Immunogenicity and safety of a plasma-derived heat-inactivated hepatitis B vaccine (CLB). Studies in volunteers at a low risk of infection with hepatitis B virus

NARCIS (Netherlands)

Lelie, P. N.; Reesink, H. W.; de Jong-van Manen, S. T.; Dees, P. J.; Reerink-Brongers, E. E.

1984-01-01

The safety and immunogenicity of a plasma-derived heat-inactivated hepatitis B vaccine (CLB) were evaluated in 471 healthy human volunteers, who, both in their occupations and in their private lives, had been at minimal risk of being infected with hepatitis B virus. The first 202 individuals

[Safety profile of dolutegravir].

Science.gov (United States)

Rivero, Antonio; Domingo, Pere

2015-03-01

Integrase inhibitors are the latest drug family to be added to the therapeutic arsenal against human immunodeficiency virus infection. Drugs in this family that do not require pharmacological boosting are characterized by a very good safety profile. The latest integrase inhibitor to be approved for use is dolutegravir. In clinical trials, dolutegravir has shown an excellent tolerability profile, both in antiretroviral-naïve and previously treated patients. Discontinuation rates due to adverse effects were 2% and 3%, respectively. The most frequent adverse effects were nausea, headache, diarrhea and sleep disturbance. A severe hypersensitivity reaction has been reported in only one patient. In patients coinfected with hepatropic viruses, the safety profile is similar to that in patients without coinfection. The lipid profile of dolutegravir is similar to that of raltegravir and superior to those of Atripla® and darunavir/ritonavir. Dolutegravir induces an early, predictable and non-progressive increase in serum creatinine of around 10% of baseline values in treatment-naïve patients and of 14% in treatment-experienced patients. This increase is due to inhibition of tubular creatinine secretion through the OCT2 receptor and does not lead to a real decrease in estimated glomerular filtration rate with algorithms that include serum creatinine. The effect of the combination of dolutegravir plus Kivexa(®) on biomarkers of bone remodeling is lower than that of Atripla(®). Dolutegravir has an excellent tolerability profile with no current evidence of long-term adverse effects. Its use is accompanied by an early and non-progressive increase in serum creatinine due to OCT2 receptor inhibition. In combination with abacavir/lamivudine, dolutegravir has a lower impact than enofovir/emtricitabine/efavirenz on bone remodelling markers. Copyright © 2015 Elsevier España, S.L.U. All rights reserved.

Functional Safety Specification of Communication Profile PROFIsafe

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Jan Rofar

2006-01-01

Full Text Available Paper maps the trends in area of safety-related communication within PROFIBUS and PROFINET industry networks. There are analyses safety measures and Fail-safe parameters of PROFIsafe profile in version V2 and their localisation in Safety Communication Layer SCL, which guarantees Safety Integrity Level SIL according to standard IEC 61508. The last chapter analyses the reaction in the event of fault during transmission of messages.

Dietary intake of ain-93 standard diet induces Fatty liver with altered hepatic fatty acid profile in Wistar rats.

Science.gov (United States)

Farias Santos, Juliana; Suruagy Amaral, Monique; Lima Oliveira, Suzana; Porto Barbosa, Júnia; Rego Cabral, Cyro; Sofia Melo, Ingrid; Bezerra Bueno, Nassib; Duarte Freitas, Johnatan; Goulart Sant'ana, Antônio; Rocha Ataíde, Terezinha

2015-05-01

There are several standard diets for animals used in scientific research, usually conceived by scientific institutions. The AIN-93 diet is widely used, but there are some reports of fatty liver in Wistar rats fed this diet. We aimed to evaluate the hepatic repercussions of the AIN-93 diet intake in Wistar rats. Forty newly-weaned 21-day-old male Wistar rats were fed either the AIN-93 diet or a commercial diet for either 1 month or 4 months. Weight gain, serum biochemistry, hepatic histology, and hepatic fatty acid profile were analyzed. Hepatic steatosis was observed, especially in the group fed the AIN-93 diet. Serum blood glucose, absolute and relative liver weight and hepatic levels of oleic, palmitoleic, stearic, and palmitic fatty acids were related to the observed steatosis, while lipidogram and serum markers of liver function and injury were not. AIN-93 diet induced acute hepatic steatosis in Wistar rats, which may compromise its use as a standard diet for experimental studies with rodents. The hepatic fatty acid profile was associated with steatosis, with possible implications for disease prognosis. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

Profile of Inflammation-associated genes during Hepatic Differentiation of Human Pluripotent Stem Cells

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Joseph Ignatius Irudayam

2015-12-01

Full Text Available Expression of genes associated with inflammation was analyzed during differentiation of human pluripotent stem cells (PSCs to hepatic cells. Messenger RNA transcript profiles of differentiated endoderm (day 5, hepatoblast (day 15 and hepatocyte-like cells (day 21 were obtained by RNA sequencing analysis. When compared to endoderm cells an immature cell type, the hepatic cells (days 15 and 21 had significantly higher expression of acute phase protein genes including complement factors, coagulation factors, serum amyloid A and serpins. Furthermore, hepatic phase of cells expressed proinflammatory cytokines IL18 and IL32 as well as cytokine receptors IL18R1, IL1R1, IL1RAP, IL2RG, IL6R, IL6ST and IL10RB. These cells also produced CCL14, CCL15, and CXCL- 1, 2, 3, 16 and 17 chemokines. Endoderm cells had higher levels of chemokine receptors, CXCR4 and CXCR7, than that of hepatic cells. Sirtuin family of genes involved in aging, inflammation and metabolism were differentially regulated in endoderm and hepatic phase cells. Ligands and receptors of the tumor necrosis factor (TNF family as well as downstream signaling factors TRAF2, TRAF4, FADD, NFKB1 and NFKBIB were differentially expressed during hepatic differentiation.

Efficacy and safety of rilpivirine in treatment-naive, HIV-1-infected patients with hepatitis B virus/hepatitis C virus coinfection enrolled in the Phase III randomized, double-blind ECHO and THRIVE trials

DEFF Research Database (Denmark)

Nelson, Mark; Amaya, Gerardo; Clumeck, Nathan

2012-01-01

OBJECTIVES: The efficacy and hepatic safety of the non-nucleoside reverse transcriptase inhibitors rilpivirine (TMC278) and efavirenz were compared in treatment-naive, HIV-infected adults with concurrent hepatitis B virus (HBV) and/or hepatitis C virus (HCV) infection in the pooled week 48 analys...

Risk Profile of Hepatitis E Virus from Pigs or Pork in Canada.

Science.gov (United States)

Wilhelm, B; Fazil, A; Rajić, A; Houde, A; McEwen, S A

2017-12-01

The role and importance of pigs and pork as sources of zoonotic hepatitis E virus (HEV) has been debated in Canada and abroad for over 20 years. To further investigate this question, we compiled data to populate a risk profile for HEV in pigs or pork in Canada. We organized the risk profile (RP) using the headings prescribed for a foodborne microbial risk assessment and used research synthesis methods and inputs wherever possible in populating the fields of this RP. A scoping review of potential public health risks of HEV, and two Canadian field surveys sampling finisher pigs, and retail pork chops and pork livers, provided inputs to inform this RP. We calculated summary estimates of prevalence using the Comprehensive Meta-analysis 3 software, employing the method of moments. Overall, we found the incidence of sporadic locally acquired hepatitis E in Canada, compiled from peer-reviewed literature or from diagnosis at the National Microbiology Laboratory to be low relative to other non-endemic countries. In contrast, we found the prevalence of detection of HEV RNA in pigs and retail pork livers, to be comparable to that reported in the USA and Europe. We drafted risk categories (high/medium/low) for acquiring clinical hepatitis E from exposure to pigs or pork in Canada and hypothesize that the proportion of the Canadian population at high risk from either exposure is relatively small. © 2016 Crown copyright.

Safety and security profiles of industry networks used in safety- critical applications

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Mária FRANEKOVÁ

2008-01-01

Full Text Available The author describes the mechanisms of safety and security profiles of industry and communication networks used within safety – related applications in technological and information levels of process control recommended according to standards IEC 61784-3,4. Nowadays the number of vendors of the safety – related communication technologies who guarantees besides the standard communication, the communication amongst the safety – related equipment according to IEC 61508 is increasing. Also the number of safety – related products is increasing, e. g. safety Fieldbus, safety PLC, safety curtains, safety laser scanners, safety buttons, safety relays and other. According to world survey the safety Fieldbus denoted the highest growth from all manufactured safety products.The main part of this paper is the description of the safety-related Fieldbus communication system, which has to guaranty Safety Integrity Level.

Value of preapproval safety data in predicting postapproval hepatic safety and assessing the legitimacy of class warning.

Science.gov (United States)

Lin, Yeong-Liang; Wu, Ya-Chi; Gau, Churn-Shiouh; Lin, Min-Shung

2012-02-01

The objective of this study was to systematically evaluate whether preapproval safety data for nonhepatotoxic drugs and hepatotoxic drugs can be compared to improve preapproval prediction of postapproval hepatic safety and to assess the legitimacy of applying class warnings. Drugs within a therapeutic class that included at least one drug that had been withdrawn from the market because of liver toxicity or had a warning of potential liver toxicity issued by major regulatory agencies, and at least one drug free from such regulatory action, were identified and divided into two groups: drugs with and drugs without regulatory action. Preapproval clinical data [including the elevation rates of alanine aminotransferse (ALT) and withdrawal due to liver toxicity, the number of patients with combined elevation of ALT and bilirubin, and liver failure] and nonclinical data (including chemical structures, metabolic pathways, and other significant findings in animal studies) were compared between the two groups. Six drug classes were assessed in this study: thiazolidinediones, cyclooxygenase-2 inhibitors, fluoroquinolones, catechol-O-methyltransferase (COMT) inhibitors, leukotriene receptor inhibitors, and endothelin receptor antagonists. In two classes (COMT inhibitors and endothelin receptor antagonists), drugs with regulatory action had significantly higher rates of ALT elevation of more than threefold and greater numbers of patients with combined elevation of ALT and bilirubin than drugs without regulatory action. Drugs with regulatory action also had chemical structures or metabolic pathways associated with the toxicity. The legitimacy of class warnings was refuted in all six classes of drugs. Preapproval safety data may help predict postapproval hepatic safety and can be used to assess the legitimacy of applying class warnings.

High Fat Diet Exposure during Fetal Life Enhances Plasma and Hepatic Omega-6 Fatty Acid Profiles in Fetal Wistar Rats

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Marlon E. Cerf

2015-08-01

Full Text Available Pregnant rats were fed a high fat diet (HFD for the first (HF1, second (HF2, third (HF3 or all three weeks (HFG of gestation. Maintenance on a HFD during specific periods of gestation was hypothesized to alter fetal glycemia, insulinemia, induce insulin resistance; and alter fetal plasma and hepatic fatty acid (FA profiles. At day 20 of gestation, fetal plasma and hepatic FA profiles were determined by gas chromatography; body weight, fasting glycemia, insulinemia and the Homeostasis Model Assessment (HOMA-insulin resistance were also determined. HF3 fetuses were heaviest concomitant with elevated glycemia and insulin resistance (p < 0.05. HFG fetuses had elevated plasma linoleic (18:2 n-6 and arachidonic (20:4 n-6 acid proportions (p < 0.05. In the liver, HF3 fetuses displayed elevated linoleic, eicosatrienoic (20:3 n-6 and arachidonic acid proportions (p < 0.05. HFG fetuses had reduced hepatic docosatrienoic acid (22:5 n-3 proportions (p < 0.05. High fat maintenance during the final week of fetal life enhances hepatic omega-6 FA profiles in fetuses concomitant with hyperglycemia and insulin resistance thereby presenting a metabolically compromised phenotype.

Update on entecavir in the management of severe forms of Hepatitis B

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Sacco R

2012-05-01

Full Text Available Rodolfo SaccoDepartment of Gastroenterology, Pisa University Hospital, Pisa, ItalyAbstract: Despite the effective management of most cases of hepatitis B virus (HBV infection, there is still much room for improvement in the treatment of more severe cases of hepatitis B, such as those occurring in patients with decompensated cirrhosis, in transplanted subjects, and in patients with exacerbations of HBV infection. Among the treatments currently approved for the therapy of hepatitis B, entecavir determines a rapid suppression of viral load. This drug is also associated with a high genetic barrier and an overall favorable safety profile. This review provides an overview of recent evidence related to the use of entecavir in the management of the most severe forms of hepatitis B. The results obtained for this drug in real-life clinical practice are also reviewed.Keywords: entecavir, HBV, hepatitis B, chronic hepatitis

Direct Acting Antivirals in Patients with Chronic Hepatitis C and Down Syndrome

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Eric R. Yoo

2016-01-01

Full Text Available Patients with Down syndrome who received blood transfusions, likely in conjunction with cardiothoracic surgery for congenital heart disease and prior to the implementation of blood-donor screening for hepatitis C virus infection, face a substantial risk of acquiring the infection. In the past, interferon-based therapy for chronic hepatitis C infection in patients with Down syndrome was noted to have lower efficacy and potentially higher risk of adverse effects. Recently, the treatment for chronic hepatitis C has been revolutionized with the introduction of interferon-free direct acting antivirals with favorable safety, tolerability, and efficacy profile. Based on our experiences, the newly approved sofosbuvir-based direct acting antiviral therapy is well tolerated and highly efficacious in this subpopulation of hepatitis C virus infected patients with Down syndrome.

Sex specific differences in hepatic and plasma lipid profiles in healthy cats pre and post spaying and neutering : relationship with feline hepatic lipidosis

NARCIS (Netherlands)

Valtolina, Chiara|info:eu-repo/dai/nl/412503034; Vaandrager, Arie B|info:eu-repo/dai/nl/073165506; Favier, Robert P|info:eu-repo/dai/nl/304828742; Tuohetahuntila, Maidina; Kummeling, Anne|info:eu-repo/dai/nl/304828793; Jeusette, Isabelle; Rothuizen, Jan|info:eu-repo/dai/nl/071276033; Robben, Joris H|info:eu-repo/dai/nl/266740790

2017-01-01

BACKGROUND: A link between lipid metabolism and disease has been recognized in cats. Since hepatic lipidosis is a frequent disorder in cats, the aim of the current study was to evaluate liver and plasma lipid dimorphism in healthy cats and the effects of gonadectomy on lipid profiling. From six

Immunogenicity and safety of concomitant administration of a combined hepatitis A/B vaccine and a quadrivalent meningococcal conjugate vaccine in healthy adults.

Science.gov (United States)

Alberer, Martin; Burchard, Gerd; Jelinek, Tomas; Reisinger, Emil C; Meyer, Seetha; Forleo-Neto, Eduardo; Dagnew, Alemnew F; Arora, Ashwani Kumar

2015-01-01

This phase 3b randomized, open-label study evaluated the immunogenicity and safety of coadministration of a hepatitis A and/or B vaccine with a quadrivalent oligosaccharide meningococcal CRM197 -conjugate vaccine (MenACWY-CRM), in the context of an accelerated hepatitis A and/or B immunization schedule. A total of 252 healthy adult subjects were randomized to three groups to receive hepatitis A/B only (HepA/B), hepatitis A/B coadministered with MenACWY-CRM (HepA/B+MenACWY-CRM), or MenACWY-CRM only (MenACWY-CRM). Hepatitis A and/or B vaccination was administered in the form of a single booster dose or a primary three-dose series, depending on the hepatitis A and/or B vaccination history of subjects. Antibody responses to hepatitis A/B vaccination were assessed 1 month following the last hepatitis A and/or B dose. Serum bactericidal activity with human complement (hSBA) against meningococcal serogroups A, C, W-135, and Y was assessed 1 month post-MenACWY-CRM vaccination. Safety was monitored throughout the study. At 1 month following the final hepatitis A and/or B vaccination, concomitant administration of hepatitis A/B and MenACWY-CRM was non-inferior to administration of hepatitis A/B alone in terms of geometric mean concentrations of antibodies against the hepatitis A and B antigens. One month post-MenACWY-CRM vaccination, the percentages of subjects achieving hSBA titers ≥8 for serogroups A, C, W-135, and Y in the HepA/B+MenACWY-CRM group (76, 87, 99, and 94%, respectively) were comparable to those in the MenACWY-CRM group (67, 82, 96, and 88%, respectively). The percentages of subjects reporting adverse events (AEs) were similar across study groups and a majority of the reported AEs were mild to moderate in nature. There were no study vaccine-related serious AEs. MenACWY-CRM can be administered concomitantly with a hepatitis A and/or B vaccine in the context of an accelerated hepatitis A and/or B immunization schedule without increasing safety concerns

Distinct changing profiles of hepatitis A and E virus infection among patients with acute hepatitis, patients on maintenance hemodialysis and healthy individuals in Japan.

Science.gov (United States)

Mitsui, Takehiro; Tsukamoto, Yukie; Hirose, Akinori; Suzuki, Shigeru; Yamazaki, Chikao; Masuko, Kazuo; Tsuda, Fumio; Endo, Kazunori; Takahashi, Masaharu; Okamoto, Hiroaki

2006-08-01

To compare the epidemiologic profiles of hepatitis A virus (HAV) and hepatitis E virus (HEV) infections in Japan, the prevalence of clinical or subclinical HAV and HEV infections was investigated serologically and molecularly among 128 consecutive patients (age, mean +/- standard deviation, 37.5 +/- 14.7 years) who contracted acute hepatitis between 1989 and 2005 in a city hospital, and among 416 hemodialysis patients (60.1 +/- 12.6 years) and 266 medical staff members (34.6 +/- 11.4 years) at the same hospital, using stored periodic serum samples collected since the start of hemodialysis or employment, respectively. Between 1989 and 1995, among 93 patients with acute hepatitis, 51 (54.8%) were diagnosed with hepatitis A and only one patient with hepatitis E. Between 1996 and 2005, however, among 35 patients, only 3 (8.6%) were diagnosed with hepatitis A and 2 (5.7%) with hepatitis E. Although subclinical HEV infection was recognized in four hemodialysis patients (one each in 1979, 1980, 1988, and 2003) and two medical staff members (1978 and 2003) in previous studies, none of the 191 hemodialysis patients who had been negative for anti-HAV at the start of hemodialysis contracted HAV infection during the observation period of 7.6 +/- 6.4 years. Only one (0.4%) of the 246 medical staff members who had been negative for anti-HAV at the start of employment acquired hepatitis A during the observation period of 7.9 +/- 8.0 years: none had subclinical HAV infection. Clinical or subclinical HEV infection has occurred rarely during the last three decades, while HAV infection has markedly decreased at least since 1996. 2006 Wiley-Liss, Inc.

Laser safety at high profile projects

Science.gov (United States)

Barat, K.

2011-03-01

Laser Safety at high profile laser facilities tends to be more controlled than in the standard laser lab found at a research institution. The reason for this is the potential consequences for such facilities from incidents. This ranges from construction accidents, to equipment damage to personnel injuries. No laser user wants to sustain a laser eye injury. Unfortunately, many laser users, most commonly experienced researchers and inexperienced graduate students, do receive laser eye injuries during their careers. . More unforgiveable is the general acceptance of this scenario, as part of the research & development experience. How do senior researchers, safety personnel and management stop this trend? The answer lies in a cultural change that involves institutional training, user mentoring, hazard awareness by users and administrative controls. None of these would inhibit research activities. As a matter of fact, proper implementation of these controls would increase research productivity. This presentation will review and explain the steps needed to steer an institution, research division, group or individual lab towards a culture that should nearly eliminate laser accidents. As well as how high profile facilities try to avoid laser injuries. Using the definition of high profile facility as one who's funding in the million to billions of dollars or Euros and derives form government funding.

Subacute effects of hexabromocyclododecane (HBCD) on hepatic gene expression profiles in rats

International Nuclear Information System (INIS)

Canton, Rocio F.; Peijnenburg, Ad A.C.M.; Hoogenboom, Ron L.A.P.; Piersma, Aldert H.; Ven, Leo T.M. van der; Berg, Martin van den; Heneweer, Marjoke

2008-01-01

Hexabromoyclododecane (HBCD), used as flame retardant (FR) mainly in textile industry and in polystyrene foam manufacture, has been identified as a contaminant at levels comparable to other brominated FRs (BFRs). HBCD levels in biota are increasing slowly and seem to reflect the local market demand. The toxicological database of HBCD is too limited to perform at present a solid risk assessment, combining data from exposure and effect studies. In order to fill in some gaps, a 28-day HBCD repeated dose study (OECD407) was done in Wistar rats. In the present work liver tissues from these animals were used for gene expression profile analysis. Results show clear gender specificity with females having a higher number of regulated genes and therefore being more sensitive to HBCD than males. Several specific pathways were found to be affected by HBCD exposure, like PPAR-mediated regulation of lipid metabolism, triacylglycerol metabolism, cholesterol biosynthesis, and phase I and II pathways. These results were corroborated with quantitative RT-PCR analysis. Cholesterol biosynthesis and lipid metabolism were especially down-regulated in females. Genes involved in phase I and II metabolism were up-regulated predominantly in males, which could explain the observed lower HBCD hepatic disposition in male rats in this 28-day study. These sex-specific differences in gene expression profiles could also underlie sex-specific differences in toxicity (e.g. decreased thyroid hormone or increased serum cholesterol levels). To our knowledge, this is the fist study that describes the changes in rat hepatic gene profiles caused by this commonly used flame retardant

Natural history and treatment of hepatitis B virus and hepatitis C virus coinfection

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Keeffe Emmet B

2005-09-01

Full Text Available Abstract Hepatitis B virus (HBV and hepatitis C virus (HCV coinfection is not uncommon as a result of similar routes of infection. Patients who are coinfected represent a unique group with diverse serologic profiles. Combined chronic hepatitis B and C leads to more severe liver disease and an increased risk of hepatocellular carcinoma. Furthermore, coinfected patients represent a treatment challenge. No standard recommendations exist for treatment of viral hepatitis due to dual HBV/HCV infection, and therefore treatment must be individualized based on patient variables such as serologic and virologic profiles, patient's prior exposure to antiviral treatment, and the presence of other parenterally transmitted viruses such as hepatitis D virus and human immunodeficiency virus. The natural history and treatment of patients with HBV and HCV coinfection is reviewed.

Alternative Cell Sources to Adult Hepatocytes for Hepatic Cell Therapy.

Science.gov (United States)

Pareja, Eugenia; Gómez-Lechón, María José; Tolosa, Laia

2017-01-01

Adult hepatocyte transplantation is limited by scarce availability of suitable donor liver tissue for hepatocyte isolation. New cell-based therapies are being developed to supplement whole-organ liver transplantation, to reduce the waiting-list mortality rate, and to obtain more sustained and significant metabolic correction. Fetal livers and unsuitable neonatal livers for organ transplantation have been proposed as potential useful sources of hepatic cells for cell therapy. However, the major challenge is to use alternative cell sources for transplantation that can be derived from reproducible methods. Different types of stem cells with hepatic differentiation potential are eligible for generating large numbers of functional hepatocytes for liver cell therapy to treat degenerative disorders, inborn hepatic metabolic diseases, and organ failure. Clinical trials are designed to fully establish the safety profile of such therapies and to define target patient groups and standardized protocols.

Safety Profile of Eslicarbazepine Acetate as Add-On Therapy in Adults with Refractory Focal-Onset Seizures: From Clinical Studies to 6 Years of Post-Marketing Experience.

Science.gov (United States)

Gama, Helena; Vieira, Mariana; Costa, Raquel; Graça, Joana; Magalhães, Luís M; Soares-da-Silva, Patrício

2017-12-01

Eslicarbazepine acetate was first approved in the European Union in 2009 as adjunctive therapy in adults with partial-onset seizures with or without secondary generalization. The objective of this study was to review the safety profile of eslicarbazepine acetate analyzing the data from several clinical studies to 6 years of post-marketing surveillance. We used a post-hoc pooled safety analysis of four phase III, double-blind, randomized, placebo-controlled studies (BIA-2093-301, -302, -303, -304) of eslicarbazepine acetate as add-on therapy in adults. Safety data of eslicarbazepine acetate in special populations of patients aged ≥65 years with partial-onset seizures (BIA-2093-401) and subjects with moderate hepatic impairment (BIA-2093-111) and renal impairment (BIA-2093-112) are also considered. The incidences of treatment-emergent adverse events, treatment-emergent adverse events leading to discontinuation, and serious adverse events were analyzed. The global safety database of eslicarbazepine acetate was analyzed for all cases from post-marketing surveillance from 1 October, 2009 to 21 October, 2015. From a pooled analysis of four phase III studies, it was concluded that the incidence of treatment-emergent adverse events, treatment-emergent adverse events leading to discontinuation, and adverse drug reactions were dose dependent. Dizziness, somnolence, headache, and nausea were the most common treatment-emergent adverse events (≥10% of patients) and the majority were of mild-to-moderate intensity. No dose-dependent trend was observed for serious adverse events and individual serious adverse events were reported in less than 1% of patients. Hyponatremia was classified as a possibly related treatment-emergent adverse event in phase III studies (1.2%); however, after 6 years of post-marketing surveillance it represents the most frequently (10.2%) reported adverse drug reaction, with more than half of these cases occurring with eslicarbazepine acetate at

Pharmacokinetics and safety of sacubitril/valsartan (LCZ696) in patients with mild and moderate hepatic impairment
.

Science.gov (United States)

Kulmatycki, Kenneth M; Langenickel, Thomas; Ng, Wai Hong; Pal, Parasar; Zhou, Wei; Lin, Tsu-Han; Rajman, Iris; Chandra, Priyamvada; Sunkara, Gangadhar

2017-09-01

To assess the protein binding and pharmacokinetics of sacubitril/valsartan analytes (sacubitril, sacubitrilat, and valsartan) in an open-label, single oral dose (200 mg), parallel-group study in patients with mild and moderate hepatic impairment (Child-Pugh class A and B) and matched healthy subjects. This study enrolled 32 subjects (n = 8 in each hepatic impairment and matched healthy subjects groups). Blood samples were collected at pre-determined time points to assess pharmacokinetics of sacubitril, sacubitrilat, and valsartan. Subjects with severe hepatic impairment were excluded as valsartan exposure is expected to be substantially increased in these patients. Sacubitril exposure (AUC) increased by 53% and 245% while the exposure to sacubitrilat was increased by 48% and 90% in patients with mild and moderate hepatic impairment, respectively. Sacubitril Cmax increased by 57% and 210% in mild and moderate hepatic impairment; however, for both sacubitrilat and valsartan, Cmax was unchanged. Valsartan AUC increased in patients with mild and moderate hepatic impairment by 19 - 109%, respectively. The increase in systemic exposures to all sacubitril/valsartan analytes correlated with the severity of liver disease. The plasma unbound fraction of sacubitrilat in patients with moderate hepatic impairment was slightly higher than in matched healthy subjects. This difference was not considered clinically significant. Safety assessments showed that sacubitril/valsartan was safe and well tolerated across all the study groups.
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Differential plasma microRNA profiles in HBeAg positive and HBeAg negative children with chronic hepatitis B

DEFF Research Database (Denmark)

Winther, Thilde Nordmann; Bang-Berthelsen, Claus Heiner; Heiberg, Ida Louise

2013-01-01

Children chronically infected with hepatitis B virus (HBV) are at high risk of progressive liver disease. However, no treatment is available that is consistently effective in curing chronic hepatitis B (CHB) in children. Improved understanding of the natural course of disease is warranted....... Identification of specific microRNA (miRNA) profiles in children chronically infected with HBV may provide insight into the pathogenesis of CHB and lead to advances in the management of children with CHB....

Dietary Supplementation with Virgin Coconut Oil Improves Lipid Profile and Hepatic Antioxidant Status and Has Potential Benefits on Cardiovascular Risk Indices in Normal Rats.

Science.gov (United States)

Famurewa, Ademola C; Ekeleme-Egedigwe, Chima A; Nwali, Sophia C; Agbo, Ngozi N; Obi, Joy N; Ezechukwu, Goodness C

2018-05-04

Research findings that suggest beneficial health effects of dietary supplementation with virgin coconut oil (VCO) are limited in the published literature. This study investigated the in vivo effects of a 5-week VCO-supplemented diet on lipid profile, hepatic antioxidant status, hepatorenal function, and cardiovascular risk indices in normal rats. Rats were randomly divided into 3 groups: 1 control and 2 treatment groups (10% and 15% VCO-supplemented diets) for 5 weeks. Serum and homogenate samples were used to analyze lipid profile, hepatorenal function markers, hepatic activities of antioxidant enzymes, and malondialdehyde level. Lipid profile of animals fed VCO diets showed significant reduction in total cholesterol (TC), triglyceride (TG), and low-density lipoprotein (LDL) levels; high-density lipoprotein (HDL) level increased significantly (p risk indices. The level of malondialdehyde (MDA), a lipid peroxidation marker, remarkably reduced and activities of hepatic antioxidant enzymes-superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx)-were markedly increased in VCO diet-fed rats. The VCO diet significantly modulated creatinine, sodium (Na + ), potassium (K + ), chloride (Cl - ), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) compared to control. The findings suggest a beneficial effect of VCO on lipid profile, renal status, hepatic antioxidant defense system, and cardiovascular risk indices in rats.

Effects of strain and age on hepatic gene expression profiles in murine models of HFE-associated hereditary hemochromatosis.

Science.gov (United States)

Lee, Seung-Min; Loguinov, Alexandre; Fleming, Robert E; Vulpe, Christopher D

2015-01-01

Hereditary hemochromatosis is an iron overload disorder most commonly caused by a defect in the HFE gene. While the genetic defect is highly prevalent, the majority of individuals do not develop clinically significant iron overload, suggesting the importance of genetic modifiers. Murine hfe knockout models have demonstrated that strain background has a strong effect on the severity of iron loading. We noted that hepatic iron loading in hfe-/- mice occurs primarily over the first postnatal weeks (loading phase) followed by a timeframe of relatively static iron concentrations (plateau phase). We thus evaluated the effects of background strain and of age on hepatic gene expression in Hfe knockout mice (hfe-/-). Hepatic gene expression profiles were examined using cDNA microarrays in 4- and 8-week-old hfe-/- and wild-type mice on two different genetic backgrounds, C57BL/6J (C57) and AKR/J (AKR). Genes differentially regulated in all hfe-/- mice groups, compared with wild-type mice, including those involved in cell survival, stress and damage responses and lipid metabolism. AKR strain-specific changes in lipid metabolism genes and C57 strain-specific changes in cell adhesion and extracellular matrix protein genes were detected in hfe-/- mice. Mouse strain and age are each significantly associated with hepatic gene expression profiles in hfe-/- mice. These affects may underlie or reflect differences in iron loading in these mice.

Circular RNA Profiling and Bioinformatic Modeling Identify Its Regulatory Role in Hepatic Steatosis.

Science.gov (United States)

Guo, Xing-Ya; He, Chong-Xin; Wang, Yu-Qin; Sun, Chao; Li, Guang-Ming; Su, Qing; Pan, Qin; Fan, Jian-Gao

2017-01-01

Circular RNAs (circRNAs) exhibit a wide range of physiological and pathological activities. To uncover their role in hepatic steatosis, we investigated the expression profile of circRNAs in HepG2-based hepatic steatosis induced by high-fat stimulation. Differentially expressed circRNAs were subjected to validation using QPCR and functional analyses using principal component analysis, hierarchical clustering, target prediction, gene ontology (GO), and pathway annotation, respectively. Bioinformatic integration established the circRNA-miRNA-mRNA regulatory network so as to identify the mechanisms underlying circRNAs' metabolic effect. Here we reported that hepatic steatosis was associated with a total of 357 circRNAs. Enrichment of transcription-related GOs, especially GO: 0006355, GO: 004589, GO: 0045944, GO: 0045892, and GO: 0000122, demonstrated their specific actions in transcriptional regulation. Lipin 1 (LPIN1) was recognized to mediate the transcriptional regulatory effect of circRNAs on metabolic pathways. circRNA-miRNA-mRNA network further identified the signaling cascade of circRNA_021412/miR-1972/LPIN1, which was characterized by decreased level of circRNA_021412 and miR-1972-based inhibition of LPIN1. LPIN1-induced downregulation of long chain acyl-CoA synthetases (ACSLs) expression finally resulted in the hepatosteatosis. These findings identify circRNAs to be important regulators of hepatic steatosis. Transcription-dependent modulation of metabolic pathways may underlie their effects, partially by the circRNA_021412/miR-1972/LPIN1 signaling.

A diet high in α-linolenic acid and monounsaturated fatty acids attenuates hepatic steatosis and alters hepatic phospholipid fatty acid profile in diet-induced obese rats.

Science.gov (United States)

Hanke, Danielle; Zahradka, Peter; Mohankumar, Suresh K; Clark, Jaime L; Taylor, Carla G

2013-01-01

This study investigated the efficacy of the plant-based n-3 fatty acid, α-linolenic acid (ALA), a dietary precursor of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), for modulating hepatic steatosis. Rats were fed high fat (55% energy) diets containing high oleic canola oil, canola oil, a canola/flax oil blend (C/F, 3:1), safflower oil, soybean oil, or lard. After 12 weeks, C/F and weight-matched (WM) groups had 20% less liver lipid. Body mass, liver weight, glucose and lipid metabolism, inflammation and molecular markers of fatty acid oxidation, synthesis, desaturation and elongation did not account for this effect. The C/F group had the highest total n-3 and EPA in hepatic phospholipids (PL), as well as one of the highest DHA and lowest arachidonic acid (n-6) concentrations. In conclusion, the C/F diet with the highest content of the plant-based n-3 ALA attenuated hepatic steatosis and altered the hepatic PL fatty acid profile. © 2013 Published by Elsevier Ltd.

Profile of dengue hepatitis in children from India and its correlation with WHO dengue case classifiation

Directory of Open Access Journals (Sweden)

Neelam Mohan

2017-06-01

Full Text Available Objective: To study the profile of liver involvement in children with dengue fever and to compare the severity of liver involvement with World Health Organization case definition. Methods: A prospective study was carried out from October 2013 to December 2014. Serologically confirmed dengue patients were grouped into three categories according to the World Health Organization classification. Groups 1 and 2 were dengue fever without and with warning signs, respectively; Group 3 was severe dengue. Biochemical and clinical profile of hepatic involvement was studied. Results: A total of 162 children with dengue fever (M:F = 2.37 were included in the study. Median (inter quartile range age was 12 years (IQR: 0.5–18 years. Hepatitis was observed in 151 (93.2% patients. Analysis revealed that out of all liver function test parameters, total bilirubin was found to be a significant predictor of dengue category two and three and albumin and ALT levels were significant predictors for category three. Eight cases presented with ALF. Their median AST was 4 817 (range 61–26 957; median ALT was 2 386 (range 39–11 100; median INR was 2.57 (range 1.6–4.2 and their median serum bilirubin was 2.95 (range 0.6–9.0. Conclusions: Some degree of hepatitis is very common in dengue infection with rise in AST being more than ALT irrespective of the severity of dengue. Severity of hepatitis correlates well with the severity of dengue and can help in triaging of dengue patients. Of all liver function parameters, total bilirubin levels correlate best with severity of dengue infection.

Serum metabolome profiles characterized by patients with hepatocellular carcinoma associated with hepatitis B and C.

Science.gov (United States)

Saito, Takafumi; Sugimoto, Masahiro; Okumoto, Kazuo; Haga, Hiroaki; Katsumi, Tomohiro; Mizuno, Kei; Nishina, Taketo; Sato, Sonoko; Igarashi, Kaori; Maki, Hiroko; Tomita, Masaru; Ueno, Yoshiyuki; Soga, Tomoyoshi

2016-07-21

To clarify the characteristics of metabolite profiles in virus-related hepatocellular carcinoma (HCC) patients using serum metabolome analysis. The serum levels of low-molecular-weight metabolites in 68 patients with HCC were quantified using capillary electrophoresis chromatography and mass spectrometry. Thirty and 38 of the patients suffered from hepatitis B virus-related HCC (HCC-B) and hepatitis C virus-related HCC (HCC-C), respectively. The main metabolites characteristic of HCC were those associated with glutathione metabolism, notably 13 γ-glutamyl peptides, which are by-products of glutathione induction. Two major profiles, i.e., concentration patterns, of metabolites were identified in HCC patients, and these were classified into two groups: an HCC-B group and an HCC-C group including some of the HCC-B cases. The receiver operating characteristic curve for the multiple logistic regression model discriminating HCC-B from HCC-C incorporating the concentrations of glutamic acid, methionine and γ-glutamyl-glycine-glycine showed a highly significant area under the curve value of 0.94 (95%CI: 0.89-1.0, P < 0.0001). The serum levels of γ-glutamyl peptides, as well as their concentration patterns, contribute to the development of potential biomarkers for virus-related HCC. The difference in metabolite profiles between HCC-B and HCC-C may reflect the respective metabolic reactions that underlie the different pathogeneses of these two types of HCC.

Prediction of Clinically Relevant Safety Signals of Nephrotoxicity through Plasma Metabolite Profiling

Directory of Open Access Journals (Sweden)

W. B. Mattes

2013-01-01

Full Text Available Addressing safety concerns such as drug-induced kidney injury (DIKI early in the drug pharmaceutical development process ensures both patient safety and efficient clinical development. We describe a unique adjunct to standard safety assessment wherein the metabolite profile of treated animals is compared with the MetaMap Tox metabolomics database in order to predict the potential for a wide variety of adverse events, including DIKI. To examine this approach, a study of five compounds (phenytoin, cyclosporin A, doxorubicin, captopril, and lisinopril was initiated by the Technology Evaluation Consortium under the auspices of the Drug Safety Executive Council (DSEC. The metabolite profiles for rats treated with these compounds matched established reference patterns in the MetaMap Tox metabolomics database indicative of each compound’s well-described clinical toxicities. For example, the DIKI associated with cyclosporine A and doxorubicin was correctly predicted by metabolite profiling, while no evidence for DIKI was found for phenytoin, consistent with its clinical picture. In some cases the clinical toxicity (hepatotoxicity, not generally seen in animal studies, was detected with MetaMap Tox. Thus metabolite profiling coupled with the MetaMap Tox metabolomics database offers a unique and powerful approach for augmenting safety assessment and avoiding clinical adverse events such as DIKI.

Influenza vaccines: Evaluation of the safety profile

Science.gov (United States)

Trombetta, Claudia Maria; Gianchecchi, Elena; Montomoli, Emanuele

2018-01-01

ABSTRACT The safety of vaccines is a critical factor in maintaining public trust in national vaccination programs. Vaccines are recommended for children, adults and elderly subjects and have to meet higher safety standards, since they are administered to healthy subjects, mainly healthy children. Although vaccines are strictly monitored before authorization, the possibility of adverse events and/or rare adverse events cannot be totally eliminated. Two main types of influenza vaccines are currently available: parenteral inactivated influenza vaccines and intranasal live attenuated vaccines. Both display a good safety profile in adults and children. However, they can cause adverse events and/or rare adverse events, some of which are more prevalent in children, while others with a higher prevalence in adults. The aim of this review is to provide an overview of influenza vaccine safety according to target groups, vaccine types and production methods. PMID:29297746

Direct-acting antiviral agent efficacy and safety in renal transplant recipients with chronic hepatitis C virus infection

OpenAIRE

Chen, Keliang; Lu, Pei; Song, Rijin; Zhang, Jiexiu; Tao, Rongzhen; Wang, Zijie; Zhang, Wei; Gu, Min

2017-01-01

Abstract Background: The efficacy and safety of direct-acting antivirals (DAAs) for treating hepatitis C virus (HCV)-infected renal transplant recipients (RTRs) has not been determined. Methods: We searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials and assessed the quality of eligible studies using the Joanna Briggs Institute scale. DAA efficacy and safety were assessed using standard mean difference (SMD) with 95% confidence intervals (95%CIs). Results: Six studi...

Hepatitis B Virus Blood Screening: Need for Reappraisal of Blood Safety Measures?

Directory of Open Access Journals (Sweden)

Daniel Candotti

2018-02-01

Full Text Available Over the past decades, the risk of HBV transfusion–transmission has been steadily reduced through the recruitment of volunteer donors, the selection of donors based on risk-behavior evaluation, the development of increasingly more sensitive hepatitis B antigen (HBsAg assays, the use of hepatitis B core antibody (anti-HBc screening in some low-endemic countries, and the recent implementation of HBV nucleic acid testing (NAT. Despite this accumulation of blood safety measures, the desirable zero risk goal has yet to be achieved. The residual risk of HBV transfusion–transmission appears associated with the preseroconversion window period and occult HBV infection characterized by the absence of detectable HBsAg and extremely low levels of HBV DNA. Infected donations tested false-negative with serology and/or NAT still persist and derived blood components were shown to transmit the virus, although rarely. Questions regarding the apparent redundancy of some safety measures prompted debates on how to reduce the cost of HBV blood screening. In particular, accumulating data strongly suggests that HBsAg testing may add little, if any HBV risk reduction value when HBV NAT and anti-HBc screening also apply. Absence or minimal acceptable infectious risk needs to be assessed before considering discontinuing HBsAg. Nevertheless, HBsAg remains essential in high-endemic settings where anti-HBc testing cannot be implemented without compromising blood availability. HBV screening strategy should be decided according to local epidemiology, estimate of the infectious risk, and resources.

Immunity to hepatitis A and B persists for at least 15 years after immunisation of adolescents with a combined hepatitis A and B vaccine.

Science.gov (United States)

Beran, Jiri; Van Der Meeren, Olivier; Leyssen, Maarten; D'silva, Priya

2016-05-23

The exact duration of antibody persistence to hepatitis A and B and the need for booster dosing following primary immunisation remains undefined. A long-term study was designed to follow antibody persistence and immune memory on an annual basis for up to 15 years following vaccination during adolescence. Subjects received a combined hepatitis A and B vaccine (Twinrix™, GSK Vaccines, Belgium) at 12-15 years of age, either as 2-dose of the adult formulation or 3-dose of the paediatric formulation. Blood samples were taken every year thereafter to assess antibody persistence and immune memory to hepatitis A and B. Antibodies to hepatitis A virus (anti-HAV) and hepatitis B surface antigen (anti-HBs) were measured at Years 11-15. At Year 15 immune memory was further assessed by measuring the anamnestic response to a challenge dose of the monovalent vaccine, which was administered to subjects whose antibody concentrations fell below the pre-defined cut-offs (anti-HAV: hepatitis B vaccine challenge dose administration to 19 subjects, all except one in the 3-dose group, mounted a robust anamnestic response. The safety and reactogenicity profile of the hepatitis B challenge was consistent with previous experience. Immunity to hepatitis A and B persists 15 years after adolescent vaccination with a combined hepatitis A and B vaccine. Highly effective anamnestic response indicates that a booster dose should not be required for 15 years after primary vaccination. http://www.clinicaltrials.govNCT00875485. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Metabolomics (liver and blood profiling) in a mouse model in response to fasting: A study of hepatic steatosis

NARCIS (Netherlands)

Ginneken, V. van; Verhey, E.; Poelmann, R.; Ramakers, R.; Dijk, K.W. van; Ham, L.; Voshol, P.; Havekes, L.; Eck, M. van; Greef, J. van der

2007-01-01

A metabolomic approach was applied to a mouse model of starvation-induced hepatic steatosis. After 24 h of fasting it appears that starvation reduced the phospholipids (PL), free cholesterol (FC), and cholesterol esters (CE) content of low-density lipoproteins (LDL). In liver lipid profiles major

Defibrotide for children and adults with hepatic veno-occlusive disease post hematopoietic cell transplantation.

Science.gov (United States)

Corbacioglu, Selim; Richardson, Paul G

2017-10-01

Hepatic veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is a complication that is typically associated with conditioning for hematopoietic stem cell transplantation (HSCT). In patients with concomitant multi-organ dysfunction, mortality may be >80%. Recently, the European Society for Blood and Marrow Transplantation established separate criteria for diagnosis and severity of VOD/SOS for adults and children, to better reflect current understanding of the disease. Areas covered: This review provides an overview of post-HSCT hepatic VOD/SOS and defibrotide, including its pharmacological, clinical, and regulatory profile. In children and adults following HSCT, defibrotide is approved for the treatment of hepatic VOD/SOS with concomitant renal or pulmonary dysfunction in the United States and for the treatment of severe hepatic VOD/SOS in the European Union. Day +100 survival rates with defibrotide are superior to those of historical controls receiving best supportive care only, and safety profiles are similar. Expert commentary: Defibrotide appears to act through multiple mechanisms to restore thrombo-fibrinolytic balance and protect endothelial cells, and there are promising data on the use of defibrotide for VOD/SOS prophylaxis in high-risk children undergoing HSCT. An ongoing randomized controlled trial in children and adults will better assess the clinical value of defibrotide as a preventive medication.

Pharmacokinetics of serelaxin in patients with hepatic impairment: a single-dose, open-label, parallel group study.

Science.gov (United States)

Kobalava, Zhanna; Villevalde, Svetlana; Kotovskaya, Yulia; Hinrichsen, Holger; Petersen-Sylla, Marc; Zaehringer, Andreas; Pang, Yinuo; Rajman, Iris; Canadi, Jasna; Dahlke, Marion; Lloyd, Peter; Halabi, Atef

2015-06-01

Serelaxin is a recombinant form of human relaxin-2 in development for treatment of acute heart failure. This study aimed to evaluate the pharmacokinetics (PK) of serelaxin in patients with hepatic impairment. Secondary objectives included evaluation of immunogenicity, safety and tolerability of serelaxin. This was an open-label, parallel group study (NCT01433458) comparing the PK of serelaxin following a single 24 h intravenous (i.v.) infusion (30 μg kg(-1)  day(-1) ) between patients with mild, moderate or severe hepatic impairment (Child-Pugh class A, B, C) and healthy matched controls. Blood sampling and standard safety assessments were conducted. Primary non-compartmental PK parameters [including area under the serum concentration-time curve AUC(0-48 h) and AUC(0-∞) and serum concentration at 24 h post-dose (C24h )] were compared between each hepatic impairment group and healthy controls. A total of 49 subjects (including 25 patients with hepatic impairment) were enrolled, of which 48 subjects completed the study. In all groups, the serum concentration of serelaxin increased over the first few hours of infusion, reached steady-state at 12-24 h and then declined following completion of infusion, with a mean terminal half-life of 7-8 h. All PK parameter estimates were comparable between each group of patients with hepatic impairment and healthy controls. No serious adverse events, discontinuations due to adverse events or deaths were reported. No serelaxin treatment-related antibodies developed during this study. The PK and safety profile of serelaxin were not affected by hepatic impairment. No dose adjustment is needed for serelaxin treatment of 48 h i.v. infusion in patients with hepatic impairment. © 2014 The British Pharmacological Society.

Biological and haematological safety profile of oral amodiaquine ...

African Journals Online (AJOL)

Biological and haematological safety profile of oral amodiaquine and chloroquine in healthy volunteers with or without Plasmodium falciparum infection in northeast Tanzania. JJ Massaga, JP Lusingu, R Makunde, HM Malebo, MM Chile, JA Akida, MM Lemnge, AM Rønn, TG Theander, IC Bygbjerg, AY Kitua ...

Review of 10 years of marketing experience with Chinese domestic inactivated hepatitis A vaccine Healive®

Science.gov (United States)

Wu, Jun-Yu; Liu, Yan; Chen, Jiang-Ting; Xia, Ming; Zhang, Xiao-Mei

2012-01-01

In 2002, the first Chinese domestic preservative-free inactivated hepatitis A vaccine, Healive®, was introduced in China. It is highly immunogenic, and provides lasting protection in healthy individuals and generates protective levels of antibodies in other at-risk individuals. Over 10 years since its first licensure, postmarketing surveillance data have confirmed the outstanding safety profile of the vaccine. Comparative clinical trials indicated that Healive® induce equal or similar immunogenicity with other currently available inactivated hepatitis A vaccines and are interchangeable for the course of HAV immunization in Chinese children. The vaccine is effective in curbing outbreaks of hepatitis A due to rapid seroconversion and the long incubation period of the disease. Additional issues surrounding the use of the vaccine are also reviewed. PMID:23032165

Safety and Tolerability Profile of Artemisinin-Based Antimalarial ...

African Journals Online (AJOL)

The WHO in 2001 advocated artemisinin- based antimalarial combination therapy (ACT), which was adopted by Nigeria in 2005. The objective of this study was to characterize the safety and tolerability profile of the ACTs in adult patients with uncomplicated malaria. A descriptive longitudinal study was conducted in the ...

Metabolic profiles and bile acid extraction rate in the liver of cows with fasting-induced hepatic lipidosis.

Science.gov (United States)

Mohamed, T; Oikawa, S; Iwasaki, Y; Mizunuma, Y; Takehana, K; Endoh, D; Kurosawa, T; Sato, H

2004-04-01

This study was designed to monitor lipid profile in the portal and hepatic blood of cows with fasting-induced hepatic lipidosis, and to compare the results with those in the jugular blood. The work was also carried out to investigate bile acid (BA) in these vessels, and further to investigate BA extraction rate in the liver. Five cows were equipped with catheters in the portal, hepatic and jugular veins (day 0), fasted for 4 days (day 1-day 4) and then refed (day 5-day 11). Before morning feeding, blood was sampled before, during and after fasting from the catheterized vessels. In the portal blood, the concentration of non-esterified fatty acids (NEFA) showed a progressive increase and at day 5 there was an approximate twofold rise. Increased NEFA concentrations were also found similarly in the other two veins. At day 5, beta-hydroxybutyrate (BHBA) in the portal, hepatic and jugular blood rose to 197, 190 and 186% of the pre-fasting value, respectively. However, the concentrations of NEFA and BHBA in the three veins gradually returned to pre-fasting concentration during the refeeding period. Compared with the pre-fasting value at day 0, the content of liver triglyceride (TG) increased significantly at day 5 (P hepatic extraction rate of BA dropped from 3.1 times pre-fasting to 2.2 times during fasting. There were no significant differences in the concentrations of glucose, TG, total cholesterol, cholesterol esters, free cholesterol and phospholipids. The results of the current study show that metabolic alterations occur in the portal, hepatic and jugular veins during induction of hepatic lipidosis in cows, and mostly metabolites, with exception of BA concentration, run parallel. The decreased BA extraction rate in the liver of fasted cows was considered to reflect hepatic cell impairment caused by TG accumulation. Hopefully, the findings, at least in part, contribute to the explanation of the pathophysiology of hepatic lipidosis in dairy cows.

Efficacy and safety of 8 weeks versus 12 weeks of treatment with grazoprevir (MK-5172) and elbasvir (MK-8742) with or without ribavirin in patients with hepatitis C virus genotype 1 mono-infection and HIV/hepatitis C virus co-infection (C-WORTHY)

DEFF Research Database (Denmark)

Sulkowski, Mark; Hezode, Christophe; Gerstoft, Jan

2015-01-01

BACKGROUND: Both hepatitis C virus (HCV) mono-infected and HIV/HCV co-infected patients are in need of safe, effective, all-oral HCV regimens. In a phase 2 study we aimed to assess the efficacy and safety of grazoprevir (MK-5172; HCV NS3/4A protease inhibitor) and two doses of elbasvir (MK-8742......; HCV NS5A inhibitor) in patients with HCV mono-infection and HIV/HCV co-infection. METHODS: The C-WORTHY study is a phase 2, multicentre, randomised controlled trial of grazoprevir plus elbasvir with or without ribavirin in patients with HCV; here, we report findings for previously untreated (genotype......%) and was associated with emergence of resistance-associated variants to one or both drugs. The safety profile of grazoprevir plus elbasvir with or without ribavirin was similar in mono-infected and co-infected patients. No patient discontinued due to an adverse event or laboratory abnormality. The most common adverse...

Effect of Chronic Pioglitazone Treatment on Hepatic Gene Expression Profile in Obese C57BL/6J Mice

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Chunming Jia

2015-05-01

Full Text Available Pioglitazone, a selective ligand of peroxisome proliferator-activated receptor gamma (PPARγ, is an insulin sensitizer drug that is being used in a number of insulin-resistant conditions, including non-alcoholic fatty liver disease (NAFLD. However, there is a discrepancy between preclinical and clinical data in the literature and the benefits of pioglitazone treatment as well as the precise mechanism of action remain unclear. In the present study, we determined the effect of chronic pioglitazone treatment on hepatic gene expression profile in diet-induced obesity (DIO C57BL/6J mice in order to understand the mechanisms of NAFLD induced by PPARγ agonists. DIO mice were treated with pioglitazone (25 mg/kg/day for 38 days, the gene expression profile in liver was evaluated using Affymetrix Mouse GeneChip 1.0 ST array. Pioglitazone treatment resulted in exacerbated hepatic steatosis and increased hepatic triglyceride and free fatty acids concentrations, though significantly increased the glucose infusion rate in hyperinsulinemic-euglycemic clamp test. The differentially expressed genes in liver of pioglitazone treated vs. untreated mice include 260 upregulated and 86 downregulated genes. Gene Ontology based enrichment analysis suggests that inflammation response is transcriptionally downregulated, while lipid metabolism is transcriptionally upregulated. This may underlie the observed aggravating liver steatosis and ameliorated systemic insulin resistance in DIO mice.

Effects of Arctium lappa aqueous extract on lipid profile and hepatic enzyme levels of sucrose-induced metabolic syndrome in female rats

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Akram Ahangarpour

Full Text Available ABSTRACT Arctium lappa is known to have antioxidant and antidiabetic effects in traditional medicine. Objectives: The aim of this paper was to study the effects of A. lappa root extract (AE on lipid profile and hepatic enzyme levels in sucrose-induced metabolic syndrome (MS in female rats. The study used 40 adult female Wistar rats weighing 150 g-250 g randomly divided into five groups: control, metabolic syndrome (MS, metabolic syndrome+AE at 50,100, 200 mg/kg. MS was induced by administering 50% sucrose in drinking water for 6 weeks. AE was intra-peritoneally administered daily at doses of 50,100, and 200 mg/kg for two sequential weeks at the end of the fourth week in metabolic syndrome rats. Twenty-four hours after the last administration of AE, blood was collected and centrifuged, and then the serum was used for the measurement of lipid profile and hepatic enzyme. Serum glucose, insulin, fasting insulin resistance index, body weight, water intake, lipid profile, and hepatic enzymes were significantly increased although food intake was decreased in MS rats compared to the control rats. The lipids and liver enzymes were reduced by AE extracts in the MS group. This study showed that the A. lappa root aqueous extract exhibits a hypolipidemic activity of hyperlipidemic rats. This activity is practically that of a triple-impact antioxidant, hypolipidemic, and hepatoprotective.

Laser safety at high profile laser facilities

International Nuclear Information System (INIS)

Barat, K.

2010-01-01

Complete text of publication follows. Laser safety has been an active concern of laser users since the invention of the laser. Formal standards were developed in the early 1970's and still continue to be developed and refined. The goal of these standards is to give users guidance on the use of laser and consistent safety guidance and requirements for laser manufacturers. Laser safety in the typical research setting (government laboratory or university) is the greatest challenge to the laser user and laser safety officer. This is due to two factors. First, the very nature of research can put the user at risk; consider active manipulation of laser optics and beam paths, and user work with energized systems. Second, a laser safety culture that seems to accept laser injuries as part of the graduate student educational process. The fact is, laser safety at research settings, laboratories and universities still has long way to go. Major laser facilities have taken a more rigid and serious view of laser safety, its controls and procedures. Part of the rationale for this is that these facilities draw users from all around the world presenting the facility with a work force of users coming from a wide mix of laser safety cultures. Another factor is funding sources do not like bad publicity which can come from laser accidents and a poor safety record. The fact is that injuries, equipment damage and lost staff time slow down progress. Hence high profile/large laser projects need to adapt a higher safety regimen both from an engineering and administrative point of view. This presentation will discuss all these points and present examples. Acknowledgement. This work has been supported by the University of California, Director, Office of Science.

Cytokine Signatures Discriminate Highly Frequent Acute Hepatitis a Virus and Hepatitis E Virus Coinfections from Monoinfections in Mexican Pediatric Patients.

Science.gov (United States)

Realpe-Quintero, Mauricio; Copado-Villagrana, Edgar Daniel; Trujillo-Ochoa, Jorge Luis; Alvarez, Angel Hilario; Panduro, Arturo; Fierro, Nora Alma

2017-07-01

The frequency of hepatitis A virus and hepatitis E virus infections and their cytokine profiles were analyzed in Mexican pediatric patients with acute hepatitis. A high frequency of coinfections was found. Significant overexpression of interleukin (IL)-4, IL-12, IL-13 and interferon-gamma during hepatitis A virus monoinfections and limited secretion of cytokines in hepatitis E virus infections were observed.

Chinese medicinal herbs for chronic hepatitis B

DEFF Research Database (Denmark)

Liu, J; McIntosh, H; Lin, Haili

2001-01-01

Chronic hepatitis B is a serious health problem worldwide. Chinese medicinal herbs are widely used for treatment of chronic hepatitis B in China and many clinical trials have been conducted. This systematic review is to assess the efficacy and safety of Chinese medicinal herbs for chronic hepatitis...

Susceptibility to experimental biliary atresia linked to different hepatic gene expression profiles in two mouse strains.

Science.gov (United States)

Leonhardt, Johannes; Kuebler, Joachim F; Turowski, Carmen; Tschernig, Thomas; Geffers, Robert; Petersen, Claus

2010-02-01

To compare hepatic gene expression during the development of experimental biliary atresia (BA) in two different mouse strains. Balb/c mice and C57Black/6 (Black/6) mice were infected with rhesus rotavirus (RRV) postpartum, clinical signs of BA and survival were noted. Liver sections were assessed for cluster of differentiation antigen (CD) 3, CD4 and CD8 expression, and the hepatic virus load was determined. Second, mice of both strains were sacrificed three days after infection. Isolated hepatic RNA was subjected to gene expression analysis using Affymetrix Gene Chip MOE 430 2.0. The incidence of BA was significantly lower in Black/6 mice compared to Balb/c mice (13.5% vs. 67%, P < 0.05). The mean virus titers were higher in mice with BA compared to mice without BA. Different gene profiles three days after virus infection were noted, with differential expression of 201 genes, including those regulating apoptosis, nucleic acid binding, transport function and particularly the immune response (chemokine C-C motif ligand 2, toll-like receptor 3, CD antigen 14, chemokine (C-X-C motif) ligands 10 and 11). This correlated with a significant increase of CD4 positive cells only in Balb/c mice with BA compared to healthy mice (13.5 vs. 5.0; P < 0.05). Black/6 mice did not exhibit any significant increase of CD3 or CD4 leukocytes despite cholestasis. The different susceptibility to experimental BA was associated with an increase of CD4 T-cells in the liver of Balb/c mice, which is linked to different gene profiles at the onset of bile duct obstruction.

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....

Management of hepatitis C infection in the era of direct-acting antiviral therapy

Science.gov (United States)

Zain, L. H.; Sungkar, T.

2018-03-01

Hepatitis C viral infection globally affects millions of people and commonly results in debilitating complications and mortality. Initial mainstay therapy consisted of pegylated interferon α (pegIFNα) with additional ribavirin that showed unsatisfactory cure rate, common side effects and complicated dosing, contributing to high discontinuation rate. Over the last few years, newer antivirals have been extensively studied, that are Direct-Acting Antivirals (DAAs). Specifically targeting viral protein mainly during replication phase, DAAs showed greater cure rate (commonly measured as sustained virologic response), improved safety profile and shorter treatment duration compared to traditional interferon-ribavirin therapy. Current guidelines have also included Interferon-free, often ribavirin-free, DAAs combinations that suggest promising outcomes. The current review highlights development of rapidly growing hepatitis C treatment including DAAs recommendations.

Transcriptional profiling of the bovine hepatic response to experimentally induced E. coli mastitis

DEFF Research Database (Denmark)

Jørgensen, Hanne Birgitte Hede; Buitenhuis, Bart; Røntved, Christine Maria

2012-01-01

The mammalian liver works to keep the body in a state of homeostasis and plays an important role in systemic acute phase response to infections. In this study we investigated the bovine hepatic acute phase response at the gene transcription level in dairy cows with experimentally E. coli-induced ......The mammalian liver works to keep the body in a state of homeostasis and plays an important role in systemic acute phase response to infections. In this study we investigated the bovine hepatic acute phase response at the gene transcription level in dairy cows with experimentally E. coli......-induced mastitis. At time = 0, each of 16 periparturient dairy cows received 20-40 CFU of live E. coli in one front quarter of the udder. A time series of liver biopsies was collected at -144, 12, 24 and 192 hours relative to time of inoculation. Changes in transcription levels in response to E. coli inoculation...... were analyzed using the Bovine Genome Array and tested significant for 408 transcripts over the time series (adjusted p0.05; abs(fold-change)>2). After 2-D clustering, transcripts represented three distinct transcription profiles: 1) regulation of gene transcription and apoptosis, 2) responses...

Efficacy and safety of rilpivirine in treatment-naive, HIV-1-infected patients with hepatitis B virus/hepatitis C virus coinfection enrolled in the Phase III randomized, double-blind ECHO and THRIVE trials.

Science.gov (United States)

Nelson, Mark; Amaya, Gerardo; Clumeck, Nathan; Arns da Cunha, Clovis; Jayaweera, Dushyantha; Junod, Patrice; Li, Taisheng; Tebas, Pablo; Stevens, Marita; Buelens, Annemie; Vanveggel, Simon; Boven, Katia

2012-08-01

The efficacy and hepatic safety of the non-nucleoside reverse transcriptase inhibitors rilpivirine (TMC278) and efavirenz were compared in treatment-naive, HIV-infected adults with concurrent hepatitis B virus (HBV) and/or hepatitis C virus (HCV) infection in the pooled week 48 analysis of the Phase III, double-blind, randomized ECHO (NCT00540449) and THRIVE (NCT00543725) trials. Patients received 25 mg of rilpivirine once daily or 600 mg of efavirenz once daily, plus two nucleoside/nucleotide reverse transcriptase inhibitors. At screening, patients had alanine aminotransferase/aspartate aminotransferase levels ≤5× the upper limit of normal. HBV and HCV status was determined at baseline by HBV surface antigen, HCV antibody and HCV RNA testing. HBV/HCV coinfection status was known for 670 patients in the rilpivirine group and 665 in the efavirenz group. At baseline, 49 rilpivirine and 63 efavirenz patients [112/1335 (8.4%)] were coinfected with either HBV [55/1357 (4.1%)] or HCV [57/1333 (4.3%)]. The safety analysis included all available data, including beyond week 48. Eight patients seroconverted during the study (rilpivirine: five; efavirenz: three). A higher proportion of patients achieved viral load <50 copies/mL (intent to treat, time to loss of virological response) in the subgroup without HBV/HCV coinfection (rilpivirine: 85.0%; efavirenz: 82.6%) than in the coinfected subgroup (rilpivirine: 73.5%; efavirenz: 79.4%) (rilpivirine, P = 0.04 and efavirenz, P = 0.49, Fisher's exact test). The incidence of hepatic adverse events (AEs) was low in both groups in the overall population (rilpivirine: 5.5% versus efavirenz: 6.6%) and was higher in HBV/HCV-coinfected patients than in those not coinfected (26.7% versus 4.1%, respectively). Hepatic AEs were more common and response rates lower in HBV/HCV-coinfected patients treated with rilpivirine or efavirenz than in those who were not coinfected.

Lyapunov-based distributed control of the safety-factor profile in a tokamak plasma

International Nuclear Information System (INIS)

Bribiesca Argomedo, Federico; Witrant, Emmanuel; Prieur, Christophe; Brémond, Sylvain; Nouailletas, Rémy; Artaud, Jean-François

2013-01-01

A real-time model-based controller is developed for the tracking of the distributed safety-factor profile in a tokamak plasma. Using relevant physical models and simplifying assumptions, theoretical stability and robustness guarantees were obtained using a Lyapunov function. This approach considers the couplings between the poloidal flux diffusion equation, the time-varying temperature profiles and an independent total plasma current control. The actuator chosen for the safety-factor profile tracking is the lower hybrid current drive, although the results presented can be easily extended to any non-inductive current source. The performance and robustness of the proposed control law is evaluated with a physics-oriented simulation code on Tore Supra experimental test cases. (paper)

Liver safety assessment in special populations (hepatitis B, C, and oncology trials).

