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Sample records for ribavirin hcv-infected cirrhotic

  1. Rheumatoid arthritis following a treatment with IFN-alpha/ribavirin against HCV infection.

    Science.gov (United States)

    Izumi, Yasumori; Komori, Atsumasa; Yasunaga, Yuki; Hashimoto, Satoru; Miyashita, Taiichiro; Abiru, Seigo; Yatsuhashi, Hiroshi; Ishibashi, Hiromi; Migita, Kiyoshi

    2011-01-01

    We report a 48-year-old man who developed rheumatoid arthritis (RA) after a successful treatment with peg-IFN-alpha plus ribavirin for chronic hepatitis C virus (HCV) infection. He had a history of smoking and a single copy of the HLA-DRB1 shared epitope (SE). In a retrospective analysis, he exhibited the anti-CCP antibodies before the start of IFN plus ribavirin treatment. However, the titers of anti-CCP antibodies and BAFF levels were elevated by the IFN plus ribavirin therapy. These observations suggest that IFN plus ribavirin therapy may work as a "trigger" for RA in genetically and environmentally predisposed individuals by affecting the cytokine network.

  2. MBL2 Genetic Variants in HCV Infection Susceptibility, Spontaneous Viral Clearance and Pegylated Interferon Plus Ribavirin Treatment Response.

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    Zupin, L; Polesello, V; Alberi, G; Moratelli, G; Crocè, S L; Masutti, F; Pozzato, G; Crovella, S; Segat, L

    2016-07-01

    Hepatitis C is disease that damages the liver, and it is caused by the hepatitis C virus (HCV). The pathology became chronic in about 80% of the cases due to virus persistence in the host organism. The standard of care consists of pegylated interferon plus ribavirin; however, the treatment response is very variable and different host/viral factors may concur in the disease outcome. The mannose-binding protein C (MBL) is a component of the innate immune system, able to recognize HCV and consecutively activating the immune response. MBL is encoded by MBL2 gene, and polymorphisms, two in the promoter region (H/L and X/Y) and three in exon 1 (at codon 52, 54 and 57), have been described as functionally influencing protein expression. In this work, 203 Italian HCV patients and 61 healthy controls were enrolled and genotyped for the five MBL2 polymorphisms mentioned above to investigate their role in HCV infection susceptibility, spontaneous viral clearance and treatment response. MBL2 polymorphisms were not associated with HCV infection susceptibility and with spontaneous viral clearance, while MBL2 O allele, O/O genotype, HYO haplotype and DP combined genotype (all correlated with low or deficient MBL expression) were associated with sustained virological response. Moreover, a meta-analysis to assess the role of MBL2 polymorphisms in HCV infection susceptibility was also performed: YA haplotype could be associated with protection towards HCV infection.

  3. T-cell homeostasis in chronic HCV-infected patients treated with interferon and ribavirin or an interferon-free regimen

    DEFF Research Database (Denmark)

    Hartling, Hans Jakob; Birch, Carsten; Gaardbo, Julie C

    2015-01-01

    Direct-acting antiviral has replaced pegylated interferon-α and ribavirin-based treatment in the treatment of chronic hepatitis C virus (HCV) infection. While interferon-α is immune modulating and causes lymphopenia, interferon-free regimens seem to be well-tolerated. This study aimed to compare T......-cell homeostasis before, during, and after HCV treatment with or without interferon-α in patients with chronic HCV infection. A total of 20 patients with chronic HCV infection were treated with pegylated interferon-α and ribavirin, and six patients were treated with an interferon-free regimen. All patients were...... treated for a minimum of 12 weeks. Interferon-α treatment caused an increase in the density of the receptor for IL-7 (IL-7Rα) during treatment, while interferon-free regimens caused a decrease in IL-7Rα density. After a sustained viral response, proportions of IL-7Rα+ T cells and IL-7Rα density decreased...

  4. HCV clearance patterns in saliva and serum of patients with chronic HCV infection under interferon plus ribavirin therapy.

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    Diz Dios, P; Castro, A; Rodríguez, I; Reforma, N G; Castro, M; Eirea, M; Hermida, M

    2005-05-01

    Hepatitis C virus (HCV)-RNA is often present in saliva of HCV-infected patients, with plasma viral load being the only known predictable factor. Interferon plus ribavirin therapy yields a sustained reduction in HCV viremia. This study aimed to assess the presence of HCV in saliva and serum specimens from patients undergoing this combination therapy (CT). Paired serum and saliva specimens were collected from 44 chronic HCV-infected patients at basal time, 4 and 12 weeks after CT onset, at the end of treatment and 6 months latter. Serum HCV-RNA levels were determined by the polymerase chain reaction (PCR) Amplicor system. Presence of HCV-RNA in saliva was tested by a highly sensitive non-commercialized nested-PCR. The HCV-RNA was detected in 26 saliva specimens at basal time (59.1%). In 34.1% of cases, a concordance viral clearance pattern in serum and saliva was observed in both responders (pattern 1a) and non-responders (pattern 1b). In pattern 2 (13.6% of cases), HCV was detected longer during CT in serum than in saliva (pattern 2a) or in saliva than in serum (pattern 2b). In 11.3% of patients, viral clearance was corroborated either in their serum (pattern 3a) or in their saliva (pattern 3b), but not in both fluids. Of the eight primary responders with 1a clearance pattern, seven were sustained responders. None of the patients with 2a clearance pattern was a sustained responder. Of the two primary responders showing the 3b salivary pattern, one had already relapsed in the first 6 months of follow up. The present results suggest that the monitoring of salivary levels of HCV would be a helpful means of determining sustained antiviral effects of interferon and ribavirin in the treatment of HCV disease.

  5. Real-world effect of ribavirin on quality of life in HCV-infected patients receiving interferon-free treatment.

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    Höner Zu Siederdissen, Christoph; Schlevogt, Bernhard; Solbach, Philipp; Port, Kerstin; Cornberg, Markus; Manns, Michael P; Wedemeyer, Heiner; Deterding, Katja

    2017-09-28

    Ribavirin (RBV) is commonly used for the treatment of hepatitis C virus (HCV) infection. However, RBV is associated with a reduced quality of life (QOL). We aim to assess the impact of RBV on QOL in a real-world setting. In a prospective study, QOL was measured by a SF-36 questionnaire in 174 patients. 85 patients were treated with RBV and 89 patients without RBV. QOL was assessed at baseline, week 12 of treatment and 24 weeks after treatment. Patients treated with RBV were more likely to have HCV genotype 2 and 3 infection and cirrhosis (all p free treatment led to an increase in all measured dimensions of quality of life, whereas RBV treatment led to a decrease in the emotional and physical functioning. After treatment all dimensions for QOL showed improvement across the study cohort, regardless whether RBV was part of the treatment regimen However, 28.8%- 45.2% of treated patients perceive a sustained reduction in their physical or mental capacity after treatment, not related to RBV usage or SVR, but related to older age (p = 0.03) and cirrhosis (p = 0.02). During treatment RBV leads to a reduced QOL, whereas RBV-free treatment leads to an increased QOL. After treatment, QOL strongly increases in both, RBV and RBV-free treated patients. Some patients perceived a sustained reduction in QOL, which seems unrelated to treatment. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  6. The influence of HAART on the efficacy and safety of pegylated interferon and ribavirin therapy for the treatment of chronic HCV infection in HIV-positive individuals

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    Vogel M

    2010-03-01

    Full Text Available Abstract Objective This study was performed to investigate the impact of HAART versus no HAART and nucleoside free versus nucleoside containing HAART on the efficacy and safety of pegylated interferon and ribavirin therapy for the treatment of chronic HCV infection in HIV/HCV co-infected patients. In addition a control group of HCV mono-infected patients undergoing anti-HCV therapy was evaluated. Methods Multicenter, partially randomized, controlled clinical trial. HIV-negative and -positive patients with chronic HCV infection were treated with pegylated interferon alfa-2a and ribavirin (800 - 1200 mg/day for 24 - 48 weeks in one of four treatment arms: HIV-negative (A, HIV-positive without HAART (B and HIV-positive on HAART (C. Patients within arm C were randomized to receive open label either a nucleoside containing (C1 or a nucleoside free HAART (C2. Results 168 patients were available for analysis. By intent-to-treat analysis similar sustained virological response rates (SVR, negative HCV-RNA 24 weeks after the end of therapy were observed comparing HIV-negative and -positive patients (54% vs. 54%, p = 1.000. Among HIV-positive patients SVR rates were similar between patients off and on HAART (57% vs. 52%, p = 0.708. Higher SVR rates were observed in patients on a nucleoside free HAART compared to patients on a nucleoside containing HAART, though confounding could not be ruled out and in the intent-to-treat analysis the difference was not statistically significant (64% vs. 46%, p = 0.209. Conclusions Similar response rates for HCV therapy can be achieved in HIV-positive and -negative patients. Patients on nucleoside free HAART reached at least equal rates of sustained virological response compared to patients on standard HAART.

  7. Emergence of occult minority genotype 2b hepatitis C infection in an HIV-1-co-infected patient treated for genotype 5a HCV infection with 48 weeks of pegylated-interferon-alpha 2b and ribavirin.

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    Buckton, A J; Kulasegaram, R; Ngui, S L; Fisher, M; James, R; Rangarajan, S; Teo, C G

    2007-09-01

    An HIV-1/hepatitis C virus (HCV) co-infected patient with haemophilia received a 48-week course of pegylated interferon-alpha-2b and ribavirin therapy for genotype 5a HCV infection. Virological response was achieved at week 24. At the end of treatment, HCV RNA in serum was detected and identified to belong to genotype 2b, rather than genotype 5a. A sensitive method for identifying minority HCV genotypes in pre-treatment serum showed genotype 2b HCV carriage prior to treatment. Sequencing the interferon sensitivity-determining region of the HCV NS5A gene obtained from pre-, intra- and post-treatment sera revealed emergence of quasispecies bearing R-->K and M-->A/T mutations at codons 2222 and 2223, respectively. Occult presence of minority HCV subpopulations and their acquisition of mutations following therapy can result in poor treatment outcome.

  8. Tissue-specific transplantation antigen P35B (TSTA3) immune response-mediated metabolism coupling cell cycle to postreplication repair network in no-tumor hepatitis/cirrhotic tissues (HBV or HCV infection) by biocomputation.

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    Wang, Lin; Huang, Juxiang; Jiang, Minghu; Lin, Hong

    2012-06-01

    We constructed the low-expression tissue-specific transplantation antigen P35B (TSTA3) immune response-mediated metabolism coupling cell cycle to postreplication repair network in no-tumor hepatitis/cirrhotic tissues (HBV or HCV infection) compared with high-expression (fold change ≥ 2) human hepatocellular carcinoma in GEO data set, by using integration of gene regulatory network inference method with gene ontology analysis of TSTA3-activated up- and downstream networks. Our results showed TSTA3 upstream-activated CCNB2, CKS1B, ELAVL3, GAS7, NQO1, NTN1, OCRL, PLA2G1B, REG3A, SSTR5, etc. and TSTA3 downstream-activated BAP1, BRCA1, CCL20, MCM2, MS4A2, NTN1, REG1A, TP53I11, VCAN, SLC16A3, etc. in no-tumor hepatitis/cirrhotic tissues. TSTA3-activated network enhanced the regulation of apoptosis, cyclin-dependent protein kinase activity, cell migration, insulin secretion, transcription, cell division, cell proliferation, DNA replication, postreplication repair, cell differentiation, T-cell homeostasis, neutrophil-mediated immunity, neutrophil chemotaxis, interleukin-8 production, inflammatory response, immune response, B-cell activation, humoral immune response, actin filament organization, xenobiotic metabolism, lipid metabolism, phospholipid metabolism, leukotriene biosynthesis, organismal lipid catabolism, phosphatidylcholine metabolism, arachidonic acid secretion, activation of phospholipase A2, deoxyribonucleotide biosynthesis, heterophilic cell adhesion, activation of MAPK activity, signal transduction by p53 class mediator resulting in transcription of p21 class mediator, G-protein-coupled receptor protein signaling pathway, response to toxin, acute-phase response, DNA damage response, intercellular junction assembly, cell communication, and cell recognition, as a result of inducing immune response-mediated metabolism coupling cell cycle to postreplication repair in no-tumor hepatitis/cirrhotic tissues.

  9. [Chronic hepatitis and occult HCV infection].

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    Kowala-Piaskowska, Arleta; Mozer-Lisewska, Iwona; Pham, Tram N Q; Michalak, Tomasz I

    2010-01-01

    Hepatitis C virus (HCV) was discovered in 1989. HCV is a positive single-strand RNA. We all have thought, that HCV can replicate only in liver tissue, but now we know, that HCV can replicate in extrahepatic tissue as well. In about 48-86% of HCV infected patients, chronic hepatitis C (CHC) has been noticed and eventually, after tens of years, liver insufficiency, cirrhosis or hepatocellular carcinoma. The current recommended treatment for CHC is a combination of pegylated-interferon alpha and Ribavirin. Presently it is known, that HCV infection can persist as an occult infection. RNA HCV can be detected in patients after successful treatment for CHC or spontaneous elimination. Persistent HCV replication in hepatocytes or lymphoid cells would likely lead to continuous antigenic stimulation of the immune system. This prolonged replication may contribute to the immune tolerance of HCV, impairment of immune response and even further virus persistence. This occult infection grows more important in transplantation.

  10. Dynamic of Mixed HCV Infection in Plasma and PBMC of HIV/HCV Patients Under Treatment With Peg-IFN/Ribavirin.

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    Bagaglio, Sabrina; Uberti-Foppa, Caterina; Di Serio, Clelia; Trentini, Filippo; Andolina, Andrea; Hasson, Hamid; Messina, Emanuela; Merli, Marco; Porrino, Lucy; Lazzarin, Adriano; Morsica, Giulia

    2015-10-01

    The extent of mixed hepatitis C virus (HCV) genotype in different compartments (plasma and peripheral blood mononuclear cell, PBMC) and possible association with treatment efficacy in HIV/HCV coinfected patients remains to be unknown.The objective of this study was to elucidate the frequency of mixed genotype infection (MG), its profile in different compartments during anti-HCV treatment, and the possible influence of different genotypes on the response rate.The compartmentalization of HCV population was investigated by next-generation sequencing in 19 HIV/HCV coinfected patients under anti-HCV treatment with peginterferon/ribavirin (P-R). Ten individuals were nonresponder (NR) or relapser (RE) to P-R treatment and 9 had a sustained virological response (SVR).Eleven/nineteen (58%) patients had MG in plasma compartment. Ten or 12 patients infected by a difficult to treat genotype (DTG) 1 or 4 as dominant strain, had an MG, whereas only 1/7 individuals infected by easy to treat genotype (ETG) harbored a mixed genotype, P = 0.006. HCV-RNA was more frequently detected in PBMC of NR (10/10) than in those of SVR (5/9), P = 0.032. Mixed genotype infection was detected in 6/15 (40%) PBMC-positive cases and was not associated with P-R treatment response. By multivariate analysis, MG in plasma samples was the most important viral factor affecting the treatment response (P = 0.0237).Detection of MG in plasma of HIV/HCV coinfected patients seems to represent the major determinant of response to P-R treatment. This finding may have important clinical implication in light of the new therapeutic approach in HIV/HCV coinfected individuals suggesting that combination treatment with direct acting antivirals could be less effective in MG.

  11. Rheumatoid Case with HCV Infection

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    Bita Behnava

    2005-03-01

    history of hepatitis should be included in the history of present illness of any patient with polyarthritis(7. In such patients serologic studies for hepatitis C should be performed(7. Some authors recommend that any patient presenting with new onset of polyarthritis should be tested for HCV(3. Furthermore, it is recommended to test for HCV infection in patients with Sjogren's syndrome and fibromyalgia(4, 5.What Is the Best Treatment for HCV-related Arthritis?The optimal treatment for HCV-related arthritis has not yet been established and a few data about HCVra treatment are reported in the literature(5. Hydroxychloroquine, low doses of corticosteroids and NSAIDs are frequently administered to patients with HCV-related arthritis, but some authors describe an incomplete relief of symptoms, especially in the rheumatoid-like subset(9. Intake of low doses of corticosteroids and NSAIDs is more effective in subjects belonging to the monooligoarthritis group(9. On the other hand, Kessel et al. emphasized that HCV-related arthritis treated with steroids or cytotoxic agents can exacerbate HCV infection, and methotrexate or hepatotoxic drugs may negatively affect liver function(7. Once the diagnosis of HCVra is made, combination therapy with interferon alpha and ribavirin should be initiated. Use of antiviral drugs shows good results, but interferon alpha can worsen autoimmune disorders(9, 5. Low dose oral corticosteroids, nonsteroidal anti-inflammatory drugs, hydroxychloroquine or sulfasalazine in addition to the antiviral therapy can be used to control arthritis-related symptoms(5. Anti TNFtherapy for RA in the setting of HCV appears to be safe and well tolerated without apparent influence on the underlying HCV infection; however, the usually non aggressive course of HCV-related arthritis does not justify their use as a current therapy(10, 11.Recommendations1- It may be recommended to test for HCV in any patient presenting with polyarthritis especially that high risk for HCV

  12. Safety and effectiveness of a 12-week course of sofosbuvir and simeprevir ± ribavirin in HCV-infected patients with or without HIV infection: a multicentre observational study.

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    Bruno, Giuseppe; Saracino, Annalisa; Fabrizio, Claudia; Scudeller, Luigia; Milano, Eugenio; Dell'Acqua, Raffaele; Ladisa, Nicoletta; Fasano, Massimo; Minniti, Salvatore; Buccoliero, Giovanni; Tartaglia, Alessandra; Giammario, Adele; Milella, Michele; Angarano, Gioacchino

    2017-03-01

    The combination of sofosbuvir and simeprevir ± ribavirin (SOF + SMV ± RBV) for hepatitis C virus (HCV) treatment has been associated with high rates of sustained virological response (SVR). Few data are available regarding this regimen in HIV/HCV co-infected patients. This study evaluated the effectiveness and safety of a 12-week course of SOF + SMV ± RBV in a cohort of HCV monoinfected and HIV/HCV co-infected individuals. HCV-infected patients, with or without HIV infection, receiving a 12-week course of SOF + SMV ± RBV in four Italian centres from February to October 2015, were included in this retrospective observational study. Clinical and biochemical data were retrieved for all patients. A total of 88 individuals were evaluated: 29 (33.0%) HIV/HCV co-infected and 59 (67.0%) monoinfected. Most patients were males with HCV genotype 1b (62.5%) and 1a (25%) infection. RBV was used in 41 HCV monoinfected and 6 HIV/HCV co-infected patients. Cirrhosis was found in 67 patients (76.1%). The most common adverse events (AEs) were rash and/or pruritus (23.9%), fatigue (13.6%) and anaemia (9.1%). Serious AEs occurred in three patients (3.4%). No treatment discontinuations were observed. RBV use was associated with multiple AEs (P = 0.02). An overall SVR12 of 93.2% was achieved; 96.6% in HCV monoinfected and 86.2% in HIV/HCV co-infected individuals, without significance both in univariate (P = 0.09) and multivariate analyses (P = 0.12). A baseline platelet count ≥90 000/mm(3) was associated with higher rates of SVR (P = 0.005). A 12-week course of SOF + SMV ± RBV was associated with good safety and high SVR12 rate both in HCV monoinfected and HIV-HCV co-infected individuals.

  13. Silymarin for HCV infection.

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    Polyak, Stephen J; Oberlies, Nicholas H; Pécheur, Eve-Isabelle; Dahari, Harel; Ferenci, Peter; Pawlotsky, Jean-Michel

    2013-01-01

    Silymarin, an extract of milk thistle seeds, and silymarin-derived compounds have been considered hepatoprotective since the plant was first described in ancient times. Hepatoprotection is defined as several non-mutually exclusive biological activities including antiviral, antioxidant, anti-inflammatory and immunomodulatory functions. Despite clear evidence for silymarin-induced hepatoprotection in cell culture and animal models, evidence for beneficial effects in humans has been equivocal. This review will summarize the current state of knowledge on silymarin in the context of HCV infection. The information was collated from a recent workshop on silibinin in Germany.

  14. Grading antiviral therapy in HCV-infected cirrhotic patients%丙型肝炎各级肝硬化患者的抗病毒治疗策略

    Institute of Scientific and Technical Information of China (English)

    张颖; 魏欣; 贾战生

    2013-01-01

    Chronic hepatitis C ( CHC) is a major cause of cirrhosis, end — stage liver disease, and hepatocellular carcinoma. The combination drug regimen of pegylated interferon - alpha (PEG - IFNa) and ribavirin is the approved and well - accepted standard - of - care for CHC. However, CHC patients with decompensated cirrhosis usually have contraindications for the use of PEG - IFNa and ribavirin, and the results of therapy are generally poor. To address China's high prevalence of hepatitis C virus ( HCV) - related cirrhosis, difficulties of implementing liver transplantation, and the higher sustained virological response rate seen in Chinese cirrhotic patients, we developed a grading strategy of antiviral therapy for Chinese patients with HCV - related cirrhosis based upon the clinical practice guidelines published by the A-merican Association for the Study of Liver Diseases ( AASLD) and the European Association for the Study of the Liver ( EASL) . Clinical application of this strategy demonstrated it to be effective for slowing down the rate of cirrhosis progression, preventing complications of HCV -related liver disease, and improving the patients' quality of life.%丙型肝炎病毒(HCV)感染是引起肝硬化、终末期肝病以及肝细胞癌的重要原因.慢性丙型肝炎的标准化治疗方案——聚乙二醇化干扰素α联合利巴韦林已取得了良好的效果,但进展至肝硬化尤其是失代偿期的患者多难以耐受干扰素的不良反应,给抗病毒治疗带来困难.面对我国丙型肝炎肝硬化比例较高、肝移植实施困难、对标准的抗病毒治疗方案应答率高的特点,参考国际指南,作者在国内率先探索和提出了丙型肝炎肝硬化分级标准及相应的抗病毒治疗策略,并进行了相关的临床研究和应用.依据作者提出的丙型肝炎肝硬化的分级方法,先采取不同的处置方法缓解脾亢或减少副作用后,再采用标准化抗病毒治疗方案,可以有效地延

  15. Adverse events associated with ribavirin in sofosbuvir-based therapies for patients with chronic hepatitis C: A community practice experience.

    Science.gov (United States)

    Tong, Myron John; Chang, Patrick Weijen; Huynh, Thatcher Thi; Rosinski, Alexander Anthony; Tong, Lori Terese

    2016-02-01

    Due to high sustained virological response (SVR) rates, sofosbuvir-based regimens are currently a mainstay for hepatitis C virus (HCV) therapies. The addition of pegylated interferon (PEG-IFN) and ribavirin impacts patients' quality of life during treatment. This study aimed to compare severe adverse events (SAEs) amongst therapeutic combinations for HCV in a community clinic setting. From December 2013 to July 2014, 128 chronic HCV-infected patients were treated with sofosbuvir, ribavirin and weekly PEG-IFN for 12 weeks (cohort 1), 12 or 24 weeks of sofosbuvir and ribavirin (cohorts 2 and 3) or sofosbuvir plus simeprevir for 12 weeks (cohort 4). Adverse events were recorded from baseline to 12 or 24 weeks of treatment. SAEs appeared in 15.6-53.8% of ribavirin-inclusive treated patients compared to 4.8% of the ribavirin-free regimen. PEG-IFN, sofosbuvir plus ribavirin had the highest frequencies of fatigue, headache and rash compared to either 12 or 24 weeks of ribavirin and sofosbuvir. However, sofosbuvir and ribavirin regimens led to significant increases in dyspnea, need for ribavirin dose reductions and withdrawal from treatment due to SAEs. Anemia was also more frequent in ribavirin-inclusive combinations (P < 0.001). Conversely, sofosbuvir plus simeprevir reached similar SVR rates at week 12 post-treatment compared to all ribavirin-containing regimens, but with significantly fewer adverse events (P = 0.006). At week 12 post-treatment, cirrhotic patients experienced a higher virological relapse rate than non-cirrhotic patients (P = 0.019). Ribavirin-inclusive HCV therapies increased the frequencies of SAEs, had higher dropout rates and increased patient morbidity. © 2016 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.

  16. Safety and antiviral activity of JTK-652: a novel HCV infection inhibitor

    NARCIS (Netherlands)

    J. de Bruijne; J.F. Bergmann; C.J. Weegink; C.M.J. van Nieuwkerk; R.J. de Knegt; Y. Komoda; J.J. van de Wetering de Rooij; A. van Vliet; P.L.M. Jansen; R. Molenkamp; J. Schinkel; H. Reesink; H.L.A. Janssen

    2010-01-01

    Standard treatment of chronic hepatitis C with pegylated interferon and ribavirin is associated with suboptimal virological response rates and substantial side effects. This study describes the in vitro and in vivo development of JTK-652, a novel pyrrolopyridazin-derived HCV infection inhibitor. JTK

  17. Sustained Virologic Response at 24 Weeks after the End of Treatment Is a Better Predictor for Treatment Outcome in Real-World HCV-Infected Patients Treated by HCV NS3/4A Protease Inhibitors with Peginterferon plus Ribavirin

    Science.gov (United States)

    Kanda, Tatsuo; Nakamoto, Shingo; Sasaki, Reina; Nakamura, Masato; Yasui, Shin; Haga, Yuki; Ogasawara, Sadahisa; Tawada, Akinobu; Arai, Makoto; Mikami, Shigeru; Imazeki, Fumio; Yokosuka, Osamu

    2016-01-01

    Background. Direct-acting antiviral agents against HCV with or without peginterferon plus ribavirin result in higher eradication rates of HCV and shorter treatment duration. We examined which is better for predicting persistent virologic response, the assessment of serum HCV RNA at 12 or 24 weeks after the end of treatment for predicting sustained virologic response (SVR12 or SVR24, respectively) in patients treated by HCV NS3/4A protease inhibitors with peginterferon plus ribavirin. Methods. In all, 149 Japanese patients infected with HCV genotype 1b treated by peginterferon plus ribavirin with telaprevir or simeprevir were retrospectively analyzed: 59 and 90 patients were treated with telaprevir- and simeprevir-including regimens, respectively. HCV RNA was measured by TaqMan HCV Test, version 2.0, real-time PCR assay. SVR12 or SVR24, respectively, was defined as HCV RNA negativity at 12 or 24 weeks after ending treatment. Results. Total SVR rates were 78.0% and 66.7% in the telaprevir and simeprevir groups, respectively. In the telaprevir group, all 46 patients with SVR12 finally achieved SVR24. In the simeprevir group, 60 (93.8%) of the total 64 patients with SVR12 achieved SVR24, with the other 4 patients all being previous-treatment relapsers. Conclusions. SVR12 was suitable for predicting persistent virologic response in almost all cases. In simeprevir-including regimens, SVR12 could not always predict persistent virologic response. Clinicians should use SVR24 for predicting treatment outcome in the use of HCV NS3/4A protease inhibitors with peginterferon plus ribavirin for any group of real-world patients chronically infected with HCV. PMID:27076789

  18. Combination of "low-dose" ribavirin and interferon alfa-2a therapy followed by interferon alfa-2a monotherapy in chronic HCV-infected non-responders and relapsers after interferon alfa-2a monotherapy

    Institute of Scientific and Technical Information of China (English)

    Perdita Wietzke-Braun; Volker Meier; Felix Braun; Giuliano Ramadori

    2001-01-01

    AIM To report on the efficacy, safety and tolerability of interferon alfa-2a combined with a "low dose" of ribavirin for relapsers and non responders to alpha interferon monotherapy.METHODS Thirty-four chronic hepatitis C virus-infected non-responders to interferon alfa2a monotherapy (a course of at least 3 months treatment) and 13 relapsers to interferon alfa 2a monotherapy (a dose of 3 to 6 million units three times per week for at least 20 weeks but not more than 18 months) were treated with the same dose of interferon alfa-2a used before (3 to 6 million units three times per week) and ribavirin (10 mg/ kg daily) for 6 months. In complete responders, interferon alfa-2a was administered for further 6 months at the same dose used before as monotherapy.RESULTS Seven (20.6%) of 34 non-responders stopped the combined therapy due to adverse events, including two patients with histological and clinical Child A cirrhosis. In 17/27 (63%)non-responders, the combined therapy was stopped after three months because of non-response. Ten of the 27 non-responders completed the 1;2-month treatment course. At a mean follow up of 28 months (16- 37 months)after the treatment, 4/10 (15%) previous non-responders still remained complete responders,All 13 previous relapsers completed the 12-month treatment course. At a mean follow up of 22months (9 - 36 months) after treatment, 6/13(46%) the previous relapsers were stillsustained complete responders.CONCLUSION Our treatment schedule of the combined therapy for 6 months of interferon alfa2a with a low dose of ribavirin (10 mg/kg/day)followed by 6 months of interferon alfa-2amonotherapy is able to induce a sustainedcomplete response rate in 15% of non-responders and 46% of relapsers with chronic hepatitis C virus-related liver diseases comparable to those obtained with the standarddoses of ribavirin 1000 - 1200 mg/day.Randomized prospective controlled trials using lower total amounts of ribavirin in combination with interferon should be

  19. New Insights in Recurrent HCV Infection after Liver Transplantation

    Directory of Open Access Journals (Sweden)

    Shih-Hsien Hsu

    2013-01-01

    Full Text Available Hepatitis C virus (HCV is a small-enveloped RNA virus belonging to the Flaviviridae family. Since first identified in 1989, HCV has been estimated to infect 170 million people worldwide. Mostly chronic hepatitis C virus has a uniform natural history, from liver cirrhosis to the development of hepatocellular carcinoma. The current therapy for HCV infection consists of a combination of Pegylated interferon and ribavirin. On the other hand, HCV-related liver disease is also the leading indication for liver transplantation. However, posttransplant HCV re-infection of the graft has been reported to be universal. Furthermore, the graft after HCV re-infection often results in accelerated progression to liver failure. In addition, treatment of recurrent HCV infection after liver transplantation is often compromised by enhanced adverse effects and limited efficacy of interferon-based therapies. Taken together, poor outcome after HCV re-infection, regardless of grafts or recipients, poses a major issue for the hepatologists and transplant surgeons. The aim of this paper is to review several specific aspects regarding HCV re-infection after transplant: risk factors, current therapeutics for HCV in different stages of liver transplantation, cellular function of HCV proteins, and molecular mechanisms of HCV entry. Hopefully, this paper will inspire new strategies and novel inhibitors against recurrent HCV infection after liver transplantation and greatly improve its overall outcome.

  20. Interferon Response in Hepatitis C Virus (HCV) Infection: Lessons from Cell Culture Systems of HCV Infection.

    Science.gov (United States)

    Sung, Pil Soo; Shin, Eui-Cheol; Yoon, Seung Kew

    2015-01-01

    Hepatitis C virus (HCV) is a positive-stranded RNA virus that infects approximately 130-170 million people worldwide. In 2005, the first HCV infection system in cell culture was established using clone JFH-1, which was isolated from a Japanese patient with fulminant HCV infection. JFH-1 replicates efficiently in hepatoma cells and infectious virion particles are released into the culture supernatant. The development of cell culture-derived HCV (HCVcc) systems has allowed us to understand how hosts respond to HCV infection and how HCV evades host responses. Although the mechanisms underlying the different outcomes of HCV infection are not fully understood, innate immune responses seem to have a critical impact on the outcome of HCV infection, as demonstrated by the prognostic value of IFN-λ gene polymorphisms among patients with chronic HCV infection. Herein, we review recent research on interferon response in HCV infection, particularly studies using HCVcc infection systems.

  1. HCV Infection and B-Cell Lymphomagenesis

    Directory of Open Access Journals (Sweden)

    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.

  2. Management of Antiviral Induced Anemia in HCV Infected Patients

    Directory of Open Access Journals (Sweden)

    Mitra Ranjbar

    2005-03-01

    Full Text Available IntroductionHepatitis C virus (HCV infection affects more than 170 million people worldwide(1,2. Approximately 80% of patients with acute infection will subsequently develop chronic disease, and an estimated 20% to 30% will develop cirrhosis and hepatocellular carcinoma(3. The maost effective therapeutic regimen for chronic hepatitis C is the combination of pegylated interferon alpha and ribavirin, which yields a sustained virologic response (SVR in up to 56% of patients(4, 5. However, combination therapy is also associated with significant adverse events and is contraindicated in certain patient populations. Development of side effects, particularly hematologic ones, may result in suboptimal dosing or discontinuation of therapy that can reduce the likelihood of SVR.IncidenceIn clinical trials, significant anemia (hemoglobin 10.6 mg/kg/d is 65% compared with a rate of 50% for those receiving peginterferon alfa-2b plus ribavirin at dosages of 10.6 mg/kg/d or less.It has been shown that SVR rates are significantly higher in patients who receive more than 80% of their full interferon alfa-2b plus ribavirin doses for more than 80% of the time for more than 80% of the intended duration of therapy(14. In the Hepatitis C Long-term Treatment Against Cirrhosis (HALT-C trial, a trial involving patients who were previous nonresponders to or relapsers after therapy, reduction of ribavirin dose from> 80% to 10.6 mg/kg/d. The standard-of-care management of ribavirin induced anemia has been dose reduction to 600 mg/d when the hemoglobin level decreases to =2g/dL decrease inhemoglobinduring any 4-weektreatment period 12g/dL despite 4weeks at reduceddose Recombinant human erythropoietin therapy in the HCV-infected patient who becomes anemic during antiviral therapy represents an alternative to ribavirin dose reduction or discontinuation. Erythropoietin is mainly produced by the kidney in adults in response to tissue hypoxia, and it increases the number of

  3. Antiviral therapy in hepatitis C virus cirrhotic patients in compensated and decompensated condition

    Institute of Scientific and Technical Information of China (English)

    Angelo Iacobellis; Antonio Ippolito; Angelo Andriulli

    2008-01-01

    The main goals of treating cirrhotic patients with antiviral therapy are to attain sustained viral clearance (SVR), halt disease progression, and prevent re-infection of the liver graft. However, while the medical need is great, the use of interferon and ribavirin might expose these patients to severe treated-related side effects as a large proportion of them have pre-existing hematological cytopenias. We have reviewed potential benefits and risks associated with antiviral drugs in patients with liver cirrhosis, due to hepatitis C virus (HCV) infection. In cases presenting with bridging fibrosis or cirrhosis, current regimens of antiviral therapy have attained a 44%-48% rate of SVR. In cirrhotic patients with portal hypertension, the SVR rate was 22% overall, 12.5% in patients with genotype 1, and 66.7% in those with genotypes 2 and 3 following therapy with low doses of either Peg-IFN alpha-2b and of ribavirin. In patients with decompensated cirrhosis, full dosages of Peg-IFN alpha-2b and of ribavirin produced a SVR rate of 35% overall, 16% in patients with genotype 1 and 4, and 59% in those with genotype 2 and 3. Use of hematological cytokines will either ensure full course of treatment to be accomplished with and prevent development of treatment-associated side effects. Major benefits after HCV eradication were partial recovery of liver metabolic activity, prevention of hepatitis C recurrence after transplantation, and removal of some patients from the waiting list for liver transplant. Several observations highlighted that therapy is inadvisable for individuals with poor hepatic reserve (ChUd-Pugh-Turcotte score ≥ 10). Although SVR rates are low in decompensated cirrhotics due to hepatitis C, these patients have the most to gain as successful antiviral therapy is potentially lifesaving. C 2008 The W.1G Press. All dghts reserved.

  4. Dental problems delaying the initiation of interferon therapy for HCV-infected patients

    Directory of Open Access Journals (Sweden)

    Nagao Yumiko

    2010-08-01

    Full Text Available Abstract Background There has been little discussion about the importance of oral management and interferon (IFN therapy, although management of the side effects of therapy for chronic hepatitis C has been documented. This study determined whether dental problems delayed the initiation of IFN therapy for hepatitis C virus (HCV-infected patients. Results We analyzed 570 HCV-infected patients who were admitted to our hospital from December 2003 to June 2010 for treatment consisting of pegylated IFN (Peg-IFN monotherapy or Peg-IFN/ribavirin combination therapy. The group comprised 274 men and 296 women with a mean age 57.2 years. Of the 570 patients, six could not commence Peg-IFN therapy, despite their admission, because of dental problems such as periodontitis, pupitis, and pericoronitis. The ages of six whose dental problems delayed the initiation of Peg-IFN ranged from 25 to 67 years, with a mean age of 47.3 ± 15.2 years. IFN therapy was deferred for 61.3 ± 47.7 days. Among the six subjects for whom IFN treatment was delayed, only one had a salivary flow that was lower than the normal value. Conclusions Treatment of dental infections is required before IFN therapy for HCV infection can be started. To increase the depth of understanding of oral health care, it is hoped that dentists and medical specialists in all areas will hold discussions to generate cooperation.

  5. Dental problems delaying the initiation of interferon therapy for HCV-infected patients

    Science.gov (United States)

    2010-01-01

    Background There has been little discussion about the importance of oral management and interferon (IFN) therapy, although management of the side effects of therapy for chronic hepatitis C has been documented. This study determined whether dental problems delayed the initiation of IFN therapy for hepatitis C virus (HCV)-infected patients. Results We analyzed 570 HCV-infected patients who were admitted to our hospital from December 2003 to June 2010 for treatment consisting of pegylated IFN (Peg-IFN) monotherapy or Peg-IFN/ribavirin combination therapy. The group comprised 274 men and 296 women with a mean age 57.2 years. Of the 570 patients, six could not commence Peg-IFN therapy, despite their admission, because of dental problems such as periodontitis, pupitis, and pericoronitis. The ages of six whose dental problems delayed the initiation of Peg-IFN ranged from 25 to 67 years, with a mean age of 47.3 ± 15.2 years. IFN therapy was deferred for 61.3 ± 47.7 days. Among the six subjects for whom IFN treatment was delayed, only one had a salivary flow that was lower than the normal value. Conclusions Treatment of dental infections is required before IFN therapy for HCV infection can be started. To increase the depth of understanding of oral health care, it is hoped that dentists and medical specialists in all areas will hold discussions to generate cooperation. PMID:20712912

  6. Sustained virological response after ten days of triple anti-hepatitis C virus (HCV) therapy with telaprevir plus pegylated interferon and ribavirin in an HIV/HCV co-infected cirrhotic woman.

    Science.gov (United States)

    Hasson, Hamid; Messina, Emanuela; Merli, Marco; Della Torre, Liviana; Morsica, Giulia; Bagaglio, Sabrina; Lazzarin, Adriano; Uberti-Foppa, Caterina

    2014-12-01

    The introduction of first-generation protease inhibitors for the treatment of chronic hepatitis C in subjects infected with hepatitis C virus (HCV) genotype 1 has significantly improved the sustained virological response (SVR) rate. As liver cirrhosis reduces the probability of achieving SVR, current guidelines discourage response-guided therapy in cirrhotic patients. We report the first case of a cirrhotic woman with chronic HCV and HIV co-infection achieving virological response after an ultra-short course of therapy. A 40-year-old HIV/HCV co-infected woman with compensated liver cirrhosis was treated with anti-HCV triple therapy containing telaprevir plus pegylated interferon and ribavirin. Baseline plasma HCV RNA was 3.6 log IU/ml and transaminases were within the normal range. She harboured IL28B rs12979860C/C alleles. Ten days after starting therapy, the patient stopped treatment because of mild anorexia and nausea. Virological response was detected at treatment discontinuation and was maintained up to 24 weeks. This case describes an unexpected SVR after a 10-day course of antiviral therapy in a cirrhotic HIV/HCV co-infected woman presenting positive predictive factors for a response (low viral load, IL28B genotype). Nonetheless, there is no evidence to suggest a shorter duration of treatment in this subset of patients.

  7. Sustained virological response after ten days of triple anti-hepatitis C virus (HCV therapy with telaprevir plus pegylated interferon and ribavirin in an HIV/HCV co-infected cirrhotic woman

    Directory of Open Access Journals (Sweden)

    Hamid Hasson

    2014-12-01

    Full Text Available The introduction of first-generation protease inhibitors for the treatment of chronic hepatitis C in subjects infected with hepatitis C virus (HCV genotype 1 has significantly improved the sustained virological response (SVR rate. As liver cirrhosis reduces the probability of achieving SVR, current guidelines discourage response-guided therapy in cirrhotic patients. We report the first case of a cirrhotic woman with chronic HCV and HIV co-infection achieving virological response after an ultra-short course of therapy. A 40-year-old HIV/HCV co-infected woman with compensated liver cirrhosis was treated with anti-HCV triple therapy containing telaprevir plus pegylated interferon and ribavirin. Baseline plasma HCV RNA was 3.6 log IU/ml and transaminases were within the normal range. She harboured IL28B rs12979860 C/C alleles. Ten days after starting therapy, the patient stopped treatment because of mild anorexia and nausea. Virological response was detected at treatment discontinuation and was maintained up to 24 weeks. This case describes an unexpected SVR after a 10-day course of antiviral therapy in a cirrhotic HIV/HCV co-infected woman presenting positive predictive factors for a response (low viral load, IL28B genotype. Nonetheless, there is no evidence to suggest a shorter duration of treatment in this subset of patients.

  8. Differences in viral kinetics between genotypes 1 and 3 of hepatitis C virus and between cirrhotic and non-cirrhotic patients during antiviral therapy

    Institute of Scientific and Technical Information of China (English)

    José Eymard Medeiros-Filho; Isabel Maria Vicente Guedes de Carvalho Mello; Jo(a)o Renato Rebello Pinho; Avidan U Neumann; Fernanda de Mello Malta; Luiz Caetano da Silva; Flair José Carrilho

    2006-01-01

    AIM: To evaluate the impact of hepatitis C virus (HCV)infection with genotype 1 or 3 and the presence or absence of liver cirrhosis (LC) in the early viral kinetics response to treatment.METHODS: Naive patients (n = 46) treated with interferon-α (IFN-α) and ribavirin and followed up with frequent early HCV-RNA determinations were analysed.Patients were infected with genotype 1 (n = 28, 7 with LC) or 3 (n = 18, 5 with LC).RESULTS: The first phase decline was larger in genotype 3 patients than in genotype 1 patients (1.72 vs 0.95log IU/mL, P < 0.001). The second phase slope decline was also larger in genotype 3 patients than in genotype 1 patients (0.87 vs 0.15 log/wk, P < 0.001). Differences were found in both cirrhotic and non-cirrhotic patients.Genotype 1 cirrhotic patients had a slower 2nd phase slope than non-cirrhotic patients (0.06 vs 0.18 log/wk, P< 0,02). None of genotype 1 cirrhotic patients had a 1stphase decline larger than 1 log (non-cirrhotic patients:55%, P < 0.02). A similar trend toward a slower 2ndphase slope was observed in genotype 3 cirrhotic patients but the 1st phase slope decline was not different.Sustained viral response was higher in genotype 3 patients than in genotype 1 patients ,(72% vs14%, P <0.001) and in genotype 1 non-cirrhotic patients than in genotype 1 cirrhotic patients (19% vs 0%). A second phase decline slower than 0.3 log per week was predictive of non-response in all groups.CONCLUSION: Genotype 3 has faster early viral decline than genotype 1. Cirrhosis correlates with a slower 2nd phase decline and possibly with a lower 1st phase slope decline in genotype 1 patients.

  9. Innate and adaptive immune responses in HCV infections.

    Science.gov (United States)

    Heim, Markus H; Thimme, Robert

    2014-11-01

    Hepatitis C virus has been identified a quarter of a decade ago as a leading cause of chronic viral hepatitis that can lead to cirrhosis and hepatocellular carcinoma. Only a minority of patients can clear the virus spontaneously during acute infection. Elimination of HCV during acute infection correlates with a rapid induction of innate, especially interferon (IFN) induced genes, and a delayed induction of adaptive immune responses. However, the majority of patients is unable to clear the virus and develops viral persistence in face of an ongoing innate and adaptive immune response. The virus has developed several strategies to escape these immune responses. For example, to escape innate immunity, the HCV NS3/4A protease can efficiently cleave and inactivate two important signalling molecules in the sensory pathways that react to HCV pathogen-associated molecular patterns (PAMPs) to induce IFNs, i.e., the mitochondrial anti-viral signalling protein (MAVS) and the Toll-IL-1 receptor-domain-containing adaptor-inducing IFN-β (TRIF). Despite these escape mechanisms, IFN-stimulated genes (ISGs) are induced in a large proportion of patients with chronic infection. Of note, chronically HCV infected patients with constitutive IFN-stimulated gene (ISG) expression have a poor response to treatment with pegylated IFN-α (PegIFN-α) and ribavirin. The mechanisms that protect HCV from IFN-mediated innate immune reactions are not entirely understood, but might involve blockade of ISG protein translation at the ribosome, localization of viral replication to cell compartments that are not accessible to anti-viral IFN-stimulated effector systems, or direct antagonism of effector systems by viral proteins. Escape from adaptive immune responses can be achieved by emergence of viral escape mutations that avoid recognition by antibodies and T cells. In addition, chronic infection is characterized by the presence of functionally and phenotypically altered NK and T cell responses that

  10. Socioeconomic status in HCV infected patients - risk and prognosis

    DEFF Research Database (Denmark)

    Omland, Lars Haukali Hvass; 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....

  11. Maternal HCV infection is associated with intrauterine fetal growth disturbance

    Science.gov (United States)

    Huang, Qi-tao; Hang, Li-lin; Zhong, Mei; Gao, Yun-fei; Luo, Man-ling; Yu, Yan-hong

    2016-01-01

    Abstract Since the evidence regarding the association between maternal hepatitis C virus (HCV) infection and impaired intrauterine fetal growth had not been conclusive, the aim of the present study was to evaluate the risk of maternal HCV infection in association with intrauterine fetal growth restriction (IUGR) and/or low birth weight infants (LBW). We performed an extensive literature search of PubMed, MEDLINE, and EMBASE through December 1, 2015. The odds ratios (ORs) of HCV infection and IUGR/LBW were calculated and reported with 95% confidence intervals (95% CIs). Statistical analysis was performed using RevMen 5.3 and Stata 10.0. Seven studies involving 4,185,414 participants and 5094 HCV infection cases were included. Significant associations between HCV infection and IUGR (OR = 1.53, 95% CI: 1.40–1.68, fixed effect model) as well as LBW were observed (OR = 1.97, 95% CI: 1.43–2.71, random effect model). The results still indicated consistencies after adjusting for multiple risk factors which could affect fetal growth, including maternal age, parity, maternal smoking, alcohol abuse, drugs abuse, coinfected with HBV/HIV and preeclampsia. Our findings suggested that maternal HCV infection was significantly associated with an increased risk of impaired intrauterine fetal growth. In clinical practice, a closer monitoring of intrauterine fetal growth by a series of ultrasound might be necessary for HCV-infected pregnant population. PMID:27583932

  12. The Natural History of Hepatitis C Virus (HCV Infection

    Directory of Open Access Journals (Sweden)

    2006-04-01

    Full Text Available Hepatitis C virus (HCV is a leading cause of chronic liver disease, cirrhosis, and hepatocellular carcinoma, as well as the most common indication for liver transplantation in many countries. Although the incidence of hepatitis C infection has dramatically decreased during the past decade, the worldwide reservoir of chronically infected persons is estimated at 170 million, or 3% of the global population. There is much controversy surrounding the natural history of hepatitis C infection. The rate of chronic HCV infection is affected by a person's age, gender, race, and viral immune response. Approximately 75%-85% of HCV-infected persons will progress to chronic HCV infection, and are at risk for the development of extrahepatic manifestations, compensated and decompensated cirrhosis, and hepatocellular carcinoma (HCC. The rate of progression to cirrhosis is highly variable, and is influenced by several factors, including the amount of alcohol consumption, age of initial HCV infection, degree of inflammation and fibrosis on liver biopsy, HIV and HBV coinfection, and comordid conditions. An estimated 10%-15% of HCV-infected persons will advance to cirrhosis within the first 20 years. Persons with cirrhosis are at increased risk of developing HCC. An understanding of the natural history of hepatitis C is essential to effectively manage, treat, and counsel individuals with HCV infection.

  13. Hepatitis C virus RNA kinetics: Drug efficacy and the rate of HCV-infected cells loss

    Institute of Scientific and Technical Information of China (English)

    Harel Dahari; Alan S Perelson

    2007-01-01

    @@ TO THE EDITOR We read the study by Medeiros-Filho et al[1] with much interest. The study shed light on early HCV RNA kinetics in conjunction with liver cirrhosis, different genotypes (gen-1 vs gen-3) of HCV and sustained viral response (SVR) rates. In particular, Medeiros-Filho et al[1]showed that the HCV RNA first phase decline, under interferon-α (IFN) and ribavirin therapy, which represents the effectiveness (ε) of IFN to block viral production[2,3],was significantly larger in gen-3 cirrhotic patients (mean ε = 0.99) than gen-1 cirrhotic patients (mean ε = 0.8). In addition, in these cirrhotic patients, they found that the HCV RNA second phase decay slope in gen-3 patients was significantly faster than in gen-1 patients, and suggested that the immune response against infected HCV cells in gen-1 patients may be less potent than in gen-3 patients.

  14. High prevalence of antibodies to core+1/ARF protein in HCV-infected patients with advanced cirrhosis.

    Science.gov (United States)

    Kassela, Katerina; Karakasiliotis, Ioannis; Charpantidis, Stefanos; Koskinas, John; Mylopoulou, Theodora; Mimidis, Konstantinos; Sarrazin, Christoph; Grammatikos, Georgios; Mavromara, Penelope

    2017-07-01

    Hepatitis C virus (HCV) possesses a second open reading frame (ORF) within the core gene encoding an additional protein, known as the alternative reading frame protein (ARFP), F or core+1. The biological significance of the core+1/ARF protein remains elusive. However, several independent studies have shown the presence of core+1/ARFP antibodies in chronically HCV-infected patients. Furthermore, a higher prevalence of core+1/ARFP antibodies was detected in patients with HCV-associated hepatocellular carcinoma (HCC). Here, we investigated the incidence of core+1/ARFPantibodies in chronically HCV-infected patients at different stages of cirrhosis in comparison to chronically HCV-infected patients at earlier stages of disease. Using ELISA, we assessed the prevalence of anti-core+1 antibodies in 30 patients with advanced cirrhosis [model for end-stage liver disease (MELD) ≥15] in comparison with 50 patients with mild cirrhosis (MELD core+1 antibodies, in contrast with 16.5 % of non-cirrhotic HCV patients. Moreover, there was significantly higher positivity for anti-core+1 antibodies in HCV patients with advanced cirrhosis (36.7 %) compared to those with early cirrhosis (24 %) (Pcore+1 antibodies in HCV patients with HCC, suggest that core+1 protein may have a role in virus-associated pathogenesis, and provide evidence to suggest that the levels of anti-core+1 antibodies may serve as a marker for disease progression.

  15. Socioeconomic status in HCV infected patients - risk and prognosis.

    Science.gov (United States)

    Omland, Lars Haukali; Osler, Merete; Jepsen, Peter; Krarup, Henrik; Weis, Nina; Christensen, Peer Brehm; Roed, Casper; Sørensen, Henrik Toft; Obel, Niels

    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. 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. 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 medium income persons. The OR was 1.35 (95% CI: 1.20-1.52) for low education (no more than basic schooling). When compared to employed patients, MRRs were 1.71 (95% CI: 1.22-2.40) for unemployed patients and 2.24 (95% CI: 1.63-3.08) for disability pensioners. When compared to high income patients, MRRs were 1.47 (95% CI: 1.05-2.05) for medium income patients and 1.64 (95% CI: 1.13-2.34) for low income patients. Educational status was not associated with mortality. Low SES was associated with an increased risk of HCV infection and with poor prognosis in HCV infected patients.

  16. Antiviral Therapy for Chronic HCV Infection - Tolerability and Outcome

    NARCIS (Netherlands)

    R. Maan (Raoel)

    2016-01-01

    textabstractThis thesis describes the safety and outcome of antiviral therapy for chronic HCV infection. In the first chapters, the authors investigated (hematological) adverse events during interferon-based therapy among patients with compensated cirrhosis. By using a patient-tailored approach, int

  17. Are the Real HCV Infection Features in Iranian Patients the Same As What Is Expected?

    Directory of Open Access Journals (Sweden)

    Seyed-Moayed Alavian

    2005-03-01

    Full Text Available Hepatitis Monthly issue 7 contained four clinical trials of pegylated interferon (Peg- IFN plus ribavirin for Iranian patients with chronic hepatitis C infection conducted in four various centers(1-4. Apart from one trial(2, which enrolled only patients with inherited bleeding disorders, three others enrolled heterogeneous HCV infected populations. However, reported sustained virologic response (SVR rate was varied from 50% to 78% in these studies. This wide SVR range might make difficulties for the readers to gain clear data regarding efficacy of this therapeutic regimen on Iranian patients.Almost analogous inclusion and exclusion criteria as well as the details of these four studies allow us to intervene and join the cases and reanalyze the datafrom a single pool. However, the slight differences among these studies will obviously diminish the accuracy and make us discuss the results conservatively. For instance, in the study by Merat et al. none of the patients underwent liver biopsy(2 or Zali et al. excluded cirrhotic patients from the study(4. Moreover, the sensitivities of RT-PCR tests applied to define response to treatment were varied from 100 copies/ml to 600 copies/ml in various studies. In spite of these inevitable biases, our intervention is able to provide useful information.To analyze the data, we applied intention to treat analysis (ITT. ITT analysis is generally interpreted as including all patients who received at least one dose of medication(s, regardless of whether they actually satisfied the entry criteria, the treatment actually received, and subsequent withdrawal or deviation from the protocol(5. Therefore, all patients who do not complete the study are considered to have failure to treatment. It is a strategy to avoid the problems created by omitting dropouts and noncompliant patients, which can introduce bias in the trial, and overestimate clinical effectiveness. Although there is a debate about the validity of excluding

  18. Characterization of chronic HCV infection in Northwest Spain: Impact of the treatment strategic plan of the Spanish National Health Service on HCV cure.

    Science.gov (United States)

    Grandal, Marta; Pernas, Berta; Mariño, Ana; Álvarez, Hortensia; Tabernilla, Andrés; Castro-Iglesias, Ángeles; Mena, Álvaro; Delgado, Manuel; Pértega, Sonia; Poveda, Eva

    2017-01-12

    The aim of the study was to characterize HCV infection in Northwest Spain and assess the impact of the Spanish Strategic Plan to cure HCV infection. Overall, 387 patients were included (60.9% HIV/HCV coinfected and 28.2% cirrhotic). Of these, 72.9% of patients that were recognized as priority for HCV treatment according to the Spanish Strategic Plan (≥F2, transplant or extrahepatic manifestations), initiated treatment during 2015. Globally, SVR12 was achieved in 96.5% of patients. The implementation of the Spanish Strategic Plan has been critical to advance in HCV cure, but 27.1% of priority patients still remain awaiting HCV treatment initiation. This article is protected by copyright. All rights reserved.

  19. Determination of telaprevir in plasma of HCV-infected patients by HPLC-UV.

    Science.gov (United States)

    Tempestilli, Massimo; Milano, Elisa; D'Offizi, Gianpiero; Montalbano, Marzia; D'Avolio, Antonio; Gasperi, Tecla; Narciso, Pasquale; Ascenzi, Paolo; Pucillo, Leopoldo P

    2013-09-01

    Telaprevir is a direct acting antiviral agent, used with pegylated interferon and ribavirin for the management of chronic hepatitis C virus (HCV) genotype 1 infection, in patients not responding to therapy with pegylated interferon and ribavirin only. Although 75% of patients achieve a sustained virological response after treatment with telaprevir, adverse drug-drug interactions and undesirable events often occur. Therefore, telaprevir monitoring is pivotal to improve the management of HCV infection. Here, the first High-Performance Liquid Chromatography-Ultraviolet (HPLC-UV) method to quantify telaprevir in human plasma of HCV-genotype 1-infected patients is reported. The volume of the plasma sample was 700 μL. This method involved automated solid-phase extraction with Oasis HLB Cartridge 1 cc (divinylbenzene and N-vinylpyrrolidone). The extracted samples were reconstituted with 150 μL of 60/40 water/acetonitrile. Thirty microliters of these samples was injected into a HPLC-UV system, and the analytes were eluted on a X Terra(®) RP18 column (250 mm × 4.6 mm i.d.) with a particle size of 5 μm. The mobile phase (ammonium acetate buffer, 150 mM, pH 8.0, and methanol:acetonitrile 50:50) was delivered at 1.0 mL/min with linear gradient elution. The total run time for a single analysis was 16 min; telaprevir was detected by UV at 276 and 286 nm. The calibration curve was linear from 312.5 to 20,000 ng/mL (r(2) > 0.996). The absolute recovery of telaprevir ranged between 89 and 93% at concentrations of quality control samples of 800, 4,000, 8,000, and 16,000 ng/mL. Both precision and accuracy were always <15%. The HPLC-UV method reported here: (i) has been validated, (ii) is currently applied to monitor telaprevir in plasma of HCV-infected patients, and (iii) appears useful in a routine laboratory. ,

  20. Managing HCV infection in pediatric age group: Suggested recommendations

    Directory of Open Access Journals (Sweden)

    Danish Fazal

    2010-01-01

    Full Text Available Hepatitis C virus (HCV infection in children is different from the adult infection in many ways, like natural course of the disease; duration, therapeutic response and side effects profile of the drug therapy; and prognosis. Special considerations include consideration on what could be the appropriate time to investigate a suspected child, when to institute drug therapy and how to prevent vertical transmission. Although over the past one decade many landmark studies have greatly increased our insight on this subject, yet we are far from developing a consensus statement. In this article, a concise yet comprehensive review of HCV infection in children - diagnosis and treatment - is given, followed by suggested recommendations at the end. It is hoped that these recommendations will help develop local guidelines on this subject.

  1. Cirrhotic cardiomyopathy

    DEFF Research Database (Denmark)

    Møller, Søren; Henriksen, Jens H

    2010-01-01

    and electrophysiological abnormalities. This syndrome is termed cirrhotic cardiomyopathy. Results of experimental studies indicate the involvement of several mechanisms in the pathophysiology, such as reduced beta-adrenergic receptor signal transduction, altered transmembrane currents and electromechanical coupling...... of the cirrhotic patients and it may be normalised by beta-blockers. No specific therapy for cirrhotic cardiomyopathy can be recommended, but treatment should be supportive and directed against the cardiac dysfunction. Future research should better describe the prevalence, impact on morbidity and survival...

  2. 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

  3. On-Treatment Elevation in Hepatic Transaminases during HCV Treatment with Ombitasvir, Paritaprevir, Dasabuvir, Ritonavir, and Ribavirin: A Case Series

    Science.gov (United States)

    Tang, Lydia; Kottilil, Shyam

    2016-01-01

    Eradication of chronic hepatitis C virus (HCV) infection is now possible with all oral antiviral medications, including the combination of ombitasvir, paritaprevir, dasabuvir, and ritonavir (PrOD) with or without ribavirin. While high rates of sustained virologic response (SVR) can be achieved, a small subset of patients experience on-treatment liver enzyme elevations, in particular women using concurrent estradiol-containing oral contraceptive medications (OCPs). Herein, we describe four cases of liver enzyme elevations within 2-3 weeks of PrOD initiation in African-American men infected with HCV genotype 1a or 1b. Three patients with varying degrees of hepatic fibrosis received a full treatment course without medication modification, achieved SVR, and experienced resolution of liver enzyme abnormalities. One patient with cirrhosis was switched mid-treatment to an alternate HCV regimen, experienced subsequent resolution of liver enzyme abnormalities, and achieved SVR. In summary, these cases suggest that all HCV patients treated with PrOD, independent of gender or concurrent medications, should have laboratory monitoring for liver enzyme elevations, with a particular emphasis on early monitoring in cirrhotic patients. PMID:27313921

  4. Alterations of seminal and hormonal parameters: An extrahepatic manifestation of HCV infection?

    Institute of Scientific and Technical Information of China (English)

    Marilena Durazzo; Alberto Premoli; Cataldo Di Bisceglie; Angela Bertagna; Emanuela Fagà; Giampaolo Biroli; Chiara Manieri; Simona Bo; Gianfranco Pagano

    2006-01-01

    AIM: To evaluate the possible influences of HCV infection and relative antiviral treatment on seminal parameters and reproductive hormonal serum levels.METHODS: Ten male patients with HCV-related chronic hepatitis and 16 healthy male volunteers were studied.In all subjects seminal parameters (nemaspermic concentration, progressive motility, morphology) and hormonal levels were determined. Seminal parameters and inhibin B, follicle-stimulating hormone, luteinizing hormone, total and free testosterone, estradiol, prolactine in patients were measured after six and twelve months of antiviral combined (interferon + ribavirin) treatment.RESULTS: Patients before treatment showed a significantly lower nemaspermic motility and morphology as well as lower inhibin B and free testosterone levels than controls. Inhibin B levels in cases were improved six and 12 mo after treatment in five responders (161.9 ± 52.8 pg/mL versus 101.7 ± 47.0 pg/mL and 143.4 ± 46.1 pg/mL versus 95.4 ± 55.6 pg/mL, respectively). Hormonal pattern of patients did not significantly change after treatment, with the exception of estradiol levels with an initial reduction and an overall subsequent increment (19.7 ± 6.4 pg/mL versus 13.6 ± 5.0 pg/mL versus 17.3 ± 5.7 pg/mL). However in 1-year responders a significant increment of free testosterone (14.2 ± 2.54 pg/mL versus 17.1 ± 2.58 pg/mL) occurred. An impairment of nemaspermic morphology occurred, while other seminal parameters did not change significantly during antiviral treatment.CONCLUSION: Patients with HCV infection show worse spermatic parameters than controls, suggesting a possible negative influence of virus on spermatogenesis, with further mild impairment during antiviral treatment. However therapy could improve the spermatic function, as suggested by the increased inhibin B levels and improved hormonal pattern in responders. Further studies are needed to confirm these preliminary intriguing results.

  5. THE CYTOKINE IP-10 IN CHRONIC HBV AND HCV INFECTION

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    Nina S. Nikolova

    2013-08-01

    Full Text Available Introduction: IP-10 it has been studied as a predictor of treatment response in chronic HCV infected patients. The data for the HBV infection are not enough.Aim: To compare IP-10 levels in patients with chronic HBV /CHB/ and HCV infection /CHC/ and their relation to liver disease and treatment response. Material and methods: 20 patients - with CHC genotype 1 infection /on standard bi-therapy/ and 32 patients with CHB /21 pts - NUC; 11 pts - IFN/. Results: The IP-10 did not correlate with sex, age, ALT and liver fibrosis. The basal IP-10 were lower in patients with CHB (p=0,017. There was a difference in IP-10 baseline levels among the HCV patients with or without RVR (p=0,007. A negative correlation was found between basal IP-10 and RVR (r= -0,508; p=0,008. Conclusion: IP-10 could predict virological response in patients with CHC on standard bi-therapy, but not in HBV infected patients on standard therapy.

  6. Epigenetic analysis of the IFNλ3 gene identifies a novel marker for response to therapy in HCV-infected subjects.

    Science.gov (United States)

    Waring, J F; Davis, J W; Dumas, E; Cohen, D; Idler, K; Abel, S; Georgantas, R; Podsadecki, T; Dutta, S

    2016-12-07

    Chronic hepatitis C virus (HCV) infection is characterized by high interindividual variability in response to pegylated interferon and ribavirin. A genetic polymorphism on chromosome 19 (rs12979860) upstream of interferon-λ3 (IFNλ3) is associated with a twofold change in sustained virologic response rate after 48 weeks of treatment with pegylated interferon/ribavirin in HCV genotype 1 (GT1) treatment-naïve patients. We conducted epigenetic analysis on the IFNλ3 promoter to investigate whether DNA methylation is associated with response to HCV therapy. DNA samples from HCV GT1-infected subjects receiving an interferon-free paritaprevir-containing combination regimen (N=540) and from HCV-uninfected, healthy controls (N=124) were analysed for IFNλ3 methylation levels. Methylation was strongly associated with rs12979860 allele status whether adjusting for HCV status (r=65.0%, 95% CI: [60.2%, 69.5%]), or not (r=64.4%), both with PHCV GT1-infected subjects, C/C genotypes had significantly lower methylation levels relative to C/T or T/T genotypes (PHCV therapy; however, continuing therapy for a sufficient duration can overcome this difference. These findings may provide mechanistic insight into the role of IFNλ3 genetic variants in HCV treatment response.

  7. 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.

  8. Prevalence of anti HCV infection in patients with beta-thalassemia in Isfahan-Iran

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    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.

  9. Cirrhotic cardiomyopathy

    DEFF Research Database (Denmark)

    Wiese, Signe; Hove, Jens D; Bendtsen, Flemming

    2014-01-01

    Cirrhosis is known to cause alterations in the systemic haemodynamic system. Cirrhotic cardiomyopathy designates a cardiac dysfunction that includes impaired cardiac contractility with systolic and diastolic dysfunction, as well as electromechanical abnormalities in the absence of other known...... biomarkers could improve the diagnostic assessm+ent. Cirrhotic cardiomyopathy contributes to various complications in cirrhosis, especially as an important factor in the development of hepatic nephropathy. Additionally, cirrhotic cardiomyopathy seems to be associated with the development of heart failure...... in relation to invasive procedures such as shunt insertion and liver transplantation. Current pharmacological treatment is nonspecific and directed towards left ventricular failure, and liver transplantation is currently the only proven treatment with specific effect on cirrhotic cardiomyopathy....

  10. The role of patient religiosity in the evaluation and treatment outcomes for chronic HCV infection.

    Science.gov (United States)

    Raghavan, Rajeev; Ferlic-Stark, Laura; Clarke, Cinda; Rungta, Manish; Goodgame, Richard

    2013-03-01

    To determine the influence of patient religiosity on the outcome of treatment of hepatitis C infection, a prospective, blinded, cohort study was performed on hepatitis C-infected patients categorized as 'higher religiosity' and 'lower religiosity' based on responses to a religiosity questionnaire. Comparisons were made between high and low religiosity patients on demographics, pre-treatment laboratory values, and response to treatment. Eighty-seven patients with complete questionnaires were placed in either higher (38) or lower (49) religiosity cohort. The patients (60% female) were ethnically diverse: African-American 39%; Hispanic 31%; white 29%. African-American race (P = 0.001) and female gender (P = 0.026) were associated with higher religiosity. The frequency of being offered treatment, accepting treatment, and completing treatment was similar in both religiosity cohorts (P = 0.234, 0.809, 0.367). Fifty-six patients completed the 24- or 48-week treatment with peginterferon and ribavirin. Depression was more frequent in the low religiosity group (38.2% vs. 4.6%, P = 0.005). Sustained viral response rate at 3-6-month post-therapy was similar in the higher (50%) and lower (57.6%) religiosity cohorts (P = 0.580; n = 55). Logistic regression modeling revealed that males having higher religiosity gave greater odds of SVR than those with lower religiosity (OR 21.3; 95% CI 1.1-403.9). The level of religiosity did not affect the decision to begin treatment for chronic HCV infection and was not associated with a better treatment outcome. A higher level of religiosity was associated with less depression among patients.

  11. Contribution of donor age to the recent decrease in patient survival among HCV-infected liver transplant recipients.

    Science.gov (United States)

    Berenguer, Marina; Prieto, Martín; San Juan, Fernando; Rayón, José M; Martinez, Fernando; Carrasco, Domingo; Moya, Angel; Orbis, Francisco; Mir, José; Berenguer, Joaquín

    2002-07-01

    Recurrent hepatitis occurs in the majority of patients undergoing liver transplantation for hepatitis C virus (HCV) cirrhosis, with progression to cirrhosis in up to 30% after 5 years. Based on these data, a decrease in survival can be anticipated with prolonged follow-up. Furthermore, posttransplantation HCV-fibrosis progression has been shown in recent years to increase. Our aims were (1) to describe the natural history of HCV-infected recipients, particularly to determine whether survival has decreased in recent years; (2) to compare this outcome with that observed in non-HCV-infected cirrhosis controls; and (3) to determine the factors associated with disease severity and survival. Among 522 cirrhotic patients undergoing transplantation between 1991 and 2000, 283 (54%) were infected with HCV. Yearly biopsies were performed in these recipients and at 1 and 5 years in the remainder. With similar follow-up, the percentage of deaths in the HCV(+) group was significantly higher than in the HCV- group (37% vs. 22%, P <.001), and patient survival was lower (77%, 61%, 55% vs. 87%, 76%, 70% at 1, 5, and 7 years, respectively; P =.0001). Although survival has increased in the HCV- group in recent years, it has significantly decreased in HCV recipients (P <.0001). The main cause of death among the latter was decompensated graft cirrhosis (n = 23/105, 22%), whereas that of HCV- patients was infections (n = 10/52, 19%). Reasons for the recent worse outcome in HCV+ recipients include the increased donor age and stronger immunosuppression. In conclusion, patient survival is lower among HCV+ recipients than among HCV- ones and has been decreasing in recent years. The aging of donors is a major contributor to this worse outcome.

  12. Effectiveness of treatment with pegylated interferon and ribavirin in an unselected population of patients with chronic hepatitis C: A Danish nationwide cohort study

    DEFF Research Database (Denmark)

    Hansen, Nanna; Obel, Niels; Christensen, Peer B

    2011-01-01

    The effect of peginterferon and ribavirin treatment on chronic hepatitis C virus (HCV) infection has been established in several controlled clinical studies. However, the effectiveness of treatment and predictors of treatment success in routine clinical practice remains to be established. Our aim...... was to estimate the effectiveness of peginterferon and ribavirin treatment in unselected HCV patients handled in routine clinical practice. The endpoint was sustained virological response (SVR), determined by the absence of HCV RNA 24 weeks after the end of treatment....

  13. Antiviral Treatment of HCV-Infected Patients with B-Cell Non-Hodgkin Lymphoma: ANRS HC-13 Lympho-C Study

    Science.gov (United States)

    Alric, Laurent; Besson, Caroline; Lapidus, Nathanael; Jeannel, Juliette; Michot, Jean-Marie; Cacoub, Patrice; Canioni, Danielle; Pol, Stanislas; Davi, Frédéric; Rabiega, Pascaline; Ysebaert, Loic; Bonnet, Delphine; Hermine, Olivier

    2016-01-01

    Hepatitis C virus (HCV) infection is associated with lymphoproliferative disorders and B-cell non-Hodgkin lymphomas (B-NHLs). Evaluation of the efficacy and safety profiles of different antiviral therapies in HCV patients with B-NHL is warranted. Methods: First, we evaluated the sustained virologic response (SVR) and safety of Peg-interferon-alpha (Peg-IFN) + ribavirin +/- first protease inhibitors (PI1s) therapy in 61 HCV patients with B-NHL enrolled in a nationwide observational survey compared with 94 matched HCV-infected controls without B-NHL. In a second series, interferon-free regimens using a newly optimal combination therapy with direct-acting antiviral drugs (DAAs) were evaluated in 10 patients with HCV and B-NHL. Results: The main lymphoma type was diffuse large B-cell lymphoma (38%) followed by marginal zone lymphoma (31%). In the multivariate analysis, patients with B-NHL treated by Peg-IFN-based therapy exhibited a greater SVR rate compared with controls, 50.8% vs 30.8%, respectively, p<0.01, odds ratio (OR) = 11.2 [2.3, 52.8]. B-NHL response was better (p = 0.02) in patients with SVR (69%) than in patients without SVR (31%). Premature discontinuation of Peg-IFN-based therapy was significantly more frequent in the B-NHL group (19.6%) compared with the control group (6.3%), p<0.02. Overall, survival was significantly enhanced in the controls than in the B-NHL group (hazard ratio = 34.4 [3.9, 304.2], p< 0.01). Using DAAs, SVR was achieved in 9/10 patients (90%). DAAs were both well tolerated and markedly efficient. Conclusions: The virologic response of HCV-associated B-NHL is high. Our study provides a comprehensive evaluation of different strategies for the antiviral treatment of B-NHL associated with HCV infection. PMID:27749916

  14. Ribavirin-induced anemia in hepatitis C virus patients undergoing combination therapy.

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    Sheeja M Krishnan

    Full Text Available The current standard of care for hepatitis C virus (HCV infection - combination therapy with pegylated interferon and ribavirin - elicits sustained responses in only ∼50% of the patients treated. No alternatives exist for patients who do not respond to combination therapy. Addition of ribavirin substantially improves response rates to interferon and lowers relapse rates following the cessation of therapy, suggesting that increasing ribavirin exposure may further improve treatment response. A key limitation, however, is the toxic side-effect of ribavirin, hemolytic anemia, which often necessitates a reduction of ribavirin dosage and compromises treatment response. Maximizing treatment response thus requires striking a balance between the antiviral and hemolytic activities of ribavirin. Current models of viral kinetics describe the enhancement of treatment response due to ribavirin. Ribavirin-induced anemia, however, remains poorly understood and precludes rational optimization of combination therapy. Here, we develop a new mathematical model of the population dynamics of erythrocytes that quantitatively describes ribavirin-induced anemia in HCV patients. Based on the assumption that ribavirin accumulation decreases erythrocyte lifespan in a dose-dependent manner, model predictions capture several independent experimental observations of the accumulation of ribavirin in erythrocytes and the resulting decline of hemoglobin in HCV patients undergoing combination therapy, estimate the reduced erythrocyte lifespan during therapy, and describe inter-patient variations in the severity of ribavirin-induced anemia. Further, model predictions estimate the threshold ribavirin exposure beyond which anemia becomes intolerable and suggest guidelines for the usage of growth hormones, such as erythropoietin, that stimulate erythrocyte production and avert the reduction of ribavirin dosage, thereby improving treatment response. Our model thus facilitates, in

  15. Different Responses of Two Highly Permissive Cell Lines Upon HCV Infection

    Institute of Scientific and Technical Information of China (English)

    Honghe Chen; Rongjuan Pei; Xinwen Chen

    2013-01-01

    The construction of the first infectious clone JFH-1 speeds up the research on hepatitis C virus (HCV).However,Huh7 cell line was the only highly permissive cell line for HCV infection and only a few clones were fully permissive.In this study,two different fully permissive clones of Huh7 cells,Huh7.5.1 and Huh7-Lunet-CD81 (Lunet-CD81) cells were compared for their responses upon HCV infection.The virus replication level was found slightly higher in Huh7.5.1 cells than that in Lunet-CD81 cells.Viability of Huh7.5.1 cells but not of Lunet-CD81 cells was reduced significantly after HCV infection.Further analysis showed that the cell cycle of infected Huh7.5.1 cells was arrested at G1 phase.The G1/S transition was blocked by HCV infection in Huh7.5.1 cells as shown by the cell cycle synchronization analysis.Genes related to cell cycle regulation was modified by HCV infection and gene interaction analysis in GeneSpring GX in Direct Interactions mode highlighted 31 genes.In conclusion,the responses of those two cell lines were different upon HCV infection.HCV infection blocked G1/S transition and cell cycle progress,thus reduced the cell viability in Huh7.5.1 cells but not in Lunet-CD81 cells.Lunet-CD81 cells might be suitable for long term infection studies of HCV.

  16. Impact of Safety-Related Dose Reductions or Discontinuations on Sustained Virologic Response in HCV-Infected Patients: Results from the GUARD-C Cohort.

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    Graham R Foster

    Full Text Available Despite the introduction of direct-acting antiviral agents for chronic hepatitis C virus (HCV infection, peginterferon alfa/ribavirin remains relevant in many resource-constrained settings. The non-randomized GUARD-C cohort investigated baseline predictors of safety-related dose reductions or discontinuations (sr-RD and their impact on sustained virologic response (SVR in patients receiving peginterferon alfa/ribavirin in routine practice.A total of 3181 HCV-mono-infected treatment-naive patients were assigned to 24 or 48 weeks of peginterferon alfa/ribavirin by their physician. Patients were categorized by time-to-first sr-RD (Week 4/12. Detailed analyses of the impact of sr-RD on SVR24 (HCV RNA <50 IU/mL were conducted in 951 Caucasian, noncirrhotic genotype (G1 patients assigned to peginterferon alfa-2a/ribavirin for 48 weeks. The probability of SVR24 was identified by a baseline scoring system (range: 0-9 points on which scores of 5 to 9 and <5 represent high and low probability of SVR24, respectively.SVR24 rates were 46.1% (754/1634, 77.1% (279/362, 68.0% (514/756, and 51.3% (203/396, respectively, in G1, 2, 3, and 4 patients. Overall, 16.9% and 21.8% patients experienced ≥1 sr-RD for peginterferon alfa and ribavirin, respectively. Among Caucasian noncirrhotic G1 patients: female sex, lower body mass index, pre-existing cardiovascular/pulmonary disease, and low hematological indices were prognostic factors of sr-RD; SVR24 was lower in patients with ≥1 vs. no sr-RD by Week 4 (37.9% vs. 54.4%; P = 0.0046 and Week 12 (41.7% vs. 55.3%; P = 0.0016; sr-RD by Week 4/12 significantly reduced SVR24 in patients with scores <5 but not ≥5.In conclusion, sr-RD to peginterferon alfa-2a/ribavirin significantly impacts on SVR24 rates in treatment-naive G1 noncirrhotic Caucasian patients. Baseline characteristics can help select patients with a high probability of SVR24 and a low probability of sr-RD with peginterferon alfa-2a/ribavirin.

