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Sample records for induced viral hepatitis

  1. Viral Hepatitis

    MedlinePlus

    ... Public Home » For Veterans and the Public Viral Hepatitis Menu Menu Viral Hepatitis Viral Hepatitis Home For ... the Public Veterans and Public Home How is Hepatitis C Treated? Find the facts about the newest ...

  2. Viral Hepatitis

    MedlinePlus

    ... with hepatitis? How does a pregnant woman pass hepatitis B virus to her baby? If I have hepatitis B, what does my baby need so that she ... Can I breastfeed my baby if I have hepatitis B? More information on viral hepatitis What is hepatitis? ...

  3. Viral Hepatitis Induces Hepatocellular Cancer: What Can We Learn from Epidemiology Comparing Iran and Worldwide Findings?

    PubMed Central

    Smolle, Elisabeth; Zöhrer, Evelyn; Bettermann, Kira; Haybaeck, Johannes

    2012-01-01

    Context Several risk factors play the role in the development of hepatocellular carcinoma (HCC) from which chronic hepatitis B and C infections are the most important ones. DNA integration of hepatitis viruses alters the function of critical genes promoting malignant transformation of virus-infected liver cells. Evidence Acquisition There are remarkable geographic differences in prevalence of chronic viral hepatitis and incidence of HCC. Middle Eastern countries are characterized by a moderate to high prevalence rate of chronic viral hepatitis in the population. This review discusses about epidemiologic findings of hepatitis B and C infections, and HCC, as well as focuses on Middle East countries, particularly Iran. We provide an overview about risk factors, prevention and treatment, and bring up the role of HCC induced by chronic viral hepatitis. Results Vaccination against hepatitis B virus (HBV) in the early childhood is highly effective to lower infection rates, substantially. For hepatitis C, adequate hygiene when dealing with human blood and screening programs for blood donors can mainly reduce infection rates. As HCC is strongly associated with chronic viral hepatitis, prevention against the infection is crucial for preventing against HCC too. Conclusions Although prevention and treatment of chronic hepatitis B and C have improved within the last decades even in high-risk countries, effective and sustainable reduction of these infections still needs more actions. PMID:23233866

  4. Viral hepatitis: Indian scenario.

    PubMed

    Satsangi, Sandeep; Chawla, Yogesh K

    2016-07-01

    Viral hepatitis is a cause for major health care burden in India and is now equated as a threat comparable to the "big three" communicable diseases - HIV/AIDS, malaria and tuberculosis. Hepatitis A virus and Hepatitis E virus are predominantly enterically transmitted pathogens and are responsible to cause both sporadic infections and epidemics of acute viral hepatitis. Hepatitis B virus and Hepatitis C virus are predominantly spread via parenteral route and are notorious to cause chronic hepatitis which can lead to grave complications including cirrhosis of liver and hepatocellular carcinoma. Around 400 million people all over the world suffer from chronic hepatitis and the Asia-Pacific region constitutes the epicentre of this epidemic. The present article would aim to cover the basic virologic aspects of these viruses and highlight the present scenario of viral hepatitis in India. PMID:27546957

  5. [Viral hepatitis in travellers].

    PubMed

    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

  6. HIV and Viral Hepatitis

    MedlinePlus

    ... prevalent among blacks as among whites. Viral Hepatitis Transmission People can be infected with the three most ... risk for HAV. • • New data suggest that sexual transmission of HCV among MSM with HIV occurs more ...

  7. Immigration and viral hepatitis.

    PubMed

    Sharma, Suraj; Carballo, Manuel; Feld, Jordan J; Janssen, Harry L A

    2015-08-01

    WHO estimates reveal that the global prevalence of viral hepatitis may be as high as 500 million, with an annual mortality rate of up to 1.3 million individuals. The majority of this global burden of disease is borne by nations of the developing world with high rates of vertical and iatrogenic transmission of HBV and HCV, as well as poor access to healthcare. In 2013, 3.2% of the global population (231 million individuals) migrated into a new host nation. Migrants predominantly originate from the developing countries of the south, into the developed economies of North America and Western Europe. This mass migration of individuals from areas of high-prevalence of viral hepatitis poses a unique challenge to the healthcare systems of the host nations. Due to a lack of universal standards for screening, vaccination and treatment of viral hepatitis, the burden of chronic liver disease and hepatocellular carcinoma continues to increase among migrant populations globally. Efforts to increase case identification and treatment among migrants have largely been limited to small outreach programs in urban centers, such that the majority of migrants with viral hepatitis continue to remain unaware of their infection. This review summarizes the data on prevalence of viral hepatitis and burden of chronic liver disease among migrants, current standards for screening and treatment of immigrants and refugees, and efforts to improve the identification and treatment of viral hepatitis among migrants. PMID:25962882

  8. [Update chronic viral hepatitis].

    PubMed

    Ziegenhagen, D J

    2016-03-01

    More than 500,000 people in Germany have chronic viral hepatitis. The interferon-based treatments formerly used in hepatitis B have been widely replaced by life-long oral medication with nucleoside or nucleotide analogues. Treatment for chronic hepatitis C has been improved substantially by the development of new and very expensive drug combinations. Up to 90% of patients can now be cured with certainty, and one to two years after successful treatment there is no relevant risk of recurrence. These individuals expect to receive insurance cover under appropriate conditions. Vaccination programmes are very efficient at decreasing the incidence of hepatitis B, but no vaccine against hepatitis C is likely to become available in the next decade. PMID:27111951

  9. Murine viral hepatitis involves NK cell depletion associated with virus-induced apoptosis

    PubMed Central

    LEHOUX, M; JACQUES, A; LUSIGNAN, S; LAMONTAGNE, L

    2004-01-01

    Mouse hepatitis virus type 3 (MHV3), a coronavirus, is an excellent animal model for the study of immunological disorders related to acute and chronic hepatitis. In this study, we have verified if the fulminant hepatitis induced by MHV3 could be related to an impairment of innate immunity. Groups of three C57BL/6 mice were infected with the pathogenic L2-MHV3 or attenuated YAC-MHV3 viruses, and the natural killer (NK) cell populations from liver, spleen and bone marrow were analysed. The percentage of intrahepatic NK1·1+T cell receptor (TCR)− cells did not increase while NK1·1+TCRinter cells decreased in both L2-MHV3- and YAC-MHV3-infected mice. Concurrently, splenic and myeloid NK1·1+ cells decreased in L2-MHV3-infected mice. However, the cytotoxic activity of NK cells increased in liver and decreased in bone marrow from pathogenic L2-MHV3-infected mice while no modification was detected in YAC-MHV3-infected mice. Flow cytometric analysis revealed that both normal and larger splenic or myeloid NK cells decreased more in pathogenic L2-MHV3-infected mice than in attenuated YAC-MHV3-infected mice. In vitro viral infections of interleukin (IL)-15-stimulated lymphoid cells from liver and bone marrow revealed that L2-MHV3 induced higher decreases in cell viability of NK1·1+ cells than the YAC-MHV3 variant. The NK cell decreases were due to the viral permissivity leading to cytopathic effects characterized by cell rounding, syncytia formation and apoptosis. Larger NK+ syncytia were observed in L2-MHV3-infected cells than in YAC-MHV3-infected cells. These results suggest that NK cell production is impaired by viral infection favouring fulminant hepatitis. PMID:15196242

  10. Transposon mouse models to elucidate the genetic mechanisms of hepatitis B viral induced hepatocellular carcinoma.

    PubMed

    Chiu, Amy P; Tschida, Barbara R; Lo, Lilian H; Moriarity, Branden S; Rowlands, Dewi K; Largaespada, David A; Keng, Vincent W

    2015-11-14

    The major type of human liver cancer is hepatocellular carcinoma (HCC), and there are currently many risk factors that contribute to this deadly disease. The majority of HCC occurrences are associated with chronic hepatitis viral infection, and hepatitis B viral (HBV) infection is currently a major health problem in Eastern Asia. Elucidating the genetic mechanisms associated with HBV-induced HCC has been difficult due to the heterogeneity and genetic complexity associated with this disease. A repertoire of animal models has been broadly used to study the pathophysiology and to develop potential treatment regimens for HBV-associated HCC. The use of these animal models has provided valuable genetic information and has been an important contributor to uncovering the factors involved in liver malignant transformation, invasion and metastasis. Recently, transposon-based mouse models are becoming more widely used in liver cancer research to interrogate the genome by forward genetics and also used to validate genes rapidly in a reverse genetic manner. Importantly, these transposon-based rapid reverse genetic mouse models could become crucial in testing potential therapeutic agents before proceeding to clinical trials in human. Therefore, this review will cover the use of transposon-based mouse models to address the problems of liver cancer, especially HBV-associated HCC occurrences in Asia. PMID:26576100

  11. Transposon mouse models to elucidate the genetic mechanisms of hepatitis B viral induced hepatocellular carcinoma

    PubMed Central

    Chiu, Amy P; Tschida, Barbara R; Lo, Lilian H; Moriarity, Branden S; Rowlands, Dewi K; Largaespada, David A; Keng, Vincent W

    2015-01-01

    The major type of human liver cancer is hepatocellular carcinoma (HCC), and there are currently many risk factors that contribute to this deadly disease. The majority of HCC occurrences are associated with chronic hepatitis viral infection, and hepatitis B viral (HBV) infection is currently a major health problem in Eastern Asia. Elucidating the genetic mechanisms associated with HBV-induced HCC has been difficult due to the heterogeneity and genetic complexity associated with this disease. A repertoire of animal models has been broadly used to study the pathophysiology and to develop potential treatment regimens for HBV-associated HCC. The use of these animal models has provided valuable genetic information and has been an important contributor to uncovering the factors involved in liver malignant transformation, invasion and metastasis. Recently, transposon-based mouse models are becoming more widely used in liver cancer research to interrogate the genome by forward genetics and also used to validate genes rapidly in a reverse genetic manner. Importantly, these transposon-based rapid reverse genetic mouse models could become crucial in testing potential therapeutic agents before proceeding to clinical trials in human. Therefore, this review will cover the use of transposon-based mouse models to address the problems of liver cancer, especially HBV-associated HCC occurrences in Asia. PMID:26576100

  12. Viral Hepatitis: A through E and Beyond

    MedlinePlus

    Viral Hepatitis: A through E and Beyond NATIONAL INSTITUTES OF HEALTH U.S. Department of Health and Human Services National Digestive Diseases Information Clearinghouse What is viral hepatitis? Viral hepatitis is inflammation of the liver caused ...

  13. Chronic hepatitis C viral infection subverts vaccine‐induced T‐cell immunity in humans

    PubMed Central

    Kelly, Christabel; Swadling, Leo; Capone, Stefania; Brown, Anthony; Richardson, Rachel; Halliday, John; von Delft, Annette; Oo, Ye; Mutimer, David; Kurioka, Ayako; Hartnell, Felicity; Collier, Jane; Ammendola, Virginia; Sorbo, Mariarosaria Del; Grazioli, Fabiana; Esposito, Maria Luisa; Marco, Stefania Di; Siani, Loredana; Traboni, Cinzia; Hill, Adrian V.S.; Colloca, Stefano; Nicosia, Alfredo; Cortese, Riccardo; Folgori, Antonella; Klenerman, Paul

    2016-01-01

    Adenoviral vectors encoding hepatitis C virus (HCV) nonstructural (NS) proteins induce multispecific, high‐magnitude, durable CD4+ and CD8+ T‐cell responses in healthy volunteers. We assessed the capacity of these vaccines to induce functional HCV‐specific immune responses and determine T‐cell cross‐reactivity to endogenous virus in patients with chronic HCV infection. HCV genotype 1‐infected patients were vaccinated using heterologous adenoviral vectors (ChAd3‐NSmut and Ad6‐NSmut) encoding HCV NS proteins in a dose escalation, prime‐boost regimen, with and without concomitant pegylated interferon‐α/ribavirin therapy. Analysis of immune responses ex vivo used human leukocyte antigen class I pentamers, intracellular cytokine staining, and fine mapping in interferon‐γ enzyme‐linked immunospot assays. Cross‐reactivity of T cells with population and endogenous viral variants was determined following viral sequence analysis. Compared to healthy volunteers, the magnitude of HCV‐specific T‐cell responses following vaccination was markedly reduced. CD8+ HCV‐specific T‐cell responses were detected in 15/24 patients at the highest dose, whereas CD4+ T‐cell responses were rarely detectable. Analysis of the host circulating viral sequence showed that T‐cell responses were rarely elicited when there was sequence homology between vaccine immunogen and endogenous virus. In contrast, T cells were induced in the context of genetic mismatch between vaccine immunogen and endogenous virus; however, these commonly failed to recognize circulating epitope variants and had a distinct partially functional phenotype. Vaccination was well tolerated but had no significant effect on HCV viral load. Conclusion: Vaccination with potent HCV adenoviral vectored vaccines fails to restore T‐cell immunity except where there is genetic mismatch between vaccine immunogen and endogenous virus; this highlights the major challenge of overcoming T‐cell exhaustion

  14. Comparative analysis of portal hepatic infiltrating leucocytes in acute drug-induced liver injury, idiopathic autoimmune and viral hepatitis.

    PubMed

    Foureau, D M; Walling, T L; Maddukuri, V; Anderson, W; Culbreath, K; Kleiner, D E; Ahrens, W A; Jacobs, C; Watkins, P B; Fontana, R J; Chalasani, N; Talwalkar, J; Lee, W M; Stolz, A; Serrano, J; Bonkovsky, H L

    2015-04-01

    Drug-induced liver injury (DILI) is often caused by innate and adaptive host immune responses. Characterization of inflammatory infiltrates in the liver may improve understanding of the underlying pathogenesis of DILI. This study aimed to enumerate and characterize leucocytes infiltrating liver tissue from subjects with acute DILI (n = 32) versus non-DILI causes of acute liver injury (n = 25). Immunostains for CD11b/CD4 (Kupffer and T helper cells), CD3/CD20 (T and B cells) and CD8/CD56 [T cytotoxic and natural killer (NK) cells] were evaluated in biopsies from subjects with acute DILI, either immunoallergic (IAD) or autoimmune (AID) and idiopathic autoimmune (AIH) and viral hepatitis (VH) and correlated with clinical and pathological features. All biopsies showed numerous CD8(+) T cells and macrophages. DILI cases had significantly fewer B lymphocytes than AIH and VH and significantly fewer NK cells than VH. Prominent plasma cells were unusual in IAD (three of 10 cases), but were associated strongly with AIH (eight of nine) and also observed in most with AID (six of nine). They were also found in five of 10 cases with VH. Liver biopsies from subjects with DILI were characterized by low counts of mature B cells and NK cells in portal triads in contrast to VH. NK cells were found only in cases of VH, whereas AIH and VH both showed higher counts of B cells than DILI. Plasma cells were associated most strongly with AIH and less so with AID, but were uncommon in IAD. PMID:25418487

  15. Endoplasmic Reticulum Stress Induced Synthesis of a Novel Viral Factor Mediates Efficient Replication of Genotype-1 Hepatitis E Virus

    PubMed Central

    Nair, Vidya P.; Madhvi, Abhilasha; Bakshi, Karishma; Srivastava, Akriti; Shalimar; Nayak, Baibaswata; CT, Ranjith Kumar; Surjit, Milan

    2016-01-01

    Hepatitis E virus (HEV) causes acute hepatitis in many parts of the world including Asia, Africa and Latin America. Though self-limiting in normal individuals, it results in ~30% mortality in infected pregnant women. It has also been reported to cause acute and chronic hepatitis in organ transplant patients. Of the seven viral genotypes, genotype-1 virus infects humans and is a major public health concern in South Asian countries. Sporadic cases of genotype-3 and 4 infection in human and animals such as pigs, deer, mongeese have been reported primarily from industrialized countries. Genotype-5, 6 and 7 viruses are known to infect animals such as wild boar and camel, respectively. Genotype-3 and 4 viruses have been successfully propagated in the laboratory in mammalian cell culture. However, genotype-1 virus replicates poorly in mammalian cell culture and no other efficient model exists to study its life cycle. Here, we report that endoplasmic reticulum (ER) stress promotes genotype-1 HEV replication by inducing cap-independent, internal initiation mediated translation of a novel viral protein (named ORF4). Importantly, ORF4 expression and stimulatory effect of ER stress inducers on viral replication is specific to genotype-1. ORF4 protein sequence is mostly conserved among genotype-1 HEV isolates and ORF4 specific antibodies were detected in genotype-1 HEV patient serum. ORF4 interacted with multiple viral and host proteins and assembled a protein complex consisting of viral helicase, RNA dependent RNA polymerase (RdRp), X, host eEF1α1 (eukaryotic elongation factor 1 isoform-1) and tubulinβ. In association with eEF1α1, ORF4 stimulated viral RdRp activity. Furthermore, human hepatoma cells that stably express ORF4 or engineered proteasome resistant ORF4 mutant genome permitted enhanced viral replication. These findings reveal a positive role of ER stress in promoting genotype-1 HEV replication and pave the way towards development of an efficient model of the

  16. Viral hepatitis vaccination during pregnancy.

    PubMed

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

    2016-04-01

    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. PMID:26833263

  17. [Microbiological diagnosis of viral hepatitis].

    PubMed

    Alonso, Roberto; Aguilera, Antonio; Córdoba, Juan; Fuertes, Antonio

    2015-11-01

    Liver inflammation or hepatitis has many different causes, both infectious and non-infectious. Among the former, viral infection is responsible for at least half of all hepatitis worldwide. Different viruses have been described with primary tropism for liver tissue. These microorganisms have been successively named with letters of the alphabet: A, B, C, D, E and G. The aim of this paper is to review this heterogeneous group of viruses in its most basic aspects, including clinical implications, treatment, main control, and prophylactic measures and, of special interest, diagnostic approaches, both serological and molecular, which are used for their detection, quantification and characterization. PMID:25742731

  18. Aplastica Anemia And Viral Hepatitis

    PubMed Central

    Cudillo, Laura

    2009-01-01

    Acquired aplastic anemia (aAA) is a severe and rare disease, characterized by hematopoietic bone marrow failure and peripheral cytopenia. The pathophysiology is immune mediated in most cases, activated T1 lymphocytes have been identified as effector cells. The disease can be successfully treated with combined immunosuppressive therapy or allogeneic hematopoietic stem cell transplantation. Hepatitis-associated aplastic anemia (HAA) is a syndrome of bone marrow failure following the development of acute seronegative hepatitis. HAA syndrome most often affects young males who presented severe pancytopenia two to three months after an episode of acute hepatitis. The clinical course of hepatitis is more frequently benign but a fulminant severe course is also described. The bone marrow failure can be explosive and severe and it is usually fatal if untreated, no correlations have been observed between severity of hepatitis and AA. In none of the studies a specific virus could be identified and most cases are seronegative for known hepatitis viruses. The clinical characteristics and response to immunotherapy indicate a central role for immune-mediated mechanism in the pathogenesis of HAA. The initial target organ of the immune response is the liver as suggested by the time interval between hepatitis and the onset of bone marrow failure. Liver histology is characterized by T cell infiltrating the parenchyma as reported in acute hepatitis. Recently in HAA it has been demonstrated intrahepatic and blood lymphocytes with T cell repertoire similar to that of confirmed viral acute hepatitis. The expanded T cell clones return to a normal distribution after response to immunosuppressive treatment, suggesting the antigen or T cell clearance. Therapeutic options are the same as acquired aplastic anemia. PMID:21415960

  19. Natural Killer Cells in Viral Hepatitis

    PubMed Central

    Rehermann, Barbara

    2015-01-01

    Natural killer (NK) cells are traditionally regarded as first-line effectors of the innate immune response, but they also have a distinct role in chronic infection. Here, we review the role of NK cells against hepatitis C virus (HCV) and hepatitis B virus (HBV), two agents that cause acute and chronic hepatitis in humans. Interest in NK cells was initially sparked by genetic studies that demonstrated an association between NK cell–related genes and the outcome of HCV infection. Viral hepatitis also provides a model to study the NK cell response to both endogenous and exogenous type I interferon (IFN). Levels of IFN-stimulated genes increase in both acute and chronic HCV infection and pegylated IFNα has been the mainstay of HCV and HBV treatment for decades. In chronic viral hepatitis, NK cells display decreased production of antiviral cytokines. This phenotype is found in both HCV and HBV infection but is induced by different mechanisms. Potent antivirals now provide the opportunity to study the reversibility of the suppressed cytokine production of NK cells in comparison with the antigen-induced defect in IFNγ and tumor necrosis factor-α production of virus-specific T cells. This has implications for immune reconstitution in other conditions of chronic inflammation and immune exhaustion, such as human immunodeficiency virus infection and cancer. PMID:26682281

  20. Update on Alcohol and Viral Hepatitis

    PubMed Central

    Gitto, Stefano; Vitale, Giovanni; Villa, Erica; Andreone, Pietro

    2014-01-01

    Alcohol consumption is often associated with viral hepatitis. Although alcohol is known to worsen viral liver disease, the interactions between alcohol and viral hepatitis are not fully understood. Molecular alterations in the liver due to alcohol and viral hepatitis include effects on viral replication, increased oxidative stress, cytotoxicity, and a weakened immune response. Clinically, alcohol enhances disease progression and favors induction of primitive liver neoplasm. The use of new antivirals for hepatitis C and well-established drugs for hepatitis B will determine how viral hepatitis can be controlled in a large percentage of these patients. However, alcohol-related liver disease continues to represent a barrier for access to antivirals, and it remains an unresolved health issue. PMID:26356547

  1. Thrombosis Associated with Viral Hepatitis

    PubMed Central

    Galli, Luca; Gerdes, Victor E.A.; Guasti, Luigina; Squizzato, Alessandro

    2014-01-01

    Viral hepatitis may promote the development of venous thromboembolism (VTE) and, more specifically, portal vein thrombosis (PVT). In this narrative review, we summarize the clinical data and discuss the possible pathogenetic roles of cytomegalovirus (CMV), Epstein-Barr virus (EBV), and hepatitis A, B, and C viruses (HAV, HBV, HCV) in the occurrence of VTE. CMV is the first qualified candidate to enter the list of VTE minor risk factors, and in the rare case of fulminant infection, both EBV and CMV, like any severe infection or inflammatory disease, increase risk for thrombosis. In chronic hepatitis B and C, it remains controversial whether antiphospholipid antibodies are important for thrombotic complications or merely an epiphenomenon. Retinal vein occlusion described in chronic hepatitis C is usually attributed to the treatment with interferon. Eltrombopag, used for HCV-related thrombocytopenia, has been associated with increased thrombotic risk. The imbalance between procoagulant and anticoagulant factors associated with chronic liver disease may have clinical implications. This may help to explain why these patients are not protected from clinical events such as VTE, PVT, and the progression of liver fibrosis. PMID:26357629

  2. Viral Hepatitis: Information for Gay and Bisexual Men

    MedlinePlus

    ... common types of viral hepatitis are Hepatitis A, Hepatitis B, and Hepatitis C. While all three types of ... new Hepatitis A cases and 20% of new Hepatitis B cases occur in gay or bisexual men. Gay ...

  3. Antifibrotic effect of aloe vera in viral infection-induced hepatic periportal fibrosis

    PubMed Central

    Hegazy, Sahar K; El-Bedewy, Mohamed; Yagi, Akira

    2012-01-01

    AIM: To investigate the anti-oxidative and anti-fibrotic effects of aloe vera in patients with liver fibrosis. METHODS: Aloe vera high molecular weight fractions (AHM) were processed by patented hyper-dry system in combination of freeze-dry technique with microwave and far infrared-ray radiation. Fifteen healthy volunteers as the control group and 40 patients were included. The patients were randomly subdivided into two equal groups: the conventional group was treated with placebo (starch), and AHM group was treated with 0.15 gm/d AHM, both for 12 consecutive weeks. The patients were investigated before and after treatment. Serum activity of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), hyaluronic acid (HA), transforming growth factor-β (TGF-β) and matrixmetalloproteinase-2 (MMP-2) were determined. The reduced glutathione (GSH) and malondialdehyde (MDA) levels in liver were assayed and the expression of hepatic α-smooth muscle actin (α-SMA) was identified by immunohistochemistry. RESULTS: At the start of the study, the hematoxylin and eosin staining revealed fibro-proliferated bile ductules, thick fibrous septa and dense inflammatory cellular infiltration in the patients before treatment. The use of AHM for 12 wk significantly ameliorated the fibrosis, inhibited the inflammation, and resulted in minimal infiltration and minimal fibrosis compared to the conventional group. The enzyme activities of the liver (ALT, AST and ALP) were attenuated after treatment in both groups, and the decrease in the AHM group was more significant as compared with the conventional group. Similar to the AST, the MDA levels were significantly higher before treatment, and were attenuated after treatment in both groups. In contrast, the hepatic glutathione content in the patients were decreased significantly in the AHM group compared to the controls. The serum levels of the fibrosis markers (HA, TGF-β and MMP-2) were also reduced

  4. Therapeutic Efficacy and Safety of Paeoniae Radix Rubra Formulae in Relieving Hyperbilirubinemia Induced by Viral Hepatitis: A Meta-Analysis

    PubMed Central

    Huang, Yin-Qiu; Ma, Xiao; Wang, Jian; Zhao, Yan-Ling; Wang, Jia-Bo; Chen, Zhe; Zhu, Yun; Shan, Li-Mei; Wei, Shi-Zhang; Wang, Ji; Xiao, Xiao-He

    2016-01-01

    Objective: Hyperbilirubinemia is one of the most devastating pathologies induced by various liver diseases. Formulae related to Paeoniae Radix Rubra (PRR) at high doses have been applied to treat hyperbilirubinemia in traditional Chinese medicine (TCM). The aim of this systematic review and meta-analysis is to assess the efficacy and safety of formulae relevant to high-dose PRR in patients suffering from hyperbilirubinemia induced by viral hepatitis. Methods: We performed a meta-analysis of randomized-controlled clinical trials to evaluate the efficacy and safety of formulae that apply a high dose of PRR for hyperbilirubinemia. Seven databases were searched until April, 2015. All studies were included according to detailed criteria and assessed for methodological quality. The outcome measurements were recorded for further analysis using the RevMan 5.2.11 software. Results: Fifteen articles involving 1323 patients with hyperbilirubinemia were included. Formulae with high-dose PRR might promote the efficacy of either a combined application ([OR: 3.98, 95% CI (2.91, 5.43)]; P < 0.01) or a single application ([OR: 4.00, 95% CI (1.50, 10.68)]; P < 0.01) for hyperbilirubinemia. The indices of TBIL, ALT, and AST significantly decreased ([MD: –75.57, 95% CI (−94.88, −56.26)], [MD: −26.54, 95% CI (−36.19, −16.88)], and ([MD: −28.94, 95% CI (−46.26, −11.61)]; P < 0.01), respectively. In addition, formulae with high-dose PRR could enhance the treatment efficacy of hyperbilirubinemia triggered by hepatitis B ([OR: 2.98, 95% CI (1.75, 5.05)]; P < 0.01). Furthermore, the efficacy was enhanced with an increasing dosage of PRR. Two articles reported that no side effects occurred in clinical trials, and three studies noted that patients presented light digestive tract symptoms. Conclusion: Formulae relevant to high-dose PRR ameliorate hyperbilirubinemia and might constitute a promising therapeutic approach. For widespread acceptance by practitioners, more

  5. Doubly Spliced RNA of Hepatitis B Virus Suppresses Viral Transcription via TATA-Binding Protein and Induces Stress Granule Assembly

    PubMed Central

    Tsai, Kuen-Nan; Chong, Chin-Liew; Chou, Yu-Chi; Huang, Chien-Chiao; Wang, Yi-Ling; Wang, Shao-Win; Chen, Mong-Liang

    2015-01-01

    ABSTRACT The risk of liver cancer in patients infected with the hepatitis B virus (HBV) and their clinical response to interferon alpha therapy vary based on the HBV genotype. The mechanisms underlying these differences in HBV pathogenesis remain unclear. In HepG2 cells transfected with a mutant HBVG2335A expression plasmid that does not transcribe the 2.2-kb doubly spliced RNA (2.2DS-RNA) expressed by wild-type HBV genotype A, the level of HBV pregenomic RNA (pgRNA) was higher than that in cells transfected with an HBV genotype A expression plasmid. By using cotransfection with HBV genotype D and 2.2DS-RNA expression plasmids, we found that a reduction of pgRNA was observed in the cells even in the presence of small amounts of the 2.2DS-RNA plasmid. Moreover, ectopic expression of 2.2DS-RNA in the HBV-producing cell line 1.3ES2 reduced the expression of pgRNA. Further analysis showed that exogenously transcribed 2.2DS-RNA inhibited a reconstituted transcription in vitro. In Huh7 cells ectopically expressing 2.2DS-RNA, RNA immunoprecipitation revealed that 2.2DS-RNA interacted with the TATA-binding protein (TBP) and that nucleotides 432 to 832 of 2.2DS-RNA were required for efficient TBP binding. Immunofluorescence experiments showed that 2.2DS-RNA colocalized with cytoplasmic TBP and the stress granule components, G3BP and poly(A)-binding protein 1 (PABP1), in Huh7 cells. In conclusion, our study reveals that 2.2DS-RNA acts as a repressor of HBV transcription through an interaction with TBP that induces stress granule formation. The expression of 2.2DS-RNA may be one of the viral factors involved in viral replication, which may underlie differences in clinical outcomes of liver disease and responses to interferon alpha therapy between patients infected with different HBV genotypes. IMPORTANCE Patients infected with certain genotypes of HBV have a lower risk of hepatocellular carcinoma and exhibit a more favorable response to antiviral therapy than patients

  6. [Treatment for viral hepatitis in institutionalized individuals].

    PubMed

    Horvat, Jadranka

    2009-12-01

    The presence and spread of viral hepatitis infection in the prison population is much higher than in the general population. Prisoners represent a combination of several high risk subpopulations and are therefore generally considered a high risk category. When outside the prison system, members of these high risk groups are generally not available for education, prevention and therapy. While within the prison system, they are available for systematic and continuing monitoring and therapy. This includes testing of their HBV, HCV and HIV status. Due to the high incidence of viral hepatitis in the prison population and based on the results of a study from 2007, we established the Prison System Viral Hepatitis Counseling Center. The Center operates within the internal ward of the Prison Hospital. Currently, 42 patients are treated for chronic hepatitis C. The Center's Plan and Operating Program and treatment results are presented. PMID:20198905

  7. Improved Survival in Patients with Viral Hepatitis-Induced Hepatocellular Carcinoma Undergoing Recommended Abdominal Ultrasound Surveillance in Ontario: A Population-Based Retrospective Cohort Study

    PubMed Central

    Thein, Hla-Hla; Campitelli, Michael A.; Yeung, Latifa T.; Zaheen, Ahmad; Yoshida, Eric M.; Earle, Craig C.

    2015-01-01

    The optimal schedule for ultrasonographic surveillance of patients with viral hepatitis for the detection of hepatocellular carcinoma (HCC) remains unclear owing to a lack of reliable studies. We examined the timing of ultrasonography in patients with viral hepatitis-induced HCC and its impact on survival and mortality risk while determining predictors of receiving surveillance before HCC diagnosis. A population-based retrospective cohort analysis of patients with viral hepatitis-induced HCC in Ontario between 2000 and 2010 was performed using data from the Ontario Cancer Registry linked health administrative data. HCC surveillance for 2 years preceding diagnosis was assigned as: i) ≥2 abdominal ultrasound screens annually; ii) 1 screen annually; iii) inconsistent screening; and iv) no screening. Survival rates were estimated using the Kaplan-Meier method and parametric models to correct for lead-time bias. Associations between HCC surveillance and the risk of mortality after diagnosis were examined using proportional-hazards regression adjusting for confounding factors. Overall, 1,483 patients with viral hepatitis-induced HCC were identified during the study period; 20.2% received ≥1 ultrasound screen annually (routine surveillance) for the 2 years preceding diagnosis. The 5-year survival of those receiving routine surveillance was 31.93% (95% CI: 25.77–38.24%) and 31.84% (95% CI: 25.69–38.14%) when corrected for lead-time bias (HCC sojourn time 70 days and 140 days, respectively). This is contrasted with 20.67% (95% CI: 16.86–24.74%) 5-year survival in those who did not undergo screening. In the fully adjusted model, compared to unscreened patients, routine surveillance was associated with a lower mortality risk and a hazard ratio of 0.76 (95% CI: 0.64–0.91) and 0.81 (95% CI: 0.68–0.97), corrected for the respective lead-time bias. Our findings suggest that routine ultrasonography in patients with viral hepatitis is associated with improved survival

  8. Hepatitis C Viral Kinetics in Special Populations

    PubMed Central

    Dahari, Harel; Layden-Almer, Jennifer E.; Perelson, Alan S.; Layden, Thomas J.

    2008-01-01

    Mathematical models of hepatitis C viral (HCV) kinetics provide a means of estimating the antiviral effectiveness of therapy, the rate of virion clearance and the rate of loss of HCV-infected cells. They have also proved useful in evaluating the extrahepatic contribution to HCV plasma viremia and they have suggested mechanisms of action for both interferon-α and ribavirin. Viral kinetic models can explain the observed HCV RNA profiles under treatment, e.g., flat partial response, biphasic and triphasic viral decay and viral rebound. Current therapy with (pegylated) interferon-α and ribavirin has a poorer success in patients having insulin resistance, hepatic fibrosis, African American ethnicity, HCV/HIV-coinfection, HCV genotype-1 and high baseline viral load. The use of mathematical modeling and statistical analysis of experimental data have been useful in understanding some of these treatment obstacles. PMID:19148305

  9. The Hepatitis C Virus-Induced Membranous Web and Associated Nuclear Transport Machinery Limit Access of Pattern Recognition Receptors to Viral Replication Sites.

    PubMed

    Neufeldt, Christopher J; Joyce, Michael A; Van Buuren, Nicholas; Levin, Aviad; Kirkegaard, Karla; Gale, Michael; Tyrrell, D Lorne J; Wozniak, Richard W

    2016-02-01

    Hepatitis C virus (HCV) is a positive-strand RNA virus of the Flaviviridae family and a major cause of liver disease worldwide. HCV replicates in the cytoplasm, and the synthesis of viral proteins induces extensive rearrangements of host cell membranes producing structures, collectively termed the membranous web (MW). The MW contains the sites of viral replication and assembly, and we have identified distinct membrane fractions derived from HCV-infected cells that contain replication and assembly complexes enriched for viral RNA and infectious virus, respectively. The complex membrane structure of the MW is thought to protect the viral genome limiting its interactions with cytoplasmic pattern recognition receptors (PRRs) and thereby preventing activation of cellular innate immune responses. Here we show that PRRs, including RIG-I and MDA5, and ribosomes are excluded from viral replication and assembly centers within the MW. Furthermore, we present evidence that components of the nuclear transport machinery regulate access of proteins to MW compartments. We show that the restricted assess of RIG-I to the MW can be overcome by the addition of a nuclear localization signal sequence, and that expression of a NLS-RIG-I construct leads to increased immune activation and the inhibition of viral replication. PMID:26863439

  10. The Hepatitis C Virus-Induced Membranous Web and Associated Nuclear Transport Machinery Limit Access of Pattern Recognition Receptors to Viral Replication Sites

    PubMed Central

    Neufeldt, Christopher J.; Joyce, Michael A.; Van Buuren, Nicholas; Levin, Aviad; Kirkegaard, Karla; Gale Jr., Michael; Tyrrell, D. Lorne J.; Wozniak, Richard W.

    2016-01-01

    Hepatitis C virus (HCV) is a positive-strand RNA virus of the Flaviviridae family and a major cause of liver disease worldwide. HCV replicates in the cytoplasm, and the synthesis of viral proteins induces extensive rearrangements of host cell membranes producing structures, collectively termed the membranous web (MW). The MW contains the sites of viral replication and assembly, and we have identified distinct membrane fractions derived from HCV-infected cells that contain replication and assembly complexes enriched for viral RNA and infectious virus, respectively. The complex membrane structure of the MW is thought to protect the viral genome limiting its interactions with cytoplasmic pattern recognition receptors (PRRs) and thereby preventing activation of cellular innate immune responses. Here we show that PRRs, including RIG-I and MDA5, and ribosomes are excluded from viral replication and assembly centers within the MW. Furthermore, we present evidence that components of the nuclear transport machinery regulate access of proteins to MW compartments. We show that the restricted assess of RIG-I to the MW can be overcome by the addition of a nuclear localization signal sequence, and that expression of a NLS-RIG-I construct leads to increased immune activation and the inhibition of viral replication. PMID:26863439

  11. Viral hepatitis in the Arctic. A review from a Circumpolar Workshop on Viral hepatitis, ICCH13.

    PubMed

    Tulisov, Andrei; McMahon, Brian J; Koch, Anders; Minuk, Gerald; Chulanov, Vladimir; Bruce, Michael G; Uhanova, Julia; Børresen, Malene; Williams, James; Osiowy, Carla; Gelvan, Allan; Alexeeva, Marfa; Larke, Bryce; Watt, Kymberly

    2007-01-01

    This article is a review of the viral hepatitis workshop, held during the 13th International Congress of the Circumpolar Health consists of a review of data on viral hepatitis in the Arctic territories of four countries: Canada, Greenland, Russia and United States (Alaska). The main purpose of the workshop was to exchange knowledge on viral hepatitis in the Arctic and identify further needs for collaborative hepatitis research, which is planned to be implemented through the established Viral Hepatitis Working Group in the Arctic. The review is based on the available published research results, surveillance data and professional opinions of the authors. The information is presented by Arctic country. Viral hepatitis constitutes an important problem among Aboriginal peoples of the Arctic; the incidence of most types of viral hepatitis is higher among indigenous populations than in the general public. However, due to differences in the available information from each of the four Arctic countries, it is difficult to compare differences in types of disease in them. The main areas for future research are: HBV genotypes distribution, relations between different types of HBV, HCV and disease outcomes, HBV mutation rate and specific substitutions in the HBV genome over time in the Arctic, and occurrence of active liver disease in HBsAg carriers living in the Arctic, as well as further research in viral hepatitis A, C, D and E. PMID:17929632

  12. Disparities in HIV/AIDS, Viral Hepatitis, STDs, and TB

    MedlinePlus

    ... Submit Search The CDC Health Disparities in HIV/AIDS, Viral Hepatitis, STDs, and TB Note: Javascript is ... Hawaiians/Other Pacific Islanders MMWR Publications HIV and AIDS Viral Hepatitis STDs Tuberculosis Training and Networking Resources ...