Science.gov (United States)

Kullak-Ublick, Gerd A; Merz, Michael; Griffel, Louis; Kaplowitz, Neil; Watkins, Paul B

2014-11-01

The FDA guidance for industry in the premarketing clinical evaluation of drug-induced liver injury (DILI) is the most specific regulatory guidance currently available and has been useful in setting standards for the great majority of clinical indications involving subjects with a low risk of liver disorders. However, liver safety assessment faces challenges in populations with underlying liver disease, such as viral hepatitis or metastatic cancer. This is an important issue because there are currently many promising anti-viral and oncologic therapies in clinical development, with a trend toward oral therapies with reduced side effects. Without clearer guidelines, questions regarding liver safety may become a major factor in regulatory approval and ultimately physician uptake of the new treatments. The lack of consensus in defining stopping rules based on serum alanine aminotransferase (ALT) levels underscores the need for precompetitive data sharing to improve our understanding of DILI in these populations and to allow evidence-based rather than empirical definition of stopping rules. A workshop was convened to discuss best practices for the assessment of drug-induced liver injury (DILI) in clinical trials.

Immunogenicity and safety of high-dose hepatitis B vaccine among drug users: A randomized, open-labeled, blank-controlled trial.

Science.gov (United States)

Feng, Yongliang; Shi, Jing; Gao, Linying; Yao, Tian; Feng, Dan; Luo, Dan; Li, Zhansheng; Zhang, Yawei; Wang, Fuzhen; Cui, Fuqiang; Li, Li; Liang, Xiaofeng; Wang, Suping

2017-06-03

Due to the low uptake, adherence, and completion of vaccination among drug users, and their compromised immune responses to hepatitis B vaccination, the current practice of hepatitis B vaccination may not provide optimal protection. The aim of this study was to evaluate the immunogenicity and safety of 60 µg and 20 µg hepatitis B vaccines among drug users. A randomized, open-labeled, blank-controlled trial was conducted among drug users at 2 drug rehabilitation centers in China. The eligible participants were drug users who were serologically negative for the hepatitis B surface antigen (HBsAg) and the hepatitis B surface antibody (anti-HBs). Participants were randomized in a ratio of 1:1:1 to receive 20 µg (IM20 group) or 60 µg (IM60 group) of hepatitis B vaccine or blank control at months 0, 1, and 6, and followed at months 6, 7, and 12. Seroconversion rates of 94.7% and 92.6% were observed in IM20 and IM60 groups at month 7, and correspondingly decreased to 89.5% and 91.7% respectively at month 12. The IM60 group showed significantly higher geometric mean concentrations (GMCs) of anti-HBs (2022.5 and 676.7 mIU mL-1) than the IM20 group did (909.6 and 470.5 mIU mL-1) at months 7 and 12 (P B vaccines showed good immunogenicity among the drug users.

Profiling of hepatic gene expression in rats treated with fibric acid analogs

International Nuclear Information System (INIS)

Cornwell, Paul D.; Souza, Angus T. de; Ulrich, Roger G.

2004-01-01

Peroxisome proliferator-activated receptors (PPARs) are a group of nuclear receptors whose ligands include fatty acids, eicosanoids and the fibrate class of drugs. In humans, fibrates are used to treat dyslipidemias. In rodents, fibrates cause peroxisome proliferation, a change that might explain the observed hepatomegaly. In this study, rats were treated with multiple dose levels of six fibric acid analogs (including fenofibrate) for up to two weeks. Pathological analysis identified hepatocellular hypertrophy as the only sign of hepatotoxicity, and only one compound at the highest dose caused any significant increase in serum ALT or AST activity. RNA profiling revealed that the expression of 1288 genes was related to dose or length of treatment and correlated with hepatocellular hypertrophy. This gene list included expression changes that were consistent with increased mitochondrial and peroxisomal β-oxidation, increased fatty acid transport, increased hepatic uptake of LDL-cholesterol, decreased hepatic uptake of glucose, decreased gluconeogenesis and decreased glycolysis. These changes are likely linked to many of the clinical benefits of fibrate drugs, including decreased serum triglycerides, decreased serum LDL-cholesterol and increased serum HDL-cholesterol. In light of the fact that all six compounds stimulated similar or identical changes in the expression of this set of 1288 genes, these results indicate that hepatomegaly is due to PPARα activation, although signaling through other receptors (e.g. PPARγ, RXR) or through non-receptor pathways cannot be excluded

Percutaneous Isolated Hepatic Perfusion as a Treatment for Isolated Hepatic Metastases of Uveal Melanoma: Patient Outcome and Safety in a Multi-centre Study

International Nuclear Information System (INIS)

Vogl, Thomas J.; Koch, Silvia A.; Lotz, Gösta; Gebauer, Bernhard; Willinek, Winfried; Engelke, Christoph; Brüning, Roland; Zeile, Martin; Wacker, Frank; Vogel, Arndt; Radeleff, Boris; Scholtz, Jan-Erik

2017-01-01

PurposePercutaneous isolated hepatic perfusion (PIHP) with Melphalan has been developed as a treatment for patients with isolated hepatic metastases of uveal melanoma. We discuss patient outcome and safety in a retrospective multi-centre study.Materials and MethodsBetween 2012 and 2016 18 patients with un-resectable isolated hepatic metastases of uveal melanoma received single or repeated PIHP with Melphalan (n = 35) at seven sites. Progression-free time, overall survival time (OS) and tumour response by means of RECIST 1.1 criteria were evaluated. Peri- and post-procedural adverse events (AE) were registered. Patients’ life quality was assessed using four-point scale questionnaires.ResultsOf 18 patients, initial PIHP treatment resulted in partial response (PR) in eight, stable disease (SD) in seven and progressive disease (PD) in three cases. Nine patients underwent second PIHP with PR in eight cases and PD in one case. Six patients were evaluated after third PIHP with PR in five patients and SD in one patient. Two patients received fourth PIHP with PD in both cases. Median OS was 9.6 months (range 1.6–41.0 months). Median progression-free survival time was 12.4 months (range 0.9–41.0 months) with 1-year survival of 44%. Most common post-procedural AE grade 3 and 4 were temporary leukopenia (n = 11) and thrombocytopenia (n = 8). Patients’ self-assessments showed good ratings for overall health and quality of life with only slight changes after PIHP, and a high degree of satisfaction with PIHP treatment.ConclusionPIHP with Melphalan proved to be a relatively safe, minimal-invasive and repeatable treatment for patients with non-resectable hepatic metastases of uveal melanoma.

Percutaneous Isolated Hepatic Perfusion as a Treatment for Isolated Hepatic Metastases of Uveal Melanoma: Patient Outcome and Safety in a Multi-centre Study

Energy Technology Data Exchange (ETDEWEB)

Vogl, Thomas J., E-mail: t.vogl@em.uni-frankfurt.de; Koch, Silvia A., E-mail: silvia.koch@web.de [University Hospital Frankfurt, Department of Diagnostic and Interventional Radiology (Germany); Lotz, Gösta, E-mail: goesta.lotz@kgu.de [University Hospital Frankfurt, Department of Anesthesiology, Intensive-Care Medicine and Pain Therapy (Germany); Gebauer, Bernhard, E-mail: bernhard.gebauer@charite.de [Universitätsmedizin Berlin, Department of Diagnostic and Interventional Radiology, Campus Charité Mitte (Germany); Willinek, Winfried, E-mail: w.willinek@bk-trier.de [Brüderkrankenhaus Trier, Department of Diagnostic and Interventional Radiology (Germany); Engelke, Christoph, E-mail: engelke@ekweende.de [Evangelisches Krankenhaus Göttingen-Weende gGmbH, Department of Diagnostic and Interventional Radiology (Germany); Brüning, Roland, E-mail: r.bruening@asklepios.com; Zeile, Martin, E-mail: m.zeile@asklepios.com [Asklepios Klinik Barmbek, Department of Diagnostic and Interventional Radiology (Germany); Wacker, Frank, E-mail: wacker.frank@mh-hannover.de [Medizinische Hochschule Hannover, Department of Diagnostic and Interventional Radiology (Germany); Vogel, Arndt, E-mail: vogel.arndt@mh-hannover.de [Medizinische Hochschule Hannover, Department of Gastroenterology, Hepatology and Endocrinology (Germany); Radeleff, Boris, E-mail: boris.radeleff@med.uni-heidelberg.de [Heidelberg University Hospital, Department of Diagnostic and Interventional Radiology (Germany); Scholtz, Jan-Erik, E-mail: janerikscholtz@gmail.com [University Hospital Frankfurt, Department of Diagnostic and Interventional Radiology (Germany)

2017-06-15

PurposePercutaneous isolated hepatic perfusion (PIHP) with Melphalan has been developed as a treatment for patients with isolated hepatic metastases of uveal melanoma. We discuss patient outcome and safety in a retrospective multi-centre study.Materials and MethodsBetween 2012 and 2016 18 patients with un-resectable isolated hepatic metastases of uveal melanoma received single or repeated PIHP with Melphalan (n = 35) at seven sites. Progression-free time, overall survival time (OS) and tumour response by means of RECIST 1.1 criteria were evaluated. Peri- and post-procedural adverse events (AE) were registered. Patients’ life quality was assessed using four-point scale questionnaires.ResultsOf 18 patients, initial PIHP treatment resulted in partial response (PR) in eight, stable disease (SD) in seven and progressive disease (PD) in three cases. Nine patients underwent second PIHP with PR in eight cases and PD in one case. Six patients were evaluated after third PIHP with PR in five patients and SD in one patient. Two patients received fourth PIHP with PD in both cases. Median OS was 9.6 months (range 1.6–41.0 months). Median progression-free survival time was 12.4 months (range 0.9–41.0 months) with 1-year survival of 44%. Most common post-procedural AE grade 3 and 4 were temporary leukopenia (n = 11) and thrombocytopenia (n = 8). Patients’ self-assessments showed good ratings for overall health and quality of life with only slight changes after PIHP, and a high degree of satisfaction with PIHP treatment.ConclusionPIHP with Melphalan proved to be a relatively safe, minimal-invasive and repeatable treatment for patients with non-resectable hepatic metastases of uveal melanoma.

Hepatic profile of domestic cats anestetized with propofol in continuos infusion rate

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Janh Carlo de Amorim Ferreira

2015-06-01

Full Text Available ABSTRACT. Ferreira J.C.A., Botelho G.G. & Acceta J.L. [Hepatic profile of domestic cats anestetized with propofol in continuos infusion rate.] Perfil hepático de gatos domésticos anestesiados com Propofol em infusão contínua. Revista Brasileira de Medicina Veterinária, 37(2:127-132, 2015. Curso de Medicina Veterinária, Departamento de Medicina e Cirurgia Veterinária, Universidade Federal Rural do Rio de Janeiro, BR 465 Km 7, Seropédica, RJ 23890-000, Brasil. E-mail: janhcarlo@yahoo.com.br This study was performed to evaluate the hepatic biochemical profile of cats when submitted to continuous infusion of propofol at a 0,3 mg/kg/min in dosage, for 90 minutes, and comparing to the results obtained from cats receiving continuous infusion of saline solution. Both groups were analyzed during a pre-determined period of time totalizing 12 hours of observation and analysis. The following enzymes activity levels were determined: Aspartate-Aminotransferase (AST, Alanina-Aminotransferase (ALT, Gamma Glutamyl Transpeptidase (GGT and Alkaline Phosphatase (AP; serum levels of Albumin (A, Total Bilirrubin (BT and Total Serum Proteins (sTP. Twenty healthy cats were analyzed on this study, their weights varying from two to four kg and ages between three to five years old, submitted to experimental procedures performed during the months of January and February, 2010. The analysis of these results showed a major difference (p<0,05 between the ALT serum activities at the following moments: T2 (30 minutes, T3 (60 minutes, and T5 (12 hours; AST and AP serum activities at T2. None of the animals presented averages of the results above parameters of normality. The other parameters examined did not present any significant differences, concluding that total intravenous anesthesia using continuous infusion of propofol was safe to hold cats for invasive surgical procedures, therefore providing more information regarding the safe use of this drug in this species.

Hepatic profile of domestic cats anestetized with propofol in continuos infusion rate

Directory of Open Access Journals (Sweden)

Janh Carlo de Amorim Ferreira

2014-06-01

Full Text Available ABSTRACT. Ferreira J.C.A., Botelho G.G. & Accetta J.L. [Hepatic profile of domestic cats anestetized with propofol in continuos infusion rate.] Perfil hepático de gatos domésticos anestesiados com propofol em infusão contínua. Revista Brasileira de Medicina Veterinária, 36(2:116-120, 2014. Cirurgia e Anatomia Topográfica, UNIPLI/Anhanguera, Rua Visconde do Rio Branco, 137, Centro, Niterói, RJ 24020-001, Brasil. E-mail: janhcarlo@yahoo.com.br This study was performed to monitor the hepatic biochemical profile of cats when submitted to continuous infusion of propofol at a 0.3 mg/kg/min dosage, for 90 minutes, and comparing to results obtained from cats who received continuous infusion of saline solution. Both groups were analyzed during a pre-determined period of time totalizing 12 hours of observation and analysis. The following enzymes activity levels were determined: Aspartate-Aminotransferase (AST, Alanina-Aminotransferase (ALT, Gamma Glutamyl Transpeptidase (GGT and Alkaline Fosfatasis (FA; serum levels of Albumin (A, Total Bilirrubin (BT and Total Serum Proteins (PT. Twenty healthy cats were analyzed on this study, their weights varying from two to four kg and ages between three to five years old, submitted to experimental procedures performed during the months of January and February, 2010. The analysis of these results showed a major difference (p<0.05 between the ALT serum activities at the following moments: T2 (30 minutes, T3 (60 minutes, and T5 (12 hours; AST and FA serum activities at T2. None of the animals presented averages of the results above parameters of normality. The other parameters examined did not present any significant differences, concluding that total intravenous anesthesia using continuous infusion of propofol was safe to hold cats for invasive surgical procedures, therefore providing more information regarding the safe use of this drug in this species.

Establishment of a hepatic cirrhosis and portal hypertension model by hepatic arterial perfusion with 80% alcohol.

Science.gov (United States)

Wang, Lei; He, Fu-Liang; Liu, Fu-Quan; Yue, Zhen-Dong; Zhao, Hong-Wei

2015-08-28

To determine the feasibility and safety of establishing a porcine hepatic cirrhosis and portal hypertension model by hepatic arterial perfusion with 80% alcohol. Twenty-one healthy Guizhou miniature pigs were randomly divided into three experimental groups and three control groups. The pigs in the three experimental groups were subjected to hepatic arterial perfusion with 7, 12 and 17 mL of 80% alcohol, respectively, while those in the three control groups underwent hepatic arterial perfusion with 7, 12 and 17 mL of saline, respectively. Hepatic arteriography and direct portal phlebography were performed on all animals before and after perfusion, and the portal venous pressure and diameter were measured before perfusion, immediately after perfusion, and at 2, 4 and 6 wk after perfusion. The following procedures were performed at different time points: routine blood sampling, blood biochemistry, blood coagulation and blood ammonia tests before surgery, and at 2, 4 and 6 wk after surgery; hepatic biopsy before surgery, within 6 h after surgery, and at 1, 2, 3, 4 and 5 wk after surgery; abdominal enhanced computed tomography examination before surgery and at 6 wk after surgery; autopsy and multi-point sampling of various liver lobes for histological examination at 6 wk after surgery. In experimental group 1, different degrees of hepatic fibrosis were observed, and one pig developed hepatic cirrhosis. In experimental group 2, there were cases of hepatic cirrhosis, different degrees of increased portal venous pressure, and intrahepatic portal venous bypass, but neither extrahepatic portal-systemic bypass circulation nor death occurred. In experimental group 3, two animals died and three animals developed hepatic cirrhosis, and different degrees of increased portal venous pressure and intrahepatic portal venous bypass were also observed, but there was no extrahepatic portal-systemic bypass circulation. It is feasible to establish an animal model of hepatic cirrhosis and

Influence of transcatheter hepatic artery embolization using iodized oil on radiofrequency ablation of hepatic neoplasms

International Nuclear Information System (INIS)

Du Xilin; Ma Qingjiu; Wang Yiqing; Wang Zhimin; Zhang Hongxin

2004-01-01

Objective: To observe the effect of iodized oil on radiofrequency thermal ablation (RFA) of hepatic neoplasms by using a cluster array of ten separate electrodes. Methods: The patients were divided into 2 groups, group A with transcatheter hepatic artery embolization, group B without transcatheter hepatic artery embolization. All patients were undergone radiofrequency ablation of hepatic neoplasms. Results: The time of RFA for group A was (9 ± 2.1) minutes, showing the diameter of necrosis of (5.3 ± 1.4) cm. The time of RFA for group B was (16 ± 4. 6) minutes demonstrating the diameter of necrosis of (3.5 ± 1.8) cm (P<0.01). Conclusions: These findings suggest that radiofrequency thermal ablation of hepatic neoplasms with transcatheter hepatic artery embolization using iodized oil might improve the safety and synergic effect

One Family's Struggles with Hepatitis B

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Full Text Available ... publications schedules & records support statements vaccine initiative vaccine safety about bucking the herd dr. offit's testimony not vaccinating the abcs of mmr & dtp thimerosal vaccine safety q & a videos chickenpox (varicella) hepatitis b hib ...

Profile of hepatitis B and C virus infection in prisoners in Lubuk Pakam correctional facilities

Science.gov (United States)

Rey, I.; Saragih, R. H.; Effendi-YS, R.; Sembiring, J.; Siregar, G. A.; Zain, L. H.

2018-03-01

Prisoners in correctional facilities are predisposed to chronic viral infections because of their high-risk behaviors or unsafe lifestyle. The economic and public health burden of chronic hepatitis B and C and its sequelae need to be addressed, such as by finding the risk factors and therefore reducing the spread of HCV and HBV infection in prisons. This study aimed to see the profile of Hepatitis B and C Virus Infection in prisoners in Lubuk Pakam Correctional Facilities. This cross-sectional study was in Lubuk Pakam Correctional Facilities in 2016. From 1114 prisoners in Lubuk Pakam correctional facility, we randomly examined 120 prisoners for HBV and HCV serology markers. From 120 prisoners, six prisoners were HBV positive, 21 prisoners were HCV positive and one prisoner positive for both HCV and HBV infection. The most common risk factors for prisoners getting HBV infection are tattoos and free sex (36.4% and 36.4%, respectively). The most common risk factors for HCV infection in prisoners are tattoos and free sex (40% and 35%, respectively).

Polyomic profiling reveals significant hepatic metabolic alterations in glucagon-receptor (GCGR knockout mice: implications on anti-glucagon therapies for diabetes

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Molloy Mark P

2011-06-01

Full Text Available Abstract Background Glucagon is an important hormone in the regulation of glucose homeostasis, particularly in the maintenance of euglycemia and prevention of hypoglycemia. In type 2 Diabetes Mellitus (T2DM, glucagon levels are elevated in both the fasted and postprandial states, which contributes to inappropriate hyperglycemia through excessive hepatic glucose production. Efforts to discover and evaluate glucagon receptor antagonists for the treatment of T2DM have been ongoing for approximately two decades, with the challenge being to identify an agent with appropriate pharmaceutical properties and efficacy relative to potential side effects. We sought to determine the hepatic & systemic consequence of full glucagon receptor antagonism through the study of the glucagon receptor knock-out mouse (Gcgr-/- compared to wild-type littermates. Results Liver transcriptomics was performed using Affymetric expression array profiling, and liver proteomics was performed by iTRAQ global protein analysis. To complement the transcriptomic and proteomic analyses, we also conducted metabolite profiling (~200 analytes using mass spectrometry in plasma. Overall, there was excellent concordance (R = 0.88 for changes associated with receptor knock-out between the transcript and protein analysis. Pathway analysis tools were used to map the metabolic processes in liver altered by glucagon receptor ablation, the most notable being significant down-regulation of gluconeogenesis, amino acid catabolism, and fatty acid oxidation processes, with significant up-regulation of glycolysis, fatty acid synthesis, and cholesterol biosynthetic processes. These changes at the level of the liver were manifested through an altered plasma metabolite profile in the receptor knock-out mice, e.g. decreased glucose and glucose-derived metabolites, and increased amino acids, cholesterol, and bile acid levels. Conclusions In sum, the results of this study suggest that the complete ablation

Safety Profile of Cough and Cold Medication Use in Pediatrics.

Science.gov (United States)

Green, Jody L; Wang, George Sam; Reynolds, Kate M; Banner, William; Bond, G Randall; Kauffman, Ralph E; Palmer, Robert B; Paul, Ian M; Dart, Richard C

2017-06-01

The safety of cough and cold medication (CCM) use in children has been questioned. We describe the safety profile of CCMs in children pediatric (75.5%), and single-ingredient (77.5%) formulations were most commonly involved. AEs occurring in >20% of all cases included tachycardia, somnolence, hallucinations, ataxia, mydriasis, and agitation. Twenty cases (0.6%) resulted in death; most were in children pediatric liquid formulations were the most commonly reported products. These characteristics present an opportunity for targeted prevention efforts. Copyright © 2017 by the American Academy of Pediatrics.

One Family's Struggles with Hepatitis B

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Full Text Available ... prevention publications schedules & records support statements vaccine initiative vaccine safety about bucking the herd dr. offit's testimony not vaccinating the abcs of mmr & dtp thimerosal vaccine safety q & a videos chickenpox (varicella) hepatitis b hib ...

Investigation of chronic efficacy and safety profile of two potential anti-inflammatory bipyrazole-based compounds in experimental animals

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Domiati S

2018-04-01

examination of the stomach revealed normal mucosa for both tested compounds and controls. Likewise, kidneys showed neither significant histologic alteration nor biomarkers increase as compared to the control over both 7- and 30-day treatment periods. Mice that received the tested compounds or diclofenac exhibited transient liver damage specifically; congestion, vacuolization, necrosis and inflammation after 7 days of treatment which decreased significantly after 30 days of treatment as emphasized by the Suzuki score and biomarker levels. Conclusion: Since the tested compounds, specifically compound I, presented a satisfactory chronic safety profile as well as anti-inflammatory effect, it is worth conducting further molecular pharmacological, toxicological and bioavailability studies to elucidate the efficacy of these potential anti-inflammatory bipyrazole compounds. Keywords: peptic ulcer, hepatic injury, kidney injury, nonsteroidal anti-inflammatory drugs, pyrazole, histology

Liver regeneration signature in hepatitis B virus (HBV-associated acute liver failure identified by gene expression profiling.

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Oriel Nissim

Full Text Available The liver has inherent regenerative capacity via mitotic division of mature hepatocytes or, when the hepatic loss is massive or hepatocyte proliferation is impaired, through activation of hepatic stem/progenitor cells (HSPC. The dramatic clinical course of acute liver failure (ALF has posed major limitations to investigating the molecular mechanisms of liver regeneration and the role of HSPC in this setting. We investigated the molecular mechanisms of liver regeneration in 4 patients who underwent liver transplantation for hepatitis B virus (HBV-associated ALF.Gene expression profiling of 17 liver specimens from the 4 ALF cases and individual specimens from 10 liver donors documented a distinct gene signature for ALF. However, unsupervised multidimensional scaling and hierarchical clustering identified two clusters of ALF that segregated according to histopathological severity massive hepatic necrosis (MHN; 2 patients and submassive hepatic necrosis (SHN; 2 patients. We found that ALF is characterized by a strong HSPC gene signature, along with ductular reaction, both of which are more prominent in MHN. Interestingly, no evidence of further lineage differentiation was seen in MHN, whereas in SHN we detected cells with hepatocyte-like morphology. Strikingly, ALF was associated with a strong tumorigenesis gene signature. MHN had the greatest upregulation of stem cell genes (EpCAM, CK19, CK7, whereas the most up-regulated genes in SHN were related to cellular growth and proliferation. The extent of liver necrosis correlated with an overriding fibrogenesis gene signature, reflecting the wound-healing process.Our data provide evidence for a distinct gene signature in HBV-associated ALF whose intensity is directly correlated with the histopathological severity. HSPC activation and fibrogenesis positively correlated with the extent of liver necrosis. Moreover, we detected a tumorigenesis gene signature in ALF, emphasizing the close relationship between

Efficacy and safety of tenofovir in chronic hepatitis B: Australian real world experience.

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Lovett, Grace C; Nguyen, Tin; Iser, David M; Holmes, Jacinta A; Chen, Robert; Demediuk, Barbara; Shaw, Gideon; Bell, Sally J; Desmond, Paul V; Thompson, Alexander J

2017-01-08

To evaluate the long-term treatment outcomes of tenofovir therapy in patients in a real world Australian tertiary care setting. We performed a retrospective analysis of treatment outcomes among treatment-naïve and treatment-experienced patients receiving a minimum 3 mo tenofovir therapy through St Vincent's Hospital Melbourne, Australia. We included patients receiving tenofovir [tenofovir disoproxil fumarate (TDF)] monotherapy, as well as patients treated with TDF in combination with a second antiviral agent. Patients were excluded if they demonstrated human immune-deficiency virus/hepatitis C virus/hepatitis delta virus coinfection or were less than 18 years of age. We considered virological and biochemical response, as well as safety outcomes. Virological response was determined by measurement of hepatitis B virus (HBV) DNA using sensitive assays; biochemical response was determined via serum liver function tests; histological response was determined from liver biopsy and fibroscan; safety analysis focused on glomerular renal function and bone mineral density. The primary efficacy endpoint was complete virological suppression over time, defined by HBV DNA < 20 IU/mL. Secondary efficacy endpoints included rates of biochemical response, and HB e antigen (HBeAg)/HB surface antigen loss and seroconversion over time. Ninety-two patients were identified who fulfilled the enrolment criteria. Median follow-up was 26 mo (range 3-114). Mean age was 46 (24-78) years, 64 (70%) were male and 77 (84%) were of Asian origin. 55 (60%) patients were treatment-naïve and 62 patients (67%) were HBeAg-negative. Complete virological suppression was achieved by 45/65 (71%) patients at 12 mo, 37/46 (80%) at 24 mo and 25/28 (89%) at 36 mo. Partial virological response (HBV DNA 20-2000 IU/mL) was achieved by 89/92 (96.7%) of patients. Multivariate analysis showed a significant relationship between virological suppression at end of follow-up and baseline HBV DNA level (OR = 0.897, 95%CI

Profiling of hepatic gene expression in rats treated with fibric acid analogs

Energy Technology Data Exchange (ETDEWEB)

Cornwell, Paul D.; Souza, Angus T. de; Ulrich, Roger G

2004-05-18

Peroxisome proliferator-activated receptors (PPARs) are a group of nuclear receptors whose ligands include fatty acids, eicosanoids and the fibrate class of drugs. In humans, fibrates are used to treat dyslipidemias. In rodents, fibrates cause peroxisome proliferation, a change that might explain the observed hepatomegaly. In this study, rats were treated with multiple dose levels of six fibric acid analogs (including fenofibrate) for up to two weeks. Pathological analysis identified hepatocellular hypertrophy as the only sign of hepatotoxicity, and only one compound at the highest dose caused any significant increase in serum ALT or AST activity. RNA profiling revealed that the expression of 1288 genes was related to dose or length of treatment and correlated with hepatocellular hypertrophy. This gene list included expression changes that were consistent with increased mitochondrial and peroxisomal {beta}-oxidation, increased fatty acid transport, increased hepatic uptake of LDL-cholesterol, decreased hepatic uptake of glucose, decreased gluconeogenesis and decreased glycolysis. These changes are likely linked to many of the clinical benefits of fibrate drugs, including decreased serum triglycerides, decreased serum LDL-cholesterol and increased serum HDL-cholesterol. In light of the fact that all six compounds stimulated similar or identical changes in the expression of this set of 1288 genes, these results indicate that hepatomegaly is due to PPAR{alpha} activation, although signaling through other receptors (e.g. PPAR{gamma}, RXR) or through non-receptor pathways cannot be excluded.

Impact of axial burnup profile on criticality safety of ANPP spent fuel cask

International Nuclear Information System (INIS)

Bznuni, S.

2006-01-01

Criticality safety assessment for WWER-440 NUHOMS cask with spent nuclear fuel from Armenian NPP has been performed. The cask was designed in such way that the neutron multiplication factor k eff must be below 0,95 for all operational modes and accident conditions. Usually for criticality analysis, fresh fuel approach with the highest enrichment is taken as conservative assumption as it was done for ANPP. NRSC ANRA in order to improve future fuel storage efficiency initiated research with taking into account burn up credit in the criticality safety assessment. Axial burn up profile (end effect) has essential impact on criticality safety justification analysis. However this phenomenon was not taken into account in the Safety Analysis Report of NUHOMS spent fuel storage constructed on the site of ANPP. Although ANRA does not yet accept burn up credit approach for ANPP spent fuel storage, assessment of impact of axial burnup profile on criticality of spent fuel assemblies has important value for future activities of ANRA. This paper presents results of criticality calculations of spent fuel assemblies with axial burn up profile. Horizontal burn up profile isn't taken account since influence of the horizontal variation of the burn up is much less than the axial variation. The actinides and actinides + fission products approach are discussed. The calculations were carried out with STARBUCS module of SCALE 5.0 code package developed at Oak Ridge National laboratory. SCALE5.0 sequence CSAS26 (KENO-VI) was used for evaluation the k eff for 3-D problems. Obtained results showed that criticality of ANPP spent fuel cask is very sensitive to the end effect

Drug safety evaluation of defibrotide.

Science.gov (United States)

Richardson, Paul G; Corbacioglu, Selim; Ho, Vincent Trien-Vinh; Kernan, Nancy A; Lehmann, Leslie; Maguire, Craig; Maglio, Michelle; Hoyle, Margaret; Sardella, Marco; Giralt, Sergio; Holler, Ernst; Carreras, Enric; Niederwieser, Dietger; Soiffer, Robert

2013-01-01

Hepatic veno-occlusive disease (VOD), also known as sinusoidal obstruction syndrome (SOS), is a potentially life-threatening complication of chemotherapeutic conditioning used in preparation for hematopoietic stem-cell transplantation (SCT). Defibrotide (DF) has been shown in Phase II and III trials to improve complete response in patients with severe VOD (sVOD). None of the articles, to date, provide a comprehensive review of the safety of DF in VOD and/or a range of other conditions. This article reviews current clinical findings on DF, primarily in terms of safety for use in treatment and prophylaxis of VOD, and relevant safety data for its use in other diseases. The literature review was conducted using a PubMed search with the fixed term 'defibrotide' in combination with ≥ 1 of 'safety', 'veno-occlusive disease' (with and without 'treatment', 'prevention'), 'oncology', 'myeloma', 'microangiopathy', 'anti-thrombotic' and 'peripheral vascular disorder'. Related articles from the EBMT and ASH conference websites were also included. DF was well tolerated in majority of the studies. The safety profile of DF is largely favourable with toxicities comparable to control populations in the setting of SCT complicated by sVOD.

Hepatic transcriptomic profiles from barramundi, Lates calcarifer, as a means of assessing organism health and identifying stressors in rivers in northern Queensland.

Science.gov (United States)

Hook, Sharon E; Kroon, Frederieke J; Greenfield, Paul A; Warne, Michael St J; Smith, Rachael A; Turner, Ryan D

2017-08-01

Resource managers need to differentiate between sites with and without contaminants and those where contaminants cause impacts. Potentially, transcriptomes could be used to evaluate sites where contaminant-induced effects may occur, to identify causative stressors of effects and potential adverse outcomes. To test this hypothesis, the hepatic transcriptomes in Barramundi, a perciforme teleost fish, (Lates calcarifer) from two reference sites, two agriculturally impacted sites sampled during the dry season, and an impacted site sampled during the wet season were compared. The hepatic transcriptome was profiled using RNA-Seq. Multivariate analysis showed that transcriptomes were clustered based on site and by inference water quality, but not sampling time. The largest differences in transcriptomic profile were between reference sites and a site sampled during high run-off, showing that impacted sites can be identified via RNA-Seq. Transcripts with altered abundance were linked to xenobiotic metabolism, peroxisome proliferation and stress responses, indicating putative stressors with the potential for adverse outcomes in barramundi. Copyright © 2017. Published by Elsevier Ltd.

Safety and effectiveness of repeat arterial closure using the AngioSeal device in patients with hepatic malignancy.

Science.gov (United States)

Hieb, Robert A; Neisen, Melissa J; Hohenwalter, Eric J; Molnar, Jim A; Rilling, William S

2008-12-01

To retrospectively evaluate the safety and effectiveness of the use of the AngioSeal device for repeat arterial closure in patients with hepatic malignancy. A retrospective analysis of patients with hepatic malignancy who had undergone repeated arterial closure with the AngioSeal device was performed. All charts for patients undergoing transarterial chemoembolization or TheraSphere radioembolization were reviewed for the method of hemostasis and the number of arterial closures. A total of 53 patients (58.5% men, 41.5% women; mean age, 58.7 years) had repeat AngioSeal arterial puncture closure after chemoembolization or TheraSphere treatment. Percutaneous closure of the common femoral artery with the AngioSeal device was performed in accordance with the manufacturer's recommendations. The patients were examined for complications on follow-up. Effectiveness was defined by the ability to obtain satisfactory hemostasis. Safety was assessed by the absence of groin complications and by vessel patency on follow-up angiograms of the puncture site obtained at subsequent liver-directed therapy sessions. Fifty-three patients in this study group had a total of 203 common femoral artery punctures. There were a total of 161 closures with the AngioSeal device (79.3%): 58 (36%) single closures and 103 (64.0%) repeat closures. Of the 161 attempts at AngioSeal closure, there was one closure failure in the single-puncture group, yielding a success rate of 98.3%; and one closure failure in the repeat-puncture group, yielding a success rate of 99%. In these two patients, hemostasis was achieved with traditional manual compression without the need for any other device, and no complications were noted. The overall success rate of AngioSeal device closure was 98.7%. The repeat use of the AngioSeal closure device is safe and effective in patients with hepatic malignancy undergoing regional oncologic interventional procedures.

Hepatitis E and blood donation safety in selected European countries

DEFF Research Database (Denmark)

Domanović, Dragoslav; Tedder, Richard; Blümel, Johannes

2017-01-01

The public health implications of hepatitis E virus (HEV) in Europe have changed due to increasing numbers of hepatitis E cases and recent reports of chronic, persistent HEV infections associated with progression to cirrhosis in immunosuppressed patients. The main infectious risk...

Safety and anti-hyperglycemic efficacy of various tea types in mice

Science.gov (United States)

Han, Manman; Zhao, Guangshan; Wang, Yijun; Wang, Dongxu; Sun, Feng; Ning, Jingming; Wan, Xiachun; Zhang, Jinsong

2016-01-01

Tea, a beverage consumed worldwide, has proven anti-hyperglycemic effects in animal models. Better efficacies of tea beverages are frequently associated with high-dose levels, whose safety attracts considerable attention. Based on the inherent nature of tea catechin oxidation, fresh tea leaves are manufactured into diverse tea types by modulating the oxidation degree of catechins. The present study aimed to assess various tea types for their safety properties and anti-hyperglycemic effects. Mice were allowed free access to tea infusion (1:30, w/v) for one week, and the rare smoked tea caused salient adverse reactions, including hepatic and gastrointestinal toxicities; meanwhile, the widely-consumed green and black teas, unlike the rare yellow tea, suppressed growth in fast-growing healthy mice. When mice were fed a high-fat diet and allowed free access to tea infusion (1:30, w/v) for 25 days, only yellow tea significantly reduced blood glucose. Therefore, various teas showed different safety profiles as well as anti-hyperglycemic efficacy strengths. To achieve an effective and safe anti-hyperglycemic outcome, yellow tea, which effectively suppressed high-fat diet-induced early elevation of hepatic thioredoxin-interacting protein, is an optimal choice. PMID:27531374

Hepatic decompensation/serious adverse events in post-liver transplantation recipients on sofosbuvir for recurrent hepatitis C virus.

Science.gov (United States)

Patel, Neal; Bichoupan, Kian; Ku, Lawrence; Yalamanchili, Rachana; Harty, Alyson; Gardenier, Donald; Ng, Michel; Motamed, David; Khaitova, Viktoriya; Bach, Nancy; Chang, Charissa; Grewal, Priya; Bansal, Meena; Agarwal, Ritu; Liu, Lawrence; Im, Gene; Leong, Jennifer; Kim-Schluger, Leona; Odin, Joseph; Ahmad, Jawad; Friedman, Scott; Dieterich, Douglas; Schiano, Thomas; Perumalswami, Ponni; Branch, Andrea

2016-03-07

To determine the safety profile of new hepatitis C virus (HCV) treatments in liver transplant (LT) recipients with recurrent HCV infection. Forty-two patients were identified with recurrent HCV infection that underwent LT at least 12 mo prior to initiating treatment with a Sofosbuvir-based regimen during December 2013-June 2014. Cases were patients who experienced hepatic decompensation and/or serious adverse events (SAE) during or within one month of completing treatment. Controls had no evidence of hepatic decompensation and/or SAE. HIV-infected patients were excluded. Cumulative incidence of decompensation/SAE was calculated using the Kaplan Meier method. Exact logistic regression analysis was used to identify factors associated with the composite outcome. Median age of the 42 patients was 60 years [Interquartile Range (IQR): 56-65 years], 33% (14/42) were female, 21% (9/42) were Hispanic, and 9% (4/42) were Black. The median time from transplant to treatment initiation was 5.4 years (IQR: 2.1-8.8 years). Thirteen patients experienced one or more episodes of hepatic decompensation and/or SAE. Anemia requiring transfusion, the most common event, occurred in 62% (8/13) patients, while 54% (7/13) decompensated. The cumulative incidence of hepatic decompensation/SAE was 31% (95%CI: 16%-41%). Risk factors for decompensation/SAE included lower pre-treatment hemoglobin (OR = 0.61 per g/dL, 95%CI: 0.40-0.88, P < 0.01), estimated glomerular filtration rate (OR = 0.95 per mL/min per 1.73 m(2), 95%CI: 0.90-0.99, P = 0.01), and higher baseline serum total bilirubin (OR = 2.43 per mg/dL, 95%CI: 1.17-8.65, P < 0.01). The sustained virological response rate for the cohort of 42 patients was 45%, while it was 31% for cases. Sofosbuvir/ribavirin will continue to be used in the post-transplant population, including those with HCV genotypes 2 and 3. Management of anemia remains an important clinical challenge.

Changing trends of hepatitis b seromarkers amongst pakistani population: a laboratory-based review

International Nuclear Information System (INIS)

Zafar, A.; Khan, E.; Khan, M.S.; Moiz, B.; Jafri, W.

2013-01-01

Objective: To study the changing trends of hepatitis B markers tested at Aga Khan University Hospital clinical laboratory according to the internationally recognised classification of hepatitis B profile. Methods: The retrospective study involved analysis of laboratory records of hepatitis B profiles of all patients collected from January 2001 to December 2008 at the Aga Khan University Hospital's clinical laboratory. Patients with complete profile tested were categorised according to the Centre for Diseases Control classification of hepatitis B profile. SPSS 16 was used for statistical analysis. Results: A total of 185,825 patients had serological markers for hepatitis B tested. Mean-age of reactive hepatitis B surface antigen (HBsAg) patients was 30+-12.5 years. HBsAg reactivity was significantly higher in males than females (34% vs 12%; p <0.0001). HBsAg showed a slight decline in the percentage reactivity during the 8-year study period, while a gradual increase in hepatitis B surface antibody (HBsAb) reactivity was observed. Of the total, 23% patients belonged to the 'susceptible to infection' category; 39% patients were classified as 'chronically-ill'; 12% patients were categorised as 'immune due to hepatitis B vaccination'. 3% patients were classed as 'acutely infected'. Overall, samples received from Peshawar, Quetta and Larkana showed very high reactivity rates. Conclusion: The study substantiated the general perception that levels of HBsAg is showing a decreasing trend, while levels of HBsAb are increasing perhaps due to better vaccination of population. (author)

Clinical Profile, Maternal and Fetal Outcomes of Acute Hepatitis E in ...

African Journals Online (AJOL)

serologically confirmed pregnant women with hepatitis E, selected by screening in ... in India. The first retrospectively described outbreak of hepatitis E occurred in India in 1955-1956. .... hemorrhage and intra-uterine fetal death and poor fetal.

Serum metabolomic profiling in acute alcoholic hepatitis identifies multiple dysregulated pathways.

Science.gov (United States)

Rachakonda, Vikrant; Gabbert, Charles; Raina, Amit; Bell, Lauren N; Cooper, Sara; Malik, Shahid; Behari, Jaideep

2014-01-01

While animal studies have implicated derangements of global energy homeostasis in the pathogenesis of acute alcoholic hepatitis (AAH), the relevance of these findings to the development of human AAH remains unclear. Using global, unbiased serum metabolomics analysis, we sought to characterize alterations in metabolic pathways associated with severe AAH and identify potential biomarkers for disease prognosis. This prospective, case-control study design included 25 patients with severe AAH and 25 ambulatory patients with alcoholic cirrhosis. Serum samples were collected within 24 hours of the index clinical encounter. Global, unbiased metabolomics profiling was performed. Patients were followed for 180 days after enrollment to determine survival. Levels of 234 biochemicals were altered in subjects with severe AAH. Random-forest analysis, principal component analysis, and integrated hierarchical clustering methods demonstrated that metabolomics profiles separated the two cohorts with 100% accuracy. Severe AAH was associated with enhanced triglyceride lipolysis, impaired mitochondrial fatty acid beta oxidation, and upregulated omega oxidation. Low levels of multiple lysolipids and related metabolites suggested decreased plasma membrane remodeling in severe AAH. While most measured bile acids were increased in severe AAH, low deoxycholate and glycodeoxycholate levels indicated intestinal dysbiosis. Several changes in substrate utilization for energy homeostasis were identified in severe AAH, including increased glucose consumption by the pentose phosphate pathway, altered tricarboxylic acid (TCA) cycle activity, and enhanced peptide catabolism. Finally, altered levels of small molecules related to glutathione metabolism and antioxidant vitamin depletion were observed in patients with severe AAH. Univariable logistic regression revealed 15 metabolites associated with 180-day survival in severe AAH. Severe AAH is characterized by a distinct metabolic phenotype spanning

Assessment of oral safety profile of aqueous extract blend of three ...

African Journals Online (AJOL)

... did not reveal any pathological changes attributable to treatment with the spice blend extract. Conclusions: These findings indicate that oral consumption of a spice blend of garlic, ginger and cayenne pepper in humans may be safe. Keywords: Spice blend, Toxicity, Histology, Marker enzymes, Medicinal, Safety profile ...

Molecular and epidemiological profiles of hepatitis C virus genotype 4 in Denmark

DEFF Research Database (Denmark)

Eriksen, Mette Brandt; Jørgensen, Louise Bruun; Krarup, Henrik

2010-01-01

The prevalence of hepatitis C virus (HCV) genotype 4 has increased throughout Europe. This is an epidemiological study of patients infected chronically with HCV genotype 4 in Denmark. The HCV strains analyzed originated from patient samples collected between 1999 and 2007 as part of the national...... patients (22%) were infected with subtypes 4h, 4k, 4l, 4n, 4o, or 4Unclassified. Three epidemiological profiles were identified: (1) patients infected with HCV by intravenous drug use were infected solely with subtype 4d. They were all of European origin, and 15 of the 16 patients were ethnic Danes....... No single transmission event could be confirmed, but the pairwise nucleotide identity within the patients of Danish origin was relatively high (~95%), suggesting a recent introduction into Denmark. (2) The 21 patients infected with subtype 4a all came from Northern Africa, Egypt, Pakistan, or the Middle...

Comparison of the Adverse Event Profile of TheraSphere® with SIR-Spheres® for the Treatment of Unresectable Hepatocellular Carcinoma: A Systematic Review.

Science.gov (United States)

Kallini, Joseph Ralph; Gabr, Ahmed; Thorlund, Kristian; Balijepalli, Chakrapani; Ayres, Dieter; Kanters, Steve; Ebrahim, Shanil; Mills, Edward; Lewandowski, Robert J; Salem, Riad

2017-07-01

To compare the safety profiles of TheraSphere ® (glass) and SIR-Spheres ® (resin) Y90 microspheres for the treatment of hepatocellular carcinoma. A systematic review was conducted using the databases MEDLINE, Embase, and Cochrane Trials Register to identify all relevant studies. Baseline characteristics and adverse events of all grades related to gastrointestinal, hepatobiliary, and respiratory systems were collected along with commonly reported outcomes related to post-embolization syndrome. For all outcomes, data from each study were tabulated for each intervention. Adverse events and patients were summed across studies on TheraSphere ® and SIR-Spheres ® , respectively, and the resulting proportion of patients experiencing an outcome for both interventions was calculated. Thirty-one observational studies were included in the review. In the adverse events of all grades, more patients treated with resin microspheres reported gastric ulcers, hepatic encephalopathy, cholecystitis, hepatic failure, and pleural effusion. Patients treated with resin microspheres also had more hepatobiliary adverse events of grade 3 or higher. In the events related to post-embolization syndrome, glass microspheres exhibited a similar safety profile compared to resin microspheres. Ascites and nausea grade 3 or higher were recorded more frequently with glass microsphere treatment. Based on this review of the published literature, glass microspheres exhibit a safety profile with fewer gastrointestinal and pulmonary adverse events compared to resin microspheres in the treatment of hepatocellular carcinoma.

Viral hepatitis vaccination during pregnancy.

Science.gov (United States)

Zhao, Yueyuan; Jin, Hui; Zhang, Xuefeng; Wang, Bei; Liu, Pei

2016-04-02

Viral hepatitis is a serious global public health problem. It is also a common cause of jaundice and gestational complications in pregnant women. Moreover, infected mothers can transmit the virus to their fetus or neonate, which may increase disease burden and decrease quality of life. To date, commercial vaccines have been developed for hepatitis A, B, and E and are available to the general population. The Advisory Committee on Immunization Practices currently accepts emergency vaccination against hepatitis A and B during pregnancy due to benefits that overweight the potential risks. While there are limited data from trials with limited numbers of samples that suggest the efficacy or safety of hepatitis B and E vaccines in pregnant women, additional data are necessary to provide evidence of vaccination during pregnancy.

Efficacy and safety of radiofrequency ablation of hepatocellular carcinoma in the hepatic dome with the CT-guided extrathoracic transhepatic approach

International Nuclear Information System (INIS)

Kim, Young Kon; Kim, Chong Soo; Lee, Jeong Min; Chung, Gyung Ho; Chon, Su Bin

2006-01-01

Purpose: The purpose of this study was to determine the efficacy and safety of radiofrequency (RF) ablation for the treatment of hepatocellular carcinoma (HCC) in the hepatic dome with CT-guided extrathoracic transhepatic approach. Materials and methods: Fifteen patients with 15 HCCs (size range: 0.8-4 cm, mean size: 1.8 cm) in the hepatic dome were treated by RF ablation using cooled-tip electrodes and with CT-guided extrathoracic transhepatic approach. Therapeutic response of the tumor to RF ablation and procedure-related complications including hepatic injury, hemoperitoneum, and thermal injury of diaphragm were evaluated. Results: The average number of needle punctures to ensure the correct needle position in the targeted tumor was 3.7 (range: 1-6 punctures). The average ablation time was 14.7 min (range: 8-25 min). Complete necrosis without marginal recurrence after at least 13-month follow-up was attained in 13 tumors (86.7%). There were no major complications related to the procedures. Six patients had shoulder pain that lasted three days to two weeks after the procedures and their symptoms were resolved with conservative treatment. Conclusions: RF ablation using CT-guided extrathoracic transhepatic approach is an effective and safe technique for the treatment of HCC in the hepatic dome

Profile of paritaprevir/ritonavir/ombitasvir plus dasabuvir in the treatment of chronic hepatitis C virus genotype 1 infection

Directory of Open Access Journals (Sweden)

Smith MA

2015-11-01

Full Text Available Michael A Smith, Alice LimDepartment of Pharmacy Practice and Pharmacy Administration, Philadelphia College of Pharmacy, University of the Sciences, Philadelphia, PA, USAAbstract: Over the last several years, many advances have been made in the treatment of chronic hepatitis C virus (HCV infection with the development of direct-acting antivirals. Paritaprevir/ritonavir/ombitasvir with dasabuvir (PrOD is a novel combination of a nonstructural (NS 3/4A protein inhibitor boosted by ritonavir, an NS5A protein inhibitor, and an NS5B nonnucleoside polymerase inhibitor. This review aims to discuss the pharmacology, efficacy, safety, drug interactions, and viral drug resistance of PrOD in the treatment of HCV genotype 1 infections. Phase I, II, and III human and animal studies that describe the pharmacology, pharmacokinetics, efficacy, and safety of PrOD for HCV were identified and included. Studies that evaluated patients without cirrhosis (n=2,249 and with cirrhosis (n=422 demonstrated that PrOD for 12 or 24 weeks was effective at achieving sustained virologic response rates (>90% in patients with genotype 1a or 1b HCV infection. Although indicated for the treatment of HCV genotype 1 infection, PrOD is also recommended for the treatment of HCV in patients coinfected with HIV. Additionally, promising data exist for the use of PrOD in liver-transplant recipients. The most common adverse drug events associated with PrOD included nausea, pruritus, insomnia, diarrhea, asthenia, dry skin, vomiting, and anemia. The high efficacy rates seen coupled with a favorable side effect profile seen with PrOD with or without ribavirin have led to its addition as a recommended treatment regimen for HCV genotype 1 infection.Keywords: direct-acting antiviral, interferon-free, ribavirin-free

Method of calculating the safety factor profile on the HT-7 tokamak

International Nuclear Information System (INIS)

Zhang Xianmei; Lu Yuancheng; Wan Baonian

2001-01-01

A method of calculating the safety factor profile on the HT-7 tokamak has been described. It is derived from Maxwell's equations, among which the authors mainly use two of them: one is the magnetic field diffusion equation, and the other is Ampere's Law. This method can be also used to evaluate the safety factor on other devices with a circular cross sections. It is helpful to the study of the plasma MHD behavior on the HT-7 tokamak

Inactivation of 10(15) chimpanzee-infectious doses of hepatitis B virus during preparation of a heat-inactivated hepatitis B vaccine

NARCIS (Netherlands)

Lelie, P. N.; Reesink, H. W.; Niessen, J.; Brotman, B.; Prince, A. M.

1987-01-01

The safety of a plasma-derived hepatitis-B vaccine inactivated by two heating steps (90 sec at 103 degrees C followed by 10 hr pasteurization at 65 degrees C) was validated in chimpanzees; 10(3) chimpanzee-infectious doses (CID50) of hepatitis-B virus (HBV), subjected to the purification steps

Safety factor profile dependence of turbulent structure formation in relevant to internal transport barrier relaxation

International Nuclear Information System (INIS)

Tokunaga, S.; Yagi, M.; Itoh, S.-I.; Itoh, K.

2009-01-01

Full text: It is widely understood that the improved confinement mode with transport barrier is necessary to achieve the self-ignition condition in ITER. The negative magnetic shear, mean ExB flow shear, and zonal flow are considered to play important roles for ITB formation. In our previous study, it is found that the non-linear interaction between the meso-scale modes produces non-local energy transfer to the off-resonant mode in the vicinity of q min surface and brings global relaxation of the temperature profile involving ITB collapse. Experimental studies indicate that a relationship exists between the ITB formation and safety factor q-profile, with a reversed magnetic shear (RS) configuration. Transitional ITB events occur on the low-order rational resonant surface. The ITB shape and location depend on the q-profile and q min position. These observations indicate that the q-profile might play an essential role in determining the turbulent structure. In this study, the effect of safety factor profile on the ion temperature gradient driven drift wave (ITG) turbulence is investigated using a global non-linear simulation code based on the gyro-fluid model. A heat source and toroidal momentum source are introduced. Dependence of safety factor profiles on ITB formation and its stability is examined to clarify the influence of the radial distribution of the rational surfaces and the q min value. It is found that the nonlinearly excited meso-scale mode in the vicinity of q min depends on the value of q min . A detailed analysis of the structure selection rule is in progress. (author)

Weekend ethanol consumption and high-sucrose diet: resveratrol effects on energy expenditure, substrate oxidation, lipid profile, oxidative stress and hepatic energy metabolism.

Science.gov (United States)

Rocha, Katiucha Karolina Honório Ribeiro; Souza, Gisele Aparecida; Seiva, Fábio Rodrigues Ferreira; Ebaid, Geovana Xavier; Novelli, Ethel Lourenzi Barbosa

2011-01-01

The present study analyzed the association between weekend ethanol and high-sucrose diet on oxygen consumption, lipid profile, oxidative stress and hepatic energy metabolism. Because resveratrol (RS, 3,5,4'-trans-trihydroxystilbene) has been implicated as a modulator of alcohol-independent cardiovascular protection attributed to red wine, we also determined whether RS could change the damage done by this lifestyle. Male Wistar 24 rats receiving standard chow were divided into four groups (n = 6/group): (C) water throughout the experimental period; (E) 30% ethanol 3 days/week, water 4 days/week; (ES) a mixture of 30% ethanol and 30% sucrose 3 days/week, drinking 30% sucrose 4 days/week; (ESR) 30% ethanol and 30% sucrose containing 6 mg/l RS 3 days/week, drinking 30% sucrose 4 days/week. After 70 days the body weight was highest in ESR rats. E rats had higher energy expenditure (resting metabolic rate), oxygen consumption (VO(2)), fat oxidation, serum triacylglycerol (TG) and very low-density lipoprotein (VLDL) than C. ES rats normalized calorimetric parameters and enhanced carbohydrate oxidation. ESR ameliorated calorimetric parameters, reduced TG, VLDL and lipid hydroperoxide/total antioxidant substances, as well enhanced high-density lipoprotein (HDL) and HDL/TG ratio. Hepatic hydroxyacyl coenzyme-A dehydrogenase (OHADH)/citrate synthase ratio was lower in E and ES rats than in C. OHADH was highest in ESR rats. The present study brought new insights on weekend alcohol consumption, demonstrating for the first time, that this pattern of ethanol exposure induced dyslipidemic profile, calorimetric and hepatic metabolic changes which resemble that of the alcoholism. No synergistic effects were found with weekend ethanol and high-sucrose intake. RS was advantageous in weekend drinking and high-sucrose intake condition ameliorating hepatic metabolism and improving risk factors for cardiovascular damage.

Demonstration of Risk Profiling for promoting safety in SME´s

DEFF Research Database (Denmark)

Jørgensen, Kirsten; Duijm, Nijs Jan; Troen, Hanne

2011-01-01

Purpose – The purpose of this paper is to identify and assess the risks and potential risks that may lead to accidents. It aims to look at how to improve risk assessment within SMEs for the benefit of all staff. Design/methodology/approach – The research included results from a Dutch project which...... identifies accident risks and safety barriers that are presented in a huge database and risk calculator. The method was first to develop a simple way of accessing this enormous amount of data, second, to develop a tool to observe risks and safety barriers in SMEs and to investigate the usefulness...... of the developed tools in real life, third, to collect data on risks and safety barriers in SMEs for two occupations by following 20 people for three days each and to create a risk profile for each occupations. Findings – The result is a simple way to go through all types of risks for accidents – a tool for risk...

Clinical features and predictors of outcome in acute hepatitis A and hepatitis E virus hepatitis on cirrhosis.

Science.gov (United States)

Radha Krishna, Yellapu; Saraswat, Vivek Anand; Das, Khaunish; Himanshu, Goel; Yachha, Surender Kumar; Aggarwal, Rakesh; Choudhuri, Gour

2009-03-01

Acute hepatitis A and E are recognized triggers of hepatic decompensation in patients with cirrhosis, particularly from the Indian subcontinent. However, the resulting acute-on-chronic liver failure (ACLF) has not been well characterized and no large studies are available. Our study aimed to evaluate the clinical profile and predictors of 3-month mortality in patients with this distinctive form of liver failure. ACLF was diagnosed in patients with acute hepatitis A or E [abrupt rise in serum bilirubin and/or alanine aminotransferase with positive immunoglobulin M anti-hepatitis A virus (HAV)/anti-hepatitis E virus (HEV)] presenting with clinical evidence of liver failure (significant ascites and/or hepatic encephalopathy) and clinical, biochemical, endoscopic (oesophageal varices at least grade II in size), ultrasonographical (presence of nodular irregular liver with porto-systemic collaterals) or histological evidence of cirrhosis. Clinical and laboratory profile were evaluated, predictors of 3-month mortality were determined using univariate and multivariate logistic regression and a prognostic model was constructed. Receiver-operating curves were plotted to measure performance of the present prognostic model, model for end-stage liver disease (MELD) score and Child-Turcotte-Pugh (CTP) score. ACLF occurred in 121 (3.75%) of 3220 patients (mean age 36.3+/-18.0 years; M:F 85:36) with liver cirrhosis admitted from January 2000 to June 2006. It was due to HEV in 80 (61.1%), HAV in 33 (27.2%) and both in 8 (6.1%). The underlying liver cirrhosis was due to HBV (37), alcohol (17), Wilson's disease (8), HCV (5), autoimmune (6), Budd-Chiari syndrome (2), haemochromatosis (2) and was cryptogenic in the rest (42). Common presentations were jaundice (100%), ascites (78%) and hepatic encephalopathy (55%). Mean (SD) CTP score was 11.4+/-1.6 and mean MELD score was 28.6+/-9.06. Three-month mortality was 54 (44.6%). Complications seen were sepsis in 42 (31.8%), renal failure in

Prevention of hepatitis B

Directory of Open Access Journals (Sweden)

Marta Estera Kowalska

2017-07-01

Full Text Available Hepatitis B (Hepatitis B is a hepatitis B virus (HBV -based liver disease. This virus has an affinity for liver cells, it can cause both acute and chronic viral infections of varying severity. The consequences of chronic HBV infection can be cirrhosis and liver cancer. In Poland in 1989 a preventive program was implemented to reduce HBV infection. Universal vaccinations have been introduced to reduce the prevalence of Type B hepatitis B from 40.3 / 100,000 in 1989 to 7/100 in 2000. In the last 20 years in Poland there has been huge progress in the prevention and suppression of HBV infections. Decrease in the incidence of hepatitis B is mainly the result of the introduction of compulsory vaccination and improving hygiene procedures and improve sanitation aimed at aborting the pathways of the virus. However, still a large part of society is not immune on HBV infection acting potential group of the risk of infection. In addition, in the era of a growing group of followers. movements of the anti vaccine it is necessary to continue to promote knowledge of HBV and the efficacy and safety of vaccination.

Difference in clinical presentation, immunology profile and treatment response of type 1 autoimmune hepatitis between United Kingdom and Singapore patients

OpenAIRE

Than, Nwe Ni; Ching, Doreen Koay Siew; Hodson, James; McDowell, Patrick; Mann, Jake; Gupta, Ravi; Salazar, Ennaliza; Ngu, Jing Hieng; Oo, Ye Htun

2016-01-01

Background Autoimmune hepatitis (AIH) is an immune-mediated liver disease of unknown etiology. Increasing incidence of AIH in Asian patients has been reported. However, the phenotypic difference of Asian patients in Europe and Asia has still not been explored. Aim To evaluate the clinical presentation, biochemical and immunological profiles, treatment response and survival outcome of type 1 AIH from two tertiary liver transplant centres (United Kingdom and Singapore). Method Patients who fulf...

Hepatic vascular injury: Clinical profile, endovascular management and outcomes

Directory of Open Access Journals (Sweden)

Bishav Mohan

2013-01-01

Conclusion: Prompt endovascular management is the modality of choice in comparison to NOM without AE in both pediatric and adult patients with hemodynamically compromised inaccessible intra hepatic vascular trauma.

The immunogenicity of GSK's recombinant hepatitis B vaccine in children: a systematic review of 30 years of experience.

Science.gov (United States)

van den Ende, Caroline; Marano, Cinzia; van Ahee, Ayla; Bunge, Eveline M; De Moerlooze, Laurence

2017-08-01

The World Health Organization recommends hepatitis B virus (HBV) vaccines to be included in national immunization schedules everywhere, and has adopted the strategic goal of halting viral hepatitis as a major public health threat by 2030, under which vaccination plays a major role. Engerix™ B (GSK HepB, GSK, Belgium) was the first recombinant HBV vaccine to be licensed, and marked its 30th anniversary in 2016. Areas covered: We conducted a systematic review of the literature summarizing 30 years of immunogenicity and safety data for GSK HepB in children and adolescents. Expert commentary: Primary 3-dose vaccination of healthy infants and children, including infants born to HBsAg-positive mothers, using the standard 0, 1, 6 month schedule was associated with seroprotection rates ≥96.0%. In high-risk infants, vaccine efficacy at year 5 was 96.0% after 3-dose priming in infancy and immunoglobulin at birth. Lower seroprotection rates were observed in children with severe underlying disease including human immunodeficiency virus infection and cancer. GSK HepB had a clinically acceptable safety profile in all of the populations studied. HBV vaccines have demonstrated long-term impacts on rates of fulminant hepatitis, chronic liver disease and hepatocellular carcinoma. GSK HepB will continue to contribute to global HBV control for the foreseeable future.

Comparative pharmacokinetics and tissue distribution profiles of lignan components in normal and hepatic fibrosis rats after oral administration of Fuzheng Huayu recipe.

Science.gov (United States)

Yang, Tao; Liu, Shan; Zheng, Tian-Hui; Tao, Yan-Yan; Liu, Cheng-Hai

2015-05-26

Fuzheng Huayu recipe (FZHY) is formulated on the basis of Chinese medicine theory in treating liver fibrosis. To illuminate the influence of the pathological state of liver fibrosis on the pharmacokinetics and tissue distribution profiles of lignan components from FZHY. Male Wistar rats were randomly divided into normal group and Hepatic fibrosis group (induced by dimethylnitrosamine). Six lignan components were detected and quantified by ultrahigh performance liquid chromatography-tandem mass spectrometry(UHPLC-MS/MS)in the plasma and tissue of normal and hepatic fibrosis rats. A rapid, sensitive and convenient UHPLC-MS/MS method has been developed for the simultaneous determination of six lignan components in different rat biological samples successfully. After oral administration of FZHY at a dose of 15g/kg, the pharmacokinetic behaviors of schizandrin A (SIA), schizandrin B (SIB), schizandrin C (SIC), schisandrol A (SOA), Schisandrol B (SOB) and schisantherin A (STA) have been significantly changed in hepatic fibrosis rats compared with the normal rats, and their AUC(0-t) values were increased by 235.09%, 388.44%, 223.30%, 669.30%, 295.08% and 267.63% orderly (Pdistribution results showed the amount of SIA, SIB, SOA and SOB were significant increased in heart, lung, spleen and kidney of hepatic fibrosis rats compared with normal rats at most of the time point (Pdistribution of lignan components in normal and hepatic fibrosis rats. The hepatic fibrosis could alter the pharmacokinetics and tissue distribution properties of lignan components in rats after administration of FZHY. The results might be helpful for guide the clinical application of this medicine. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Experimental induction of hepatic lipidosis in cats.

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Biourge, V C; Groff, J M; Munn, R J; Kirk, C A; Nyland, T G; Madeiros, V A; Morris, J G; Rogers, Q R

1994-09-01

The effect of long-term voluntary fasting on hematologic variables, biochemical profiles, and liver histologic findings was assessed in 15 obese cats (> 40% overweight). Clinical signs and laboratory results consistent with hepatic lipidosis were observed in 12 of 15 cats after 5 to 7 weeks of fasting, and were associated with 30 to 35% reduction of initial body weight. Histologic examination of successive liver biopsy specimens revealed that obesity was not associated with liver parenchymal lipid accumulation, but that fasting resulted in lipidosis in all 15 cats. The long-term fast was associated with an early (after 2 to 4 weeks of fasting) and significant (P hepatic-associated enzyme activities and in total and direct serum bilirubin concentrations. Significant (P hepatic lipidosis, cats appeared to tolerate the fast without other adverse effect. This study confirmed that long-term fasting may induce clinical hepatic lipidosis in obese cats. Fasting appears to induce a syndrome of hepatic lipidosis that is indistinguishable from feline idiopathic hepatic lipidosis and may be an appropriate model to study the pathophysiologic features and treatment of hepatic lipidosis.