  17. Impact of Safety-Related Dose Reductions or Discontinuations on Sustained Virologic Response in HCV-Infected Patients: Results from the GUARD-C Cohort

    Science.gov (United States)

    Foster, Graham R.; Coppola, Carmine; Derbala, Moutaz; Ferenci, Peter; Orlandini, Alessandra; Reddy, K. Rajender; Tallarico, Ludovico; Shiffman, Mitchell L.; Ahlers, Silke; Bakalos, Georgios; Hassanein, Tarek

    2016-01-01

    Background Despite the introduction of direct-acting antiviral agents for chronic hepatitis C virus (HCV) infection, peginterferon alfa/ribavirin remains relevant in many resource-constrained settings. The non-randomized GUARD-C cohort investigated baseline predictors of safety-related dose reductions or discontinuations (sr-RD) and their impact on sustained virologic response (SVR) in patients receiving peginterferon alfa/ribavirin in routine practice. Methods A total of 3181 HCV-mono-infected treatment-naive patients were assigned to 24 or 48 weeks of peginterferon alfa/ribavirin by their physician. Patients were categorized by time-to-first sr-RD (Week 4/12). Detailed analyses of the impact of sr-RD on SVR24 (HCV RNA <50 IU/mL) were conducted in 951 Caucasian, noncirrhotic genotype (G)1 patients assigned to peginterferon alfa-2a/ribavirin for 48 weeks. The probability of SVR24 was identified by a baseline scoring system (range: 0–9 points) on which scores of 5 to 9 and <5 represent high and low probability of SVR24, respectively. Results SVR24 rates were 46.1% (754/1634), 77.1% (279/362), 68.0% (514/756), and 51.3% (203/396), respectively, in G1, 2, 3, and 4 patients. Overall, 16.9% and 21.8% patients experienced ≥1 sr-RD for peginterferon alfa and ribavirin, respectively. Among Caucasian noncirrhotic G1 patients: female sex, lower body mass index, pre-existing cardiovascular/pulmonary disease, and low hematological indices were prognostic factors of sr-RD; SVR24 was lower in patients with ≥1 vs. no sr-RD by Week 4 (37.9% vs. 54.4%; P = 0.0046) and Week 12 (41.7% vs. 55.3%; P = 0.0016); sr-RD by Week 4/12 significantly reduced SVR24 in patients with scores <5 but not ≥5. Conclusions In conclusion, sr-RD to peginterferon alfa-2a/ribavirin significantly impacts on SVR24 rates in treatment-naive G1 noncirrhotic Caucasian patients. Baseline characteristics can help select patients with a high probability of SVR24 and a low probability of sr-RD with

  18. Occult HCV infection: an unexpected finding in a population unselected for hepatic disease.

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    Laura De Marco

    Full Text Available BACKGROUND: Occult Hepatitis C virus (HCV infection is a new pathological entity characterized by presence of liver disease and absence or very low levels of detectable HCV-RNA in serum. Abnormal values of liver enzymes and presence of replicative HCV-RNA in peripheral blood mononuclear cells are also observed. Aim of the study was to evaluate occult HCV occurrence in a population unselected for hepatic disease. METHODOLOGY/PRINCIPAL FINDINGS: We chose from previous epidemiological studies three series of subjects (n = 276, age range 40-65 years unselected for hepatic disease. These subjects were tested for the presence of HCV antibodies and HCV-RNA in plasma and in the peripheral blood mononuclear cells (PBMCs by using commercial systems. All subjects tested negative for HCV antibodies and plasma HCV-RNA and showed normal levels of liver enzymes; 9/276 patients (3.3% were positive for HCV-RNA in PBMCs, identifying a subset of subjects with potential occult HCV infection. We could determine the HCV type for 8 of the 9 patients finding type 1a (3 patients, type 1b (2 patients, and type 2a (3 patients. CONCLUSIONS: The results of this study show evidence that occult HCV infection may occur in a population unselected for hepatic disease. A potential risk of HCV infection spread by subjects harbouring occult HCV infection should be considered. Design of prospective studies focusing on the frequency of infection in the general population and on the clinical evolution of occult HCV infection will be needed to verify this unexpected finding.

  19. Treatment of HCV Infection in Multitransfused Thalassemic Patients: Does Liver Iron Status Affect the Outcome of Response?

    Directory of Open Access Journals (Sweden)

    Shahram Mirmomen

    2005-03-01

    Full Text Available IntroductionPatients with transfusion dependent thalassemia (TDT require blood transfusion program throughout their life to sustain their growth and development during childhood. Transfusion not only exposes these patients to increased risk of blood borne viruses (the most important one is HCV infection(1, but also causes an inevitable accumulation in body iron(2. Regular chelating program can delay the secondary iron overload but not completely avert the development of hepatic fibrosis. The secondary Iron overload and HCV infection are the two main causes of chronic liver fibrosis in patients with TDT(3, which is a common cause of death after the age of 15 in TDT patients(4. Notably in the last 3 decades we have witnessed profound changes in the management of patients with thalassemia major. Regular red blood cell transfusions and iron chelating permit a normal development throughout childhood, and extend survival. So treatment of HCV infection would have a great influence in the survival of a great number of TDT patients who pass their second decade of life.Iran is located in thalassemia belt with more than 25,000 registered TDT. Epidemiologic studies have shown that around 20 to 40% of Iranian TDT patients are infected with HCV virus(5,6,7. It should be mentioned that after initiation of donor screening for HCV in 1995 and exclusion of high risk groups from donation pool, the prevalence of HCV infection in thalassemic patients had decreased significantly(7a. On the other hand, similar rate of HCV infection has been shown in TDT patients worldwide(8, which in turn puts another emphasis on the importance of HCV treatment in this group of patients.History of HCV Treatment in ThalassemiaInterferon-alpha (IFN-a monotherapy is currently approved as the first line treatment for HCV infection in TDT patients. Because of hemolytic complications of ribavirin, currently combination of IFN and ribavirin is preserved for IFN non-responders and only under

  20. Dynamics of an HBV/HCV infection model with intracellular delay and cell proliferation

    Science.gov (United States)

    Zhang, Fengqin; Li, Jianquan; Zheng, Chongwu; Wang, Lin

    2017-01-01

    A new mathematical model of hepatitis B/C virus (HBV/HCV) infection which incorporates the proliferation of healthy hepatocyte cells and the latent period of infected hepatocyte cells is proposed and studied. The dynamics is analyzed via Pontryagin's method and a newly proposed alternative geometric stability switch criterion. Sharp conditions ensuring stability of the infection persistent equilibrium are derived by applying Pontryagin's method. Using the intracellular delay as the bifurcation parameter and applying an alternative geometric stability switch criterion, we show that the HBV/HCV infection model undergoes stability switches. Furthermore, numerical simulations illustrate that the intracellular delay can induce complex dynamics such as persistence bubbles and chaos.

  1. Safety of cyclosporin A in HCV-infected patients: experience with cyclosporin A in patients affected by rheumatological disorders and concomitant HCV infection.

    Science.gov (United States)

    Galeazzi, Mauro; Bellisai, Francesca; Giannitti, Chiara; Manganelli, Stefania; Morozzi, Gabriella; Sebastiani, Gian Domenico

    2007-09-01

    Because of the relatively high prevalence of both hepatitis C virus (HCV) infection and autoimmune disorders (ADs), it is not rare to encounter in daily clinical practice patients with ADs also carrying HCV. Corticosteroids and/or immunosuppressant drugs are needed to treat ADs, but they place HCV-infected patients at risk of worsening the infection. So, rheumatologists have often refrained from using corticosteroids or immunosuppressants in AD when HCV-RNA is also present. Cyclosporin A (CsA) is an immunosuppressive agent used to treat a wide range of ADs, but there is a large evidences in the literature, both in vitro and in vivo, suggesting that CsA also exerts an inhibitory effect on HCV replication at standard therapeutic dose. Therefore, this evidence has opened new ways to improve the therapy and the prognosis in patients with HCV-related liver diseases, including those with transplants. Recent reports, although limited in number, also suggest the safety of CsA in the treatment of patients with AD and concomitant HCV infection. In this review we also report our personal experience on the combination treatment with CsA and anti-TNF-alpha agents in rheumatoid arthritis.

  2. The effect of IFN-based therapies on the short-term dynamics of alt in HCV-infected patients

    Energy Technology Data Exchange (ETDEWEB)

    Ribeiro, R. M. (Ruy M.); Talal, A. H. (Andrew H.); Layden, J. E. (Jennifer E.); Powers, K. A. (Kimberly A.); Layden, T. J. (Thomas J.); Perelson, Alan S.,

    2002-01-01

    IFN therapy of HCV-infection has been shown to reduce production of virus from infected cells, but its effect on hepatocytes is less well understood. One indicator of liver damage is ALT, which has been used as an associated diagnostic for HCV infection.

  3. Triple therapy of interferon and ribavirin with zinc supplementation for patients with chronic hepatitis C: A randomized controlled clinical trial

    Institute of Scientific and Technical Information of China (English)

    Hideyuki Suzuki; Hitoshi Takaqi; Naondo Sohara; Daisuke Kanda; Satoru Kakizaki; Ken Sato; Masatomo Mori

    2006-01-01

    AIM: To study the therapeutic effect of interferon (IFN)and ribavirin with zinc supplement on patients with chronic hepatitis C viral (HCV) infection.METHODS: A total of 102 patients confirmed histologically to have chronic HCV infection with genotype 1b and more than 100 KIU/mL of HCV were randomly assigned to each arm of the study and each received 10 million units of pegylated interferon (IFN-alpha-2b) daily for 4 wk followed by the same dose every other day for 20 wk plus ribavirin (600 or 800 mg/d depending on body weight), with or without polaprezinc (150 mg/d) orally for 24 wk. The primary endpoint was sustained virological response (SVR) defined as negative HCV-RNA in the serum 6 mo after treatment.RESULTS: There were no differences in the clinical background between the two groups except for more females in the dual therapy group than in the other group (P< 0.05). SVR was observed in 33.3% of the triple therapy group and 33.3% of the dual therapy group. The side effects were almost the same in both groups except for gastrointestinal symptoms, which were less in the triple therapy group (P= 0.019).CONCLUSION: Considered together, triple therapy of zinc plus IFN and ribavirin for HCV infection patients with genotype 1b and high viral load is not better than dual therapy except for lower incidence of gastrointestinal side effects.

  4. Onset of Type 1 Diabetes Mellitus During Pegylated-interferon Alfa and Ribavirin Therapy for Chronic Hepatitis C Virus Infection

    Science.gov (United States)

    Ranganathan, Raghini; Janarthanan, Krishnaveni; Rajasekaran, Senthilkumar

    2012-01-01

    A 16-year-old female was treated with pegylated-interferon (PEG-IFN) alfa (a)-2b and ribavirin combination therapy for chronic hepatitis C virus (HCV) infection. She attained rapid virological response. She presented with diabetic ketoacidosis after 41 weeks of therapy. Anti-glutamic acid decarboxylase antibodies and islet cell antibodies were negative. Her fasting serum C-peptide level was <0.1 ng/mL, and the treatment course was completed. This case underlines the importance of periodic plasma glucose monitoring in patients during and after PEG-IFN and ribavirin therapy. PMID:25755410

  5. Miliary tuberculosis infection during hepatitis C treatment with sofosbuvir and ledipasvir plus ribavirin.

    Science.gov (United States)

    Ballester-Ferré, Maria Pilar; Martínez, Fernando; Garcia-Gimeno, Natalia; Mora, Francisco; Serra, Miguel A

    2017-01-28

    Chronic hepatitis C virus (HCV) infection is one of the main causes of chronic liver disease worldwide. In the last 5 years, treatment for HCV infection has experienced a marked development. In 2014, the use of ledipasvir/sofosbuvir with or without concomitant weight-based ribavirin was approved with a very significant increase in the sustained virological response. However, new side effects have been associated. We report the first case of an HCV infected patient treated for 12 wk with the combination of sofosbuvir/ledipasvir plus ribavirin who developed a miliary tuberculosis (TB) infection while on therapy. The patient was a 65-year-old woman, who referred malaise, asthenia, hyporexia, 7 kg weight loss, productive cough, evening fever and night sweats, right after finishing the treatment. The chest computed tomography-scan revealed a superior mediastinal widening secondary to numerous lymphadenopathies with extensive necrosis and bilateral diffuse lung miliary pattern with little subsequent bilateral pleural effusion, highly suggestive of lymph node tuberculosis with lung miliary spread. A bronchoscopy was performed and bronchial suction showed more than 50 acid-alcohol resistant bacillus per line. A Mycobacterium tuberculosis DNA was detected in blood by polymerase chain reaction, which confirmed the diagnosis of miliary tuberculosis. Some cases of TB infection have been identified with α-interferon-based therapy and with the triple therapy of pegylated interferon, ribavirin and boceprevir or telaprevir. However, significant infection has not been reported with sofosbuvir/ledipasvir plus ribavirin. We believe that the case is relevant to increase awareness of opportunistic infections and particularly TB infection. Although the international guidelines offer no recommendation regarding TB screening, we wonder whether it would be advisable to screen for opportunistic infections prior to the introduction of HCV therapy.

  6. Discovery of cellular proteins required for the early steps of HCV infection using integrative genomics.

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    Ji Hoon Park

    Full Text Available 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.

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

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    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.

  8. 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

  9. Function of monocytes in chronic HCV infection: Role for IL-10 and interferon

    NARCIS (Netherlands)

    B. Liu (Bi Sheng)

    2011-01-01

    textabstractHepatitis C virus (HCV) establishes persistent infection in about 80% of the infected individuals. The symptoms are initially mild in those persistently infected patients, and it may take decades before the serious consequences of chronic HCV infection become apparent. Up to 20% of infec

  10. Antiviral Therapy for Chronic HCV Infection: Virological Response and Long-Term Outcome

    NARCIS (Netherlands)

    A.J.P. van der Meer (Adriaan)

    2014-01-01

    markdownabstract__Abstract__ Hepatitis C is a major global health problem which is responsible for over 350,000 deaths each year.1 In total, there are thought to be around 150 million hepatitis C virus (HCV) carriers, which comprise about 3% of the world population. The prevalence of HCV infection,

  11. Treatment for hepatitis B virus (HBV) and hepatitis C virus (HCV) infection - Danish national guidelines 2011

    DEFF Research Database (Denmark)

    Christensen, Peer Brehm; Clausen, Mette Rye; Krarup, Henrik Bygum;

    2012-01-01

    countries, probably infected at birth or early childhood in their country of origin, while the majority of patients with HCV infection have been infected by drug use. For both groups it is estimated that only half of the patients have been diagnosed, of whom only 20% attends specialized care...

  12. Immune complexed (IC) hepatitis C virus (HCV) in chronically and acutely HCV-infected patients.

    Science.gov (United States)

    Riva, E; Maggi, F; Abbruzzese, F; Bellomi, F; Giannelli, G; Picardi, A; Scagnolari, C; Folgori, A; Spada, E; Piccolella, E; Dianzani, F; Antonelli, G

    2009-02-01

    In infected individuals, hepatitis C virus (HCV) exists in various forms of circulating particles which role in virus persistence and in HCV resistance to IFN therapy is still debated. Here, the proportion of HCV bound to immunoglobulin was determined in plasma of 107 chronically infected patients harbouring different HCV genotypes and, for comparison, of six patients with acute HCV infection. The results showed that, in spite of wide individual variability, chronically HCV-infected patients exhibited an extremely high proportion of immune complexed (IC) virus regardless of plasma HCV load and infecting genotype. Moreover, no significant association was found between baseline proportion of IC HCV and response to IFN treatment. Plasma samples collected within 2 weeks of treatment from 20 patients revealed a significant decline of mean IC HCV values relative to baseline that clearly paralleled the decay of total HCV load. In acutely infected patients, circulating HCV was not IC or IC at very low levels only in patients developing chronic HCV infection. Collectively, these findings strengthen the possibility that IC virus could play a critical role in the pathogenesis of HCV infection.

  13. Recent advances in managing chronic HCV infection: Focus on therapy in patients with severe liver disease

    NARCIS (Netherlands)

    R. Maan (Raoel); A.J.P. van der Meer (Adriaan)

    2016-01-01

    textabstractChronic hepatitis C virus (HCV) infection still represents a major public health problem, as it is thought to be responsible for more than 350,000 deaths around the globe on a yearly basis. Fortunately, successful eradication of the virus has been associated with improved clinical outcom

  14. Association between IL28B rs12979860 single nucleotide polymorphism and the frequency of colonic Treg in chronically HCV-infected patients.

    Science.gov (United States)

    Mehta, Minesh; Hetta, Helal F; Abdel-Hameed, Enass A; Rouster, Susan D; Hossain, MdMonir; Mekky, Mohamed A; Khalil, Nasr K; Mohamed, Wegdan A; El-Feky, Mohamed A; Ahmed, Shabaan H; Daef, Enas A; El-Mokhtar, Mohamed A; Abdelwahab, Sayed F; Medhat, Ahmed; Sherman, Kenneth E; Shata, Mohamed Tarek M

    2016-11-01

    The IL28B gene is associated with spontaneous or treatment-induced HCV viral clearance. However, the mechanism by which the IL28B single nucleotide polymorphism (SNP) affects the extra-hepatic HCV immune responses and its relationship to HCV pathogenesis have not been thoroughly investigated. To examine the mechanism by which IL28B affects HCV clearance. Forty Egyptian patients with chronic HCV infection receiving an Interferon/ribavirin treatment regimen were enrolled into this study. There were two groups: non-responders (NR; n = 20) and sustained virologic responders (SVR; n = 20). The initial plasma HCV viral loads prior to treatment and IL28B genotypes were determined by quantitative RT-PCR and sequencing, respectively. Liver biopsies were examined to determine the inflammatory score and the stage of fibrosis. Colonic regulatory T cell (Treg) frequency was estimated by immunohistochemistry. No significant association between IL28B genotypes and response to therapy was identified, despite an odds ratio of 3.4 to have the TT genotype in NR compared to SVR (95 % confidence interval 0.3-35.3, p = 0.3). Patients with the TT-IL28Brs12979860 genotype (unfavorable genotype) have significantly higher frequencies of colonic Treg compared to the CT (p = 0.04) and CC (p = 0.03) genotypes. The frequency of colonic Treg cells in HCV-infected patients had a strong association with the IL-28B genotype and may have a significant impact on HCV clearance.

  15. Treatment of acute hepatitis C virus infection with interferon-α 2b and ribavirin: Case report and review of the literature

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    Sunbul Mustafa

    2002-10-01

    Full Text Available Abstract Hepatitis C virus (HCV infection becomes chronic in about 85 % of individuals as demonstrated by the persistence of HCV. It is necesseray to treat acute hepatitis C infection. Interferon-α is generally used for the treatment of acute HCV infection. Case presentation A 55-year-old woman with a history of fatique and icter was diagnosed as acute hepatitis C virus infection. She was treated with interferon-α 2b 3 million unite sc three times in a week and ribavirin 1000 mg daily for 6 months. Within 2 weeks of therapy, the alanine aminotransferase (ALT had became normal. At the end of the 3 months of therapy, HCV RNA was negative and remained negative 6 months after the end of interferon treatment (sustained response. Conclusion This report suggests that interferon-α 2b and ribavirin may have a role in treatment of acute hepatitis C virus infection.

  16. The present and future disease burden of hepatitis C virus (HCV) infection with today's treatment paradigm

    DEFF Research Database (Denmark)

    Razavi, H; Waked, I; Sarrazin, C;

    2014-01-01

    The disease burden of hepatitis C virus (HCV) is expected to increase as the infected population ages. A modelling approach was used to estimate the total number of viremic infections, diagnosed, treated and new infections in 2013. In addition, the model was used to estimate the change in the total...... number of HCV infections, the disease progression and mortality in 2013-2030. Finally, expert panel consensus was used to capture current treatment practices in each country. Using today's treatment paradigm, the total number of HCV infections is projected to decline or remain flat in all countries...... studied. However, in the same time period, the number of individuals with late-stage liver disease is projected to increase. This study concluded that the current treatment rate and efficacy are not sufficient to manage the disease burden of HCV. Thus, alternative strategies are required to keep...

  17. What future for ribavirin?

    Science.gov (United States)

    Shiffman, Mitchell L

    2009-01-01

    The optimal therapy for patients with the chronic hepatitis C virus (HCV) is a combination of peginterferon and ribavirin. Treating HCV without ribavirin or prematurely discontinuing, frequently missing doses of ribavirin is associated with a significant decline in virological response, and an increase in both breakthrough viraemia and relapse. The major limitation of ribavirin is adverse events, the most common of which is haemolytic anaemia. Haemolysis is modest when ribavirin is utilized as monotherapy, but is significantly increased when combined with interferon or peginterferon. For these reasons, attempts to replace ribavirin with a less toxic alternative have been advanced. Unfortunately, even when ribavirin is replaced by a potent protease inhibitor, relapse is significantly increased and SVR is reduced. The future of HCV treatment is to combine peginterferon and ribavirin with several protease and/or polymerase inhibitors. Whether this strategy will allow ribavirin to be removed from the treatment paradigm remains to be proven. However, based on the results of clinical trials conducted to date, it is much more likely that peginterferon, not ribavirin, could be expendable.

  18. Protective KIR-HLA interactions for HCV infection in intravenous drug users

    Science.gov (United States)

    Zúñiga, Joaquin; Romero, Viviana; Azocar, José; Terreros, Daniel; Vargas-Rojas, María Inés; Torres-García, Diana; Jimenez-Alvarez, Luis; Vargas-Alarcón, Gilberto; Granados-Montiel, Julio; Husain, Zaheed; Chung, Raymond T.; Alper, Chester A.; Yunis, Edmond J.

    2009-01-01

    Intravenous drug use has become the principal route of hepatitis C virus (HCV) transmission due to the sharing of infected needles. In this study, we analyzed the distribution of HLA-KIR genotypes among 160 Puerto Rican intravenous drug users (IDUs) with HCV infection and 92 HCV-negative Puerto Rican IDUs. We found a significant association between the presence of different combinations of KIR inhibitory receptor genes (KIR2DL2 and/or KIR2DL3, pC = 0.01, OR = 0.07; KIR2DL2 and/or KIR2DL3+KIR2DS4, pC = 0.01, OR = 0.39) and HLA-C1 homozygous genotypes (HLA-C1+KIR2DS4, pC = 0.02, OR = 0.43; HLA-C1+KIR2DL2+KIR2DS4, pC = 0.02, OR = 0.40) together with the activating receptor KIR2DS4 (HLA-C1+KIR2DS4+KIR2DL3 and/or KIR2DL2, pC = 0.004, OR = 0.38) with protection from HCV infection. Our findings in HCV-infected and non-infected IDUs suggest an important role for KIRs (KIR2DL2 and KIR2DL3) with group HLA-C1 molecules, in the presence of activating KIR2DS4, in protection from HCV infection. These results support the hypothesis that activator signaling, mediated by KIR2DS4, is a determinant in the regulation of NK cell antiviral-activity. PMID:19552960

  19. Inflammatory pseudotumor of the liver in a patient with congenital granulocytopenia and HCV infection

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    Schneider, G. E-mail: ragsne@uniklink-saarland.de; Fries, P.; Samaras, P.; Remberger, K.; Uder, M.; Kramann, B

    2003-12-01

    Inflammatory pseudotumor (IPT) of the liver is a rare pathologic lesion. Although IPTs within the liver shows spontaneous regression, these lesions are frequently misdiagnosed as malignant on the basis of the clinical manifestation and the results of diagnostic imaging. With special regard to magnetic resonance imaging (MRI), differential diagnosis such as hepatocellular or cholangiocellular carcinoma (HCC/CCC) as well as regenerative liver lesions are discussed in a case of IPT with concomitant hepatitis C virus (HCV) infection and congenital granulocytopenia.

  20. 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.

  1. Association of interleukin-12 p40 gene 3'-untranslated region polymorphism and outcome of HCV infection

    Institute of Scientific and Technical Information of China (English)

    Li-Min Yin; Qi-Xin Wang; Yan Gao; Hui Zhuang; Wan-Fu Zhu; Lai Wei; Xiao-Yuan Xu; De-Gui Sun; Yan-Bin Wang; Wen-Mei Fan; Min Yu; Xiu-Lan Tian

    2004-01-01

    AIM: To investigate the effect of interleukin-12 p40 gene (IL12B) 3'-untranslated region polymorphism on the outcome of HCV infection.METHODS: A total of 133 patients who had been infected with HCV for 12-25 (18.2±3.8) years, were enrolled in this study. Liver biochemical tests were performed with an automated analyzer and HCV RNA was detected by fiuorogenic quantitative polymerase chain reaction. B-mode ultrasound was used for liver examination. Polymerase chain reactionrestriction fragment length polymorphism (PCR-RFLP) was used for the detection of IL12B (1188A/C) polymorphism.RESULTS: Self-limited infection was associated with AC genotype (OR = 3.48; P = 0.001) and persistent infection was associated with AA genotype (OR = 0.34; P = 0.014)at site 1188 of IL12B. In patients with persistent HCV infection, no significant differences were found regarding the age, gender, duration of infection and biochemical characteristics (P>0.05). According to B-mode ultrasound imaging and clinical diagnosis, patients with persistent infection were divided into groups based on the severity of infection. No significant differences were found in the frequency of IL-12 genotype (1188A/C) between different groups (P>0.05).CONCLUSION: The polymorphism of IL12B (1188A/C)appears to have some influence on the outcome of HCV infection.

  2. SKI-1/S1P inhibitor PF-429242 impairs the onset of HCV infection.

    Science.gov (United States)

    Blanchet, Matthieu; Sureau, Camille; Guévin, Carl; Seidah, Nabil G; Labonté, Patrick

    2015-03-01

    Worldwide, approximately 170 million individuals are afflicted with chronic hepatitis C virus (HCV) infection. To prevent the development of inherent diseases such as cirrhosis and hepatocellular carcinoma, tremendous efforts have been made, leading to the development of promising new treatments. However, their efficiency is still dependent on the viral genotype. Additionally, these treatments that target the virus directly can trigger the emergence of resistant variants. In a previous study, we have demonstrated that a long-term (72h) inhibition of SKI-1/S1P, a master lipogenic pathway regulator through activation of SREBP, resulted in impaired HCV genome replication and infectious virion secretion. In the present study, we sought to investigate the antiviral effect of the SKI-1/S1P small molecule inhibitor PF-429242 at the early steps of the HCV lifecycle. Our results indicate a very potent antiviral effect of the inhibitor early in the viral lifecycle and that the overall action of the compound relies on two different contributions. The first one is SREBP/SKI-1/S1P dependent and involves LDLR and NPC1L1 proteins, while the second one is SREBP independent. Overall, our study confirms that SKI-1/S1P is a relevant target to impair HCV infection and that PF-429242 could be a promising candidate in the field of HCV infection treatment.

  3. Schistosomiasis as a possible risk factor for acquiring hepatitis C virus (HCV infection among Saudis

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    Arif Mohammed

    1997-01-01

    Full Text Available Background -Risk factors for acquiring hepatitis C virus (HCV infection have been elucidated in many developed countries but the picture is still not clear in many Middle Eastern Countries including Saudi Arabia. Aim -To investigate possible risk factors for acquiring HCV among Saudis. Methods -Various demographic and medical risk factors that might be associated with the spread of HCV among Saudis were investigated. The population studied included 20 anti-HCV-positive with chronic liver disease (CLD, 30 anti-HCV-positive patients without CLD and 272 anti-HCV-negative Saudi blood donors. All people investigated were of the same age group (>40 years of age. Results -None of the demographic parameters studied (type of job, type of housing, education was found to be significantly associated with acquiring HCV infection among our Saudi patients. On the other hand up to 40% of the anti-HCV-positive patients and irrespective of the condition of liver disease had a history of surgery, and 25% of them had a history of multiple injections. Furthermore, at least 20% of our anti-HCV-positive patients had a history of schistosomiasis which is significantly higher than schistosomiasis among the blood donors (P< 0.005. Conclusion -In addition to blood and blood products, schistosomiasis seems to be a possible risk factor for acquiring HCV among the Saudi population. The association between schistosomiasis and enhancement of HCV infection need to be further elucidated.

  4. Human monoclonal antibody HCV1 effectively prevents and treats HCV infection in chimpanzees.

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    Trevor J Morin

    Full Text Available Hepatitis C virus (HCV infection is a leading cause of liver transplantation and there is an urgent need to develop therapies to reduce rates of HCV infection of transplanted livers. Approved therapeutics for HCV are poorly tolerated and are of limited efficacy in this patient population. Human monoclonal antibody HCV1 recognizes a highly-conserved linear epitope of the HCV E2 envelope glycoprotein (amino acids 412-423 and neutralizes a broad range of HCV genotypes. In a chimpanzee model, a single dose of 250 mg/kg HCV1 delivered 30 minutes prior to infusion with genotype 1a H77 HCV provided complete protection from HCV infection, whereas a dose of 50 mg/kg HCV1 did not protect. In addition, an acutely-infected chimpanzee given 250 mg/kg HCV1 42 days following exposure to virus had a rapid reduction in viral load to below the limit of detection before rebounding 14 days later. The emergent virus displayed an E2 mutation (N415K/D conferring resistance to HCV1 neutralization. Finally, three chronically HCV-infected chimpanzees were treated with a single dose of 40 mg/kg HCV1 and viral load was reduced to below the limit of detection for 21 days in one chimpanzee with rebounding virus displaying a resistance mutation (N417S. The other two chimpanzees had 0.5-1.0 log(10 reductions in viral load without evidence of viral resistance to HCV1. In vitro testing using HCV pseudovirus (HCVpp demonstrated that the sera from the poorly-responding chimpanzees inhibited the ability of HCV1 to neutralize HCVpp. Measurement of antibody responses in the chronically-infected chimpanzees implicated endogenous antibody to E2 and interference with HCV1 neutralization although other factors may also be responsible. These data suggest that human monoclonal antibody HCV1 may be an effective therapeutic for the prevention of graft infection in HCV-infected patients undergoing liver transplantation.

  5. Point-of-care testing for HCV infection: recent advances and implications for alternative screening.

    Science.gov (United States)

    Parisi, Maria Rita; Soldini, Laura; Vidoni, Gianmarino; Mabellini, Chiara; Belloni, Teresa; Brignolo, Livia; Negri, Silvia; Schlusnus, Karin; Dorigatti, Fernanda; Lazzarin, Adriano

    2014-10-01

    Over the last few years, hepatitis C virus (HCV) infection has emerged as one of the most significant causes of chronic liver disease worldwide, with an estimated prevalence ranging from 2.2 to 3.0%. In Italy, approximately 2% of subjects are infected with HCV. Considering that acute HCV infection is usually asymptomatic, early diagnosis is rare. Those people who develop chronic infection, even though undiagnosed, may suffer serious liver damage, making chronic HCV infection a major health problem. New initiatives are needed to identify a submerged portion of patients with chronic viral hepatitis and to propose controls and antiviral treatments to avoid the progression to liver cirrhosis or hepatocellular carcinoma (HCC). Since January 2011, the Infectious Diseases Department of San Raffaele Scientific Institute in Milan has been carrying out a prevention program called "EASY test project", using a new oral test, the OraQuick® HCV rapid antibody test (OraSure technologies, Inc.). The main objective of the project is to evaluate the acceptability of an alternative, free and anonymous HCV test offer, available in different settings (Points of Care, STDs Prevention clinics and General Practitioner clinics). From January 2011 to April 2014, 29,600 subjects were approached to inform them about HCV infection and other sexually transmitted diseases; 4,507 (15.2% of the contacted subjects) of them, total eligible volunteers, performed HCV tests on saliva and completed the interview in the alternative POCTs. Twenty-seven subjects (0.6% of the total) turned HCV oral test reactive (27/4.507) during the evaluation period; all of them were confirmed by conventional test. All 27 patients were asymptomatic and without a history of HCV-re- lated symptoms. The results from this analysis suggest that the promotion of alternative HCV test screening has not yet been fully developed as a strategy to increase levels of HCV testing among people at risk for HCV infection. Increasing

  6. 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.

  7. Total and high molecular weight adiponectin and hepatocellular carcinoma with HCV infection.

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    Shuji Sumie

    Full Text Available BACKGROUND: Adiponectin is shown to be inversely associated with development and progression of various cancers. We evaluated whether adiponectin level was associated with the prevalence and histological grade of hepatocellular carcinoma (HCC, and liver fibrosis in patients with hepatitis C virus (HCV infection. METHODS: A case-control study was conducted on 97 HCC patients (cases and 97 patients (controls matched for sex, Child-Pugh grade and platelet count in patients with HCV infection. The serum total and high molecular weight (HMW adiponectin levels were measured by enzyme-linked immunosorbent assays and examined in their association with the prevalence of HCC. In addition, the relationship between these adiponectin levels and body mass index (BMI, progression of liver fibrosis, and histological grade of HCC was also evaluated. Liver fibrosis was assessed using the aspartate aminotransferase to platelet ratio index (APRI. RESULTS: There were no significant differences in the serum total and HMW adiponectin levels between cases and controls. Moreover, there were no inverse associations between serum total and HMW adiponectin levels and BMI in both cases and controls. On the other hand, serum total and HMW adiponectin levels are positively correlated with APRI in both cases (r = 0.491, P<0.001 and r = 0.485, P<0.001, respectively and controls (r = 0.482, P<0.001 and r = 0.476, P<0.001, respectively. Interestingly, lower serum total (OR 11.76, 95% CI: 2.97-46.66 [P<0.001] and HMW (OR 10.24, CI: 2.80-37.40 [P<0.001] adiponectin levels were independent risk factors of worse histological grade of HCC. CONCLUSIONS: Our results suggested that serum total and HMW adiponectin levels were predictors of liver fibrosis, but not prevalence of HCC in patients with HCV infection. Moreover, low these adiponectin levels were significantly associated with worse histological grades.

  8. 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.

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

    Science.gov (United States)

    Bandeira, Larissa Melo; de Rezende, Grazielli Rocha; Dorisbor, Luiz Fernando Paiva; Tanaka, Tayana Serpa Ortiz; Cesar, Gabriela Alves; Novais, Alisson Richard Teixeira; Nepomuceno, Bruna; Castro, Lisie Souza; Motta-Castro, Ana Rita Coimbra

    2017-01-01

    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 (pprisoners, 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. PMID:28060860

  10. Toward a simple risk assessment screening tool for HCV infection in Egypt.

    Science.gov (United States)

    El-Ghitany, Engy M; Farghaly, Azza G; Abdel Wahab, Moataza M; Farag, Shehata; Abd El-Wahab, Ekram W

    2016-10-01

    Asymptomatic patients with HCV infection identified through screening program could benefit not only from treatment but also from other interventions such as counseling to maintain health and avoid risk behaviors. This might prevent the spread of infection and result in significant public health benefits. However, mass screening would quickly deplete resources. This work aims to develop a brief HCV risk assessment questionnaire that inquires initially about a wide range of risk factors found to be potentially associated with HCV infection in order to identify the few most significant questions that could be quickly used to facilitate cost-effective HCV case-finding in the general population in Egypt. An exhaustive literature search was done to include all reported HCV risk factors that were pooled in a 65 item questionnaire. After an initial pilot study, a case-control study was performed that included 1,024 cases and 1,046 controls. In a multivariable model, a list of independent risk factors were found to be significant predictors for being HCV seropositive among two age strata (45 years) for each gender. A simplified model that assigned values of the odds ratio as a weight for each factor present predicted HCV infection with high diagnostic accuracy. Attaining the defined cut-off value of the total risk score enhances the effectiveness of screening. HCV risk factors in the Egyptian population vary by age and gender. An accurate prediction screening tool can be used to identify those at high risk who may benefit most from HCV serologic testing. These results are to be further validated in a large scale cross-sectional study to assess the wider use of this tool. J. Med. Virol. 88:1767-1775, 2016. © 2016 Wiley Periodicals, Inc.

  11. Oral mucosa alterations in chronic hepatitis and cirrhosis due to HBV or HCV infection.

    Science.gov (United States)

    Sulka, Agnieszka; Simon, Krzysztof; Piszko, Paweł; Kalecińska, Ewa; Dominiak, Marzena

    2006-03-01

    The aim of the study was to evaluate the character of lesions within oral mucosa in patients suffering from chronic hepatitis and cirrhosis of the liver due to either HBV or HCV infection. A total of 74 patients treated at the Clinic of Infectious Diseases in Wrocław for chronic hepatitis B (20 patients, group I) and for chronic hepatitis C (23 patients group III) and cirrhosis of the liver due to HBV (15 patients , group II) and HCV (16 patients, group IV) infection. The control group comprised 29 healthy subjects. Lesions within the oral mucosa found on clinical examinations were confirmed with a histopathological evaluation. Patients suffering from chronic hepatitis B revealed leukoplakia (1/20), melanoplakia (1/20), petechiae (1/20), 17 patients from this group did not show any changes. Patients suffering from chronic hepatitis C revealed leukoplakia (6/23), Delbanco's disease (2/23), melanoplakia (1/23), lichen planus (1/23), petechiae (1/23), 12 patients from this group did not show any changes. Patients suffering from cirrhosis of the liver due of HBV infection revealed leukoplakia (3/15) petechiae (2/15), Delbanco's disease (1/15), angular cheilitis (1/15), aphthae (1/15), 7 patients from this group did not reveal any changes. Patients suffering from cirrhosis of the liver due of HCV infection revealed petechiae (2/16), melanoplakia (1/16), candidosis (1/16), labial herpes (1/16), 11 patients from this group did not reveal any changes. In control group we observed leukoplakia (3/29), Delbanco's disease (1/29), labial herpes (1/29), petechiae (1/29), and 23 subjects did not present pathological lesions within the oral mucosa. Results indicate the lack of connection between chronic HBV and HCV infection as well as the stage of the disease with the incidence and character of oral lesions in oral mucosa.

  12. Occurrence of occult HCV infection among Hiv infected patients in Georgia.

    Science.gov (United States)

    Gatserelia, L; Sharvadze, L; Karchava, M; Dolmazashvili, E; Tsertsvadze, T

    2014-01-01

    Occult hepatitis C (OCI) infection has been known as detectable HCV-RNA in the liver or peripheral blood mononuclear cells (PBMCs) in the absence of detectable serum or plasma HCV-RNA. OCI has been detected among different patients groups worldwide, it has been found not only in chronic hepatitis patients of unknown origin, but also among several groups at risk for HCV infection (hemodialysis patients or family members of patients with occult HCV). This occult infection has been reported also in healthy populations without evidence of liver disease. Prevalence of occult Hepatitis C virus has not been investigated in Georgian population, where a rate of HCV infection is highest (6.7%) among Eastern European Countries. The aim of this study was to investigate the occurrence of occult HCV infection among HIV infected individuals in Georgia. As a pilot study, we have selected three groups of HIV infected patients for analyses: Group 1- HIV infected patients without evidence of liver disease (n=98), group 2- HIV infected patients with cryptogenic liver disease (n=34) and group 3- HIV/HBV co infected patients (n=29). HCV RNA was tested in PBMCs samples by real-time polymerase chain reaction. HCV genotyping was performed by Line-probe assay based on reverse-hybridization technology. Liver fibrosis was evaluated by transient elastography (FibroScan®). HCV-RNA was detected in PBMCs specimens among 2 (2%) subjects from group 1, 4 (12%) subjects from group 2, and 9 (31%) subjects from group 3. HCV genotypes were determined for 14 of 15 OCI subjects resulting following genotype distribution: 6 (46%) - 1b, 3 (23%) - 2a/2c and 5 (38%) - 3a. One samples failed to be genotyped due to extremely low HCV viral load. Our data revealed the occurrence of occult HCV infection in HIV infected patients. No single HCV genotype was predominant in the present study. Liver fibrosis was found more frequently and the fibrosis score was significantly higher in OCI patients versus negative ones

  13. Treatment for hepatitis B virus (HBV) and hepatitis C virus (HCV) infection - Danish national guidelines 2011

    DEFF Research Database (Denmark)

    Christensen, Peer Brehm; Clausen, Mette Rye; Krarup, Henrik Bygum

    2012-01-01

    countries, probably infected at birth or early childhood in their country of origin, while the majority of patients with HCV infection have been infected by drug use. For both groups it is estimated that only half of the patients have been diagnosed, of whom only 20% attends specialized care...... for their chronic viral hepatitis. Clinical care: According to the Danish National Board of Health, patients with chronic viral hepatitis should be followed with regular intervals, at clinics specialized in either infectious diseases or gastroenterology/hepatology. The primary aim is to identify patients...

  14. Cryptococcal meningitis in a patient with chronic hepatitis C treated with pegylated-interferon and ribavirin.

    Science.gov (United States)

    Lee, Tae-Hee; Lee, Kee-Ook; Kim, Yong-Seok; Kim, Sun-Moon; Huh, Kyu-Chan; Choi, Young-Woo; Kang, Young-Woo

    2014-05-01

    Various adverse events have been reported during combination therapy with pegylated (PEG)-interferon-α and ribavirin, although opportunistic infections, especially cryptococcal meningitis, are very rare. A 61-year-old woman complained of headaches and a fever during treatment of a chronic hepatitis C virus (HCV) infection. She had been treated for 7 months. Her headaches were refractory to analgesics, and she developed subtle nuchal rigidity. The cerebral spinal fluid (CSF) revealed a white blood cell count of 205/mm(3), 51 mg/dL protein, 35 mg/dL glucose, and negative Cryptococcus antigen. The CSF culture resulted in no growth. Five days later, the CSF was positive for Cryptococcus antigen. We administered amphotericin B and flucytosine, followed by fluconazole. Approximately 2 months later, she was discharged. For the first time, we report a case of cryptococcal meningitis during the treatment of chronic HCV with PEG-interferon-α and ribavirin.

  15. A New Twist to a Chronic HCV Infection: Occult Hepatitis C

    Directory of Open Access Journals (Sweden)

    Bashar M. Attar

    2015-01-01

    Full Text Available Background. The prevalence of occult hepatitis C infection (OCI in the population of HCV-RNA negative but anti-HCV positive individuals is presently unknown. OCI may be responsible for clinically overt recurrent disease following an apparent sustained viral response (SVR weeks to years later. Purpose. To review the available current literature regarding OCI, prevalence, pathogenic mechanisms, clinical characteristics, and future directions. Data Sources. Searching MEDLINE, article references, and national and international meeting abstracts for the diagnosis of OCI (1990–2014. Data Synthesis. The long-term followup of individuals with an OCI suggests that the infection can be transient with the loss of detectable HCV-RNA in PPBMCs after 12–18 months or alternatively exist intermittently and potentially long term. The ultimate outcome of HCV infection is decided by interplay between host immune responses, antiviral therapies, and the various well-identified viral evasion mechanisms as well as the presence of HCV infection within extrahepatic tissues. Conclusion. The currently widely held assumption of a HCV-cure in individuals having had “SVR” after 8–12 weeks of a course of DAA therapy as recently defined may not be entirely valid. Careful longitudinal followup utilizing highly sensitive assays and unique approaches to viral isolation are needed.

  16. Absence of occult HCV infection in patients experiencing an immunodepression condition.

    Science.gov (United States)

    Pisaturo, Mariantonietta; Guastafierro, Salvatore; Filippini, Pietro; Tonziello, Gilda; Sica, Antonello; Di Martino, Filomena; Sagnelli, Caterina; Ferrara, Maria Giovanna; Martini, Salvatore; Cozzolino, Domenico; Sagnelli, Evangelista; Coppola, Nicola

    2013-12-01

    The aim of our study was to evaluate the presence of occult HCV infection in two settings of patients experiencing immunosuppression: patients with Human Immunodeficiency Virus (HIV) infection and those with onco-haematological disease. Sixty consecutive HIV-positive/anti-HCV-negative/HCV RNA-negative patients (HIV group) and 32 consecutive anti-HCV/HCV RNA negative patients with an onco-haematological disease first undergoing chemotherapy (Onco-haematological group) were enrolled. HCV-RNA was sought by real time RT-PCR in plasma and Peripheral Blood Mononuclear Cell (PBMC) samples obtained at enrolment and during follow-up, in the patients in the HIV group every three months and in those in the onco-haematological group at months 1 and 3 during chemotherapy and then every three months after treatment discontinuation. No plasma or PBMC sample collected at enrolment and during the follow-up in the HIV and onco-haematological groups was HCV RNA positive. The results of this study rule out the existence of occult HCV infection in patients with strong immunosuppression due to different conditions, HIV infection and onco-haematological diseases.

  17. A New Twist to a Chronic HCV Infection: Occult Hepatitis C.

    Science.gov (United States)

    Attar, Bashar M; Van Thiel, David

    2015-01-01

    Background. The prevalence of occult hepatitis C infection (OCI) in the population of HCV-RNA negative but anti-HCV positive individuals is presently unknown. OCI may be responsible for clinically overt recurrent disease following an apparent sustained viral response (SVR) weeks to years later. Purpose. To review the available current literature regarding OCI, prevalence, pathogenic mechanisms, clinical characteristics, and future directions. Data Sources. Searching MEDLINE, article references, and national and international meeting abstracts for the diagnosis of OCI (1990-2014). Data Synthesis. The long-term followup of individuals with an OCI suggests that the infection can be transient with the loss of detectable HCV-RNA in PPBMCs after 12-18 months or alternatively exist intermittently and potentially long term. The ultimate outcome of HCV infection is decided by interplay between host immune responses, antiviral therapies, and the various well-identified viral evasion mechanisms as well as the presence of HCV infection within extrahepatic tissues. Conclusion. The currently widely held assumption of a HCV-cure in individuals having had "SVR" after 8-12 weeks of a course of DAA therapy as recently defined may not be entirely valid. Careful longitudinal followup utilizing highly sensitive assays and unique approaches to viral isolation are needed.

  18. Arbidol: a broad-spectrum antiviral that inhibits acute and chronic HCV infection

    Directory of Open Access Journals (Sweden)

    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. Activation of unfolded protein response and autophagy during HCV infection modulates innate immune response.

    Science.gov (United States)

    Estrabaud, Emilie; De Muynck, Simon; Asselah, Tarik

    2011-11-01

    Autophagy, a process for catabolizing cytoplasmic components, has been implicated in the modulation of interactions between RNA viruses and their host. However, the mechanism underlying the functional role of autophagy in the viral life cycle still remains unclear. Hepatitis C virus (HCV) is a single-stranded, positive-sense, membrane-enveloped RNA virus that can cause chronic liver disease. Here we report that HCV induces the unfolded protein response (UPR), which in turn activates the autophagic pathway to promote HCV RNA replication in human hepatoma cells. Further analysis revealed that the entire autophagic process through to complete autolysosome maturation was required to promote HCV RNA replication and that it did so by suppressing innate antiviral immunity. Gene silencing or activation of the UPR-autophagy pathway activated or repressed, respectively, IFN-β activation mediated by an HCV-derived pathogen-associated molecular pattern (PAMP). Similar results were achieved with a PAMP derived from Dengue virus (DEV), indicating that HCV and DEV may both exploit the UPR-autophagy pathway to escape the innate immune response. Taken together, these results not only define the physiological significance of HCV-induced autophagy, but also shed light on the knowledge of host cellular responses upon HCV infection as well as on exploration of therapeutic targets for controlling HCV infection.

  20. IFN‐λ3 polymorphism indirectly influences NK cell phenotype and function during acute HCV infection

    Science.gov (United States)

    Depla, Marion; Pelletier, Sandy; Bédard, Nathalie; Brunaud, Camille; Bruneau, Julie

    2016-01-01

    Abstract Introduction Polymorphisms in the type III interferon IFN‐λ3 and the killer cell immunoglobulin‐like receptor (KIR) genes controlling the activity of natural killer (NK) cells can predict spontaneous resolution of acute hepatitis C virus (HCV) infection. We hypothesized that IFN‐λ3 polymorphism may modulate NK cell function during acute HCV. Methods We monitored the plasma levels of type III IFNs in relation to the phenotype and the function of NK cells in a cohort of people who inject drugs (PWID) during acute HCV infection with different outcomes. Results Early acute HCV was associated with high variability in type III IFNs plasma levels and the favorable IFN‐λ3 CC genotype was associated with higher viral loads. Reduced expression of Natural Killer Group Protein 2A (NKG2A) was associated with lower IFN‐λ3 plasma levels and the CC genotype. IFN‐γ production by NK cells was higher in individuals with the CC genotype during acute infection but this did not prevent viral persistence. IFN‐λ3 plasma levels did not correlate with function of NK cells and IFN‐λ3 prestimulation did not affect NK cell activation and function. Conclusions These results suggest that IFN‐λ3 polymorphism indirectly influences NK cell phenotype and function during acute HCV but other factors may act in concert to determine the outcome of the infection. PMID:27621819

  1. Risk-taking behavior and impulsivity among HCV-infected patients.

    Science.gov (United States)

    Dantas-Duarte, Adriana; Morais-de-Jesus, Mychelle; Nunes, Ana Paula; Miranda-Pettersen, Karine; Araújo-de-Freitas, Lucas; Netto, Liana R; Santos, Carlos Teles; Codes, Liana; Quarantini, Lucas C

    2016-09-30

    The association between risk behaviors and hepatitis C virus (HCV) has been extensively studied. It is also proved that impulsivity is associated with risk behaviors. However, there is a lack of studies investigating the association between HCV and impulsivity, a characteristic that can contribute directly to these risk behaviors. This study aimed to investigate HCV-infected individuals' impulsivity and whether this feature mediates risk behavior. Adult patients with liver diseases (n=269) were divided into two groups: viral group (n=157) - patients with HCV and nonviral group (n=112). Risk behaviors were evaluated by a sociodemographic questionnaire. Impulsivity was assessed through Barratt Impulsiveness Scale - BIS-11. Psychiatric comorbidities were investigated by the Mini International Neuropsychiatric Interview 5.0.0. The viral group patients had higher impulsivity than the nonviral group in all domains: attentional impulsivity, motor impulsivity, and nonplanning. Risk behaviors were also shown to be associated with impulsivity levels. Our results suggest that HCV-infected patients are more impulsive than individuals with other liver diseases, even when analyses are controlled for the presence of comorbid mental disorders. In addition, at-risk behavior was significantly mediated by impulsivity.

  2. Anti-retroviral drugs do not facilitate hepatitis C virus (HCV) infection in vitro.

    Science.gov (United States)

    Sandmann, Lisa; Wilson, Matthew; Back, David; Wedemeyer, Heiner; Manns, Michael P; Steinmann, Eike; Pietschmann, Thomas; von Hahn, Thomas; Ciesek, Sandra

    2012-10-01

    An estimated 4 to 5 million people are co-infected with HIV/HCV worldwide. Recently observed outbreaks of acute HCV infection among HIV-positive men who have sex with men (MSM) have been linked to behavioral factors such as high risk sexual practices and recreational drug use. However, at the molecular level, many drugs such as glucocorticoids or cyclosporine A have been found to modulate viral replication. Thus, it is conceivable that drugs used in highly active antiretroviral therapy (HAART) may heighten susceptibility to HCV infection and contribute to the recent outbreaks. We therefore performed a comprehensive screen of antiretroviral drugs covering all available drug classes both individually and in typical combinations used during HAART to probe for direct effects on HCV cell entry, replication, new particle assembly and release. Importantly, no significant enhancement or inhibition of HCV cell entry, replication or new particle production was detected. While raltegravir and ritonavir boosted atazanavir reduce HCV replication, a tenfold reduction of HCVcc entry by the CCR5 antagonist maraviroc was observed. In conclusion, commonly used HAART agents do not specifically enhance HCV replication. Thus recent epidemic outbreaks of acute HCV in HIV-infected MSM are unlikely to be related to enhancing effects of HAART drugs.

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

    Directory of Open Access Journals (Sweden)

    Katja Pfafferott

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  5. 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.

  6. Soluble egg antigen of Schistosoma Haematobium induces HCV replication in PBMC from patients with chronic HCV infection

    OpenAIRE

    2006-01-01

    Abstract Background This study was conducted to examine, in vitro , the effect of soluble egg antigen (SEA) of S. haematobium on intracellular HCV RNA load in peripheral mononuclear cells (PBMC) as well as on cell proliferation in patients with chronic HCV infection. Methods PBMC from 26 patients with chronic HCV infection were cultured for 72 hours in presence and absence of 50 μg SEA/ml medium. Intracellular HCV RNA quantification of plus and minus strands was assessed before and after stim...

  7. Daclatasvir with sofosbuvir and ribavirin for hepatitis C virus infection with advanced cirrhosis or post‐liver transplantation recurrence

    OpenAIRE

    Poordad, Fred; Schiff, Eugene R.; Vierling, John M.; Landis, Charles,A.; Fontana, Robert J.; Yang, Rong; McPhee, Fiona; Hughes, Eric A.; Noviello, Stephanie; Swenson, Eugene S.

    2016-01-01

    Chronic hepatitis C virus (HCV) infection with advanced cirrhosis or post‐liver transplantation recurrence represents a high unmet medical need with no approved therapies effective across all HCV genotypes. The open‐label ALLY‐1 study assessed the safety and efficacy of a 60‐mg once‐daily dosage of daclatasvir (pan‐genotypic NS5A inhibitor) in combination with sofosbuvir at 400 mg once daily (NS5B inhibitor) and ribavirin at 600 mg/day for 12 weeks with a 24‐week follow‐up in two cohorts of p...

  8. Treatment of glomerulonephritis associated with hepatitis C virus in patient with cirrhosis: only pegylated interferon and ribavirin

    Institute of Scientific and Technical Information of China (English)

    Adnan Ta(s); Erdem Ko(c)ak; Erdem Akbal; Seyfettin K(o)klü

    2011-01-01

    @@ To the editor: Hepatitis C virus (HCV) is a hepatotropic virus and a common cause of chronic hepatitis.Several extrahepatic complications have been associated with HCV including autoimmune and kidney diseases.It can cause a variety of extrahepatic immunological manifestations.1 Chronic HCV infection and cirrhosis are risk factors of a variety of extrahepatic diseases such as mixed cryoglobulinemia and membranoproliferative glomerulonephritis (MPGN).2 We presented a cirrhosis patient with mixed cryoglobulinemia (MC) associated with HCV; the diagnosis was made by renal biopsy and improved completely after interferon (IFN) and ribavirin treatment.

  9. Ribavirin at the Era of Novel Direct Antiviral Agents for the Treatment of Hepatitis C Virus Infection: Relevance of Pharmacological Monitoring

    Directory of Open Access Journals (Sweden)

    Pierre Pradat

    2014-01-01

    Full Text Available Ribavirin is often used for the treatment of hepatitis C virus (HCV infection. Although its mechanisms of action remain to be clearly elucidated, ribavirin plays a beneficial role for achieving virological response and decreasing the rate of virological relapse after treatment cessation. However, ribavirin may induce side effects leading to early treatment discontinuation. Among them, hemolytic anemia is the most frequent and results from intraerythrocyte accumulation. Pharmacological studies have shown that early ribavirin exposure assessed by the area under the curve (AUC at day 0 and ribavirin trough concentration during the first three months of therapy were correlated with sustained virological response (SVR. These studies highlighted the relevance of ribavirin pharmacologic monitoring and early dose adaptation during therapy. Although the role of ribavirin within new direct acting antiviral (DAA combinations will probably decrease in the future, its potential benefit in difficult-to-treat patients such as patients with severe hepatopathy or patients who failed triple therapy including patients with multiresistance will need to be further investigated.

  10. Serum albumin and mortality risk in a hyperendemic area of HCV infection in Japan

    Directory of Open Access Journals (Sweden)

    Sata Michio

    2010-12-01

    Full Text Available Abstract Background Hypoalbuminemia has been shown to be associated with increased mortality. We reported a mass screening in 1990 of X town in Japan, which demonstrated a high prevalence of hepatitis C virus (HCV infection. This follow-up study determined, through a period of 12 years, whether serum albumin levels impact on the life prognosis of the residents of X town. Results Of the 509 subjects, 69 had died and 55 had moved to other regions by 2002. Therefore, we analyzed 454 people for whom we could confirm life and death between 1990 and 2002. Albumin levels were assigned to two groups, low ( Conclusions We show that the serum albumin level is an independent risk factor for mortality from all causes in the residents of X town and an important prognostic indicator. Improvement of hypoalbuminaemia should be considered for improvement of prognosis.

  11. Changes in HIV RNA and CD4 cell count after acute HCV infection in chronically HIV-infected individuals

    NARCIS (Netherlands)

    Gras, L.; Wolf, F. de; Smit, C.; Prins, M.; Meer, J.T. van der; Vanhommerig, J.W.; Zwinderman, A.H.; Schinkel, J.; Geskus, R.B.; Warris, A.

    2015-01-01

    OBJECTIVE: Little is known about the impact of acute hepatitis C virus (HCV) co-infection on HIV-1 disease progression. We investigated CD4 cell count and HIV RNA concentration changes after HCV infection in individuals chronically infected with HIV-1. METHODS: We selected individuals that had the l

  12. The present and future disease burden of hepatitis C virus (HCV) infections with today's treatment paradigm - volume 2

    NARCIS (Netherlands)

    Hatzakis, A.; Chulanov, V.; Gadano, A. C.; Bergin, C.; Ben-Ari, Z.; Mossong, J.; Schreter, I.; Baatarkhuu, O.; Acharya, S.; Aho, I.; Anand, A. C.; Andersson, M. I.; Arendt, V.; Arkkila, P.; Barclay, K.; Bessone, F.; Blach, S.; Blokhina, N.; Brunton, C. R.; Choudhuri, G.; Cisneros, L.; Croes, E. A.; Dahgwahdorj, Y. A.; Dalgard, O.; Daruich, J. R.; Dashdorj, N. R.; Davaadorj, D.; de Knegt, R. J.; de Vree, M.; Estes, C.; Flisiak, R.; Gane, E.; Gower, E.; Halota, W.; Henderson, C.; Hoffmann, P.; Hornell, J.; Houlihan, D.; Hrusovsky, S.; Jarcuska, P.; Kershenobich, D.; Kostrzewska, K.; Kristian, P.; Leshno, M.; Lurie, Y.; Mahomed, A.; Mamonova, N.; Mendez-Sanchez, N.; Norris, S.; Nurmukhametova, E.; Nymadawa, P.; Oltman, M.; Oyunbileg, J.; Oyunsuren, Ts.; Papatheodoridis, G.; Pimenov, N.; Prabdial-Sing, N.; Prins, M.; Radke, S.; Rakhmanova, A.; Razavi-Shearer, K.; Reesink, H. W.; Ridruejo, E.; Safadi, R.; Sagalova, O.; Sanchez Avila, J. F.; Sanduijav, R.; Saraswat, V.; Seguin-Devaux, C.; Shah, S. R.; Shestakova, I.; Shevaldin, A.; Shibolet, O.; Silva, M. O.; Sokolov, S.; Sonderup, M.; Souliotis, K.; Spearman, C. W.; Staub, T.; Stedman, C.; Strebkova, E. A.; Struck, D.; Sypsa, V.; Tomasiewicz, K.; Undram, L.; van der Meer, A. J.; van Santen, D.; Veldhuijzen, I.; Villamil, F. G.; Willemse, S.; Zuckerman, E.; Zuure, F. R.; Puri, P.; Razavi, H.

    2015-01-01

    Morbidity and mortality attributable to chronic hepatitis C virus (HCV) infection are increasing in many countries as the infected population ages. Models were developed for 15 countries to quantify and characterize the viremic population, as well as estimate the number of new infections and HCV rel

  13. 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.

  14. Evaluation of Nitric Oxide (NO Levels in Hepatitis C Virus (HCV Infection: Relationship to Schistosomiasis and Liver Cirrhosis among Egyptian Patients

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    Mahmoud Ismail Hassan

    2002-01-01

    Full Text Available Nitric oxide (NO, a recently discovered free radical, is overproduced in liver cirrhosis. Hepatitis C virus (HCV might increase NO levels via increased inducible NO synthase (iNOS. This work was carried out to study the effect of HCV-induced liver cirrhosis on NO levels among Egyptian patients. The study included 46 patients with liver cirrhosis, and 30 healthy individuals of matched age and sex. NO levels determined as the stable endproduct nitrate, showed a statistically significant increase among patients compared to the control group (P < 0.001. Furthermore, NO levels increased proportionally with the severity of liver cirrhosis as assessed by Child’s classification (P < 0.05. Moreover, schistosomial infection enhanced NO levels in cirrhotic patients with HCV infection compared to non-bilharzial patients (P < 0.001. Polymerase chain reaction (PCR and branched DNA assays were used for detection of HCV RNA positivity, and measurement of the virus load, respectively. Both showed a positive correlation with the NO levels (P < 0.001. At a nitrate cutoff value of 70 μmol/L, the sensitivity and specificity were 83.0% and 37.0% respectively. Chi square analysis showed a significant correlation between ALT levels and both HCV RNA positivity by polymerase chain reaction (PCR (P < 0.02, and virus load (P < 0.05. Interestingly enough, there was a significant positive correlation between HCV RNA and schistosomal antibody titer as measured by hemaglutination inhibition assay (HAI (P < 0.05. The data presented in this report indicated an association between NO levels and the development and progression of liver cirrhosis. Furthermore, the findings obtained from this study demonstrated that schistomiasis is an important risk factor involved in enhancement of NO levels and virus replication. The latter may aggravate liver cell injury and hence the development of cirrhosis.

  15. Evaluation of Nitric Oxide (NO) Levels in Hepatitis C Virus (HCV) Infection: Relationship to Schistosomiasis and Liver Cirrhosis among Egyptian Patients

    Science.gov (United States)

    Hassan, Mahmoud Ismail; Kassim, Samar Kamal; Ali, Hebatalla Said; Sayed, El-Dieb Abd ElSattar; Khalifa, Ali

    2002-01-01

    Nitric oxide (NO), a recently discovered free radical, is overproduced in liver cirrhosis. Hepatitis C virus (HCV) might increase NO levels via increased inducible NO synthase (iNOS). This work was carried out to study the effect of HCV-induced liver cirrhosis on NO levels among Egyptian patients. The study included 46 patients with liver cirrhosis, and 30 healthy individuals of matched age and sex. NO levels determined as the stable endproduct nitrate, showed a statistically significant increase among patients compared to the control group (P < 0.001). Furthermore, NO levels increased proportionally with the severity of liver cirrhosis as assessed by Child’s classification (P < 0.05). Moreover, schistosomial infection enhanced NO levels in cirrhotic patients with HCV infection compared to non-bilharzial patients (P < 0.001). Polymerase chain reaction (PCR) and branched DNA assays were used for detection of HCV RNA positivity, and measurement of the virus load, respectively. Both showed a positive correlation with the NO levels (P < 0.001). At a nitrate cutoff value of 70 μmol/L, the sensitivity and specificity were 83.0% and 37.0% respectively. Chi square analysis showed a significant correlation between ALT levels and both HCV RNA positivity by polymerase chain reaction (PCR) (P < 0.02), and virus load (P < 0.05). Interestingly enough, there was a significant positive correlation between HCV RNA and schistosomal antibody titer as measured by hemaglutination inhibition assay (HAI) (P < 0.05). The data presented in this report indicated an association between NO levels and the development and progression of liver cirrhosis. Furthermore, the findings obtained from this study demonstrated that schistomiasis is an important risk factor involved in enhancement of NO levels and virus replication. The latter may aggravate liver cell injury and hence the development of cirrhosis. PMID:12515909

  16. Analysis of the factors motivating HCV-infected patients to accept interferon therapy

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    Nagao Yumiko

    2012-08-01

    Full Text Available Abstract Background The aims of this study were to analyze factors motivating the acceptance of interferon (IFN therapy and to clarify the prevalence of oral mucosal diseases in hepatitis C virus (HCV-infected Japanese patients treated with IFN. Findings A total of 94 HCV-infected patients who were admitted to our hospital for IFN therapy were asked questions regarding their motivation to accept IFN therapy and were investigated for the presence of oral lichen planus (OLP before and during IFN treatment. Recommendation and encouragement from other people were the most common factors motivating the acceptance of IFN therapy (49/94, 52.13%. The other motivators were independent decision (30.85%, economic reasons (5.32%, and others. According to multivariate analysis, three factors – sex (male, retreatment after previous IFN therapy, and independent decision to accept IFN therapy - were associated with patients after curative treatment of hepatocellular carcinoma (HCC. The adjusted odds ratios for these three factors were 26.06, 14.17, and 8.72, respectively. The most common oral mucosal lesions included OLP in 11 cases (11.70%. One patient with OLP had postoperative squamous cell carcinoma of the tongue. The rate of sustained virological response (SVR was 45.45% in cases with OLP and 54.55% in cases without OLP. There were no patients who discontinued IFN therapy because of side effects such as oral mucosal diseases. Conclusions We should give full explanation and recommend a course of treatment for a patient to accept IFN therapy. The system to support liver disease as well as oral diseases is also necessary for patient treated for IFN therapy.

  17. Prevalence, genotypes and factors associated with HCV infection among prisoners in Northeastern Brazil

    Science.gov (United States)

    de Oliveira Santos, Bruno Fernandes; de Santana, Nathalie Oliveira; Franca, Alex Vianey Callado

    2011-01-01

    AIM: To determine hepatitis C virus (HCV) seroprevalence and its genotypes, and to identify the factors associated with HCV infection. METHODS: This cross-sectional study, conducted in two prisons (one male and one female) in the State of Sergipe, Brazil, comprised 422 subjects. All of the prisoners underwent a rapid test for the detection of HCV antibodies. Patients with a positive result were tested for anti-HCV by enzyme linked immunosorbent assay and for HCV RNA by qualitative polymerase chain reaction (PCR). The virus genotype was defined in every serum sample that presented positive for PCR-HCV. In order to determine the factors independently associated with positive serology for HCV, multivariate logistic regression was used. RESULTS: HCV seroprevalence was 3.1%. Of the 13 subjects with positive anti-HCV, 11 had viremia confirmed by PCR. Of these, 90.9% had genotype 1. A total of 43 (10.2%) were injecting drug users, and HCV seroprevalence in this subgroup was 20.6%. The variable most strongly associated with positive serology for HCV was use of injecting drugs [odds ratio (OR), 23.3; 95% confidence interval (CI), 6.0-90.8]. Age over 30 years (OR, 5.5; 95%CI, 1.1-29.2), history of syphilis (OR, 9.8; 95%CI, 1.7-55.2) and history of household contact with HCV positive individual (OR, 14.1; 95%CI, 2.3-85.4) were also independently associated with HCV infection. CONCLUSION: Most of the HCV transmissions result from parenteral exposure. However, there is evidence to suggest a role for sex and household contact with an infected subject in virus transmission. PMID:21799649

  18. Lipoprotein lipase inhibits hepatitis C virus (HCV infection by blocking virus cell entry.

    Directory of Open Access Journals (Sweden)

    Patrick Maillard

    Full Text Available A distinctive feature of HCV is that its life cycle depends on lipoprotein metabolism. Viral morphogenesis and secretion follow the very low-density lipoprotein (VLDL biogenesis pathway and, consequently, infectious HCV in the serum is associated with triglyceride-rich lipoproteins (TRL. Lipoprotein lipase (LPL hydrolyzes TRL within chylomicrons and VLDL but, independently of its catalytic activity, it has a bridging activity, mediating the hepatic uptake of chylomicrons and VLDL remnants. We previously showed that exogenously added LPL increases HCV binding to hepatoma cells by acting as a bridge between virus-associated lipoproteins and cell surface heparan sulfate, while simultaneously decreasing infection levels. We show here that LPL efficiently inhibits cell infection with two HCV strains produced in hepatoma cells or in primary human hepatocytes transplanted into uPA-SCID mice with fully functional human ApoB-lipoprotein profiles. Viruses produced in vitro or in vivo were separated on iodixanol gradients into low and higher density populations, and the infection of Huh 7.5 cells by both virus populations was inhibited by LPL. The effect of LPL depended on its enzymatic activity. However, the lipase inhibitor tetrahydrolipstatin restored only a minor part of HCV infectivity, suggesting an important role of the LPL bridging function in the inhibition of infection. We followed HCV cell entry by immunoelectron microscopy with anti-envelope and anti-core antibodies. These analyses demonstrated the internalization of virus particles into hepatoma cells and their presence in intracellular vesicles and associated with lipid droplets. In the presence of LPL, HCV was retained at the cell surface. We conclude that LPL efficiently inhibits HCV infection by acting on TRL associated with HCV particles through mechanisms involving its lipolytic function, but mostly its bridging function. These mechanisms lead to immobilization of the virus at the cell

  19. Prevalence, genotypes and factors associated with HCV infection among prisoners in Northeastern Brazil

    Institute of Scientific and Technical Information of China (English)

    Bruno Fernandes de Oliveira Santos; Nathalie Oliveira de Santana; Alex Vianey Callado Franca

    2011-01-01

    AIM: To determine hepatitis C virus (HCV) seroprevalence and its genotypes, and to identify the factors associated with HCV infection. METHODS: This cross-sectional study, conducted in two prisons (one male and one female) in the State of Sergipe, Brazil, comprised 422 subjects. All of the prisoners underwent a rapid test for the detection of HCV antibodies. Patients with a positive result were tested for anti- HCV by enzyme linked immunosorbent assay and for HCV RNA by qualitative polymerase chain reaction (PCR). The virus genotype was defined in every serum sample that presented positive for PCR-HCV. In order to determine the factors independently associated with positive serology for HCV, multivariate logistic regression was used. RESULTS: HCV seroprevalence was 3.1%. Of the 13 subjects with positive anti-HCV, 11 had viremia confirmed by PCR. Of these, 90.9% had genotype 1. A total of 43 (10.2%) were injecting drug users, and HCV seroprevalence in this subgroup was 20.6%. The variable most strongly associated with positive serology for HCV was use of injecting drugs [odds ratio (OR), 23.3; 95% confidence interval (CI), 6.0-90.8]. Age over 30 years (OR, 5.5; 95%CI, 1.1-29.2), history of syphilis (OR, 9.8; 95%CI, 1.7-55.2) and history of household contact with HCV positive individual (OR, 14.1; 95%CI, 2.3-85.4) were also independently associated with HCV infection. CONCLUSION: Most of the HCV transmissions result from parenteral exposure. However, there is evidence to suggest a role for sex and household contact with an infected subject in virus transmission.

  20. Effect of interferon therapy on radionuclide imaging in chronic liver diseases due to HCV infection

    Energy Technology Data Exchange (ETDEWEB)

    Ghaffar, Y.; Dorgham, L.; Lotfy, N. [Ain Shams Univ., Imbaba, Giza (Egypt)]|[Menofia Unif., Shebin El Kom (Egypt)] [and others

    1995-09-01

    Interferon (alpha-IFN) exerts a modulating effect on the immune system. Kupffer cells of the liver play an important immunological role by their uptake of various agents and particles, including colloids. We sought to discover if alpha-IFN could enhance the colloid uptake function of the Kupffer cells. The effect of alpha-IFN therapy on radioisotope scans of the liver was studied in 20 patients with chronic liver disease due to hepatitic C virus (HCV) infection who received therapy at a dose of 3 million IU for 6 mo, in another patients who received the same therapy for 12 mo and in matched control groups (10 patients with HCV infection for each study group) who did not received alpha-IFN. A {sup 99m}Tc-sulfur colloid scan of the liver was obtained for each group before and after therapy and, for control subjects, at the start and end of the study periods. The liver-to-spleen geometric mean ratio of colloid uptake was assessed. In the first study group, the mean rate of improvement in the liver-to-spleen ratio was 48% in 70% of the patients, compared to 8% in 20% of controls (p<0.05). In the second study group, mean liver-to-spleen ratio was 88% in 85% of patients, compared to 12% in 40% of controls (p<0.001). Alpha-IFN therapy appears to enhance the colloidal uptake function of Kupffer cells, which adds a new dimension to the immunomodulatory effect of interferon. 13 refs., 2 tabs.

  1. Incidence of recent HCV infection among persons seeking voluntary counselling and testing for HIV and sexually transmitted infections in Taiwan

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    Yi-Ching Su

    2014-11-01

    Full Text Available Introduction: The incidence of recent hepatitis C virus infection (HCV infection has been noted to be increasing among men who have sex with men (MSM, especially those with HIV infection, in several resource-rich settings. In Taiwan, the incidence of recent HCV infection increased from 0 in 1994–2000, 2.29 in 2001–2005 to 10.13 per 1000 person-years of follow-up (PYFU in 2006–2010. In this study, we aimed to estimate the incidence rate of recent HCV infection among those individuals who sought voluntary counselling and testing (VCT service at a University Hospital. Methods: Between May 2006 and December 2013, 18,246 tests for HIV antibody were performed among 12,143 individuals at the VCT services. A total of 2157 clients without HIV or HCV infection at baseline were included for estimation of incidence rate of recent HCV infection. Antibodies to HCV were determined with a third-generation enzyme immunoassay. A nested case-control study with four matched controls without HCV seroconversion for one HCV seroconverter was conducted to investigate the factors associated with recent HCV infection. Phylogenetic analysis was performed among the HCV strains obtained from VCT clients and patients coinfected with HIV and HCV between 2006 and 2013. Results: During the study period, 2157 clients received a total of 8260 tests. The HCV seroprevalence at baseline was 0.3%. Of the 2150 HCV-negative clients who contributed 5074.99 PYFU, 17 developed HCV seroconversion (incidence rate, 3.35 per 1000 PYFU; 95% CI, 1.76–4.94; the rate increased from 2.28 per 1000 PYFU (95% CI, 0.05–4.51 in 2006–2009, to 3.33 per 1000 PYFU (95% CI, 0.86–5.80 in 2010–2011, to 4.94 per 1000 PYFU (95% CI, 0.99–8.99 in 2012–2013. In case-control study, HCV seroconverters were more likely to have HIV-infected partners, recent syphilis and a Rapid Plasma Reagin (RPR titre of 4 or greater. In multivariate analysis, having HIV-infected partners remained as the only

  2. The Impact of HCV Infection Duration on HIV Disease Progression and Response to cART amongst HIV Seroconverters in the UK.

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    Jamie Inshaw

    Full Text Available The effect of HCV infection on HIV disease progression remains unclear; the effect of HCV infection duration on HIV disease progression is unknown.We used data from a cohort of HIV seroconverters to investigate the effect of HCV infection duration on time from HIV seroconversion to CD4 4 years. We additionally compared CD4 cell decline following HCV infection to that of mono-infected individuals with similar HIV infection duration by fitting a random effects model. In a separate analysis, we used linear mixed models to we examine the effect of HCV infection and its duration on CD4 increase over 48 weeks following cART.Of 1655 individuals, 97 (5.9% were HCV co-infected. HCV4 years respectively, compared to mono-infected individuals. However, we found no evidence of an association for those with HCV>2 years (all p>0.89. Individuals experienced a somewhat greater decrease in CD4 count following HCV infection lasting 13 months, relative to individuals with HIV alone, (estimate = -3.33, 95% CI [-7.29, 0.63] cells/mm3 per month, p = 0.099. Of 1502 initiating cART, 106 (7.1% were HCV co-infected, with no evidence of HCV duration at cART being associated with immunological response (p = 0.45.The impact of HCV co-infection on HIV disease progression appears to be restricted to the first year after HCV infection.

  3. Host-specific response to HCV infection in the chimeric SCID-beige/Alb-uPA mouse model: role of the innate antiviral immune response.

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    Kathie-Anne Walters

    2006-06-01

    Full Text Available The severe combined immunodeficiency disorder (SCID-beige/albumin (Alb-urokinase plasminogen activator (uPA mouse containing a human-mouse chimeric liver is currently the only small animal model capable of supporting hepatitis C virus (HCV infection. This model was utilized to characterize the host transcriptional response to HCV infection. The purpose of these studies was to investigate the genetic component of the host response to HCV infection and also to distinguish virus-induced gene expression changes from adaptive HCV-specific immune-mediated effects. Gene expression profiles from HCV-infected mice were also compared to those from HCV-infected patients. Analyses of the gene expression data demonstrate that host factors regulate the response to HCV infection, including the nature of the innate antiviral immune response. They also indicate that HCV mediates gene expression changes, including regulation of lipid metabolism genes, which have the potential to be directly cytopathic, indicating that liver pathology may not be exclusively mediated by HCV-specific adaptive immune responses. This effect appears to be inversely related to the activation of the innate antiviral immune response. In summary, the nature of the initial interferon response to HCV infection may determine the extent of viral-mediated effects on host gene expression.

  4. Management of cirrhotic ascites

    DEFF Research Database (Denmark)

    Pedersen, Julie Steen; Bendtsen, Flemming; Møller, Søren

    2015-01-01

    The most common complication to chronic liver failure is ascites. The formation of ascites in the cirrhotic patient is caused by a complex chain of pathophysiological events involving portal hypertension and progressive vascular dysfunction. Since ascites formation represents a hallmark in the na......The most common complication to chronic liver failure is ascites. The formation of ascites in the cirrhotic patient is caused by a complex chain of pathophysiological events involving portal hypertension and progressive vascular dysfunction. Since ascites formation represents a hallmark...... in the natural history of chronic liver failure it predicts a poor outcome with a 50% mortality rate within 3 years. Patients with ascites are at high risk of developing complications such as spontaneous bacterial peritonitis, hyponatremia and progressive renal impairment. Adequate management of cirrhotic...

  5. Upregulation of SOCS-3 and PIAS-3 impairs IL-12-mediated interferon-gamma response in CD56 T cells in HCV-infected heroin users.

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    Li Ye

    Full Text Available BACKGROUND: CD56(+ T cells are abundant in liver and play an important role in host innate immunity against viral infections, including hepatitis C virus (HCV infection, a common infection among heroin abusers. We thus investigated the in vivo impact of heroin use or heroin use plus HCV infection on the CD56(+ T cell frequency and function. METHODOLOGY/PRINCIPAL FINDINGS: A total of 37 heroin users with (17 or without (20 HCV infection and 17 healthy subjects were included in the study. Although there was no significant difference in CD56(+ T cell frequency in PBMCs among three study groups, CD56(+ T cells isolated from the heroin users had significantly lower levels of constitutive interferon-gamma (IFN-gamma expression than those from the normal subjects. In addition, when stimulated by interleukin (IL-12, CD56(+ natural T cells from HCV-infected heroin users produced significantly lower levels of IFN-gamma than those from the normal subjects. This diminished ability to produce IFN-gamma by CD56(+ T cells was associated with the increased plasma HCV viral loads in the HCV-infected heroin users. Investigation of the mechanisms showed that although heroin use or heroin use plus HCV infection had little impact on the expression of the key positive regulators (IL-12 receptors, STAT-1, 3, 4, 5, JAK-2, and TYK-2 in IL-12 pathway, heroin use or heroin use plus HCV infection induced the expression of suppressor of cytokine signaling protein-3 (SOCS-3 and protein inhibitors of activated STAT-3 (PIAS-3, two key inhibitors of IL-12 pathway. CONCLUSION/SIGNIFICANCE: These findings provide compelling in vivo evidence that heroin use or heroin use plus HCV infection impairs CD56(+ T cell-mediated innate immune function, which may account for HCV infection and persistence in liver.

  6. [Efficacy of combined antiviral therapy with interferon alfa and ribavirin in chronic hepatitis C patients with extrahepatic manifestations].

    Science.gov (United States)

    Zarebska-Michaluk, Dorota; Lebensztejn, Dariusz Marek; Kryczka, Wiesław

    2007-01-01

    The aim of the study was to assess the efficacy and safety of treatment with interferon alpha and ribavirin in patients with chronic hepatitis C and extrahepatic manifestations as well as to determine prognostic factors of therapy effectiveness. 179 consecutive naive patients with chronic hepatitis C treated with interferon alpha and ribavirin were studied. 120 patients (67%) presented extrahepatic manifestations. The most frequent were cryoglobulinaemia, thrombocytopenia and thyroid gland pathology. Efficacy of antiviral treatment was lower (SVR 33.3% vs. 52.5%, p=0.013) and frequency of adverse events higher in patients with chronic hepatitis C and extrahepatic manifestations in comparison to those without extrahepatic pathology. Younger age, shorter duration of HCV infection and less advanced liver fibrosis were prognostic factors of better response to antiviral therapy in group of patients with chronic hepatitis C and extrahepatic manifestations.