  13. [Clinical aspects and diagnosis of viral hepatitis].

    PubMed

    Vince, Adriana

    2003-01-01

    Viral hepatitides are common diseases of modern man in both industrialized and developing countries, with a varying prevalence of particular types and mode of transmission. In current medicine, viral hepatitides are classified in the A-E nomenclature, differentiating viruses that can be etiologically defined with certainty on the basis of serum markers and hepatitides exhibiting all clinical and laboratory characteristics of viral hepatitis but of as yet nondemonstrable causative agents, classified in the non-A, non-E hepatitis group. Two issues are of high relevance in the pathogenesis of viral hepatitides: route of transmission (fecal-oral or parenteral) and basic mechanism of hepatocyte lesion. Although all hepatitis viruses replicate within the hepatocyte, the exact mechanism of hepatocyte necrosis has not yet been fully elucidated, i.e. direct cytotoxicity or hepatoprogressive immune response mediated primarily by the specific cytotoxic CD8 lymphocytes. Depending on the site of entry, the virus replicates in the adjacent lymphatic tissue for some time, followed by primary viremia, virus replication in the lymphoreticular organs (lymph nodes, liver, spleen), and eventual entry in the target cells--hepatocytes, accompanied by a varying grade of necrosis and inflammatory reaction. The clinical and laboratory signs of the disease correspond to the degree of liver necrosis and are not specific for particular types of viral hepatitis. The most frequent symptoms common to all types of viral hepatitis of moderate severity include elevated body temperature persisting for days, fatigue, gradual loss of appetite, nausea, dull pain and discomfort on DRL, vomiting, multiple loose stools, dark urine, jaundice of the skin and mucosa, and light stools. Generally, the ultimate outcome of the disease is elimination of the virus and complete recovery, however, a fulminant course with lethal outcome or transition to chronic disease may also occur, making viral hepatitides a major

  14. The multiple aetiology of viral hepatitis

    PubMed Central

    Zuckerman, A. J.

    1971-01-01

    Infectious hepatitis is epidemiologically and immunologically distinct from serum hepatitis. The Australia antigen is related more specifically to serum hepatitis. The possible role of coronavirus—and paramyxovirus-like particles in the aetiology of some infections of the liver in man and in marmosets inoculated with human infectious hepatitis material is discussed and the difficulties in the interpretation of the currently available data are emphasized. The recent studies in Melbourne of a faecal antigen found in some patients with infectious hepatitis and the discovery of an antiserum in Milan which reacted with an antigen associated with epidemic hepatitis are discussed. Mention is made of the recent isolation in Detroit-6 cells of virus-like particles from patients with infectious hepatitis. It is concluded that viral hepatitis is an infection of multiple aetiology and that the successful cultivation in vitro of the agent or agents of hepatitis remains the outstanding and most urgent problem. ImagesFig. 1Fig. 2Fig. 3Fig. 4 PMID:4327058

  15. Drug-induced hepatitis

    MedlinePlus

    Toxic hepatitis ... to get liver damage. Some drugs can cause hepatitis with small doses, even if the liver breakdown ... liver. Many different drugs can cause drug-induced hepatitis. Painkillers and fever reducers that contain acetaminophen are ...

  16. Management issues in chronic viral hepatitis: hepatitis C.

    PubMed

    Sievert, William

    2002-04-01

    The natural history of chronic hepatitis C virus (HCV) infection and intervention with antiviral therapy are closely linked issues that cause the greatest controversy and concern for the person infected with HCV, as well as for the clinician involved in the assessment and treatment of people with chronic HCV infection. The outstanding challenge of natural history is to identify the person who is likely to develop serious liver disease, and to make that determination early in the course of chronic HCV infection when treatment is likely to be of the greatest benefit. Significant advances in the therapy of chronic HCV infection have occurred over the past decade. A sustained virological response (SVR), defined as undetectable HCV-RNA in blood 6 months after completing antiviral treatment, is the best indicator of a beneficial treatment effect. Relapse, breakthrough or non-response should all be regarded as unsuccessful outcomes of therapy. Interferons are still the mainstay of antiviral therapy for chronic HCV infection. The combination of interferon and ribavirin has improved SVR by decreasing the relapse rate. Treatment responses vary according to host factors such as age and gender, fibrotic severity and to viral factors like genotype and viral load. Patients with genotype 1 HCV and a high viral load require 12 months of treatment to achieve a SVR in approximately 30%, compared to those with genotypes 2 or 3 who achieve a SVR in approximately 65% after 6 months. Patients who relapse after an end-of-treatment response to interferon monotherapy have a good chance of responding to combination interferon and ribavirin given for 6 months, but a longer treatment course should be considered in less optimal cases. At present, the treatment of those with non-response is less clear, but there is interest in more intense forms of interferon therapy, such as induction dosing or pegylated interferon in combination with ribavirin. Clinicians need to be aware of the common side

  17. Viral hepatitis: a sexually transmitted disease?

    PubMed

    Buzby, M

    1996-03-01

    Sexually transmitted diseases (STDs) are often discussed in the context of herpes, gonorrhea, chlamydia, and AIDS. Viral hepatitis, specifically hepatitis B, is also an STD often omitted from these discussions. The incidence of hepatitis B virus (HBV) is variable throughout the world. In North America, the highest incidence occurs in patients who are between the ages of 15 and 25 years. Safe and effective vaccines are available to prevent HBV infection, which has an associated increased risk of chronic liver disease and hepatocellular carcinoma in the carrier state. Hepatitis C virus (HCV) is a newly identified hepatotrophic virus that may also be sexually transmitted. There are no vaccines for the prevention of HCV infection and the majority of those who are infected become chronic carriers with chronic liver disease. Discussions focused on the prevention of STDs must include counseling for the prevention of HBV and HCV. PMID:8788658

  18. Hepatitis C Virus Induces Epidermal Growth Factor Receptor Activation via CD81 Binding for Viral Internalization and Entry

    PubMed Central

    Diao, Jingyu; Pantua, Homer; Ngu, Hai; Komuves, Laszlo; Diehl, Lauri; Schaefer, Gabriele

    2012-01-01

    While epidermal growth factor receptor (EGFR) has been shown to be important in the entry process for multiple viruses, including hepatitis C virus (HCV), the molecular mechanisms by which EGFR facilitates HCV entry are not well understood. Using the infectious cell culture HCV model (HCVcc), we demonstrate that the binding of HCVcc particles to human hepatocyte cells induces EGFR activation that is dependent on interactions between HCV and CD81 but not claudin 1. EGFR activation can also be induced by antibody mediated cross-linking of CD81. In addition, EGFR ligands that enhance the kinetics of HCV entry induce EGFR internalization and colocalization with CD81. While EGFR kinase inhibitors inhibit HCV infection primarily by preventing EGFR endocytosis, antibodies that block EGFR ligand binding or inhibitors of EGFR downstream signaling have no effect on HCV entry. These data demonstrate that EGFR internalization is critical for HCV entry and identify a hitherto-unknown association between CD81 and EGFR. PMID:22855500

  19. Hepatoprotective and anti-hepatitis C viral activity of Platycodon grandiflorum extract on carbon tetrachloride-induced acute hepatic injury in mice.

    PubMed

    Kim, Tae-Won; Lim, Jong-Hwan; Song, In-Bae; Park, Sang-Jin; Yang, Jae-Won; Shin, Jung Cheul; Suh, Joo-Won; Son, Hwa-Young; Cho, Eun-Sang; Kim, Myoung-Seok; Lee, Sang-Wook; Kim, Jong-Woo; Yun, Hyo-In

    2012-01-01

    The present study aims to evaluate the anti-HCV activity of hotwater extract from Platycodon grandiflorum (BC703) with HCV genotype 1b subgenomic replicon system and investigate its hepatoprotective activity on carbon tetrachloride (CCl(4))-induced acute liver damage in mice. BC703 produced significant hepatoprotective effects against CCl(4)-induced acute hepatic injury by decreasing the activities of serum enzymes, nitric oxide and lipid peroxidation. Histopathological studies further substantiated the protective effect of BC703. Furthermore, BC703 inhibited the HCV RNA replication with an EC(50) value and selective index (CC(50)/EC(50)) of 2.82 µg/mL and above 35.46, respectively. However, digested BC703 using a simulated gastric juice showed poor protective effect against CCl(4)-induced hepatotoxicity in mice and decreased anti-HCV activity as compared to the intact BC703. Although further studies are necessary, BC703 may be a beneficial agent for the management of acute hepatic injury and chronic HCV infection. PMID:22878389

  20. Liver transplantation for viral hepatitis in 2015

    PubMed Central

    Ferrarese, Alberto; Zanetto, Alberto; Gambato, Martina; Bortoluzzi, Ilaria; Nadal, Elena; Germani, Giacomo; Senzolo, Marco; Burra, Patrizia; Russo, Francesco Paolo

    2016-01-01

    Liver transplantation (LT) is a life-saving treatment for patients with end-stage liver disease and for patients with liver cell cancer related to liver disease. Acute and chronic liver diseases related to hepatitis viruses are between the main indications for liver transplantation. The risk of viral reinfection after transplantation is the main limiting factor in these indications. Before the availability of antiviral prophylaxis, hepatitis B virus (HBV) recurrence was universal in patients who were HBV DNA-positive before transplantation. The natural history of recurrent HBV was accelerated by immunosuppression, and it progressed rapidly to graft failure and death. Introduction of post-transplant prophylaxis with immunoglobulin alone first, and associated to antiviral drugs later, drastically reduced HBV recurrence, resulting in excellent long-term outcomes. On the contrary, recurrence of hepatitis C is the main cause of graft loss in most transplant programs. Overall, patient and graft survival after LT for hepatitis C virus (HCV)-associated cirrhosis is inferior compared with other indications. However, successful pretransplant or post transplant antiviral therapy has been associated with increased graft and overall survival. Until recently, the combination of pegylated interferon and ribavirin was the standard of care for the treatment of patients with chronic hepatitis C. Highly active antiviral compounds have been developed over the past decade, thanks to new in vitro systems to study HCV entry, replication, assembly, and release. PMID:26819523

  1. Establishing a viral hepatitis prevention and control program: Florida's experience.

    PubMed

    Baldy, Linda M; Urbas, Cheryl; Harris, Jennie L; Jones, T Stephen; Reichert, Philip E

    2007-01-01

    In 1999, the Florida State Legislature established and funded the statewide Hepatitis Prevention Program (HPP) to address growing concern about hepatitis C virus (HCV) and its potential public health burden. HPP supports county health departments' (CHDs') provision of viral hepatitis prevention services to at-risk adults through free hepatitis A and B vaccine in most CHDs and hepatitis serologic testing and statewide viral hepatitis-related education, consultation, and referral services. Some CHDs are directly funded by HPP. In 2001-2005, HPP support helped CHDs provide 59,228 hepatitis A and 74,039 hepatitis B vaccinations statewide. In 2005, HPP supported almost 17,000 hepatitis B and C tests. From January to June 2005, 1,603 positive HCV tests were reported, a 9.5% seropositivity rate. With $24 million from the Florida State Legislature through 2006, HPP has helped CHDs statewide provide substantial viral hepatitis prevention services to at-risk adults. PMID:17542449

  2. Pregnancy outcomes associated with viral hepatitis.

    PubMed

    Reddick, K L B; Jhaveri, R; Gandhi, M; James, A H; Swamy, G K

    2011-07-01

    The aim of this study was to examine the contribution of hepatitis B virus (HBV) and hepatitis C virus (HCV) to pregnancy-related complications including gestational diabetes mellitus (GDM), preterm birth (PTB), intrauterine growth restriction (IUGR), pre-eclampsia, antepartum haemorrhage and cholestasis. The Nationwide Inpatient Sample was queried for all pregnancy-related discharges, pregnancy complications and viral hepatitis from 1995 to 2005. Logistic regression was used to examine the association between HBV, HCV, HBV + HCV and pregnancy-related complications including GDM, PTB, IUGR, pre-eclampsia, antepartum haemorrhage, cholestasis and caesarean delivery. Model covariates included maternal age, race, insurance status, substance use and medical complications including liver complication, hypertension, HIV, anaemia, thrombocytopenia and sexually transmitted infections. Of 297 664 pregnant women data available for analysis, 1446 had a coded diagnosis of HBV, HCV or both. High-risk behaviours, such as smoking, alcohol and substance use were higher in women with either HBV or HCV. Women with HBV had an increased risk for PTB (aOR 1.65, CI [1.3, 2.0]) but a decreased risk for caesarean delivery (aOR 0.686, CI [0.53, 0.88]). Individuals with HCV had an increased risk for GDM (aOR 1.6, CI [1.0, 2.6]). Individuals with both HBV and HCV co-infection had an increased risk for antepartum haemorrhage (aOR 2.82, CI [1.1, 7.2]). There was no association of viral hepatitis with IUGR or pre-eclampsia. Women with hepatitis have an increased risk for complications during pregnancy. Research to determine the efficacy and cost-effectiveness of counselling patients about potential risks for adverse outcomes is warranted. PMID:21692952

  3. Autophagic response in the Rabbit Hemorrhagic Disease, an animal model of virally-induced fulminant hepatic failure

    PubMed Central

    2014-01-01

    The Rabbit Hemorrhagic Disease Virus (RHDV) induces a severe disease that fulfils many requirements of an animal model of fulminant hepatic failure. However, a better knowledge of molecular mechanisms contributing to liver damage is required, and it is unknown whether the RHDV induces liver autophagy and how it relates to apoptosis. In this study, we attempted to explore which signalling pathways were involved in the autophagic response induced by the RHDV and to characterize their role in the context of RHDV pathogenesis. Rabbits were infected with 2 × 104 hemmaglutination units of a RHDV isolate. The autophagic response was measured as presence of autophagic vesicles, LC3 staining, conversion of LC3-I to autophagosome-associated LC3-II and changes in expression of beclin-1, UVRAG, Atg5, Atg12, Atg16L1 and p62/SQSTM1. RHDV-triggered autophagy reached a maximum at 24 hours post-infection (hpi) and declined at 30 and 36 hpi. Phosphorylation of mTOR also augmented in early periods of infection and there was an increase in the expression of the endoplasmic reticulum chaperones BiP/GRP78, CHOP and GRP94. Apoptosis, measured as caspase-3 activity and expression of PARP-1, increased significantly at 30 and 36 hpi in parallel to the maximal expression of the RHDV capsid protein VP60. These data indicate that RHDV infection initiates a rapid autophagic response, perhaps in an attempt to protect liver, which associates to ER stress development and is independent from downregulation of the major autophagy suppressor mTOR. As the infection continues and the autophagic response declines, cells begin to exhibit apoptosis. PMID:24490870

  4. Interferon Alpha Induces Sustained Changes in NK Cell Responsiveness to Hepatitis B Viral Load Suppression In Vivo

    PubMed Central

    Gill, Upkar S.; Peppa, Dimitra; Micco, Lorenzo; Singh, Harsimran D.; Carey, Ivana; Foster, Graham R.; Maini, Mala K.; Kennedy, Patrick T. F.

    2016-01-01

    NK cells are important antiviral effectors, highly enriched in the liver, with the potential to regulate immunopathogenesis in persistent viral infections. Here we examined whether changes in the NK pool are induced when patients with eAg-positive CHB are ‘primed’ with PegIFNα and importantly, whether these changes are sustained or further modulated long-term after switching to nucleos(t)ides (sequential NUC therapy), an approach currently tested in the clinic. Longitudinal sampling of a prospectively recruited cohort of patients with eAg+CHB showed that the cumulative expansion of CD56bright NK cells driven by 48-weeks of PegIFNα was maintained at higher than baseline levels throughout the subsequent 9 months of sequential NUCs. Unexpectedly, PegIFNα-expanded NK cells showed further augmentation in their expression of the activating NK cell receptors NKp30 and NKp46 during sequential NUCs. The expansion in proliferating, functional NK cells was more pronounced following sequential NUCs than in comparison cohorts of patients treated with de novo NUCs or PegIFNα only. Reduction in circulating HBsAg concentrations, a key goal in the path towards functional cure of CHB, was only achieved in those patients with enhancement of NK cell IFNγ and cytotoxicity but decrease in their expression of the death ligand TRAIL. In summary, we conclude that PegIFNα priming can expand a population of functional NK cells with an altered responsiveness to subsequent antiviral suppression by NUCs. Patients on sequential NUCs with a distinct NK cell profile show a decline in HBsAg, providing mechanistic insights for the further optimisation of treatment strategies to achieve sustained responses in CHB. PMID:27487232

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

    PubMed

    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. PMID:26675364

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

    PubMed Central

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

    2015-01-01

    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. PMID:26675364

  7. Prediction of fibrosis progression in chronic viral hepatitis.

    PubMed

    Wong, Grace Lai-Hung

    2014-09-01

    Prediction of liver fibrosis progression has a key role in the management of chronic viral hepatitis, as it will be translated into the future risk of cirrhosis and its various complications including hepatocellular carcinoma. Both hepatitis B and C viruses mainly lead to fibrogenesis induced by chronic inflammation and a continuous wound healing response. At the same time direct and indirect profibrogenic responses are also elicited by the viral infection. There are a handful of well-established risk factors for fibrosis progression including older age, male gender, alcohol use, high viral load and co-infection with other viruses. Metabolic syndrome is an evolving risk factor of fibrosis progression. The new notion of regression of advanced fibrosis or even cirrhosis is now strongly supported various clinical studies. Even liver biopsy retains its important role in the assessment of fibrosis progression, various non-invasive assessments have been adopted widely because of their non-invasiveness, which facilitates serial applications in large cohorts of subjects. Transient elastography is one of the most validated tools which has both diagnostic and prognostic role. As there is no single perfect test for liver fibrosis assessment, algorithms combining the most validated noninvasive methods should be considered as initial screening tools. PMID:25320725

  8. Perihepatic lymphadenopathy in children with chronic viral hepatitis

    PubMed Central

    Schreiber-Dietrich, Dagmar; Pohl, Margret; Cui, Xin-Wu; Braden, Barbara; Chiorean, Liliana

    2015-01-01

    Objective To assess whether lymph node enlargement in the hepatoduodenal ligament occurs in children with chronic viral hepatitis B and C in comparison to healthy controls. Subject and methods In 49 patients with chronic viral hepatitis (38 with chronic hepatitis B, 11 with chronic hepatitis C, 31 male, 18 female; age range 1 to 17 years), and in 51 healthy controls (25 male, 26 female; age range 4 to 16 years), the total perihepatic lymph node volume was assessed using transabdominal ultrasonography as previously described in adult patients. Results Adequate visualization of the liver hilum was achieved in 46/49 (94%) pediatric patients with chronic viral hepatitis and in 46/51 (90%) pediatric healthy controls. In patients with adequate liver hilum visualization, enlarged perihepatic lymph nodes (longitudinal diameter >14 mm) were detected in 32/46 (70%) patients with chronic viral hepatitis and in 5/46 (11%) healthy controls. The total perihepatic lymph nodes volume [mean ± SD] was 1.0 ± 1.2 mL (0.1–5.4 mL) in patients with chronic viral hepatitis and 0.1 ± 0.1 mL (0.0–0.4 mL) in healthy controls (p < 0.05). A maximal lymph node diameter >14 mm identified patients with chronic viral hepatitis with 70% sensitivity and 89% specificity. Conclusion Transabdominal ultrasound can detect lymph nodes within the hepatoduodenal ligament not only in adults but also in children. Paediatric patients with chronic viral hepatitis have significantly enlarged perihepatic lymph nodes compared to controls. Therefore, sonographic assessment of perihepatic lymphadenopathy might be a non-invasive diagnostic tool to screen paediatric patients for chronic viral hepatitis. PMID:26676184

  9. Drug-induced hepatitis

    MedlinePlus

    ... induced hepatitis. Painkillers and fever reducers that contain acetaminophen are a common cause of liver inflammation. These ... problem. However, if you took high doses of acetaminophen , treatment should be started as soon as possible ...

  10. Identification of alpha interferon-induced envelope mutations of hepatitis C virus in vitro associated with increased viral fitness and interferon resistance.

    PubMed

    Serre, Stéphanie B N; Krarup, Henrik B; Bukh, Jens; Gottwein, Judith M

    2013-12-01

    Alpha interferon (IFN-α) is an essential component of innate antiviral immunity and of treatment regimens for chronic hepatitis C virus (HCV) infection. Resistance to IFN might be important for HCV persistence and failure of IFN-based therapies. Evidence for HCV genetic correlates of IFN resistance is limited. Experimental studies were hampered by lack of HCV culture systems. Using genotype (strain) 1a(H77) and 3a(S52) Core-NS2 JFH1-based recombinants, we aimed at identifying viral correlates of IFN-α resistance in vitro. Long-term culture with IFN-α2b in Huh7.5 cells resulted in viral spread with acquisition of putative escape mutations in HCV structural and nonstructural proteins. Reverse genetic studies showed that primarily amino acid changes I348T in 1a(H77) E1 and F345V/V414A in 3a(S52) E1/E2 increased viral fitness. Single-cycle assays revealed that I348T and F345V/V414A enhanced viral entry and release, respectively. In assays allowing viral spread, these mutations conferred a level of IFN-α resistance exceeding the observed fitness effect. The identified mutations acted in a subtype-specific manner but were not found in genotype 1a and 3a patients, who failed IFN-α therapy. Studies with HCV recombinants with different degrees of culture adaptation confirmed the correlation between viral fitness and IFN-α resistance. In conclusion, in vitro escape experiments led to identification of HCV envelope mutations resulting in increased viral fitness and conferring IFN-α resistance. While we established a close link between viral fitness and IFN-α resistance, identified mutations acted via different mechanisms and appeared to be relatively specific to the infecting virus, possibly explaining difficulties in identifying signature mutations for IFN resistance. PMID:24049176

  11. A review of hepatitis viral infections in Pakistan.

    PubMed

    Bosan, Altaf; Qureshi, Huma; Bile, Khalif Mohamud; Ahmad, Irtaza; Hafiz, Rehan

    2010-12-01

    A review of published literature on viral hepatitis infections in Pakistan is presented. A total of 220 abstracts available in the Pakmedinet and Medline have been searched. All relevant articles were reviewed to determine the prevalence of hepatitis viral infections in Pakistan. Two hundred and three (203) relevant articles/abstracts including twenty nine supporting references are included in this review. Of the articles on prevalence of hepatitis infection, seven were related to Hepatitis A, fifteen to Hepatitis E while the remaining articles were on frequency of hepatitis B and C in different disease and healthy population groups. These included eight studies on healthy children, three on vertical transmission, nineteen on pregnant women, fifteen on healthy individuals, six on army recruits, thirty one on blood donors, thirteen on health care workers, five on unsafe injections, seventeen on high risk groups, five on patients with provisional diagnosis of hepatitis, thirty three on patients with chronic liver disease, four on genotypes of HBV and five on genotypes of HCV. This review highlights the lack of community-based epidemiological work as the number of subjects studied were predominantly patients, high risk groups and healthy blood donors. High level of Hepatitis A seroconversion was found in children and this viral infection accounts for almost 50%-60% of all cases of acute viral hepatitis in children in Pakistan. Hepatitis E is endemic in the country affecting mostly the adult population and epidemic situations have been reported from many parts of the country. The mean results of HBsAg and Anti-HCV prevalence on the basis of data aggregated from several studies was calculated which shows 2.3% and 2.5% prevalence of HBsAg and Anti-HCV in children, 2.5% and 5.2% among pregnant women, 2.6% and 5.3% in general population, 3.5% and 3.1% in army recruits, 2.4% and 3.6% in blood donors, 6.0% and 5.4% in health care workers, 13.0% and 10.3% in high risk groups

  12. [Novel treatments for hepatitis C viral infection and the hepatic fibrosis].

    PubMed

    Lugo-Baruqui, Alejandro; Bautista López, Carlos Alfredo; Armendáriz-Borunda, Juan

    2009-02-01

    Hepatitis C virus (HCV) infection represents a global health problem due to its evolution to hepatic cirrhosis and hepatocellular carcinoma. The viral pathogenesis and infectious processes are not yet fully understood. The development of natural viral resistance towards the host immune system represents a mayor challenge for the design of alternative therapeutic interventions and development of viral vaccines. The molecular mechanisms of hepatic fibrosis are well described. New alternatives for the treatment of patients with HCV infection and hepatic cirrhosis are under intensive research. New drugs such as viral protease inhibitors and assembly inhibitors, as well as immune modulators have been studied in clinical trials. Additional alternatives include antifibrotic drugs, which reverse the hepatic cellular damage caused by HCV infection. This review makes reference to viral infective mechanisms, molecular pathways of liver fibrosis and overviews conventional and new treatments for HCV infection and liver fibrosis. PMID:19543653

  13. [Autoimmune hepatitis induced by isotretionine].

    PubMed

    Guzman Rojas, Patricia; Gallegos Lopez, Roxana; Ciliotta Chehade, Alessandra; Scavino, Yolanda; Morales, Alejandro; Tagle, Martín

    2016-01-01

    We describe a case of a teenage patient with the diagnosis of drug induced autoimmune hepatitis. The patient is a 16 years old female, with the past medical history of Hashimoto’s hypothyroidism controlled with levothyroxine, who started treatment with Isotretionin (®Accutane) 20 mg q/12 hours for a total of 3 months for the treatment of severe acne. The physical examination was within normal limits and the results of the laboratory exams are: Baseline values of ALT 28 U/L, AST 28 U/L. Three months later: AST 756 U/L, ALT 1199U/L, alkaline phosphatase 114 U/L, with normal bilirrubin levels throughout the process. The serology studies were negative for all viral hepatitis; ANA titers were positive (1/160) and igG levels were also elevated. A liver biopsy was performed, and was compatible with the diagnosis of autoimmune hepatitis. Corticosteroid therapy was started with Prednisone 40 mg per day one week after stopping the treatment with isotretionin, observing an improvement in the laboratory values. We describe this case and review the world literature since there are no reported cases of Isotretinoin-induced autoimmune hepatitis. PMID:27131947

  14. Human Interferon Regulatory Factor 2 Gene Expression is Induced in Chronic Hepatitis C Virus Infection—A Possible Mode of Viral Persistence

    PubMed Central

    Mukherjee, Rathindra M; Bansode, Budhapriyavilas; Gangwal, Puja; Jakkampudi, Aparna; Reddy, Panyala B; Rao, Padaki N; Gupta, Rajesh; Reddy, D Nageshwar

    2012-01-01

    Background The interferon regulatory factors (IRFs) are a family of transcription factors known to be involved in the modulation of cellular responses to interferons (IFNs) and viral infection. While IRF-1 acts as a positive regulator, IRF-2 is known to repress IFN-mediated gene expression. The increase in the IRF-1/IRF-2 ratio is considered as an important event in the transcriptional activation of IFN-α gene toward development of the cellular antiviral response. Objective This study was performed to assess the expression of IRF mRNAs along with the expression level of IFN-α, its receptor (IFNAR-1), and the signal transduction factor (STAT-1) in treatment naive hepatitis C virus (HCV)-infected subjects. Materials Thirty-five chronically infected (CHC) patients and 39 voluntary blood donors as controls were included in the study. Quantification of HCV-RNA (ribonucleic acid) and genotyping were done by real-time polymerase chain reaction (PCR) and hybridization assays, respectively, using patient's serum/plasma. In both controls and patients, the serum level of IFN-α and IFN-α was measured by flow cytometry. Target gene expressions were studied by retro-transcription of respective mRNAs extracted from peripheral blood mononuclear cells (PBMCs) followed by PCR amplification and densitometry. Minus-strand HCV-RNA as a marker of viral replication in PBMCs was detected by an inhouse PCR assay. Results Both IRF-1 and IRF-2 genes were significantly enhanced in CHC than in control subjects (P < 0.001). A significant positive correlation (r2 = 0.386, P <0.01) was obtained between higher IRF-2 gene expression and increasing level of HCV-RNA. Chronically infected subjects (13%) harboring replicating HCV in PBMCs showed no significant differences in gene expressions than the subjects without HCV in PBMCs. Conclusion Our findings indicate that HCV modulates host immunity by inducing IRF-2 gene to counteract IRF-1-mediated IFN-α gene expression. Since the IRF-2 gene is

  15. Surveillance for Viral Hepatitis - United States, 2012

    MedlinePlus

    ... available; numbers likely are underestimates. Table 2.3 Number and rate* of deaths with hepatitis A listed ... available; numbers likely are underestimates. Table 3.3 Number of laboratory-confirmed, chronic hepatitis B* case reports†...

  16. Viral Hepatitis: A through E and Beyond

    MedlinePlus

    ... A be prevented? The hepatitis A vaccine offers immunity to adults and children older than age 1. ... Treatment with immune globulin can provide short-term immunity to hepatitis A when given before exposure or ...

  17. Viral hepatitis and hepatitis B antigen: recent advances

    PubMed Central

    Krugman, Saul

    1974-01-01

    Recent advances in hepatitis research have shed new light on the etiology, pathogenesis, epidemiology and prevention of type B hepatitis infection. The so-called ‘Dane’ particle is probably the complete hepatitis B virion; its outer coat is the hepatitis B (Australia) antigen (HB Ag) and its inner core is an immunologically distinct particle. Subtypes of HB Ag (a, d, y, w and r) are useful indices for epidemiological surveys. Concepts of epidemiology have changed: type B hepatitis is transmissible by contact as well as by inoculation. The presence of HB Ag in blood is indicative of the presence of hepatitis B virus. Tests to detect antigen and use of voluntary blood donors have played a major role in the decreased incidence of post transfusion hepatitis. A special hepatitis B gammaglobulin preparation and a heat-inactivated hepatitis B vaccine have proved to be effective in preliminary studies. PMID:4219230

  18. Classical and Modern Approaches Used for Viral Hepatitis Diagnosis

    PubMed Central

    Heiat, Mohammad; Ranjbar, Reza; Alavian, Seyed Moayed

    2014-01-01

    Context: Viral hepatitis diagnosis is an important issue in the treatment procedure of this infection. Late diagnosis and delayed treatment of viral hepatitis infections can lead to irreversible liver damages and occurrence of liver cirrhosis and hepatocellular carcinoma. A variety of laboratory methods including old and new technologies are being applied to detect hepatitis viruses. Here we have tried to review, categorize, compare and illustrate the classical and modern approaches used for diagnosis of viral hepatitis. Evidence Acquisition: In order to achieve a comprehensive aspect in viral hepatitis detection methods, an extensive search using related keywords was done in major medical library and data were collected, categorized and summarized in different sections. Results: Analyzing of collected data resulted in the wrapping up the hepatitis virus detection methods in separate sections including 1) immunological methods such as enzyme immunoassay (EIA), radio-immunoassay (RIA) immuno-chromatographic assay (ICA), and immuno-chemiluminescence 2) molecular approaches including non-amplification and amplification based methods, and finally 3) advanced biosensors such as mass-sensitive, electrical, electrochemical and optical based biosensors and also new generation of detection methods. Conclusions: Detection procedures in the clinical laboratories possess a large diversity; each has their individual advantages and facilities' differences. PMID:24829586

  19. Viral Hepatitis and Diabetes: Clinical Implications of Diabetes Prevention Through Hepatitis Vaccination.

    PubMed

    Karnchanasorn, Rudruidee; Ou, Horng-Yih; Lin, James; Chuang, Lee-Ming; Chiu, Ken C

    2016-10-01

    Viral hepatitis has been posited to play a role in the development of type 2 diabetes. Thus, prevention of viral hepatitis through vaccination has the potential to reduce the burden of type 2 diabetes. We have shown that successful hepatitis B vaccination reduces the risk of diabetes by 33 %. Although diabetes can be prevented by behavior modification and pharmaceutical agents, these require significant personal commitment and cost. In contrast, diabetes prevention through hepatitis B vaccination would require little personal commitment and relatively low cost. In this review, we discuss hepatitis viruses A, B, and C and their interaction with diabetes; explore the potential underlying mechanisms and potential for hepatitis vaccination to reduce diabetes; and estimate the medical expense savings that would result from such an intervention. Given the projected increase of diabetes prevalence in the developing regions, where hepatitis B is endemic, exploration of such an intervention is very timely. PMID:27620495

  20. The discovery of viral hepatitis: a military perspective.

    PubMed

    Martin, N A

    2003-06-01

    Viral hepatitis is one of the most common infectious diseases and over the years the jaundice associated with it has been known by many names. Several viruses are now known to cause hepatitis in humans, but sixty years ago, these viruses were unknown. In the years before and during the Second World War, there emerged a significant understanding of the clinical and epidemiological nature of the disease due to the dedicated efforts of doctors and scientists around the world. By the end of the war years, the discrete entities of Hepatitis A and B had been identified and preventative measures were proving to be effective. However, the bane of viral hepatitis was far from being resolved. PMID:12929519

  1. Viral hepatitis in Hawai'i--differing perspectives.

    PubMed

    Tice, Alan D; Bannan, Michael; Bauman, Kay; Collis, Tarquin; Hall, Alba; Haning, William; Hannemann, Shoshana; Hare, C Bradley; Humphry, Joseph; Jao, Robert; Leevy, Carroll; Lusk, Heather; Ochoa, Edward; Palafox, Neal; Withers, Nancy; Akinaka, Kenneth

    2010-04-01

    This publication contains information from a conference titled "Individual Perspectives on the Silent Epidemic of Viral Hepatitis in Hawai'i" held in October of 2007 with updates and additional contributions from annual conferences in 2008 and 2009. These conferences were sponsored by the Hepatitis Support Network of Hawai'i and held in Honolulu, Hawai'i at the Queen's Conference Center. The primary objectives of the conferences have been to heighten awareness of viral hepatitis in Hawai'i and to bring together health care professionals to learn about these infections and to help them respond to the challenges they bring to the people of Hawai'i. The initial conference was oriented to present the unique and individual perspectives of patients, physicians, and other healthcare providers specific to the complex issues of hepatitis in an effort to help them understand their role in the context of others and to develop a team approach in responding to this epidemic. PMID:20533191

  2. [Host factors and viral factors in hepatitis C treatment].