LONG-TERM CONSEQUENCES OF HEPATITIS A IN CHILDREN

Directory of Open Access Journals (Sweden)

V. F. Uchaikin

2014-01-01

Full Text Available Various embodiments of lingering forms of hepatitis A, for the aggravation still cause differential diagnostic difficulties and mistakes. Continuing to the present heavy and cholestasis form of hepatitis A in children, fulminant form of adolescents, adults and pregnant women let to suggest this issue to be relevance. The task of vaccine prevention of hepatitis A in the National Immunization ScheduleRussiakeeping up to be relevance and perspective. Numerous studies have shown that the French vaccine AVAXIM 80 showed good immunogenicity and safety vaccinate in children.

Metabolomic biomarkers correlating with hepatic lipidosis in dairy cows.

Science.gov (United States)

Imhasly, Sandro; Naegeli, Hanspeter; Baumann, Sven; von Bergen, Martin; Luch, Andreas; Jungnickel, Harald; Potratz, Sarah; Gerspach, Christian

2014-06-02

Hepatic lipidosis or fatty liver disease is a major metabolic disorder of high-producing dairy cows that compromises animal performance and, hence, causes heavy economic losses worldwide. This syndrome, occurring during the critical transition from gestation to early lactation, leads to an impaired health status, decreased milk yield, reduced fertility and shortened lifetime. Because the prevailing clinical chemistry parameters indicate advanced liver damage independently of the underlying disease, currently, hepatic lipidosis can only be ascertained by liver biopsy. We hypothesized that the condition of fatty liver disease may be accompanied by an altered profile of endogenous metabolites in the blood of affected animals. To identify potential small-molecule biomarkers as a novel diagnostic alternative, the serum samples of diseased dairy cows were subjected to a targeted metabolomics screen by triple quadrupole mass spectrometry. A subsequent multivariate test involving principal component and linear discriminant analyses yielded 29 metabolites (amino acids, phosphatidylcholines and sphingomyelines) that, in conjunction, were able to distinguish between dairy cows with no hepatic lipidosis and those displaying different stages of the disorder. This proof-of-concept study indicates that metabolomic profiles, including both amino acids and lipids, distinguish hepatic lipidosis from other peripartal disorders and, hence, provide a promising new tool for the diagnosis of hepatic lipidosis. By generating insights into the molecular pathogenesis of hepatic lipidosis, metabolomics studies may also facilitate the prevention of this syndrome.

In vivo (1)H-MRS hepatic lipid profiling in nonalcoholic fatty liver disease: an animal study at 9.4 T.

Science.gov (United States)

Lee, Yunjung; Jee, Hee-Jung; Noh, Hyungjoon; Kang, Geun-Hyung; Park, Juyeun; Cho, Janggeun; Cho, Jee-Hyun; Ahn, Sangdoo; Lee, Chulhyun; Kim, Ok-Hee; Oh, Byung-Chul; Kim, Hyeonjin

2013-09-01

The applicability of the in vivo proton magnetic resonance spectroscopy hepatic lipid profiling (MR-HLP) technique in nonalcoholic fatty liver disease was investigated. Using magnetic resonance spectroscopy, the relative fractions of diunsaturated (fdi), monounsaturated (fmono), and saturated (fsat) fatty acids as well as total hepatic lipid content were estimated in the livers of 8 control and 23 CCl4-treated rats at 9.4 T. The mean steatosis, necrosis, inflammation, and fibrosis scores of the treated group were all significantly higher than those of the control group (P steatosis and fibrosis are positively correlated with fmono and negatively correlated with fdi. Both necrosis and inflammation, however, were not correlated with any of the MR-HLP parameters. Hepatic lipid composition appears to be changed in association with the severity of steatosis and fibrosis in nonalcoholic fatty liver disease, and these changes can be depicted in vivo by using the MR-HLP method at 9.4 T. Thus, while it may not likely be that MR-HLP helps differentiate between steatohepatitis in its early stages and simple steatosis, these findings altogether are in support of potential applicability of in vivo MR-HLP at high field in nonalcoholic fatty liver disease. Copyright © 2012 Wiley Periodicals, Inc.

Reactivation of hepatitis B in patients of chronic hepatitis C with hepatitis B virus infection treated with direct acting antivirals.

Science.gov (United States)

Yeh, Ming-Lun; Huang, Chung-Feng; Hsieh, Meng-Hsuan; Ko, Yu-Min; Chen, Kuan-Yu; Liu, Ta-Wei; Lin, Yi-Hung; Liang, Po-Cheng; Hsieh, Ming-Yen; Lin, Zu-Yau; Chen, Shinn-Cherng; Huang, Ching-I; Huang, Jee-Fu; Kuo, Po-Lin; Dai, Chia-Yen; Yu, Ming-Lung; Chuang, Wan-Long

2017-10-01

Hepatitis B virus (HBV) may reactivate when treating chronic hepatitis C (CHC) with direct acting antivirals (DAA). We aim to investigate the risk of HBV reactivation during DAA therapy. Chronic hepatitis C patients receiving pan-oral DAA therapy from December 2013 to August 2016 were evaluated. Fifty-seven patients that had a past HBV infection (negative hepatitis B surface antigen [HBsAg] and positive hepatitis B core antibody) and seven patients that had a current HBV infection (positive HBsAg) were enrolled. Serum HBV and hepatitis C virus (HCV) markers were regularly measured. The endpoints were the HCV sustained virological response (SVR) and the HBV virological/clinical reactivation. The overall SVR 12 rate was 96.9%, and two patients, one with positive HBsAg, had a relapse of HCV. No episodes of HBV virological reactivation were observed among the patients with a past HBV infection. For the seven patients with a current HBV infection, HBV virological reactivation was found in four (57.1%) of the seven patients. Clinical reactivation of HBV was observed in one patient with pretreatment detectable HBV DNA and recovered after entecavir administration. For the other three patients with HBV virological reactivation, the reappearance of low level HBV DNA without clinical reactivation was observed. HBsAg levels demonstrated only small fluctuations in all the patients. There was a minimal impact of hepatitis B core antibody seropositivity on HCV efficacy and safety. For CHC patients with current HBV infection, the risk of HBV reactivation was present, and monitoring the HBV DNA level during therapy is warranted. © 2017 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

Safety against formation of through cracks of profiled fibre-reinforced cement sheets for roofing

DEFF Research Database (Denmark)

Hansen, Klavs Feilberg; Stang, Birgitte Friis Dela

2009-01-01

  Loads due to wind, snow or traffic on a roof determine the requirements to the strength and stiffness properties of profiled sheets for roofing. Apart from these loads, locked-in stresses can occur due to differences in temperature and moisture strains in the profiled sheets and the wooden laths...... supporting the sheets. These tensile and compressive stresses are induced in the sheets if they are firmly fastened to the laths with fastening screws. The purpose of this investigation was to analyse the safety of the profiled sheets in transmitting these loads without the formation of through cracks...

The importance of Pharmacovigilance for the drug safety: Focus on cardiovascular profile of incretin-based therapy.

Science.gov (United States)

Sportiello, Liberata; Rafaniello, Concetta; Scavone, Cristina; Vitale, Cristiana; Rossi, Francesco; Capuano, Annalisa

2016-01-01

With the recent introduction of the new European Pharmacovigilance legislation, all new drugs must be carefully monitored after admission on the European market, in order to assess the long safety profile. Currently, special attention is given to several hypoglycemic agents with recent market approval (agonists of glucagon-like peptide-1 [GLP-1] receptor and dipeptidyl peptidase 4 inhibitors [DPP-4i]), which act through the potentiation of incretin hormone signaling. Their inclusion in European additional monitoring is also due to safety problems, which seem to characterize their pharmacological class. In fact, these drugs initially showed a good tolerability profile with mainly gastrointestinal adverse events, low risk of hypoglycemia and minor effects on body weight. But, new concerns such as infections, pancreatitis, pancreatic cancer and above all cardiovascular events (especially risk of heart failure requiring hospitalization) are now arising. In this review, we highlighted aspects of the new Pharmacovigilance European dispositions, and then we investigated the tolerability profile of incretin-based therapies, in particular DPP-4 inhibitors. Notably, we focused our attention on new safety concerns, which are emerging mostly in the post-marketing period, as the cardiovascular risk profile. Evidence in literature and opinions of regulatory agencies (e.g., European Medicines Agency and Food and Drug Administration) about risks of incretin-based therapies are yet controversial, and there are many open questions in particular on cancer and cardiovascular effects. Thus, it is important to continue to monitor closely the use of these drugs in clinical practice to improve the knowledge on their long-term safety and their place in diabetes therapy. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

One Family's Struggles with Hepatitis B

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Full Text Available ... resources M.O.V.E. parents for prevention publications schedules & records support statements vaccine initiative vaccine safety ... Gonna Lose M.O.V.E. newsfeeds PSAs publications infectious disease workshop pediatric hepatitis report someone you ...

The Influence of Hepatic and Renal Impairment on the Pharmacokinetics of a Treatment for Herpes Zoster, Amenamevir (ASP2151): Phase 1, Open-Label, Single-Dose, Parallel-Group Studies.

Science.gov (United States)

Kusawake, Tomohiro; Kowalski, Donna; Takada, Akitsugu; Kato, Kota; Katashima, Masataka; Keirns, James J; Lewand, Michaelene; Lasseter, Kenneth C; Marbury, Thomas C; Preston, Richard A

2017-12-01

Amenamevir (ASP2151) is a nonnucleoside human herpesvirus helicase-primase inhibitor that was approved in Japan for the treatment of herpes zoster (shingles) in 2017. This article reports the results of two clinical trials that investigated the effects of renal and hepatic impairment on the pharmacokinetics of amenamevir. These studies were phase 1, open-label, single-dose (oral 400 mg), parallel-group studies evaluating the pharmacokinetics, safety, and tolerability of amenamevir in healthy participants and participants with moderate hepatic impairment and mild, moderate, and severe renal impairment. In the hepatic impairment study, the pharmacokinetic profile of amenamevir in participants with moderate hepatic impairment was generally similar to that of participants with normal hepatic function. In the renal impairment study, the area under the amenamevir concentration versus time curve from the time of dosing up to the time of the last sample with extrapolation to infinity of the terminal phase was increased by 78.1% in participants with severe renal impairment. There was a positive relationship between creatinine clearance and oral and renal clearance for amenamevir in the renal impairment study. In both studies, amenamevir was safe and well tolerated. The findings of the hepatic impairment study indicate that no dosing adjustment is required in patients with moderate hepatic impairment. In the renal impairment study, systemic amenamevir exposure was increased by renal impairment. However, it is unlikely that renal impairment will have a significant effect on the safety of amenamevir given that in previous pharmacokinetic and safety studies in healthy individuals amenamevir was safe and well tolerated after a single dose (5-2400 mg, fasted condition) and repeated doses for 7 days (300 or 600 mg, fed condition), and the amount of amenamevir exposure in the renal impairment study was covered by those studies. These findings suggest that amenamevir does not

Transarterial Chemoembolization for Hepatocellular Carcinoma with a New Generation of Beads: Clinical–Radiological Outcomes and Safety Profile

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Spreafico, Carlo, E-mail: carlo.spreafico@istitutotumori.mi.it; Cascella, Tommaso, E-mail: tommaso.cascella@istitutotumori.mi.it [Fondazione Istituto Tumori, Department of Radiology (Italy); Facciorusso, Antonio, E-mail: antonio.facciorusso@istitutotumori.mi.it; Sposito, Carlo, E-mail: carlo.sposito@istitutotumori.mi.it [Fondazione Istituto Tumori, Department of Liver Surgery and Transplant (Italy); Rodolfo, Lanocita, E-mail: rodolfo.lanocita@istitutotumori.mi.it; Morosi, Carlo, E-mail: carlo.morosi@istitutotumori.mi.it; Civelli, Enrico M., E-mail: enrico.civelli@istitutotumori.mi.it; Vaiani, Marta, E-mail: marta.vaiani@istitutotumori.mi.it [Fondazione Istituto Tumori, Department of Radiology (Italy); Bhoori, Sherrie, E-mail: sherrie.bhoori@istitutotumori.mi.it [Fondazione Istituto Tumori, Department of Liver Surgery and Transplant (Italy); Pellegrinelli, Alessandro, E-mail: alessandro.pellegrinelli@istitutotumori.mi.it [Fondazione Istituto Tumori, Department of Pathology (Italy); Marchianò, Alfonso, E-mail: alfonso.marchiano@istitutotumori.mi.it [Fondazione Istituto Tumori, Department of Radiology (Italy); Mazzaferro, Vincenzo, E-mail: vincenzo.mazzaferro@istitutotumori.mi.it [Fondazione Istituto Tumori, Department of Liver Surgery and Transplant (Italy)

2015-02-15

PurposeTo evaluate the short-term safety and efficacy of the new generation of 70–150 µm drug-eluting beads (M1 DEB) in patients with hepatocellular carcinoma undergoing transarterial chemoembolization (TACE) as a primary therapy or as a bridge to liver transplantation (LT).MethodsForty-five consecutive patients underwent TACE with M1 DEB loaded with doxorubicin (DEBDOX/M1). Clinical data were recorded at 12, 24, and 48 h, 7 and 30 days after treatment. Response was assessed by computed tomographic scan according to the modified response evaluation criteria in solid tumors criteria, and a second DEBDOX/M1 TACE was scheduled within 6 weeks in case of a noncomplete response.ResultsAll patients had well-compensated cirrhosis (97.7 % Child A, 44.4 % hepatitis C virus, median age 61 years). Twenty patients (44.4 %) had Barcelona Clinic for Liver Cancer class B disease; the median number of nodules and their sum of diameters were 2 (range 1–6) and 43 mm (range 10–190), respectively. The mean number of TACE procedures per patient was 1.4. Objective response rate (complete + partial response) was 77.7 % with a median time to best response of 3 months (95 % confidence interval 2–4). In 13 patients, DEBDOX/M1 TACE served as a bridge/downstaging to LT/surgery. Pathology showed that more than 90 % necrosis was achieved in 10 of 28 nodules. DEBDOX/M1 TACE was well tolerated, and the grade 3/4 adverse event rate was low (1 of 65 procedures).ConclusionDEBDOX/M1 TACE is an effective procedure with a favorable safety profile and promising results in terms of objective response rate, tumor downstaging, and necrosis.

A randomized study to evaluate the immunogenicity and safety of a heptavalent diphtheria, tetanus, pertussis, hepatitis B, poliomyelitis, haemophilus influenzae b, and meningococcal serogroup C combination vaccine administered to infants at 2, 4 and 12 months of age.

Science.gov (United States)

Thollot, Franck; Scheifele, David; Pankow-Culot, Heidemarie; Cheuvart, Brigitte; Leyssen, Maarten; Ulianov, Liliana; Miller, Jacqueline M

2014-12-01

The immunogenicity and safety of the investigational diphtheria, tetanus, acellular pertussis, hepatitis B, poliomyelitis, Haemophilus influenzae type b (Hib) and meningococcal serogroup C (MenC) heptavalent combination vaccine were compared with those of licensed control vaccines. In this open, phase II, randomized study (NCT01090453), 480 infants from Germany, France and Canada received the heptavalent vaccine (Hepta group) or hexavalent and monovalent MenC control vaccines (HexaMenC group) co-administered with a 13-valent pneumococcal conjugate vaccine at 2, 4 and 12 months of age. Immunogenicity was measured 1 month after the second primary dose, and before and 1 month after the booster dose. Safety and reactogenicity were also evaluated. Non-inferiority of immune responses to MenC and Hib induced by 2-dose primary vaccination with the heptavalent vaccine versus control vaccines was demonstrated. In exploratory analyses, postprimary and postbooster functional antibody geometric mean titers against MenC tended to be lower (1119.5 vs. 3200.5; 2653.8 vs. 6028.4) and antibody geometric mean concentrations against Hib higher (1.594 vs. 0.671 μg/mL; 17.678 vs. 13.737 μg/mL) in the Hepta versus the HexaMenC group. The heptavalent and control vaccines were immunogenic to all other antigens, although immune responses to poliovirus were lower than expected in both groups. No differences in safety and reactogenicity profiles were detected between groups. The heptavalent vaccine induced non-inferior MenC and Hib responses compared with control vaccines. Both vaccination regimens, when administered at 2, 4 and 12 months of age, had comparable safety profiles and were immunogenic to all antigens, with lower-than-expected responses to poliomyelitis.

Efficacy and safety of entecavir versus lamivudine over 5 years of treatment: A randomized controlled trial in Korean patients with hepatitis B e antigen-negative chronic hepatitis B

Directory of Open Access Journals (Sweden)

Kwan Sik Lee

2017-12-01

Full Text Available Background/Aims Long-term data on antiviral therapy in Korean patients with hepatitis B e antigen (HBeAg-negative chronic hepatitis B (CHB are limited. This study evaluated the efficacy and safety of entecavir (ETV and lamivudine (LAM over 240 weeks. Methods Treatment-naive patients with HBeAg-negative CHB were randomized to receive ETV 0.5 mg/day or LAM 100 mg/day during the 96 week double-blind phase, followed by open-label treatment through week 240. The primary endpoint was the proportion of patients with virologic response (VR; hepatitis B virus [HBV] DNA16 years old were included (ETV, n=56; LAM, n=64. Baseline characteristics were comparable between the two groups. A significantly higher proportion of ETV-treated patients achieved VR compared to LAM at week 24 (92.9% vs. 67.2%, P=0.0006, week 96 (94.6% vs. 48.4%, P<0.0001, and week 240 (95.0% vs. 47.6%, P<0.0001. At week 96, ALT normalization was observed in 87.5% and 51.6% of ETV and LAM patients, respectively (P<0.0001. Virologic breakthrough occurred in one patient (1.8% receiving ETV and 26 patients (42.6% receiving LAM (P<0.0001 up to week 96. Emergence of resistance to ETV was not detected. The incidence of serious adverse events was low and unrelated to the study medications. Conclusions Long-term ETV treatment was superior to LAM, with a significantly higher proportion of patients achieving VR. Both treatments were well tolerated.

Hepatitis Associated Aplastic Anemia: A review

Science.gov (United States)

2011-01-01

Hepatitis-associated aplastic anemia (HAAA) is an uncommon but distinct variant of aplastic anemia in which pancytopenia appears two to three months after an acute attack of hepatitis. HAAA occurs most frequently in young male children and is lethal if leave untreated. The etiology of this syndrome is proposed to be attributed to various hepatitis and non hepatitis viruses. Several hepatitis viruses such as HAV, HBV, HCV, HDV, HEV and HGV have been associated with this set of symptoms. Viruses other than the hepatitis viruses such as parvovirus B19, Cytomegalovirus, Epstein bar virus, Transfusion Transmitted virus (TTV) and non-A-E hepatitis virus (unknown viruses) has also been documented to develop the syndrome. Considerable evidences including the clinical features, severe imbalance of the T cell immune system and effective response to immunosuppressive therapy strongly present HAAA as an immune mediated mechanism. However, no association of HAAA has been found with blood transfusions, drugs and toxins. Besides hepatitis and non hepatitis viruses and immunopathogenesis phenomenon as causative agents of the disorder, telomerase mutation, a genetic factor has also been predisposed for the development of aplastic anemia. Diagnosis includes clinical manifestations, blood profiling, viral serological markers testing, immune functioning and bone marrow hypocellularity examination. Patients presenting the features of HAAA have been mostly treated with bone marrow or hematopoietic cell transplantation from HLA matched donor, and if not available then by immunosuppressive therapy. New therapeutic approaches involve the administration of steroids especially the glucocorticoids to augment the immunosuppressive therapy response. Pancytopenia following an episode of acute hepatitis response better to hematopoietic cell transplantation than immunosuppressive therapy. PMID:21352606

Hepatitis delta in HIV-infected individuals in Europe

DEFF Research Database (Denmark)

Soriano, Vincent; Grint, Daniel; Monforte, Antonellad'arminio

2011-01-01

BACKGROUND:: Hepatitis delta virus (HDV) infection results in the most aggressive form of chronic viral hepatitis. There is scarce information about the prevalence, epidemiology, virological profile and natural historyof hepatitis delta in HIV patients. METHODS:: From 16,597 HIV patients enrolled......-RNA was quantified using a real-time PCR method. RESULTS:: A total of 61/422 HBsAg+ carriers were anti-HDV+ (prevalence: 14.5%). Hepatitis delta predominated in intravenous drug users and for this reason in South and/or East Europe. Serum HDV-RNA was detectable in 87% of tested anti-HDV+ patients, with a median...... titer of 1.76x10¿copies/ml. Overall, delta hepatitis patients showed lower serum HBV-DNA than the rest of HBsAg+ carriers, although the inhibitory effect of HDV on HBV replication was not recognized in HBV genotype D patients.Whereas HDV was not associated with progression to AIDS, it significantly...

Safety factor profile control in a tokamak

CERN Document Server

Bribiesca Argomedo, Federico; Prieur, Christophe

2014-01-01

Control of the Safety Factor Profile in a Tokamak uses Lyapunov techniques to address a challenging problem for which even the simplest physically relevant models are represented by nonlinear, time-dependent, partial differential equations (PDEs). This is because of the  spatiotemporal dynamics of transport phenomena (magnetic flux, heat, densities, etc.) in the anisotropic plasma medium. Robustness considerations are ubiquitous in the analysis and control design since direct measurements on the magnetic flux are impossible (its estimation relies on virtual sensors) and large uncertainties remain in the coupling between the plasma particles and the radio-frequency waves (distributed inputs). The Brief begins with a presentation of the reference dynamical model and continues by developing a Lyapunov function for the discretized system (in a polytopic linear-parameter-varying formulation). The limitations of this finite-dimensional approach motivate new developments in the infinite-dimensional framework. The t...

The serological profile of the autoimmune hepatitis/primary biliary cirrhosis overlap syndrome.

Science.gov (United States)

Muratori, Paolo; Granito, Alessandro; Pappas, Georgios; Pendino, Gaspare M; Quarneti, Chiara; Cicola, Ronny; Menichella, Rita; Ferri, Silvia; Cassani, Fabio; Bianchi, Francesco B; Lenzi, Marco; Muratori, Luigi

2009-06-01

During the last decade patients with concomitant clinical, biochemical, immunoserological, and histological features of both autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC) were sporadically described, but definite diagnostic criteria and specific serological markers to support the diagnosis of AIH/PBC overlap syndrome (AIH/PBC OS) are still lacking. Clinical, biochemical, and histological features, autoantibody profile, and treatment response of 15 patients with coexistent hepatitic and cholestatic liver damage, all fulfilling strict diagnostic criteria for both AIH and PBC, were compared with those of 120 patients with pure PBC and 120 patients with pure AIH. At diagnosis, the AIH/PBC OS patients' median age was 51 years, similar to that of the PBC patients (52 years, P=NS), but significantly higher than that of the AIH patients (40 years, P=0.04). Anti-dsDNA antibodies were detected in 60% of AIH/PBC OS patients, but only in 4% of PBC patients and 26% of AIH patients (P<0.0001 and 0.01, respectively). Double positivity for antimitochondrial antibodies (AMA) and anti-dsDNA was present in 47% of those with AIH/PBC OS, but only in 2% of the pathological controls (P<0.0001; specificity: 98; 95% confidence interval (CI): 97-99.2; positive likelihood ratio: 28; 95% CI: 9.8-79.4). Combined therapy (ursodeoxycholic acid (UDCA) plus steroids) achieved biochemical response in 77% of AIH/PBC OS patients. Concomitant AMA/anti-dsDNA seropositivity can be considered the serological profile of AIH/PBC OS. The combination of UDCA and steroids is effective in achieving persistent biochemical amelioration in most AIH/PBC OS patients.

Modifying locally the safety profile to improve the confinement of magnetic field lines in tokamak plasmas

International Nuclear Information System (INIS)

Constantinescu, D.; Firpo, M.-C.

2012-01-01

Using Hamiltonian models for the magnetic field lines, we propose a methodology to improve their confinement through the creation of transport barriers. A local modification of the safety profile creating a low-shear zone is shown to be sufficient to locally enhance drastically the regularity of the magnetic field lines without requesting a reversed shear. The optimal benefits of low-shear are obtained when the value q 0 of the safety profile in the low-shear zone is sufficiently far from the main resonance values m/n with low m and n, in the case of large enough values of those (m, n) mode amplitudes. A practical implementation in tokamak plasmas should involve electron cyclotron current drive to locally modify the magnetic shear. (paper)

Arginase Inhibition Ameliorates Hepatic Metabolic Abnormalities in Obese Mice

Science.gov (United States)

Moon, Jiyoung; Do, Hyun Ju; Cho, Yoonsu; Shin, Min-Jeong

2014-01-01

Objectives We examined whether arginase inhibition influences hepatic metabolic pathways and whole body adiposity in diet-induced obesity. Methods and Results After obesity induction by a high fat diet (HFD), mice were fed either the HFD or the HFD with an arginase inhibitor, Nω-hydroxy-nor-L-arginine (nor-NOHA). Nor-NOHA significantly prevented HFD-induced increases in body, liver, and visceral fat tissue weight, and ameliorated abnormal lipid profiles. Furthermore, nor-NOHA treatment reduced lipid accumulation in oleic acid-induced hepatic steatosis in vitro. Arginase inhibition increased hepatic nitric oxide (NO) in HFD-fed mice and HepG2 cells, and reversed the elevated mRNA expression of hepatic genes in lipid metabolism. Expression of phosphorylated 5′ AMPK-activated protein kinase α was increased by arginase inhibition in the mouse livers and HepG2 cells. Conclusions Arginase inhibition ameliorated obesity-induced hepatic lipid abnormalities and whole body adiposity, possibly as a result of increased hepatic NO production and subsequent activation of metabolic pathways involved in hepatic triglyceride metabolism and mitochondrial function. PMID:25057910

Long-term soft drink and aspartame intake induces hepatic damage via dysregulation of adipocytokines and alteration of the lipid profile and antioxidant status.

Science.gov (United States)

Lebda, Mohamed A; Tohamy, Hossam G; El-Sayed, Yasser S

2017-05-01

Dietary intake of fructose corn syrup in sweetened beverages is associated with the development of metabolic syndrome and obesity. We hypothesized that inflammatory cytokines play a role in lipid storage and induction of liver injury. Therefore, this study intended to explore the expression of adipocytokines and its link to hepatic damage. Rats were assigned to drink water, cola soft drink (free access) and aspartame (240 mg/kg body weight/day orally) for 2 months. The lipid profiles, liver antioxidants and pathology, and mRNA expression of adipogenic cytokines were evaluated. Subchronic intake of soft drink or aspartame substantially induced hyperglycemia and hypertriacylglycerolemia, as represented by increased serum glucose, triacylglycerol, low-density lipoprotein and very low-density lipoprotein cholesterol, with obvious visceral fatty deposition. These metabolic syndromes were associated with the up-regulation of leptin and down-regulation of adiponectin and peroxisome proliferator activated receptor-γ (PPAR-γ) expression. Moreover, alterations in serum transaminases accompanied by hepatic oxidative stress involving induction of malondialdehyde and reduction of superoxide dismutase, catalase, and glutathione peroxidase and glutathione levels are indicative of oxidative hepatic damage. Several cytoarchitecture alterations were detected in the liver, including degeneration, infiltration, necrosis, and fibrosis, predominantly with aspartame. These data suggest that long-term intake of soft drink or aspartame-induced hepatic damage may be mediated by the induction of hyperglycemia, lipid accumulation, and oxidative stress with the involvement of adipocytokines. Copyright © 2017 Elsevier Inc. All rights reserved.

Gene expression profiling and secretome analysis differentiate adult-derived human liver stem/progenitor cells and human hepatic stellate cells.

Directory of Open Access Journals (Sweden)

Silvia Berardis

Full Text Available Adult-derived human liver stem/progenitor cells (ADHLSC are obtained after primary culture of the liver parenchymal fraction. The cells are of fibroblastic morphology and exhibit a hepato-mesenchymal phenotype. Hepatic stellate cells (HSC derived from the liver non-parenchymal fraction, present a comparable morphology as ADHLSC. Because both ADHLSC and HSC are described as liver stem/progenitor cells, we strived to extensively compare both cell populations at different levels and to propose tools demonstrating their singularity. ADHLSC and HSC were isolated from the liver of four different donors, expanded in vitro and followed from passage 5 until passage 11. Cell characterization was performed using immunocytochemistry, western blotting, flow cytometry, and gene microarray analyses. The secretion profile of the cells was evaluated using Elisa and multiplex Luminex assays. Both cell types expressed α-smooth muscle actin, vimentin, fibronectin, CD73 and CD90 in accordance with their mesenchymal origin. Microarray analysis revealed significant differences in gene expression profiles. HSC present high expression levels of neuronal markers as well as cytokeratins. Such differences were confirmed using immunocytochemistry and western blotting assays. Furthermore, both cell types displayed distinct secretion profiles as ADHLSC highly secreted cytokines of therapeutic and immuno-modulatory importance, like HGF, interferon-γ and IL-10. Our study demonstrates that ADHLSC and HSC are distinct liver fibroblastic cell populations exhibiting significant different expression and secretion profiles.

Safety of the 2D/3D direct-acting antiviral regimen in HCV-induced Child-Pugh A cirrhosis - A pooled analysis.

Science.gov (United States)

Poordad, Fred; Nelson, David R; Feld, Jordan J; Fried, Michael W; Wedemeyer, Heiner; Larsen, Lois; Cohen, Daniel E; Cohen, Eric; Mobashery, Niloufar; Tatsch, Fernando; Foster, Graham R

2017-10-01

Chronic hepatitis C virus (HCV)-infected patients with cirrhosis are a high-priority population for treatment. To help inform the benefit-risk profile of the all-oral direct-acting antiviral (DAA) combination regimen of ombitasvir, paritaprevir, and ritonavir, with or without dasabuvir (OBV/PTV/r±DSV) in patients with Child-Pugh A cirrhosis, we undertook a comprehensive review of AbbVie-sponsored clinical trials enrolling patients with Child-Pugh A cirrhosis. Twelve phase II or III clinical trials of the 2-DAA regimen of OBV/PTV/r±ribavirin (RBV) or the 3-DAA regimen of OBV/PTV/r+DSV±RBV that included patients with Child-Pugh A cirrhosis were reviewed; patients who completed treatment by November 16, 2015 were included in a pooled, post hoc safety assessment. The number and percentage of patients with treatment-emergent adverse events (TEAEs), serious TEAEs, and TEAEs consistent with hepatic decompensation were reported. In 1,066 patients with Child-Pugh A cirrhosis, rates of serious TEAEs and TEAEs leading to study drug discontinuation were 5.3% (95% confidence interval [CI]: 4.1-6.8) and 2.2% (95% CI: 1.4-3.2), respectively. Thirteen patients (1.2%; 95% CI: 0.7-2.1) had a TEAE that was consistent with hepatic decompensation. The most frequent TEAEs consistent with hepatic decompensation were ascites (n=8), esophageal variceal hemorrhage (n=4), and hepatic encephalopathy (n=2). This pooled analysis in 1,066 HCV-infected patients with Child-Pugh A cirrhosis confirms the safety of OBV/PTV/r±DSV±RBV in this population. These results support the use of OBV/PTV/r±DSV±RBV in this high-priority population. Lay summary: This pooled safety analysis in 1,066 HCV-infected patients with compensated cirrhosis, receiving treatment with ombitasvir, paritaprevir, and ritonavir with or without dasabuvir, with or without ribavirin, shows that the rate of hepatic decompensation events was similar to previously reported rates in untreated patients. Copyright © 2017 European

Diagnosis and therapy of autoimmune hepatitis.

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Granito, Alessandro; Muratori, Paolo; Ferri, Silvia; Pappas, Georgios; Quarneti, Chiara; Lenzi, Marco; Bianchi, Francesco B; Muratori, Luigi

2009-06-01

Autoimmune hepatitis (AIH) is a chronic progressive hepatitis, characterized by interface hepatitis with lymphoplasmacellular infiltrates on liver biopsy, high serum globulin level and circulating autoantibodies. It is classified into two types, according to autoantibody profile: type 1 is characterized by anti-nuclear (ANA) and/or anti-smooth muscle (SMA) antibodies; type 2 by anti-liver kidney microsomal type 1 (anti-LKM-1) antibodies. AIH affects all ages, may be asymptomatic, frequently has an acute onset, and can present as fulminant hepatitis. The diagnosis of AIH is based on a scoring system codified by an international consensus. Corticosteroids alone or in conjunction with azathioprine is the treatment of choice in patients with AIH and results in remission induction in over 80% of patients. Alternative proposed strategies in patients who have failed to achieve remission on standard therapy or patients with drug toxicity include the use of cyclosporine, tacrolimus, budesonide or mycophenolate mofetil. Liver transplantation is the treatment of choice in managing decompensated disease, however AIH can recur or develop de novo after liver transplantation.

Imaging of gastrointestinal and hepatic diseases during pregnancy.

LENUS (Irish Health Repository)

Hodnett, Philip A

2012-02-03

Imaging of the abdomen for suspected gastrointestinal and hepatic disease during pregnancy is assuming greater importance. Like clinical evaluation, imaging of the abdomen and pelvis is challenging but is vitally important to prevent delayed diagnosis or unnecessary interventions. Also choice of imaging modality is influenced by factors which could impact on fetal safety such as the use of ionising radiation and magnetic resonance imaging. This article discusses important issues in imaging of gastrointestinal and hepatic disease in pregnancy and the puerperium.

Preclinical safety profile of trastuzumab emtansine (T-DM1): Mechanism of action of its cytotoxic component retained with improved tolerability

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Poon, Kirsten Achilles, E-mail: achilles.kirsten@gene.com [Genentech, Inc., South San Francisco, CA (United States); Flagella, Kelly; Beyer, Joseph [Genentech, Inc., South San Francisco, CA (United States); Tibbitts, Jay [UCB, Brussels (Belgium); Kaur, Surinder; Saad, Ola; Yi, Joo-Hee; Girish, Sandhya; Dybdal, Noel; Reynolds, Theresa [Genentech, Inc., South San Francisco, CA (United States)

2013-12-01

Trastuzumab emtansine (T-DM1) is the first antibody-drug conjugate (ADC) approved for patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer. The therapeutic premise of ADCs is based on the hypothesis that targeted delivery of potent cytotoxic drugs to tumors will provide better tolerability and efficacy compared with non-targeted delivery, where poor tolerability can limit efficacious doses. Here, we present results from preclinical studies characterizing the toxicity profile of T-DM1, including limited assessment of unconjugated DM1. T-DM1 binds primate ErbB2 and human HER2 but not the rodent homolog c-neu. Therefore, antigen-dependent and non-antigen-dependent toxicity was evaluated in monkeys and rats, respectively, in both single- and repeat-dose studies; toxicity of DM1 was assessed in rats only. T-DM1 was well tolerated at doses up to 40 mg/kg (∼ 4400 μg DM1/m{sup 2}) and 30 mg/kg (∼ 6000 μg DM1/m{sup 2}) in rats and monkeys, respectively. In contrast, DM1 was only tolerated up to 0.2 mg/kg (1600 μg DM1/m{sup 2}). This suggests that at least two-fold higher doses of the cytotoxic agent are tolerated in T-DM1, supporting the premise of ADCs to improve the therapeutic index. In addition, T-DM1 and DM1 safety profiles were similar and consistent with the mechanism of action of DM1 (i.e., microtubule disruption). Findings included hepatic, bone marrow/hematologic (primarily platelet), lymphoid organ, and neuronal toxicities, and increased numbers of cells of epithelial and phagocytic origin in metaphase arrest. These adverse effects did not worsen with chronic dosing in monkeys and are consistent with those reported in T-DM1-treated patients to date. - Highlights: • T-DM1 was well tolerated in preclinical studies in rats and cynomolgus monkeys. • T-DM1 is associated with bone marrow/hematologic, hepatic, and neuronal toxicities. • T-DM1 toxicities are related to DM1 mechanisms of action and pharmacologic

Systematic review: cardiovascular safety profile of 5-HT(4) agonists developed for gastrointestinal disorders.

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Tack, J; Camilleri, M; Chang, L; Chey, W D; Galligan, J J; Lacy, B E; Müller-Lissner, S; Quigley, E M M; Schuurkes, J; De Maeyer, J H; Stanghellini, V

2012-04-01

The nonselective 5-HT(4) receptor agonists, cisapride and tegaserod have been associated with cardiovascular adverse events (AEs). To perform a systematic review of the safety profile, particularly cardiovascular, of 5-HT(4) agonists developed for gastrointestinal disorders, and a nonsystematic summary of their pharmacology and clinical efficacy. Articles reporting data on cisapride, clebopride, prucalopride, mosapride, renzapride, tegaserod, TD-5108 (velusetrag) and ATI-7505 (naronapride) were identified through a systematic search of the Cochrane Library, Medline, Embase and Toxfile. Abstracts from UEGW 2006-2008 and DDW 2008-2010 were searched for these drug names, and pharmaceutical companies approached to provide unpublished data. Retrieved articles on pharmacokinetics, human pharmacodynamics and clinical data with these 5-HT(4) agonists, are reviewed and summarised nonsystematically. Articles relating to cardiac safety and tolerability of these agents, including any relevant case reports, are reported systematically. Two nonselective 5-HT(4) agonists had reports of cardiovascular AEs: cisapride (QT prolongation) and tegaserod (ischaemia). Interactions with, respectively, the hERG cardiac potassium channel and 5-HT(1) receptor subtypes have been suggested to account for these effects. No cardiovascular safety concerns were reported for the newer, selective 5-HT(4) agonists prucalopride, velusetrag, naronapride, or for nonselective 5-HT(4) agonists with no hERG or 5-HT(1) affinity (renzapride, clebopride, mosapride). 5-HT(4) agonists for GI disorders differ in chemical structure and selectivity for 5-HT(4) receptors. Selectivity for 5-HT(4) over non-5-HT(4) receptors may influence the agent's safety and overall risk-benefit profile. Based on available evidence, highly selective 5-HT(4) agonists may offer improved safety to treat patients with impaired GI motility. © 2012 Blackwell Publishing Ltd.

Systematic review: cardiovascular safety profile of 5-HT4 agonists developed for gastrointestinal disorders

Science.gov (United States)

Tack, J; Camilleri, M; Chang, L; Chey, W D; Galligan, J J; Lacy, B E; Müller-Lissner, S; Quigley, E M M; Schuurkes, J; Maeyer, J H; Stanghellini, V

2012-01-01

Summary Background The nonselective 5-HT4 receptor agonists, cisapride and tegaserod have been associated with cardiovascular adverse events (AEs). Aim To perform a systematic review of the safety profile, particularly cardiovascular, of 5-HT4 agonists developed for gastrointestinal disorders, and a nonsystematic summary of their pharmacology and clinical efficacy. Methods Articles reporting data on cisapride, clebopride, prucalopride, mosapride, renzapride, tegaserod, TD-5108 (velusetrag) and ATI-7505 (naronapride) were identified through a systematic search of the Cochrane Library, Medline, Embase and Toxfile. Abstracts from UEGW 2006–2008 and DDW 2008–2010 were searched for these drug names, and pharmaceutical companies approached to provide unpublished data. Results Retrieved articles on pharmacokinetics, human pharmacodynamics and clinical data with these 5-HT4 agonists, are reviewed and summarised nonsystematically. Articles relating to cardiac safety and tolerability of these agents, including any relevant case reports, are reported systematically. Two nonselective 5-HT4 agonists had reports of cardiovascular AEs: cisapride (QT prolongation) and tegaserod (ischaemia). Interactions with, respectively, the hERG cardiac potassium channel and 5-HT1 receptor subtypes have been suggested to account for these effects. No cardiovascular safety concerns were reported for the newer, selective 5-HT4 agonists prucalopride, velusetrag, naronapride, or for nonselective 5-HT4 agonists with no hERG or 5-HT1 affinity (renzapride, clebopride, mosapride). Conclusions 5-HT4 agonists for GI disorders differ in chemical structure and selectivity for 5-HT4 receptors. Selectivity for 5-HT4 over non-5-HT4 receptors may influence the agent's safety and overall risk–benefit profile. Based on available evidence, highly selective 5-HT4 agonists may offer improved safety to treat patients with impaired GI motility. PMID:22356640

Tomato Juice Consumption Modifies the Urinary Peptide Profile in Sprague-Dawley Rats with Induced Hepatic Steatosis

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Gala Martín-Pozuelo

2016-10-01

Full Text Available Non-alcoholic fatty liver disease (NAFLD is the most common liver disorder in Western countries, with a high prevalence, and has been shown to increase the risk of type 2 diabetes, cardiovascular disease (CVD, etc. Tomato products contain several natural antioxidants, including lycopene—which has displayed a preventive effect on the development of steatosis and CVD. Accordingly, the aim of the present work was to evaluate the effect of tomato juice consumption on the urinary peptide profile in rats with NAFLD induced by an atherogenic diet and to identify potential peptide biomarkers for diagnosis. Urine samples, collected weekly for four weeks, were analyzed by capillary electrophoresis (CE coupled to a mass spectrometer (MS. A partial least squares-discriminant analysis (PLS-DA was carried out to explore the association between differential peptides and treatments. Among the 888 peptides initially identified, a total of 55 were obtained as potential biomarkers. Rats with steatosis after tomato juice intake showed a profile intermediate between that of healthy rats and that of rats with induced hepatic steatosis. Accordingly, tomato products could be considered as a dietary strategy for the impairment of NAFLD, although further research should be carried out to develop a specific biomarkers panel for NAFLD.

Tomato Juice Consumption Modifies the Urinary Peptide Profile in Sprague-Dawley Rats with Induced Hepatic Steatosis.

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Martín-Pozuelo, Gala; González-Barrio, Rocío; Barberá, Gonzalo G; Albalat, Amaya; García-Alonso, Javier; Mullen, William; Mischak, Harald; Periago, María Jesús

2016-10-26

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disorder in Western countries, with a high prevalence, and has been shown to increase the risk of type 2 diabetes, cardiovascular disease (CVD), etc. Tomato products contain several natural antioxidants, including lycopene-which has displayed a preventive effect on the development of steatosis and CVD. Accordingly, the aim of the present work was to evaluate the effect of tomato juice consumption on the urinary peptide profile in rats with NAFLD induced by an atherogenic diet and to identify potential peptide biomarkers for diagnosis. Urine samples, collected weekly for four weeks, were analyzed by capillary electrophoresis (CE) coupled to a mass spectrometer (MS). A partial least squares-discriminant analysis (PLS-DA) was carried out to explore the association between differential peptides and treatments. Among the 888 peptides initially identified, a total of 55 were obtained as potential biomarkers. Rats with steatosis after tomato juice intake showed a profile intermediate between that of healthy rats and that of rats with induced hepatic steatosis. Accordingly, tomato products could be considered as a dietary strategy for the impairment of NAFLD, although further research should be carried out to develop a specific biomarkers panel for NAFLD.

Relative safety profiles of high dose statin regimens

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Carlos Escobar

2008-06-01

Full Text Available Carlos Escobar, Rocio Echarri, Vivencio BarriosDepartment of Cardiology, Hospital Ramón y Cajal, Madrid, SpainAbstract: Recent clinical trials recommend achieving a low-density lipoprotein cholesterol level of <100 mg/dl in high-risk and <70 mg/dl in very high risk patients. To attain these goals, however, many patients will need statins at high doses. The most frequent side effects related to the use of statins, myopathy, rhabdomyolysis, and increased levels of transaminases, are unusual. Although low and moderate doses show a favourable profile, there is concern about the tolerability of higher doses. During recent years, numerous trials to analyze the efficacy and tolerability of high doses of statins have been published. This paper updates the published data on the safety of statins at high doses.Keywords: statins, high doses, tolerability, liver, muscle

Distinct changing profiles of hepatitis A and E virus infection among patients with acute hepatitis in Mongolia: The first report of the full genome sequence of a novel genotype 1 hepatitis E virus strain.

Science.gov (United States)

Tsatsralt-Od, Bira; Primadharsini, Putu Prathiwi; Nishizawa, Tsutomu; Ohnishi, Hiroshi; Nagashima, Shigeo; Takahashi, Masaharu; Jirintai, Suljid; Nyamkhuu, Dulmaa; Okamoto, Hiroaki

2018-01-01

In January 2012, Mongolia started a hepatitis A vaccination program, which has not yet been evaluated. The first occurrence of autochthonous acute hepatitis E in 2013, caused by genotype 4 hepatitis E virus (HEV), suggests the need for a routine study to monitor its prevalence. One hundred fifty-four consecutive patients who were clinically diagnosed with acute hepatitis between 2014 and 2015 in Ulaanbaatar, Mongolia were studied. By serological and molecular testing followed by sequencing and phylogenetic analysis, only one patient (0.6%) was diagnosed with acute hepatitis A, caused by genotype IA hepatitis A virus (HAV), and 32 (20.8%) patients were diagnosed with acute hepatitis E, caused by genotype 1 HEV. The 32 HEV isolates obtained in this study shared 99.5-100% nucleotide identity and were grouped into a cluster separated from those of subtypes 1a to 1f. Upon comparison of p-distances over the entire genome, the distances between one representative HEV isolate (MNE15-072) and 1a-1f strains were 0.071-0.137, while those between 1b and 1c were 0.062-0.070. In conclusion, the prevalence of acute hepatitis A has decreased in Mongolia since the start of the vaccination program, while the monophyletic genotype 1 HEV strain of a probably novel subtype has been prevalent. © 2017 Wiley Periodicals, Inc.

Counter-attack on viral hepatitis. [Hepatitis A; Hepatitis B

Energy Technology Data Exchange (ETDEWEB)

Prozesky, O W [Pretoria Univ. (South Africa). Dept. of Medical Virology; Jupp, P G; Joubert, J J; Taylor, M B; Grabow, W O.K.

1985-07-01

The most highly developed radioimmunoassay test system in medical virology is proving of exceptional value in research aimed at controlling and eventually eradicating the scourge of human hepatitis. The use of radioimmunoassay in detecting hepatitis A (HAV) and hepatitis B (HBV) viruses is discussed. The hepatitis A virus is an enterovirus which infects the gastrointestinal tract and is usually transmitted by contaminated food, milk or water. Hepatitis B spreads mainly by the parenteral rate. Bedbugs and ticks are considered as possible transmitters of HBV. Another important contribution of radioimmunoassay is the ability to monitor the immune response of persons at risk who are vaccinated against hepatitis B.

Evaluation of immunogenicity and safety of Genevac B: A new recombinant hepatitis b vaccine in comparison with Engerix B and Shanvac B in healthy adults

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Vijayakumar V

2004-01-01

Full Text Available PURPOSE: Genevac B, a new indigenous recombinant hepatitis B vaccine was evaluated for its immunogenicity and safety in comparison with Engerix B (Smithkline Beecham Biologicals, Belgium and Shanvac B (Shantha Biotechnics, India in healthy adult volunteers. METHODS: While 240 study subjects were included in the Genevac B group, 80 each were the subjects for Engerix B and Shanvac B. A three dose regimen of 0,1,2 months was adopted with 20 gm dosage uniformly in all the three groups. Vaccinees were assessed during prevaccination, followup and post vaccination periods for clinical, haematological, biochemical and immunological parameters for safety and immunogenicity. RESULTS: Successful follow-up in all parameters for four months could be achieved in 92.5% (222/240 for Genevac B study subjects and the same was 85% (68/80 and 80% (64/80 for Engerix B and Shanvac B respectively. While 100% seroconversion was observed in all the three groups, the rate of seroprotectivity was 99.5% by Genevac B, 98.5% by Engerix B and 98.4% for Shanvac B. However the difference was not statistically significant (p>0.05. The GMT values of anti HBs after one month of completion of the vaccination were 735.50, 718.23 and 662.20 mIU/mL respectively. No systemic reaction was either seen or reported by the volunteers during the vaccination process of Genevac B and other two vaccines. Clinical, haematological and biochemical safety parameters remained within normal limits throughout the study period. CONCLUSION: The study confirms that Genevac B, the new recombinant Hepatitis B vaccine has the acceptable international standards of safety and immunogenicity.

New geometric design consistency model based on operating speed profiles for road safety evaluation.

Science.gov (United States)

Camacho-Torregrosa, Francisco J; Pérez-Zuriaga, Ana M; Campoy-Ungría, J Manuel; García-García, Alfredo

2013-12-01

To assist in the on-going effort to reduce road fatalities as much as possible, this paper presents a new methodology to evaluate road safety in both the design and redesign stages of two-lane rural highways. This methodology is based on the analysis of road geometric design consistency, a value which will be a surrogate measure of the safety level of the two-lane rural road segment. The consistency model presented in this paper is based on the consideration of continuous operating speed profiles. The models used for their construction were obtained by using an innovative GPS-data collection method that is based on continuous operating speed profiles recorded from individual drivers. This new methodology allowed the researchers to observe the actual behavior of drivers and to develop more accurate operating speed models than was previously possible with spot-speed data collection, thereby enabling a more accurate approximation to the real phenomenon and thus a better consistency measurement. Operating speed profiles were built for 33 Spanish two-lane rural road segments, and several consistency measurements based on the global and local operating speed were checked. The final consistency model takes into account not only the global dispersion of the operating speed, but also some indexes that consider both local speed decelerations and speeds over posted speeds as well. For the development of the consistency model, the crash frequency for each study site was considered, which allowed estimating the number of crashes on a road segment by means of the calculation of its geometric design consistency. Consequently, the presented consistency evaluation method is a promising innovative tool that can be used as a surrogate measure to estimate the safety of a road segment. Copyright © 2012 Elsevier Ltd. All rights reserved.

Right Hepatic Artery: A Cadaver Investigation and Its Clinical Significance

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Usha Dandekar

2015-01-01

Full Text Available The right hepatic artery is an end artery and contributes sole arterial supply to right lobe of the liver. Misinterpretation of normal anatomy and anatomical variations of the right hepatic artery contribute to the major intraoperative mishaps and complications in hepatobiliary surgery. The frequency of inadvertent or iatrogenic hepatobiliary vascular injury rises with the event of an aberrant anatomy. This descriptive study was carried out to document the normal anatomy and different variations of right hepatic artery to contribute to existing knowledge of right hepatic artery to improve surgical safety. This study conducted on 60 cadavers revealed aberrant replaced right hepatic artery in 18.3% and aberrant accessory right hepatic artery in 3.4%. Considering the course, the right hepatic artery ran outside Calot’s triangle in 5% of cases and caterpillar hump right hepatic artery was seen in 13.3% of cases. The right hepatic artery (normal and aberrant crossed anteriorly to the common hepatic duct in 8.3% and posteriorly to it in 71.6%. It has posterior relations with the common bile duct in 16.7% while in 3.4% it did not cross the common hepatic duct or common bile duct. The knowledge of such anomalies is important since their awareness will decrease morbidity and help to keep away from a number of surgical complications.

A Randomized Controlled Trial to Evaluate a Potential Hepatitis B Booster Vaccination Strategy Using Combined Hepatitis A and B Vaccine.

Science.gov (United States)

Li, Fangjun; Hu, Yuansheng; Zhou, Youming; Chen, Lixin; Xia, Wei; Song, Yufei; Tan, Zhengliang; Gao, Lidong; Yang, Zhong; Zeng, Gang; Han, Xing; Li, Junhua; Li, Jing

2017-05-01

Booster doses could play a major role in no responders or low responders to primary hepatitis B (HB) vaccine. Planed time point for hepatitis A vaccination in China provides a good opportunity to carry out HB booster dose by using combined hepatitis A and B vaccine. A randomized, double-blinded clinical trial was conducted to compare the immunogenicity and safety of toddlers 18-24 months of age receiving 3 different vaccination regimens: 2 doses of inactivated hepatitis A vaccine (group 1), 1 dose of inactivated hepatitis A vaccine plus 1 dose of combined hepatitis A and B vaccine (group 2) or 2 doses of combined hepatitis A and B vaccine (group 3). All 3 groups showed 100% seroprotection for antihepatitis A virus antibody after vaccination. Seroprotection rate for anti-HB antibody before vaccination ranged from 79.5% to 92.9% in the 3 groups. After second inoculation, anti-HBs seroprotection increased from 92.9% to 100% in group 2 with postvaccination geometric mean concentration (GMC) of 2258.3 mIU/mL and from 79.5% to 98.9% in group 3 with postvaccination GMC of 2055.3 mIU/mL. The adverse events were not statistically different among groups (P = 0.345). Combined hepatitis A and B vaccine could stimulate high level of both antihepatitis A virus and anti-HBs antibodies and not increase adverse events, providing a new choice for HB booster.

Safety and Efficacy Profile of Commercial Veterinary Vaccines against Rift Valley Fever: A Review Study

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Moataz Alhaj

2016-01-01

Full Text Available Rift Valley Fever (RVF is an infectious illness with serious clinical manifestations and health consequences in humans as well as a wide range of domestic ruminants. This review provides significant information about the prevention options of RVF along with the safety-efficacy profile of commercial vaccines and some of RVF vaccination strategies. Information presented in this paper was obtained through a systematic investigation of published data about RVF vaccines. Like other viral diseases, the prevention of RVF relies heavily on immunization of susceptible herds with safe and cost-effective vaccine that is able to confer long-term protective immunity. Several strains of RVF vaccines have been developed and are available in commercial production including Formalin-Inactivated vaccine, live attenuated Smithburn vaccine, and the most recent Clone13. Although Formalin-Inactivated vaccine and live attenuated Smithburn vaccine are immunogenic and widely used in prevention programs, they proved to be accompanied by significant concerns. Despite Clone13 vaccine being suggested as safe in pregnant ewes and as highly immunogenic along with its potential for differentiating infected from vaccinated animals (DIVA, a recent study raised concerns about the safety of the vaccine during the first trimester of gestation. Accordingly, RVF vaccines that are currently available in the market to a significant extent do not fulfill the requirements of safety, potency, and DIVA. These adverse effects stressed the need for developing new vaccines with an excellent safety profile to bridge the gap in safety and immunity. Bringing RVF vaccine candidates to local markets besides the absence of validated serological test for DIVA remain the major challenges of RVF control.

Hepatitis E virus coinfection with hepatotropic viruses in Egyptian children.

Science.gov (United States)

Zaki, Maysaa El Sayed; Salama, Osama Saad; Mansour, Fathy Awaad; Hossein, Shaimaa

2008-06-01

Major hepatotropic viruses continue to be important causes of acute viral hepatitis in developing countries. This work was carried out to detect the seroprevalence of hepatitis E virus (HEV) markers in children with acute viral hepatitis due to hepatotropic viruses (A, B and C) and non-A, non-B, non-C acute hepatitis, and to ascertain the influence of HEV superinfection in individuals infected with hepatitis viruses (A, B and C). We studied prospectively 162 children with sporadic acute hepatitis who reported to our hospital. Thirteen healthy controls were also included in the study. Laboratory investigations were performed, including complete liver function tests. Complete serological profiles for hepatitis viruses A, B, C and E were evaluated. HEV immunoglobulin G was detected with highest percentage among patients with hepatitis B (56.7%), followed by patients with hepatitis C virus (52.0%), hepatitis A virus (34.1%) and combined hepatitis B and C viruses (30.0%). The detection rate among patients with non-A, non-B, non-C hepatitis was 7.1%. HEV immunoglobulin M was found in 4.5% of hepatitis A virus patients and in 3.3% of hepatitis B patients. The prevalence of HEV immunoglobulin G and immunoglobulin M correlated with the levels of hepatic aspartate aminotransferase and alanine aminotransferase in patients with dual markers of infection with hepatitis E and other viruses compared to patients with acute hepatitis due to A and C viruses. HEV serological markers are common among children with acute viral hepatitis, especially from hepatitis C and B viruses. There may be increased sensitivity to HEV coinfection in association with hepatitis B and C infections. Dual infection with HEV and other hepatotropic viruses was associated with greater elevation of aspartate and alanine aminotransferases.

Chemosaturation with Percutaneous Hepatic Perfusion for Unresectable Isolated Hepatic Metastases from Sarcoma

Energy Technology Data Exchange (ETDEWEB)

Deneve, Jeremiah L., E-mail: Jeremiah.Deneve@Moffitt.org [Moffitt Cancer Center, Department of Cutaneous and Sarcoma Oncology (United States); Choi, Junsung [Moffitt Cancer Center, Department of Interventional Radiology (United States); Gonzalez, Ricardo J.; Conley, Anthony P.; Stewart, Steven; Han, Dale [Moffitt Cancer Center, Department of Cutaneous and Sarcoma Oncology (United States); Werner, Philip; Chaudhry, Tariq A. [Moffitt Cancer Center, Department of Anesthesia (United States); Zager, Jonathan S., E-mail: Jonathan.Zager@Moffitt.org [Moffitt Cancer Center, Department of Cutaneous and Sarcoma Oncology (United States)

2012-12-15

Purpose: Treatment of patients with unresectable liver metastases is challenging. Regional therapies to the liver have been developed that maximize treatment of the localized disease process without systemic toxic adverse effects. We discuss the procedural aspects of liver chemosaturation with percutaneous hepatic perfusion (CS-PHP). Methods: We present as an illustration of this technique a case report of the treatment of unresectable metastatic leiomyosarcoma of the liver. Results: A randomized phase III trial for unresectable liver metastases from melanoma was recently completed comparing CS-PHP with melphalan vs. best alternative care (BAC). When compared with BAC, CS-PHP was associated with a significant improvement in hepatic progression-free survival (8.0 months CS-PHP vs. 1.6 months BAC, p < 0.0001) and overall progression-free survival (6.7 months CS-PHP vs. 1.6 months BAC, p < 0.0001), respectively. On the basis of these results, and given our experience as one of the treating institutions for this phase III trial, we appealed for compassionate use of CS-PHP in a patient with isolated bilobar unresectable hepatic metastases from leiomyosarcoma. Four target lesions were identified and monitored to assess treatment response. A total of 4 CS-PHP procedures were performed, with a 25 % reduction in size of the largest lesion observed and 16 month hepatic progression-free survival. Toxicity was mild (neutropenia) and manageable on an outpatient basis. Conclusion: CS-PHP offers several advantages for unresectable hepatic sarcoma metastases. CS-PHP is minimally invasive and repeatable, and it has a predictable and manageable systemic toxicity profile. For appropriately selected patients, CS-PHP can delay tumor progression and could potentially improve survival.

Chemosaturation with Percutaneous Hepatic Perfusion for Unresectable Isolated Hepatic Metastases from Sarcoma

International Nuclear Information System (INIS)

Deneve, Jeremiah L.; Choi, Junsung; Gonzalez, Ricardo J.; Conley, Anthony P.; Stewart, Steven; Han, Dale; Werner, Philip; Chaudhry, Tariq A.; Zager, Jonathan S.

2012-01-01

Purpose: Treatment of patients with unresectable liver metastases is challenging. Regional therapies to the liver have been developed that maximize treatment of the localized disease process without systemic toxic adverse effects. We discuss the procedural aspects of liver chemosaturation with percutaneous hepatic perfusion (CS-PHP). Methods: We present as an illustration of this technique a case report of the treatment of unresectable metastatic leiomyosarcoma of the liver. Results: A randomized phase III trial for unresectable liver metastases from melanoma was recently completed comparing CS-PHP with melphalan vs. best alternative care (BAC). When compared with BAC, CS-PHP was associated with a significant improvement in hepatic progression-free survival (8.0 months CS-PHP vs. 1.6 months BAC, p < 0.0001) and overall progression-free survival (6.7 months CS-PHP vs. 1.6 months BAC, p < 0.0001), respectively. On the basis of these results, and given our experience as one of the treating institutions for this phase III trial, we appealed for compassionate use of CS-PHP in a patient with isolated bilobar unresectable hepatic metastases from leiomyosarcoma. Four target lesions were identified and monitored to assess treatment response. A total of 4 CS-PHP procedures were performed, with a 25 % reduction in size of the largest lesion observed and 16 month hepatic progression-free survival. Toxicity was mild (neutropenia) and manageable on an outpatient basis. Conclusion: CS-PHP offers several advantages for unresectable hepatic sarcoma metastases. CS-PHP is minimally invasive and repeatable, and it has a predictable and manageable systemic toxicity profile. For appropriately selected patients, CS-PHP can delay tumor progression and could potentially improve survival.

Efficacy and safety of daclatasvir and asunaprevir for hepatitis C virus genotype 1b infection

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Hee Chul Nam

2016-06-01

Full Text Available Background/Aims: The treatment strategy for hepatitis C virus (HCV has been changing rapidly since the introduction of direct-acting antivirals such as daclatasvir (DCV and asunaprevir (ASV. We evaluated the efficacy and safety of DCV and ASV for HCV in real-life practice. Methods: Patients were treated with 60 mg of DCV once daily plus 200 mg of ASV twice daily for 24 weeks, and followed for 12 weeks. The primary endpoint was a sustained virological response at 12 weeks after treatment (SVR12 and safety. Results: This retrospective study included eight patients with chronic HCV genotype 1b infection. All of the enrolled patients were diagnosed with liver cirrhosis, and their mean age was 65.75 years. One patient was a nonresponder and two patients relapsed with previous pegylated interferon (PegIFN and ribavirin (RBV treatment. None of the patient showed NS5A mutation. An SVR12 was achieved in 88% of cases by the DCV and ASV combination therapy. The serum transaminase level and the aspartate-aminotransferase-to-platelet ratio were improved after the treatment. DCV and ASV were well tolerated in most of the patients, with treatment discontinuation due to adverse events (elevated liver enzyme and decompensation occurring in two patients. Conclusion: In this study, combination of DCV and ASV treatment achieved a high sustained virological response with few adverse events even in those with cirrhosis, advanced age, and nonresponse/relapse to previous interferon-based therapy. Close monitoring of safety issues may be necessary when treating chronic HCV patients receiving DCV and ASV, especially in older patient and those with cirrhosis.

Safety profile and long-term engraftment of human CD31+ blood progenitors in bone tissue engineering.

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Zigdon-Giladi, Hadar; Elimelech, Rina; Michaeli-Geller, Gal; Rudich, Utai; Machtei, Eli E

2017-07-01

Endothelial progenitor cells (EPCs) participate in angiogenesis and induce favorable micro-environments for tissue regeneration. The efficacy of EPCs in regenerative medicine is extensively studied; however, their safety profile remains unknown. Therefore, our aims were to evaluate the safety profile of human peripheral blood-derived EPCs (hEPCs) and to assess the long-term efficacy of hEPCs in bone tissue engineering. hEPCs were isolated from peripheral blood, cultured and characterized. β tricalcium phosphate scaffold (βTCP, control) or 10 6 hEPCs loaded onto βTCP were transplanted in a nude rat calvaria model. New bone formation and blood vessel density were analyzed using histomorphometry and micro-computed tomography (CT). Safety of hEPCs using karyotype analysis, tumorigenecity and biodistribution to target organs was evaluated. On the cellular level, hEPCs retained their karyotype during cell expansion (seven passages). Five months following local hEPC transplantation, on the tissue and organ level, no inflammatory reaction or dysplastic change was evident at the transplanted site or in distant organs. Direct engraftment was evident as CD31 human antigens were detected lining vessel walls in the transplanted site. In distant organs human antigens were absent, negating biodistribution. Bone area fraction and bone height were doubled by hEPC transplantation without affecting mineral density and bone architecture. Additionally, local transplantation of hEPCs increased blood vessel density by nine-fold. Local transplantation of hEPCs showed a positive safety profile. Furthermore, enhanced angiogenesis and osteogenesis without mineral density change was found. These results bring us one step closer to first-in-human trials using hEPCs for bone regeneration. Copyright © 2017 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Effects of hydroalcoholic extract of Rhus coriaria seed on glucose and insulin related biomarkers, lipid profile, and hepatic enzymes in nicotinamide-streptozotocin-induced type II diabetic male mice.