  7. Efficacy of combined antiviral therapy with pegylated interferon α-2a and ribavirin for chronic hepatitis C infection in intravenous drug users

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    Ružić Maja

    2010-01-01

    Full Text Available Introduction. Hepatitis C Virus infection represents not just a medical, but also a socio-economic problem. It is estimated that among 170 million infected, 60% belongs to the category of intravenous drug users (IDUs. Objective. The aim of this paper was to compare the response to the combined therapy of pegylated interferon alfa 2a and ribavirin, in the group of patients with HCV infection who were intravenous drug users (IDUs and in patients who were identified in the other way of transmission of HCV. Also to identify the influence of the therapy on diseases of addiction, during the course of HCV infection and on the effects of the combined therapy of pegylated interferon alfa 2a and ribavirin. Methods. We conducted a retrospective-prospective study, on 60 patients, treated with combined antiviral therapy-pegylated interferon alfa 2a and ribavirin. 30 patients were from the group of IDUs, and 30 patients from other epidemiological groups. Results. There were significant differences between the age of the patients (30.2±7.1 vs. 39.3±11.2 years; p=0.002, but no significant difference in the duration of the HCV infection between the two groups of patients (8.9±7.4 vs. 13.1±7.0 years; p>0.05. A large number of the patients in the group of IDUs had a problem with the abstinence of the drug abuse. In this group, there was the influence of alcohol (30% and other substances with potential hepatotoxicity: marihuana (23.3% and psycho-active drugs (73.6%. Staging of the liver fibrosis was not influenced by those two parameters and was similar in both groups (p>0.05. The genotype 3a was dominant in intravenous drug users (50.0% and genotype 1b in the control group of the patients (76.6%. In both groups, SVR was achieved at a higher percentage (86% vs. 70.00%; p>0.05, but among the intravenous drug users the relapses of HCV infection were at a lower percentage (3.3% vs. 20.0%; p=0.044. Side effects were noticed in solitary cases in both of the examined

  8. [Spontaneous remission of HCV infection after autologous stem cell transplantation in a 58-year-old man].

    Science.gov (United States)

    Reinhardt, L; Eiffert, H; Wulf, G; Ströbel, P; Bremer, S C B; Amanzada, A; Ellenrieder, V; Neesse, A

    2017-02-24

    We report about a 58-year-old man with a chronic and treatment-naive hepatitis C virus (HCV) infection of genotype 1b, who had undergone autologous stem cell transplantation twice due to multiple myeloma. Subsequently, a high-level viremic reactivation of an occult hepatitis B virus (HBV) infection and also a reverse seroconversion was observed. Furthermore, a sustained spontaneous remission of HCV infection was seen. Antiviral therapy of HBV infection was initiated with tenofovir. Seven months after therapy initiation, the patient acquired an "anti-HBc-only" status. Antiviral therapy with tenofovir is still continued. The patient is in a good clinical condition.

  9. Prevalence of HCV infection and associated factors among illicit drug users in Breves, State of Pará, northern Brazil

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    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.

  10. Detection of occult hepatitis C virus among healthy spouses of patients with HCV infection.

    Science.gov (United States)

    El Shazly, Yahia; Hemida, Khaled; Rafik, Mona; Al Swaff, Reham; Ali-Eldin, Zainab A; GadAllah, Shaimaa

    2015-03-01

    The criterion standard for the diagnosis of occult hepatitis C virus (HCV) infection is detection of HCV-RNA in liver cells. However, because of the invasive nature of liver biopsy, other methods have been studied. The present study aimed to identify subjects with occult HCV-4 infection among healthy sexual partners of patients with chronic HCV-4 infection by detecting HCV-RNA in peripheral blood mononuclear cells (PBMCs) using real-time polymerase chain reaction (PCR). Fifty healthy Egyptian spouses of patients with chronic HCV-4 infection were included in this study. Real-time PCR was used to detect HCV-RNA in PBMCs in all the study subjects. The prevalence of occult HCV-4 infection was 4%, and a statistically significant higher prevalence was found among patients with a history of sexually transmitted infection. The results of the present study indicate the importance of intra-spousal transmission of HCV-4 infection, especially in subjects with a history of sexually transmitted infection.

  11. Association of genotypes with viral load and biochemical markers in HCV-infected Sindhi patients

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    Saba Riaz

    Full Text Available Abstract The presented study had two objectives. The first was to examine distributions of Hepatitis C Virus (HCV genotypes in Sindh, Pakistan, where HCV is prevalent. The other was to explore clinically relevant relationships between the genotypes, viral load (measured by real-time polymerase chain reaction assays and biochemical markers. For this, 1471 HCV-infected patients in six cities in Sindh were recruited and sampled. HCV genotype distributions varied among the cities, but genotype 3a was most prevalent, followed by 3b, 1a and 1b (detected in 51.5, 22.7. 9.25 and 3.2% of the cases, respectively. No type-specific sequences were detected in serum samples from 189 (12.8% of the 1471 patients. Frequencies of low (600,000 IU/mL serum viral loads were respectively 45.4, 16.5 and 38.1% for patients infected with genotype 3, and 16.9, 36.9 and 46.2%, respectively, for patients with other genotypes. Infection with genotype 1a was associated with significantly higher (p < 0.005 alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase titers than infection with genotype 3a. The results will help in the formulation of treatment strategies.

  12. Impact of psychiatric disorders on the quality of life of brazilian HCV-infected patients

    Directory of Open Access Journals (Sweden)

    Susana Batista-Neves

    2009-02-01

    Full Text Available The aim of our study was to determine the impact of psychiatric comorbidities on the health-related quality of life of HCV-infected patients. Assessment of clinical, socio-demographic and quality of life data of the patients followed up at a Hepatology unit was performed by using a standard questionnaire and the SF-36 instrument. Psychiatric diagnoses were confirmed by using the Mini International Neuropsychiatric Interview, Brazilian version 5.0.0 (MINI Plus. Evaluation using the MINI plus demonstrated that 46 (51% patients did not have any psychiatric diagnosis, while 44 (49% had at least one psychiatric diagnosis. Among patients with a psychiatric comorbidity, 26 (59.1% had a current mental disorder, out of which 22 (84.6% had not been previously diagnosed. Patients with psychiatric disorders had lower scores in all dimensions of the SF-36 when compared to those who had no psychiatric diagnosis. Scores of physical functioning and bodily pain domains were lower for those suffering from a current psychiatric disorder when compared to those who had had a psychiatric disorder in the past. Females had lower scores of bodily pain and mental health dimensions when compared to males. Scores for mental health dimension were also lower for patients with advanced fibrosis. The presence of a psychiatric comorbidity was the variable that was most associated with the different scores in the SF-36, compared to other variables such as age, gender, aminotransferase levels, and degree of fibrosis.

  13. Prevalence of oral lichen planus in HCV infected patients: the effective factors

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    Khatibi M

    2008-11-01

    Full Text Available "nBackground: Hepatitis C is a major cause of chronic liver disease and hepatocellular carcinoma. Hepatitis C infection also has extrahepatic manifestations, including cryoglobulinemia and lichen planus. Lichen planus is a relatively common mucocutaneous disorder, and, due to its chronic pattern and increased incidence of malignancy, diagnosis and treatment of this disease are very important. The aim of the present study was to investigate the prevalence of oral lichen planus in HCV-infected patients. "nMethods: In this cross sectional- descriptive study, the prevalence of oral lichen planus was evaluated by means of observation, clinical examination, questionnaire and evaluation of the medical records of 150 patients referred to the hepatitis clinic, gastrointentrology and infectious disease wards of Imam Khomeini Hospital and the Iran Blood Transfusion Organization, Tehran, Iran. We used a sequential method for sampling. Data were analyzed using statistical software (SPSS ver. 11 and the chi-square test. "nResults: From a total 150 patients, 133 were male and 17 female. Six cases (4% had oral lichen planus. All patients with oral lichen planus were male and the buccal mucosa was the most common site. "nConclusions: According to this study, the prevalence of oral lichen planus in patients afflicted with HCV is higher than in the normal population. We should pay more attention to oral lichen planus as one of the extrahepatic manifestations of hepatitis C.

  14. A phase 3b study of sofosbuvir plus ribavirin in treatment-naive and treatment-experienced Korean patients chronically infected with genotype 2 hepatitis C virus.

    Science.gov (United States)

    Ahn, S H; Lim, Y S; Lee, K S; Paik, S W; Lee, Y J; Jeong, S H; Kim, J H; Yoon, S K; Yim, H J; Tak, W Y; Han, S Y; Yang, J C; Mo, H; Mathias, A; Han, L; Knox, S J; Brainard, D M; Kim, Y J; Byun, K S; Kim, Y S; Heo, J; Han, K H

    2016-05-01

    In Korea, patients with chronic hepatitis C virus (HCV) infection are typically treated with pegylated interferon-alpha plus ribavirin, but interferons are contraindicated in many patients and are often poorly tolerated, particularly by the elderly and those with advanced liver disease. No interferon-free treatment regimens are approved in Korea. Sofosbuvir is an oral nucleotide analog inhibitor of the HCV nonstructural 5B RNA polymerase. It is approved in the USA, European Union and Japan for treating a number of HCV genotypes, including genotype 2. Genotype 2 has a seroprevalence of 38-46% in Korea. This single-arm, phase 3b study (NCT02021643) examined the efficacy and safety of sofosbuvir plus ribavirin (12-week duration) in chronic genotype 2 HCV-infected treatment-naive and treatment-experienced Korean patients with and without cirrhosis. The proportion of patients with sustained virologic response 12 weeks after treatment discontinuation (SVR12) was 97% (125/129), with 96% (101/105) of treatment-naive and 100% (24/24) of treatment-experienced patients achieving SVR12. Two patients experienced virologic failure (n = 1, on-treatment failure; n = 1, relapse). No patient discontinued study treatment due to an adverse event (AE). The most common treatment-emergent AEs were headache (18%, 23/129) and pruritus (15%, 19/129). Few patients had grade 3 AEs (5%, 6/129) or grade 3 laboratory abnormalities (12%, 15/129). No grade 4 AE was reported. These data suggest that 12 weeks of treatment with the all-oral, interferon-free regimen of sofosbuvir plus ribavirin is effective and well tolerated in Korean patients with chronic genotype 2 HCV infection.

  15. Superior outcomes in HIV-positive kidney transplant patients compared with HCV-infected or HIV/HCV-coinfected recipients.

    Science.gov (United States)

    Sawinski, Deirdre; Forde, Kimberly A; Eddinger, Kevin; Troxel, Andrea B; Blumberg, Emily; Tebas, Pablo; Abt, Peter L; Bloom, Roy D

    2015-08-01

    The prerequisite for an 'undetectable' HIV viral load has restricted access to transplantation for HIV-infected kidney recipients. However, HCV-infected recipients, owing to the historic limitations of HCV therapy in patients with renal disease, are commonly viremic at transplant and have universal access. To compare the effect of HIV, HCV, and HIV/HCV coinfection on kidney transplant patient and allograft outcomes, we performed a retrospective study of kidney recipients transplanted from January 1996 through December 2013. In multivariable analysis, patient (hazard ratio 0.90, 95% confidence interval 0.66-1.24) and allograft survival (0.60, 40-0.88) in 492 HIV patients did not differ significantly from the 117,791 patient-uninfected reference group. This was superior to outcomes in both the 5605 patient HCV group for death (1.44, 1.33-1.56) and graft loss (1.43, 1.31-1.56), as well as the 147 patient HIV/HCV coinfected group for death (2.26, 1.45-3.52) and graft loss (2.59, 1.60-4.19). HIV infection did not adversely affect recipient or allograft survival and was associated with superior outcomes compared with both HCV infection and HIV/HCV coinfection in this population. Thus, pretransplant viral eradication and/or immediate posttransplant eradication should be studied as potential strategies to improve posttransplant outcomes in HCV-infected kidney recipients.

  16. Sustained Virological Response after 8-Week Treatment of Simeprevir with Peginterferon α-2a plus Ribavirin in a Japanese Female with Hepatitis C Virus Genotype 1b and IL28B Minor Genotype

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    Tatsuo Kanda

    2015-07-01

    Full Text Available Direct-acting antivirals with or without peginterferon α (PEG-IFN α plus ribavirin are now available for the treatment of hepatitis C virus (HCV infection. Direct-acting antivirals are potent inhibitors of HCV replication, but some of them occasionally possess serious adverse events. We experienced a 64-year-old female with chronic HCV genotype 1b infection who showed elevated alanine aminotransferase of 528 IU/l at week 9 after the commencement of treatment of simeprevir with PEG-IFN α-2a plus ribavirin. However, she achieved sustained virological response at week 24 after the end of treatment. In Japan, we also have to treat elderly patients infected with HCV and/or advanced hepatic fibrosis. Until an effective interferon-free regimen is established, direct-acting antivirals with PEG-IFN plus ribavirin may still play a role in the treatment for certain patients. To avoid serious results from adverse events, careful attention and follow-up will be needed in the treatment course of simeprevir with PEG-IFN plus ribavirin for chronic HCV infection.

  17. Combined hepatitis C virus (HCV) antigen-antibody detection assay does not improve diagnosis for seronegative individuals with occult HCV infection.

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    Quiroga, Juan A; Castillo, Inmaculada; Pardo, Margarita; Rodríguez-Iñigo, Elena; Carreño, Vicente

    2006-12-01

    A combined hepatitis C virus (HCV) antigen-antibody assay was evaluated for 115 seronegative individuals with occult HCV infection. The assay was reactive in one patient and negative to weakly reactive in three others (all four gave indeterminate results by supplemental assay) but failed to detect HCV in the remaining patients. Despite increased sensitivity the combined assay does not improve serodiagnosis of occult HCV infection.

  18. Occult hepatitis B infection in egyptian chronic hepatitis C patients: prevalence, impact on pegylated interferon/ribavirin therapy

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    Mohamed Lamiaa A

    2010-11-01

    Full Text Available Abstract Background Chronic HCV infection combined with occult hepatitis B infection has been associated with liver enzymes flare, advanced hepatic fibrosis and cirrhosis, poor response to standard interferon-α, and increased risk of HCC. This study aimed to elucidate the prevalence of occult hepatitis B infection in Egyptian chronic HCV patients, and to clarify its role in non-response of those patients to pegylated interferon/ribavirin therapy. This study enrolled 155 consecutive chronic HCV patients under pegylated interferon/ribavirin therapy. All patients were exposed to clinical assessment, biochemical, histological and virological examinations. HBV parameters (HBV DNA, anti-HBc, anti-HBs and patients' response status to the combination therapy were determined. Results In this study, occult hepatitis B infection occurs in 3.9% of Egyptian chronic HCV patients; tends to affect younger age patients, associated with higher base line HCV viral load, less hepatic fibrosis than monoinfected patients. This occult hepatitis B infection is not a statistically significant cause of non-response to pegylated interferon/ribavirin therapy. Anti-HBs was not associated with any biochemical, histological or virological abnormalities in those patients, contrary to low response rate to therapy and higher HCV viral load that was observed with anti-HBc. Conclusions Detection of HBV DNA in HBsAg negative chronic HCV patients plays a non significant role in non-response of Egyptian patients to pegylated interferon/ribavirin therapy.

  19. Efficacy and safety of elbasvir/grazoprevir and sofosbuvir/pegylated interferon/ribavirin

    DEFF Research Database (Denmark)

    Sperl, Jan; Horvath, Gabor; Halota, Waldemar;

    2016-01-01

    BACKGROUND & AIMS: Direct-acting antiviral agents have improved treatment outcomes for patients with hepatitis C virus (HCV) infection; however, head-to-head comparisons are limited. The C-EDGE Head-2-Head Study compared the safety and efficacy of elbasvir/grazoprevir (EBR/GZR) with sofosbuvir plus...... of patients were non-cirrhotic (83.1%), treatment-naïve (74.9%) and had HCV GT1b infection (82.0%). SVR12 rates were 99.2% (128/129) and 90.5% (114/126) in the EBR/GZR and SOF/PR groups, respectively. The estimated adjusted difference in SVR12 was 8.8% (95% confidence interval [CI], 3.6-15.3%). Because......, 27.0% [95% CI, -35.5% to -19.6%; phepatitis C...

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

    Science.gov (United States)

    Adinolfi, Luigi Elio; Rinaldi, Luca; Guerrera, Barbara; Restivo, Luciano; Marrone, Aldo; Giordano, Mauro; Zampino, Rosa

    2016-05-25

    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.

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

    Science.gov (United States)

    Adinolfi, Luigi Elio; Rinaldi, Luca; Guerrera, Barbara; Restivo, Luciano; Marrone, Aldo; Giordano, Mauro; Zampino, Rosa

    2016-01-01

    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. PMID:27231906

  2. Logical Analysis of Regulation of Interleukin-12 Expression Pathway Regulation During HCV Infection.

    Science.gov (United States)

    Farooqi, Zia-Ur-Rehman; Tareen, Samar H K; Ahmed, Jamil; Zaidi, Najam-Us-Sahar S

    2016-01-01

    Hepatitis C virus (HCV) triggers coordinated innate and adaptive response in host cell. HCV genome and proteins of the replicating virus are recognized as non-self-antigens by host cell to activate Toll Like Receptors (TLRs). Activated TLRs ultimately express cytokines, which can clear virus either by activating interferon (IFN), protein kinase C (PKC) and RNA Lase system or through activation of cytotoxic T-lymphocytes. Interleukin-12 (IL-12) is a potent antiviral cytokine, capable of clearing HCV by bridging both innate and adaptive antiviral immune response. Activation of TLR-4 on macrophages surface induces expression of IL-12 via NF-κB and AP-1 transcriptional pathway. After expression, IL- 12 releases IFN-γ, which activates anti-HCV cytotoxic lymphocytes. Conversely, in chronic HCV infection downregulation of IL-12 has been reported instead of by number of studies. Keeping in view of the above mentioned facts, this study was designed to evaluate HCV-core mediated down-regulation of IL-12 transcriptional pathway by employing a logical modeling approach based on the Ren´e Thomas formalism. The logical parameters of entities were estimated by using SMBioNet. The Logical model represents all possible dynamics of protein expression involved during course of HCV pathology. Results demonstrated that at chronic stage of infection, though TLR-4 was constantly active but yet it failed to express the NF-κB, AP-1, IL-12 and IFN-γ. This mechanism was indicative of incorporation of core mediated changes in IL-12 regulatory pathway. Moreover, results also indicate that HCV adopts different trajectories to accomplish the persistence of chronic phase of infection. It also implicated that human immune system tries to clear HCV but core is capable of inducing system oscillations to evade the immunity.

  3. 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.

  4. Regional differences in hepatitis C treatment with peginterferon and ribavirin in Japan: a retrospective cohort study

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    Ide K

    2016-03-01

    Full Text Available Kazuki Ide,1 Yohei Kawasaki,1 Hiroshi Yamada,1 Naohiko Masaki2 1Department of Drug Evaluation and Informatics, Graduate School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, 2The Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, Chiba, JapanPurpose: The aims of this study were to investigate regional differences in hepatitis C virus (HCV infection treatment with peginterferon and ribavirin in Japan and to develop and validate statistical models for analysis of regional differences, using generalized linear mixed models.Methods: Individuals with chronic HCV infection were identified from the Japanese Interferon Database (registered from December 2009 to April 2013. The total sustained virologic response rate and the rate in each prefecture were calculated. In the analysis using generalized linear mixed models, the following four models were constructed: 1 prefecture as a fixed effect, 2 prefecture and other confounding variables as fixed effects, 3 prefecture as a random effect, and 4 prefecture as a random effect and other confounding variables as fixed effects. The quality of the model fit was assessed using the Akaike information criterion and the Bayesian information criterion. All statistical analyses were performed using SAS Version 9.4 for Windows.Results: From 36 prefectures, 16,349 cases were recorded in the study period. Of these, 4,677 were excluded according to certain criteria. The total sustained virologic response rate was 59.9% (range, 43.9%–71.6%. The statistical model including prefecture as a random effect and other confounding variables as fixed effects showed the best fit based on the Akaike information criterion (13,830.92 and Bayesian information criterion (13,845.17.Conclusion: Regional differences may exist in HCV infection treatment in Japan. The model including prefecture as a random effect and other confounding variables as fixed effects was appropriate for

  5. Significance of the hepatitis C virus (HCV core antigen as an alternative plasma marker of active HCV infection

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    Daniel HDJ

    2007-01-01

    Full Text Available Purpose: To evaluate the role of core antigen (Ortho trak-C assay as a marker of active HCV infection in comparison to HCV RNA as detected by reverse transcription polymerase chain reaction (RT-PCR. Methods: This evaluation was carried out during January 2000 to December 2003 in HCV infected individuals who were treatment naοve or were on anti-viral therapy. Additionally, sequential plasma samples from patients on clinical follow-up were included in this study. A total of 167 samples from 61 patients were tested by trak-C and RT-PCR. HCV RNA detection was achieved by a RT-PCR. Trak-C assay results were also compared in a limited proportion of these samples with known HCV viral load and genotype. Results: Of 167 samples tested, 56.9% were RNA positive and 43.1% were RNA negative while 50.3% were trak-C positive and 49.7% were trak-C negative, yielding a sensitivity of 85.3% and a specificity of 95.8% for the trak-C assay (Kappa co-efficient = 0.8. The concentration of HCVcAg and HCV RNA showed significant correlation (n=38, r=0.334, P =0.04. The trak-C assay detected the most prevalent HCV genotypes in India without significant difference ( P =0.335. The difference between mean absorbance values of HCV RNA positive samples compared to HCV RNA negative samples in the trak-C assay was highly significant ( P < 0.000. Qualitative results of trak-C assay and RT-PCR were comparable in 93% of follow-up samples. Conclusions: Trak-C assay can be recommended for confirmation of HCV infection and follow-up in laboratories with resource-poor facilities.

  6. HBV vaccination of HCV-infected patients with occult HBV infection and anti-HBc-positive blood donors.

    Science.gov (United States)

    Pereira, J S F; Gonçales, N S L; Silva, C; Lazarini, M S K; Pavan, M H P; Fais, V C; Gonçales Júnior, F L

    2006-04-01

    Anti-HBc positivity is a frequent cause of donation rejection at blood banks. Hepatitis B virus (HBV) infection may also occur in HBsAg-negative patients, a situation denoted occult infection. Similarly, very low levels of HBV-DNA have also been found in the sera of patients with chronic hepatitis C virus (HCV) infection, even in the absence of serum HBsAg. Initially we searched for HBV-DNA in serum of 100 blood donors and 50 HCV-infected patients who were HBsAg negative/anti-HBc positive by nested-PCR and by an HBV monitor commercial test for HBV-DNA. Anti-HBs seroconversion rates were measured in 100 blood donors and in 22 patients with chronic HCV infection after HBV vaccination to determine if the HBV vaccination could eliminate an occult HBV infection in these individuals. Occult HBV infection was detected in proportionally fewer blood donors (6/100 = 6%) than chronic hepatitis C patients (12/50 = 24%) (P 0.05). All subjects who were HBV-DNA(+) before the first dose of HBV vaccine (D1), became HBV-DNA(-) after D1, D2, and D3. Among 22 HCV-positive patients, 10 HBV-DNA(+) and 12 HBV-DNA(-), seroconversion was observed in 9/10 (90%) HBV-DNA(+) and in 9/12 (75%) HBV-DNA(-) subjects (P > 0.05). The disappearance of HBV-DNA in the majority of vaccinated patients suggests that residual HBV can be eliminated in patients with occult infection.

  7. HBV vaccination of HCV-infected patients with occult HBV infection and anti-HBc-positive blood donors

    Directory of Open Access Journals (Sweden)

    J.S.F. Pereira

    2006-04-01

    Full Text Available Anti-HBc positivity is a frequent cause of donation rejection at blood banks. Hepatitis B virus (HBV infection may also occur in HBsAg-negative patients, a situation denoted occult infection. Similarly, very low levels of HBV-DNA have also been found in the sera of patients with chronic hepatitis C virus (HCV infection, even in the absence of serum HBsAg. Initially we searched for HBV-DNA in serum of 100 blood donors and 50 HCV-infected patients who were HBsAg negative/anti-HBc positive by nested-PCR and by an HBV monitor commercial test for HBV-DNA. Anti-HBs seroconversion rates were measured in 100 blood donors and in 22 patients with chronic HCV infection after HBV vaccination to determine if the HBV vaccination could eliminate an occult HBV infection in these individuals. Occult HBV infection was detected in proportionally fewer blood donors (6/100 = 6% than chronic hepatitis C patients (12/50 = 24% (P 0.05. All subjects who were HBV-DNA(+ before the first dose of HBV vaccine (D1, became HBV-DNA(- after D1, D2, and D3. Among 22 HCV-positive patients, 10 HBV-DNA(+ and 12 HBV-DNA(-, seroconversion was observed in 9/10 (90% HBV-DNA(+ and in 9/12 (75% HBV-DNA(- subjects (P > 0.05. The disappearance of HBV-DNA in the majority of vaccinated patients suggests that residual HBV can be eliminated in patients with occult infection.

  8. Application of functional genomics to the chimeric mouse model of HCV infection: optimization of microarray protocols and genomics analysis

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    Smith Maria W

    2006-05-01

    Full Text Available Abstract Background Many model systems of human viral disease involve human-mouse chimeric tissue. One such system is the recently developed SCID-beige/Alb-uPA mouse model of hepatitis C virus (HCV infection which involves a human-mouse chimeric liver. The use of functional genomics to study HCV infection in these chimeric tissues is complicated by the potential cross-hybridization of mouse mRNA on human oligonucleotide microarrays. To identify genes affected by mouse liver mRNA hybridization, mRNA from identical human liver samples labeled with either Cy3 or Cy5 was compared in the presence and absence of known amounts of mouse liver mRNA labeled in only one dye. Results The results indicate that hybridization of mouse mRNA to the corresponding human gene probe on Agilent Human 22 K oligonucleotide microarray does occur. The number of genes affected by such cross-hybridization was subsequently reduced to approximately 300 genes both by increasing the hybridization temperature and using liver samples which contain at least 80% human tissue. In addition, Real Time quantitative RT-PCR using human specific probes was shown to be a valid method to verify the expression level in human cells of known cross-hybridizing genes. Conclusion The identification of genes affected by cross-hybridization of mouse liver RNA on human oligonucleotide microarrays makes it feasible to use functional genomics approaches to study the chimeric SCID-beige/Alb-uPA mouse model of HCV infection. This approach used to study cross-species hybridization on oligonucleotide microarrays can be adapted to other chimeric systems of viral disease to facilitate selective analysis of human gene expression.

  9. Prevalence of hepatitis C virus (HCV infection and HCV genotypes of hemodialysis patients in Salvador, Northeastern Brazil

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    Silva L.K.

    2006-01-01

    Full Text Available Hepatitis C virus (HCV infection has been identified as the major cause of chronic liver disease among patients on chronic hemodialysis (HD, despite the important reduction in risks obtained by testing candidate blood donors for anti-HCV antibodies and the use of recombinant erythropoietin to treat anemia. A cross-sectional study was performed to estimate the prevalence of HCV infection and genotypes among HD patients in Salvador, Northeastern Brazil. Anti-HCV seroprevalence was determined by ELISA in 1243 HD patients from all ten different dialysis centers of the city. HCV infection was confirmed by RT-PCR and genotyping was performed by restriction fragment length polymorphism. Anti-HCV seroprevalence among HD patients was 10.5% (95% CI: 8.8-12.3 (Murex anti-HCV, Abbott Murex, Chicago, IL, USA. Blood samples for qualitative HCV detection and genotyping were collected from 125/130 seropositive HD patients (96.2%. HCV-RNA was detected in 92/125 (73.6% of the anti-HCV-positive patients. HCV genotype 1 (77.9% was the most prevalent, followed by genotype 3 (10.5% and genotype 2 (4.6%. Mixed infections of genotypes 1 and 3 were found in 7.0% of the total number of patients. The present results indicate a significant decrease in anti-HCV prevalence from 23.8% detected in a study carried out in 1994 to 10.5% in the present study. The HCV genotype distribution was closely similar to that observed in other hemodialysis populations in Brazil, in local candidate blood donors and in other groups at risk of transfusion-transmitted infection.

  10. High seroprevalence of HBV and HCV infection in HIV-infected adults in Kigali, Rwanda.

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    John Rusine

    Full Text Available BACKGROUND: Data on prevalence and incidence of hepatitis B virus (HBV and hepatitis C virus (HCV infection in Rwanda are scarce. METHODS: 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 women initiating antiretroviral therapy (ART at baseline, and 200 women not yet eligible for ART. RESULTS: Baseline prevalence of active HBV infection (HBsAg positive, past or occult HBV infection (anti-HBc positive and HBsAg negative and anti-HCV was 5.2%, 42.9%, and 5.7%, respectively. The active HBV incidence rate was 4.2/1,000 person years (PY. In a multivariable logistic regression model using baseline data, participants with WHO stage 3 or 4 HIV disease were 4.19 times (95% CI 1.21-14.47 more likely to have active HBV infection, and older patients were more likely to have evidence of past exposure to HBV (aRR 1.03 per year; 95%CI 1.01-1.06. Older age was also positively associated with having anti-HCV antibodies (aOR 1.09; 95%CI 1.04-1.14 while having a higher baseline HIV viral load was negatively associated with HCV (aOR 0.60; 95% CI 0.40-0.98. The median CD4 increase during the first 12 months of ART was lower for those with active HBV infection or anti-HCV at baseline. Almost all participants (88% with active HBV infection who were on ART were receiving lamivudine monotherapy for HBV. CONCLUSION: HBV and HCV are common in HIV-infected patients in Rwanda. Regular HBsAg screening is needed to ensure that HIV-HBV co-infected patients receive an HBV-active ART regimen, and the prevalence of occult HBV infection should be determined. Improved access to HBV vaccination is recommended. Active HCV prevalence and incidence should be investigated further to determine whether HCV RNA PCR testing should be introduced in Rwanda.

  11. Proteome analysis of liver cells expressing a full-length hepatitis C virus (HCV) replicon and biopsy specimens of posttransplantation liver from HCV-infected patients.

    Science.gov (United States)

    Jacobs, Jon M; Diamond, Deborah L; Chan, Eric Y; Gritsenko, Marina A; Qian, Weijun; Stastna, Miroslava; Baas, Tracey; Camp, David G; Carithers, Robert L; Smith, Richard D; Katze, Michael G

    2005-06-01

    The development of a reproducible model system for the study of hepatitis C virus (HCV) infection has the potential to significantly enhance the study of virus-host interactions and provide future direction for modeling the pathogenesis of HCV. While there are studies describing global gene expression changes associated with HCV infection, changes in the proteome have not been characterized. We report the first large-scale proteome analysis of the highly permissive Huh-7.5 cell line containing a full-length HCV replicon. We detected >4,200 proteins in this cell line, including HCV replicon proteins, using multidimensional liquid chromatographic (LC) separations coupled to mass spectrometry. Consistent with the literature, a comparison of HCV replicon-positive and -negative Huh-7.5 cells identified expression changes of proteins involved in lipid metabolism. We extended these analyses to liver biopsy material from HCV-infected patients where a total of >1,500 proteins were detected from only 2 mug of liver biopsy protein digest using the Huh-7.5 protein database and the accurate mass and time tag strategy. These findings demonstrate the utility of multidimensional proteome analysis of the HCV replicon model system for assisting in the determination of proteins/pathways affected by HCV infection. Our ability to extend these analyses to the highly complex proteome of small liver biopsies with limiting protein yields offers the unique opportunity to begin evaluating the clinical significance of protein expression changes associated with HCV infection.

  12. Role of IL-28B polymorphisms in virologic response to combined pegylated interferon and ribavirin therapy in genotype 4 chronic HCV infected patients with and without cirrhosis

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    Amira Youssef Shaala

    2015-09-01

    Conclusion: In Egypt, where chronic HCV genotype 4 and schistosoma coinfection predominate, both schistosoma infection and cirrhosis are more potent than IL28B polymorphisms as strong baseline negative predictors of hepatitis C treatment response.

  13. Response of TT virus to IFN plus ribavirin treatment in patients with chronic hepatitis C

    Institute of Scientific and Technical Information of China (English)

    Javier Moreno; Gloria Moraleda; Rafael Barcena; Mluisa Mateos; Santos del Campo

    2004-01-01

    AIM: TT virus (FTV) is a newly described DNA virus related to postransfusion hepatitis that produces persistent viremia in the absence of clinical manifestations. PEG-IFN plus ribavirin have been useful in the treatment of chronic hepatitis C infection. This study investigated the responses of TTvirus (TTV) and hepatitis C virus (HCV) to PEG-IFN plus ribavirin therapy.METHODS: Fifteen patients infected with HCV were treated with PEG-IFN(0.5 μg/body weight/week) and ribavirin (1 000 mg-1 200 mg/daily) for 48 weeks. Blood samples were drawn at the beginning and the end of the therapy. Serum TTV DNA and HCV RNA were quantified by real time PCR.RESULTS: At the beginning of treatment, TTV infection was detected in 10/15 (66.6%) of HCV-infected patients. Loss of serum TTV DNA at the end of therapy occurred in 6/10(60%) patients. Out of these 6 patients, 4 (67%) became positive for TTV DNA after 6 months of therapy. Regarding HCV viremia, 11/15 (73%) patients were negative for serum HCV RNA after 48 weeks of therapy, 7/11 (64%) of these cases also became negative for TTV DNA following the combined treatment. In the 3/4 (75%) patients who were positive for HCV RNA at the end of therapy, TTV DNA was detected as well. Sustained HCV response at 6 months after treatment was 53% (8/15).CONCLUSION: No TTV sustained response can be achievedin any patient after PEG-IFN plus ribavirin administration.

  14. Hypothyroidism in Noninterferon Treated-HCV Infected Individuals Is Associated with Abnormalities in the Regulation of Th17 Cells.

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    Salazar, Luis A; Garcia-Samper, Xóchitl; Suarez-Carpio, Rafael; Jimenez-Martínez, María C; Rendón-Huerta, Erika P; Masso, Felipe A; Fortoul, Teresa I; Montaño, Luis F

    2010-01-01

    HCV-Ag-specific TH17 cells secrete IL17, a cytokine involved in autoimmune diseases and regulated by IL10 and TGF-b. 5-12% of patients with chronic HCV infection have hypothyroidism. We evaluated the role of these cytokines in this patients by determining serum concentration of TsH, T3, free T4, IL2, IL10, IL12, IL17, TGF-b, anti-TG, TPO, CCP, GBM, and cardiolipin antibodies in 87 chronically noninterferon treated HCV-infected patients. 20 patients (group A) had elevated TsH values (>5 μUI/ml) whereas the remaining 67 (group B) had normal values. The percentage of anti-TPO, TG, GBM, and cardiolipin antibodies in group A patients (33%, 41%, 5% and 5%, resp.) as well as IL17, IL2 and TGF-b concentrations (25 ± 23 pg/ml, 643 ± 572 pg/ml, and 618 ± 221 pg/ml, resp.) were significantly higher than group B. Abnormal Th17 regulation mediated by IL-2 and low TGF-b concentrations is associated with hypothyroidism in chronically-infected HCV patients.

  15. HCV infection and specific T lymphocyte immunity%HCV感染与特异性T淋巴细胞免疫

    Institute of Scientific and Technical Information of China (English)

    史继静; 张纪元; 张学秀; 王福生

    2016-01-01

    Adaptive immunity,especially the cellular immunity mediated by T lymphocytes,plays an important role in the body's fight against hepatitis C virus (HCV) infection.The clearance of HCV requires a strong,sustained,and multi-epitope response from specific T lymphocytes,and the dysfunction of specific T lymphocytes is the major reason for chronic infection.Effective treatment can restore the function of specific T lymphocytes to a certain extent.This article reviews the features and related mechanisms of immune response from specific T lymphocytes when the prognosis of patients with HCV infection is different.%适应性免疫尤其是T淋巴细胞介导的细胞免疫在机体抗HCV感染中具有重要作用.病毒的清除需要强烈、持久、多表位的HCV特异性T淋巴细胞应答,后者功能障碍是导致感染慢性化的主要因素,有效的抗HCV治疗可在一定程度上恢复特异性T淋巴细胞功能.现就HCV感染不同转归时机体HCV特异性T淋巴细胞免疫应答的特点及机制进行讨论.

  16. Hypothyroidism in Noninterferon Treated-HCV Infected Individuals Is Associated with Abnormalities in the Regulation of Th17 Cells

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    Luis A. Salazar

    2010-01-01

    Full Text Available HCV-Ag-specific TH17 cells secrete IL17, a cytokine involved in autoimmune diseases and regulated by IL10 and TGF-b. 5–12% of patients with chronic HCV infection have hypothyroidism. We evaluated the role of these cytokines in this patients by determining serum concentration of TsH, T3, free T4, IL2, IL10, IL12, IL17, TGF-b, anti-TG, TPO, CCP, GBM, and cardiolipin antibodies in 87 chronically noninterferon treated HCV-infected patients. 20 patients (group A had elevated TsH values (>5 μUI/ml whereas the remaining 67 (group B had normal values. The percentage of anti-TPO, TG, GBM, and cardiolipin antibodies in group A patients (33%, 41%, 5% and 5%, resp. as well as IL17, IL2 and TGF-b concentrations (25±23 pg/ml, 643±572 pg/ml, and 618±221 pg/ml, resp. were significantly higher than group B. Abnormal Th17 regulation mediated by IL-2 and low TGF-b concentrations is associated with hypothyroidism in chronically-infected HCV patients.

  17. High dead-space syringes and the risk of HIV and HCV infection among injecting drug users.

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    Zule, William A; Bobashev, Georgiy

    2009-03-01

    This study examines the association between using and sharing high dead-space syringes (HDSSs)--which retain over 1000 times more blood after rinsing than low dead-space syringes (LDSSs)--and prevalent HIV and hepatitis C virus (HCV) infections among injecting drug users (IDUs). A sample of 851 out-of-treatment IDUs was recruited in Raleigh-Durham, North Carolina, between 2003 and 2005. Participants were tested for HIV and HCV antibodies. Demographic, drug use, and injection practice data were collected via interviews. Data were analyzed using multiple logistic regression analysis. Participants had a mean age of 40 years and 74% are male, 63% are African American, 29% are non-Hispanic white, and 8% are of other race/ethnicity. Overall, 42% of participants had ever used an HDSS and 12% had shared one. HIV prevalence was 5% among IDUs who had never used an HDSS compared with 16% among IDUs who had shared one. The HIV model used a propensity score approach to adjust for differences between IDUs who had used an HDSS and those who had never used one. The HCV models included all potential confounders as covariates. A history of sharing HDSSs was associated with prevalent HIV (odds ratio=2.50; 95% confidence interval=1.01, 6.15). Use and sharing of HDSSs were also associated with increased odds of HCV infection. Prospective studies are needed to determine if sharing HDSSs is associated with increased HIV and HCV incidence among IDUs.

  18. Serum Immunoglobulin G Antibodies to the GOR Autoepitope Are Present in Patients with Occult Hepatitis C Virus (HCV) Infection despite Lack of HCV-Specific Antibodies▿

    Science.gov (United States)

    Quiroga, Juan A.; Castillo, Inmaculada; Bartolomé, Javier; Carreño, Vicente

    2007-01-01

    Antibody responses to the GOR autoepitope are frequently detected among anti-hepatitis C virus (anti-HCV)-positive patients with chronic hepatitis. Sera from 110 anti-HCV-negative patients with occult HCV infection, as diagnosed by detection of HCV RNA in hepatic tissue, were investigated for GOR antibody reactivity. A positive test for anti-GOR immunoglobulin G (IgG) was found for 22 (20%) of them. The frequency and titers of anti-GOR IgG were significantly lower than those in chronic hepatitis C patients (70/110, 63.6%; P < 0.001). Anti-GOR IgG was not detected in any of the 120 patients with HCV-unrelated liver disease. The anti-GOR IgG assay showed specificity and sensitivity values of 100% and 20%, respectively, among the sera from patients with occult HCV infection; the positive and negative predictive values were 100% and 44.3%, respectively. None of the clinical, laboratory, or histological characteristics of the patients with occult HCV infection were different according to GOR antibody status, except that the percentage of HCV RNA-positive hepatocytes was significantly greater (P = 0.042) in patients with occult HCV infection who tested positive for anti-GOR IgG. In conclusion, serum anti-GOR IgG is present in patients with occult HCV infection, despite a lack of detectable HCV-specific antibodies as determined by commercial tests. Testing for anti-GOR IgG in patients in whom HCV RNA is not detected in their sera may help with the identification of a subset of patients with occult HCV infection without the need to perform a liver biopsy. PMID:17699833

  19. Serum immunoglobulin G antibodies to the GOR autoepitope are present in patients with occult hepatitis C virus (HCV) infection despite lack of HCV-specific antibodies.

    Science.gov (United States)

    Quiroga, Juan A; Castillo, Inmaculada; Bartolomé, Javier; Carreño, Vicente

    2007-10-01

    Antibody responses to the GOR autoepitope are frequently detected among anti-hepatitis C virus (anti-HCV)-positive patients with chronic hepatitis. Sera from 110 anti-HCV-negative patients with occult HCV infection, as diagnosed by detection of HCV RNA in hepatic tissue, were investigated for GOR antibody reactivity. A positive test for anti-GOR immunoglobulin G (IgG) was found for 22 (20%) of them. The frequency and titers of anti-GOR IgG were significantly lower than those in chronic hepatitis C patients (70/110, 63.6%; P HCV-unrelated liver disease. The anti-GOR IgG assay showed specificity and sensitivity values of 100% and 20%, respectively, among the sera from patients with occult HCV infection; the positive and negative predictive values were 100% and 44.3%, respectively. None of the clinical, laboratory, or histological characteristics of the patients with occult HCV infection were different according to GOR antibody status, except that the percentage of HCV RNA-positive hepatocytes was significantly greater (P = 0.042) in patients with occult HCV infection who tested positive for anti-GOR IgG. In conclusion, serum anti-GOR IgG is present in patients with occult HCV infection, despite a lack of detectable HCV-specific antibodies as determined by commercial tests. Testing for anti-GOR IgG in patients in whom HCV RNA is not detected in their sera may help with the identification of a subset of patients with occult HCV infection without the need to perform a liver biopsy.

  20. Sensitivity of a ribavirin resistant mutant of hepatitis C virus to other antiviral drugs.

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    Kathleen B Mihalik

    Full Text Available BACKGROUND: While ribavirin mono-therapy regimens have minimal effect on patients with chronic hepatitis C virus (HCV infections, they can be efficacious when combined with interferon. Clinical studies show that interferon-free combination therapies containing ribavirin are also efficacious, suggesting that an interferon-free therapy could be adopted in the near future. However, generation of drug resistant mutants and cross resistance to other drugs could impair the efficacy of the treatment. Therefore, understanding the mechanism of HCV resistance to ribavirin and cross resistance to other antiviral drugs could be of major importance. METHODS: We tested the ability of a J6/JFH1 derived HCV ribavirin resistant mutant to grow in tissue cultured Huh7D cells in the presence of the mutagen 5-Fluorouracil and the nucleoside analog 2'-C-Methylcytidine. Virus replication was assessed by detecting HCV antigens by immunofluorescence and by titrating virus present in the supernatants. Recovered viruses were amplified by RT-PCR and sequenced. RESULTS: The sensitivity of HCV-RR relative to parental J6/JFH1 to the tested drugs varied. HCV-RR was more resistant than J6/JFH1 to 5-Fluorouracil but was not more resistant than J6/JFH1 to 2'-C-Methylcytidine. Growth of HCV-RR in 5-Fluorouracil allowed the selection of an HCV-RR derived mutant resistant to 5-Fluorouracil (HCV-5FU. HCV-5FU grows to moderate levels in the presence of high concentrations of 5-Fluorouracil and to parental levels in the absence of the drug. Sequence of its genome shows that HCV-5FU accumulated multiple synonymous and non-synonymous mutations. CONCLUSIONS: These results indicate that determinants of resistance to ribavirin could also confer resistance to other anti-HCV drugs, shedding light toward understanding the mechanism of action of ribavirin and highlighting the importance of combination drug selection for HCV treatment. The results also show that it is possible to select a 5

  1. Viral genotype and HLA class II alleles influence on extra-hepatic manifestations of chronic HCV infection

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    M. Galeazzi

    2011-09-01

    Full Text Available Objective: To test whether an association between HCV genotype, HLA class II alleles distribution and extra-hepatic manifestations (EHM can be demonstrated in a group of Italian patients with chronic HCV infection . Methods: Sixty patients affected by HCV infection with EHM were consecutively enrolled. 163 HCV patients without EHM were tested as controls for the prevalence of HCV genotypes, while we referred to literature as to the controls for HLA distribution. HCV-RNA was quantified by a RT-PCR. HLA class II alleles typing was performed using a standard microlymphocytotoxicity assay. We used chi-square or Fisher test (p<0.05 significant. Odds Ratio (OR was performed by 2X2 contingency table. Results: HCV 2c genotype was found in 63.46% of patients compared to 19.63% of controls (p<0.0001; OR=7.11. Furthermore, it correlated with carpal tunnel syndrome (p=0.03; OR=4.5 and autoimmune thyroiditis (p=0.02; OR=9.2. On the contrary, 1b genotype protected from EHM in toto (p=0.0004; OR=0.21 and particularly from carpal tunnel syndrome (p=0.0014; OR=0.07. Moreover, 3a genotype prevented HCV people from having cryoglobulinemia (p=0.05; OR=0.11. As to HLA, DR6 seemed to facilitate EHM in HCV patients (p=0.041; OR=1.61, while DQ2 (p=0.03; OR=0.5 and DQ3 (p=0.002; OR= 0.5 may play a protective role. In addition, HLA DR3 was associated with cryoglobulinemia (p=0.02; OR=9.5. Conclusions: According to our findings, 2c genotype can be considered as a major risk factor for developing HCVrelated EHM, while 1b genotype seems to prevent their onset; there are also evidences suggesting that HLA might play a role in chronic HCV infected patients.

  2. Broad Anti-Hepatitis C Virus (HCV) Antibody Responses Are Associated with Improved Clinical Disease Parameters in Chronic HCV Infection

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    Swann, Rachael E.; Cowton, Vanessa M.; Robinson, Mark W.; Cole, Sarah J.; Barclay, Stephen T.; Mills, Peter R.; Thomson, Emma C.; McLauchlan, John

    2016-01-01

    ABSTRACT During hepatitis C virus (HCV) infection, broadly neutralizing antibody (bNAb) responses targeting E1E2 envelope glycoproteins are generated in many individuals. It is unclear if these antibodies play a protective or a pathogenic role during chronic infection. In this study, we investigated whether bNAb responses in individuals with chronic infection were associated with differences in clinical presentation. Patient-derived purified serum IgG was used to assess the breadth of HCV E1E2 binding and the neutralization activity of HCV pseudoparticles. The binding and neutralization activity results for two panels bearing viral envelope proteins representing either an intergenotype or an intragenotype 1 group were compared. We found that the HCV load was negatively associated with strong cross-genotypic E1E2 binding (P = 0.03). Overall, we observed only a modest correlation between total E1E2 binding and neutralization ability. The breadth of intergenotype neutralization did not correlate with any clinical parameters; however, analysis of individuals with genotype 1 (gt1) HCV infection (n = 20), using an intragenotype pseudoparticle panel, found a strong association between neutralization breadth and reduced liver fibrosis (P = 0.006). A broad bNAb response in our cohort with chronic infection was associated with a single nucleotide polymorphism (SNP) in the HLA-DQB1 gene (P = 0.038), as previously reported in a cohort with acute disease. Furthermore, the bNAbs in these individuals targeted more than one region of E2-neutralizing epitopes, as assessed through cross-competition of patient bNAbs with well-characterized E2 antibodies. We conclude that the bNAb responses in patients with chronic gt1 infection are associated with lower rates of fibrosis and host genetics may play a role in the ability to raise such responses. IMPORTANCE Globally, there are 130 million to 150 million people with chronic HCV infection. Typically, the disease is progressive and is a

  3. Topological analysis of protein co-abundance networks identifies novel host targets important for HCV infection and pathogenesis

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    McDermott Jason E

    2012-04-01

    Full Text Available Abstract Background High-throughput methods for obtaining global measurements of transcript and protein levels in biological samples has provided a large amount of data for identification of 'target' genes and proteins of interest. These targets may be mediators of functional processes involved in disease and therefore represent key points of control for viruses and bacterial pathogens. Genes and proteins that are the most highly differentially regulated are generally considered to be the most important. We present topological analysis of co-abundance networks as an alternative to differential regulation for confident identification of target proteins from two related global proteomics studies of hepatitis C virus (HCV infection. Results We analyzed global proteomics data sets from a cell culture study of HCV infection and from a clinical study of liver biopsies from HCV-positive patients. Using lists of proteins known to be interaction partners with pathogen proteins we show that the most differentially regulated proteins in both data sets are indeed enriched in pathogen interactors. We then use these data sets to generate co-abundance networks that link proteins based on similar abundance patterns in time or across patients. Analysis of these co-abundance networks using a variety of network topology measures revealed that both degree and betweenness could be used to identify pathogen interactors with better accuracy than differential regulation alone, though betweenness provides the best discrimination. We found that though overall differential regulation was not correlated between the cell culture and liver biopsy data, network topology was conserved to an extent. Finally, we identified a set of proteins that has high betweenness topology in both networks including a protein that we have recently shown to be essential for HCV replication in cell culture. Conclusions The results presented show that the network topology of protein co

  4. Recent advances in cirrhotic cardiomyopathy.

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    Karagiannakis, Dimitrios S; Papatheodoridis, George; Vlachogiannakos, Jiannis

    2015-05-01

    Cirrhotic cardiomyopathy, a cardiac dysfunction presented in patients with cirrhosis, represents a recently recognized clinical entity. It is characterized by altered diastolic relaxation, impaired contractility, and electrophysiological abnormalities, in particular prolongation of the QT interval. Several mechanisms seem to be involved in the pathogenesis of cirrhotic cardiomyopathy, including impaired function of beta-receptors, altered transmembrane currents, and overproduction of cardiodepressant factors, like nitric oxide, tumor necrosis factor α, and endogenous cannabinoids. Diastolic dysfunction is the first manifestation of cirrhotic cardiomyopathy and reflects the increased stiffness of the cardiac mass, which leads to delayed left ventricular filling. On the other hand, systolic incompetence is presented later, is usually unmasked during pharmacological or physical stress, and predisposes to the development of hepatorenal syndrome. The prolongation of QT is found in about 50 % of cirrhotic patients, but rarely leads to fatal arrhythmias. Cirrhotics with blunted cardiac function seem to have poorer survival rates compared to those without, and the risk is particularly increased during the insertion of transjugular intrahepatic portosystemic shunt or liver transplantation. Till now, there is no specific treatment for the management of cirrhotic cardiomyopathy. New agents, targeting to its pathogenetical mechanisms, may play some role as future therapeutic options.

  5. Dilated cardiomyopathy and hypothyroidism associated with pegylated interferon and ribavirin treatment for chronic hepatitis C: case report and literature review

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    Wenxue Zhao

    2014-01-01

    Full Text Available Pegylated interferon alpha (Peg IFN-α in combination with ribavirin is the backbone of treatment in chronic hepatitis C (CHC. Cardiotoxicity due to interferon therapy is rare. The most frequent cardiovascular complications are arrhythmias and ischemic manifestations. Cardiomyopathy is extremely rare but can be life threatening. We present the case of a 41-year-old female patient with CHC in whom Peg IFN-α induced dilated cardiomyopathy and hypothyroidism. Chest radiography showed an enlarged and globular cardiac silhouette and pulmonary congestion. Echocardiography showed decreased left ventricular systolic function with an ejection fraction of 32% and fractional shortening of 15%. Cardiomyopathy had a complete remission after cessation of antiviral therapy with short-term heart failure medications and supportive care. Then we review the current literature about interferon induced cardiomyopathy in patients with HCV infection, as well as share our clinical experience in diagnosing and managing this rare complication.

  6. Cryoglobulinemic glomerulonephritis: an extrahepatic manifestation of hepatitis C virus (HCV infection

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    Giovanni Garini

    2007-12-01

    Full Text Available A 66-year-old woman was admitted to our Department for evaluation of a nephrotic syndrome. Physical examination revealed ankle edema, palpable purpura of the legs and hypertension. There was no hepatosplenomegaly. The main laboratory findings were haemoglobin 11.4 g/dl, serum creatinine 1.4 mg/dl, proteinuria 3.5 g/day with reduced serum albumin (3.1 g/dl, rheumatoid factor (RF activity 125 IU/ml, and serum C4 levels 2.3 mg/dl. Cryocrit was 24%, with type II (IgG-IgM-κ cryoglobulins. The patient was positive for HCV antibodies and serum HCV RNA; the genotype was 1b. A percutaneous renal biopsy showed a cryoglobulinemic membranoproliferative glomerulonephritis with moderate histologic severity. The primary goal in patients with mild-to-moderate disease is viral clearance, so combination therapy with interferon-α (3 MU thrice weekly and ribavirin (800 mg/day was started. Twelve weeks later, serum HCV RNA had disappeared, a result that was confirmed at the end of antiviral therapy in week 48, and during the post-treatment follow-up. Proteinuria returned to the normal range, cryoglobulins decreased to undetectable levels and serum C4 levels normalized. RF activity decreased, but remained above normal. The message provided by this illustrative case is that antiviral therapy represents the first-line treatment for HCV-related cryoglobulinemic patients with mild-to-moderate kidney involvement, because it provides the best chance of viral clearance and subsequent disease improvement.

  7. Accumulation of Intrahepatic TNF-α-Producing NKp44+ NK Cells Correlates With Liver Fibrosis and Viral Load in Chronic HCV Infection

    Science.gov (United States)

    Nel, Isabelle; Lucar, Olivier; Petitdemange, Caroline; Béziat, Vivien; Lapalus, Martine; Bédossa, Pierre; Debré, Patrice; Asselah, Tarik; Marcellin, Patrick; Vieillard, Vincent

    2016-01-01

    Abstract In the setting of chronic hepatitis C virus (HCV) infection, changes in natural killer (NK) cells have been shown to reflect activation in response to virus stimulation. The contribution of individual natural cytotoxicity receptors to HCV infection remains to be clarified. NKp44 is the sole specific natural cytotoxicity receptor expressed only on activated NK cells. In this study, peripheral blood and liver NK-cell subsets were purified from 31 patients with chronic C hepatitis or nonalcoholic steatohepatitis, and then characterized by flow cytometry. Their polyfunctional activity was determined by expression of the CD107a degranulation marker, together with intracellular cytokine production. Unlike the patients with nonalcoholic steatohepatitis, patients with chronic HCV infection had a higher frequency of NKp44+ NK cells in the liver than in their peripheral blood (P < 0.0001). Intrahepatic NKp44+ NK cells from HCV+ individuals produced higher levels of tumor necrosis factor-α than did NKp44− NK cells (P = 0.0011). Importantly, the frequency of intrahepatic NKp44+ NK cells was correlated with both HCV-RNA levels (P = 0.0234) and stage of fibrosis (P = 0.0003). Our findings suggest that the accumulation of intrahepatic tumor necrosis factor-α-producing NKp44+ resident NK cells play a role in the liver damage associated with chronic HCV infection. PMID:27175704

  8. Comprehensive longitudinal analysis of hepatitis C virus (HCV)-specific T cell responses during acute HCV infection in the presence of existing HIV-1 infection

    NARCIS (Netherlands)

    C.H.S.B. van den Berg; T.A. Ruys; N.M. Nanlohy; S.E. Geerlings; J.T. van der Meer; J.W. Mulder; J.A. Lange; D. van Baarle

    2009-01-01

    The aim of this study was to study the development of HCV-specific T cell immunity during acute HCV infection in the presence of an existing HIV-1 infection in four HIV-1 infected men having sex with men. A comprehensive analysis of HCV-specific T cell responses was performed at two time points duri

  9. Detection of hepatitis C virus (HCV) core-specific antibody suggests occult HCV infection among blood donors.

    Science.gov (United States)

    Quiroga, Juan A; Avellón, Ana; Bartolomé, Javier; Andréu, María; Flores, Elena; González, María I; González, Rocío; Pérez, Sonia; Richart, Luis A; Castillo, Inmaculada; Alcover, Javier; Palacios, Ricardo; Carreño, Vicente; Echevarría, José M

    2016-07-01

    Blood transfusion safety is based on reliable donor screening for transmissible infections such as the hepatitis C virus (HCV) infection. A novel HCV core-specific antibody was assayed on random single donations from 2007 first-time blood donors who tested negative for anti-HCV and HCV RNA on routine screening. Sample collection broke the code between donations and donors for ethical reasons. Forty-two donations (2.1%) displayed reactivity in the novel test. The specificity of the reactivity was evaluated by a peptide inhibition assay, and testing against additional nonoverlapping HCV core peptide epitopes and other HCV antigens was performed on these samples. Six donations (14.3%; 0.30% from the total) were considered to contain anti-HCV after such supplemental testing. HCV RNA detection was also performed in peripheral blood mononuclear cells (PBMNCs) and serum or plasma samples from reactive donors after virus concentration by ultracentrifugation. HCV RNA tested negative in all PBMNCs samples, and a very low amount of viral genome was detected in serum or plasma concentrates from three anti-HCV core-reactive donors (7.1%) but not among concentrates from 100 randomly selected nonreactive donors. Sequencing of these polymerase chain reaction products revealed differences between the isolates that excluded partially sample contamination from a common source. These findings argue in favor of an ongoing occult HCV infection among these blood donors and account for some rather low, but perhaps not negligible, infection risk for such donations. Future studies involving larger samples of donations from traceable donors would enlighten the significance of these findings for the viral safety of the blood supply. © 2016 AABB.

  10. Soluble egg antigen of Schistosoma Haematobium induces HCV replication in PBMC from patients with chronic HCV infection

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    Tabll Ashraf A

    2006-06-01

    Full Text Available Abstract Background This study was conducted to examine, in vitro , the effect of soluble egg antigen (SEA of S. haematobium on intracellular HCV RNA load in peripheral mononuclear cells (PBMC as well as on cell proliferation in patients with chronic HCV infection. Methods PBMC from 26 patients with chronic HCV infection were cultured for 72 hours in presence and absence of 50 μg SEA/ml medium. Intracellular HCV RNA quantification of plus and minus strands was assessed before and after stimulation. PBMC from five healthy subjects were cultured for 7 days, flow cytometric analysis of DNA content was used to assess the mitogenic effect of SEA on PBMC proliferation compared to phytoheamaglutinine (PHA. Results Quantification of the intracellular viral load showed increased copy number/cell of both or either viral strands after induction with SEA in 18 of 26 patients (69.2% thus indicating stimulation of viral replication. Flow cytometric analysis showed that mean ± S.D. of percent values of cell proliferation was induced from 3.2 ± 1.5% in un-stimulated cells to 16.7 ± 2.5 % and 16.84 ± 1.7 % in cells stimulated with PHA and SEA respectively. Conclusion the present study supports earlier reports on SEA proliferative activity on PBMC and provides a strong evidence that the higher morbidity observed in patients co-infected with schistosomiasis and HCV is related, at least in part, to direct stimulation of viral replication by SEA.

  11. 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.

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    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.

  12. Focal adhesion kinase (FAK) mediates the induction of pro-oncogenic and fibrogenic phenotypes in hepatitis C virus (HCV)-infected cells.

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    Alisi, Anna; Arciello, Mario; Petrini, Stefania; Conti, Beatrice; Missale, Gabriele; Balsano, Clara

    2012-01-01

    Hepatitis C Virus (HCV) infection is one of the most common etiological factors involved in fibrosis development and its progression to hepatocellular carcinoma (HCC). The pivotal role of hepatic stellate cells (HCSs) and extracellular matrix (ECM) in fibrogenesis is now certainly accepted, while the network of molecular interactions connecting HCV is emerging as a master regulator of several biological processes including proliferation, inflammation, cytoskeleton and ECM remodeling. In this study, the effects of HCV proteins expression on liver cancer cells, both pro-invasive and pro-fibrogenic phenotypes were explored. As a model of HCV infection, we used permissive Huh7.5.1 hepatoma cells infected with JFH1-derived ccHCV. Conditioned medium from these cells was used to stimulate LX-2 cells, a line of HSCs. We found that the HCV infection of Huh7.5.1 cells decreased adhesion, increased migration and caused the delocalization of alpha-actinin from plasma membrane to cytoplasm and increased expression levels of paxillin. The treatment of LX-2 cells, with conditioned medium from HCV-infected Huh7.5.1 cells, caused an increase in cell proliferation, expression of alpha-smooth muscle actin, hyaluronic acid release and apoptosis rate measured as cleaved poly ADP-ribose polymerase (PARP). These effects were accompanied in Huh7.5.1 cells by an HCV-dependent increasing of FAK activation that physically interacts with phosphorylated paxillin and alpha-actinin, and a rising of tumor necrosis factor alpha production/release. Silencing of FAK by siRNA reverted all effects of HCV infection, both those directed on Huh7.5.1 cells, and those indirect effects on the LX-2 cells. Moreover and interestingly, FAK inhibition enhances apoptosis in HCV-conditioned LX-2 cells. In conclusion, our findings demonstrate that HCV, through FAK activation, may promote cytoskeletal reorganization and a pro-oncogenic phenotype in hepatocyte-like cells, and a fibrogenic phenotype in HSCs.

  13. Proteome Analysis of Liver Cells Expressing a Full- Length Hepatitis C Virus (HCV) Replicon and Biopsy Specimens of Posttransplantation Liver from HCV-Infected Patients

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    Jacobs, Jon M.; Diamond, Deborah L.; Chan, Eric Y.; Gritsenko, Marina A.; Qian, Weijun; Stastna, Miroslava; Baas, Tracey; Camp, David G.; Carithers, Jr., Robert L.; Smith, Richard D.; Katze, Michael G.

    2005-06-01

    The development of a reproducible model system for the study of Hepatitis C virus (HCV) infection has the potential to significantly enhance the study of virus-host interactions and provide future direction for modeling the pathogenesis of HCV. While there are studies describing global gene expression changes associated with HCV infection, changes in the proteome have not been characterized. We report the first large scale proteome analysis of the highly permissive Huh-7.5 cell line containing a full length HCV replicon. We detected > 4,400 proteins in this cell line, including HCV replicon proteins, using multidimensional liquid chromatographic (LC) separations coupled to mass spectrometry (MS). The set of Huh-7.5 proteins confidently identified is, to our knowledge, the most comprehensive yet reported for a human cell line. Consistent with the literature, a comparison of Huh-7.5 cells (+) and (-) the HCV replicon identified expression changes of proteins involved in lipid metabolism. We extended these analyses to liver biopsy material from HCV-infected patients where > 1,500 proteins were detected from 2 {micro}g protein lysate using the Huh-7.5 protein database and the accurate mass and time (AMT) tag strategy. These findings demonstrate the utility of multidimensional proteome analysis of the HCV replicon model system for assisting the determination of proteins/pathways affected by HCV infection. Our ability to extend these analyses to the highly complex proteome of small liver biopsies with limiting protein yields offers the unique opportunity to begin evaluating the clinical significance of protein expression changes associated with HCV infection.

  14. Ribavirin monotherapy for chronic hepatitis C infection

    DEFF Research Database (Denmark)

    Brok, Jesper; Gluud, Lise L; Gluud, Christian

    2006-01-01

    Adding ribavirin to interferon improves treatment response for patients with chronic hepatitis C, but the effects of ribavirin monotherapy are unclear. We conducted a systematic review to assess the benefits and harms of ribavirin monotherapy for patients with chronic hepatitis C....

  15. New insights into cirrhotic cardiomyopathy

    DEFF Research Database (Denmark)

    Møller, Søren; Hove, Jens D; Dixen, Ulrik

    2013-01-01

    Cirrhotic cardiomyopathy designates a cardiac dysfunction, which includes reduced cardiac contractility with systolic and diastolic dysfunction, and presence of electrophysiological abnormalities in particular prolongation of the QT interval. Several pathophysiological mechanisms including reduced...... beta-receptor function seem involved in the autonomic and cardiac dysfunction. Cirrhotic cardiomyopathy can be revealed by tissue Doppler imaging but is best demasked by physical or pharmacological stress. Liver transplantation may revert cardiac dysfunction but surgery and shunt insertion may also...... aggravate the condition. Moreover, cirrhotic cardiomyopathy may contribute to heart failure after invasive procedures and to development of hepatic nephropathy as part of a cardiorenal syndrome. Whether beta-blockers have a deleterious effect in this clinical situation remains to be settled....

  16. Efficacy and Safety of Low-Dose Peginterferon Alpha-2a Plus Ribavirin on Chronic Hepatitis C

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    Zehui Yan

    2012-01-01

    Full Text Available Background. The purpose of this study was to assess the efficacy and safety of low-dose peg-IFN α-2a plus ribavirin on the treatment of patients with chronic hepatitis C virus (HCV infection. Patients and Methods. A total of 243 HCV patients treated with different doses of peg-IFN α-2a plus ribavirin were stratified into three groups. End-of-treatment response (ETR and sustained viral response (SVR were evaluated for efficacy. Adverse events and laboratory abnormalities were conducted for safety. Results. ETR and SVR in group I were obtained in 83.9% and 68.9% of the patients, separately, which was similar to groups II (84.1% and 68.3% and III (81.7% and 66.7%. The received peg-IFN α-2a dose was not the independent factor-related SVR in our population (OR, 1.31; 95% CI, 0.94–1.81; P=0.106. The frequency of no adverse events reported in group III (24.7% was significantly higher than that in group I (11.5% and group II (12.7% (P=0.036. Conclusions. The peg-IFN α-2a 90 μg/week plus ribavirin is as effective as, and better tolerated than, peg-IFN α-2a standard dose with ribavirin in the treatment of chronic hepatitis C. This low-dose combination achieves high SVR rates and may be cost-saving.

  17. HCV infection prevalence lower than expected among 18-40-year-old injection drug users in San Diego, CA.

    Science.gov (United States)

    Garfein, Richard S; Rondinelli, Amanda; Barnes, Richard F W; Cuevas, Jazmine; Metzner, Mitcheal; Velasquez, Michele; Rodriguez, David; Reilly, Meredith; Xing, Jian; Teshale, Eyasu H

    2013-06-01

    San Diego, California shares the world's busiest land border crossing with Tijuana, Mexico-a city where 95 % of injection drug users (IDUs) test hepatitis C virus (HCV) antibody-positive. Yet, little is known about the prevalence and risk behaviors for HCV among IDUs in San Diego. In 2009-2010, 18-40-year-old IDUs in San Diego County completed a risk assessment interview and serologic testing for HCV and HIV infection. Recruitment involved respondent-driven sampling, venue-based sampling at a syringe exchange program, and convenience sampling. Correlates of HCV infection were identified by multivariable logistic regression. Among 510 current IDUs, 26.9 % (95 % CI 23.0-30.7 %) and 4.2 % (95 % CI 2.4-5.9 %) had been infected with HCV and HIV, respectively. Overall, median age was 28 years; 74 % were male; 60 % white and 29 % Hispanic; and 96 % were born in the U.S. Median years of injecting was 6; 41 % injected daily; 60 % injected heroin most often; 49 % receptively shared syringes and 68 % shared other injection paraphernalia; and only 22 % reported always using new syringes in the past 3 months. Two thirds had ever traveled to Mexico and 19 % injected in Mexico. HCV infection was independently associated with sharing injection paraphernalia (adjusted odds ratio [AOR] = 1.69) and SEP use (AOR = 2.17) in the previous 3 months, lifetime history of drug overdose (AOR = 2.66), and increased years of injecting (AOR = 2.82, all P values Diego was modest compared to other US cities and much lower than Tijuana. Given that known individual-level HCV risk factors were common in San Diego, the city's lower HCV prevalence might be due to differences in social and structural factors between the cities.

  18. Aspartate aminotransferase to platelet ratio index and sustained virologic response are associated with progression from hepatitis C associated liver cirrhosis to hepatocellular carcinoma after treatment with pegylated interferon plus ribavirin

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    Ng KJ

    2016-08-01

    without sustained virologic response (SVR (hazard ratio [HR] 5.795; 95% confidence interval [CI] 1.370–24.5; P=0.017 and high APRI (HR 5.548; 95% CI 1.191–25.86; P=0.029 had a significantly higher risk of HCC occurrence. The cumulative incidence of HCC was significantly higher (P=0.009 in patients without SVR (3-year cumulative incidence 21.4%; 95% CI 7.4%–35.5%; 5-year cumulative incidence 31.1%; 95% CI 11.2%–51.1% compared to those with SVR (3- and 5-year cumulative incidence 6.2%; 95% CI 0%–1.3%. Further, the cumulative incidence of HCC was significantly higher (P=0.006 in patients with high APRI (3-year cumulative incidence 21.8%; 95% CI 8.2%–35.3%; 5-year cumulative incidence 30.5%, 95% CI 11.8%–49.3% compared to those with low APRI (3- and 5-year cumulative incidence 4.2%, 95% CI 0%–1.0%.Conclusion: In HCV-infected cirrhotic patients who received combination therapy, APRI and SVR are the two major predictors of HCC development. Keywords: aspartate aminotransferase to platelet ratio index, chronic hepatitis C, hepatitis C virus, hepatocellular carcinoma, liver cirrhosis, sustained virologic response

  19. Outcomes of Interferon/Ribavirin Therapy in Patients with HCV Defined by Expression of Plasma Soluble Human Leukocyte Antigen-G but Not IL-37

    Science.gov (United States)

    Ding, Shi-xiong; Ma, Jian-bo; Hu, Yao-ren; Hu, Ai-rong; Shen, Qiang; Gao, Guo-sheng

    2016-01-01

    Background Chronic hepatitis C virus (HCV) infection leads to life-threatening complications worldwide. Immunomodulation signals the response to virus clearance. The immune-suppressive molecule human leukocyte antigen-G (HLA-G) has been shown to function in inhibiting both innate and adaptive immune responses. The objective of this study was to investigate the expression of HLA-G and IL-37 in sustained virological response (SVR) and non-SVR HCV-positive patients before and after complete treatment with a combination of pegylated interferon (IFN) and ribavirin (RBV). Material/Methods Our study included 132 chronic hepatitis C patents who received combined therapy with IFN-α and RBV. Both SVR and non-SVR patients were included. The end-of-treatment response was defined as undetectable HCV RNA at week 48. Patients with end-of-treatment response were detected by HCV RNA at 24 weeks after therapy. The expression levels of HLA-G and IL-37 at the end and 24 weeks after treatment were detected by ELISA. Results Plasma HLA-G and IL-37 were significantly increased in HCV-infected patients compared with healthy individuals before treatment. Furthermore, HLA-G in SVR patients was noticeably decreased after treatment, while HLA-G in non-SVR patients had no changes after treatment. Additionally, both in SVR and non-SVR patients, the expression of IL-37 was remarkably reduced compared with baseline after treatment. Conclusions These findings suggest that elevation of HLA-G and IL-37 in HCV may play an important role in response to combined therapy with IFN-α and RBV. Monitoring the expression of HLA-G during therapy could contribute to adjusting the treatment program of HCV-infected patients. PMID:27112970

  20. CD8+ T cells of chronic HCV-infected patients express multiple negative immune checkpoints following stimulation with HCV peptides.

    Science.gov (United States)

    Barathan, Muttiah; Mohamed, Rosmawati; Vadivelu, Jamuna; Chang, Li Yen; Vignesh, Ramachandran; Krishnan, Jayalakshmi; Sigamani, Panneer; Saeidi, Alireza; Ram, M Ravishankar; Velu, Vijayakumar; Larsson, Marie; Shankar, Esaki M

    2017-03-01

    Hepatitis C virus (HCV)-specific CD4+ and CD8+ T cells are key to successful viral clearance in HCV disease. Accumulation of exhausted HCV-specific T cells during chronic infection results in considerable loss of protective functional immune responses. The role of T-cell exhaustion in chronic HCV disease remains poorly understood. Here, we studied the frequency of HCV peptide-stimulated T cells expressing negative immune checkpoints (PD-1, CTLA-4, TRAIL, TIM-3 and BTLA) by flow cytometry, and measured the levels of Th1/Th2/Th17 cytokines secreted by T cells by a commercial Multi-Analyte ELISArray™ following in vitro stimulation of T cells using HCV peptides and phytohemagglutinin (PHA). HCV peptide-stimulated CD4+ and CD8+ T cells of chronic HCV (CHC) patients showed significant increase of CTLA-4. Furthermore, HCV peptide-stimulated CD4+ T cells of CHC patients also displayed relatively higher levels of PD-1 and TRAIL, whereas TIM-3 was up-regulated on HCV peptide-stimulated CD8+ T cells. Whereas the levels of IL-10 and TGF-β1 were significantly increased, the levels of pro-inflammatory cytokines IL-2, TNF-α, IL-17A and IL-6 were markedly decreased in the T cell cultures of CHC patients. Chronic HCV infection results in functional exhaustion of CD4+ and CD8+ T cells likely contributing to viral persistence.

  1. Loss of immune escape mutations during persistent HCV infection in pregnancy enhances replication of vertically transmitted viruses.

    Science.gov (United States)

    Honegger, Jonathan R; Kim, Seungtaek; Price, Aryn A; Kohout, Jennifer A; McKnight, Kevin L; Prasad, Mona R; Lemon, Stanley M; Grakoui, Arash; Walker, Christopher M

    2013-11-01

    Globally, about 1% of pregnant women are persistently infected with the hepatitis C virus (HCV). Mother-to-child transmission of HCV occurs in 3-5% of pregnancies and accounts for most new childhood infections. HCV-specific CD8(+) cytotoxic T lymphocytes (CTLs) are vital in the clearance of acute HCV infections, but in the 60-80% of infections that persist, these cells become functionally exhausted or select for mutant viruses that escape T cell recognition. Increased HCV replication during pregnancy suggests that maternofetal immune tolerance mechanisms may further impair HCV-specific CTLs, limiting their selective pressure on persistent viruses. To assess this possibility, we characterized circulating viral quasispecies during and after consecutive pregnancies in two women. This revealed a loss of some escape mutations in HLA class I epitopes during pregnancy that was associated with emergence of more fit viruses. CTL selective pressure was reimposed after childbirth, at which point escape mutations in these epitopes again predominated in the quasispecies and viral load dropped sharply. Importantly, the viruses transmitted perinatally were those with enhanced fitness due to reversion of escape mutations. Our findings indicate that the immunoregulatory changes of pregnancy reduce CTL selective pressure on HCV class I epitopes, thereby facilitating vertical transmission of viruses with optimized replicative fitness.

  2. New direct-acting antivirals for patients with chronic HCV infection: can we monitor treatment using an HCV core antigen assay?

    Science.gov (United States)

    Alonso, R; Pérez-García, F; Ampuero, D; Reigadas, E; Bouza, E

    2017-03-01

    We evaluated the diagnostic usefulness of an HCV core antigen (HCV-Ag) assay in HCV-infected patients undergoing treatment with direct-acting antivirals. We analyzed 103 samples from 28 patients. Compared with RT-PCR, sensitivity was 96.2% and specificity was 100%. The correlation between techniques was excellent (Pearson coefficient: 0.871). HCV-Ag proved to be useful in patients with sustained viral response and in patients who experienced treatment failures.

  3. T lymphocytes from chronic HCV-infected patients are primed for activation-induced apoptosis and express unique pro-apoptotic gene signature.

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    Bin-Bin Zhao

    Full Text Available Although extensive studies have demonstrated the functional impairment of antigen-specific CD4(+ and CD8(+ T-cells during chronic hepatitis C virus (HCV infection, the functional status of global CD4(+ and CD8(+ T-cells remains unclear. In this report, we recruited 42 long-term (~20 years treatment-naïve chronic HCV (CHC patients and 15 healthy donors (HDs to investigate differences in global CD4(+ and CD8(+ T-cells function. We show that CD4(+ and CD8(+ T-cells from CHC patients underwent increased apoptosis after TCR stimulation. Furthermore, IFN-γ, IL-9 and IP-10 were elevated in CHC patients' plasma and promoted activation-induced T-cells death. Global CD4(+ and CD8(+ T-cells also showed unique transcriptional profiles in the expression of apoptosis-related genes. We identified BCL2, PMAIP1, and CASP1 in CD4(+ T-cells and IER3 and BCL2A1 in CD8(+ T-cells from CHC patients as HCV-specific gene signatures. Importantly, the gene expression patterns of CD4(+ and CD8(+ T-cells from CHC patients differ from those in CD4(+ and CD8(+ T-cells from human immunodeficiency virus type 1 (HIV-1 or hepatitis B virus (HBV infected individuals. Our results indicate that chronic HCV infection causes a systemic change in cytokine levels that primes T-cells for activation-induced apoptosis. Furthermore, HCV infection programs unique apoptosis-related gene expression profiles in CD4(+ and CD8(+ T-cells, leading to their enhanced activation-induced apoptosis. These results provide novel insights to the pathogenesis of chronic HCV infection.

  4. Role of interferon gamma and tumor necrosis factor-related apoptosis-inducing ligand receptor 1 single nucleotide polymorphism in natural clearance and treatment response of HCV infection.

    Science.gov (United States)

    Azam, Sikandar; Manzoor, Sobia; Imran, Muhammad; Ashraf, Javed; Ashraf, Sarah; Resham, Saleha; Ghani, Eijaz

    2015-05-01

    Hepatitis C virus (HCV) pathogenesis and treatment outcomes are multifactorial phenomena involving both viral and host factors. This study was designed to determine the role of tumor necrosis factor-related apoptosis-inducing ligand receptor 1(TRAIL-R1) and interferon gamma (IFN-γ) genetic mutations in susceptibility and response to interferon-based therapy of hepatitis C virus (HCV) infection. The detection of TRAIL-R1 rs4242392 and IFN-γ rs2069707 single nucleotide polymorphisms was completed in 118 chronic HCV patients and 96 healthy controls by allele-specific polymerase chain reaction and restriction fragment length polymorphisms polymerase chain reaction. Patients were further categorized into sustained virological responder (SVR) and nonresponder (NR) groups on the basis of their response to interferon-based therapy for HCV infection. Real-time PCR was used for HCV quantification. HCV genotyping was performed by Ohno's method. The results demonstrated that the distribution of the TRAIL-R1 rs4242392TT genotype was significantly higher in the SVR group (78%) compared to the NR group (36%). It showed that chronic HCV patients possessing the TRAIL-R1 rs4242392TT genotype are better responders to interferon-based therapy (p0.05). The distribution of IFN-γ rs2069707 was the opposite to TRAIL-R1 rs4242392 prevalence, that is, there was high distribution of the IFN-γ rs2069707GG genotype in patients and healthy controls (p0.05). In conclusion, genetic variation of TRAIL-R1 rs4242392 is linked with response to interferon-based therapy for HCV infection, and genetic variation IFN-γ rs2069707 is associated with natural clearance of HCV infection.