    PubMed

    Sakamoto, Minoru; Enomoto, Nobuyuki

    2015-02-01

    In the interferon-based therapy for hepatitis C, host factors such as age, gender, liver fibrosis and steatosis are important as a therapeutic effect predictor, and viral factors such as HCV genotype, HCV viral load, HCV gene (IL28B, ITPA) are also important. In addition in genotype 1b, ISDR/IRRDR and core amino acid substitution are important. Also in the DAA treatment, viral factors are also important at the view of therapeutic effect and difficulty of acquisition of drug resistance mutation. In addition, the goal of treatment of hepatitis C are suppression of liver fibrosis progression and liver cancer and improvement of quality of life due to this (quality of life: QOL) and life prognosis, it is important to understand the host factors and HCV viral factors. PMID:25764672

  3. Adsorption of viral particles from the blood plasma of patients with viral hepatitis on nanodiamonds.

    PubMed

    Baron, A V; Osipov, N V; Yashchenko, S V; Kokotukha, Yu A; Baron, I J; Puzyr, A P; Olkhovskiy, I A; Bondar, V S

    2016-07-01

    Adsorption of viral particles from the blood plasma of patients with viral hepatitis B and C on modified nanodiamonds (MNDs) was shown in the in vitro experiments. PCR method showed the treatment of plasma with MNDs leads to a decrease in the viral load by 2-3 orders of magnitude or more in both cases studied. These results make it possible to predict the applicability of MNDs for the development of new technologies of hemodialysis and plasmapheresis for binding and removal of viral particles from the blood of infected patients. PMID:27599503

  4. Evolution of the Viral Hepatitis Prevention Board--VHPB.

    PubMed

    McCloy, E; Meheus, A

    1998-11-01

    The Viral Hepatitis Prevention Board (VHPB) was formed in 1992 to provide authoritative information and advice on hepatitis B as an occupational hazard and to act as a scientific lobby group to promote hepatitis B vaccination as part of an overall risk reduction strategy. The VHPB published Viral Hepatitis, a newsletter whose format and content was designed to appeal to both professional and lay readers seeking information on hepatitis. The VHPB was successful in lobbying the European Parliament to add the Code of Practice on Vaccination to legislation protecting workers from occupationally acquired infections. The first initiative on occupational hepatitis B culminated in an international congress in March 1993 and the publication of 'Hepatitis B as an Occupational Hazard' in the WHO occupational health series. Since 1993 the Board has discussed HBV as a community acquired infection; control of hepatitis A (HAV) and eligibility for hepatitis A vaccine and combined hepatitis A and B vaccines; hepatitis C; and reviewed progress towards the control of HBV and the adoption of universal vaccination programmes in countries of low endemicity. A major international congress in Cannes in November 1993 took stock of actions taken to control hepatitis B as a community health risk in industrialised countries. The constitution and membership of the Board underwent significant change at the end of 1994. A Secretarial was located within the Centre for the Evaluation of Vaccination at the University of Antwerp to deal with all administrative matters and publications in peer reviewed journals. The format of Viral Hepatitis was re-focused to increase the scientific content. The Board extended its actions geographically in 1996 to include the countries of Central and Eastern Europe (CEE) and the Newly Independent States (NIS) of the former Soviet Union. The success of the VHPB has exceeded all the expectations of the founding members. The major focus of the annual programme of

  5. Dynamics of viral hepatitis B epidemiological process in Plovdiv region.

    PubMed

    Kevorkyan-Sariyan, Ani K

    2013-01-01

    Registration of viral hepatitis cases by type started in 1982 in Bulgaria, and in August 1991 Bulgaria launched a mass immunisation programme to vaccinate infants against hepatitis B. The objective of this dissertation thesis is to study the epidemiological status of hepatitis B virus (HBV) infection in Plovdiv region (the second largest administrative region in Bulgaria with a population of 683,027 people in 2011), and assess the epidemiological process dynamics as a result of the administration of a recombinant vaccine that has been used over the past two decades. PMID:24191410

  6. Hepatitis of viral origin in Leporidae: introduction and aetiological hypotheses.

    PubMed

    Morisse, J P; Le Gall, G; Boilletot, E

    1991-06-01

    In less than ten years, two very serious viral hepatic diseases have spread through Leporidae populations (rabbits and hares) in numerous countries. In May 1989, the Office International des Epizooties designated this new disease of rabbits "viral haemorrhagic disease" and entered it as a List B disease in the International Animal Health Code. Clinically, the disease is very similar to the European brown hare syndrome. However, numerous uncertainties prevail today on the true nature of the viruses of the two species. Although they are related, the viruses appear to be different and cross infection between species has given contradictory results. Hepatitis of Leporidae have probably existed in Europe for several years, although their viral aetiology has been demonstrated only recently. The acute form has occurred in hares in Northern Europe since approximately 1980, while the inapparent (or ignored) form has been present in rabbits in Czechoslovakia since 1975. These diseases of Leporidae are true viral hepatitis which, in their fulminating forms, bear a remarkable resemblance to human viral hepatitis (B and non-A non-B) with regard to clinical symptoms, pathological lesions and mode of transmission. The dominant faecal-oral transmission observed for types A and E hepatitis would explain the particular susceptibility of family-kept rabbits, as they are fed potentially contaminated fodder. As the clinically similar fulminating hepatitis in human beings is caused by a diversity of viruses (both RNA and DNA), the disease in Leporidae might also be caused by different viruses.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1760579

  7. Hepatitis E virus is the leading cause of acute viral hepatitis in Lothian, Scotland.

    PubMed

    Kokki, I; Smith, D; Simmonds, P; Ramalingam, S; Wellington, L; Willocks, L; Johannessen, I; Harvala, H

    2016-03-01

    Acute viral hepatitis affects all ages worldwide. Hepatitis E virus (HEV) is increasingly recognized as a major cause of acute hepatitis in Europe. Because knowledge of its characteristics is limited, we conducted a retrospective study to outline demographic and clinical features of acute HEV in comparison to hepatitis A, B and C in Lothian over 28 months (January 2012 to April 2014). A total of 3204 blood samples from patients with suspected acute hepatitis were screened for hepatitis A, B and C virus; 913 of these samples were also screened for HEV. Demographic and clinical information on patients with positive samples was gathered from electronic patient records. Confirmed HEV samples were genotyped. Of 82 patients with confirmed viral hepatitis, 48 (59%) had acute HEV. These patients were older than those infected by hepatitis A, B or C viruses, were more often male and typically presented with jaundice, nausea, vomiting and/or malaise. Most HEV cases (70%) had eaten pork or game meat in the few months before infection, and 14 HEV patients (29%) had a recent history of foreign travel. The majority of samples were HEV genotype 3 (27/30, 90%); three were genotype 1. Acute HEV infection is currently the predominant cause of acute viral hepatitis in Lothian and presents clinically in older men. Most of these infections are autochthonous, and further studies confirming the sources of infection (i.e. food or blood transfusion) are required. PMID:26904201

  8. Hepatitis E virus is the leading cause of acute viral hepatitis in Lothian, Scotland

    PubMed Central

    Kokki, I.; Smith, D.; Simmonds, P.; Ramalingam, S.; Wellington, L.; Willocks, L.; Johannessen, I.; Harvala, H.

    2015-01-01

    Acute viral hepatitis affects all ages worldwide. Hepatitis E virus (HEV) is increasingly recognized as a major cause of acute hepatitis in Europe. Because knowledge of its characteristics is limited, we conducted a retrospective study to outline demographic and clinical features of acute HEV in comparison to hepatitis A, B and C in Lothian over 28 months (January 2012 to April 2014). A total of 3204 blood samples from patients with suspected acute hepatitis were screened for hepatitis A, B and C virus; 913 of these samples were also screened for HEV. Demographic and clinical information on patients with positive samples was gathered from electronic patient records. Confirmed HEV samples were genotyped. Of 82 patients with confirmed viral hepatitis, 48 (59%) had acute HEV. These patients were older than those infected by hepatitis A, B or C viruses, were more often male and typically presented with jaundice, nausea, vomiting and/or malaise. Most HEV cases (70%) had eaten pork or game meat in the few months before infection, and 14 HEV patients (29%) had a recent history of foreign travel. The majority of samples were HEV genotype 3 (27/30, 90%); three were genotype 1. Acute HEV infection is currently the predominant cause of acute viral hepatitis in Lothian and presents clinically in older men. Most of these infections are autochthonous, and further studies confirming the sources of infection (i.e. food or blood transfusion) are required. PMID:26904201

  9. Hepatic transcriptome analysis of hepatitis C virus infection in chimpanzees defines unique gene expression patterns associated with viral clearance.

    PubMed

    Nanda, Santosh; Havert, Michael B; Calderón, Gloria M; Thomson, Michael; Jacobson, Christian; Kastner, Daniel; Liang, T Jake

    2008-01-01

    Hepatitis C virus infection leads to a high rate of chronicity. Mechanisms of viral clearance and persistence are still poorly understood. In this study, hepatic gene expression analysis was performed to identify any molecular signature associated with the outcome of hepatitis C virus (HCV) infection in chimpanzees. Acutely HCV-infected chimpanzees with self-limited infection or progression to chronicity were studied. Interferon stimulated genes were induced irrespective of the outcome of infection. Early induction of a set of genes associated with cell proliferation and immune activation was associated with subsequent viral clearance. Specifically, two of the genes: interleukin binding factor 3 (ILF3) and cytotoxic granule-associated RNA binding protein (TIA1), associated with robust T-cell response, were highly induced early in chimpanzees with self-limited infection. Up-regulation of genes associated with CD8+ T cell response was evident only during the clearance phase of the acute self-limited infection. The induction of these genes may represent an initial response of cellular injury and proliferation that successfully translates to a "danger signal" leading to induction of adaptive immunity to control viral infection. This primary difference in hepatic gene expression between self-limited and chronic infections supports the concept that successful activation of HCV-specific T-cell response is critical in clearance of acute HCV infection. PMID:18927617

  10. [Amniocentesis and viral risk (hepatitis B, C virus and HIV)].

    PubMed

    Ducarme, G; Ceccaldi, P-F; Bernuau, J; Luton, D

    2009-10-01

    Very few studies have properly addressed to the risk of fetal hepatitis B (HBV), hepatitis C (HCV) or human immunodeficiency virus (HIV) infection through amniocentesis. For HBV, this risk is low. However, knowledge of the maternal hepatitis B e antigen status is valuable in the counselling of risks associated with amniocentesis. For HCV, the risk is not well known but cannot be excluded. For HIV, it seems rational to propose a viral test before amniocentesis for patients with contamination's risk and to postpone the sampling in cases with positive results in order to obtain an undetectable HIV-1 RNA viral load. For these reasons, it can be useful to analyse for each virus the benefit of amniocentesis and the risk of mother-to-infant transmission, and to inform the patient. PMID:19679409

  11. [Antibacterial therapy of cholecystocholangitis in viral hepatitis].

    PubMed

    Andreĭchin, M A; Kiĭko, L G; Il'ina, N I

    1984-04-01

    The chemotherapy of cholecystocholangitis in patients with virus hepatitis was estimated. Antibiotics, furagin and pathogenetic drugs were used for the treatment. The antibiotics were chosen with regard to their sensitivity to the bile microflora. This resulted in sanation of the bile ducts. Furagin was less effective. The use of the pathogenetic drugs alone was ineffective in the majority of patients. PMID:6378081

  12. Herpes viral hepatitis in a toucan.

    PubMed

    Charlton, B R; Barr, B C; Castro, A E; Davis, P L; Reynolds, B J

    1990-01-01

    Herpesvirus infection was diagnosed in a toucan. The herpesvirus was isolated from the liver and identified by electron microscopy in the liver and in cell culture. A negative immunofluorescent reaction was obtained when virus-infected cell cultures were reacted with a conjugate to the herpesvirus of Pacheco's disease. The main pathologic finding in the toucan consisted of a severe necrotizing hepatitis with intranuclear inclusions in the liver and spleen. A presumptive diagnosis of chlamydiosis was also made, based on a positive direct fluorescent monoclonal antibody reaction to chlamydial antigens in impression smears of liver and spleen. Chlamydial isolation attempts were unsuccessful. The toucan had been in contact with two macaws that had died 5 days before the toucan died and were diagnosed by histology as having herpesvirus hepatitis. PMID:2173540

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

    PubMed Central

    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

  14. Bermuda Triangle for the liver: alcohol, obesity, and viral hepatitis.

    PubMed

    Zakhari, Samir

    2013-08-01

    Despite major progress in understanding and managing liver disease in the past 30 years, it is now among the top 10 most common causes of death globally. Several risk factors, such as genetics, diabetes, obesity, excessive alcohol consumption, viral infection, gender, immune dysfunction, and medications, acting individually or in concert, are known to precipitate liver damage. Viral hepatitis, excessive alcohol consumption, and obesity are the major factors causing liver injury. Estimated numbers of hepatitis B virus (HBV) and hepatitis C virus (HCV)-infected subjects worldwide are staggering (370 and 175 million, respectively), and of the 40 million known human immunodeficiency virus positive subjects, 4 and 5 million are coinfected with HBV and HCV, respectively. Alcohol and HCV are the leading causes of end-stage liver disease worldwide and the most common indication for liver transplantation in the United States and Europe. In addition, the global obesity epidemic that affects up to 40 million Americans, and 396 million worldwide, is accompanied by an alarming incidence of end-stage liver disease, a condition exacerbated by alcohol. This article focuses on the interactions between alcohol, viral hepatitis, and obesity (euphemistically described here as the Bermuda Triangle of liver disease), and discusses common mechanisms and synergy. PMID:23855291

  15. Nucleic Acid-Based Approaches for Detection of Viral Hepatitis

    PubMed Central

    Behzadi, Payam; Ranjbar, Reza; Alavian, Seyed Moayed

    2014-01-01

    Context: To determining suitable nucleic acid diagnostics for individual viral hepatitis agent, an extensive search using related keywords was done in major medical library and data were collected, categorized, and summarized in different sections. Results: Various types of molecular biology tools can be used to detect and quantify viral genomic elements and analyze the sequences. These molecular assays are proper technologies for rapidly detecting viral agents with high accuracy, high sensitivity, and high specificity. Nonetheless, the application of each diagnostic method is completely dependent on viral agent. Conclusions: Despite rapidity, automation, accuracy, cost-effectiveness, high sensitivity, and high specificity of molecular techniques, each type of molecular technology has its own advantages and disadvantages. PMID:25789132

  16. Current issues in the management of paediatric viral hepatitis.

    PubMed

    Yeung, Latifa T F; Roberts, Eve A

    2010-01-01

    Viral hepatitis poses important problems for children. In preschoolers, hepatitis A virus (HAV) infection frequently causes acute liver failure. Vaccinating toddlers against HAV in countries with high endemicity is expected to decrease mortality. HAV vaccine demonstrates efficacy (comparable to immunoglobulin) as post-exposure prophylaxis. A recently developed vaccine against hepatitis E virus (HEV) may benefit fetal health, because pregnant women are most prone to acute liver failure as a result of HEV. Hepatitis B vaccine continues to demonstrate value and versatility for preventing serious liver disease. With chronic infection, undetectable levels of serum HBV DNA complement e-seroconversion as the preferred outcome measure; suppressed viral load correlates with long-term complications better than HBeAg status. Among Taiwanese children, low pretreatment HBV DNA (<2 x 10(8) copies/ml) strongly predicted response to interferon-alpha. Future paediatric studies must incorporate HBV DNA levels. The rationale for routine treatment of immunotolerant hepatitis B during childhood remains uncertain. Any treatment of chronic hepatitis B in childhood requires consideration of the risks and benefits. Childhood hepatitis C virus (HCV) infection results mainly from mother-to-infant transmission. Babies of HCV-infected women should be tested for serum HCV RNA at 1 month of age. If negative, confirmatory anti-HCV antibody testing may be performed between 12 and 15 months of age. Children with chronic hepatitis C may develop progressive fibrosis/cirrhosis, particularly in the setting of obesity and insulin resistance. Treatment of children chronically infected with genotype 2 or 3 is highly successful: combination therapy of pegylated interferon-alpha and ribavirin is well tolerated and superior to pegylated interferon-alpha alone. PMID:19840256

  17. Viral Load Analysis of Hepatitis C Virus in Huh7.5 Cell Culture System

    PubMed Central

    Teimourpour, Roghayeh; Meshkat, Zahra; Gholoubi, Aida; Nomani, Hosein; Rostami, Sina

    2015-01-01

    Background: Previous studies using cell culture systems for the replication of hepatitis C virus have opened new research dimensions, and paved the ways for further and detailed studies of the virus in vitro. Objectives: The purpose of the present study was to cultivate hepatitis C virus in a cell culture system and evaluate viral amplification. Materials and Methods: In order to propagate hepatitis C virus, cloned whole genome of virus, JFH-1, was used. JFH-1 cDNA was introduced into strain JM109 of Escherichia coli and plasmid, containing the viral genome was purified from transformed bacteria. After XbaI digestion, RNA synthesis was induced using T7 RNA polymerase enzyme. Next, eukaryotic cell line Huh 7.5 was transfected by the purified RNA. Finally, Huh-7.5 cell line was infected with replicated virus and viral load was determined using real-time PCR (Polymerase Chain Reaction). Results: The amount of viral load, which was measured using real-time PCR was 17592 IU/mL. Conclusions: In the present study, using cell culture, a high titer (in acceptable range) of infectious hepatitis C virus was produced. This method could be used in future studies. PMID:26290686

  18. TYPE A VIRAL HEPATITIS: EFFECT OF CHLORINE ON INFECTIVITY

    EPA Science Inventory

    The objective of this study was to determine the effect of (HOCl) treatment on the infectivity of hepatitis A virus (HAV). Prodromal chimpanzee feces, shown to induce hepatitis in marmosets (Saginus sp.), was clarified (JA 20/8K/30 min/5C), the virus precipitated with 7% PEG 6000...

  19. Hepatitis B antigen and viral hepatitis type B in India*

    PubMed Central

    John, T. Jacob; Carman, Robert H.; Hill, Peter G.

    1974-01-01

    Surveys were conducted to determine the occurrence of overt hepatitis manifested by jaundice in groups of hospital patients who had survived their initial illness. Of those who had been given blood that had not been screened for the presence of hepatitis B antigen (HB Ag) 9.4% reported that they had had jaundice during the 6 months following transfusion. During a similar period jaundice was reported by only 1.1% of those who had received blood found to be negative for HB Ag by the cross-over electrophoresis test. This difference is highly significant. Jaundice was reported by 25.5% of recipients of HB Ag-positive blood. Of a control population of hospitalized but non-transfused patients 2.2% reported jaundice within 6 months of hospitalization. The risk of overt hepatitis from HB Ag in transfused blood is high in southern India and is similar to that in temperate countries where the occurrence of antigen carriers, and presumably of immune status, are lower than in the tropics. PMID:4549611

  20. Direct Acting Antivirals for the Treatment of Chronic Viral Hepatitis

    PubMed Central

    Karayiannis, Peter

    2012-01-01

    The development and evaluation of antiviral agents through carefully designed clinical trials over the last 25 years have heralded a new dawn in the treatment of patients chronically infected with the hepatitis B and C viruses, but not so for the D virus (HBV, HCV, and HDV). The introduction of direct acting antivirals (DDAs) for the treatment of HBV carriers has permitted the long-term use of these compounds for the continuous suppression of viral replication, whilst in the case of HCV in combination with the standard of care [SOC, pegylated interferon (PegIFN), and ribavirin] sustained virological responses (SVRs) have been achieved with increasing frequency. Progress in the case of HDV has been slow and lacking in significant breakthroughs.This paper aims to summarise the current state of play in treatment approaches for chonic viral hepatitis patients and future perspectives. PMID:24278700

  1. Bridging basic science and clinical research: the EASL Monothematic Conference on Translational Research in Viral Hepatitis.

    PubMed

    Boettler, Tobias; Moradpour, Darius; Thimme, Robert; Zoulim, Fabien

    2014-09-01

    The EASL Monothematic Conference on Translational Research in Viral Hepatitis brought together a group of leading scientists and clinicians working on both, basic and clinical aspects of viral hepatitis, thereby building bridges from bench to bedside. This report recapitulates the presentations and discussions at the conference held in Lyon, France on November 29-30, 2013. In recent years, great advances have been made in the field of viral hepatitis, particularly in hepatitis C virus (HCV) infection. The identification of IL28B genetic polymorphisms as a major determinant for spontaneous and treatment-induced HCV clearance was a seminal discovery. Currently, hepatologists are at the doorstep of even greater advances, with the advent of a wealth of directly acting antivirals (DAAs) against HCV. Indeed, promising results have accumulated over the last months and few years, showing sustained virological response (SVR) rates of up to 100% with interferon-free DAA combination therapies. Thus, less than 25 years after its identification, HCV infection may soon be curable in the vast majority of patients, highlighting the great success of HCV research over the last decades. However, viral hepatitis and its clinical complications such as liver cirrhosis and hepatocellular carcinoma (HCC) remain major global challenges. New therapeutic strategies to tackle hepatitis B virus (HBV) and hepatitis D virus (HDV) infection are needed, as current therapies have undeniable limitations. Nucleoside/nucleotide analogues (NUC) can efficiently control HBV replication and reduce or even reverse liver damage. However, these drugs have to be given for indefinite periods in most patients to maintain virological and biochemical responses. Although sustained responses off treatment can be achieved by treatment with (pegylated) interferon-α, only about 10-30% of patients effectively resolve chronic hepatitis B. It was the goal of this conference to review the progress made over the last

  2. Mechanisms of Hepatitis C Viral Resistance to Direct Acting Antivirals

    PubMed Central

    Ahmed, Asma; Felmlee, Daniel J.

    2015-01-01

    There has been a remarkable transformation in the treatment of chronic hepatitis C in recent years with the development of direct acting antiviral agents targeting virus encoded proteins important for viral replication including NS3/4A, NS5A and NS5B. These agents have shown high sustained viral response (SVR) rates of more than 90% in phase 2 and phase 3 clinical trials; however, this is slightly lower in real-life cohorts. Hepatitis C virus resistant variants are seen in most patients who do not achieve SVR due to selection and outgrowth of resistant hepatitis C virus variants within a given host. These resistance associated mutations depend on the class of direct-acting antiviral drugs used and also vary between hepatitis C virus genotypes and subtypes. The understanding of these mutations has a clear clinical implication in terms of choice and combination of drugs used. In this review, we describe mechanism of action of currently available drugs and summarize clinically relevant resistance data. PMID:26694454

  3. Viral Hepatitis in Hawai‘i - Differing Perspectives

    PubMed Central

    Bannan, Michael; Bauman, Kay; Collis, Tarquin; Hall, Alba; Haning, William; Hannemann, Shoshana; Hare, C Bradley; Humphry, Joseph; Jao, Robert; Leevy, Carroll; Lusk, Heather; Ochoa, Edward; Palafox, Neal; Withers, Nancy; Akinaka, Kenneth

    2010-01-01

    This publication contains information from a conference titled “Individual Perspectives on the Silent Epidemic of Viral Hepatitis in Hawai‘i” held in October of 2007 with updates and additional contributions from annual conferences in 2008 and 2009. These conferences were sponsored by the Hepatitis Support Network of Hawai‘i and held in Honolulu, Hawai‘i at the Queen's Conference Center. The primary objectives of the conferences have been to heighten awareness of viral hepatitis in Hawai‘i and to bring together health care professionals to learn about these infections and to help them respond to the challenges they bring to the people of Hawai‘i. The initial conference was oriented to present the unique and individual perspectives of patients, physicians, and other healthcare providers specific to the complex issues of hepatitis in an effort to help them understand their role in the context of others and to develop a team approach in responding to this epidemic. PMID:20533191

  4. Attenuated viral hepatitis in Trem1-/- mice is associated with reduced inflammatory activity of neutrophils.

    PubMed

    Kozik, Jan-Hendrik; Trautmann, Tanja; Carambia, Antonella; Preti, Max; Lütgehetmann, Marc; Krech, Till; Wiegard, Christiane; Heeren, Joerg; Herkel, Johannes

    2016-01-01

    TREM1 (Triggering Receptor Expressed on Myeloid Cells 1) is a pro-inflammatory receptor expressed by phagocytes, which can also be released as a soluble molecule (sTREM1). The roles of TREM1 and sTREM1 in liver infection and inflammation are not clear. Here we show that patients with hepatitis B virus (HBV) or hepatitis C virus (HCV) infection manifest elevated serum levels of sTREM1. In mice, experimental viral hepatitis induced by infection with Lymphocytic Choriomeningitis Virus (LCMV)-WE was likewise associated with increased sTREM1 in serum and urine, and with increased TREM1 and its associated adapter molecule DAP12 in the liver. Trem1-/- mice showed accelerated clearance of LCMV-WE and manifested attenuated liver inflammation and injury. TREM1 expression in the liver of wild-type mice was mostly confined to infiltrating neutrophils, which responded to LCMV by secretion of CCL2 and TNF-α, and release of sTREM1. Accordingly, the production of CCL2 and TNF-α was decreased in the livers of LCMV-infected Trem1-/- mice, as compared to LCMV-infected wildtype mice. These findings indicate that TREM1 plays a role in viral hepatitis, in which it seems to aggravate the immunopathology associated with viral clearance, mainly by increasing the inflammatory activity of neutrophils. PMID:27328755

  5. Theoretical basis of a beneficial role for vitamin D in viral hepatitis

    PubMed Central

    Lương, Khanh vinh quốc; Nguyễn, Lan Thi Hoàng

    2012-01-01

    Abnormal bone metabolism and dysfunction of the calcium-parathyroid hormone-vitamin D axis have been reported in patients with viral hepatitis. Some studies suggested a relationship between vitamin D and viral hepatitis. Genetic studies have provided an opportunity to identify the proteins that link vitamin D to the pathology of viral hepatitis (i.e., the major histocompatibility complex class II molecules, the vitamin D receptor, cytochrome P450, the renin-angiotensin system, apolipoprotein E, liver X receptor, toll-like receptor, and the proteins regulated by the Sp1 promoter gene). Vitamin D also exerts its effects on viral hepatitis via non-genomic factors, i.e., matrix metalloproteinase, endothelial vascular growth factor, prostaglandins, cyclooxygenase-2, and oxidative stress. In conclusion, vitamin D could have a beneficial role in viral hepatitis. Calcitriol is best used for viral hepatitis because it is the active form of the vitamin D3 metabolite. PMID:23082050

  6. [MOLECULAR BIOLOGY OF HEPATITIS B VIRUS AND IMMUNOPATHOGENESIS OF CHRONIC VIRAL HEPATITIS B].

    PubMed

    Balmasova, I P; Sepiashvili, R I; Malova, E S

    2016-01-01

    Chronic hepatitis B belongs to a category of socially significant diseases due to its wide abundance in the world and high frequency of unfavourable outcomes of this disease. Features of interaction of hepatitis B virus with human immune system, accompanying development of mechanisms of escape from immunological control, is the basis of development of chronic hepatitis B. Molecular-biological features of hepatitis B virus are the basis of the indicated mechanisms, and the content of this review is their examination. Herewith, stages of immunopathogenesis of this disease is the basis of characteristics of interaction of viral proteins with cells of immune system, and isolation of those is accepted in contemporary foreign literature. PMID:27228681

  7. Hepatitis B Virus X and Regulation of Viral Gene Expression.

    PubMed

    Slagle, Betty L; Bouchard, Michael J

    2016-03-01

    The efficient replication of hepatitis B virus (HBV) requires the HBV regulatory hepatitis B virus X (HBx) protein. The exact contributions of HBx are not fully understood, in part because of the limitations of the assays used for its study. When HBV replication is driven from a plasmid DNA, the contribution of HBx is modest. However, there is an absolute requirement for HBx in assays that recapitulate the infectious virus life cycle. There is much evidence that HBx can contribute directly to HBV replication by acting on viral promoters embedded within protein coding sequences. In addition, HBx may also contribute indirectly by modulating cellular pathways to benefit virus replication. Understanding the mechanism(s) of HBx action during virus replication may provide insight into novel ways to disrupt chronic HBV replication. PMID:26747833

  8. Analysis of hepatitis C viral dynamics using Latin hypercube sampling

    NASA Astrophysics Data System (ADS)

    Pachpute, Gaurav; Chakrabarty, Siddhartha P.

    2012-12-01

    We consider a mathematical model comprising four coupled ordinary differential equations (ODEs) to study hepatitis C viral dynamics. The model includes the efficacies of a combination therapy of interferon and ribavirin. There are two main objectives of this paper. The first one is to approximate the percentage of cases in which there is a viral clearance in absence of treatment as well as percentage of response to treatment for various efficacy levels. The other is to better understand and identify the parameters that play a key role in the decline of viral load and can be estimated in a clinical setting. A condition for the stability of the uninfected and the infected steady states is presented. A large number of sample points for the model parameters (which are physiologically feasible) are generated using Latin hypercube sampling. An analysis of the simulated values identifies that, approximately 29.85% cases result in clearance of the virus during the early phase of the infection. Results from the χ2 and the Spearman's tests done on the samples, indicate a distinctly different distribution for certain parameters for the cases exhibiting viral clearance under the combination therapy.

  9. Education and counseling in the methadone treatment setting improves knowledge of viral hepatitis.

    PubMed

    Larios, Sandra E; Masson, Carmen L; Shopshire, Michael S; Hettema, Jennifer; Jordan, Ashly E; McKnight, Courtney; Young, Christopher; Khalili, Mandana; Seewald, Randy M; Min, Albert; Hengl, Nicholas; Sorensen, James L; Des Jarlais, Don C; Perlman, David C

    2014-04-01

    The aim of this study was to evaluate the effectiveness of an educational method of providing viral hepatitis education for methadone maintenance patients. Four hundred forty participants were randomly assigned to either a control or a motivationally-enhanced viral hepatitis education and counseling intervention. Viral hepatitis A (HAV), B (HBV), and C (HCV) knowledge tests were administered at baseline, following each of two education sessions (post-education), and at a 3-month follow-up assessment. Results indicated a significant increase in knowledge of HAV, HBV, and HCV over time. No differences were found in knowledge between the intervention groups in knowledge acquisition regarding any of the hepatitis viruses suggesting that a motivational interviewing style may not augment hepatitis knowledge beyond standard counseling. A two-session viral hepatitis education intervention effectively promotes hepatitis knowledge and can be integrated in methadone treatment settings. PMID:24462241

  10. Therapy of chronic viral hepatitis: a critical view.

    PubMed

    Rizzetto, M

    1999-11-01

    Many oral nucleoside analogues that are potent inhibitors of hepatitis B virus have recently been developed for the treatment of hepatitis B. The problems with these drugs are bioavailability, toxicity and the time-dependent emergence of resistant hepatitis B virus mutants. Lamivudine appears to be the most useful in terms of clinical benefit, safety and tolerance. It is active on wild type hepatitis B virus as well as on HBeAg-minus variants of the virus. However, although hepatitis B virus is consistently repressed while on therapy, only a minority of patients are cured or remain in remission after Lamivudine withdrawal. Maintenance therapy would appear to be in order, but the long-term use of Lamivudine is precluded by the emergence of polymerase gene-mutants which may rekindle disease. Combination with other antivirals (Adefovir?) active also against Lamivudine escape mutants opens promising new prospects. There is, as yet, no valid therapy for chronic hepatitis D virus hepatitis. Attempts to improve the results of alpha-interferon therapy in chronic hepatitis C with new interferons, or the manipulation of interferon monotherapy so as to obtain the maximum results compatible with tolerance, have not produced significantly better results than the classic protocols of alpha-interferon monotherapy. A more concrete improvement has been achieved by the combination of interferon with Ribavirin, with the overall rate of response increasing three times compared to interferon monotherapy. Anaemia, however, is a common additional side-effect induced by Ribavirin. Combination therapy has become the treatment of choice for interferon naive patients as well as for interferon relapses; it is not efficacious in patients who have not responded to interferon. PMID:10730571

  11. Overview of hepatitis B viral replication and genetic variability.

    PubMed

    Tong, Shuping; Revill, Peter

    2016-04-01

    Chronic infection with hepatitis B virus (HBV) greatly increases the risk for liver cirrhosis and hepatocellular carcinoma (HCC). HBV isolates worldwide can be divided into ten genotypes. Moreover, the immune clearance phase selects for mutations in different parts of the viral genome. The outcome of HBV infection is shaped by the complex interplay of the mode of transmission, host genetic factors, viral genotype and adaptive mutations, as well as environmental factors. Core promoter mutations and mutations abolishing hepatitis B e antigen (HBeAg) expression have been implicated in acute liver failure, while genotypes B, C, subgenotype A1, core promoter mutations, preS deletions, C-terminal truncation of envelope proteins, and spliced pregenomic RNA are associated with HCC development. Our efforts to treat and prevent HBV infection are hampered by the emergence of drug resistant mutants and vaccine escape mutants. This paper provides an overview of the HBV life cycle, followed by review of HBV genotypes and mutants in terms of their biological properties and clinical significance. PMID:27084035

  12. Viral genome imaging of hepatitis C virus to probe heterogeneous viral infection and responses to antiviral therapies.

    PubMed

    Ramanan, Vyas; Trehan, Kartik; Ong, Mei-Lyn; Luna, Joseph M; Hoffmann, Hans-Heinrich; Espiritu, Christine; Sheahan, Timothy P; Chandrasekar, Hamsika; Schwartz, Robert E; Christine, Kathleen S; Rice, Charles M; van Oudenaarden, Alexander; Bhatia, Sangeeta N

    2016-07-01

    Hepatitis C virus (HCV) is a positive single-stranded RNA virus of enormous global health importance, with direct-acting antiviral therapies replacing an immunostimulatory interferon-based regimen. The dynamics of HCV positive and negative-strand viral RNAs (vRNAs) under antiviral perturbations have not been studied at the single-cell level, leaving a gap in our understanding of antiviral kinetics and host-virus interactions. Here, we demonstrate quantitative imaging of HCV genomes in multiple infection models, and multiplexing of positive and negative strand vRNAs and host antiviral RNAs. We capture the varying kinetics with which antiviral drugs with different mechanisms of action clear HCV infection, finding the NS5A inhibitor daclatasvir to induce a rapid decline in negative-strand viral RNAs. We also find that the induction of host antiviral genes upon interferon treatment is positively correlated with viral load in single cells. This study adds smFISH to the toolbox available for analyzing the treatment of RNA virus infections. PMID:27128351

  13. Structure, sequence and expression of the hepatitis delta (δ) viral genome

    NASA Astrophysics Data System (ADS)

    Wang, Kang-Sheng; Choo, Qui-Lim; Weiner, Amy J.; Ou, Jing-Hsiung; Najarian, Richard C.; Thayer, Richard M.; Mullenbach, Guy T.; Denniston, Katherine J.; Gerin, John L.; Houghton, Michael

    1986-10-01

    Biochemical and electron microscopic data indicate that the human hepatitis δ viral agent contains a covalently closed circular and single-stranded RNA genome that has certain similarities with viroid-like agents from plants. The sequence of the viral genome (1,678 nucleotides) has been determined and an open reading frame within the complementary strand has been shown to encode an antigen that binds specifically to antisera from patients with chronic hepatitis δ viral infections.

  14. 78 FR 32392 - CDC/HRSA Advisory Committee on HIV, Viral Hepatitis and STD Prevention and Treatment

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-30

    ... CDC/HRSA Advisory Committee on HIV, Viral Hepatitis and STD Prevention and Treatment In accordance... Administrator, HRSA, regarding activities related to prevention and control of HIV/AIDS, Viral Hepatitis and... professionals and the public about HIV/AIDS, Viral Hepatitis and other STDs. Matters To Be Discussed:...

  15. Mutual antagonism between hepatitis B viral mRNA and host microRNA let-7.

    PubMed

    Takata, Akemi; Otsuka, Motoyuki; Ohno, Motoko; Kishikawa, Takahiro; Yoshikawa, Takeshi; Koike, Kazuhiko

    2016-01-01

    The interplay between viral and host factors plays a major role in viral pathogenesis. Hepatitis B virus (HBV) infection is a global health problem that leads to liver cirrhosis and hepatocellular carcinoma (HCC). Although HBV proteins have been studied extensively about their implication in hepatocarcinogenesis, the molecular mechanisms of oncogenesis are still largely unknown. A recent concept in gene regulation, in which competitive endogenous RNAs compete for common microRNAs (miRNAs), suggests that mRNA targets are key elements in the regulation of miRNA availability. Here, we show that HBV mRNA in the preS2 region can be targeted by host miRNA let-7 g. This leads to the sequestration of let-7 g and inhibition of let-7 g function. The expression of HBV transcripts, including the preS2 region, de-repressed let-7 g targets, which may contribute to long-term oncogenesis. HBV transcript-expressing transgenic mice, but not non-targeted transcript-expressing mice, were more prone to chemically induced hepatoocarcinogenesis. Let-7 target protein expression was upregulated in human HCC tissues derived from HBV-infected patients. On the other hand, let-7 g inhibited HBV preS2 protein expression and viral products. These results suggest that the interplay between viral intermediate transcripts during HBV replication and host miRNAs is crucial to the pathogenesis of chronic viral infection. PMID:26979389

  16. Mutual antagonism between hepatitis B viral mRNA and host microRNA let-7

    PubMed Central

    Takata, Akemi; Otsuka, Motoyuki; Ohno, Motoko; Kishikawa, Takahiro; Yoshikawa, Takeshi; Koike, Kazuhiko

    2016-01-01

    The interplay between viral and host factors plays a major role in viral pathogenesis. Hepatitis B virus (HBV) infection is a global health problem that leads to liver cirrhosis and hepatocellular carcinoma (HCC). Although HBV proteins have been studied extensively about their implication in hepatocarcinogenesis, the molecular mechanisms of oncogenesis are still largely unknown. A recent concept in gene regulation, in which competitive endogenous RNAs compete for common microRNAs (miRNAs), suggests that mRNA targets are key elements in the regulation of miRNA availability. Here, we show that HBV mRNA in the preS2 region can be targeted by host miRNA let-7 g. This leads to the sequestration of let-7 g and inhibition of let-7 g function. The expression of HBV transcripts, including the preS2 region, de-repressed let-7 g targets, which may contribute to long-term oncogenesis. HBV transcript-expressing transgenic mice, but not non-targeted transcript-expressing mice, were more prone to chemically induced hepatoocarcinogenesis. Let-7 target protein expression was upregulated in human HCC tissues derived from HBV-infected patients. On the other hand, let-7 g inhibited HBV preS2 protein expression and viral products. These results suggest that the interplay between viral intermediate transcripts during HBV replication and host miRNAs is crucial to the pathogenesis of chronic viral infection. PMID:26979389

  17. Hepatitis E Virus Genotype 3 in Colombia: Survey in Patients with Clinical Diagnosis of Viral Hepatitis

    PubMed Central

    Rendon, Julio; Hoyos, Maria Cristina; di Filippo, Diana; Cortes-Mancera, Fabian; Mantilla, Carolina; Velasquez, Maria Mercedes; Sepulveda, Maria Elsy; Restrepo, Juan Carlos; Jaramillo, Sergio; Arbelaez, Maria Patricia; Correa, Gonzalo; Navas, Maria-Cristina

    2016-01-01

    Background Hepatitis E virus is a major cause of outbreaks as well as sporadic hepatitis cases worldwide. The epidemiology of this enterically transmitted infection differs between developing and developed countries. The aims of this study were to describe HEV infection in Colombian patients and to characterize the genotype. Methods A prospective study was carried out on 40 patients aged over 15 with a clinical diagnosis of viral hepatitis, recruited from five primary health units in the city of Medellin, Colombia. Fecal samples obtained from the 40 consecutives cases were analyzed for HEV RNA using nested reverse transcription PCR for both ORF1 and ORF2-3. The amplicons were sequenced for phylogenetic analyses. Results Nine (22.5%) cases of HEV infection were identified in the study population. Three HEV strains obtained from patients were classified as genotype 3. No significant association was found between cases of Hepatitis E and the variables water drinking source, garbage collection system and contact with pigs. Conclusions This is the first prospective study of hepatitis E in Colombian patients. The circulation of the genotype 3 in this population is predictable considering the reports of the region and the identification of this genotype from pigs in the state of Antioquia, of which Medellin is the capital. Further studies are necessary to establish whether zoonotic transmission of HEV is important in Colombia. PMID:26886728

  18. A Hospital-based Retrospective Study on Frequency and Distribution of Viral Hepatitis

    PubMed Central

    Antony, Jimmy; Celine, TM

    2014-01-01

    Background: Viral hepatitis is a major public health problem throughout the world. It is the inflammation of the liver due to the infection of any of the five main hepatic viruses A to E and it affects the liver through different modes of transmission. This study mainly aims at the frequency and distribution of viral hepatitis based on age and sex during a time period of 5 years. Materials and Methods: This is a hospital-based retrospective study of 5 years at a tertiary level hospital in Kerala state in India. Medical records department of the hospital follow the guidelines of International Classification of Diseases-10 for coding the diseases. The data on frequency and distribution of viral hepatitis based on age and sex during a period of 5 years from April 2005 to March 2010 were collected and analyzed and ‘z’ test was used for finding out the difference in proportions. Result: Out of 818 cases, 76.03% were males and 23.96% were females. The preponderance of males was apparent in all types of viral hepatitis infection. The high risk groups were the adults in the age group of 20-39 years. The main cause in the present study was hepatitis E virus (HEV) and followed by hepatitis A virus (HAV). Of total viral hepatitis cases, 31.54% were due to HAV, 6.35% hepatitis B virus, 0.85% hepatitis C virus and 61.24% were due to HEV respectively. In the present study, there was no case of hepatitis D virus has reported. The case fatality rate of viral hepatitis in the present study was minor than 1% (0.98%); whereas males were 0.96%; females of 1.02%. Conclusion: Taking the safety measures including vaccination and proper management of waste materials are the only solution to control or eradicate this infection. PMID:25191049

  19. Linker phosphorylation of Smad3 promotes fibro-carcinogenesis in chronic viral hepatitis of hepatocellular carcinoma.