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Ahangarpour, Akram; Heidari, Hamid; Junghani, Majid Salehizade; Absari, Reza; Khoogar, Mehdi; Ghaedi, Ehsan

2017-10-01

Type 2 diabetes often leads to dislipidemia and abnormal activity of hepatic enzymes. The purpose of this study was to evaluate the antidiabetic and hypolipidemic properties of Rhus coriaria ( R. coriaria ) seed extrac on nicotinamide-streptozotocin induced type 2 diabetic mice. In this experimental study, 56 male Naval Medical Research Institute mice (30-35 g) were randomly separated into seven groups: control, diabetic group, diabetic mice treated with glibenclamide (0.25 mg/kg, as standard antidiabetic drug) or R. coriaria seed extract in doses of 200 and 300 mg/kg, and control groups received these two doses of extract orally for 28 days. Induction of diabetes was done by intraperitoneal injection of nicotinamide and streptozotocin. Ultimately, body weight of mice, blood levels of glucose, insulin, hepatic enzymes, leptin, and lipid profile were assayed. After induction of type 2 diabetes, level of glucose, cholesterol, low density lipoprotein, serum glutamic oxaloacetic transaminase, and serum glutamic pyruvic transaminase increased and level of insulin and high density lipoprotein decreased remarkably. Administration of both doses of extract decreased level of glucose and cholesterol significantly in diabetic mice. LDL level decreased in treated group with dose of 300 mg/kg of the extract. Although usage of the extract improved level of other lipid profiles, insulin and hepatic enzymes, changes weren't significant. This study showed R. coriaria seeds administration has a favorable effect in controlling some blood parameters in type 2 diabetes. Therefore it may be beneficial in the treatment of diabetes.

Urgency to treat patients with chronic hepatitis C in Asia.

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Kao, Jia-Horng; Ahn, Sang Hoon; Chien, Rong-Nan; Cho, Mong; Chuang, Wan-Long; Jeong, Sook-Hyang; Liu, Chen-Hua; Paik, Seung-Woon

2017-05-01

Chronic hepatitis C (CHC) infection poses a global healthcare burden, being associated with serious complications if untreated. The prevalence of hepatitis C virus (HCV) infection is highest in areas of Central, South, and East Asia; over 50% of HCV patients worldwide live in the region, where HCV genotypes 1b, 2, 3, and 6 are the most prevalent. Treatment outcomes for chronic hepatitis C vary by ethnicity, and Asian patients achieve higher sustained virologic response rates following interferon (IFN)-based therapy than non-Asians. However, low efficacy, poor safety profile, and subcutaneous administration limit the use of IFN-based therapies. Superior virologic outcomes have been observed with different classes of direct-acting antivirals (DAAs) alone or in combination, and several all-oral DAA regimens are available in Asia. These regimens have shown excellent efficacy and favorable tolerability in clinical trials, yet there is a need for further studies of DAAs in a real world context, particularly in Asia. Furthermore, IFN-free treatment may not be accessible for many patients in the region, and IFN-based regimens remain an option in some countries. There is a need to improve current clinical practices for HCV management in Asia, including effective screening, disease awareness, and prevention programs, and to further understand the cost-effectiveness of IFN-free regimens. The evolution of potent treatments makes HCV eradication a possibility that should be available to all patients. However, access to these therapies in Asian countries has been slow, primarily because of economic barriers that continue to present a hurdle to optimal treatment. © 2016 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

Multicenter study on the immunogenicity and safety of two recombinant vaccines against hepatitis B

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Reinaldo Menezes Martins

2004-12-01

Full Text Available The immunogenicity and safety of a new recombinant hepatitis B vaccine from the Instituto Butantan (Butang® were evaluated in a multicenter, double-blind, prospective equivalence study in three centers in Brazil. Engerix B® was the standard vaccine. A total of 3937 subjects were recruited and 2754 (70% met all protocol criteria at the end of the study. All the subjects were considered healthy and denied having received hepatitis B vaccine before the study. Study subjects who adhered to the protocol were newborn infants (566, children 1 to 10 years old (484, adolescents from 11 to 19 years (740, adults from 20 to 30 years (568, and adults from 31 to 40 years (396. Vaccine was administered in three doses on the schedule 0, 1, and 6 months (newborn infants, adolescents, and adults or 0, 1, and 7 months (children. Vaccine dose was intramuscular 10 µg (infants, children, and adolescents or 20 µg (adults. Percent seroprotection (assumed when anti-HBs titers were > 10mIU/ml and geometric mean titer (mIU/ml were: newborn infants, 93.7% and 351.1 (Butang® and 97.5% and 1530.6 (Engerix B®; children, 100% and 3600.0 (Butang® and 97.7% and 2753.1 (Engerix B®; adolescents, 95.1% and 746.3 (Butang® and 96% and 1284.3 (Engerix B®; adults 20-30 years old, 91.8% and 453.5 (Butang® and 95.5% and 1369.0 (Engerix B®; and adults 31-40 years old, 79.8% and 122.7 (Butang® and 92.4% and 686.2 (Engerix B®. There were no severe adverse events following either vaccine. The study concluded that Butang® was equivalent to Engerix B® in children, and less immunogenic but acceptable for use in newborn infants, adolescents, and young adults.

Peginterferon Treatment In Children: A Review Of Chronic Hepatitis B And Chronic Hepatitis C Treatment

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Makbule EREN

2009-11-01

Full Text Available Despite of extensive blood product screening and national immunization programs, chronic hepatitis B and C infections continues to be a global problem with high mortality, morbidity and economic impact. Even though acquisition of these infections mostly occurs in childhood, major problems appear in adulthood. Cirrhosis and HCC are two major expected late events related to chronic hepatitis B and C infections. Rarely, children may also face these complications. To avoid these complications and increase the life expectancy in adults treatment of these two type infections should be started in childhood with appropriate patient selection. In contrast to children, adults are luckier in terms of treatment alternatives. They have the chance to use more potent antivirals with higher genetic barrier and pegylated form of interferons. Recently, the use of pegylated interferon and ribavirin combinations has been approved in children in Chronic HCV infection. However, chronic hepatitis B treatment in children is still dependent on the use of one type antiviral drug and conventional interferon. Treatment in early ages with an antiviral agent that has limited genetic barrier may block the chance of treatment or reduce the response rate in adulthood in chronic hepatitis B infection. This burden indicates the necessity of new therapeutic modalities in children. In this term pegylated interferons may be one of the optiones. In this article we aimed to reviewe the efficacy and safety of conventional and pegylated interferons, for the treatment of Hepatitis C and B infections in children.

Recent RF Experiments and Application of RF Waves to Real-Time Control of Safety Factor Profile in JT-60U

International Nuclear Information System (INIS)

Suzuki, T.; Isayama, A.; Ide, S.; Fujita, T.; Oikawa, T.; Sakata, S.; Sueoka, M.; Hosoyama, H.; Seki, M.

2005-01-01

Two topics of applications of RF waves to current profile control in JT-60U are presented; application of lower-hybrid (LH) waves to safety factor profile control and electron cyclotron (EC) waves to neo-classical tearing mode (NTM) control. A real-time control system of safety factor (q) profile was developed. This system, for the first time, enables 1) real time evaluation of q profile using local magnetic pitch angle measurement by motional Stark effect (MSE) diagnostic and 2) control of current drive (CD) location (ρCD) by controlling the parallel refractive index N parallel of LH waves through control of phase difference (Δφ) of LH waves between multi-junction launcher modules. The method for real-time q profile evaluation was newly developed, without time-consuming reconstruction of equilibrium, so that the method requires less computational time. Safety factor profile by the real-time calculation agrees well with that by equilibrium reconstruction with MSE. The control system controls ρCD through Δφ in such a way to decrease the largest residual between the real-time evaluated q profile q(r) and its reference profile qref(r). The real-time control system was applied to a positive shear plasma (q(0)∼1). The reference q profile was set to monotonic positive shear profile having qref(0)=1.3. The real-time q profile approached to the qref(r) during application of real-time control, and was sustained for 3s, which was limited by the duration of the injected LH power. Temporal evolution of current profile was consistent with relaxation of inductive electric field induced by theoretical LH driven current. An m/n=3/2 NTM that appeared at βN∼3 was completely stabilized by ECCD applied to a fully-developed NTM. Precise ECCD at NTM island was essential for the stabilization. ECCD that was applied to resonant rational surface (q=3/2) before an NTM onset suppressed appearance of NTM. In order to keep NTM intensity below a level, ECCD before the mode onset was

Gene expression profiles associated with anaemia and ITPA genotypes in patients with chronic hepatitis C (CH-C).

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Birerdinc, A; Estep, M; Afendy, A; Stepanova, M; Younossi, I; Baranova, A; Younossi, Z M

2012-06-01

Anaemia is a common side effect of ribavirin (RBV) which is used for the treatment of hepatitis C. Inosine triphosphatase gene polymorphism (C to A) protects against RBV-induced anaemia. The aim of our study was to genotype patients for inosine triphosphatase gene polymorphism rs1127354 SNP (CC or CA) and associate treatment-induced anaemia with gene expression profile and genotypes. We used 67 hepatitis C patients with available gene expression, clinical, laboratory data and whole-blood samples. Whole blood was used to determine inosine triphosphatase gene polymorphism rs1127354 genotypes (CC or CA). The cohort with inosine triphosphatase gene polymorphism CA genotype revealed a distinct pattern of protection against anaemia and a lower drop in haemoglobin. A variation in the propensity of CC carriers to develop anaemia prompted us to look for additional predictors of anaemia during pegylated interferon (PEG-IFN) and RBV. Pretreatment blood samples of patients receiving a full course of PEG-IFN and RBV were used to assess expression of 153 genes previously implicated in host response to viral infections. The gene expression data were analysed according to presence of anaemia and inosine triphosphatase gene polymorphism genotypes. Thirty-six genes were associated with treatment-related anaemia, six of which are involved in the response to hypoxia pathway (HIF1A, AIF1, RHOC, PTEN, LCK and PDGFB). There was a substantial overlap between sustained virological response (SVR)-predicting and anaemia-related genes; however, of the nine JAK-STAT pathway-related genes associated with SVR, none were implicated in anaemia. These observations exclude the direct involvement of antiviral response in the development of anaemia associated with PEG-IFN and RBV treatment, whereas another, distinct component within the SVR-associated gene expression response may predict anaemia. We have identified baseline gene expression signatures associated with RBV-induced anaemia and identified

Comparison of test performance profile for blood tests of liver fibrosis in chronic hepatitis C.

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Halfon, Philippe; Bacq, Yannick; De Muret, Anne; Penaranda, Guillaume; Bourliere, Marc; Ouzan, Denis; Tran, Albert; Botta, Danielle; Renou, Christophe; Bréchot, Marie-Claude; Degott, Claude; Paradis, Valérie

2007-03-01

We evaluated the test performance profile (TPP) of blood tests of liver fibrosis. Three hundred and fifty-six patients with C chronic hepatitis were included in two centers. Metavir staging of liver specimens by two independent pathologists and the following tests were evaluated: Fibrotest (FT), APRI, FibroMeter (FM), and Hepascore (HS). Metavir stages were: F0: 4%, F1: 55%, F2: 26%, F3: 11%, and F4: 4%. The AUROCs were not significantly different, respectively, FT, FM, APRI, HS: >or=F2: 0.79, 0.78, 0.76, >or=0.76; F3: 0.81, 0.85, 0.81, 0.81; and F4: 0.86, 0.94, 0.92, 0.89. The TPP relies on the paired comparison of blood-test misclassification based on liver specimen, e.g. FT vs FM, respectively: F0+1: 18 vs 28% (p=0.0003), >or=F2: 43 vs 31% (p=0.004). There was no center effect. In those populations, the four blood tests had a similar performance for significant fibrosis (F>or=2), lying in the lower range of published results which is attributable to a low >or=F2 prevalence, and for >or=F3 and F4. However, FM and FT had performance profiles significantly different as a function of fibrosis stages or diagnostic target (fibrosis cut-off). This has to be considered during the interpretation process. Moreover, the performance should be reported with different diagnostic targets.

The Safety of Tenofovir-Emtricitabine for HIV Pre-Exposure Prophylaxis (PrEP) in Individuals With Active Hepatitis B.

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Solomon, Marc M; Schechter, Mauro; Liu, Albert Y; McMahan, Vanessa M; Guanira, Juan V; Hance, Robert J; Chariyalertsak, Suwat; Mayer, Kenneth H; Grant, Robert M

2016-03-01

Pre-exposure prophylaxis (PrEP) with daily oral emtricitabine and tenofovir disoproxil fumarate (FTC/TDF) prevents HIV infection. The safety and feasibility of HIV PrEP in the setting of hepatitis B virus (HBV) infection were evaluated. The Iniciativa Profilaxis Pre-Exposición study randomized 2499 HIV-negative men and transgender women who have sex with men to once-daily oral FTC/TDF versus placebo. Hepatitis serologies and transaminases were obtained at screening and at the time PrEP was discontinued. HBV DNA was assessed by polymerase chain reaction, and drug resistance was assessed by population sequencing. Vaccination was offered to individuals susceptible to HBV infection. Of the 2499 participants, 12 (0.5%; including 6 randomized to FTC/TDF) had chronic HBV infection. After stopping FTC/TDF, 5 of the 6 participants in the active arm had liver function tests performed at follow-up. Liver function tests remained within normal limits at post-stop visits except for a grade 1 elevation in 1 participant at post-stop week 12 (alanine aminotransferase = 90, aspartate aminotransferase = 61). There was no evidence of hepatic flares. Polymerase chain reaction of stored samples showed that 2 participants in the active arm had evidence of acute HBV infection at enrollment. Both had evidence of grade 4 transaminase elevations with subsequent resolution. Overall, there was no evidence of TDF or FTC resistance among tested genotypes. Of 1633 eligible for vaccination, 1587 (97.2%) received at least 1 vaccine; 1383 (84.7%) completed the series. PrEP can be safely provided to individuals with HBV infection if there is no evidence of cirrhosis or substantial transaminase elevation. HBV vaccination rates at screening were low globally, despite recommendations for its use, yet uptake and efficacy were high when offered.

The Safety of Tenofovir–Emtricitabine for HIV Pre-Exposure Prophylaxis (PrEP) in Individuals With Active Hepatitis B

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Schechter, Mauro; Liu, Albert Y.; McManhan, Vanessa M.; Guanira, Juan V.; Hance, Robert J.; Chariyalertsak, Suwat; Mayer, Kenneth H.; Grant, Robert M.

2016-01-01

Background: Pre-exposure prophylaxis (PrEP) with daily oral emtricitabine and tenofovir disoproxil fumarate (FTC/TDF) prevents HIV infection. The safety and feasibility of HIV PrEP in the setting of hepatitis B virus (HBV) infection were evaluated. Methods: The Iniciativa Profilaxis Pre-Exposición study randomized 2499 HIV-negative men and transgender women who have sex with men to once-daily oral FTC/TDF versus placebo. Hepatitis serologies and transaminases were obtained at screening and at the time PrEP was discontinued. HBV DNA was assessed by polymerase chain reaction, and drug resistance was assessed by population sequencing. Vaccination was offered to individuals susceptible to HBV infection. Results: Of the 2499 participants, 12 (0.5%; including 6 randomized to FTC/TDF) had chronic HBV infection. After stopping FTC/TDF, 5 of the 6 participants in the active arm had liver function tests performed at follow-up. Liver function tests remained within normal limits at post-stop visits except for a grade 1 elevation in 1 participant at post-stop week 12 (alanine aminotransferase = 90, aspartate aminotransferase = 61). There was no evidence of hepatic flares. Polymerase chain reaction of stored samples showed that 2 participants in the active arm had evidence of acute HBV infection at enrollment. Both had evidence of grade 4 transaminase elevations with subsequent resolution. Overall, there was no evidence of TDF or FTC resistance among tested genotypes. Of 1633 eligible for vaccination, 1587 (97.2%) received at least 1 vaccine; 1383 (84.7%) completed the series. Conclusions: PrEP can be safely provided to individuals with HBV infection if there is no evidence of cirrhosis or substantial transaminase elevation. HBV vaccination rates at screening were low globally, despite recommendations for its use, yet uptake and efficacy were high when offered. PMID:26413853

Triple therapy in chronic hepatitis C: initial series in a public health program in the South of Brazil.

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Almeida, Paulo R L; Fonseca, Carla Bortolin; Koch, Vivian W; Souza, Amanda M; Feltrin, Alberi A; Tovo, Cristiane Valle

2015-01-01

Chronic hepatitis C has great impact on world's health. Current therapy for genotype 1 hepatitis C virus includes protease inhibitors boceprevir and telaprevir, associated to standard therapy - peginterferon alfa + ribavirin. There are no published data in Brazil on the results of this new therapy, and it is interesting an evaluation of what was accomplished up to this moment. Objectives To evaluate virologic response to triple therapy, as well as the safety profile and tolerability. This study is a clinical series of patients receiving triple therapy for C hepatitis in a single center of a Public Health System of South Brasil. Out of the 121 patients that initiated the triple therapy, the first patients that finished the treatment and evaluated the sustained virological response (24 weeks after the end of treatment) were included. Twenty four genotype 1 chronic hepatitis C monoinfected patients were included. Nineteen (79.2%) patients had been previously treated. Thirteen (54.2%) patients were cirrhotic. Nineteen (79.2%) patients completed the planned therapy. By the end of the treatment, 14 (58.3%) out of 24 patients had undetectable viral load. Sustained virologic response occurred in 12 (50.0%) out of 24 patients, 07 (58.3%) in telaprevir group and 05 (41.7%) in boceprevir group. Out of 24 patients under triple therapy, 58% (n=14) presented anemia. In conclusion, despite the small number of patients treated with triple therapy evaluated in the current study, it possibly reflects the population under this therapy in real-life.

Feature Hepatitis: Hepatitis Can Strike Anyone

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... Navigation Bar Home Current Issue Past Issues Feature Hepatitis Hepatitis Can Strike Anyone Past Issues / Spring 2009 Table ... from all walks of life are affected by hepatitis, especially hepatitis C, the most common form of ...

Toxicity and Safety Profiles of Methanolic Extract of Pistacia integerrima J. L. Stewart ex Brandis (PI for Wistar Rats

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Gotmi Sharwan

2016-09-01

Full Text Available Objectives: The goals of this research were to evaluate acute (single-dose and sub-acute (repeated-dose toxicity profiles of methanolic extract of Pistacia integerrima J. L. Stewart ex Brandis (PI for Wistar rats and to assess the safety profile of PI by observing physiological changes, mortality, changes in body weight

Activated rat hepatic stellate cells influence Th1/Th2 profile in vitro.

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Xing, Zhi-Zhi; Huang, Liu-Ye; Wu, Cheng-Rong; You, Hong; Ma, Hong; Jia, Ji-Dong

2015-06-21

To investigate the effects of activated rat hepatic stellate cells (HSCs) on rat Th1/Th2 profile in vitro. Growth and survival of activated HSCs and CD4(+) T lymphocytes cultured alone or together was assessed after 24 or 48 h. CD4(+) T lymphocytes were then cultured with or without activated HSCs for 24 or 48 h and the proportion of Th1 [interferon (IFN)-γ(+)] and Th2 [interleukin (IL)-4(+)] cells was assessed by flow cytometry. Th1 and Th2 cell apoptosis was assessed after 24 h of co-culture using a caspase-3 staining procedure. Differentiation rates of Th1 and Th2 cells from CD4(+) T lymphocytes that were positive for CD25 but did not express IFN-γ or IL-4 were also assessed after 48 h of co-culture with activated HSCs. Galectin-9 expression in HSCs was determined by immunofluorescence and Western blotting. ELISA was performed to assess galectin-9 secretion from activated HSCs. Co-culture of CD4(+) T lymphocytes with activated rat HSCs for 48 h significantly reduced the proportion of Th1 cells compared to culture-alone conditions (-1.73% ± 0.71%; P Th1/Th2 ratio was significantly decreased (-0.44 ± 0.13; P Th1 cells was decreased (-65.71 ± 9.67; P Th1 (12.27% ± 0.99%; P Th1 cell apoptosis rate was significantly higher than in Th2 cells (P Th1 and Th2 cells; however, the increase in the proportion of Th2 cells was significantly higher than that of Th1 cells (1.85% ± 0.48%; P Th1/Th2 profile, inhibiting the Th1 response and enhancing the Th2 response, and this may be a novel pathway for liver fibrogenesis.

Bioenergetic Changes during Differentiation of Human Embryonic Stem Cells along the Hepatic Lineage

DEFF Research Database (Denmark)

Hopkinson, Branden M; Madsen, Claus Desler; Kalisz, Mark

2017-01-01

Mitochondrial dysfunction has been demonstrated to result in premature aging due to its effects on stem cells. Nevertheless, a full understanding of the role of mitochondrial bioenergetics through differentiation is still lacking. Here we show the bioenergetics profile of human stem cells...... of embryonic origin differentiating along the hepatic lineage. Our study reveals especially the transition between hepatic specification and hepatic maturation as dependent on mitochondrial respiration and demonstrates that even though differentiating cells are primarily dependent on glycolysis until induction...

Safety profile of the 9-valent HPV vaccine

DEFF Research Database (Denmark)

Moreira, Edson D; Block, Stan L; Ferris, Daron G

2016-01-01

OBJECTIVES: The overall safety profile of the 9-valent human papillomavirus (9vHPV) vaccine was evaluated across 7 Phase III studies, conducted in males and females (nonpregnant at entry), 9 to 26 years of age. METHODS: Vaccination was administered as a 3-dose regimen at day 1, and months 2 and 6....... More than 15 000 subjects received ≥1 dose of 9vHPV vaccine. In 2 of the studies, >7000 control subjects received ≥1 dose of quadrivalent HPV (qHPV) vaccine. Serious and nonserious adverse events (AEs) and new medical conditions were recorded throughout the study. Subjects testing positive...... for pregnancy at day 1 were not vaccinated; those who became pregnant after day 1 were discontinued from further vaccination until resolution of the pregnancy. Pregnancies detected after study start (n = 2950) were followed to outcome. RESULTS: The most common AEs (≥5%) experienced by 9vHPV vaccine recipients...

Hepatic Encephalopathy

Medline Plus

Full Text Available ... Disease Type 1 (von Gierke) Hemochromatosis Hepatic Encephalopathy Hepatitis A Hepatitis B Hepatitis C Intrahepatic Cholestasis of Pregnancy ( ... Disease Type 1 (von Gierke) Hemochromatosis Hepatic Encephalopathy Hepatitis A Hepatitis B Hepatitis C Intrahepatic Cholestasis of Pregnancy ( ...

Autoimmune hepatitis in Italy: the Bologna experience.

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Muratori, Paolo; Granito, Alessandro; Quarneti, Chiara; Ferri, Silvia; Menichella, Rita; Cassani, Fabio; Pappas, Georgios; Bianchi, Francesco B; Lenzi, Marco; Muratori, Luigi

2009-06-01

Autoimmune hepatitis affects mainly women. It is subdivided into type 1 and type 2 according to the autoantibody profile and without immunosuppression usually evolves to cirrhosis and end-stage liver failure. We evaluated clinical, biochemical, immunological and genetic features and treatment response of 163 consecutive Italian patients with autoimmune hepatitis. At diagnosis, type 1 autoimmune hepatitis showed more inflamed liver histology and more pronounced cholestasis, whereas type 2 was more common in children. Male and female patients shared similar clinical, biochemical and immunological features. Of 89 patients with 5-year follow-up or longer, 23 patients irrespective of presenting clinical, biochemical and immunological features achieved complete remission (normal transaminases and gammaglobulin levels) which was maintained with minimal steroid dosage; attempt at treatment withdrawal led to disease exacerbation. Complete responders had more often HLA DRB1*0401 (p = 0.011) and their risk of disease progression was lower (p < 0.0001). Type 1 and type 2 autoimmune hepatitis is one and the same disease. Autoimmune hepatitis has similar features in male and female patients. HLA DRB1*0401 positive patients are more likely to achieve complete remission. Continuous low-dose steroids are necessary to maintain remission, significantly reducing the risk of disease progression.

Pharmacokinetics of Rolapitant in Patients With Mild to Moderate Hepatic Impairment.

Science.gov (United States)

Wang, Jing; Wang, Xiaodong; Zhang, Zhi-Yi; Arora, Sujata; Lu, Sharon; Kansra, Vikram

2018-05-01

Rolapitant is a selective and long-acting neurokinin-1 receptor antagonist approved in an oral formulation in combination with other antiemetic agents for the prevention of delayed chemotherapy-induced nausea and vomiting in adults. This was a phase 1 open-label, parallel-group pharmacokinetic and safety study of a single oral dose of 180 mg of rolapitant and its major active metabolite, M19, in subjects with mild and moderate hepatic impairment compared with healthy matched controls. Pharmacokinetics were assessed by a mixed-model analysis of variance of log-transformed values for maximum observed plasma concentration (C max ), observed time at C max (t max ), area under the plasma concentration-time curve (AUC) from time 0 to the time of the last quantifiable concentration (AUC 0-t ), and AUC from time 0 to 120 hours (AUC 0-120 ), with hepatic group as a fixed effect. Mean rolapitant C max , AUC 0-t , and AUC 0-120 were similar in the mild hepatic impairment and healthy control groups. In subjects with moderate hepatic impairment, AUC 0-t was similar and C max was 25% lower than in healthy controls. Mean M19 C max and AUC 0-t were similar in the mild hepatic impairment group and healthy controls, but impairment versus healthy controls. Fraction of unbound rolapitant was comparable in all groups for rolapitant and M19. Rolapitant was well tolerated in all groups, without serious adverse events. Pharmacokinetic differences between healthy subjects and those with mild or moderate hepatic impairment are unlikely to pose a safety risk and do not warrant predefined dosage adjustment in the presence of hepatic impairment. © 2018, The American College of Clinical Pharmacology.

Input-profile-based software failure probability quantification for safety signal generation systems

International Nuclear Information System (INIS)

Kang, Hyun Gook; Lim, Ho Gon; Lee, Ho Jung; Kim, Man Cheol; Jang, Seung Cheol

2009-01-01

The approaches for software failure probability estimation are mainly based on the results of testing. Test cases represent the inputs, which are encountered in an actual use. The test inputs for the safety-critical application such as a reactor protection system (RPS) of a nuclear power plant are the inputs which cause the activation of protective action such as a reactor trip. A digital system treats inputs from instrumentation sensors as discrete digital values by using an analog-to-digital converter. Input profile must be determined in consideration of these characteristics for effective software failure probability quantification. Another important characteristic of software testing is that we do not have to repeat the test for the same input value since the software response is deterministic for each specific digital input. With these considerations, we propose an effective software testing method for quantifying the failure probability. As an example application, the input profile of the digital RPS is developed based on the typical plant data. The proposed method in this study is expected to provide a simple but realistic mean to quantify the software failure probability based on input profile and system dynamics.

Hepatitis B and A vaccination in HIV-infected adults: A review.

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Mena, G; García-Basteiro, A L; Bayas, J M

2015-01-01

Hepatitis B and A account for considerable morbidity and mortality worldwide. Immunization is the most effective means of preventing hepatitis B and A. However, the immune response to both hepatitis vaccines seems to be reduced in HIV-infected subjects. The aim of this review was to analyze the immunogenicity, safety, long-term protection and current recommendations of hepatitis B and A vaccination among HIV-infected adults. The factors most frequently associated with a deficient level of anti-HBs or IgG anti-HAV after vaccination are those related to immunosuppression (CD4 level and HIV RNA viral load) and to the frequency of administration and/or the amount of antigenic load per dose. The duration of the response to both HBV and HAV vaccines is associated with suppression of the viral load at vaccination and, in the case of HBV vaccination, with a higher level of antibodies after vaccination. In terms of safety, there is no evidence of more, or different, adverse effects compared with HIV-free individuals. Despite literature-based advice on the administration of alternative schedules, revaccination after the failure of primary vaccination, and the need for periodic re-evaluation of antibody levels, few firm recommendations are found in the leading guidelines.

Hepatitis B and A vaccination in HIV-infected adults: A review

Science.gov (United States)

Mena, G; García-Basteiro, AL; Bayas, JM

2015-01-01

Hepatitis B and A account for considerable morbidity and mortality worldwide. Immunization is the most effective means of preventing hepatitis B and A. However, the immune response to both hepatitis vaccines seems to be reduced in HIV-infected subjects. The aim of this review was to analyze the immunogenicity, safety, long-term protection and current recommendations of hepatitis B and A vaccination among HIV-infected adults. The factors most frequently associated with a deficient level of anti-HBs or IgG anti-HAV after vaccination are those related to immunosuppression (CD4 level and HIV RNA viral load) and to the frequency of administration and/or the amount of antigenic load per dose. The duration of the response to both HBV and HAV vaccines is associated with suppression of the viral load at vaccination and, in the case of HBV vaccination, with a higher level of antibodies after vaccination. In terms of safety, there is no evidence of more, or different, adverse effects compared with HIV-free individuals. Despite literature-based advice on the administration of alternative schedules, revaccination after the failure of primary vaccination, and the need for periodic re-evaluation of antibody levels, few firm recommendations are found in the leading guidelines. PMID:26208678

Systematic review: cardiovascular safety profile of 5-HT4 agonists developed for gastrointestinal disorders

OpenAIRE

Tack, J; Camilleri, M; Chang, L; Chey, W D; Galligan, J J; Lacy, B E; Müller-Lissner, S; Quigley, E M M; Schuurkes, J; Maeyer, J H; Stanghellini, V

2012-01-01

Summary Background The nonselective 5-HT4 receptor agonists, cisapride and tegaserod have been associated with cardiovascular adverse events (AEs). Aim To perform a systematic review of the safety profile, particularly cardiovascular, of 5-HT4 agonists developed for gastrointestinal disorders, and a nonsystematic summary of their pharmacology and clinical efficacy. Methods Articles reporting data on cisapride, clebopride, prucalopride, mosapride, renzapride, tegaserod, TD-5108 (velusetrag) an...

Differential effect of corn oil-based low trans structured fat on the plasma and hepatic lipid profile in an atherogenic mouse model: comparison to hydrogenated trans fat

Directory of Open Access Journals (Sweden)

Kim Hye-Jin

2011-01-01

Full Text Available Abstract Background Trans fat are not desirable in many aspects on health maintenance. Low trans structured fats have been reported to be relatively more safe than trans fats. Methods We examined the effects of low trans structured fat from corn oil (LC, compared with high trans fat shortening, on cholesterol and fatty acid metabolism in apo E deficient mice which is an atherogenic animal model. The animals were fed a high trans fat (10% fat: commercial shortening (CS or a low trans fat (LC diet for 12 weeks. Results LC decreased apo B and hepatic cholesterol and triglyceride concentration compared to the CS group but significantly increased plasma total cholesterol and triglyceride concentration and fecal lipids with a simultaneous increase in HDL-cholesterol level, apo A-I, and the ratio of HDL-cholesterol to total cholesterol (HTR. Reduction of hepatic lipid levels by inclusion of LC intake was observed alongside modulation of hepatic enzyme activities related to cholesterol esterification, fatty acid metabolism and fecal lipids level compared to the CS group. The differential effects of LC intake on the plasma and hepatic lipid profile seemed to be partly due to the fatty acid composition of LC which contains higher MUFA, PUFA and SFA content as well as lower content of trans fatty acids compared to CS. Conclusions We suggest that LC may exert a dual effect on plasma and hepatic lipid metabolism in an atherogenic animal model. Accordingly, LC, supplemented at 10% in diet, had an anti-atherogenic effect on these apo E-/- mice, and increased fecal lipids, decreased hepatic steatosis, but elevated plasma lipids. Further studies are needed to verify the exact mode of action regarding the complex physiological changes and alteration in lipid metabolism caused by LC.

Differential effect of corn oil-based low trans structured fat on the plasma and hepatic lipid profile in an atherogenic mouse model: comparison to hydrogenated trans fat

Science.gov (United States)

2011-01-01

Background Trans fat are not desirable in many aspects on health maintenance. Low trans structured fats have been reported to be relatively more safe than trans fats. Methods We examined the effects of low trans structured fat from corn oil (LC), compared with high trans fat shortening, on cholesterol and fatty acid metabolism in apo E deficient mice which is an atherogenic animal model. The animals were fed a high trans fat (10% fat: commercial shortening (CS)) or a low trans fat (LC) diet for 12 weeks. Results LC decreased apo B and hepatic cholesterol and triglyceride concentration compared to the CS group but significantly increased plasma total cholesterol and triglyceride concentration and fecal lipids with a simultaneous increase in HDL-cholesterol level, apo A-I, and the ratio of HDL-cholesterol to total cholesterol (HTR). Reduction of hepatic lipid levels by inclusion of LC intake was observed alongside modulation of hepatic enzyme activities related to cholesterol esterification, fatty acid metabolism and fecal lipids level compared to the CS group. The differential effects of LC intake on the plasma and hepatic lipid profile seemed to be partly due to the fatty acid composition of LC which contains higher MUFA, PUFA and SFA content as well as lower content of trans fatty acids compared to CS. Conclusions We suggest that LC may exert a dual effect on plasma and hepatic lipid metabolism in an atherogenic animal model. Accordingly, LC, supplemented at 10% in diet, had an anti-atherogenic effect on these apo E-/- mice, and increased fecal lipids, decreased hepatic steatosis, but elevated plasma lipids. Further studies are needed to verify the exact mode of action regarding the complex physiological changes and alteration in lipid metabolism caused by LC. PMID:21247503

Patients with hepatic breast cancer metastases demonstrate highly specific profiles of matrix metalloproteinases MMP-2 and MMP-9 after SIRT treatment as compared to other primary and secondary liver tumours

International Nuclear Information System (INIS)

Golubnitschaja, Olga; Yeghiazaryan, Kristina; Stricker, Helena; Trog, Daniela; Schild, Hans H.; Berliner, Leonard

2016-01-01

Patients with primary and metastatic liver malignancies represent a highly heterogeneous patient pool characterised by some of the shortest life expectancies amongst oncology patients. Investigation and better understanding of liver malignancies is an emerging field which requires high-quality multidisciplinary research and collaboration. A study of 158 patients with primary hepatic carcinomas and secondary liver metastases, altogether 15 cancer types of different origin, who underwent selective internal radiation therapy (SIRT) with Yttrium 90 or transarterial chemoembolisation, was undertaken in an effort to detect distinguishing features with respect to activity profiles of both blood matrix metalloproteinase (MMP-2 and MMP-9). Noteworthy, stratification of all hepatic cancer groups with respect to MMP-2 and MMP-9 activities revealed characteristic patterns specifically in patients with hepatic breast cancer metastases who had undergone SIRT. In contrast to all other groups, these patients demonstrated well-consolidated profiles of both MMPs, reflecting a common feature, namely an immediate and durable increase of their activity after the SIRT treatment. Although the total number of patients in the breast cancer group is relatively small (15 patients), since increased activities of MMP-2 and MMP-9 are well known prognostic factors for poor outcomes of oncologic patients, the significance and clear group-specificity (from 15 ones investigated here) of this previously unanticipated finding requires particular attention and further investigations. Particularly important is to determine, whether this increase of the metalloproteinase activity was provoked by SIRT, as well as whether special selection criteria are required for patients with breast cancer metastases to the liver who are being considered for SIRT. It is recommended that a more focused, multidisciplinary and large-scaled investigations of the possible adverse effects of SIRT in patients with advanced

Hepatically-metabolized and -excreted artificial oxygen carrier, hemoglobin vesicles, can be safely used under conditions of hepatic impairment

International Nuclear Information System (INIS)

Taguchi, Kazuaki; Miyasato, Mayumi; Ujihira, Hayato; Watanabe, Hiroshi; Kadowaki, Daisuke; Sakai, Hiromi; Tsuchida, Eishun; Horinouchi, Hirohisa; Kobayashi, Koichi; Maruyama, Toru; Otagiri, Masaki

2010-01-01

The hemoglobin vesicle (HbV) is an artificial oxygen carrier in which a concentrated Hb solution is encapsulated in lipid vesicles. Our previous studies demonstrated that HbV is metabolized by the mononuclear phagocyte system, and the lipid components are excreted from the liver. It is well-known that many hepatically-metabolized and -excreted drugs show altered pharmaceutics under conditions of liver impairment, which results in adverse effects. The aim of this study was to determine whether the administration of HbV causes toxicity in rats with carbon tetrachloride induced liver cirrhosis. Changes in plasma biochemical parameters, histological staining and the pharmacokinetic distribution of HbV were evaluated after an HbV injection of the above model rats at a putative clinical dose (1400 mgHb/kg). Plasma biochemical parameters were not significantly affected, except for a transient elevation of lipase, lipid components and bilirubin, which recovered within 14 days after an HbV infusion. Negligible morphological changes were observed in the kidney, liver, spleen, lung and heart. Hemosiderin, a marker of iron accumulation in organs, was observed in the liver and spleen up to 14 days after HbV treatment, but no evidence of oxidative stress in the plasma and liver were observed. HbV is mainly distributed in the liver and spleen, and the lipid components are excreted into feces within 7 days. In conclusion, even under conditions of hepatic cirrhosis, HbV and its components exhibit the favorable metabolic and excretion profile at the putative clinical dose. These findings provide further support for the safety and effectiveness of HbV in clinical settings.

Efficacy and Safety of Radiofrequency Ablation for Focal Hepatic Lesions Adjacent to Gallbladder: Reconfiguration of the Ablation Zone through Probe Relocation and Ablation Time Reduction.

Science.gov (United States)

Choi, In Young; Kim, Pyo Nyun; Lee, Sung Gu; Won, Hyung Jin; Shin, Yong Moon

2017-10-01

To evaluate the safety and efficacy of radiofrequency (RF) ablation for treatment of focal hepatic lesions adjacent to the gallbladder with electrode relocation and ablation time reduction. Thirty-nine patients who underwent RF ablation for focal hepatic lesions adjacent to the gallbladder (≤ 10 mm) were evaluated retrospectively from January 2011 to December 2014 (30 men and 9 women; age range, 51-85 y; mean age, 65 y). Of 36 patients with hepatocellular carcinoma, 3 had a second treatment for recurrence (mean tumor size, 15 mm ± 6). Patients were divided into 2 subgroups based on lesion distance from the gallbladder: nonabutting (> 5 mm; n = 19) and abutting (≤ 5 mm; n = 20). Electrodes were inserted parallel to the gallbladder through the center of a tumor in the nonabutting group and through the center of the expected ablation zone between a 5-mm safety zone on the liver side and the gallbladder in the abutting group. Ablation time was decreased in proportion to the transverse diameter of the expected ablation zone. Technical success and technical effectiveness rates were 89.7% and 97.4%, respectively, with no significant differences between groups (P = 1.00). Local tumor progression was observed in 3 patients (1 in the nonabutting group and 2 in the abutting group; P = 1.00). There were no major complications. The gallbladder was thickened in 10 patients, with no significant difference between groups (P = .72). Biloma occurred in 1 patient in the nonabutting group. RF ablation with electrode relocation and reduction of ablation time can be a safe and effective treatment for focal hepatic lesions adjacent to the gallbladder. Copyright © 2017 SIR. Published by Elsevier Inc. All rights reserved.

Hepatitis C

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... Workshops Follow Us Home Health Information Liver Disease Hepatitis (Viral) Hepatitis C Related Topics English English Español Section Navigation Hepatitis (Viral) What Is Viral Hepatitis? Hepatitis A Hepatitis B ...

Theatre and laboratory workers' awareness of and safety practices ...

African Journals Online (AJOL)

Introduction: The consistent use of barrier protection among theatre workers is low in this region, so also is hepatitis B virus (HBV) vaccination. We assessed the level of awareness of HBV and hepatitis C virus (HCV), HBV vaccination and adoption of safety measures by theatre and laboratory workers. Methods: Structured ...

Hepatitis A through E (Viral Hepatitis)

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... Treatment Eating, Diet, & Nutrition Clinical Trials Wilson Disease Hepatitis (Viral) View or Print All Sections What is Viral Hepatitis? Viral hepatitis is an infection that causes liver inflammation ...

Comparative pharmacokinetic and tissue distribution profiles of four major bioactive components in normal and hepatic fibrosis rats after oral administration of Fuzheng Huayu recipe.

Science.gov (United States)

Yang, Tao; Liu, Shan; Wang, Chang-Hong; Tao, Yan-Yan; Zhou, Hua; Liu, Cheng-Hai

2015-10-10

Fuzheng Huayu recipe (FZHY) is a herbal product for the treatment of liver fibrosis approved by the Chinese State Food and Drug Administration (SFDA), but its pharmacokinetics and tissue distribution had not been investigated. In this study, the liver fibrotic model was induced with intraperitoneal injection of dimethylnitrosamine (DMN), and FZHY was given orally to the model and normal rats. The plasma pharmacokinetics and tissue distribution profiles of four major bioactive components from FZHY were analyzed in the normal and fibrotic rat groups using an ultrahigh performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method. Results revealed that the bioavailabilities of danshensu (DSS), salvianolic acid B (SAB) and rosmarinic acid (ROS) in liver fibrotic rats increased 1.49, 3.31 and 2.37-fold, respectively, compared to normal rats. There was no obvious difference in the pharmacokinetics of amygdalin (AMY) between the normal and fibrotic rats. The tissue distribution of DSS, SAB, and AMY trended to be mostly in the kidney and lung. The distribution of DSS, SAB, and AMY in liver tissue of the model rats was significantly decreased compared to the normal rats. Significant differences in the pharmacokinetics and tissue distribution profiles of DSS, ROS, SAB and AMY were observed in rats with hepatic fibrosis after oral administration of FZHY. These results provide a meaningful basis for developing a clinical dosage regimen in the treatment of hepatic fibrosis by FZHY. Copyright © 2015 Elsevier B.V. All rights reserved.

Hepatitis A - frequency in children with non-specific abdominal symptoms

International Nuclear Information System (INIS)

Malik, R.; Ghafoor, T.; Sarfraz, M.; Hasan, N.

2004-01-01

Objective: To study the frequency of subclinical hepatitis 'A' in children having non-specific abdominal symptoms. Subjects and Methods: Three hundred and sixty children of either gender, < 12 years of age, presenting with vague abdominal symptoms and no jaundice were evaluated for hepatitis. Eighty-eight (24.4%) children meeting the inclusion criteria of elevated serum alanine aminotransferase (ALT), twice the upper limits of normal (90 IU/L), and normal serum bilirubin were labeled as subclinical hepatitis. Results: A total of 360 children were evaluated for vague abdominal symptoms and 96 (26.7%) of them had hepatitis on laboratory profile. Eight patients developed early jaundice and were excluded from the study. Out of 88 (24.4%) cases of subclinical hepatitis, 82 (93.2%) had hepatitis-A, 03 (3.4%) had hepatitis-B, while no causative agent was found in 03 (3.4%) children. The common presenting symptoms were abdominal pain/discomfort, loss of appetite, nausea, vomiting, malaise, fatigue and fever. Hepatomegaly and splenomegaly was documented in 56% and 43% cases respectively. A history of exposure to a patient with hepatitis was present in 14/88 (15.9%) cases whereas no child was vaccinated against HAV. Serum ALT level declined to normal limits within 4 weeks for 77/88 (87.5%) cases and within 6 weeks for 84/88 (95.4%). All cases recovered spontaneously with out any complication. Conclusion: Hepatitis-A was rampant in children presenting with vague abdominal symptoms in our series. (author)

Hepatitis A--frequency in children with non-specific abdominal symptoms.

Science.gov (United States)

Malik, Rahat; Ghafoor, Tariq; Sarfraz, Muhammad; Hasan, Najmul

2004-06-01

To study the frequency of subclinical hepatitis 'A' in children having non-specific abdominal symptoms. A descriptive study. This study was conducted at Combined Military Hospital (CMH), Peshawar from June to December 2000. Three hundred and sixty children of either gender, hepatitis. Eighty eight (24.4%) children meeting the inclusion criteria of elevated serum alanine aminotransferase (ALT), twice the upper limits of normal (90 IU/L), and normal serum bilirubin were labelled as subclinical hepatitis. A total of 360 children were evaluated for vague abdominal symptoms and 96 (26.7%) of them had hepatitis on laboratory profile. Eight patients developed early jaundice and were excluded from the study. Out of 88 (24.4%) cases of subclinical hepatitis, 82 (93.2%) had hepatitis-A, 03 (3.4%) had hepatitis-B, while no causative agent was found in 03 (3.4%) children. The common presenting symptoms were abdominal pain/discomfort, loss of appetite, nausea, vomiting, malaise, fatigue and fever. Hepatomegaly and splenomegaly was documented in 56% and 43% cases respectively. A history of exposure to a patient with hepatitis was present in 14/88 (15.9%) cases whereas no child was vaccinated against HAV. Serum ALT level declined to normal limits within 4 weeks for 77/88 (87.5%) cases and within 6 weeks for 84/88 (95.4%). All cases recovered spontaneously with out any complication. Hepatitis-A was rampant in children presenting with vague abdominal symptoms in our series.

Changing Epidemiological Characteristics of Hepatitis A in Zhejiang Province, China: Increased Susceptibility in Adults.

Science.gov (United States)

Wang, Zhifang; Chen, Yaping; Xie, Shuyun; Lv, Huakun

2016-01-01

Hepatitis A is a common acute hepatitis caused by hepatitis A virus (HAV). Annually, it affects 1.4 million people worldwide. Between 1991 and 1994, HAV infections were highly endemic in Zhejiang Province (China), with 78,720 reported HAV infections per year. Hepatitis A vaccine came on the market in 1995 and was implemented for voluntary immunization. Since 2008, hepatitis A vaccine has been integrated into the national childhood routine immunization program. To understand the current epidemiological profile of hepatitis A in Zhejiang Province since hepatitis A vaccine has been available for nearly two decades. This study used the 2005-2014 National Notifiable Diseases Reporting System data to evaluate the incidence rate of notified hepatitis A cases in Zhejiang Province. The overall trend of incidence rate of notified hepatitis A cases significantly decreased from 2005 to 2014 (Pstrategy with hepatitis A vaccine seemed to be effective in decreasing notified hepatitis A incidence rate in individuals aged ≤19 years. Those aged ≥20 years were observed to be the most susceptible population. The vast majority of hepatitis A cases were notified among Laborers. Therefore, we strongly suggest that future preventive and control measures should focus more on adults, particularly Laborers, in addition to the current childhood hepatitis A vaccination programme.

Plasma lipids, lipoprotein composition and profile during induction and treatment of hepatic lipidosis in cats and the metabolic effect of one daily meal in healthy cats.

Science.gov (United States)

Blanchard, G; Paragon, B M; Sérougne, C; Férézou, J; Milliat, F; Lutton, C

2004-04-01

Anorexia in obese cats may result in feline hepatic lipidosis (FHL). This study was designed to determine plasma lipids and lipoprotein profiles in queens at different stages during experimental induction of FHL (lean, obese, FHL), and after 10 weeks of treatment. Results were compared with those obtained from lean queens of same age fed the same diet but at a maintenance level, once a day. Hepatic lipidosis led to an increase in plasma triacylglycerol (TG), very low density lipoprotein (VLDL) and low density lipoprotein (LDL), and an enrichment of LDL with TG and of high density lipoprotein (HDL) with cholesterol, suggesting that VLDL secretion is enhanced, VLDL and LDL catabolism is lowered, and lipoprotein exchanges are impaired in FHL. This study also showed that cholesterolaemia is increased in cats fed at a dietary rhythm of one meal per day compared to ad libitum feeding.

Daclatasvir: potential role in hepatitis C

Directory of Open Access Journals (Sweden)

Lee C

2013-10-01

Full Text Available Choongho Lee College of Pharmacy, Dongguk University-Seoul, Goyang, Republic of Korea  Abstract: Chronic hepatitis C virus (HCV infection is responsible for the development of liver cirrhosis and hepatocellular carcinoma. It has been a tremendous burden on global health care systems. With the advent of a number of new direct-acting and host-targeting antiviral agents, current interferon-α- and ribavirin-based HCV therapy has started to move towards an interferon-sparing or even interferon-free strategy. In this regard, a recently identified NS5A inhibitor, daclatasvir, showed a great promise in clinical trials as another new class of direct-acting anti-HCV therapeutics, with a distinct mechanism of action. In this review, a variety of preclinical as well as clinical proof-of-concept studies of daclatasvir, including the studies of its discovery, mechanism of action, viral resistance, and host polymorphism profiles are reviewed. In addition, a role of daclatasvir in the future therapy for HCV patients is discussed briefly. Keywords: hepatitis C virus, nonstructural protein 5A, NS5A inhibitor, hepatitis C treatment

Tangshen formula attenuates hepatic steatosis by inhibiting hepatic lipogenesis and augmenting fatty acid oxidation in db/db mice.

Science.gov (United States)

Kong, Qin; Zhang, Haojun; Zhao, Tingting; Zhang, Weiku; Yan, Meihua; Dong, Xi; Li, Ping

2016-12-01

Tangshen formula (TSF), a well-prescribed traditional Chinese formula, has been used in the treatment of diabetic nephropathy. However, whether TSF ameliorates dyslipidemia and liver injury associated with diabetes remains unclear. In this study, we examined the effects of TSF on lipid profiles and hepatic steatosis in db/db mice. For this purpose, 8‑week-old db/db mice were treated with TSF or saline for 12 weeks via gavage and db/m mice were used as controls. Body weight and blood glucose levels were monitored weekly and bi-weekly, respectively. Blood samples were obtained for the analysis of lipids and enzymes related to hepatic function, and liver tissues were analyzed by histology, immunohistochemistry and molecular examination. The results revealed that TSF markedly reduced body weight, liver index [liver/body weight (LW/BW)] and improved lipid profiles, hepatic function and steatosis in db/db mice. TSF induced the phosphoralation of AMP-activated protein kinase and inhibited the activity of sterol regulatory element-binding protein 1 together with the inhibition of the expression of genes involved in de novo lipogenesis (DNL) and gluconeogenesis, such as fatty acid synthase (FAS), acetyl-CoA carboxylase (ACC), stearoyl CoA desaturase 1 (SCD1), glucose-6-phosphatase (G6pc) and phosphoenolpyruvate carboxykinase 1 (Pck1). Additionally, the silent mating type information regulation 2 homolog 1 (Sirt1)/peroxisome proliferator-activated receptor α (PPARα)/malonyl-CoA decarboxylase (MLYCD) cascade was potently activated by TSF in the liver and skeletal muscle of db/db mice, which led to enhanced fatty acid oxidation. These findings demonstrated that TSF attenuated hepatic fat accumulation and steatosis in db/db mice by inhibiting lipogenesis and augmenting fatty acid oxidation.

Hepatitis isquémica Ischemic hepatitis

Directory of Open Access Journals (Sweden)

Marcos Amuchástegui (h

2006-10-01

Full Text Available La hepatitis isquémica es una complicación sumamente infrecuente de cirugía cardiovascular. Las biopsias muestran necrosis centrolobulillar. El término de "hepatitis" fue propuesto debido al aumento de transaminasas similar a aquellas de origen infeccioso, e "isquémica" por falla en la perfusión hepática. Posteriormente se definió el término de hepatitis isquémica como cuadro de elevación aguda y reversible (dentro de las 72 horas de transaminasas de hasta 20 veces el valor normal, asociado a trastornos en la perfusión hepática, luego de haber excluido otras causas de hepatitis aguda o daño hepatocelular. Se describe el caso de un paciente de 53 años que consulta por dolor epigástrico de 12 h de evolución sin fiebre, náuseas ni vómitos, resistente a la medicación. Tenía antecedentes inmediatos de reemplazo de válvula aórtica, y estaba anticoagulado. Evolucionó con shock y fallo multiorgánico. El examen evidenció marcada ictericia y signos de taponamiento pericárdico, asociado a un aumento considerable de enzimas hepáticas. Un ecocardiograma informó signos de taponamiento cardíaco y ausencia de disección aórtica. Se decidió pericardiocentesis, extrayéndose 970 cc. de líquido sanguinolento, y hemodiálisis, con notable mejoría de su estado hemodinámico. Los valores enzimáticos disminuyeron. Los marcadores virales fueron negativos.Ischemic hepatitis is an uncommon cardiovascular surgery complication. Hepatic biopsies show centrolobulillar necrosis. The term "hepatitis" was proposed because of a raise in hepatic enzymes similar with infectious disease, and "ischemic" because of failure in hepatic perfusion. Ischemic hepatitis was then defined as an acute and reversible elevation of hepatic enzymes (within 72 h, associated with disturbance in hepatic perfusion after excluding other causes of acute hepatitis. A 53 year-old male presented complaining of a 12 h epigastric pain, without nausea or vomiting, resistant

Glecaprevir + pibrentasvir for treatment of hepatitis C.

Science.gov (United States)

Carrion, Andres F; Martin, Paul

2018-03-01

Glecaprevir/pibrentasvir is a fixed-dose combination regimen of a new generation NS3/4A inhibitor and an NS5A inhibitor with potent antiviral activity against all hepatitis C virus (HCV) genotypes. This regimen offers a shorter course of therapy (8 weeks) for selected patients regardless of genotype and has demonstrated high virological efficacy for retreatment of individuals who previously failed an NS5A containing regimen. Glecaprevir and pibrentasvir are minimally excreted by the kidneys; thus this regimen can safely be used in individuals with severe chronic kidney disease (CKD), including those undergoing hemodialysis. Areas covered: This review covers the mechanism of action, pharmacokinetics, clinical applications, efficacy, and safety profile of glecaprevir/pibrentasvir. It also covers key phase 2 and 3 clinical trials that led to licensure of this regimen. Expert opinion: Glecaprevir/pibrentasvir is the latest antiviral regimen licensed in the United States for treatment of HCV infection. Although several other direct-acting antiviral agents (DAAs) are currently available, glecaprevir/pibrentasvir has some unique characteristics that expand treatment options for HCV infection, including patients with comorbidities such as advanced stage CKD or prior treatment failure to antiviral regimens containing other DAAs.

Separation of Hepatitis C genotype 4a into IgG-depleted and IgG-enriched fractions reveals a unique quasispecies profile.

LENUS (Irish Health Repository)

Moreau, Isabelle

2012-02-03

BACKGROUND: Hepatitis C virus (HCV) circulates in an infected individual as a heterogeneous mixture of closely related viruses called quasispecies. The E1\\/E2 region of the HCV genome is hypervariable (HVR1) and is targeted by the humoral immune system. Hepatitis C virions are found in two forms: antibody associated or antibody free. The objective of this study was to investigate if separation of Hepatitis C virions into antibody enriched and antibody depleted fractions segregates quasispecies populations into distinctive swarms. RESULTS: A HCV genotype 4a specimen was fractionated into IgG-depleted and IgG-enriched fractions by use of Albumin\\/IgG depletion spin column. Clonal analysis of these two fractions was performed and then compared to an unfractionated sample. Following sequence analysis it was evident that the antibody depleted fraction was significantly more heterogeneous than the antibody enriched fraction, revealing a unique quasispecies profile. An in-frame 3 nt insertion was observed in 26% of clones in the unfractionated population and in 64% of clones in the IgG-depleted fraction. In addition, an in-frame 3 nt indel event was observed in 10% of clones in the unfractionated population and in 9% of clones in the IgG-depleted fraction. Neither of these latter events, which are rare occurrences in genotype 4a, was identified in the IgG-enriched fraction. CONCLUSION: In conclusion, the homogeneity of the IgG-enriched species is postulated to represent a sequence that was strongly recognised by the humoral immune system at the time the sample was obtained. The heterogeneous nature of the IgG-depleted fraction is discussed in the context of humoral escape.

Decline and changing profile of hepatitis delta among injection drug users in Spain.

Science.gov (United States)

Aguilera, Antonio; Trastoy, Rocio; Barreiro, Pablo; Costa, José Javier; de Mendoza, Carmen; Peña, Jose M; Soriano, Vicente

2018-01-01

Roughly 15 million people worldwide have hepatitis delta, the most severe form of chronic viral hepatitis that often leads to cirrhosis and liver cancer. Injection drug users (IDUs) are the largest HDV reservoir. Their resurgence in North America and Europe may represent a new opportunity for HDV to spread more widely. We examined all consecutive active IDUs seen for the first time and enrolled in detoxification programmes at two clinics in Spain during two periods (1993-1996 and 2011-2014, respectively). Serum markers of HIV, HBV and HDV infection were tested. A total of 209 IDUs were examined in the first period. Mean age was 27-years-old. All had markers of past or current HBV infection. The rate of HIV-antibody (Ab), hepatitis B surface antigen (HBsAg) and HDV-Ab was as follows: 122 (58.4%), 73 (34.9%) and 62 (29.7%), respectively. Serum HDV-Ab was recognized in 53.4% of HBsAg+ and 16.9% of HBsAg- patients (Pforeign immigrants. It may reflect the benefit of universal HBV vaccination as well as the success of needle exchange programmes in Spain.

Changing Epidemiological Characteristics of Hepatitis A in Zhejiang Province, China: Increased Susceptibility in Adults

Science.gov (United States)

Wang, Zhifang; Chen, Yaping; Xie, Shuyun; Lv, Huakun

2016-01-01

Background Hepatitis A is a common acute hepatitis caused by hepatitis A virus (HAV). Annually, it affects 1.4 million people worldwide. Between 1991 and 1994, HAV infections were highly endemic in Zhejiang Province (China), with 78,720 reported HAV infections per year. Hepatitis A vaccine came on the market in 1995 and was implemented for voluntary immunization. Since 2008, hepatitis A vaccine has been integrated into the national childhood routine immunization program. Objective To understand the current epidemiological profile of hepatitis A in Zhejiang Province since hepatitis A vaccine has been available for nearly two decades. Methods This study used the 2005–2014 National Notifiable Diseases Reporting System data to evaluate the incidence rate of notified hepatitis A cases in Zhejiang Province. Results The overall trend of incidence rate of notified hepatitis A cases significantly decreased from 2005 to 2014 (Phepatitis A vaccine seemed to be effective in decreasing notified hepatitis A incidence rate in individuals aged ≤19 years. Those aged ≥20 years were observed to be the most susceptible population. The vast majority of hepatitis A cases were notified among Laborers. Therefore, we strongly suggest that future preventive and control measures should focus more on adults, particularly Laborers, in addition to the current childhood hepatitis A vaccination programme. PMID:27093614

Paired comparison of iopamidol and iopromide in hepatic arteriography

International Nuclear Information System (INIS)

Choi, Young Ho; Chung, Jin Wook; Choi, Guk Myung; Yoon, Chang Jin; Kim, Keon Ha; Moon, Seung Gyu; Kim, Hyo Cheol; Park, Jae Hyung

2003-01-01

To compare the clinical efficacy of iopamidol 370 and iopromide 370, as used in hepatic arteriography, in terms of their safety, patient tolerance, and image quality. Between February and April 2001, 30 patients (M:F=27:3; mean age, 57 years) with hepatocellular carcinoma underwent hepatic angiography in which iopamidol 370 was used for transcatheter arterial chemoembolization (TAE). Sensations of heat or pain following contrast injection, a patient's distress or discomfort levels, and any side effects of the contrast media were monitored, and afterwards patients were asked whether they were aware of any differences between iopamidol 370 and iopromide 370, which had been used in hepatic angiography for previous TAE prior to February 2001. Three experienced independent radiologists assessed the diagnostic efficacy of the contrast media in terms of overall image quality, which was statistically analysed using Wilcoxon's signed ranks test. No patient experienced sensations of heat or pain during angiography, or showed any objective distress or discomfort, though two suffered mild nausea during angiography with iopamidol 370. None was aware of any difference between iopromide 370 and iopamidol 370. In terms of overall image quality, the diagnostic efficacy of contrast media in all patients was 'good' to 'excellent', with no significant difference between iopromide 370 and iopamidol 370 (p>0.05). In hepatic arteriography, the clinical efficacy of iopamidol 370 is comparable with that of another nonionic contrast medium, iopromide 370, in terns of safety, tolerance, and image quality. Iopamidol 370 is thus a useful alternative medium

Hepatic Encephalopathy

Medline Plus

Full Text Available ... Related Liver Disease Alpha-1 Antitrypsin Deficiency Autoimmune Hepatitis Benign Liver Tumors Biliary Atresia Cirrhosis of the ... Disease Type 1 (von Gierke) Hemochromatosis Hepatic Encephalopathy Hepatitis A Hepatitis B Hepatitis C Intrahepatic Cholestasis of ...

Hepatic Encephalopathy

Medline Plus

Full Text Available ... Hemochromatosis Hepatic Encephalopathy Hepatitis A Hepatitis B Hepatitis C Intrahepatic Cholestasis of Pregnancy (ICP) Jaundice In Newborns ... are the common causes of cirrhosis? Hepatitis B & C Alcohol-related Liver Disease Non-alcoholic Fatty Liver ...

Hepatic Encephalopathy

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Full Text Available ... 1 (von Gierke) Hemochromatosis Hepatic Encephalopathy Hepatitis A Hepatitis B Hepatitis C Intrahepatic Cholestasis of Pregnancy (ICP) Jaundice ... diseases. What are the common causes of cirrhosis? Hepatitis B & C Alcohol-related Liver Disease Non-alcoholic Fatty ...

Recent advances in Hepatitis E virus.

Science.gov (United States)

Meng, X J

2010-03-01

Hepatitis E virus (HEV), the causative agent of hepatitis E, belongs to the family Hepeviridae. At least four major genotypes of HEV have been recognized: genotypes 1 and 2 are restricted to humans and associated with epidemics in developing countries, whereas genotypes 3 and 4 are zoonotic and infect humans and several other animals in both developing and industrialized countries. Besides humans, strains of HEV have been genetically identified from swine, chickens, sika deer, mongeese, and rabbits. The genome of HEV consists of three open reading frames (ORFs): ORF1 codes for nonstructural proteins, ORF2 codes for capsid protein, and ORF3 codes for a small multifunctional protein. The ORF2 and ORF3 proteins are translated from a single bicistronic mRNA and overlap each other but neither overlaps ORF1. The recent determination of the 3D crystal structure of the HEV capsid protein should facilitate the development of vaccines and antivirals. The identification and characterization of animal strains of HEV from pigs and chickens and the demonstrated ability of cross-species infection by swine HEV raise public health concerns for zoonosis. Accumulating evidence indicated that hepatitis E is a zoonotic disease and pigs and more likely other animal species are reservoirs for HEV. This article provides an overview of the recent advances in hepatitis E and its causative agent, including nomenclature and genomic organization, gene expression and functions, 3D structure of the virions, changing perspectives on higher mortality during pregnancy and chronic hepatitis E, animal reservoirs, zoonotic risk, food safety, and novel animal models.

LIVER TRANSPLANTATION IN HEPATITIS DELTA: SOUTH AMERICA EXPERIENCE

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Daniel Souza LIMA

Full Text Available ABSTRACT BACKGROUND: The Amazon region is one of the main endemic areas of hepatitis delta in the world and the only one related to the presence of genotype 3 of the delta virus. OBJECTIVE: To analyze the profile, mortality and survival of cirrhotic patients submitted to liver transplantation for chronic hepatitis delta virus and compare with those transplanted by hepatitis B virus monoinfection. METHODS: Retrospective, observational and descriptive study. From May 2002 to December 2011, 629 liver transplants were performed at the Walter Cantídio University Hospital, of which 29 patients were transplanted due to cirrhosis caused by chronic delta virus infection and 40 by hepatitis B chronic monoinfection. The variables analyzed were: age, sex, MELD score, Child-Pugh score, upper gastrointestinal bleeding and hepatocellular carcinoma occurrence before the transplantation, perioperative platelet count, mortality and survival. RESULTS: The Delta Group was younger and all came from the Brazilian Amazon Region. Group B presented a higher proportion of male patients (92.5% compared to Group D (58.6%. The occurrence of upper gastrointestinal bleeding before transplantation, MELD score, and Child-Pugh score did not show statistical differences between groups. The occurrence of hepatocellular carcinoma and mortality were higher in the hepatitis B Group. The survival in 4 years was 95% in the Delta Group and 75% in the B Group, with a statistically significant difference (P=0.034. Patients with hepatitis delta presented more evident thrombocytopenia in the pre-transplantation and in the immediate postoperative period. CONCLUSION: The hepatitis by delta virus patients who underwent liver transplantation were predominantly male, coming from the Brazilian Amazon region and with similar liver function to the hepatitis B virus patients. They had a lower incidence of hepatocellular carcinoma, more marked perioperative thrombocytopenia levels and frequent

Health risk profile of prostitutes in Dublin.