  5. Efficacy of sofosbuvir-based therapies in HIV/HCV infected patients and persons who inject drugs.

    Science.gov (United States)

    Puoti, Massimo; Panzeri, Claudia; Rossotti, Roberto; Baiguera, Chiara

    2014-12-15

    In the era of Directly Acting anti HCV Antivirals treatment of hepatitis C is successful in the majority of persons treated. However, treatment of persons with HIV or who inject drugs remains challenging because of special issues: drug-drug interactions with antiretroviral, psychiatric and drug substitution therapies, treatment adherence, impact of treatment on HIV disease course or on risk of bacterial infections. Sofosbuvir induced sustained virologic response in 91% of 23 HIV/HCV coinfected persons treated in combination with ribavirin and pegylated interferon, in 83% of 497 treated in combination with ribavirin and in all 50 patients infected with HCV GT1 treated in combination with ledipasvir and ribavirin. The rates of efficacy in HCV-HIV coinfected were almost the same as those observed in HCV monoinfected suggesting that the efficacy of sofosbuvir is not reduced by HIV coinfection. There are no data on the efficacy of sofosbuvir in injection drugs users. The pangenotypic activity, the high barrier to resistance, the modest potential for drug-drug interactions makes sofosbuvir a reference drug for the treatment of these two special populations.

  6. Ribavirin can be mutagenic for arenaviruses.

    Science.gov (United States)

    Moreno, Héctor; Gallego, Isabel; Sevilla, Noemí; de la Torre, Juan Carlos; Domingo, Esteban; Martín, Verónica

    2011-07-01

    Arenaviruses include several important human pathogens, and there are very limited options of preventive or therapeutic interventions to combat these viruses. An off-label use of the purine nucleoside analogue ribavirin (1-β-d-ribofuranosyl-1-H-1,2,4-triazole-3-carboxamide) is the only antiviral treatment currently available for arenavirus infections. However, the ribavirin antiviral mechanism action against arenaviruses remains unknown. Here we document that ribavirin is mutagenic for the prototypic arenavirus lymphocytic choriomeningitis virus (LCMV) in cell culture. The mutagenic activity of ribavirin on LCMV was observed under single- and multiple-passage regimes and could not be accounted for by a decrease of the intracellular GTP pool promoted by ribavirin-mediated inhibition of inosine monophosphate dehydrogenase (IMPDH). Our findings suggest that the antiviral activity of ribavirin on arenaviruses might be exerted, at least partially, by lethal mutagenesis. Implications for antiarenavirus therapy are discussed.

  7. Focal adhesion kinase (FAK mediates the induction of pro-oncogenic and fibrogenic phenotypes in hepatitis C virus (HCV-infected cells.

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    Anna Alisi

    Full Text Available Hepatitis C Virus (HCV infection is one of the most common etiological factors involved in fibrosis development and its progression to hepatocellular carcinoma (HCC. The pivotal role of hepatic stellate cells (HCSs and extracellular matrix (ECM in fibrogenesis is now certainly accepted, while the network of molecular interactions connecting HCV is emerging as a master regulator of several biological processes including proliferation, inflammation, cytoskeleton and ECM remodeling. In this study, the effects of HCV proteins expression on liver cancer cells, both pro-invasive and pro-fibrogenic phenotypes were explored. As a model of HCV infection, we used permissive Huh7.5.1 hepatoma cells infected with JFH1-derived ccHCV. Conditioned medium from these cells was used to stimulate LX-2 cells, a line of HSCs. We found that the HCV infection of Huh7.5.1 cells decreased adhesion, increased migration and caused the delocalization of alpha-actinin from plasma membrane to cytoplasm and increased expression levels of paxillin. The treatment of LX-2 cells, with conditioned medium from HCV-infected Huh7.5.1 cells, caused an increase in cell proliferation, expression of alpha-smooth muscle actin, hyaluronic acid release and apoptosis rate measured as cleaved poly ADP-ribose polymerase (PARP. These effects were accompanied in Huh7.5.1 cells by an HCV-dependent increasing of FAK activation that physically interacts with phosphorylated paxillin and alpha-actinin, and a rising of tumor necrosis factor alpha production/release. Silencing of FAK by siRNA reverted all effects of HCV infection, both those directed on Huh7.5.1 cells, and those indirect effects on the LX-2 cells. Moreover and interestingly, FAK inhibition enhances apoptosis in HCV-conditioned LX-2 cells. In conclusion, our findings demonstrate that HCV, through FAK activation, may promote cytoskeletal reorganization and a pro-oncogenic phenotype in hepatocyte-like cells, and a fibrogenic phenotype in

  8. Patient Characteristics and Prescribing Patterns Associated with Sofosbuvir Treatment for Chronic HCV Infection in a Commercially Insured Population

    Science.gov (United States)

    Tambourine, Brent M.; Sadeghi, Arash; Yang, Jianing; Stockl, Karen M.; Lew, Heidi C.; Solow, Brian K.; Tran, Josephine N.

    2016-01-01

    Background In December 2013, the US Food and Drug Administration (FDA) approved sofosbuvir (Sovaldi) for the treatment of patients with chronic hepatitis C virus (HCV) infection. Given the potential “warehousing” of patients before the launch of sofosbuvir and the possibility that some patients and providers may have elected to continue deferring treatment in anticipation of more promising, interferon-free therapies in the pipeline, the early landscape for sofosbuvir treatment is difficult to ascertain. Objective To describe the demographics, clinical characteristics, and prescribing patterns associated with members requesting treatment with sofosbuvir in a commercially insured population in the United States. Methods A descriptive analysis was conducted using a randomly selected sample of commercially insured members who were identified as having a prior authorization request for sofosbuvir between March and June 2014. Member and provider characteristics, as well as treatment information, were collected using a prior authorization database from OptumRx, a national pharmacy care services company. The results were analyzed using descriptive statistics. Results A total of 338 members were selected for inclusion in the analysis. Chronic HCV genotype 1 infection was present in 74.3% of the members. Chronic HCV genotype 2, 3, or 4 was identified in 13.9%, 9.5%, and 1.2% of the members, respectively. Gastroenterologists and hepatologists accounted for 90% of providers. Among the 251 members with chronic HCV genotype 1, an interferon-free regimen was requested for 59.4% (N = 149) of them; the most frequently requested (51.4%) regimen for members with chronic HCV genotype 1 was the off-label combination of sofosbuvir plus simeprevir. Of the members with chronic HCV genotype 1, 19.1% had liver fibrosis equivalent to METAVIR stage F0 to F2 fibrosis, and 24.7% had liver fibrosis equivalent to METAVIR stage F3 to F4 fibrosis. For the remaining 56.2%, the degree of liver

  9. Expression of core antigen of HCV genotype 3a and its evaluation as screening agent for HCV infection in Pakistan

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    Rehman Irshad U

    2011-07-01

    Full Text Available Abstract Background Pakistan is facing a threat from hepatitis C infection which is increasing at an alarming rate throughout the country. More specific and sensitive screening assays are needed to timely and correctly diagnose this infection. Methods After RNA extraction from specimen (HCV-3a, cDNA was synthesized that was used to amplify full length core gene of HCV 3a. After verification through PCR, DNA sequencing and BLAST, a properly oriented positive recombinant plasmid for core gene was digested with proper restriction enzymes to release the target gene which was then inserted downstream of GST encoding DNA in the same open reading frame at proper restriction sites in multiple cloning site of pGEX4t2 expression vector. Recombinant expression vector for each gene was transformed in E. coli BL21 (DE3 and induced with IPTG for recombinant fusion protein production that was then purified through affinity chromatography. Western blot and Enzyme Linked Immunosorbant Assay (ELISA were used to detect immuno-reactivity of the recombinant protein. Results The HCV core antigen produced in prokaryotic expression system was reactive and used to develop a screening assay. After validating the positivity (100% and negativity (100% of in-house anti-HCV screening assay through a standardized panel of 200 HCV positive and 200 HCV negative sera, a group of 120 serum specimens of suspected HCV infection were subjected to comparative analysis of our method with commercially available assay. The comparison confirmed that our method is more specific than the commercially available assays for HCV strains circulating in this specific geographical region of the world and could thus be used for HCV screening in Pakistan. Conclusion In this study, we devised a screening assay after successful PCR amplification, isolation, sequencing, expression and purification of core antigen of HCV genotype 3a. Our developed screening assay is more sensitive, specific and

  10. Effect of oral care gel on the quality of life for oral lichen planus in patients with chronic HCV infection

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    Sata Michio

    2011-07-01

    Full Text Available Abstract Background Oral lichen planus (OLP decreases the quality of life because it can cause spontaneous pain during eating and tooth-brushing and an uncomfortable feeling in the mouth. In addition, OLP may be associated with HCV-related liver disease. We investigated the visual analogue scale (VAS and effects of oral care gel, REFRECARE-H®, on patients with OLP associated with HCV infection. Results Nine OLP patients (mean age 67.9 ± 7.6 years with HCV-related liver diseases were recruited and their VAS score determined along with a biochemical examination of the blood. Types of OLP included erosive (6 patients and reticular (3. REFRECARE-H®, an oral care gel (therapeutic dentifrice containing hinokitiol, was applied by each patient as a thin layer on the oral membrane, after each meal and at bedtime for 30 days. Application of REFRECARE-H® improved the quality of life in all terms of dry mouth, breath odor, oral freshness, oral pain during rest, oral pain at a mealtimes, taste disorder, loss of appetite, sleep disorder, depressive mood and jitteriness. VAS scores of dry mouth, breath odor, oral freshness, and sleep disorder were significantly increased 30 days after application of REFRECARE-H® (P = 0.01, P = 0.05, P = 0.03, P = 0.04. VAS scores of oral pain at a mealtimes and taste disorder were increased 30 days after application of REFRECARE-H® (P = 0.06. There was an absence of side effects. Conclusions REFRECARE-H® improved the quality of life for OLP. It is necessary for the hepatologist to educate patients regarding oral hygiene, as well as provide treatment of liver disease.

  11. Impaired hepatosplenic elimination of circulating cryoglobulins in patients with essential mixed cryoglobulinaemia and hepatitis C virus (HCV) infection

    Science.gov (United States)

    ROCCATELLO, D; MORSICA, G; PICCIOTTO, G; CESANO, G; ROPOLO, R; BERNARDI, M T; CACACE, G; CAVALLI, G; SENA, L M; LAZZARIN, A; PICCOLI, G; RIFAI, A

    1997-01-01

    The pathogenic mechanisms that lead to renal deposition of the cryoprecipitable IgM rheumatoid factor–IgG complexes in essential mixed cryoglobulinaemia (EMC) are unknown. Defective removal of cryoprecipitable complexes from the circulation has been postulated in EMC-associated nephritis. To test this hypothesis, the kinetics and fate of a trace dose of 123I-radiolabelled autologous cryoglobulins were analysed in 13 patients with EMC grouped according to renal involvement. The time course of radioactivity distribution in the blood and organ uptake were measured by gamma camera scintigraphy. In blood sampled 30–300 s after injection, only a minor fraction ( 4 h) biphasic pattern. In patients with quiescent or mild nepthritis, the liver and to a lesser extent the spleen were the major organs that mediated the rapid uptake and processing of the cryoglobulins from the circulation. In contrast, patients with active mesangiocapillary glomerulonephritis showed significantly (P< 0.001) less hepatic uptake, low liver-to-precordium ratio, and slower processing of cryoglobulins, prolonged liver mean transit time, than quiescent patients or mild nephritis patients. To elucidate the role and influence of HCV infection in the pathogenesis of EMC-nephritis, sera and cryoglobulins from all patients were assayed for HCV. None of the control group cases without nephritis showed any evidence of HCV-RNA in serum or cryoglobulin pellet. In contrast, all 10 EMC-nephritis patients' sera, and eight corresponding cryoglobulin pellets contained HCV-RNA. Collectively, these findings suggest an impaired reticuloendothelial system removal of IgM–IgG–HCV complexes may underlie their renal deposition. PMID:9353142

  12. HCV Infection Induces Autocrine Interferon Signaling by Human Liver Endothelial Cell and Release of Exosomes, Which Inhibits Viral Replication

    Science.gov (United States)

    Giugliano, Silvia; Kriss, Michael; Golden-Mason, Lucy; Dobrinskikh, Evgenia; Stone, Amy E.L.; Soto-Gutierrez, Alejandro; Mitchell, Angela; Khetani, Salman R.; Yamane, Daisuke; Stoddard, Mark; Li, Hui; Shaw, George M.; Edwards, Michael G.; Lemon, Stanley M.; Gale, Michael; Shah, Vijay H.; Rosen, Hugo R.

    2014-01-01

    Background & Aims Liver sinusoidal endothelial cells (LSECs) make up a large proportion of the non-parenchymal cells in the liver. LSECs are involved in induction of immune tolerance, but little is known about their functions during hepatitis C virus (HCV) infection. Methods Primary human LSECs (HLSECs) and immortalized liver endothelial cells (TMNK-1) were exposed to various forms of HCV, including full-length transmitted/founder virus, sucrose-purified Japanese Fulminant Hepatitis-1 (JFH-1), a virus encoding a luciferase reporter, and the HCV-specific pathogen-associated molecular pattern molecules. Cells were analyzed by confocal immunofluorescence, immunohistochemical, and PCR assays. Results HLSECs internalized HCV, independent of cell–cell contacts; HCV RNA was translated but not replicated. Through pattern recognition receptors (TLR7 and retinoic acid inducible gene 1), HCV RNA induced consistent and broad transcription of multiple interferons (IFNs); supernatants from primary HLSECs transfected with HCV-specific pathogen-associated molecular pattern molecules increased induction of IFNs and IFN-stimulated genes in HLSECs. Recombinant type I and type III IFNs strongly up-regulated HLSEC transcription of interferon λ 3 (IFNL3) and viperin (RSAD2), which inhibit replication of HCV. Compared to CD8+ T cells, HLSECs suppressed HCV replication within Huh7.5.1 cells, also inducing IFN-stimulated genes in co-culture. Conditioned media from IFN-stimulated HLSECs induced expression of antiviral genes by uninfected primary human hepatocytes. Exosomes, derived from HLSECs following stimulation with either type I or type III IFNs, controlled HCV replication in a dose-dependent manner. Conclusions Cultured HLSECs produce factors that mediate immunity against HCV. HLSECs induce self-amplifying IFN-mediated responses and release of exosomes with antiviral activity. PMID:25447848

  13. Tiny staining spots in liver cirrhosis associated with HCV infection observed by computed tomographic hepatic arteriography. Follow-up study

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    Tsuchiyama, Tomoya; Terasaki, Shuichi; Kaneko, Shuichi; Kaji, Kyosuke; Kobayashi, Kenichi; Matsui, Osamu [Kanazawa Univ. (Japan). Hospital

    2002-10-01

    It is important to distinguish small lesions with increased arterial perfusion observed by computed tomographic arteriography (CT-A) from hepatocellular carcinoma (HCC). However, the clinical characteristics and prognosis of such lesions have not been clarified. We retrospectively examined 200 patients with cirrhosis related to hepatitis C virus (HCV) infection who had undergone both CT-A and CT arterioportography between 1995 and 1998, and found 80 tiny staining spots (TSS)s, with a diameter of 5-10 mm, by CT-A (35 patients). The mean TSS observation period was 29.0 months. If the major axis was larger than 10 mm and showed a 1.5-fold or more increase, the lesion was regarded as tumor growth (TG). The TSS lesions were divided into two groups according to whether the patient had or did not have HCC. The prognosis of TSS was classified into three groups; HCC-suspected group, nontumor group, and unclassified group, in which TG was negative although transcatheter arterial embolization (TAE) had been performed. Of the 40 TSSs in 14 patients without HCC, 2 (5%) were suspected as HCC. Of the 40 TSSs in 21 patients with HCC, 13 (32.5%) were suspected as HCC. There were no significant differences in the size, position, and morphology of TSSs among the three prognostic groups. Of the 7 TSSs with a high signal intensity on T2-weighted magnetic resonance (MR) images, 5 were in the HCC-suspected group. We recommend early treatment of TSSs accompanying HCC or showing features of malignancy at the imaging workup. (author)

  14. Correlates of HIV, HBV, and HCV infections in a prison inmate population: results from a multicentre study in Italy.

    Science.gov (United States)

    Babudieri, S; Longo, B; Sarmati, L; Starnini, G; Dori, L; Suligoi, B; Carbonara, S; Monarca, R; Quercia, G; Florenzano, G; Novati, S; Sardu, A; Iovinella, V; Casti, A; Romano, A; Uccella, I; Maida, I; Brunetti, B; Mura, M S; Andreoni, M; Rezza, G

    2005-07-01

    A cross-sectional study was undertaken on the correlates of infection for the human immunodeficiency virus (HIV) and hepatitis viruses B and C (HBV and HCV) in a sample of inmates from eight Italian prisons. A total of 973 inmates were enrolled [87.0% males, median age of 36 years, 30.4% intravenous drug users (IDUs), 0.6% men who have sex with men (MSWM)]. In this sample, high seroprevalence rates were found (HIV: 7.5%; HCV: 38.0%; anti-HBc: 52.7%; HBsAg: 6.7%). HIV and HCV seropositivity were associated strongly with intravenous drug use (OR: 5.9 for HIV; 10.5 for HCV); after excluding IDUs and male homosexuals, the HIV prevalence remained nonetheless relatively high (2.6%). HIV prevalence was higher for persons from Northern Italy and Sardinia. The age effect was U-shaped for HIV and HCV infections; HBV prevalence increased with age. Tattoos were associated with HCV positivity (OR: 2.9). The number of imprisonments was associated with HIV infection, whereas the duration of imprisonment was only associated with anti-HBc. The probability of being HIV-seropositive was higher for HCV-seropositive individuals, especially if IDUs. In conclusion, a high prevalence of HIV, HCV, and HBV infections among inmates was observed: these high rates are in part attributable to the high proportion of IDUs. Frequency of imprisonment and tattoos were associated, respectively, with HIV and HCV positivity. Although it is possible that the study population is not representative of Italy's prison inmate population, the results stress the need to improve infection control measures users was prisons. Copyright (c) 2005 Wiley-Liss, Inc.

  15. A CCL5 Haplotype Is Associated with Low Seropositivity Rate of HCV Infection in People Who Inject Drugs.

    Directory of Open Access Journals (Sweden)

    Kristi Huik

    Full Text Available The role of CC chemokine receptor 5 (CCR5 and its ligand CCL5 on the pathogenesis of HIV infection has been well studied but not for HCV infection. Here, we investigated whether CCL5 haplotypes influence HIV and HCV seropositivity among 373 Caucasian people who inject drugs (PWID from Estonia.Study included 373 PWID; 56% were HIV seropositive, 44% HCV seropositive and 47% co-infected. Four CCL5 haplotypes (A-D were derived from three CCL5 polymorphisms (rs2107538/rs2280788/rs2280789 typed by Taqman allelic discrimination assays. The data of CCR5 haplotypes were used from our previous study. The association between CCL5 haplotypes with HIV and/or HCV seropositivity was determined using logistic regression analysis.Possessing CCL5 haplotype D (defined by rs2107538A/rs2280788G/rs2280789C decreased the odds of HCV seropositivity compared to those not possessing it (OR = 0.19; 95% CI 0.09-0.40, which remained significant after adjustment to co-variates (OR = 0.08; 95% CI 0.02-0.29. An association of this haplotype with HIV seropositivity was not found. In step-wise logistic regression with backward elimination CCL5 haplotype D and CCR5 HHG*1 had reduced odds for HCV seropositivity (OR = 0.28 95% CI 0.09-0.92; OR = 0.23 95% CI 0.08-0.68, respectively compared to those who did not possess these haplotypes, respectively.Our results suggest that among PWID CCL5 haplotype D and CCR5 HHG*1 independently protects against HCV. Our findings highlight the importance of CCL5 genetic variability and CCL5-CCR5 axis on the susceptibility to HCV.

  16. Effect of hepatic iron concentration and viral factors in chronic hepatitis C-infected patients with thalassemia major, treated with interferon and ribavirin

    Directory of Open Access Journals (Sweden)

    Jafroodi M

    2011-07-01

    Full Text Available Maryam Jafroodi, Ramin Asadi, Abtin Heydarzadeh, Sepiedeh BesharatiDepartment of Hematology, Gulian University of Medical Sciences, Rasht, Guilan, IranBackground: Beta thalassemia major patients are vulnerable to transfusion-transmitted infection, especially hepatitis C virus (HCV, and iron overload. These comorbidities lead to cirrhosis and hepatocellular carcinoma in these patients. In order to prevent these complications, treatment of HCV infection and regular iron chelating seems to be necessary. The aim of this study was to evaluate the effect of hepatic iron concentration (HIC and viral factors on the sustained virological response (SVR in chronic HCV-infected patients, with beta thalassemia major being treated with interferon and ribavirin.Materials and methods: We enrolled 30 patients with thalassemia major and chronic HCV who were referred to the Hematology Clinic of Guilan University of Medical Sciences, between December 2002 and April 2006. HIC was measured by atomic absorption spectroscopy before treatment. The viral factors (viral load, genotype and HIC were compared between those who achieved a SVR and nonresponders.Results: Mean age of the 30 thalassemic patients, was 22.56 ± 4.28 years (14–30 years. Most patients were male (56.7%. Genotype 1a was seen in 24 (80% cases. SVR was achieved in 15 patients (50%. There were no significant correlations between HIC (P = 1.00, viral load (P = 0.414, HCV genotype (P = 0.068, and SVR. No difference was observed in viral load (P = 0.669 and HIC (P = 0.654 between responders and nonresponders.Conclusion: HIC, HCV viral load, and HCV genotype were not correlated with virological response, and it seems that there is no need to postpone antiviral treatment for more vigorous iron chelating therapy.Keywords: hepatitis C virus, hepatic iron concentration, combination therapy, thalassemia major, interferon alfa, ribavirin

  17. Identification of hepatitis C virus genotype 2a replicon variants with reduced susceptibility to ribavirin.

    Science.gov (United States)

    Hmwe, Su Su; Aizaki, Hideki; Date, Tomoko; Murakami, Kyoko; Ishii, Koji; Miyamura, Tatsuo; Koike, Kazuhiko; Wakita, Takaji; Suzuki, Tetsuro

    2010-03-01

    Ribavirin (RBV), a nucleoside analogue, is used in the treatment of hepatitis C virus (HCV) infection in combination with interferons. However, potential mechanisms of RBV resistance during HCV replication remain poorly understood. Serial passage of cells harboring HCV genotype 2a replicon in the presence of RBV resulted in the reduced susceptibility of the replicon to RBV. Transfection of fresh cells with RNA from RBV-resistant replicon cells demonstrated that the RBV resistance observed is largely replicon-derived. Four major amino acid substitutions: T1134S in NS3, P1969S in NS4B, V2405A in NS5A, and Y2471H in NS5B region, were identified. Site-directed mutagenesis of these mutations into the replicon indicated that Y2471H plays a role in the reduced susceptibility to RBV and leads to decrease in replication fitness. The results, in addition to analysis of sequence database, suggest that HCV variants with reduced susceptibility to RBV identified are preferential to genotype 2a.

  18. Ribavirin monotherapy for chronic hepatitis C

    DEFF Research Database (Denmark)

    Brok, J; Gluud, L L; Gluud, C

    2005-01-01

    Hepatitis C is a major cause of liver-related morbidity and mortality. The disease progresses without symptoms for several decades. Ribavirin monotherapy may represent a treatment for some patients.......Hepatitis C is a major cause of liver-related morbidity and mortality. The disease progresses without symptoms for several decades. Ribavirin monotherapy may represent a treatment for some patients....

  19. Adrenomedullin in cirrhotic and non-cirrhotic portal hypertension

    Institute of Scientific and Technical Information of China (English)

    V Tahan; C Kalayci; A Okten; N Tozun; E Avsar; C Karaca; E Uslu; F Eren; S Aydin; H Uzun; HO Hamzaoglu; F Besisik

    2003-01-01

    AIM:Adrenomedullin (ADM) is a potent vasodilator peptide.ADM and nitric oxide (NO) are produced in vascular endothelial cells. Increased ADM level has been linked to hyperdynamic circulation and arterial vasodilatation in cirrhotic portal hypertension (CPH). The role of ADM in non-cirrhotic portal hypertension (NCPH) is unknown, plasma ADM levels were studied in patients with NCPH, compensated and decompensated cirrhosis in order to determine its contribution to portal hypertension (PH) in these groups.METHODS: There were 4 groups of subjects. Group 1consisted of 27 patients (F/M: 12/15) with NCPH due to portal and/or splenic vein thrombosis (mean age: 41±12years), group 2 consisted of 14 patients (F/M: 6/8) with compensated (Child-Pugh A) cirrhosis (mean age: 46±4),group 3 consisted of 16 patients (F/M: 6/10) with decompensated (Child-Pugh C) cirrhosis (mean age: 47±12).Fourteen healthy subjects (F/M: 6/8) (mean age: 44±8) were used as controls in Group 4. ADM level was measured by ELISA. NO was determined as nitrite/nitrate level by chemoluminescence.RESULTS: Adl level in Group 11 (236±61.4 pg/mL) was significantly higher than that in group 2 (108.4±28.3 pg/mL)and group 4 (84.1±31.5 pg/mL) (both P<0.0001) but was lower than that in Group3 (324±93.7 pg/mL) (P=0.002). NO level in group 1 (27±1.4 μmol/L) was significantly higher than that in group 2 (19.8±2.8 μmol/L) and group 4 (16.9±1.6μmol/L) but was lower than that in Group 3 (39±3.6 μmol/L)(for all three P<0.0001). A strong correlation was observed between ADM and NO levels (r=0.827, P<0.0001).CONCLUSION: Adrenomedullin and NO levels were high in both non-cirrhotic and cirrhotic portal hypertension and were closely correlated, Adrenomedullin and NO levels increased proportionally with the severity of cirrhosis, and were significantly higher than those in patients with NCPH.Portal hypertension plays an important role in the increase of ADM and NO. Parenchymal damage in cirrhosis may

  20. 广州地区吸毒人员HBV、HCV感染流行病学特征%HBV and HCV infection among drug addicts in Guangzhou

    Institute of Scientific and Technical Information of China (English)

    熊华平; 花文峰; 王敏; 廖峭; 戎霞; 黄杰庭; 黄珂; 许茹; 付涌水

    2013-01-01

    Objective To investigate the infection rates and the impact of HBV and HCV infection among drug addicts in Guangzhou.Methods Questionnaire survey was conducted in this study.Blood samples from the drug addicts were collected.HBsAg and HCV antibodies were detected by ELISA assays.The correlation between infection and possible impact factors were analyzed by SPSS16.0 software.Results Of the 1 375 drug addicts,the percentage of HBV and HCV infection was 20.8% and 39.2%,respectively.106 cases (7.7%) were found to have HBV and HCV co-infection.412 cases were intravenous drug users (IDUs),in which the HBV and HCV infection rate was 24.5% and 84.5%,respectively.Elderly and those with a long history of drug addiction had a higher risk of having HBV and HCV infection.Conclusions Drug addiction,especially through the intravenous injection,is the risk factor of HBV and HCV infection.Age,the history of drug addiction,and intravenous drug injection are correlated with HBV and HCV infection.%目的 了解广州地区吸毒人员乙型肝炎病毒(HBV)、丙型肝炎病毒(HCV)的感染状况及其影响因素.方法 收集广州地区吸毒人员的血液标本,采用ELISA检测HBsAg及HCV抗体,并对吸毒人员采取统一调查表进行问卷调查,采用统计学方法进行相关性分析.结果 1 375名吸毒者HBV、HCV的感染率分别为20.8%、39.2%,HBV/HCV合并感染率为7.7%(106/1 375).其中采用静脉吸毒者HBV、HCV的感染率分别24.5%、84.5%,均高于非静脉吸毒者的19.2%、19.8%,差异有统计学意义(P<0.05).吸毒者年龄越大、吸毒时间越长越容易发生HBV或HCV感染.结论 吸毒尤其是静脉吸毒是HBV、HCV感染的高危因素.吸毒者年龄、吸毒时间长短及吸毒方式与HBV、HCV感染相关.

  1. Superior outcomes in HIV-positive kidney transplant patients compared to HCV-infected or HIV/HCV co-infected recipients

    Science.gov (United States)

    Sawinski, Deirdre; Forde, Kimberly A.; Eddinger, Kevin; Troxel, Andrea B.; Blumberg, Emily; Tebas, Pablo; Abt, Peter L.; Bloom, Roy D.

    2015-01-01

    The prerequisite for an “undetectable” HIV viral load has restricted access to transplantation for HIV-infected kidney recipients. However, HCV-infected recipients, due the historic limitations of HCV therapy in patients with renal disease, are commonly viremic at transplant and have universal access. In order to compare the effect of HIV, HCV and HIV/HCV co-infection on kidney transplant patient and allograft outcomes, we performed a retrospective study of kidney recipients transplanted from January 1996 through December 2013. In multivariable analysis, patient (hazard ratio 0.90, 95% confidence interval 0.66–1.24) and allograft survival (0.60, 40–0.88) in 492 HIV patients did not differ significantly from the 117,791 patient uninfected reference group. This was superior to outcomes in both the 5605 patient HCV group for death (1.44, 1.33–1.56) and graft loss (1.43, 1.31–1.56) as well as the 147 patient HIV/HCV co-infected group for death (2.26, 1.45–3.52) and graft loss (2.59, 1.60–4.19). HIV infection did not adversely affect recipient or allograft survival and was associated with superior outcomes compared to both HCV infection and HIV/HCV co-infection in this population. Thus, pre-transplant viral eradication and/ or immediate post-transplant eradication should be studied as potential strategies to improve post-transplant outcomes in HCV-infected kidney recipients. PMID:25807035

  2. TRAIL receptor I (DR4 polymorphisms C626G and A683C are associated with an increased risk for hepatocellular carcinoma (HCC in HCV-infected patients

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    Körner Christian

    2012-03-01

    Full Text Available Abstract Background Tumour surveillance via induction of TRAIL-mediated apoptosis is a key mechanism, how the immune system prevents malignancy. To determine if gene variants in the TRAIL receptor I (DR4 gene affect the risk of hepatitis C virus (HCV-induced liver cancer (HCC, we analysed DR4 mutations C626G (rs20575 and A683C (rs20576 in HCV-infected patients with and without HCC. Methods Frequencies of DR4 gene polymorphisms were determined by LightSNiP assays in 159 and 234 HCV-infected patients with HCC and without HCC, respectively. 359 healthy controls served as reference population. Results Distribution of C626G and A683C genotypes were not significantly different between healthy controls and HCV-positive patients without HCC. DR4 variants 626C and 683A occurred at increased frequencies in patients with HCC. The risk of HCC was linked to carriage of the 626C allele and the homozygous 683AA genotype, and the simultaneous presence of the two risk variants was confirmed as independent HCC risk factor by Cox regression analysis (Odds ratio 1.975, 95% CI 1.205-3.236; p = 0.007. Furthermore HCV viral loads were significantly increased in patients who simultaneously carried both genetic risk factors (2.69 ± 0.36 × 106 IU/ml vs. 1.81 ± 0.23 × 106 IU/ml, p = 0.049. Conclusions The increased prevalence of patients with a 626C allele and the homozygous 683AA genotype in HCV-infected patients with HCC suggests that these genetic variants are a risk factor for HCC in chronic hepatitis C.

  3. Successful Treatment of Mixed Hepatitis C Genotypes in a Cirrhotic Patient With an All-Oral, Interferon-Free Regimen

    Science.gov (United States)

    Ahmed Sakr, Ayman; Hanifi, Jasmine M.

    2017-01-01

    Mixed hepatitis C virus (HCV) genotype infection is emerging with improved methods of detection. It is commonly seen in hemodialysis patients and intravenous drug users due to repeated HCV exposure and absence of protective immunity, and can contribute to treatment failure. Direct-acting antiviral regimens have been extensively studied in patients with different individual HCV genotypes; however, there are no reported data on their use in patients with mixed HCV genotype. We present a case of mixed HCV genotype 1a and 2 infection in a decompensated cirrhotic patient treated successfully with sofosbuvir, ledipasvir, and ribavirin. PMID:28184373

  4. Evaluation of a new, rapid test for detecting HCV infection, suitable for use with blood or oral fluid.

    Science.gov (United States)

    Lee, Stephen R; Kardos, Keith W; Schiff, Eugene; Berne, Cheryl A; Mounzer, Karam; Banks, Alpha T; Tatum, Harvey A; Friel, Timothy J; Demicco, Michael P; Lee, William M; Eder, Scott E; Monto, Alexander; Yearwood, Graham D; Guillon, Geraldine B; Kurtz, Lisa A; Fischl, Mark; Unangst, Jay Lynn; Kriebel, Laura; Feiss, Gary; Roehler, Michele

    2011-03-01

    oral fluid appeared generally robust to conditions of oral health, consumption of food and drink and use of oral care products. The OraQuick® HCV Rapid Antibody Test demonstrated clinical performance that was equivalent to current laboratory-based EIA. This new, HCV rapid test appears suitable as an aid in the diagnosis of HCV infection and may increase testing opportunities due to its simplicity and flexibility to use multiple specimen types, including fingerstick blood and oral fluid.

  5. Serum Immunoglobulin G Antibodies to the GOR Autoepitope Are Present in Patients with Occult Hepatitis C Virus (HCV) Infection despite Lack of HCV-Specific Antibodies▿

    OpenAIRE

    Quiroga, Juan A.; Castillo, Inmaculada; Bartolomé, Javier; CARREÑO, VICENTE

    2007-01-01

    Antibody responses to the GOR autoepitope are frequently detected among anti-hepatitis C virus (anti-HCV)-positive patients with chronic hepatitis. Sera from 110 anti-HCV-negative patients with occult HCV infection, as diagnosed by detection of HCV RNA in hepatic tissue, were investigated for GOR antibody reactivity. A positive test for anti-GOR immunoglobulin G (IgG) was found for 22 (20%) of them. The frequency and titers of anti-GOR IgG were significantly lower than those in chronic hepati...

  6. The Cedar Project: high incidence of HCV infections in a longitudinal study of young Aboriginal people who use drugs in two Canadian cities

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    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

  7. A Potential Inhibitory Profile of Liver CD68+ Cells during HCV Infection as Observed by an Increased CD80 and PD-L1 but Not CD86 Expression

    Science.gov (United States)

    Said, Elias A.; Al-Reesi, Iman; Al-Riyami, Marwa; Al-Naamani, Khalid; Al-Sinawi, Shadia; Al-Balushi, Mohammed S.; Koh, Crystal Y.; Al-Busaidi, Juma Z.; Idris, Mohamed A.; Al-Jabri, Ali A.

    2016-01-01

    Aim The lack of potent innate immune responses during HCV infection might lead to a delay in initiating adaptive immune responses. Kupffer cells (KCs) and liver-infiltrating monocytes/macrophages (CD68+ cells) are essential to establish effective anti-HCV responses. They express co-stimulatory molecules, CD80 and CD86. CD86 upregulation induces activator responses that are then potentially regulated by CD80. The relative levels of expression of CD80, CD86 and the inhibitory molecule, PD-L1, on CD68+ cells modulate T cell activation. A few studies have explored CD80 and PD-L1 expression on KCs and infiltrating monocytes/macrophages in HCV-infected livers, and none investigated CD86 expression in these cells. These studies have identified these cells based on morphology only. We investigated the stimulatory/inhibitory profile of CD68+ cells in HCV-infected livers based on the balance of CD80, CD86 and PD-L1 expression. Methods CD80, CD86 and PD-L1 expression by CD68+ cells in the lobular and portal areas of the liver of chronic HCV-infected (n = 16) and control (n = 14) individuals was investigated using double staining immunohistochemistry. Results The count of CD68+ KCs in the lobular areas of the HCV-infected livers was lower than that in the control (p = 0.041). The frequencies of CD68+CD80+ cells and CD68+PD-L1+ cells in both lobular and total areas of the liver were higher in HCV-infected patients compared with those in the control group (p = 0.001, 0.031 and 0.007 respectively). Moreover, in the lobular areas of the HCV-infected livers, the frequency of CD68+CD80+ cells was higher than that of CD68+CD86+ and CD68+PD-L1+ cells. In addition, the frequencies of CD68+CD80+ and CD68+CD86+ cells were higher in the lobular areas than the portal areas. Conclusions Our results show that CD68+ cells have an inhibitory profile in the HCV-infected livers. This might help explain the delayed T cell response and viral persistence during HCV infection. PMID:27065104

  8. Safety and efficacy of sofosbuvir plus velpatasvir with or without ribavirin for chronic hepatitis C virus infection: A systematic review and meta-analysis.

    Science.gov (United States)

    Ahmed, Hussien; Abushouk, Abdelrahman Ibrahim; Attia, Attia; Gadelkarim, Mohamed; Gabr, Mohamed; Negida, Ahmed; Abdel-Daim, Mohamed M

    2017-09-29

    Velpatasvir is a newly FDA-approved inhibitor of hepatitis C virus (HCV) NS5A protein. We performed this systematic review and meta-analysis to investigate the safety and efficacy of velpatasvir plus sofosbuvir in the treatment of chronic HCV infection. A computerized literature search of PubMed, SCOPUS, EMBASE, EBSCO, Web of science, and Cochrane CENTRAL was conducted using relevant keywords. Data from eligible studies were pooled in a fixed effect meta-analysis model, using OpenMeta[Analyst] software. Pooled data from six randomized trials (n=1427 patients) showed that velpatasvir plus sofosbuvir achieved sustained virological response (SVR12) rates of 98.2% in genotype-1, 99.4% in genotype-2, 94.7% in genotype-3, 99.6% in genotype-4, 97.1% in genotype-5, and 98.8% in genotype-6 patients. The addition of ribavirin did not significantly increase the SVR12 (RR=0.95, 95%CI [0.88, 1.02]) or decrease relapse rates (RR=2.52, 95% CI [0.49, 12.87]) in HCV genotype-1 patients. However, adding ribavirin significantly increased SVR12 (RR=89.5, 95% CI [80.4, 99.5]) in genotype-3 patients. In conclusion, the 12-week regimen of sofosbuvir plus velpatasvir was highly effective in HCV patients, including those with cirrhosis and former treatment experience. Except for genotype-3, adding ribavirin was not associated with significant improvements in SVR12 rates. Further studies should investigate the effect of adding ribavirin to this regimen, especially in HCV genotype-3 patients. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  9. Peginterferon plus ribavirin versus interferon plus ribavirin for chronic hepatitis C

    DEFF Research Database (Denmark)

    Hauser, Goran; Awad, Tahany; Brok, Jesper

    2014-01-01

    BACKGROUND: Pegylated interferon (peginterferon) plus ribavirin is the recommended treatment for patients with chronic hepatitis C, but systematic assessment of the effect of this treatment compared with interferon plus ribavirin is needed. OBJECTIVES: To systematically evaluate the benefits...... and harms of peginterferon plus ribavirin versus interferon plus ribavirin for patients with chronic hepatitis C. SEARCH METHODS: We searched the Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, Science Citation Index......-Expanded, and LILACS. We also searched conference abstracts, journals, and grey literature. The last searches were conducted in September 2013. SELECTION CRITERIA: We included randomised clinical trials comparing peginterferon plus ribavirin versus interferon plus ribavirin with or without co-intervention(s) (e...

  10. Reversible Inhibition of Cellular Metabolism by Ribavirin

    Science.gov (United States)

    Larsson, Alf; Stenberg, Kjell; Öberg, Bo

    1978-01-01

    The broad spectrum antiviral drug ribavirin (Virazole, 1-β-d-ribofuranosyl-1,2,4-triazole-3-carboxamide) inhibits cellular macromolecular synthesis as well as cell division in eucaryotic cells. The concentration and time dependence have been studied. One-hour treatment with 25 μM ribavirin or 18 h with 2 μM inhibited the deoxyribonucleic acid synthesis to 50%. Higher concentrations of ribavirin were required to obtain a similar inhibition of ribonucleic acid and protein synthesis. This effect on cell metabolism and cell division can be reversed by removing the drug from the cells. PMID:646339

  11. Ribavirin

    Science.gov (United States)

    ... or irregular menstruation (period) muscle or bone pain hair loss Some side effects can be serious. The ... to your pharmacist or contact your local garbage/recycling department to learn about take-back programs in ...

  12. Daclatasvir with sofosbuvir and ribavirin for hepatitis C virus infection with advanced cirrhosis or post‐liver transplantation recurrence

    Science.gov (United States)

    Schiff, Eugene R.; Vierling, John M.; Landis, Charles; Fontana, Robert J.; Yang, Rong; McPhee, Fiona; Hughes, Eric A.; Noviello, Stephanie; Swenson, Eugene S.

    2016-01-01

    Chronic hepatitis C virus (HCV) infection with advanced cirrhosis or post‐liver transplantation recurrence represents a high unmet medical need with no approved therapies effective across all HCV genotypes. The open‐label ALLY‐1 study assessed the safety and efficacy of a 60‐mg once‐daily dosage of daclatasvir (pan‐genotypic NS5A inhibitor) in combination with sofosbuvir at 400 mg once daily (NS5B inhibitor) and ribavirin at 600 mg/day for 12 weeks with a 24‐week follow‐up in two cohorts of patients with chronic HCV infection of any genotype and either compensated/decompensated cirrhosis or posttransplantation recurrence. Patients with on‐treatment transplantation were eligible to receive 12 additional weeks of treatment immediately after transplantation. The primary efficacy measure was sustained virologic response at posttreatment week 12 (SVR12) in patients with a genotype 1 infection in each cohort. Sixty patients with advanced cirrhosis and 53 with posttransplantation recurrence were enrolled; HCV genotypes 1 (76%), 2, 3, 4, and 6 were represented. Child‐Pugh classifications in the advanced cirrhosis cohort were 20% A, 53% B, and 27% C. In patients with cirrhosis, 82% (95% confidence interval [CI], 67.9%‐92.0%) with genotype 1 infection achieved SVR12, whereas the corresponding rates in those with genotypes 2, 3, and 4 were 80%, 83%, and 100%, respectively; SVR12 rates were higher in patients with Child‐Pugh class A or B, 93%, versus class C, 56%. In transplant recipients, SVR12 was achieved by 95% (95% CI, 83.5%‐99.4%) and 91% of patients with genotype 1 and 3 infection, respectively. Three patients received peritransplantation treatment with minimal dose interruption and achieved SVR12. There were no treatment‐related serious adverse events. Conclusion: The pan‐genotypic combination of daclatasvir, sofosbuvir, and ribavirin was safe and well tolerated. High SVR rates across multiple HCV genotypes were achieved by patients with

  13. CCR5△32 mutation does not influence the susceptibility to HCV infection, severity of liver disease and response to therapy in patients with chronic hepatitis C

    Institute of Scientific and Technical Information of China (English)

    Ankur Goyal; PV Suneetha; GT Kumar; Deepak K Shukla; Naveen Arora; Shiv K Sarin

    2006-01-01

    AIM: To study whether CCR5△32 mutation was associated with viral infection and severity of liver disease.METHODS: Two hundred and fifty two histologically proven, chronic HCV patients (mean age: 41 ± 14 years;M/F: 164/88) were genotyped. PCR based genotyping of 32 bp deletion at the CCR5 locus was done. Fourhundred and eight matched healthy controls were studied to assess susceptibility to HCV infection. To assess correlation of immune gene polymorphism with severity of HCV related liver disease, patients with chronic HCV infection were divided into those with a fibrosis score of ≤ 2 (mild) or > 2 (severe) and histological activity index (HAI) of ≤ 5 or > 5. For correlation between CCR5△32 mutations and response to therapy, 129 patients who completed therapy were evaluated.RESULTS: The majority (89.4%) of the patients were infected with genotype 3. The frequency of homozygous CCR5△32 mutants was comparable to HCV patients as compared to the healthy controls (0.7% vs 0%, P = 0.1).Further more, the frequency of CCR5△32 mutation was comparable in patients with mild or severe liver disease.(P = NS). There was also no association observed with response to therapy and CCR5△32 mutation.CONCLUSION: CCR5△32 mutation does not have a role in disease susceptibility, severity or response to therapy in patients with chronic hepatitis C infection.

  14. Kushenin induces the apoptosis of HCV-infected cells by blocking the PI3K-Akt-mTOR pathway via inhibiting NS5A.

    Science.gov (United States)

    Zhou, Yi; Chen, Na; Liu, Xiaojing; Lin, Shumei; Luo, Wenjuan; Liu, Min

    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.

  15. No evidence of occult hepatitis C virus (HCV) infection in serum of HCV antibody-positive HCV RNA-negative kidney-transplant patients.

    Science.gov (United States)

    Nicot, Florence; Kamar, Nassim; Mariamé, Bernard; Rostaing, Lionel; Pasquier, Christophe; Izopet, Jacques

    2010-06-01

    Persistence of hepatitis C virus (HCV) in patients who cleared HCV is still debated. Occult HCV infection is described as the presence of detectable HCV RNA in liver or peripheral blood mononuclear cells (PBMCs) of patients with undetectable plasma HCV-RNA by conventional PCR assays. We have assessed the persistence of HCV in 26 kidney-transplant patients, followed up for 10.5 years (range 2-16), after HCV elimination while on hemodialysis. If HCV really did persist, arising out of the loss of immune control caused by institution of the regimen of immunosuppressive drugs after kidney transplantation, HCV reactivation would have taken place. Their immunosuppression relied on calcineurin inhibitors (100%), and/or steroids (62%), and/or antimetabolites (94%). An induction therapy, given to 22 patients, relied on rabbit antithymocyte globulin (59%) or anti-IL2-receptor blockers (32%). All patients had undetectable HCV RNA as ascertained by several conventional tests. At the last follow-up, no residual HCV RNA was detected in the five liver biopsies, the 26 plasma, and in the 37 nonstimulated and 24 stimulated PBMCs tested with an ultrasensitive RT-PCR assay (detection limit, 2 IU/ml). No biochemical or virologic relapse was seen during follow-up. The absence of HCV relapse in formerly HCV-infected immunocompromised patients suggests the complete eradication of HCV after its elimination while on dialysis.

  16. HCV感染过程中的相关免疫反应%Innate and adaptive immune responses in chronic HCV infection

    Institute of Scientific and Technical Information of China (English)

    姚敏(综述); 吕欣(审校)

    2016-01-01

    丙型肝炎病毒( Hepatitis C Virus, HCV)是慢性丙型病毒性肝炎的主要病因,也是引发肝硬化和肝癌的主要诱因。在HCV感染过程中,伴随着干扰素信号通路的激活和干扰素刺激基因( IFN-stimulated gene,ISG)的持续表达,且有HCV独特的免疫逃逸和免疫细胞的功能损伤。现就HCV感染过程中机体的固有免疫反应和适应性免疫反应的研究进展作一综述。%Hepatitis C virus ( HCV) is a leading cause for chronic hepatitis C , which is also a major inducing cause to re-sult in cirrhosis and hepatocellular carcinoma. In the process of HCV infection, along with activated interferon signaling pathways and constitutive IFN-stimulated gene( ISG) expression, both the viral escape from the immune responses and dys-function of NK and T cell most likely contribute to the ongoing liver disease. In this review, we will summarize current knowledge about the role of innate and adaptive immune responses in HCV infection.

  17. HCV derived from sera of HCV-infected patients induces pro-fibrotic effects in human primary fibroblasts by activating GLI2

    Science.gov (United States)

    Granato, M.; Zompetta, C.; Vescarelli, E.; Rizzello, C.; Cardi, A.; Valia, S.; Antonelli, G.; Marchese, C.; Torrisi, M. R.; Faggioni, A.; Cirone, M.

    2016-01-01

    Hepatitis C virus (HCV) infection is a leading cause of liver fibrosis, especially in developing countries. The process is characterized by the excess accumulation of ECM that may lead, over time, to hepatic cirrhosis, liver failure and also to hepatocarcinoma. The direct role of HCV in promoting fibroblasts trans-differentiation into myofibroblasts, the major fibrogenic cells, has not been fully clarified. In this study, we found that HCV derived from HCV-infected patients infected and directly induced the trans-differentiation of human primary fibroblasts into myofibroblasts, promoting fibrogenesis. This effect correlated with the activation of GLI2, one of the targets of Hedgehog signaling pathway previously reported to be involved in myofibroblast generation. Moreover, GLI2 activation by HCV correlated with a reduction of autophagy in fibroblasts, that may further promoted fibrosis. GLI2 inhibition by Gant 61 counteracted the pro-fibrotic effects and autophagy inhibition mediated by HCV, suggesting that targeting HH/GLI2 pathway might represent a promising strategy to reduce the HCV-induced fibrosis. PMID:27476557

  18. Ribavirin monotherapy for chronic hepatitis C

    DEFF Research Database (Denmark)

    Brok, Jesper; Gluud, Lise Lotte; Gluud, Christian

    2009-01-01

    BACKGROUND: Hepatitis C is a major cause of liver-related morbidity and mortality. A high proportion of patients never experience symptoms. Peginterferon plus ribavirin is the recommended treatment for chronic hepatitis C. However, ribavirin monotherapy may be considered for some patients....... OBJECTIVES: To assess the beneficial and harmful effects of ribavirin monotherapy for patients with chronic hepatitis C. SEARCH STRATEGY: We identified trials through electronic databases, manual searches of bibliographies and journals, authors of trials, and pharmaceutical companies until March 2009....... SELECTION CRITERIA: We included all randomised trials irrespective of blinding, language, or publication status comparing ribavirin versus no intervention, placebo, or interferon for chronic hepatitis C. DATA COLLECTION AND ANALYSIS: The primary outcome measures were serum sustained virological response...

  19. Interleukin-10.rs1800896 and Interleukin-18.rs1946518 gene polymorphisms could not predict the outcome of hepatitis C virus infection in Egyptian patients treated with pegylated interferon plus ribavirin.

    Science.gov (United States)

    Abdelraheem, Wedad M; Hassuna, Noha A; Abuloyoun, Sahar M; Abdel Ghany, Hend M; Rizk, Hazem A; Abdelwahab, Sayed F

    2016-09-01

    A single-nucleotide polymorphism (SNP) in the interleukin (IL)-28B gene was used as a major predictor of the response to treatment in patients with hepatitis C virus (HCV) infection. Data examining the role of IL-10 and IL-18 gene polymorphisms among HCV genotype 4 (G4)-infected Egyptians in response to pegylated interferon (PEG-IFN) plus ribavirin (RBV) therapy are limited. This study investigated the impact of SNP at IL-10.rs1800896 (at position -1082) and IL-18.rs1946518 genes (at position -607) on the response to PEG-IFN/RBV therapy in HCV-infected Egyptians. This study was carried out on 100 HCV patients treated with PEG-IFN plus RBV and 100 healthy controls. The HCV patients included 50 treatment non-responders (NR) and 50 subjects with sustained virologic response (SVR). Genomic DNA from venous blood of subjects was extracted and IL-10.rs1800896 and IL-18.rs1946518 genotypes were determined using allele-specific amplification and SYBR Green real-time PCR. Linkage disequilibrium between the two SNPs was estimated using Haploview software. The frequency of the IL-10.rs1800896 AA, AG and GG genotypes among non-responders were 16 %, 70 % and 14 % while among SVR subjects, the frequency was 34 %, 60 % and 6 %, respectively (p=0.073). On the other hand, the frequency of the IL-18.rs1946518 AA, AC and CC genotypes among non-responders was 14 %, 50 % and 36 %, respectively, while among responders, these frequencies were 28 %, 44 % and 28 %, (p = 0.220). Both markers were in linkage equilibrium (D' = 0.23; r (2) = 0.052). SNPs in the IL-10.rs1800896 and IL-18.rs1946518 genes could not predict the outcome of HCV infection in Egyptians treated with PEG-IFN/RBV.

  20. Ayurvedic management of cirrhotic ascites

    Directory of Open Access Journals (Sweden)

    G Aswathy

    2016-01-01

    Full Text Available Cirrhosis is the final stage of most of the chronic liver diseases and is most invariably complicated by portal hypertension resulting in ascites. A case of chronic liver disease with portal hypertension (cryptogenic cirrhosis, managed at Amrita School of Ayurveda is discussed in this paper. The clinical picture was that of an uncomplicated cirrhotic ascites. Snehapāna (therapeutic oral administration of lipids followed by virecana (purgation was done after an initial course of nityavirecana (daily purgation. Later Vardhamāna pippalī rasāyana [administration of single drug - pippalī (piper longum in a structured dose pattern] was administered with an intention of rejuvenating liver cells. Ascites and lower limb oedema were completely resolved after the therapy. No recurrence of ascites has been reported after a follow up period of one year.

  1. Efficacy and Tolerability of Pegylated Interferon and Ribavirin in Combination with Simeprevir to Treat Hepatitis C Virus Infections After Living Donor Liver Transplantation.

    Science.gov (United States)

    Miuma, Satoshi; Ichikawa, Tatsuki; Miyaaki, Hisamitsu; Haraguchi, Masafumi; Tamada, Yoko; Shibata, Hidetaka; Taura, Naota; Soyama, Akihiko; Hidaka, Masaaki; Takatsuki, Mitsuhisa; Eguchi, Susumu; Nakao, Kazuhiko

    2016-06-01

    Pegylated interferon and ribavirin plus simeprevir therapy (simeprevir-based triple therapy) has been recently introduced, providing excellent results for nontransplant patients with hepatitis C virus (HCV) infection. However, there are limited data available on its effect on liver transplant recipients. In the present study, we evaluated the efficacy and tolerability of simeprevir-based triple therapy in liver transplant recipients. We treated 9 liver transplant recipients for genotype 1b HCV reinfection with simeprevir-based triple therapy. The efficacy and adverse effects were evaluated until 24 weeks after therapy. All recipients continued immunosuppressive therapy at the same dose as that before therapy induction. Seven of the 9 recipients (77.8%) achieved sustained virological response at 24 weeks. Two recipients (22.2%) experienced viral breakthrough (BT) at 12 and 16 weeks; NS3 HCV mutations conferring resistance to simeprevir were detected in both these patients after BT. Anemia was the most common adverse effect, requiring ribavirin dose reduction and blood transfusion. However, all recipients, except those with BT, completed the 24-week therapy. No recipient experienced cellular rejection during therapy. In conclusion, simeprevir-based triple therapy exhibited high efficacy and tolerability in liver transplant recipients with genotype 1b HCV reinfection.

  2. Indian National Association for Study of the Liver (INASL) Guidance for Antiviral Therapy Against HCV Infection: Update 2016.

    Science.gov (United States)

    Puri, Pankaj; Saraswat, Vivek A; Dhiman, Radha K; Anand, Anil C; Acharya, Subrat K; Singh, Shivaram P; Chawla, Yogesh K; Amarapurkar, Deepak N; Kumar, Ajay; Arora, Anil; Dixit, Vinod K; Koshy, Abraham; Sood, Ajit; Duseja, Ajay; Kapoor, Dharmesh; Madan, Kaushal; Srivastava, Anshu; Kumar, Ashish; Wadhawan, Manav; Goel, Amit; Verma, Abhai; Shalimar; Pandey, Gaurav; Malik, Rohan; Agrawal, Swastik

    2016-06-01

    India contributes significantly to the global burden of HCV. While the nucleoside NS5B inhibitor sofosbuvir became available in the Indian market in March 2015, the other directly acting agents (DAAs), Ledipasvir and Daclatasvir, have only recently become available in the India. The introduction of these DAA in India at a relatively affordable price has led to great optimism about prospects of cure for these patients as not only will they provide higher efficacy, but combination DAAs as all-oral regimen will result in lower side effects than were seen with pegylated interferon alfa and ribavirin therapy. Availability of these newer DAAs has necessitated revision of INASL guidelines for the treatment of HCV published in 2015. Current considerations for the treatment of HCV in India include the poorer response of genotype 3, nonavailability of many of the DAAs recommended by other guidelines and the cost of therapy. The availability of combination DAA therapy has simplified therapy of HCV with decreased reliance of evaluation for monitoring viral kinetics or drug related side effects.

  3. Dendritic cells activation is associated with sustained virological response to telaprevir treatment of HCV-infected patients.

    Science.gov (United States)

    Sacchi, Alessandra; Tumino, Nicola; Turchi, Federica; Refolo, Giulia; Fimia, GianMaria; Ciccosanti, Fabiola; Montalbano, Marzia; Lionetti, Raffaella; Taibi, Chiara; D'Offizi, Gianpiero; Casetti, Rita; Bordoni, Veronica; Cimini, Eleonora; Martini, Federico; Agrati, Chiara

    2017-07-20

    First anti-HCV treatments, that include protease inhibitors in conjunction with IFN-α and Ribavirin, increase the sustained virological response (SVR) up to 80% in patients infected with HCV genotype 1. The effects of triple therapies on dendritic cell (DC) compartment have not been investigated. In this study we evaluated the effect of telaprevir-based triple therapy on DC phenotype and function, and their possible association with treatment outcome. HCV+ patients eligible for telaprevir-based therapy were enrolled, and circulating DC frequency, phenotype, and function were evaluated by flow-cytometry. The antiviral activity of plasmacytoid DC was also tested. In SVR patients, myeloid DC frequency transiently decreased, and returned to baseline level when telaprevir was stopped. Moreover, an up-regulation of CD80 and CD86 on mDC was observed in SVR patients as well as an improvement of IFN-α production by plasmacytoid DC, able to inhibit in vitro HCV replication. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Peg-interferon plus ribavirin in chronic hepatitis C: cost-efficacy and pharmacoutilization in clinical practice

    Directory of Open Access Journals (Sweden)

    Luisa Cavalletto

    2008-12-01

    Full Text Available The current standard of care for the treatment of chronic hepatitis C virus (HCV infection is combination therapy with Peg-interferon (IFN alpha-2a or alpha-2b type plus ribavirin (RBV. This antiviral schedule can in fact avoid the three fold mortality rates associated to untreated cases with HCV infection, by inducing viral eradication and liver damage regression, so as to define the patients “definitively cured” from liver disease. This analysis describes the modalities of antiviral treatment in the Veneto region, in particular the therapy-schedule mainly used and compares the cost-effectiveness of treatment with the 2 available Peg-IFNs with strategies proposed as in the every day practice. Twelve on line hepatologic units, centralized by a network program on “Surveillance and Control of HCV Infection in the Veneto Region”, prospectively collected data and, of these, we evaluated 450 subjects that underwent antiviral therapy for chronic hepatitis or cirrhosis. A post hoc retrospective analysis of cases treated from January 2003 to December 2005 was performed, grouping the study population in 166 cases treated with Peg-IFN alpha-2a (Pegasys®, Roche, fixed-dose of 180 μg/weekly and 284 that received Peg-IFN alpha-2b (Peg-Intron®, Schering-Plough, weight-adjusted-dose from 50 to 150 μg/weekly, both in combination therapy with ribavirin (Copegus®, Roche, or Rebetol®, Schering-Plough, weight-adjusted-dose of 15 mg/kg/daily. Epidemiological characteristics and cumulative rate of end-of-therapy response and Sustained Virological Response (SVR were similar in the 2 groups, but 78% of cases treated with Peg-IFN alpha-2b and RBV received a significantly lower dose with respect to the weight-adjusted dose. This event conditioned efficacy to therapy as demonstrated in cases that received a < 1 μg/kg dose with respect to those treated with > 1 μg/kg (respectively SVR: 49% vs 66%, p < 0,01, particularly in genotype HCV-1 (SVR: 29% vs 51%, p

  5. Modulation of monocyte/macrophage-derived cytokine and chemokine profile by persistent Hepatitis C virus (HCV infection leads to chronic inflammation

    Directory of Open Access Journals (Sweden)

    Penelope Mavromara

    2012-02-01

    Full Text Available HCV infection presents a major public health problem, with more than 170 million people infected worldwide. Chronicity and persistence of infection constitute the hallmark of the disease. Although HCV is a hepatotropic virus, subsets of immune cells have been found to be permissive to infection and viral replication. Peripheral blood monocytes, attracted to the site of infection and differentiated into macrophages, and resident hepatic macrophages, known as Kupffer cells, are important mediators of innate immunity, through production of several chemokines and cytokines in addition to their phagocytic activity. HCV proteins have been shown to modulate the cytokine and chemokine production profile of monocytes/macrophages, as it is suggested by both in vitro and clinical studies. This modified expression profile appears crucial for the establishment of aberrant inflammation that leads to liver cirrhosis and hepatocellular carcinoma.

  6. Expression of bcl-2 protein in chronic hepatitis C: Effect of interferon alpha 2b with ribavirin therapy

    Institute of Scientific and Technical Information of China (English)

    Panasiuk Anatol; Prokopowicz Danuta; Dzieciol Janusz; Panasiuk Bozena

    2005-01-01

    AIM: Mechanisms responsible for persistence of HCV infection and liver damage in chronic hepatitis C are not clear. Apoptosis is an important form of host immune response against viral infections. Anti-apoptotic proteinbcl-2 expression on liver tissue as well as the influence of interferon alpha 2b (IFNα2b) and ribavirin (RBV) were analyzed in patients with chronic hepatitis C. METHODS: In 30 patients with chronic hepatitis C (responders - R and non-responders - NR) treated with IFNα2b+RBV, protein bcl-2 was determined in hepatocytes and in liver associated lymphocytes before and after the treatment.RESULTS: The treatment diminished bcl-2 protein accumulation in liver cells in_patients with hepatitis C (P<0.05). Before and after the therapy, we detected bcl-2 protein in R in 87±15% and 83±20% of hepatocytes andin 28± 18% and 26±10% of liver-associated lymphocytes, respectively. In NR, the values before treatment decreased from 94±32% to 88±21% of hepatocytes and 39±29% to 28±12% of lymphocytes with bcl-2 expression. There was no statistical correlation between bcl-2 expression on liver tissue with inflammatory activity, fibrosis and biochemical parameters before and after the treatment.CONCLUSION: IFNα2b+RBV treatment, by bcl-2 protein expression decrease, enables apoptosis of hepatocytes and associated liver lymphocytes, which in turn eliminate hepatitis C viruses.

  7. Interferon alfa with or without ribavirin for chronic hepatitis C

    DEFF Research Database (Denmark)

    Kjaergard, L L; Krogsgaard, K; Gluud, C

    2001-01-01

    To assess the efficacy and safety of interferon alfa with or without ribavirin for treatment of chronic hepatitis C.......To assess the efficacy and safety of interferon alfa with or without ribavirin for treatment of chronic hepatitis C....

  8. Cloning and expression of NS3 helicase fragment of hepatitis C virus and the study of its immunoreactivity in HCV infected patients

    Directory of Open Access Journals (Sweden)

    Mahrou Sadri

    2015-02-01

    Full Text Available Objective(s: Hepatitis C is a major cause of liver failure worldwide. Current therapies applied for this disease are not fully effective and produce side effects in most cases. Non-structural protein 3 helicase (NS3 of HCV is one of the key enzymes in viral replication and infection. Therefore, this region is a promising target to design new drugs and therapies against HCV infection. The aim of this study was cloning and expression of HCV NS3 helicase fragment in Escherichia coli BL21 (DE3 using pET102/D-TOPO expression vector and studying immunoreactivity of the expressed antigen in Iranian infected with hepatitis C. Materials and Methods: The viral RNA was extracted from the serum of HCV infected patient. The NS3 helicase region was amplified by RT-PCR. The PCR product was directionally cloned into the expression vector pET102/D-TOPO and transformed into the BL21 strain of E. coli (DE3. The transformed bacteria were then induced by adding 1mM isopropyl-β-D-thiogalactopyranoside (IPTG into the culture medium to enhance the protein expression. SDS-PAGE and western blotting were carried out to identify the protein under investigation, and finally purified recombinant fusion protein was used as the antigen for ELISA method. Results: Theinsertion of theDNA fragment of the NS3 regioninto the expression vectorwas further confirmed by PCR and sequencing. SDS-PAGE analysis showed the successful expression of the recombinant protein of interest. Furthermore, immunoreactivity of fusion NS3 helicase was confirmed by ELISA and western blotting. Conclusion: It seems that this recombinant protein could be a useful source of antigen for future studies on HCV diagnosis and therapy.

  9. During Hepatitis C Virus (HCV) Infection and HCV-HIV Coinfection, an Elevated Plasma Level of Autotaxin Is Associated With Lysophosphatidic Acid and Markers of Immune Activation That Normalize During Interferon-Free HCV Therapy.

    Science.gov (United States)

    Kostadinova, Lenche; Shive, Carey L; Judge, Chelsey; Zebrowski, Elizabeth; Compan, Anita; Rife, Kelsey; Hirsch, Amy; Falck-Ytter, Yngve; Schlatzer, Daniela M; Li, Xiaolin; Chance, Mark R; Rodriguez, Benigno; Popkin, Daniel L; Anthony, Donald D

    2016-11-01

     Immune activation predicts morbidity during hepatitis C virus (HCV) infection and human immunodeficiency virus (HIV) infection, although mechanisms underlying immune activation are unclear. Plasma levels of autotaxin and its enzymatic product, lysophosphatidic acid (LPA), are elevated during HCV infection, and LPA activates immunocytes, but whether this contributes to immune activation is unknown.  We evaluated plasma levels of autotaxin, interleukin 6 (IL-6), soluble CD14 (sCD14), soluble CD163 (sCD163), and Mac2 binding protein (Mac2BP) during HCV infection, HIV infection, and HCV-HIV coinfection, as well as in uninfected controls, before and after HIV antiretroviral therapy (ART) initiation and during interferon-free HCV therapy.  We observed greater plasma autotaxin levels in HCV-infected and HCV-HIV-coinfected participants, compared with uninfected participants, primarily those with a higher ratio of aspartate aminotransferase level to platelet count. Autotaxin levels correlated with IL-6, sCD14, sCD163, Mac2BP, and LPA levels in HCV-infected participants and with Mac2BP levels in HCV-HIV-coinfected participants, while in HIV-infected individuals, sCD14 levels correlated with Mac2BP levels. Autotaxin, LPA, and sCD14 levels normalized, while sCD163 and Mac2BP levels partially normalized within 6 months of starting interferon-free HCV therapy. sCD163 and IL-6 levels normalized within 6 months of starting ART for HIV infection. In vitro, LPA activated monocytes.  These data indicate that elevated levels of autotaxin and soluble markers of immune activation during HCV infection are partially reversible within 6 months of initiating interferon-free HCV treatment and that autotaxin may be causally linked to immune activation during HCV infection and HCV-HIV coinfection. Published by Oxford University Press for the Infectious Diseases Society of America 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  10. Evolution of viral RNA in a Chinese patient to interferon/ribavirin therapy for hepatitis C

    Institute of Scientific and Technical Information of China (English)

    Xian-Zi Wen; Zhi-Hai Chen; Ya-Zhi Wei; Jia-Fu Ji

    2012-01-01

    Objective:The combination of interferon (IFN) and ribavirin (RBV) is the standard therapy for hepatitis C virus (HCV) infection.HCV genotype 2a has proved more amenable to the therapy,but its efficacy is yet limited.This study aimed to investigate the mechanism of the poor response in a case of HCV genotype 2a infection.Methods:We analyzed dynamic change of HCV RNA from a patient,infected with HCV genotype 2a,showing a poor virological response to IFN/RBV as judged 12 weeks after initiation of the therapy by HCV clone sequencing.Then we constructed subgenomic Japanese fulminant hepatitis-1 (JFH1) replicon and different chimeric replicons with humanized Gaussia luciferase gene.The chimeric replicons were derived from subgenomic JFH1 replicon,in which the NS5A region was replaced by the patient's sequence from the pre/post-treatment,and the chimeric replicons' susceptibility to IFN were evaluated by relative Gausia Luciferase activity.Results:The pretreatment HCV sequences appeared almost uniform,and the quasispecies variation was further more simplified after 12 weeks of therapy.Besides,the quasispecies variation seemed to be more diversified in the NS5A,relatively,a region crucial for IFN response,and each of chimeric replicons exhibited distinct response to IFN.Conclusions:During the course of the chronic infection,HCV population seems to be adapted to the patient's immunological system,and further to be selected by combination of IFN/RBV therapy,indicating quasispecies may completely eliminated by addition of other drugs with targets different from those of IFN.In addition,each different response of chimeric replicon to IFN is most likely related to amino acid changes in or near the IFN-sensitivity determining region (ISDR) of NS5A during chronic infection and IFN/RBV therapy.

  11. Inosine triphosphatase allele frequency and association with ribavirin-induced anaemia in Brazilian patients receiving antiviral therapy for chronic hepatitis C

    Directory of Open Access Journals (Sweden)

    Nathália Delvaux

    2015-08-01

    Full Text Available Inosine triphosphatase (ITPA single nucleotide polymorphisms (SNPs are strongly associated with protection against ribavirin (RBV-induced anaemia in European, American and Asian patients; however, there is a paucity of data for Brazilian patients. The aim of this study was to evaluate the ITPA SNP (rs7270101/rs1127354 frequency in healthy and hepatitis C virus (HCV-infected patients from Brazil and the association with the development of severe anaemia during antiviral therapy. ITPA SNPs were determined in 200 HCV infected patients and 100 healthy individuals by sequencing. Biochemical parameters and haemoglobin (Hb levels were analysed in 97 patients who underwent antiviral therapy. A combination of AArs7270101+CCrs1127354 (100% ITPase activity was observed in 236/300 individuals. Anaemia was observed in 87.5% and 86.2% of treated patients with AA (rs7270101 and CC genotypes (rs1127354, respectively. Men with AA (rs7270101 showed a considerable reduction in Hb at week 12 compared to those with AC/CC (p = 0.1475. In women, there was no influence of genotype (p = 0.5295. For rs1127354, men with the CC genotype also showed a sudden reduction in Hb compared to those with AC. Allelic distribution of rs7270101 and rs1127354 shows high rates of the genotypes AA and CC, respectively, suggesting that the study population had a great propensity for developing RBV-induced anaemia. A progressive Hb reduction during treatment was observed; however, this reduction was greater in men at week 12 than in women.

  12. Inosine triphosphatase allele frequency and association with ribavirin-induced anaemia in Brazilian patients receiving antiviral therapy for chronic hepatitis C

    Science.gov (United States)

    Delvaux, Nathália; da Costa, Vanessa Duarte; da Costa, Maristella Matos; Villar, Livia Melo; Coelho, Henrique Sérgio Moraes; Esberard, Eliane Bordalo Cathalá; Flores, Priscila Pollo; Brandão-Mello, Carlos Eduardo; Villela-Nogueira, Cristiane Alves; de Almeida, Adilson José; Lampe, Elisabeth

    2015-01-01

    Inosine triphosphatase (ITPA) single nucleotide polymorphisms (SNPs) are strongly associated with protection against ribavirin (RBV)-induced anaemia in European, American and Asian patients; however, there is a paucity of data for Brazilian patients. The aim of this study was to evaluate the ITPA SNP (rs7270101/rs1127354) frequency in healthy and hepatitis C virus (HCV)-infected patients from Brazil and the association with the development of severe anaemia during antiviral therapy. ITPA SNPs were determined in 200 HCV infected patients and 100 healthy individuals by sequencing. Biochemical parameters and haemoglobin (Hb) levels were analysed in 97 patients who underwent antiviral therapy. A combination of AArs7270101+CCrs1127354 (100% ITPase activity) was observed in 236/300 individuals. Anaemia was observed in 87.5% and 86.2% of treated patients with AA (rs7270101) and CC genotypes (rs1127354), respectively. Men with AA (rs7270101) showed a considerable reduction in Hb at week 12 compared to those with AC/CC (p = 0.1475). In women, there was no influence of genotype (p = 0.5295). For rs1127354, men with the CC genotype also showed a sudden reduction in Hb compared to those with AC. Allelic distribution of rs7270101 and rs1127354 shows high rates of the genotypes AA and CC, respectively, suggesting that the study population had a great propensity for developing RBV-induced anaemia. A progressive Hb reduction during treatment was observed; however, this reduction was greater in men at week 12 than in women. PMID:26154744

  13. Determination of ribavirin by flow injection chemiluminescence

    Institute of Scientific and Technical Information of China (English)

    Juqing Jin; Yuhai Tang; Langchong He; Hong Yao; Yuanyuan Sun

    2006-01-01

    Objective: To establish a rapid and precise continuous flow-injection chemiluminescence (CL) method to determine ribavirin. Methods: The ribavirin could restrain strongly CL reaction of luminol in sodium hydroxide (NaOH) solution with potassium chlorate(KClO3). The different experimental parameters affecting the CL intensity were studied carefully. Results:Under optimum conditions(The concentrations of luminol,KClO3, and NaOH were at 0.1 mmol/L,0.5 μmol/L,and 0.2 mol/L, respectively), the linear range of the working curves was 0.01-7.00 μg/ml with a detection limit of 0.004 μg/ml. Conclusion: The method is simple, rapid and sensitive, and successfully applied to the determination of ribavirin in pharmaceutical preparations and biological fluids.

  14. Survey of serum procalcitonin in cirrhotic patients.

    Science.gov (United States)

    Rahimkhani, Monireh; Einollahi, Nahid; Khavari Daneshvar, Hossein; Dashti, Nasrin

    2013-04-06

    Procalcitonin (PCT) is a prohormone that has been used as a marker for the diagnosis of bacterial infections. The aim of this study was to survey PCT levels in patients with cirrhosis. Sixty-four patients with hepatic cirrhosis and 32 healthy blood donors were enrolled in this study. Serum PCT levels was detected using immunoluminometric assay. The rate of positive PCT was higher in patients with hepatitis C cirrhosis (92.8%) than the other groups. Among other cirrhotic patients, positive PCT levels were 77% for hepatitis B, 70% for cancer and 53.3% for unknown groups respectively. Serum procalcitonin levels were significantly higher in cirrhotic patients with bacterial infection (2.65±1.11 ng/ml) than those without infection (0.59±0.16 ng/ml, P=0.0001). PCT assay in cirrhotic patients may help diagnosis of sepsis and reduce unnecessary antibiotic use.

  15. Survey of Serum Procalcitonin in Cirrhotic Patients

    Directory of Open Access Journals (Sweden)

    Monireh Rahimkhani

    2013-03-01

    Full Text Available Procalcitonin (PCT is a prohormone that has been used as a marker for the diagnosis of bacterial infections. The aim of this study was to survey PCT levels in patients with cirrhosis. Sixty-four patients with hepatic cirrhosis and 32 healthy blood donors were enrolled in this study. Serum PCT levels was detected using immunoluminometric assay. The rate of positive PCT was higher in patients with hepatitis C cirrhosis (92.8% than the other groups. Among other cirrhotic patients, positive PCT levels were 77% for hepatitis B, 70% for cancer and 53.3% for unknown groups respectively. Serum procalcitonin levels were significantly higher in cirrhotic patients with bacterial infection (2.65±1.11 ng/ml than those without infection (0.59±0.16 ng/ml, P=0.0001. PCT assay in cirrhotic patients may help diagnosis of sepsis and reduce unnecessary antibiotic use

  16. The preliminary efficacy of interferon-α and ribavirin combination treatment of chronic hepatitis C in HIV-infected patients

    Institute of Scientific and Technical Information of China (English)

    ZHENG Yu-huang; ZHANG Chun-ying; HE Yan; ZHOU Hua-ying; ZOU Wen; DING Pei-pei; HUANG Li; LI Hui

    2005-01-01

    Background It is internationally accepted that in drug-nave individuals with hepatitis C virus (HCV) and human immunodeficiency virus (HIV) co-infection, chronic hepatitis C should be treated first if the CD4 cell count does not require the initiation of anti-retroviral therapy. Present paper evaluated the clinical effect and side-effect of interferon-α (IFN-α) and ribavirin (RBV) combination therapy for Chinese patients with HCV-HIV co-infection, and compared with them for HIV infection alone. Methods Ten patients with HCV-HIV and 17 patients with HCV received 5 million unit IFNα-2b every other day intramuscularly, and 300 mg RBV triple daily by oral. Dynamic observations were made for HCV RNA and HIV RNA loads, CD4+ and CD8+ T lymphocyte counts, liver function and blood cell measurement, and the medicine side-effects. Results After 12-week and 24-week treatments of IFN-α and RBV combination therapy, mean HCV RNA levels reduced 1.14 logs and 1.56 logs from the baseline at week 0 in HCV-HIV co-infection, and reduced 1.48 logs and 1.75 logs in HCV infection, respectively. The HIV RNA levels decreased 1.22 logs and 1.32 logs from the base line; however, there were no obvious different changes at T lymphocyte counts of HCV-HIV and HCV patients through 24-week treatments. Whole 27 patients showed satisfactory biochemical response to therapy. There were some mild or mediate influence-like symptoms, intestinal uncomfortable and depressed blood cell counts in early stage of the treatments. No neuropsychiatric and auto-immune disorders were found. Conclusions IFN-α and RBV combination therapy had similar anti-HCV effects during 24-week treatment for HCV-HIV and HCV infected Chinese patients, and some anti-HIV effect. There were no obvious different biochemical responses and side-effects between two groups above.

  17. Progress in the development of experimental animal models of HCV infection%HCV实验动物模型研究进展

    Institute of Scientific and Technical Information of China (English)

    陶万银; 张岩; 钟劲

    2012-01-01

    HCV是威胁人类健康的重要病原体之一,可在人体肝脏形成持续性感染,导致慢性肝炎、肝纤维化、肝硬化和肝癌.HCV的实验动物模型不仅是HCV免疫学、病理学和病毒学等基础科学的重要研究手段,还为HCV疫苗和药物的研发提供了关键的工具和平台.黑猩猩是除了人类以外唯一可以被HCV感染的灵长类动物,为HCV的研究做出了重要贡献,但其使用受到了成本及伦理上的限制.近年在利用树鼩和人源化小鼠建立HCV小动物模型的研究上取得良好的进展.本文将总结常用HCV实验动物模型的现状和挑战.%HCV is one of the major pathogens that pose threats to human public health. It can establish persistent infection in human liver, leading to chronic hepatitis, liver fibrosis/cirrhosis and hepatocellular carcinoma. The experimental animal models for HCV infection are not only important research means for investigating immunology, pathology and virology of HCV infection, but also serve as the means and platform for the development of HCV vaccines and novel agents. Chimpanzees, the sole primate except hu man beings who can be infected by HCV, have made significant contributions to HCV research. However, their application has been hampered due to their cost and ethical issues. A big progress has been made in developing small animal models for HCV research using tupaia and humanized mice in recent years. This review summarizes the current status and challenges of the development of HCV animal models.

  18. 丙型肝炎病毒感染与脑出血的关系研究%Relationship between HCV Infection and Cerebral Hemorrhage

    Institute of Scientific and Technical Information of China (English)

    袁磊

    2016-01-01

    目的:探讨丙型肝炎病毒(HCV)感染与脑出血的关系。方法选取2010—2015年在河南省南阳市第二人民医院神经内科住院治疗的患者342例,根据脑出血发生情况分为脑出血组64例与非脑出血组278例。根据既往文献报道及临床经验筛选脑出血的相关因素,并分析 HCV 感染与脑出血的关系。结果两组患者性别、年龄、吸烟率、饮酒率及冠心病、心房颤动、颅内动脉狭窄发生率比较,差异均无统计学意义( P >0.05);脑出血组患者高血压、糖尿病、高脂血症、高同型半胱氨酸血症及 HCV 感染发生率高于非脑出血组(P 0. 05),while incidence of hypertension,diabetes,hyperlipidaemia,hyperhomocysteinemia and HCV infection of A group was statistically significantly higher than that of B group,respectively(P < 0. 05). Multivariate logistic regression analysis showed that,hypertension〔OR= 4. 163,95% CI(1. 174,15. 870),P = 0. 023〕,diabetes〔 OR = 4. 578,95% CI(1. 366,15. 482),P = 0. 012〕, hyperhomocysteinemia〔OR = 4. 382,95% CI(1. 325,16. 738),P = 0. 018〕 and HCV infection〔 OR = 3. 306,95% CI (1. 028,10. 605),P = 0. 015〕were risk factors of cerebral hemorrhage. Conclusion HCV infection is one of risk factors of cerebral hemorrhage,which may play an important role in the genesis and development of cerebral hemorrhage.