    PubMed

    Murata, Miki; Yoshida, Katsunori; Yamaguchi, Takashi; Matsuzaki, Koichi

    2014-11-01

    Epidemiological and clinical data point to a close association between chronic hepatitis B virus infection or chronic hepatitis C virus infection and development of hepatocellular carcinoma (HCC). HCC develops over several decades and is associated with fibrosis. This sequence suggests that persistent viral infection and chronic inflammation can synergistically induce liver fibrosis and hepatocarcinogenesis. The transforming growth factor-β (TGF-β) signaling pathway plays a pivotal role in diverse cellular processes and contributes to hepatic fibro-carcinogenesis under inflammatory microenvironments during chronic liver diseases. The biological activities of TGF-β are initiated by the binding of the ligand to TGF-β receptors, which phosphorylate Smad proteins. TGF-β type I receptor activates Smad3 to create COOH-terminally phosphorylated Smad3 (pSmad3C), while pro-inflammatory cytokine-activated kinases phosphorylates Smad3 to create the linker phosphorylated Smad3 (pSmad3L). During chronic liver disease progression, virus components, together with pro-inflammatory cytokines and somatic mutations, convert the Smad3 signal from tumor-suppressive pSmad3C to fibro-carcinogenic pSmad3L pathways, accelerating liver fibrosis and increasing the risk of HCC. The understanding of Smad3 phosphorylation profiles may provide new opportunities for effective chemoprevention and personalized therapy for patients with hepatitis virus-related HCC in the future. PMID:25386050

  20. Linker phosphorylation of Smad3 promotes fibro-carcinogenesis in chronic viral hepatitis of hepatocellular carcinoma

    PubMed Central

    Murata, Miki; Yoshida, Katsunori; Yamaguchi, Takashi; Matsuzaki, Koichi

    2014-01-01

    Epidemiological and clinical data point to a close association between chronic hepatitis B virus infection or chronic hepatitis C virus infection and development of hepatocellular carcinoma (HCC). HCC develops over several decades and is associated with fibrosis. This sequence suggests that persistent viral infection and chronic inflammation can synergistically induce liver fibrosis and hepatocarcinogenesis. The transforming growth factor-β (TGF-β) signaling pathway plays a pivotal role in diverse cellular processes and contributes to hepatic fibro-carcinogenesis under inflammatory microenvironments during chronic liver diseases. The biological activities of TGF-β are initiated by the binding of the ligand to TGF-β receptors, which phosphorylate Smad proteins. TGF-β type I receptor activates Smad3 to create COOH-terminally phosphorylated Smad3 (pSmad3C), while pro-inflammatory cytokine-activated kinases phosphorylates Smad3 to create the linker phosphorylated Smad3 (pSmad3L). During chronic liver disease progression, virus components, together with pro-inflammatory cytokines and somatic mutations, convert the Smad3 signal from tumor-suppressive pSmad3C to fibro-carcinogenic pSmad3L pathways, accelerating liver fibrosis and increasing the risk of HCC. The understanding of Smad3 phosphorylation profiles may provide new opportunities for effective chemoprevention and personalized therapy for patients with hepatitis virus-related HCC in the future. PMID:25386050

  1. [THE ROLE OF CYTOKINES AND CHEMOKINES IN LABORATORY DIAGNOSTIC OF CHRONIC VIRAL HEPATITIS C].

    PubMed

    Semenov, A V; Arsentieva, N A; Lubimova, N E; Tulienev, S V; Basina, V V; Esaulenko, E V; Totolyan, A A

    2015-08-01

    The chronic viral hepatitis C is widely prevalent disease with prolonged persistence of virus and obliterated clinical picture. The present techniques of diagnostic of degree of fibrosis of liver and prognosis of course of disease have particular shortcomings. Hence, search of safe low invasive methods based on blood biomarkers is an actual task. The cytokines/chemokines (mediators of chronic inflammation) directly involved into immunopathogenesis of chronic viral hepatitis C can act in the capacity of biomarkers. The study was carried out to comprehensively analyze content of cytokines/chemokines in peripheral blood of patients with chronic viral hepatitis C at various stages of disease and infected by different genotypes of virus of hepatitis C. The concentration of cytokines/chemokines was identified in blood plasma of patients with chronic viral hepatitis C (n = 73) and conditionally healthy donors (n =3 7): IFNα, IFNγ, IFNλ/IL28α, TNFα, CCL2/MCP-1, CCL3/MIP-lα, CCL4/MIP-lβ, CCL5/RANTES, CCL8/MCP-2, CCL20/AIP-3α, CXCL9/MIG, CXCL10/P-10, CXCLII/ITAC. The multiplex analysis using technology xMAP was applied. The increasing of level of TNFα, CCL2/MCP-1, CCL4/ MIP-l, CCL8/ACP-2, CCL20/MIP-3α, CXCL9/MIG, CXCL10/IP-10, CXCL11/ITA C was established in blood plasma of patients with chronic viral hepatitis C as compared with control group. The levels of analyzed interferons IFNα, IFNγ, IFNλ/IL28α had no difference in studied groups. As far as chronic viral hepatitis C progresses and fibrosis of hepatic tissue develops the concentrations of TNFα, CCL2/MCP-1, CCL20/MIP-3α, CXCL9/MIG, CXCL10/IP-l0, CXCL11/ITAC increased significantly. The concentrations of chemokine CXCL11/IT4 C can be used as informative indicator for differentiating diagnostic of early stages of liver fibrosis. Depending on genotype of virus of hepatitis C, in patients with chronic viral hepatitis C change in content of CCL8/MCP-2 was established. Hence, detection in blood plasma of

  2. Viral hepatitis in incarcerated adults: a medical and public health concern.

    PubMed

    Hunt, Douglas R; Saab, Sammy

    2009-04-01

    Viral hepatitis is a common problem in the incarcerated population. It causes significant morbidity and mortality, and incarcerated inmates receive their health care almost exclusively from corrections-based health systems. The seroprevalence of hepatitis B and C infections is increased in this population, and a number of risk factors for viral hepatitis are particularly common and infer higher risk among inmates, including injection drug use (IDU), high-risk sexual activity, and tattoos. IDU, in particular, has been identified as an important and common risk factor for viral hepatitis in inmates, and variable rates of IDU among inmates have been found to be the most important cause of the marked variability of seroprevalence rates for exposure to hepatitis C virus. A number of risk reduction and management strategies have been identified that can decrease transmission to other inmates. Prison-based hepatitis A and hepatitis B vaccination programs, needle exchange programs, methadone maintenance programs, risk education programs, and hepatitis C virus antiviral programs, for example, have been shown to be safe and effective risk reduction and management strategies. Preliminary studies have shown that these strategies are underutilized in the United States. Reasons for this phenomenon are multifactorial, involving financial as well as ethical and political considerations. Additional funding, research, and formal consideration / discussion of the complex issues involving viral hepatitis in the US incarcerated population are clearly important for the sake of inmates and the community at large. In this article, the published medical literature regarding this important topic is reviewed. PMID:19240708

  3. RNA Structural Elements of Hepatitis C Virus Controlling Viral RNA Translation and the Implications for Viral Pathogenesis

    PubMed Central

    Piñeiro, David; Martinez-Salas, Encarnación

    2012-01-01

    Hepatitis C virus (HCV) genome multiplication requires the concerted action of the viral RNA, host factors and viral proteins. Recent studies have provided information about the requirement of specific viral RNA motifs that play an active role in the viral life cycle. RNA regulatory motifs controlling translation and replication of the viral RNA are mostly found at the 5' and 3' untranslated regions (UTRs). In particular, viral protein synthesis is under the control of the internal ribosome entry site (IRES) element, a complex RNA structure located at the 5'UTR that recruits the ribosomal subunits to the initiator codon. Accordingly, interfering with this RNA structural motif causes the abrogation of the viral cycle. In addition, RNA translation initiation is modulated by cellular factors, including miRNAs and RNA-binding proteins. Interestingly, a RNA structural motif located at the 3'end controls viral replication and establishes long-range RNA-RNA interactions with the 5'UTR, generating functional bridges between both ends on the viral genome. In this article, we review recent advances on virus-host interaction and translation control modulating viral gene expression in infected cells. PMID:23202462

  4. [The use of a dried protein mixture in treating patients with viral hepatitis].

    PubMed

    Dunaevskiĭ, G A; Karpenko, P A; Denisiako, E I; Tsimbal, A E; Iurkovskaia, N B

    1989-07-01

    The authors studied the effect of a dry protein mixture on the clinical course and protein and pigmentary metabolism, functional tests of the liver in 223 patients with viral hepatitis. It was found that this mixture favours reduction of the icteric period, more rapid restoration of the liver function and improves prognosis. The dry protein mixture is recommended to be included in dietotherapy of patients with viral hepatitis. PMID:2800480

  5. [Study of clinical character and medicinal therapy of viral hepatitis in hospital based on real world].

    PubMed

    Li, Yun-ru; Wang, Lian-xin; Xie, Yan-ming; Yang, Wei; Wang, Zhuo-yue; Yi, Dan-hui; Wang, Yong-yan

    2014-09-01

    Viral hepatitis was the most common infectious disease in china. But the diagnosis and treatment were varied because the viral hepatitis patients were hospitalized in different kinds of hospital such as infectious disease hospital, general hospital and Chinese medical hospital. It was necessary to know clinical characters and information of viral hepatitis patients in different hospitals. The general information, subtype distribution, prognosis, complication, medication and relations of onset with solar term from 41 180 viral hepatitis patients based on HIS data were analyzed. It was found that the age of patients between 18 to 59 years old was most; most patients were males. The national basic medical insurance was the most type of payment. The outcome of viral hepatitis in the youth and female were better than that in the old and male. Acute hepatitis was easer to restore than chronic hepatitis. Liver cirrhosis and hepatocellular carcinoma were the two most complications. The peak of onset was during summer solstice, slight heat and great heat. The most common Chinese medicine was Diammonium glycyrrhizinate and the most common western medicine was reduced glutathione. The combination of D. glycyrrhizinate with reduced glutathione, polyene phosphatidylcholine and thymosin was the main pattern. But It was not knew if the combination of western and Chinese medicine was the most effective therapy to protect liver function. It was necessary to take deeply research of the relationship between the combination therapy and their effectiveness. PMID:25532376

  6. Hepatic Cells Derived from Induced Pluripotent Stem Cells of Pigtail Macaques Support Hepatitis C Virus infection

    PubMed Central

    Sourisseau, Marion; Goldman, Orit; He, Wenqian; Gori, Jennifer L.; Kiem, Hans-Peter; Gouon-Evans, Valerie; Evans, Matthew J.

    2013-01-01

    The narrow species tropism of hepatitis C virus (HCV) limits animal studies. We found that pigtail macaque (Macaca nemestrina) hepatic cells derived from induced pluripotent stem cells support the entire HCV life cycle, although infection efficiency was limited by defects in the HCV cell entry process. This block was overcome by either increasing occludin expression, complementing the cells with human CD81, or infecting them with a strain of HCV with less-restricted requirements for CD81. Using this system, we can modify viral and host cell genetics to make pigtail macaques a suitable, clinically relevant model for the study of HCV infection. PMID:23891978

  7. 78 FR 64221 - CDC/HRSA Advisory Committee on HIV, Viral Hepatitis and STD Prevention and Treatment; Notice of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-10-28

    ... Hepatitis and STD Prevention and Treatment; Notice of Meeting In accordance with section l0(a)(2) of the... meeting. Name: CDC/HRSA Advisory Committee on HIV, Viral Hepatitis and STD Prevention and Treatment Dates... related to prevention and control of HIV/AIDS, Viral Hepatitis and other STDs, the support of health...

  8. 77 FR 66469 - CDC/HRSA Advisory Committee on HIV, Viral Hepatitis and STD Prevention and Treatment

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-11-05

    ... Hepatitis and STD Prevention and Treatment In accordance with section 10(a)(2) of the Federal Advisory... Client Level Data Update; (3) Viral Hepatitis Action Plan and Implementation Update; (4) Update on... Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, CDC, 1600 Clifton Road NE., Mailstop...

  9. Integrating viral hepatitis prevention services into an urban STD clinic: Denver, Colorado.

    PubMed

    Subiadur, Julie; Harris, Jennie L; Rietmeijer, Cornelis A

    2007-01-01

    The Centers for Disease Control and Prevention recommends integrating viral hepatitis prevention services with services for adults evaluated for sexually transmitted diseases (STDs). The Denver Public Health STD clinic began hepatitis B vaccination in 1999, hepatitis C virus (HCV) antibody (anti-HCV) testing in 2000, and hepatitis A vaccination in 2002. Rapid human immunodeficiency virus (HIV) testing began in late 2004. Hepatitis B vaccinations peaked in 2003 (31/100 client visits) when a full-time nurse was hired to vaccinate and eligibility was expanded. The proportion of clients documented to have received their anti-HCV test results declined from an average of 71% in 2000-2003 to 22% in 2004-2005, coinciding with the introduction of rapid HIV testing. Viral hepatitis prevention services can be incorporated into a busy STD clinic if staff and resources are available. Rapid HIV testing may be associated with lower receipt of anti-HCV test results. PMID:17542447

  10. Bloodborne Viral Hepatitis Infections among Drug Users: The Role of Vaccination

    PubMed Central

    Lugoboni, Fabio; Quaglio, Gianluca; Civitelli, Paolo; Mezzelani, Paolo

    2009-01-01

    Drug use is a prevalent world-wide phenomenon and hepatitis virus infections are traditionally a major health problem among drug users (DUs). HBV and HCV, and to a lesser extent HAV, are easily transmitted through exposure to infected blood and body fluids. Viral hepatitis is not inevitable for DUs. Licensed vaccines are available for hepatitis A and hepatitis B. The purpose of this overview is to show some epidemiological data about HBV and the other blood-borne viral hepatitis among DUs and to summarize and discuss use of hepatitis vaccinations in this population. Successful vaccination campaigns among DUs are feasible and well described. We try to focus on the most significant results achieved in successful vaccination programs as reported in scientific literature. Vaccination campaigns among DUs represent a highly effective form of health education and they are cost-saving. PMID:19440291

  11. [How to use viral genomic analysis in clinical practice: chronic hepatitis B and C].

    PubMed

    Izumi, Namiki

    2006-04-01

    Viral genomic analysis has been developed recently, and is utilized in clinical practice. The genotype of HB virus has the most important clinical implication, and in Japan, genotype C shows worse prognosis than genotype B. Basic core promoter (BCP) mutation is associated with hepatic fibrosis, and HBe antigen seronegativity is frequently observed after lamivudine administration than wild type. Polymerase domain B mutation was shown to be associated with lamivudine resistance concomitantly with domain C mutation. In the treatment of chronic hepatitis C genotype 1b infection, peginterferon and ribavirin combination therapy was introduced, and this combination therapy has been shown to induce 50% sustained virological response (SVR). To predict the virological response to combination therapy, monitoring viral decline provides the most important information. Real-time PCR is expensive, therefore, highly sensitive core antigen quantitation is valuable in clinical practice. When patients treated by combination therapy achieve a 2 log drop in HCV antigen until twelve weeks, they are estimated to have obtained 75% SVR by monitoring the amount of serum core antigen. PMID:16722459

  12. [Latest Treatment of Viral Hepatitis--Overcoming Hepatitis C and Reactivation of Hepatitis B].

    PubMed

    Tanaka, Yasuhito

    2016-02-01

    Hepatitis B virus (HBV) and hepatitis C virus (HCV), discovered as causative viruses of post-transfusion hepatitis, become persistent infections, leading to chronic hepatitis, cirrhosis, and hepatocellular carcinoma (HCC). For HCV, recent IFN-free direct-acting antiviral (DAA) therapies have increased sustained virological response (SVR) rates and reduced adverse events. IFN-based therapies, still the standard of care in Asian countries, are influenced by IL28B genetic variants and the liver fibrosis stage, but the DAA combinations obscure the influence of these factors. These new therapies can eradicate HCV and prevent HCC development. On the other hand, it is difficult to eradicate HBV completely. Although HBV infection can be prevented by vaccination, reactivation of HBV following anti-cancer chemotherapy and immunosuppressive therapy is a well-known complication. HBV reactivation has been reported to be associated with anti-CD20 monoclonal antibody rituximab-containing chemotherapy and TNF-α inhibitor-containing immunosuppressive therapy in HBV-resolved patients. Our prospective observational study revealed that monthly monitoring of HBV DNA was useful for preventing HBV reactivation-related hepatitis among B-cell non-Hodgkin lymphoma patients with resolved HBV infection following rituximab-steroid-chemo, suggesting that preemptive therapy guided by serial HBV DNA monitoring should be recommended. Recently, highly sensitive HBsAg detection by Lumipulse HBsAg-HQ may be useful for several clinical applications. The sensitivity of this assay (5 mIU/mL) was approximately 10-fold higher than Abbott ARCHITECT, but still lower than HBV-DNA assays. The convenient HBsAg-HQ may be useful for detecting occult HBV infection and HBV reactivation in relatively low-risk groups except for those receiving rituximab-steroid-chemo. [ PMID:27311286

  13. The management of chronic viral hepatitis: A Canadian consensus conference 2004

    PubMed Central

    Sherman, Morris; Bain, Vincent; Villeneuve, Jean-Pierre; Myers, Robert P; Cooper, Curtis; Martin, Steven; Lowe, Catherine

    2004-01-01

    Several government and nongovernment organizations held a consensus conference on the management of acute and chronic viral hepatitis to update previous management recommendations. The conference became necessary because of the introduction of new forms of therapy for both hepatitis B and hepatitis C. The conference issued recommendations on the investigation and management of chronic hepatitis B, including the use of lamivudine, adefovir and interferon. The treatment of hepatitis B in several special situations was also discussed. There were also recommendations on the investigation and treatment of chronic hepatitis C and hepatitis C-HIV coinfection. In addition, the document makes some recommendations about the provision of services by provincial governments to facilitate the delivery of care to patients with hepatitis virus infection. The present document is meant to be used by practitioners and other health care providers, including public health staff and others not directly involved in patient care. PMID:18159509

  14. Attenuated viral hepatitis in Trem1−/− mice is associated with reduced inflammatory activity of neutrophils

    PubMed Central

    Kozik, Jan-Hendrik; Trautmann, Tanja; Carambia, Antonella; Preti, Max; Lütgehetmann, Marc; Krech, Till; Wiegard, Christiane; Heeren, Joerg; Herkel, Johannes

    2016-01-01

    TREM1 (Triggering Receptor Expressed on Myeloid Cells 1) is a pro-inflammatory receptor expressed by phagocytes, which can also be released as a soluble molecule (sTREM1). The roles of TREM1 and sTREM1 in liver infection and inflammation are not clear. Here we show that patients with hepatitis B virus (HBV) or hepatitis C virus (HCV) infection manifest elevated serum levels of sTREM1. In mice, experimental viral hepatitis induced by infection with Lymphocytic Choriomeningitis Virus (LCMV)-WE was likewise associated with increased sTREM1 in serum and urine, and with increased TREM1 and its associated adapter molecule DAP12 in the liver. Trem1−/− mice showed accelerated clearance of LCMV-WE and manifested attenuated liver inflammation and injury. TREM1 expression in the liver of wild-type mice was mostly confined to infiltrating neutrophils, which responded to LCMV by secretion of CCL2 and TNF-α, and release of sTREM1. Accordingly, the production of CCL2 and TNF-α was decreased in the livers of LCMV-infected Trem1−/− mice, as compared to LCMV-infected wildtype mice. These findings indicate that TREM1 plays a role in viral hepatitis, in which it seems to aggravate the immunopathology associated with viral clearance, mainly by increasing the inflammatory activity of neutrophils. PMID:27328755

  15. Evidence for hepatitis C viral infection in patients with primary hepatocellular carcinoma.

    PubMed Central

    Tong, M J; Lee, S Y; Hwang, S J; Co, R L; Lai, P P; Chien, D; Kuo, G

    1994-01-01

    In testing for antibodies to the hepatitis C virus (anti-HCV) in 112 patients with primary hepatocellular carcinoma, 10 of 33 white patients (30%) and 15 of 79 Asian patients (19%) had a positive response to the antibody. The antibody profile to individual hepatitis C viral antigens and the presence of circulating hepatitis C viral RNA were determined in the 25 patients. The anti-HCV antibodies most frequently detected were toward the antigens from the core (C22) and NS3 regions. Serum hepatitis C viral RNA was present in 17 of the 25 patients (68%), and these patients tended to have serum levels of alanine and aspartate aminotransferases higher than those patients without viremia (136 +/- 22 U per liter versus 64 +/- 11 U per liter and 161 +/- 26 U per liter versus 79 +/- 14 U per liter, respectively, both P < .05). Of the 15 Asian patients with hepatocellular carcinoma and anti-HCV, 4 (27%) had coexisting hepatitis B surface antigen (HBsAg) and 13 (87%) had antibodies to either hepatitis B core or surface antigen. Of the 10 white patients with anti-HCV, however, only 1 (10%) had hepatitis B virus antibodies (P < .01). Among 4 Asian patients with coexisting anti-HCV and HBsAg, 1 was found to have serum hepatitis B viral DNA and the other 3 had hepatitis C viral RNA. A history of blood transfusion was obtained from 12 of the 25 patients with anti-HCV (48%); 20 (80%) had coexisting cirrhosis. Our findings support the hypothesis that hepatitis C virus is an important etiologic agent in the development of primary hepatocellular carcinoma in both white and Asian patients in the United States. PMID:7512778

  16. Dysplastic Hepatocytes Develop Nuclear Inclusions in a Mouse Model of Viral Hepatitis

    PubMed Central

    Thakur, Priyanka; Lamoke, Folami; Chaffin, Joanna M.; Bartoli, Manuela; Lee, Jeffrey R.; Duncan, Michael B.

    2014-01-01

    Viral hepatitis resulting in chronic liver disease is an important clinical challenge and insight into the cellular processes that drive pathogenesis will be critical in order to develop new diagnostic and therapeutic options. Nuclear inclusions in viral and non-viral hepatitis are well documented and have diagnostic significance in some disease contexts. However, the origins and functional consequences of these nuclear inclusions remain elusive. To date the clinical observation of nuclear inclusions in viral and non-viral hepatitis has not been explored at depth in murine models of liver disease. Herein, we report that in a transgenic model of hepatitis B surface antigen mediated hepatitis, murine hepatocytes exhibit nuclear inclusions. Cells bearing nuclear inclusions were more likely to express markers of cell proliferation. We also established a correlation between these inclusions and oxidative stress. N-acetyl cysteine treatment effectively reduced oxidative stress levels, relieved endoplasmic reticulum (ER) stress, and the number of nuclear inclusions we observed in the transgenic mice. Our results suggest that the presence of nuclear inclusions in hepatocytes correlates with oxidative stress and cellular proliferation in a model of antigen mediated hepatitis. PMID:24932583

  17. Acute Exacerbation of Chronic Hepatitis B: The Dilemma of Differentiation from Acute Viral Hepatitis B

    PubMed Central

    Puri, Pankaj

    2013-01-01

    Exacerbations of chronic hepatitis B are common in endemic countries. Acute exacerbation of chronic hepatitis B virus (CHB-AE) causing derangement of liver functions may be seen in a flare of HBV in immune clearance phase or as a reactivation of HBV in patients with inactive or resolved HBV infection. While reactivation of HBV is usually seen in HBsAg positive patients, it is being increasingly recognized in patients with apparently resolved HBV infection who do not have HBsAg in serum but have IgG antibody to core antigen (anti-HBc) in the serum, especially so in patients on chemotherapy, immunosuppressive therapy or undergoing hematopoietic stem cell transplantation. In an icteric patient who is HBsAg positive, it may be difficult to differentiate CHB-AE from acute viral hepatitis B (AVH-B). Both may have similar clinical presentation and even IgM anti-HBc, the traditional diagnostic marker of AVH-B, may also appear at the time of exacerbation of CHB. The differentiation between CHB-AE and AVH-B is important not only for prognostication but also because management strategies are different. Most cases of AVH-B will resolve on their own, HBsAg clearance is achieved spontaneously in 90–95% of adults and treatment is rarely indicated except in the few with severe/fulminant disease. In contrast, in CHB-AE, the onset of jaundice may lead to decompensation of liver disease and treatment is warranted. The mechanisms of acute exacerbation and the differentiating features between AVH-B and CHB-AE are reviewed. PMID:25755518

  18. Molecular Mechanism and Treatment of Viral Hepatitis-Related Liver Fibrosis

    PubMed Central

    Su, Tung-Hung; Kao, Jia-Horng; Liu, Chun-Jen

    2014-01-01

    Hepatic fibrosis is a wound-healing response to various chronic stimuli, including viral hepatitis B or C infection. Activated myofibroblasts, predominantly derived from the hepatic stellate cells (HSCs), regulate the balance between matrix metalloproteinases and their tissue inhibitors to maintain extracellular matrix homeostasis. Transforming growth factor-β and platelet-derived growth factor are classic profibrogenic signals that activate HSC proliferation. In addition, proinflammatory cytokines and chemokines coordinate macrophages, T cells, NK/NKT cells, and liver sinusoidal endothelial cells in complex fibrogenic and regression processes. In addition, fibrogenesis involves angiogenesis, metabolic reprogramming, autophagy, microRNA, and epigenetic regulations. Hepatic inflammation is the driving force behind liver fibrosis; however, host single nucleotide polymorphisms and viral factors, including the genotype, viral load, viral mutation, and viral proteins, have been associated with fibrosis progression. Eliminating the underlying etiology is the most crucial antifibrotic therapy. Growing evidence has indicated that persistent viral suppression with antiviral therapy can result in fibrosis regression, reduced liver disease progression, decreased hepatocellular carcinoma, and improved chances of survival. Preclinical studies and clinical trials are currently examining several investigational agents that target key fibrogenic pathways; the results are promising and shed light on this debilitating illness. PMID:24927147

  19. Inhibition of viral replication reduces regulatory T cells and enhances the antiviral immune response in chronic hepatitis B

    SciTech Connect

    Stoop, Jeroen N. . E-mail: j.n.stoop@erasmusmc.nl; Molen, Renate G. van der . E-mail: r.vandermolen@erasmusmc.nl; Kuipers, Ernst J. . E-mail: e.j.kuipers@erasmusmc.nl; Kusters, Johannes G. . E-mail: j.g.kusters@erasmusmc.nl; Janssen, Harry L.A. . E-mail: h.janssen@erasmusmc.nl

    2007-04-25

    Regulatory T cells (Treg) play a key role in the impaired immune response that is typical for a chronic Hepatitis B virus (HBV) infection. To gain more insight in the mechanism that is responsible for this impaired immune response, the effect of viral load reduction resulting from treatment with the nucleotide analogue adefovir dipivoxil on the percentages of Treg and HBV-specific T-cell responses was analyzed. Peripheral blood mononuclear cells (PBMC) of 12 patients were collected at baseline and during treatment. In parallel to the decline in viral load, we found a decline in circulating Treg, combined with an increase in HBV core antigen-specific IFN-{gamma} production and proliferation. The production of IL10 did not decrease during therapy. In conclusion, adefovir induced viral load reduction results in a decline of circulating Treg together with a partial recovery of the immune response.

  20. CRISPR/Cas9 cleavage of viral DNA efficiently suppresses hepatitis B virus

    PubMed Central

    Ramanan, Vyas; Shlomai, Amir; Cox, David B.T.; Schwartz, Robert E.; Michailidis, Eleftherios; Bhatta, Ankit; Scott, David A.; Zhang, Feng; Rice, Charles M.; Bhatia, Sangeeta N.

    2015-01-01

    Chronic hepatitis B virus (HBV) infection is prevalent, deadly, and seldom cured due to the persistence of viral episomal DNA (cccDNA) in infected cells. Newly developed genome engineering tools may offer the ability to directly cleave viral DNA, thereby promoting viral clearance. Here, we show that the CRISPR/Cas9 system can specifically target and cleave conserved regions in the HBV genome, resulting in robust suppression of viral gene expression and replication. Upon sustained expression of Cas9 and appropriately chosen guide RNAs, we demonstrate cleavage of cccDNA by Cas9 and a dramatic reduction in both cccDNA and other parameters of viral gene expression and replication. Thus, we show that directly targeting viral episomal DNA is a novel therapeutic approach to control the virus and possibly cure patients. PMID:26035283

  1. Treatment of Chronic Viral Hepatitis in Woodchucks by Prolonged Intrahepatic Expression of Interleukin-12▿

    PubMed Central

    Crettaz, Julien; Otano, Itziar; Ochoa, Laura; Benito, Alberto; Paneda, Astrid; Aurrekoetxea, Igor; Berraondo, Pedro; Rodríguez-Madoz, Juan Roberto; Astudillo, Aurora; Kreppel, Florian; Kochanek, Stefan; Ruiz, Juan; Menne, Stephan; Prieto, Jesus; Gonzalez-Aseguinolaza, Gloria

    2009-01-01

    Chronic hepatitis B is a major cause of liver-related death worldwide. Interleukin-12 (IL-12) induction accompanies viral clearance in chronic hepatitis B virus infection. Here, we tested the therapeutic potential of IL-12 gene therapy in woodchucks chronically infected with woodchuck hepatitis virus (WHV), an infection that closely resembles chronic hepatitis B. The woodchucks were treated by intrahepatic injection of a helper-dependent adenoviral vector encoding IL-12 under the control of a liver-specific RU486-responsive promoter. All woodchucks with viral loads below 1010 viral genomes (vg)/ml showed a marked and sustained reduction of viremia that was accompanied by a reduction in hepatic WHV DNA, a loss of e antigen and surface antigen, and improved liver histology. In contrast, none of the woodchucks with higher viremia levels responded to therapy. The antiviral effect was associated with the induction of T-cell immunity against viral antigens and a reduction of hepatic expression of Foxp3 in the responsive animals. Studies were performed in vitro to elucidate the resistance to therapy in highly viremic woodchucks. These studies showed that lymphocytes from healthy woodchucks or from animals with low viremia levels produced gamma interferon (IFN-γ) upon IL-12 stimulation, while lymphocytes from woodchucks with high viremia failed to upregulate IFN-γ in response to IL-12. In conclusion, IL-12-based gene therapy is an efficient approach to treat chronic hepadnavirus infection in woodchucks with viral loads below 1010 vg/ml. Interestingly, this therapy is able to break immunological tolerance to viral antigens in chronic WHV carriers. PMID:19116251

  2. Viral hepatitis B and C outbreak related to parenteral treatment at an oncological department in Slovakia.

    PubMed

    Kološová, A; Gašparovič, J

    2016-06-01

    The Regional Public Health Authority was notified about four cases of viral hepatitis (B and C) among patients with pre-event history of hospitalization at an oncological ward. An outbreak investigation was commenced in response. Forty-seven cases of viral hepatitis B and C in 39 patients hospitalized during the period from September 2009 to July 2010 were registered. We found an association between parenteral treatment and disease (hepatitis B: χ(2) = 49.53; P < 0.001; hepatitis C: χ(2) = 22.42; P < 0.001). Despite using disposable materials, there remains a risk of transmission of bloodborne virus infections in hospitals due to poor adherence to standard procedures. PMID:26944899

  3. Prevention and control of viral hepatitis through adolescent health programmes in Europe.

    PubMed

    FitzSimons, David; Vorsters, Alex; Hoppenbrouwers, Karel; Van Damme, Pierre

    2007-12-17

    The Viral Hepatitis Prevention Board jointly organized with the European Union for School and University Health and Medicine a meeting on the prevention and control of viral hepatitis through adolescent health programmes in Europe, held in Ljubljana, Slovenia, 15-16 March 2007. Participants from some 16 countries in Europe as well as the United States of America emphasized the importance of reaching adolescents mainly through school health programmes, provided an overview of currently existing youth health systems and reviewed their experiences with childhood and adolescent immunization programmes. The meeting concluded with a discussion of issues, lessons learnt, opportunities and action points for the future. PMID:18036709

  4. Vaccine, Transmission and Treatment: An Exploratory Study of Viral Hepatitis Knowledge among Attendees of a Metropolitan Australian University

    ERIC Educational Resources Information Center

    Hopwood, Max; Brener, Loren; Wilson, Hannah

    2012-01-01

    Aim: A cross-sectional study was conducted to explore knowledge of viral hepatitis among attendees of an Australian metropolitan university. Method: A short survey enquiring into viral hepatitis A, B and C (HAV, HBV and HCV, respectively) was administered to a convenience sample of people at a campus in Sydney, Australia during September 2011.…

  5. Effect of Quercetin on Hepatitis C Virus Life Cycle: From Viral to Host Targets.

    PubMed

    Rojas, Ángela; Del Campo, Jose A; Clement, Sophie; Lemasson, Matthieu; García-Valdecasas, Marta; Gil-Gómez, Antonio; Ranchal, Isidora; Bartosch, Birke; Bautista, Juan D; Rosenberg, Arielle R; Negro, Francesco; Romero-Gómez, Manuel

    2016-01-01

    Quercetin is a natural flavonoid, which has been shown to have anti hepatitis C virus (HCV) properties. However, the exact mechanisms whereby quercetin impacts the HCV life cycle are not fully understood. We assessed the effect of quercetin on different steps of the HCV life cycle in Huh-7.5 cells and primary human hepatocytes (PHH) infected with HCVcc. In both cell types, quercetin significantly decreased i) the viral genome replication; ii) the production of infectious HCV particles and iii) the specific infectivity of the newly produced viral particles (by 85% and 92%, Huh7.5 and PHH respectively). In addition, when applied directly on HCV particles, quercetin reduced their infectivity by 65%, suggesting that it affects the virion integrity. Interestingly, the HCV-induced up-regulation of diacylglycerol acyltransferase (DGAT) and the typical localization of the HCV core protein to the surface of lipid droplets, known to be mediated by DGAT, were both prevented by quercetin. In conclusion, quercetin appears to have direct and host-mediated antiviral effects against HCV. PMID:27546480

  6. Effect of Quercetin on Hepatitis C Virus Life Cycle: From Viral to Host Targets

    PubMed Central

    Rojas, Ángela; Del Campo, Jose A.; Clement, Sophie; Lemasson, Matthieu; García-Valdecasas, Marta; Gil-Gómez, Antonio; Ranchal, Isidora; Bartosch, Birke; Bautista, Juan D.; Rosenberg, Arielle R.; Negro, Francesco; Romero-Gómez, Manuel

    2016-01-01

    Quercetin is a natural flavonoid, which has been shown to have anti hepatitis C virus (HCV) properties. However, the exact mechanisms whereby quercetin impacts the HCV life cycle are not fully understood. We assessed the effect of quercetin on different steps of the HCV life cycle in Huh-7.5 cells and primary human hepatocytes (PHH) infected with HCVcc. In both cell types, quercetin significantly decreased i) the viral genome replication; ii) the production of infectious HCV particles and iii) the specific infectivity of the newly produced viral particles (by 85% and 92%, Huh7.5 and PHH respectively). In addition, when applied directly on HCV particles, quercetin reduced their infectivity by 65%, suggesting that it affects the virion integrity. Interestingly, the HCV-induced up-regulation of diacylglycerol acyltransferase (DGAT) and the typical localization of the HCV core protein to the surface of lipid droplets, known to be mediated by DGAT, were both prevented by quercetin. In conclusion, quercetin appears to have direct and host-mediated antiviral effects against HCV. PMID:27546480

  7. An Investigation of an Outbreak of Viral Hepatitis B in Modasa Town, Gujarat, India

    PubMed Central

    Patel, Disha A; Gupta, Praveg A; Kinariwala, Deepa M; Shah, Hetal S; Trivedi, Grishma R; Vegad, Mahendra M

    2012-01-01

    Background: Most outbreaks of viral hepatitis in India are caused by hepatitis E. Recently in the year 2009, Modasa town of Sabarkantha district in Gujarat witnessed the outbreak of hepatitis B. Purpose: An attempt was made to study the outbreak clinically and serologically, to estimate the seropositivity of hepatitis B Virus among the cases and their contacts and to know the seroprevalence of hepatitis B envelope antigen (HBeAg) and IgM antibody against hepatitis B core antigen (IgM HBcAb) out of all the Hepatitis B surface Antigen (HBsAg) positive ones. Materials and Methods: Eight hundred and fifty-six (856) cases and 1145 contacts were evaluated for hepatitis B markers namely HBsAg, HBeAg and IgM HBcAb by enzyme-linked immuno Sorbent Assay (ELISA) test. Results: This outbreak of viral hepatitis B in Modasa, Gujarat was most likely due to unsafe injection practices. Evidence in support of this was collected by Government authorities. Most of the patients and approximately 40% of the surveyed population gave history of injections in last 1.5–6 months. Total 664/856 (77.57%) cases and 20/1145 (1.75%) contacts were found to be positive for HBsAg. 53.41% of the positive cases and 52.93% of the positive contacts were HBeAg-positive and thus in a highly infectious stage. Conclusions: Inadequately sterilized needles and syringes are an important cause of transmission of hepatitis B in India. Our data reflects the high positivity rate of a hepatitis B outbreak due to such unethical practices. There is a need to strengthen the routine surveillance system, and to organise a health education campaign targeting all health care workers including private practitioners, especially those working in rural areas, as well as the public at large, to take all possible measures to prevent this often fatal infection. PMID:22529628

  8. Inorganic Nanoparticle as a Carrier for Hepatitis B Viral Capsids

    NASA Astrophysics Data System (ADS)

    Dekhtyar, Yu.; Romanova, M.; Kachanovska, A.; Skrastiņa, D.; Reinhofa, R.; Pumpens, P.; Patmalnieks, A.