LENUS (Irish Health Repository)

McDonnell, R J

1998-08-01

This study examined the health risk profile of prostitutes in Dublin. Clinical records of all 150 new prostitutes who attended a drop-in clinic for prostitutes in Dublin city during the period 1991-1997 were reviewed. Variables examined included: age, use of injectable drugs, human immunodeficiency virus (HIV) status, hepatitis B and C status, presence of sexually transmitted disease (STD), cervical cytology. Results showed the mean age of the women was 32 years. Among those tested, 2.5% were HIV positive, 5% were hepatitis B positive, 8% were hepatitis C positive and 25% had an STD. Almost 8% were injecting drug users (IDU) with higher prevalences of HIV, hepatitis B and C compared with non-IDU (P < 0.001). The clinic has been successful in providing a health-care facility for the specific health needs of this patient cohort.

Prevalence of hepatitis A virus, hepatitis B virus, hepatitis C virus, hepatitis D virus and hepatitis E virus as causes of acute viral hepatitis in North India: a hospital based study.

Science.gov (United States)

Jain, P; Prakash, S; Gupta, S; Singh, K P; Shrivastava, S; Singh, D D; Singh, J; Jain, A

2013-01-01

Acute viral hepatitis (AVH) is a major public health problem and is an important cause of morbidity and mortality. The aim of the present study is to determine the prevalence of hepatitis A virus (HAV), hepatitis B virus (HBV), hepatitis C virus (HCV), hepatitis D virus (HDV) and hepatitis E virus (HEV) as causes of AVH in a tertiary care hospital of North India. Blood samples and clinical information was collected from cases of AVH referred to the Grade I viral diagnostic laboratory over a 1-year period. Samples were tested for hepatitis B surface antigen, anti-HCV total antibodies, anti-HAV immunoglobulin M (IgM) and anti-HEV IgM by the enzyme-linked immunosorbent assay. PCR for nucleic acid detection of HBV and HCV was also carried out. Those positive for HBV infection were tested for anti-HDV antibodies. Fisher's exact test was used and a P hepatitis cases, 62 (23.22%) patients presented as acute hepatic failure. HAV (26.96%) was identified as the most common cause of acute hepatitis followed by HEV (17.97%), HBV (16.10%) and HCV (11.98%). Co-infections with more than one virus were present in 34 cases; HAV-HEV co-infection being the most common. HEV was the most important cause of acute hepatic failure followed by co-infection with HAV and HEV. An indication towards epidemiological shift of HAV infection from children to adults with a rise in HAV prevalence was seen. To the best of our knowledge, this is the first report indicating epidemiological shift of HAV in Uttar Pradesh.

Miscellaneous Endovascular Treatment of Ruptured Hepatic Artery Pseudoaneurysms after Pylorus Preserving Pancreaticoduodenectomy

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Kang, Ung Rae; Lee, Young Hwan [Dept. of Radiology, Daegu Catholic University Medical Center, Catholic of Daegu University School of Medicine, Daegu (Korea, Republic of); Ahn, Eun Joung; Kim, See Hyung; Kim, Young Hwan [Dept. of Radiology, Keimyung University Dongsan Medical Center, Keimyung University College of Medicine, Daegu (Korea, Republic of)

2012-03-15

To assess the feasibility and safety of the endovascular treatment of ruptured hepatic artery pseudoaneurysms after pylorus preserving pancreaticoduodenectomy (PPPD). Thirteen patients with hepatic artery pseudoaneurysm after PPPD were enrolled. Various endovascular techniques were used depending on the sites and morphologies of the pseudoaneurysms. Five cases were treated by coil embolization, five with stent-graft, one by thrombin injection and coil embolization, one with stent-graft and coil embolization, and one with N-butyl cyanoacrylate (NBCA) injection. Computed tomography scans and liver function test were performed after the procedures. Pseudoaneurysm exclusion and bleeding cessation was achieved in all patients. In four patients that underwent coil or NBCA embolization of the hepatic artery, aspartate transaminase (AST) and alanine transaminase (ALT) were markedly elevated. Two of these four patients with narrowing of the portal vein due to surrounding hematoma died of hepatic infarction or hepatic abscess. In other nine patients, AST and ALT were unchanged. In the 11 surviving patients, normal hepatic function and complete pseudoaneurysm disappearance were achieved during follow-up. Endovascular treatment of ruptured hepatic artery pseudoaneurysms can be considered as a feasible and safe method. However, complete occlusion of the hepatic artery with coils should be avoided in patients with inadequate portal flow.

Globalization and the Changing Epidemiology of Hepatitis A Virus.

Science.gov (United States)

Jacobsen, Kathryn H

2018-03-02

Increased economic interdependence, social integration, and other aspects of globalization are contributing to significant changes in hepatitis A epidemiology. Globally, the incidence of hepatitis A virus (HAV) infection is decreasing, the age at midpoint of population immunity (AMPI) is increasing, and the proportion of symptomatic cases is increasing as the average age at infection increases. In low-income countries, HAV remains endemic but improved water and sanitation systems are reducing transmission rates among young children. In high-income countries, most adults remain susceptible to HAV and foodborne outbreaks are becoming more frequent. Middle-income countries have diverse epidemiological profiles, and they play important roles in the global spread of HAV through international trade and travel. Future changes in the epidemiology of hepatitis A will be heavily influenced by globalization processes. Copyright © 2018 Cold Spring Harbor Laboratory Press; all rights reserved.

Acute Hepatitis Induced by Chinese Hepatoprotective Herb, Xiao-Chai-Hu-Tang

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Li-Ming Hsu

2006-02-01

Full Text Available Xiao-chai-hu-tang (syo-saiko-to in Japanese is a herbal remedy that has been widely used in China for treatment of respiratory, hepatobiliary, and gastrointestinal diseases, particularly among patients with chronic liver disease. However, its safety has recently been challenged. We, herein, report a Chinese patient with acute hepatitis induced by this herb. A 52-year-old woman presented with weakness, fatigue, and tea-colored urine after continual consumption of the decoction of xiao-chai-hu-tang for 1.5 months. Laboratory studies disclosed acute hepatitis even though all of the viral hepatitis markers were negative. Liver biopsy also revealed a picture of acute hepatocellular hepatitis. The symptoms improved after discontinuing the drug, and liver biochemical tests normalized 2 months later. The case report reminds us of the probable adverse drug reaction of herbs, even in some that are claimed to have hepatoprotective effects.

Failure to incriminate hepatitis B, hepatitis C, and hepatitis E viruses in the aetiology of fulminant non-A non-B hepatitis.

OpenAIRE

Mutimer, D; Shaw, J; Neuberger, J; Skidmore, S; Martin, B; Hubscher, S; McMaster, P; Elias, E

1995-01-01

Sporadic non-A, non-B hepatitis is the most common indication for liver transplantation in patients presenting with fulminant and subacute liver failure. This study used serological, histological, and molecular biological techniques to examine specimens from 23 consecutive patients transplanted for sporadic non-A, non-B hepatitis. No evidence was found of hepatitis C virus, hepatitis E virus, or 'cryptic' hepatitis B virus infection.

[Safety profile of zolpidem: two studies of 3805 patients by Swiss practitioners].

Science.gov (United States)

Ganzoni, E; Gugger, M

1999-06-24

Evaluation and treatment of insomnia are frequent procedures in the physician's everyday practice, since many patients seek medical treatment for this condition. Knowledge of pharmacological therapeutical alternatives is therefore decisive, in order to identify the most efficaceous and safe therapy for the patient among the available hypnotics. The short-acting hypnotic zolpidem has been investigated in Switzerland in two multicenter safety studies in ambulatory practice. In the first study 8.9% (n = 125 of 1,972 treated patients), and in the second 7.2% of the patients (n = 175 of 1,833 treated patients) reported an adverse event. The most frequent events were related to the central nervous system (CNS) (somnolence, headache, confusion, vertigo); gastrointestinal and cutaneous symptoms were the most frequent non CNS-dependent effects. New, unknown or serious adverse events were not found and no specific risk factor or population at risk was identified. The safety profile of zolpidem is consistent with its known pharmacological properties, the results of previous clinical trials and the international experience obtained in large patients groups.

Hepatitis

Science.gov (United States)

... most common types of viral hepatitis. What Is Hepatitis A? For kids, hep A is the most common ... they recover, it does not come back. Can Hepatitis A Be Prevented? The following will help keep people ...

Clinical and virological improvement of hepatitis B virus-related or hepatitis C virus-related chronic hepatitis with concomitant hepatitis A virus infection.

Science.gov (United States)

Sagnelli, Evangelista; Coppola, Nicola; Pisaturo, Mariantonietta; Pisapia, Raffaella; Onofrio, Mirella; Sagnelli, Caterina; Catuogno, Antonio; Scolastico, Carlo; Piccinino, Felice; Filippini, Pietro

2006-06-01

We evaluated the clinical and virological characteristics of hepatitis A virus infection in persons concomitantly infected with hepatitis B virus (HBV) or hepatitis C virus (HCV). We enrolled 21 patients with acute hepatitis A and chronic hepatitis with no sign of liver cirrhosis, 13 patients who were positive for hepatitis B surface antigen (case B group), 8 patients who were anti-HCV positive (case C group), and 21 patients with acute hepatitis A without a preexisting liver disease (control A group). Two control groups of patients with chronic hepatitis B (control B group) or C (control C group) were also chosen. All control groups were pair-matched by age and sex with the corresponding case group. Fulminant hepatitis A was never observed, and hepatitis A had a severe course in 1 patient in the case B group and in 1 patient in the control A group. Both patients recovered. On admission, HBV DNA was detected in 1 patient in the case B group (7.7%) and in 13 patients (50%) in the control B group; HCV RNA was found in no patient in the case C group and in 16 patients (81.2%) in the control C group. Of 9 patients in the case B group who were followed up for 6 months, 3 became negative for hepatitis B surface antigen and positive for hepatitis B surface antibody, 2 remained positive for hepatitis B surface antigen and negative for HBV DNA, and 4 became positive for HBV DNA with a low viral load [corrected] Of 6 patients in the case C group who were followed up for 6 months, 3 remained negative for HCV RNA, and 3 had persistently low viral loads. Concomitant hepatitis A was always self-limited, associated with a marked inhibition of HBV and HCV genomes, and possibly had a good prognosis for the underlying chronic hepatitis.

Analysis of hepatic transcript profile and plasma lipid profile in early lactating dairy cows fed grape seed and grape marc meal extract.

Science.gov (United States)

Gessner, Denise K; Winkler, Anne; Koch, Christian; Dusel, Georg; Liebisch, Gerhard; Ringseis, Robert; Eder, Klaus

2017-03-23

It was recently reported that dairy cows fed a polyphenol-rich grape seed and grape marc meal extract (GSGME) during the transition period had an increased milk yield, but the underlying reasons remained unclear. As polyphenols exert a broad spectrum of metabolic effects, we hypothesized that feeding of GSGME influences metabolic pathways in the liver which could account for the positive effects of GSGME in dairy cows. In order to identify these pathways, we performed genome-wide transcript profiling in the liver and lipid profiling in plasma of dairy cows fed GSGME during the transition period at 1 week postpartum. Transcriptomic analysis of the liver revealed 207 differentially expressed transcripts, from which 156 were up- and 51 were down-regulated, between cows fed GSGME and control cows. Gene set enrichment analysis of the 155 up-regulated mRNAs showed that the most enriched gene ontology (GO) biological process terms were dealing with cell cycle regulation and the most enriched Kyoto Encyclopedia of Genes and Genomes pathways were p53 signaling and cell cycle. Functional analysis of the 43 down-regulated mRNAs revealed that a great part of these genes are involved in endoplasmic reticulum (ER) stress-induced unfolded protein response (UPR) and inflammatory processes. Accordingly, protein folding, response to unfolded protein, unfolded protein binding, chemokine activity and heat shock protein binding were identified as one of the most enriched GO biological process and molecular function terms assigned to the down-regulated genes. In line with the transcriptomics data the plasma concentrations of the acute phase proteins serum amyloid A (SAA) and haptoglobin were reduced in cows fed GSGME compared to control cows. Lipidomic analysis of plasma revealed no differences in the concentrations of individual species of major and minor lipid classes between cows fed GSGME and control cows. Analysis of hepatic transcript profile in cows fed GSGME during the

Hepatitis Vaccines

OpenAIRE

Ogholikhan, Sina; Schwarz, Kathleen B.

2016-01-01

Viral hepatitis is a serious health problem all over the world. However, the reduction of the morbidity and mortality due to vaccinations against hepatitis A and hepatitis B has been a major component in the overall reduction in vaccine preventable diseases. We will discuss the epidemiology, vaccine development, and post-vaccination effects of the hepatitis A and B virus. In addition, we discuss attempts to provide hepatitis D vaccine for the 350 million individuals infected with hepatitis B ...

Hepatitis Vaccines

Directory of Open Access Journals (Sweden)

Sina Ogholikhan

2016-03-01

Full Text Available Viral hepatitis is a serious health problem all over the world. However, the reduction of the morbidity and mortality due to vaccinations against hepatitis A and hepatitis B has been a major component in the overall reduction in vaccine preventable diseases. We will discuss the epidemiology, vaccine development, and post-vaccination effects of the hepatitis A and B virus. In addition, we discuss attempts to provide hepatitis D vaccine for the 350 million individuals infected with hepatitis B globally. Given the lack of a hepatitis C vaccine, the many challenges facing the production of a hepatitis C vaccine will be shown, along with current and former vaccination trials. As there is no current FDA-approved hepatitis E vaccine, we will present vaccination data that is available in the rest of the world. Finally, we will discuss the existing challenges and questions facing future endeavors for each of the hepatitis viruses, with efforts continuing to focus on dramatically reducing the morbidity and mortality associated with these serious infections of the liver.

Hepatitis Vaccines

Science.gov (United States)

Ogholikhan, Sina; Schwarz, Kathleen B.

2016-01-01

Viral hepatitis is a serious health problem all over the world. However, the reduction of the morbidity and mortality due to vaccinations against hepatitis A and hepatitis B has been a major component in the overall reduction in vaccine preventable diseases. We will discuss the epidemiology, vaccine development, and post-vaccination effects of the hepatitis A and B virus. In addition, we discuss attempts to provide hepatitis D vaccine for the 350 million individuals infected with hepatitis B globally. Given the lack of a hepatitis C vaccine, the many challenges facing the production of a hepatitis C vaccine will be shown, along with current and former vaccination trials. As there is no current FDA-approved hepatitis E vaccine, we will present vaccination data that is available in the rest of the world. Finally, we will discuss the existing challenges and questions facing future endeavors for each of the hepatitis viruses, with efforts continuing to focus on dramatically reducing the morbidity and mortality associated with these serious infections of the liver. PMID:26978406

Primary hepatic artery embolization in pediatric blunt hepatic trauma.

Science.gov (United States)

Ong, Caroline C P; Toh, Luke; Lo, Richard H G; Yap, Te-Lu; Narasimhan, Kannan

2012-12-01

Non-operative management of isolated blunt hepatic trauma is recommended except when hemodynamic instability requires immediate laparotomy. Hepatic artery angioembolization is increasingly used for hepatic injuries with ongoing bleeding as demonstrated by contrast extravasation on the CT scan. It is used primarily or after laparotomy to control ongoing hemorrhage. Hepatic angioembolization as part of multimodality management of hepatic trauma is reported mainly in adults, with few pediatric case reports. We describe our institution experience with primary pediatric hepatic angioembolization and review the literature with regard to indications and complications. Two cases (3 and 8 years old), with high-grade blunt hepatic injuries with contrast extravasation on the CT scan were successfully managed by emergency primary hepatic angioembolization with minimal morbidity and avoided laparotomy. To date, the only reports of pediatric hepatic angioembolization for trauma are 5 cases for acute bleeding and 15 delayed cases for pseudoaneurysm. The role of hepatic angioembolization in the presence of an arterial blush on CT in adults is accepted, but contested in a pediatric series, despite higher transfusion rate and mortality rate. We propose that hepatic angioembolization should be considered adjunct treatment, in lieu of, or in addition to emergency laparotomy for hemostasis in pediatric blunt hepatic injury. Copyright © 2012 Elsevier Inc. All rights reserved.

Hepatitis C in Pregnancy: Review of Current Knowledge and Updated Recommendations for Management.

Science.gov (United States)

Page, Charlotte M; Hughes, Brenna L; Rhee, Eleanor H J; Kuller, Jeffrey A

2017-06-01

An estimated 1% to 2.5% of pregnant women in the United States are infected with hepatitis C virus (HCV), which carries approximately a 6% risk of mother-to-infant transmission. The aims of this article are to review the current evidence on HCV in pregnancy and to provide updated recommendations for management. Original research articles, review articles, and guidelines on HCV in general and specifically in pregnancy were reviewed, as were drug safety profiles from the Food and Drug Administration. Pregnancy appears to have a beneficial effect on the course of maternal chronic HCV infection. However, it is associated with an increased risk of adverse fetal outcomes, including fetal growth restriction and low birth weight, and can be transmitted to the infant in utero or during the peripartum period. No perinatal intervention has been shown to reduce the risk of vertical transmission, but some may increase this risk. To date, no treatment regimens for HCV have been approved for use in pregnancy, but the new ribavirin-free, direct-acting antiviral regimens are being used with high efficacy outside pregnancy. Hepatitis C virus infection in pregnancy generally does not adversely affect maternal well-being but is associated with adverse effects on the fetus because of pregnancy complications and vertical transmission. There are currently no approved treatment regimens for HCV in pregnancy; this should be an active area of research in obstetrics.

Feature Hepatitis: Hepatitis Symptoms, Diagnosis, Treatment & Prevention

Science.gov (United States)

... Navigation Bar Home Current Issue Past Issues Feature Hepatitis Hepatitis: Symptoms, Diagnosis, Treatment & Prevention Past Issues / Spring 2009 ... No appetite Fever Headaches Diagnosis To check for hepatitis viruses, your doctor will test your blood. You ...

Impact of Short Hepatic Vein Reconstruction in Living Donor Adult Liver Transplantation Using a Left Liver Plus Caudate Lobe Graft

Directory of Open Access Journals (Sweden)

Koji Mikami

2010-01-01

Conclusion: Although no definite advantage from the V1 reconstruction was demonstrated, hepatic vein reconstruction with a significantly-sized short hepatic vein might provide an additional margin of safety for marginally-sized liver grafts during the early phase of graft regeneration.

Viral Hepatitis

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... Home A-Z Health Topics Viral hepatitis Viral hepatitis > A-Z Health Topics Viral hepatitis (PDF, 90 ... liver. Source: National Cancer Institute Learn more about hepatitis Watch a video. Learn who is at risk ...

Prevalence of hepatitis B surface antigen sero-positivity and

African Journals Online (AJOL)

2016-07-31

Jul 31, 2016 ... health burden. ... Five hundred and thirty consecutively recruited voluntary blood ... The prevalence of hepatitis infection among the blood donors was 51 (9.6%). ... of countries endemic for HBV infection with a current ... undermining the blood safety in Sub-Sahara Africa .... found in the work of Bhatti et al.

Efficacy and safety of immunosuppressive therapy in the treatment of seronegative hepatitis associated aplastic anemia

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Chen HF

2014-09-01

Full Text Available Hai-Fei Chen,* Bin-Xian Xu, Hong-Shi Shen,* Zheng-Yang Li, Ling-Juan Jin, Jie-Qing Tang, Jing Wang, Jing-Jing Zhu, Long-Mei Qin, Qing-Ya Cui, Yong-Ya Ren, Tian-Qin Wu Department of hematology, 100th hospital of People’s Liberation Army, Suzhou, Jiangsu province, The People’s Republic of China *These authors have contributed equally to this paper Objective: To investigate the clinical characteristics of seronegative hepatitis-associated aplastic anemia (AA (SNHAA and hepatitis B virus (HBV infection complicating AA (HBVAA, and thereby compare the efficacy of immunosuppressive therapy (IST.Methods: An analysis was conducted on the clinical data of ten patients with SNHAA out of 332 cases of AA from our center at AA diagnosis, and on the efficacy of IST. This was compared to 22 cases of HBVAA at AA onset as well as the associated IST outcomes.Results: Nine patients with SNHAA developed severe aplastic anemia, with a median age of 18 years. After IST, six (60% of the SNHAA patients achieved complete remission and two achieved partial remission. The patients with HBVAA had a total response rate of 82.3%. The disease recurred in two HBVAA patients. No statistically significant differences were observed in response rate, mortality, and recurrence rate between both groups. As compared with HBVAA, patients with SNHAA had a shorter interval from the acute episode of hepatitis to AA onset (4 months versus 92 months, P=0.00, a quicker response to IST (2.5 months versus 4.5 months, P=0.018, a lower proportion of bone marrow hematopoietic tissues (20.6% versus 23.6%, P=0.03, and lower white blood cell and absolute neutrophil count (0.8×109/L versus 1.23×109/L and 0.26×109/L versus 0.58×109/L, P=0.026 and P=0.0009, respectively. No significant liver damage or hepatitis B fulminant infection was observed in either group during the follow-up. Conclusion: The prevalence of SNHAA is 3.01%. SNHAA often presents as severe AA and responds to IST quickly

Safety profile of solid lipid nanoparticles loaded with rosmarinic acid for oral use: in vitro and animal approaches.

Science.gov (United States)

Madureira, Ana Raquel; Nunes, Sara; Campos, Débora A; Fernandes, João C; Marques, Cláudia; Zuzarte, Monica; Gullón, Beatriz; Rodríguez-Alcalá, Luís M; Calhau, Conceição; Sarmento, Bruno; Gomes, Ana Maria; Pintado, Maria Manuela; Reis, Flávio

2016-01-01

Rosmarinic acid (RA) possesses several protective bioactivities that have attracted increasing interest by nutraceutical/pharmaceutical industries. Considering the reduced bioavailability after oral use, effective (and safe) delivery systems are crucial to protect RA from gastrointestinal degradation. This study aims to characterize the safety profile of solid lipid nanoparticles produced with Witepsol and Carnauba waxes and loaded with RA, using in vitro and in vivo approaches, focused on genotoxicity and cytotoxicity assays, redox status markers, hematological and biochemical profile, liver and kidney function, gut bacterial microbiota, and fecal fatty acids composition. Free RA and sage extract, empty nanoparticles, or nanoparticles loaded with RA or sage extract (0.15 and 1.5 mg/mL) were evaluated for cell (lymphocytes) viability, necrosis and apoptosis, and antioxidant/prooxidant effects upon DNA. Wistar rats were orally treated for 14 days with vehicle (control) and with Witepsol or Carnauba nanoparticles loaded with RA at 1 and 10 mg/kg body weight/d. Blood, urine, feces, and several tissues were collected for analysis. Free and loaded RA, at 0.15 mg/mL, presented a safe profile, while genotoxic potential was found for the higher dose (1.5 mg/mL), mainly by necrosis. Our data suggest that both types of nanoparticles are safe when loaded with moderate concentrations of RA, without in vitro genotoxicity and cytotoxicity and with an in vivo safety profile in rats orally treated, thus opening new avenues for use in nutraceutical applications.

Hepatitis B

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... B Entire Lesson Viral Hepatitis Menu Menu Viral Hepatitis Viral Hepatitis Home For Veterans and the Public Veterans ... in their blood (sometimes referred to as the hepatitis B viral load) and an unusually high level of a ...

Hepatic Encephalopathy

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Full Text Available ... A Hepatitis B Hepatitis C Intrahepatic Cholestasis of Pregnancy (ICP) Jaundice In Newborns Diseases of the Liver ... A Hepatitis B Hepatitis C Intrahepatic Cholestasis of Pregnancy (ICP) Jaundice In Newborns Diseases of the Liver ...

Alcohol and Hepatitis

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... Home » Living with Hepatitis » Daily Living: Alcohol Viral Hepatitis Menu Menu Viral Hepatitis Viral Hepatitis Home For ... heavy drinking, most heavy drinkers have developed cirrhosis. Hepatitis C and cirrhosis In general, someone with hepatitis ...

Hepatitis C: Treatment

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... Public Home » Hepatitis C » Hepatitis C Treatment Viral Hepatitis Menu Menu Viral Hepatitis Viral Hepatitis Home For ... Enter ZIP code here Enter ZIP code here Hepatitis C Treatment for Veterans and the Public Treatment ...

Safety assessment of genetically modified rice expressing human serum albumin from urine metabonomics and fecal bacterial profile.

Science.gov (United States)

Qi, Xiaozhe; Chen, Siyuan; Sheng, Yao; Guo, Mingzhang; Liu, Yifei; He, Xiaoyun; Huang, Kunlun; Xu, Wentao

2015-02-01

The genetically modified (GM) rice expressing human serum albumin (HSA) is used for non-food purposes; however, its food safety assessment should be conducted due to the probability of accidental mixture with conventional food. In this research, Sprague Dawley rats were fed diets containing 50% (wt/wt) GM rice expressing HSA or non-GM rice for 90 days. Urine metabolites were detected by (1)H NMR to examine the changes of the metabolites in the dynamic process of metabolism. Fecal bacterial profiles were detected by denaturing gradient gel electrophoresis to reflect intestinal health. Additionally, short chain fatty acids and fecal enzymes were investigated. The results showed that compared with rats fed the non-GM rice, some significant differences were observed in rats fed with the GM rice; however, these changes were not significantly different from the control diet group. Additionally, the gut microbiota was associated with blood indexes and urine metabolites. In conclusion, the GM rice diet is as safe as the traditional daily diet. Furthermore, urine metabonomics and fecal bacterial profiles provide a non-invasive food safety assessment rat model for genetically modified crops that are used for non-food/feed purposes. Fecal bacterial profiles have the potential for predicting the change of blood indexes in future. Copyright © 2014 Elsevier Ltd. All rights reserved.

Short and long-term impact of lipectomy on expression profile of hepatic anabolic genes in rats: a high fat and high cholesterol diet-induced obese model.

Science.gov (United States)

Ling, Bey-Leei; Chiu, Chun-Tang; Lu, Hsiu-Chin; Lin, Jin-Jin; Kuo, Chiung-Yin; Chou, Fen-Pi

2014-01-01

To understand the molecular basis of the short and long-term effects of an immediate shortage of energy storage caused by lipectomy on expression profile of genes involved in lipid and carbohydrate metabolism in high fat and high cholesterol diet-induced obese rats. The hepatic mRNA levels of enzymes, regulator and transcription factors involved in glucose and lipid metabolism were analyzed by quantitative real time polymerase chain reaction (RT-qPCR) ten days and eight weeks after lipectomy in obese rats. Body and liver weights and serum biochemical parameters, adiponectin, leptin and insulin were determined. No significant difference was observed on the food intake between the lipectomized and sham-operated groups during the experimental period. Ten days after the operation, the lipectomized animals showed significant higher triacylglycerol, glucose and insulin levels, a lower adiponectin concentration than the sham-operated rats, along with significant higher hepatic mRNA levels of hepatocyte nuclear factor 4α (HNF4α) and the enzymes involved in lipogenesis, sterol biosynthesis and gluconeogenesis. The results of immunohistochemical (IHC) analysis also confirmed increased levels of lipogenic enzymes in the liver of lipectomized versus sham-operated animals. The lipectomized group had a significantly lower adiponectin/leptin ratio that was positively correlated to the level of LDL (r = 0.823, Pshort term enhancement of the expression of hepatic anabolic genes involved in lipid and carbohydrate metabolism was triggered that might eventually lead to the final extra weight gain. These metabolic changes could be the results of reduced circulating adiponectin that further influences the functions of insulin and hepatic HNF4α.

Viral hepatitis in Latin America and the Caribbean: a public health challenge

Directory of Open Access Journals (Sweden)

Núria Díez-Padrisa

2013-10-01

Full Text Available Viral hepatitis (VH is an emergent concern in public health agendas worldwide. More than one million people die annually from hepatitis and 57% and 78% of global cirrhosis and hepatocellular carcinoma cases, respectively, are caused by VH. The burden of disease caused by hepatitis in Latin America and the Caribbean (LAC is high. Data on hepatitis has been collected in several countries, but more accurate and comparable studies are needed. Hepatitis B vaccination and screening of donated blood are routine practices in the region. However, integrated policies covering prevention and control of disease caused by all types of hepatitis viruses are scarce. Existing preventive measures need to be reinforced. Attention must be paid to at-risk populations, awareness campaigns, and water and food safety. Affordable access to diagnosis and treatment, population screening, referral to health services and monitoring of positive cases are among the main challenges currently posed by VH in LAC. The World Health Organization framework and Pan American Health Organization regional strategy, defined in response to resolution WHA63.18 of the World Health Assembly, may help to overcome these difficulties. Successful experiences in the fight against hepatitis in some LAC countries may also provide very interesting solutions for the region.

Maternal chocolate and sucrose soft drink intake induces hepatic steatosis in rat offspring associated with altered lipid gene expression profile

DEFF Research Database (Denmark)

Kjærgaard, Maj; Nilsson, C.; Rosendal, A.

2014-01-01

weight gain and adiposity in offspring born to chow-fed dams. Conclusion: Our results suggest that supplementation of chocolate and soft drink during gestation and lactation contributes to early onset of hepatic steatosis associated with changes in hepatic gene expression and lipid handling....... until weaning, giving four dietary groups. Results: At postnatal day 1, offspring from high-fat/high-sucrose-fed dams were heavier and had increased hepatic triglycerides (TG), hepatic glycogen, blood glucose and plasma insulin compared with offspring from chow-fed dams. Hepatic genes involved in lipid...... oxidation, VLDL transport and insulin receptor were down-regulated, whereas FGF21 expression was up-regulated. Independent of postnatal litter size, offspring from high-fat/high-sucrose-fed dams aged 21 days had still increased hepatic TG and up-regulated FGF21 expression, while plasma insulin started...

Direct measurements of safety factor profiles with motional Stark effect for KSTAR tokamak discharges with internal transport barriers

Science.gov (United States)

Ko, J.; Chung, J.

2017-06-01

The safety factor profile evolutions have been measured from the plasma discharges with the external current drive mechanism such as the multi-ion-source neutral beam injection for the Korea Superconducting Tokamak Advanced Research (KSTAR) for the first time. This measurement has been possible by the newly installed motional Stark effect (MSE) diagnostic system that utilizes the polarized Balmer-alpha emission from the energetic neutral deuterium atoms induced by the Stark effect under the Lorentz electric field. The 25-channel KSTAR MSE diagnostic is based on the conventional photoelastic modulator approach with the spatial and temporal resolutions less than 2 cm (for the most of the channels except 2 to 3 channels inside the magnetic axis) and about 10 ms, respectively. The strong Faraday rotation imposed on the optical elements in the diagnostic system is calibrated out from a separate and well-designed polarization measurement procedure using an in-vessel reference polarizer during the toroidal-field ramp-up phase before the plasma experiment starts. The combination of the non-inductive current drive during the ramp-up and shape control enables the formation of the internal transport barrier where the pitch angle profiles indicate flat or slightly hollow profiles in the safety factor.

Occult hepatitis B among Iranian hepatitis C patients

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Ahmad shavakhi

2009-02-01

Full Text Available

• BACKGROUND: Occult hepatitis B is defined as presence of HBV DNA in tissue or serum without hepatitis B surface antigen. The aim of this study is to determine frequency of occult hepatitis B among hepatitis C patients in Tehran and compare the route of transmission and liver enzymes between positive and negative HBV DNA patients.
• METHODS: In a cross sectional study, serum of 103 hepatitis C cases (79.6% men and 20.4% women were analyzed for s, x and core genes via a nested polymerase chain reaction technique.
• RESULTS: HBV DNA was detectable in serum of 20 patients (19.4%. No significant difference in age, sex and route of transmission were seen in HBV DNA positive and negative patients. In HBV DNA positive and negative groups, mean of AST was 73, 47 (p < 0.05 and mean of ALT was 76 and 36 respectively (p < 0.05.
• CONCLUSION: Occult hepatitis B was observed in a considerable number of hepatitis C patients in Tehran. It was associated with elevation in liver enzyme but was not related to route of transmission.
• KEY WORD: Occult hepatitis B, hepatitis C, cirrhosis.

Hepatic artery infusion (HAI) for hepatic metastases in combination with hepatic resection and hepatic radiation

International Nuclear Information System (INIS)

Merrick, H.W.; Dobelbower, R.R.; Ringleint, J.F.; Skeel, R.T.

1986-01-01

Renewed interest in hepatic artery infusion has been stimulated by the development of a totally implantable pump which eliminates many of the problems encountered by the external pumps and catheters. As the potential benefit of hepatic artery infusion would be greater if either all gross disease were removed by prior resection, or alternatively, if non-resectable disease were irradiated in conjunction with hepatic artery infusion, the authors initiated a phase I-II trial to evaluate combined modality therapy

Short and long-term impact of lipectomy on expression profile of hepatic anabolic genes in rats: a high fat and high cholesterol diet-induced obese model.

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Bey-Leei Ling

Full Text Available OBJECTIVE: To understand the molecular basis of the short and long-term effects of an immediate shortage of energy storage caused by lipectomy on expression profile of genes involved in lipid and carbohydrate metabolism in high fat and high cholesterol diet-induced obese rats. METHODS: The hepatic mRNA levels of enzymes, regulator and transcription factors involved in glucose and lipid metabolism were analyzed by quantitative real time polymerase chain reaction (RT-qPCR ten days and eight weeks after lipectomy in obese rats. Body and liver weights and serum biochemical parameters, adiponectin, leptin and insulin were determined. RESULTS: No significant difference was observed on the food intake between the lipectomized and sham-operated groups during the experimental period. Ten days after the operation, the lipectomized animals showed significant higher triacylglycerol, glucose and insulin levels, a lower adiponectin concentration than the sham-operated rats, along with significant higher hepatic mRNA levels of hepatocyte nuclear factor 4α (HNF4α and the enzymes involved in lipogenesis, sterol biosynthesis and gluconeogenesis. The results of immunohistochemical (IHC analysis also confirmed increased levels of lipogenic enzymes in the liver of lipectomized versus sham-operated animals. The lipectomized group had a significantly lower adiponectin/leptin ratio that was positively correlated to the level of LDL (r = 0.823, P<0.05 and negatively to glucose and insulin (r = -0.821 and -0.892 respectively, P<0.05. Eight weeks after the operation, the lipectomized animals revealed significant higher body and liver weights, weight gain, liver to body weight ratio, hepatic triacylglycerol and serum insulin level. CONCLUSIONS: In response to lipectomy a short term enhancement of the expression of hepatic anabolic genes involved in lipid and carbohydrate metabolism was triggered that might eventually lead to the final extra weight gain. These

Insulin Regulates Hepatic Triglyceride Secretion and Lipid Content via Signaling in the Brain.

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Scherer, Thomas; Lindtner, Claudia; O'Hare, James; Hackl, Martina; Zielinski, Elizabeth; Freudenthaler, Angelika; Baumgartner-Parzer, Sabina; Tödter, Klaus; Heeren, Joerg; Krššák, Martin; Scheja, Ludger; Fürnsinn, Clemens; Buettner, Christoph

2016-06-01

Hepatic steatosis is common in obesity and insulin resistance and results from a net retention of lipids in the liver. A key mechanism to prevent steatosis is to increase secretion of triglycerides (TG) packaged as VLDLs. Insulin controls nutrient partitioning via signaling through its cognate receptor in peripheral target organs such as liver, muscle, and adipose tissue and via signaling in the central nervous system (CNS) to orchestrate organ cross talk. While hepatic insulin signaling is known to suppress VLDL production from the liver, it is unknown whether brain insulin signaling independently regulates hepatic VLDL secretion. Here, we show that in conscious, unrestrained male Sprague Dawley rats the infusion of insulin into the third ventricle acutely increased hepatic TG secretion. Chronic infusion of insulin into the CNS via osmotic minipumps reduced the hepatic lipid content as assessed by noninvasive (1)H-MRS and lipid profiling independent of changes in hepatic de novo lipogenesis and food intake. In mice that lack the insulin receptor in the brain, hepatic TG secretion was reduced compared with wild-type littermate controls. These studies identify brain insulin as an important permissive factor in hepatic VLDL secretion that protects against hepatic steatosis. © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Regressive Effect of Myricetin on Hepatic Steatosis in Mice Fed a High-Fat Diet

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Shu-Fang Xia

2016-12-01

Full Text Available Myricetin is an effective antioxidant in the treatment of obesity and obesity-related metabolic disorders. The objective of this study was to explore the regressive effect of myricetin on pre-existing hepatic steatosis induced by high-fat diet (HFD. C57BL/6 mice were fed either a standard diet or a HFD for 12 weeks and then half of the mice were treated with myricetin (0.12% in the diet, w/w while on their respective diets for further 12 weeks. Myricetin treatment significantly alleviated HFD-induced steatosis, decreased hepatic lipid accumulation and thiobarbituric acid reactive substance (TBARS levels, and increased antioxidative enzyme activities, including catalase (CAT, superoxide dismutase (SOD, and glutathione peroxidase (GPx activities. Microarray analysis of hepatic gene expression profiles showed that myricetin significantly altered the expression profiles of 177 genes which were involved in 12 biological pathways, including the peroxisome proliferator activated receptor (PPAR signaling pathway and peroxisome. Further research indicated that myricetin elevated hepatic nuclear Nrf2 translocation, increased the protein expression of heme oxygenase-1 (HO-1 and NAD(PH quinone dehydrogenase 1 (NQO1, reduced the protein expression of PPARγ, and normalized the expressions of genes that were involved in peroxisome and the PPAR signaling pathway. Our data indicated that myricetin might represent an effective therapeutic agent to treat HFD-induced hepatic steatosis via activating the Nrf2 pathway and the PPAR signaling pathway.

Reporting and understanding the safety and adverse effect profile of mobile apps for psychosocial interventions: An update.

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Naeem, Farooq; Gire, Nadeem; Xiang, Shuo; Yang, Megan; Syed, Yumeen; Shokraneh, Farhad; Adams, Clive; Farooq, Saeed

2016-06-22

Recent years have seen a rapidly increasing trend towards the delivery of health technology through mobile devices. Smartphones and tablet devices are thus becoming increasingly popular for accessing information and a wide range of services, including health care services. Modern mobile apps can be used for a variety of reasons, ranging from education for the patients and assistance to clinicians to delivery of interventions. Mobile phone apps have also been established to benefit patients in a scope of interventions across numerous medical specialties and treatment modalities. Medical apps have their advantages and disadvantages. It is important that clinicians have access to knowledge to make decisions regarding the use of medical apps on the basis of risk-benefit ratio. Mobile apps that deliver psycho social interventions offer unique challenges and opportunities. A number of reviews have highlighted the potential use of such apps. There is a need to describe, report and study their side effects too. The adverse effects associated with these apps can broadly be divided into: (1) those resulting from the security and safety concerns; (2) those arising from the use of a particular psycho social intervention; and (3) those due to the interaction with digital technology. There is a need to refine and reconsider the safety and adverse effects in this area. The safety profile of a mobile PSI app should describe its safety profile in: (1) privacy and security; (2) adverse effects of psychotherapy; and (3) adverse effects unique to the use of apps and the internet. This is, however, a very new area and further research and reporting is required to inform clinical decision making.

HIV, hepatitis B, and hepatitis C in Zambia

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Kenneth C Kapembwa

2011-01-01

Full Text Available Objectives : Epidemiologic data of HIV and viral hepatitis coinfection are needed in sub-Saharan Africa to guide health policy for hepatitis screening and optimized antiretroviral therapy (ART. Materials and Methods: We screened 323 HIV-infected, ART-eligible adults for hepatitis B surface antigen (HBsAg and hepatitis C antibody (HCV Ab at a tertiary hospital in Lusaka, Zambia. We collected basic demographic, medical, and laboratory data to determine predictors for coinfection. Results: Of 323 enrolled patients, 32 (9.9%; 95% CI=6.7-13.2% were HBsAg positive, while 4 (1.2%; 95% CI=0.03-2.4% were HCV Ab positive. Patients with hepatitis B coinfection were more likely to be 200 IU/L was uncommon and did not differ between the two groups (3.4% vs. 2.3%; P=0.5. We were unable to determine predictors of hepatitis C infection due to the low prevalence of disease. Conclusions: HIV and hepatitis B coinfection was common among patients initiating ART at this tertiary care facility. Routine screening for hepatitis B should be considered for HIV-infected persons in southern Africa.

Hepatitis (For Parents)

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... Staying Safe Videos for Educators Search English Español Hepatitis KidsHealth / For Parents / Hepatitis Print en español Hepatitis What Is Hepatitis? Hepatitis is an inflammation of the liver. The ...

Patient safety climate profiles across time: Strength and level of safety climate associated with a quality improvement program in Switzerland—A cross-sectional survey study

Science.gov (United States)

Mascherek, Anna C.

2017-01-01

Safety Climate has been acknowledged as an unspecific factor influencing patient safety. However, studies rarely provide in-depth analysis of climate data. As a helpful approach, the concept of “climate strength” has been proposed. In the present study we tested the hypotheses that even if safety climate remains stable on mean-level across time, differences might be evident in strength or shape. The data of two hospitals participating in a large national quality improvement program were analysed for differences in climate profiles at two measurement occasions. We analysed differences on mean-level, differences in percent problematic response, agreement within groups, and frequency histograms in two large hospitals in Switzerland at two measurement occasions (2013 and 2015) applying the Safety Climate Survey. In total, survey responses of 1193 individuals were included in the analyses. Overall, small but significant differences on mean-level of safety climate emerged for some subgroups. Also, although agreement was strong at both time-points within groups, tendencies of divergence or consensus were present in both hospitals. Depending on subgroup and analyses chosen, differences were more or less pronounced. The present study illustrated that taking several measures into account and describing safety climate from different perspectives is necessary in order to fully understand differences and trends within groups and to develop interventions addressing the needs of different groups more precisely. PMID:28753633

Correlation of hepatic 18F-fluorodeoxyglucose uptake with fatty liver

International Nuclear Information System (INIS)

An, Young Sil; Yoon, Joon Kee; Hong, Seon Pyo; Joh, Chul Woo; Yoon, Seok Nam

2006-01-01

Liver demonstrates heterogeneous FDG uptake and sometimes it shows abnormally increased uptake even though there is no malignant tissue. However, there was no previous study to correlate these various pattern of hepatic FDG uptake with benign liver disease. Therefore, we evaluated the significance of hepatic FDG uptake associated with various clinical factors including fatty liver, liver function tests and lipid profiles. We reviewed a total of 188 patients (male/female: 120/68, mean age: 50 ± 9) who underwent PET/CT for screening of malignancy. Patients with DM, impaired glucose tolerance, previous severe hepatic disease or long-term medication history were excluded. The FDG uptake in liver was analyzed semi-quantitatively using ROI on transaxial images (segment 8) and we compared mean standardized uptake value (SUV) between fatty liver and non-fatty liver group. We also evaluated the correlation between hepatic FDG uptake and various clinical factors including serum liver function test (ALT, AST), γ -GT, total cholesterol and triglyceride concentration. The effect of alcoholic history and body mass index on hepatic FDG uptake was analyzed within the fatty liver patients. The hepatic FDG uptake of fatty liver group was significantly higher than that of non-fatty liver group. Serum total cholesterol and triglyceride concentration showed significant correlation with hepatic FDG uptake. However, there was no significant correlation between other factors (ALT, AST, and γ -GT) and FDG uptake. Also there was no difference of mean SUV between normal and abnormal groups on the basis of alcoholic history and body mass index within fatty liver patients. Fatty liver and high serum triglyceride concentration were the independent factors affecting hepatic FDG uptake according to multivariate analysis. In conclusion, hepatic FDG uptake was strongly correlated with fatty liver and serum triglyceride concentration

Epidemiology of hepatitis E virus in China: results from the Third National Viral Hepatitis Prevalence Survey, 2005-2006.

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Zhiyuan Jia

Full Text Available In China, hepatitis E virus (HEV is prevalent and causes disease, but its epidemiological profile is not well understood. We used a commercial enzyme-linked immunosorbent assay to detect total antibodies to hepatitis E virus in 15,862 serum samples collected during the Third National Viral Hepatitis Prevalence Survey. The results were analyzed to calculate estimates of HEV seroprevalence and to examine the effects of some putative risk factors. The seroprevalence of HEV in the general Chinese population during the period from 2005 through 2006 was 23.46% (95% confidence interval [CI], 18.41%-28.50%. The farming population, the age group of 15-60 year olds, and those living in the Midwest or Mideast region and in Xinjiang province had the highest seroprevalence estimates. The prevalence of HEV is high in China. The seroprevalence rate of HEV shows an unbalanced distribution among areas with different geographic location and economic development levels. The characteristics of the distribution associated may be due to the route of HEV transmission (via contaminated water or animal reservoirs. Within the same region, the seroprevalence of HEV is generally increased with age.

Rapid development of fasting-induced hepatic lipidosis in the American mink (Neovison vison): effects of food deprivation and re-alimentation on body fat depots, tissue fatty acid profiles, hematology and endocrinology.

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Rouvinen-Watt, Kirsti; Mustonen, Anne-Mari; Conway, Rebecca; Pal, Catherine; Harris, Lora; Saarela, Seppo; Strandberg, Ursula; Nieminen, Petteri

2010-02-01

Hepatic lipidosis is a common pathological finding in the American mink (Neovison vison) and can be caused by nutritional imbalance due to obesity or rapid body weight loss. The objectives of the present study were to investigate the timeline and characterize the development of hepatic lipidosis in mink in response to 0-7 days of food deprivation and liver recovery after 28 days of re-feeding. We report here the effects on hematological and endocrine variables, body fat mobilization, the development of hepatic lipidosis and the alterations in the liver lipid classes and tissue fatty acid (FA) sums. Food deprivation resulted in the rapid mobilization of body fat, most notably visceral, causing elevated hepatosomatic index and increased liver triacylglycerol content. The increased absolute amounts of liver total phospholipids and phosphatidylcholine suggested endoplasmic reticulum stress. The hepatic lipid infiltration and the altered liver lipid profiles were associated with a significantly reduced proportion of n-3 polyunsaturated FA (PUFA) in the livers and the decrease was more evident in the females. Likewise, re-feeding of the female mink resulted in a more pronounced recovery of the liver n-3 PUFA. The rapid decrease in the n-3/n-6 PUFA ratio in response to food deprivation could trigger an inflammatory response in the liver. This could be a key contributor to the pathophysiology of fatty liver disease in mink influencing disease progression.

Hepatitis B reactivation and current clinical impact Reactivación de la hepatitis B y su impacto clínico actual

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B. Álvarez Suárez

2010-09-01

Full Text Available Hepatitis B virus (HBV reactivation results from increased viral replication in inactive carriers or patients with prior infection with HBV. Reactivation may occur spontaneously or secondary to immunomodulating or immunosuppressive chemotherapy. Reactivation may manifest with no symptoms but on occasion results in acute or even severe acute hepatitis. Prevention is the best management approach, hence HBV screening using serology should be performed for all patients undergoing any immunomodulating, immunosuppressive or chemotherapeutic treatment. Antiviral prophylaxis has proven effective in inactive carriers and in some patients with former infection with HBV undergoing selected immunosuppressive therapies.La reactivación del virus de la hepatitis B se debe a un aumento de la replicación del virus en pacientes portadores inactivos o con infecciones pasadas de VHB. La reactivación puede producirse espontáneamente o de manera secundaria a tratamientos de quimioterapia, inmunomoduladores o inmunosupresores. La reactivación puede manifestarse de manera asintomática pero en algunos casos puede causar hepatitis agudas e incluso hepatitis agudas graves. El mejor tratamiento es la prevención por lo que se debe realizar un cribado del VHB mediante una serología a todos los pacientes que vayan a someterse a cualquier tratamiento inmunomodulador, de quimioterapia o inmunosupresor. El tratamiento profiláctico antiviral ha demostrado ser eficaz en los pacientes portadores inactivos y en algunos pacientes con infecciones pasadas de VHB sometidos a ciertos tratamientos inmunosupresores.

Hepatitis B (HBV)

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... Staying Safe Videos for Educators Search English Español Hepatitis B KidsHealth / For Teens / Hepatitis B What's in ... Prevented? Print en español Hepatitis B What Is Hepatitis B? Hepatitis B is an infection of the ...

Hepatitis A Vaccine

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Twinrix® (as a combination product containing Hepatitis A Vaccine, Hepatitis B Vaccine) ... Why get vaccinated against hepatitis A?Hepatitis A is a serious liver disease. It is caused by the hepatitis A virus (HAV). HAV is spread from ...

Development, Production, and Postmarketing Surveillance of Hepatitis A Vaccines in China

Science.gov (United States)

Cui, Fuqiang; Liang, Xiaofeng; Wang, Fuzhen; Zheng, Hui; Hutin, Yvan J; Yang, Weizhong

2014-01-01

China has long experience using live attenuated and inactivated vaccines against hepatitis A virus (HAV) infection. We summarize this experience and provide recent data on adverse events after immunization (AEFIs) with hepatitis A vaccines in China. We reviewed the published literature (in Chinese and English) and the published Chinese regulatory documents on hepatitis A vaccine development, production, and postmarketing surveillance of AEFI. We described the safety, immunogenicity, and efficacy of hepatitis A vaccines and horizontal transmission of live HAV vaccine in China. In clinical trials, live HAV vaccine was associated with fever (0.4%–5% of vaccinees), rash (0%–1.1%), and elevated alanine aminotransferase (0.015%). Inactivated HAV vaccine was associated with fever (1%–8%), but no serious AEFIs were reported. Live HAV vaccine had seroconversion rates of 83% to 91%, while inactivated HAV vaccine had seroconversion rates of 95% to 100%. Community trials showed efficacy rates of 90% to 95% for live HAV and 95% to 100% for inactivated HAV vaccine. Postmarketing surveillance showed that HAV vaccination resulted in an AEFI incidence rate of 34 per million vaccinees, which accounted for 0.7% of adverse events reported to the China AEFI monitoring system. There was no difference in AEFI rates between live and inactivated HAV vaccines. Live and inactivated HAV vaccines manufactured in China were immunogenic, effective, and safe. Live HAV vaccine had substantial horizontal transmission due to vaccine virus shedding; thus, further monitoring of the safety of virus shedding is warranted. PMID:24681843

Epidemiology of Hepatitis C Virus in the private blood banking ...

African Journals Online (AJOL)

Background: Hepatitis C Virus (HCV) is an agent of Transfusion Transmissible Infection (TTI) which serves as a threat to blood safety and sufficiency of blood and blood products supply. Objectives: This study aimed at determining the distribution patterns of HCV among potential blood donors in a private Blood Bank in ...

The effects of the non-contingent presentation of safety signals on the elimination of safety behaviors: An experimental comparison between individuals with low and high obsessive-compulsive profiles.

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Angelakis, Ioannis; Austin, Jennifer L

2018-06-01

Safety behaviors, defined as engagement in avoidance within safe environments, are a key symptom of obsessive-compulsive and related disorders. They may interfere with daily functioning and as such their emission should be reduced. The purpose of the current study is to investigate the effects of the non-contingent presentation of safety signals (cues produced by safety behaviors) on reducing safety behaviors in participants self-reporting low and high OCD profiles. In total, 32 participants were asked to play a game to gain points and avoid their loss. After having developed avoidance behavior, evidenced by maintaining all of their earned points, they were exposed to safe environments where no point loss was programmed. In Test 1, safety cues (blue bar) were produced contingent on performing safety behaviors. In Test 2, safety cues were presented continuously without any response requirement. Findings demonstrated that high OCD group displayed higher rates of safety behaviors than low OCD group. However, exposure to the non-contingent presentation of safety signals eliminated their emission in both groups. Future studies need to evaluate the effects of different non-contingent schedules on the suppression of safety behaviors. These findings contribute to the literature by demonstrating that non-contingent introduction of safety signals eliminated safety behaviors completely, even in high OCD participants, who performed safety behavior at higher rates. Such a treatment protocol may ameliorate exposure therapy in which response prevention constitutes a key element and is generally associated with increased drop-out rates. Copyright © 2017 Elsevier Ltd. All rights reserved.

Hepatitis C: Managing Pain

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... Pain: Entire Lesson Viral Hepatitis Menu Menu Viral Hepatitis Viral Hepatitis Home For Veterans and the Public Veterans and the Public Home Hepatitis A Hepatitis B Hepatitis C Hepatitis C Home Getting ...

[Hepatitis E virus: Blood transfusion implications].

Science.gov (United States)

Gallian, P; Piquet, Y; Assal, A; Djoudi, R; Chiaroni, J; Izopet, J; Tiberghien, P

2014-11-01

Hepatitis E virus (HEV) is a non-enveloped RNA virus transmitted by the fecal-oral route. Autochthonous hepatitis E occurring in developed countries is caused by genotypes 3 and 4 and is a zoonotic infection. Humans are infected mostly after ingestion of undercooked meat from infected animals. Most HEV 3 and 4 infections are clinically inapparent. However, genotype 3 (HEV 3) can lead to chronic hepatitis in immuno-compromised patients such as organ-transplant recipients and patients with haematological malignancies. In Europe, HEV 3 is implicated in transfusion-transmitted HEV infection. In France, as observed in several European countries, prevalence of HEV RNA and specific IgG antibodies are high indicating that viral circulation is important. The systematic HEV NAT screening of blood donations used for preparation of solvent detergent plasma indicate that 1 to 2218 donation is infected by HEV RNA. The need or implementation's impacts of safety measures to prevent HEV transmission by blood transfusion are under reflexion by French's health authorities. The HEV NAT screening is the only available tool of prevention. Alternative strategies are under investigation including individual or mini pool NAT testing all or part of blood donations. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Hypoksisk hepatitis

DEFF Research Database (Denmark)

Amadid, Hanan; Schiødt, Frank Vinholt

2014-01-01

Hypoxic hepatitis (HH), also known as ischaemic hepatitis or shock liver, is an acute liver injury caused by hepatic hypoxia. Cardiac failure, respiratory failure and septic shock are the main underlying conditions. In each of these conditions, several haemodynamic mechanisms lead to hepatic...... hypoxia. A shock state is observed in only 50% of cases. Thus, shock liver and ischaemic hepatitis are misnomers. HH can be a diagnostic pitfall but the diagnosis can be established when three criteria are met. Prognosis is poor and prompt identification and treatment of the underlying conditions...

Chronic Hepatitis B with Spontaneous Severe Acute Exacerbation

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Wei-Lun Tsai

2015-11-01

Full Text Available Chronic hepatitis B virus (HBV infection is a major global health problem with an estimated 400 million HBV carriers worldwide. In the natural history of chronic hepatitis B (CHB, spontaneous acute exacerbation (AE is not uncommon, with a cumulative incidence of 10%–30% every year. While exacerbations can be mild, some patients may develop hepatic decompensation and even die. The underlying pathogenesis is possibly related to the activation of cytotoxic T lymphocyte-mediated immune response against HBV. An upsurge of serum HBV DNA usually precedes the rise of alanine aminotransferase (ALT and bilirubin. Whether antiviral treatment can benefit CHB with severe AE remains controversial, but early nucleos(tide analogues treatment seemed to be associated with an improved outcome. There has been no randomized study that compared the effects of different nucleos(tide analogues (NA in the setting of CHB with severe AE. However, potent NAs with good resistance profiles are recommended. In this review, we summarized current knowledge regarding the natural history, pathogenetic mechanisms, and therapeutic options of CHB with severe AE.

Investigation of hepatic fibrosis with synchrotron X-ray diffraction enhanced imaging

International Nuclear Information System (INIS)

Li Hui; Beijing Univ., Health Science Center, Beijing; Wang Xueyan; Zhao Tao; Hu Chunhong; Lu Weiyuan; Luo Shuqian; Wang Tailing; Wang Baoen; Zhao Xinyan; Zhu Peiping; Huang Wanxia; Yuan Qingxi; Wang Junyue

2008-01-01

In this paper, imaging investigation of hepatic fibrosis in rats induced by human albumin with hard X-ray diffraction enhanced imaging (DEI) is reported. The experiments were performed at 4W1A beamline of Beijing Synchrotron Radiation Facility (BSRF). The results show that great differences can be observed in DEI images between the normal and diseased rats in different stages of liver fibrosis. The difference can also be revealed by the profile curve and texture measurements on regions of interest. The results show that DEI may be a potential way for diagnosis of hepatic fibrosis. (authors)

Sofosbuvir treatment and hepatitis C virus infection

Science.gov (United States)

Nakamura, Masato; Kanda, Tatsuo; Haga, Yuki; Sasaki, Reina; Wu, Shuang; Nakamoto, Shingo; Yasui, Shin; Arai, Makoto; Imazeki, Fumio; Yokosuka, Osamu

2016-01-01

Hepatitis C virus (HCV) infection is a serious problem worldwide. The use of interferon-based therapy has made HCV eradication challenging. The recent appearance of direct-acting antiviral agents (DAAs) has changed HCV therapy. Combining the use of DAAs with peginterferon and ribavirin has improved treatment efficacy. Furthermore, the combination of different orally administered DAAs has enabled interferon-free therapy with much higher efficacy and safety. In particular, sofosbuvir, a nucleotide-based NS5B inhibitor, prevents HCV RNA synthesis by acting as a “chain terminator”. Treatment with sofosbuvir has attained an extremely high rate of sustained virologic response. The current review summarizes the efficacy and safety of sofosbuvir therapy. PMID:26839641

Final Results of the Telaprevir Access Program: FibroScan Values Predict Safety and Efficacy in Hepatitis C Patients with Advanced Fibrosis or Cirrhosis.

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Antonia Lepida

Full Text Available Liver stiffness determined by transient elastography is correlated with hepatic fibrosis stage and has high accuracy for detecting severe fibrosis and cirrhosis in chronic hepatitis C patients. We evaluated the clinical value of baseline FibroScan values for the prediction of safety and efficacy of telaprevir-based therapy in patients with advanced fibrosis and cirrhosis in the telaprevir Early Access Program HEP3002.1,772 patients with HCV-1 and bridging fibrosis or cirrhosis were treated with telaprevir plus pegylated interferon-α and ribavirin (PR for 12 weeks followed by PR alone, the total treatment duration depending on virological response and previous response type. Liver fibrosis stage was determined either by liver biopsy or by non-invasive markers. 1,282 patients (72% had disease stage assessed by FibroScan; among those 46% were classified as Metavir F3 at baseline and 54% as F4.Overall, 1,139 patients (64% achieved a sustained virological response (SVR by intention-to-treat analysis. Baseline FibroScan values were tested for association with SVR and the occurrence of adverse events. By univariate analysis, higher baseline FibroScan values were predictive of lower sustained virological response rates and treatment-related anemia. By multivariate analysis, FibroScan was no longer statistically significant as an independent predictor, but higher FibroScan values were correlated with the occurrence of infections and serious adverse events.FibroScan has a limited utility as a predictor of safety and efficacy in patients treated with telaprevir-based triple therapy. Nevertheless it can be used in association with other clinical and biological parameters to help determine patients who will benefit from the triple regiments.ClinicalTrials.gov NCT01508286.

Factors in enhancing blood safety by nucleic acid technology testing for human immunodeficiency virus, hepatitis C virus and hepatitis B virus.

Science.gov (United States)

Shyamala, Venkatakrishna

2014-01-01

In the last few decades through an awareness of transfusion transmitted infections (TTI), a majority of countries have mandated serology based blood screening assays for Human immunodeficiency virus (HIV), Hepatitis C virus (HCV), and Hepatitis B virus (HBV). However, despite improved serology assays, the transfusion transmission of HIV, HCV, and HBV continues, primarily due to release of serology negative units that are infectious because of the window period (WP) and occult HBV infections (OBI). Effective mode of nucleic acid technology (NAT) testing of the viruses can be used to minimize the risk of TTIs. This review compiles the examples of NAT testing failures for all three viruses; analyzes the causes for failure, and the suggestions from retrospective studies to minimize such failures. The results suggest the safest path to be individual donation testing (ID) format for highest sensitivity, and detection of multiple regions for rapidly mutating and recombining viruses. The role of blood screening in the context of the donation and transfusion practices in India, the donor population, and the epidemiology is also discussed. World wide, as the public awareness of TTIs increases, as the recipient rights for safe blood are legally upheld, as the possibility to manage diseases such as hepatitis through expensive and prolonged treatment becomes accessible, and the societal responsibility to shoulder the health costs as in the case for HIV becomes routine, there is much to gain by preventing infections than treating diseases.

Factors in enhancing blood safety by nucleic acid technology testing for human immunodeficiency virus, hepatitis C virus and hepatitis B virus

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Venkatakrishna Shyamala

2014-01-01

Full Text Available In the last few decades through an awareness of transfusion transmitted infections (TTI, a majority of countries have mandated serology based blood screening assays for Human immunodeficiency virus (HIV, Hepatitis C virus (HCV, and Hepatitis B virus (HBV. However, despite improved serology assays, the transfusion transmission of HIV, HCV, and HBV continues, primarily due to release of serology negative units that are infectious because of the window period (WP and occult HBV infections (OBI. Effective mode of nucleic acid technology (NAT testing of the viruses can be used to minimize the risk of TTIs. This review compiles the examples of NAT testing failures for all three viruses; analyzes the causes for failure, and the suggestions from retrospective studies to minimize such failures. The results suggest the safest path to be individual donation testing (ID format for highest sensitivity, and detection of multiple regions for rapidly mutating and recombining viruses. The role of blood screening in the context of the donation and transfusion practices in India, the donor population, and the epidemiology is also discussed. World wide, as the public awareness of TTIs increases, as the recipient rights for safe blood are legally upheld, as the possibility to manage diseases such as hepatitis through expensive and prolonged treatment becomes accessible, and the societal responsibility to shoulder the health costs as in the case for HIV becomes routine, there is much to gain by preventing infections than treating diseases.

Changing Epidemiological Characteristics of Hepatitis A in Zhejiang Province, China: Increased Susceptibility in Adults.

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Zhifang Wang

Full Text Available Hepatitis A is a common acute hepatitis caused by hepatitis A virus (HAV. Annually, it affects 1.4 million people worldwide. Between 1991 and 1994, HAV infections were highly endemic in Zhejiang Province (China, with 78,720 reported HAV infections per year. Hepatitis A vaccine came on the market in 1995 and was implemented for voluntary immunization. Since 2008, hepatitis A vaccine has been integrated into the national childhood routine immunization program.To understand the current epidemiological profile of hepatitis A in Zhejiang Province since hepatitis A vaccine has been available for nearly two decades.This study used the 2005-2014 National Notifiable Diseases Reporting System data to evaluate the incidence rate of notified hepatitis A cases in Zhejiang Province.The overall trend of incidence rate of notified hepatitis A cases significantly decreased from 2005 to 2014 (P< 0.001. During the study period, the reported incidence rate in individuals aged ≤19 years declined to the historically lowest record in 2014. Compared with individuals aged ≤19 years, those aged ≥20 years showed the highest incidence rate (P< 0.001. Majority of HAV infected cases were Laborers, accounting for approximately 70% of reported cases.Childhood immunization strategy with hepatitis A vaccine seemed to be effective in decreasing notified hepatitis A incidence rate in individuals aged ≤19 years. Those aged ≥20 years were observed to be the most susceptible population. The vast majority of hepatitis A cases were notified among Laborers. Therefore, we strongly suggest that future preventive and control measures should focus more on adults, particularly Laborers, in addition to the current childhood hepatitis A vaccination programme.