  19. Portal Vein Thrombosis in non cirrhotic patients

    NARCIS (Netherlands)

    M.C.W. Spaander (Manon)

    2010-01-01

    textabstractExtrahepatic portal vein thrombosis (EPVT) is the most common cause of portal hypertension in non- cirrhotic patients. EPVT has been defined as an obstruction of the extrahepatic portal vein with or without involvement of the intrahepatic portal veins. Although the portal vein accounts f

  20. 增强丙型肝炎病毒DNA疫苗免疫原性的策略%Progress in the development and immunogenicity improvement of DNA vaccine against chronic HCV infection

    Institute of Scientific and Technical Information of China (English)

    殷霄; 文波; 谭文杰

    2011-01-01

    当前全世界有超过1.7亿慢性丙型肝炎(CHC)感染者,目前尚无有效的疫苗.最近丙型肝炎病毒(HCV)实验性疫苗的研制有不少进展.本文综述了增强HCV DNA疫苗免疫原性的策略及相关进展.%More than 170 million people are currently affected by chronic hepatitis C virus (HCV) infection worldwide. Currently,there is no vaccine available. There are many HCV experimental vaccines developed and progressed recently. Here, we would discuss strategies of enhancing immunogenicity of DNA vaccine and review some progress towards development of DNA vaccine against chronic HCV infection.

  1. Persistent hepatitis C virus (HCV) infection impairs HCV-specific cytotoxic T cell reactivity through Mcl-1/Bim imbalance due to CD127 down-regulation.

    Science.gov (United States)

    Larrubia, J R; Lokhande, M U; García-Garzón, S; Miquel, J; González-Praetorius, A; Parra-Cid, T; Sanz-de-Villalobos, E

    2013-02-01

    In persistent hepatitis C virus (HCV) infection, HCV-specific cytotoxic T lymphocyte (CTL) reactivity is impaired and this affects HCV control. Interleukin-7 receptor (CD127) expression on these cells could regulate CTL reactivity through Mcl-1/Bim balance modulation. Bim is a pro-apoptotic molecule blocked by the action of Mcl-1. Mcl-1/Bim expression and T cell reactivity on HCV-specific CTLs were compared according to CD127 phenotype. Peripheral blood lymphocytes (PBL) from HLA-A2(+) HCV(+) patients were obtained. HCV-specific CTLs were visualized by staining PBL with anti-CD8 and HLA-A2/peptide pentameric complexes (pentamer). Mcl-1/Bim/CD127 phenotype of HCV-specific CTLs was tested by staining detectable CD8(+)/pentamer(+) cells with anti-Mcl-1/Bim/CD127 antibodies. HCV-specific CTL proliferation ability after specific in vitro challenge was tested in the presence and absence of pancaspase inhibitor z-VAD-fmk. All stained cells were analysed by flow cytometry. CD127(low)-expressing HCV-specific CTLs associated with high HCV viraemia, while CD127(high) correlated with undetectable viral loads (P Bim was up-regulated after antigen encounter (P Bim expression on pentamer(+) cells correlated positively with CD127 expression level (P Bim up-regulation after antigen encounter are involved in CD127(low) HCV-specific CTL hyporeactivity during chronic infection, but it can be overcome by apoptosis blockade.

  2. PD-1/PD-L1 signal pathway participates in HCV F protein-induced T cell dysfunction in chronic HCV infection.

    Science.gov (United States)

    Xiao, Wen; Jiang, Long Feng; Deng, Xiao Zhao; Zhu, Dan Yan; Pei, Jia Ping; Xu, Mao Lei; Li, Bing Jun; Wang, Chang Jun; Zhang, Jing Hai; Zhang, Qi; Zhou, Zhen Xian; Ding, Wei Liang; Xu, Xiao Dong; Yue, Ming

    2016-04-01

    Programmed cell death-1/programmed cell death-1 ligand 1 (PD-1/PD-L1) inhibitory signal pathway has been verified to be involved in the establishment of persistent viral infections. Blockade of PD-1/PD-L1 engagement to reinvigorate T cell activity is supposed to be a potential therapeutic scheme. Studies have verified the participation of PD-1/PD-L1 in hepatitis C virus (HCV) core protein-regulated immune response. To determine the roles of PD-1/PD-L1 signal pathway in HCV F protein-induced immunoreaction in chronic HCV infection, variations in T cells were examined. The results showed that PD-1 expression on CD8(+) and CD4(+) T cells was increased with HCV F stimulation in both chronic HCV patients and healthy controls, and could be reduced partly by PD-1/PD-L1 blocking. Additionally, by PD-1/PD-L1 blocking, HCV F-induced inhibition of T cell proliferation and promotion of cellular apoptosis were partly or even totally recovered. Furthermore, levels of both Th1 and Th2 cytokines were elevated in the presence of anti-PD-L1 antibody. All these results indicated that PD-1/PD-L1 signal pathway also participates in HCV F protein-induced immunoregulation. PD-1/PD-L1 blocking plays important roles in the restoration of effective functionality of the impaired T cells in chronic HCV patients.

  3. Recent advances in managing chronic HCV infection: focus on therapy in patients with severe liver disease [version 1; referees: 3 approved

    Directory of Open Access Journals (Sweden)

    Raoel Maan

    2016-03-01

    Full Text Available Chronic hepatitis C virus (HCV infection still represents a major public health problem, as it is thought to be responsible for more than 350,000 deaths around the globe on a yearly basis. Fortunately, successful eradication of the virus has been associated with improved clinical outcome and reduced mortality rates. In the past few years, treatment has improved considerably by the implementation of direct-acting antivirals (DAAs. From 2014 onwards, sofosbuvir, simeprevir, daclatasvir, ledipasvir, paritaprevir, ombitasvir, and dasabuvir have been approved by the US Food and Drug Administration (FDA and European Medicines Agency (EMA. Regimens with various combinations of these new drugs, without the use of interferon (IFN, proved to be very effective and well tolerated, even among patients with advanced liver disease. Moreover, treatment duration could be shortened to 12 weeks in the majority of patients. The high costs of these DAAs, however, limit the availability of IFN-free therapy worldwide. Even in wealthy countries, it is deemed necessary to prioritize DAA treatment in order to limit the immediate impact on the health budget. As patients with advanced liver disease are in most need of HCV clearance, many countries decided to treat those patients first. In the current review, we focus on the currently available IFN-free treatment options for patients with cirrhosis. We discuss the virological efficacy as well as the clinical relevance of these regimens among this specific patient population.

  4. Presence of Rheumatoid Factor during Chronic HCV Infection Is Associated with Expansion of Mature Activated Memory B-Cells that Are Hypo-Responsive to B-Cell Receptor Stimulation and Persist during the Early Stage of IFN Free Therapy.

    Science.gov (United States)

    Reyes-Avilés, Elane; Kostadinova, Lenche; Rusterholtz, Anne; Cruz-Lebrón, Angelica; Falck-Ytter, Yngve; Anthony, Donald D

    2015-01-01

    Approximately half of those with chronic hepatitis C virus (HCV) infection have circulating rheumatoid factor (RF), and a portion of these individuals develop cryoglobulinemic vasculitis. B cell phenotype/function in relation to RF in serum has been unclear. We examined B cell subset distribution, activation state (CD86), cell cycle state (Ki67), and ex-vivo response to BCR, TLR9 and TLR7/8 stimulation, in chronic HCV-infected donors with or without RF, and uninfected donors. Mature-activated B-cells of HCV-infected donors had lower CD86 expression compared to uninfected donors, and in the presence of RF they also showed reduced CD86 expression in response to BCR and TLR9 stimulation. Additionally, mature activated memory B cells of HCV RF+ donors less commonly expressed Ki67+ than HCV RF- donors, and did not proliferate as well in response to BCR stimulation. Proportions of mature-activated B cells were enhanced, while naïve B-cells were lower in the peripheral blood of HCV-RF+ compared to RF- and uninfected donors. None of these parameters normalize by week 8 of IFN free direct acting antiviral (DAA) therapy in HCV RF+ donors, while in RF- donors, mature activated B cell proportions did normalize. These data indicate that while chronic HCV infection alone results in a lower state of activation in mature activated memory B cells, the presence of RF in serum is associated with a more pronounced state of unresponsiveness and an overrepresentation of these B cells in the blood. This phenotype persists at least during the early time window after removal of HCV from the host.

  5. Evaluation of Echocardiographic Findings in Cirrhotic Patients

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    M Seidian

    2005-10-01

    Full Text Available Introduction: Cardiovascular abnormalities have been reported in liver cirrhosis (LC. In these patients, cardiac symptoms and physical signs occur as the liver functions worsen. Cirrhosis is associated with hyper dynamic circulation and beta-adrenergic system changes responsible for the cardiovascular abnormalities. The purpose of the present study was to explore the echocardiographic findings in cirrhotic patients. Methods: A total of 90 patients (63 men, 27 women with imaging or biopsy-proven cirrhosis of various etiologies without any known cardiac dysfunction were included in the study. Ninety healthy persons of the same age and sex were enrolled as the control group. Cirrhotic patients and controls were investigated by echocardiography. Left ventricle diastolic function (E/A ratio, systolic function (ejection fraction, and wall thickness (left ventricle posterior wall thickness + interventricular septum thickness along with left and right ventricular dimensions were evaluated. Results: Right & left atrium and ventricle diameters were enlarged in 3 cirrhotic patients and the E/A ratio was decreased in class C patients (0.9 ± 0.2 as compared to class B and A (1.3 ± 0.4 and controls (1.3± 1 (P value < 0.05. The left ventricular end diastolic volumes were increased in 3 cirrhotic patients(5.9+/- 0.3(normal 3.5-4.7 cm. The estimated ejection fraction was decreased in39 cirrhotic patients; 28 patients with ascites (35 -47% as compared to 11 patients without ascites (40-48% and controls (50-75% (P < 0.05. Conclusion: Liver cirrhosis is associated with enlarged left cardiac chambers, but wall thickness and right ventricle functions and diameters are normal. LV Diastolic dysfunction and decreased ejection fraction are evident in cirrhotic patients with ascites in class C children. This demonstration of diastolic dysfunction together with the dilated left cardiac chambers suggests that the patients indeed have cardiac abnormalities. Cardiovascular

  6. Long-term effect of interferon plus ribavirin on hepatitis B surface antigen seroclearance in patients dually infected with hepatitis B and C viruses.

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    Ming-Lun Yeh

    Full Text Available BACKGROUND: Interferon-α/ribavirin combination therapy might promote hepatitis B surface antigen (HBsAg seroclearance in patients dually infected with hepatitis B and C viruses (HBV/HCV, but the long-term effect remains unclear. We aimed to investigate the rate of and the factors associated with HBsAg seroclearance during long-term follow-up after interferon-α/ribavirin combination therapy in HBV/HCV dually-infected patients. METHODOLOGY/PRINCIPAL FINDINGS: Eighty-one patients who received interferon-α/ribavirin combination therapy for 24 weeks with a follow-up period of >24 weeks were enrolled. HBV serological markers and HBV DNA were determined every 6 months. Early and late HBsAg seroclearance were defined as HBsAg loss in less or more than 6 months after end-of-treatment, respectively. Fifteen (18.5% patients had HBsAg seroclearance during a mean follow-up period of 3.4 (0.5-5.1 years. The 5-year cumulative incidence was 25.6%. Baseline cirrhosis and HBV DNA negativity 1 year after end-of-treatment were independently predictive of HBsAg seroclearance with an odds ratio (OR, 95% confidence intervals (CI of 16.6, 1.8-153 and 9.2, 1.4-62.1, respectively, by Cox regression hazard analysis. Four patients developed early and 11 developed late HBsAg seroclearance, respectively. Cox regression hazard analysis showed no factor was associated with early HBsAg seroclearance, whilst HBV DNA negativity 1 year after end-of-treatment was the only significant factor predicting late HBsAg loss (OR, 43.0; CI, 2.5-745. Five patients had HBsAg seroconversion with a 5-year cumulative incidence of 8.3%. HBV DNA negativity at baseline and one year after EOT had a trend for HBsAg seroconversion. HCV response did not correlate to HBsAg loss. CONCLUSIONS: We demonstrated that interferon-α/ribavirin had long-term effect on HBsAg seroclearance in dually HBV/HCV-infected patients. Baseline cirrhosis and seroclearance of HBV DNA 1 year after end-of-treatment were

  7. Extrahepatic manifestations of chronic hepatitis C and their influence on response to treatment with Pegylated interferon alfa-2a and ribavirin

    Directory of Open Access Journals (Sweden)

    Fabri Milotka

    2013-01-01

    Full Text Available Introduction. Thirty to 50% of patients with chronic hepatitis C (CHC have one or more extrahepatic manifestations (EHMs of hepatitis C virus (HCV infection. Objective. The aim of this study was to evaluate the frequency of EHMs and to investigate the efficacy of pegylated interferon (Peg­IFN­α­2a plus ribavirin therapy in patients with HCV­related EHMs. Methods. The study included 280 patients suffering from CHC and treated with Peg­IFN­α­2a and ribavirin. The patients were divided in two groups according to presence or absence of EHMs. We evaluated virological response to antiviral therapy. Results. One or more EHMs were found among 27.9% of patients. Most frequently they had rheumatoid factor in serum (12.5%, organ­nonspecific antibodies ANA and AGMA (12.4%, thyroid hormone disorders (9.3%, vasculitis (5.7%, diabetes mellitus (4.65%, glomerulonephritis (0.71%, and porphyria cutanea tarda (0.36%. Among the patients with EHMs there was 52.6% of females vs. 30.2% of females in the group of patients without EHMs (p=0.001. HCV genotypes 1 and 4 had 85.9% patients with EHMs vs. 58.4% of patients without EHMs (p=0.000. Progressive fibrosis and cirrhosis were more frequently recorded in the EHM group of patients (32% vs. 23.2%, but without statistically significant difference (p=0.532. Serious adverse events of Peg­IFN­α­2a and ribavirin were statistically significantly recorded among the patients with EHMs (46.1% vs. 12.9%; p=0.000. Sustained virological response among the patients with and without EHMs rated 56.9% and 70.8% respectively (p=0.125. Conclusion. Patients with CHC and EHMs treated with combined Peg­IFN­α­2a and ribavirin experience handling difficulties, more often have serious adverse events, while successful outcome is achieved in about 50% of patients.

  8. Biowaiver Monographs for Immediate Release Solid Oral Dosage Forms: Ribavirin.

    Science.gov (United States)

    Goodarzi, Navid; Barazesh Morgani, Ahmadreza; Abrahamsson, Bertil; Cristofoletti, Rodrigo; Groot, D W; Langguth, Peter; Mehta, Mehul U; Polli, James E; Shah, Vinod P; Dressman, Jennifer B

    2016-04-01

    Literature data relevant to the decision to allow a waiver of in vivo bioequivalence (BE) testing for the approval of immediate release solid oral dosage forms containing ribavirin are reviewed. Ribavirin is highly soluble, but its permeability characteristics are not well defined. Therefore according to the Biopharmaceutical Classification System, and taking a "worst case" approach, ribavirin should be assigned to class III. As ribavirin is transported across the brush border membrane of the human jejunum by hCNT2, it shows saturable uptake in the intestine. However, no common excipients have been shown to compete for ribavirin absorption, nor have problems with BE of immediate release ribavirin formulations containing different excipients and produced by different manufacturing methods been reported in the open literature. So the risk of bioinequivalence caused by these factors appears to be low. Ribavirin is considered a narrow therapeutic index drug, as judged by comparing the minimum effective concentration and minimum toxic concentrations in blood. Although ribavirin would not be eligible for approval via a Biopharmaceutical Classification System-based biowaiver procedure according to today's guidances due to its narrow therapeutic index, the risks of biowaiving should be weighed against the considerable risks associated with studying BE of ribavirin products in healthy subjects.

  9. Coagulation abnormalities in the cirrhotic patient.

    Science.gov (United States)

    Muciño-Bermejo, Jimena; Carrillo-Esper, Raúl; Uribe, Misael; Méndez-Sánchez, Nahum

    2013-01-01

    The clotting process is a dynamic array of multiple processes which can be described in four phases: platelet plug initiation and formation, clotting process propagation by the coagulation cascade, clotting termination by antithrombotic mechanisms and clot removal by fibrinolysis. The liver plays a central role in each of these phases of clotting process, as it synthesizes the majority of coagulation factors and proteins involved in fibrinolysis as well as thrombopoeitin, which is responsible for platelet production from megakaryocytes. Many pathological processes associated with cirrhosis, such as portal hypertension and endothelial dysfunction, as well as co-morbid conditions, may also alter the coagulation process. Consequently, patients with liver disease have a disturbed balance of procoagulant and anti-coagulant factors which deviates from the normal coagulation cascade. This situation poses an additional problem in the diagnostic and therapeutic approach to this group of patients, since traditional coagulation test may not be reliable for assessing bleeding or thrombotic risk and traditional transfusional strategies may not be applicable in cirrhotic patients. In this article, we review the pathophysiological bases of coagulation abnormalities, in cirrhotic patients, the diagnostic therapeutic strategies to be followed and its impact on the clinical outcome in the cirrhotic patient.

  10. A GENOTYPIC STUDY OF SEN VIRUS INFECTION IN HEALTHY BLOOD DONORS AND THALASSEMIA PATIENTS: WITH OR WITHOUT HCV INFECTION AND ITS CLINICAL IMPORTANCE

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    BASHAR M. KHAZAAL

    2016-01-01

    Full Text Available Background: SEN-Virus (SEN-V-D and SEN-V-H is a DNA virus which associated with acute post transfusion hepatitis and blood transfusion is the most common mode of transmission of this virus like HCV, HBV and HIV among population. Beta thalassemia is a disease need continuous blood transfusions to manage the patient’s life; so these patients are at increased risk of infection with SEN-V. Aims of this study: This study was designed to search the prevalence of SEN-V among thalassemia patients and blood donors and to evaluate the clinical importance of SEN-Virus in thalassemia patients with or without HCV infection in Iraq and to detect the exact genomic characterization of SEN-V-D and SEN-V-H genotypes in Iraq and study of similarity of these genomes with other countries especially the neighboring countries and the homology between each isolate. Methods: One hundred and fifty eight thalassemia patients (57.6% male, 42.4% female, with mean age of 16.8±8.5 year, and one hundred and fifty healthy blood donors with randomly selected persons (58.7%male, 41.3% female, with mean age of 16.7±8.6 year; all these samples involved in this study. SEN-V and HCV had been identified by nested conventional PCR. Liver transaminases (Aspartate Transaminase and Alanine Transaminase had been determined, in addition of measure of serum ferritin levels by VIDAS. Gene sequencing and phylogenetic analysis had been studied of randomly selected amplified SEN-V D and H DNA samples. Results: SEN-V was detected in 68 from 158 (43% of thalassemia patients and 16 from 150 (10.7% of blood donors. HCV prevalence was (11.4% in thalassemia patients. There was significant increase in prevalence of SEN-V or HCV infection with age but there was no significant difference in prevalence in both with gender. SEN-V and HCV co-infection significantly increases AST level above normal range. SEN-V significantly increases ALT level above normal range and has a great significant ALT level

  11. Cyclophilin Inhibitors Remodel the Endoplasmic Reticulum of HCV-Infected Cells in a Unique Pattern Rendering Cells Impervious to a Reinfection.

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    Udayan Chatterji

    Full Text Available The mechanisms of action by which cyclophilin inhibitors (CypI interfere with the HCV life cycle remain poorly understood. We reported that CypI and NS5A inhibitors (NS5Ai, but not other classes of anti-HCV agents, prevent assembly of double membrane vesicles (DMVs, which protect replication complexes. We demonstrated that both NS5A and the isomerase cyclophilin A (CypA are required for DMV formation. Here, we examined whether CypI mediate an additional antiviral effect that could further explain the high efficacy of CypI. We identified a unique action of CypI. CypI remodel the organization of the endoplasmic reticulum (ER of HCV-infected cells, but not of uninfected cells. This effect is specific since it was not observed for other classes of anti-HCV agents including NS5Ai, and has no effect on the viability of CypI-treated cells. Since ER serves as platform for the establishment of HCV replication complexes, we asked whether the ER reorganization by CypI would prevent cells from being newly infected. Remarkably, CypI-treated HCV-pre-infected cells remain totally impervious to a reinfection, suggesting that the CypI-mediated ER reorganization prevents a reinfection. This block is not due to residual CypI since CypI-resistant HCV variants also fail to infect these cells. The ER reorganization by CypI is rapid and reversible. This study provides the first evidence that CypI trigger a unique ER reorganization of infected cells, rendering cells transiently impervious to a reinfection. This study further suggests that the HCV-induced ER rearrangement represents a key target for the development of new therapies.

  12. Cyclophilin Inhibitors Remodel the Endoplasmic Reticulum of HCV-Infected Cells in a Unique Pattern Rendering Cells Impervious to a Reinfection

    Science.gov (United States)

    Chatterji, Udayan; Bobardt, Michael; Schaffer, Lana; Wood, Malcolm; Gallay, Philippe A.

    2016-01-01

    The mechanisms of action by which cyclophilin inhibitors (CypI) interfere with the HCV life cycle remain poorly understood. We reported that CypI and NS5A inhibitors (NS5Ai), but not other classes of anti-HCV agents, prevent assembly of double membrane vesicles (DMVs), which protect replication complexes. We demonstrated that both NS5A and the isomerase cyclophilin A (CypA) are required for DMV formation. Here, we examined whether CypI mediate an additional antiviral effect that could further explain the high efficacy of CypI. We identified a unique action of CypI. CypI remodel the organization of the endoplasmic reticulum (ER) of HCV-infected cells, but not of uninfected cells. This effect is specific since it was not observed for other classes of anti-HCV agents including NS5Ai, and has no effect on the viability of CypI-treated cells. Since ER serves as platform for the establishment of HCV replication complexes, we asked whether the ER reorganization by CypI would prevent cells from being newly infected. Remarkably, CypI-treated HCV-pre-infected cells remain totally impervious to a reinfection, suggesting that the CypI-mediated ER reorganization prevents a reinfection. This block is not due to residual CypI since CypI-resistant HCV variants also fail to infect these cells. The ER reorganization by CypI is rapid and reversible. This study provides the first evidence that CypI trigger a unique ER reorganization of infected cells, rendering cells transiently impervious to a reinfection. This study further suggests that the HCV-induced ER rearrangement represents a key target for the development of new therapies. PMID:27442520

  13. Hepatitis C virus (HCV infection & risk factors for HCV positivity in injecting & non-injecting drug users attending a de-addiction centre in northern India

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    Debasish Basu

    2015-01-01

    Full Text Available Background & objectives: Injecting drug use is a major route of hepatitis C virus (HCV infection in India, but there may be other risk factors also. This study was carried out to determine the seroprevalence of anti-HCV antibody in injecting drug users (IDUs vs. non-IDUs (NIDUs, and to study the risk estimates for HCV seropositivity in the total sample of substance users with regard to various demographic, clinical, behavioural and personality factors. Methods: The IDUs (n = 201 and NIDUs (n = 219 were assessed for demographic, clinical and behavioural information, and were rated on instruments for severity of dependence, risk behaviour and personality profiles. Anti-HCV antibody was tested by ELISA and confirmed by recombinant immunoblot assay (RIBA test. Results: Almost one-third of the IDUs (64 of 201; 31.8% were positive for anti-HCV antibody, as opposed to only seven (3.2% of the NIDUs. The four risk factors strongly associated with HCV positivity in multivariate analysis were sharing syringe [Exp(B 75.04; 95%CI 18.28-307.96; P<0.001], reuse of injection accessories (16.39; 3.51-76.92; P<0.001, blood transfusion (5.88; 1.63-21.23; P=0.007 and IDU status (3.60; 1.26-10.31; P=0.017. Other variables less strongly but significantly associated with HCV positivity were multiple sex partners, opioid dependence, risk behaviour scores, impulsivity, and lower age of onset of drug use. Interpretation & conclusions: Our study showed a high seroprevalence of anti-HCV antibody in IDUs. In the substance users, HCV positivity was significantly and independently associated with several clinical, behavioural, and personality risk factors.

  14. HCV-RNA positivity in peripheral blood mononuclear cells of patients with chronic HCV-infection: does it really mean viral replication?

    Institute of Scientific and Technical Information of China (English)

    Volker Meier; Sabine Mihm; Perdita Wietzke-Braun; Guliano Ramadori

    2001-01-01

    AIM To analyze the association of HCV-RNA with peripheral blood mononuclear cells (PBMC)and to answer the question whether HCV-RNA positivity in PBMC is due to viral replication,METHODS HCV-RNA was monitored in serumand PBMC preparations from 15 patients with chronic HCV infection before, during and after an IFN-α therapy using a nested RT/ PCRtechnique. In a second approach, PBMC from healthy donors were incubated in HCV positive plasma.RESULTS In the IFN-α responding patients,HCV-RNA disappeared first from total RNApreparations of PBMC and then from serum. In contrast, in relapsing patients, HCV-RNAreappeared first in serum and then in PBMC. A quantitative analysis of the HCV-RNAconcentration in serum was performed before and after transition from detectable to nondetectable HCV-RNA in PBMC-RNA and vice versa. When HCV-RNA was detectable in PBMCpreparations, the HCV concentration in serum was significantly higher than the serum HCV-RNA concentration when HCV-RNA in PBMC was not detectable. Furthermore, at no time during the observation period was HCV specific RNA observed in PBMC, if HCV-RNA in serum was under the detection limit. Incubation of PBMCfrom healthy donors with several dilutions of HCV positive plasma for two hours showed a concentration-dependent PCR-positivity for HCV-RNA in reisolated PBMC.CONCLUSION The detectability of HCV-RNA in total RNA from PBMC seems to depend on the HCV concentration in serum. Contamination or passive adsorption by circulating virus could be the reason for detection of HCV-RNA in PBMCpreparations of chronically infected patients.

  15. Polymorphisms of HLA-DM on Treatment Response to Interferon/Ribavirin in Patients with Chronic Hepatitis C Virus Type 1 Infection

    Science.gov (United States)

    Chen, Hongbo; Yao, Yinan; Wang, Yifan; Zhou, Hua; Xu, Tianxiang; Liu, Jing; Wang, Guocheng; Zhang, Yongfeng; Chen, Xiang; Liu, Qingwei; Huang, Peng; Yu, Rongbin

    2016-01-01

    Background: HLA-DM gene, which is related to antigen processing and presentation and located in the non-classical class-II region of human leukocyte antigen (HLA) region, may play a crucial role in chronic hepatitis C virus (HCV) infection treatment outcomes. The study was conducted to evaluate the role of the variant of several single nucleotide polymorphisms (SNPs) in HLA-DM gene in HCV treatment outcomes. Methods: We genotyped four SNPs from the candidate genes (HLA-DMA and DMB) in 336 patients who were treated with pegylated interferon-alpha and ribavirin (PEG IFN-α/RBV). Multivariate analysis of factors predicting sustained virological response (SVR) was conducted. Results: HLA-DMA rs1063478 and DMB rs23544 were independent factors of HCV treatment outcomes in Chinese Han population. Individuals who carried favorable genotypes of rs1063478TT and rs23544GG were more likely to achieve SVR {Dominant model: odds ratio (OR) = 2.05, 95% confidence interval (CI) = 1.24–3.41; OR = 2.04, 95% CI =1.23–3.35, respectively}. Rs23544, rs1063478, baseline glucose, baseline platelet and T4 level were independent predictors of SVR. The area under the receiver operating characteristic (ROC) curve (AUC) was 0.740. Conclusions: The genetic variation of rs1063478 and rs23544 are associated with the treatment outcomes in the Chinese Han population. PMID:27775635

  16. Polymorphisms of HLA-DM on Treatment Response to Interferon/Ribavirin in Patients with Chronic Hepatitis C Virus Type 1 Infection

    Directory of Open Access Journals (Sweden)

    Hongbo Chen

    2016-10-01

    Full Text Available Background: HLA-DM gene, which is related to antigen processing and presentation and located in the non-classical class-II region of human leukocyte antigen (HLA region, may play a crucial role in chronic hepatitis C virus (HCV infection treatment outcomes. The study was conducted to evaluate the role of the variant of several single nucleotide polymorphisms (SNPs in HLA-DM gene in HCV treatment outcomes. Methods: We genotyped four SNPs from the candidate genes (HLA-DMA and DMB in 336 patients who were treated with pegylated interferon-alpha and ribavirin (PEG IFN-α/RBV. Multivariate analysis of factors predicting sustained virological response (SVR was conducted. Results: HLA-DMA rs1063478 and DMB rs23544 were independent factors of HCV treatment outcomes in Chinese Han population. Individuals who carried favorable genotypes of rs1063478TT and rs23544GG were more likely to achieve SVR {Dominant model: odds ratio (OR = 2.05, 95% confidence interval (CI = 1.24–3.41; OR = 2.04, 95% CI =1.23–3.35, respectively}. Rs23544, rs1063478, baseline glucose, baseline platelet and T4 level were independent predictors of SVR. The area under the receiver operating characteristic (ROC curve (AUC was 0.740. Conclusions: The genetic variation of rs1063478 and rs23544 are associated with the treatment outcomes in the Chinese Han population.

  17. Ribavirin contributes to eradicate hepatitis C virus throughpolarization of T helper 1/2 cell balance into T helper 1dominance

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    The mechanism of action of ribavirin (RBV) as an immunomodulatory and antiviral agent and its clinicalsignificance in the future treatment of patients withhepatitis C virus (HCV) infection are reviewed. RBVup-regulates type 1 and/or 2 cytokines to modulatethe T helper (Th) 1/2 cell balance to Th1 dominance.Examination of co-stimulatory signaling indicated thatRBV down-modulates inducible co-stimulator on Thcells, which contributes to differentiating na?ve Thcells into Th2 cells while reducing their interleukin-10production. The effects on T-regulatory (Treg) cells werealso investigated, and RBV inhibited the differentiationof na?ve Th cells into adaptive Treg cells by downmodulatingforkhead box-P3. These findings indicatethat RBV mainly down-regulates the activity of Th2cells, resulting in the maintenance of Th1 activity thatcontributes to abrogating HCV-infected hepatocytes.Although an interferon-free treatment regimen exhibitsalmost the same efficacy without serious complications,regimens with RBV will be still be used because oftheir ability to facilitate the cellular immune response,which may contribute to reducing the development ofhepatocellular carcinogenesis in patients infected withHCV.

  18. Ribavirin Prophylaxis and Therapy for Experimental Argentine Hemorrhagic Fever

    Science.gov (United States)

    1988-09-01

    subsequently developed a late-onset central nervous system infection which was fatal in two of three animals. Side effects of ribavirin included thrombocytosis ... Thrombocytosis is a recognized side effect of ribavirin F. E. Hahn (ed.). Antibiotics, vol. VI. Springer-Verlag, Berlin. administration in rhesuis

  19. Efficacy of ribavirin against malignant glioma cell lines

    Science.gov (United States)

    OGINO, AKIYOSHI; SANO, EMIKO; OCHIAI, YUSHI; YAMAMURO, SHUN; TASHIRO, SHINYA; YACHI, KAZUNARI; OHTA, TAKASHI; FUKUSHIMA, TAKAO; OKAMOTO, YUTAKA; TSUMOTO, KOUHEI; UEDA, TAKUYA; YOSHINO, ATSUO; KATAYAMA, YOICHI

    2014-01-01

    Ribavirin (1-β-D-ribofuranosy-1,2,4-triazole-3-carboxamide) has been widely administered as an antiviral agent against RNA and DNA viruses. Ribavirin, in combination with interferon, has predominantly been applied in the treatment of the hepatitis C virus infection and its potential antitumor efficacy has recently become a point of interest. The aim of the present study was to evaluate the effect of ribavirin on the growth of malignant glioma cells, to identify novel predictive genes in malignant glioma cells (by analyzing gene expression profiles) and to assess the influence of ribavirin on the cell cycle of malignant glioma cells. The present study evaluated the antitumor efficacy of ribavirin against various malignant glioma cell lines (A-172, AM-38, T98G, U-87MG, U-138MG, U-251MG and YH-13). After culturing the cells in ribavirin-containing culture medium (final concentration, 0–1,000 μM) for 72 h, the viable proliferated cells were harvested and counted. The half maximal inhibitory concentration of ribavirin, with regard to the growth of the malignant glioma cell lines, was determined from the concentration of ribavirin required for 50% growth inhibition in comparison to the untreated control cells. Furthermore, the current study identified the genes in which the gene expression levels correlated with the ribavirin sensitivity of the malignant glioma cells lines, using a high-density oligonucleotide array. Finally, cell cycle analysis was performed on the U-87MG cell line. It was identified that ribavirin inhibited the growth of all of the malignant glioma cell lines in a dose-dependent manner, although the ribavirin sensitivity varied between each cell line. Of the extracted genes, PDGFRA demonstrated the strongest positive correlation between gene expression level and ribavirin sensitivity. Cell cycle analysis of the U-87MG cell line demonstrated that ribavirin treatment induces G0/G1 arrest and thus may be an effective agent for inhibiting malignant

  20. Hemoperitoneum in cirrhotic patients without abdominal trauma or tumor

    Institute of Scientific and Technical Information of China (English)

    Yuan-Ji Ma; En-Qiang Chen; Jia-Jie Lu; Ming-Zhen Tan; Hong Tang

    2011-01-01

    BACKGROUND: Hemoperitoneum is associated with several emergency conditions and is especially evident when it occurs in patients with liver cirrhosis. This study aimed to assess the clinical characteristics of cirrhotic patients who did not have abdominal trauma or tumor but who developed hemoperitoneum. METHODS: Wereviewedtheclinicalrecordsof1276consecutive cirrhotic patients with hemoperitoneum at our center between January 2007 and December 2009. Hemoperitoneum was confirmed by abdominal paracentesis. RESULTS: Of the 1276 cirrhotic patients, 19 were found to have hemoperitoneum, but only 6 did not have abdominal trauma or tumor. The occurrence of spontaneous hemoperitoneum in the cirrhotic patients was therefore 0.5%. Hemoperitoneum can occur spontaneously in severely decompensated cirrhotic patients with intra-abdominal collateral vessels and high scores on the model for end-stage liver disease and Child-Pugh-Turcotte test. Most patients presented with abdominal distension, abdominal pain, increased abdominal girth and hemodynamic instability with a significant drop in the hemoglobin level. Three patients died of hemorrhagic shock within 24 hours, and the other 3 died of hepatic encephalopathy or spontaneous bacterial peritonitis after 5 to 10 days because of further decompensation of the liver. CONCLUSIONS: Hemoperitoneum can occur in cirrhotic patients who do not have abdominal trauma or tumor. It mainly occurs in severely decompensated end-stage cirrhotic patients. Cirrhotic patients with hemoperitoneum have a poor prognosis.

  1. HCV感染者血清及外周血单个核细胞HCV RNA检测及其意义%SIGNIFICANCE OF PERIPHERAL BLOOD MONONUCLEAR CELL HC V RNA IN PATIENTS WITH HCV INFECTION

    Institute of Scientific and Technical Information of China (English)

    刘文恩; 谭德明; 范学工; 张铮; 甘晓明; 欧阳颗; 谢玉桃

    2001-01-01

    探讨同时检测HCV感染者血清及外周血单个核细胞(PBMC)中H CV RNA的意义。方法:应用RT-PCR方法对31例HCV感染者进行血清及PBMC HCV RNA检测。结 果PBMC HCV RNA阳性率(74.19%,23/31)显著高于血清HCV RNA阳性率(23.03%,9/31)。 结论 :同时检测HCV感染者血清及外周血单个核细胞(PBMC)中HCV RNA可减少漏诊,PBMC中的HCV 可能是HCV感染慢性化的重要原因之一。通过对HCV感染者同时进行血清及PBMC中HCV RNA检 测,可为丙型肝炎的诊断、治疗及预后的判断提供较为可靠的指标,对丙型肝炎慢性化机制 的研究具有重要意义。%To investigate the significance of HCV RNA detection in PBMC in patients with HCV infection.Methods:Al l of 31 sera and PBMC taken from HCV infection were used for HCV RNA detection by RT-PCR.Results:PBMC HCV RNA positive rate (74.19%,23/31)was sig ni ficant higher than those of sera HCV RNA (23.03%,9/31)(χ2=11.770,P>0.005).Conclusions:PBMC HCV may be one of important reasons for mechani sm of chronicity pathogenesis HCV infection

  2. 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.

  3. Drug Authorization for Sofosbuvir/Ledipasvir (Harvoni for Chronic HCV Infection in a Real-World Cohort: A New Barrier in the HCV Care Cascade.

    Directory of Open Access Journals (Sweden)

    Albert Do

    Full Text Available New treatments for hepatitis C (HCV infection hold great promise for cure, but numerous challenges to diagnosing, establishing care, and receiving therapy exist. There are limited data on insurance authorization for these medications.We performed a retrospective chart review of patients receiving sofosbuvir/ledipasvir (SOF/LED from October 11-December 31, 2014 to determine rates and timing of drug authorization. We also determined predictors of approval, and those factors associated with faster decision and approval times.Of 174 patients prescribed HCV therapy during this period, 129 requests were made for SOF/LED, of whom 100 (77.5% received initial approval, and an additional 17 patients (13.9% ultimately received approval through the appeals process. Faster approval times were seen in patients with Child-Pugh Class B disease (14.4 vs. 24.7 days, p = 0.048. A higher proportion of patients were initially approved in those with Medicare/Medicaid coverage (92.2% vs. 71.4%, p = 0.002 and those with baseline viral load ≥ 6 million IU/mL (84.1% vs. 62.5%, p = 0.040. Linear regression modeling identified advanced fibrosis, high Model of End Stage Liver Disease (MELD score, and female gender as significant predictors of shorter decision and approval times. On logistic regression, Medicare/Medicaid coverage (OR 5.96, 95% CI 1.66-21.48 and high viral load (OR 4.52, 95% CI 1.08-19.08 were significant predictors for initial approval.Early analysis of real-world drug authorization outcomes between October-December 2014 reveals that nearly one in four patients are initially denied access to SOF/LED upon initial prescription, although most patients are eventually approved through appeal, which delays treatment initiation. Having Medicare/Medicaid and advanced liver disease resulted in a higher likelihood of approval as well as earlier decision and approval times. More studies are needed to determine factors resulting in higher likelihood of denial and to

  4. Intracellular expression of the proliferative marker Ki-67 and viral proteins (NS3, NS5A and C in chronic, long lasting hepatitis C virus (HCV infection.

    Directory of Open Access Journals (Sweden)

    Karolina Olejniczak

    2008-01-01

    Full Text Available Hepatitis C virus (HCV continues to represent the main causative agent of the hepatitis, which leads to chronic transformation of the process in 60-80% individuals. It remains unclear how far cellular expression of HCV proteins in vivo may represent an index of progression of the disease and of proliferative activity in the liver in chronic hepatitis C. Aim of the studies included detection and subcellular localization of three HCV proteins (NS3, NS5A and C in liver biopsies from adults (n=19 with chronic, long lasting hepatitis C as related to hepatocyte proliferative activity. The immunocytochemical ABC (avidin biotin-peroxidase complex technique was applied, alone or associated with the ImmunoMax technique. Results of the immunocytochemical tests were compared to histological alterations in liver biopsies, proliferation index and with selected clinical data. A significantly higher expression of NS3 protein was noted, as compared to expressions of NS5A and C proteins. In all the patients, cytoplasmic localization of all proteins dominated over nuclear localization (p0.05. At the level of electron microscopy, protein localization in endoplasmic reticulum (ER membranes, mitochondria, perinuclear region and/or in hepatocyte cell nucleus was observed. No direct relationships could be demonstrated between expressions of HCV proteins and of Ki-67 antigen. No correlations could also be demonstrated between cellular expression of any HCV protein on one hand and grading or staging, alanine transaminase (ALT, serum level of HCV RNA or alpha-fetoprotein (AFP on the other. However, positive correlations were disclosed between proliferative activity of hepatocytes on one hand and patient's age, grading and staging on the other. Advanced hepatic fibrosis correlated also with serum levels of AFP. The studies were supplemented with data on subcellular localization of HCV proteins. Moreover, they indicated that in HCV infection grading and staging

  5. Intracellular expression of the proliferative marker Ki-67 and viral proteins (NS3, NS5A and C) in chronic, long lasting hepatitis C virus (HCV) infection.

    Science.gov (United States)

    Kasprzak, Aldona; Adamek, Agnieszka; Biczysko, Wieslawa; Seidel, Jolanta; Przybyszewska, Wieslawa; Olejniczak, Karolina; Juszczyk, Jacek; Zabel, Maciej

    2007-01-01

    Hepatitis C virus (HCV) continues to represent the main causative agent of the hepatitis, which leads to chronic transformation of the process in 60-80% individuals. It remains unclear how far cellular expression of HCV proteins in vivo may represent an index of progression of the disease and of proliferative activity in the liver in chronic hepatitis C. Aim of the studies included detection and subcellular localization of three HCV proteins (NS3, NS5A and C) in liver biopsies from adults (n=19) with chronic, long lasting hepatitis C as related to hepatocyte proliferative activity. The immunocytochemical ABC (avidin biotin-peroxidase complex) technique was applied, alone or associated with the ImmunoMax technique. Results of the immunocytochemical tests were compared to histological alterations in liver biopsies, proliferation index and with selected clinical data. A significantly higher expression of NS3 protein was noted, as compared to expressions of NS5A and C proteins. In all the patients, cytoplasmic localization of all proteins dominated over nuclear localization (p0.05). At the level of electron microscopy, protein localization in endoplasmic reticulum (ER) membranes, mitochondria, perinuclear region and/or in hepatocyte cell nucleus was observed. No direct relationships could be demonstrated between expressions of HCV proteins and of Ki-67 antigen. No correlations could also be demonstrated between cellular expression of any HCV protein on one hand and grading or staging, alanine transaminase (ALT), serum level of HCV RNA or alpha-fetoprotein (AFP) on the other. However, positive correlations were disclosed between proliferative activity of hepatocytes on one hand and patient's age, grading and staging on the other. Advanced hepatic fibrosis correlated also with serum levels of AFP. The studies were supplemented with data on subcellular localization of HCV proteins. Moreover, they indicated that in HCV infection grading and staging, proliferative activity

  6. Endotoxemia, encephalopathy, and mortality in cirrhotic patients.

    Science.gov (United States)

    Bigatello, L M; Broitman, S A; Fattori, L; Di Paoli, M; Pontello, M; Bevilacqua, G; Nespoli, A

    1987-01-01

    Endotoxemia without sepsis was detected with a chromogenic Limulus assay in 36 of 39 (92.3%) cirrhotic patients and was absent in seven healthy volunteers. In 11 patients who underwent elective portasystemic shunt, portal vein endotoxemia was higher than inferior vena caval: p less than 0.05, systemic endotoxin levels did not change, compared to preoperative levels, on the 1st, 2nd, and 3rd postoperative days, attendant to an uneventful recovery. In 21 patients in hepatic encephalopathy after esophagogastric hemorrhage, systemic endotoxemia was higher than in well-compensated cirrhotics: p less than 0.001; it was higher in deep than in light coma: p less than 0.05; it was higher in those who died than in those who survived: p less than 0.001. Endotoxin levels showed a positive correlation with serum bilirubin: r = 0.59, p less than 0.001, and a negative correlation with prothrombin activity: r = -0.59, p less than 0.001. These data show endotoxemia without sepsis is a constant finding in cirrhosis and increasing levels of endotoxemia are associated with hepatic failure, encephalopathy, and death.

  7. A novel combinatory paradigm for chronic hepatitis C treatment using liver-targeted carrier erythrocytes co-encapsulated with interferon alpha-2b, ribavirin and boceprevir

    Directory of Open Access Journals (Sweden)

    Mahshid Foroozesh

    2010-10-01

    Full Text Available "nDespite outstanding developments in medical knowledge and technologies, Hepatitis C virus (HCV affecting almost 180 million people worldwide, is still described as "a serious global health crisis" and its standard of care (combination therapy with pegylated interferon alpha and ribavirin is just effective in at most 50% of all patients. This suboptimal efficacy and apparent side effects underscore the need for "new anti-HCV agents", "novel combination strategies" and "smart delivery systems". As a response to the urgent need for new anti-HCV drugs, specifically targeted antiviral therapy agents for HCV (STAT-C has gained many interests these years. Considering the obligation of multidrug therapy in HCV infection and the results of clinical trials, STAT-C will probably supplement interferon/ribavirin combination. Boceprevir as a HCV protease inhibitor is among the most widely studied STAT-C compounds with promising results in clinical trials. Thus, its combination with current double therapy paradigm would be an alternative combination strategy in the treatment of hepatitis C. On the other hand, drug carriers has now evoked much attentions as new trends to increase the efficacy of available therapies by protecting the therapeutic agents from unwanted reactions and/or targeting them directly to their site of action. Carrier erythrocytes are among the most widely studied cellular and particulate carriers suitable for targeted delivery of various drugs to reticuloendothelial system organs like liver, but, with no report about their application for HCV-targeted therapy. Since the majority of recent efforts are focused on new agents' discovery/development and alternative combinations and no reports are available on targeted delivery of double and/or triple drug combinations directly to the liver, an idea has been raised that combination of all 3 approaches mentioned earlier (a completely combinatory paradigm addressing all 3 mentioned needs by

  8. Prediction of sustained virologic responses to combination therapy of pegylated interferon-α and ribavirin in patients with chronic hepatitis C infection

    Directory of Open Access Journals (Sweden)

    Mona H Ismail

    2013-01-01

    Full Text Available Background and Aim: Hepatitis C virus (HCV infection is a major health problem worldwide. Genotype-4 is the most common genotype in Saudi Arabia. The response to treatment with pegylated interferon-α combined with ribavirin in chronic HCV infection varies. This study aimed at investigating the pre- and on-treatment predictors of sustained virologic response (SVR in patients with chronic hepatitis C (CHC infection. Patients and Methods : Clinical data of 48 patients with CHC treated with standard HCV antiviral combination therapy, between January 2005 and December 2010, at a Saudi University hospital, were retrospectively reviewed for age, sex, body mass index, liver enzymes, HCV-RNA viral load, liver biopsy, and response to treatment. The primary end point was SVR defined as undetectable HCV-RNA by polymerase chain reaction (PCR 24 weeks after the end of treatment. Univariable logistic regression was used to explore the association between the different variables and SVR. These independent predictors of SVR were then analyzed with multivariable logistic regression analysis. Results: Of the 48 treated patients, 25 (52% were females and 27 (56% were Saudi. The mean age was 43 years (43 ± 10 years. Twenty-four (50% had genotype-4, and 26 (54% had liver biopsy. The overall SVR rate was 75% (36/48 and was 83.3% (20/24 among genotype-4 patients. Baseline factors associated with SVR identified by univariate logistic regression were genotype-4 and early viral response (EVR, defined as a drop of ≥2 log in serum HCV viral load after 12 weeks of initiation of combination therapy (P = 0.001. However, in stepwise regression analysis, the independent factor associated with the effect of antiviral therapy was genotype-4. When on-treatment variables were included, EVR (P = 0.003 and low baseline viral load (P = 0.048 were highly predictive of SVR. Conclusions: Of our HCV-treated patients, 75% had SVR. HCV genotype-4, EVR, and low baseline viral load were

  9. IL-6 significantly correlates with p-STAT3 expression and presents high variceal bleeding with mortality in cirrhotic patients: A cross-sectional study.

    Science.gov (United States)

    Kao, Jung-Ta; Yu, Cheng-Ju; Feng, Chun-Lung; Tsai, Shu-Mei; Chen, Yao-Li; Wu, Yi-Ying

    2017-06-01

    Effective mediators activate downstream transducers regulating inflammation and angiogenesis. Correlation among mediators IL-6, IL-27, TNF-α, and VEGF with STAT proteins at diverse clinical-pathologic stages of cirrhotic patients remains limited. Plasma mediators were assayed from 158 naïve liver cirrhosis (LC-total group) and 144 non-LC individuals. The LC-total group included 69 hepatitis B virus-infected (LC-HBV) patients, 40 hepatitis C virus-infected (LC-HCV) patients, and 49 patients without HBV-/HCV- infection (LC-NBNC). Another 144 non-LC individuals comprised 54 healthy persons (HG) and 90 chronic hepatitis patients (CH-total) as the control group. To correlate with plasma mediators, 52 paired liver tissues (CH: 41 and LC: 11 cases) served for p-STAT1 and p-STAT3 immunostaining. Although IL-6, IL-27, TNF-α, and VEGF were expressed significantly in CH-total versus HG (p = 0.011, p p = 0.007, p = 0.004, respectively) and overall viral hepatitis patients versus HG (p p p p p p = 0.001; LC-HCV vs. HG, p = 0.001, vs. CH-HCV, p = 0.031; LC-NBNC vs. HG, p p p = 0.001; INR: r = 0.308, p p = 0.001, p = 0.007, respectively), variceal severity (p = 0.045), and bleeding (p = 0.047), as well as patients' mortality (p = 0.005). Furthermore, plasma IL-6 significantly correlated with tissues p-STAT3 expression (r = 0.737, p = 0.010) (IL-27: r = 0.078, p = 0.820; TNF-α: r = -0.145, p = 0.670; VEGF: r = 0.142, p = 0.678) in cirrhotic patients than noncirrhotic patients. Over-expression of IL-6 reflects hepatic dysfunction and varices bleeding with mortality, as well as correlates p-STAT3 expression in cirrhotic patients. Copyright © 2015. Published by Elsevier B.V.

  10. Statin (3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor-based therapy for hepatitis C virus (HCV infection-related diseases in the era of direct-acting antiviral agents [version 2; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Sara Kishta

    2016-07-01

    Full Text Available Recent improvements have been made in the treatment of hepatitis C virus (HCV infection with the introduction of direct-acting antiviral agents (DAAs. However, despite successful viral clearance, many patients continue to have HCV-related disease progression. Therefore, new treatments must be developed to achieve viral clearance and prevent the risk of HCV-related diseases. In particular, the use of pitavastatin together with DAAs may improve the antiviral efficacy as well as decrease the progression of liver fibrosis and the incidence of HCV-related hepatocellular carcinoma. To investigate the management methods for HCV-related diseases using pitavastatin and DAAs, clinical trials should be undertaken. However, concerns have been raised about potential drug interactions between statins and DAAs. Therefore, pre-clinical trials using a replicon system, human hepatocyte-like cells, human neurons and human cardiomyocytes from human-induced pluripotent stem cells should be conducted. Based on these pre-clinical trials, an optimal direct-acting antiviral agent could be selected for combination with pitavastatin and DAAs. Following the pre-clinical trial, the combination of pitavastatin and the optimal direct-acting antiviral agent should be compared to other combinations of DAAs (e.g., sofosbuvir and velpatasvir according to the antiviral effect on HCV infection, HCV-related diseases and cost-effectiveness.

  11. Ribavirin Inhibits Parrot Bornavirus 4 Replication in Cell Culture.

    Science.gov (United States)

    Musser, Jeffrey M B; Heatley, J Jill; Koinis, Anastasia V; Suchodolski, Paulette F; Guo, Jianhua; Escandon, Paulina; Tizard, Ian R

    2015-01-01

    Parrot bornavirus 4 is an etiological agent of proventricular dilatation disease, a fatal neurologic and gastrointestinal disease of psittacines and other birds. We tested the ability of ribavirin, an antiviral nucleoside analog with antiviral activity against a range of RNA and DNA viruses, to inhibit parrot bornavirus 4 replication in duck embryonic fibroblast cells. Two analytical methods that evaluate different products of viral replication, indirect immunocytochemistry for viral specific nucleoprotein and qRT-PCR for viral specific phosphoprotein gene mRNA, were used. Ribavirin at concentrations between 2.5 and 25 μg/mL inhibited parrot bornavirus 4 replication, decreasing viral mRNA and viral protein load, in infected duck embryonic fibroblast cells. The addition of guanosine diminished the antiviral activity of ribavirin suggesting that one possible mechanism of action against parrot bornavirus 4 may likely be through inosine monophosphate dehydrogenase inhibition. This study demonstrates parrot bornavirus 4 susceptibility to ribavirin in cell culture.

  12. Ribavirin Inhibits Parrot Bornavirus 4 Replication in Cell Culture.

    Directory of Open Access Journals (Sweden)

    Jeffrey M B Musser

    Full Text Available Parrot bornavirus 4 is an etiological agent of proventricular dilatation disease, a fatal neurologic and gastrointestinal disease of psittacines and other birds. We tested the ability of ribavirin, an antiviral nucleoside analog with antiviral activity against a range of RNA and DNA viruses, to inhibit parrot bornavirus 4 replication in duck embryonic fibroblast cells. Two analytical methods that evaluate different products of viral replication, indirect immunocytochemistry for viral specific nucleoprotein and qRT-PCR for viral specific phosphoprotein gene mRNA, were used. Ribavirin at concentrations between 2.5 and 25 μg/mL inhibited parrot bornavirus 4 replication, decreasing viral mRNA and viral protein load, in infected duck embryonic fibroblast cells. The addition of guanosine diminished the antiviral activity of ribavirin suggesting that one possible mechanism of action against parrot bornavirus 4 may likely be through inosine monophosphate dehydrogenase inhibition. This study demonstrates parrot bornavirus 4 susceptibility to ribavirin in cell culture.

  13. Virologic responses and tolerance of peginterferon alfa plus ribavirin ...

    African Journals Online (AJOL)

    Conclusions:Increasing age negatively affected the efficacy of peginterferon and ribavirin therapy in the treatment ... peginterferon alfa‑2a (Pegasys, Hoffmann‑La Roche, Shanghai, ... 40 mg of leucogen tablets (Jiangsu Jibeier Pharmaceutical.

  14. Nutritional assessment in cirrhotic patients with hepaticencephalopathy

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    Hepatic encephalopathy (HE) is one of the worstcomplications of liver disease and can be greatly influencedby nutritional status. Ammonia metabolism, inflammationand muscle wasting are relevant processes inHE pathophysiology. Malnutrition worsens the prognosisin HE, requiring early assessment of nutritional statusof these patients. Body composition changes inducedby liver disease and limitations superimposed by HEhamper the proper accomplishment of exams in thispopulation, but evidence is growing that assessmentof muscle mass and muscle function is mandatory dueto the role of skeletal muscles in ammonia metabolism.In this review, we present the pathophysiologicalaspects involved in HE to support further discussionabout advantages and drawbacks of some methods forevaluating the nutritional status of cirrhotic patients withHE, focusing on body composition.

  15. Ribavirin plus interferon versus interferon for chronic hepatitis C

    DEFF Research Database (Denmark)

    Brok, Jesper; Gluud, Lise Lotte; Gluud, Christian

    2010-01-01

    Hepatitis C is a major cause of liver-related morbidity and mortality. Standard therapy is ribavirin plus pegylated interferon to achieve undetectable level of virus in the blood, but the effect on clinical outcomes is controversial.......Hepatitis C is a major cause of liver-related morbidity and mortality. Standard therapy is ribavirin plus pegylated interferon to achieve undetectable level of virus in the blood, but the effect on clinical outcomes is controversial....

  16. Treatment of chronic hepatitis C in non-responsive patients with pegylated interferon associated with ribavirin and thalidomide: report of six cases of total remission Tratamento de hepatite C crônica em pacientes não respondedores, com a associação interferon peguilado, ribavirina e talidomida: Relato de seis casos

    Directory of Open Access Journals (Sweden)

    Marcos Montani Caseiro

    2006-04-01

    Full Text Available Hepatitis C virus (HCV infection is an important public health issue worldwide. It is estimated that over 170 million people are infected with the virus. The present study reports six cases in which patients did not respond to combination therapy with pegylated interferon and ribavirin. However, after the addition of thalidomide to the therapy, the patients presented negative RNA PCR. The use of thalidomide combined with pegylated interferon and ribavirin for the treatment of hepatitis C is described here for the first time in the related literature.A infecção pelo vírus da Hepatite C (HCV representa um importante problema de saúde pública no mundo, estima-se que mais de 170 milhões de pessoas estejam infectadas. Relatamos o encontro de 6 pacientes não respondedores à associação de Interferon Peguilado e Ribavirina que negativaram seu PCRRNA após a associação com talidomida. Trata-se do primeiro relato desta associação no tratamento da hepatite C encontrado na literatura.

  17. VEGF in hepatocellular carcinoma and surrounding cirrhotic liver tissues

    Institute of Scientific and Technical Information of China (English)

    Muriel Mathonnet; Bernard Descottes; Denis Valleix; Francois Labrousse; Yves Denizot

    2006-01-01

    @@ TO THE EDITOR We read with a great interest the recent work of Deli and colleagues.[1] in the World Journal of Gastroenterology reporting vascular endothelial growth factor (VEGF) expression in hepatocellular carcinoma (HCC) and cirrhotic liver tissues.

  18. Sciatic Hernia Mimicking Perianal Abscess in a Cirrhotic Patient

    Directory of Open Access Journals (Sweden)

    Wellington Andraus

    2012-01-01

    Full Text Available Abdominal hernias are very frequent in cirrhotic patients with ascites. The hernias usually present as umbilical, inguinal, incisional, or femoral. However, these patients can also develop uncommon hernias such as pelvic hernias because of pelvic floor weakness and high abdominal pressure due to ascites. We present the first case of a cirrhotic patient with ascites that developed a giant sciatic hernia mimicking a perianal abscess.

  19. Early quantification of HCV core antigen may help to determine the duration of therapy for chronic genotype 2 or 3 HCV infection

    DEFF Research Database (Denmark)

    Alsiö, A; Jannesson, A; Langeland, N;

    2012-01-01

    The aim of the present study was to evaluate the utility of hepatitis C virus (HCV) core antigen (coreAg) assessment for the identification of candidates for short-term therapy. Plasma samples from HCV genotype 2 or 3-infected patients participating in the NORDynamIC trial (n = 382) comparing 12...... and 24 weeks of combination treatment with pegylated interferon-α2a and a fixed dose of 800 mg ribavirin daily were analyzed for coreAg. Among the 126 patients (33% of the intention-to-treat population) achieving HCV coreAg levels in plasma below 0.2 pg/mL when assayed on treatment day 3, sustained viral...... were 89% and 95%, respectively. Twelve weeks of combination treatment may be sufficient for genotype 2 or 3-infected patients achieving HCV coreAg levels below 0.2 pg/mL by day 3, signaling a rapid clearance of HCV viremia....

  20. Sofosbuvir and Simeprevir Combination Therapy for HCV Genotype 1 Infection: Results of a Single-Center VA Experience.

    Science.gov (United States)

    Sclair, Seth N; Hernandez, Maria Del Pilar; Vance, Evan; Gilinski, Dani; Youtseff, Helen; Toro, Maribel; Antoine, Marie; Jeffers, Lennox J; Peyton, Adam

    2016-08-01

    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.

  1. Hepatitis E virus mutations associated with ribavirin treatment failure result in altered viral fitness and ribavirin sensitivity.

    Science.gov (United States)

    Debing, Yannick; Ramière, Christophe; Dallmeier, Kai; Piorkowski, Géraldine; Trabaud, Mary-Anne; Lebossé, Fanny; Scholtès, Caroline; Roche, Magali; Legras-Lachuer, Catherine; de Lamballerie, Xavier; André, Patrice; Neyts, Johan

    2016-09-01

    Ribavirin monotherapy is the preferred treatment for chronic hepatitis E, although occasional treatment failure occurs. We present a patient with chronic hepatitis E experiencing ribavirin treatment failure with a completely resistant phenotype. We aimed to identify viral mutations associated with treatment failure and explore the underlying mechanisms. Viral genomes were deep-sequenced at different time points and the role of identified mutations was assessed in vitro using mutant replicons, antiviral assays, cell culture of patient-derived virus and deep-sequencing. Ribavirin resistance was associated with Y1320H, K1383N and G1634R mutations in the viral polymerase, but also an insertion in the hypervariable region comprising a duplication and a polymerase-derived fragment. Analysis of these genome alterations in vitro revealed replication-increasing roles for Y1320H and G1634R mutations and the hypervariable region insertion. In contrast, the K1383N mutation in the polymerase F1-motif suppressed viral replication and increased the in vitro sensitivity to ribavirin, contrary to the clinical phenotype. Analysis of the replication of mutant full-length virus and in vitro culturing of patient-derived virus confirmed that sensitivity to ribavirin was retained. Finally, deep-sequencing of hepatitis E virus genomes revealed that ribavirin is mutagenic to viral replication in vitro and in vivo. Mutations Y1320H, G1634R and the hypervariable region insertion compensated for K1383N-associated replication defects. The specific role of the K1383N mutation remains enigmatic, but it appears to be of importance for the ribavirin resistant phenotype in this patient. Ribavirin is the most common treatment for chronic hepatitis E and is mostly effective, although some cases of ribavirin treatment failure have been described. Here, we report on a particular case of ribavirin resistance and investigate the underlying causes of treatment failure. Mutations in the viral polymerase

  2. Ribavirin shows immunomodulatory effects on activated microglia.

    Science.gov (United States)

    Savic, Danijela; Stojiljkovic, Mirjana; Lavrnja, Irena; Parabucki, Ana; Bjelobaba, Ivana; Nedeljkovic, Nadezda; Herdegen, Thomas; Pekovic, Sanja

    2014-12-01

    Abstract Ribavirin (RBV) is synthetic purine nucleoside analogue, licensed as anti-viral drug that displays immunomodulatory actions on various immune cells. Our previous ex vivo studies have demonstrated immunosuppressive effects of RBV on reactive T-lymphocytes in experimental autoimmune encephalomyelitis. Here, we examined the effects of RBV on inflammatory response of microglia. RBV potency to down-regulate microglia inflammatory response was assessed by measuring microglia cell body size, and the production of nitric oxide (NO) and pro- and anti-inflammatory cytokines. RBV exerted cytotoxic effects on LPS-stimulated microglia, leaving non-stimulated microglia unaffected. The exposure of activated microglia to RBV led to: decrease in the level of NO as a result of decreased cell number, lower average cell surface, the reduction of membrane ruffling, the suppression of interleukin-6 release and promoted interleukin-10 production. On the other hand, RBV promoted LPS-induced interleukin-1 beta release. Our results imply that RBV is a complex immunomodulator showing both anti- and pro-inflammatory effects on activated microglia.

  3. Directly observed therapy of sofosbuvir/ribavirin +/- peginterferon with minimal monitoring for the treatment of chronic hepatitis C in people with a history of drug use in Chennai, India (C-DOT).

    Science.gov (United States)

    Solomon, S S; Sulkowski, M S; Amrose, P; Srikrishnan, A K; McFall, A M; Ramasamy, B; Kumar, M S; Anand, S; Thomas, D L; Mehta, S H

    2017-07-18

    We assessed the feasibility of field-based directly observed therapy (DOT) with minimal monitoring to deliver HCV treatment to people with a history of drug use in Chennai, India. Fifty participants were randomized 1:1 to sofosbuvir+peginterferon alfa 2a+ribavirin (SOF+PR) for 12 weeks (Arm 1) vs sofosbuvir+ribavirin (SOF+R) for 24 weeks (Arm 2). SOF+R was delivered daily at participant chosen venues and weekly peginterferon injections at the study clinic. HCV RNA testing was performed to confirm active HCV infection and sustained virologic response 12 weeks after treatment completion (SVR12). No baseline genotyping or on-treatment viral loads were performed. Median age was 46 years. All were male and 20% had significant fibrosis/cirrhosis. All self-reported history of injection drug use, 18% recent noninjection drug use and 38% alcohol dependence. Six discontinued treatment (88% completed treatment in each arm). Of 22 who completed SOF+PR, all achieved SVR12 (22/25=88%); 15 of 22 who completed SOF+R achieved SVR12 (15/25=60%; P=.05). Among those completing SOF+R, SVR12 was significantly less common in participants reporting ongoing substance use (36% vs 100%) and missed doses. Active substance use and missed doses did not impact SVR with SOF+PR. Field-based DOT of HCV therapy without real-time HCV RNA monitoring was feasible; however, achieving 100% adherence was challenging. SOF+PR appeared superior to SOF+R in achieving SVR12, even when doses were missed with no discontinuations due to side effects. Further exploration of short duration treatment with peginterferon plus direct-acting antivirals is warranted. © 2017 John Wiley & Sons Ltd.

  4. Behavior of soluble HLA-A, -B, -C and HLA-G molecules in patients with chronic hepatitis C virus infection undergoing pegylated interferon-α and ribavirin treatment: potential role as markers of response to antiviral therapy.

    Science.gov (United States)

    Murdaca, Giuseppe; Contini, Paola; Cagnati, Paola; Marenco, Simona; Pieri, Giulia; Lantieri, Francesca; Picciotto, Antonino; Puppo, Francesco

    2017-02-01

    The serum levels of soluble HLA class I antigens (sHLA-A, -B, -C and sHLA-G) were determined in 40 HCV genotype 1-infected patients before (T 0), after 3, 6, and 12 months (T 3, T 6, and T 12) of pegylated-IFN-α plus ribavirin therapy and 6 months (T 18) after the end of treatment. Twenty patients were sustained virological responders (SVR), and 20 were non-responders (NR). sHLA-A, -B, -C levels at T 0 were significantly higher in both SVR (mean 10.48 μg/ml) and NR (mean 11.87 μg/ml) patients as compared to healthy controls (mean 0.34 μg/ml, p G levels at T 0 were significantly higher in SVR (mean 24.78 ng/ml) and NR (mean 24.93 ng/ml) patients as compared to healthy controls (mean 10.34 ng/ml, p = 0.015 and p = 0.014, respectively) but were lower as compared to HIV-infected subjects (mean 48.00 ng/ml, p G significantly decreased in SVR from T 0 to T 18 (mean 1.64 and 1.43 ng/ml, respectively, p < 0.0001) and correlated with HCV-RNA, AST, ALT, γGT, and ALP levels. The determination of soluble HLA class I levels could be proposed as a surrogate marker to discriminate SVR and NR HCV-infected patients during PEG-IFN-α plus ribavirin therapy.

  5. Health-Related Quality of Life in Chronic HCV-Infected Patients Switching to Pegylated-Interferon-Free Regimens (ANRS CO20 CUPIC Cohort Study and SIRIUS Trial).

    Science.gov (United States)

    Carrieri, Maria Patrizia; Protopopescu, Camelia; Younossi, Zobair; Vilotitch, Antoine; Fontaine, Hélène; Petrov-Sanchez, Ventzislava; Marcellin, Fabienne; Carrat, Fabrice; Hézode, Christophe; Bourlière, Marc

    2017-03-28

    We aimed to compare health-related quality of life (HRQL) during and after hepatitis C virus (HCV) treatment in patients receiving pegylated-interferon (PEG-IFN)-containing therapy (including boceprevir or telaprevir-ANRS CO20 CUPIC cohort) who subsequently switched to PEG-IFN-free regimens (sofosbuvir + ledipasvir with or without ribavirin [RBV]-SIRIUS trial). Two analyses were performed. The first compared physical (PCS) and mental (MCS) HRQL (MOS SF-12) scores during treatment between CUPIC and SIRIUS. The second compared PCS and MCS scores after treatment end between CUPIC and SIRIUS. The analyses used linear regression mixed models adjusted for pre-treatment HRQL scores, gender, and age at each visit. Among patients enrolled successively in both studies, 43 (corresponding to 212 HRQL assessments) and 43 (82 HRQL assessments) were eligible for the 'during' and 'post' treatment analyses, respectively. In the 'during-treatment' analysis, we found significantly higher PCS and MCS values during PEG-IFN-free treatment than for PEG-IFN-containing treatment. In the 'post-treatment' analysis, results showed significantly higher MCS values after PEG-IFN-free treatment than after PEG-IFN-containing treatment. No significant difference was found for PCS in the post-treatment analysis. These results highlight an improvement in both physical and mental HRQL during HCV treatment, but no major improvement in physical HRQL after treatment end, when comparing PEG-IFN-free regimens with PEG-IFN-containing regimens. This suggests that in the PEG-IFN-free regimens era, screening and comprehensive care of comorbidities and residual somatic symptoms during treatment, and especially after HCV clearance, are still needed to improve patient outcomes.

  6. None of the six SNPs of IL28B could predict treatment responses in genotype 2 chronic HCV infected patients by propensity score matching analysis.

    Directory of Open Access Journals (Sweden)

    Wen-Juei Jeng

    Full Text Available BACKGROUND & AIMS: A combination of pegylated interferon-alpha and ribavirin (PR is the standard therapy for patients with chronic hepatitis C. The impact of polymorphism of interleukin-28B (IL28B on sustained virological response (SVR to PR has been well documented in patients with CHC genotype-1 (GT1, but it is controversial in genotype-2 (GT2 CHC patients. This study investigated the predictability of six single nucleotide polymorphisms (SNP of IL28B on the treatment responses of PR in patients with CHC GT2. METHOD: 197 CHC GT2 consecutive patients who received PR treatment in our prospective cohort were enrolled. Hepatitis C virus (HCV genotyping, quantification of HCV-RNA and genotyping of the ten SNPs of IL28B were performed. Six SNPs of IL28B were chosen for analysis. The propensity score matching (PSM analysis was applied using patients with CHC GT1 in another prospective cohort as a positive comparison to avoid covariate bias. RESULTS: The distribution of the six SNPs was similar in GT1 and GT2 patients. Five of these SNPs had strong association with treatment responses in GT1 but not in GT2 patients. After PSM analysis, these five SNPs still showed strong association with rapid virological response (RVR, cEVR and SVR in GT1 and had no influence in GT2 patients. Furthermore, rs12979860 and baseline viral load were the predictors for both RVR and SVR in GT1 patients. However, only baseline viral load could predict RVR and SVR in GT2 patients. In addition, in patients without RVR, rs12979860 was the only predictor for SVR in GT1 but no predictor for SVR was found in GT2. CONCLUSIONS: The genetic polymorphisms of IL28B had no impact on treatment responses in GT2 patients.

  7. 美沙酮门诊治疗人员617例感染HIV和HCV分析%Analysis on 617 Cases of HIV and HCV Infection among Patients in Methadone Maintenance Treatment Clinics

    Institute of Scientific and Technical Information of China (English)

    幸小弘; 王志成; 彭孝武

    2011-01-01

    [Objective]To study the status of HIV and HCV infection among drug addicts in methadone maintenance treatment clinics and its influencing factors in Jingzhou city. [ Methods ] The questionnaire survey for drug use behavior, liver function, nutritional status and complication was conducted among drug addicts, and blood samples were collected to test HIV antibody and HCV antibod-y. [Results] Among 617 drug addicts, the infection rate of HIV and HCV was 2.1% and 70. 5% respectively, and the HCV infection was related to the drug addiction years. There were significant differences in age of first drug use and drug addiction years between male and female drug addicts ( P 0.05 all). The incidence of complications in female drug addicts ( 21.43% ) was higher than that in male ( 12. 83% ) significantly ( P 0. 05 ) , but differences in the incidence of abnormal liver function and complications among drug addicts with different nutritional status were significant (P<0.01). The multiple logistic regression analysis showed that the main influencing factors of HCV infection were age of first drug use, amount of drug use, liver function, complications and age, and age of first drug use had a negative correlation with HCV infection. [Conclusion] The intervention measures for high-risk behavior should be adopted among drug addicts, and education of knowledge about AIDS should be carried out on this population.%目的 了解荆州市美沙酮门诊吸毒人员HIV、HCV的感染状况及其影响因素。方法 对吸毒人员吸毒行为、肝功能有无异常、营养情况、并发症等进行问卷调查,并采血样检测HIV抗体、HCV抗体。结果 617名吸毒者中,HIV、HCV感染率分别为2.1%和70.5%。HCV感染与吸毒年限有关。男女吸毒人员吸毒行为比较:初吸毒年龄和吸毒年限差异有统计学意义(均P<0.01和P<0.05),但平均吸毒频次、平均吸毒量差异无统计学意义(均P>0.05)。女性吸

  8. Clinical significance of HCV RNA assay in patients with HCV infection or co-infection of HBV%HCV及其与HBV重叠感染患者血清HCV RNA检测的临床意义

    Institute of Scientific and Technical Information of China (English)

    夏伟; 陈芳

    2012-01-01

    Objective To investigate the clinical significance of HCV RNA assay in patients of HCV infection or co-infection with HBV. Methods 179 cases of patients includes chronic hepatitis C group (n = 101), liver cirrhosis group (n = 45) and hepatomas group (n = 33). Anti-HCV and HCV RNA in 179 serum samples from patients with HCV infection or co-infection with HBV were detected. HBV DNA was assayed for 31 co-infection patients. Results The positive rate of Anti- HCV was higher than HCV RNA in the 179 patients (97.8% vs 69.8%, P < 0.01). The positive rate in liver cirrhosis group and hepatomas group were 82.2% and 84.8%, inspectively, which were higher than that in chronic hepatitis C group (64.4%, P < 0.05). HCV RNA positive rate of HCV and HBV co-infection group was lower than that in simple HCV infection group (48.4% vs 71.6%, P < 0.05). HBV DNA positive rate of HCV and HBV co-infection group was also lower than that in simple HBV infection group (35.5% vs 76.7%, P < 0.01). ALT abnormal rate in HCV RNA positive group was higher than that in HCV RNA negative group (60.8% vs 35.2%, P < 0.05). Conclusion Combined detection of anti-HCV, HCV RNA and ALT is helpful to diagnosis, curative effect observation and prognosis for patients with HCV infection related diseases. And HBV DNA should be detected simultaneously for HCV and HBV co-infection patients.%目的 探讨HCV及其与HBV重叠感染患者血清HCV RNA检测的临床意义.方法 收集我院HCV感染及其与HBV重叠患者血清标本共179例,分为慢性丙型肝炎组(n = 101)、肝硬化组(n = 45)和肝癌组(n = 33).采用ELISA法检测血清抗HCV,用荧光定量PCR检测HCV RNA;对重叠感染HCV和HBV的31例患者同时检测HBV DNA.结果 179例患者抗HCV的总阳性率为97.8%,高于HCV RNA的阳性率(69.8%)(P < 0.01).肝硬化组和肝癌组HCV RNA的阳性率分别为82.2%和84.8%,高于慢性丙型肝炎组阳性率64.4%(P < 0.05).HCV与HBV重叠感染组的HCV RNA的阳性率为48.4%,

  9. Ribavirin stimulates the immune response of Atlantic salmon.

    Science.gov (United States)

    Rivas-Aravena, A; Guajardo, S; Valenzuela, B; Cartagena, J; Imarai, M I; Spencer, E; Sandino, A M

    2015-03-15

    Ribavirin is a synthetic nucleotide analog capable of inhibiting or even preventing some viral infections in mammals and also in fish. It has been seen by others that ribavirin by itself is able to stimulate the immune system of mammals, causing a differentiation of T-cells to T helper 1 cells (Th)-1. In this work, we evaluated the immune effect of ribavirin in vitro on kidney cells from Atlantic salmon and in vivo by oral administration of ribavirin to Atlantic salmon. For this purpose, the transcripts of immune molecules Tbet, GATA3, CD8, CD4, IFNα, IFNγ, IL-4/13, IL-10, IL-12, IL-15 and TGF-B were quantified. The results show that ribavirin administered orally in food to Atlantic salmon increased IFNγ and CD4 transcripts in the in vivo assays and, in addition, increased IL-12, IL-15 and CD8 in the in vitro analyses, indicating that the treatment stimulates a Th1 type response in salmon.

  10. Neutropenia in chronic hepatitis C during Interferon and Ribavirin Therapy.

    Directory of Open Access Journals (Sweden)

    Saadia Farid, Hala Morad and Samya Sweilam.

    2011-10-01

    Full Text Available Background: Neutropenia is a condition characterized by an abnormally low number of a type of white blood cells called Neutrophils, up to 25 % of people who take pegylated interferon, ribavirin and an HCV protease inhibitor experience Neutropenia. Aim of the work: The study will be intended to analyze neutrophil counts and associated conditions of the liver and spleen , platelet count, liver enzymes and infections, during Interferon and Ribavirin therapy. Patients and methods: One hundred forty two patients with chronic hepatitis C virus infection, their age between (18-59 years, selected from the National Hepatology and Tropical Medicine Research Institute were included in this study, during Interferon and Ribavirin therapy. All the patients were subjected to the following history, through clinical examination, abdominal ultrasonography and collection of blood samples for routine investigations, CBCs and serological assay for ALT, Bilirubin. Resuls: Our results revealed presence of 32.4 % anaemia, 18.3 % Thrombocytopenia, 16.9 % elevated ALT, 2.8 % elevated bilirubine, 16.9 % coarse liver, 25.4 % hepatomegaly, 16.2 % splenomegaly, and 16.9 % of cases complained different shapes of infection, associated with Neutropenia in patients of chronic hepatitis C during interferon and ribavirin therapy. Conclusion: Our study concluded that the prevalence of Neutropenia in chronic hepatitis C virus infection patients 23.8 % during interferon and ribavirin therapy but it is not usually associated with infection. Recommendations: Neutropenia is a complicated process that requires expert guidance from a medical provider.

  11. Idiopathic non-cirrhotic portal hypertension

    Directory of Open Access Journals (Sweden)

    CHEN Jie

    2013-07-01

    Full Text Available The pathogenesis of idiopathic non-cirrhotic portal hypertension (INCPH remains unknown and the disease is diagnosed by the absence of recognized clinical indicators of cirrhosis and of any other known etiologies of portal hypertension. To promote understanding of this disease, a comprehensive overview of potential etiologies, clinical manifestations, histopathological features, methods of diagnosis and potential differential diagnoses, and outcome of clinical management is presented in this review. In particular, we discuss the findings from INCPH studies and their implications in regards to each of the above-mentioned categories. For example, associations with various comorbidities have suggested a possible immune system component to INCPH development and/or progression. In addition, the common clinical characteristics of patients upon presentation can not only help to recognize disease suspects but may also provide insights into the pathogenesis and prognosis. Finally, prognosis following the various intervention strategies appears to depend mainly on severity of the portal hypertension, as well as its various accompanying complications.

  12. Is travel-time to a specialist centre a risk factor for non-referral, non-attendance and loss to follow-up among patients with hepatitis C (HCV) infection?