    Virus like particles (VLP) are used to transport immune response-modulating agents to target cells to treat them. In order to deliver a high concentration of VLP to the cell, a number of VLP can be attached to a nanoparticle to be used as a nanolorry. In this study, SiO2 nanoparticles were attached to Hepatitis B VLP. Spectrophotometry measurements, electron, and fluorescent microscopy evidence showed that the SiO2 - Hepatitis B VLP complexes were formed.

  9. Potential mechanisms of hepatitis B virus induced liver injury.

    PubMed

    Suhail, Mohd; Abdel-Hafiz, Hany; Ali, Ashraf; Fatima, Kaneez; Damanhouri, Ghazi A; Azhar, Esam; Chaudhary, Adeel Ga; Qadri, Ishtiaq

    2014-09-21

    Chronic active hepatitis (CAH) is acknowledged as an imperative risk factor for the development of liver injury and hepatocellular carcinoma. The histological end points of CAH are chronic inflammation, fibrosis and cirrhosis which are coupled with increased DNA synthesis in cirrhotic vs healthy normal livers. The potential mechanism involved in CAH includes a combination of processes leading to liver cell necrosis, inflammation and cytokine production and liver scaring (fibrosis). The severity of liver damage is regulated by Hepatitis B virus genotypes and viral components. The viral and cellular factors that contribute to liver injury are discussed in this article. Liver injury caused by the viral infection affects many cellular processes such as cell signaling, apoptosis, transcription, DNA repair which in turn induce radical effects on cell survival, growth, transformation and maintenance. The consequence of such perturbations is resulted in the alteration of bile secretion, gluconeogenesis, glycolysis, detoxification and metabolism of carbohydrates, proteins, fat and balance of nutrients. The identification and elucidation of the molecular pathways perturbed by the viral proteins are important in order to design effective strategy to minimize and/or restore the hepatocytes injury. PMID:25253946

  10. Potential mechanisms of hepatitis B virus induced liver injury

    PubMed Central

    Suhail, Mohd; Abdel-Hafiz, Hany; Ali, Ashraf; Fatima, Kaneez; Damanhouri, Ghazi A; Azhar, Esam; Chaudhary, Adeel GA; Qadri, Ishtiaq

    2014-01-01

    Chronic active hepatitis (CAH) is acknowledged as an imperative risk factor for the development of liver injury and hepatocellular carcinoma. The histological end points of CAH are chronic inflammation, fibrosis and cirrhosis which are coupled with increased DNA synthesis in cirrhotic vs healthy normal livers. The potential mechanism involved in CAH includes a combination of processes leading to liver cell necrosis, inflammation and cytokine production and liver scaring (fibrosis). The severity of liver damage is regulated by Hepatitis B virus genotypes and viral components. The viral and cellular factors that contribute to liver injury are discussed in this article. Liver injury caused by the viral infection affects many cellular processes such as cell signaling, apoptosis, transcription, DNA repair which in turn induce radical effects on cell survival, growth, transformation and maintenance. The consequence of such perturbations is resulted in the alteration of bile secretion, gluconeogenesis, glycolysis, detoxification and metabolism of carbohydrates, proteins, fat and balance of nutrients. The identification and elucidation of the molecular pathways perturbed by the viral proteins are important in order to design effective strategy to minimize and/or restore the hepatocytes injury. PMID:25253946

  11. Hepatitis C: Treatment

    MedlinePlus

    ... 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 ...

  12. ALLYLISOPROPYLACETAMIDE INDUCES RAT HEPATIC ORNITHINE DECARBOXYLASE

    EPA Science Inventory

    In rat liver, allylisopropylacetamide (AIA) treatment strongly induced (25-fold) the activity of rat hepatic ornithine decarboxylase (ODC). y either the oral or the subcutaneous routes, AIA produced a long-lasting induction (30 to 4O hours) of hepatic ODC activity. hree analogs o...

  13. Exploitation of Lipid Components by Viral and Host Proteins for Hepatitis C Virus Infection

    PubMed Central

    Moriishi, Kohji; Matsuura, Yashiharu

    2012-01-01

    Hepatitis C virus (HCV), which is a major causative agent of blood-borne hepatitis, has chronically infected about 170 million individuals worldwide and leads to chronic infection, resulting in development of steatosis, cirrhosis, and eventually hepatocellular carcinoma. Hepatocellular carcinoma associated with HCV infection is not only caused by chronic inflammation, but also by the biological activity of HCV proteins. HCV core protein is known as a main component of the viral nucleocapsid. It cooperates with host factors and possesses biological activity causing lipid alteration, oxidative stress, and progression of cell growth, while other viral proteins also interact with host proteins including molecular chaperones, membrane-anchoring proteins, and enzymes associated with lipid metabolism to maintain the efficiency of viral replication and production. HCV core protein is localized on the surface of lipid droplets in infected cells. However, the role of lipid droplets in HCV infection has not yet been elucidated. Several groups recently reported that other viral proteins also support viral infection by regulation of lipid droplets and core localization in infected cells. Furthermore, lipid components are required for modification of host factors and the intracellular membrane to maintain or up-regulate viral replication. In this review, we summarize the current status of knowledge regarding the exploitation of lipid components by viral and host proteins in HCV infection. PMID:22347882

  14. [Incidence of various types of viral hepatitis in Poland 1988].

    PubMed

    Kalinowska, B; Małolepsza, E; Magdzik, W; Naruszewicz-Lesiuk, D; Nowosławski, A

    1990-01-01

    109 sera from patients in the early phase of acute hepatitis non-B were tested by immunoenzymatic methods for presence of serologic markers of infections with HBV, HAV and CMV. The analysis of the results showed that 14 patients were infected with HBV, 20 with HAV and 2 with CMV. The remaining 73 cases could apparently be attributed to the infection with HCV. It has been estimated that in 1988, 69.5% of hepatitis cases in Poland could have resulted from the infection with HBV, 24%--from the infection with NANB viruses and only, and only 6.5%--from the infection with HAV. These data even if representing a slight overestimate of the incidence of hepatitis due to the parenteral spread of infections agents support the postulate that measures to prevent these infections should be strengthened. PMID:1966117

  15. Web-based Distributed Medical Information System for Chronic Viral Hepatitis

    NASA Astrophysics Data System (ADS)

    Yang, Ying; Qin, Tuan-fa; Jiang, Jian-ning; Lu, Hui; Ma, Zong-e.; Meng, Hong-chang

    2008-11-01

    To make a long-term dynamic monitoring to the chronically ill, especially patients of HBV A, we build a distributed Medical Information System for Chronic Viral Hepatitis (MISCHV). The Web-based system architecture and its function are described, and the extensive application and important role are also presented.

  16. Systematic analysis of funding awarded for viral hepatitis-related research to institutions in the United Kingdom, 1997–2010

    PubMed Central

    Head, M G; Fitchett, J R; Cooke, G S; Foster, G R; Atun, R

    2015-01-01

    Viral hepatitis is responsible for great health, social and economic burden both globally and in the UK. This study aimed to assess the research funding awarded to UK institutions for viral hepatitis research and the relationship of funded research to clinical and public health burden of viral hepatitis. Databases and websites were systematically searched for information on infectious disease research studies funded for the period 1997–2010. Studies specifically related to viral hepatitis research were identified and categorized in terms of funding by pathogen, disease and by a research and development value chain describing the type of science. The overall data set included 6165 studies (total investment £2.6 billion) of which £76.9 million (3.0%) was directed towards viral hepatitis across 323 studies (5.2%). By pathogen, there were four studies specifically investigating hepatitis A (£3.8 million), 69 studies for hepatitis B (21.4%) with total investment of £14.7 million (19.1%) and 236 (73.1%) hepatitis C studies (£62.7 million, 81.5%). There were 4 studies investigating hepatitis G, and none specifying hepatitis D or E. By associated area, viral hepatitis and therapeutics research received £17.0 million, vaccinology £3.1 million and diagnostics £2.9 million. Preclinical research received £50.3 million (65.4%) across 173 studies, whilst implementation and operational research received £19.4 million (25.3%) across 128 studies. The UK is engaged in much hepatology research, but there are areas where the burden is great and may require greater focus, such as hepatitis E, development of a vaccine for hepatitis C, and further research into hepatitis-associated cancers. Private sector data, and funding information from other countries, would also be useful in priority setting. PMID:25146854

  17. Systematic analysis of funding awarded for viral hepatitis-related research to institutions in the United Kingdom, 1997-2010.

    PubMed

    Head, M G; Fitchett, J R; Cooke, G S; Foster, G R; Atun, R

    2015-03-01

    Viral hepatitis is responsible for great health, social and economic burden both globally and in the UK. This study aimed to assess the research funding awarded to UK institutions for viral hepatitis research and the relationship of funded research to clinical and public health burden of viral hepatitis. Databases and websites were systematically searched for information on infectious disease research studies funded for the period 1997-2010. Studies specifically related to viral hepatitis research were identified and categorized in terms of funding by pathogen, disease and by a research and development value chain describing the type of science. The overall data set included 6165 studies (total investment £2.6 billion) of which £76.9 million (3.0%) was directed towards viral hepatitis across 323 studies (5.2%). By pathogen, there were four studies specifically investigating hepatitis A (£3.8 million), 69 studies for hepatitis B (21.4%) with total investment of £14.7 million (19.1%) and 236 (73.1%) hepatitis C studies (£62.7 million, 81.5%). There were 4 studies investigating hepatitis G, and none specifying hepatitis D or E. By associated area, viral hepatitis and therapeutics research received £17.0 million, vaccinology £3.1 million and diagnostics £2.9 million. Preclinical research received £50.3 million (65.4%) across 173 studies, whilst implementation and operational research received £19.4 million (25.3%) across 128 studies. The UK is engaged in much hepatology research, but there are areas where the burden is great and may require greater focus, such as hepatitis E, development of a vaccine for hepatitis C, and further research into hepatitis-associated cancers. Private sector data, and funding information from other countries, would also be useful in priority setting. PMID:25146854

  18. Temporal pathogenesis of experimental neonatal woodchuck hepatitis virus infection: increased initial viral load and decreased severity of acute hepatitis during the development of chronic viral infection.

    PubMed

    Cote, P J; Toshkov, I; Bellezza, C; Ascenzi, M; Roneker, C; Ann Graham, L; Baldwin, B H; Gaye, K; Nakamura, I; Korba, B E; Tennant, B C; Gerin, J L

    2000-10-01

    Acute hepatitis B virus (HBV) infections either resolve or progress to chronicity. Identification of early deviations in host-virus responses associated with these outcomes can further differentiate cause-effect mechanisms that initiate and maintain chronicity. Neonatal woodchucks were infected experimentally with the woodchuck hepatitis virus (WHV) at 3 days of age. At 8 or 14 weeks of age (i.e. , the early- or mid-acute stage of infection), whole blood and large surgical biopsies of the liver were obtained from infected animals and uninfected controls. These were stored for later correlating histopathologic responses and viral load with the subsequently determined outcome of infection. As of 1 year postinfection, half of the surgically treated infected woodchucks had developed self-limited infections, while the other half developed chronic infections. The self-limited outcome was characterized by decreased viral load in acute-phase liver and plasma and a generally robust acute hepatic inflammatory response. Comparisons at the same early time points revealed that the chronic outcome was characterized by increasing initial viral load in liver and plasma, and a detectable, but diminished, acute hepatic inflammation. These cotemporal comparisons indicate that there is an early host-response deviation during the acute phase of a developing chronic infection. Continued analysis of the tissues banked from this study will facilitate further temporal characterization of acute-phase mechanisms that determine resolution versus chronicity in WHV infection. Understanding such mechanisms may be useful in the rational design of therapy for established chronic HBV infection. PMID:11003627

  19. Reducing the neglected burden of viral hepatitis in Africa: strategies for a global approach.

    PubMed

    Lemoine, Maud; Eholié, Serge; Lacombe, Karine

    2015-02-01

    The burden of liver disease may dramatically increase in the near future in Africa, where screening and access to care and treatment are hampered by inadequate disease surveillance, lack of high-quality tools to assess chronic liver disease, and underestimated needs for human and financial resources. Chronic hepatitis may be considered as silent and neglected killer, fuelled by many years of global inertia from stakeholders and policy makers alike. However, the global battle against viral hepatitis is facing a new era owing to the advent of highly effective drugs, innovative tools for screening and clinical follow-up, and recent signs that governments, advocacy groups and global health organizations are mobilizing to advocate universal access-to-treatment. This review details the barriers to prevention, screening and treatment of viral hepatitis on the African continent, focuses on the urgent need for operational and research programmes, and suggests integrated ways to tackle the global epidemic. PMID:25457207

  20. Hepatitis C: viral and host factors associated with non-response to pegylated interferon plus ribavirin

    PubMed Central

    Asselah, Tarik; Estrabaud, Emilie; Bieche, Ivan; Lapalus, Martine; De Muynck, Simon; Vidaud, Michel; Saadoun, David; Soumelis, Vassili; Marcellin, Patrick

    2010-01-01

    Treatment for chronic hepatitis C virus (HCV) infection has evolved considerably in the last years. The standard of care (SOC) for HCV infection consists in the combination of pegylated interferon (PEG-IFN) plus ribavirin. However, it only induces a sustained virological response (SVR) in half of genotype 1-infected patients. Several viral and host factors have been associated with non-response: steatosis, obesity, insulin resistance, age, male sex, ethnicity and genotypes. Many studies have demonstrated that in non-responders, some interferon-stimulated genes were upregulated before treatment. Those findings associated to clinical, biochemical and histological data may help detect responders before starting any treatment. This is a very important issue because the standard treatment is physically and economically demanding. The future of HCV treatment would probably consist in the addition of specifically targeted antiviral therapy for HCV such as protease and/or polymerase inhibitors to the SOC. In genotype 1 patients, very promising results have been reported when the protease inhibitor telaprevir or boceprevir is added to the SOC. It increases the SVR rates from approximately 50% (PEG-IFN plus ribavirin) to 70% (for patients treated with a combination of PEG-IFN plus ribavirin plus telaprevir). Different elements are associated with non-response: (i) viral factors, (ii) host factors and (iii) molecular mechanisms induced by HCV proteins to inhibit the IFN signalling pathway. The goal of this review is to present the mechanisms of non-response, to overcome it and to identify factors that can help to predict the response to anti-HCV therapy. PMID:20633102

  1. Molecular and Functional Analysis of the Human Prothrombinase Gene (HFGL2) and Its Role in Viral Hepatitis

    PubMed Central

    Levy, Gary A.; Liu, Mingfeng; Ding, Jinwen; Yuwaraj, Shankary; Leibowitz, Julian; Marsden, Philip A.; Ning, Qin; Kovalinka, Ana; Phillips, M. James

    2000-01-01

    In the present studies, we report the cloning and structural characterization of the HFGL2 gene and its functional role in human fulminant hepatitis. The HFGL2 gene is approximately 7 kb in length with 2 exons. The putative promoter contains cis element consensus sequences that strongly suggest the inducibility of its expression. From the nucleotide sequence of the human gene, a 439-amino acid long protein is predicted. The overall identity between the murine fgl2 and hfgl2 coded proteins is over 70%. About 225 amino acids at the carboxyl end of these molecules are almost 90% identical, and correspond to a well-conserved fibrinogen-related domain. Both HFGL2 and FGL2 encode a type II transmembrane protein with a predicted catalytic domain toward the amino terminus of the protein. Transient transfection of Chinese hamster ovary (CHO) cells with a full-length cDNA of HFGL2 coding region resulted in high levels of prothrombinase activity. Livers from 8 patients transplanted for fulminant viral hepatitis were examined for extent of necrosis, inflammation, fibrin deposition, and HFGL2 induction. In situ hybridization showed positive staining of macrophages in areas of active hepatocellular necrosis. Fibrin stained positively in these areas and was confirmed by electron microscopy. These studies define a unique prothrombinase gene (HFGL2) and implicate its importance in the pathogenesis of fulminant viral hepatitis. PMID:10751347

  2. Viral load and clinicopathological features of chronic hepatitis C (1b) in a homogeneous patient population.

    PubMed

    Fanning, L; Kenny, E; Sheehan, M; Cannon, B; Whelton, M; O'Connell, J; Collins, J K; Shanahan, F

    1999-03-01

    Monitoring the progression of hepatitis C virus (HCV) includes clinical, biochemical, and histological parameters. Quantitation of viral load by reverse-transcription polymerase chain reaction (RT-PCR) may offer a more reliable marker of disease status. Conflicting reports on viral titers may reflect heterogeneity of patient population, mode of infection, and viral type/subtype. The aim of this study was to correlate quantitative serum viral load with alanine transaminase (ALT) and histological status in a homogenous population. The study population consisted of 77 Rhesus-negative women with chronic hepatitis C type 1b. Homogenous features of this study population included: same defined source of infection (contaminated anti-D immunoglobulin); same duration of disease (17 years at the time of study); same viral type/subtype; same ethnic origin; all healthy child-bearing females at the time of infection; and an absence of competing risk factors for infectious and other liver diseases. None of the patients had received antiviral treatment at the time of study. Liver biopsy was performed on all patients. All biopsies were scored by a single histopathologist who was blinded to the clinical and viral status of each patient. A weak, but statistically significant, correlation (rs =.26; P <.05) between serum viral load and the degree of inflammation (mean value: 3.87 +/- 2.17 [SD]) was found. There was no significant correlation between serum viral load and the degree of fibrosis (mean value: 0.84 +/- 0.8 [SD]; P =.06). There was no significant correlation between serum viral load and ALT, although there was a correlation between ALT and the degree of inflammation (rs =.241; P =.035). PMID:10051496

  3. Inducible viral receptor, A possible concept to induce viral protection in primitive immune animals.

    PubMed

    Pasharawipas, Tirasak

    2011-01-01

    A pseudolysogen (PL) is derived from the lysogenic Vibrio harveyi (VH) which is infected with the VHS1 (Vibrio harveyi Siphoviridae-like 1) bacteriophage. The lysogenic Vibrio harveyi undergoes an unequivalent division of the extra-chromosomal VHS1 phage genome and its VH host chromosome and produces a true lysogen (TL) and pseudolysogen (PL). The PL is tolerant to super-infection of VHS1, as is of the true lysogen (TL), but the PL does not contain the VHS1 phage genome while the TL does. However, the PL can become susceptible to VHS1 phage infection if the physiological state of the PL is changed. It is postulated that this is due to a phage receptor molecule which can be inducible to an on-and-off regulation influence by an alternating condition of the bacterial host cell. This characteristic of the PL leads to speculate that this phenomenon can also occur in high organisms with low immunity such as shrimp. This article proposes a hypothesis that the viral receptor molecule on the target cell can play a crucial role in which the invertebrate aquaculture animals can become tolerant to viral infection. A possible mechanism may be that the target cell disrupts the viral receptor molecule to prevent super infection. This concept can explain a mechanism for the prevention of viral infection in invertebrate animals which do not have acquired immunity in response to pathogens. It can guide us to develop a mechanism of immunity to viral infection in low-evolved-immune animals. Also, it can be an additional mechanism that exists in high immune organism, as in human for the prevention of viral infection. PMID:21711515

  4. Segmental Difference of the Hepatic Fibrosis from Chronic Viral Hepatitis due to Hepatitis B versus C Virus Infection: Comparison Using Dual Contrast Material-Enhanced MRI

    PubMed Central

    Shim, Jae Ho; Chung, Jae-Joon; Kim, Joo Hee; Kim, Ki Whang

    2011-01-01

    Objective We wanted to identify the geographic differences in hepatic fibrosis and their associations with the atrophy-hypertrophy complex in patients with chronic viral hepatitis using the dual-contrast material-enhanced MRI (DC-MRI) with gadopentetate dimeglumine and ferucarbotran. Materials and Methods Patients with chronic C (n = 22) and B-viral hepatitis (n = 35) were enrolled for determining the subjective grade of fibrosis (the extent and thickness of fibrotic reticulations) in the right lobe (RL), the caudate lobe (CL), the medial segment (MS) and the lateral segment (LS) of the liver, with using a 5-grade scale, on the gradient echo T2*-weighted images of DC-MRI. The fibrosis grades of different segments were compared using the Kruskal-Wallis test followed by post-hoc analysis to establish the segment-by-segment differences. The incidences of two pre-established morphologic signs of cirrhosis were also compared with each other between the two groups of patients. Results There were significant intersegmental differences in fibrosis grades of the C-viral group (p = 0.005), and the CL showed lower fibrosis grades as compared with the grades of the RL and MS, whereas all lobes were similarly affected in the B-viral group (p = 0.221). The presence of a right posterior hepatic notch was significantly higher in the patients with intersegmental differences of fibrosis between the RL and the CL (19 out of 25, 76%) than those without such differences (6 out of 32, 19%) (p < 0.001). An expanded gallbladder fossa showed no significant relationship (p = 0.327) with the segmental difference of the fibrosis grades between the LS and the MS. Conclusion The relative lack of fibrosis in the CL with more advanced fibrosis in the RL can be a distinguishing feature to differentiate chronic C-viral hepatitis from chronic B-viral hepatitis and this is closely related to the presence of a right posterior hepatic notch. PMID:21852903

  5. [From the national competence network for viral hepatitis (HepNet) emerged the German Liver Foundation (Deutsche Leberstiftung)].

    PubMed

    Hardtke, S; Wiebner, B; Manns, M P

    2016-04-01

    The competence network for viral hepatitis (HepNet) was founded in 2002 with funding from the German government and has influenced the research on viral hepatitis in Germany. HepNet collaborator sites have been involved in numerous national and international investigator-initiated, as well as industry-sponsored, phase 1-3 studies. Within the HepNet Study-House, many groundbreaking investor-initiated trials have been completed and are still ongoing. For example, the acute hepatitis C trials and trials on chronic hepatitis D (delta), which led to therapy optimization. Continuation of the competence network on viral hepatitis has been achieved by the foundation of the German Liver Foundation, which has been an external cooperation partner of the German Center for Infection Research (DZIF) for two years. The well-established HepNet Study-House acts here as the clinical trial platform for all DZIF hepatitis trials. PMID:26942931

  6. Insulin-Inducible SMILE Inhibits Hepatic Gluconeogenesis.

    PubMed

    Lee, Ji-Min; Seo, Woo-Young; Han, Hye-Sook; Oh, Kyoung-Jin; Lee, Yong-Soo; Kim, Don-Kyu; Choi, Seri; Choi, Byeong Hun; Harris, Robert A; Lee, Chul-Ho; Koo, Seung-Hoi; Choi, Hueng-Sik

    2016-01-01

    The role of a glucagon/cAMP-dependent protein kinase-inducible coactivator PGC-1α signaling pathway is well characterized in hepatic gluconeogenesis. However, an opposing protein kinase B (PKB)/Akt-inducible corepressor signaling pathway is unknown. A previous report has demonstrated that small heterodimer partner-interacting leucine zipper protein (SMILE) regulates the nuclear receptors and transcriptional factors that control hepatic gluconeogenesis. Here, we show that hepatic SMILE expression was induced by feeding in normal mice but not in db/db and high-fat diet (HFD)-fed mice. Interestingly, SMILE expression was induced by insulin in mouse primary hepatocyte and liver. Hepatic SMILE expression was not altered by refeeding in liver-specific insulin receptor knockout (LIRKO) or PKB β-deficient (PKBβ(-/-)) mice. At the molecular level, SMILE inhibited hepatocyte nuclear factor 4-mediated transcriptional activity via direct competition with PGC-1α. Moreover, ablation of SMILE augmented gluconeogenesis and increased blood glucose levels in mice. Conversely, overexpression of SMILE reduced hepatic gluconeogenic gene expression and ameliorated hyperglycemia and glucose intolerance in db/db and HFD-fed mice. Therefore, SMILE is an insulin-inducible corepressor that suppresses hepatic gluconeogenesis. Small molecules that enhance SMILE expression would have potential for treating hyperglycemia in diabetes. PMID:26340929

  7. Rethinking the immune properties of bilirubin in viral hepatitis: from bench to bedside

    PubMed Central

    Corral-Jara, Karla F; Trujillo-Ochoa, Jorge L; Realpe, Mauricio; Panduro, Arturo; Roman, Sonia; Fierro, Nora A

    2015-01-01

    Communication between the immune system and metabolic components can be exemplified by the process of heme catabolism. The immunomodulatory functions of the enzymes, substrates and active products related to catabolism of the heme group have been extensively studied. Bilirubin (BR), the final breakdown product of heme, is primarily considered to be a toxic waste product but has recently been considered to be an immunomodulatory metabolite. Through mechanisms that include intracellular signaling and transcriptional control, BR affects those immune cell functions that regulate cell proliferation, differentiation and apoptosis. During the pathogenesis of viral hepatitis, the heme degradation pathway is disrupted, resulting in changes to normal BR concentrations. These alterations have been previously studied mainly as a consequence of the infection. However, little is known about the potential immunomodulatory role played by BR in the development of infectious hepatocellular diseases. Differences in BR levels in the context of viral hepatitis are likely to provide important insights into the metabolite-mediated mechanisms controlling the immune responses underlying both the long-term persistence of hepatitis C virus (HCV) infection and the resolution of hepatitis A virus (HAV) infection during the acute phase. In this review, the cross-talk between heme catabolism and immune function is described in detail. Special emphasis is given to discoveries that hold promise for identifying immunologic features of metabolic products in the resolution of viral diseases. PMID:26719800

  8. Influence of host resistance on viral adaptation: hepatitis C virus as a case study

    PubMed Central

    Plauzolles, Anne; Lucas, Michaela; Gaudieri, Silvana

    2015-01-01

    Genetic and cellular studies have shown that the host’s innate and adaptive immune responses are an important correlate of viral infection outcome. The features of the host’s immune response (host resistance) reflect the coevolution between hosts and pathogens that has occurred over millennia, and that has also resulted in a number of strategies developed by viruses to improve fitness and survival within the host (viral adaptation). In this review, we discuss viral adaptation to host immune pressure via protein–protein interactions and sequence-specific mutations. Specifically, we will present the “state of play” on viral escape mutations to host T-cell responses in the context of the hepatitis C virus, and their influence on infection outcome. PMID:25897250

  9. Photo-distributed lichenoid eruption secondary to direct anti-viral therapy for hepatitis C.

    PubMed

    Simpson, Cory L; McCausland, Drew; Chu, Emily Y

    2015-10-01

    Novel direct anti-viral agents are emerging as effective treatments for hepatitis C virus (HCV) and provide an alternative to the year-long standard therapy with interferon and ribavirin. However, cutaneous side effects from these new medications, including rash, pruritus and photosensitivity, are among the most commonly reported adverse events and have resulted in therapy discontinuation in some cases. Here, we report two cases of a photo-distributed lichenoid eruption that occurred within 1  month of starting anti-viral therapy with simeprevir and sofosbuvir without interferon or ribavirin. This report provides the first histologic description of the cutaneous eruption associated with direct anti-viral therapy for HCV and highlights the importance of recognizing and treating the often intolerable dermatologic side effects of these novel medications, the incidence of which is likely to increase as direct anti-viral agents may become the standard of care for HCV. PMID:25974215

  10. Modeling viral and drug kinetics: hepatitis C virus treatment with pegylated interferon alfa-2b.

    PubMed

    Powers, Kimberly A; Dixit, Narendra M; Ribeiro, Ruy M; Golia, Preeti; Talal, Andrew H; Perelson, Alan S

    2003-01-01

    Administration of peginterferon alfa-2b plus ribavirin results in an early hepatitis C virus (HCV) RNA decay followed by an increase as the drug concentration declines between doses. Upon administration of the next dose 1 week later, the same pattern is observed. We have incorporated pharmacokinetic/pharmacodynamic analysis into a model of viral dynamics to describe the effect that changes in drug concentration and effectiveness can have on viral levels. To illustrate the relationship between pharmacokinetics and viral dynamics, we fit the model to data from four HCV/human immunodeficiency virus co-infected patients, and obtained good agreement with the measured serum HCV RNA levels. We were able to account for the observed increases in HCV RNA, and estimate virion and drug half-lives that are in agreement with previous reports. Models incorporating pharmacokinetics are needed to correctly interpret viral load changes and estimate drug effectiveness in treatment protocols using peginterferon alfa-2b. PMID:12934163

  11. [Hepatitis C patients' record in the Sentinel Units for viral Hepatitis in Argentina 2007- 2014. Distribution by year of birth].

    PubMed

    Vladimirsky, Sara Noemí; Munné, Maria Silvina; Otegui, Lucio Oscar; Altabert, Nancy Roxana; Soto, Sonia Soledad; Brajterman, Leonardo; González, Jorge Enrique

    2015-06-01

    Recommendations for Hepatitis C screening based on risk factorsfor transmission proved to be ineffcient. Accordingly, the CDC recommended to screen all American individuals born between 1945-1965, based on data from population prevalence of infection. The effectiveness of implementing these recommendations in other contexts and/or populations can be estimated, in principle, knowing the age distribution of infected individuals. There is no data on population prevalence in our country. Yet we can know the age distribution of cases of Hepatitis C who accessed the health system. The aim of this paper is to analyze the distribution by birth cohort ofcases registered as "Hepatitis C" in the Sentinel Units for Viral Hepatitis in the 2007-2014 period. This will contribute to the identification, if any, ofa cohort in which case the recommendation of screening could be addressed, based on risk factors inherent to our country and our epidemiological reality. The age distribution of our cases was wider and younger than those of the population supporting the recommendation of the CDC and this suggests -beyond the difference in the populations being compared- is due to a range of risk factors and age at different infection between USA and Argentina. Thus, based on these results, the recommendation of the Argentine Consensus for Hepatitis C in 2013 to screen all individuals once in life is supported. PMID:26353460

  12. Screening for viral hepatitis prior to rituximab chemotherapy.

    PubMed

    Leonard, A N; Love, B L; Norris, L B; Siddiqui, S K; Wallam, M N; Bennett, C L

    2016-01-01

    In 2008, the CDC published guidelines recommending screening of all persons undergoing treatment with rituximab to identify persons at risk of hepatitis B virus (HBV) reactivation. We evaluated implementation of this recommendation in veterans, who are at increased risk of HBV, and determined characteristics of those screened. We also evaluated a control setting, rates of hepatitis C virus (HCV) screening among the same rituximab-treated patients. There are no guidelines that recommend HCV screening prior to initiation of rituximab. Medical records of patients receiving rituximab between January 2006 and December 2012 were reviewed according to two time periods: 2006-2008 (period 1, pre-guidelines) and 2009-2012 (period 2, post-guidelines). Patient demographics, concomitant chemotherapy regimen (protocol, dose, duration), treatment indication, risk factors for hepatitis infection (substance abuse, homelessness, human immunodeficiency virus (HIV)), and HBV/HCV screening status were documented. During the study period, 102 patients were treated with rituximab (49 in period 1 and 53 in period 2). During periods 1 and 2, 22 and 32 % of rituximab-treated patients were screened for HBV, respectively (p = 0.375). Treatment during 2009 was the only significant predictor of HBV screening in the adjusted model (p = 0.01). For HCV during periods 1 and 2, 22 and 21 % of patients were screened, respectively (p = 1.00). There were no significant predictors of HCV screening. Rates of screening for HBV among rituximab-treated patients were low, both before and after dissemination of guidelines recommending universal HBV screening of rituximab-treated patients. PMID:26382277

  13. Hepatitis

    MedlinePlus

    ... be serious. Some can lead to scarring, called cirrhosis, or to liver cancer. Sometimes hepatitis goes away by itself. If it does not, it can be treated with drugs. Sometimes hepatitis lasts a lifetime. Vaccines can help prevent some viral forms.

  14. [Autoimmunization induced by interferon alpha therapy in chronic hepatitis C].

    PubMed

    Rocca, Pierre; Codes, Liana; Chevallier, Michèle; Trépo, Christian; Zoulim, Fabien

    2004-11-01

    We report the case of a 56 year-old woman with post-transfusion chronic hepatitis C who presented with a severe ALT flare up associated with a rapid progression of liver fibrosis during interferon alpha 2b therapy. Several hypotheses were considered to explain the etiology of this ALT flare: there was no viral super infection by other hepatotropic viruses, no toxic hepatitis, no metabolic disease, and no other specific liver diseases could be identified. HLA typing showed a specific profile A1 B8 DR3 (risk factor of auto-immunization during interferon alpha therapy) with antinuclear antibodies and anti smooth muscle antibodies. This case suggests that auto-immunization induced by interferon alpha should be investigated in case of ALT flare that is not followed by an HCV breakthrough. PMID:15657545

  15. Border Control in Hepatitis C Virus Infection: Inhibiting Viral Entry.

    PubMed

    Schweitzer, Cameron J; Liang, T Jake

    2015-09-11

    A new era has begun in the treatment of hepatitis C virus (HCV) infection with powerful yet expensive therapies. New treatments are emerging that target the entry step of HCV and could potentially block reinfection after liver transplant. These treatments include antibodies, which target the virus or host receptors required by HCV. Additionally, several new and previously approved small-molecule compounds have been described that target unique aspects of HCV entry. Overall, the blocking entry represents an attractive strategy that could yield powerful combination therapies to combat HCV. PMID:27617924

  16. New treatment strategies against hepatitis C viral infection

    PubMed Central

    Bilodeau, Marc; Lamarre, Daniel

    2006-01-01

    Treatment of hepatitis C virus infection is currently based on a combination of pegylated interferon and ribavirin. Because efficacy of this therapy remains suboptimal and side effects sometimes problematic, major efforts have been put forward by scientists and the pharmaceutical industry to develop alternative treatments for this chronic infection. Over the past few years, clinical studies performed with some of these new agents have been presented at major international meetings. The present paper aims to review the rationale underlying the development of these new forms of treatment as well as the current available data concerning their clinical efficacy. PMID:17111056

  17. Hepatitis B virus e antigen induces activation of rat hepatic stellate cells

    SciTech Connect

    Zan, Yanlu; Zhang, Yuxia; Tien, Po

    2013-06-07

    Highlights: •HBeAg expression in HSCs induced production of ECM protein and liver fibrotic markers. •The activation and proliferation of HSCs were mediated by TGF-β. •HBeAg protein purified from cell medium directly activated HSCs. -- Abstract: Chronic hepatitis B virus infection is a major cause of hepatic fibrosis, leading to liver cirrhosis and hepatocellular carcinoma. Hepatitis B virus e antigen (HBeAg) is an accessory protein of HBV, not required for viral replication but important for natural infection in vivo. Hepatic stellate cells (HSCs) are the major producers of excessive extracellular matrix during liver fibrogenesis. Therefore, we examined the influence of HBeAg on HSCs. The rat HSC line HSC-T6 was transfected with HBeAg plasmids, and expression of α-smooth muscle actin, collagen I, transforming growth factor-β1 (TGF-β), and tissue inhibitors of metalloproteinase 1 (TIMP-1) was investigated by quantitative real-time PCR. The proliferation of HSCs was determined by MTS analysis. HBeAg transduction induced up-regulation of these fibrogenic genes and proliferation of HSCs. We found that HBeAg induced TGF-β secretion in HSCs, and the activation of HSCs was prevented by a neutralizing anti-TGF-β antibody. Depletion and addition of HBeAg protein in conditioned medium from HSC-T6 cells transduced with HBeAg indicated that HBeAg directly induced the activation and proliferation of rat primary HSCs. Taken together, HBeAg induces the activation and proliferation of HSCs, mainly mediated by TGF-β, and HBeAg protein purified from cell medium can directly activate HSCs.

  18. Inhibition of hepatitis C virus replication and viral helicase by ethyl acetate extract of the marine feather star Alloeocomatella polycladia.