Gene expression profiling reveals multiple toxicity endpoints induced by hepatotoxicants

Energy Technology Data Exchange (ETDEWEB)

Huang Qihong; Jin Xidong; Gaillard, Elias T.; Knight, Brian L.; Pack, Franklin D.; Stoltz, James H.; Jayadev, Supriya; Blanchard, Kerry T

2004-05-18

Microarray technology continues to gain increased acceptance in the drug development process, particularly at the stage of toxicology and safety assessment. In the current study, microarrays were used to investigate gene expression changes associated with hepatotoxicity, the most commonly reported clinical liability with pharmaceutical agents. Acetaminophen, methotrexate, methapyrilene, furan and phenytoin were used as benchmark compounds capable of inducing specific but different types of hepatotoxicity. The goal of the work was to define gene expression profiles capable of distinguishing the different subtypes of hepatotoxicity. Sprague-Dawley rats were orally dosed with acetaminophen (single dose, 4500 mg/kg for 6, 24 and 72 h), methotrexate (1 mg/kg per day for 1, 7 and 14 days), methapyrilene (100 mg/kg per day for 3 and 7 days), furan (40 mg/kg per day for 1, 3, 7 and 14 days) or phenytoin (300 mg/kg per day for 14 days). Hepatic gene expression was assessed using toxicology-specific gene arrays containing 684 target genes or expressed sequence tags (ESTs). Principal component analysis (PCA) of gene expression data was able to provide a clear distinction of each compound, suggesting that gene expression data can be used to discern different hepatotoxic agents and toxicity endpoints. Gene expression data were applied to the multiplicity-adjusted permutation test and significantly changed genes were categorized and correlated to hepatotoxic endpoints. Repression of enzymes involved in lipid oxidation (acyl-CoA dehydrogenase, medium chain, enoyl CoA hydratase, very long-chain acyl-CoA synthetase) were associated with microvesicular lipidosis. Likewise, subsets of genes associated with hepatotocellular necrosis, inflammation, hepatitis, bile duct hyperplasia and fibrosis have been identified. The current study illustrates that expression profiling can be used to: (1) distinguish different hepatotoxic endpoints; (2) predict the development of toxic endpoints; and

Nur77 modulates hepatic lipid metabolism through suppression of SREBP1c activity

International Nuclear Information System (INIS)

Pols, Thijs W.H.; Ottenhoff, Roelof; Vos, Mariska; Levels, Johannes H.M.; Quax, Paul H.A.; Meijers, Joost C.M.; Pannekoek, Hans; Groen, Albert K.; Vries, Carlie J.M. de

2008-01-01

NR4A nuclear receptors are induced in the liver upon fasting and regulate hepatic gluconeogenesis. Here, we studied the role of nuclear receptor Nur77 (NR4A1) in hepatic lipid metabolism. We generated mice expressing hepatic Nur77 using adenoviral vectors, and demonstrate that these mice exhibit a modulation of the plasma lipid profile and a reduction in hepatic triglyceride. Expression analysis of >25 key genes involved in lipid metabolism revealed that Nur77 inhibits SREBP1c expression. This results in decreased SREBP1c activity as is illustrated by reduced expression of its target genes stearoyl-coA desaturase-1, mitochondrial glycerol-3-phosphate acyltransferase, fatty acid synthase and the LDL receptor, and provides a mechanism for the physiological changes observed in response to Nur77. Expression of LXR target genes Abcg5 and Abcg8 is reduced by Nur77, and may suggest involvement of LXR in the inhibitory action of Nur77 on SREBP1c expression. Taken together, our study demonstrates that Nur77 modulates hepatic lipid metabolism through suppression of SREBP1c activity

Hepatic encephalopathy associated with hepatic lipidosis in llamas (Lama glama).

Science.gov (United States)

Pillitteri, C A; Craig, L E

2013-01-01

Hepatic encephalopathy has been listed as a differential for llamas displaying neurologic signs, but it has not been histopathologically described. This report details the neurologic histopathologic findings associated with 3 cases of hepatic lipidosis with concurrent neurologic signs and compares them to 3 cases of hepatic lipidosis in the absence of neurologic signs and 3 cases without hepatic lipidosis. Brain from all 3 llamas displaying neurologic signs contained Alzheimer type II cells, which were not detected in either subset of llamas without neurologic signs. Astrocytic immunohistochemical staining intensity for glial fibrillary acid protein was decreased in llamas with neurologic signs as compared to 2 of 3 llamas with hepatic lipidosis and without neurologic signs and to 2 of 3 llamas without hepatic lipidosis. Immunohistochemical staining for S100 did not vary between groups. These findings suggest that hepatic encephalopathy may be associated with hepatic lipidosis in llamas.

Usefulness of screening ultrasonography for hepatocellular carcinoma detection: chronic hepatitis versus hepatic cirrhosis caused by hepatitis B virus

International Nuclear Information System (INIS)

Chang, Sam Uel; Choi, Don Gil; Lim, Jae Hoon

2004-01-01

To evaluate the usefulness of screening liver ultrasonography (US) for hepatocellular carcinoma (HCC) detection in patients with chronic hepatitis or hepatic cirrhosis caused by hepatitis B virus (HBV). A retrospective study was performed with 1,189 patients with clinical hepatopathy caused by HBV who underwent screening liver US for HCC detection at least twice. All patients were followed up with liver US examinations (mean, 8.3 times), CT, or MR for at least 3 months (range, 3-102 months; mean, 47 months) for the detection of HCC. The study population was divided into two groups: chronic hepatitis (n=492) and hepatic cirrhosis (n=697), which was further divided into two groups with (n=156) or without (n=541) evident shrinkage. The radiologic examinations that had detected HCC for the first time were analyzed and compared between the groups. Among 20 (4.1%) patients with chronic hepatitis and 132 (18.9%) patients with hepatic cirrhosis diagnosed as HCC, screening US was the modality of detection in 17 (85.0%) of 20 patients with chronic hepatitis and 76 (57.6%) of 132 patients with hepatic cirrhosis (p=0.038, Chi-square test). The detection rate of HCC on screening US between the chronic hepatitis and hepatic cirrhosis with evident shrinkage (51.4%, 19/37) showed a significant difference (p=0.027, Chi-square test). For chronic liver disease caused by HBV, screening US for HCC detection is more useful in patients with chronic hepatitis than with hepatic cirrhosis with evident shrinkage

The role of eltrombopag in the management of hepatitis C virus-related thrombocytopenia

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Danish FA

2013-03-01

Full Text Available Fazal-i-Akbar Danish,1 Saeeda Yasmin21James Paget University Hospital, Great Yarmouth, Norfolk, United Kingdom; 2Shifa International Hospital, Islamabad, PakistanAbstract: Eltrombopag is a 2nd generation thrombopoietin-receptor agonist. It binds with the thrombopoietin-receptors found on the surfaces of the megakaryocytes & increases platelet production. Many recent studies have suggested a potential role for this novel agent in the treatment of thrombocytopenia associated with hepatitis-C infection. Studies have shown that adjunct treatment with Eltrombopag can help avoid dose reductions/withdrawals of pegylated interferon secondary to thrombocytopenia. It may also have a role in priming up platelet levels to help initiate antiviral therapy. Similarly, chronic liver disease patients with thrombocytopenia who need to undergo an invasive procedure may be potential candidates for short two-week courses of eltrombopag in the periprocedural period to help reduce the risk of bleeding. Besides the price (deemed very expensive and probably not cost-effective, there are some legitimate concerns about the safety profile of this novel agent (most importantly, portal vein thrombosis, bone marrow fibrosis and hepatotoxicity. In this article, the potential role of eltrombopag in the context of hepatitis C virus (HCV-related thrombocytopenia is reviewed. To write this article, a MEDLINE search was conducted (1990 to November 2012 using the search terms “eltrombopag,” “HCV,” and “thrombocytopenia.”Keywords: liver disease, chronic immune thrombocytopenic purpura, thrombopoietin-receptor agonist, romiplostim

Safety aspects of protease inhibitors for chronic hepatitis C: adverse events and drug-to-drug interactions

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Rosângela Teixeira

Full Text Available The standard of care therapy of chronic hepatitis C with the combination of pegylated interferon and ribavirin for 24 or 48 weeks was a remarkable accomplishment of the past decade. However, sustained virological responses rates of about 80% (genotypes 2-3 and 50% (geno 3 type 1 were not satisfactory especially for patients infected with genotype 1. Important advances in the biology of HCV have made possible the development of the direct-acting antiviral agents boceprevir and telaprevir with substantial increase in the rates of sustained virological response with shorter duration of therapy for a large number of patients. However, the complexity of triple therapy is higher and several new side effects are expected suggesting greater expertise in the patient management. Anemia and disgeusia are frequent with boceprevir while cutaneous rash, ranging from mild to severe, is expected with telaprevir. Higher risk of drug-drug interactions demand further clinical consideration of the previous well-known adverse events of pegylated interferon and ribavirin. Identification and prompt management of these potential new problems with boceprevir and telaprevir are crucial in clinical practice for optimizing treatment and assuring safety outcomes to HCV-genotype 1 patients.

Safety aspects of protease inhibitors for chronic hepatitis C: adverse events and drug-to-drug interactions

Directory of Open Access Journals (Sweden)

Rosângela Teixeira

2013-04-01

Full Text Available The standard of care therapy of chronic hepatitis C with the combination of pegylated interferon and ribavirin for 24 or 48 weeks was a remarkable accomplishment of the past decade. However, sustained virological responses rates of about 80% (genotypes 2-3 and 50% (geno 3 type 1 were not satisfactory especially for patients infected with genotype 1. Important advances in the biology of HCV have made possible the development of the direct-acting antiviral agents boceprevir and telaprevir with substantial increase in the rates of sustained virological response with shorter duration of therapy for a large number of patients. However, the complexity of triple therapy is higher and several new side effects are expected suggesting greater expertise in the patient management. Anemia and disgeusia are frequent with boceprevir while cutaneous rash, ranging from mild to severe, is expected with telaprevir. Higher risk of drug-drug interactions demand further clinical consideration of the previous well-known adverse events of pegylated interferon and ribavirin. Identification and prompt management of these potential new problems with boceprevir and telaprevir are crucial in clinical practice for optimizing treatment and assuring safety outcomes to HCV-genotype 1 patients.

Comprehensive analysis of PPARa-dependent regulation of hepatic lipid metabolism by expression profiling

NARCIS (Netherlands)

Rakhshandehroo, Maryam; Sanderson-Kjellberg, L.M.; Matilainen, Merja; Stienstra, Rinke; Carlberg, Carsten; Groot, de Philip; Muller, Michael; Kersten, Sander

2007-01-01

PPARalpha is a ligand-activated transcription factor involved in the regulation of nutrient metabolism and inflammation. Although much is already known about the function of PPARalpha in hepatic lipid metabolism, many PPARalpha-dependent pathways and genes have yet to be discovered. In order to

Perinatal hepatitis B virus detection by hepatitis B virus-DNA analysis.

OpenAIRE

De Virgiliis, S; Frau, F; Sanna, G; Turco, M P; Figus, A L; Cornacchia, G; Cao, A

1985-01-01

Maternal transmission of hepatitis B virus infection in relation to the hepatitis B e antigen/antibody system and serum hepatitis B virus-DNA were evaluated. Results indicate that hepatitis B virus-DNA analysis can identify hepatitis B serum antigen positive mothers who may transmit infection to their offspring.

A review of immunogenicity and tolerability of live attenuated Hepatitis A vaccine in children

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Rao, Sameer; Mao, J. S.; Motlekar, Salman; Fangcheng, Zhuang; Kadhe, Ganesh

2016-01-01

ABSTRACT Changing epidemiology of Hepatitis A virus (HAV) has led to an increased susceptibility of adolescents and adults to the infection. Vaccination can remarkably reduce the incidence and associated morbidity of HAV infection. This review is focused on the safety and efficacy of H2 strain derived live attenuated Hepatitis A vaccine. We found the vaccine to be highly immunogenic with minimal or negligible safety issues. Moreover, a single dose of live attenuated vaccine persists a long term immune response and can be a preferred option for developing countries. In 2014, Indian Academy of Paediatrics (IAP) also updated their recommendations for H2 vaccine as a single dose as against the previous 2 dose schedule. A focused approach to include the vaccine in national immunization program should be explored. PMID:27532370

Noninvasive diagnosis of hepatic fibrosis in chronic hepatitis C

OpenAIRE

Stauber, Rudolf E; Lackner, Carolin

2007-01-01

Assessment of hepatic fibrosis is important for determining prognosis, guiding management decisions, and monitoring disease. Histological evaluation of liver biopsy specimens is currently considered the reference test for staging hepatic fibrosis. Since liver biopsy carries a small but significant risk, noninvasive tests to assess hepatic fibrosis are desirable. This editorial gives an overview on noninvasive methods currently available to determine hepatic fibrosis and their diagnostic accur...

Hepatitis B Foundation

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... worldwide 2 Billion People have been infected with Hepatitis B Worldwide The Hepatitis B Foundation is working ... of people living with hepatitis B. Learn About Hepatitis B in 11 Other Languages . Resource Video See ...

What Is Hepatitis?

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... Navigation Alt+1 Content Alt+2 What is hepatitis? Online Q&A Reviewed July 2016 Q: What ... Question and answer archives Submit a question World Hepatitis Day Posters: Eliminate hepatitis World Hepatitis Day 2017 ...

Correlation of hepatic {sup 18}F-fluorodeoxyglucose uptake with fatty liver

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An, Young Sil; Yoon, Joon Kee; Hong, Seon Pyo; Joh, Chul Woo; Yoon, Seok Nam [Ajou University School of Medicine, Suwon (Korea, Republic of)

2006-10-15

Liver demonstrates heterogeneous FDG uptake and sometimes it shows abnormally increased uptake even though there is no malignant tissue. However, there was no previous study to correlate these various pattern of hepatic FDG uptake with benign liver disease. Therefore, we evaluated the significance of hepatic FDG uptake associated with various clinical factors including fatty liver, liver function tests and lipid profiles. We reviewed a total of 188 patients (male/female: 120/68, mean age: 50 {+-} 9) who underwent PET/CT for screening of malignancy. Patients with DM, impaired glucose tolerance, previous severe hepatic disease or long-term medication history were excluded. The FDG uptake in liver was analyzed semi-quantitatively using ROI on transaxial images (segment 8) and we compared mean standardized uptake value (SUV) between fatty liver and non-fatty liver group. We also evaluated the correlation between hepatic FDG uptake and various clinical factors including serum liver function test (ALT, AST), {gamma} -GT, total cholesterol and triglyceride concentration. The effect of alcoholic history and body mass index on hepatic FDG uptake was analyzed within the fatty liver patients. The hepatic FDG uptake of fatty liver group was significantly higher than that of non-fatty liver group. Serum total cholesterol and triglyceride concentration showed significant correlation with hepatic FDG uptake. However, there was no significant correlation between other factors (ALT, AST, and {gamma} -GT) and FDG uptake. Also there was no difference of mean SUV between normal and abnormal groups on the basis of alcoholic history and body mass index within fatty liver patients. Fatty liver and high serum triglyceride concentration were the independent factors affecting hepatic FDG uptake according to multivariate analysis. In conclusion, hepatic FDG uptake was strongly correlated with fatty liver and serum triglyceride concentration.

Diagnostic value of liver scintigraphy in fulminant hepatitis and severe acute hepatitis

International Nuclear Information System (INIS)

Shiomi, Susumu; Ikeoka, Naoko; Minowa, Takami; Kuroki, Tetsuo; Harihara, Shigeyoshi; Yamamoto, Sukeo; Ochi, Hironobu; Monna, Takeyuki

1985-01-01

Liver scintigraphy was performed in 12 cases with fulminant hepatitis, in 8 cases with severe acute hepatitis and in 44 cases with acute hepatitis. Scintiphotoes of severe hepatitis showed reduction of liver size, marked visualization of the bone marrow and the spleen, so this pattern was useful to differentiate from acute hepatitis. Relative size of the liver calculated by A.L.I. (anterior liver index) showed significant reduction in severe hepatitis compared with that of acute hepatitis. Three of five patients with died of severe hepatitis showed high uptake in the lung and ribs, but none of fifteen patients with severe hepatitis who recovered showed the abnormal accumulation in the lung and in the ribs. (author)

Hepatitis C

Science.gov (United States)

... an inflammation of the liver. One type, hepatitis C, is caused by the hepatitis C virus (HCV). It usually spreads through contact with ... childbirth. Most people who are infected with hepatitis C don't have any symptoms for years. If ...

Serum Hepatitis C virus and hepatitis B surface antigenaemia in ...

African Journals Online (AJOL)

Acute hepatitis is common in Nigeria and hepatitis B virus (HBV) infection has been a major aetiological factor. However, the role of Hepatitis C virus (HCV) infection is yet undetermined. Forty-five consecutive Nigerian patients with acute Icteric hepatitis (AIH) attending the Medical Clinic of the University College Hospital, ...

Stentgraft Implantation for the Treatment of Postoperative Hepatic Artery Pseudoaneurysm

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Pedersoli, F., E-mail: fpedersoli@ukaachen.de; Isfort, P.; Keil, S.; Goerg, F.; Zimmermann, M.; Liebl, M.; Schulze-Hagen, M. [RWTH Aachen University Hospital, Department of Diagnostic and Interventional Radiology (Germany); Schmeding, M. [RWTH Aachen University Hospital, Clinic for General, Visceral and Transplant Surgery (Germany); Kuhl, C. K.; Bruners, P. [RWTH Aachen University Hospital, Department of Diagnostic and Interventional Radiology (Germany)

2016-04-15

PurposeHepatic artery pseudoaneurysms are a rare but potentially life-threatening complication of major pancreaticobiliary surgery. We evaluated the safety and efficacy of endovascular stentgraft implantation for the management of such vascular lesions.Materials and MethodsBetween May 2013 and October 2015, ten patients with postoperative hepatic artery pseudoaneurysm, of which eight presented with active hemorrhage, were treated with endovascular stentgraft implantation. All patients had undergone major pancreatic or hepatic surgery before (pylorus-preserving pancreaticoduodenectomy, pancreatectomy, hemihepatectomy, extended hemihepatectomy). The pseudoaneurysms were diagnosed 13–202 days after surgery and were associated with postsurgical complications (e.g., leakage of pancreaticojejunal anastomosis).ResultsIn 9/10 patients, the pseudoaneurysm was completely excluded via stentgraft implantation. In 1/10 patient, the pseudoaneurysm ruptured during the procedure and was successfully treated by immediate open surgery. In 1/10 patient, a second intervention was performed after 6 days because of rebleeding; this was successfully treated by implantation of a second overlapping stentgraft. Mean follow-up time is 51 days. None of the patients died due to stentgraft- or aneurysm-related complications. Further episodes of hemorrhage were not observed. In one patient, clinically asymptomatic complete occlusion of the stentgraft was discovered at follow-up imaging.ConclusionStentgraft implantation is a safe and effective technique to treat hepatic artery pseudoaneurysms related to major pancreatic or hepatic surgery, especially in the setting of acute hemorrhage.

Stentgraft Implantation for the Treatment of Postoperative Hepatic Artery Pseudoaneurysm

International Nuclear Information System (INIS)

Pedersoli, F.; Isfort, P.; Keil, S.; Goerg, F.; Zimmermann, M.; Liebl, M.; Schulze-Hagen, M.; Schmeding, M.; Kuhl, C. K.; Bruners, P.

2016-01-01

PurposeHepatic artery pseudoaneurysms are a rare but potentially life-threatening complication of major pancreaticobiliary surgery. We evaluated the safety and efficacy of endovascular stentgraft implantation for the management of such vascular lesions.Materials and MethodsBetween May 2013 and October 2015, ten patients with postoperative hepatic artery pseudoaneurysm, of which eight presented with active hemorrhage, were treated with endovascular stentgraft implantation. All patients had undergone major pancreatic or hepatic surgery before (pylorus-preserving pancreaticoduodenectomy, pancreatectomy, hemihepatectomy, extended hemihepatectomy). The pseudoaneurysms were diagnosed 13–202 days after surgery and were associated with postsurgical complications (e.g., leakage of pancreaticojejunal anastomosis).ResultsIn 9/10 patients, the pseudoaneurysm was completely excluded via stentgraft implantation. In 1/10 patient, the pseudoaneurysm ruptured during the procedure and was successfully treated by immediate open surgery. In 1/10 patient, a second intervention was performed after 6 days because of rebleeding; this was successfully treated by implantation of a second overlapping stentgraft. Mean follow-up time is 51 days. None of the patients died due to stentgraft- or aneurysm-related complications. Further episodes of hemorrhage were not observed. In one patient, clinically asymptomatic complete occlusion of the stentgraft was discovered at follow-up imaging.ConclusionStentgraft implantation is a safe and effective technique to treat hepatic artery pseudoaneurysms related to major pancreatic or hepatic surgery, especially in the setting of acute hemorrhage.

Integration profile and safety of an adenovirus hybrid-vector utilizing hyperactive sleeping beauty transposase for somatic integration.

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Wenli Zhang

Full Text Available We recently developed adenovirus/transposase hybrid-vectors utilizing the previously described hyperactive Sleeping Beauty (SB transposase HSB5 for somatic integration and we could show stabilized transgene expression in mice and a canine model for hemophilia B. However, the safety profile of these hybrid-vectors with respect to vector dose and genotoxicity remains to be investigated. Herein, we evaluated this hybrid-vector system in C57Bl/6 mice with escalating vector dose settings. We found that in all mice which received the hyperactive SB transposase, transgene expression levels were stabilized in a dose-dependent manner and that the highest vector dose was accompanied by fatalities in mice. To analyze potential genotoxic side-effects due to somatic integration into host chromosomes, we performed a genome-wide integration site analysis using linker-mediated PCR (LM-PCR and linear amplification-mediated PCR (LAM-PCR. Analysis of genomic DNA samples obtained from HSB5 treated female and male mice revealed a total of 1327 unique transposition events. Overall the chromosomal distribution pattern was close-to-random and we observed a random integration profile with respect to integration into gene and non-gene areas. Notably, when using the LM-PCR protocol, 27 extra-chromosomal integration events were identified, most likely caused by transposon excision and subsequent transposition into the delivered adenoviral vector genome. In total, this study provides a careful evaluation of the safety profile of adenovirus/Sleeping Beauty transposase hybrid-vectors. The obtained information will be useful when designing future preclinical studies utilizing hybrid-vectors in small and large animal models.

Hepatitis A

Science.gov (United States)

... is an inflammation of the liver. One type, hepatitis A, is caused by the hepatitis A virus (HAV). The disease spreads through contact with ... suggest medicines to help relieve your symptoms. The hepatitis A vaccine can prevent HAV. Good hygiene can also ...

FULL-LENGTH PEPTIDE ASSAY OF ANTIGENIC PROFILE OF ENVELOPE PROTEINS FROM SIBERIAN ISOLATES OF HEPATITIS C VIRUS

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A. A. Grazhdantseva

2010-01-01

Full Text Available Antigenic profiles of envelope glycoproteins of hepatitis C virus presented by three genotypes 1b, 2a/2c and 3a, which are most widespread in the territory of Russia and, in particular, in Novosibirsk, were studied using a panel of overlapping synthetic peptides. It was shown that highly immunogenic peptide epitopes of Е1 and Е2 proteins common for all HCV genotypes, are located in amino acid positions 250-260, 315-325 (Е1 protein, 390-400 (hypervariable region 1, 430-440, and 680-690 (Е2 protein. The greatest inter-genotypic differences were recorded in positions 280-290, 410-430 and 520-540. A novel antigenic determinant was detected in the region of aa 280-290 of the Е1 protein which was typical only for HCV 2a/2c genotype. A broad variation in the boundaries for the most epitopes suggests a high variability of the Е1 and Е2 viral proteins; however, a similar repertoire of antibodies induced by different HCV genotypes indicates to an opportunity of designing a new generation of cross-reactive HCV vaccines based on mapping of the E1 and E2 antigenic regions.

Impairments of hepatic gluconeogenesis and ketogenesis in PPARα-deficient neonatal mice.

Science.gov (United States)

Cotter, David G; Ercal, Baris; d'Avignon, D André; Dietzen, Dennis J; Crawford, Peter A

2014-07-15

Peroxisome proliferator activated receptor-α (PPARα) is a master transcriptional regulator of hepatic metabolism and mediates the adaptive response to fasting. Here, we demonstrate the roles for PPARα in hepatic metabolic adaptations to birth. Like fasting, nutrient supply is abruptly altered at birth when a transplacental source of carbohydrates is replaced by a high-fat, low-carbohydrate milk diet. PPARα-knockout (KO) neonatal mice exhibit relative hypoglycemia due to impaired conversion of glycerol to glucose. Although hepatic expression of fatty acyl-CoA dehydrogenases is imparied in PPARα neonates, these animals exhibit normal blood acylcarnitine profiles. Furthermore, quantitative metabolic fate mapping of the medium-chain fatty acid [(13)C]octanoate in neonatal mouse livers revealed normal contribution of this fatty acid to the hepatic TCA cycle. Interestingly, octanoate-derived carbon labeled glucose uniquely in livers of PPARα-KO neonates. Relative hypoketonemia in newborn PPARα-KO animals could be mechanistically linked to a 50% decrease in de novo hepatic ketogenesis from labeled octanoate. Decreased ketogenesis was associated with diminished mRNA and protein abundance of the fate-committing ketogenic enzyme mitochondrial 3-hydroxymethylglutaryl-CoA synthase (HMGCS2) and decreased protein abundance of the ketogenic enzyme β-hydroxybutyrate dehydrogenase 1 (BDH1). Finally, hepatic triglyceride and free fatty acid concentrations were increased 6.9- and 2.7-fold, respectively, in suckling PPARα-KO neonates. Together, these findings indicate a primary defect of gluconeogenesis from glycerol and an important role for PPARα-dependent ketogenesis in the disposal of hepatic fatty acids during the neonatal period. Copyright © 2014 the American Physiological Society.

The functional hepatic volume assessed by 99mTc-GSA hepatic scintigraphy

International Nuclear Information System (INIS)

Wu, Jin; Ishikawa, Nobuyoshi; Takeda, Tohoru; Pan, Xiao-Qing; Sato, Motohiro; Todoroki, Takeshi; Itai, Yuji; Tanaka, Yumiko; Hatakeyama, Rokurou.

1995-01-01

The accuracy of measurement of the functional hepatic volume by single photon emission computed tomography (SPECT) with 99m Tc-galactosyl serum albumin ( 99m Tc-GSA) was evaluated. 99m Tc-GSA planar scintigraphic images were obtained dynamically and the hepatic SPECT imaging was then performed in 25 patients with hepatobiliary tumors. The patients were divided into 4 groups with normal hepatic function, mild, moderate and severe hepatic dysfunction. The functional hepatic volume determined by SPECT was compared with the morphological hepatic volume determined by computed tomography. The ratio of the hepatic volumes obtained by the two methods was calculated. The mean hepatic volume ratio was 96.6±2.3% in the normal hepatic function group and 95.9±2.2% in the mild dysfunction group (n.s.). In both the moderate and severe hepatic dysfunction groups, the hepatic volume ratio was smaller than that in the normal group (87.9±5.2%, p 15 (r=0.83, p 15 (r=0.74, p 15 (r=0.75, p 99m Tc-GSA faithfully reflects the functioning hepatocyte mass. 99m Tc-GSA scintigraphy and hepatic SPECT therefore provide information regarding global and regional reserve hepatic function. (author)

A Multicenter Study To Evaluate The Safety And Efficacy Of Heber On (Interferon Alfa-2b In Combination With Ribavirin For The Treatment Of Chronic Hepatitis C In Iran

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H. Mirmomen

2005-05-01

Full Text Available Combination therapy with interferon and ribavirin is the most effective treatment for chronic hepatitis C today. The aim of this study was to evaluate the efficacy and safety of thrice-weekly Heberon (interferon alfa-2b in combination with ribavirin as first -line treatment of chronic hepatitis C. Methods: A total of97 treatment-naive patients received Heberon three million units thrice-weekly subcutaneously in combination with ribavirin for 12 months. Serum HCV RNA levels were measured before and during therapy and 6 months after the end of therapy. End-of-treatment and sustained virological responses was defmed as an undetectable HCV-RNA level at the end of treatment, and 6 months after treatment was completed (end of follow-up, respectively. Results: In an intent-to-treat analysis, HCV-RNA was undetectable at the end of treatment in 49.5% of patients. At the end of follow-up, sustained virological response was 36.1 %. Combination treatment was generally well tolerated. Six patients stopped therapy because of side effects: severe cytopenia (n=4, depression (n=1, and hyperthyroidism (n= 1 . Common side effects of therapy include: Flu-like syndrome (85.6%, generalized alopecia (41.2% , injection site inflammation (37.1% , mood changes (36% , anorexia (34% and weight loss (32% . Conclusion: Heberon as an IFN product in combination with ribavirin for treat-ment of patients with chronic hepatitis Cis relatively safe, feasible, and potentially efficacious. It has comparable results in achieving end-of-treatment and sustained virological responses in chronic hepatitis C.

The Last Ten Years of Advancements in Plant-Derived Recombinant Vaccines against Hepatitis B

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Young Hee Joung

2016-10-01

Full Text Available Disease prevention through vaccination is considered to be the greatest contribution to public health over the past century. Every year more than 100 million children are vaccinated with the standard World Health Organization (WHO-recommended vaccines including hepatitis B (HepB. HepB is the most serious type of liver infection caused by the hepatitis B virus (HBV, however, it can be prevented by currently available recombinant vaccine, which has an excellent record of safety and effectiveness. To date, recombinant vaccines are produced in many systems of bacteria, yeast, insect, and mammalian and plant cells. Among these platforms, the use of plant cells has received considerable attention in terms of intrinsic safety, scalability, and appropriate modification of target proteins. Research groups worldwide have attempted to develop more efficacious plant-derived vaccines for over 30 diseases, most frequently HepB and influenza. More inspiring, approximately 12 plant-made antigens have already been tested in clinical trials, with successful outcomes. In this study, the latest information from the last 10 years on plant-derived antigens, especially hepatitis B surface antigen, approaches are reviewed and breakthroughs regarding the weak points are also discussed.

Cost-effectiveness of hepatitis A vaccination for individuals with chronic hepatitis C.

Science.gov (United States)

Chapko, Michael K; Yee, Helen S; Monto, Alexander; Dominitz, Jason A

2010-02-17

The incidence of hepatitis A infection in the United States has decreased dramatically in recent years because of childhood immunization programs. A decision analysis of the cost-effectiveness of hepatitis A vaccination for adults with hepatitis C was conducted. No vaccination strategy is cost-effective for adults with hepatitis C using the recent lower anticipated hepatitis A incidence, private sector costs, and a cost-effectiveness criterion of $100,000/QALY. Vaccination is cost-effective only for individuals who have cleared the hepatitis C virus when Department of Veterans Affairs costs are used. The recommendation to vaccinate adults with hepatitis C against hepatitis A should be reconsidered. Published by Elsevier Ltd.

Hepatitis E virus and fulminant hepatitis--a virus or host-specific pathology?

Science.gov (United States)

Smith, Donald B; Simmonds, Peter

2015-04-01

Fulminant hepatitis is a rare outcome of infection with hepatitis E virus. Several recent reports suggest that virus variation is an important determinant of disease progression. To critically examine the evidence that virus-specific factors underlie the development of fulminant hepatitis following hepatitis E virus infection. Published sequence information of hepatitis E virus isolates from patients with and without fulminant hepatitis was collected and analysed using statistical tests to identify associations between virus polymorphisms and disease outcome. Fulminant hepatitis has been reported following infection with all four hepatitis E virus genotypes that infect humans comprising multiple phylogenetic lineages within genotypes 1, 3 and 4. Analysis of virus sequences from individuals infected by a common source did not detect any common substitutions associated with progression to fulminant hepatitis. Re-analysis of previously reported associations between virus substitutions and fulminant hepatitis suggests that these were probably the result of sampling biases. Host-specific factors rather than virus genotype, variants or specific substitutions appear to be responsible for the development of fulminant hepatitis. © 2014 The Authors. Liver International Published by John Wiley & Sons Ltd.

Hepatic steatosis is associated with cardiometabolic risk in a rural Indian population: A prospective cohort study.

Science.gov (United States)

Barik, Anamitra; Shah, Ravi V; Spahillari, Aferdita; Murthy, Venkatesh L; Ambale-Venkatesh, Bharath; Rai, Rajesh Kumar; Das, Kaushik; Santra, Amal; Hembram, Jaba Ranjan; Bhattacharya, Dilip; Freedman, Jane E; Lima, Joao; Das, Ranendra; Bhattacharyya, Pinakpani; Das, Saumya; Chowdhury, Abhijit

2016-12-15

While adiposity and hepatic steatosis are linked to cardiovascular risk in developed countries, their prevalence and impact in low-income countries are poorly understood. We investigated the association of anthropomorphic variables and hepatic steatosis with cardiometabolic risk profiles and subclinical cardiovascular disease (CVD) in a large rural Indian cohort. In 4691 individuals in the Birbhum Population Project in West Bengal, India, we performed liver ultrasonography, carotid ultrasound and biochemical and clinical profiling. We assessed the association of hepatic steatosis and anthropomorphic indices (BMI, waist circumference) with CVD risk factors (dysglycemia, dyslipidemia, hypertension) and subclinical CVD (by carotid intimal-medial thickness). Rural Indians exhibited a higher visceral adiposity index and pro-atherogenic dyslipidemia at a lower BMI than Americans. Individuals with any degree of hepatic steatosis by ultrasound had a greater probability of dysglycemia (adjusted odds ratio, OR=1.67, 95% CI 1.31-2.12, P<0.0001) and pro-atherogenic dyslipidemia (OR=1.33, 95% CI 1.07-1.63, P=0.009). We observed a positive association between liver fat, adiposity and carotid intimal-medial thickness (CIMT) in an unadjusted model (β=0.02, P=0.0001); the former was extinguished after adjustment for cardiometabolic risk factors. In a large population of rural Indians, hepatic steatosis and waist circumference were associated with prevalent cardiometabolic risk and subclinical CVD at lower BMI relative to multi-ethnic Americans, though the association of the former with subclinical CVD was extinguished after adjustment. These results underscore the emerging relevance of hepatic steatosis and adiposity in the developing world, and suggest efforts to target these accessible phenotypes for cardiometabolic risk prevention. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Tenofovir and its potential in the treatment of hepatitis B virus

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Laura Reynaud

2009-02-01

Full Text Available Laura Reynaud, Maria Aurora Carleo, Maria Talamo, Guglielmo BorgiaDepartment of Public Medicine and Social Security – Section of Infectious Disease University of Naples “Federico II”, ItalyAbstract: Recent literature is reviewed about treatment of chronic hepatitis B virus (CHB, focusing on tenofovir disoproxil fumarate (TDF; Viread®, among the nucleotide and nucleoside analogs. TDF pharmacokinetics and pharmacodynamics, activity in respect of hepatitis B virus (HBV multi-drug-resistant mutations, efficacy in treatment-naïve and treatment-experienced patients, and side effects are described. The most predictive response factors to TDF therapy are discussed and all available combination therapies to optimize clinical outcome in the various patient profiles are analyzed, such as compensated and/or decompensated cirrhotic patients. The use of TDF in pregnancy, and prophylaxis after exposure to HBV and post-liver transplantation are also evaluated.Keywords: HBV, chronic hepatitis B, tenofovir, antiviral therapy

Blood lipids analysis in patients with hepatitis and hepatic fibrosis

International Nuclear Information System (INIS)

Si Jianhong

2007-01-01

Objective: To investigate the correlationship between blood hepatic fibrosis markers and blood lipids levels. Methods: Serum hepatic fibrosis markers (HA, PC III, IV-C, LN) levels were determined with RIA and serum lipids (TG, TCh HDL; LDL, apoA1, apoB) were measured with biochemical methods in 98 patients with hepatitis in various stages and 50 controls. Liver biopsy was done in all the hepatitis patients. Results: Hepatic fibrosis was classified into 5 grades (S0-S4) according to the pathology shown in the biopsy specimen. The serum lipid levels decreased along with the increase of severity of fibrosis from S0 to S4. Levels in S4 patients were significantly lower than those in controls (P 0.05). Conclusion: The serum hepatic fibrosis markers levels increased and lipids levels decreased along with the progress of hepatitis from acute to cirrhosis. (authors)

Hepatic Encephalopathy

Science.gov (United States)

... Caregiver Support Caregiver Stories Home › What is Hepatic Encephalopathy? Why Your Liver is Important The Connection Between HE and Liver ... Why it’s Important to Treat HE Symptoms of Liver Failure Glossary of terms ... is Hepatic Encephalopathy? Hepatic Encephalopathy, sometimes referred to as portosystemic encephalopathy ...

Hepatitis B immunisation for newborn infants of hepatitis B surface antigen-positive mothers

DEFF Research Database (Denmark)

Lee, C; Gong, Yanzhang; Brok, J

2006-01-01

Hepatitis B vaccine and hepatitis B immunoglobulin are considered for newborn infants of HBsAg-positive mothers to prevent hepatitis B infection.......Hepatitis B vaccine and hepatitis B immunoglobulin are considered for newborn infants of HBsAg-positive mothers to prevent hepatitis B infection....

Safety Profile of the Newest Antiepileptic Drugs: A Curated Literature Review.

Science.gov (United States)

Palleria, Caterina; Cozza, Giuseppe; Khengar, Rajeshree; Libri, Vincenzo; De Sarro, Giovambattista

2017-01-01

Despite the introduction of new antiepileptic drugs (AEDs), the quality of life and therapeutic response for patients with epilepsy remain unsatisfactory. In addition, whilst several antiepileptic drugs (AEDs) have been approved and consequently marketed in recent years, little is known about their long-term safety and tolerability. Availability of the newest AEDs, characterized by improved pharmacokinetic profiles, has positively impacted the treatment approach for patients with partial seizures in clinical practice. However, the main cause of treatment failure is still poor patient compliance due to the occurrence of adverse drug reactions (ADRs) that lead to treatment withdrawal in about 25% of cases before achieving maximal efficacy, and is associated with increasing health care costs. In this Review, we conducted an online database search using Medline, PubMed, Embase, and the Cochrane Online Library to review the available studies highlighting the clinical relevance of side effects, pharmacological interactions, safety and tolerability of the newest AEDs: Brivaracetam (BRV), Cannabidiol (CBD), Eslicarbazepine acetate (ESL), Lacosamide (LCM), and Perampanel (PER). The principal benefit of the newest AEDs, in addition to reduced frequency and seizure severity, is the low number and severity of ADRs reported compared to more historic drugs. Early detection of ADRs could lead to an improvement in patients' quality of life, therefore it is important to monitor ADRs and to adequately perform post marketing surveillance in the clinical practice setting. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

How hepatitis D virus can hinder the control of hepatitis B virus.

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Maria Xiridou

Full Text Available BACKGROUND: Hepatitis D (or hepatitis delta virus is a defective virus that relies on hepatitis B virus (HBV for transmission; infection with hepatitis D can occur only as coinfection with HBV or superinfection of an existing HBV infection. Because of the bond between the two viruses, control measures for HBV may have also affected the spread of hepatitis D, as evidenced by the decline of hepatitis D in recent years. Since the presence of hepatitis D is associated with suppressed HBV replication and possibly infectivity, it is reasonable to speculate that hepatitis D may facilitate the control of HBV. METHODOLOGY AND PRINCIPAL FINDINGS: We introduced a mathematical model for the transmission of HBV and hepatitis D, where individuals with dual HBV and hepatitis D infection transmit both viruses. We calculated the reproduction numbers of single HBV infections and dual HBV and hepatitis D infections and examined the endemic prevalences of the two viruses. The results show that hepatitis D virus modulates not only the severity of the HBV epidemic, but also the impact of interventions for HBV. Surprisingly we find that the presence of hepatitis D virus may hamper the eradication of HBV. Interventions that aim to reduce the basic reproduction number of HBV below one may not be sufficient to eradicate the virus, as control of HBV depends also on the reproduction numbers of dual infections. CONCLUSIONS AND SIGNIFICANCE: For populations where hepatitis D is endemic, plans for control programs ignoring the presence of hepatitis D may underestimate the HBV epidemic and produce overoptimistic results. The current HBV surveillance should be augmented with monitoring of hepatitis D, in order to improve accuracy of the monitoring and the efficacy of control measures.

Travelers' Health: Hepatitis C

Science.gov (United States)

... Chapter 3 - Hepatitis B Chapter 3 - Hepatitis E Hepatitis C Deborah Holtzman INFECTIOUS AGENT Hepatitis C virus ( ... mother to child. Map 3-05. Prevalence of hepatitis C virus infection 1 PDF Version (printable) 1 ...

Travelers' Health: Hepatitis A

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... 3 - Helminths, Soil-Transmitted Chapter 3 - Hepatitis B Hepatitis A Noele P. Nelson INFECTIOUS AGENT Hepatitis A ... hepatitis/HAV Table 3-02. Vaccines to prevent hepatitis A VACCINE TRADE NAME (MANUFACTURER) AGE (Y) DOSE ...

Travelers' Health: Hepatitis B

Science.gov (United States)

... Chapter 3 - Hepatitis A Chapter 3 - Hepatitis C Hepatitis B Francisco Averhoff INFECTIOUS AGENT Hepatitis B virus ( ... progression of disease. Map 3-04. Prevalence of hepatitis B virus infection 1 PDF Version (printable) 1 ...

Urinary proteomic profiling reveals diclofenac-induced renal injury and hepatic regeneration in mice

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Swelm, Rachel P.L. van [Department of Pharmacology and Toxicology, Radboud University Nijmegen Medical Centre, P.O. Box 9101, 6500 HB Nijmegen (Netherlands); Laarakkers, Coby M.M. [Department of Laboratory Medicine, Radboud University Nijmegen Medical Centre, P.O. Box 9101, 6500 HB Nijmegen (Netherlands); Pertijs, Jeanne C.L.M.; Verweij, Vivienne; Masereeuw, Rosalinde [Department of Pharmacology and Toxicology, Radboud University Nijmegen Medical Centre, P.O. Box 9101, 6500 HB Nijmegen (Netherlands); Russel, Frans G.M., E-mail: F.Russel@pharmtox.umcn.nl [Department of Pharmacology and Toxicology, Radboud University Nijmegen Medical Centre, P.O. Box 9101, 6500 HB Nijmegen (Netherlands)

2013-06-01

Diclofenac (DF) is a widely used non-steroidal anti-inflammatory drug for the treatment of rheumatic disorders, but is often associated with liver injury. We applied urinary proteomic profiling using MALDI-TOF MS to identify biomarkers for DF-induced hepatotoxicity in mice. Female CH3/HeOUJIco mice were treated with 75 mg/kg bw DF by oral gavage and 24 h urine was collected. Proteins identified in urine of DF-treated mice included epidermal growth factor, transthyretin, kallikrein, clusterin, fatty acid binding protein 1 and urokinase, which are related to liver regeneration but also to kidney injury. Both organs showed enhanced levels of oxidative stress (TBARS, p < 0.01). Kidney injury was confirmed by histology and increased Kim1 and Il-6 mRNA expression levels (p < 0.001 and p < 0.01). Liver histology and plasma ALT levels in DF-treated mice were not different from control, but mRNA expression of Stat3 (p < 0.001) and protein expression of PCNA (p < 0.05) were increased, indicating liver regeneration. In conclusion, urinary proteome analysis revealed that DF treatment in mice induced kidney and liver injury. Within 24 h, however, the liver was able to recover by activating tissue regeneration processes. Hence, the proteins found in urine of DF-treated mice represent kidney damage rather than hepatic injury. - Highlights: • The urinary proteome shows biological processes involved in adverse drug reactions. • Urine proteins of DF-treated mice relate to kidney injury rather than liver injury. • Liver regeneration, not liver injury, is apparent 24h after oral DF administration. • Pretreatment with LPS does not enhance DF-induced liver injury in mice.

Changing Epidemiology of Hepatitis A and Hepatitis E Viruses in China, 1990-2014.

Science.gov (United States)

Ren, Xiang; Wu, Peng; Wang, Liping; Geng, Mengjie; Zeng, Lingjia; Zhang, Jun; Xia, Ningshao; Lai, Shengjie; Dalton, Harry R; Cowling, Benjamin J; Yu, Hongjie

2017-02-01

We compared the epidemiology of hepatitis A and hepatitis E cases in China from 1990-2014 to better inform policy and prevention efforts. The incidence of hepatitis A cases declined dramatically, while hepatitis E incidence increased. During 2004-2014, hepatitis E mortality rates surpassed those of hepatitis A.

Hepatitis B vaccination of male neonates and autism diagnosis, NHIS 1997-2002.

Science.gov (United States)

Gallagher, Carolyn M; Goodman, Melody S

2010-01-01

Universal hepatitis B vaccination was recommended for U.S. newborns in 1991; however, safety findings are mixed. The association between hepatitis B vaccination of male neonates and parental report of autism diagnosis was determined. This cross-sectional study used weighted probability samples obtained from National Health Interview Survey 1997-2002 data sets. Vaccination status was determined from the vaccination record. Logistic regression was used to estimate the odds for autism diagnosis associated with neonatal hepatitis B vaccination among boys age 3-17 years, born before 1999, adjusted for race, maternal education, and two-parent household. Boys vaccinated as neonates had threefold greater odds for autism diagnosis compared to boys never vaccinated or vaccinated after the first month of life. Non-Hispanic white boys were 64% less likely to have autism diagnosis relative to nonwhite boys. Findings suggest that U.S. male neonates vaccinated with the hepatitis B vaccine prior to 1999 (from vaccination record) had a threefold higher risk for parental report of autism diagnosis compared to boys not vaccinated as neonates during that same time period. Nonwhite boys bore a greater risk.

Hepatitis C: Clinical Trials

Science.gov (United States)

... and Public Home » Hepatitis C » Treatment Decisions Viral Hepatitis Menu Menu Viral Hepatitis Viral Hepatitis Home For ... can I find out about participating in a hepatitis C clinical trial? Many trials are being conducted ...

Hepatitis C: Mental Health

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... the Public Home Hepatitis A Hepatitis B Hepatitis C Hepatitis C Home Getting Tested Just Diagnosed Treatment Choice Program ... Pain Mental Health Sex and Sexuality (for Hepatitis C) Success Stories FAQs For Health Care Providers Provider ...

Epidemiological study of hepatitis B and C in a municipality with rural characteristics: Cássia dos Coqueiros, State of São Paulo, Brazil.

Science.gov (United States)

Melo, Laura Valdiane Luz; Silva, Marcondes Alves Barbosa da; Perdoná, Gleici da Silva Castro; Nascimento, Margarida Maria Passeri; Secaf, Marie; Monteiro, Rosane Aparecida; Martinelli, Ana de Lourdes Candolo; Passos, Afonso Dinis Costa

2015-01-01

Hepatitis B and C viral infections remain an important cause of global morbidity and mortality. Studies have been conducted in population groups of large cities, leaving gaps in the knowledge regarding the situation in small municipalities. We aimed to measure the prevalence of hepatitis B and C markers and presence of infection-associated factors. All inhabitants of Cássia dos Coqueiros aged ≥18 years who agreed to participate in the research were included. We collected blood as well as information via a questionnaire between March 2011 and December 2013. Univariate and multivariate analyses were conducted. Among the 1,001 participants, 41 (4.1%) participants had a serological profile of hepatitis B viral exposure, and only one (0.1%) participant was considered a virus carrier. The frequency of isolated antibody to hepatitis B virus surface antigen (anti-HBs) markers was 17.8% for the overall population. In the multivariate analysis, hepatitis B virus (HBV) infection was associated with age, birth outside the State of São Paulo, history of hepatitis, ≥2 sexual partners in the last 6 months, and tattoos. Four (0.4%) participants had a serological profile of hepatitis C viral exposure. However, after confirmation using viral ribonucleic acid (RNA) evaluation, only one (0.1%) individual remained positive. The positivity rates for hepatitis B and C were low, despite greater sexual freedom and the recent emergence of illicit drugs, as observed by the health personnel working in Cássia dos Coqueiros.

The T allele of rs7903146 TCF7L2 is associated with impaired insulinotropic action of incretin hormones, reduced 24 h profiles of plasma insulin and glucagon, and increased hepatic glucose production in young healthy men

DEFF Research Database (Denmark)

Pilgaard, K; Jensen, C; Schou, J

2009-01-01

h glucose, insulin and glucagon profiles; OGTT; mixed meal test; IVGTT; hyperglycaemic clamp with co-infusion of glucagon-like peptide (GLP)-1 or glucose-dependent insulinotropic polypeptide (GIP); and a euglycaemic-hyperinsulinaemic clamp combined with glucose tracer infusion to study hepatic...... and peripheral insulin action. RESULTS: Carriers of the T allele were characterised by reduced 24 h insulin concentrations (p ...-phase insulinotropic action of GLP-1 (p = 0.03) and GIP (p = 0.07) during a 7 mmol/l hyperglycaemic clamp. Secretion of GLP-1 and GIP during the mixed meal test was normal. Despite elevated hepatic glucose production, carriers of the T allele had significantly reduced 24 h glucagon concentrations (p

Hepatic Encephalopathy

Medline Plus

Full Text Available ... Caregiver Support Caregiver Stories Home › What is Hepatic Encephalopathy? Why Your Liver is Important The Connection Between HE and Liver ... Why it’s Important to Treat HE Symptoms of Liver Failure Glossary of terms ... is Hepatic Encephalopathy? Hepatic Encephalopathy, sometimes referred to as portosystemic encephalopathy ...

The seroprevalance of hepatitis A in Adiyaman

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Burak Ekrem Citil

2015-09-01

Materials and Methods: In this study, the seropositivity of hepatitis A infection of people who had admitted to Adiyaman University training and research hospital and primary care provider from central regions of Adiyaman city from March 2012 to April 2013 were evaluated, retrospectively. Existence of anti- HAV IgG antibodies were studied by macro ELISA devices belonging two different manufacturers (Abbott Laboratories and Roche Diagnostics. Results: One thousand seven hundred twenty male and 1844 female were included the study (a total of 3564 cases. Anti HAV IgG seropositivity was 77,5% (2761/3564. It was determined that the prevalance was increasing with age. This study found no difference in HAV antibody prevalence between men and women.(p>0,05 Conclusion: Hepatitis A infection's serological prevalence profiles vary geographically in the world. In the intermediate endemic areas like Turkey, the latency in the exposure to the virus has constitute a vast number of susceptible adolescents and extremely increased the average age at infection. The severity of illness increases by age. Implement and not;ing vaccination programs for HAV infection, as well as improved hygiene, sanitation, and drinking water quality and quantity are associated with decreased risk of HAV infection. Key Words: Hepatitis A, seroprevalence, Adiyaman [J Contemp Med 2015; 5(3.000: 157-162

Fulminant Hepatic Failure Secondary to Primary Hepatic Angiosarcoma

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Ayokunle T. Abegunde

2015-01-01

Full Text Available Background. Hepatic angiosarcoma is a rare and aggressive tumor that often presents at an advanced stage with nonspecific symptoms. Objective. To report a case of primary hepatic angiosarcoma in an otherwise healthy man with normal liver function tests two months prior to presenting with a short period of jaundice that progressed to fulminant hepatic failure. Methods. Case report and review of literature. Conclusion. This case illustrates the rapidity of progression to death after the onset of symptoms in a patient with hepatic angiosarcoma. Research on early diagnostic strategies and newer therapies are needed to improve prognosis in this rare and poorly understood malignancy with limited treatment options.

Transfusion-associated hepatitis before the screening of blood for hepatitis risk factors

DEFF Research Database (Denmark)

Engle, Ronald E; Bukh, Jens; Alter, Harvey J

2014-01-01

%) with HBV alone, and one (3%) with both viruses. Overall, 100% of patients with hepatitis and 39% of those without hepatitis were infected with HBV and/or HCV; one patient was also infected with hepatitis E virus. The donor carrier rate for HBV and/or HCV was estimated to be more than 6%; contemporaneously......%) developed biochemical evidence of hepatitis; of these, 20 (67%) were infected with hepatitis C virus (HCV) alone, four (13%) with hepatitis B virus (HBV) alone, and six (20%) with both viruses. Among the 36 patients who did not develop hepatitis, four (11%) were newly infected with HCV alone, nine (25...... prepared pooled normal human plasma was also contaminated with multiple hepatitis viruses. CONCLUSION: TAH virus infections were a larger problem than perceived 50 years ago and HCV was the predominant agent transmitted. All hepatitis cases could be attributed to HCV and/or HBV and hence...

[Viral hepatitis in travellers].

Science.gov (United States)

Abreu, Cândida

2007-01-01

Considering the geographical asymmetric distribution of viral hepatitis A, B and E, having a much higher prevalence in the less developed world, travellers from developed countries are exposed to a considerable and often underestimated risk of hepatitis infection. In fact a significant percentage of viral hepatitis occurring in developed countries is travel related. This results from globalization and increased mobility from tourism, international work, humanitarian and religious missions or other travel related activities. Several studies published in Europe and North America shown that more than 50% of reported cases of hepatitis A are travel related. On the other hand frequent outbreaks of hepatitis A and E in specific geographic areas raise the risk of infection in these restricted zones and that should be clearly identified. Selected aspects related with the distribution of hepatitis A, B and E are reviewed, particularly the situation in Portugal according to the published studies, as well as relevant clinical manifestations and differential diagnosis of viral hepatitis. Basic prevention rules considering enteric transmitted hepatitis (hepatitis A and hepatitis E) and parenteral transmitted (hepatitis B) are reviewed as well as hepatitis A and B immunoprophylaxis. Common clinical situations and daily practice "pre travel" advice issues are discussed according to WHO/CDC recommendations and the Portuguese National Vaccination Program. Implications from near future availability of a hepatitis E vaccine, a currently in phase 2 trial, are highlighted. Potential indications for travellers to endemic countries like India, Nepal and some regions of China, where up to 30% of sporadic cases of acute viral hepatitis are caused by hepatitis E virus, are considered. Continued epidemiological surveillance for viral hepatitis is essential to recognize and control possible outbreaks, but also to identify new viral hepatitis agents that may emerge as important global health

Clinical observation on coil embolization in treatment of hepatic arterial pseudoaneurysm

International Nuclear Information System (INIS)

Chen Yaoting; Xu Linfeng; Jiang Rongjian; Zhou Jingxing; Luo Jianghong; Tang Qiyun; Hu Renmei

2007-01-01

Objective: To discuss the method, mid-long term clinical therapeutic effect and safety of coil embolization in treating patients with hepatic arterial pseudoaneurysm (HAPA). Methods: Seven patients with repeatedly massive hemorrhage of gastrointestinal tract were undertaken DSA of celiac arteries and hepatic arteries and embolization of the feeding artery by coils or microcoils after correct diagnosis. All cases underwent follow-up from 6 to 60 months(mean 38). Results: The blood loss before angiography was ranged from 1200 to 4 000 (mean 2 385) ml. There were 3 cases with normal hepatic function and 4 with hepatic dysfunction including ALT increase in 2 and obstructive jaundice in another. Digital substraction angiography (DSA) clearly showed the location, shape and feeding arteries of HAPA. There were 2 types of HAPA namely intrahepatic (n=3)and extrahepatic (n=4), adding one case with arteriovenous fistula (AVF). Embolization was successful in all cases by coils (n=13) or microcoils (n=12). No recurrence and any definite clinical complication occurred during follow-up. Conclusion: Coil embolization in treating HAPA is safe and effective with mid-long term positive clinical therapeutic efficiency without severe complications. (authors)

Long-term safety profile of belimumab plus standard therapy in patients with systemic lupus erythematosus.

Science.gov (United States)

Merrill, Joan T; Ginzler, Ellen M; Wallace, Daniel J; McKay, James D; Lisse, Jeffrey R; Aranow, Cynthia; Wellborne, Frank R; Burnette, Michael; Condemi, John; Zhong, Z John; Pineda, Lilia; Klein, Jerry; Freimuth, William W

2012-10-01

To evaluate the safety profile of long-term belimumab therapy combined with standard therapy for systemic lupus erythematosus (SLE) in patients with active disease. Patients who were randomized to receive intravenous placebo or belimumab 1, 4, or 10 mg/kg, plus standard therapy, and completed the initial 52-week double-blind treatment period were then allowed to enter a 24-week open-label extension phase. During the extension period, patients in the belimumab group either received the same dose or were switched to 10 mg/kg and patients in the placebo group were switched to belimumab 10 mg/kg. Patients who achieved a satisfactory response during the 24-week extension period were allowed to participate in the long-term continuation study of monthly belimumab 10 mg/kg. Adverse events (AEs) and abnormal laboratory results were analyzed per 100 patient-years in 1-year intervals. Of the 364 patients who completed the 52-week double-blind treatment period, 345 entered the 24-week extension, and 296 continued treatment with belimumab in the long-term continuation study. Safety data through 4 years of belimumab exposure (1,165 cumulative patient-years) are reported. Incidence rates of AEs, severe/serious AEs, infusion reactions, infections, malignancies, grades 3/4 laboratory abnormalities, and discontinuations due to AEs were stable or declined during 4-year belimumab exposure. The most common AEs included arthralgia, upper respiratory tract infection, headache, fatigue, and nausea. Serious infusion reactions were rare: only 1 occurred during the 4-year followup period. Rates of serious infection decreased from 5.9/100 patient-years to 3.4/100 patient-years, and no specific type of infection predominated. Belimumab added to standard therapy was generally well-tolerated over the 4-year treatment period in patients with SLE, which suggests that belimumab can be administered long term with an acceptable safety profile. Copyright © 2012 by the American College of Rheumatology.

Attitudes and Awareness Regarding Hepatitis B and Hepatitis C ...

African Journals Online (AJOL)

in many cases hepatitis B and C can lead to permanent liver ... Department of Public Health Dentistry, Gian Sagar Dental College and Hospital, 1Department of Oral Surgery, Gian ... training among HCWs to prevent the spread of hepatitis B virus and hepatitis C virus. ..... primary care physicians following the Department of.

Outbreak of hepatitis E virus infection in Darfur, Sudan: effectiveness of real-time reverse transcription-PCR analysis of dried blood spots.

Science.gov (United States)

Mérens, Audrey; Guérin, Philippe Jean; Guthmann, Jean-Paul; Nicand, Elisabeth

2009-06-01

Biological samples collected in refugee camps during an outbreak of hepatitis E were used to compare the accuracy of hepatitis E virus RNA amplification by real-time reverse transcription-PCR (RT-PCR) for sera and dried blood spots (concordance of 90.6%). Biological profiles (RT-PCR and serology) of asymptomatic individuals were also analyzed.

Application of Serum Hepatic Fibrosis Indices in the Diagnosis of Hepatic Disease

International Nuclear Information System (INIS)

Lu Yanting; Wang Taisong; Gu Xin

2010-01-01

To investigate the significance of combined detection of laminin (LN), collagen type IV (CIV), hyaluronic acid (HA) and precollagen type III (PCIII) in the diagnosis of hepatic fibrosis. The serum levels of LN, CIV, HA and PCIII in 143 patients with hepatic disease and 41 healthy controls were measured by radioimmunoassay (RIA). The results showed that the serum levels of LN, CIV, HA and PCIII in patients with hepatic disease were significantly higher than those of the control group (P<0.01), and the serum levels of those markers were related to the severity of the chronic hepatic disease. The highest serum levels were found in serious chronic hepatitis group and hepatic fibrosis group,and the increase of serum HA and PCIII was most remarkable. Combined detection of LN, CIV, HA and PCIII is a sensitive and reliable method in the diagnosis of hepatic fibrosis, but the four serum indices can not be used in differentiating serious chronic hepatitis and hepatic fibrosis. (authors)

Emergence of hepatitis C virus genotype 4: phylogenetic analysis reveals three distinct epidemiological profiles

NARCIS (Netherlands)

de Bruijne, Joep; Schinkel, Janke; Prins, Maria; Koekkoek, Sylvie M.; Aronson, Sem J.; van Ballegooijen, Marijn W.; Reesink, Hendrik W.; Molenkamp, Richard; van de Laar, Thijs J. W.

2009-01-01

Hepatitis C virus (HCV) genotype 4 (HCV-4) infection is considered to be difficult to treat and has become increasingly prevalent in European countries, including The Netherlands. Using a molecular epidemiological approach, the present study investigates the genetic diversity and evolutionary origin

Chronic Liver Diseases in Children: Clinical Profile and Histology.

Science.gov (United States)

Dhole, Sachin Devidas; Kher, Archana S; Ghildiyal, Radha G; Tambse, Manjusha P

2015-07-01

The main aim of the study is to study the clinical profile of disorders of the liver and hepatobiliary system in paediatric patients and to correlate the histopathology findings of liver biopsy in chronic liver disease. Another aim being to assess the prognosis and to know the outcome and the effects of treatment in chronic liver diseases in paediatric age group. It was a prospective study, included the clinical profile of Chronic Liver Diseases (CLD) in children and the histopathological correlation. A total of 55 children were thoroughly investigated by doing relevant investigations and liver biopsy. A male predominance (60%) was noted with maximum incidence in the age group of 6-12 years. The incidence of CLD was 1.1% of total admissions. The most common presenting complaint was jaundice and abdominal distension. Hepatic encephalopathy was noted in 29% patients. Hepatomegaly was seen in 63% patients and spleenomegaly was seen in 60% patients. The incidence of cirrhosis on liver biopsy was 42% (23cases) in CLD patients. The most common diagnosis on histopathology was Wilson's disease (22%), followed by hepatitis and autoimmune hepatitis. The predominant spectrum of CLD was metabolic liver disease and also the predominant cause of death. As the incidence of CLD is quite low, a very high index of suspicion is required for its diagnosis. Some uncommon causes of CLD in children were seen in our study like neutral lipid storage disease, α1-Antitrypsin deficiency disease, lupus hepatitis, Alagille syndrome and Budd-Chiari syndrome. A patient of CLD with jaundice and hepatomegaly should be treated aggressively as those are the poor prognostic indicators of the disease. Hepatic encephalopathy and cirrhosis are also associated with poor outcome in patients with CLD. Liver biopsy histopathology by an expert and its correlation with laboratory investigations plays an important role in the diagnosis of CLD. The major cause of deaths in patients with CLD is due to end stage

Real-world efficacy and safety of ritonavir-boosted paritaprevir, ombitasvir, dasabuvir ± ribavirin for hepatitis C genotype 1 - final results of the REV1TAL study.

Science.gov (United States)

Lubel, John; Strasser, Simone; Stuart, Katherine A; Dore, Gregory; Thompson, Alexander; Pianko, Stephen; Bollipo, Steven; Mitchell, Joanne L; Fragomeli, Vincenzo; Jones, Tracey; Chivers, Sarah; Gow, Paul; Iser, David; Levy, Miriam; Tse, Edmund; Gazzola, Alessia; Cheng, Wendy; Nazareth, Saroj; Galhenage, Sam; Wade, Amanda; Weltman, Martin; Wigg, Alan; MacQuillan, Gerry; Sasadeusz, Joe; George, Jacob; Zekry, Amany; Roberts, Stuart K

2017-01-01

Limited data exist on the outcomes of ritonavir-boosted paritaprevir with ombitasvir and dasabuvir (PrOD) ± ribavirin in a real-world setting. The aim of this study was to compare the efficacy and safety of PrOD-based therapy in hepatitis C genotype 1 patients with and without cirrhosis, and to explore pre-treatment factors predictive of sustained viral response (SVR) and serious adverse events (SAEs) on treatment. 451 patients with hepatitis C genotype 1 treated in 20 centres across Australia were included. Baseline demographic, clinical and laboratory information, on-treatment biochemical, virological and haematological indices and details on serious adverse events were collected locally. Cirrhosis was present in 340 patients (75.4%). Overall SVR was 95.1% with no differences in SVR between the cirrhosis and non-cirrhosis groups (94.7% versus 96.4%). SVR in subgenotypes 1a and 1b was 93.1% and 99.2%, respectively. On multivariate analysis, baseline bilirubin level and early treatment cessation predicted SVR. SAEs occurred in 10.9% of patients including hepatic decompensation (2.7%) and hepatocellular carcinoma (1.8%). On multivariate analysis of factors predictive of SAEs in the overall group, Child-Turcotte-Pugh (CTP) B was the only significant factor, while in those with cirrhosis, baseline albumin and creatinine levels were significant. In this large real-world cohort of HCV genotype 1 subjects, treatment with PrOD was highly effective and similar to clinical trials. Important determinants of reduced SVR include early cessation of therapy and baseline bilirubin concentration. SAEs were not infrequent with CTP B patients being at greatest risk.