    Science.gov (United States)

    Astell-Burt, Thomas; Flowerdew, Robin; Boyle, Paul; Dillon, John

    2012-07-01

    Little is known about why many people diagnosed with hepatitis C virus (HCV) infection fail to reach and stay within specialist care services. We used a Geographic Information System and logit regression to investigate whether travel-time to a specialist centre was associated with an increased likelihood of non-referral, non-attendance and loss to follow-up among persons diagnosed with HCV between 1991 and 2003 in Tayside, Scotland (UK). Information was available on referral to, and utilisation of, the single HCV specialist centre in Tayside between 1991 and 2006. Longer travel-time to a specialist centre was associated with an increased likelihood of non-referral to a specialist centre following diagnosis (Odds Ratio: 1.25, 95% Confidence Interval: 1.09, 1.44). Patients living further from an HCV specialist centre were less likely to be referred to it for treatment that could cure their HCV infection. Neither a history of intravenous drug use (IDU), nor area deprivation predicted non-referral. Subsequent to referral, travel-time to a specialist centre was not associated with either non-attendance (0.83 (0.56, 1.21)) or loss to follow-up (0.98 (0.78, 1.22)), although a history of IDU was a strong predictor of both non-attendance and loss to follow-up. Non-attendance was less likely among older patients, while loss to follow-up was more common among those living in deprived areas. Once referred, patients appear able to cope with stress and financial cost of long and frequent journeys to hospital. However, as rates of referral improve from more geographically remote areas, long travel-times to an HCV specialist centre may become an important factor determining future utilisation. Copyright © 2012 Elsevier Ltd. All rights reserved.

  13. Efficacy and safety of simeprevir in combination with peginterferon and ribavirin for patients with hepatitis C genotype 1 infection: a meta-analysis of randomized trials

    Directory of Open Access Journals (Sweden)

    Cui Xianghua

    Full Text Available Background and aim: A simeprevir (SMV-based regimen has shown promising results in treating chronic hepatitis C virus (HCV infection. This meta-analysis aimed to assess the efficacy and safety of simeprevir for treating HCV genotype 1 infection. Methods: MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were searched, along with the reference lists of retrieved articles. The meta-analysis only included randomized controlled trials (RCTs that compared the efficacy and safety of addition of SMV to peginterferon (PegIFN and ribavirin (RBV (triple regimen with PegIFN/RBV alone (dual regimen in treating chronic HCV genotype 1 infection. Results: A total of seven RCTs involving 2,301 patients were included. The triple regimen had a higher pooled sustained virologic response (SVR rate [odds ratio (OR = 4.57; 95% confidence interval (CI: 3.34-6.27; p < 0.001] and lower pooled relapse rate [relative risk (RR = 0.41; 95% CI: 0.33-0.50; p < 0.001] than the dual regimen had. The pooled incidence of adverse events (AEs was comparable between the two regimens (RR = 1.01; 95% CI: 0.99-1.03; p = 0.339, whereas the incidence of serious AEs in the triple regimen was lower (RR = 0.7; 95% CI: 0.50-0.98; p < 0.05. Conclusions: The meta-analysis demonstrates that the addition of SMV to pegIFN and RBV is effective and well-tolerated in treating chronic HCV genotype 1 infection, with a low incidence of AEs.

  14. Efficacy and safety of peginterferon alfa-2a and ribavirin treatment of chronic hepatitis C in the Republic of Serbia

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    Božić Milena

    2012-01-01

    Full Text Available Introduction. Hepatitis C virus (HCV infection is one of the main causes of chronic liver disease worldwide. Pegylated interferon alfa-2a or 2b (PEG IFN alfa-2a or 2b and ribavirin (RBV represent a standard treatment of chronic hepatitis C (CHC. Sustained virological response (SVR, defined as continued undetectable HCV RNA 24 weeks after completion of treatment, is universally considered as an indicator of treatment efficacy. Objective. The aim of this study was to determine efficacy and safety of PEG IFN alfa-2a and RBV treatment in patients with CHC in Serbia. Methods. One hundred seventy-six patients with CHC were included in this multicenter trial from 8 reference centers in Serbia. The patients were treated with standard PEG IFN alfa- 2a and RBV protocol. We performed the following virological testing: anti-HCV (ELISA, HCV RNK (quantitative PCR, HCV genotype (type-specific PCR, HBsAg, anti-HBs, anti-HBc and anti-HIV (ELISA. Histological activity and the degree of fibrosis were determined according to the Metavir scoring system. Potential predictors for achieving SVR were evaluated using multivariable logistic regression analysis. Results. Of the treated patients with CHC 65.9% were male, and 60.2% of them aged over 40 years. Of the treated patients 68.2% had infection over 5 years, 63% had HCV RNA >400.000 IU/mL, 76.1% had HCV G1/4, and 60.1% had a mild to moderate liver fibrosis. SVR was achieved in 78.9% of patients (G1/4 79.1%; G2/3 78.1%. The factors that indicated a poorer efficacy of the treatment were age >40 (p<0.05, high basal viremia (p=0.013, and the reduction of PEG IFN alfa-2a and RBV doses, with interruption of therapy (p<0.001. Of the treated patients 45.9% had adverse affects (G1/4 50.8%; G2/3 29.7%. Conclusion. Treatment of CHC with PEG IFN alfa-2a and RBV was efficient in 78.9% of patients. The safety profile of therapy was satisfactory. Longer therapy increases the possibility of the development of adverse affects. No

  15. Features of Hemodialysis in Cirrhotic Patients: Single Center Experience

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    Süleyman KÖZ

    2015-09-01

    Full Text Available OBJECTIVE: End-stage kidney disease and advanced cirrhosis are sometimes seen concomitantly. Our purpose was to compare hemodialysis (HD sessions in critically ill cirrhotic patients from ICU versus stable cirrhotic patients from outpatient clinic, and observe endurance of both stable and acutely ill cirrhotic patients to intermittent HD. MATERIAL and METHODS: All of the Child-Pugh class B or C cirrhotic patients requiring renal replacement therapy during a period of three years were included in the study. If hypotension, arrhythmia, bleeding, or any other health problems were present during dialysis, the dialysis session was regarded as a troubled session. RESULTS: There were two groups of patients. All of the stable patients lived more than three months, whereas all patients in the ICU group died within a month. Mean ultrafiltration volume per session was 1786±210 ml in ICU and 1616±266 ml in stable patients (p>0.05. The number of the troubled sessions was 24 in ICU and 1 in stable patients (p<0.0001. Bleeding was a problem in a minority of the patients. CONCLUSION: Intermittent HD may be an acceptable choice for stable cirrhotic dialysis patients. Hypotension is a frequent complication of intermittent HD in ICU patients.

  16. [Evaluation and treatment of the critically ill cirrhotic patient].

    Science.gov (United States)

    Fernández, Javier; Aracil, Carles; Solà, Elsa; Soriano, Germán; Cinta Cardona, Maria; Coll, Susanna; Genescà, Joan; Hombrados, Manoli; Morillas, Rosa; Martín-Llahí, Marta; Pardo, Albert; Sánchez, Jordi; Vargas, Victor; Xiol, Xavier; Ginès, Pere

    2016-11-01

    Cirrhotic patients often develop severe complications requiring ICU admission. Grade III-IV hepatic encephalopathy, septic shock, acute-on-chronic liver failure and variceal bleeding are clinical decompensations that need a specific therapeutic approach in cirrhosis. The increased effectiveness of the treatments currently used in this setting and the spread of liver transplantation programs have substantially improved the prognosis of critically ill cirrhotic patients, which has facilitated their admission to critical care units. However, gastroenterologists and intensivists have limited knowledge of the pathogenesis, diagnosis and treatment of these complications and of the prognostic evaluation of critically ill cirrhotic patients. Cirrhotic patients present alterations in systemic and splanchnic hemodynamics, coagulation and immune dysfunction what further increase the complexity of the treatment, the risk of developing new complications and mortality in comparison with the general population. These differential characteristics have important diagnostic and therapeutic implications that must be known by general intensivists. In this context, the Catalan Society of Gastroenterology and Hepatology requested a group of experts to draft a position paper on the assessment and treatment of critically ill cirrhotic patients. This article describes the recommendations agreed upon at the consensus meetings and their main conclusions. Copyright © 2015 Elsevier España, S.L.U. y AEEH y AEG. All rights reserved.

  17. Platelet-activating factor in cirrhotic liver and hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Muriel Mathonnet; Bernard Descottes; Denis Valleix; Véronique Truffinet; Francois Labrousse; Yves Denizot

    2006-01-01

    AIM: Platelet-activating factor (PAF) is a pro-inflammatory and angiogenic lipid mediator. Here we aimed to investigate levels of PAF, lyso-PAF (the PAF precursor),phospholipase A2 (PLA2, the enzymatic activity generating lyso-PAF), acetylhydrolase activity (AHA, the PAF degrading enzyme) and PAF receptor (PAF-R) transcripts in cirrhotic liver and hepatocellular carcinoma (HCC).METHODS: Twenty-nine patients with HCC were ehrolled in this study. Cirrhosis was present in fourteen patients and seven had no liver disease. Tissue PAF levels were investigated by a platelet-aggregation assay. LysoPAF was assessed after its chemical acetylation into PAF.AHA was determined by degradation of [3H]-PAF. PLA2 levels were assessed by EIA. PAF-R transcripts were investigated using RT-PCR.RESULTS: Elevated amounts of PAF and PAF-R transcripts 1 (leukocyte-type) were found in cirrhotic tissues as compared with non-cirrhotic ones. Higher amounts of PAF and PAF-R transcripts 1 and 2 (tissue-type) were found in HCC tissues as compared with non-tumor tissues. PLA2, lyso-PAF and AHA levels were not changed in cirrhotic tissues and HCC.CONCLUSION: While the role of PAF is currently unknown in liver physiology, this study suggests its potential involvement in the inflammatory network found in the cirrhotic liver and in the angiogenic response during HCC.

  18. Dual sofosbuvir and ribavirin therapy for chronic hepatitis C infection.

    Science.gov (United States)

    Tang, L; Ward, H; Kattakuzhy, S; Wilson, E; Kottilil, S

    2016-01-01

    Sofosbuvir is the first pan-genotypic direct acting antiviral agent to be approved. This article provides an overview of the pharmacology of sofosbuvir and ribavirin and a comprehensive summary of the phase 2 and 3 studies supporting dual sofosbuvir and ribavirin therapy for chronic hepatitis C infection. With the production of generic formulations of sofosbuvir, we anticipate this regimen leading the first wave for widespread, IFN-free treatment and becoming first line for all genotypes (including genotype 1) for much of the world-in particular in developing and middle income countries. We discuss the continued challenges with this regimen including among patients with decompensated liver disease and post-liver transplant, and renal failure. We address concerns of emerging resistance. We also discuss the future prospects including the global uptake of sofosbuvir and ribavirin for the treatment of all genotypes.

  19. Cirrhosis and Rapid Virological Response to Peginterferon Plus Ribavirin Determine Treatment Outcome in HCV-1 IL28B rs12979860 CC Patients

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    Alessio Aghemo

    2013-01-01

    Full Text Available Background. The rs12979860 CC genotype of the interleukin 28B (IL28B polymorphism is associated with high rates of sustained virological response (SVR to peginterferon (PegIFN and ribavirin (Rbv in hepatitis C virus genotype-1 (HCV-1 patients. The impact of baseline predictors of treatment outcome and their interplay with viral kinetics in HCV-1 CC patients has not been fully evaluated. Aim. To identify baseline and on-therapy predictors of treatment failure in HCV-1 IL28B CC patients. Methods. Treatment-naïve HCV-1 patients, compliant to PegIFN and Rbv who did not discontinue treatment for nonvirological reasons, were analyzed. Results. 109 HCV-1 IL28B CC were studied. Sixty were males, 39 with BMI >25, 69 with >600,000 IU/mL HCV RNA, 15 with HCV1a, and 30 with cirrhosis. Overall, 75 (69% achieved an SVR; cirrhosis was the only baseline predictor of treatment failure (OR: 2.58, 95% CI: 1.07–6.21 as SVR rates were 53% in cirrhotics versus 75% in noncirrhotics (P=0.03. HCV RNA undetectability (<50 IU/mL at week 4 (RVR was achieved by 58 patients (53%. The SVR rates were independent of RVR in noncirrhotics, 76% (34/45 RVR (+ and 74% (25/34 RVR (− (P=0.9. In cirrhotic patients, SVR rates were significantly higher in RVR (+ compared to RVR (− (10/13 (77% versus 6/17 (35% P=0.03. Conclusions. In HCV-1 IL28B CC patients, cirrhosis is the only clinical baseline predictor of PegIFN and Rbv treatment failure. However, in IL28B CC cirrhotics, the achievement of RVR identifies those patients who still have high rates of SVR to Peg-IFN/Rbv therapy.

  20. Prevalence of simple liver cysts and hemangiomas in cirrhotic and non-cirrhotic patients submitted to magnetic resonance imaging

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    Breno Victor Tomaz Galvao

    2013-07-01

    Full Text Available Objective To determine the prevalence of liver cysts and hemangiomas in the general population and in cirrhotic patients. Materials and Methods Retrospective, observational, and cross-sectional study selecting consecutive magnetic resonance imaging studies performed in the period from February to July 2011. A total of 303 patients (187 women and 116 men with mean age of 53.3 years were included in the present study. Patients with previously known liver lesions were excluded. The images were consensually analyzed by two observers in the search for simple liver cysts and typical liver hemangiomas, according to universally accepted imaging criteria. Lesions prevalence, diameters and location were determined in both cirrhotic and non-cirrhotic individuals. Results The authors observed prevalence of 8.6% for hemangiomas and 14.5% for simple cysts. No statistically significant difference was observed in relation to prevalence of hemangiomas and cysts among cirrhotic and non-cirrhotic patients (p = 0.954; p = 0.472. Conclusion In the present study, the prevalence of cysts and hemangiomas was higher than the prevalence reported by autopsy series. No influence of cirrhosis was observed on the prevalence and appearance of such incidental lesions.

  1. Metformin reduces hepatic resistance and portal pressure in cirrhotic rats.

    Science.gov (United States)

    Tripathi, Dinesh M; Erice, Eva; Lafoz, Erica; García-Calderó, Héctor; Sarin, Shiv K; Bosch, Jaime; Gracia-Sancho, Jordi; García-Pagán, Juan Carlos

    2015-09-01

    Increased hepatic vascular resistance is the primary factor in the development of portal hypertension. Metformin ameliorates vascular cells function in several vascular beds. Our study was aimed at evaluating the effects, and the underlying mechanisms, of metformin on hepatic and systemic hemodynamics in cirrhotic rats and its possible interaction with the effects of propranolol (Prop), the current standard treatment for portal hypertension. CCl4-cirrhotic rats received by gavage metformin 300 mg/kg or its vehicle once a day for 1 wk, before mean arterial pressure (MAP), portal pressure (PP), portal blood flow (PBF), hepatic vascular resistance, and putative molecular/cellular mechanisms were measured. In a subgroup of cirrhotic rats, the hemodynamic response to acute Prop (5 mg/kg iv) was assessed. Effects of metformin ± Prop on PP and MAP were validated in common bile duct ligated-cirrhotic rats. Metformin-treated CCl4-cirrhotic rats had lower PP and hepatic vascular resistance than vehicle-treated rats, without significant changes in MAP or PBF. Metformin caused a significant reduction in liver fibrosis (Sirius red), hepatic stellate cell activation (α-smooth muscle actin, platelet-derived growth factor receptor β polypeptide, transforming growth factor-βR1, and Rho kinase), hepatic inflammation (CD68 and CD163), superoxide (dihydroethidium staining), and nitric oxide scavenging (protein nitrotyrosination). Prop, by decreasing PBF, further reduced PP. Similar findings were observed in common bile duct ligated-cirrhotic rats. Metformin administration reduces PP by decreasing the structural and functional components of the elevated hepatic resistance of cirrhosis. This effect is additive to that of Prop. The potential impact of this pharmacological combination, otherwise commonly used in patients with cirrhosis and diabetes, needs clinical evaluation.

  2. CONCENTRATION AND HEMODYNAMICS PATTERN CHANGES IN CIRRHOTIC RATS

    Institute of Scientific and Technical Information of China (English)

    黄颖秋; 萧树东; 莫剑忠; 张德中

    2000-01-01

    Objective To investigate the effects of hemoglobin (Hb) on serum nitric oxide (NO) concentration and hemodynamics pattern changes in rats with cirrhosis. Methods Cirrhosis model was induced in male SD rats by injection of 60% CCl4 oily solution subcutaneously. Cirrhotic rats were treated with erythropoietin (l00U/kg) injected subcutaneously for 2 weeks. Mean arterial pressure (MAP), cardiac output (CO), cardiac index (CI), splanchnic vascular resistance (SVR), splanchnic blood flow (SBF) and serum NO concentration were determined in erythropoietin - treated, erythropoietin - untreated cirrhotic rats and controls by using 57Co- labelled microsphere technique and a fluorometric assay, respectively. In addition, blood Hb levels were also measured in the 3 groups. Results Untreated cirrhotic rats had significantly lower MAP, SVR, Hb and higher CO, CI, SBF and NO concentration than those of the controls (P<0.01). In treated cirrhotic rats, erythropoietin significantly attenuated the increase of CO, CI, SBF, NO concentration and the decrease of MAP and SVR. In cirrhotic rats,epoetin beta in subcutaneous dose of 100U· kg-1· d-1 induced a markedly increment of blood Hb levels and decrement of NO concentration in comparison with untreated cirrhotic rats (181±11g/L vs 120±15g/L;1.14±0.62μmol/L vs 4.20±1.25μmol/L). Conclusion The endogenous NO may play an important role in the changes of hemodynamics pattern in cirrhosis, and hyperdynamic circulatory status in rats with cirrhosis might be ameliorated by inactivation of overproduced NO by increasing hemoglobin with erythropoietin.

  3. The role of glucocorticoids in sodium retention in cirrhotic patients

    DEFF Research Database (Denmark)

    Hansen, Martin Højmark; Kristensen, Steffen Skott; Schaffalitzky de Muckadell, Ove B

    2012-01-01

    Abstract Objective. Cirrhotic patients have an increased ratio of urinary cortisol to cortisone metabolites, indicating decreased renal 11-β-hydroxysteroid dehydrogenase type-2 activity. This suggests that cortisol - by activation of the mineralocorticoid receptor - may contribute to the abnormal...... sodium retention evident in cirrhosis. The aim was to elucidate the role of glucocorticoids in sodium retention in decompensated cirrhotic patients. Methods. A randomized, double-blind, placebo-controlled, crossover study was performed in nine patients with alcoholic cirrhosis of the liver. A washout....... Conclusion. These results indicate that endogenous glucocorticoids contribute to the sodium retention in patients with alcoholic cirrhosis of the liver....

  4. Aplastic anemia and severe pancytopenia during treatment with peg-interferon, ribavirin and telaprevir for chronic hepatitis C.

    Science.gov (United States)

    Lens, Sabela; Calleja, Jose L; Campillo, Ana; Carrión, Jose A; Broquetas, Teresa; Perello, Christie; de la Revilla, Juan; Mariño, Zoe; Londoño, María-Carlota; Sánchez-Tapias, Jose M; Urbano-Ispizua, Álvaro; Forns, Xavier

    2015-05-07

    Telaprevir and Boceprevir are the first direct acting antivirals approved for chronic hepatitis C in combination with peg-interferon alfa and ribavirin. Pancytopenia due to myelotoxicity caused by these drugs may occur, but severe hematological abnormalities or aplastic anemia (AA) have not been described. We collected all cases of severe pancytopenia observed during triple therapy with telaprevir in four Spanish centers since approval of the drug in 2011. Among 142 cirrhotic patients receiving treatment, 7 cases of severe pancytopenia (5%) were identified and three were consistent with the diagnosis of AA. Mean age was 59 years, five patients had compensated cirrhosis and two patients had severe hepatitis C recurrence after liver transplantation. Severe pancytopenia was diagnosed a median of 10 wk after the initiation of therapy. Three patients had pre-treatment hematological abnormalities related to splenomegaly. In six patients, antiviral treatment was interrupted at the onset of hematological abnormalities. Two patients died due to septic complications and one patient due to acute alveolar hemorrhage. The remaining patients recovered. Severe pancytopenia and especially AA, are not rare during triple therapy with telaprevir in patients with advanced liver disease. Close monitoring is imperative in this setting to promptly detect serious hematological disorders and to prevent further complications.

  5. Ribavirin with or without alpha interferon for chronic hepatitis C

    DEFF Research Database (Denmark)

    Kjaergard, L L; Krogsgaard, K; Gluud, C

    2002-01-01

    Hepatitis C is a major cause of liver-related morbidity and mortality. Ribavirin plus interferon combination therapy is presently considered the optimal treatment of interferon naive patients with chronic hepatitis C, but its role in relapsers and non-responders to previous interferon therapy...

  6. Evidence that plasma concentration rather than dose per kilogram body weight predicts ribavirin-induced anaemia.

    Science.gov (United States)

    Lindahl, K; Schvarcz, R; Bruchfeld, A; Ståhle, L

    2004-01-01

    Ribavirin in combination with interferon alpha-2 or pegylated interferon is the standard treatment for chronic hepatitis C. The current dosage recommendations for ribavirin are based on body weight (bw). Ribavirin is mainly eliminated by the kidneys and we have recently shown that ribavirin plasma concentrations are determined primarily by renal function. It is therefore reasonable to hypothesize that side-effects of ribavirin, i.e. anaemia, should be more closely related to plasma concentrations of ribavirin than to the dose per kg bw. A total of 108 consecutive patients eligible for treatment of chronic hepatitis C were studied. Ribavirin concentrations in plasma were measured by high-performance liquid chromatography (HPLC)-UV after solid-phase extraction in trough samples taken 4, 8 and 12 weeks after the treatment commenced. A total of 213 samples were obtained and the change in the haemoglobin level and the creatinine concentration was measured in addition to ribavirin. The dose of ribavirin per kg bw did not correlate with the drop in haemoglobin level induced by ribavirin. The concentration of ribavirin was non-linearly related to the drop in the haemoglobin level as revealed by fitting a standard Hill equation type dose-response curve. The half maximal drop in haemoglobin was obtained at 4.4 microm. The results from this study suggest that the anaemia induced by ribavirin depends primarily on the concentration of ribavirin, and not on the dose per kg bw. This lends further support to the idea that ribavirin should be dosed according to renal function.

  7. Hepatocellular carcinoma (HCC) in non-cirrhotic liver: clinical, radiological and pathological findings

    Energy Technology Data Exchange (ETDEWEB)

    Di Martino, Michele; Di Miscio, Rossella; Lombardo, Concetta Valentina; Catalano, Carlo [University of Rome ' ' Sapienza' ' , Department of Radiological Sciences, Oncology and Anatomical Pathology, Rome (Italy); Saba, Luca; Piga, Mario [Department of Radiology Azienda Ospedaliera Universitaria (A.O.U.), Monserrato (Italy); Bosco, Sandro [University of Rome ' ' Sapienza' ' , Department of Molecular Medicine, Rome (Italy); Rossi, Massimo [University of Rome ' ' Sapienza' ' , Department of General Surgery, Division of Organ Transplantation, Rome (Italy); Miles, Kirchin A. [Worldwide Medical and Regulatory Affairs, Milan (Italy); Tamponi, Elisabetta [Azienda Ospedaliera Universitaria (A.O.U.), Department of Anatomical Pathology, Monserrato (Italy)

    2014-07-15

    Our aim was to evaluate the clinical and pathological findings, mutidetector-row computed tomography (MDCT) and magnetic resonance imaging (MRI) appearances, treatment and 1-year survival of patients with HCC in non-cirrhotic liver. Histopathological and laboratory findings of 30 non-cirrhotic patients with 32 HCCs were reviewed retrospectively. MDCT and gadobenate dimeglumine-enhanced MR images were evaluated in consensus by two radiologists in terms of HCC size, presence of tumour capsule, necrosis, haemorrhage, fat and calcification, and vascular involvement. Imaging patterns were compared directly with HCC findings in a matched group of cirrhotic patients. No differences between non-cirrhotic and cirrhotic patients were noted in terms of serum α-fetoprotein levels (elevated in 11 [36.7 %] and 21 [35 %] patients, respectively). The imaging appearance at CT and contrast-enhanced MRI was typical in 27 (84.3 %) and 28 (87.5 %) cases respectively. Most lesions presented as a well-differentiated large solitary mass, with well-defined margins, areas of necrosis and peripheral capsule. No significant differences in HCC pattern were observed between cirrhotic and non-cirrhotic liver. In non-cirrhotic patients, HCC is more likely to manifest as an asymptomatic mass with elevation of serum tumour markers similar to that seen in cirrhotic patients. HCC in cirrhotic and non-cirrhotic livers show similar enhancement patterns. (orig.)

  8. Adenosine receptor blockade reduces splanchnic hyperemia in cirrhotic rats.

    Science.gov (United States)

    Lee, S S; Chilton, E L; Pak, J M

    1992-06-01

    To explore a possible role for adenosine in the pathogenesis of the splanchnic hyperemia of cirrhosis, we administered 8-phenyltheophylline, a specific adenosine receptor antagonist, to rats with biliary cirrhosis caused by bile duct ligation and to control sham-operated rats. Micro-Doppler flow studies showed that a 10-mumol/kg dose of 8-phenyltheophylline completely abolished the superior mesenteric hyperemic response to infusions of exogenous adenosine in both cirrhotic and control rats. Analysis of regional blood flows by radioactive microspheres demonstrated that this dose of 8-phenyltheophylline in cirrhotic rats significantly increased portal tributary vascular resistance by 60% and decreased portal tributary blood flow by 26%. This decrease was entirely the result of a 42% reduction in the intestinal blood flow. 8-phenyltheophylline did not affect cardiac output, arterial pressure or any other extrasplanchnic hemodynamic variables in cirrhotic rats. No detectable effect of 8-phenyltheophylline was seen in sham-operated rats. These results suggest that adenosine may be involved in the genesis of splanchnic hyperemia in cirrhotic rats.

  9. 丙型肝炎病毒核心抗原在丙肝检测中的应用分析%Clinical value of HCV core antigen detection on the diagnosis of HCV infection

    Institute of Scientific and Technical Information of China (English)

    高会广; 卞爱娜

    2011-01-01

    目的 探讨丙型肝炎病毒核心抗原在丙肝感染诊断中的临床应用价值.方法 采用荧光定量聚合酶链反应(FQ-PCR)对162例疑似HCV感染者血清进行HCV RNA检测,同时用ELISA法对其进行HCV核心抗原和抗-HCV检测.结果 162例样本中,抗-HCV阳性率64.20%(104/162),HCV RNA阳性率51.85%(84/162),HCV核心抗原阳性率35.19%(57/162);HCV RNA和HCV核心抗原均阳性样本57例,二者符合率为67.86%;HCV核心抗原和HCV RNA阳性而抗-HCV阴性者1例.结论 HCV核心抗原是HIV早期感染的标志之一,检测HCV核心抗原有利于HCV感染的早期诊断.%Objective To explore the clinical value of hepatitis C virus (HCV) core antigen detection on the diagnosis of HCV infection. Methods Plasma samples were collected from 162 HCV infection suspected patients. Plasma samples were tested for HCV RNA by the method of Fluorescence Quantitative-polymerase chain reaction (FQ-PCR). The core antigen of HCV (HCVcAg) and anti-HCV were also tested by ELISA. Results The positive rates of HCV antibody, HCV RNA and HCVcAg were 64.20% (104/162), 51.85% (84/162) and 35.19% (57/162) respectively. HCVcAg was detected in 67.86% (57/84) of HCV RNA positive specimens. All HCVcAg positive specimens were positive for HCV RNA. There was only one patient who was negative for HCV antibody, but positive for HCV RNA and HCVcAg. Conclusion HCVcAg is a marker of early infection of HCV and may help early diagnosis of HCV.

  10. HCV infection and morphologic study in B lymphocytes of patient with hepatitis C%丙型肝炎病毒对人B淋巴细胞系的感染及其形态学研究

    Institute of Scientific and Technical Information of China (English)

    姚鹏; 陈良标; 胡学玲; 陈佩兰; 胡大荣

    2001-01-01

    目的 研究HCV对人B淋巴细胞的感染,建立HCV感染的丙型肝炎患者B淋巴细胞模型(CBCL),并进行HCV的形态学研究。方法用EB病毒转化B细胞建立B细胞系,以逆转录多聚酶链反应(RT-PCR)、免疫组织化学、原位杂交方法检测B细胞系上清液及细胞内的HCV抗原及HCV RNA,并通过电镜对HCV进行形态学研究。结果细胞系上清液中HCV RNA呈阳性,细胞内HCV抗原及HCV RNA均呈阳性,电镜观察结果发现细胞内存在65nm和110nm圆球型病毒颗粒,并可见病毒芽生形成现象。结论 HCV可感染人B细胞并在其中复制。病毒在感染细胞胞质空泡部位合成和组装,以芽生方式进入胞质空泡内形成病毒颗粒。%Objective To study HCV infection in B lymphocytes of patients with hepatitis C and to establish a B cell line with HCV infection and observe the hepatitis C virus like particles. Methods A B lymphoblastoid cell line was established by Epstein-Barr virus induced transformation directly from peripheral blood mononuclecyte cells of a patient with hepatitis C. The HCV antigen and HCV RNA were detected by immunohistochemical technique. Reverse transcription-polymerase chain reaction(RT-PCR) and in situ hybridization and HCV particle were detected by electron microscopy. Results Positive HCV RNA was found in supernatants of B cell line. HCV Ag and HCV RNA were also showed positive. Electron microscopy observed HCV spherical virus like particles with a diameter of approximately 65 nm and 110nm and the "bud mutation"of HCV in the cytoplasmic vesicles of B lymphocytes. Conclusion HCV could infect B lymphocytes and replicate in the cell line. HCV particles are formed by "bud mutation" of HCV in the cytoplasmic vesicles of B-lymphocytes.

  11. Incidence of bacteremia in cirrhotic patients undergoing upper endoscopic ultrasonography.

    Science.gov (United States)

    Fernández-Esparrach, Gloria; Sendino, Oriol; Araujo, Isis; Pellisé, Maria; Almela, Manel; González-Suárez, Begoña; López-Cerón, María; Córdova, Henry; Sanabria, Erwin; Uchima, Hugo; Llach, Josep; Ginès, Àngels

    2014-01-01

    The incidence of bacteremia after endoscopic ultrasonography (EUS) or EUS-guided fine-needle aspiration (EUS-FNA) is between 0% and 4%, but there are no data on this topic in cirrhotic patients. To prospectively assess the incidence of bacteremia in cirrhotic patients undergoing EUS and EUS-FNA. We enrolled 41 cirrhotic patients. Of these, 16 (39%) also underwent EUS-FNA. Blood cultures were obtained before and at 5 and 30 min after the procedure. When EUS-FNA was used, an extra blood culture was obtained after the conclusion of radial EUS and before the introduction of the sectorial echoendoscope. All patients were clinically followed up for 7 days for signs of infection. Blood cultures were positive in 16 patients. In 10 patients, blood cultures grew coagulase-negative Staphylococcus, Corynebacterium species, Propionibacterium species or Acinetobacterium Lwoffii, which were considered contaminants (contamination rate 9.8%, 95% CI: 5.7-16%). The remaining 6 patients had true positive blood cultures and were considered to have had true bacteremia (15%, 95% CI: 4-26%). Blood cultures were positive after diagnostic EUS in five patients but were positive after EUS-FNA in only one patient. Thus, the frequency of bacteremia after EUS and EUS-FNA was 12% and 6%, respectively (95% CI: 2-22% and 0.2-30%, respectively). Only one of the patients who developed bacteremia after EUS had a self-limiting fever with no other signs of infection. Asymptomatic Gram-positive bacteremia developed in cirrhotic patients after EUS and EUS-FNA at a rate higher than in non-cirrhotic patients. However, this finding was not associated with any clinically significant infections. Copyright © 2013 Elsevier España, S.L. and AEEH y AEG. All rights reserved.

  12. HCVerso3: An Open-Label, Phase IIb Study of Faldaprevir and Deleobuvir with Ribavirin in Hepatitis C Virus Genotype-1b-Infected Patients with Cirrhosis and Moderate Hepatic Impairment

    Science.gov (United States)

    Sarrazin, Christoph; Manns, Michael; Calleja, Jose Luis; Garcia-Samaniego, Javier; Forns, Xavier; Kaste, Renee; Bai, Xiaofei; Wu, Jing; Stern, Jerry O.

    2016-01-01

    This study evaluated the interferon-free, oral combination of deleobuvir (non-nucleoside HCV NS5-RNA-polymerase inhibitor) and faldaprevir (HCV NS3/4A-protease inhibitor) with ribavirin in patients with HCV genotype-1b and moderate (Child-Pugh B [CPB], n = 17) or mild hepatic impairment (Child-Pugh A [CPA], n = 18). Patients received faldaprevir 120 mg and deleobuvir (600 mg [CPA], 400 mg [CPB]) twice-daily with weight-based ribavirin for 24 weeks. Baseline characteristics were similar between groups. Among CPA patients, 13/18 completed treatment; discontinuations were for adverse events (AEs, n = 1), lack of efficacy (n = 3) and withdrawal (n = 1). Among CPB patients, 8/17 completed treatment; discontinuations were for AEs (n = 6), withdrawal (n = 1) and ‘other’ (n = 2). Sustained virologic response at post-treatment Week 12 (SVR12) was achieved by 11 (61%) CPA patients (95% confidence interval: 38.6%–83.6%) and 9 (53%) CPB patients (95% confidence interval: 29.2%–76.7%), including most CPA (11/16) patients with Week 4 HCV RNA CPB (8/9) patients with Week 4 HCV RNA CPB patients with Week 4 HCV RNA CPB patients and 1 (6%) CPA patient. Plasma trough concentrations of deleobuvir and faldaprevir were not substantially different between the CPA and CPB groups. In conclusion, in this small study the safety and efficacy profiles for 24 weeks of treatment with faldaprevir+deleobuvir+ribavirin in patients with mild or moderate hepatic impairment were consistent with the safety and efficacy profile of this regimen in non-cirrhotic patients. Faldaprevir+deleobuvir+ribavirin resulted in SVR12 in 53–61% of patients: proportions achieving SVR4 but not SVR12 were higher than in non-cirrhotic patients and overall response rates were lower than rates reported with other all-oral regimens in patients with cirrhosis. Trial Registration: ClinicalTrials.gov NCT01830127. PMID:28030579

  13. Randomized Trial Evaluating the Impact of Ribavirin Mono-Therapy and Double Dosing on Viral Kinetics, Ribavirin Pharmacokinetics and Anemia in Hepatitis C Virus Genotype 1 Infection

    DEFF Research Database (Denmark)

    Waldenström, Jesper; Westin, Johan; Nyström, Kristina

    2016-01-01

    In this pilot study (RibaC), 58 hepatitis C virus (HCV) genotype 1 infected treatment-naïve patients were randomized to (i) 2 weeks ribavirin double dosing concomitant with pegylated interferon-α (pegIFN-α), (ii) 4 weeks ribavirin mono-therapy prior to adding pegIFN-α, or (iii) standard-of-care (...

  14. Intraocular complications of IFN-a and ribavirin therapy in patients with chronic viral hepatitis C

    Institute of Scientific and Technical Information of China (English)

    Damien Sene; Valerie Touitou; Bahram Bodaghi; David Saadoun; Gabriel Perlemuter; Nathalie Cassoux; Jean-Charles Piette; Phuc Le Hoang; Patrice Cacoub

    2007-01-01

    We report a panel of severe inflammatory and vascular intraocular disorders occurring during interferon-alpha (IFN-a) treatment in eight hepatitis C virus (HCV)-infected patients. These events include three cases of Vogt-Koyanagi-Harada like (VKH) disease (an association of panuveitis, retinal detachment, ear and meningeal detachment and skin and hair changes), two cases of central retinal vein occlusion, one case of central retinal artery occlusion, one case of severe hypertensive retinopathy and one case of bilateral ischemic optic neuropathy with severe visual impairment. Rare as they are, such severe ophthalmological complications require a close follow-up of HCV-infected patients under IFN-a treatment with ophthalmological monitoring if any ocular manifestation occurs.

  15. Prevalence of subclinical hepatic encephalopathy in cirrhotic patients in China

    Institute of Scientific and Technical Information of China (English)

    Yu-Yuan Li; Yu-Qiang Nie; Wei-Hong Sha; Zheng Zeng; Fu-Ying Yang; Li Ping; Lin Jia

    2004-01-01

    AIM: Subclinical hepatic encephalopathy (SHE) is a common complication of liver diseases. The aim of this study was to find out the normal value of psychometric test and to investigate the prevalence of SHE in Chinese patients with stabilized hepatic cirrhosis.METHODS: Four hundred and nine consecutive cirrhotic patients without overt clinical encephalopathy were screened for SHE by using number connection test part A (NCT-A) and symbol digit test (SDT). SHE was defined as presence of at least one abnormal psychometric test. The age-corrected normal values were defined as the mean±2times standard deviation (2SD), and developed in 356 healthy persons as normal controls. Four hundred and sixteen patients with chronic viral hepatitis were tested as negative controls to assess the diagnostic validity of this test battery.RESULTS: There was no significant difference in NCT scores and SDT quotients between healthy controls and chronic hepatitis group (P>0.05). In all age subgroups,the NCT and SDT measurements of cirrhotic patients differed significantly from those of the controls (P<0.05).When mean±2SD of SDT and NCT measurements from healthy control group was set as the normal range, 119cirrhotic patients (29.1%) were found to have abnormal NCT-A and SDT tests, 53 (13.0%) were abnormal only in SDT and 36 (8.8%) only in NCT-A. Taken together, SHE was diagnosed in 208 (50.9%) cirrhotic patients by this test battery. The prevalence of SHE increased from 39.9%and 55.2% in Child-Pugh's grade A and B groups to 71.8%in Child-Pugh's grade C group (P<0.05). After the adjustment of age and residential areas required from the tests, no correlation was found in the rate of SHE and causes of cirrhosis, education level and smoking habit.CONCLUSION: Psychometric tests are simple and reliable indicators for screening SHE among Chinese cirrhotic patients. By using a NCT and SDT battery, SHE could be found in 50.9% of cirrhotic patients without overt clinical encephalopathy. The

  16. An Efficient Chemoenzymatic Process for Preparation of Ribavirin

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    Vladimir Sakharov

    2015-01-01

    Full Text Available Ribavirin is an important antiviral drug, which is used for treatment of many diseases. The pilot-scale chemoenzymatic process for synthesis of the active pharmaceutical ingredient Ribavirin was developed with 32% overall yield and more than 99.5% purity. The described method includes the chemical synthesis of 1,2,4-triazole-3-carboxamide, which is a key intermediate and enzyme-catalyzed transglycosylation reaction for preparation of the desired product. 1,2,4-Triazole-3-carboxamide was synthesized from 5-amino-1,2,4-triazole-3-carboxylic acid by classical Chipen-Grinshtein method. Isolated from E. сoli BL21(DE3/pERPUPHHO1 strain the purine nucleoside phosphorylase was used as a biocatalytical system. All steps of this process were optimized and scaled.

  17. Autoimmune Hepatitis Triggered by Treatment With Pegylated Interferon α-2a and Ribavirin for Chronic Hepatitis C

    Science.gov (United States)

    Pipaliya, Nirav; Choksi, Dhaval; Parikh, Pathik; Ingle, Meghraj; Sawant, Prabha

    2015-01-01

    Hepatitis flare is rarely observed during treatment with pegylated interferon alpha for hepatitis C virus (HCV) infection. A 49-year-old man receiving pegylated interferon α-2a for HCV infection had icterus and hyperbiliru-binemia in the 14th week of therapy, with HCV RNA undetectable after the 12th dose. Liver biopsy was suggestive of chronic hepatitis with cirrhosis without interface pattern. Pegylated interferon was discontinued; a few weeks later, his aminotransferases and immunoglobulin levels increased significantly. Antibody to cytosolic liver antigen-1 was positive, and liver biopsy revealed lymphoplasmacytic infiltrate with intense interface hepatitis, consistent with autoimmune hepatitis. PMID:26203454

  18. Effect of Ribavirin Alone or Combined with Silymarin on Carbon Tetrachloride Induced Hepatic Damage in Rats

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    Omar M.E. Abdel Salam

    2007-01-01

    Full Text Available The effect of the antiviral agent ribavirin given alone or in combination with silymarin on the development of liver injury induced in rats with carbon tetrachloride (CCl4; 2.8 ml/kg followed by 1.4 ml/kg after one week was studied. Ribavirin at three dose levels (30, 60 or 90 mg/kg, silymarin (25 mg/kg or combination of ribavirin (60 mg/kg and silymarin (25 mg/kg was administered once daily orally for 14 days, starting at time of administration of CCl4. The administration of ribavirin decreased the elevations in serum alanine aminotransferase (ALT by 78.5, 82.1, 75.1%, aspartate aminotransferase (AST 47.5, 37.4, 38.8%, and alkaline phosphatase (ALP by 23.4, 16, 21.6%, respectively and also prevented the development of hepatic necrosis caused by CCl4. In comparison, the elevated serum ALT, AST and ALP levels decreased to 43.3%, 46%, and 37.5% of controls, respectively by silymarin. When silymarin was combined with ribavirin, the serum activities of AST and ALP were further decreased, indicating a benefi cial additive effect. Morphometric analysis indicated signifi cant reduction in the area of necrosis and fi brosis on ribavirin treatment and this was further reduced after the addition of silymarin. Metabolic pertuberations caused by CCl4 as refl ected in a decrease in intracellular protein content in hepatocytes were improved by ribavirin monotherapy and to higher extent by combined silymarin and ribavirin therapy. Proliferating cell nuclear antigen was reduced in nuclei of hepatocytes by ribavirin montherapy or the combination of ribavirin and silymarin compared with CCl4-control group. The study demonstrates that ribavirin treatment in the model of CCl4- induced liver injury results in less liver damage. Results also indicate that the combined application of ribavirin and silymarin is likely to be a useful additive in reducing liver injury.

  19. Quercetin Treatment Ameliorates Systemic Oxidative Stress in Cirrhotic Rats

    Science.gov (United States)

    Vieira, Emanuelle Kerber; Bona, Silvia; Di Naso, Fábio Cangeri; Porawski, Marilene; Tieppo, Juliana; Marroni, Norma Possa

    2011-01-01

    Our aim was to investigate whether the antioxidant quercetin protects against liver injury and ameliorates the systemic oxidative stress in rats with common bile duct ligation. Secondary biliary cirrhosis was induced through 28 days of bile duct obstruction. Animals received quercetin (Q) after 14 days of obstruction. Groups of control (CO) and cirrhotic (CBDL) animals received a daily 50 mg/kg body weight i.p. injection of quercetin (CO + Q; CBDL + Q) or vehicle (CO; CBDL). Quercetin corrected the reduction in superoxide dismutase (SOD), catalase CAT, and glutathione peroxidase GPx activities and prevented the increase of thiobarbituric acid reactive substances (TBARS), aminotransferases, and alkaline phosphatase in cirrhotic animals. Quercetin administration also corrected the reduced total nitrate concentration in the liver and prevented liver fibrosis and necrosis. These effects suggest that quercetin might be a useful agent to preserve liver function and prevent systemic oxidative stress. PMID:21991520

  20. Umbilical paracentesis for acute hernia reduction in cirrhotic patients

    OpenAIRE

    2013-01-01

    Emergent repair of umbilical hernias in cirrhotic patients is associated with a high risk for morbidity and mortality. We propose a new technique, umbilical paracentesis, for reduction of incarcerated hernias in the patient with ascites. Under ultrasound guidance, removal of ascitic fluid from the umbilical hernia sac can reduce the local pressure and thereby allow for easy hernia reduction, thus avoiding the need for an emergent operation.

  1. Umbilical paracentesis for acute hernia reduction in cirrhotic patients.

    Science.gov (United States)

    Russell, Katie W; Mone, Mary C; Scaife, Courtney L

    2013-10-16

    Emergent repair of umbilical hernias in cirrhotic patients is associated with a high risk for morbidity and mortality. We propose a new technique, umbilical paracentesis, for reduction of incarcerated hernias in the patient with ascites. Under ultrasound guidance, removal of ascitic fluid from the umbilical hernia sac can reduce the local pressure and thereby allow for easy hernia reduction, thus avoiding the need for an emergent operation.

  2. Umbilical hernia in cirrhotic patients: outcome of elective repair.

    Science.gov (United States)

    Lasheen, Adel; Naser, Hatem M; Abohassan, Ahmed

    2013-12-01

    Cirrhotic patients with umbilical hernia have an increased likelihood of complications following repair. The aim of this study was to assess the outcomes of elective umbilical hernia repair in cirrhotic patients. Fifty patients having uncomplicated umbilical hernia with a cirrhotic liver were studied prospectively. These patients divided into three groups' according to Child-Turcotte-Pugh (CTP) classification. After management of coagulopathy, correction of hypoalbuminaemia and electrolytes imbalance, and control of ascites, all patients underwent elective hernia repair under regional anesthesia. A comparison was made between the three groups as regard the size of the defect in the linea Alba, operative time, postoperative morbidity and mortality, length of hospital stay, time of return to daily life and postoperative changes in liver function tests (LFTs) in relation to the regional anesthesia applied. hernioplasty was done under spinal anesthesia in 13 patients (26%), under epidural anesthesia in 10 patients (20%), under intercostal nerve block in 7 patients (14%), and under local anesthesia in 20 patients (40%). There was an increased safety (less changes in LFTs) in cases done under local anesthesia and intercostal nerve block. The overall complications rate was 30%. There was an increased complications rate towards the decompensated cases. The differences in the mean length of hospital stay and mean time of return to daily life are statistically significant between the three groups. Umbilical hernia recurrence rate was 2% and no mortality was reported in the study groups.

  3. Does hepatocellular carcinoma in non-alcoholic steatohepatitis exist in cirrhotic and non-cirrhotic patients?

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    A.L. Chagas

    2009-10-01

    Full Text Available Non-alcoholic steatohepatitis (NASH has been associated with hepatocellular carcinoma (HCC often arising in histologically advanced disease when steatohepatitis is not active (cryptogenic cirrhosis. Our objective was to characterize patients with HCC and active, histologically defined steatohepatitis. Among 394 patients with HCC detected by ultrasound imaging over 8 years and staged by the Barcelona Clinic Liver Cancer (BCLC criteria, we identified 7 cases (1.7% with HCC occurring in the setting of active biopsy-proven NASH. All were negative for other liver diseases such as hepatitis C, hepatitis B, autoimmune hepatitis, Wilson disease, and hemochromatosis. The patients (4 males and 3 females, age 63 ± 13 years were either overweight (4 or obese (3; 57% were diabetic and 28.5% had dyslipidemia. Cirrhosis was present in 6 of 7 patients, but 1 patient had well-differentiated HCC in the setting of NASH without cirrhosis (fibrosis stage 1 based on repeated liver biopsies, the absence of portal hypertension by clinical and radiographic evaluations and by direct surgical inspection. Among the cirrhotic patients, 71.4% were clinically staged as Child A and 14.2% as Child B. Tumor size ranged from 1.0 to 5.2 cm and 5 of 7 patients were classified as early stage; 46% of all nodules were hyper-echoic and 57% were <3 cm. HCC was well differentiated in 1/6 and moderately differentiated in 5/6. Alpha-fetoprotein was <100 ng/mL in all patients. HCC in patients with active steatohepatitis is often multifocal, may precede clinically advanced disease and occurs without diagnostic levels of alpha-fetoprotein. Importantly, HCC may occur in NASH in the absence of cirrhosis. More aggressive screening of NASH patients may be warranted.

  4. Does hepatocellular carcinoma in non-alcoholic steatohepatitis exist in cirrhotic and non-cirrhotic patients?

    Directory of Open Access Journals (Sweden)

    A.L. Chagas

    Full Text Available Non-alcoholic steatohepatitis (NASH has been associated with hepatocellular carcinoma (HCC often arising in histologically advanced disease when steatohepatitis is not active (cryptogenic cirrhosis. Our objective was to characterize patients with HCC and active, histologically defined steatohepatitis. Among 394 patients with HCC detected by ultrasound imaging over 8 years and staged by the Barcelona Clinic Liver Cancer (BCLC criteria, we identified 7 cases (1.7% with HCC occurring in the setting of active biopsy-proven NASH. All were negative for other liver diseases such as hepatitis C, hepatitis B, autoimmune hepatitis, Wilson disease, and hemochromatosis. The patients (4 males and 3 females, age 63 ± 13 years were either overweight (4 or obese (3; 57% were diabetic and 28.5% had dyslipidemia. Cirrhosis was present in 6 of 7 patients, but 1 patient had well-differentiated HCC in the setting of NASH without cirrhosis (fibrosis stage 1 based on repeated liver biopsies, the absence of portal hypertension by clinical and radiographic evaluations and by direct surgical inspection. Among the cirrhotic patients, 71.4% were clinically staged as Child A and 14.2% as Child B. Tumor size ranged from 1.0 to 5.2 cm and 5 of 7 patients were classified as early stage; 46% of all nodules were hyper-echoic and 57% were <3 cm. HCC was well differentiated in 1/6 and moderately differentiated in 5/6. Alpha-fetoprotein was <100 ng/mL in all patients. HCC in patients with active steatohepatitis is often multifocal, may precede clinically advanced disease and occurs without diagnostic levels of alpha-fetoprotein. Importantly, HCC may occur in NASH in the absence of cirrhosis. More aggressive screening of NASH patients may be warranted.

  5. Test of IL28B polymorphisms in chronic hepatitis C patients treated with PegIFN and ribavirin depends on HCV genotypes: results from a meta-analysis.

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    Zhifang Jia

    Full Text Available BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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

  6. Organizing Pneumonia Associated with Pegylated Interferon α and Ribavirin Therapy

    Directory of Open Access Journals (Sweden)

    Amit Chopra

    2015-01-01

    Full Text Available Hepatitis C virus infection is the leading cause of chronic liver disease in the United States of America. Pegylated interferon α and ribavirin combination is the mainstay of treatment. Severe pulmonary toxicities are rarely reported. We report here a case of severe form of organizing pneumonia secondary to pegylated interferon α therapy presenting as acute respiratory failure. Patient has near complete recovery with withdrawal of pegylated interferon α and steroid therapy. We report this case to raise the awareness of this rare but potentially life-threatening pulmonary complication of pegylated interferon α therapy.

  7. Organizing Pneumonia Associated with Pegylated Interferon α and Ribavirin Therapy.

    Science.gov (United States)

    Chopra, Amit; Marak, Creticus; Alappan, Narendrakumar; Shim, Chang

    2015-01-01

    Hepatitis C virus infection is the leading cause of chronic liver disease in the United States of America. Pegylated interferon α and ribavirin combination is the mainstay of treatment. Severe pulmonary toxicities are rarely reported. We report here a case of severe form of organizing pneumonia secondary to pegylated interferon α therapy presenting as acute respiratory failure. Patient has near complete recovery with withdrawal of pegylated interferon α and steroid therapy. We report this case to raise the awareness of this rare but potentially life-threatening pulmonary complication of pegylated interferon α therapy.

  8. Randomized Trial Evaluating the Impact of Ribavirin Mono-Therapy and Double Dosing on Viral Kinetics, Ribavirin Pharmacokinetics and Anemia in Hepatitis C Virus Genotype 1 Infection.

    Directory of Open Access Journals (Sweden)

    Jesper Waldenström

    Full Text Available In this pilot study (RibaC, 58 hepatitis C virus (HCV genotype 1 infected treatment-naïve patients were randomized to (i 2 weeks ribavirin double dosing concomitant with pegylated interferon-α (pegIFN-α, (ii 4 weeks ribavirin mono-therapy prior to adding pegIFN-α, or (iii standard-of-care (SOC ribavirin dosing concurrent with pegIFN-α. Four weeks of ribavirin mono-therapy resulted in a mean 0.46 log(10 IU/mL HCV RNA reduction differentially regulated across IL28B genotypes (0.89 vs. 0.21 log(10 IU/mL for CC and CT/TT respectively; P = 0.006, increased likelihood of undetectable HCV RNA week 4 after initiating pegIFN-α and thus shortened treatment duration (P<0.05, and decreased median IP-10 concentration from 550 to 345 pg/mL (P<0.001. Both experimental strategies impacted on ribavirin concentrations, and high levels were achieved after one week of double dosing. However, by day 14, double dosing entailed a greater hemoglobin decline as compared to SOC (2.2 vs. 1.4 g/dL; P = 0.03. Conclusion: Ribavirin down-regulates IP-10, and may have an anti-viral effect differently regulated across IL28B genotypes.

  9. The incidence of venous thromboembolism and practice of deep venous thrombosis prophylaxis in hospitalized cirrhotic patients

    Directory of Open Access Journals (Sweden)

    Alqahtani Saad

    2011-01-01

    Full Text Available Abstract Background Cirrhotic patients are characterized by a decreased synthesis of coagulation and anticoagulation factors. The coagulopathy of cirrhotic patients is considered to be auto-anticoagulation. Our aim was to determine the incidence and predictors of venous thromboembolism (VTE and examine the practice of deep venous thrombosis (DVT prophylaxis among hospitalized cirrhotic patients. Methods A retrospective cohort study was performed in a tertiary teaching hospital. We included all adult patients admitted to the hospital with a diagnosis of liver cirrhosis from January 1, 2009 to December 31, 2009. We grouped our cohort patients in two groups, cirrhotic patients without VTE and cirrhotic with VTE. Results Over one year, we included 226 cirrhotic patients, and the characteristics of both groups were similar regarding their clinical and laboratory parameters and their outcomes. Six patients (2.7% developed VTE, and all of the VTEs were DVT. Hepatitis C was the most common (51% underlying cause of liver cirrhosis, followed by hepatitis B (22%; 76% of the cirrhotic patients received neither pharmacological nor mechanical DVT prophylaxis. Conclusion Cirrhotic patients are at risk for developing VTE. The utilization of DVT prophylaxis was suboptimal.

  10. The diminished expression of proangiogenic growth factors and their receptors in gastric ulcers of cirrhotic patients.

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    Jiing-Chyuan Luo

    Full Text Available OBJECTIVES: The pathogenesis of the higher occurrence of peptic ulcer disease in cirrhotic patients is complex. Platelets can stimulate angiogenesis and promote gastric ulcer healing. We compared the expressions of proangiogenic growth factors and their receptors in the gastric ulcer margin between cirrhotic patients with thrombocytopenia and those of non-cirrhotic patients to elucidate possible mechanisms. METHODS: Eligible cirrhotic patients (n = 55 and non-cirrhotic patients (n = 55 who had gastric ulcers were enrolled. Mucosa from the gastric ulcer margin and non-ulcer areas were sampled and the mRNA expressions of the proangiogenic growth factors (vascular endothelial growth factor [VEGF], platelet derived growth factor [PDGF], basic fibroblast growth factor [bFGF] and their receptors (VEGFR1, VEGFR2, PDGFRA, PDGFRB, FGFR1, FGFR2 were measured and compared. Platelet count and the expressions of these growth factors and their receptors were correlated with each other. RESULTS: The two groups were comparable in terms of gender, ulcer size and infection rate of Helicobacter pylori. However, the cirrhotic group were younger in age, had a lower platelet count than those in the non-cirrhotic group (p0.5, p<0.001. CONCLUSIONS: Our findings implied that diminished activity of proangiogenic factors and their receptors may contribute to the pathogenesis of gastric ulcers in cirrhotic patients.

  11. Pituitary glycoprotein hormone a-subunit secretion by cirrhotic patients

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    Oliveira M.C.

    1999-01-01

    Full Text Available Secretion of the a-subunit of pituitary glycoprotein hormones usually follows the secretion of intact gonadotropins and is increased in gonadal failure and decreased in isolated gonadotropin deficiency. The aim of the present study was to determine the levels of the a-subunit in the serum of patients with cirrhosis of the liver and to compare the results obtained for eugonadal cirrhotic patients with those obtained for cirrhotic patients with hypogonadotropic hypogonadism. Forty-seven of 63 patients with cirrhosis (74.6% presented hypogonadism (which was central in 45 cases and primary in 2, 7 were eugonadal, and 9 women were in normal menopause. The serum a-subunit was measured by the fluorimetric method using monoclonal antibodies. Cross-reactivity with LH, TSH, FSH and hCG was 6.5, 1.2, 4.3 and 1.1%, respectively, with an intra-assay coefficient of variation (CV of less than 5% and an interassay CV of 5%, and sensitivity limit of 4 ng/l. The serum a-subunit concentration ranged from 36 to 6253 ng/l, with a median of 273 ng/l. The median was 251 ng/l for patients with central hypogonadism and 198 ng/l for eugonadal patients. The correlation between the a-subunit and basal LH levels was significant both in the total sample (r = 0.48, P<0.01 and in the cirrhotic patients with central hypogonadism (r = 0.33, P = 0.02. Among men with central hypogonadism there was a negative correlation between a-subunit levels and total testosterone levels (r = 0.54, P<0.01 as well as free testosterone levels (r = -0.53, P<0.01. In conclusion, although the a-subunit levels are correlated with LH levels, at present they cannot be used as markers for hypogonadism in patients with cirrhosis of the liver.

  12. Pharmacokinetic Study of Frusemide in Healthy and Cirrhotic Indian Subjects

    Directory of Open Access Journals (Sweden)

    Dr. Yuvrajsing Dhunnoo

    2008-01-01

    Full Text Available Liver cirrhosis is associated with various complications such as ascites and fluid retention, progressing to development of hepatorenal syndrome, further compromising fluid elimination. Frusemide, a loop diuretic is normally administered to relieve fluid retentions. The kinetics of frusemide has not been conclusively reported in the three types of cirrhosis and among Indian subjects. The aim of the current study was to evaluate the kinetics of frusemide among healthy and Child’s A, B and C cirrhosis and compare with earlier data. 24 cirrhotic were selected and classified according to the Child’s-Pugh classification. 12 healthy male volunteers were screened and included in the study. 40 mg of frusemide was administered orally to both groups and blood samples were withdrawn at various intervals of time for a duration of 8 hrs. The amount of frusemide present in plasma was analyzed using HPLC. The volumes of distribution (Vd, area under curve (AUC, systemic clearance (CL, maximum concentration (Cmax, time for maximum concentration (tmax in healthy volunteers were respectively 4.56 ± 0.15 L, 2258 ± 530.7, 4.97 ± 1.67 L/h, 892 ± 49.4 ng/ml, 85.20± 7.49 mins. Corresponding values in Group A were 5.00 ± 0.31 L, 2471 ± 228.6, 6.60 ± 2.90L/h, 1021 ± 47.97 ng/ml and 88.25 V 2.12 mins; in Group B 7.73 ± 1.10 L, 4038 ± 154.7, 8.84 ± 0.45 L/h, 1448 ± 43.20 ng/ml and 120 ± 1.89 mins; In group C cirrhosis 9.69 ± 1.32 L, 4085 ± 131.75, 3.49 ± 1.40 L/h, 1551± 59.02 ng/ml and 185.7 ± 2.68 mins respectively. Significant differences at 1% and 5% were observed among the cirrhotic groups and between healthy v/s cirrhotic patients. Data from current study do not correlate with earlier reports, carried mainly in Western population, due to possibly differences in instrumentation, etc but a possible genetic interplay should not be ruled out. Data from cirrhotic patients could not be effectively compared with earlier studies as kinetics of frusemide

  13. [A case of hepatic sarcoidosis presenting with cirrhotic symptoms].

    Science.gov (United States)

    Kaji, Kiichiro; Ogino, Hidero; Hirai, Satoshi; Shimatani, Akiyoshi; Horita, Yosuke; Matsuda, Kouichiro; Hiramatsu, Katsushi; Matsuda, Mitsuru; Shimizu, Koichi; Nakanishi, Yuko; Noda, Yatsugi

    2014-03-01

    A man in 40s with skin sarcoidosis presented with signs and symptoms of liver injury and thrombocytopenia. Enhanced computed tomography and magnetic resonance imaging revealed cholecystolithiasis, hepatic deformation, and giant splenomegaly. Gastrointestinal endoscopy showed esophageal varices. Cholecystectomy, splenectomy, and wedge biopsy of the liver were performed. Histopathology of the liver revealed many granulomas and severe periportal fibrosis without lobular reconstruction. These findings were compatible with hepatic sarcoidosis, but not liver cirrhosis. Here we report a rare case of hepatic sarcoidosis presenting with cirrhotic symptoms.

  14. [Israeli guidelines for the treatment of chronic hepatitis C infection--2012 Israeli Association for the Study of the Liver].

    Science.gov (United States)

    Zuckerman, Eli; Safadi, Rifaat; Oren, Ran; Shibolet, Oren; Baruch, Yaakov; Bruck, Refael; Lurei, Yoav; Kaspa, Ran Tur; Abu-Mouch, Saif; Shouval, Daniel; Ben-Ari, Ziv

    2012-12-01

    The current standard of care for the treatment of hepatitis C virus (HCV) is a combination of pegylated interferon alpha (PeglFN] -2a/2b and ribavirin for 24-48 weeks, according to the viral genotype. This treatment is associated with significant side effects and achieves sustained virologic response (SVR) in only 40%-50% of genotype 1 HCV-infected patients. The recent development of direct-acting antiviral agents (DAAs] targeting critical steps of the virus life-cycle led to a major breakthrough in the management of HCV infection. The DAAs include protease inhibitors and polymerase inhibitors. The recently approved protease inhibitors boceprevir and telaprevir, when given with PeglFN and ribavirin in HCV genotype 1 patients, result in a much higher SVR rate [70%] among treatment-naïve and treatment-experienced patients, compared with Peg-IFN and ribavirin. In specific groups of patients this enables a shorter duration of treatment. The DAA-containing regimens are approved for HCV genotype 1 infection in HCV treatment-naïve and HCV treatment-experienced including cirrhotic patients. The Israeli Ministry of Health has recently approved the use of boceprevir (Victretis) and telaprevir (Incivo) in combination with PeglFN and ribavirin for the current standard of care treatment of HCV genotype 1 patients. The consensus opinion of a panel of national HCV-experts appointed by the Israeli Association for the Study of the Liver is presented in this report. These Israeli consensus guidelines indicate the current best practice for the use of boceprevir and telaprevir in the management of genotype 1 chronic HCV infection.

  15. Statins activate the canonical hedgehog-signaling and aggravate non-cirrhotic portal hypertension, but inhibit the non-canonical hedgehog signaling and cirrhotic portal hypertension.

    Science.gov (United States)

    Uschner, Frank E; Ranabhat, Ganesh; Choi, Steve S; Granzow, Michaela; Klein, Sabine; Schierwagen, Robert; Raskopf, Esther; Gautsch, Sebastian; van der Ven, Peter F M; Fürst, Dieter O; Strassburg, Christian P; Sauerbruch, Tilman; Diehl, Anna Mae; Trebicka, Jonel

    2015-09-28

    Liver cirrhosis but also portal vein obstruction cause portal hypertension (PHT) and angiogenesis. This study investigated the differences of angiogenesis in cirrhotic and non-cirrhotic PHT with special emphasis on the canonical (Shh/Gli) and non-canonical (Shh/RhoA) hedgehog pathway. Cirrhotic (bile duct ligation/BDL; CCl4 intoxication) and non-cirrhotic (partial portal vein ligation/PPVL) rats received either atorvastatin (15 mg/kg; 7d) or control chow before sacrifice. Invasive hemodynamic measurement and Matrigel implantation assessed angiogenesis in vivo. Angiogenesis in vitro was analysed using migration and tube formation assay. In liver and vessel samples from animals and humans, transcript expression was analyzed using RT-PCR and protein expression using Western blot. Atorvastatin decreased portal pressure, shunt flow and angiogenesis in cirrhosis, whereas atorvastatin increased these parameters in PPVL rats. Non-canonical Hh was upregulated in experimental and human liver cirrhosis and was blunted by atorvastatin. Moreover, atorvastatin blocked the non-canonical Hh-pathway RhoA dependently in activated hepatic steallate cells (HSCs). Interestingly, hepatic and extrahepatic Hh-pathway was enhanced in PPVL rats, which resulted in increased angiogenesis. In summary, statins caused contrary effects in cirrhotic and non-cirrhotic portal hypertension. Atorvastatin inhibited the non-canonical Hh-pathway and angiogenesis in cirrhosis. In portal vein obstruction, statins enhanced the canonical Hh-pathway and aggravated PHT and angiogenesis.

  16. 乙型和丙型肝炎病毒感染检测试剂的标准化:问题与对策%Problems and solutions on standardization of reagents for detection of HBV and HCV infection

    Institute of Scientific and Technical Information of China (English)

    李金明

    2010-01-01

    国产HBV和HCV感染检测试剂与国外同类试剂相比,存在过度追求操作简便化和定量检测缺乏量值溯源等问题.将HBsAg的双抗体夹心ELISA试剂的"一步法"改为"两步法",并保证足够的温育时间;同时,选择多个单抗作为包被抗体,不但可以避免"钩状效应"或HBsAg变异造成的假阴性结果,而且将改善试剂的测定下限.将HBV和HCV核酸检测试剂的标本处理由简单的煮沸裂解改为核酸纯化,并增加用于核酸提取的标本量和提取后扩增加样量,同时加入内标,不但可以改善测定下限和检测重复性,而且可以有效地监控假阴性结果的出现.定量检测试剂标准品系列与国家或国际标准物质的量值溯源,可使不同试剂得到的检测结果具有可比性.%Compared with commercial reagents manufactured by foreign companies for detection of HBV and HCV infection, domestic reagents have poorer performance because of the over-pursuit of easy operation and lack of metrological traceability in quantitative measurement. If "two-step" sandwich ELISA model and multiple monoclonal coating antibodies were used, false-negative results caused by the hook-effect and HBsAg mutant would be avoided. Moreover, sufficient incubation time in each step would improve the detection-limit of the reagents. By replacing the boiling lysis with nucleic acid purification in sample preparation and increasing the sample volume of nucleic acid purification and amplification detection could improve the detection-limit and reproducibility of HBV and HCV nucleic acid testing. The use of internal control could effectively monitor the of false negative results as well Application of international or national reference materials for metrological traceability of calibrators in reagents also plays an important role in assuring result concordance among different commercial reagent kits, methods and clinical laboratories.

  17. Research advances in non-cirrhotic portal hypertension

    Directory of Open Access Journals (Sweden)

    ZHANG Bojing

    2016-02-01

    Full Text Available Although liver cirrhosis is the most common cause of portal hypertension (PH, about 20% of PH cases are caused by non-cirrhotic reasons, which are referred to as non-cirrhotic portal hypertension (NCPH, with a high incidence rate in developing countries. NCPH is a group of heterogeneous hepatic vascular diseases, including idiopathic portal hypertension (IPH and extrahepatic portal vein obstruction (EHPVO, as well as the rare diseases in clinical practice such as Budd-Chiari syndrome, congenital hepatic fibrosis, and nodular regenerative hyperplasia. The patients with NCPH usually have the symptoms of portal hypertension, such as recurrent variceal bleeding and splenomegaly, but liver function is well preserved in these patients. At present, the diagnosis of NCPH lacks a universally accepted standard and remains a challenge. In clinical practice, the method of exclusion is usually applied for the diagnosis of HCPH, and liver biopsy is performed when necessary to make a confirmed diagnosis. This paper introduces the pathogenesis and pathological manifestations of IPH and EHPVO, as well as the selection of diagnostic methods and therapeutic strategies. If upper gastrointestinal bleeding can be effectively controlled, NCPH is considered to have a relatively good prognosis.

  18. MANAGEMENT OF PORTAL VEIN THROMBOSIS IN CIRRHOTIC PATIENTS

    Directory of Open Access Journals (Sweden)

    Lucio Amitrano

    2009-11-01

    Full Text Available Portal vein thrombosis (PVT not associated with hepatocellular carcinoma is considered a frequent complication of liver cirrhosis but, unlike PVT occurring in non-cirrhotic patients, very few data are available on its natural history and management.  The reduced portal blood flow velocity is the main determinant of PVT but, as in other venous thromboses, multiple factors local and systemic, inherited or acquired often can concur with. PVT has a variety of clinical presentations ranging from asymptomatic to life-threatening diseases like gastroesophageal bleeding or acute intestinal ischemia. It is usually diagnosed by Doppler ultrasound but computed tomography and magnetic resonance imaging are useful to study the extent of thrombosis and the involvement of the abdominal organs. The risk of bleeding mainly determined by the presence of gastroesophageal varices and clotting alterations causes concern for the treatment of PVT in cirrhotic patients. To date, anticoagulant therapy seems to be indicated only in patients awaiting liver transplantation. This review focuses on the definition of the subgroups of patients with cirrhosis that might benefit from treatment of PVT and examines the pros and cons of the available treatments in terms of efficacy, monitoring and safety, providing also perspectives for future studies.

  19. MANAGEMENT OF PORTAL VEIN THROMBOSIS IN CIRRHOTIC PATIENTS

    Directory of Open Access Journals (Sweden)

    Maria Anna Guardascione

    2009-11-01

    Full Text Available

    Portal vein thrombosis (PVT not associated with hepatocellular carcinoma is considered a frequent complication of liver cirrhosis but, unlike PVT occurring in non-cirrhotic patients, very few data are available on its natural history and management.  The reduced portal blood flow velocity is the main determinant of PVT but, as in other venous thromboses, multiple factors local and systemic, inherited or acquired often can concur with. PVT has a variety of clinical presentations ranging from asymptomatic to life-threatening diseases like gastroesophageal bleeding or acute intestinal ischemia. It is usually diagnosed by Doppler ultrasound but computed tomography and magnetic resonance imaging are useful to study the extent of thrombosis and the involvement of the abdominal organs. The risk of bleeding mainly determined by the presence of gastroesophageal varices and clotting alterations causes concern for the treatment of PVT in cirrhotic patients. To date, anticoagulant therapy seems to be indicated only in patients awaiting liver transplantation. This review focuses on the definition of the subgroups of patients with cirrhosis that might benefit from treatment of PVT and examines the pros and cons of the available treatments in terms of efficacy, monitoring and safety, providing also perspectives for future studies.

  20. Peginterferon plus ribavirin for chronic hepatitis C in patients with human immunodeficiency virus

    DEFF Research Database (Denmark)

    Gluud, Lise Lotte; Marchesini, Emanuela; Iorio, Alfonso

    2009-01-01

    OBJECTIVES: The aim of this study was to assess the effects of peginterferon plus ribavirin for chronic hepatitis C in patients with human immunodeficiency virus (HIV). METHODS: Trials were identified through manual and electronic searches. Randomized trials comparing peginterferon plus ribavirin...... with interferon plus ribavirin, the proportion with a sustained virological response was 26% (109 of 423) for patients with genotype 1 or 4 and 57% (130 of 230) for genotype 2 or 3. Several adverse events occurred, including fatal lactic acidosis and liver failure, but there were no significant differences...

  1. Influences of HCV Infection on Incidence of Occult HBV Infection in Patients Infected with HIV-1%HIV-1感染者中HCV感染对于隐匿性HBV感染的影响

    Institute of Scientific and Technical Information of China (English)

    梁红霞; 余祖江; 张倩; 李志勤; 潘延凤; 李娟; 江河清; 李建生; 何云

    2011-01-01

    Objective To investigate the influences of HCV infection on occult HBV infection in patients infected with HIV-1.Methods The study enrolled 178 HBsAg-negative treatment-naive HIV-1 patients who transmitted by commercial blood donation in an HIV/AIDS CARE site in Henan province. Many parameters were detected, including liver function, HBV serologic markers (HBsAg,Anti-HBs, HBeAg, anti-HBe and anti-HBc), HCV antibody, HBV DNA and HCV RNA. Analyses were performed to compare the differences of HBV etiological markers in anti-HCV + group, anti-HCV- group and different HCV RNA groups. Results Among the 178 HBsAg-negative HIV-infected patients, 35 were HBV-M negative, 25 anti-HBs positive only, 25 anti-HBc positive only, 34 with both anti-HBs and anti-HBo positive. There were no significant differences in ages and gender between anti-HCV + group and anti-HCV- group (P >0.05). There were significant differences in ALT and AST(P < 0.05 ) but not total bilirubin between anti-HCV + group and antiHCV- group. There were no significant differences in HBV-M negative, isolated HBsAb positive only, isolated anti-HBc positive only,anti-HBs and anti-HBc double positive, HBV DNA positive between anti-HCV + group and anti-HCV- group. There were no significant differences in HBV DNA positive rate between different HCV RNA groups ( P > 0.05 ). Conclusion In the HIV-infected patients who transmitted by commercial blood donation, HCV infection and viral loads of HCV RNA had no correlation with incidence of occult HBV infection, but HCV co-infection could aggravate the liver damage.%目的 探讨在人免疫缺陷病毒-1(human immunodeficiency virus-1,HIV-1)感染者中丙型肝炎病毒(hepatitis C virus,HCV)感染对于隐匿性乙型肝炎病毒(hepatitis B virus,HBV)感染的影响.方法 研究对象为河南某艾滋病治疗示范区中178例乙型肝炎表面抗原(hepatitis B surface antigen,HBsAg)阴性的经有偿献血感染HIV-1未经抗病毒治疗的患者,检测项

  2. Randomized Trial Evaluating the Impact of Ribavirin Mono-Therapy and Double Dosing on Viral Kinetics, Ribavirin Pharmacokinetics and Anemia in Hepatitis C Virus Genotype 1 Infection

    DEFF Research Database (Denmark)

    Waldenström, Jesper; Westin, Johan; Nyström, Kristina;

    2016-01-01

    In this pilot study (RibaC), 58 hepatitis C virus (HCV) genotype 1 infected treatment-naïve patients were randomized to (i) 2 weeks ribavirin double dosing concomitant with pegylated interferon-α (pegIFN-α), (ii) 4 weeks ribavirin mono-therapy prior to adding pegIFN-α, or (iii) standard-of-care (......In this pilot study (RibaC), 58 hepatitis C virus (HCV) genotype 1 infected treatment-naïve patients were randomized to (i) 2 weeks ribavirin double dosing concomitant with pegylated interferon-α (pegIFN-α), (ii) 4 weeks ribavirin mono-therapy prior to adding pegIFN-α, or (iii) standard......, by day 14, double dosing entailed a greater hemoglobin decline as compared to SOC (2.2 vs. 1.4 g/dL; P = 0.03). Conclusion: Ribavirin down-regulates IP-10, and may have an anti-viral effect differently regulated across IL28B genotypes....

  3. Synergistic antiviral activity of ribavirin and interferon-α against parrot bornaviruses in avian cells.

    Science.gov (United States)

    Reuter, Antje; Horie, Masayuki; Höper, Dirk; Ohnemus, Annette; Narr, Andreas; Rinder, Monika; Beer, Martin; Staeheli, Peter; Rubbenstroth, Dennis

    2016-09-01

    Avian bornaviruses are the causative agents of proventricular dilatation disease (PDD), a widely distributed and often fatal disease in captive psittacines. Because neither specific prevention measures nor therapies against PDD and bornavirus infections are currently available, new antiviral strategies are required to improve animal health. We show here that the nucleoside analogue ribavirin inhibited bornavirus activity in a polymerase reconstitution assay and reduced viral load in avian cell lines infected with two different parrot bornaviruses. Furthermore, we observed that ribavirin enhanced type I IFN signalling in avian cells. Combined treatment of avian bornavirus-infected cells with ribavirin and recombinant IFN-α strongly enhanced the antiviral efficiency compared to either drug alone. The combined use of ribavirin and type I IFN might represent a promising new strategy for therapeutic treatment of captive parrots persistently infected with avian bornaviruses.

  4. Arenaviruses and lethal mutagenesis. Prospects for new ribavirin-based interventions.

    Science.gov (United States)

    Moreno, Héctor; Grande-Pérez, Ana; Domingo, Esteban; Martín, Verónica

    2012-11-06

    Lymphocytic choriomeningitis virus (LCMV) has contributed to unveil some of the molecular mechanisms of lethal mutagenesis, or loss of virus infectivity due to increased mutation rates. Here we review these developments, and provide additional evidence that ribavirin displays a dual mutagenic and inhibitory activity on LCMV that can be relevant to treatment designs. Using 5-fluorouracil as mutagenic agent and ribavirin either as inhibitor or mutagen, we document an advantage of a sequential inhibitor-mutagen administration over the corresponding combination treatment to achieve a low LCMV load in cell culture. This advantage is accentuated in the concentration range in which ribavirin acts mainly as an inhibitor, rather than as mutagen. This observation reinforces previous theoretical and experimental studies in supporting a sequential inhibitor-mutagen administration as a possible antiviral design. Given recent progress in the development of new inhibitors of arenavirus replication, our results suggest new options of ribavirin-based anti-arenavirus treatments.

  5. Suboptimal endogenous erythropoietin response in chronic hepatitis C patients during ribavirin and PEG interferon treatment.

    NARCIS (Netherlands)

    Vlerken, L.G. Van; Soest, H. van; Janssen, M.P.E.; Boland, G.J.; Drenth, J.P.H.; Burger, D.M.; Siersema, P.D.; Erpecum, K.J. van

    2010-01-01

    BACKGROUND: During the treatment of hepatitis C, anaemia may necessitate pegylated-interferon and ribavirin dose reductions with reduced sustained viral response rates. Although erythropoietic growth factors are frequently used to improve anaemia, it is controversial whether endogenous erythropoieti

  6. Arenaviruses and Lethal Mutagenesis. Prospects for New Ribavirin-based Interventions

    Directory of Open Access Journals (Sweden)

    Ana Grande-Pérez

    2012-11-01

    Full Text Available Lymphocytic choriomeningitis virus (LCMV has contributed to unveil some of the molecular mechanisms of lethal mutagenesis, or loss of virus infectivity due to increased mutation rates. Here we review these developments, and provide additional evidence that ribavirin displays a dual mutagenic and inhibitory activity on LCMV that can be relevant to treatment designs. Using 5-fluorouracil as mutagenic agent and ribavirin either as inhibitor or mutagen, we document an advantage of a sequential inhibitor-mutagen administration over the corresponding combination treatment to achieve a low LCMV load in cell culture. This advantage is accentuated in the concentration range in which ribavirin acts mainly as an inhibitor, rather than as mutagen. This observation reinforces previous theoretical and experimental studies in supporting a sequential inhibitor-mutagen administration as a possible antiviral design. Given recent progress in the development of new inhibitors of arenavirus replication, our results suggest new options of ribavirin-based anti-arenavirus treatments.

  7. [Fatal pulmonary mycosis in a diabetic and cirrhotic patient].

    Science.gov (United States)

    Ayadi-Kaddour, Aïda; Braham, Emna; Marghli, Adel; Ismail, Olfa; Helal, Imen; Mlika, Mona; Kilani, Tarak; El Mezni, Faouzi

    2015-04-01

    Pulmonary mucormycosis is a rare, devastating, opportunistic fungal infection, caused by the ubiquitous filamentous fungi of the Mucorales order of the class of Zygomycetes. This infection occurs principally in some particular conditions, specially in diabetic patients and immunocompromised host, and rarely in cirrhotic patients. The diagnosis of mucormycosis can only be confirmed by pathological and mycological examination of biopsy specimens. We report a case of pulmonary mucormycosis in a 68-year-old woman with underlying liver cirrhosis and diabetes mellitus. Endoscopic and radiologic findings supported the diagnosis of hydatid cyst of the lung. The patient underwent surgical resection and was started on amphotericin B, after pathological examination. Unfortunately, she succumbed to the infection within one month of surgery.