    PubMed

    Yamashita, Atsuya; Salam, Kazi Abdus; Furuta, Atsushi; Matsuda, Yasuyoshi; Fujita, Osamu; Tani, Hidenori; Fujita, Yoshihisa; Fujimoto, Yuusuke; Ikeda, Masanori; Kato, Nobuyuki; Sakamoto, Naoya; Maekawa, Shinya; Enomoto, Nobuyuki; Nakakoshi, Masamichi; Tsubuki, Masayoshi; Sekiguchi, Yuji; Tsuneda, Satoshi; Akimitsu, Nobuyoshi; Noda, Naohiro; Tanaka, Junichi; Moriishi, Kohji

    2012-04-01

    Hepatitis C virus (HCV) is a causative agent of acute and chronic hepatitis, leading to the development of hepatic cirrhosis and hepatocellular carcinoma. We prepared extracts from 61 marine organisms and screened them by an in vitro fluorescence assay targeting the viral helicase (NS3), which plays an important role in HCV replication, to identify effective candidates for anti-HCV agents. An ethyl acetate-soluble fraction of the feather star Alloeocomatella polycladia exhibited the strongest inhibition of NS3 helicase activity, with an IC(50) of 11.7 µg/mL. The extract of A. polycladia inhibited interaction between NS3 and RNA but not ATPase of NS3. Furthermore, the replication of the replicons derived from three HCV strains of genotype 1b in cultured cells was suppressed by the extract with an EC(50) value of 23 to 44 µg/mL, which is similar to the IC(50) value of the NS3 helicase assay. The extract did not induce interferon or inhibit cell growth. These results suggest that the unknown compound(s) included in A. polycladia can inhibit HCV replication by suppressing the helicase activity of HCV NS3. This study may present a new approach toward the development of a novel therapy for chronic hepatitis C. PMID:22690141

  19. Human hepatitis B viral e antigen and its precursor P20 inhibit T lymphocyte proliferation

    SciTech Connect

    Purvina, Maija; Hoste, Astrid; Rossignol, Jean-Michel; Lagaudriere-Gesbert, Cecile

    2012-01-27

    Highlights: Black-Right-Pointing-Pointer P20, precursor of the HBeAg, interacts with the cellular protein gC1qR. Black-Right-Pointing-Pointer HBeAg and P20 bind to T cell surface and inhibit mitogen-induced T cell division. Black-Right-Pointing-Pointer HBeAg and P20 inhibition of T cell proliferation is gC1qR and IL-1RAcP-independent. -- Abstract: The hepatitis B virus (HBV) Precore protein is processed through the secretory pathway directly as HBeAg or with the generation of an intermediate (P20). Precore gene has been shown to be implicated in viral persistence, but the functions of HBeAg and its precursors have not been fully elucidated. We show that the secreted proteins HBeAg and P20 interact with T cell surface and alter Kit-225 and primary T cells proliferation, a process which may facilitate the establishment of HBV persistence. Our data indicate that the N-terminal end of Precore is important for these inhibitory effects and exclude that they are dependent on the association of HBeAg and P20 with two characterized cell surface ligands, the Interleukin-1 Receptor Accessory Protein and gC1qR (present study).

  20. Integration of hepatitis B vaccination into national immunisation programmes. Viral Hepatitis Prevention Board.

    PubMed Central

    Van Damme, P.; Kane, M.; Meheus, A.

    1997-01-01

    Hepatitis B is a major public health problem even though safe and effective vaccines have been available for over 10 years. Because hepatitis B infection is largely asymptomatic with long term complications occurring after many years it has not received the attention it deserves. Strategies to immunise those at high risk have failed to control the disease. Delegates to the World Health Assembly of the World Health Organisation recommended in May 1992 that all countries should integrate hepatitis B vaccination into their national immunisation programmes by 1997. Some western European countries remain unconvinced that the burden of disease warrants the expense of universal vaccination. However, epidemiological data and economic evaluation show that universal hepatitis B vaccination is cost effective in countries with low endemicity and that it will control hepatitis B, reinforcing the necessity for action. PMID:9112852

  1. Viral hepatitis in the U.S. Air Force, 1980-89: an epidemiological and serological study.

    PubMed

    Stout, R W; Mitchell, S B; Parkinson, M D; Warner, R D; Miles, R E; Franz, B D; Wolfe, W H

    1994-05-01

    This paper reports the epidemiology of hospital-diagnosed acute viral hepatitis in U.S. Air Force personnel from 1980-89. First hospitalizations for viral hepatitis generally declined, ranging from 24.6 to 47.2 per 100,000 personnel. Hepatitis rates were higher among men, (RR = 1.3; 95% C.I., 1.1-1.5) and higher among blacks, compared to whites (RR = 1.4; 95% C.I., 1.3-1.6). Analysis of risk associated with various occupations demonstrated an increased risk of viral hepatitis for procedurally oriented medical personnel (physicians, clinical nurses, dentists) when compared to all other occupations (RR = 1.5; 95% C.I., 1.1-1.9). Pilots and navigators demonstrated a decreased risk of acute viral hepatitis. Members hospitalized for hepatitis B had a prior or concurrent diagnosis for sexually transmitted disease in 37% of cases; for drug abuse, 32% of cases. Serum samples from 332 individuals demonstrated that hepatitis A had the highest rate of agreement (84%) between serology and hospital discharge diagnosis. Only 3% of individuals with the diagnosis of NANB hepatitis were positive for hepatitis C. PMID:8018082

  2. Hepatitis C: Clinical Trials

    MedlinePlus

    ... 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 ...

  3. [Consequences of extrahepatic manifestations of hepatitis C viral infection (HCV)].

    PubMed

    Pawełczyk, Agnieszka

    2016-01-01

    The hepatitis C virus (HCV) is a primarily hepatotropic virus. However, numerous extrahepatic symptoms are observed in patients chronically infected with HCV, e.g. cryoglobulinemia, lymphoproliferative disorders, kidney diseases, disturbances of the central and peripheral nervous system, thyroid gland, pancreas, lymph nodes and pituitary gland, that develop at various times after the infection. Complex mechanisms underlie these processes, both molecular, related to direct effects of the virus on cells or tissues and indirect mechanisms, resulting from the response of the immune system to infection (via cytokines or oxidative stress), and from the antiviral treatment used. Understanding these mechanisms may contribute to the definition of new prognostic factors, important for the early diagnosis of the infection, which in turn may improve treatment efficacy. This paper is a review of the incidence of selected extrahepatic manifestations of HCV infection and their underlying pathogenetic mechanisms and risk factors. PMID:27117111

  4. Observational descriptive study of cutaneous manifestations in patients from Mato Grosso with viral chronic hepatitis*

    PubMed Central

    Rostey, Renato Roberto Liberato; Souto, Francisco José Dutra

    2015-01-01

    BACKGROUND Extrahepatic manifestations are seen in association with chronic infection by hepatitis B or C virus including cutaneous disorders. The frequency of these findings seems to vary among different places and reports. There is a lack of information about this issue in Brazil. OBJECTIVES To estimate the prevalence of cutaneous findings affecting HBV or HCV carriers from a reference outpatient unit in Mato Grosso. METHODS A cross-sectional observational study. RESULTS 108 patients were studied. 88.9% presented some cutaneous findings but must of them were nonrelated to chronic viral infection. Four patients had cutaneous or autoimmune syndromes that may be HBV or HCV related. CONCLUSION In our study we found no statistical association between viral hepatitis and skin diseases. PMID:26734863

  5. Hepatitis C Virus NS2 Protein Triggers Endoplasmic Reticulum Stress and Suppresses its Own Viral Replication

    PubMed Central

    von dem Bussche, Annette; Machida, Raiki; Li, Ke; Loevinsohn, Gideon; Khander, Amrin; Wang, Jianguo; Wakita, Takaji; Wands, Jack R.; Li, Jisu

    2010-01-01

    Background & Aims We previously reported that the NS2 protein of hepatitis C virus (HCV) inhibits the expression of reporter genes driven by a variety of cellular and viral promoters. The aim of the study was to determine whether the broad transcriptional repression is caused by endoplasmic reticulum (ER) stress. Methods Phosphorylation of the translation initiation factor eIF2α and HCV replication were detected by Western and Northern blot, respectively. De novo protein synthesis was measured by metabolic labeling. Activation of ER stress responsive genes was determined by promoter reporter assay, as well as mRNA and protein measurement by real time PCR and Western blot. Results Transient or inducible NS2 protein expression increased eIF2α phosphorylation and reduced de novo protein synthesis. It up-regulated promoter activities and transcript levels of ER stress inducible genes including GRP78, ATF6, and GADD153, as well as GRP78 protein level. The same effect was observed when NS2 was synthesized as part of the core-E1-E2-p7-NS2 polypeptide. NS2 protein also inhibited reporter gene expression from the HCV internal ribosome entry site and consequently reduced HCV replication. The full-length HCV replicon activated GRP78, ATF6, and GADD153 promoters more efficiently than the subgenomic replicon lacking the coding sequence for both the structural proteins and NS2. Abrogation of HCV infection/replication, by an inhibitor of the NS3 protease, relieved ER stress. Conclusions HCV infection can induce ER stress, with NS2 protein being a major mediator. The stress can be relieved by a feedback mechanism. PMID:20801537

  6. Peripheral blood mononuclear cells and regulatory T cells in acute viral hepatitis.

    PubMed Central

    Barnaba, V; Tamburrini, E; Laghi, V; Cauda, R; Levrero, M; Ruocco, G; Ortona, L; Balsano, F

    1985-01-01

    During acute viral hepatitis, we observed a significant decrease in OKT4/OKT8 ratio with a significant increase in the OKT8 positive subset in acute type B and non-A-non-B hepatitis. This altered ratio persisted in type B for a long time until HBsAg antibody became detectable, while it soon returned to normal in type A and non-A-non-B hepatitis. In the majority of acute hepatitis the altered ratio is because of an increase and not to a decrease in the whole T cell population, as described in chronic HBV infection. The number of HNK-1 positive cells remained raised during the recovery phase of type B and non-A-non-B hepatitis, a finding consistent with the hypothesis that NK cells play a role in the host defence against B and non-A-non-B virus infections. Serum beta 2-microglobulin concentrations were increased only in acute hepatitis B and non-A-non-B where immunological mechanisms are suspected to be involved, and showed a good correlation with the population of activated OKIa positive cells. PMID:2862096

  7. Genotypes and viral variants in chronic hepatitis B: A review of epidemiology and clinical relevance

    PubMed Central

    Croagh, Catherine MN; Desmond, Paul V; Bell, Sally J

    2015-01-01

    The Hepatitis B Virus (HBV) has a worldwide distribution and is endemic in many populations. It is constantly evolving and 10 genotypic strains have been identified with varying prevalences in different geographic regions. Numerous stable mutations in the core gene and in the surface gene of the HBV have also been identified in untreated HBV populations. The genotypes and viral variants have been associated with certain clinical features of HBV related liver disease and Hepatocellular carcinoma. For example Genotype C is associated with later hepatitis B e antigen (HBeAg) seroconversion, and more advanced liver disease. Genotype A is associated with a greater risk of progression to chronicity in adult acquired HBV infections. Genotype D is particularly associated with the precore mutation and HBeAg negative chronic hepatitis B (CHB). The genotypes prevalent in parts of West Africa, Central and South America, E, F and H respectively, are less well studied. Viral variants especially the Basal Core Promotor mutation is associated with increased risk of fibrosis and cancer of the liver. Although not currently part of routine clinical care, evaluation of genotype and viral variants may provide useful adjunctive information in predicting risk about liver related morbidity in patients with CHB. PMID:25848459

  8. Multi-scale model for hepatitis C viral load kinetics under treatment with direct acting antivirals.

    PubMed

    Clausznitzer, Diana; Harnisch, Julia; Kaderali, Lars

    2016-06-15

    Hepatitis C virus (HCV) infections are a global health problem, and extensive research over the last decades has been targeted at understanding its molecular biology and developing effective antiviral treatments. Recently, a number of potent direct acting antiviral drugs have been developed targeting specific processes in the viral life cycle. Here, we developed a mathematical multi-scale model of the within-host dynamics of HCV infection by integrating a standard model for viral infection with a detailed model of the viral replication cycle inside infected cells. We use this model to study patient time courses of viral load under treatment with daclatasvir, an inhibitor of the viral non-structural protein NS5A. Model analysis predicts that treatment efficacy can be increased by combining daclatasvir with dedicated viral polymerase inhibitors, corresponding to promising current strategies in drug development. Hence, our model presents a predictive tool for in silico simulations, which can be used to study and optimize direct acting antiviral drug treatment. PMID:26409026

  9. Hepatitis C: Sex and Sexuality

    MedlinePlus

    ... 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 ...

  10. Evaluation of Percutaneous Liver Biopsy Complications in Patients with Chronic Viral Hepatitis

    PubMed Central

    Kose, Sukran; Ersan, Gursel; Tatar, Bengu; Adar, Pelin; Sengel, Buket Erturk

    2015-01-01

    Objective: Liver biopsy is still the gold standard for the determination of liver fibrosis and necroinflammatory activity. It is an invasive method and may lead to severe complications. The aim of this study was to determine the evaluation of percutaneous liver biopsy complications in patients with chronic viral hepatitis. Materials and Methods: 1165 patients, who were followed with the diagnosis of chronic viral hepatitis and who were applied percutaneous liver biopsy between January 2000 and February 2013 at the out-patient clinic of Infectious Diseases and Clinical Microbiology, were included in the study. Results: Of 1165 patients who underwent liver biopsy, 196 (86 male, 110 female) were diagnosed with chronic hepatitis C, 969 (559 male, 410 female) were diagnosed with chronic hepatitis B. The mean age was 43.3 and 55.4% were male. 11% of the patients were diagnosed with chronic renal failure and underwent haemodialysis. Minor complication rate was about 20% (severe pain required usage of analgesic drugs in 19.8%, abdominal pain in 22.6%) whereas major complication rate was 1.15% (pneumothorax in 0.17%, heamobilia in 0.08%, hematoma in 0.9%). We did not observe severe complications such as fever, abscess, anaphylaxis, bacteraemia, organ perforations, sepsis or death. Conclusion: Despite being an invasive procedure, percutaneous liver biopsy can be considered a safe method because of the low rates of severe complications observed in our patients. PMID:26644763

  11. Specific CD8+ T cell response immunotherapy for hepatocellular carcinoma and viral hepatitis

    PubMed Central

    Moreno-Cubero, Elia; Larrubia, Juan-Ramón

    2016-01-01

    Hepatocellular carcinoma (HCC), chronic hepatitis B (CHB) and chronic hepatitis C (CHC) are characterized by exhaustion of the specific CD8+ T cell response. This process involves enhancement of negative co-stimulatory molecules, such as programmed cell death protein-1 (PD-1), cytotoxic T-lymphocyte antigen-4 (CTLA-4), 2B4, Tim-3, CD160 and LAG-3, which is linked to intrahepatic overexpression of some of the cognate ligands, such as PD-L1, on antigen presenting cells and thereby favouring a tolerogenic environment. Therapies that disrupt these negative signalling mechanisms represent promising therapeutic tools with the potential to restore reactivity of the specific CD8+ T cell response. In this review we discuss the impressive in vitro and in vivo results that have been recently achieved in HCC, CHB and CHC by blocking these negative receptors with monoclonal antibodies against these immune checkpoint modulators. The article mainly focuses on the role of CTLA-4 and PD-1 blocking monoclonal antibodies, the first ones to have reached clinical practice. The humanized monoclonal antibodies against CTLA-4 (tremelimumab and ipilimumab) and PD-1 (nivolumab and pembrolizumab) have yielded good results in testing of HCC and chronic viral hepatitis patients. Trelimumab, in particular, has shown a significant increase in the time to progression in HCC, while nivolumab has shown a remarkable effect on hepatitis C viral load reduction. The research on the role of ipilimumab, nivolumab and pembrolizumab on HCC is currently underway.

  12. Specific CD8(+) T cell response immunotherapy for hepatocellular carcinoma and viral hepatitis.

    PubMed

    Moreno-Cubero, Elia; Larrubia, Juan-Ramón

    2016-07-28

    Hepatocellular carcinoma (HCC), chronic hepatitis B (CHB) and chronic hepatitis C (CHC) are characterized by exhaustion of the specific CD8(+) T cell response. This process involves enhancement of negative co-stimulatory molecules, such as programmed cell death protein-1 (PD-1), cytotoxic T-lymphocyte antigen-4 (CTLA-4), 2B4, Tim-3, CD160 and LAG-3, which is linked to intrahepatic overexpression of some of the cognate ligands, such as PD-L1, on antigen presenting cells and thereby favouring a tolerogenic environment. Therapies that disrupt these negative signalling mechanisms represent promising therapeutic tools with the potential to restore reactivity of the specific CD8(+) T cell response. In this review we discuss the impressive in vitro and in vivo results that have been recently achieved in HCC, CHB and CHC by blocking these negative receptors with monoclonal antibodies against these immune checkpoint modulators. The article mainly focuses on the role of CTLA-4 and PD-1 blocking monoclonal antibodies, the first ones to have reached clinical practice. The humanized monoclonal antibodies against CTLA-4 (tremelimumab and ipilimumab) and PD-1 (nivolumab and pembrolizumab) have yielded good results in testing of HCC and chronic viral hepatitis patients. Trelimumab, in particular, has shown a significant increase in the time to progression in HCC, while nivolumab has shown a remarkable effect on hepatitis C viral load reduction. The research on the role of ipilimumab, nivolumab and pembrolizumab on HCC is currently underway. PMID:27605882

  13. Immunoglobulin M-specific serologic testing in an outbreak of foodborne viral hepatitis, type A.

    PubMed

    Osterholm, M T; Kantor, R J; Bradley, D W; Hall, W N; Francis, D P; Aaron, H C; Washburn, J W; Velde, D

    1980-07-01

    Ninety-seven symptomatic and five asymptomatic infections with viral hepatitis, type A (102 cases) were identified in members, guests and employees of a private country club in an outbreak associated with consuming food and ice prepared or handled by an employee of the club's kitchen pantry. Twenty-three symptomatic persons were tested by differential radioimmunoassay for immunoglobulin M (IgM) (acute-phase) hepatitis A antibody (anti-HAV) and all 23 were documented to be infected with hepatitis A virus (HAV). Forty-one member/guest cases had only a single exposure at the county club. Their incubation periods ranged from 21 to 40 days, with a mean of 30 days. The exposure of these single-day patrons occurred over a 14-day period. The index case was not icteric and only moderately symptomatic and was diagnosed retrospectively to have viral hepatitis, type A by serologic determination of IgM anti-HAV in blood samples. Four items implicated in disease transmission were potato salad, hot dogs, molded salmon and ice handled by the index case. Serologic screening of controls did not appear to alter the conclusions of the food item analysis. PMID:6249120

  14. Hepatitis C Viral Infection in Children: Updated Review

    PubMed Central

    2016-01-01

    Hepatitis C virus (HCV) infection is a major medical challenge affecting around 200 million people worldwide. The main site of HCV replication is the hepatocytes of the liver. HCV is a positive enveloped RNA virus from the flaviviridae family. Six major HCV genotypes are implicated in the human infection. In developed countries the children are infected mainly through vertical transmission during deliveries, while in developing countries it is still due to horizontal transmission from adults. Minimal nonspecific and brief symptoms are initially found in approximately 15% of children. Acute and chronic HCV infection is diagnosed through the recognition of HCV RNA. The main objective for treatment of chronic HCV is to convert detected HCV viremia to below the detection limit. Children with chronic HCV infection are usually asymptomatic and rarely develop severe liver damage. Therefore, the benefits from current therapies, pegylated-Interferon plus ribavirin, must be weighed against their adverse effects. This combined treatment offers a 50-90% chance of clearing HCV infection according to several studies and on different HCV genotype. Recent direct acting antiviral (DAA) drugs which are well established for adults have not yet been approved for children and young adults below 18 years. The most important field for the prevention of HCV infection in children would be the prevention of perinatal and parenteral transmission. There are areas of focus for new lines of research in pediatric HCV-related disease that can be addressed in the near future. PMID:27437184

  15. Cell surface expression of LDL receptor in chronic hepatitis C: correlation with viral load.

    PubMed

    Petit, Jean-Michel; Minello, Anne; Duvillard, Laurence; Jooste, Valérie; Monier, Serge; Texier, Véronique; Bour, Jean-Baptiste; Poussier, Alix; Gambert, Philippe; Verges, Bruno; Hillon, Patrick

    2007-07-01

    The LDL receptor (LDL-R) has been proposed as the viral receptor for Hepatitis C virus (HCV). This hypothesis has been based exclusively on in vitro studies. In human mononuclear cells, LDL-R gene expression has been demonstrated to be parallel and be coordinately regulated to gene expression in the human liver. The purpose of the current study was to determine the mononuclear cell surface expression of the LDL receptor in patients with HCV chronic infection according to viral load. Sixty-eight consecutive untreated chronic hepatitis C patients were studied to determine the mononuclear cell surface expression of the LDL-R. LDL-Rs were quantified at the surface of mononuclear cells in fresh blood samples taken after fasting using flow cytometry. LDL-R expression was significantly associated with LDL-cholesterol (r = -0.25; P = 0.03) and HCV-viral load (r = 0.37, P = 0.002). In multivariate analysis, the LDL-R expression was significantly associated with HCV viral load, whereas genotype, age, body mass index, and fibrosis were not. In conclusion, our data provided by a human study, suggest that the LDL-R may be one of the receptors implicated in HCV replication. PMID:17473053

  16. Antihistamine-Induced Hepatitis: 2 Cases Involving Loratidine

    PubMed Central

    Arshad, Hafiz; Khan, Arsalan; Assad, Usama; Kittaneh, Muaiad

    2016-01-01

    Antihistamine-induced hepatitis is rare. We present 2 cases of antihistamine-induced hepatitis with autoimmune features, caused by loratidine. One case was confirmed by rechallenge. Identifying and discontinuing the offending agent are essential for treatment. PMID:27293922

  17. Acute and chronic drug-induced hepatitis.

    PubMed

    Pessayre, D; Larrey, D

    1988-04-01

    Adverse drug reactions may mimic almost any kind of liver disease. Acute hepatitis is often due to the formation of reactive metabolites in the liver. Despite several protective mechanisms (epoxide hydrolases, conjugation with glutathione), this formation may lead to predictable toxic hepatitis after hugh overdoses (e.g. paracetamol), or to idiosyncratic toxic hepatitis after therapeutic doses (e.g. isoniazid). Both genetic factors (e.g. constitutive levels of cytochrome P-450 isoenzymes, or defects in protective mechanisms) and acquired factors (e.g. malnutrition, or chronic intake of alcohol or other microsomal enzyme inducers) may explain the unique susceptibility of some patients. Formation of chemically reactive metabolites may also lead to allergic hepatitis, probably through immunization against plasma membrane protein epitopes modified by the covalent binding of the reactive metabolites. This may be the mechanism for acute hepatitis produced by many drugs (e.g. amineptine, erythromycin derivatives, halothane, imipramine, isaxonine, alpha-methyldopa, tienilic acid, etc.). Genetic defects in several protective mechanisms (e.g. epoxide hydrolase, acetylation) may explain the unique susceptibility of some patients, possibly by increasing exposure to allergenic, metabolite-altered plasma membrane protein epitopes. Like toxic idiosyncratic hepatitis, allergic hepatitis occurs in a few patients only. Unlike toxic hepatitis, allergic hepatitis is frequently associated with fever, rash or other hypersensitivity manifestations; it may be hepatocellular, mixed or cholestatic; it promptly recurs after inadvertent drug rechallenge. Lysosomal phospholipidosis occurs frequently with three antianginal drugs (diethylaminoethoxyhexestrol, amiodarone and perhexiline). These cationic, amphiphilic drugs may form phospholipid-drug complexes within lysosomes. Such complexes resist phospholipases and accumulate within enlarged lysosomes, forming myeloid figures. This

  18. Viral cross talk: intracellular inactivation of the hepatitis B virus during an unrelated viral infection of the liver.

    PubMed Central

    Guidotti, L G; Borrow, P; Hobbs, M V; Matzke, B; Gresser, I; Oldstone, M B; Chisari, F V

    1996-01-01

    Hepatitis B virus (HBV) infection is thought to be controlled by virus-specific cytotoxic T lymphocytes (CTL). We have recently shown that HBV-specific CTL can abolish HBV replication noncytopathically in the liver of transgenic mice by secreting tumor necrosis factor alpha (TNF-alpha) and interferon gamma (IFN-gamma) after antigen recognition. We now demonstrate that hepatocellular HBV replication is also abolished noncytopathically during lymphocytic choriomeningitis virus (LCMV) infection, and we show that this process is mediated by TNF-alpha and IFN-alpha/beta produced by LCMV-infected hepatic macrophages. These results confirm the ability of these inflammatory cytokines to abolish HBV replication; they elucidate the mechanism likely to be responsible for clearance of HBV in chronically infected patients who become superinfected by other hepatotropic viruses; they suggest that pharmacological activation of intrahepatic macrophages may have therapeutic value in chronic HBV infection; and they raise the possibility that conceptually similar events may be operative in other viral infections as well. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 PMID:8643448

  19. Clinical application of transient elastography in patients with chronic viral hepatitis receiving antiviral treatment.

    PubMed

    Kim, Jun Hyung; Kim, Mi Na; Han, Kwang-Hyub; Kim, Seung Up

    2015-04-01

    Accurate evaluation of the degree of liver fibrosis in patients with chronic liver diseases (CLD) is crucial, as liver fibrosis is important in determining the prognosis of liver diseases. Currently, liver biopsy (LB) is considered the gold standard for staging liver fibrosis or cirrhosis. However, utilization of LB in clinical practice is often limited because of its invasive nature, sampling error and interobserver variability. Recently, transient elastography (TE) was introduced as a noninvasive, highly reproducible technique for assessing the degree of liver fibrosis. After extensive studies, TE is now regarded as a reliable surrogate marker for grading the severity of liver fibrosis in patients with CLD. In the past few years, the role of TE in monitoring liver stiffness and determining prognosis in patients with chronic hepatitis B (CHB) or chronic hepatitis C (CHC) who are undergoing antiviral treatment has been investigated. In patients with CHB, liver stiffness values decrease with antiviral treatment. TE can also be used to predict the incidence of liver-related events during antiviral treatment. In patients with CHC, TE can be used to monitor potential regression of liver fibrosis after antiviral treatment and may predict the treatment outcome of CHC. In addition, TE is an adjunct tool for distinguishing inactive hepatitis B virus carriers from patients with chronic active hepatitis. This review article discusses the important findings from recent studies focusing on the clinical application of TE in patients with chronic viral hepatitis who are undergoing antiviral treatments. PMID:24976523

  20. Hepatitis B viral infection of hepatic progenitor cells. Resolving unresolved questions?

    PubMed

    Minuk, G Y; Baruch, Y

    2016-06-01

    Accumulated data to date do not entirely explain the; propensity of the hepatitis B virus (HBV) to cause chronic infections in newborns; failure of antiviral agents to resolve infections or precise mechanism whereby HBV causes hepatocellular carcinoma (HCC). Based on the increased numbers of hepatic stem/progenitor cells (HPCs) present within the neonatal liver, the refractoriness of these cells to the effects of interferons and xenobiotics and their ability to undergo malignant transformation, we hypothesize that HBV infection of HPCs could explain these and perhaps other clinical features of chronic HBV. PMID:27142136

  1. Liver Shear-Wave Velocity and Serum Fibrosis Markers to Diagnose Hepatic Fibrosis in Patients with Chronic Viral Hepatitis B

    PubMed Central

    Liu, Jianxue; Ji, Yonghao; Ai, Hong; Ning, Bo; Zhao, Junzhi; Zhang, Yaoren

    2016-01-01

    Objective To compare several noninvasive indices of fibrosis in chronic viral hepatitis B, including liver shear-wave velocity (SWV), hyaluronic acid (HA), collagen type IV (CIV), procollagen type III (PCIII), and laminin (LN). Materials and Methods Acoustic radiation force impulse (ARFI) was performed in 157 patients with chronic viral hepatitis B and in 30 healthy volunteers to measure hepatic SWV (m/s) in a prospective study. Serum markers were acquired on the morning of the same day of the ARFI evaluation. Receiver operating characteristic (ROC) analysis was performed to evaluate and compare the accuracies of SWV and serum markers using METAVIR scoring from liver biopsy as a reference standard. Results The most accurate test for diagnosing fibrosis F ≥ 1 was SWV with the area under the ROC curve (AUC) of 0.913, followed by LN (0.744), HA (0.701), CIV (0.690), and PCIII (0.524). The best test for diagnosing F ≥ 2 was SWV (AUC of 0.851), followed by CIV (0.671), HA (0.668), LN (0.562), and PCIII (0.550). The best test for diagnosing F ≥ 3 was SWV (0.854), followed by CIV (0.693), HA (0.675), PCIII (0.591), and LN (0.548). The best test for diagnosing F = 4 was SWV (0.965), followed by CIV (0.804), PCIII (0.752), HA (0.744), and LN (0.662). SWV combined with HA and CIV did not improve diagnostic accuracy (AUC = 0.931 for F ≥ 1, 0.863 for F ≥ 2, 0.855 for F ≥ 3, 0.960 for F = 4). Conclusion The performance of SWV in diagnosing liver fibrosis is superior to that of serum markers. However, the combination of SWV, HA, and CIV does not increase the accuracy of diagnosing liver fibrosis and cirrhosis. PMID:27134527

  2. Role of chemokines and their receptors in viral persistence and liver damage during chronic hepatitis C virus infection.

    PubMed

    Larrubia, Juan R; Benito-Martínez, Selma; Calvino, Miryam; Sanz-de-Villalobos, Eduardo; Parra-Cid, Trinidad

    2008-12-21

    Chemokines produced in the liver during hepatitis C virus (HCV) infection induce migration of activated T cells from the periphery to infected parenchyma. The milieu of chemokines secreted by infected hepatocytes is predominantly associated with the T-helper cell/Tc1 T cell (Th1/Tc1) response. These chemokines consist of CCL3 (macrophage inflammatory protein-1 alpha; MIP-1 alpha), CCL4 (MIP-1 beta), CCL5 (regulated on activation normal T cell expressed and secreted; RANTES), CXCL10 (interferon-gamma-inducible protein-10; IP-10), CXCL11 (interferon-inducible T-cell alpha chemoattractant; I-TAC), and CXCL9 (monokine induced by interferon gamma; Mig) and they recruit T cells expressing either CCR5 or CXCR3 chemokine receptors. Intrahepatic and peripheral blood levels of these chemokines are increased during chronic hepatitis C. The interaction between chemokines and their receptors is essential in recruiting HCV-specific T cells to control the infection. When the adaptive immune response fails in this task, non-specific T cells without the capacity to control the infection are also recruited to the liver, and these are ultimately responsible for the persistent hepatic damage. The modulation of chemokine receptor expression and chemokine secretion could be a viral escape mechanism to avoid specific T cell migration to the liver during the early phase of infection, and to maintain liver viability during the chronic phase, by impairing non-specific T cell migration. Some chemokines and their receptors correlate with liver damage, and CXCL10 (IP-10) and CXCR3 levels have shown a clinical utility as predictors of treatment response outcome. The regulation of chemokines and their receptors could be a future potential therapeutic target to decrease liver inflammation and to increase specific T cell migration to the infected liver. PMID:19084927

  3. A comparative review of HLA associations with hepatitis B and C viral infections across global populations

    PubMed Central

    Singh, Rashmi; Kaul, Rashmi; Kaul, Anil; Khan, Khalid

    2007-01-01

    Hepatitis B (HBV) and hepatitis C (HCV) viral infection or co-infection leads to risk of development of chronic infection, cirrhosis and hepatocellular carcinoma (HCC). Immigration and globalization have added to the challenges of public health concerns regarding chronic HBV and HCV infections worldwide. The aim of this study is to review existing global literature across ethnic populations on HBV and HCV related human leukocyte antigen (HLA) associations in relation to susceptibility, viral persistence and treatment. Extensive literature search was conducted to explore the HLA associations in HBV and HCV infections reported across global populations over the past decade to understand the knowledge status, weaknesses and strengths of this information in different ethnic populations. HLA DR13 is consistently associated with HBV clearance globally. HLADRB1*11/*12 alleles and DQB1*0301 are associated with HBV persistence but with HCV clearance worldwide. Consistent association of DRB1*03 and *07 is observed with HCV susceptibility and non-responsiveness to HBV vaccination across the population. HLA DR13 is protective for vertical HBV and HCV transmission in Chinese and Italian neonates, but different alleles are associated with their susceptibility in these populations. HLA class Imolecule interactions with Killer cell immunoglobulin like receptors (KIR) of natural killer (NK) cells modulate HCV infection outcome via regulating immune regulatory cells and molecules. HLA associations with HBV vaccination, interferon therapy in HBV and HCV, and with extra hepatic manifestations of viral hepatitis are also discussed. Systematic studies in compliance with global regulatory standards are required to identify the HLA specific viral epitope, stage specific T cell populations interacting with different HLA alleles during disease progression and viral clearance of chronic HBV or HCV infections among different ethnic populations. These studies would facilitate stage specific

  4. Prevalence of Hepatitis B and C Viral Infection Among Pregnant Women in Peshawar, Pakistan

    PubMed Central

    Ahmad, Irshad

    2016-01-01

    Background Viral hepatitis during pregnancy is associated with a high risk of maternal complications. The virus has a high risk of vertical transmission and it has been reported as the leading cause of maternal death. Objectives To study the prevalence of hepatitis B (HBV) and hepatitis C (HCV) viral infections among pregnant women in the Peshawar district of Pakistan. Materials and Methods The cross-sectional study took place between July 2013 and April 2014. A total of 10,288 samples were collected from pregnant women living in different areas of the Peshawar district. The samples were centrifuged at a high speed in order to obtain a clear supernatant serum. All samples were screened for HBV and HCV using the immunochromatographic technique. Results The overall prevalence of HBV was found to be 1.16%, although it varied throughout the study period. The highest prevalence of HBV (1.69%) was observed during January 2014. The overall prevalence of HCV infection among the pregnant women was observed to be 1.42%. The highest prevalence of HCV infection (2.22%) was found during March 2014. Conclusions The overall prevalence of HBV and HCV was 1.16% and 1.42%, respectively. The incidence of HCV infection among the pregnant women was higher than that of HBV infection.

  5. Molecular mechanism of hepatitis B virus-induced hepatocarcinogenesis

    PubMed Central

    Tarocchi, Mirko; Polvani, Simone; Marroncini, Giada; Galli, Andrea

    2014-01-01

    Hepatitis B virus (HBV) infection is a global public health problem with approximately 2 billion people that have been exposed to the virus. HBV is a member of a family of small, enveloped DNA viruses called hepadnaviruses, and has a preferential tropism for hepatocytes of mammals and birds. Epidemiological studies have proved a strong correlation between chronic hepatitis B virus infection and the development of hepatocellular carcinoma (HCC). HCC is the fifth most common malignancy with about 700000 new cases each year, and more than 50% of them arise in HBV carriers. A large number of studies describe the way in which HBV can contribute to HCC development. Multiple mechanisms have been proposed, including the accumulation of genetic damage due to immune-mediated hepatic inflammation and the induction of oxidative stress. There is evidence of the direct effects of the viral proteins HBx and HBs on the cell biology. Integration of HBV-DNA into the human genome is considered an early event in the carcinogenic process and can induce, through insertional mutagenesis, the alteration of gene expression and chromosomal instability. HBV has also epigenetic effects through the modification of the genomic methylation status. Furthermore, the virus plays an important role in the regulation of microRNA expression. This review will summarize the many mechanisms involved in HBV-related liver carcinogenesis. PMID:25206269

  6. Treatment of chronic hepatitis C in Croatian war veterans: experiences from Croatian reference center for viral hepatitis

    PubMed Central

    Papić, Neven; Židovec Lepej, Snježana; Kurelac, Ivan; Čajić, Vjeran; Budimir, Jelena; Dušek, Davorka; Vince, Adriana

    2011-01-01

    Aim To examine the risk factors, comorbidity, severity of liver disease, treatment course, and outcome in Croatian war veterans with chronic hepatitis C, especially those suffering from posttraumatic stress disorder (PTSD). Methods We collected medical records of 170 adult men diagnosed with chronic hepatitis C who started treatment with a combination of pegylated interferon-alpha and ribavirin between January 2003 and June 2009 at the Croatian Reference Centre for Viral Hepatitis. Results Participants’ mean age was 43 ± 9 years. Among 170 participants, there were 37 war veterans (22%). The main risk factor in veteran patients were operative procedures with transfusions (46% vs 5% in non-veterans; P < 0.001) and in non-veteran patients intravenous drug use (42.1% vs 13%; P < 0.001). The average duration of infection was longer in war veterans (14.5 ± 3.4 vs 12.2 ± 7.2 years; P = 0.020). The percentage of PTSD comorbidity in the whole group was 11% (18/170) and in the war veterans group 49% (18/37). The prevalence of sustained virological response in patients with PTSD was 50% and in patients without PTSD 56%. Treatment reduction in patients with PTSD (33%) was higher than in patients without PTSD (12%;P = 0.030). Conclusion Croatian war veterans are a group with high risk of chronic hepatitis C infection because many of them were wounded during the Croatian War 1991-1995. Considerations about PTSD as a contraindication for interferon treatment are unjustified. If treated, patients with PTSD have an equal chance of achieving sustained virological response as patients without PTSD. PMID:21328718

  7. Alverine citrate induced acute hepatitis

    PubMed Central

    Arhan, Mehmet; Köklü, Seyfettin; Köksal, Aydln S; Yolcu, Ömer F; Koruk, Senem; Koruk, Irfan; Kayacetin, Ertugrul

    2004-01-01

    Alverine citrate is a commonly used smooth muscle relaxant agent. A MEDLINE search on January 2004 revealed only 1 report implicating the hepatotoxicity of this agent. A 34-year-old woman was investigated because of the finding of elevated liver function tests on biochemical screening. Other etiologies of hepatitis were appropriately ruled out and elevated enzymes were ascribed to alverine citrate treatment. Although alverine citrate hepatotoxicity was related to an immune mechanism in the first case, several features such as absence of predictable dose-dependent toxicity of alverine citrate in a previous study and absence of hypersensitivity manifestations in our patient are suggestive of a metabolic type of idiosyncratic toxicity. PMID:15259090

  8. LIVER BIOPSY: IMPORTANCE OF SPECIMEN SIZE IN THE DIAGNOSIS AND STAGING OF CHRONIC VIRAL HEPATITIS

    PubMed Central

    CORAL, Gabriela P.; ANTUNES, Aline Dal Pozzo; SERAFINI, Ana Paula Almeida; ARAUJO, Fernanda B.; de MATTOS, Angelo Alves

    2016-01-01

    Liver biopsy is the gold standard method for the grading and staging of chronic viral hepatitis, but optimal biopsy specimen size remains controversial. The aim of this study was to evaluate the quality of liver specimen (number of portal tracts) and to evaluate the impact of the number of portal tracts in the staging of chronic hepatitis. Material and Methods: 468 liver biopsies from consecutive patients with hepatitis C virus and hepatitis B virus infection from 2009 to 2010 were evaluated. Results: The length of fragment was less than 10 mm in 43 cases (9.3%), between 10 and 14 mm in 114 (24.3%), and ≥ 15 mm in 311 (64.4%); of these, in 39 (8.3%) cases were ≥ 20 mm. The mean representation of portal tracts was 17.6 ± 2.1 (5-40); in specimens ≥ 15 mm the mean portal tract was 13.5 ± 4.7 and in cases ≤ 15 mm was 11.4 ± 5.0 (p = 0.002). Cases with less than 11 portal tracts were associated with F3, and cases with 11 or more portal tracts with F2 (p = 0.001). Conclusion: this study demonstrated the good quality of liver biopsy and a relationship between the macroscopic size of the fragment and the number of portal tracts. PMID:26910447

  9. Hyaluronic Acid Levels Predict Risk of Hepatic Encephalopathy and Liver-Related Death in HIV/Viral Hepatitis Coinfected Patients

    PubMed Central

    Peters, Lars; Mocroft, Amanda; Soriano, Vincent; Rockstroh, Jürgen; Rauch, Andri; Karlsson, Anders; Knysz, Brygida; Pradier, Christian; Zilmer, Kai; Lundgren, Jens D.