Hepatitis A seroprevalence in patients with chronic viral hepatitis in Konya, Turkey.

Science.gov (United States)

Özden, Hale T

2016-03-01

Hepatitis A is among the diseases that can be prevented with vaccination in our time. Acute hepatitis A progresses more severely in individuals with a liver disease. Therefore, patients with a chronic liver disease (because of hepatitis B or hepatitis C) are advised vaccination with the hepatitis A vaccine. This study is aimed to determine the seroprevalence of hepatitis A virus (HAV) antibodies in patients infected with hepatitis C virus or hepatitis B virus in Konya province of Turkey. A total of 537 patients who had chronic viral hepatitis between January 2011 and December 2014 were included in the study. Serum samples were collected from each patient and tested for anti-HAV using the chemiluminescent microparticle immunoassay. The overall seroprevalence of total anti-HAV IgG was 94.2%. The overall prevalence of anti-HAV IgG in patients with chronic hepatitis B virus and hepatitis C virus infection was 97.5 and 93.6%, respectively. Anti-HAV IgG positivity was 97.4% in cirrhotic patients and 93.9% in noncirrhotic individuals. At the end of the study, being older than 40 years and living in a rural area were found to be independent risk factors for anti-HAV IgG seropositivity. In conclusion, we recommend that patients younger than 40 years and/or those living in cities and having a chronic liver disease should be vaccinated with the hepatitis A vaccine.

Hepatitis A seroprevalence in patients with chronic viral hepatitis in Konya, Turkey

Science.gov (United States)

2016-01-01

Aim Hepatitis A is among the diseases that can be prevented with vaccination in our time. Acute hepatitis A progresses more severely in individuals with a liver disease. Therefore, patients with a chronic liver disease (because of hepatitis B or hepatitis C) are advised vaccination with the hepatitis A vaccine. This study is aimed to determine the seroprevalence of hepatitis A virus (HAV) antibodies in patients infected with hepatitis C virus or hepatitis B virus in Konya province of Turkey. Methods A total of 537 patients who had chronic viral hepatitis between January 2011 and December 2014 were included in the study. Serum samples were collected from each patient and tested for anti-HAV using the chemiluminescent microparticle immunoassay. Results The overall seroprevalence of total anti-HAV IgG was 94.2%. The overall prevalence of anti-HAV IgG in patients with chronic hepatitis B virus and hepatitis C virus infection was 97.5 and 93.6%, respectively. Anti-HAV IgG positivity was 97.4% in cirrhotic patients and 93.9% in noncirrhotic individuals. Conclusion At the end of the study, being older than 40 years and living in a rural area were found to be independent risk factors for anti-HAV IgG seropositivity. In conclusion, we recommend that patients younger than 40 years and/or those living in cities and having a chronic liver disease should be vaccinated with the hepatitis A vaccine. PMID:26703930

INFEKSI VIRUS HEPATITIS B DAN HEPATITIS C PADA PENDERITA HEPATITIS KRONIS DAN HEMODIALISIS DI JAKARTA

Directory of Open Access Journals (Sweden)

Djoko Yuwono

2012-10-01

Full Text Available Virus Hepatitis C dan Hepatitis B merupakan penyebab hepatitis kronik aktif yang dapat berkembang menjadi hepatoselular karsinoma. Untuk mengetahui peranan kedua jenis virus tersebut sebagai penyebab hepatoselular karsinoma, telah dilakukan pemeriksaan HbsAg, anti-VHC dan RNA-VHC pada 17 penderita hepatitis kronis. 19 Pasien hemodialisis dan 198 donor darah PMI. Pemeriksaan HbsAg dilakukan dengan RPHA Cell: pemeriksaan anti-VHC dengan dipstik anti-VHC kit diagnotik produksi NTB Mataram, Lombok. Deteksi RNA-VHC dilakukan dengan teknik RT-PCR, menggunakan primer spesifik untuk daerah 5'NCR. Hasil pemeriksaan menunjukkan bahwa pada penderita hepatitis kronis ditemukan 5 orang (23,5% positif HbsAg dan 1 orang (5,8% anti-VHC. Pada penderita hemodialisis ditemukan 14 orang (73,6% positif anti-VHC, persentase anti-VHC meningkat sesuai dengan meningkatnya frekuensi hemodialisis. Pada donor darah PMI ditemukan 5 orang (2,2% positif HbsAg dan tidak satupun ditemukan anti-VHC positif.

Experimental study of CT perfusion in hepatitis, hepatic fibrosis and early stage of cirrhosis

International Nuclear Information System (INIS)

Guan Sheng; Zhao Weidong; Zhou Kangrong; Peng Weijun; Mao Jian; Tang Feng; Wang Yong; Cao Guang; Sun Fei

2005-01-01

Objective: To investigate the value of CT perfusion in the early diagnosis of hepatic diffuse disease. Methods: Fourteen male Wistar rats of control group and 14 of test group at stages of hepatitis, hepatic fibrosis, hepatic cirrhosis which were induced with diethylnitrosamine (DEN), were studied with CT perfusion respectively. CT perfusion data of different stages were compared and pathologic analysis were performed. Results: Density-time curves of CT perfusion were satisfactory and all perfusion data could be obtained. During the period of hepatitis developing into early stage of hepatic cirrhosis, hepatic artery flow (HAF) trended to increase in test group, mean transmit time (MTT) prolonged obviously, blood flow (BF) and volume (BV) declined. While in control group, HAF declined slightly, MTT, BV and BF increased. Statistic analysis showed the differences of HAF and MTT at different stages between control and test groups were significant (P<0.05 ); the differences of BV and BF between hepatitis and hepatic cirrhosis, hepatic fibrosis and early stage of hepatic cirrhosis in test group were significant (P<0.05), but no significant difference between hepatitis and hepatic fibrosis. The corresponding pathologic changes at stage of hepatitis was swelling of hepatic cells; sinusoids cap illarization and deposition of collagen in the extravascular Disse's spaces were the main changes relating to hepatic blood perfusion at stage of fibrosis and early stage of cirrhosis. Conclusion: The method of CT scan can reflect some changes of hepatic blood perfusion in rats with hepatitis, hepatic fibrosis and early stage of cirrhosis. The data of CT perfusion, especially the changes should be valuable for clinical early diagnosis, treatment and follow-up. (authors)

Fetomaternal Outcome with Hepatitis E in Pregnancy

International Nuclear Information System (INIS)

Yasmeen, T.; Hashmi, H.A.; Taj, A.

2013-01-01

Objective: To assess the maternal morbidity and mortality and fetal outcome with hepatitis E (HEV) in pregnancy. Study Design: Cross-sectional study. Place and Duration of Study: Liaquat National Hospital, Karachi, from May 2008 to April 2010. Methodology: Thirty patients admitted at Gynae Ward with serologically proven HEV in pregnancy were included in the study. All these patients were followed during their hospital stay with liver function tests and coagulation profile. Maternal morbidity and mortality and fetal outcome were recorded. Results: Maximum maternal morbidities were noted in patients who presented in 3rd trimester, both clinically and derangement of haematological and biochemical tests. Out of 30 patients, 08 patients expired with maternal mortality rate of 29.3% and rest were discharged safely. Perinatal mortality rate was 30.3 per 1000 live births. Conclusion: Hepatitis E runs a fulminant course during pregnancy with very high mortality rate especially during third trimester and postpartum period. (author)

Interventional treatment of emergent hepatic artery thrombosis after liver transplantation

International Nuclear Information System (INIS)

Liu Fengyong; Wang Maoqiang; Wang Zhijun; Wang Zhongpu; Shi Xianjie; Zhou Ningxin

2006-01-01

Objective: To evaluate the safety and efficacy of the endovascular interventional techniques for the management of emergent hepatic artery thrombosis (HAT) after orthotopic liver transplantation (OLT). Methods: Ten patients (8 men and 2 women with mean age of 47 years) diagnosed with HAT after OLT were treated with interventional procedures. All patients presented with elevation of liver enzymes and bilirubin levels. The diagnosis of the HAT was suggested by doppler ultrasonography and confirmed by angiography at 16 hours to 10 days (mean, 4.5 days) after OLT. Interventional techniques consisted of indwelling transcatheter hepatic arterial thrombolysis with a low dose of urokinase monitored under ultrasonography every 6-12 hours and stent placement in the stenotic segment of the hepatic artery was undertaken. Systemic intravenous low dose of heparin was given contemporaneously. Results: Complete occlusion of the proper HA was achieved in 10 patients. Hepatic arterial flow was re-established in 8 of the 10 patients (80%) at 12 hours to 9 days (mean, 4.8 days) after the intra-arterial thrombolysis, with significant improvement of liver function. Hepatic artery stenosis at the anastomosis was found in the 8 patients, and a stent placement in the stenotic segment was performed successfully in 7 patients with degree of stenosis over 90%.Intra-arterial thrombolysis was failed in 2 cases. Intraperitoneal hemorrhage from the anastomosis occurred in 1 patient at 12 hours after the treatment, and was emergently taken for the graft revision with reanastomosis. One patient with complete occlusion of the hepatic artery at 7 days after the treatment, but having collateral flow of the liver for maintaining liver function and thus sparing further intervention. 8 patients with successful hepatic arterial recanalization carried along a good clinical course with normal graft function at a median 12 months (range, 4 to 20 months), and patent hepatic arterial flow was identified by

Hepatitis Risk Assessment

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... please visit this page: About CDC.gov . Hepatitis Risk Assessment Recommend on Facebook Tweet Share Compartir Viral Hepatitis. Are you at risk? Take this 5 minute Hepatitis Risk Assessment developed ...

Yeast-recombinant hepatitis B vaccine: efficacy with hepatitis B immune globulin in prevention of perinatal hepatitis B virus transmission

International Nuclear Information System (INIS)

Stevens, C.E.; Taylor, P.E.; Tong, M.J.; Toy, P.T.; Vyas, G.N.; Nair, P.V.; Weissman, J.Y.; Krugman, S.

1987-01-01

A yeast-recombinant hepatitis B vaccine was licensed recently by the Food and Drug administration and is now available. To assess the efficacy of the yeast-recombinant vaccine, the authors administered the vaccine in combination with hepatitis B immune globulin to high-risk newborns. If infants whose mothers were positive for both hepatitis B surface antigen and the e antigen receive no immunoprophylaxis, 70% to 90% become infected with the virus, and almost all become chronic carriers. Among infants in this study who received hepatitis B immune globulin at birth and three 5- + g doses of yeast-recombinant hepatitis B vaccine, only 4.8% became chronic carriers, a better than 90% level of protection and a rate that is comparable with that seen with immune globulin and plasma-derived hepatitis B vaccine. Hepatitis surface antigen and antibodies were detected by radioimmunoassay. These data suggest that, in this high-risk setting, the yeast-recombinant vaccine is as effective as the plasma-derived vaccine in preventing hepatitis B virus infection and the chronic carrier state

Nonalcoholic fatty liver disease and hepatic cirrhosis: Comparison with viral hepatitis-associated steatosis.

Science.gov (United States)

Haga, Yuki; Kanda, Tatsuo; Sasaki, Reina; Nakamura, Masato; Nakamoto, Shingo; Yokosuka, Osamu

2015-12-14

Nonalcoholic fatty liver disease (NAFLD) including nonalcoholic steatohepatitis (NASH) is globally increasing and has become a world-wide health problem. Chronic infection with hepatitis B virus or hepatitis C virus (HCV) is associated with hepatic steatosis. Viral hepatitis-associated hepatic steatosis is often caused by metabolic syndrome including obesity, type 2 diabetes mellitus and/or dyslipidemia. It has been reported that HCV genotype 3 exerts direct metabolic effects that lead to hepatic steatosis. In this review, the differences between NAFLD/NASH and viral hepatitis-associated steatosis are discussed.

Liver Cancer and Hepatitis B

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... Clinical Trials Physician Directory HBV Meeting What Is Hepatitis B? What Is Hepatitis B? The ABCs of Viral Hepatitis Liver Cancer and Hepatitis B Hepatitis Delta Coinfection Hepatitis C Coinfection HIV/AIDS ...

Normal variation of hepatic artery

International Nuclear Information System (INIS)

Kim, Inn; Nam, Myung Hyun; Rhim, Hyun Chul; Koh, Byung Hee; Seo, Heung Suk; Kim, Soon Yong

1987-01-01

This study was an analyses of blood supply of the liver in 125 patients who received hepatic arteriography and abdominal aortography from Jan. 1984 to Dec. 1986 at the Department of Radiology of Hanyang University Hospital. A. Variations in extrahepatic arteries: 1. The normal extrahepatic artery pattern occurred in 106 of 125 cases (84.8%) ; Right hepatic and left hepatic arteries arising from the hepatic artery proper and hepatic artery proper arising from the common hepatic artery. 2. The most common type of variation of extrahepatic artery was replaced right hepatic artery from superior mesenteric artery: 6 of 125 cases (4.8%). B. Variations in intrahepatic arteries: 1. The normal intrahepatic artery pattern occurred in 83 of 125 cases (66.4%). Right hepatic and left hepatic arteries arising from the hepatic artery proper and middle hepatic artery arising from lower portion of the umbilical point of left hepatic artery. 2. The most common variation of intrahepatic arteries was middle hepatic artery. 3. Among the variation of middle hepatic artery; Right, middle and left hepatic arteries arising from the same location at the hepatic artery proper was the most common type; 17 of 125 cases (13.6%)

Hepatitis B & C and HIV

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... Find Services HIV SERVICES LOCATOR Locator Search Search Hepatitis B & C Topics Hepatitis B Hepatitis C Hepatitis ... Infections Sexually Transmitted Diseases Smoking Women's Health Issues Hepatitis B Virus and Hepatitis C Virus Infection People ...

Hepatitis C: Sex and Sexuality

Science.gov (United States)

... with Hepatitis » Sex and Sexuality: Entire Lesson Viral Hepatitis Menu Menu Viral Hepatitis Viral Hepatitis Home For ... hepatitis C virus through sex. Can you pass hepatitis C to a sex partner? Yes, but it ...

Hepatitis C: Diet and Nutrition

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... with Hepatitis » Daily Living: Diet and Nutrition Viral Hepatitis Menu Menu Viral Hepatitis Viral Hepatitis Home For ... have high cholesterol and have fatty liver. How hepatitis C affects diet If you have hepatitis, you ...

Hepatic retinoid levels in seven fish species (teleosts) from a tropical coastal lagoon receiving effluents from iron-ore mining and processing.

Science.gov (United States)

Pereira, Adriana A; van Hattum, Bert; Brouwer, Abraham

2012-02-01

The present study was undertaken to investigate the possible effects of Fe and trace element exposure on hepatic levels of retinoids in seven fish species. Concentrations of retinoids were measured in fish collected from a coastal lagoon in Brazil that receives effluents from an iron-ore mining and processing plant. Fish from nearby coastal lagoons were also included to assess possible differences related to chemical exposure. Results indicated considerable differences in hepatic retinoid composition among the various species investigated. The most striking differences were in retinol and derivative-specific profiles and in didehydro retinol and derivative-specific profiles. The Perciformes species Geophagus brasiliensis, Tilapia rendalli, Mugil liza, and Cichla ocellaris and the Characiforme Hoplias malabaricus were characterized as retinol and derivative-specific, while the Siluriformes species Hoplosternum littorale and Rhamdia quelen were didehydro retinol and derivative-specific fish species. A negative association was observed between Al, Pb, As, and Cd and hepatic didehydro retinoid levels. Fish with higher levels of hepatic Fe, Cu, and Zn showed unexpectedly significant positive correlations with increased hepatic retinol levels. This finding, associated with the positive relationships between retinol and retinyl palmitate with lipid peroxidation, may suggest that vitamin A is mobilized from other tissues to increase hepatic antioxidant levels for protection against oxidative damage. These data show significant but dissimilar associations between trace element exposure and hepatic retinoid levels in fish species exposed to iron-ore mining and processing effluents, without apparent major impacts on fish health and condition. Copyright © 2011 SETAC.

Comprehensive analysis of PPARα-dependent regulation of hepatic lipid metabolism by expression profiling - 5

NARCIS (Netherlands)

Rakhshandehroo, Maryam; Sanderson-Kjellberg, L.M.; Matilainen, Merja; Stienstra, Rinke; Carlberg, Carsten; Groot, de Philip; Muller, Michael; Kersten, Sander

2007-01-01

PPARα is a ligand-activated transcription factor involved in the regulation of nutrient metabolism and inflammation. Although much is already known about the function of PPARα in hepatic lipid metabolism, many PPARα-dependent pathways and genes have yet to be discovered. In order to obtain an

Does chronic hepatitis B infection affect the clinical course of acute hepatitis A?

Science.gov (United States)

Shin, Su Rin; Moh, In Ho; Jung, Sung Won; Kim, Jin Bae; Park, Sang Hoon; Kim, Hyoung Su; Jang, Myung Kuk; Lee, Myung Seok

2013-01-01

The impact of chronic hepatitis B on the clinical outcome of acute hepatitis A remains controversial. The aim of present study was to evaluate the clinical characteristics of acute hepatitis A in cases with underlying chronic hepatitis B compared to cases of acute hepatitis A alone. Data on 758 patients with acute hepatitis A admitted at two university-affiliated hospitals were reviewed. Patients were classified into three groups: group A, patients with both acute hepatitis A and underlying chronic hepatitis B (n = 27); group B, patients infected by acute hepatitis A alone whose sexes and ages were matched with patients in group A (n  = 54); and group C, patients with acute hepatitis A alone (n = 731). None of the demographic features of group A were significantly different from those of group B or C, except for the proportion of males and body weight, which differed from group C. When comparing to group B, clinical symptoms were more frequent, and higher total bilirubin and lower albumin levels were observed in group A. When comparing to group C, the albumin levels were lower in group A. There were no differences in the duration of hospital stay, occurrence of acute kidney injury, acute liver failure, prolonged cholestasis, or relapsing hepatitis. This study revealed that clinical symptoms and laboratory findings were less favorable for patients with acute hepatitis A and chronic hepatitis B compared to those with acute hepatitis A alone. However, there were no differences in fatal outcomes or serious complications. Copyright © 2012 Wiley Periodicals, Inc.

Mutation profiling of the hepatitis B virus strains circulating in North Indian population.

Directory of Open Access Journals (Sweden)

Amit Tuteja

Full Text Available AIMS: The aim of this study was to investigate the genomic mutations in the circulating Hepatitis B virus strains causing infection in the Indian population. Further, we wanted to analyze the biological significance of these mutations in HBV mediated disease. METHODS: 222 HBsAg positive patients were enrolled in the study. The genotype and mutation profile was determined for the infecting HBV isolate by sequencing overlapping fragments. These sequences were analyzed by using different tools and compared with previously available HBV sequence information. Mutation Frequency Index (MFI for the Genes and Diagnosis group was also calculated. RESULTS: HBV Genotype D was found in 55% (n = 121 of the patient group and genotype A was found in 30% (n = 66 of samples. The majority (52% of the HBV-infected individuals in the present study were HBeAg-negative in all the age groups studied. Spontaneous drug associated mutations implicated in resistance to antiviral therapy were also identified in about quarter of our patients, which is of therapeutic concern. The MFI approach used in the study indicated that Core peptide was the most conserved region in both genotypes and Surface peptide had highest mutation frequency. Few mutations in X gene (T36A and G50R showed high frequency of association with HCC. A rare recombinant strain of HBV genotype A and D was also identified in the patient group. CONCLUSIONS: HBV genotype D was found out to be most prevalent. More than half of the patients studied had HBeAg negative disease. Core region was found to be most conserved. Drug Associated mutations were detected in 22% of the patient group and T36A and G50R mutations in X gene were found to be associated with HCC.

Acute hepatitis B virus infection with simultaneous high HBsAg and high anti-HBs signals in a previously HBV vaccinated HIV-1 positive patient

NARCIS (Netherlands)

van Dommelen, Laura; Verbon, Annelies; van Doorn, H. Rogier; Goossens, Valère J.

2010-01-01

We present a case of a clinical manifest hepatitis B virus infection and a potentially misleading HBV serological profile in an HIV-1 positive patient despite previous HBV vaccination. The patient presented with an acute hepatitis B and there was no indication of chronic HBV infection or the

How Hepatitis D Virus Can Hinder the Control of Hepatitis B Virus

NARCIS (Netherlands)

Xiridiou, M.; Borkent-Raven, B.; Hulshof, J.; Wallinga, J.

2009-01-01

Background: Hepatitis D (or hepatitis delta) virus is a defective virus that relies on hepatitis B virus (HBV) for transmission; infection with hepatitis D can occur only as coinfection with HBV or superinfection of an existing HBV infection. Because of the bond between the two viruses, control

Microbiological diagnostics of viral hepatitis

OpenAIRE

HASDEMİR, Ufuk

2016-01-01

Viral hepatitis is an infection that primarily affects the liverbut may also have systemic clinical manifestations. The vastmajority of viral hepatitis are caused by one of five hepatotropicviruses: hepatitis A virus (HAV), hepatitis B virus (HBV),hepatitis C virus (HCV), hepatitis D (delta) virus (HDV), andhepatitis E virus (HEV) (Table I) [1]. HBV, HCV, and HDValso cause chronic hepatitis, whereas HAV does not. HEVcauses acute hepatitis in normal hosts but can cause protractedand chronic he...

Efficacy and safety on tenofovire therapy in patients with hepatitis B viral infections resistent to lamivudin

Directory of Open Access Journals (Sweden)

Katanić N.

2015-01-01

Full Text Available Chronic viral hepatitis B (CHB still represents a significant world health problem despite obligatory and worldwide immunization against infections of viral hepatitis B. In some patients with chronic viral hepatitis B infections, in the natural course of the disease, progression towards cirhossis and hepatocellular carcinoma is primarily targeted by antiviral CHB therapy stopping further progression of the disease. Today on the market there exist two classes of pharmnaceutical drugs for treatment of CHB: a immunomodulatory therapy with conventional interferon alpha (INF and PEGylated interferon alpha-2a, b and oral antiviral therapy with nucleos( tide analogues. Lamivudine was for quite a period the only medicament available on our market for the treatment of HVB and in most of our patients led to the development of resistance. As of two years ago, a new oral analogue from the group of nucleotides is being registered in Serbia for market use: tenofovir disoproxil (TDF. In our work we have analysed 69 patients with chronic viral hepatitis B treated in the Clinic for Infectious and Tropical Diseases KCS Belgrade in the period between years 2012 and 2014. All patients involved in this reasearch were previously treated with LAM, and on subsequent development of resistance to LAM, TDF was used. TDF showed an excellent efficacy, a high resistance barrier and very few unwanted side effects over several years of treatment. Our experience with the use of this drug does not pertain to and acount for its long term use, in view of its brief availability on our market.

Safety of statins

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Debasish Maji

2013-01-01

Full Text Available Statins are an established class of drugs with proven efficacy in cardiovascular risk reduction. The concern over statin safety was first raised with the revelation of myopathy and rhabdomyolysis with the use of now withdrawn cerivastatin. Enhanced understanding of the mechanisms behind adverse effects of statins including an insight into the pharmacokinetic properties have minimised fear of statin use among clinicians. Studies reveal that occurrence of myopathy and rhabdomyolysis are rare 1/100000 patient-years. The risk of myopathy/rhabdomyolysis varies between statins due to varying pharmacokinetic profiles. This explains the differing abilities of statins to adverse effects and drug interaction potentials that precipitate adverse effects. Higher dose of rosuvastatin (80 mg/day was associated with proteinuria and hematuria while lower doses were devoid of such effects. Awareness of drugs interacting with statins and knowledge of certain combinations such as statin and fibrates together with monitoring of altered creatine kinase activity may greatly minimise associated adverse effects. Statins also asymptomatically raise levels of hepatic transaminases but are not correlated with hepatotoxicity. Statins are safe and well tolerated including more recent potent statins such as, rosuvastatin. The benefits of intensive statin use in cardiovascular risk reduction greatly outweigh risks. The present review discusses underlying causes of statin-associated adverse effects including management in high risk groups.

Feature Hepatitis: The Dangers of Hepatitis: What you should know from A to E

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... Navigation Bar Home Current Issue Past Issues Feature Hepatitis The Dangers of Hepatitis: What you should know from A to E ... drugs. In some cases, hepatitis lasts a lifetime. Hepatitis: Acute or Chronic? Acute hepatitis is the initial ...

Hepatitis C virus core protein induces hepatic steatosis via Sirt1-dependent pathway.

Science.gov (United States)

Zhang, Chuanhai; Wang, Jingjing; Zhang, Hanlin; Liu, Shunai; Lee, Hyuek Jong; Jin, Wanzhu; Cheng, Jun

2018-05-01

Hepatic steatosis is a common feature of patients with chronic hepatitis C. Previous reports have shown that the overexpression of hepatitis C virus core-encoding sequences (hepatitis C virus genotypes 3a and 1b) significantly induces intracellular triglyceride accumulation. However, the underlying mechanism has not yet been revealed. To investigate whether Sirt1 is involved in hepatitis C virus-mediated hepatic steatosis, the overexpression of hepatitis C virus core 1b protein and Sirt1 and the knockdown of Sirt1 in HepG2 cells were performed. To confirm the results of the cellular experiment liver-specific Sirt1 KO mice with lentivirus-mediated hepatitis C virus core 1b overexpression were studied. Our results show that hepatitis C virus core 1b protein overexpression led to the accumulation of triglycerides in HepG2 cells. Notably the expression of PPARγ2 was dramatically increased at both the mRNA and protein levels by hepatitis C virus core 1b overexpression. The protein expression of Sirt1 is an upstream regulator of PPARγ2 and was also significantly increased after core 1b overexpression. In addition, the overexpression or knockdown of Sirt1 expression alone was sufficient to modulate p300-mediated PPARγ2 deacetylation. In vivo studies showed that hepatitis C virus core protein 1b-induced hepatic steatosis was attenuated in liver-specific Sirt1 KO mice by downregulation of PPARγ2 expression. Sirt1 mediates hepatitis C virus core protein 1b-induced hepatic steatosis by regulation of PPARγ2 expression. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Hepatitis B Test

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... Links Patient Resources For Health Professionals Subscribe Search Hepatitis B Testing Send Us Your Feedback Choose Topic At ... Known As HBV Tests Hep B anti-HBs Hepatitis B Surface Antibody HBsAg Hepatitis B Surface Antigen HBeAg ...

Safety profile of solid lipid nanoparticles loaded with rosmarinic acid for oral use: in vitro and animal approaches

Directory of Open Access Journals (Sweden)

Madureira AR

2016-08-01

Full Text Available Ana Raquel Madureira,1 Sara Nunes,2 Débora A Campos,1 João C Fernandes,2 Cláudia Marques,3 Monica Zuzarte,2 Beatriz Gullón,1 Luís M Rodríguez-Alcalá,1 Conceição Calhau,3,4 Bruno Sarmento,5–7 Ana Maria Gomes,1 Maria Manuela Pintado,1 Flávio Reis2 1Catholic University of Portugal, CBQF – Center for Biotechnology and Fine Chemistry – Associate Laboratory, Faculty of Biotechnology, Porto, Portugal; 2Laboratory of Pharmacology and Experimental Therapeutics, Institute for Biomedical Imaging and Life Sciences (IBILI, Faculty of Medicine, and CNC.IBILI Consortium, University of Coimbra, Coimbra, Portugal; 3Department of Biochemistry, Faculty of Medicine, University of Porto, Porto, Portugal; 4Center for Health Technology and Services Research (CINTESIS, Porto, Portugal; 5Department of Pharmaceutical Sciences, Institute of Health Sciences-North, CESPU, Gandra, Portugal; 6“I3S” Instituto de Investigação e Inovação em Saúde, University of Porto, Porto, Portugal; 7INEB, Institute of Biomedical Engineering, University of Porto, Porto, Portugal Abstract: Rosmarinic acid (RA possesses several protective bioactivities that have attracted increasing interest by nutraceutical/pharmaceutical industries. Considering the reduced bioavailability after oral use, effective (and safe delivery systems are crucial to protect RA from gastrointestinal degradation. This study aims to characterize the safety profile of solid lipid nanoparticles produced with Witepsol and Carnauba waxes and loaded with RA, using in vitro and in vivo approaches, focused on genotoxicity and cytotoxicity assays, redox status markers, hematological and biochemical profile, liver and kidney function, gut bacterial microbiota, and fecal fatty acids composition. Free RA and sage extract, empty nanoparticles, or nanoparticles loaded with RA or sage extract (0.15 and 1.5 mg/mL were evaluated for cell (lymphocytes viability, necrosis and apoptosis, and antioxidant

Aberrant hepatic artery

International Nuclear Information System (INIS)

Konstam, M.A.; Novelline, R.A.; Athanasoulis, C.A.

1979-01-01

In a patient undergoing selective hepatic arteriography for suspected liver trauma, a nonopacified area of the liver, initially thought to represent a hepatic hematoma, was later discovered to be due to the presence of an accessory right hepatic artery arising from the superior mesenteric artery. This case illustrates the need for a search for aberrant vasculature whenever a liver hematoma is suspected on the basis of a selective hepatic arteriogram. (orig.) [de

Seroprevalence and risk factors of Hepatitis B and Hepatitis C ...

African Journals Online (AJOL)

Undertaking blood transfusion, tattooing and sharing of needles were associated with hepatitis C infection (P=0.001). HBV was not associated with any of the risk factors (P>0.05). Conclusion: Our findings suggest a high prevalence of hepatitis B and hepatitis C among pregnant women; blood transfusion, tattooing and ...

Twenty years of universal vaccination against hepatitis B in Italy: achievements and challanges

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Luisa Romano'

2012-04-01

Full Text Available Viral hepatitis B is a vaccine-preventable disease. Vaccination has proved to be safe and highly effective in reducing the incidence, the carrier rate and HBV-related mortality on a global scale. In Italy, universal vaccination against hepatitis B started in 1991 in infants as well as in adolescents, providing an outstanding record of safety and effectiveness. Within a few years, over 95% coverage was consistently reported. Today, some 17 million people are immune against hepatitis B and their immunity has been shown to be long-lasting. At present, no booster is required in healthy vaccinated people to sustain protection. Surveillance data from Italy have shown a clear overall decline in hepatitis B among successfully vaccinated individuals. Furthermore, a generation of children and young people (at present cohorts ranging from 0 to 32 years is emerging with practically no markers of HBV infection. Italy’s vaccination programme has resulted in substantial progress being made towards the prevention and control of hepatitis B. The vaccination programme must continue. Maintaining mandatory vaccination of infants and increasing HBV vaccination coverage in high-risk groups, including households of HBsAg carriers as well as immigrants, remain a priority for the future.

Road safety performance indicators : country profiles. SafetyNet, Building the European Road Safety Observatory, Workpackage 3, Deliverable 3.7b.

NARCIS (Netherlands)

Riguelle, F. Eksler, V. Holló, P. Morsink, P. Gent, A. van Gitelman, V. Assum, T. & Rackliff, L.

2009-01-01

The EC 6th Framework Integrated Project SafetyNet aims to accelerate the availability and use of harmonised road safety data in Europe. Having such data available throughout Europe would be tremendously beneficial for road safety, since it would enable the evaluation of road safety measures, the

Lower doses venlafaxine-associated toxic hepatitis in a patient with chronic hepatitis

International Nuclear Information System (INIS)

Sencan, I.; Sahin, I.; Ozcetin, A.

2003-01-01

Toxic hepatitis is observed with high doses of Venlafaxine. But toxic hepatitis has not been yet reported at lower doses of Venlafaxine such as 37.5 mg per day. In this case report, a case of Venlafaxine associated toxic hepatitis with lower doses in patient with history of chronic hepatitis is presented. We suggest that liver function should be regularly monitored in patients with history of chronic hepatitis receiving Venlafaxine even at lower doses and even when their liver enzymes are normal. (author)

Virus-specific immune response in HBeAg-negative chronic hepatitis B: relationship with clinical profile and HBsAg serum levels.

Directory of Open Access Journals (Sweden)

Elisabetta Loggi

Full Text Available BACKGROUND AIMS: The immune impairment characterizing chronic hepatitis B (cHBV infection is thought to be the consequence of persistent exposure to viral antigens. However, the immune correlates of different clinical stages of cHBV and their relation with different levels of HBsAg have not been investigated. The aim of the present study was to evaluate the relationship between HBV-specific T cells response and the degree of in vivo HBV control and HBsAg serum levels in HBeAg-HBeAb+ cHBV. METHODS: Peripheral blood mononuclear cells from 42 patients with different clinical profiles (treatment-suppressed, inactive carriers and active hepatitis of cHBV, 6 patients with resolved HBV infection and 10 HBV-uninfected individuals were tested with overlapping peptides spanning the entire HBV proteome. The frequency and magnitude of HBV-specific T cell responses was assessed by IFNγ ELISPOT assay. Serum HBsAg was quantified with a chemiluminescent immunoassay. RESULTS: The total breadth and magnitude of HBV-specific T cell responses did not differ significantly between the four groups. However, inactive carriers targeted preferentially the core region. In untreated patients, the breadth of the anti-core specific T cell response was inversely correlated with serum HBsAg concentrations as well as HBV-DNA and ALT levels and was significantly different in patients with HBsAg levels either above or below 1000 IU/mL. The same inverse association between anti-core T cell response and HBsAg levels was found in treated patients. CONCLUSIONS: Different clinical outcomes of cHBV infection are associated with the magnitude, breadth and specificity of the HBV-specific T cell response. Especially, robust anti-core T cell responses were found in the presence of reduced HBsAg serum levels, suggesting that core-specific T cell responses can mediate a protective effect on HBV control.

Disease Modeling and Gene Therapy of Copper Storage Disease in Canine Hepatic Organoids

NARCIS (Netherlands)

Nantasanti, Sathidpak; Spee, Bart; Kruitwagen, Hedwig S.; Chen, Chen; Geijsen, Niels; Oosterhoff, Loes A.; van Wolferen, Monique E.; Pelaez, Nicolas; Fieten, Hille; Wubbolts, Richard W.; Grinwis, Guy C.; Chan, Jefferson; Huch, Meritxell; Vries, Robert R. G.; Clevers, Hans; de Bruin, Alain; Rothuizen, Jan; Penning, Louis C.; Schotanus, Baukje A.

2015-01-01

The recent development of 3D-liver stem cell cultures (hepatic organoids) opens up new avenues for gene and/or stem cell therapy to treat liver disease. To test safety and efficacy, a relevant large animal model is essential but not yet established. Because of its shared pathologies and disease

Hepatic Encephalopathy

Medline Plus

Full Text Available ... Donate Today Enroll in 123 What is Hepatic Encephalopathy? Hepatic Encephalopathy, sometimes referred to as portosystemic encephalopathy or PSE, is a condition that causes temporary ...

Direct-acting antiviral agent efficacy and safety in renal transplant recipients with chronic hepatitis C virus infection: A PRISMA-compliant study.

Science.gov (United States)

Chen, Keliang; Lu, Pei; Song, Rijin; Zhang, Jiexiu; Tao, Rongzhen; Wang, Zijie; Zhang, Wei; Gu, Min

2017-07-01

The efficacy and safety of direct-acting antivirals (DAAs) for treating hepatitis C virus (HCV)-infected renal transplant recipients (RTRs) has not been determined. We searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials and assessed the quality of eligible studies using the Joanna Briggs Institute scale. DAA efficacy and safety were assessed using standard mean difference (SMD) with 95% confidence intervals (95%CIs). Six studies (360 RTRs) were included. Two hundred thirty six RTRs (98.3%) achieved sustained virological response within 12 weeks; HCV infection was cleared in 239 RTRs after 24-week treatment. Liver function differed significantly pre- and posttreatment (alanine aminotransferase, SMD: 0.96, 95%CIs: 0.65, 1.26; aspartate aminotransferase, SMD: 0.89, 95%CIs: 0.60, 1.18); allograft function pre- and posttreatment was not statistically different (serum creatinine, SMD: -0.13, 95%CIs: -0.38, 0.12; estimated glomerular filtration rate, SMD: 0.20, 95%CIs: -0.11, 0.51). General symptoms (fatigue nausea dizziness or headache) were the most common adverse events (AEs) (39.3%). Severe AEs, that is, anemia, portal vein thrombosis, and streptococcus bacteraemia and pneumonia, were present in 1.1%, 0.6%, and 1.1% of RTRs, respectively. Our findings suggest that DAAs are highly efficacious and safe for treating HCV-infected RTRs and without significant AE.

Biological and haematological safety profile of oral amodiaquine and chloroquine in healthy volunteers with or without Plasmodium falciparum infection in northeast Tanzania.

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Massaga, J J; Lusingu, J P; Makunde, R; Malebo, H M; Chile, M M; Akida, J A; Lemnge, M M; Rønn, A M; Theander, T G; Bygbjerg, I C; Kitua, A Y

2008-07-01

Amodiaquine (AQ), an effective antimalarial drug for uncomplicated malaria, has been greatly restricted after cases of life-threatening agranulocytosis and hepatic toxicity during prophylactic use. We conducted a hospital based open-label randomised clinical trial in 40 indigenous semi-immune healthy adult male volunteers with and without malaria parasites. The objective was to collect data on biological and haematological safety, tolerability, and parasitological efficacy to serve as baseline in the evaluation of the effectiveness of AQ preventive intermittent treatment against malaria morbidity in infants. Volunteers were stratified according to parasitaemia status and randomly assigned 20 participants each arm to three days treatment with either AQ or chloroquine (CQ). The level of difference of selected haematological and hepatological values pre-and post-trial were marginal and within the normal limits. Clinical adverse effects mostly mild and transient were noticed in 33.3% CQ treated-aparasitaemic, 23.8% of CQ treated-parasitaemic, 28.6% ofAQ-treated parasitaemic and 14.3% of aparasitaemic receiving AQ. Amodiaquine attained 100% parasitological clearance rate versus 70% in CQ-treated volunteers. The findings indicate that there was no agranulocytosis or hepatic toxicity suggesting that AQ may pose no public health risk in its wide therapeutic dosage uses. Larger studies are needed to exclude rare adverse effects.

Cocoa butter and safflower oil elicit different effects on hepatic gene expression and lipid metabolism in rats.

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Gustavsson, Carolina; Parini, Paolo; Ostojic, Jovanca; Cheung, Louisa; Hu, Jin; Zadjali, Fahad; Tahir, Faheem; Brismar, Kerstin; Norstedt, Gunnar; Tollet-Egnell, Petra

2009-11-01

The aim of this study was to compare the effects of cocoa butter and safflower oil on hepatic transcript profiles, lipid metabolism and insulin sensitivity in healthy rats. Cocoa butter-based high-fat feeding for 3 days did not affect plasma total triglyceride (TG) levels or TG-rich VLDL particles or hepatic insulin sensitivity, but changes in hepatic gene expression were induced that might lead to increased lipid synthesis, lipotoxicity, inflammation and insulin resistance if maintained. Safflower oil increased hepatic beta-oxidation, was beneficial in terms of circulating TG-rich VLDL particles, but led to reduced hepatic insulin sensitivity. The effects of safflower oil on hepatic gene expression were partly overlapping with those exerted by cocoa butter, but fewer transcripts from anabolic pathways were altered. Increased hepatic cholesterol levels and increased expression of hepatic CYP7A1 and ABCG5 mRNA, important gene products in bile acid production and cholesterol excretion, were specific effects elicited by safflower oil only. Common effects on gene expression included increased levels of p8, DIG-1 IGFBP-1 and FGF21, and reduced levels of SCD-1 and SCD-2. This indicates that a lipid-induced program for hepatic lipid disposal and cell survival was induced by 3 days of high-fat feeding, independent on the lipid source. Based on the results, we speculate that hepatic TG infiltration leads to reduced expression of SCD-1, which might mediate either neutral, beneficial or unfavorable effects on hepatic metabolism upon high-fat feeding, depending on which fatty acids were provided by the diet.

Hepatitis A Virus and Hepatitis E Virus: Emerging and Re-Emerging Enterically Transmitted Hepatitis Viruses.

Science.gov (United States)

Lemon, Stanley M; Walker, Christopher M

2018-05-07

Over the past two decades, progress in understanding human infections with hepatitis A virus (HAV) and hepatitis E virus (HEV) has been eclipsed by the priority of combating persistent hepatitis B virus (HBV) and hepatitis C virus (HCV) infections. During that time, the global burden of liver disease caused by enteric hepatitis viruses has not abated. Because of vaccines, hepatitis A has become increasingly a disease of adults instead of early childhood in many regions of the world, resulting in an age-related shift toward more severe disease. HEV has remained endemic in many developing countries, and in well-developed, economically advanced countries it is now recognized as a cause of chronic, progressive liver disease in individuals with compromised immunity. The goal of this collection of articles is to review recent progress and to shine a bright light on gaps in our understanding of how these viruses replicate, cause disease, interact with the liver and host immune system, and are transmitted, along with prospects for improved control in human populations. Renewed efforts to study and compare HAV and HEV biology in humans and animal models have high potential to enhance our understanding of host-pathogen balance in the liver, and may contribute ultimately to the control of other infectious diseases of the liver. Copyright © 2018 Cold Spring Harbor Laboratory Press; all rights reserved.

The hepatic bridge.

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Sugarbaker, Paul H

2018-07-01

The hepatic bridge forms a tunnel of liver parenchyma that may obscure peritoneal metastases associated with the round ligament. Visualization and then resection of nodules associated with this structure is necessary. The incidence of a hepatic bridge and the extent that it covered the round ligament was determined in consecutive patients. Extent of coverage of the round ligament by the hepatic bridge was determined: Class 1 indicates up to one-third of the round ligament obscured, Class 2 up to two-thirds and Class 3 more than two-thirds. In 102 patients in whom the round ligament of the liver could be completely visualized, 50 had a hepatic bridge. Class 1 was 22 (44%) of the bridges, Class 2 was 16 (32%) and Class 3 was 12 (24%). A hepatic bridge was more frequently present in 28 of 45 male patients (62%) vs. 22 of 57 female patients (38%). Approximately one-half of our patients having cytoreductive surgery for peritoneal metastases were observed to have a hepatic bridge. Up to 56% of these patients have Class 2 or 3 hepatic bridge and may require division of the hepatic bridge to completely visualize the contents of the tunnel created by this structure. Copyright © 2018 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

Accessory hepatic vein: MR imaging

International Nuclear Information System (INIS)

Lee, Chang Hee; Rho, Tack Soo; Cha, Sang Hoon; Park, Cheol Min; Cha, In Ho

1995-01-01

To evaluate the MR appearance of the accessory hepatic veins. The study included 87 consecutive patients for whom abdominal MR images were obtained. The subjects who had liver lesion or hepatic vascular abnormalities were excluded. Couinaud classified accessory hepatic veins into inferior and middle right hepatic veins. Our major interests were evaluation of the incidence, morphology, and location of the accessory hepatic vein. Inferior right hepatic vein was demonstrated in 43 out of 87 patients (49%). The morphology was linear in 35 patients (80.5%), and V-shaped in 8 patients (19.5%). In 40 patients (93%), the inferior right hepatic vein was located in the posteroinferior aspect of the right lobe. Middle right hepatic vein was demonstrated in 7 out of 87 patients (8%). All were single linear in morphology, combined with the inferior right hepatic vein, and located between the right hepatic vein and inferior right hepatic vein. The accessory hepatic vein was demonstrated in 49% among the Korean adult population, and was located in posteroinferior portion of the liver, in 93%

Features of Hepatitis in Hepatitis-associated Aplastic Anemia: Clinical and Histopathologic Study.

Science.gov (United States)

Patel, Kalyani R; Bertuch, Alison; Sasa, Ghadir S; Himes, Ryan W; Wu, Hao

2017-01-01

Hepatitis-associated aplastic anemia (HAA) is a rare variant of aplastic anemia in which patients present with severe pancytopenia after an episode of acute hepatitis. The marrow failure is often rapid, severe, and usually fatal if untreated. The preceding hepatitis is largely under-studied. Retrospective study of the clinical and histopathologic features of hepatitis in pediatric patients who subsequently developed aplastic anemia and comparison with consecutive cases of acute liver failure and random cases of autoimmune hepatitis during the same time frame. All 7 patients of HAA had significant elevations in aminotransferases and conjugated hyperbilirubinemia at initial presentation. Echoing liver function indices, cholestatic hepatitis with sinusoidal obstruction-type endothelial injury was seen histomorphologically. Autoimmune hepatitis serology such as anti-F-actin, anti-liver/kidney microsome, and hypergammaglobulinemia was negative in all patients. Five of 7 patients (71.4%) had, however, elevated antinuclear antibody, all with a speckled pattern. Hepatitis virus serology was negative in all patients. By immunohistochemical staining, the lobular CD8/CD4 lymphocyte ratio was markedly elevated in all of the initial samples with significant reduction in this ratio (P = 0.03) in 3 patients post treatment (ursodiol, antibiotics, and/or immunosuppressive therapy). Hepatitis preceding HAA is characterized by marked elevation of aminotransferases, conjugated hyperbilirubinemia, elevated antinuclear antibody with a speckled pattern, cholestatic hepatitis with sinusoidal obstruction morphology, and CD8 dominant lobular infiltrates. The present study suggests HAA may result from cytotoxic T-cell-mediated sinusoidal endothelial and hepatocytic injury.

Radiographical findings in patients with liver cirrhosis and hepatic encephalopathy.

Science.gov (United States)

Elwir, Saleh; Hal, Hassan; Veith, Joshua; Schreibman, Ian; Kadry, Zakiyah; Riley, Thomas

2016-08-01

Hepatic encephalopathy is a common complication encountered in patients with liver cirrhosis. Hepatic encephalopathy is not reflected in the current liver transplant allocation system. Correlation was sought between hepatic encephalopathy with findings detected on radiographic imaging studies and the patient's clinical profile. A retrospective analysis was conducted of patients with cirrhosis, who presented for liver transplant evaluation in 2009 and 2010. Patients with hepatocellular carcinoma, ejection fraction less than 60% and who had a TIPS (transjugular intrahepatic portosystemic shunting) procedure or who did not complete the evaluation were excluded. Statistical analysis was performed and variables found to be significant on univariate analysis (P encephalopathy group (n = 58) and a control group (n = 59). Univariate analysis found that a smaller portal vein diameter, smaller liver antero-posterior diameter, liver nodularity and use of diuretics or centrally acting medications showed significant correlation with hepatic encephalopathy. This association was confirmed for smaller portal vein, use of diuretics and centrally acting medications in the multivariate analysis. A decrease in portal vein diameter was associated with increased risk of encephalopathy. Identifying patients with smaller portal vein diameter may warrant screening for encephalopathy by more advanced psychometric testing, and more aggressive control of constipation and other factors that may precipitate encephalopathy. © The Author(s) 2015. Published by Oxford University Press and the Digestive Science Publishing Co. Limited.

Identification of acute self-limited hepatitis B among patients presenting with hepatitis B virus-related acute hepatitis: a hospital-based epidemiological and clinical study.

Science.gov (United States)

Han, Y-N

2009-01-01

This study aimed to identify acute self-limited hepatitis B (ASL-HB) among patients presenting with hepatitis B virus (HBV)-related acute hepatitis. Data were available for 220 patients diagnosed with HBV-related acute hepatitis, of whom 164 had acute hepatitis B (AHB). Of these, 160 were confirmed as ASL-HB: three (1.9%) evolved to chronic hepatitis B and one (0.6%) developed fulminant hepatitis and died. Comparisons were also made between AHB and acute infections with hepatitis A (HA) and hepatitis E (HE) viruses. During the study period, the number of patients with AHB exceeded the sum of those with acute HA and acute HE infections. There was no distinct seasonal peak for AHB infection, whereas both acute HA and acute HE infections occurred more frequently in the spring. Clinical symptoms and physical signs were similar for all three types of hepatitis, but significant differences were seen in some biochemical parameters. In conclusion, this study suggests that symptomatic AHB is not rare in China but it seldom evolves to chronic hepatitis B.

18F-fluorodeoxyglucose positron emission tomography might be useful for diagnosis of hepatic amyloidosis

Directory of Open Access Journals (Sweden)

Tawada A

2014-06-01

Full Text Available Akinobu Tawada,1 Tatsuo Kanda,1 Takashi Oide,2 Toshio Tsuyuguchi,1 Fumio Imazeki,1,3 Yukio Nakatani,2 Osamu Yokosuka11Department of Gastroenterology, 2Department of Diagnostic Pathology, Chiba University Hospital, Chuo-ku, Chiba, Japan; 3Safety and Health Organization, Chiba University, Inage-ku, Chiba, JapanAbstract: We report on a woman with hepatic involvement of primary systemic (immunoglobulin light chain, AL amyloidosis. Her diagnosis was confirmed by liver biopsy. Clinical symptoms of hepatic amyloidosis are generally mild at its first stage, with most frequent findings being hepatomegaly and alkaline phosphatase elevation. Recent advances in the understanding of the pathophysiology of systemic amyloidosis have made several treatments available. However, its prognosis is occasionally poor. Because liver biopsy is not always safe, other modalities for the diagnosis are needed. Of interest was that fluorodeoxyglucose (FDG uptake into the liver was observed, compared with that into the spleen, in this patient, indicating that FDG positron emission tomography and computed tomography might be useful for the diagnosis of hepatic amyloidosis with mild liver dysfunction.Keywords: amyloidosis, diagnosis, hepatic involvement, FDG PET

RNA-sequencing and pathway analysis reveal alteration of hepatic steroid biosynthesis and retinol metabolism by tributyltin exposure in male rare minnow (Gobiocypris rarus).

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Zhang, Jiliang; Zhang, Chunnuan; Sun, Ping; Huang, Maoxian; Fan, Mingzhen; Liu, Min

2017-07-01

Tributyltin (TBT) is widely spread in aquatic ecosystems. Although adverse effects of TBT on reproduction and lipogenesis are observed in fishes, the underlying mechanisms, especially in livers, are still scarce and inconclusive. Thus, RNA-sequencing runs were performed on the hepatic libraries of adult male rare minnow (Gobiocypris rarus) after TBT exposure for 60d. After differentially expressed genes were identified, enrichment analysis and validation by quantitative real-time PCR were conducted. The results showed that TBT up-regulated the profile of hepatic genes in the steroid biosynthesis pathway and down-regulated the profile of hepatic genes in the retinol metabolism pathway. In the hepatic steroid biosynthesis pathway, TBT might induce biosynthesis of cholesterol, which could affect the bioavailability of steroid hormones. More important, 3beta-hydroxysteroid 3-dehydrogenase, a key enzyme in the biosynthesis of all active steroid hormones, was up-regulated by TBT exposure. In the hepatic retinol metabolism pathway, TBT impaired retinoic acid homeostasis which plays essential roles in both reproduction and lipogenesis. The results of two pathways offered new mechanisms underlying the toxicology of TBT and represented a starting point from which detailed mechanistic links should be explored. Copyright © 2017 Elsevier B.V. All rights reserved.

HIV and Viral Hepatitis

Science.gov (United States)

... common causes of viral hepatitis are hepatitis A virus (HAV), hepatitis B virus (HBV), and hepatitis C virus (HCV). HBV and HCV are common ... gov/ mmwr/ preview/ mmwrhtml/ rr5516a1. htm? s_ cid= rr5516a1_ e. The Numbers • • Of people with HIV in the ...

Altered Immune Profiles of Natural Killer Cells in Chronic Hepatitis B Patients: A Systematic Review and Meta-Analysis.

Directory of Open Access Journals (Sweden)

Qiong-Fang Zhang

Full Text Available Natural killer (NK cells are the main effective component of the innate immune system that responds to chronic hepatitis B (CHB infection. Although numerous studies have reported the immune profiles of NK cells in CHB patients, they are limited by inconsistent results. Thus, we performed a meta-analysis to characterize reliably the immune profiles of NK cells after CHB infection, specifically frequency, phenotype, and function.A literature search of the computer databases MEDLINE, PUBMED, EMBASE, and Cochrane Center Register of Controlled Trails was performed and 19 studies were selected. The standard mean difference (SMD and 95% confidence interval (CI of each continuous variable was estimated with a fixed effects model when I2 < 50% for the test for heterogeneity, or the random effects model otherwise. Publication bias was evaluated using Begg's and Egger's tests.The meta-analysis of publications that reported frequency of peripheral NK cells showed that NK cell levels in CHB patients were significantly lower compared with that of healthy controls. A higher frequency of CD56bright NK subsets was found in CHB patients, but the CD56dim NK subsets of CHB patients and healthy controls were similar. CHB patients before and after antiviral therapy with nucleotide analogues (NUCs showed no statistical difference in NK frequency. The activating receptors were upregulated, whereas inhibitory receptors were comparable in the peripheral NK cells of CHB individuals and healthy controls. NK cells of CHB patients displayed higher cytotoxic potency as evidenced by CD107a protein levels and conserved potency to produce interferon-gamma (IFNγ, compared with their healthy counterparts.Our results revealed that CHB patients had a lower frequency of NK cells compared with healthy individuals not treatable with antiviral NUC therapy. With an activating phenotype, NK cells in CHB patients showed better cytotoxic potency and conserved IFNγ production.

Recurrent paratyphoid fever A co-infected with hepatitis A reactivated chronic hepatitis B.

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Liu, Yanling; Xiong, Yujiao; Huang, Wenxiang; Jia, Bei

2014-05-12

We report here a case of recurrent paratyphoid fever A with hepatitis A co-infection in a patient with chronic hepatitis B. A 26-year-old male patient, who was a hepatitis B virus carrier, was co-infected with Salmonella enterica serovar Paratyphi A and hepatitis A virus. The recurrence of the paratyphoid fever may be ascribed to the coexistence of hepatitis B, a course of ceftriaxone plus levofloxacin that was too short and the insensitivity of paratyphoid fever A to levofloxacin. We find that an adequate course and dose of ceftriaxone is a better strategy for treating paratyphoid fever. Furthermore, the co-infection of paratyphoid fever with hepatitis A may stimulate cellular immunity and break immunotolerance. Thus, the administration of the anti-viral agent entecavir may greatly improve the prognosis of this patient with chronic hepatitis B, and the episodes of paratyphoid fever and hepatitis A infection prompt the use of timely antiviral therapy.

Agmatine protects rat liver from nicotine-induced hepatic damage via antioxidative, antiapoptotic, and antifibrotic pathways.

Science.gov (United States)

El-Sherbeeny, Nagla A; Nader, Manar A; Attia, Ghalia M; Ateyya, Hayam

2016-12-01

Tobacco smoking with its various forms is a global problem with proved hazardous effects to human health. The present work was planned to study the defending role of agmatine (AGM) on hepatic oxidative stress and damage induced by nicotine in rats. Thirty-two rats divided into four groups were employed: control group, nicotine-only group, AGM group, and AGM-nicotine group. Measurements of serum hepatic biochemical markers, lipid profile, and vascular cell adhesion molecule-1 were done. In addition, malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH) activity, and nitrate/nitrite (NOx) levels were estimated in the liver homogenates. Immunohistochemistry for Bax and transforming growth factor beta (TGF-β1) and histopathology of the liver were also included. Data of the study demonstrated that nicotine administration exhibited marked liver deterioration, an increase in liver enzymes, changes in lipid profile, and an elevation in MDA with a decline in levels of SOD, GSH, and NOx (nitrate/nitrite). Also, levels of proapoptotic Bax and profibrotic TGF-β1 showed marked elevation in the liver. AGM treatment to rats in nicotine-only group ameliorated all the previous changes. These findings indicate that AGM could successfully overcome the nicotine-evoked hepatic oxidative stress and tissue injury, apoptosis, and fibrosis.

Peginterferon alfa-2b and weight-based or flat-dose ribavirin in chronic hepatitis C patients: a randomized trial.

Science.gov (United States)

Jacobson, Ira M; Brown, Robert S; Freilich, Bradley; Afdhal, Nezam; Kwo, Paul Y; Santoro, John; Becker, Scott; Wakil, Adil E; Pound, David; Godofsky, Eliot; Strauss, Robert; Bernstein, David; Flamm, Steven; Pauly, Mary Pat; Mukhopadhyay, Pabak; Griffel, Louis H; Brass, Clifford A

2007-10-01

This prospective, multicenter, community-based and academic-based, open-label, investigator-initiated, U.S. study evaluated efficacy and safety of pegylated interferon (PEG-IFN) alfa-2b plus a flat or weight-based dose of ribavirin (RBV) in adults with chronic hepatitis C. Patients (n = 5027) were randomly assigned to receive PEG-IFN alfa-2b 1.5 microg/kg/week plus flat-dose (800 mg/day) or weight-based (800-1400 mg/day) RBV for 48 weeks (patients with genotype 1, 4, 5, or 6) and for 24 or 48 weeks (genotype 2/3 patients). Primary end point was sustained virologic response (undetectable [<125 IU/mL] serum hepatitis C virus RNA at 24-week follow-up). Sustained virologic response, but not end-of-treatment, rates were significantly higher with weight-based than with flat-dose RBV (44.2% versus 40.5%; P = 0.008). Sustained virologic response rates by intention-to-treat analysis were 34.0% and 28.9%, respectively, in genotype 1 patients (P = 0.005) and 31.2% and 26.7%, respectively, in genotype 1 patients with high baseline viral load (P = 0.056). In genotype 2/3 patients, rates were not significantly different (61.8% and 59.5%, respectively) regardless of treatment duration. Besides greater hemoglobin reductions with weight-based RBV, safety profiles were similar across RBV dosing groups, including the 1400-mg/day group. PEG-IFN alfa-2b plus weight-based RBV is more effective than flat-dose RBV, particularly in genotype 1 patients, providing equivalent efficacy across all weight groups. RBV 1400 mg/day is appropriate for patients 105 to 125 kg. For genotype 2/3 patients, 24 weeks of treatment with flat-dose RBV is adequate; no evidence of additional benefit of extending treatment to 48 weeks was demonstrated.

Detection of occult hepatitis B virus among chronic hepatitis C patients

African Journals Online (AJOL)

Background: Concurrent infections with hepatitis B virus (HBV) and hepatitis C virus (HCV) are increasingly recognized in patients with chronic hepatitis. In Egypt, the last decade showed a remarkable decline in HBV infection associated with remarkable rise in HCV infection. The probable impact of occult HBV in patients ...

Hepatitis viruses overview

African Journals Online (AJOL)

Hepatitis is major cause of morbidity or mortality worldwide, particularly in the developing world. The major causes of infective hepatitis are hepatitis viruses. A, B, C, D or E. In the acute phase, there are no clinical features that can reliably differentiate between these viruses. Infection may be asymptomatic or can present as.

Hepatic SIRT1 attenuates hepatic steatosis and controls energy balance in mice by inducing fibroblast growth factor 21.

Science.gov (United States)

Li, Yu; Wong, Kimberly; Giles, Amber; Jiang, Jianwei; Lee, Jong Woo; Adams, Andrew C; Kharitonenkov, Alexei; Yang, Qin; Gao, Bin; Guarente, Leonard; Zang, Mengwei

2014-02-01

The hepatocyte-derived hormone fibroblast growth factor 21 (FGF21) is a hormone-like regulator of metabolism. The nicotinamide adenine dinucleotide-dependent deacetylase SIRT1 regulates fatty acid metabolism through multiple nutrient sensors. Hepatic overexpression of SIRT1 reduces steatosis and glucose intolerance in obese mice. We investigated mechanisms by which SIRT1 controls hepatic steatosis in mice. Liver-specific SIRT1 knockout (SIRT1 LKO) mice and their wild-type littermates (controls) were divided into groups that were placed on a normal chow diet, fasted for 24 hours, or fasted for 24 hours and then fed for 6 hours. Liver tissues were collected and analyzed by histologic examination, gene expression profiling, and real-time polymerase chain reaction assays. Human HepG2 cells were incubated with pharmacologic activators of SIRT1 (resveratrol or SRT1720) and mitochondrion oxidation consumption rate and immunoblot analyses were performed. FGF21 was overexpressed in SIRT1 LKO mice using an adenoviral vector. Energy expenditure was assessed by indirect calorimetry. Prolonged fasting induced lipid deposition in livers of control mice, but severe hepatic steatosis in SIRT1 LKO mice. Gene expression analysis showed that fasting up-regulated FGF21 in livers of control mice but not in SIRT1 LKO mice. Decreased hepatic and circulating levels of FGF21 in fasted SIRT1 LKO mice were associated with reduced hepatic expression of genes involved in fatty acid oxidation and ketogenesis, and increased expression of genes that control lipogenesis, compared with fasted control mice. Resveratrol or SRT1720 each increased the transcriptional activity of the FGF21 promoter (-2070/+117) and levels of FGF21 messenger RNA and protein in HepG2 cells. Surprisingly, SIRT1 LKO mice developed late-onset obesity with impaired whole-body energy expenditure. Hepatic overexpression of FGF21 in SIRT1 LKO mice increased the expression of genes that regulate fatty acid oxidation, decreased

Defibrotide for the Treatment of Hepatic Veno-Occlusive Disease: Final Results From the International Compassionate-Use Program.

Science.gov (United States)

Corbacioglu, Selim; Carreras, Enric; Mohty, Mohamad; Pagliuca, Antonio; Boelens, Jaap Jan; Damaj, Gandhi; Iacobelli, Massimo; Niederwieser, Dietger; Olavarría, Eduardo; Suarez, Felipe; Ruutu, Tapani; Verdonck, Leo; Hume, Robin; Nejadnik, Bijan; Lai, Chinglin; Finetto, Giorgia; Richardson, Paul

2016-10-01

Hepatic veno-occlusive disease, also called sinusoidal obstruction syndrome (VOD/SOS), is an unpredictable and potentially fatal complication of hematopoietic cell transplantation (HCT) or nontransplantation-associated chemotherapy/radiotherapy. In cases of severe hepatic VOD/SOS, typically defined by associated multiorgan failure (MOF, also known as multiorgan dysfunction), mortality exceeds 80%. Preclinical and early clinical data have provided a rationale for defibrotide treatment in hepatic VOD/SOS. Based on this evidence and in recognition of the dismal prognosis for these patients, defibrotide was made available through an international multicenter compassionate-use program conducted from December 1998 to March 2009. Physicians participating in the program voluntarily provided demographic and outcome data for patients given defibrotide. Efficacy and safety analyses were performed using the data received for 710 treated patients. Defibrotide was given at 10, 25, 40, 60, or 80 mg/kg/day for a median of 15 days (range, 1 to 119 days). By Kaplan-Meier analysis, the estimated overall day +100 survival was 54% (58% in the 25 mg/kg/day dose group). Adverse events (AEs) were reported in 53% of patients. The most common AEs were MOF, progression of hepatic VOD/SOS, sepsis, and graft-versus-host disease, which were consistent with the AEs expected for this patient population. No clinically meaningful trends in AEs were identified by gender, age, or dose group. Safety and efficacy resultswere consistent with prior studies of defibrotide in hepatic VOD/SOS, and subgroup analyses lend support to the use of the 25 mg/kg/day dose. Copyright © 2016 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Hepatitis B Foundation Newsletter: B Informed

Science.gov (United States)

... Clinical Trials Physician Directory HBV Meeting What Is Hepatitis B? What Is Hepatitis B? The ABCs of Viral Hepatitis Liver Cancer and Hepatitis B Hepatitis Delta Coinfection Hepatitis C Coinfection HIV/AIDS ...