  8. Hepatorenal Syndrome with Cirrhotic Cardiomyopathy: Case Report and Literature Review

    Directory of Open Access Journals (Sweden)

    Luis Mocarzel

    2015-01-01

    Full Text Available The hepatorenal syndrome (HRS is defined as a potentially reversible kidney failure in patients with cirrhosis and ascites. An association of HRS and cirrhotic cardiomyopathy has been reported recently, but there are no result studies about the use of positive inotropes as part of the acute phase treatment. We report the case of a patient diagnosed with HRS, with high levels of NT pro-BNP, but with normal ejection fraction of the left ventricle, which showed abnormalities in systolic function through speckle tracking in echocardiography, reversible after the infusion of dobutamine. The patient showed clinical and laboratory improvement of his renal function after the infusion of dobutamine. Clinical studies are needed on HRS therapeutic approach taking into account the myocardial dysfunction as a major contributing factor to renal dysfunction.

  9. Magnetic resonance imaging of the cirrhotic liver: Anupdate

    Institute of Scientific and Technical Information of China (English)

    Agnes Watanabe; Miguel Ramalho; Mamdoh AlObaidy; Hye Jin Kim; Fernanda G Velloni; Richard C Semelka

    2015-01-01

    Noninvasive imaging has become the standard forhepatocellular carcinoma (HCC) diagnosis in cirrhoticlivers. In this review paper, we go over the basics ofMR imaging in cirrhotic livers and describe the imagingappearance of a spectrum of hepatic nodules markingthe progression from regenerative nodules to low- andhigh-grade dysplastic nodules, and ultimately to HCCs.We detail and illustrate the typical imaging appearancesof different types of HCC including focal, multifocal,massive, diffuse/infiltrative, and intra-hepaticmetastases; with emphasis on the diagnostic value ofMR in imaging these lesions. We also shed some lighton liver imaging reporting and data system, and therole of different magnetic resonance imaging (MRI)contrast agents and future MRI techniques includingthe use of advanced MR pulse sequences and utilizationof hepatocyte-specific MRI contrast agents, and howthey might contribute to improving the diagnosticperformance of MRI in early stage HCC diagnosis.

  10. A Case of Giant Cell Hepatitis Recurring after Liver Transplantation and Treated with Ribavirin

    Directory of Open Access Journals (Sweden)

    Ziad Hassoun

    2000-01-01

    Full Text Available A patient who underwent orthotopic liver transplantation for giant cell hepatitis with cirrhosis and in whom giant cell hepatitis recurred twice after orthotopic liver transplantation is reported. He was treated with ribavirin with an excellent result. The literature on this subject is reviewed. This observation clearly confirms the efficacy of ribavirin for the treatment of giant cell hepatitis, thus providing evidence for its viral origin.

  11. Increased survival of cirrhotic patients with septic shock.

    Science.gov (United States)

    Sauneuf, Bertrand; Champigneulle, Benoit; Soummer, Alexis; Mongardon, Nicolas; Charpentier, Julien; Cariou, Alain; Chiche, Jean-Daniel; Mallet, Vincent; Mira, Jean-Paul; Pène, Frédéric

    2013-04-19

    The overall outcome of septic shock has been recently improved. We sought to determine whether this survival gain extends to the high-risk subgroup of patients with cirrhosis. Cirrhotic patients with septic shock admitted to a medical intensive care unit (ICU) during two consecutive periods (1997-2004 and 2005-2010) were retrospectively studied. Forty-seven and 42 cirrhotic patients presented with septic shock in 1997-2004 and 2005-2010, respectively. The recent period differed from the previous one by implementation of adjuvant treatments of septic shock including albumin infusion as fluid volume therapy, low-dose glucocorticoids, and intensive insulin therapy. ICU and hospital survival markedly improved over time (40% in 2005-2010 vs. 17% in 1997-2004, P = 0.02 and 29% in 2005-2010 vs. 6% in 1997-2004, P = 0.009, respectively). Furthermore, this survival gain in the latter period was sustained for 6 months (survival rate 24% in 2005-2010 vs. 6% in 1997-2004, P = 0.06). After adjustment with age, the liver disease stage (Child-Pugh score), and the critical illness severity score (SOFA score), ICU admission between 2005 and 2010 remained an independent favorable prognostic factor (odds ratio (OR) 0.09, 95% confidence interval (CI) 0.02-0.4, P = 0.004). The stage of the underlying liver disease was also independently associated with hospital mortality (Child-Pugh score: OR 1.42 per point, 95% CI 1.06-1.9, P = 0.018). In the light of advances in management of both cirrhosis and septic shock, survival of such patients substantially increased over recent years. The stage of the underlying liver disease and the related therapeutic options should be included in the decision-making process for ICU admission.

  12. HCV-RNA检测在提高 HCV感染患者检出率的试验研究%Experimental study of HCV-RNA in improvement of detection rate for patients with HCV infection

    Institute of Scientific and Technical Information of China (English)

    刘颖; 季忠庶

    2015-01-01

    Objective:To analyze the clinical significance of combined detection of HCV-cAg and anti-HCV with joint HCV-RNA detection in diagnosis of HCV infection. Methods:The levels of HCV antibody and HCV antigen in 13,117 patients were detec-ted. The HCV-cAg and anti-HCV positive samples were confirmed with HCV-RNA test. Results: In the 13,117 cases, there were 188 positive cases of anti-HCV, 52 positive cases of HCV-cAg, 48 positive cases of anti-HCV and HCV-cAg, 4 cases of positive HCV-cAg and negative anti-HCV, and the total positive number was 192. Among the 188 cases of positive HCV antibody, the rate of positive HCV-RNA was measured as 64. 4% (122/188), and the rate of positive HCV antigen was measured as 25. 5% (48/188). Among the 48 cases of positive HCV antigen and positive HCV antibody, the rate of positive HCV-RNA was measured as 93. 75%(45/48). Among the 4 cases of positive HCV antigen and negative HCV antibody, the rate of positive HCVRNA was measured as 75% (3/4). Conclusions:The joint detection of HCV-cAg and anti-HCV combined with HCV-RNA detection provides a higher de-tection rate and a lower false-positive rate. The findings indicate that it is effective laboratory procedures for early Diagnosis and treat-ment of hepatitis C virus infection in the clinic.%目的::探讨组合检测丙肝抗体和丙肝核心抗原并联合丙肝RNA在丙肝临床诊断中的意义。方法:对13117例患者进行HCV抗体和HCV抗原组合检测,对两种方法中的阳性标本进行HCV-RNA确证检测。结果:13117例患者中,丙肝抗体阳性188例,丙肝核心抗原阳性52例,其中丙肝抗体和核心抗原均阳性者48例,单独核心抗原阳性4例,总阳性数192例。丙肝抗体阳性188例中HCV抗体阳性标本中有121例HCV-RNA阳性,检出率为64.4%;有48例HCV-cAg阳性,检出率为25.5%(48/188)。丙肝抗体和核心抗原均阳性者HCV-RNA阳性45例,检出率为93.75%;单独核心抗原阳性4例中有3

  13. Study on the diagnosis value of combination of HCV-cAg and anti-HCV in HCV infection%HCV-cAg和HCV-Ab联合检测对HCV感染诊断价值的研究

    Institute of Scientific and Technical Information of China (English)

    林俊填; 余晋林; 伍伟健; 陈展泽; 龚道元

    2015-01-01

    Objective To explore the clinical value of combination of HCV-cAg and anti-HCV detection in HCV infection. Methods The serum samples from outpatients and inpatients were detected for HCV-cAg,anti-HCV and HCV-RNA. The quanti-tative real-time PCR was applied to detect HCV-RNA,and enzyme-linked immunosorbent assay (ELISA) kits were utilized to test anti-HCV and HCV-cAg). Result The sensitivity and specificity of anti-HCV detection were 90.91% and 99.17% respectively, and that of HCV-cAg were 70.25%and 100%respectively. Notably,the sensitivity(99.17%) and specificity(99.17%) increased sig-nificantly in case of combinational detection method. In addition,no consistency between the results of anti-HCV and HCV-cAg was detected. Conclusion Combination detection of anti-HCV and HCV-cAg was recommended because of its remarkable advan-tage in screening and diagnosis of HIV infection.%目的:探讨HCV-cAg和HCV-Ab两个指标联合检测对HCV感染的临床价值。方法对门诊和住院患者血液标本进行HCV-cAg、HCV-Ab 及HCV-RNA联合检测,采用实时荧光定量 PCR 法检测 HCV-RNA,采用酶联免疫吸附法(ELISA)检测试剂盒检测HCV-Ab和HCV-cAg。结果 HCV-Ab检测的灵敏度和特异度分别为90.91%和99.17%;HCV-cAg检测的灵敏度和特异度分别为70.25%和100%,两者的特异度相近,但是HCV-Ab检测的灵敏度比HCV-cAg的要高。两者联合检测时灵敏度和特异度分别为99.17%和99.17%,灵敏度明显增加。此外,HCV-Ab和HCV-cAg两者之间的检测结果无一致性。结论 HCV-Ab和HCV-cAg检测相互间无法替代,将抗-HCV和HCV-cAg两种指标结合起来检测,对临床上提高HCV感染的筛查和诊断具有重要的价值。

  14. Murine norovirus (MNV-1) exposure in vitro to the purine nucleoside analog Ribavirin increases quasispecies diversity.

    Science.gov (United States)

    Julian, Timothy R; Baugher, Joseph D; Rippinger, Christine M; Pinekenstein, Rebecca; Kolawole, Abimbola O; Mehoke, Thomas S; Wobus, Christiane E; Feldman, Andrew B; Pineda, Fernando J; Schwab, Kellogg J

    2016-01-04

    Ribavirin is a pharmaceutical antiviral used for the treatment of RNA virus infections including norovirus, hepatitis C virus, hepatitis E virus, Lassa virus, respiratory syncytial virus, and rhinovirus. Despite the drug's history and documented efficacy, the antiviral mechanism of Ribavirin remains unclear. Mechanisms proposed include depletion of the intracellular GTP pool, immunomodulatory effects, induction of error catastrophe, inhibition of viral polymerase activity, and/or inhibition of viral capping. In the present study, we leveraged deep sequencing data to demonstrate that Ribavirin increases murine norovirus (MNV-1) viral diversity. By serial passaging MNV-1 in RAW 264.7 cells for twenty generations in the presence of Ribavirin, we demonstrated statistically significant increases in both the number of unique haplotypes and the average pairwise difference (APD). Based on statistically significant differences in the probability of nucleotide mutations based on Roche 454 sequencing, we also demonstrated that single nucleotide substitutions are increased in the presence of Ribavirin. Finally, we demonstrated Ribavirin's impact on statistically significantly reducing the relative proportion of the dominant sequence within the quasispecies.

  15. Ribavirin Protects Syrian Hamsters against Lethal Hantavirus Pulmonary Syndrome — After Intranasal Exposure to Andes Virus

    Science.gov (United States)

    Ogg, Monica; Jonsson, Colleen B.; Camp, Jeremy V.; Hooper, Jay W.

    2013-01-01

    Andes virus, ANDV, harbored by wild rodents, causes the highly lethal hantavirus pulmonary syndrome (HPS) upon transmission to humans resulting in death in 30% to 50% of the cases. As there is no treatment for this disease, we systematically tested the efficacy of ribavirin in vitro and in an animal model. In vitro assays confirmed antiviral activity and determined that the most effective doses were 40 µg/mL and above. We tested three different concentrations of ribavirin for their capability to prevent HPS in the ANDV hamster model following an intranasal challenge. While the highest level of ribavirin (200 mg/kg) was toxic to the hamster, both the middle (100 mg/kg) and the lowest concentration (50 mg/kg) prevented HPS in hamsters without toxicity. Specifically, 8 of 8 hamsters survived intranasal challenge for both of those groups whereas 7 of 8 PBS control-treated animals developed lethal HPS. Further, we report that administration of ribavirin at 50 mg/kg/day starting on days 6, 8, 10, or 12 post-infection resulted in significant protection against HPS in all groups. Administration of ribavirin at 14 days post-infection also provided a significant level of protection against lethal HPS. These data provide in vivo evidence supporting the potential use of ribavirin as a post-exposure treatment to prevent HPS after exposure by the respiratory route. PMID:24217424

  16. Ribavirin Protects Syrian Hamsters against Lethal Hantavirus Pulmonary Syndrome — After Intranasal Exposure to Andes Virus

    Directory of Open Access Journals (Sweden)

    Jay W. Hooper

    2013-11-01

    Full Text Available Andes virus, ANDV, harbored by wild rodents, causes the highly lethal hantavirus pulmonary syndrome (HPS upon transmission to humans resulting in death in 30% to 50% of the cases. As there is no treatment for this disease, we systematically tested the efficacy of ribavirin in vitro and in an animal model. In vitro assays confirmed antiviral activity and determined that the most effective doses were 40 µg/mL and above. We tested three different concentrations of ribavirin for their capability to prevent HPS in the ANDV hamster model following an intranasal challenge. While the highest level of ribavirin (200 mg/kg was toxic to the hamster, both the middle (100 mg/kg and the lowest concentration (50 mg/kg prevented HPS in hamsters without toxicity. Specifically, 8 of 8 hamsters survived intranasal challenge for both of those groups whereas 7 of 8 PBS control-treated animals developed lethal HPS. Further, we report that administration of ribavirin at 50 mg/kg/day starting on days 6, 8, 10, or 12 post-infection resulted in significant protection against HPS in all groups. Administration of ribavirin at 14 days post-infection also provided a significant level of protection against lethal HPS. These data provide in vivo evidence supporting the potential use of ribavirin as a post-exposure treatment to prevent HPS after exposure by the respiratory route.

  17. Association Between Proton Pump Inhibitor Use and Spontaneous Bacterial Peritonitis in Cirrhotic Patients with Ascites

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    Mélissa Ratelle

    2014-01-01

    Full Text Available BACKGROUND: There are data suggesting a link between proton pump inhibitor (PPI use and the development of spontaneous bacterial peritonitis (SBP in cirrhotic patients with ascites; however, these data are controversial.

  18. Unusual cause of gastrointestinal bleeding in a cirrhotic patient:hepatocellular carcinoma with gastric invasion

    Institute of Scientific and Technical Information of China (English)

    Marcos Vinicius Perini; Paulo Herman; Rodrigo Pessoa; Willian Abraao Saad

    2009-01-01

    BACKGROUND: Upper gastrointestinal (GI) bleeding is a common complication of portal hypertension in cirrhotic patients, and hepatocellular carcinoma (HCC) is the most common tumor in cirrhotic livers. Bleeding from tumor erosion into the GI tract is very rare. A patient with HCC and gastric tumor invasion was described and the previously reported cases were reviewed. METHOD: A patient with upper GI bleeding was treated in a tertiary hospital. RESULTS: A cirrhotic patient with a HCC invading the stomach leading to upper GI bleeding was treated by left lateral segmentectomy and sub-total gastrectomy. The bleeding was controlled and a good surgical outcome was achieved. CONCLUSIONS: HCC with gastric invasion should be differentially diagnosed from upper GI bleeding in cirrhotic patients. Bleeding can be controlled and symptomatic relief marked in selected cases.

  19. No effect of oral testosterone treatment on sexual dysfunction in alcoholic cirrhotic men

    DEFF Research Database (Denmark)

    Gluud, C; Wantzin, P; Eriksen, J

    1988-01-01

    The prevalence and course of sexual dysfunction was evaluated in 221 alcoholic cirrhotic men participating in a double-blind, placebo-controlled study on the effect of oral testosterone treatment on liver disease. At entry, 67% (95% confidence limits, 61%-74%) complained of sexual dysfunction....... In conclusion, oral testosterone treatment does not significantly influence the type or course of sexual dysfunction in alcoholic cirrhotic men. However, sexual function improved after reduction of ethanol consumption in these patients....

  20. The effects of Helicobacter pylori infection on hyperammonaemia and hepatic encephalopathy in cirrhotic patients

    Institute of Scientific and Technical Information of China (English)

    王良静

    2006-01-01

    Objective To evaluate the relationship among Helicobacter pylori (Hp) infection, blood ammonia concentrations , and hepatic encephalopathy (HE) status, and to investigate the effect of Hp eradication on blood ammonia levels and hepatic encephalopathy status in cirrhotic patients. Methods From July 2003 to Jan 2005, cirrhotic patients in 5 regions of Zhejiang Province were enrolled. Patients were evaluated for the demographic checklists, number connection test, Hp infection, liver impairment level, blood ammonia concentrations and he-

  1. Toll-like receptors 7 and 8 mRNA in monocytes of Egyptian children with chronic hepatitis C infection genotype 4 as predictor to “response” interferon and ribavirin treatment

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    Mohammed A. Khedr

    2016-03-01

    Conclusions: TLRs 7&8 and TNF have great importance in controlling HCV infection and the responses to IFN therapy. Further research covering other stages of CHC at large numbers and at different monocytes subsets levels will be needed.

  2. Peginterferon alfa-2a plus ribavirin for hemophilic patients with chronic hepatitis C virus infection in Taiwan

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    Jung-An Lin

    2014-10-01

    Conclusion: Our study shows that the SVR rates are similar in hemophilic and nonhemophilic patients with chronic HCV infection who receive PEG-IFN-α-2a plus RBV in Taiwan. The rate of AEs also resembled other studies in nonhemophilic patients in Taiwan. No patient suffered from severe bleeding. However, large-scale, well-conducted studies are still needed to verify the treatment efficacy and safety.

  3. Ribavirin for Crimean-Congo hemorrhagic fever: systematic review and meta-analysis

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    G Gail

    2010-07-01

    Full Text Available Abstract Background Crimean-Congo hemorrhagic fever epidemics often occur in areas where health services are limited, and result in high case fatality rates. Besides intensive care, ribavirin is often recommended. A solid evidence base for the use of this drug will help justify assuring access to the drug in areas where epidemics are common. Methods We carried out a systematic review of observational and experimental studies of people with suspected or confirmed Crimean-Congo hemorrhagic fever that included comparisons between patients given ribavirin and those not. We extracted data on mortality, hospital stay, and adverse events. Risk of bias was assessed using a standard checklist, and data were presented in meta-analytical graphs, stratified by study design, and GRADE tables presented. The risk of bias was summarised using the GRADE method. Results 21 unique studies, including one randomised controlled trial of ribavirin, were included. Quality of the evidence was very low, with a Down and Black median score of 4 (maximum possible 33. Ribavirin treatment was not shown to be superior to no ribavirin treatment for mortality rate in a single RCT (RR: 1.13, 95%CI: 0.29 to 4.32, 136 participants, GRADE=low quality evidence; but ribavirin was associated with reduced mortality by 44% when compared to no ribavirin treatment in the pooled observational studies (RR: 0.56, 95%CI: 0.35 to 0.90, 955 participants; GRADE=very low quality evidence. Adverse events were more common with the ribavirin patients, but no severe adverse events were reported. No difference in length of hospital stay was reported. Conclusions No clear message of benefit is available from the current data on ribavirin as observational data are heavily confounded, and the one trial carried out has limited power. However, ribavirin could potentially have benefits in this condition and these results clearly indicate a pragmatic, randomised controlled trial in the context of good quality

  4. Low-dose ribavirin treatments attenuate neuroinflammatory activation of BV-2 Cells by interfering with inducible nitric oxide synthase.

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    Bozic, Iva; Savic, Danijela; Jovanovic, Marija; Bjelobaba, Ivana; Laketa, Danijela; Nedeljkovic, Nadezda; Stojiljkovic, Mirjana; Pekovic, Sanja; Lavrnja, Irena

    2015-01-01

    Microglia play a key role in defending central nervous system from various internal and external threats. However, their excessive and/or chronic activation is associated with deleterious effects in a variety of neurodegenerative diseases. Previously, we have shown that ribavirin when applied in clinically relevant dosage (10 μM) modulates activated microglia in complex fashion inducing both anti- and proinflammatory effects, simultaneously causing cytotoxicity. Here, we examined potential of low-dose ribavirin (0.1 and 1 μM) to modulate activated BV-2 microglia. Morphological and functional activation of BV-2 cells was achieved with lipopolysaccharide (LPS) stimulation. Our results demonstrated that low-dose ribavirin did not induce cell death, while 10 μM ribavirin promoted LPS induced apoptosis. We determined that 1 μM ribavirin was equally efficient in deactivation of LPS induced morphological changes as 10 μM ribavirin treatment. Ribavirin showed halfway success in reducing markers of functional activation of microglia. Namely, none of the doses had effect on LPS triggered production of proinflammatory cytokine tumor necrosis factor alpha. On the other hand, low-dose ribavirin proved its effectiveness in reduction of another inflammatory mediator, nitric oxide, by inhibiting inducible form of nitric oxide synthase. Our results imply that low-dose ribavirin may alleviate nitrosative stress during neuroinflammation.

  5. Low-Dose Ribavirin Treatments Attenuate Neuroinflammatory Activation of BV-2 Cells by Interfering with Inducible Nitric Oxide Synthase

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    Iva Bozic

    2015-01-01

    Full Text Available Microglia play a key role in defending central nervous system from various internal and external threats. However, their excessive and/or chronic activation is associated with deleterious effects in a variety of neurodegenerative diseases. Previously, we have shown that ribavirin when applied in clinically relevant dosage (10 μM modulates activated microglia in complex fashion inducing both anti- and proinflammatory effects, simultaneously causing cytotoxicity. Here, we examined potential of low-dose ribavirin (0.1 and 1 μM to modulate activated BV-2 microglia. Morphological and functional activation of BV-2 cells was achieved with lipopolysaccharide (LPS stimulation. Our results demonstrated that low-dose ribavirin did not induce cell death, while 10 μM ribavirin promoted LPS induced apoptosis. We determined that 1 μM ribavirin was equally efficient in deactivation of LPS induced morphological changes as 10 μM ribavirin treatment. Ribavirin showed halfway success in reducing markers of functional activation of microglia. Namely, none of the doses had effect on LPS triggered production of proinflammatory cytokine tumor necrosis factor alpha. On the other hand, low-dose ribavirin proved its effectiveness in reduction of another inflammatory mediator, nitric oxide, by inhibiting inducible form of nitric oxide synthase. Our results imply that low-dose ribavirin may alleviate nitrosative stress during neuroinflammation.

  6. Influence of Ribavirin Serum Levels on Outcome of Antiviral Treatment and Anemia in Hepatitis C Virus Infection.

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    Thomas Kuntzen

    Full Text Available Ribavirin blood levels vary considerably between patients with standard weight-based dosing. Their impact on sustained virological response (SVR with pegylated interferon and ribavirin is controversial, but has mostly been studied before the IL28b gene polymorphism as a possible confounder was discovered.The impact of serum ribavirin trough levels at week 4, at the end of treatment and of mean levels across the entire antiviral treatment with pegylated interferon and ribavirin on relapse, SVR rates and anemia was retrospectively studied by univariate and multivariable logistic regression analyses in 214 patients with HCV genotype 1-4 infection, including 88 patients with available IL28b genotyping.Mean ribavirin levels varied between 0.68-5.65 mg/l and significantly differed between patients with or without SVR. By multivariable regression including age, sex, HCV viral load, HCV genotype, liver fibrosis stage, prior treatments, immunosuppression and IL28b genotype, ribavirin levels consistently displayed significant influence on SVR and relapse without indication for a specific importance of higher concentrations early or late in the treatment course. Although hemoglobin decline was on average more pronounced in patients with higher ribavirin levels, hemoglobin remained relatively stable in a significant proportion of these, indicating that ribavirin levels alone are insufficient to predict anemia.While data are scarce to draw conclusions applicable for modern DAA therapies, these results support ribavirin treatment based on serum levels instead of purely weight-based dosing in combination with pegylated interferon.

  7. Clinical Significance of a Myeloperoxidase Gene Polymorphism and Inducible Nitric Oxide Synthase Expression in Cirrhotic Patients with Hepatopulmonary Syndrome

    Institute of Scientific and Technical Information of China (English)

    王燕颖; 王文多; 张艳霞; 赵欣; 杨东亮

    2010-01-01

    The clinical significance of a myeloperoxidase (MPO) gene polymorphism and inducible nitric oxide synthase (iNOS) expression in cirrhotic patients with hepatopulmonary syndrome (HPS) was explored. Enrolled subjects were divided into three groups according to their disease/health conditions: the HPS group (cirrhotic patients with HPS; n=63), the non-HPS group (cirrhotic patients without HPS; n=182), and the control group (healthy subjects without liver disease; n=35). The distribution of the MPO-463 G/A geno...

  8. In vitro and in vivo activity of ribavirin against Andes virus infection.

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    David Safronetz

    Full Text Available Pathogenic hantaviruses are a closely related group of rodent-borne viruses which are responsible for two distinct diseases in humans, hemorrhagic fever with renal syndrome and hantavirus pulmonary syndrome (HPS, otherwise known as hantavirus cardiopulmonary syndrome, HCPS. The antiviral effect of ribavirin against Old World hantaviruses, most notably Hantaan virus, is well documented; however, only a few studies have addressed its inhibitory effect on New World hantaviruses. In the present study, we demonstrate that ribavirin is highly active against Andes virus (ANDV, an important etiological agent of HPS, both in vitro and in vivo using a lethal hamster model of HPS. Treatment of ANDV infected Vero E6 cells with ribavirin resulted in dose-dependent reductions in viral RNA and protein as well as virus yields with a half maximal inhibitory concentration between 5 and 12.5 µg ml(-1. In hamsters, treatment with as little as 5 mg kg(-1 day(-1 was 100% effective at preventing lethal HPS disease when therapy was administered by intraperitoneal injection from day 1 through day 10 post-infection. Significant reductions were observed in ANDV RNA and antigen positive cells in lung and liver tissues. Ribavirin remained completely protective when administered by intraperitoneal injections up to three days post-infection. In addition, we show that daily oral ribavirin therapy initiated 1 day post-infection and continuing for ten days is also protective against lethal ANDV disease, even at doses of 5 mg kg(-1 day(-1. Our results suggest ribavirin treatment is beneficial for postexposure prophylaxis against HPS-causing hantaviruses and should be considered in scenarios where exposure to the virus is probable. The similarities between the results obtained in this study and those from previous clinical evaluations of ribavirin against HPS, further validate the hamster model of lethal HPS and demonstrate its usefulness in screening antiviral agents against

  9. Counteracting quasispecies adaptability: extinction of a ribavirin-resistant virus mutant by an alternative mutagenic treatment.

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    Celia Perales

    Full Text Available BACKGROUND: Lethal mutagenesis, or virus extinction promoted by mutagen-induced elevation of mutation rates of viruses, may meet with the problem of selection of mutagen-resistant variants, as extensively documented for standard, non-mutagenic antiviral inhibitors. Previously, we characterized a mutant of foot-and-mouth disease virus that included in its RNA-dependent RNA polymerase replacement M296I that decreased the sensitivity of the virus to the mutagenic nucleoside analogue ribavirin. METHODOLOGY AND PRINCIPAL FINDINGS: Replacement M296I in the viral polymerase impedes the extinction of the mutant foot-and-mouth disease virus by elevated concentrations of ribavirin. In contrast, wild type virus was extinguished by the same ribavirin treatment and, interestingly, no mutants resistant to ribavirin were selected from the wild type populations. Decreases of infectivity and viral load of the ribavirin-resistant M296I mutant were attained with a combination of the mutagen 5-fluorouracil and the non-mutagenic inhibitor guanidine hydrocloride. However, extinction was achieved with a sequential treatment, first with ribavirin, and then with a minimal dose of 5-fluorouracil in combination with guanidine hydrochloride. Both, wild type and ribavirin-resistant mutant M296I exhibited equal sensitivity to this combination, indicating that replacement M296I in the polymerase did not confer a significant cross-resistance to 5-fluorouracil. We discuss these results in relation to antiviral designs based on lethal mutagenesis. CONCLUSIONS: (i When dominant in the population, a mutation that confers partial resistance to a mutagenic agent can jeopardize virus extinction by elevated doses of the same mutagen. (ii A wild type virus, subjected to identical high mutagenic treatment, need not select a mutagen-resistant variant, and the population can be extinguished. (iii Extinction of the mutagen-resistant variant can be achieved by a sequential treatment of a

  10. Daclatasvir plus peginterferon and ribavirin is noninferior to peginterferon and ribavirin alone, and reduces the duration of treatment for HCV genotype 2 or 3 infection

    DEFF Research Database (Denmark)

    Dore, Gregory J; Lawitz, Eric; Hézode, Christophe

    2015-01-01

    BACKGROUND & AIMS: Twenty-four weeks of treatment with peginterferon and ribavirin for chronic hepatitis C virus (HCV) genotype 2 or 3 infection produces a sustained virologic response (SVR) in 70%-80% of patients. We performed a randomized, double-blind, phase 2b study to assess whether adding d...

  11. Cost-effectiveness of sofosbuvir plus ribavirin with or without pegylated interferon for the treatment of chronic hepatitis C in Italy.

    Science.gov (United States)

    Cure, Sandrine; Guerra, Ines; Cammà, Calogero; Craxì, Antonio; Carosi, Giampiero

    2015-01-01

    Across Italy up to 7.3% of the population is infected with hepatitis C virus (HCV), with long-term complications resulting in high medical costs and significant morbidity and mortality. Current treatment options have limitations due to side effects, interferon intolerability and ineligibility, long treatment durations and low sustained virological response (SVR) rates, especially for the most severe patients). Sofosbuvir is the first nucleotide polymerase inhibitor with pan-genotypic activity. Sofosbuvir, administered with ribavirin (RBV) and with or without pegylated interferon (PEG-INF), resulted in >90% SVR across treatment-naïve (TN) genotype (GT) 1-6 patients. It is also the first treatment option for patients that are unsuitable for interferon (UI). This analysis evaluates the cost - effectiveness of sofosbuvir for GTs 1-6 in Italy. A Markov model followed a cohort of 10,000 patients until they reached 80 years old. Approximately 20% of naïve and 30% of experienced patients initiated treatment at the cirrhosis stage. Comparators included PEG-INF + RBV for all GTs and plus telaprevir or boceprevir for GT1, or no treatment. Costs and outcomes were discounted at 3% and the cost perspective was that of the National Health Service in Italy. Sofosbuvir was cost-effective with incremental cost-effectiveness ratios (ICERs) below €40,000/QALY in all patient populations, particularly in cirrhotic patients. The exception was for a mixed cohort of GT2 TN patients where the ICER was €68,500/QALY and for a cirrhotic cohort of GT4/5/6 where the ICER was €68,434/QALY. Nevertheless, the prevalence of HCV in this patient population is expected to be low. Results were robust to sensitivity analysis. Sofosbuvir-based regimens are cost-effective in Italy, particular for the most severe patients. The interferon-free regimens are a real treatment option for UI patients. The high cure rates of this breakthrough treatment are expected to substantially reduce the burden of

  12. Motor vehicle accidents: How should cirrhotic patients be managed?

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    Kawaguchi, Takumi; Taniguchi, Eitaro; Sata, Michio

    2012-01-01

    Motor vehicle accidents (MVAs) are serious social issues worldwide and driver illness is an important cause of MVAs. Minimal hepatic encephalopathy (MHE) is a complex cognitive dysfunction with attention deficit, which frequently occurs in cirrhotic patients independent of severity of liver disease. Although MHE is known as a risk factor for MVAs, the impact of diagnosis and treatment of MHE on MVA-related societal costs is largely unknown. Recently, Bajaj et al demonstrated valuable findings that the diagnosis of MHE by rapid screening using the inhibitory control test (ICT), and subsequent treatment with lactulose could substantially reduce the societal costs by preventing MVAs. Besides the ICT and lactulose, there are various diagnostic tools and therapeutic strategies for MHE. In this commentary, we discussed a current issue of diagnostic tools for MHE, including neuropsychological tests. We also discussed the advantages of the other therapeutic strategies for MHE, such as intake of a regular breakfast and coffee, and supplementation with zinc and branched chain amino acids, on the MVA-related societal costs. PMID:22690067

  13. Motor vehicle accidents: How should cirrhotic patients be managed?

    Institute of Scientific and Technical Information of China (English)

    Takumi Kawaguchi; Eitaro Taniguchi; Michio Sata

    2012-01-01

    Motor vehicle accidents (MVAs) are serious social issues worldwide and driver illness is an important cause of MVAs.Minimal hepatic encephalopathy (MHE) is a complex cognitive dysfunction with attention deficit,which frequently occurs in cirrhotic patients independent of severity of liver disease.Although MHE is known as a risk factor for MVAs,the impact of diagnosis and treatment of MHE on MVA-related societal costs is largely unknown.Recently,Bajaj et al demonstrated valuable findings that the diagnosis of MHE by rapid screening using the inhibitory control test (ICT),and subsequent treatment with lactulose could substantially reduce the societal costs by preventing MVAs,Besides the ICT and lactulose,there are various diagnostic tools and therapeutic strategies for MHE.In this commentary,we discussed a current issue of diagnostic tools for MHE,including neuropsychological tests.We also discussed the advantages of the other therapeutic strategies for MHE,such as intake of a regular breakfast and coffee,and supplementation with zinc and branched chain amino acids,on the MVA-related societal costs.

  14. Differential distribution of age and HBV serological markers in liver cirrhosis and non-cirrhotic patients with primary liver cancer

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    XU Xiuhua

    2013-03-01

    Full Text Available ObjectiveTo compare the age distributions and presence of hepatitis B virus (HBV serological markers between primary hepatic cancer (PHC patients with and without liver cirrhosis. MethodsA total of 547 PHC cases were analyzed retrospectively. After dividing into two groups according to liver cirrhosis status, the between-group differences in age and HBV serological markers, such as hepatitis B e antigen (HBeAg status, were statistically compared using the Chi-squared test. ResultsThe number of cirrhotic and non-cirrhotic PHC patients was 265 and 282, respectively. HBV infection was present in 221 cirrhotic PHC patients and 256 non-cirrhotic PHC patients (834% vs. 90.8%. There was a substantial bias in the proportion of males to females in the cirrhotic PHC patients (7.83∶1. The number of PHC patients <60 years old was similar between the cirrhotic and non-cirrhotic groups, but the non-cirrhotic group had significantly more patients >60 years old (P<0.005. In cirrhotic PHC patients, the HBV infection rate was highest in the <40 years old age group (96.7% and the HBeAg serological conversion rate was highest in the 40-60 years old age group (89.5%. In non-cirrhotic PHC patients, the 40-60 years old age group showed the highest HBV infection rate (90.3% but the lowest HBeAg serological conversion rate (80.0%. ConclusionPHC with liver cirrhosis mainly occurred in males, with the HBV infection rate being higher in individuals <60 years old. Non-cirrhotic PHC patients were more often >60 years old. Many of the HBV-infected PHC patients with cirrhosis had high HBeAg serological conversion rate.

  15. Daclatasvir–sofosbuvir combination therapy with or without ribavirin for hepatitis C virus infection: from the clinical trials to real life

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    Pol S

    2016-03-01

    Full Text Available Stanislas Pol, Marion Corouge, Anaïs Vallet-Pichard Université Paris Descartes, Liver Department, Assistance Publique Hôpitaux de Paris, Cochin Hospital, French Institute of Health and Medical Research UMS20, Institut Pasteur, Paris, France Abstract: The treatment of hepatitis C virus has changed dramatically with the rapid advent of numerous new antiviral agents, including direct-acting antivirals and agents with non-viral targets (cyclophilin inhibitors, interferon-lambda, vaccine therapy. Given the better safety profile and high antiviral potency of direct-acting antivirals, their combination in interferon-free oral regimens is becoming the standard of care for hepatitis C virus infection, tailored to individual patients according to the degree of disease progression (fibrosis, hepatitis C virus genotype and subtype, resistance profile, and prior therapeutic history. Results from clinical studies as well as preliminary real-life data regarding the combination of sofosbuvir (a nucleotide polymerase inhibitor and daclatasvir, a first-in-class NS5A replication complex inhibitor, demonstrate that it is one of the most promising antiviral therapies, with once-daily oral dosing, a low pill burden, good tolerability, and limited drug–drug interactions, in addition to high antiviral potency, with >90% sustained virologic response rates. This combination has high pangenotypic antiviral potency regardless of the severity and patient characteristics. The combination of sofosbuvir and an NS5A inhibitor with ribavirin for 12 weeks appears to be a very good further treatment option in both cirrhotic and treatment-experienced patients whatever the stage of fibrosis. Keywords: hepatitis C virus, direct-acting antivirals, sofosbuvir, daclatasvir

  16. EXHALED AND PLASMA NITRITE: a comparative study among healthy, cirrhotic and liver transplant patients

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    Viviane S AUGUSTO

    2014-03-01

    Full Text Available Context There is a relative lack of studies about exhaled nitrite (NO2- concentrations in cirrhotic and transplanted patients. Objective Verify possible differences and correlations between the levels of NO2-, measured in plasma and exhaled breath condensate collected from patients with cirrhosis and liver transplant. Method Sixty adult male patients, aged between 27 and 67 years, were subdivided into three groups: a control group comprised of 15 healthy volunteers, a cirrhosis group composed of 15 volunteers, and a transplant group comprised of 30 volunteers. The NO2- concentrations were measured by chemiluminescence. Results 1 The analysis of plasma NO2- held among the three groups showed no statistical significance. 2 The comparison between cirrhotic and control groups, control and transplanted and cirrhotic and transplanted was not statistically significant. 3 The measurements performed on of NO2- exhaled breath condensate among the three groups showed no statistical difference. 4 When comparing the control group samples and cirrhotic, control and transplanted and cirrhotic and transplanted, there was no significant changes in the concentrations of NO2-. Conclusion No correlations were found between plasma and exhaled NO2-, suggesting that the exhaled NO2- is more reflective of local respiratory NO release than the systemic circulation.

  17. Prognostic Value of AIMS65 Score in Cirrhotic Patients with Upper Gastrointestinal Bleeding

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    Vinaya Gaduputi

    2014-01-01

    Full Text Available Introduction. Unlike Rockall scoring system, AIMS65 is based only on clinical and laboratory features. In this study we investigated the correlation between the AIMS65 score and Endoscopic Rockall score, in cirrhotic and noncirrhotic patients. Methods. This is a retrospective study of patients admitted with overt UGIB and undergoing esophagogastroduodenoscopy (EGD. AIMS65 and Rockall scores were calculated at the time of admission. We investigated the correlation between both scores along with stigmata of bleed seen on endoscopy. Results. A total of 1255 patients were studied. 152 patients were cirrhotic while 1103 patients were noncirrhotic. There was significant correlation between AIMS65 and Total Rockall scores in patients of both groups. There was significant correlation between AIMS65 score and Endoscopic Rockall score in noncirrhotics but not cirrhotics. AIMS65 scores in both cirrhotic and noncirrhotic groups were significantly higher in patients who died from UGIB than in patients who did not. Conclusion. We observed statistically significant correlation between AIMS65 score and length of hospitalization and mortality in noncirrhotic patients. We found that AIMS65 score paralleled the endoscopic grading of lesion causing UGIB in noncirrhotics. AIMS65 score correlated only with mortality but not the length of hospitalization or endoscopic stigmata of bleed in cirrhotics.

  18. Local regulator adrenomedullin contributes to the circulatory disturbance in cirrhotic rats

    Institute of Scientific and Technical Information of China (English)

    Shinya Sakurai; Hideyuki Kojima; Masahito Uemura; Hiroyasu Satoh; Hiroshi Fukui

    2006-01-01

    AIM: To investigate whether adrenomedullin, a potent vasodilator peptide, plays a role in the circulatory disturbance in cirrhosis.METHODS: Cirrhosis was induced in rats by weekly gavage of carbon tetrachloride. Hemodynamic studies were performed in vivo using radioactive microspheres andin vitro using isolated aortic rings.The adrenomedullin concentrations were measured by radioimmunoassay.RESULTS: Acute administration of adrenomedullin to the control rats reduced the systemic arterial pressure along with an increase of serum levels of the stable metabolite of nitric oxide (NOx), in a dose-dependent manner. Chronic infusion of adrenomedullin reduced the vascular resistance and increased the blood flow in the systemic and splanchnic circulation. Intravenous administration of anti-adrenomedullin antibody did not affect any hemodynamic parameters in the cirrhotic rats, whereas this antibody ameliorated the blunted contractile response to phenylephrine, a-adrenergic receptor agonist, in the aortic rings of the cirrhotic rats.The adrenomedullin concentrations in the aorta were higher in the cirrhotic rats than in the controls, and correlated with the mean arterial pressure in the cirrhotic rats. Moreover, adrenomedullin blunted the contractile response to phenylephrine in both of the control aorta and cirrhotic aorta, but not in the presence of NG-nitroL-arginine methyl ester, an NO synthase inhibitor.CONCLUSION: Adrenomedullin overproduced in the vascular wall may contribute to the circulatory disturbance in cirrhosis as a local regulator of the vascular tonus rather than a circulating hormone.

  19. In-hospital mortality among a cohort of cirrhotic patients admitted to a Tertiary Hospital

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    Mohammad A Alsultan

    2011-01-01

    Full Text Available Background/Aim : To determine the mortality rate in a cohort of hospitalized patients with cirrhosis and examine their resuscitation status at admission. Materials and Methods : A retrospective chart review was conducted of patients with cirrhosis who were admitted to a tertiary care hospital in Riyadh, Saudi Arabia, from January 1, 2009, to December 31, 2009. Results: We reviewed 226 cirrhotic patients during the study period. The hospital mortality rate was 35%. A univariate analysis revealed that worse outcomes were seen in patients with advanced age or who had worse child-turcotte-pugh (CPT scores, worse model for end-stage liver disease (MELD scores, low albumin and high serum creatinine. Using a multivariate analysis, we found that advanced age (P=0.004 and high MELD (P=0.001 scores were independent risk factors for the mortality of cirrhotic patients. The end-of-life decision were made in 34% of cirrhotic patients, and the majority of deceased patients were "no resuscitation" status (90% vs. 4%, P<0.001. Conclusions : The relatively high mortality in cirrhotic patients admitted for care in a tertiary hospital, Saudi Arabia was comparable to that reported in the literature. Furthermore, end-of-life discussions should be addressed early in the hospitalization of cirrhotic patients.

  20. Changes in serum ammonia concentration in cirrhotic patients with Helicobacter pylori infection

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Objective To study whether liver cirrhosis associated with Helicopacter pylori (H. pylori)infection will induce increased serum ammonia and whether the peripheral serum ammonia reflects the level of portal vein serum ammonia. Methods Blood was taken from the portal vein and the cubital vein in cirrhotic patients with and without H.pylori infection and non-cirrhotic patients (splenic rupiure) with and without H. pylori infection, and the serum ammonia was measured. Results The mean levels of serum ammonia in the group of cirrhotic patients with H. pylori infection were 167.82±8.97 μmol/L (pertal vein) and 142.2±13.35 μmol/L (cubital vein). They were increased significantly as compared with cirrhotic patients without H.pyiori infection(47.68±12.03 μmol/L portal vein and 37.23±7.04 μmol/L cubital vein),and also compared with the groups of splenic rupture patients with and without H. pylori infection (P<0.0t).There was no significant difference between the serum ammonia level of the cubital vein and pertal vein(P>0.05). Conclusions H.pylori intection can induce an increase in serum ammonia in patients with liver dysfunction,and the peripheral serum ammonia measurement may replace the portal vein serum ammania as a monitoring method. Eradication of H.pylori in cirrhotic patients may prevent hepatic encephalopathy(HE).

  1. Increased anandamide induced relaxation in mesenteric arteries of cirrhotic rats: role of cannabinoid and vanilloid receptors

    Science.gov (United States)

    Domenicali, M; Ros, J; Fernández-Varo, G; Cejudo-Martín, P; Crespo, M; Morales-Ruiz, M; Briones, A M; Campistol, J-M; Arroyo, V; Vila, E; Rodés, J; Jiménez, W

    2005-01-01

    Background and aims: Anandamide is an endocannabinoid that evokes hypotension by interaction with peripheral cannabinoid CB1 receptors and with the perivascular transient receptor potential vanilloid type 1 protein (TRPV1). As anandamide has been implicated in the vasodilated state in advanced cirrhosis, the study investigated whether the mesenteric bed from cirrhotic rats has an altered and selective vasodilator response to anandamide. Methods: We assessed vascular sensitivity to anandamide, mRNA and protein expression of cannabinoid CB1 receptor and TRPV1 receptor, and the topographical distribution of cannabinoid CB1 receptors in resistance mesenteric arteries of cirrhotic and control rats. Results: Mesenteric vessels of cirrhotic animals displayed greater sensitivity to anandamide than control vessels. This vasodilator response was reverted by CB1 or TRPV1 receptor blockade, but not after endothelium denudation or nitric oxide inhibition. Anandamide had no effect on distal femoral arteries. CB1 and TRPV1 receptor protein was higher in cirrhotic than in control vessels. Neither CB1 mRNA nor protein was detected in femoral arteries. Immunochemistry showed that CB1 receptors were mainly in the adventitia and in the endothelial monolayer, with higher expression observed in vessels of cirrhotic rats than in controls. Conclusions: These results indicate that anandamide is a selective splanchnic vasodilator in cirrhosis which predominantly acts via interaction with two different types of receptors, CB1 and TRPV1 receptors, which are mainly located in perivascular sensory nerve terminals of the mesenteric resistance arteries of these animals. PMID:15753538

  2. Suppression of angiotensin II stimulated responses in aortic vascular smooth muscle cells of experimental cirrhotic rats

    Institute of Scientific and Technical Information of China (English)

    1999-01-01

    Functional responses to angiotensin II(AT-II) were determined in aortic vascular smooth muscle cells (VSMCs) from experimental cirrhotic rats.Our data showed that AT-II-stimulated extracellular acidification rate (ECAR),which was measured by Cytosesor microphysiometry,was significantly reduced in the aortic VSMCs from the cirrhotic rats as compared to those from the control animals.The ability of AT-II to promote formation of inositol phosphates,the second messenger produced by the activation of Gq-coupled receptors,was also considerably suppressed in the cirrhotic VSMCs.Furthermore,the maximal p42/44 MAPK phosphorylation stimulated by AT-II was significantly reduced in the cirrhotic VSMCs in contrast to that in the normal VSMCs.Taken together,our data clearly demonstrated that the functional responses to AT-II was severely suppressed in aortic VSMCs in cirrhosis,indicating the impairment of general Gq-coupled receptor signaling and subsequent biological function in the cirrhotic VSMCs.

  3. The Role of Serum Cytokines in the Pathogenesis of Hepatic Osteodystrophy in Male Cirrhotic Patients

    Directory of Open Access Journals (Sweden)

    Ali Riza Soylu

    2012-01-01

    Full Text Available Objective. In this study, we aimed to investigate the possible role of serum cytokines in the development of hepatic osteodystrophy. Matherial and Methods. 44 consecutive male cirrhotic patients (17 alcoholic, 20 hepatitis B, 7 hepatitis C, 15 age- and sex-matched chronic alcoholics without liver disease, and 17 age- and sex-matched healthy controls were included in the study during one year period. Bone mineral density was measured by dual X-ray absorptiometry in the lumbar vertebrate and femoral neck. Serum interleukin levels were measured by ELISA method. Results. Although osteopenia frequency between our cirrhotic patients was 20%, there was no difference in T-scores among the controls and other groups. Serum interleukin-1, interleukin-8, and tumor necrosis factor-alpha levels were not different between all groups. Serum interleukin-2 and interleukin-6 levels were higher in the cirrhotics than controls (P<0.001. However, there were no significant difference between osteopenic and nonosteopenic cirrhotics. Conclusion. According to the results of the study in this small population of 44 male cirrhotic patients, frequency of hepatic osteopenia is small and serum interleukins 1, 2, 6, 8, and tumor necrosis factor-alpha may not play a role in the pathogenesis of hepatic osteodystrophy. Further studies in which large number of patients involved are necessary in this field.

  4. Short interferon and ribavirin treatment for HCV genotype 2 or 3 infection

    DEFF Research Database (Denmark)

    Waldenström, Jesper; Färkkilä, Martti; Rembeck, Karolina;

    2016-01-01

    OBJECTIVE: Interferon-free therapy for hepatitis C virus (HCV) infection is costly, and therefore patients with advanced fibrosis are prioritized. Although coupled with considerable side effects, a large proportion of genotype 2/3 infected patients achieve a sustained virological response (SVR...... predictors, e.g. age, ITPA and IL28B genetic variants, IP-10, liver histopathology and early viral kinetics on outcome was evaluated among HCV genotype 2/3 infected patients enrolled in the NORDynamIC trial. Similarly outcome was evaluated among Finnish and Swedish real-life genotype 2/3 infected patients...... treated for 12-16 weeks in accordance with national guidelines. RESULTS: In the NORDynamIC trial, age HCV RNA 

  5. A combination of doxycycline and ribavirin alleviated chikungunya infection.

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    Hussin A Rothan

    Full Text Available Lack of vaccine and effective antiviral drugs against chikungunya virus (CHIKV outbreaks have led to significant impact on health care in the developing world. Here, we evaluated the antiviral effects of tetracycline (TETRA derivatives and other common antiviral agents against CHIKV. Our results showed that within the TETRA derivatives group, Doxycycline (DOXY exhibited the highest inhibitory effect against CHIKV replication in Vero cells. On the other hand, in the antiviral group Ribavirin (RIBA showed higher inhibitory effects against CHIKV replication compared to Aciclovir (ACIC. Interestingly, RIBA inhibitory effects were also higher than all but DOXY within the TETRA derivatives group. Docking studies of DOXY to viral cysteine protease and E2 envelope protein showed non-competitive interaction with docking energy of -6.6±0.1 and -6.4±0.1 kcal/mol respectively. The 50% effective concentration (EC50 of DOXY and RIBA was determined to be 10.95±2.12 μM and 15.51±1.62 μM respectively, while DOXY+RIBA (1:1 combination showed an EC50 of 4.52±1.42 μM. When compared, DOXY showed higher inhibition of viral infectivity and entry than RIBA. In contrast however, RIBA showed higher inhibition against viral replication in target cells compared to DOXY. Assays using mice as animal models revealed that DOXY+RIBA effectively inhibited CHIKV replication and attenuated its infectivity in vivo. Further experimental and clinical studies are warranted to investigate their potential application for clinical intervention of CHIKV disease.

  6. A combination of doxycycline and ribavirin alleviated chikungunya infection.

    Science.gov (United States)

    Rothan, Hussin A; Bahrani, Hirbod; Mohamed, Zulqarnain; Teoh, Teow Chong; Shankar, Esaki M; Rahman, Noorsaadah A; Yusof, Rohana

    2015-01-01

    Lack of vaccine and effective antiviral drugs against chikungunya virus (CHIKV) outbreaks have led to significant impact on health care in the developing world. Here, we evaluated the antiviral effects of tetracycline (TETRA) derivatives and other common antiviral agents against CHIKV. Our results showed that within the TETRA derivatives group, Doxycycline (DOXY) exhibited the highest inhibitory effect against CHIKV replication in Vero cells. On the other hand, in the antiviral group Ribavirin (RIBA) showed higher inhibitory effects against CHIKV replication compared to Aciclovir (ACIC). Interestingly, RIBA inhibitory effects were also higher than all but DOXY within the TETRA derivatives group. Docking studies of DOXY to viral cysteine protease and E2 envelope protein showed non-competitive interaction with docking energy of -6.6±0.1 and -6.4±0.1 kcal/mol respectively. The 50% effective concentration (EC50) of DOXY and RIBA was determined to be 10.95±2.12 μM and 15.51±1.62 μM respectively, while DOXY+RIBA (1:1 combination) showed an EC50 of 4.52±1.42 μM. When compared, DOXY showed higher inhibition of viral infectivity and entry than RIBA. In contrast however, RIBA showed higher inhibition against viral replication in target cells compared to DOXY. Assays using mice as animal models revealed that DOXY+RIBA effectively inhibited CHIKV replication and attenuated its infectivity in vivo. Further experimental and clinical studies are warranted to investigate their potential application for clinical intervention of CHIKV disease.

  7. Effects of adding ribavirin to interferon to treat chronic hepatitis C infection

    DEFF Research Database (Denmark)

    Brok, Jesper; Gluud, Lise L; Gluud, Christian

    2005-01-01

    , EMBASE, manual searches of bibliographies and journals, and correspondence with experts (in May 2004). Data were extracted independently by 2 reviewers. The primary outcomes were morbidity plus mortality and viral clearance. Secondary outcomes included histologic response, quality of life, and adverse....... In conclusion, the effect of ribavirin plus interferon on viral clearance may lead to reduced mortality and morbidity in patients with chronic hepatitis C infection. However, combination therapy is associated with increased risk for adverse events.......Evidence shows that a combination therapy of ribavirin plus interferon clears hepatitis C virus from the blood in about 40% of patients with chronic hepatitis C infection, but the effects on clinical outcomes are unclear. We evaluated the beneficial and harmful effects of ribavirin plus interferon...

  8. Optimizing ribavirin dose in HIV/hepatitis C (HCV co-infected individuals treated for HCV

    Directory of Open Access Journals (Sweden)

    J Farley

    2012-11-01

    Full Text Available Hepatitis C (HCV and HIV share common transmission pathways and the acquisition of both viruses are relatively common. Concurrent treatment for HCV with highly active anti-retroviral therapy (HAART should be considered in HIV co-infected individuals to decrease the progression of liver damage. Adverse effects and less satisfactory treatment outcomes are often concerns when treating co-infected individuals. Although, direct acting antivirals (DAAs may increase SVR, they may not be possible because of drug-drug interactions. he objective of this study is to investigate the difference in response rates of HCV treatment in HIV co-infected inmates with varying doses of ribavirin. Retrospective medical chart reviews of 52 HCV/HIV co-infected inmates who underwent HCV therapy between 2003 and 2010. All received standard doses of pegylated interferon alpha 2a or 2b and 800–1600 mg of ribavirin depending on weight. The recommended dosage for genotypes 2 and 3 is 800 mg/day. For other genotypes, if weight is<75 kg, the recommended ribavirin dose is 1000 mg/day or 1200 mg/day if>75 kg. Efficacy was defined as attaining sustained virological response (SVR six months post treatment. Univariate analyses was performed using SPSS-18; Chi-square test with p-value<0.05 was defined significant. 52 co-infected (3 females & 49 males were identified. Mean age was 40±7 years. Caucasians accounted for 84.6%; First Nations for 13.5% and Asians 1.9%. 36 were concurrently on HAART. The genotype distribution was: geno 1, 66.0%; geno 2, 7.5%; geno 3, 26.4%. SVR by ribavirin dosage ratio (actual dosage/recommended dosage:=1.0; 41.2% (14/34,>1.0; 58.8% (20/34. Doses greater than 1.5 times were associated with higher adverse events and lower SVR. Suboptimal doses of weight-based ribavirin may be contributing to a lower treatment response in HCV/HIV co-infectants. In our experience, the optimal dose of ribavirin is between 1 and 1.2 times the current recommended dose. We

  9. Increased Ribavirin Bioavailability Associated With Telaprevir Use in Hepatitis C Patients Treated With PEGylated -Interferon/Ribavirin/Telaprevir Triple Therapy

    Directory of Open Access Journals (Sweden)

    Pradat

    2015-09-01

    Full Text Available Background Anemia is more frequent in patients receiving telaprevir with PEGylated interferon/ribavirin (PEG-IFN/RBV than in those receiving PEG-IFN/RBV alone. Objectives The objective was to measure the impact of telaprevir on RBV bioavailability and to assess the concomitant renal function. Materials and Methods Thirty-seven hepatitis C virus (HCV patients non-responders to a previous course of PEG-IFN/RBV therapy and re-treated with triple therapy combining PEG-IFN/RBV and telaprevir were analyzed. RBV bioavailability was measured before the triple therapy initiation, during telaprevir treatment at week (W 4 and W8, and after telaprevir cessation (post W16. The renal function was assessed by estimating the glomerular filtration rate (eGFR. Results At W4, RBV bioavailability, expressed as mg/L/daily dose/kg body weight, was significantly increased (median increase = 0.06 mg/L/dose/kg; P < 0.001. In parallel, the renal function was impaired with a mean eGFR decrease of -6.8 mL/minutes/1.73 m² (P = 0.109. Between W4 and W8, RBV bioavailability continued to increase (P < 0.001 but subsequently decreased slightly after telaprevir discontinuation with a concomitant restoration of the renal function (eGFR increase of 6.34 mL/minutes/1.73 m². Conclusions Our results indicated a reversible increase in RBV bioavailability after telaprevir exposure, which might be linked to the impairment of the GFR. This also suggests a RBV-telaprevir pharmacological interaction, a possible source of severe anemia observed under triple therapy. These results suggest that RBV pharmacological monitoring may be clinically relevant, especially in the context of first-generation HCV protease inhibitor-based therapy.

  10. The thalamus in cirrhotic patients with and without hepatic encephalopathy: A volumetric MRI study

    Energy Technology Data Exchange (ETDEWEB)

    Tao, Ran, E-mail: taoran1648@yahoo.cn [Department of Radiology, Southwest Hospital, Third Military Medical University, Chongqing 400038 (China); Department of Radiology, Bethune International Peace Hospital of People' s Liberty Army, Shijiazhuang 050082, Hebei Province (China); Zhang, Jiuquan, E-mail: jiuquanzhang@yahoo.com [Department of Radiology, Southwest Hospital, Third Military Medical University, Chongqing 400038 (China); You, Zhonglan, E-mail: you_zhonglan@163.com [Department of Infectious Diseases, Southwest Hospital, Third Military Medical University, Chongqing 400038 (China); Wei, Luqing, E-mail: weiluqing@foxmail.com [Department of Radiology, Southwest Hospital, Third Military Medical University, Chongqing 400038 (China); Fan, Yi, E-mail: fanyi1978@yahoo.cn [Department of Infectious Diseases, Southwest Hospital, Third Military Medical University, Chongqing 400038 (China); Cui, Jinguo, E-mail: cuijinguo2005@163.com [Department of Radiology, Bethune International Peace Hospital of People' s Liberty Army, Shijiazhuang 050082, Hebei Province (China); Wang, Jian, E-mail: wangjian_811@yahoo.com [Department of Radiology, Southwest Hospital, Third Military Medical University, Chongqing 400038 (China)

    2013-11-01

    Background and aims: The thalamus is a major relay and filter station in the central neural system. Some previous studies have suggested that the thalamus maybe implicated in the pathogenesis of hepatic encephalopathy. The aim of our study was to investigate changing thalamic volumes in cirrhotic patients with and without hepatic encephalopathy. Methods: Neuropsychological tests and structural MR scanning were performed on 24 cirrhotic patients, 23 cirrhotic patients with minimal hepatic encephalopathy, 24 cirrhotic patients during their first episode of overt hepatic encephalopathy, and 33 healthy controls. Voxel-based morphometry analysis was performed to detect gray matter morphological changes. The thalamus and whole brain volume were extrapolated. A receiver operating characteristic curve analysis of thalamic volumes was used to discriminate patients with minimal hepatic encephalopathy from those with hepatic cirrhosis. Results: Thalamic volume increased in a stepwise manner in patients with progressively worse stages of hepatic encephalopathy compared to healthy subjects. Additionally, a comparison of gray matter morphometry between patients with Child–Pugh grades A, B, or C and controls revealed a progression in thalamic volumes in parallel with the degree of liver failure. Moreover, thalamic volume was significantly correlated with the number connection test A time and digit-symbol test score in cirrhotic patients with minimal hepatic encephalopathy (r = 0.659, P = 0.001; r = −0.577, P = 0.004; respectively). The area under the receiver operating characteristic curve was 0.827 (P = 0.001). Conclusions: A significantly increased thalamic volume may be provide an objective imaging measure for predicting seizures due to minimal hepatic encephalopathy in cirrhotic patients.

  11. Inactivation of extrahepatic vascular Akt improves systemic hemodynamics and sodium excretion in cirrhotic rats.

    Science.gov (United States)

    Fernández-Varo, G; Melgar-Lesmes, P; Casals, G; Pauta, M; Arroyo, V; Morales-Ruiz, M; Ros, J; Jiménez, W

    2010-12-01

    Increased activity of the vascular Akt/eNOS signaling pathway is involved in the hemodynamic and renal complications developed by patients and rats with cirrhosis and ascites. This occurs in the setting of impaired Akt/eNOS activity within the cirrhotic liver. Here we assessed the feasibility of selectively inhibiting vascular eNOS without further impairing the intrahepatic activity of this enzyme. Ultimately, we sought to determine whether endothelial transduction of a constitutively inactive mutant of Akt (AA-Akt) improves circulatory function and sodium excretion in cirrhotic rats with ascites. First, we administered recombinant adenoviruses that encode the β-galactosidase gene (β-gal) to 5 control rats and 5 cirrhotic rats with ascites and analyzed their tissue distribution by chemiluminescence. Next, urine samples were obtained from 18 cirrhotic rats with ascites and then the animal randomly received saline or adenoviruses containing the β-gal or the AA-Akt genes. Following a 24-h urine collection period, hemodynamic studies were performed and tissue samples were obtained to analyze Akt and eNOS expressions. No β-gal activity was detected in the liver of cirrhotic rats compared to that of controls. This was paralleled by increased β-gal activity in other territories such as the thoracic aorta. AA-Akt transduction improved systemic hemodynamics, splanchnic perfusion pressure and renal excretory function in comparison with cirrhotic rats transduced with β-gal adenoviruses or receiving saline. Moreover, the AA-Akt transgene did not modify portal pressure. Inactivation of extrahepatic vascular Akt and the concomitant decrease in nitric oxide expression ameliorate systemic hemodynamics and renal excretory function in experimental cirrhosis. Copyright © 2010 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  12. Peritoneal Dialysis is Associated With A Better Survival in Cirrhotic Patients With Chronic Kidney Disease.

    Science.gov (United States)

    Chou, Che-Yi; Wang, Shu-Ming; Liang, Chih-Chia; Chang, Chiz-Tzung; Liu, Jiung-Hsiun; Wang, I-Kuan; Hsiao, Lien-Cheng; Muo, Chih-Hsin; Chung, Chi-Jung; Huang, Chiu-Ching

    2016-01-01

    Peritoneal dialysis (PD) can be an ideal treatment in cirrhotic patients with ascites and chronic kidney disease stage 5 (CKD 5D) who require dialysis. The survival of cirrhotic patients with CKD 5D on PD, however, is not clear. We compared the survival of cirrhotic patients with CKD 5D on PD and the survival of those on HD. Two datasets including a cohort study of China Medical University Hospital (CMUH) from 2004 to 2013 and the Longitudinal National Health Insurance Database for Catastrophic Illness Patients (LHID-CIP) of Taiwan from 1996 to 2011 were analyzed. The survival of cirrhotic patients on PD and the propensity score matched cirrhotic patients on HD were analyzed using Cox proportional hazards regression. In CMUH cohort of 85 PD and 340 HD patients, the all-cause mortality was lower in PD patients compared to it in HD patients (hazard ratio [HR]: 0.48, 95% confidence interval [CI]: 0.31-0.74, P model for end-stage liver disease (MELD) score, however, was not associated with all-cause mortality. In the LHID-CIP cohort of 285 PD and 1140 HD patients, the HR of all-cause mortality in PD patients was 0.61 (95% CI: 0.47 - 0.79, P < 0.01), as compared with HD patients. PD in cirrhotic patients who need dialysis is associated with lower all-cause mortality than HD is. This association is independent of patients' comorbidity, severity of liver cirrhosis, and serum albumin levels.

  13. Effect of L-NAME on nitric oxide and gastrointestinal motility alterations in cirrhotic rats

    Institute of Scientific and Technical Information of China (English)

    Xin Wang; Jie Ding; Kai-Cun Wu; Bo-Rong Pan; Dai-Ming Fan; Yue-Xia Zhong; Zong-You Zhang; Ju Lu; Mei Lan; Ji-Yan Miao; Xue-Gang Guo; Yong-Quan Shi; Yan-Qiu Zhao

    2002-01-01

    AIM: To invsstigare the effect of L-NAME on nitric oxide andgastriubtestubal motility alterations in cirrhotic ratsMETHODS: Rats with cirrhosis induced by carbontetrachloride were randomly divided into two groups, one( n= 13) receiving 0. 5 mg@ kg-1 per clay of NG-nitro-L-argininemethyl ester (L-NAME), a nitric oxide synthase inhibitor,for 10 days, whereas the other group ( n = 13) and control( n = 10) rats were administrated the same volume of 9 g@ L-1saline.Half gastric emptying time and 2 h residual rate weremeasured by SPECT, using 99m Tc-DTPA-labeled bariumsuifate as test meal. Gastrointestinal transition time wasrecorded simultaneously. Serum concentration of nitrcoxide (NO) was determined by the kinetic cadmiunreduction and colorimetric methods. ImmunohistochemicalSABC method was used to observe the expression anddistribution of three types of nitric oxide synthase (NOS)isoforms in the mt gastrointestinal tract. Western blot wasused to detect expression of gastrointestinal NOS isoforms.RESULTS: Half gastric emptying time and trans-gastrointestinal time were significantly prolonged( 124.0 ± 26.4min; 33.7± 8.9min;72.1 ± 15.3 min; P<0.01), (12.4±0.5h; 9.5±0.3 h; 8.2±0.8 h; P<0.01), 2h residual rate wasraised in cirrhotic rots than in controls and cirrhotic ratstreated with L-NAME(54.9± 7.6 % ,13.7 ± 3.2 %, 34.9± 10.3%, P< 0.01). Serum concentration of NO was significantlyincreased in cirrhotic rots than in the other groups (8.20 ± 2.48)μmol@L-1, (5.94± 1.07) μmol@L-1 ,and control (5.66± 1.60) tμmol@L-1, P< 0.01. NOS staining intensities which weremainly located in the gastrointestinal tissues were markedlylower in cirrhotic rats than in the controls and cirrhotic ratsafter treated with L- NAME.CONCLUSION: Gastrointestinal motility was remarkablyinhibited in cirrhotic rats, which could he alleviated by L-NAME. Nitric oxide may play an important role in theinhibition of gastrointestinal motility in cirrhotic rats.

  14. Hepatocellular carcinoma arising from hepatocellular adenoma in a hepatitis B virus-associated cirrhotic liver

    Energy Technology Data Exchange (ETDEWEB)

    Seo, J.M. [Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Lee, S.J., E-mail: lucia@skku.edu [Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Kim, S.H. [Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Park, C.K.; Ha, S.Y. [Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

    2012-04-15

    Hepatocellular adenoma (HCA) is a rare, benign proliferation of hepatocytes that occurs mostly in a normal liver and in extreme rare cases, occurs in a cirrhotic liver. Hepatocellular carcinomas (HCC) arising within HCA through malignant transformation is rare. The specific incidence and mechanism of malignant transformation has not been established, but the long term use of oral contraceptives is considered a causative agent. We report a case of HCC arising from HCA detected in a hepatitis B-related cirrhotic liver with serial radiologic images.

  15. Serum neutral amino acid concentrations in cirrhotic patients with impaired carbohydrate metabolism.

    Directory of Open Access Journals (Sweden)

    Watanabe,Akiharu

    1983-08-01

    Full Text Available Serum neutral amino acid levels in cirrhotic patients with abnormal oral glucose tolerance test patterns were not different from those of subjects without impaired carbohydrate metabolism. However, the characteristic features of serum aminograms in the patients, that is, increased levels of tyrosine, decreased levels of valine and leucine and the diminished ratio of branched chain amino acids to phenylalanine and tyrosine levels, were less pronounced in those treated with insulin. This finding is clinically important for evaluating the serum aminogram of cirrhotic patients under insulin therapy.

  16. RASSF1A and DOK1 Promoter Methylation Levels in Hepatocellular Carcinoma, Cirrhotic and Non-Cirrhotic Liver, and Correlation with Liver Cancer in Brazilian Patients

    Science.gov (United States)

    Araújo, Oscar C.; Rosa, Agatha S.; Fernandes, Arlete; Niel, Christian; Villela-Nogueira, Cristiane A.; Pannain, Vera; Araujo, Natalia M.

    2016-01-01

    Hepatocellular carcinoma (HCC) is the second most common cause of cancer mortality worldwide. Most cases of HCC are associated with cirrhosis related to chronic hepatitis B virus or hepatitis C virus infections. Hypermethylation of promoter regions is the main epigenetic mechanism of gene silencing and has been involved in HCC development. The aim of this study was to determine whether aberrant methylation of RASSF1A and DOK1 gene promoters is associated with the progression of liver disease in Brazilian patients. Methylation levels were measured by pyrosequencing in 41 (20 HCC, 9 cirrhotic, and 12 non-cirrhotic) liver tissue samples. Mean rates of methylation in RASSF1A and DOK1 were 16.2% and 12.0% in non-cirrhotic, 26.1% and 19.6% in cirrhotic, and 59.1% and 56.0% in HCC tissues, respectively, showing a gradual increase according to the progression of the disease, with significantly higher levels in tumor tissues. In addition, hypermethylation of RASSF1A and DOK1 was found in the vast majority (88%) of the HCC cases. Interestingly, DOK1 methylation levels in HCC samples were significantly higher in the group of younger (<40 years) patients, and higher in moderately differentiated than in poorly differentiated tumors (p < 0.05). Our results reinforce the hypothesis that hypermethylation of RASSF1A and DOK1 contributes to hepatocarcinogenesis and is associated to clinicopathological characteristics. RASSF1A and DOK1 promoter hypermethylation may be a valuable biomarker for early diagnosis of HCC and a potential molecular target for epigenetic-based therapy. PMID:27078152

  17. Discussing viral load levels after HIV/AIDS merges HBV/HCV infection and its relationship with T lymphocytes%HIV/AIDS合并HBV/HCV感染病毒载量水平及与T淋巴细胞相关性的探讨

    Institute of Scientific and Technical Information of China (English)

    张茹薏; 游晶; 杨微波; 饶少锋

    2016-01-01

    目的:探讨人类免疫缺陷病毒(HIV)/艾滋病(AIDS)合并乙型肝炎病毒(HBV)/丙型肝炎病毒(HCV)感染后病毒载量水平变化及对机体T淋巴细胞免疫机制的影响。方法分别测定 HIV/AIDS单纯感染组,HIV/HBV合并感染组,HIV/HCV合并感染组3组的 HIV RNA、HBV DNA、HCV RNA、CD4+ T淋巴细胞频数、CD8+ T淋巴细胞频数、CD4/CD8比值,并分析各组T淋巴细胞与HIV RNA的关系,HBV DNA/HCV RNA与HIV RNA、CD4+ T淋巴细胞、CD8+ T淋巴细胞、CD4/CD8比值的相关性。结果 HIV/AIDS单纯感染组、HIV/HBV合并感染组及 HIV/HCV合并感染组的CD4+ T 淋巴细胞与各自组的HIV RNA呈负相关,差异有统计学意义(P<0.05);HIV/AIDS单纯感染组、HIV/HBV合并感染组的CD8+ T淋巴细胞与各自组的HIV RNA呈负相关,差异有统计学意义(P<0.05);HIV/AIDS单纯感染组、HIV/HBV合并感染组及 HIV/HCV合并感染组的CD4/CD8与各自组的HIV RNA呈负相关,差异有统计学意义(P<0.05)。结论合并感染 HBV后,HIV/AIDS患者T细胞的数量下降更明显,致HIV RNA、HBV DNA高载量,加速了 HIV病情进展;感染 HBV后CD4+ T细胞的数量下降比感染HCV更明显。%Objective To explore the viral load levels after HIV/AIDS merges HBV/HCV infection and its relationship with T lymphocytes .Methods HIV RNA ,HBV DNA ,HCV RNA ,CD4+ T lymphocyte frequency ,CD8+ T lymphocyte frequency ,CD4/CD8 measured in HIV/AIDS simple infection group ,mixed HIV/HBV infection group and mixed HIV/HCV infection group .Ana‐lyze relationship of T lymphocyte and HIV RNA ,the correlation of HBV DNA/HCV RNA ,HIV RNA ,CD4+ T lymphocyte fre‐quency ,CD8+ T lymphocyte frequency ,CD4/CD8 .Results CD4+ T lymphocyte frequency of HIV/AIDS simple infection group , mixed HIV/HBV infection group and mixed HIV/HCV infection group showed negative correlated with their respective

  18. Characterization of hepatitis C virus intergenotypic recombinant strains and associated virological response to sofosbuvir/ribavirin

    NARCIS (Netherlands)

    Hedskog, C.; Doehle, B.; Chodavarapu, K.; Gontcharova, V.; Crespo Garcia, J.; Knegt, R.; Drenth, J.P.H.; McHutchison, J.G.; Brainard, D.; Stamm, L.M.; Miller, M.D.; Svarovskaia, E.; Mo, H.

    2015-01-01

    To date, intergenotypic recombinant hepatitis C viruses (HCVs) and their treatment outcomes have not been well characterized. This study characterized 12 novel HCV recombinant strains and their response to sofosbuvir in combination with ribavirin (SOF/RBV) treatment. Across the phase II/III studies

  19. Antiviral effect of ribavirin and acyclic nucleosid phosphonates against Radish mosaic virus

    OpenAIRE

    VOZÁBOVÁ, Tereza

    2010-01-01

    Evaluation of the antiviral effectiveness of ribavirin and acyclic nucleotide phosphonates to radish mosaic virus. Virus inoculation of plants with RaMV and immunological assay of the virus by ELISA. Subsequent application of antiviral agents and monitoring relative content of the virus in plants. Subsequent processing of data in tables and graphs, and then statistical evaluation.

  20. Production of Brugmansia plants free of Colombian datura virus by in vitro ribavirin chemotherapy

    Science.gov (United States)

    Brugmansia x candida Pers ‘Creamsickle’ plants produced by in vitro treatment with ribavirin, and no thermal therapy, remained polymerase chain reaction (PCR-) negative for Columbian datura virus (CDV) after one year. The plants were produced by establishing B. x candida ‘Creamsickle’ shoot cultures...

  1. Boceprevir, peginterferon and ribavirin for acute hepatitis C in HIV infected patients

    NARCIS (Netherlands)

    Hullegie, Sebastiaan J.; Claassen, Mark A. A.; van den Berk, Guido E. L.; Van der Meer, Jan T. M.; Posthouwer, Dirk; Lauw, Fanny N.; Leyten, Eliane M. S.; Koopmans, Peter P.; Richter, Clemens; van Eeden, Arne; Bierman, Wouter F. W.; Newsum, Astrid M.; Arends, Joop E.; Rijnders, Bart J. A.

    2016-01-01

    Background & Aims: Acute hepatitis C virus infections (AHCV) are prevalent among HIV positive men having sex with men and generally treated with pegylated interferon-alpha (PegIFN) and ribavirin (RBV) during 24 weeks. The addition of a protease inhibitor could shorten therapy without loss of efficac

  2. Predictive factors for interferon and ribavirin combination therapy in patients with chronic hepatitis C

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    AIM: To confirm the predictive factors for interferon (IFN)-α and ribavirin combination therapy for chronic hepatitis patients with hepatitis C virus (HCV) genotype 1b.METHODS: HCV RNA from 50 patients infected with HCV genotype 1b was studied by cloning and sequencing of interferon sensitivity determining region (ISDR), PKR-eIF2α phosphorylation homology domain (PePHD).Patients were treated with IFN-α and ribavirin for 6 mo and grouped by effectiveness of the therapy. A variety of factors were analyzed.RESULTS: Our data showed that age, HCV RNA titer,and ISDR type could be used as the predictive factors for combined IFN-α and ribavirin efficacy. Characteristically,mutations in PePHD appeared only when the combination therapy was effective. Other factors, such as sex and alanine aminotransferase (ALT) level, were not related to its efficacy. Adjusting for age and HCV RNA titer indicated that the ISDR type was the most potent predictive factor.CONCLUSION: HCV RNA ISDR type is an important factor for predicting efficacy of IFN-α and ribavirin combination therapy in Korean patients.

  3. Retreatment of hepatitis C non-responsive to Interferon. A placebo controlled randomized trial of Ribavirin monotherapy versus combination therapy with Ribavirin and Interferon in 121 patients in the Benelux [ISRCTN53821378

    Directory of Open Access Journals (Sweden)

    Delwaide Jean

    2003-08-01

    Full Text Available Abstract Background Evidence based medicine depends on unbiased selection of completed randomized controlled trials. For completeness it is important to publish all trials. This report describes the first large randomised controlled trial where combination therapy was compared to placebo therapy and to ribavirin monotherapy, which has not been published untill now. Methods One hundred and twenty one patients with chronic hepatitis C and elevated transaminases who did not respond to previous treatment with standard interferon monotherapy, were included from 16 centers in Belgium, the Netherlands and Luxembourg between 1992 and 1996. Patient poor-response characteristics were: genotype 1 (69%, HCV RNA above 2 × 106 copies/ml (55% and cirrhosis (38%. Patients were randomized to 6 months combination therapy with interferon alpha-2b (3 MU tiw and ribavirin (1000–1200 mg / day, 6 months ribavirin monotherapy (1000–1200 mg / day or 6 months ribavirin placebo. The study was double blinded for the ribavirin / placebo component. One patient did not fit the entry criteria, and 3 did not start. All 117 patients who received at least one dose of treatment were included in the intention to treat analysis. Results At the end of treatment, HCV RNA was undetectable in 35% of patients on combination therapy and in none of the patients treated with ribavirin monotherapy or placebo. The sustained virological response rate at 6 months after therapy was 15% for patients treated with interferon and ribavirin. During the 6 months treatment period 13% of patients on interferon ribavirin combination therapy, 13% of patients on ribavirin monotherapy and 11% of patients on placebo withdrew due to side effects or noncompliance. At 24 weeks of treatment the mean Hb level was 85% of the baseline value, which means a mean decrease from 9.1 mmol/l to 7.8 mmol/l. The Hb levels at the end of treatment were not significantly different from patients treated with ribavirin

  4. Ribavirin enhances the action of interferon-α against hepatitis C virus by promoting the p53 activity through the ERK1/2 pathway.