    2013-01-01

    Background Whereas it is well established that various soluble biomarkers can predict level of liver fibrosis, their ability to predict liver-related clinical outcomes is less clearly established, in particular among HIV/viral hepatitis co-infected persons. We investigated plasma hyaluronic acid’s (HA) ability to predict risk of liver-related events (LRE; hepatic coma or liver-related death) in the EuroSIDA study. Methods Patients included were positive for anti-HCV and/or HBsAg with at least one available plasma sample. The earliest collected plasma sample was tested for HA (normal range 0–75 ng/mL) and levels were associated with risk of LRE. Change in HA per year of follow-up was estimated after measuring HA levels in latest sample before the LRE for those experiencing this outcome (cases) and in a random selection of one sixth of the remaining patients (controls). Results During a median of 8.2 years of follow-up, 84/1252 (6.7%) patients developed a LRE. Baseline median (IQR) HA in those without and with a LRE was 31.8 (17.2–62.6) and 221.6 ng/mL (74.9–611.3), respectively (p<0.0001). After adjustment, HA levels predicted risk of contracting a LRE; incidence rate ratios for HA levels 75–250 or ≥250 vs. <75 ng/mL were 5.22 (95% CI 2.86–9.26, p<0.0007) and 28.22 (95% CI 14.95–46.00, p<0.0001), respectively. Median HA levels increased substantially prior to developing a LRE (107.6 ng/mL, IQR 0.8 to 251.1), but remained stable for controls (1.0 ng/mL, IQR –5.1 to 8.2), (p<0.0001 comparing cases and controls), and greater increases predicted risk of a LRE in adjusted models (p<0.001). Conclusions An elevated level of plasma HA, particularly if the level further increases over time, substantially increases the risk of contracting LRE over the next five years. HA is an inexpensive, standardized and non-invasive supplement to other methods aimed at identifying HIV/viral hepatitis co-infected patients at risk of hepatic complications. PMID:23724041

  10. [The use of water-soluble vitamins in viral hepatitis A].

    PubMed

    Komar, V I; Vasil'ev, V S

    1992-01-01

    To correct disbolism of vitamins C, B3, B6 and B12 due to viral hepatitis A (VHA), the patients received daily doses of the vitamins: 300 and 400 mg of ascorbic acid, 300 and 600 mg of calcium pantothenate or 90 and 180 mg of pantetin per os. 100 and 200 micrograms of cyanocobalamin alternating with 50 and 100 mg of pyridoxin was given intramuscularly every other day. The course lasted 3-4 weeks. The vitamin treatment promoted a positive trend in clinico-biochemical parameters, normalization of immunocompetent cell and serum immunoglobulins levels, of phagocytic reaction of peripheral blood neutrophils. PMID:1608218

  11. S-adenosyl methionine improves early viral responses and interferon-stimulated gene induction in hepatitis C nonresponders

    PubMed Central

    Feld, Jordan J.; Modi, Apurva A.; El-Diwany, Ramy; Rotman, Yaron; Thomas, Emmanuel; Koh, Christopher; Cherepanov, Vera; Heller, Theo; Ghany, Marc G.; Park, Yoon; Hoofnagle, Jay H.; Liang, T. Jake

    2010-01-01

    Background & Aims Fewer than half of patients infected with Hepatitis C virus (HCV) achieve sustained viral clearance after peginterferon and ribavirin therapy. S-adenosyl methionine (SAMe) increases interferon signaling in cell culture. We assessed the effect of SAMe on the kinetics of the early anti-viral response and interferon signaling in patients that did not respond to previous therapy (nonresponders) and investigated its mechanisms. Methods Nonresponders with HCV genotype-1 were given 2 weeks of peginterferon alfa-2a and ribavirin (Course A, baseline/control). After a 1-month period, patients received SAMe (1600 mg daily) for 2 weeks and then peginterferon and ribavirin for 48 weeks (Course B; completed by 21 of 24 patients). Viral kinetics and interferon-stimulated gene (ISG) expression in peripheral blood mononuclear cells (PBMCs) were compared between courses. Results The decrease in HCV RNA from 0 to 48 hours (phase 1) was similar before and after administration of SAMe. However, the slope increased for the second-phase decrease in HCV between courses A and B (Course A=0.11±0.04 log10IU/mL/week, Course B=0.27±0.06; P=0.009); 11 patients (53%) achieved an early virological response and 10 (48%) had undetectable HCV RNA by week 24. Induction of ISGs in PBMCs was significantly greater after Course B. In cultured cells, SAMe increased induction of ISGs, compared with only peginterferon and ribavirin, and the antiviral effects of interferon by increasing STAT1 methylation, which might promote binding of STAT1 to DNA. Conclusions The addition of SAMe to peginterferon and ribavirin improves the kinetics of the early anti-viral response and induces ISGs in patients with HCV genotype 1 that do not respond to interferon therapy. SAMe might be used with peginterferon-based therapies in patients with chronic HCV infections. PMID:20854821

  12. Targeting Viral Entry for Treatment of Hepatitis B and C Virus Infections.

    PubMed

    Colpitts, Che C; Verrier, Eloi R; Baumert, Thomas F

    2015-09-11

    Hepatitis B virus (HBV) and hepatitis C virus (HCV) infections remain major health problems worldwide, with 400-500 million chronically infected people worldwide. Chronic infection results in liver cirrhosis and hepatocellular carcinoma, the second leading cause of cancer death. Current treatments for HBV limit viral replication without efficiently curing infection. HCV treatment has markedly progressed with the licensing of direct-acting antivirals (DAAs) for HCV cure, yet limited access for the majority of patients is a major challenge. Preventative and curative treatment strategies, aimed at novel targets, are needed for both viruses. Viral entry represents one such target, although detailed knowledge of the entry mechanisms is a prerequisite. For HBV, the recent discovery of the NTCP cell entry factor enabled the establishment of an HBV cell culture model and showed that cyclosporin A and Myrcludex B are NTCP-targeting entry inhibitors. Advances in the understanding of HCV entry revealed it to be a complex process involving many factors, offering several antiviral targets. These include viral envelope proteins E1 and E2, virion-associated lipoprotein ApoE, and cellular factors CD81, SRBI, EGFR, claudin-1, occludin, and the cholesterol transporter NPC1L1. Small molecules targeting SR-BI, EGFR, and NPC1L1 have entered clinical trials, whereas other viral- and host-targeted small molecules, peptides, and antibodies show promise in preclinical models. This review summarizes the current understanding of HBV and HCV entry and describes novel antiviral targets and compounds in different stages of clinical development. Overall, proof-of-concept studies indicate that entry inhibitors are a promising class of antivirals to prevent and treat HBV and HCV infections. PMID:27617925

  13. Circulating and Hepatic Fas Expression in HCV-Induced Chronic Liver Disease and Hepatocellular Carcinoma

    PubMed Central

    El Bassiouny, Azza E. I.; El-Bassiouni, Nora E. I.; Nosseir, Mona M. F.; Zoheiry, Mona M.K.; El-Ahwany, Eman G.; Salah, Faten; Omran, Zeinab S.O.; Ibrahim, Raafat A.

    2008-01-01

    Apoptosis is central for control and elimination of viral infections. In chronic hepatitis C virus (HCV) infection, enhanced hepatocyte apoptosis and upregulation of the death-inducing ligands CD95/Fas occur. This study aimed to study the role of serum soluble Fas and hepatic Fas expression as early predictors of advancement of chronic hepatitis C disease. The current study included 50 cases of chronic hepatitis C (CHC) (and negative hepatitis B virus infection), 30 cases of liver cirrhosis (LC) and HCV, and 20 cases of hepatocellular carcinoma (HCC) and HCV admitted to Theodor Bilharz Research Institute, Giza, Egypt. Fifteen wedge liver biopsies, taken during laparoscopic cholecystectomy, were included in the study as normal controls. Assessment of serum soluble Fas level (sFas) and other laboratory investigations, including liver function tests, serologic markers for viral hepatitis, and serum alpha-fetoprotein level (alpha-FP), were determined for all cases. Histopathologic study and immunohistochemistry using monoclonal antibody for CD95 were also done. The sFas was significantly increased in CHC, LC, and HCC cases compared with normal controls (P < .01). The increase of sFas in HCC was also significantly higher than that of CHC (P < .01). However, positive hepatic expression of Fas antigen was higher in CHC than LC with no significant difference; meanwhile, it was significantly lower in HCC (P < .01) compared with CHC. In conclusion, circulating and hepatic Fas expression in chronic hepatitis C infection illustrate the mechanism of liver injury caused by death receptors throughout the multistep process of fibrosis/carcinogenesis. Not only the higher degree of hepatic fibrosis, but also the lower expression of Fas protein, are correlated with the increased incidence of HCC. PMID:18679533

  14. Pretransplant Hepatitis B Viral Infection Increases Risk of Death After Kidney Transplantation

    PubMed Central

    Lee, Jeonghwan; Cho, Jang-Hee; Lee, Jong Soo; Ahn, Dong-Won; Kim, Chan-Duck; Ahn, Curie; Jung, In Mok; Han, Duck Jong; Lim, Chun Soo; Kim, Yon Su; Kim, Young Hoon; Lee, Jung Pyo

    2016-01-01

    Abstract Clinical outcomes in kidney transplant recipients (KTRs) with hepatitis B virus (HBV) have not been thoroughly evaluated. Here, we investigated recent posttransplant clinical outcomes of KTRs with HBV and compared them with KTRs with hepatitis C virus (HCV) and seronegative KTRs. Of 3855 KTRs from April 1999 to December 2011, we enrolled 3482 KTRs who had viral hepatitis serology data; the patients were followed up for 89.1 ± 54.1 months. The numbers of recipients with HBV and HCV were 160 (4.6%) and 55 (1.6%), respectively. We analyzed the clinical outcomes, including overall mortality and graft failure, among patients who had undergone kidney transplantation. Patients with HBV showed poorer survival (P = 0.019; adjusted hazard ratio [HR] = 2.370; 95% confidence interval [CI]: 1.155–4.865) than KTRs without HBV. However, the graft survival of patients with chronic hepatitis B did not differ from that of patients without HBV. Hepatic complications were the primary causes of mortality of KTRs with HBV. Mortality significantly correlated with a higher grade of inflammation (P = 0.002) and with the use of lamivudine or adefovir antiviral treatment (P = 0.016). HBV-positive KTRs treated with the new-generation antiviral agent entecavir showed improved patient survival compared with KTRs receiving lamivudine (log-rank P = 0.050). HCV did not affect patient survival; however, it increased the incidence of graft failure (P = 0.010; adjusted HR = 2.899; 95% CI: 1.289–6.519). KTRs with HCV had an increased incidence of acute rejection (log-rank P = 0.005, crude HR = 2.144; 95% CI: 1.341–3.426; P = 0.001). KTRs with chronic hepatitis B may exhibit poor survival due to post-transplantation hepatic complications. Pretransplant histological liver evaluations and adequate antiviral management with potent nucleoside/nucleotide analogues are needed to improve the survival of KTRs with chronic hepatitis B even when liver

  15. The enzymes LSD1 and Set1A cooperate with the viral protein HBx to establish an active hepatitis B viral chromatin state.

    PubMed

    Alarcon, Valentina; Hernández, Sergio; Rubio, Lorena; Alvarez, Francisca; Flores, Yvo; Varas-Godoy, Manuel; De Ferrari, Giancarlo V; Kann, Michael; Villanueva, Rodrigo A; Loyola, Alejandra

    2016-01-01

    With about 350 million people chronically infected around the world hepatitis B is a major health problem. Template for progeny HBV synthesis is the viral genome, organized as a minichromosome (cccDNA) inside the hepatocyte nucleus. How viral cccDNA gene expression is regulated by its chromatin structure; more importantly, how the modulation of this structure impacts on viral gene expression remains elusive. Here, we found that the enzyme SetDB1 contributes to setting up a repressed cccDNA chromatin state. This repressive state is activated by the histone lysine demethylase-1 (LSD1). Consistently, inhibiting or reducing LSD1 levels led to repression of viral gene expression. This correlates with the transcriptionally repressive mark H3K9 methylation and reduction on the activating marks H3 acetylation and H3K4 methylation on viral promoters. Investigating the importance of viral proteins we found that LSD1 recruitment to viral promoters was dependent on the viral transactivator protein HBx. Moreover, the histone methyltransferase Set1A and HBx are simultaneously bound to the core promoter, and Set1A expression correlates with cccDNA H3K4 methylation. Our results shed light on the mechanisms of HBV regulation mediated by the cccDNA chromatin structure, offering new therapeutic targets to develop drugs for the treatment of chronically infected HBV patients. PMID:27174370

  16. The enzymes LSD1 and Set1A cooperate with the viral protein HBx to establish an active hepatitis B viral chromatin state

    PubMed Central

    Alarcon, Valentina; Hernández, Sergio; Rubio, Lorena; Alvarez, Francisca; Flores, Yvo; Varas-Godoy, Manuel; De Ferrari, Giancarlo V.; Kann, Michael; Villanueva, Rodrigo A.; Loyola, Alejandra

    2016-01-01

    With about 350 million people chronically infected around the world hepatitis B is a major health problem. Template for progeny HBV synthesis is the viral genome, organized as a minichromosome (cccDNA) inside the hepatocyte nucleus. How viral cccDNA gene expression is regulated by its chromatin structure; more importantly, how the modulation of this structure impacts on viral gene expression remains elusive. Here, we found that the enzyme SetDB1 contributes to setting up a repressed cccDNA chromatin state. This repressive state is activated by the histone lysine demethylase-1 (LSD1). Consistently, inhibiting or reducing LSD1 levels led to repression of viral gene expression. This correlates with the transcriptionally repressive mark H3K9 methylation and reduction on the activating marks H3 acetylation and H3K4 methylation on viral promoters. Investigating the importance of viral proteins we found that LSD1 recruitment to viral promoters was dependent on the viral transactivator protein HBx. Moreover, the histone methyltransferase Set1A and HBx are simultaneously bound to the core promoter, and Set1A expression correlates with cccDNA H3K4 methylation. Our results shed light on the mechanisms of HBV regulation mediated by the cccDNA chromatin structure, offering new therapeutic targets to develop drugs for the treatment of chronically infected HBV patients. PMID:27174370

  17. Persistence of infectious hepadnavirus in the offspring of woodchuck mothers recovered from viral hepatitis

    PubMed Central

    Coffin, Carla S.; Michalak, Tomasz I.

    1999-01-01

    Mother-to-child transmission is an important route for hepatitis B virus (HBV) dissemination. It has been established that HBV traces persist for years after complete clinical recovery from hepatitis B. Similarly, resolution of hepatitis caused by HBV-related woodchuck hepatitis virus (WHV) is followed by occult lifelong carriage of pathogenic virus. In this study, we documented that WHV persisting after termination of acute hepatitis is transmittable to newborns as an asymptomatic long-term infection. All 11 offspring from 4 dams studied carried transcriptionally active WHV genomes for 3.5 years after birth without immunovirological markers of infection. WHV genomes and mRNA were detected both in the liver and lymphoid tissue in the majority of offspring; WHV covalently closed circular DNA was detected in some samples. In 4 offspring, however, the virus was restricted to the lymphatic system. In the circulation, WHV DNA–reactive particles were DNase resistant and of comparable size and density to complete virions. Importantly, the virus in offspring with or without hepatic WHV DNA expression was infectious to WHV-naive woodchucks. Finally, offspring challenged with WHV were not protected against reinfection. These findings show that mothers with occult hepadnaviral carriage transmit pathogenic virus to their offspring, inducing a persistent infection invariably within the lymphatic system but not always in the liver. PMID:10411550

  18. Development of a stabilizer for lyophilization of an attenuated duck viral hepatitis vaccine.

    PubMed

    Kang, M S; Jang, H; Kim, M C; Kim, M J; Joh, S J; Kwon, J H; Kwon, Y K

    2010-06-01

    The live attenuated vaccine against duck viral hepatitis currently available in Korea requires special freezers for storage and transportation with extra costs involved. The development of a lyophilization stabilizer for live attenuated duck viral hepatitis virus (DHV) vaccines, therefore, has been highly recommended for the wider application of the vaccines. Four conventional vaccine stabilizer formulations containing a disaccharide, such as lactose, trehalose, or sucrose, and new formulations containing sorbitol were tested for their efficacy in stabilizing a new attenuated DHV type 3 vaccine candidate under different storage temperatures, 4 and 37 degrees C. The vaccine virus and each stabilizer formulation were combined and submitted to lyophilization and the viability of the virus was measured in 7-d-old specific-pathogen-free chicken embryos by determining the 50% egg lethal dose. Stabilizer formulations containing 2, 4, or 8% sorbitol preserved the viability of the vaccine virus much better than the other stabilizer formulations and 2% sorbitol was the optimal concentration in a standard stabilizing buffer, phosphate glutamate gelatin (0.0038 M KH2PO4, 0.0071 M K2HPO4, 0.0049 M monosodium L-glutamate, and 0.5% gelatin). The results demonstrate that the stabilizer formulation containing 2% sorbitol and 0.5% gelatin can be used for convenient storage and transportation of live DHV vaccines. PMID:20460663

  19. Imaging Based Methods of Liver Fibrosis Assessment in Viral Hepatitis: A Practical Approach

    PubMed Central

    Khallafi, Hicham; Qureshi, Kamran

    2015-01-01

    Liver fibrosis represents the repair mechanism in liver injury and is a feature of most chronic liver diseases. The degree of liver fibrosis in chronic viral hepatitis infections has major clinical implications and presence of advanced fibrosis or cirrhosis determines prognosis. Treatment initiation for viral hepatitis is indicated in most cases of advanced liver fibrosis and diagnosis of cirrhosis entails hepatology evaluation for specialized clinical care. Liver biopsy is an invasive technique and has been the standard of care of fibrosis assessment for years; however, it has several limitations and procedure related complications. Recently, several methods of noninvasive assessment of liver fibrosis have been developed which require either serologic testing or imaging of liver. Imaging based noninvasive techniques are reviewed here and their clinical use is described. Some of the imaging based tests are becoming widely available, and collectively they are shown to be superior to liver biopsy in important aspects. Clinical utilization of these methods requires understanding of performance and quality related parameters which can affect the results and provide wrong assessment of the extent of liver fibrosis. Familiarity with the strengths and weaknesses of each modality is needed to correctly interpret the results in appropriate clinical context. PMID:26779260

  20. Voices of multi-ethnic providers in NYC: health care for viral hepatitis to prevent hepatocellular carcinoma.

    PubMed

    Han, Hyosun; Perumalswami, Ponni V; Kleinman, Lawrence C; Jandorf, Lina H

    2014-06-01

    Worldwide, hepatocellular carcinoma (HCC) is the third leading cause of cancer deaths and the ninth in the US. Hepatitis B and C make up almost 80% of HCC cases. Based on our Hepatitis Outreach Network screening program data, approximately 40% of at-risk foreign-born community members who tested positive for viral hepatitis B and/or C did not follow up for additional care. Our aim was to use theory-driven qualitative research to identify barriers and facilitators to follow-up after viral hepatitis diagnosis among these community members from the viewpoint of primary care providers (PCPs). As viral hepatitis is a precursor of liver cancer, timely treatment of the virus has the potential to reduce the incidence and burden of liver cancer. We performed semi-structured key informant interviews with 20 primary care physicians who predominantly serve Korean, Chinese, Egyptian, and Russian communities. Barriers detected included cultural factors commonly seen amongst immigrant populations such as busy work schedules and non-English language. Common facilitators include increased primary care physician involvement and linkages to care within communities in which patients reside. Providers perceived that they are gatekeepers to specialty care for their patients and therefore key persons to engage in viral hepatitis evaluation and management by specialists. This initial study suggests that re-focusing energy into primary care physicians might offer promise for improved care for individuals from immigrant communities who have viral hepatitis to help them engage in care and thereby reduce the burden of liver cancer. PMID:24189830

  1. Inducible Expression of CXCL1 within the Central Nervous System Amplifies Viral-Induced Demyelination

    PubMed Central

    Marro, Brett S.; Grist, Jonathan J.

    2016-01-01

    The functional role of the ELR+ chemokine CXCL1 in host defense and disease following infection of the CNS with the neurotropic JHM strain of mouse hepatitis virus (JHMV) was examined. Mice in which expression of CXCL1 is under the control of a tetracycline-inducible promoter active within glial fibrillary acidic protein–positive cells were generated and this allowed for selectively increasing CNS expression of CXCL1 in response to JHMV infection and evaluating the effects on neuroinflammation, control of viral replication, and demyelination. Inducible expression of CNS-derived CXCL1 resulted in increased levels of CXCL1 protein within the serum, brain, and spinal cord that correlated with increased frequency of Ly6G+CD11b+ neutrophils present within the CNS. Elevated levels of CXCL1 did not influence the generation of virus-specific T cells, and there was no difference in control of JHMV replication compared with control mice, indicating that T cell infiltration into the CNS is CXCL1-independent. Sustained CXCL1 expression within the CNS resulted in increased mortality that correlated with elevated neutrophil infiltration, diminished numbers of mature oligodendrocytes, and an increase in the severity of demyelination. Neutrophil ablation in CXCL1-transgenic mice reduced the severity of demyelination in mice, arguing for a role for these cells in white matter damage. Collectively, these findings illustrate that sustained CXCL1 expression amplifies the severity of white matter damage and that neutrophils can contribute to this process in a model of viral-induced neurologic disease. PMID:26773148

  2. Inducible Expression of CXCL1 within the Central Nervous System Amplifies Viral-Induced Demyelination.

    PubMed

    Marro, Brett S; Grist, Jonathan J; Lane, Thomas E

    2016-02-15

    The functional role of the ELR(+) chemokine CXCL1 in host defense and disease following infection of the CNS with the neurotropic JHM strain of mouse hepatitis virus (JHMV) was examined. Mice in which expression of CXCL1 is under the control of a tetracycline-inducible promoter active within glial fibrillary acidic protein-positive cells were generated and this allowed for selectively increasing CNS expression of CXCL1 in response to JHMV infection and evaluating the effects on neuroinflammation, control of viral replication, and demyelination. Inducible expression of CNS-derived CXCL1 resulted in increased levels of CXCL1 protein within the serum, brain, and spinal cord that correlated with increased frequency of Ly6G(+)CD11b(+) neutrophils present within the CNS. Elevated levels of CXCL1 did not influence the generation of virus-specific T cells, and there was no difference in control of JHMV replication compared with control mice, indicating that T cell infiltration into the CNS is CXCL1-independent. Sustained CXCL1 expression within the CNS resulted in increased mortality that correlated with elevated neutrophil infiltration, diminished numbers of mature oligodendrocytes, and an increase in the severity of demyelination. Neutrophil ablation in CXCL1-transgenic mice reduced the severity of demyelination in mice, arguing for a role for these cells in white matter damage. Collectively, these findings illustrate that sustained CXCL1 expression amplifies the severity of white matter damage and that neutrophils can contribute to this process in a model of viral-induced neurologic disease. PMID:26773148

  3. Liver Stiffness Is Associated With Monocyte Activation in HIV-Infected Ugandans Without Viral Hepatitis

    PubMed Central

    Wendel, Sarah K.; Grabowski, Mary K.; Ocama, Ponsiano; Kiggundu, Valerian; Bbosa, Francis; Boaz, Iga; Balagopal, Ashwin; Reynolds, Steven J.; Gray, Ronald H.; Serwadda, David; Kirk, Gregory D.; Quinn, Thomas C.; Stabinski, Lara

    2013-01-01

    Abstract A high prevalence of liver stiffness, as determined by elevated transient elastography liver stiffness measurement, was previously found in a cohort of HIV-infected Ugandans in the absence of chronic viral hepatitis. Given the role of immune activation and microbial translocation in models of liver disease, a shared immune mechanism was hypothesized in the same cohort without other overt causes of liver disease. This study examined whether HIV-related liver stiffness was associated with markers of immune activation or microbial translocation (MT). A retrospective case-control study of subjects with evidence of liver stiffness as defined by a transient elastography stiffness measurement ≥9.3 kPa (cases=133) and normal controls (n=133) from Rakai, Uganda was performed. Cases were matched to controls by age, gender, HIV, hepatitis B virus (HBV), and highly active antiretroviral therapy (HAART) status. Lipopolysaccharide (LPS), endotoxin IgM antibody, soluble CD14 (sCD14), C-reactive protein (CRP), and D-dimer levels were measured. Conditional logistic regression was used to estimate adjusted matched odds ratios (adjMOR) and 95% confidence intervals. Higher sCD14 levels were associated with a 19% increased odds of liver stiffness (adjMOR=1.19, p=0.002). In HIV-infected individuals, higher sCD14 levels were associated with a 54% increased odds of having liver stiffness (adjMOR=1.54, p<0.001); however, the opposite was observed in HIV-negative individuals (adjMOR=0.57, p=0.001). No other biomarker was significantly associated with liver stiffness, and only one subject was found to have detectable LPS. Liver stiffness in HIV-infected Ugandans is associated with increased sCD14 indicative of monocyte activation in the absence of viral hepatitis or microbial translocation, and suggests that HIV may be directly involved in liver disease. PMID:23548102

  4. HAVCR1 Gene Haplotypes and Infection by Different Viral Hepatitis C Virus Genotypes

    PubMed Central

    Abad-Molina, Cristina; Garcia-Lozano, José-Raúl; Montes-Cano, Marco-Antonio; Torres-Cornejo, Almudena; Torrecillas, Fuensanta; Aguilar-Reina, José; Romero-Gómez, Manuel; López-Cortés, Luis-Fernando; Núñez-Roldan, Antonio

    2012-01-01

    The hepatitis A virus cellular receptor 1 (HAVCR1) gene is highly polymorphic, and several variants have been associated with susceptibility to allergic and autoimmune diseases. The HAVCR1 gene region was identified as a candidate for hepatitis C virus (HCV) natural clearance in a genotyping study of selected immune response genes in both European-American and African-American populations. The aim of the present study was to explore the influence of HAVCR1 in the outcome of HCV infection in the Spanish population. Three cohorts, consisting of 354 subjects with persistent HCV infection (285 with persistent HCV monoinfection and 69 with natural clearance), 182 coinfected HIV/HCV patients, and 320 controls, were included. Samples were genotyped in several polymorphic positions, insertion/deletion variants in exon 4 and tag single nucleotide polymorphisms (SNPs), in order to define previously described HAVCR1 haplotypes (haplotypes A to D). No statistically significant differences were observed with spontaneous resolution of infection or with viral clearance after treatment. Nevertheless, different rates of infection by viral genotypes (G's) were observed among the HAVCR1 haplotypes. Individuals bearing haplotype C had the highest viral G1 infection rate when compared to individuals bearing other haplotypes (75.82% versus 57.72%, respectively; corrected P value [Pc], 3.2 × 10−4; odds ratio [OR], 2.30; 95% confidence interval [CI], 1.51 to 3.47). Thus, HAVCR1 could be involved in susceptibility or resistance to infection by a particular HCV genotype. PMID:22190394

  5. Utilization of hepatitis C antibody-positive livers: genotype dominance is virally determined

    PubMed Central

    O’Leary, Jacqueline G.; Neri, Michael A.; Trotter, James F.; Davis, Gary L.; Klintmalm, Göran B.; Annette, C.; Simmons, Harold C.

    2015-01-01

    Summary Because of the unrelenting donor shortage, utilization of all potential liver donors is essential. However, when utilizing marginal donors it is critical to precisely characterize the risks, inform recipients of those risks, and allocate these higher risk organs to appropriate candidates. Towards this goal, we need to determine the safety and potential consequences, if any, of utilizing hepatitis C (HCV) antibody-positive donors in HCV infected recipients. To further characterize HCV antibody-positive donors, we analyzed prospectively collected serum samples from HCV antibody-positive donors transplanted into HCV RNA-positive recipients from 5/1993 to 10/2008 for HCV viral load (Roche Cobas AmpliPrep/Cobas Taqman HCV Assay) and genotype (Siemens Versant 2.0 LiPA HCV 5’ UTR/Core Assay). Seventeen of 32 (53%) HCV antibodypositive donors were RNA negative. Fifteen patients received an HCV RNA-positive donor and nine donor–recipient pairs had different genotypes or subtypes for analysis. When genotype 1 competed with a non-1 genotype, it was found in 5/6 recipients. In 2/3 cases of mismatched genotype 1 subtypes, genotype 1a dominated. Kaplan–Meier analysis of patient and graft survival and fibrosis progression did not reveal differences between patients who received an HCV antibody-positive donor that was viremic or aviremic. In conclusion, approximately half of HCV antibody-positive donors were aviremic. Viral dominance in viremic donor–recipient pairs seems virally determined. PMID:22643162

  6. Ecstasy-induced recurrent toxic hepatitis in a young adult

    PubMed Central

    Guneysel, Ozlem; Onur, Ozge Ecmel; Akoglu, Haldun; Denizbasi, Arzu

    2008-01-01

    BACKGROUND: The drug 3,4-methylenedioxymethamphetamine (MDMA), otherwise known as “ecstasy,” is a synthetic amphetamine that produces euphoria, increases sociability and energy, and is often used as a “weekend” recreational drug by young adults. CASE SUMMARY: A 23-year-old male (height, 184 cm; weight, 68 kg) presented to the emergency department of Marmara University Hospital, Istanbul, Turkey, with jaundice and nausea lasting for 6 days. The patient reported that he had been a chronic user of MDMA for 2 years. He also reported that 1 week before presenting, he had ingested twice (2 tablets) the usual amount (1 tablet) of the drug at the same time. Blood tests were performed and hematologic findings were as follows: aspartate aminotransferase (AST), 1423 U/L (reference range, 10–37 U/L); alanine aminotransferase (ALT), 2748 U/L (10–40 U/L); alkaline phosphatase, 271 U/L (0–270 U/L); γ-glutamyl transpeptidase, 124 U/L (7–49 U/L); total bilirubin, 13.23 mg/dL (0.2–1 mg/dL); direct bilirubin, 8.75 mg/dL (0–0.3 mg/dL); amylase, 80 U/L (0–220 U/L); prothrombin time, 21.2 sec; activated partial thromboplastin time, 37.3 sec; and international normalized ratio, 1.66. Liver enzymes and bilirubin levels were found to be extremely high (AST = 40x normal, ALT = 70x normal, and bilirubin = 13x normal). Viral, autoimmune, and metabolic causes were excluded. Serologic tests for hepatitis A, B, and C viruses, mononucleosis, cytomegalovirus, and HIV infection were all negative. A diagnosis of ecstasy-induced toxic hepatitis was made. The patient's medical history further revealed that the current incident was actually his second occurrence of jaundice and acute hepatitis associated with the ingestion of higher amounts (twice the usual amount of MDMA he ingested at the same time). Supportive therapy (IV saline and vital sign monitoring) was initiated and liver enzymes, bilirubin levels, and prothrombin times were monitored daily. All had returned to normal

  7. Epidemiology of the Viral Hepatitis-HIV Syndemic in San Francisco: A Collaborative Surveillance Approach

    PubMed Central

    Scheer, Susan; Shallow, Sue; Pipkin, Sharon; Huang, Sandra

    2014-01-01

    Objectives To describe the epidemiology of people coinfected with hepatitis B virus (HBV) or hepatitis C virus (HCV) and HIV in San Francisco, the San Francisco Department of Public Health's Communicable Disease Control and Prevention Section and the HIV Epidemiology Section collaborated to link their registries. Methods In San Francisco, hepatitis reporting is primarily through passive laboratory-based surveillance, and HIV/AIDS reporting is primarily through laboratory-initiated active surveillance. We conducted the registry linkage in 2010 using a sequential algorithm. Results The registry match included 31,997 HBV-infected people who were reported starting in 1984; 10,121 HCV-infected people who were reported starting in 2001; and 34,551 HIV/AIDS cases reported beginning in 1981. Of the HBV and HCV cases, 6.3% and 12.6% were coinfected with HIV, respectively. The majority of cases were white males; however, black people were disproportionately affected. For more than 90% of the HBV/HIV cases, male-to-male sexual contact (men who have sex with men [MSM]) was the risk factor for HIV infection. Injection drug use was the most frequent risk factor for HIV infection among the HCV/HIV cases; however, 35.6% of the HCV/HIV coinfected males were MSM but not injection drug users. Conclusions By linking the two registries, we found new ways to foster collaborative work and expand our programmatic flexibility. This analysis identified particular populations at risk for coinfection, which can be used by viral hepatitis and HIV screening, prevention, and treatment programs to integrate, enhance, target, and prioritize prevention services and clinical care within the community to maximize health outcomes. PMID:24385655

  8. Combination therapy including CpG oligodeoxynucleotides and entecavir induces early viral response and enhanced inhibition of viral replication in a woodchuck model of chronic hepadnaviral infection.

