis B (HBV and C (HCV viruses pose a serious occupational risk for the healthcare workers especially those in emergency services, laboratories and surgery wards. Vaccination and establishment of the strict biosafety procedures are the main principles to prevent blood-borne infections in healthcare workers. Additionally, serological screening of the preoperative patients could decrease the risk for exposure. In this study, we aimed to determine the seroprevalence of HBsAg, anti-HCV, anti-HIV 1/2 in preoperative patients. Methods: Hospital automation records were evaluated retrospectively for 4.367 patients who were scheduled for surgery and scanned for anti-HIV 1/2, HBsAg and anti-HCV as preoperative procedures in the preparation period of operation between January 2012 and December 2012. Results: HBsAg positivity rate was found in 7.7% (n=336, anti-HCV positivity rate was found in 2.3% (n=101. A two (0.05% of five patients were positive for anti-HIV 1/2 was found positive verification test and the other three samples were accepted as false positive test results. Conclusion: All healthcare workers must be trained about occupational diseases and vaccinated against Hepatitis B. Universal precautions must be strictly followed particularly in the operating room. In addition, all patients should be considered as potential carriers regarded as a carrier of the potential for infection. J Clin Exp Invest 2013; 4 (4: 449-452

  20. Epidemiological profile and risk factors of HIV and HBV/HCV co-infection in Fujian Province, southeastern China.

    Science.gov (United States)

    Wu, Shouli; Yan, Pingping; Yang, Tianfei; Wang, Zhenghua; Yan, Yansheng

    2017-03-01

    This study aimed to investigate the epidemiological features of HIV-infected subjects co-infected with HBV/HCV in Fujian Province, southeastern China, and identify the risk factors. Blood samples were collected from 2,028 HIV antibody-positive subjects in Fujian Province. Serum HBsAg and anti-HCV antibody were detected, and CD4 + T cell count was measured. Of the 2,028 subjects, the prevalence of HIV-HBV, HIV-HCV, and HIV-HBV-HCV co-infections was 16.22%, 3.7%, and 0.79%, respectively. Man (OR = 1.912, 95% CI: 1.371-2.667), key population (OR = 0.756, 95% CI: 0.57-0.976) and detainee (OR = 0.486, 95% CI: 0.259-0.909) were risk factors of HIV-HBV co-infection, and man (OR = 2.227, 95% CI: 1.096-4.525), minority (OR = 5.04, 95% CI: 1.696-14.98), junior high school or lower education (OR = 2.32, 95% CI: 1.071-5.025), intravenous drug use (OR = 38.46, 95% CI: 11.46-129.11) and detainee (OR = 5.687, 95% CI: 2.44-13.25) were risk factors of HIV-HCV co-infection. In addition, a lower mean CD4 + T cell count was measured in HIV/HBV and HIV/HCV co-infected subjects than in HIV-infected subjects among the untreated individuals, while in the treated populations, a higher mean CD4 + T cell count was detected in HIV/HBV and HIV/HCV co-infected subjects than in HIV-infected subjects. HIV co-infection with HBV or HCV, notably HIV-HBV co-infection, is widespread in southeastern China. Hepatitis virus screening should be included in monitoring of HIV infection, and HIV and hepatitis virus co-infection should be considered during the development of HIV antiretroviral therapy scheme. J. Med. Virol. 89:443-449, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.