    Directory of Open Access Journals (Sweden)

    Wei-Liang Liu

    Full Text Available BACKGROUND/AIMS: Ribavirin significantly enhances the antiviral response of interferon-α (IFN-α against Hepatitis C virus (HCV, but the underlying mechanisms remain poorly understood. Recently, p53 has been identified as an important factor involving the suppression of HCV replication in hepatocytes. We, therefore, decided to investigate whether and how ribavirin inhibits the replication of HCV by promoting the activity of p53. METHODS: HepG2 and HCV replicons (JFH1/HepG2 were utilized to study the relationship between ribavirin and p53. The effect of ribavirin on cell cycles was analyzed by flow cytometry. The activation of p53 and the signaling pathways were determined using immunoblotting. By knocking down ERK1/ERK2 and p53 utilizing RNA interference strategy, we further assessed the role of ERK1/2 and p53 in the suppression of HCV replication by ribavirin in a HCV replicon system. RESULTS: Using HepG2 and HCV replicons, we demonstrated that ribavirin caused the cell cycle arrest at G1 phase and stabilized and activated p53, which was associated with the antiviral activity of ribavirin. Compared to either ribavirin or IFN-α alone, ribavirin plus IFN-α resulted in greater p53 activation and HCV suppression. We further identified ERK1/2 that linked ribavirin signals to p53 activation. More importantly, knockdown of ERK1/2 and p53 partially mitigated the inhibitory effects of ribavirin on the HCV replication, indicating that ERK1/2-p53 pathway was involved in the anti-HCV effects of ribavirin. CONCLUSION: Ribavirin stimulates ERK1/2 and subsequently promotes p53 activity which at least partly contributes to the enhanced antiviral response of IFN-α plus ribavirin against HCV.

  5. Impact of ribavirin dosage in chronic hepatitis C patients treated with simeprevir, pegylated interferon plus ribavirin combination therapy.

    Science.gov (United States)

    Tahata, Yuki; Hiramatsu, Naoki; Oze, Tsugiko; Urabe, Ayako; Morishita, Naoki; Yamada, Ryoko; Yakushijin, Takayuki; Hosui, Atsushi; Oshita, Masahide; Kaneko, Akira; Hagiwara, Hideki; Mita, Eiji; Ito, Toshifumi; Yamada, Yukinori; Inada, Masami; Katayama, Kazuhiro; Tamura, Shinji; Imai, Yasuharu; Hikita, Hayato; Sakamori, Ryotaro; Yoshida, Yuichi; Tatsumi, Tomohide; Hayashi, Norio; Takehara, Tetsuo

    2016-10-01

    The factors associated with sustained virologic response (SVR) in chronic hepatitis C (CH-C) genotype 1 patients treated with simeprevir (SMV), pegylated interferon (Peg-IFN) plus ribavirin (RBV) triple therapy have not been fully investigated. Two hundred and twenty-nine treatment-naïve CH-C patients treated with SMV triple therapy were enrolled in this study. The overall SVR rate was 87% in per-protocol analysis. In multivariate analysis, the interleukin (IL) 28B genotype (rs8099917, TT vs. non-TT, odds ratio [OR]: 0.044, P = 0.001) and RBV dose (< 10/10-12/ ≥ 12 mg/kg/day, OR: 4.513, P = 0.041) were significant factors associated with SVR. In patients with the IL28B non-TT genotype, RBV dose affected SVR dose-dependently in stratified analysis of RBV dose (P = 0.015); it was 44% (8/18) for patients administered <10 mg/kg/day of RBV, 78% (14/18) for those administered 10-12 mg/kg/day of RBV, and 100% (3/3) for those administered ≥12 mg/kg/day of RBV, whereas in patients with the IL28B TT genotype, a significant correlation between SVR and RBV dose was not observed (P = 0.229). Regarding RBV dose reduction of less than 10 mg/kg/day, the inosine triphosphate pyrophosphatase (ITPA) genotype (rs1127354, CC vs. non-CC, OR: 0.239, P = 0.003) and age (by 1 y.o., OR: 1.084, P = 0.002) were significant independent factors. RBV dosage affected SVR dose-dependently in patients with the IL28B non-TT genotype treated with SMV triple therapy. Special attention to anemia progression and RBV dosage should be paid to aged patients with the ITPA CC genotype. J. Med. Virol. 88:1776-1784, 2016. © 2016 Wiley Periodicals, Inc.

  6. Sofosbuvir Inhibits Hepatitis E Virus Replication In Vitro and Results in an Additive Effect When Combined With Ribavirin.

    Science.gov (United States)

    Dao Thi, Viet Loan; Debing, Yannick; Wu, Xianfang; Rice, Charles M; Neyts, Johan; Moradpour, Darius; Gouttenoire, Jérôme

    2016-01-01

    Infection with hepatitis E virus genotype 3 may result in chronic hepatitis in immunocompromised patients. Reduction of immunosuppression or treatment with ribavirin or pegylated interferon-α can result in viral clearance. However, safer and more effective treatment options are needed. Here, we show that sofosbuvir inhibits the replication of hepatitis E virus genotype 3 both in subgenomic replicon systems as well as a full-length infectious clone. Moreover, the combination of sofosbuvir and ribavirin results in an additive antiviral effect. Sofosbuvir may be considered as an add-on therapy to ribavirin for the treatment of chronic hepatitis E in immunocompromised patients.

  7. In vitro antiviral efficacy of ribavirin against feline calicivirus, feline viral rhinotracheitis virus, and canine parainfluenza virus.

    Science.gov (United States)

    Povey, R C

    1978-01-01

    Ribavirin had marked in vitro activity against feline calcivirus, strain 255, and canine parainfluenza virus, but showed only slight antiviral effect on feline viral rhinotracheitis virus. Antiviral activity was manifested by partial to complete suppression of viral cytopathic effect and of viral replication, depending on concentration of ribavirin in the culture medium and dosage of viral inoculum. Concentrations of ribavirin as small as 3.2 microgram/ml and 1.0 microgram/ml showed some activity against feline calcivirus and canine parainfluenza virus, respectively.

  8. Significance of hepatic arterial responsiveness for adequate tissue oxygenation upon portal vein occlusion in cirrhotic livers.

    Science.gov (United States)

    Mücke, I; Richter, S; Menger, M D; Vollmar, B

    2000-11-01

    We investigated sinusoidal blood flow and hepatic tissue oxygenation during portal vein occlusion in cirrhotic rat livers to examine the effect of cirrhosis on the properties of hepatic microvascular blood flow regulation. After 8 weeks of CCl4/phenobarbital sodium treatment to induce cirrhosis Sprague-Dawley rats were prepared surgically to allow assessment of portal venous and hepatic arterial inflow using miniaturized flow probes with simultaneous analysis of hepatic microcirculation and tissue oxygenation by fluorescence microscopy and polarographic oxymetry. Age-matched noncirrhotic animals served as controls. Upon portal vein occlusion in cirrhotic livers (flow reduction to portal vein occlusion did not cause a deterioration in hepatic tissue pO2 (11 +/- 3 vs. 10 +/- 3 mmHg at baseline). Sinusoidal diameters were found unchanged, disproving a major role of the sinusoidal tone in the regulation of HABR. Microvascular response of cirrhotic livers did not generally differ from that in noncirrhotic livers upon portal inflow restriction. We conclude that HABR in cirrhotic livers operates sufficiently to meet the liver tissue oxygen demand, most probably by an increased relative contribution of arterial perfusion of hepatic sinusoids.

  9. Non-variceal upper gastrointestinal bleeding in cirrhotic patients in Nile Delta.

    Science.gov (United States)

    Gabr, Mamdouh Ahmed; Tawfik, Mohamed Abd El-Raouf; El-Sawy, Abd Allah Ahmed

    2016-01-01

    Acute upper gastrointestinal bleeding (AUGIB) in cirrhotic patients occurs mainly from esophageal and gastric varices; however, quite a large number of cirrhotic patients bleed from other sources as well. The aim of the present work is to determine the prevalence of non-variceal UGIB as well as its different causes among the cirrhotic portal hypertensive patients in Nile Delta. Emergency upper gastrointestinal (UGI) endoscopy for AUGIB was done in 650 patients. Out of these patients, 550 (84.6%) patients who were proved to have cirrhosis were the subject of the present study. From all cirrhotic portal hypertensive patients, 415 (75.5%) bled from variceal sources (esophageal and gastric) while 135 (24.5%) of them bled from non-variceal sources. Among variceal sources of bleeding, esophageal varices were much more common than gastric varices. Peptic ulcer was the most common non-variceal source of bleeding. Non-variceal bleeding in cirrhosis was not frequent, and sources included peptic ulcer, portal hypertensive gastropathy, and erosive disease of the stomach and duodenum.

  10. The effect of oral testosterone on serum TBG levels in alcoholic cirrhotic men

    DEFF Research Database (Denmark)

    Becker, U; Gluud, C; Bennett, Patrick

    1988-01-01

    , it is demonstrated that testosterone treatment significantly reduced TBG concentrations in cirrhotic men with preserved liver function, like normal men, but not in patients with moderate liver dysfunction. The lack of effect of testosterone in patients with more advanced cirrhosis may be due to a decreased function...

  11. Hepatic venous oxygen content in alcoholic cirrhosis and non-cirrhotic alcoholic liver disease

    DEFF Research Database (Denmark)

    Bendtsen, F; Henriksen, Jens Henrik Sahl; Widding, A

    1987-01-01

    Blood gas analyses and hepatic blood flow were determined during hepatic vein catheterization in order to establish a possible hypoxic component in alcoholic liver disease. Fifty-six patients (9 non-cirrhotic liver disease, 14 cirrhosis Child-Turcotte class A, 23 class B, 10 class C) and 10 control...

  12. Increase of Serum gamma-Glutamyltransferase Associated With Development of Cirrhotic Cystic Fibrosis Liver Disease

    NARCIS (Netherlands)

    Bodewes, Frank A. J. A.; van der Doef, Hubert P. J.; Houwen, Roderick H. J.; Verkade, Henkjan J.

    2015-01-01

    Background:Identification of patients at risk for developing cirrhotic cystic fibrosis liver disease (CCFLD) is essential for targeting potentially preventive treatment. We studied the evolution of serum liver enzymes and thrombocyte counts as predictors of CCFLD development.Methods:For this study,

  13. Effects of lactulose on intestinal endotoxin and bacterial translocation in cirrhotic rats

    Institute of Scientific and Technical Information of China (English)

    张顺财; 王唯; 任卫英; 戴茜; 贺伯明; 周康

    2003-01-01

    Objective To investigate the effects of lactulose on intestinal bacterial overgrowth (IBO), bacterial translocation (BT), intestinal transit and permeability in cirrhotic rats. Methods BT in all animals was assessed by bacterial culture of mesenteric lymph node (MLN), liver and spleen, and IBO was assessed by a jejunal bacterial count of the specific organism. Intestinal permeability was determined by the 24-hour urinary 99mTc-diethylenetriaminepentaacetate (99mTc-DTPA) excretion, and intestinal transit was determined by measuring the distribution of 51 Cr in the intestine. Results BT and IBO were found in 48% and 80% of the cirrhotic rats, respectively, while not in the control rats. Cirrhotic rats with IBO had significantly higher levels of intestinal endotoxin higher rates of bacterial translocation, shorter intestinal transit time and higher intestinal permeability than those without IBO. It was also found that BT was closely associated with IBO and injury of the intestinal barrier. Compared with the placebo group, lactulose-treated rats had lower rates of BT and IBO, which was closely associated with increased intestinal transit and improved intestinal permeability by lactulose. Conclusions Our study indicate that endotoxin and bacterial translocation in cirrhotic rats may attribute to IBO and increased intestinal permeability. Lactulose that accelerates intestinal transit and improves intestinal permeability might be helpful in preventing intestinal bacterial and endotoxin translocation.

  14. 维持性血液透析患者乙型肝炎和丙型肝炎病毒感染临床调查分析%Clinical investigation and analysis in maintenance hemodialysis patients with HBV and HCV infection

    Institute of Scientific and Technical Information of China (English)

    汪虹伶; 彭洪泉; 林婉萍; 颜雅怡

    2012-01-01

    Objective To analyze the maintenance hemodialysis patients complicated with hepatitis B virus (HBV) and hepatitis C virus (HCV) infection. Methods Retrospective analysis was used for maintenance hemodialysis patients and clinical data over three months in Kiang Wu Hospital from February 1985 to December 2010 were collected. Results Among the total 1155 cases , HBV-positive were 83 cases (7.18%), pre-dialysis H BV-positive were 77 cases (6.66%), 6 cases (0.57%) were positive after dialysis .The total number of HCV-positive were 59 patients (5.10% ). However, the HCV positive in pre-dialysis group was 38 cases (3.29%), 21 patients (2.01%) were positive after dialysis. The post-dialysis infection prevalence was significantly lower than that in the pre-dialysis infection (P < 0.05). Hepatitis virus infection in post-dialysis are common, particularly for HCV infection. As to HBV infection, it was uncommon to catch hepatitis B virus infection with hemodialysis. Among the whole infected group,there were seven cases of HBV-positive cases turning to negative, 2 HCV-positive cases turning to negative . Conclusion With strict and effective separation measures, widespread use of erythropoietin, and the use of disposable dialyzers , HBV and HCV infection can be effectively controlled under hemodialysis setting.%目的 调查分析维持性血液透析患者乙型肝炎病毒(HBV)及丙型肝炎病毒(HCV)的感染情况.方法 回顾性分析镜湖医院1985年2月~2010年12月期间维持性血液透析3个月以上患者的临床数据,调查分析肝炎病毒感染的情况.结果 1155例患者,HBV阳性总数83例(7.18%),其中原有感染阳性者77例(6.66%),透析后感染阳性者6例(0.57%);HCV阳性总数59例(5.10%),其中原有感染阳性者38例(3.29%),透析后感染阳性者21例(2.01%).透析后感染率明显低于原有感染率( P<0.05).透析后肝炎病毒感染,尤以HCV的感染多见,而HBV的感染则少见.原有感染组中,有7

  15. The Possible Role of Nitric Oxide and Oxidative Stress in the Enhanced Apoptosis of Cardiac Cells in Cirrhotic Rats

    Directory of Open Access Journals (Sweden)

    Hamed Shafaroodi

    2017-02-01

    Full Text Available  Cirrhosis has been related with hyperdynamic circulation, manifesting as increased cardiac output and decreased systemic vascular resistance. In the present study we examined the cirrhosis outcome on apoptosis of rat hearts. We also tried to explore the role of nitric oxide (NO and oxidative stress in the probable changed apoptosis of cirrhotic hearts. Twenty eight days after ligation of bile duct, heart tissues were tested for apoptosis. The extent of malondialdehyde (MDA, and the activities of catalase (CAT, glutathione peroxidase (GSHPx and superoxide dismutase (SOD have been calculated in heart tissues. The cirrhotic hearts exhibited structural defects and greater apoptosis. Chronic treatment of cirrhotic rats with L-NAME, a non-selective inhibitor of NO synthase, inhibited heart structural defects and reduced apoptosis of hearts. We also showed that cirrhotic rat hearts had an enhanced level of MDA and reduced activities of CAT, GSHPx and SOD. When the animals were treated by L-NAME chronically, the MDA level reduced and activities of CAT, GSHPx and SOD augmented in cirrhotic heart. In conclusion, increased apoptosis of cirrhotic hearts probably happen due to NO overproduction and increased oxidative stress in hearts of cirrhotic rats.

  16. HGF, MET, and matrix-related proteases in hepatocellular carcinoma, fibrolamellar variant, cirrhotic and normal liver.

    Science.gov (United States)

    Schoedel, Karen E; Tyner, Valerie Zajac; Kim, Tae-Hyoung; Michalopoulos, George K; Mars, Wendy M

    2003-01-01

    Fibrolamellar variant is an uncommon subcategory of hepatocellular carcinoma with a better prognostic outcome. Proteinases and growth factors that are involved in the remodeling of extracellular matrix may influence the behavior of cancers. To determine whether these factors contribute to the distinct etiologies of fibrolamellar hepatocellular carcinoma and traditional hepatocellular carcinoma, we assayed hepatocyte growth factor, the hepatocyte growth factor receptor, and two hepatocyte growth factor activators, hepatocyte growth factor activator and urokinase-type plasminogen activator, in hepatocellular carcinoma, fibrolamellar hepatocellular carcinoma, cirrhotic liver and normal liver. In addition, we examined the urokinase-type plasminogen activator receptor, the type 1 plasminogen activator inhibitor, plasmin, fibrinogen, and the type IV matrix metalloproteinases. Eighteen hepatocellular carcinomas and 11 fibrolamellar hepatocellular carcinomas were obtained as paraffin embedded sections from the University of Pittsburgh Department of Pathology. Frozen tissues from a subset of cases (9 hepatocellular carcinomas, 4 fibrolamellar hepatocellular carcinomas, 12 cirrhotic livers and 2 normal livers) were also available for analysis. Antibodies against urokinase-type plasminogen activator, urokinase-type plasminogen activator receptor, hepatocyte growth factor and hepatocyte growth factor receptor were used to analyze immunoperoxidase stained slides from the paraffin blocks. Western blot analyses using antibodies against hepatocyte growth factor, hepatocyte growth factor receptor, phosphotyrosine, hepatocyte growth factor activator, urokinase-type plasminogen activator receptor, urokinase-type plasminogen activator, plasminogen activator inhibitor-1, fibrinogen and plasmin were performed on membrane-enriched fractions from the frozen tissue, as was collagen zymography for matrix metalloproteinase-2 and matrix metalloproteinase-9. The most notable findings are as

  17. Exploration of laboratory animal standard of domesticated and bred Tupaia belangeri and construction of a technology platform of a Tupaia belangeri model of hepatitis C virus (HCV) infection%树鼩驯养繁殖实验动物标准及丙型肝炎动物模型技术平台建设的探讨

    Institute of Scientific and Technical Information of China (English)

    孙晓梅; 夏雪山; 代解杰

    2011-01-01

    At present, the Tupaia belangeri used for biomedical studies is mainly sourced from wild field capture.Due to the variation of interindividual differences, there are still some shortages in the homogeneity and the repeatability of experiments on those animals. There are problems demanding prompt solution on a series of basic scientific questions such as the management, critical techniques for breeding and the animal quality control standard in Tupaia belangeri. A lot of researches have reported that the Tupaia belangeri has a huge exploitation potential on the liver disease research compared with other laboratory animals. In the studies of animal models of hepatitis, there are problems need to be solved promptly on the cell culture system of HCV (hepatitis C virus), the infection dosage and route of HCV infection, the RNA, the antibody and the pathological examination after HCV infection in vivo and in vitro, and also how to evaluate the animal model.This paper will briefly discuss the above mentioned questions, in order to provide a scientific basis for implementing experimental animalization and the use of the Tupaia belangeri in HCV disease studies.%目前用于生物医学研究的树鼩大多数来源于野生捕获,由于个体间的差异较大,其实验结果的均匀性和可重复性较差,亟待解决树鼩人工饲养设施条件、繁殖关键技术、动物质量标准等一系列基础科学问题.许多文献报道了树鼩与其他实验动物比较,在肝病研究中具有巨大的开发应用潜力,在丙型肝炎动物模型研究中,亟待解决丙型肝炎病毒(HCV)细胞培养体系、HCV病毒感染剂量与感染途径、HCV病毒对树鼩体外、体内感染后病毒核酸检测、抗体检测和病理检测等技术方法的建立及动物模型评价标准问题.本文就上述问题系统性地进行初步报道,旨在为树鼩早日实现实验动物化和丙型肝炎疾病研究中应用提供科学依据.

  18. Renal failure after upper-gastrointestinal bleeding among cirrhotic patients in Upper Egypt.

    Science.gov (United States)

    Makhlouf, Nahed A; Morsy, Khairy H

    2012-09-01

    Renal dysfunction is a common and serious problem in patients with advanced liver disease. The study aims to assess the incidence, risk factors and short-term prognosis of renal failure after upper-gastrointestinal bleeding among cirrhotic patients in Upper Egypt. We recruited 159 cirrhotic patients with 168 episodes of upper-gastrointestinal bleeding from Tropical Medicine and Gastroenterology Department, Assiut University Hospital. For all participants, the following were conducted: clinical evaluation, abdominal ultrasonography (US) examination, laboratory investigations and upper endoscopy. Risk factors of renal failure were identified using univariate, then multivariate analysis. The incidence of renal failure among bleeding episodes was 28%. Higher risk of renal failure among cirrhotic patients with upper-gastrointestinal bleeding was observed with shock (odds ratio (OR) 0.171, 95% confidence interval (CI) 0.047:0.624), bacterial infection (OR 0.310, 95% CI 107:897), Child-Pugh class C (OR 2.79, 95% CI 1.018:7.62), higher serum bilirubin (OR 0.122, 95% CI 0.000:0.002), lower serum albumin (OR -0.188, 95% CI -0.288:-0.056) and raised baseline blood urea (OR 0.181, 95% CI 0.003:0.017) and serum creatinine (OR 0.533, 95% CI 0.002:0.004). Mortality among patients with renal failure was 31.9%. Renal failure is a frequent event among cirrhotic patients with upper-gastrointestinal bleeding and there are many contributing factors for its development. Mortality is relatively high among patients with renal failure in cirrhotics with upper-gastrointestinal bleeding. Copyright © 2012 Arab Journal of Gastroenterology. Published by Elsevier Ltd. All rights reserved.

  19. Identifying minimal hepatic encephalopathy in cirrhotic patients by measuring spontaneous brain activity.

    Science.gov (United States)

    Chen, Hua-Jun; Zhang, Ling; Jiang, Long-Feng; Chen, Qiu-Feng; Li, Jun; Shi, Hai-Bin

    2016-08-01

    It has been demonstrated that minimal hepatic encephalopathy (MHE) is associated with aberrant regional intrinsic brain activity in cirrhotic patients. However, few studies have investigated whether altered intrinsic brain activity can be used as a biomarker of MHE among cirrhotic patients. In this study, 36 cirrhotic patients (with MHE, n = 16; without MHE [NHE], n = 20) underwent resting-state functional magnetic resonance imaging (fMRI). Spontaneous brain activity was measured by examining the amplitude of low-frequency fluctuations (ALFF) in the fMRI signal. MHE was diagnosed based on the Psychometric Hepatic Encephalopathy Score (PHES). A two-sample t-test was used to determine the regions of interest (ROIs) in which ALFF differed significantly between the two groups; then, ALFF values within ROIs were selected as classification features. A linear discriminative analysis was used to differentiate MHE patients from NHE patients. The leave-one-out cross-validation method was used to estimate the performance of the classifier. The classification analysis was 80.6 % accurate (81.3 % sensitivity and 80.0 % specificity) in terms of distinguishing between the two groups. Six ROIs were identified as the most discriminative features, including the bilateral medial frontal cortex/anterior cingulate cortex, posterior cingulate cortex/precuneus, left precentral and postcentral gyrus, right lingual gyrus, middle frontal gyrus, and inferior/superior parietal lobule. The ALFF values within ROIs were correlated with PHES in cirrhotic patients. Our findings suggest that altered regional brain spontaneous activity is a useful biomarker for MHE detection among cirrhotic patients.

  20. Evaluation of Zinc Plasma Level in Iranian Cirrhotic Patients due to Hepatitis B and Hepatitis C

    Directory of Open Access Journals (Sweden)

    Mohammad Reza Zali

    2010-01-01

    Full Text Available Background and Aims: Zinc (Zn has various significant roles in physiological functions of the liver. Furthermore, it has been reported that the administration of zinc has an important role in pharmacotherapy of viral hepatitis. Cirrhotic patients with decrease in plasma zinc level have been covered in previous studies. It is seemingly necessary to assess the zinc level, in Iranian cirrhotic patients, as a distinct population, Because of the large phytate amounts in Iranians diet. Regarding to etiology, disease progress, and treatment, there are some differences in the 2 most common causes of cirrhosis in the Iranian population (hepatitis B and hepatitis C and it is possible that the zinc level may be different between the two. This study was done to shadow some lights on the subject. Methods: Between April 2008 and November 2008, plasma zinc level was determined, by atomic absorption method, in 60 cirrhotic inpatients treated due to hepatitis B or hepatitis C in Talighani hospital (a referral center for gastrointestinal and liver diseases in Tehran, Iran. Results: Mean ± standard deviation (SD plasma zinc levels determined 0.34±0.22 mg/L and 0.37±0.22 mg/L in hepatitis B and hepatitis C patients respectively. Analysis of t-test showed there is no significant difference between 2 groups regarding to plasma zinc level (P = 0.745.Conclusions: It is concluded that zinc level of studied cirrhotic patients is less than half of the normal range. Moreover, there is no difference in plasma zinc level between cirrhotic patients due to hepatitis B or hepatitis C. Regarding to this result, supplementation with complementary zinc, may be recommended in both groups in order to optimize the nutritional support and probably better the treatment response.

  1. Bleeding after invasive procedures is rare and unpredicted by platelet counts in cirrhotic patients with thrombocytopenia.

    Science.gov (United States)

    Napolitano, Grazia; Iacobellis, Angelo; Merla, Antonio; Niro, Grazia; Valvano, Maria Rosa; Terracciano, Fulvia; Siena, Domenico; Caruso, Mariangela; Ippolito, Antonio; Mannuccio, Pier Mannucci; Andriulli, Angelo

    2017-03-01

    In cirrhotics with low circulating platelets (PLT), restoration of normal cell counts has been traditionally recommended before invasive procedures. However, there is neither consensus on the PLT transfusion threshold nor evidence of its clinical efficacy. In order to fill this gap of knowledge, we prospectively collected and analyzed data on circulating PLT counts [and International Normalized Ratio (INR)] values in a case series of 363 cirrhotics scheduled to undergo invasive investigations. PLT and/or fresh-frozen plasma (FFP) units were infused at the discretion of the attending physician, and the occurrence of post-procedural bleeding was related to pre-and post-infusion results. 852 Procedures were carried out in 363 cirrhotics sub-grouped according to the Child-Pugh-Turcotte (CPT) classification (class A/B/C: 124/154/85). The infusion of PLT and/or FFP improved only marginally circulating PLT counts and INR values. Ten post-procedural bleeds occurred in the whole case series, i.e. 1 episode every 85 procedures or every 36 patients. Post-procedural bleeding was unrelated to the PLT counts, to the degree of INR abnormalities, nor to the CPT classes, but was more frequent in patients who underwent repeated investigations. In the 10 patients with the most profound alterations in PLT and/or INR values, no post-procedural bleeding occurred. In cirrhotic patients with low PLT and/or abnormal INR values undergoing invasive investigations, post-procedural bleeding was rare and unpredicted by PLT counts or abnormal INR values. In particular, the recommendation to infuse platelets when counts are <50×10(3)/L is not substantiated by this case series of cirrhotic patients. Copyright © 2016. Published by Elsevier B.V.

  2. Role of the heme oxygenases in abnormalities of the mesenteric circulation in cirrhotic rats.

    Science.gov (United States)

    Sacerdoti, David; Abraham, Nader G; Oyekan, Adebayo O; Yang, Liming; Gatta, Angelo; McGiff, John C

    2004-02-01

    Carbon monoxide (CO), a product of heme metabolism by heme-oxygenase (HO), has biological actions similar to those of nitric oxide (NO). The role of CO in decreasing vascular responses to constrictor agents produced by experimental cirrhosis induced by carbon tetrachloride was evaluated before and after inhibition of HO with tin-mesoporphyrin (SnMP) in the perfused superior mesenteric vasculature (SMV) of cirrhotic and normal rats and in normal rats transfected with the human HO-1 (HHO-1) gene. Perfusion pressure and vasoconstrictor responses of the SMV to KCl, phenylephrine (PE), and endothelin-1 (ET-1) were decreased in cirrhotic rats. SnMP increased SMV perfusion pressure and restored the constrictor responses of the SMV to KCl, PE, and ET-1 in cirrhotic rats. The relative roles of NO and CO in producing hyporeactivity of the SMV to PE in cirrhotic rats were examined. Vasoconstrictor responses to PE were successively augmented by stepwise inhibition of CO and NO production, suggesting a complementary role for these gases in the regulation of reactivity of the SMV. Expression of constitutive but not of inducible HO (HO-1) was increased in the SMV of cirrhotic rats as was HO activity. Administration of adenovirus containing HHO-1 gene produced detection of HHO-1 RNA and increased HO activity in the SMV within 7 days. Rats transfected with HO-1 demonstrated reduction in both perfusion pressure and vasoconstrictor responses to PE in the SMV. We propose that HO is an essential component in mechanisms that modulate reactivity of the mesenteric circulation in experimental hepatic cirrhosis in rats.

  3. Pegylated interferon/ribavirin-associated sudden hearing loss in a patient with chronic hepatitis C in Brazil

    Directory of Open Access Journals (Sweden)

    Maria Cassia Jacintho Mendes-Corrêa

    Full Text Available Sudden hearing loss is defined as a sensorineural hearing loss, equal to or greater than 30 dB, at three or more consecutive frequencies, which takes place within 72 hours. Both peginterferon and ribavirin are well-known to be associated with significant adverse effects, but sudden hearing loss is uncommon. We report a 65-year-old male patient who developed sudden-onset hearing loss during combination therapy with pegylated interferon-alpha and ribavirin for chronic hepatitis C. Peginterferon and ribavirin may cause sudden hearing loss that may not recover after discontinuation of therapy. Immediate treatment for all possible etiologies is essential, along with targeted investigations and early referral for an Ear, Nose and Throat specialist. Physicians should be aware of the possible ototoxic effects of peginterferon and ribavirin combination therapy requiring appropriate surveillance.

  4. Pegylated interferon/ribavirin-associated sudden hearing loss in a patient with chronic hepatitis C in Brazil

    Directory of Open Access Journals (Sweden)

    Maria Cassia Jacintho Mendes-Corrêa

    2011-02-01

    Full Text Available Sudden hearing loss is defined as a sensorineural hearing loss, equal to or greater than 30 dB, at three or more consecutive frequencies, which takes place within 72 hours. Both peginterferon and ribavirin are well-known to be associated with significant adverse effects, but sudden hearing loss is uncommon. We report a 65-year-old male patient who developed sudden-onset hearing loss during combination therapy with pegylated interferon-alpha and ribavirin for chronic hepatitis C. Peginterferon and ribavirin may cause sudden hearing loss that may not recover after discontinuation of therapy. Immediate treatment for all possible etiologies is essential, along with targeted investigations and early referral for an Ear, Nose and Throat specialist. Physicians should be aware of the possible ototoxic effects of peginterferon and ribavirin combination therapy requiring appropriate surveillance.

  5. Relapse of HCV Genotype 1b Infection After Sofosbuvir/Ledipasvir Treatment Presenting as De Novo Cryoglobulinemic Vasculitis

    Science.gov (United States)

    Moreno, Alan D.; Joseph, Nora; Kim, George; Fimmel, Claus J.

    2017-01-01

    Relapse of hepatitis C virus (HCV) genotype 1 infection after combination therapy with sofosbuvir and ledipasvir is unusual. We report a treatment-naïve, non-cirrhotic patient in whom the relapse of genotype 1b HCV infection was accompanied by de novo cryoglobulinemic vasculitis and glomerulonephritis, requiring hemodialysis for acute renal failure. Sequence analysis revealed several resistance-associated variants in the HCV NS5a gene but not in NS3/4A. The patient’s vasculitis was successfully treated with immunosuppression and plasmapheresis, followed by retreatment of HCV with a combination of sofosbuvir, simeprevir, and ribavirin. The patient achieved sustained virological response, recovered his renal function, and remains in remission from cryoglobulinemia. PMID:28184378

  6. The soluble mannose receptor is released from the liver in cirrhotic patients, but is not associated with bacterial translocation

    DEFF Research Database (Denmark)

    Laursen, Tea L; Rødgaard-Hansen, Sidsel; Møller, Holger J

    2016-01-01

    BACKGROUND & AIMS: Intestinal bacterial translocation is involved in activation of liver macrophages in cirrhotic patients. Macrophages play a key role in liver inflammation and are involved in the pathogenesis of cirrhosis and complications. Bacterial translocation may be determined by presence ...

  7. Assessment of tumor vascularization with functional computed tomography perfusion imaging in patients with cirrhotic liver disease

    Institute of Scientific and Technical Information of China (English)

    Jin-Ping Li; De-Li Zhao; Hui-Jie Jiang; Ya-Hua Huang; Da-Qing Li; Yong Wan; Xin-Ding Liu; Jin-E Wang

    2011-01-01

    BACKGROUND: Hepatocellular carcinoma (HCC) is a common malignant tumor in China, and early diagnosis is critical for patient outcome. In patients with HCC, it is mostly based on liver cirrhosis, developing from benign regenerative nodules and dysplastic nodules to HCC lesions, and a better understanding of its vascular supply and the hemodynamic changes may lead to early tumor detection. Angiogenesis is essential for the growth of primary and metastatic tumors due to changes in vascular perfusion, blood volume and permeability. These hemodynamic and physiological properties can be measured serially using functional computed tomography perfusion (CTP) imaging and can be used to assess the growth of HCC. This study aimed to clarify the physiological characteristics of tumor angiogenesis in cirrhoticliverdiseasebythisfastimagingmethod. METHODS: CTP was performed in 30 volunteers without liver disease (control subjects) and 49 patients with liver disease (experimental subjects: 27 with HCC and 22 with cirrhosis). All subjects were also evaluated by physical examination, laboratory screening and Doppler ultrasonography of the liver. The diagnosis of HCC was made according to the EASL criteria. All patients underwent contrast-enhanced ultrasonography, pre- and post-contrast triple-phase CT and CTP study. A mathematical deconvolution model was applied to provide hepatic blood flow (HBF), hepatic blood volume (HBV), mean transit time (MTT), permeability of capillary vessel surface (PS), hepatic arterial index (HAI), hepatic arterial perfusion (HAP) and hepatic portal perfusion (HPP) data. The Mann-Whitney U test was used to determine differences in perfusion parameters between the background cirrhotic liver parenchyma and HCC and between the cirrhotic liver parenchyma with HCC and that without HCC. RESULTS: In normal liver, the HAP/HVP ratio was about 1/4. HCC had significantly higher HAP and HAI and lower HPP than background liver parenchyma adjacent to the HCC. The

  8. Vascular endothelial growth factor attenuates hepatic sinusoidal capillarization in thioacetamide-induced cirrhotic rats

    Institute of Scientific and Technical Information of China (English)

    Hao Xu; Bao-Min Shi; Xiao-Fei Lu; Feng Liang; Xing Jin; Tai-Huang Wu; Jian Xu

    2008-01-01

    AIM: To investigate the effect of vascular endothelial growth factor (VEGF) transfection on hepatic sinusoidal capillarization.MEthODS: Enhanced green fluorescent protein (EGFP)/VEGF transfection was confirmed by immunofluorescencemicroscopy and immunohistoche-mistry both in primaryhepatocytes and in normal liven Cirrhotic rats weregenerated by thioacetamide (TAA) administration andthen divided into a treatment group, which receivedinjections of 400 μg of plasmid DNA encoding an EGFP-VEGF fusion protein, and a blank group, which receivedan equal amount of normal saline through the portalvein. The portal vein pressure was measured in the normal and cirrhotic state, in treated and blank groups.The average number of fenestrae per hepatic sinusoidwas determined using transmission electron microscopy(TEM), while the relative abundance of VEGF transcriptswas examined by Gene array.RESULTS: Green fluorescent protein was observed in the cytoplasms of liver cells under immunofluorescence microscopy 24 h after transfection with EGFP/VEGFplasmid in vitro. Staining with polyclonal antibodies against VEGF illustrated that hepatocytes expressed immunodetectable VEGF both in vitro and in vitro. There were significant differences in the number of fenestrae and portal vein pressures between normal and cirrhotic rats (7.40±1.71 vs 2.30± 2.26 and 9.32± 0.85 cmH2Ovs 27.92± 0.90 cmH2O1, P < 0.02), between cirrhotic and treated rats (2.30 + 1.16 cmH2O vs 4.60± 1.65 and 17.92± 0.90 cmH2O vs 15.52±0.93 cmH20, P < 0.05)and between the treatment group and the blank group (4.60±1.65 cmH20 vs 2.10 ± 1.10 cmH20 and 25.52 +0.93 cmH20 vs 17.26 ± 1.80 cmH20, P < 0.05). Gene-array analysis revealed that the relative abundance oftranscripts of VEGF family members decreased in the cirrhotic state and increased after transfection. CONCLUSION: Injection of a plasmid encoding VEGFthrough the portal vein is an effective method toinduce the formation of fenestrae and decrease portalvein

  9. The efficacy and safety of double (cepeginterferon alfa-2b and ribavirin and triple (simeprevir, cepeginterferon alfa 2b and ribavirin treatment regimens in chronic hepatitis C patients. The experience of everyday clinical practice

    Directory of Open Access Journals (Sweden)

    N. P. Blokhina

    2016-01-01

    Full Text Available The objective. To evaluate the efficacy, safety and tolerability of double (cepeginterferon alfa-2b and ribavirin and triple (simeprevir, cepeginterferon alfa 2b and ribavirin treatment regimens in chronic hepatitis C patients in everyday clinical practice of the Hepatology Center in Clinical Infectious Diseases Hospital in Moscow.Materials and methods. From 2013 to 2015 a total of 289 patients with chronic hepatitis C received antiviral therapy with cepeginterferon alfa 2b. 267 patients received combination of cepeginterferon alfa 2b and ribavirin. 22 patients received triple antiviral therapy with simeprevir, cepeginterferon alfa 2b and ribavirin. Treatment efficacy was assessed by the rate of sustained virologic response on 12/24 week after completion of antiviral therapy (SVR 12/24. In safety analysis all 289 patients were included. All cases of deterioration of the patient’s condition and laboratory abnormalities were registered throughout the treatment period and follow up.Results. 267 patients (74,5%, n=199, with 2/3 genotype, 25,5%, n = 68, with 1 genotype received cepeginterferon alfa 2b 1,5 µg/kg/week and ribavirin 800-1400 daily (weight based. 22 patients with genotype 1 (the majority of them had advanced fibrosis (F3-F4 underwent triple therapy with simeprevir 150 mg once daily in combination with cepeginterferon alfa 2b 1,5 µg/kg/week and ribavirin 800-1400 mg daily (weight based for 12 weeks, followed by cepeginterferon alfa 2b/ ribavirin therapy for 12-36 weeks. SVR was observed in 85,6% (n=113 of genotype 2/3 infected patients and in 64,6% (n=31 of genotype 1 infected patients. Among patients with mild or moderate fibrosis SVR rate was 90,7% in genotype 2/3 patients and 75% in genotype 1 patients. 21 patient completed the course of triple therapy. SVR was observed in 71,4% (n=15 of patients. Registered adverse reactions were common for interferon/ribavirin based therapy. In most cases adverse events were moderate and matched

  10. [Guidelines for diagnosis and management of cirrhotic ascites and its complications. The Israeli Association for the Study of the Liver].

    Science.gov (United States)

    Sikuler, Emanuel; Ackerman, Zvi; Braun, Marius; Baruch, Yaakov; Bruck, Refael; Safadi, Rifaat; Shlomai, Amir; Ben-Ari, Ziv

    2012-12-01

    Ascites is the most common manifestation of decompensated liver cirrhosis. The life expectancy of cirrhotic patients developing uncomplicated ascites is 50% for 3 years. Refractory ascites, electrolyte imbalance, hepato-renal syndrome and spontaneous bacterial peritonitis may develop. Successful treatment can improve symptoms and outcomes. This article summarizes the Israeli Association for the Study of the Liver guidelines for diagnosis and management of cirrhotic ascites and its complications.

  11. Pegylated Interferon (Alone or With Ribavirin for Chronic Hepatitis C in Haemodialysis Population

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    Mario Espinosa

    2015-05-01

    Full Text Available Background/Aims: Hepatitis C virus infection remains prevalent among patients undergoing long-term haemodialysis and has a detrimental impact on survival in this population. Antiviral therapy for chronic hepatitis C in haemodialysis patients is still a challenge to clinicians. The aim of the current study is to evaluate the efficacy and safety of therapy with pegylated interferon, alone or combined with ribavirin, for chronic hepatitis C among patients undergoing long-term hemodialysis. Methods: We conducted a retrospective, multicenter cohort trial with monotherapy (pegylated interferon (n=21 or combined antiviral therapy (pegylated interferon plus ribavirin (n=5 for chronic hepatitis C in patients undergoing long-term haemodialysis. Results: Sustained virological response was obtained in eleven (42% patients. Seven (26.9% patients interrupted prematurely the antiviral treatment due to serious side-effects, the most frequent cause of treatment withdrawal being hematological (n=3. HCV RNA load was lower in responder than non-responder patients, 5.44 (3.45; 6.36 vs. 5.86 (4.61; 6.46 log10 copies/mL, even if the difference was not significant (P=0.099. Blood transfusion requirement was greater in patients on combined antiviral therapy than those on pegylated interferon alone, 100% (5/5 vs. 0% (0/21, P=0.0001. No difference in sustained viral response occurred between patients on combined antiviral therapy and those on pegylated interferon monotherapy [40% (2/5 vs. 42.8% (9/21, P=0.90]. Conclusions: Results from this study showed that pegylated interferon alone or with ribavirin is unsatisfactory in terms of efficacy and safety. Prospective trials based on interferon-free regimens (i.e., sofosbuvir plus ribavirin or sofosbuvir plus daclatasvir are under way in patients with hepatitis C receiving long-term hemodialysis.

  12. PEG-Interferon-α ribavirin-induced HCV viral clearance: a pharmacogenetic multicenter Spanish study

    Directory of Open Access Journals (Sweden)

    Javier Milara

    2015-01-01

    Full Text Available Objective: Dual PEGylated interferon-(PEG-IFN and ribavirin therapy has been the main hepatitis C virus (HCV treatment of the last decade. Current direct-acting antiviral agents have improved the outcome of therapy but also have increased the cost and management complexity of treatment. The current study analyzes host genetics, viral and clinical predictors of sustained viral response (SVR to dual PEG-IFN and ribavirin therapy in a representative Spanish population. Methods: Observational prospective multicentre pharmacogenetic cohort study conducted in 12 different hospitals of 12 different Spanish regions. A total of 98 patients with SVR and 106 with non-SVR in response to PEG-IFN and ribavirin therapy were included. 33 single nucleotide polymorphisms located in 24 different genes related with inflammatory, immune and virus response were selected. Clinical and viral data were also analyzed as candidate of SVR predictors. Results: IL-28B (rs12979860, rs7248668, rs8105790, rs8099917 and TNFRSF1B (rs1061622 genotypes, as well as TNFRSF1B/IL-10/TNF(-308 non-TTG and TNFRSF1B/IL- 10/IL-4 non-TTC haplotypes together with lower age, lower basal HCV RNA load, higher basal serum LDL cholesterol values, VHC genotypes 2 and 3 and basal low grade fibrosis 0-2 were associated with a SVR in the univariate analysis. Independent predictors of SVR in the multivariate analysis were IL-28B rs12979860 CC, TNFRSF1B/IL-10/IL-4 non-TTC along with low baseline HCV RNA load and HCV genotypes 2 and 3. Conclusions: IL-28B rs12979860 CC, TNFRSF1B/ IL-10/ IL-4 non-TTC haplotype, low baseline HCV RNA load and HCV genotypes 2 and 3 may help to predict successful outcome to PEG-IFN/ribavirin therapy in Spanish population

  13. Activity of glycogen synthase and glycogen phosphorylase in normal and cirrhotic rat liver during glycogen synthesis from glucose or fructose.

    Science.gov (United States)

    Bezborodkina, Natalia N; Chestnova, Anna Yu; Okovity, Sergey V; Kudryavtsev, Boris N

    2014-03-01

    Cirrhotic patients often demonstrate glucose intolerance, one of the possible causes being a decreased glycogen-synthesizing capacity of the liver. At the same time, information about the rates of glycogen synthesis in the cirrhotic liver is scanty and contradictory. We studied the dynamics of glycogen accumulation and the activity of glycogen synthase (GS) and glycogen phosphorylase (GP) in the course of 120min after per os administration of glucose or fructose to fasted rats with CCl4-cirrhosis or fasted normal rats. Blood serum and liver pieces were sampled for examinations. In the normal rat liver administration of glucose/fructose initiated a fast accumulation of glycogen, while in the cirrhotic liver glycogen was accumulated with a 20min delay and at a lower rate. In the normal liver GS activity rose sharply and GPa activity dropped in the beginning of glycogen synthesis, but 60min later a high synthesis rate was sustained at the background of a high GS and GPa activity. Contrariwise, in the cirrhotic liver glycogen was accumulated at the background of a decreased GS activity and a low GPa activity. Refeeding with fructose resulted in a faster increase in the GS activity in both the normal and the cirrhotic liver than refeeding with glucose. To conclude, the rate of glycogen synthesis in the cirrhotic liver is lower than in the normal one, the difference being probably associated with a low GS activity.

  14. Combined treatment with ribavirin and tiazofurin attenuates response of glial cells in experimental autoimmune encephalomyelitis

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    Nedeljković Nadežda

    2012-01-01

    Full Text Available Experimental autoimmune encephalomyelitis (EAE is an animal model of multiple sclerosis (MS, a human inflammatory and demyelinating disease. Microglia and astrocytes are glial cells of the central nervous system (CNS that play a dual role in MS and EAE pathology. The aim of this study was to examine the effect of combined treatment with two nucleoside analogues, ribavirin and tiazofurin, on microglia and astrocytes in actively induced EAE. Therapeutic treatment with a combination of these two nucleoside analogues reduced disease severity, mononuclear cell infiltration and demyelination. The obtained histological results indicate that ribavirin and tiazofurin changed activated microglia into an inactive type and attenuated astrocyte reactivity at the end of the treatment period. Since reduction of reactive microgliosis and astrogliosis correlated with EAE suppression, the present study also suggests that the obtained beneficial effect of ribavirin and tiazofurin could be a consequence of their action inside as well as outside the CNS. [Acknowledgments. This work was supported by the Serbian Ministry of Education and Science, Project No: III41014.

  15. Retinal vein thrombosis associated with pegylated-interferon and ribavirin combination therapy for chronic hepatitis C

    Institute of Scientific and Technical Information of China (English)

    Iman Zandieh; Mohamed Adenwalla; Cindy Cheong-Lee; Patrick E Ma; Eric M Yoshida

    2006-01-01

    An estimated 300 million people worldwide suffer fromchronic hepatitis C with a prevalence of 0.8%-1.0% of the general population in Canada. An increasing pool of evidence exists supporting the use of pegylatedinterferon (pegIFN) and ribavirin combination therapy for hepatitis C. We report a 49-year old male of North American aboriginal descent with chronic hepatitis C (genotype 2b). Biopsy confirmed that he had cirrhosis with a 2-wk history of left eye pain and decreased visual acuity. He developed retinal vein thrombosis after 16 of 24 wk of pegIFN-α 2a and ribavirin combination therapy. He was urgently referred to a retinal specialist and diagnosed with non-ischemic central retinal vein occlusion of the left eye. PegIFN and ribavirin combination therapy was discontinued and HCV RNA was undetectable after 16 wk of treatment. Hematologic investigations revealed that the patient was a factor V Leiden heterozygote with mildly decreased protein C activity. Our patient had a number of hypercoagulable risk factors, including factor V Leiden heterozygosity, cirrhosis, and hepatitis C that alone would have most likely remained clinically silent. We speculate that in the setting of pegIFN treatment, these risk factors may coalesce and cause the retinal vein thrombosis.

  16. The Interaction of Ribavirin and DII-18-2 with RNA%Ribavirin and DII-18-2与RNA的相互作用

    Institute of Scientific and Technical Information of China (English)

    郝美荣; 杨铭

    2001-01-01

    本文对两种具有抗HIV-1活性的药物与RNA的相互作用进行了探讨.紫外Tm测定及CD光谱结果表明,两种药物均可与polyA@polyU相互作用,影响其构象的改变.流式细胞仪分析提示药物可不同程度地影响cos-7亚二倍体细胞含量,其中 ribavirin的作用更显著.%The aim of this study was to investigate the interaction between polymers polyA.polyU (RNA)and two general anti-viral drugs with anti-HIV-1 activities. Tm experiment showed that thc compounds had interacted with RNA,and CD spectra also observed the changes of RNA conformation induced by the compounds.Cytometric flow analysis indicated that ribavirin and DII-18-2 could decrease the percentage of hypodiploid cells,especially ribavirin.

  17. Modified technique for preparation of venous circulation resin casts in the cirrhotic liver

    Directory of Open Access Journals (Sweden)

    JOSÉ OLÍMPIO MAIA DE VASCONCELOS FILHO

    Full Text Available ABSTRACT This study describes two major adaptations for the preparation of resin casts in human cirrhotic liver, harvested at the time of transplantation. The first is the way of fixing the catheter in the ostia of the hepatic and portal veins through a cerclage, so as to prevent displacement of the catheter and / or leakage of the resin during its injection. The second is the extension of corrosion time in the NaOH solution, averaging 6.8 days, with daily replacement the solution until complete removal of parenchymal tissue. We applied the method in 14 cirrhotic livers, with good filling and coloring of the portal and hepatic vein territories, using different colors. This allows an anatomical study of these vessels, able to complement the knowledge of the histopathology in research work, and the planning of therapeutic procedures, such as the Trans-Jugular Intrahepatic Port-Systemic Shunt (TIPS.

  18. Non-cirrhotic portal hypertension with large regenerative nodules: A diagnostic challenge

    Institute of Scientific and Technical Information of China (English)

    Umberto Vespasiani Gentilucci; Antonio Picardi; Paolo Gallo; Giuseppe Perrone; Riccardo Del Vescovo; Giovanni Galati; Sandro Spataro; Chiara Mazzarelli; Adriano Pellicelli; Antonella Afeltra

    2011-01-01

    Non-cirrhotic portal hypertension is a poorly understood condition characterized by portal hypertension in the absence of conventional hepatic cirrhosis and described in association with blood coagulation disorders, myeloproliferative and immunological diseases and with exposure to toxic drugs. Very recently, precise classification criteria have been proposed in order to define four distinct subcategories. The present case highlights how the clinical presentation, the confounding results from imaging studies, and the difficulties in the histological evaluation often render cases of non-cirrhotic portal hypertension a real diagnostic challenge. It also underscores the classification problems which can be faced once this diagnosis is performed. Indeed, the different subcategories proposed result from the prevalent subtypes in a spectrum of hepatic regenerative responses to a variety of injuries determining microcirculatory disturbances. More flexibility in classification should derive from this etiopathogenic background.

  19. IFN-α-2a (Interferon and ribavirin induced suicidal attempt in a patient of chronic HCV: A rare case report

    Directory of Open Access Journals (Sweden)

    Deep Inder

    2011-01-01

    We present a case report of depression induced by IFN-α and ribavirin, leading to attempted suicide. Following the episode, antidepressant paroxetine (20 mg o.d. and zolpidem (10 mg h.s were added with psychotherapy. No significant improvement was observed. Patient was given a drug dechallenge (IFN-α and ribavirin. Dramatic improvement was seen over 1 month. Following rechallenge with combination, patient again experienced depressive symptoms with suicidal ideation. IFN-α and ribavirin were promptly stopped. Naranjo causality assessment scale revealed probable association with IFN-α and ribavirin. The report intends to improve awareness among clinicians to facilitate early diagnosis and intervention of similar cases.

  20. A randomized controlled clinical study of lower-dose peginterferon alfa-2b in combination with ribavirin in the treatment of chronic hepatitis C

    Institute of Scientific and Technical Information of China (English)

    罗端德

    2006-01-01

    Objective To compare the efficacy and safety of lower-dose peginterferon alfa-2b plus ribavirin versus standard interferon alfa-2b plus ribavirin for treatment of chronic hepatitis C in China. Methods 192 patients with chronic hepatitis C were assigned peginterferon alfa-2b 0.5μg/kg each week plus ribavirin 750~1050 mg/d or standard interferon alfa-2b 3 MIU TIW plus ribavirin 750~1050 mg/d for 48-week treatment and 24-week fellow

  1. Serum cystatin C level is an excellent predictor of mortality in patients with cirrhotic ascites.

    Science.gov (United States)

    Seo, Yeon Seok; Park, Soo Young; Kim, Moon Young; Kim, Sang Gyune; Park, Jun Yong; Yim, Hyung Joon; Jang, Byoung Kuk; Park, Seung Ha; Kim, Ji Hoon; Suk, Ki Tae; Kim, Jin Dong; Kim, Tae Yeob; Cho, Eun Young; Lee, Jun Sung; Jung, Soung Won; Jang, Jae Young; An, Hyonggin; Tak, Won Young; Baik, Soon Koo; Hwang, Jae Seok; Kim, Young Seok; Sohn, Joo Hyun; Um, Soon Ho

    2017-09-14

    Although serum cystatin C level is considered a more accurate marker of renal function in patients with liver cirrhosis, its prognostic efficacy remains uncertain. This study aimed to evaluate the prognostic efficacy of serum cystatin C level in patients with cirrhotic ascites. Patients with cirrhotic ascites from 15 hospitals were prospectively enrolled between September 2009 and March 2013. Cox regression analyses were performed to identify independent predictive factors of mortality and development of type 1 hepatorenal syndrome (HRS-1). In total, 350 patients were enrolled in this study. The mean age was 55.4 ± 10.8 years, and 267 patients (76.3%) were men. The leading cause of liver cirrhosis was alcoholic liver disease (64.3%), followed by chronic viral hepatitis (29.7%). Serum creatinine and cystatin C levels were 0.9 ± 0.4 mg/dL and 1.1 ± 0.5 mg/L, respectively. Multivariate analyses revealed that international normalized ratio (INR) and serum bilirubin, sodium, and cystatin C levels were independent predictors of mortality and INR and serum sodium and cystatin C levels were independent predictors of the development of HRS-1. Serum creatinine level was not significantly associated with mortality and development of HRS-1 on multivariate analysis. Serum cystatin C level was an independent predictor of mortality and development of HRS-1 in patients with cirrhotic ascites, while serum creatinine level was not. Predictive models based on serum cystatin C level instead of serum creatinine level would be more helpful in the assessment of the condition and prognosis of patients with cirrhotic ascites. This article is protected by copyright. All rights reserved.

  2. Autoimmune thrombocytopenia in response to splenectomy in cirrhotic patients with accompanying hepatitis C

    Institute of Scientific and Technical Information of China (English)

    Tetsuro Sekiguchi; Takeaki Nagamine; Hitoshi Takagi; Masatomo Mori

    2006-01-01

    AIM: To estimate the contribution of autoimmune thrombocytopenia to hepatitis C virus-related liver cirrhosis (type C cirrhosis), we evaluated the influence of splenectomy upon platelet-associated immunoglobulin G (PAIgG) levels and platelet numbers.METHODS: PAIgG titers and immune markers were determined in 24 type C cirrhotic patients with an intact spleen, 17 type C cirrhotic patients submitted to splenectomy, and 21 non-C cirrhosis with an intact spleen.RESULTS: Thrombocytopenia (PLT<15×104/μL) in type C cirrhosis was diagnosed in all patients with an intact spleen, 8 patients submitted to splenectomy, and in 19 non-C cirrhosis with intact spleen. Elevated titers of PAIgG at more than 25.0 ng/107 cells were detected in all cirrhotic patients except for one splenectomized patient.PAIgG titers (ng/107 cells) were significantly higher in the type C cirrhosis with an intact spleen (247.9 ± 197.0)compared with the splenectomized patients (125.6±87.8)or non-C cirrhosis (152.4± 127.4). PAIgG titers were negatively correlated with platelet counts in type C cirrhotic patients with an intact spleen. In comparison with the type C cirrhosis with an intact spleen, the splenectomized patients had a reduced CD4/CD8 ratio and serum neopterin levels. The spleen index (cm2) was negatively correlated with platelet counts in the non-C cirrhosis, but not in the type C cirrhosis.CONCLUSION: Our data indicate that the autoimmune mechanism plays an important role in thrombocytosis complicated by HCV-positive cirrhosis. In addition,splenectomy may impair T ceils function through, at least in part, a reduction of CD4/CD8 ratio, consequently suppressing PAIgG production.

  3. Prognostic factors associated with rebleeding in cirrhotic inpatients complicated with esophageal variceal bleeding

    Institute of Scientific and Technical Information of China (English)

    WANG Mei-tang; LIU Tao; MA Xiu-qiang; HE Jian

    2011-01-01

    Background Esophageal variceal bleeding is a frequent and severe complication in patients with cirrhosis. The aim of this study was to identify prognostic factors of esophageal variceal rebleeding in cirrhotic inpatients.Methods Consecutive cirrhotic patients who were admitted to Changhai Hospital because of esophageal variceal bleeding were retrospectively analyzed. To assess the independent factors for recurrent hemorrhage after esophageal variceal bleeding, medical assessment was completed at the time of their initial hospital admission, including documentation of clinical, biochemical, and treatment methods that might contribute to variceal rebleeding. Univariate and multivariate analyses were retrospectively performed.Results Totally 186 patients (35.8%) were assigned to a rebleeding group and the other 334 patients (64.2%) to a non-rebleeding group. Multivariate stepwise regression analysis showed that four variables were positively correlated with rebleeding: Child-pugh grade B (OR=2.664, 95% CI 1.680-4.223) (compared with Child-pugh grade A), total bilirubin (Tbil) (OR=1.0006, 95% CI 1.002-1.0107), creatinine (OR=1.008, 95% CI 1.002-1.015) and the cumulative volume of blood transfusion (OR=1.519, 95% CI 1.345-1.716). The presence of ascites (OR=0.270, 95% CI 0.136-0.536) and prophylactic antibiotics (OR=0.504, 95% CI 0.325-0.780) were negatively correlated with rebleeding of the cirrhotic inpatients. According to standardized coefficient, the importance of rebleeding predictors ranked from the most to the least was as follows: the cumulative volume of blood transfusion, Child-pugh grade B, Tbil and creatinine.Conclusion Rebleeding in cirrhotic inpatients was associated with more blood transfusions, Child-pugh grade B, higher Tbil and creatinine.

  4. Immunogenicity of recombinant hepatitis B vaccine in treatment-naive and treatment-experienced chronic hepatitis C patients: The effect of pegylated interferon plus ribavirin treatment

    Institute of Scientific and Technical Information of China (English)

    Ioannis S Elefsiniotis; Elena Vezali; Konstantinos Kamposioras; Konstantinos D Pantazis; Radostina Tontorova; Ioannis Ketikoglou; Antonios Moulakakis; George Saroglou

    2006-01-01

    AIM: To retrospectively evaluate the vaccinationinduced anti-HBs seroconversion rates in treatmentnaive and treatment-experienced chronic hepatitis C (CHC) patients. Also to prospectively evaluate the seroconversion rates in CHC patients during pegylated interferon (PEG) plus ribavirin (RIB) treatment.METHODS: Seventy treatment-naive CHC patients (group A), 22 sustained virological responders-SVR following interferon (IFN) plus RIB treatment CHC patients (group B) and 121 healthy subjects (group C) had been participated in the same HBV vaccination schedule (20 μg, 0-1-6 mo). Seroconversion was considered if anti-HBs levels were above 10 mIU/mL within 3 mo following the third dose of the vaccine.Moreover, we prospectively selected 30 non-cirrhotic CHC patients and evaluated them for the efficacy of the same vaccine schedule randomizing them in two groups:Group-1, 15 CHC patients received the first dose of the vaccine in parallel with the initiation of PEG plus RIB treatment and Group-2, 15 patients received the same vaccination schedule without concomitant treatment.Determination of anti-HBs was performed at mo 1, 2,and 7. Statistical analysis of data was based on ANOVA student's t-test and chi-square analysis (P < 0.05).RESULTS: Fifty-eight of 70 group A patients (82.85%),20/22 group B (90.9%) and 112/121 healthy subjects (92.56%) had been seroconverted. The seroconversion rates were significantly higher in the control group than in treatment-naive CHC patients (P = 0.04). The corresponding rates were comparable between group A and group B CHC patients (P = 0.38). The vast majority of non-responders (10/14, 71.43%) had been infected by genotype-1 of HCV. The seroconversion rates were comparable between group 1 and 2 CHC patients at mo 1(20% versus 26.7%, P = 0.67), mo 2 (46.7% vs 60%,P = 0.46) and mo 7 (86.7% versus 93.3%, P = 0.54) of follow-up.CONCLUSION: The immunogenicity of HBV vaccine seems to be lower in CHC patients compared to healthy subjects. SVR

  5. Endothelial nitric oxide synthase regulation is altered in pancreas from cirrhotic rats

    Institute of Scientific and Technical Information of China (English)

    Jean-Louis Frossard; Rafael Quadri; Antoine Hadengue; Philippe Morel; Catherine M Pastor

    2006-01-01

    AIM: To determine whether biliary cirrhosis could induce pancreatic dysfunction such as modifications in endothelial nitric oxide synthase(eNOS) expression and whether the regulation of eNOS could be altered by the regulatory proteins caveolin and heat shock protein 90 (Hsp90),as well as by the modifications of calmodulin binding to eNOS.METHODS: Immunoprecipitations and Western blotting analysis were performed in pancreas isolated from sham and cirrhotic rats.RESULTS: Pancreatic injury was minor in cirrhotic rats but eNOS expression importantly decreased with the length (and the severity) of the disease. Because coimmunoprecipitation of eNOS with both Hsp90 and caveolin similarly decreased in cirrhotic rats, eNOS activity was not modified by this mechanism. In contrast,cirrhosis decreased the calmodulin binding to eNOS with a concomitant decrease in eNOS activity.CONCLUSION: In biliary cirrhosis, pancreatic injury is minor but the pancreatic nitric oxide (NO) production is significantly decreased by two mechanisms: a decreased expression of the enzyme and a decreased binding of calmodulin to eNOS.

  6. Doppler study of hepatic vein in cirrhotic patients: Correlation with liver dysfunction and hepatic hemodynamics

    Institute of Scientific and Technical Information of China (English)

    KC Sudhamshu; Shoiichi Matsutani; Hitoshi Maruyama; Taro Akiike; Hiromitsu Saisho

    2006-01-01

    AIM: To elucidate the significance of Doppler measurements of hepatic vein in cirrhotic patients and to correlate with liver dysfunction and hepatic hemodynamics.METHODS: One hundred patients with liver cirrhosis and 60 non-cirrhotic controls were studied. Doppler waveforms were obtained from right hepatic vein and flow velocity measured during quiet respiration. Doppler measurements were also obtained from portal trunk,right portal vein and proper hepatic artery.RESULTS: Hepatic vein waveforms were classified into three classical patterns. Flat waveform was uncommon.Mean hepatic vein velocity was significantly higher in cirrhotic patients (12.7 ± 6.4 vs 5.1 ± 2.1 and 6.2 ± 3.2 cm/s; P < 0.0001). The poorer the grade of cirrhosis,the higher was the mean velocity. Maximum forward velocity was never greater than 40 cm/s in controls.Degree of ascites was found to be highly correlated with mean velocity. "Very high" group (≥ 20 cm/s) presented clinically with moderate to massive ascites. Correlations between right portal flow and mean velocity was significant (P < 0.0001, r = 0.687).CONCLUSION: Doppler waveforms of hepatic vein,which is independent of liver dysfunction, should be obtained during normal respiration. Mean hepatic vein velocity reflects the change in hepatic circulation associated with progression of liver cirrhosis. It can be used as a new parameter in the assessment of liver cirrhosis.

  7. Discoidin domain receptor 1: isoform expression and potential functions in cirrhotic human liver.

    Science.gov (United States)

    Song, Sunmi; Shackel, Nicholas A; Wang, Xin M; Ajami, Katerina; McCaughan, Geoffrey W; Gorrell, Mark D

    2011-03-01

    Discoidin domain receptor 1 (DDR1) is a receptor tyrosine kinase that binds and is activated by collagens. Transcriptional profiling of cirrhosis in human liver using a DNA array and quantitative PCR detected elevated mRNA expression of DDR1 compared with that in nondiseased liver. The present study characterized DDR1 expression in cirrhotic and nondiseased human liver and examined the cellular effects of DDR1 expression. mRNA expression of all five isoforms of DDR1 was detected in human liver, whereas DDR1a demonstrated differential expression in liver with hepatitis C virus and primary biliary cirrhosis compared with nondiseased liver. In addition, immunoblot analysis detected shed fragments of DDR1 more readily in cirrhotic liver than in nondiseased liver. Inasmuch as DDR1 is subject to protease-mediated cleavage after prolonged interaction with collagen, this differential expression may indicate more intense activation of DDR1 protein in cirrhotic compared with nondiseased liver. In situ hybridization and immunofluorescence localized intense DDR1 mRNA and protein expression to epithelial cells including hepatocytes at the portal-parenchymal interface and the luminal aspect of the biliary epithelium. Overexpression of DDR1a altered hepatocyte behavior including increased adhesion and less migration on extracelular matrix substrates. DDR1a regulated extracellular expression of matrix metalloproteinases 1 and 2. These data elucidate DDR1 function pertinent to cirrhosis and indicate the importance of epithelial cell-collagen interactions in chronic liver injury.

  8. Appropriate empirical antibiotic use and 30-d mortality in cirrhotic patients with bacteremia

    Science.gov (United States)

    Park, Hyun; Jang, Ki Jun; Jang, Won; Park, Sang Hoon; Park, Ji Young; Jeon, Tae Joo; Oh, Tae Hoon; Shin, Won Chang; Choi, Won-Choong; Sinn, Dong Hyun

    2015-01-01

    AIM: To analyze whether prompt and appropriate empirical antibiotic (AEA) use is associated with mortality in cirrhotic patients with bacteremia. METHODS: A total of 102 episodes of bacteremia in 72 patients with cirrhosis were analyzed. AEA was defined as a using or starting an antibiotic appropriate to the isolated pathogen at the time of bacteremia. The primary endpoint was 30-d mortality. RESULTS: The mortality rate at 30 d was 30.4% (31/102 episodes). Use of AEA was associated with better survival at 30 d (76.5% vs 46.9%, P = 0.05), and inappropriate empirical antibiotic (IEA) use was an independent factor associated with increased mortality (OR = 3.24; 95%CI: 1.50-7.00; P = 0.003, adjusted for age, sex, Child-Pugh Class, gastrointestinal bleeding, presence of septic shock). IEA use was more frequent when the isolated pathogen was a multiresistant pathogen, and when infection was healthcare-related or hospital-acquired. CONCLUSION: AEA use was associated with increased survival of cirrhotic patients who developed bacteremia. Strategies for AEA use, tailored according to the local epidemiological patterns, are needed to improve survival of cirrhotic patients with bacteremia. PMID:25834324

  9. Longitudinal intrinsic brain activity changes in cirrhotic patients before and one month after liver transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Cheng, Yue; Huang, Li Xiang; Xie, Shuang [Dept. of Radiology, Tianjin First Central Hospital, Tianjin (China); and others

    2017-04-15

    To evaluate the spontaneous brain activity alterations in liver transplantation (LT) recipients using resting-state functional MRI. Twenty cirrhotic patients as transplant candidates and 25 healthy controls (HCs) were included in this study. All patients repeated the MRI study one month after LT. Amplitude of low-frequency fluctuation (ALFF) values were compared between cirrhotic patients (both pre- and post-LT) and HCs as well as between the pre- and post-LT groups. The relationship between ALFF changes and venous blood ammonia levels and neuropsychological tests were investigated using Pearson's correlation analysis. In the cirrhotic patients, decreased ALFF in the vision-related regions (left lingual gyrus and calcarine), sensorimotor-related regions (left postcentral gyrus and middle cingulate cortex), and the default-mode network (bilateral precuneus and left inferior parietal lobule) were restored, and the increased ALFF in the temporal and frontal lobe improved in the early period after LT. The ALFF decreases persisted in the right supplementary motor area, inferior parietal lobule, and calcarine. The ALFF changes in the right precuneus were negatively correlated with changes in number connection test-A scores (r = 0.507, p < 0.05). LT improved spontaneous brain activity and the results for associated cognition tests. However, decreased ALFF in some areas persisted, and new-onset abnormal ALFF were possible, indicating that complete cognitive function recovery may need more time.

  10. Laparoscopic versus open cholecystectomy in cirrhotic patients: a prospective randomized study.

    Science.gov (United States)

    El-Awadi, Saleh; El-Nakeeb, Ayman; Youssef, Tamer; Fikry, Amir; Abd El-Hamed, Tito M; Ghazy, Hosam; Foda, Elyamany; Farid, Mohamed

    2009-02-01

    Improved laparoscopic experience and techniques have made laparoscopic cholecystectomy (LC) feasible options in cirrhotic patients. This study was designed to compare the risk and benefits of open cholecystectomy (OC) versus LC in compensated cirrhosis. A randomized prospective study, in the period from October 2002 till December 2006, where 110 cirrhotic patients with symptomatic gallstone were randomly divided into OC group (55 patients) and LC group (55 patients). There was no operative mortality. In LC group 4 (7.33%) patients were converted to OC. Mean surgical time was significantly longer in OC group than LC group (96.13+17.35 min versus 76.13+15.12) P<0.05, associated with significantly higher intraoperative bleeding in OC group (P<0.01), necessitating blood transfusions to 7 (12.72%) patients in OC group. The time to resume diet was 18.36+8.18 h in LC group which is significantly earlier than in OC group 47.84+14.6h P<0.005. Hospital stay was significantly longer in OC group than LC group (6+1.74 days versus 1.87+1.11 days) P<0.01 with low postoperative morbidity. LC in cirrhotics is still complicated and highly difficult which associates with significant morbidity compared with that of patients without cirrhosis. However, it offers lower morbidity, shorter operative time; early resume dieting with less need for blood transfusion and reducing hospital stay than OC.

  11. Per rectal portal scintigraphy as a useful tool for predicting esophageal variceal bleeding in cirrhotic patients

    Institute of Scientific and Technical Information of China (English)

    Taned Chitapanarux; Ong-ard Praisontarangkul; Satawat Thongsawat; Pises Pisespongsa; Apinya Leerapun

    2007-01-01

    AIM: To investigate potential roles of per rectal portal scintigraphy in diagnosis of esophageal varices and predicting the risk of bleeding.METHODS: Fifteen normal subjects and fifty cirrhotic patients with endoscopically confirmed esophageal varices were included. Patients were categorized into bleeder and non-bleeder groups according to history of variceal bleeding. All had completed per rectal portal scintigraphy using 99mTechnetium pertechnetate.The shunt index was calculated from the ratio of 99mTechnetium pertechnetate in the heart and the liver.Data were analyzed using Student's t-test and receiver operating characteristics.RESULTS: Cirrhotic patients showed a higher shunt index than normal subjects (63.80 ± 25.21 vs 13.54 ± 6.46, P < 0.01). Patients with variceal bleeding showed a higher shunt index than those without bleeding (78.45 ± 9.40 vs 49.35 ± 27.72, P < 0.01). A shunt index of over 20% indicated the presence of varices and that of over 60% indicated the risk of variceal bleeding.CONCLUSION: In cirrhotic patients, per rectal portal scintigraphy is a clinically useful test for identifying esophageal varices and risk of variceal bleeding.

  12. The antiviral drug ribavirin does not mimic the 7-methylguanosine moiety of the mRNA cap structure in vitro.

    Science.gov (United States)

    Westman, Belinda; Beeren, Lisa; Grudzien, Ewa; Stepinski, Janusz; Worch, Remigiusz; Zuberek, Joanna; Jemielity, Jacek; Stolarski, Ryszard; Darzynkiewicz, Edward; Rhoads, Robert E; Preiss, Thomas

    2005-10-01

    The eukaryotic initiation factor eIF4E binds the mRNA 5' cap structure and has a central role during translational initiation. eIF4E and the mechanisms to control its activity have oncogenic properties and thus have become targets for anticancer drug development. A recent study (Kentsis et al. 2004) presented evidence that the antiviral nucleoside ribavirin and its phosphorylated derivatives were structural mimics of the mRNA cap, high-affinity ligands for eIF4E, and potent repressors of eIF4E-mediated cell transformation and tumor growth. Based on these findings, we tested ribavirin, ribavirin triphosphate (RTP), and the dinucleotide RpppG for their ability to inhibit translation in vitro. Surprisingly, the ribavirin-based compounds did not affect translation at concentrations where canonical cap analogs efficiently block cap-dependent translation. Using a set of reporter mRNAs that are translated via either cap-dependent or viral internal ribosome entry sites (IRES)-dependent initiation, we found that these ribavirin-containing compounds did inhibit translation at high (millimolar) concentrations, but there was no correlation of this inhibition with an eIF4E requirement for translation. The addition of a ribavirin-containing cap to mRNA did not stimulate translation. Fluorescence titration experiments with eIF4E and the nuclear cap-binding complex CBC indicated affinities for RTP and RpppG that were two to four orders of magnitude lower than those of m(7)GTP and m(7)GpppG. We conclude that, at least with respect to translation, ribavirin does not act in vitro as a functional mimic of the mRNA cap.

  13. [Extracellular fluid, plasma and interstitial volume in cirrhotic patients without clinical edema or ascites].

    Science.gov (United States)

    Noguera Viñas, E C; Hames, W; Mothe, G; Barrionuevo, M P

    1989-01-01

    Extracellular fluid volume (E.C.F.) and plasma volume (P.V.), were measured with sodium sulfate labeled with 35I and 131I human serum albumin, respectively, by the dilution technique in control subjects and in cirrhotic patients without clinical ascites or edema, renal or hepatic failure, gastrointestinal bleeding or diuretics. Results are expressed as mean +/- DS in both ml/m2 and ml/kg. In normal subjects E.C.F. (n = 8) was 7,533 +/- 817 ml/m2 (201.3 +/- 182 ml/kg), P.V. (n = 11) 1,767 +/- 337 ml/m2 (47.2 +/- 9.3 ml/kg), and interstitial fluid (I.S.F.) (n = 7) 5,758 +/- 851 ml/m2 (Table 2). In cirrhotic patients E.C.F. (n = 11) was 10,318 +/- 2,980 ml/m2 (261.7 +/- 76.8 ml/kg), P.V. (n = 12) 2,649 +/- 558 ml/m2 (67.7 +/- 15.6 ml/kg) and I.S.F. (n = 11) 7,866 +/- 2,987 ml/m2 (Table 3). Cirrhotic patients compared with normal subjects have hypervolemia due to a significant E.C.F. and P.V. expansion (p less than 0.02 and less than 0.001 respectively) (Fig. 1). Reasons for E.C.F. and P.V. abnormalities in cirrhotic patients may reflect urinary sodium retention related to portal hipertension which stimulates aldosterone release or enhanced renal tubular sensitivity to the hormone. However, it is also possible that these patients, in the presence of hypoalbuminemia (Table 1), have no clinical edema or ascites due to increased glomerular filtration, suppressed release of vasopressin, increased natriuretic factor, and urinary prostaglandin excretion, in response to the intravascular expansion, all of which increased solute and water delivery to the distal nephron and improved renal water excretion. We conclude that in our clinical experience cirrhotic patients without ascites or edema have hypervolemia because of a disturbance in E.C.F.

  14. Vigorous, but differential mononuclear cell response of cirrhotic patients to bacterial ligands

    Institute of Scientific and Technical Information of China (English)

    Varenka J Barbero-Becerra; María Concepción Gutiérrez-Ruiz; Carmen Maldonado-Bernal; Félix I Téllez-Avila; Roberto Alfaro-Lara; Florencia Vargas-Vorácková

    2011-01-01

    AIM: To study the role of gram-positive and gram-negative bacteria in the pathogenesis of liver injury, specifically the activation of inflammatory mediators. METHODS: Peripheral blood mononuclear cells of 20 out-patients were studied, 10 of them with cirrhosis. Peripheral blood mononuclear cells were isolated and exposed to lipopolysaccharide or lipoteichoic acid. CD14, Toll-like receptor 2 and 4 expression was determined by flow cytometry, and tumor necrosis factor (TNF) α, interleukin (IL)-1β, IL-6, IL-12 and IL-10 secretion in supernatants was determined by ELISA. RESULTS: Higher CD14, Toll-like receptor 2 and 4 expression was observed in peripheral blood mononuclear cells from cirrhotic patients, (P < 0.01, P < 0.006, P < 0.111) respectively. Lipopolysaccharide and lipoteichoic acid induced a further increase in CD14 expression (P < 0.111 lipopolysaccharide, P < 0.013 lipoteichoic acid), and a decrease in Toll-like receptor 2 (P < 0.008 lipopolysaccharide, P < 0.008 lipoteichoic acid) and Toll-like receptor 4 (P < 0.008 lipopolysaccharide, P < 0.028 lipoteichoic acid) expression. With the exception of TNFα, absolute cytokine secretion of peripheral blood mononuclear cells was lower in cirrhotic patients under nonexposure conditions (P < 0.070 IL-6, P < 0.009 IL-1β, P < 0.022 IL-12). Once exposed to lipopolysaccharide or lipoteichoic acid, absolute cytokine secretion of peripheral blood mononuclear cells was similar in cirrhotic and non-cirrhotic patients, determining a more vigorous response in the former (P < 0.005 TNFα, IL-1β, IL-6, IL-2 and IL-10 lipopolysaccharide; P < 0.037 TNFα; P < 0.006 IL-1β; P < 0.005 IL-6; P < 0.007 IL-12; P < 0.014 IL-10 lipoteichoic acid). Response of peripheral blood mononuclear cells was more intense after lipopolysaccharide than after lipoteichoic acid exposure. CONCLUSION: Peripheral blood mononuclear cells of cirrhotic patients are able to respond to a sudden bacterial ligand exposure, particularly lipopolysaccharide

  15. The PHES battery does not detect all cirrhotic patients with early neurological deficits, which are different in different patients

    Science.gov (United States)

    Giménez-Garzó, Carla; Garcés, Juan José; Urios, Amparo; Mangas-Losada, Alba; García-García, Raquel; González-López, Olga; Giner-Durán, Remedios; Escudero-García, Desamparados; Serra, Miguel Angel; Soria, Emilio; Felipo, Vicente; Montoliu, Carmina

    2017-01-01

    Background and aims The psychometric hepatic encephalopathy score (PHES) is the “gold standard” for minimal hepatic encephalopathy (MHE) diagnosis. Some reports suggest that some cirrhotic patients “without” MHE according to PHES show neurological deficits and other reports that neurological alterations are not homogeneous in all cirrhotic patients. This work aimed to assess whether: 1) a relevant proportion of cirrhotic patients show neurological deficits not detected by PHES; 2) cirrhotic patients with mild neurological deficits are a homogeneous population or may be classified in sub-groups according to specific deficits. Methods Cirrhotic patients “without” (n = 56) or “with” MHE (n = 41) according to PHES and controls (n = 52) performed psychometric tests assessing attention, concentration, mental processing speed, working memory and bimanual and visuomotor coordination. Heterogeneity of neurological alterations was analysed using Hierarchical Clustering Analysis. Results PHES classified as “with” MHE 42% of patients. Around 40% of patients “without” MHE according to PHES fail two psychometric tests. Oral SDMT, d2, bimanual and visuo-motor coordination tests are failed by 54, 51, 51 and 43% of patients, respectively. The earliest neurological alterations are different for different patients. Hierarchical clustering analysis shows that patients “without” MHE according to PHES may be classified in clusters according to the tests failed. In some patients coordination impairment appear before cognitive impairment while in others concentration and attention deficits appear before. Conclusions PHES is not sensitive enough to detect early neurological alterations in a relevant proportion of cirrhotic patients. Oral SDMT, d2 and bimanual and visuo-motor coordination tests are more sensitive. The earliest neurological alterations are different in different cirrhotic patients. These data also have relevant clinical implications. Patients

  16. Eighty three cases of post transfusion HCV infection: a 10-year follow up%由一个