Tenofovir alafenamide in the treatment of chronic hepatitis B: design, development, and place in therapy

Directory of Open Access Journals (Sweden)

Ogawa E

2017-11-01

Full Text Available Eiichi Ogawa,1 Norihiro Furusyo,1 Mindie H Nguyen2 1Department of General Internal Medicine, Kyushu University Hospital, Fukuoka, Japan; 2Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University Medical Center, Palo Alto, CA, USA Abstract: Tenofovir alafenamide (TAF, a novel prodrug of tenofovir (TFV, has been approved for the treatment of chronic hepatitis B virus (HBV infection. TAF has been shown to be a potent inhibitor of HBV replication at a low dose, with high intracellular concentration and more than 90% lower systemic TFV concentration than tenofovir disoproxil fumarate (TDF. In two randomized, double-blind, multinational, Phase 3, non-inferiority trials for hepatitis B e antigen (HBeAg-positive and -negative patients (primary analysis: 48 weeks, TAF 25 mg orally once-daily was not inferior to TDF 300 mg in achieving an HBV DNA level <29 IU/mL at week 48. No amino-acid substitutions associated with viral breakthrough were detected by deep sequencing, and no resistance to TAF was found through week 96. In addition, no difference in the frequency of HBeAg or hepatitis B surface antigen loss was observed. However, TAF was associated with a significantly higher ALT normalization rate than was TDF, based on the American Association for the Study of Liver Diseases criteria (male: ALT ≤30 U/L and female: ALT ≤19 U/L. An analysis of renal safety showed that patients treated with TAF had a significantly lower decrease in the estimated glomerular filtration rate level than did patients treated with TDF. Similarly, the declines of hip and spine bone mineral density were significantly less in the TAF group. These trends of efficacy and renal/bone safety continued through week 96. Longer term follow-up and real-world data will be required to determine if the differences in viral/biochemical response and renal/bone safety seen with TAF in comparison with TDF are clinically relevant. Keywords: hepatitis B virus

Hepatic Encephalopathy

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Full Text Available ... Your Story Spread the Word Give While You Shop Contact Us Donate Now Hepatic Encephalopathy Back Hepatic ... Your Story Spread the Word Give While You Shop Contact Us Donate Now Help ALF Improve This ...

Hepatic Encephalopathy

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Full Text Available ... Now Hepatic Encephalopathy Back Hepatic Encephalopathy is a brain disorder that develops in some individuals with liver ... is a condition that causes temporary worsening of brain function in people with advanced liver disease. When ...

Pathophysiological appraisal of a rat model of total hepatic ischemia with an extracorporeal portosystemic shunt.

Science.gov (United States)

Suzuki, S; Nakamura, S; Sakaguchi, T; Mitsuoka, H; Tsuchiya, Y; Kojima, Y; Konno, H; Baba, S

1998-11-01

Animal models of total hepatic ischemia (THI) and reperfusion injury are restricted by concomitant splanchnic congestion. This study was performed to determine the requirement suitable for an extracorporeal portosystemic shunt (PSS) to maintain the intestinal integrity in a rat model of THI. Using a polyethylene tube (0.86 or 1 mm i.d.), PSS was placed between the mesenteric and jugular veins. Comparison was done between THI models with or without PSS and a partial ischemia model with hepatectomy of the nonischemic lobes. Well-tolerated hepatic ischemic period, portal pressure after 10 min of hepatic ischemia, portal endotoxin levels at 1 h after reperfusion, histological features of the small bowel just before reperfusion, and local jejunal and ileal blood hemoglobin oxygen saturation index (ISO2) were compared among the models. Animals without PSS poorly tolerated 30 min of THI. Animals receiving THI with PSS or partial hepatic ischemia tolerated a longer ischemic period (60 min) with a significantly higher small bowel ISO2, lower portal pressure and endotoxin levels (P tube as well as partial hepatic ischemia were significantly lower than those after THI with PSS using a 0.86-mm i.d. tube. THI with PSS using a 1-mm i.d. tube was strikingly similar to partial hepatic ischemia in the pathophysiological profile during hepatic ischemia. PSS with a tube 1 mm or more in inner diameter offers pathophysiological advantages in experiments on THI and reperfusion. Copyright 1998 Academic Press.

Primary hepatic lymphoma presenting as fulminant hepatic failure with hyperferritinemia: A case report

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Haider Fyeza S

2008-08-01

Full Text Available Abstract Introduction Primary hepatic lymphoma is an unusual form of non-Hodgkin's lymphoma that usually presents with constitutional symptoms, hepatomegaly and signs of cholestatic jaundice. Diffuse hepatic infiltration is uncommon and presentation with acute hepatic failure even more rare. The presence of markedly elevated ferritin levels can complicate the evaluation process and suggest alternative diagnoses. We present the case of a middle-aged woman exhibiting pancytopenia, hyperferritinemia and rapidly deteriorating to develop acute hepatic failure. Her initial clinical picture led to a working diagnosis of adult onset Still's disease with probable hemophagocytic syndrome before her worsening liver function necessitated a percutaneous liver biopsy and establishment of the final diagnosis of primary hepatic lymphoma. Conclusion Primary hepatic lymphoma is an uncommon malignancy and its manifestation as progressive hepatitis or acute fulminant hepatic failure can be difficult to diagnose. The presence of constitutional symptoms, pancytopenia and high ferritin levels can complicate the evaluation process. A liver biopsy early in the course of liver dysfunction may establish the diagnosis without a higher risk of bleeding complications seen once liver failure sets in.

Hepatic transcriptomic and metabolomic responses in the Stickleback (Gasterosteus aculeatus) exposed to ethinyl-estradiol

International Nuclear Information System (INIS)

Katsiadaki, Ioanna; Williams, Tim D.; Ball, Jonathan S.; Bean, Tim P.; Sanders, Matthew B.; Wu Huifeng; Santos, Eduarda M.; Brown, Margaret M.; Baker, Paul; Ortega, Fernando; Falciani, Francesco; Craft, John A.; Tyler, Charles R.; Viant, Mark R.; Chipman, James K.

2010-01-01

An established three-spined stickleback (Gasterosteus aculeatus) cDNA array was expanded to 14,496 probes with the addition of hepatic clones derived from subtractive and normalized libraries from control males and males exposed to model toxicants. Microarrays and one-dimensional 1 H nuclear magnetic resonance (NMR) spectroscopy, together with individual protein and gene biomarkers were employed to investigate the hepatic responses of the stickleback to ethinyl-estradiol (EE 2 ) exposure. Male fish were exposed via the water to EE 2 , including environmentally relevant concentrations (0.1-100 ng/l) for 4 days, and hepatic transcript and metabolite profiles, kidney spiggin protein and serum vitellogenin concentrations were determined in comparison to controls. EE 2 exposure did not significantly affect spiggin concentration but significantly induced serum vitellogenin protein at the threshold concentration of 32 ng/l. 1 H NMR coupled with robust univariate testing revealed only limited changes, but these did support the predicted modulation of the amino acid profile by transcriptomics. Transcriptional induction was found for hepatic vitellogenins and choriogenins as expected, together with a range of other EE 2 -responsive genes. Choriogenins showed the more sensitive responses with statistically significant induction at 10 ng/l. Real-time polymerase chain reaction (PCR) confirmed transcriptional induction of these genes. Phosvitinless vitellogenin C transcripts were highly expressed and represent a major form of the egg yolk precursors, and this is in contrast to other fish species where it is a minor component of vitellogenic transcripts. Differences in inducibility between the vitellogenins and choriogenins appear to be in accordance with the sequential formation of chorion and yolk during oogenesis in fish.

Hepatic transcriptomic and metabolomic responses in the Stickleback (Gasterosteus aculeatus) exposed to ethinyl-estradiol

Energy Technology Data Exchange (ETDEWEB)

Katsiadaki, Ioanna, E-mail: ioanna.katsiadaki@cefas.co.uk [Centre for Environment, Fisheries and Aquaculture Science, Cefas Weymouth Laboratory, Weymouth, Dorset DT4 8UB (United Kingdom); Williams, Tim D. [School of Biosciences, University of Birmingham, Birmingham, B15 2TT (United Kingdom); Ball, Jonathan S. [School of Biosciences, University of Exeter, Exeter, Devon, EX4 4QJ (United Kingdom); Bean, Tim P.; Sanders, Matthew B. [Centre for Environment, Fisheries and Aquaculture Science, Cefas Weymouth Laboratory, Weymouth, Dorset DT4 8UB (United Kingdom); Wu Huifeng [School of Biosciences, University of Birmingham, Birmingham, B15 2TT (United Kingdom); Santos, Eduarda M. [School of Biosciences, University of Exeter, Exeter, Devon, EX4 4QJ (United Kingdom); Brown, Margaret M.; Baker, Paul [School of Biological and Biomedical Sciences, Glasgow Caledonian University, Glasgow, G4 0BA (United Kingdom); Ortega, Fernando; Falciani, Francesco [School of Biosciences, University of Birmingham, Birmingham, B15 2TT (United Kingdom); Craft, John A. [School of Biological and Biomedical Sciences, Glasgow Caledonian University, Glasgow, G4 0BA (United Kingdom); Tyler, Charles R. [School of Biosciences, University of Exeter, Exeter, Devon, EX4 4QJ (United Kingdom); Viant, Mark R.; Chipman, James K. [School of Biosciences, The University of Birmingham, Birmingham, B15 2TT (United Kingdom)

2010-05-05

An established three-spined stickleback (Gasterosteus aculeatus) cDNA array was expanded to 14,496 probes with the addition of hepatic clones derived from subtractive and normalized libraries from control males and males exposed to model toxicants. Microarrays and one-dimensional {sup 1}H nuclear magnetic resonance (NMR) spectroscopy, together with individual protein and gene biomarkers were employed to investigate the hepatic responses of the stickleback to ethinyl-estradiol (EE{sub 2}) exposure. Male fish were exposed via the water to EE{sub 2}, including environmentally relevant concentrations (0.1-100 ng/l) for 4 days, and hepatic transcript and metabolite profiles, kidney spiggin protein and serum vitellogenin concentrations were determined in comparison to controls. EE{sub 2} exposure did not significantly affect spiggin concentration but significantly induced serum vitellogenin protein at the threshold concentration of 32 ng/l. {sup 1}H NMR coupled with robust univariate testing revealed only limited changes, but these did support the predicted modulation of the amino acid profile by transcriptomics. Transcriptional induction was found for hepatic vitellogenins and choriogenins as expected, together with a range of other EE{sub 2}-responsive genes. Choriogenins showed the more sensitive responses with statistically significant induction at 10 ng/l. Real-time polymerase chain reaction (PCR) confirmed transcriptional induction of these genes. Phosvitinless vitellogenin C transcripts were highly expressed and represent a major form of the egg yolk precursors, and this is in contrast to other fish species where it is a minor component of vitellogenic transcripts. Differences in inducibility between the vitellogenins and choriogenins appear to be in accordance with the sequential formation of chorion and yolk during oogenesis in fish.

Hepatic Encephalopathy

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Full Text Available ... friend, spouse, life partner, parent, sibling or other family member. What is HE? Hepatic Encephalopathy, sometimes referred ... disease is. It’s important for you and your family to become familiar with the signs of Hepatic ...

Evaluation of immune response to hepatitis A vaccination and vaccine safety in juvenile idiopathic arthritis

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Muferet Erguven

2011-05-01

Conclusion: Hepatitis A vaccine was safe in patients with JIA, and response to vaccine did not differ between healthy children and patients with JIA except for children with active systemic JIA receiving anti-tumor necrosis factor alpha drugs.

Disease Modeling and Gene Therapy of Copper Storage Disease in Canine Hepatic Organoids

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Sathidpak Nantasanti

2015-11-01

Full Text Available The recent development of 3D-liver stem cell cultures (hepatic organoids opens up new avenues for gene and/or stem cell therapy to treat liver disease. To test safety and efficacy, a relevant large animal model is essential but not yet established. Because of its shared pathologies and disease pathways, the dog is considered the best model for human liver disease. Here we report the establishment of a long-term canine hepatic organoid culture allowing undifferentiated expansion of progenitor cells that can be differentiated toward functional hepatocytes. We show that cultures can be initiated from fresh and frozen liver tissues using Tru-Cut or fine-needle biopsies. The use of Wnt agonists proved important for canine organoid proliferation and inhibition of differentiation. Finally, we demonstrate that successful gene supplementation in hepatic organoids of COMMD1-deficient dogs restores function and can be an effective means to cure copper storage disease.

Results of steroid-based therapy for the hepatitis C-autoimmune hepatitis overlap syndrome.

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Schiano, T D; Te, H S; Thomas, R M; Hussain, H; Bond, K; Black, M

2001-10-01

Overlap syndromes in which persons manifest clinical, histological, or immunological features of both hepatitis C infection and autoimmune hepatitis are well described. The discordant forms of treatment for hepatitis C and autoimmune hepatitis have made medical management of these patients difficult. We report our experience in using corticosteroids as first line therapy for the hepatitis C-autoimmune hepatitis overlap syndrome. Seven patients with this overlap syndrome (diagnosis based on the presence of serum hepatitis C antibody by RIBA and serum hepatitis C RNA by polymerase chain reaction, and serum hypergammaglobulinemia, elevated ANA or ASMA titers, or histological findings consistent with autoimmune hepatitis) were treated with prednisone with or without azathioprine or cyclosporine, and followed for a median duration of 44.5 months. Five patients (71%) showed improvement of median serum ALT level from 162 U/L to 38 U/L (p = 0.04) and median serum gamma-globulin from 2.1 g/dl to 1.4 g/dl (p = 0.04) by 6 months of therapy. The mean modified histological activity index score also decreased from 11.4 +/- 2.5 to 6.6 +/- 2.6 (p = 0.04) by at least 1 yr of therapy. One patient discontinued prednisone while taking azathioprine and experienced a rebound elevation of serum ALT that did not respond to retreatment with prednisone. Antiviral therapy was subsequently administered and resulted in biochemical and virologic response. Hepatitis C virus RNA remained detectable in all other patients. Corticosteroids are beneficial as a first line therapy for some patients with the hepatitis C-autoimmune overlap syndrome, resulting in appreciable biochemical and histological response but without viral eradication.

Meta-analysis of pemetrexed plus carboplatin doublet safety profile in first-line non-squamous non-small cell lung cancer studies.

Science.gov (United States)

Okamoto, Isamu; Schuette, Wolfgang H W; Stinchcombe, Thomas E; Rodrigues-Pereira, José; San Antonio, Belén; Chen, Jian; Liu, Jingyi; John, William J; Zinner, Ralph G

2017-05-01

This meta-analysis compared safety profiles (selected drug-related treatment-emergent adverse events [TEAEs]) of first-line pemetrexed plus carboplatin (PCb) area under the concentration-time curve 5 mg/min•mL (PCb5) or 6 mg/min•mL (PCb6), two widely used regimens in clinical practice for advanced non-squamous non-small cell lung cancer. All patients received pemetrexed 500 mg/m 2 every 21 days with either of two carboplatin doses for up to 4-6 cycles. Safety profiles of PCb doses were compared using three statistical analysis methods: frequency table analysis (FTA), generalized linear mixed effect model (GLMM), and the propensity score method. Efficacy outcomes of PCb5 and PCb6 regimens were summarized. A total of 486 patients mainly from the US, Europe, and East Asia were included in the analysis; 22% (n = 105) received PCb5 in one trial and 78% (n = 381) received PCb6 in four trials. The FTA comparison demonstrated that PCb5 vs PCb6 was associated with a statistically significantly lower incidence of TEAEs, including all-grade thrombocytopenia, anemia, fatigue, and vomiting, and grade 3/4 thrombocytopenia. In the GLMM analysis, PCb5 patients were numerically less likely to experience all-grade and grade 3/4 neutropenia, anemia, and thrombocytopenia. The propensity score regression analysis showed PCb5 group patients were significantly less likely than PCb6 group patients to experience all-grade hematologic TEAEs and grade 3/4 thrombocytopenia and anemia. After applying propensity score 1:1 matching, FTA analysis showed that the PCb5 group had significantly less all-grade and grade 3/4 hematologic toxicities. Overall efficacy outcomes, including overall survival, progression-free survival, and response rate, were similar between the two carboplatin doses. Acknowledging the limitations of this meta-analysis of five trials, heterogeneous in patient's characteristics and trial designs, the results show that the PCb5 regimen was generally associated

Hepatitis A virus antibody

International Nuclear Information System (INIS)

Novak, J.; Kselikova, M.; Urbankova, J.

1980-01-01

A description is presented of a radioimmunoassay designed to prove the presence of the antibody against the hepatitis A virus (HA Ab, anti-Ha) using an Abbott HAVAB set. This proof as well as the proof of the antibody against the nucleus of the hepatitis B virus is based on competition between a normal antibody against hepatitis A virus and a 125 I-labelled antibody for the binding sites of a specific antigen spread all over the surface of a tiny ball; this is then indirect proof of the antibody under investigation. The method is described of reading the results from the number of impulses per 60 seconds: the higher the titre of the antibody against the hepatitis A virus in the serum examined, the lower the activity of the specimen concerned. The rate is reported of incidence of the antibody against the hepatitis A virus in a total of 68 convalescents after hepatitis A; the antibody was found in 94.1%. The immunoglobulin made from the convalescents' plasma showed the presence of antibodies in dilutions as high as 1:250 000 while the comparable ratio for normal immunoglobulin Norga was only 1:2500. Differences are discussed in the time incidence of the antibodies against the hepatitis A virus, the antibodies against the surface antigen of hepatitis B, and the antibody against the nucleus of the hepatitis V virus. (author)

[SAFETY AND IMMUNOGENICITY OF A NATIONAL COMBINED VACCINE AGAINST PERTUSSIS, DIPHTHERIA, TETANUS, HEPATITIS B AND Hib-INFECTION, CONTAINING ACELLULAR PERTUSSIS COMPONENT, DURING IMMUNIZATION OF ADULTS].

Science.gov (United States)

Feldblyum, I V; Nikolaeva, A M; Pavroz, K A; Danilina, T V; Sosnina, O Yu; Vyaznikova, T V; Ershov, A E; Trofimov, D M; Polushkina, A V

2016-01-01

Study safety, reactogenicity and immunologic effectiveness of a national combined vaccine against diphtheria, pertussis (acellular component), tetanus, hepatitis B and Hib-infection during immunization of volunteers aged 18-60 years. The study was carried out in accordance with ethical standards and requirements, regulated by Helsinki declaration and Good clinical practice (ICHGCP). In a simple non-randomized clinical trial 20 adult volunteers took part, the mean age of those was 46.9 years. Registered: post-vaccination reactions (both local and systemic) were mild and of moderate degree of severity, stopped independently after 2-3 days without administration of drug treatment. Postvaccinal complications were not noted. Parameters of general and biochemical analysis of blood, urine, IgE content in dynamics of immunization were within normal limits. A single administration of aAPDT--HepB+Hib to individuals aged 18-60 years resulted in development of antibodies against all the components of the preparation. Seroconversion factor fluctuated from 6.9 to 53.5: The results obtained allow to recommend the vaccine for evaluation of its safety, reactogenicity, immunologic and prophylaxis effectiveness in randomized clinical observation trials in children.

Immunoglobulins for preventing hepatitis A

DEFF Research Database (Denmark)

Liu, Jian Ping; Nikolova, Dimitrinka; Fei, Yutong

2009-01-01

Hepatitis A (infectious hepatitis) is a common epidemic disease. Immunoglobulins for passive immunisation are used as prevention.......Hepatitis A (infectious hepatitis) is a common epidemic disease. Immunoglobulins for passive immunisation are used as prevention....

Coinfection of hepatitis E virus and other hepatitis virus in Colombia and its genotypic characterization.

Science.gov (United States)

Peláez, Dioselina; Martínez-Vargas, Daniel; Escalante-Mora, Martha; Palacios-Vivero, Mariel; Contreras-Gómez, Lady

2015-12-04

Hepatitis E virus has emerged as a public health problem, particularly in developing countries. The four genotypes identified in mammals include the G3 found in indigenous hepatitis in countries and regions with high porcine population, and the G1, associated with maternal deaths.  To determine coinfection by hepatitis E virus and the circulating genotypes in Colombia in 1,097 samples using serological markers for hepatitis A, B and C.  Serum samples of 1,097 patients from different regions of Colombia stored at the Laboratorio de Virología of the Instituto Nacional de Salud were selected to detect IgG and IgM anti-hepatitis E virus antibodies. The viral genomes of positive samples were amplified by RT-PCR, and the products were sequenced and phylogenetically analyzed by comparing ORF2 sequences deposited in the GenBank.  IgG anti-hepatitis E virus antibodies were found in 278 samples, IgM in 62, and both markers in 64. Hepatitis E virus and hepatitis A virus coinfection determined by IgG anti-hepatitis E virus was 33.6% and 16.1% by IgM; hepatitis E virus and hepatitis B virus coinfection was 23.4% and 8.1%, and hepatitis E virus and hepatitis C virus coinfection was 35.4% and 5.83%, respectively. Among the 52 positive samples by PCR nine were sequenced and grouped within genotype 3A of the American porcine strain.  The highest seropositivity was observed for hepatitis A and E. The incidence of hepatitis E virus coinfection with other hepatotropic viruses indicated that this pathogen is more frequent than expected. The circulation of genotype 3A implies that this disease may occur in outbreaks and as zoonosis in Colombia.

Efficacy and Safety of Rituximab in the Treatment of Vasculitic Leg Ulcers Associated with Hepatitis C Virus Infection

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Fabio Bonilla-Abadía

2012-01-01

Full Text Available Vasculitic leg ulcers are a cutaneous manifestation of hepatitis C virus (HCV infection often associated with cryoglobulinemia. Their treatment is difficult and is based on steroids and immunosuppressive drugs with an erratic response and a high probability of adverse reaction. We report three patients with vasculitic leg ulcers associated with hepatitis C virus infection who were treated successfully with rituximab. The pain control and healing were achieved quickly. No adverse effects with rituximab in these patients were presented.

Seroprevalence of hepatitis C, hepatitis B and HIV viruses in hemophiliacs born 1985-2010 in west Azarbaijan of Iran

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Nasim Valizadeh

2013-01-01

Full Text Available Background: Although, in the past the risk of transfusion transmitted viral infections were high in hemophilia patients, but introduction of viral inactivation methods in1985,decreased the risk of human immunodeficiency and hepatitis C and B viruses transmission significantly. The aim of study was seroprevalence of hepatitis B surface antigen (HBs Ag, hepatitis C virus antibody (HCV Ab and human immunodeficiency virus antibody (HIVAb in hemophiliacs in west Azarbaijan of Iran, born in 1985-2010. Materials and Methods: In a cross-sectional study, fifty patients with hereditary bleeding disorders born in 1985-2010, from total 250 patients who had been registered in Urmia Hemophilia Society were enrolled through the year 2010 to assess their seroprevalence for HCV Ab, HIV Ab and HBs Ag. Thirty five of 50 patients had hemophilia. Also; we performed a subset analysis for hemophilia patients. Results: All 50 patients with hereditary bleeding disorders including 35 patients with hemophilia were seronegative for HIV Ab and HBs Ag. HCV-Ab was detected in serum of 3 of 50 (6% patients with bleeding disorders. After subset analysis for hemophilia (A and B patients, we found HCV infection in 8.57% (3 of 35 of hemophiliacs. Conclusion: In this study prevalence of HCV infection was very smaller than similar studies in Iran and other countries. This study shows the safety of using viral inactivated factor concentrates and recombinant factors after year 1985.None of Hemophiliacs were seropositive for HIV Ab and HBs Ag.

Hepatitis Information for the Public

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... Hepatitis Contact Us Anonymous Feedback Quick Links to Hepatitis … A | B | C | D | E Viral Hepatitis Home ... Local Partners & Grantees Policy and Programs Resource Center Hepatitis Information for the Public Recommend on Facebook Tweet ...

Seroprevalence of Hepatitis A Virus Antibodies among the Patients with Chronic Hepatitis B in Turkey.

Science.gov (United States)

Tulek, Necla; Ozsoy, Metin; Moroglu, Cigdem; Cagla Sonmezer, Meliha; Temocin, Fatih; Tuncer Ertem, Gunay; Sebnem Erdinc, Fatma

2015-01-01

Hepatitis A virus (HAV) can cause significant pathology in patients with chronic hepatitis B virus (HBV), however, HAV can be prevented by vaccination. The aim of this study was to determine the implication of vaccination against HAV vaccine in patients with chronic hepatitis B. The seroprevalence of anti-HAV IgG antibodies was investigated in the patients with chronic hepatitis B. Anti-HAV IgG antibodies were detected by commercially available ELISA kit. A total of 673 patients (354 males, 319 females with age range of 17-78 years) with chronic hepatitis B were included the study. Hepatitis A virus seropositivity rate was 34% in the patients younger than 20 years, 79% in the age group of 20 to 29 years, and 100% after 35 years of age. Hepatitis A virus vaccination may be recommended for young adult patients with chronic hepatitis B in Turkey. Tulek N, Ozsoy M, Moroglu C, Sonmezer MC, Temocin F, Ertem GT, Erdinc FS. Seroprevalence of Hepatitis A Virus Antibodies among the Patients with Chronic Hepatitis B in Turkey. Euroasian J Hepato-Gastroenterol 2015;5(2):95-97.

Gadobutrol for contrast-enhanced magnetic resonance imaging in elderly patients: review of the safety profile from clinical trial, post-marketing surveillance, and pharmacovigilance data

International Nuclear Information System (INIS)

Endrikat, J.; Schwenke, C.; Prince, M.R.

2015-01-01

Aim: To assess the safety of gadobutrol administration in elderly patients (≥65 years) by comparing the incidence of adverse drug reactions (ADRs) following gadobutrol-enhanced magnetic resonance imaging (MRI) procedures in elderly patients with that in adults aged 18–64 years. Materials and methods: Safety data on gadobutrol administration from clinical trials, post-marketing surveillance (PMS) studies, and pharmacovigilance reports were collected in three databases. In each dataset, absolute and relative frequencies of ADRs between age groups were analysed, along with odds ratios and 95% confidence intervals. Logistic regression was used to identify significant influencing factors on ADRs in the PMS and pharmacovigilance data. Results: Rates of reported ADRs were lower in elderly patients versus adults aged <65 years due to a reduced incidence of non-serious ADRs; this was statistically significant for the clinical trials and pharmacovigilance populations, with a trend in the PMS database. Serious ADRs occurred infrequently in the clinical trials and PMS populations (too low for statistical comparison), and pharmacovigilance data demonstrated a low incidence (<0.005%) in both age groups. Conclusions: This evaluation involving three large databases demonstrated no greater incidence of ADRs following gadobutrol-enhanced MRI in elderly patients (≥65 years) compared with younger adults, with gadobutrol having a favourable safety profile in both age groups. -- Highlights: •First dedicated safety study of an extracellular contrast agent in the elderly. •Elderly patients experience fewer non-serious ADRs than younger adults. •Gadobutrol has a favourable safety profile in both age groups

Diabetes and Hepatitis B Vaccination

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Diabetes and Hepatitis B Vaccination Information for Diabetes Educators What is hepatitis B? Hepatitis B is a contagious liver disease that results from infection with the hepatitis B virus. When first infected, a person can develop ...

Alcoholic Hepatitis

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... yellow color. Confusion, drowsiness and slurred speech (hepatic encephalopathy). A damaged liver has trouble removing toxins from your body. The ... of toxins can damage your brain. Severe hepatic encephalopathy can result in ... of the liver frequently leads to liver failure. Kidney failure. A ...

Genus Phyllanthus for chronic hepatitis B virus infection

DEFF Research Database (Denmark)

Liu, J; Lin, Haili; McIntosh, H

2001-01-01

To evaluate the efficacy and safety of genus Phyllanthus for chronic hepatitis B virus (HBV) infection we performed a systematic review of randomized clinical trials. Randomized trials comparing genus Phyllanthus vs. placebo, no intervention, general nonspecific treatment, other herbal medicine.......85-17.21) compared with placebo or no intervention. There was no significant difference on clearance of serum HBsAg, HBeAg and HBV DNA between Phyllanthus and IFN. Phyllanthus species were better than nonspecific treatment or other herbal medicines for the clearance of serum HBsAg, HBeAg, HBV DNA, and liver enzyme...

Syncytial giant-cell hepatitis due to autoimmune hepatitis type II (LKM1+) presenting as subfulminant hepatitis.

Science.gov (United States)

Ben-Ari, Z; Broida, E; Monselise, Y; Kazatsker, A; Baruch, J; Pappo, O; Skappa, E; Tur-Kaspa, R

2000-03-01

Giant cell hepatitis (GCH) in adults is a rare event. The diagnosis of GCH is based on findings of syncytial giant hepatocytes. It is commonly associated with either viral infection or autoimmune hepatitis type I. A patient with GCH due to autoimmune hepatitis type II (LKM1+) is described, a combination that has not been previously reported. Corticosteroid therapy was effective in decreasing serum liver enzymes; however, the patient deteriorated rapidly and developed subfulminant hepatic failure. Although an emergency orthotopic liver transplantation was performed, the patient died because of reperfusion injury. Interestingly, only a few giant hepatocytes were noted in the explanted liver. This case stresses the association of GCH with autoimmune disorders, the possible immune mechanism involved in the formation of giant cell hepatocytes, and illustrates the rapidly progressive course and unfavorable prognosis that these patients can develop.

Hepatitis B virus (image)

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Hepatitis B is also known as serum hepatitis and is spread through blood and sexual contact. It is ... population. This photograph is an electronmicroscopic image of hepatitis B virus particles. (Image courtesy of the Centers for ...

Evaluation of intestinal phosphate binding to improve the safety profile of oral sodium phosphate bowel cleansing.

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Stef Robijn

Full Text Available Prior to colonoscopy, bowel cleansing is performed for which frequently oral sodium phosphate (OSP is used. OSP results in significant hyperphosphatemia and cases of acute kidney injury (AKI referred to as acute phosphate nephropathy (APN; characterized by nephrocalcinosis are reported after OSP use, which led to a US-FDA warning. To improve the safety profile of OSP, it was evaluated whether the side-effects of OSP could be prevented with intestinal phosphate binders. Hereto a Wistar rat model of APN was developed. OSP administration (2 times 1.2 g phosphate by gavage with a 12h time interval induced bowel cleansing (severe diarrhea and significant hyperphosphatemia (21.79 ± 5.07 mg/dl 6h after the second OSP dose versus 8.44 ± 0.97 mg/dl at baseline. Concomitantly, serum PTH levels increased fivefold and FGF-23 levels showed a threefold increase, while serum calcium levels significantly decreased from 11.29 ± 0.53 mg/dl at baseline to 8.68 ± 0.79 mg/dl after OSP. OSP administration induced weaker NaPi-2a staining along the apical proximal tubular membrane. APN was induced: serum creatinine increased (1.5 times baseline and nephrocalcinosis developed (increased renal calcium and phosphate content and calcium phosphate deposits on Von Kossa stained kidney sections. Intestinal phosphate binding (lanthanum carbonate or aluminum hydroxide was not able to attenuate the OSP induced side-effects. In conclusion, a clinically relevant rat model of APN was developed. Animals showed increased serum phosphate levels similar to those reported in humans and developed APN. No evidence was found for an improved safety profile of OSP by using intestinal phosphate binders.

Black Seed Thymoquinone Improved Insulin Secretion, Hepatic Glycogen Storage, and Oxidative Stress in Streptozotocin-Induced Diabetic Male Wistar Rats

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Heba M. A. Abdelrazek

2018-01-01

Full Text Available Diabetes mellitus is one of the metabolic diseases having several complications. Nigella sativa oil (NSO might have beneficial effects in the treatment of diabetic complications. Thirty-two mature male Wistar rats were equally divided into four experimental groups: control, control NSO 2 mL/kg, streptozotocin- (STZ- induced diabetic, and diabetic (STZ-induced treated with oral NSO 2 mg/kg for 30 days. Fasting blood glucose (FBG, insulin, and lipid profile levels were determined. Pancreatic and hepatic tissues were used for catalase and GSH. Histopathology, hepatic glycogen contents, insulin immunohistochemistry, and pancreatic islet morphometry were performed. NSO 2 mL/kg was noticed to decrease (P<0.05 FBG and increase (P<0.05 insulin levels in diabetic rats than in diabetic nontreated animals. Lipid profile showed significant (P<0.5 improvement in diabetic rats that received NSO 2 mL/kg than in the diabetic group. Both pancreatic and hepatic catalase and GSH activities revealed a significant (P<0.05 increment in the diabetic group treated with NSO than in the diabetic animals. NSO improved the histopathological picture and hepatic glycogen contents of the diabetic group as well as increased (P<0.05 insulin immunoreactive parts % and mean pancreatic islet diameter. NSO exerts ameliorative and therapeutic effects on the STZ-induced diabetic male Wistar rats.

Keto acid-supplemented low-protein diet for treatment of adult patients with hepatitis B virus infection and chronic glomerulonephritis.

Science.gov (United States)

Mou, Shan; Li, Jialin; Yu, Zanzhe; Wang, Qin; Ni, Zhaohui

2013-02-01

An open-label, randomized, controlled, single-centre clinical trial to evaluate the effects of low-protein intake, with or without keto acid supplementation, on nutritional status and proteinuria, in patients with hepatitis B virus (HBV) and early stage chronic glomerulonephritis. Patients with chronic glomerulonephritis and HBV infection were randomized to receive a low-protein diet (0.6-0.8 g/kg ideal body weight [IBW] per day) either without (LP group) or with (sLP group) keto acid supplementation (0.1 g/kg IBW per day), for 12 months. Nutritional, clinical and safety parameters were recorded. The study included 17 patients (LP group n = 9; sLP group n = 8). Proteinuria and microalbuminuria were significantly lower in the sLP group at 6 and 12 months compared with baseline, and at 12 months compared with the LP group. There were no significant differences in serum creatinine level or estimated glomerular filtration rate. Nutritional parameters (serum albumin and prealbumin) were significantly improved at 12 months, compared with baseline, in the sLP group. Restriction of dietary protein intake to 0.6-0.8 g/kg IBW per day appears to have an acceptable safety profile. Supplementation with keto acids is associated with decreased urine protein excretion.

Chronic perfluorooctane sulfonate (PFOS) exposure induces hepatic steatosis in zebrafish

International Nuclear Information System (INIS)

Cheng, Jiangfei; Lv, Suping; Nie, Shangfei; Liu, Jing; Tong, Shoufang; Kang, Ning; Xiao, Yanyan; Dong, Qiaoxiang; Huang, Changjiang; Yang, Dongren

2016-01-01

Highlights: • PFOS chronic exposure induces sex-dependent hepatic steotosis in zebrafish. • PFOS interferes with β-oxidation, lipid synthesis, and lipid hepatic export process. • Zebrafish could be used as an alternative model for PFOS chronic toxicity screening. - Abstract: Perfluorooctane sulfonate (PFOS), one persistent organic pollutant, has been widely detected in the environment, wildlife and human. Currently few studies have documented the effects of chronic PFOS exposure on lipid metabolism, especially in aquatic organisms. The underlying mechanisms of hepatotoxicity induced by chronic PFOS exposure are still largely unknown. The present study defined the effects of chronic exposure to low level of PFOS on lipid metabolism using zebrafish as a model system. Our findings revealed a severe hepatic steatosis in the liver of males treated with 0.5 μM PFOS as evidenced by hepatosomatic index, histological assessment and liver lipid profiles. Quantitative PCR assay further indicated that PFOS significantly increase the transcriptional expression of nuclear receptors (nr1h3, rara, rxrgb, nr1l2) and the genes associated with fatty acid oxidation (acox1, acadm, cpt1a). In addition, chronic PFOS exposure significantly decreased liver ATP content and serum level of VLDL/LDL lipoprotein in males. Taken together, these findings suggest that chronic PFOS exposure induces hepatic steatosis in zebrafish via disturbing lipid biosynthesis, fatty acid β-oxidation and excretion of VLDL/LDL lipoprotein, and also demonstrate the validity of using zebrafish as an alternative model for PFOS chronic toxicity screening.

Chronic perfluorooctane sulfonate (PFOS) exposure induces hepatic steatosis in zebrafish

Energy Technology Data Exchange (ETDEWEB)

Cheng, Jiangfei; Lv, Suping; Nie, Shangfei; Liu, Jing; Tong, Shoufang; Kang, Ning; Xiao, Yanyan; Dong, Qiaoxiang [Zhejiang Provincial Key Laboratory for Technology and Application of Model Organisms (China); Institute of Environmental Safety and Human Health, Wenzhou Medical University, Wenzhou, 325035 (China); Huang, Changjiang, E-mail: cjhuang5711@163.com [Zhejiang Provincial Key Laboratory for Technology and Application of Model Organisms (China); Institute of Environmental Safety and Human Health, Wenzhou Medical University, Wenzhou, 325035 (China); Yang, Dongren, E-mail: yangdongren@yahoo.com [Zhejiang Provincial Key Laboratory for Technology and Application of Model Organisms (China); Institute of Environmental Safety and Human Health, Wenzhou Medical University, Wenzhou, 325035 (China)

2016-07-15

Highlights: • PFOS chronic exposure induces sex-dependent hepatic steotosis in zebrafish. • PFOS interferes with β-oxidation, lipid synthesis, and lipid hepatic export process. • Zebrafish could be used as an alternative model for PFOS chronic toxicity screening. - Abstract: Perfluorooctane sulfonate (PFOS), one persistent organic pollutant, has been widely detected in the environment, wildlife and human. Currently few studies have documented the effects of chronic PFOS exposure on lipid metabolism, especially in aquatic organisms. The underlying mechanisms of hepatotoxicity induced by chronic PFOS exposure are still largely unknown. The present study defined the effects of chronic exposure to low level of PFOS on lipid metabolism using zebrafish as a model system. Our findings revealed a severe hepatic steatosis in the liver of males treated with 0.5 μM PFOS as evidenced by hepatosomatic index, histological assessment and liver lipid profiles. Quantitative PCR assay further indicated that PFOS significantly increase the transcriptional expression of nuclear receptors (nr1h3, rara, rxrgb, nr1l2) and the genes associated with fatty acid oxidation (acox1, acadm, cpt1a). In addition, chronic PFOS exposure significantly decreased liver ATP content and serum level of VLDL/LDL lipoprotein in males. Taken together, these findings suggest that chronic PFOS exposure induces hepatic steatosis in zebrafish via disturbing lipid biosynthesis, fatty acid β-oxidation and excretion of VLDL/LDL lipoprotein, and also demonstrate the validity of using zebrafish as an alternative model for PFOS chronic toxicity screening.

Nitazoxanide for chronic hepatitis C

DEFF Research Database (Denmark)

Nikolova, Kristiana; Gluud, Christian; Grevstad, Berit

2014-01-01

BACKGROUND: Hepatitis C infection is a disease of the liver caused by the hepatitis C virus. The estimated number of chronically infected people with hepatitis C virus worldwide is about 150 million people. Every year, another three to four million people acquire the infection. Chronic hepatitis C......) and ribavirin was the approved standard treatment for chronic hepatitis C. In 2011, first-generation direct-acting antivirals (DAAs) have been licensed, for use in combination with peginterferon and ribavirin for treating hepatitis C virus genotype 1 infection. Nitazoxanide is another antiviral drug with broad...... antiviral activity and may have potential as an effective alternative, or an addition to standard treatment for the treatment of the hepatitis C virus. OBJECTIVES: To assess the benefits and harms of nitazoxanide in people with chronic hepatitis C virus infection. SEARCH METHODS: We searched The Cochrane...

Molecular profiling of early stage liver fibrosis in patients with chronic hepatitis C virus infection

International Nuclear Information System (INIS)

Bieche, Ivan; Asselah, Tarik; Laurendeau, Ingrid; Vidaud, Dominique; Degot, Claude; Paradis, Valerie; Bedossa, Pierre; Valla, Dominique-Charles; Marcellin, Patrick; Vidaud, Michel

2005-01-01

The molecular mechanisms of acute hepatitis C virus (HCV) infection, end-stage hepatitis (cirrhosis), and hepatocellular carcinoma have been extensively studied, but little is known of the changes in liver gene expression during the early stages of liver fibrosis associated with chronic HCV infection, that is, the transition from normal liver (NL) of uninfected patients to the first stage of liver fibrosis (F1-CH-C). To obtain insight into the molecular pathogenesis of F1-CH-C, we used real-time quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) to study the mRNA expression of 240 selected genes in liver tissue with F1-CH-C, in comparison with NL. The expression of 54 (22.5%) of the 240 genes was significantly different between F1-CH-C and NL; 46 genes were upregulated and 8 were downregulated in F1-CH-C. The most noteworthy changes in gene expression mainly affected the transcriptional network regulated by interferons (IFNs), including both IFN-α/β-inducible genes (STAT1, STAT2, ISGF3G/IRF9, IFI27, G1P3, G1P2, OAS2, MX1) and IFN-γ-inducible genes (CXCL9, CXCL10, CXCL11). Interesting, upregulation of IFN-α/β-inducible genes (but not IFN-γ-inducible genes) was independent of histological scores (grade and stage of fibrosis) and HCV characteristics (hepatic HCV mRNA levels and the HCV genotype), and was specific to HCV (as compared to hepatitis B virus (HBV)). Other genes dysregulated in F1-CH-C, albeit less markedly than IFN-α/β- and IFN-γ-inducible genes, were mainly involved in the activation of lymphocytes infiltrating the liver (IFNG, TNF, CXCL6, IL6, CCL8, CXCR3, CXCR4, CCR2), cell proliferation (p16/CDKN2A, MKI67, p14/ARF), extracellular matrix remodeling (MMP9, ITGA2), lymphangiogenesis (XLKD1/LYVE), oxidative stress (CYP2E1), and cytoskeleton microtubule organization (STMN2/SCG10). Thus, a limited number of signaling pathways, and particularly the transcriptional network regulated by interferons, are dysregulated in the first

Hepatic (Liver) Function Panel

Science.gov (United States)

... Educators Search English Español Blood Test: Hepatic (Liver) Function Panel KidsHealth / For Parents / Blood Test: Hepatic (Liver) ... kidneys ) is working. What Is a Hepatic (Liver) Function Panel? A liver function panel is a blood ...

De novo hepatic steatosis drives atherogenic risk in liver transplantation recipients.

Science.gov (United States)

Idowu, Michael O; Chhatrala, Ravi; Siddiqui, M Bilal; Driscoll, Carolyn; Stravitz, R Todd; Sanyal, Arun J; Bhati, Chandra; Sargeant, Carol; Luketic, Velimir A; Sterling, Richard K; Contos, Melissa; Matherly, Scott; Puri, Puneet; Siddiqui, M Shadab

2015-11-01

Nonalcoholic fatty liver disease is associated with cardiovascular disease (CVD) in the general population. Despite a high prevalence of de novo hepatic steatosis after liver transplantation (LT), there are no data exploring the association between hepatic steatosis after LT and atherogenic risk. The aim of the study was to explore the impact of hepatic steatosis on serum atherogenic markers in liver transplantation recipients (LTRs). Biomarkers of CVD risk were compared in 89 LTRs with no known history of dyslipidemia, ischemic heart disease, or graft cirrhosis. To avoid potential confounders, LTRs on oral hypoglycemic agents, exogenous insulin, corticosteroids, or lipid-lowering therapy were excluded. Only patients for whom histological assessment was available after LT were included in the study. Thirty-five LTRs had de novo hepatic steatosis after LT, whereas 54 did not. Both cohorts were similar with regards to age, sex, ethnicity, and follow-up from LT. Additionally, the traditional lipid profile was similar between the 2 cohorts. LTRs with hepatic steatosis had higher serum concentrations of small-dense low-density lipoprotein cholesterol (sdLDL-C; 34.8 ± 16.9 versus 22.7 ± 11.2 mg/dL; P hepatic steatosis had higher serum insulin concentrations (27.8 ± 41.8 versus 11.7 ± 7.8 uU/mL; P Steatosis grade was directly related to sdLDL-C, sdLDL-P, insulin, VLDL-P, and VLDL-size. In multivariate analysis, the association between steatosis grade and sdLDL-C (β = 0.03; P = 0.029), VLDL-size (β = 0.316; P = 0.04), and low-density lipoprotein particle size (β = -0.27; P = 0.05) was independent of sex, body mass index, age, diabetes mellitus, time from transplant, and indication for LT. In conclusion, de novo hepatic steatosis after LT is associated with atherogenic lipoproteins and independent of traditional CVD risk factors. © 2015 American Association for the Study of Liver Diseases.

Refactoring Real-Time Java Profiles

DEFF Research Database (Denmark)

Søndergaard, Hans; Thomsen, Bent; Ravn, Anders Peter

2011-01-01

Just like other software, Java profiles benefits from refactoring when they have been used and have evolved for some time. This paper presents a refactoring of the Real-Time Specification for Java (RTSJ) and the Safety Critical Java (SCJ) profile (JSR-302). It highlights core concepts and makes...

Microarray multiplex assay for the simultaneous detection and discrimination of hepatitis B, hepatitis C, and human immunodeficiency type-1 viruses in human blood samples

International Nuclear Information System (INIS)

Hsia, Chu Chieh; Chizhikov, Vladimir E.; Yang, Amy X.; Selvapandiyan, Angamuthu; Hewlett, Indira; Duncan, Robert; Puri, Raj K.; Nakhasi, Hira L.; Kaplan, Gerardo G.

2007-01-01

Hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus type-1 (HIV-1) are transfusion-transmitted human pathogens that have a major impact on blood safety and public health worldwide. We developed a microarray multiplex assay for the simultaneous detection and discrimination of these three viruses. The microarray consists of 16 oligonucleotide probes, immobilized on a silylated glass slide. Amplicons from multiplex PCR were labeled with Cy-5 and hybridized to the microarray. The assay detected 1 International Unit (IU), 10 IU, 20 IU of HBV, HCV, and HIV-1, respectively, in a single multiplex reaction. The assay also detected and discriminated the presence of two or three of these viruses in a single sample. Our data represent a proof-of-concept for the possible use of highly sensitive multiplex microarray assay to screen and confirm the presence of these viruses in blood donors and patients

Hepatitis B Vaccine

Science.gov (United States)

... a combination product containing Haemophilus influenzae type b, Hepatitis B Vaccine) ... combination product containing Diphtheria, Tetanus Toxoids, Acellular Pertussis, Hepatitis B, Polio Vaccine)

Autoantibody Profiling in a Cohort of Pediatric and Adult Patients With Autoimmune Hepatitis.

Science.gov (United States)

Villalta, Danilo; Girolami, Elia; Alessio, Maria Grazia; Sorrentino, Maria Concetta; Tampoia, Marilina; Brusca, Ignazio; Daves, Massimo; Porcelli, Brunetta; Barberio, Giuseppina; Conte, Mariaelisabetta; Pantarotto, Lisa; Bizzaro, Nicola

2016-01-01

Autoimmune hepatitis (AIH) is a rare condition characterized by the presence of autoantibodies distinctive of type 1 AIH (AIH-1) and type 2 AIH (AIH-2). The aim of this study was to evaluate the autoantibody profile in a cohort of pediatric and adult AIH patients, using both indirect immunofluorescence (IIF) and a new multiplexed line-blot assay. Sera from 63 pediatric and 53 adult AIH patients were tested for antinuclear (ANA), antismooth muscle (SMA), anti-liver kidney microsome 1 (anti-LKM1), anti-liver cytosol 1 (anti-LC1) autoantibodies using IIF methods; for anti-LKM1, anti-LC1, and soluble liver antigen/liver-pancreas (anti-SLA/LP) autoantibodies using the line-blot; for anti-F-actin autoantibodies using IIF both on VSM47 cell-line and on rat intestinal epithelial cells. AIH-1 was the most common type of AIH in the adult cohort (73.6%), while AIH-2 was the most common AIH in the pediatric cohort (61.9%). Both in adult and pediatric AIH-2 anti-LKM1 were the prevalent autoantibodies. In pediatric AIH-2 anti-LC1 autoantibodies were more frequent than in adult AIH-2 (59 vs. 28.6%), and in 35.9% of cases they were present alone. In 17 patients anti-LC1 autoantibodies were detected only with the line-blot assay. The levels of anti-LKM1 and of anti-LC1 were not different between adult and pediatric AIH, and the overall agreement between the results obtained with the two IIF methods for F-actin detection was 98.8% (CI 95%: 94.4-99.7%). The line-blot assay showed a higher sensitivity than IIF for anti-LC1 detection. Anti-LKM1 and anti-LC1 autoantibody levels are not different in adults and children. An almost perfect agreement between the two IIF methods for anti-F-actin detection has been observed. © 2014 Wiley Periodicals, Inc.

Pathogenesis of Hepatic Encephalopathy

Directory of Open Access Journals (Sweden)

Irena Ciećko-Michalska

2012-01-01

Full Text Available Hepatic encephalopathy can be a serious complication of acute liver failure and chronic liver diseases, predominantly liver cirrhosis. Hyperammonemia plays the most important role in the pathogenesis of hepatic encephalopathy. The brain-blood barrier disturbances, changes in neurotransmission, neuroinflammation, oxidative stress, GABA-ergic or benzodiazepine pathway abnormalities, manganese neurotoxicity, brain energetic disturbances, and brain blood flow abnormalities are considered to be involved in the development of hepatic encephalopathy. The influence of small intestine bacterial overgrowth (SIBO on the induction of minimal hepatic encephalopathy is recently emphasized. The aim of this paper is to present the current views on the pathogenesis of hepatic encephalopathy.

Pathogenesis of Hepatic Encephalopathy

Science.gov (United States)

Ciećko-Michalska, Irena; Szczepanek, Małgorzata; Słowik, Agnieszka; Mach, Tomasz

2012-01-01

Hepatic encephalopathy can be a serious complication of acute liver failure and chronic liver diseases, predominantly liver cirrhosis. Hyperammonemia plays the most important role in the pathogenesis of hepatic encephalopathy. The brain-blood barrier disturbances, changes in neurotransmission, neuroinflammation, oxidative stress, GABA-ergic or benzodiazepine pathway abnormalities, manganese neurotoxicity, brain energetic disturbances, and brain blood flow abnormalities are considered to be involved in the development of hepatic encephalopathy. The influence of small intestine bacterial overgrowth (SIBO) on the induction of minimal hepatic encephalopathy is recently emphasized. The aim of this paper is to present the current views on the pathogenesis of hepatic encephalopathy. PMID:23316223

Comparison of autochthonous and imported cases of hepatitis A or hepatitis E.

Science.gov (United States)

Hartl, J; Kreuels, B; Polywka, S; Addo, M; Luethgehetmann, M; Dandri, M; Dammermann, W; Sterneck, M; Lohse, A W; Pischke, S

2015-07-01

Hepatitis A and hepatitis E are not limited to tropical countries but are also present in industrialized countries. Both infections share similar clinical features. There is no comparative study evaluating the clinical parameters of autochthonous and imported hepatitis A virus and hepatitis E virus infections. The aim of this study was to determine differences between autochthonous and imported hepatitis A virus (HAV) and hepatitis E virus (HEV) infections. Medical charts of all patients at our center with acute HAV and HEV infections were analyzed retrospectively (n = 50, study period 01/2009 - 08/2013). Peak bilirubin (median 8.6 vs. 4.4 mg/dL, p = 0.008) and ALT levels (median 2998 vs. 1666 IU/mL, p = 0.04) were higher in patients with hepatitis A compared to hepatitis E. In comparison to autochthones hepatitis E cases, patients with imported infections had significantly higher peak values for AST, ALT, bilirubin and INR (p = 0.009, p = 0.002, p = 0.04 and p = 0.049, respectively). In HAV infection, AST levels tended to be higher in imported infections (p = 0.08). (i) It is not possible to differentiate certainly between acute HAV and HEV infections by clinical or biochemical parameters, however, HAV infections might be associated with more cholestasis and higher ALT values. (ii) Imported HEV infections are associated with higher transaminases, INR and bilirubin levels compared to autochthonous cases and (iii) imported HAV infections tend to be associated with higher transaminases in comparison to autochthonous cases. © Georg Thieme Verlag KG Stuttgart · New York.

Relation between laboratory test results and histological hepatitis activity in individuals positive for hepatitis B surface antigen and antibodies to hepatitis B e antigen

NARCIS (Netherlands)

ter Borg, F.; ten Kate, F. J.; Cuypers, H. T.; Leentvaar-Kuijpers, A.; Oosting, J.; Wertheim-van Dillen, P. M.; Honkoop, P.; Rasch, M. C.; de Man, R. A.; van Hattum, J.; Chamuleau, R. A.; Reesink, H. W.; Jones, E. A.

1998-01-01

BACKGROUND: Hepatitis B surface antigen (HBsAg) and antibodies to hepatitis B e antigen (anti-HBe) commonly coexist, and laboratory tests are often requested to assess histological hepatitis activity. An optimum panel of tests has not been found and the usefulness of hepatitis B virus (HBV) DNA

Severity of depression in hepatitis B and hepatitis C patients

International Nuclear Information System (INIS)

Qureshi, M.O.; Khokhar, N.; Shafqat, F.

2012-01-01

Objective: To assess and compare the severity of depression in chronic hepatitis B (CHB), chronic hepatitis C (CHC) and healthy subjects. Study Design: Comparative study. Place and Duration of Study: Shifa International Hospital, Islamabad from July 2011 to February 2012. Methodology:A total of 206 subjects were divided in three groups. Group-I (chronic hepatitis C, n = 95), group-II (chronic hepatitis B, n = 29) and group-III (healthy subjects, n = 82). They were matched for age, gender and socioeconomic status and were compared for frequency and severity of depression as measured by Hospital Anxiety and Depression Scale (HADS). Results: Some degree of depression was noted in all groups. Frequency of depression was 72.6% in group-I, 58.6% in group-II and 37.8% in group-III (p value < 0.001). Conclusion: Both CHC and CHB had high frequency of some degree of depression. Hepatitis C patients had more depressive features than CHB. It is worthwhile to do more close mental health observation in them. A multidisciplinary team including a psychiatric specialist can help in this approach. (author)

Effect of different commercial fat sources on brain, liver and blood lipid profiles of rats in growth phase.

Science.gov (United States)

Angelis-Pereira, Michel Cardoso de; Barcelos, Maria de Fátima Píccolo; Pereira, Juciane de Abreu Ribeiro; Pereira, Rafaela Corrêa; Souza, Raimundo Vicente de

2017-12-01

To investigate the fatty acid content of different fat sources and evaluate the effect of them on plasma and hepatic lipids and on the fatty acid profile of the brain tissue of Wistar rats. Thirty male albino Wistar rats received for 59 days, the following diets: diet added of margarine with low content of polyunsaturated fatty acids (PUFA); diet added of margarine with high content of PUFA; diet added of butter; diet added of hydrogenated vegetable fat; diet added of soybean oil. Fatty acid profile of the lipid sources, blood and hepatic lipids fractions and fatty acid profile of the brain tissue were determined. Margarine consumption of provided different responses as to concentrations of blood and hepatic lipid fractions. Intake of butter and hydrogenated increased LDL-c/HDL-c ratio, being the steepest increase promoted by hydrogenated vegetable fat, which also raised LDL-c levels expressively. All fats used in the treatments reduced the cerebral concentration of docosahexaenoic acid when compared to soybean oil (control). The different fat sources commonly consumed by population provided different responses in vivo. This is particularly relevant considering the role of these lipids in the incidence and prevention of cardiovascular diseases.

Detection of hepatitis G virus-RNA (HGV-RNA) in serum of patients with HBV hepatitis

International Nuclear Information System (INIS)

Zhu Jingfei; Hang Shangrong; Chen Min; Pu Xiangke; Wang Yongzhong; Zhou Guoping

2007-01-01

Objective: To investigate the incidence of HGV infection in patients with HBV hepatitis and any possible adverse effect of the superinfection. Methods: Serum HGV-RNA expression was examined with PCR in 1104 patients with HBV hepatitis and 251 controls. Results: The positive rate of HGV-RNA in HBV hepatitis patients was not significantly different from that in controls (3.17% vs 2.79%, P>0.05). Among the patients with HBV hepatitis, HGV-RNA positive rate in patients with chronic hepatitis was significantly higher than that in patients with acute hepatitis (4.78% vs 0.96, P<0.05). Conclusion: HGV infection might be presented as non-symptomatic carriers or other mild form of hepatitis. The incidence of HGV infection was not especially high in HBV hepatitis patients, however, concomitant HGV and HBV infection might predispose to development of chronicity. (authors)

Hepatic Diacylglycerol-Associated Protein Kinase Cε Translocation Links Hepatic Steatosis to Hepatic Insulin Resistance in Humans

NARCIS (Netherlands)

ter Horst, Kasper W.; Gilijamse, Pim W.; Versteeg, Ruth I.; Ackermans, Mariette T.; Nederveen, Aart J.; la Fleur, Susanne E.; Romijn, Johannes A.; Nieuwdorp, Max; Zhang, Dongyan; Samuel, Varman T.; Vatner, Daniel F.; Petersen, Kitt F.; Shulman, Gerald I.; Serlie, Mireille J.

2017-01-01

Hepatic lipid accumulation has been implicated in the development of insulin resistance, but translational evidence in humans is limited. We investigated the relationship between liver fat and tissue-specific insulin sensitivity in 133 obese subjects. Although the presence of hepatic steatosis in

Canine Copper-Associated Hepatitis

NARCIS (Netherlands)

Dirksen, Karen; Fieten, Hille

2017-01-01

Copper-associated hepatitis is recognized with increasing frequency in dogs. The disease is characterized by centrolobular hepatic copper accumulation, leading to hepatitis and eventually cirrhosis. The only way to establish the diagnosis is by histologic assessment of copper distribution and copper

Hepatitis C and Incarceration

Science.gov (United States)

... Hepatitis Cdo to take care of their liver? People with Hepatitis C should not use alcohol or street drugs, as these can hurt the liver. Some other products can also hurt people with Hepatitis C, even if they appear to ...

A case of Hepatitis E in a blood donor

Directory of Open Access Journals (Sweden)

Anita A Tendulkar

2015-01-01

Full Text Available The threat of hepatitis E is being felt in blood banks in recent times. The disease is usually self-limiting, but may progress to a fulminant fatal form. We report a unique case of a hepatitis E virus (HEV-positive asymptomatic blood donor who later developed jaundice and informed the blood bank. A blood donor passed all eligibility criteria tests and donated blood. After 20 days, the blood bank was informed by the donor that he had developed vomiting and jaundice 1 day postdonation. He was investigated by a local laboratory 1 day postdonation for liver profile, which was high. There had been a major outbreak in his community of similar symptoms during the same period. HEV IgM antibody by enzyme-linked immunosorbent assay was positive. Silent infections may be lurking in apparently healthy donors. Donors need to be encouraged to revert in case of any significant developments after donation and maintain open channels of communication.

Systematic screening for novel, serologically reactive Hepatitis E Virus epitopes

Directory of Open Access Journals (Sweden)

Osterman Andreas

2012-01-01

Full Text Available Abstract Background The National Institutes of Health classified Hepatitis E as an emerging disease since Hepatitis E Virus (HEV is the major cause of acute hepatitis in developing countries. Interestingly, an increasing number of sporadic cases of HEV infections are described in industrialized countries as zoonosis from domestic livestock. Despite the increasing relevance of this pathogen in clinical virology, commercial antibody assays are mainly based on fragments of HEV open reading frame (ORF 2 and ORF3. The largest ORF1 (poly-protein, however, is not part of current testing formats. Methods From a synthesized full length HEV genotype 1 cDNA-bank we constructed a complete HEV gene library consisting of 15 respective HEV ORF domains. After bacterial expression and purification of nine recombinant HEV proteins under denaturating conditions serum profiling experiments using 55 sera from patients with known infection status were performed in microarray format. SPSS software assessed the antigenic potential of these nine ORF domains in comparison to seven commercial HEV antigens (genotype 1 and 3 by performing receiver operator characteristics, logistic regression and correlation analysis. Results HEV antigens produced with our method for serum profiling experiments exhibit the same quality and characteristics as commercial antigens. Serum profiling experiments detected Y, V and X domains as ORF1-antigens with potentially comparable diagnostic significance as the well established epitopes of ORF2 and ORF3. However no obvious additional increase in sensitivity or specificity was achieved in diagnostic testing as revealed by bioinformatic analysis. Additionally we found that the C-terminal domain of the potential transmembrane protein ORF3 is responsible for IgG and IgM seroreactivity. Data suggest that there might be a genotype specific seroreactivity of homologous ORF2-antigens. Conclusions The diagnostic value of identified ORF1 epitopes might

Primary hepatic pheochromocytoma

International Nuclear Information System (INIS)

Rimmelin, A.; Hartheiser, M.; Gangi, A.; Welsch, M.; Jeung, M.Y.; Jaeck, D.; Tongio, J.; Dietemann, J.L.

1996-01-01

Pheochromocytomas are uncommon tumors that represent a potentially curable cause of hypertension. They are usually located in the adrenal glands, but 10% arise from extra-adrenal sites, located along the paravertebral sympathetic chains. We report a case of primary hepatic pheochromocytoma responsible for a severe hypertension in a 24-year-old man. Echotomography showed a lightly heterogeneous mass located in the segment 8 of the liver. Iodine 131 -metaiodobenzylguanidine scintigraphy showed a large hepatic concentration of the tracer and no other localization. This tumor appeared highly vascularized on enhanced CT scan and on aortic angiography. Magnetic resonance imaging revealed a hepatic tumor with a high signal intensity on T2-weighted images and with a signal isointense to the liver on T1-weighted images. The hepatic venous sampling contained the highest catecholamine level, whereas the adrenal venous samping was normal. After surgical resection of the hepatic tumor, the tension level and catecholamines plasmatic level normalized. No recurrent symptoms appeared during a 3-year follow-up. (orig.)

Hepatitis in pregnancy

International Nuclear Information System (INIS)

Ain, F.U.; Amin, A.; Yasmin, F.

2007-01-01

To determine the frequency of viral hepatitis in general, spectrum of hepatitis E in particular, and to study the maternal and fetal morbidity and mortality associated with it. In this prospective study, total number of pregnant women was 4723, sera of 35 pregnant women having clinical jaundice in pregnancy were analyzed for markers of hepatitis A , B, C and E viruses. Of the 35 pregnant women with jaundice HEV IgM were 60%,HA V IgM20%, Anti HCV 8.75%,Hbs Ag 5.71%, unexplained 5.71%. Amongst HEV 23.80% had hepatic encephalopathy DIC in 42.85%, PPH in 23.80%, renal failure in 9.52% an- maternal mortality in 4.76%. Approximately two third of pregnant women with HEV infection had preterm deliveries (76.19) % and perinatal mortality of 42.8%. Hepatitis E was the commonest etiological agent in those who had fulminant disease during pregnancy and was associated with high morbidity and mortality. (author)

Severe atrophy of right hepatic lobe simulating right hepatic lobectomy

International Nuclear Information System (INIS)

Yeh, C.W.; Strashun, A.; Goldsmith, S.J.

1981-01-01

Absence of the right hepatic lobe following blunt abdominal trauma without surgical resection is reported. The usual site of the right hepatic lobe is demonstrated to be occupied by bowel by hepatobiliary imaging

Hepatitis B Virus, Hepatitis C Virus and Human Immunodeficiency ...

African Journals Online (AJOL)

Background: The epidemiology of viral hepatitis and Human immunodeficiency virus (HIV) during pregnancy is of great importance for health planners and program managers. However, few published data on viral hepatitis and HIV are available in Sudan especially during pregnancy. Objectives: The current study was ...

Hepatic manifestations of celiac disease

Directory of Open Access Journals (Sweden)

Hugh James Freeman

2010-05-01

Full Text Available Hugh James FreemanDepartment of Medicine (Gastroenterology, University of British Columbia, Vancouver, British Columbia, CanadaAbstract: Different hepatic and biliary tract disorders may occur with celiac disease. Some have been hypothesized to share genetic or immunopathogenetic factors, such as primary biliary cirrhosis, primary sclerosing cholangitis, and autoimmune hepatitis. Other hepatic changes in celiac disease may occur with malnutrition resulting from impaired nutrient absorption, including hepatic steatosis. In addition, celiac disease may be associated with rare hepatic complications, such as hepatic T-cell lymphoma.Keywords: celiac disease, autoimmune liver disease, primary biliary cirrhosis, fatty liver, gluten-free diet

Phase II, randomized, open, controlled study of AS03-adjuvanted H5N1 pre-pandemic influenza vaccine in children aged 3 to 9 years: follow-up of safety and immunogenicity persistence at 24 months post-vaccination.

Science.gov (United States)

Díez-Domingo, Javier; Baldó, José-María; Planelles-Catarino, Maria Victoria; Garcés-Sánchez, María; Ubeda, Isabel; Jubert-Rosich, Angels; Marès, Josep; Garcia-Corbeira, Pilar; Moris, Philippe; Teko, Maurice; Vanden Abeele, Carline; Gillard, Paul

2015-03-01