    PubMed

    Meng, Zhongji; Zhang, Xiaoyong; Pei, Rongjuan; Zhang, Ejuan; Kemper, Thekla; Vollmer, Jörg; Davis, Heather L; Glebe, Dieter; Gerlich, Wolfram; Roggendorf, Michael; Lu, Mengji

    2016-01-01

    CpG oligodeoxynucleotides (ODNs) stimulate immune cells via TLR9 and are potentially useful immunomodulators for the treatment of chronic viral infections. In the present study, different classes of CpGs were tested for their capacities for innate immune activation and antiviral activities in the woodchuck model. A class P CpG ODN was found to stimulate interferon (IFN) production in woodchuck peripheral blood mononuclear cells (PBMCs) in vitro, and following subcutaneous administration in vivo, it was observed to induce IFN and MxA expression in woodchuck PBMCs. Combination treatment with CpG ODN and entecavir (ETV) led to effective suppression of the woodchuck hepatitis virus (WHV) load in the woodchucks, with early viral responses and inhibition of replication. The woodchuck hepatitis surface antigen (WHsAg) serum concentrations were strongly decreased by CpG and ETV together but not by either agent alone, indicating synergistic effects. However, viral control post-treatment was still transient, similar to that observed with ETV alone. Significantly elevated levels of serum aspartate aminotransferase (AST) but not of alanine aminotransferase (ALT) in some of the woodchucks receiving CpG ODN were noted, but these increases were resolved before the completion of treatment and were not associated with an elevated serum bilirubin level or coagulation disorders, suggesting the absence of a significant safety concern. PMID:26585244

  9. Viral DNA-Dependent Induction of Innate Immune Response to Hepatitis B Virus in Immortalized Mouse Hepatocytes

    PubMed Central

    Cui, Xiuji; Clark, Daniel N.; Liu, Kuancheng; Xu, Xiao-Dong; Guo, Ju-Tao

    2015-01-01

    ABSTRACT Hepatitis B virus (HBV) infects hundreds of millions of people worldwide and causes acute and chronic hepatitis, cirrhosis, and hepatocellular carcinoma. HBV is an enveloped virus with a relaxed circular (RC) DNA genome. In the nuclei of infected human hepatocytes, conversion of RC DNA from the incoming virion or cytoplasmic mature nucleocapsid (NC) to the covalently closed circular (CCC) DNA, which serves as the template for producing all viral transcripts, is essential to establish and sustain viral replication. A prerequisite for CCC DNA formation is the uncoating (disassembly) of NCs to expose their RC DNA content for conversion to CCC DNA. We report here that in an immortalized mouse hepatocyte cell line, AML12HBV10, in which RC DNA exposure is enhanced, the exposed viral DNA could trigger an innate immune response that was able to modulate viral gene expression and replication. When viral gene expression and replication were low, the innate response initially stimulated these processes but subsequently acted to shut off viral gene expression and replication after they reached peak levels. Inhibition of viral DNA synthesis or cellular DNA sensing and innate immune signaling diminished the innate response. These results indicate that HBV DNA, when exposed in the host cell cytoplasm, can function to trigger an innate immune response that, in turn, modulates viral gene expression and replication. IMPORTANCE Chronic infection by hepatitis B virus (HBV) afflicts hundreds of millions worldwide and is sustained by the episomal covalently closed circular (CCC) DNA in the nuclei of infected hepatocytes. Release of viral genomic DNA from cytoplasmic nucleocapsids (NCs) (NC disassembly or uncoating) is a prerequisite for its conversion to CCC DNA, which can also potentially expose the viral DNA to host DNA sensors and trigger an innate immune response. We have found that in an immortalized mouse hepatocyte cell line in which efficient CCC DNA formation was

  10. Impact of ribavirin priming on viral kinetics and treatment response in chronic hepatitis C genotype 1 infection.

    PubMed

    Mihm, U; Welker, M-W; Teuber, G; Wedemeyer, H; Berg, T; Sarrazin, C; Böhm, S; Alshuth, U; Herrmann, E; Zeuzem, S

    2014-01-01

    Ribavirin amplifies the interferon-alpha (IFN) signalling cascade. As ribavirin needs 4 weeks to reach steady state, ribavirin priming may optimize hepatic IFN sensitivity before starting a pegylated (PEG)-IFN/ribavirin combination therapy. This study investigated potential benefits of ribavirin priming prior to PEG-IFN2a/ribavirin combination therapy on viral kinetics, on-treatment and sustained virological response (SVR) in chronic hepatitis C virus (HCV) genotype 1 infection. Sixty-eight treatment naive patients were randomized 2:2:1 to ribavirin (ribavirin arm) or placebo (placebo arm) or PEG-IFN2a (PEG-IFN2a arm) for 6 weeks prior to 12 weeks of PEG-IFN2a/ribavirin combination therapy within a double-blind, placebo-controlled trial. Then, standard PEG-IFN2a/ribavirin combination therapy according to the German guidelines was continued under the responsibility of the investigators. Ribavirin was given according to body weight and PEG-IFN2a at a dose of 180 μg subcutaneously once/week. During ribavirin priming, HCV RNA showed a decline of -0.58 log10  IU/mL (P < 0.001) that was unrelated to the IL28B rs12979860 genotype (CC vs CT/TT, P = 0.244). Ribavirin priming did neither increase the PEG-IFN2a-induced first- or second-phase viral decline (P values >0.100) nor on-treatment response or SVR (HCV RNA undetectable at week 12 of combination therapy: ribavirin arm 56%, placebo arm 38%, PEG-IFN2a arm 50%; SVR: ribavirin arm 41%, placebo arm 54%, PEG-IFN2a arm 50%; P values >0.300). In conclusion, ribavirin monotherapy showed a significant antiviral activity that was not influenced by the IL28B genotype. Ribavirin priming prior to PEG-IFN2a/ribavirin combination therapy did neither increase the first- or second-phase viral decline nor on-treatment response or SVR. PMID:24329856

  11. Toxic hepatitis induced by a herbal medicine: Tinospora crispa.

    PubMed

    Langrand, J; Regnault, H; Cachet, X; Bouzidi, C; Villa, A F; Serfaty, L; Garnier, R; Michel, S

    2014-01-01

    Herbal remedies are becoming increasingly popular in many countries. Tinospora species (Menispermaceae) is commonly used as a herbal medicine in South Asia, but very few toxic effects have been described. We report a case of acute hepatitis associated with chronic use of high doses of Tinospora crispa. A 49-year-old male with chronic low back pain bought a herbal medicine at a market in Vietnam that was supposed to be Tinospora crispa, and started to take 10 pellets per day. He had no medical history and did not take any other drugs or toxins. Four weeks later; he developed dark urine and pale stools, associated with asthenia and right hypochondrial pain. Two months after starting treatment, he was referred to the hepatology department with jaundice. Blood tests showed aspartate aminotransferase: 1.169 IU/l, alanine aminotransferase: 2.029 IU/l, total bilirubin: 20.47 mg/dl, direct bilirubin: 13.29 mg/dl, and γ-glutamyltransferase: 243 IU/l. Viral and autoimmune hepatitis were eliminated. Upper abdominal ultrasound was normal. Histopathological findings were consistent with a toxic reaction. The herbal medicine was stopped on admission and the patient fully recovered without treatment, with normal liver function 2 months after the acute episode. Tinospora crispa was clearly identified in the pellets by microscopic analysis of the botanical characters combined with chromatographic fingerprints. The use of herbal medicines containing Tinospora crispa can induce toxic hepatitis. Recovery can be complete after discontinuation. This case highlights the risk associated with traditional herbal remedies. PMID:24867504

  12. The Hepatitis Viral Status in Patients With Hepatocellular Carcinoma: a Study of 3843 Patients From Taiwan Liver Cancer Network

    PubMed Central

    Chang, Il-Chi; Huang, Shiu-Feng; Chen, Pei-Jer; Chen, Chi-Ling; Chen, Chao-Long; Wu, Cheng-Chung; Tsai, Cheng-Chung; Lee, Po-Huang; Chen, Miin-Fu; Lee, Chuan-Mo; Yu, Hsien-Chung; Lo, Gin-Ho; Yeh, Chau-Ting; Hong, Chih-Chen; Eng, Hock-Liew; Wang, John; Tseng, Hui-Hwa; Hsiao, Cheng-Hsiang; Wu, Hong-Dar Isaac; Yen, Tseng-Chang; Liaw, Yun-Fan

    2016-01-01

    Abstract Hepatocellular carcinoma (HCC) is the leading cancer death in Taiwan. Chronic viral hepatitis infections have long been considered as the most important risk factors for HCC in Taiwan. The previously published reports were either carried out by individual investigators with small patient numbers or by large endemic studies with limited viral marker data. Through collaboration with 5 medical centers across Taiwan, Taiwan liver cancer network (TLCN) was established in 2005. All participating centers followed a standard protocol to recruit liver cancer patients along with their biosamples and clinical data. In addition, detailed viral marker analysis for hepatitis B virus (HBV) and hepatitis C virus (HCV) were also performed. This study included 3843 HCC patients with available blood samples in TLCN (recruited from November 2005 to April 2011). There were 2153 (56.02%) patients associated with HBV (HBV group); 969 (25.21%) with HCV (HCV group); 310 (8.07%) with both HBV and HCV (HBV+HCV group); and 411 (10.69%) were negative for both HBV and HCV (non-B non-C group). Two hundred two of the 2463 HBV patients (8.20%) were HBsAg(-), but HBV DNA (+). The age, gender, cirrhosis, viral titers, and viral genotypes were all significantly different between the above 4 groups of patients. The median age of the HBV group was the youngest, and the cirrhotic rate was lowest in the non-B non-C group (only 25%). This is the largest detailed viral hepatitis marker study for HCC patients in the English literatures. Our study provided novel data on the interaction of HBV and HCV in the HCC patients and also confirmed that the HCC database of TLCN is highly representative for Taiwan and an important resource for HCC research. PMID:27082566

  13. The Hepatitis Viral Status in Patients With Hepatocellular Carcinoma: a Study of 3843 Patients From Taiwan Liver Cancer Network.

    PubMed

    Chang, Il-Chi; Huang, Shiu-Feng; Chen, Pei-Jer; Chen, Chi-Ling; Chen, Chao-Long; Wu, Cheng-Chung; Tsai, Cheng-Chung; Lee, Po-Huang; Chen, Miin-Fu; Lee, Chuan-Mo; Yu, Hsien-Chung; Lo, Gin-Ho; Yeh, Chau-Ting; Hong, Chih-Chen; Eng, Hock-Liew; Wang, John; Tseng, Hui-Hwa; Hsiao, Cheng-Hsiang; Wu, Hong-Dar Isaac; Yen, Tseng-Chang; Liaw, Yun-Fan

    2016-04-01

    Hepatocellular carcinoma (HCC) is the leading cancer death in Taiwan. Chronic viral hepatitis infections have long been considered as the most important risk factors for HCC in Taiwan. The previously published reports were either carried out by individual investigators with small patient numbers or by large endemic studies with limited viral marker data. Through collaboration with 5 medical centers across Taiwan, Taiwan liver cancer network (TLCN) was established in 2005. All participating centers followed a standard protocol to recruit liver cancer patients along with their biosamples and clinical data. In addition, detailed viral marker analysis for hepatitis B virus (HBV) and hepatitis C virus (HCV) were also performed. This study included 3843 HCC patients with available blood samples in TLCN (recruited from November 2005 to April 2011). There were 2153 (56.02%) patients associated with HBV (HBV group); 969 (25.21%) with HCV (HCV group); 310 (8.07%) with both HBV and HCV (HBV+HCV group); and 411 (10.69%) were negative for both HBV and HCV (non-B non-C group). Two hundred two of the 2463 HBV patients (8.20%) were HBsAg(-), but HBV DNA (+). The age, gender, cirrhosis, viral titers, and viral genotypes were all significantly different between the above 4 groups of patients. The median age of the HBV group was the youngest, and the cirrhotic rate was lowest in the non-B non-C group (only 25%). This is the largest detailed viral hepatitis marker study for HCC patients in the English literatures. Our study provided novel data on the interaction of HBV and HCV in the HCC patients and also confirmed that the HCC database of TLCN is highly representative for Taiwan and an important resource for HCC research. PMID:27082566

  14. [Development and evaluation of an inactivated bivalent vaccine against duck viral hepatitis].

    PubMed

    Yin, Fenggui; Jing, Li; Zhang, Shuang; Yu, Meng; Zhang, Wanlin; Fan, Guobing; Dong, Xiukai; Liu, Wenjun

    2015-11-01

    The rapid mutation and widely spread of duck hepatitis A virus (DHAV) lead to the vast economic loss of the duck industry. To prepare and evaluate bivalent inactivated vaccine laboratory products of DHAV, 6 strains were screened from 201 DHAV-1 strains and 38 DHAV-3 strains by using serotype epidemiological analysis in most of the duck factory. Vaccine candidate strains were selected by ELD50 and LD50 tests in the 6 strains. Continuously passaged, the 5th passaged duck embryos bodies grinding fluid was selected as vaccine virus seeds. The virus seeds were treated with formaldehyde and water in oil in water (W/O/W) emulsions, making into three batches of two bivalent inactivated vaccine laboratory products. The safety test, antibody neutralization test, challenged protection and cross immune protection experiment suggested that the vaccines possessed good safety, and neutralizing antibodies were detected at 7th day and the challenged protection rate reached 90% to 100% at the 14th and 21st day. Moreover, immune duration of ducklings lasted more than five weeks. However, cross-immunity protection experiments with DHAV-SH and DHAV-FS only had 20%-30%. The two bivalent inactivated vaccine laboratory products of duck viral hepatitis were effective and reliable, providing a new method as well as a new product for DHAV prevention and control. PMID:26939441

  15. Hepatitis B Virus Stimulated Fibronectin Facilitates Viral Maintenance and Replication through Two Distinct Mechanisms

    PubMed Central

    Ren, Sheng; Wang, Jun; Chen, Tie-Long; Li, Hao-Yu; Wan, Yu-Shun; Peng, Nan-Fang; Gui, Xi-En; Zhu, Ying

    2016-01-01

    Fibronectin (FN) is a high molecular weight extracellular matrix protein that functions in cell adhesion, growth, migration, and embryonic development. However, little is known about the role of FN during viral infection. In the present study, we found significantly higher levels of FN in sera, and liver tissues from hepatitis B virus (HBV) patients relative to healthy individuals. HBV expression enhanced FN mRNA and protein levels in the hepatic cell lines Huh7 and HepG2. HBV infection of susceptible HepG2-sodium taurocholate co-transporting polypeptide cells also increased FN expression. We also found that transcriptional factor specificity protein 1 was involved in the induction of FN by HBV. Knockdown of FN expression significantly inhibited HBV DNA replication and protein synthesis through activating endogenous IFN-α production. In addition, FN interacted with the transforming growth factor β-activated protein kinase 1 (TAK1) and TAK1-binding protein complex and attenuated interferon signaling by inhibiting TAK1 phosphorylation. Furthermore, the nuclear translocation of NF-κB/p65 was found to be inhibited by FN. We also observed that FN promoted HBV enhancers to support HBV expression. These results suggest novel functions of endogenous FN involved in immune evasion and maintenance of HBV replication. PMID:27023403

  16. Diminished viral replication and compartmentalization of hepatitis C virus in hepatocellular carcinoma tissue.

    PubMed

    Harouaka, Djamila; Engle, Ronald E; Wollenberg, Kurt; Diaz, Giacomo; Tice, Ashley B; Zamboni, Fausto; Govindarajan, Sugantha; Alter, Harvey; Kleiner, David E; Farci, Patrizia

    2016-02-01

    Analysis of hepatitis C virus (HCV) replication and quasispecies distribution within the tumor of patients with HCV-associated hepatocellular carcinoma (HCC) can provide insight into the role of HCV in hepatocarcinogenesis and, conversely, the effect of HCC on the HCV lifecycle. In a comprehensive study of serum and multiple liver specimens from patients with HCC who underwent liver transplantation, we found a sharp and significant decrease in HCV RNA in the tumor compared with surrounding nontumorous tissues, but found no differences in multiple areas of control non-HCC cirrhotic livers. Diminished HCV replication was not associated with changes in miR-122 expression. HCV genetic diversity was significantly higher in livers containing HCC compared with control non-HCC cirrhotic livers. Tracking of individual variants demonstrated changes in the viral population between tumorous and nontumorous areas, the extent of which correlated with the decline in HCV RNA, suggesting HCV compartmentalization within the tumor. In contrast, compartmentalization was not observed between nontumorous areas and serum, or in controls between different areas of the cirrhotic liver or between liver and serum. Our findings indicate that HCV replication within the tumor is restricted and compartmentalized, suggesting segregation of specific viral variants in malignant hepatocytes. PMID:26787866

  17. Diminished viral replication and compartmentalization of hepatitis C virus in hepatocellular carcinoma tissue

    PubMed Central

    Harouaka, Djamila; Engle, Ronald E.; Wollenberg, Kurt; Diaz, Giacomo; Tice, Ashley B.; Zamboni, Fausto; Govindarajan, Sugantha; Alter, Harvey; Kleiner, David E.; Farci, Patrizia

    2016-01-01

    Analysis of hepatitis C virus (HCV) replication and quasispecies distribution within the tumor of patients with HCV-associated hepatocellular carcinoma (HCC) can provide insight into the role of HCV in hepatocarcinogenesis and, conversely, the effect of HCC on the HCV lifecycle. In a comprehensive study of serum and multiple liver specimens from patients with HCC who underwent liver transplantation, we found a sharp and significant decrease in HCV RNA in the tumor compared with surrounding nontumorous tissues, but found no differences in multiple areas of control non-HCC cirrhotic livers. Diminished HCV replication was not associated with changes in miR-122 expression. HCV genetic diversity was significantly higher in livers containing HCC compared with control non-HCC cirrhotic livers. Tracking of individual variants demonstrated changes in the viral population between tumorous and nontumorous areas, the extent of which correlated with the decline in HCV RNA, suggesting HCV compartmentalization within the tumor. In contrast, compartmentalization was not observed between nontumorous areas and serum, or in controls between different areas of the cirrhotic liver or between liver and serum. Our findings indicate that HCV replication within the tumor is restricted and compartmentalized, suggesting segregation of specific viral variants in malignant hepatocytes. PMID:26787866

  18. Gene expression analysis during acute hepatitis C virus infection associates dendritic cell activation with viral clearance.

    PubMed

    Zabaleta, Aintzane; Riezu-Boj, Jose-Ignacio; Larrea, Esther; Villanueva, Lorea; Lasarte, Juan Jose; Guruceaga, Elizabeth; Fisicaro, Paola; Ezzikouri, Sayeh; Missale, Gabriele; Ferrari, Carlo; Benjelloun, Soumaya; Prieto, Jesús; Sarobe, Pablo

    2016-05-01

    Viral clearance during acute hepatitis C virus (HCV) infection is associated with the induction of potent antiviral T-cell responses. Since dendritic cells (DC) are essential in the activation of primary T-cell responses, gene expression was analyzed in DC from patients during acute HCV infection. By using microarrays, gene expression was compared in resting and activated peripheral blood plasmacytoid (pDC) and myeloid (mDC) DC from acute HCV resolving patients (AR) and from patients who become chronically infected (ANR), as well as in healthy individuals (CTRL) and chronically-infected patients (CHR). For pDC, a high number of upregulated genes was found in AR patients, irrespective of DC stimulation. However, for mDC, most evident differences were detected after DC stimulation, again corresponding to upregulated genes in AR patients. Divergent behavior of ANR was also observed when analyzing DC from CTRL and CHR, with ANR patients clustering again apart from these groups. These differences corresponded to metabolism-associated genes and genes belonging to pathways relevant for DC activation and cytokine responses. Thus, upregulation of relevant genes in DC during acute HCV infection may determine viral clearance, suggesting that dysfunctional DC may be responsible for the lack of efficient T-cell responses which lead to chronic HCV infection. PMID:26447929

  19. Expression of the serine/threonine kinase hSGK1 in chronic viral hepatitis.

    PubMed

    Fillon, Sophie; Klingel, Karin; Wärntges, Simone; Sauter, Martina; Gabrysch, Sabine; Pestel, Sabine; Tanneur, Valerie; Waldegger, Siegfried; Zipfel, Annette; Viebahn, Richard; Häussinger, Dieter; Bröer, Stefan; Kandolf, Reinhard; Lang, Florian

    2002-01-01

    The human serine/threonine kinase hSGK1 is expressed ubiquitously with highest transcript levels in pancreas and liver. This study has been performed to determine the hSGK1 distribution in normal liver and its putative role in fibrosing liver disease. HSGK1-localization was determined by in situ hybridization, regulation of hSGK1-transcription by Northern blotting, fibronectin synthesis and hSGK1 phosphorylation by Western blotting. In normal liver hSGK1 was mainly transcribed by Kupffer cells. In liver tissue from patients with chronic viral hepatitis, hSGK1 transcript levels were excessively high in numerous activated Kupffer cells and inflammatory cells localized within fibrous septum formations. HSGK1 transcripts were also detected in activated hepatic stellate cells. Accordingly, Western blotting revealed that tissue from fibrotic liver expresses excessive hSGK1 protein as compared to normal liver. TGF-beta1 (2 ng/ml) increases hSGK1 transcription in both human U937 macro-phages and HepG2 hepatoma cells. H(2)O(2) (0.3 mM) activated hSGK1 and increased fibronectin formation in HepG2 cells overexpressing hSGK1 but not in HepG2 cells expressing the inactive mutant hSGK1(K127R). In conclusion hSGK1 is upregulated by TGF-beta1 during hepatitis and may contribute to enhanced matrix formation during fibrosing liver disease. PMID:11914548

  20. Hepatitis C Virus Infection Induces Autophagy as a Prosurvival Mechanism to Alleviate Hepatic ER-Stress Response

    PubMed Central

    Dash, Srikanta; Chava, Srinivas; Aydin, Yucel; Chandra, Partha K.; Ferraris, Pauline; Chen, Weina; Balart, Luis A.; Wu, Tong; Garry, Robert F.

    2016-01-01

    Hepatitis C virus (HCV) infection frequently leads to chronic liver disease, liver cirrhosis and hepatocellular carcinoma (HCC). The molecular mechanisms by which HCV infection leads to chronic liver disease and HCC are not well understood. The infection cycle of HCV is initiated by the attachment and entry of virus particles into a hepatocyte. Replication of the HCV genome inside hepatocytes leads to accumulation of large amounts of viral proteins and RNA replication intermediates in the endoplasmic reticulum (ER), resulting in production of thousands of new virus particles. HCV-infected hepatocytes mount a substantial stress response. How the infected hepatocyte integrates the viral-induced stress response with chronic infection is unknown. The unfolded protein response (UPR), an ER-associated cellular transcriptional response, is activated in HCV infected hepatocytes. Over the past several years, research performed by a number of laboratories, including ours, has shown that HCV induced UPR robustly activates autophagy to sustain viral replication in the infected hepatocyte. Induction of the cellular autophagy response is required to improve survival of infected cells by inhibition of cellular apoptosis. The autophagy response also inhibits the cellular innate antiviral program that usually inhibits HCV replication. In this review, we discuss the physiological implications of the HCV-induced chronic ER-stress response in the liver disease progression. PMID:27223299

  1. Determining the Cellular Diversity of Hepatitis C Virus Quasispecies by Single-Cell Viral Sequencing

    PubMed Central

    McLauchlan, John

    2013-01-01

    Single-cell genomics is emerging as an important tool in cellular biology. We describe for the first time a system to investigate RNA virus quasispecies diversity at the cellular level utilizing hepatitis C virus (HCV) replicons. A high-fidelity nested reverse transcription (RT)-PCR assay was developed, and validation using control transcripts of known copy number indicated a detection limit of 3 copies of viral RNA/reaction. This system was used to determine the cellular diversity of subgenomic JFH-1 HCV replicons constitutively expressed in Huh7 cells. Each cell contained a unique quasispecies that was much less diverse than the quasispecies of the bulk cell population from which the single cells were derived, suggesting the occurrence of independent evolution at the cellular level. An assessment of the replicative fitness of the predominant single-cell quasispecies variants indicated a modest reduction in fitness compared to the wild type. Real-time RT-PCR methods capable of determining single-cell viral loads were developed and indicated an average of 113 copies of replicon RNA per cell, correlating with calculated RNA copy numbers in the bulk cell population. This study introduces a single-cell RNA viral-sequencing method with numerous potential applications to explore host-virus interactions during infection. HCV quasispecies diversity varied greatly between cells in vitro, suggesting different within-cell evolutionary pathways. Such divergent trajectories in vivo could have implications for the evolution and establishment of antiviral-resistant variants and host immune escape mutants. PMID:24049174

  2. The role of consensus interferon in the current treatment of chronic hepatitis C viral infection.

    PubMed

    Fish, Eleanor N; Harrison, Stephen A; Hassanein, Tarek

    2008-09-01

    The current standard-of-care for chronic hepatitis C viral infection is treatment with pegylated interferon (PegIFN) plus ribavirin for 24 to 48 weeks. Approximately 50% of HCV-infected patients achieve a sustained viral response (SVR) to this treatment. However, the remaining patients either respond during treatment but relapse upon treatment cessation, respond minimally, or do not respond at all. Much research effort has been expended in attempting to predict those patients who will achieve viral eradication with PegIFN/ribavirin treatment, and it is now clear that those who have either a rapid virologic response (RVR) by week 4 of treatment or a complete early virologic response (cEVR, HCV RNA qualitative negative) by week 12 will go on to achieve SVR at very high rates (70%-90%). Several trials have been completed in patients that fail to achieve RVR or cEVR. These trials include strategies of extending duration of therapy, induction regimens, or retreatment with similar and dissimilar alfa interferons. A recent study of 696 genotype 1 patients treated with both PegIFN and weight-based ribavirin revealed that only 1.6% (4/246) of patients without RVR or cEVR achieved SVR. Consensus interferon, a wholly synthetic interferonalfa, is one of the agents that has been utilized in patients that fail treatment with PegIFN/ribavirin. This molecule has been demonstrated to have a very high affinity for the interferon-alfa receptor, and laboratory studies have demonstrated that it has high levels of antiviral activity. In order to optimally utilize consensus interferon, it is important to understand its unique mechanism of action. In addition, the latest research showing the importance of achieving RVR or cEVR should be reviewed, along with strategies for utilizing consensus interferon in re-treatment, or more specifically upon identification of on-treatment failure in historically difficult-to-treat patients. PMID:23329909

  3. Anti-Viral Therapy and Decreased Sexual Desire in Patients with Chronic Hepatitis C

    PubMed Central

    Hsieh, Po-Fan; Peng, Cheng-Yuan; Su, Kuan-Pin

    2016-01-01

    Purpose Peg-interferon (PegIFN)α2a or PegIFNα2b plus ribavirin (RBV) is the standard therapy for chronic hepatitis C virus (HCV) infection in Taiwan and Asia. It is commonly associated with adverse effects, but the issue of sexual and mental health is not well reported. This study aimed to evaluate the impact of anti-viral therapy with PegIFNα plus RBV on sexual desire and depression. Methods This prospective cohort study from 2009 to 2014 enrolled 181 patients with HCV who received PegIFNα2a (180 mcg/week) or PegIFNα2b (1.5 mcg/Kg/week) plus RBV (800–1200 mg/day) according to response-guide therapy for 24 to 48 weeks in a tertiary medical center. Patients with decreased sexual desire (DSD) before PegIFNα plus RBV were excluded. Patients were evaluated at baseline (week 0) and after 2, 4, 8, 12, 16, 20, and 24 weeks of PegIFNα plus RBV treatment using the structured Mini-International Neuropsychiatric Interview, for the diagnosis of a major depressive episode, and the 21-item Beck Depression Inventory (BDI), for monitoring depressive symptoms. The 21st item of the BDI was used to evaluate DSD. Results During therapy, 124 (68.5%) patients had DSD. The BDI score peaked at 14.8 weeks. The severity of DSD was greatest at 16 weeks of treatment. The average score of the 21st item of the BDI correlated with DSD. Depression history and the prevalence of subsequent major depressive disorder after anti-viral therapy was correlated to DSD (p = 0.05 and 0.001). Male patients complained of DSD more significantly than females (p = 0.031). Conclusions Decreased sexual desire is common but is usually neglected in patients with chronic hepatitis C undergoing anti-viral therapy, especially among male patients. Physicians must be monitoring the side effects of sexual health and depression. PMID:27505293

  4. Prevalence of IgG autoantibody against F-actin in patients suspected of having autoimmune or acute viral hepatitis.

    PubMed

    Jaskowski, Troy D; Konnick, Eric Q; Ashwood, Edward R; Litwin, Christine M; Hill, Harry R

    2007-01-01

    Our objectives in this study were to compare results obtained by an enzyme immunoassay (EIA) for F-actin antibody (FAA) immunoglobulin G (IgG) to those determined by an indirect fluorescent antibody (IFA) assay for smooth muscle antibody (SMA) IgG, and to determine the prevalence of FAA in patient sera having serologic evidence of acute viral hepatitis. Sera from 415 patients suspected of having autoimmune hepatitis (AIH), 208 patients suspected of having acute viral hepatitis A, B, or C, and 100 healthy blood donors (HBD) were included in the study. Only one of 100 HBD showed low levels (20-30 Units) of F-actin IgG. In patients suspected of having AIH, the prevalence of FAA increased as SMA titers increased and all sera with SMA titers of >or=1:160 were FAA-positive. In contrast, there were many sera with negative (<1:20) or low (1:20-1:40) SMA titers that contained moderate to high levels (>30 Units) of FAA; many exceeding 80 Units. Moreover, 51.4% of these sera were also positive for anti-nuclear antibody (ANA), which is also utilized in diagnosing type 1 AIH. FAA was detected in 25% of viral hepatitis antibody-positive sera, with the majority (59.3%) containing low levels, and all were ANA-negative. PMID:17621360

  5. Structure of Hepatitis E Virion-Sized Particle Reveals an RNA-Dependent Viral Assembly Pathway

    SciTech Connect

    Xing, L.; Wall, J.; Li, T.-C.; Mayazaki, N.; Simon, M. N.; Moore, M.; Wang, C.-Y.; Takeda, N.; Wakita, T.; Miyamura, T.; Cheng, R. H.

    2010-10-22

    Hepatitis E virus (HEV) induces acute hepatitis in humans with a high fatality rate in pregnant women. There is a need for anti-HEV research to understand the assembly process of HEV native capsid. Here, we produced a large virion-sized and a small T=1 capsid by expressing the HEV capsid protein in insect cells with and without the N-terminal 111 residues, respectively, for comparative structural analysis. The virion-sized capsid demonstrates a T=3 icosahedral lattice and contains RNA fragment in contrast to the RNA-free T=1 capsid. However, both capsids shared common decameric organization. The in vitro assembly further demonstrated that HEV capsid protein had the intrinsic ability to form decameric intermediate. Our data suggest that RNA binding is the extrinsic factor essential for the assembly of HEV native capsids.

  6. Hepatitis C and Incarceration

    MedlinePlus

    HEPATITIS C & INCARCERATION What is hepatitis? “Hepatitis” means inflammation or swelling of the liver. The liver is an important ... viral hepatitis: Hepatitis A, Hepatitis B, and Hepatitis C. They are all different from each other and ...

  7. Vinexin β Interacts with Hepatitis C Virus NS5A, Modulating Its Hyperphosphorylation To Regulate Viral Propagation

    PubMed Central

    Xiong, Wei; Yang, Jie; Wang, Mingzhen; Wang, Hailong; Rao, Zhipeng; Zhong, Cheng; Xin, Xiu; Mo, Lin; Yu, Shujuan

    2015-01-01

    ABSTRACT Hepatitis C virus (HCV) nonstructural protein 5A (NS5A) is essential for HCV genome replication and virion production and is involved in the regulation of multiple host signaling pathways. As a proline-rich protein, NS5A is capable of interacting with various host proteins containing Src homology 3 (SH3) domains. Previous studies have suggested that vinexin, a member of the sorbin homology (SoHo) adaptor family, might be a potential binding partner of NS5A by yeast two-hybrid screening. However, firm evidence for this interaction is lacking, and the significance of vinexin in the HCV life cycle remains unclear. In this study, we demonstrated that endogenously and exogenously expressed vinexin β coimmunoprecipitated with NS5A derived from different HCV genotypes. Two residues, tryptophan (W307) and tyrosine (Y325), in the third SH3 domain of vinexin β and conserved Pro-X-X-Pro-X-Arg motifs at the C terminus of NS5A were indispensable for the vinexin-NS5A interaction. Furthermore, downregulation of endogenous vinexin β significantly suppressed NS5A hyperphosphorylation and decreased HCV replication, which could be rescued by expressing a vinexin β short hairpin RNA-resistant mutant. We also found that vinexin β modulated the hyperphosphorylation of NS5A in a casein kinase 1α-dependent on manner. Taken together, our findings suggest that vinexin β modulates NS5A phosphorylation via its interaction with NS5A, thereby regulating HCV replication, implicating vinexin β in the viral life cycle. IMPORTANCE Hepatitis C virus (HCV) nonstructural protein NS5A is a phosphoprotein, and its phosphorylation states are usually modulated by host kinases and other viral nonstructural elements. Additionally, cellular factors containing Src homology 3 (SH3) domains have been reported to interact with proline-rich regions of NS5A. However, it is unclear whether there are any relationships between NS5A phosphorylation and the NS5A-SH3 interaction, and little is known

  8. Coevolution analysis of Hepatitis C virus genome to identify the structural and functional dependency network of viral proteins

    NASA Astrophysics Data System (ADS)

    Champeimont, Raphaël; Laine, Elodie; Hu, Shuang-Wei; Penin, Francois; Carbone, Alessandra

    2016-05-01

    A novel computational approach of coevolution analysis allowed us to reconstruct the protein-protein interaction network of the Hepatitis C Virus (HCV) at the residue resolution. For the first time, coevolution analysis of an entire viral genome was realized, based on a limited set of protein sequences with high sequence identity within genotypes. The identified coevolving residues constitute highly relevant predictions of protein-protein interactions for further experimental identification of HCV protein complexes. The method can be used to analyse other viral genomes and to predict the associated protein interaction networks.

  9. Coevolution analysis of Hepatitis C virus genome to identify the structural and functional dependency network of viral proteins

    PubMed Central

    Champeimont, Raphaël; Laine, Elodie; Hu, Shuang-Wei; Penin, Francois; Carbone, Alessandra

    2016-01-01

    A novel computational approach of coevolution analysis allowed us to reconstruct the protein-protein interaction network of the Hepatitis C Virus (HCV) at the residue resolution. For the first time, coevolution analysis of an entire viral genome was realized, based on a limited set of protein sequences with high sequence identity within genotypes. The identified coevolving residues constitute highly relevant predictions of protein-protein interactions for further experimental identification of HCV protein complexes. The method can be used to analyse other viral genomes and to predict the associated protein interaction networks. PMID:27198619

  10. Coevolution analysis of Hepatitis C virus genome to identify the structural and functional dependency network of viral proteins.

    PubMed

    Champeimont, Raphaël; Laine, Elodie; Hu, Shuang-Wei; Penin, Francois; Carbone, Alessandra

    2016-01-01

    A novel computational approach of coevolution analysis allowed us to reconstruct the protein-protein interaction network of the Hepatitis C Virus (HCV) at the residue resolution. For the first time, coevolution analysis of an entire viral genome was realized, based on a limited set of protein sequences with high sequence identity within genotypes. The identified coevolving residues constitute highly relevant predictions of protein-protein interactions for further experimental identification of HCV protein complexes. The method can be used to analyse other viral genomes and to predict the associated protein interaction networks. PMID:27198619

  11. Hepatitis C FAQs

    MedlinePlus

    ... of Viral Hepatitis Contact Us Quick Links to Hepatitis ... A | B | C | D | E Viral Hepatitis Home ... Outbreaks State and Local Partners & Grantees Resource Center Hepatitis C FAQs for the Public Recommend on Facebook ...

  12. Hepatitis B FAQs

    MedlinePlus

    ... of Viral Hepatitis Contact Us Quick Links to Hepatitis ... A | B | C | D | E Viral Hepatitis Home ... Outbreaks State and Local Partners & Grantees Resource Center Hepatitis B FAQs for the Public Recommend on Facebook ...

  13. Hepatitis A FAQs

    MedlinePlus

    ... of Viral Hepatitis Contact Us Quick Links to Hepatitis ... A | B | C | D | E Viral Hepatitis Home ... Outbreaks State and Local Partners & Grantees Resource Center Hepatitis A FAQs for the Public Recommend on Facebook ...

  14. Viral Carcinogenesis: Factors Inducing DNA Damage and Virus Integration

    PubMed Central

    Chen, Yan; Williams, Vonetta; Filippova, Maria; Filippov, Valery; Duerksen-Hughes, Penelope

    2014-01-01

    Viruses are the causative agents of 10%–15% of human cancers worldwide. The most common outcome for virus-induced reprogramming is genomic instability, including accumulation of mutations, aberrations and DNA damage. Although each virus has its own specific mechanism for promoting carcinogenesis, the majority of DNA oncogenic viruses encode oncogenes that transform infected cells, frequently by targeting p53 and pRB. In addition, integration of viral DNA into the human genome can also play an important role in promoting tumor development for several viruses, including HBV and HPV. Because viral integration requires the breakage of both the viral and the host DNA, the integration rate is believed to be linked to the levels of DNA damage. DNA damage can be caused by both endogenous and exogenous factors, including inflammation induced by either the virus itself or by co-infections with other agents, environmental agents and other factors. Typically, cancer develops years to decades following the initial infection. A better understanding of virus-mediated carcinogenesis, the networking of pathways involved in transformation and the relevant risk factors, particularly in those cases where tumorigenesis proceeds by way of virus integration, will help to suggest prophylactic and therapeutic strategies to reduce the risk of virus-mediated cancer. PMID:25340830

  15. Hepatitis B viral load in dried blood spots: a validation study in Zambia

    PubMed Central

    Vinikoor, Michael J.; Zürcher, Samuel; Musukuma, Kalo; Kachuwaire, Obert; Rauch, Andri; Chi, Benjamin H.; Gorgievski, Meri; Zwahlen, Marcel; Wandeler, Gilles

    2016-01-01

    Background Access to hepatitis B viral load (VL) testing is poor in sub-Saharan Africa (SSA) due to economic and logistical reasons. Objectives To demonstrate the feasibility of testing dried blood spots (DBS) for hepatitis B virus (HBV) VL in a laboratory in Lusaka, Zambia, and to compare HBV VLs between DBS and plasma samples. Study design Paired plasma and DBS samples from HIV-HBV co-infected Zambian adults were analyzed for HBV VL using the COBAS AmpliPrep/COBAS TaqMan HBV test (Version 2.0) and for genotype by direct sequencing. We used Bland-Altman analysis to compare VLs between sample types and by HBV genotype. Logistic regression analysis was conducted to assess the probability of an undetectable DBS result by plasma VL. Results Among 68 participants, median age was 34 years, 61.8% were men, and median plasma HBV VL was 3.98 log IU/ml (interquartile range, 2.04–5.95). Among sequenced viruses, 28 were genotype A1 and 27 were genotype E. Bland-Altman plots suggested strong agreement between DBS and plasma VLs. DBS VLs were on average 1.59 log IU/ml lower compared to plasma with 95% limits of agreement of −2.40 to −0.83 log IU/ml. At a plasma VL ≥2,000 IU/ml, the probability of an undetectable DBS result was 1.8% (95% CI: 0.5–6.6). At plasma VL ≥20,000 IU/ml this probability reduced to 0.2% (95% CI: 0.03–1.7). Conclusions In a Zambian laboratory, we observed strong agreement between DBS and plasma VLs and high sensitivity in DBS at plasma VL ≥2,000 IU/ml. As HBV treatment expands, DBS could increase access to HBV VL testing in SSA settings. PMID:26356987

  16. Role of viral and host factors in interferon based therapy of hepatitis C virus infection.

    PubMed

    Imran, Muhammad; Manzoor, Sobia; Ashraf, Javed; Khalid, Madiha; Tariq, Muqddas; Khaliq, Hafiza Madeha; Azam, Sikandar

    2013-01-01

    The current standard of care (SOC) for hepatitis C virus (HCV) infection is the combination of pegylated interferon (PEG-IFN), Ribavirin and protease inhibitor for HCV genotype 1. Nevertheless, this treatment is successful only in 70-80% of the patients. In addition, the treatment is not economical and is of immense physical burden for the subject. It has been established now, that virus-host interactions play a significant role in determining treatment outcomes. Therefore identifying biological markers that may predict the treatment response and hence treatment outcome would be useful. Both IFN and Ribavirin mainly act by modulating the immune system of the patient. Therefore, the treatment response is influenced by genetic variations of the human as well as the HCV genome. The goal of this review article is to summarize the impact of recent scientific advances in this area regarding the understanding of human and HCV genetic variations and their effect on treatment outcomes. Google scholar and PubMed have been used for literature research. Among the host factors, the most prominent associations are polymorphisms within the region of the interleukin 28B (IL28B) gene, but variations in other cytokine genes have also been linked with the treatment outcome. Among the viral factors, HCV genotypes are noteworthy. Moreover, for sustained virological responses (SVR), variations in core, p7, non-structural 2 (NS2), NS3 and NS5A genes are also important. However, all considered single nucleotide polymorphisms (SNPs) of IL28B and viral genotypes are the most important predictors for interferon based therapy of HCV infection. PMID:24079723

  17. Cellular and humoral immune reactions in chronic active liver disease. II. Lymphocyte subsets and viral antigens in liver biopsies of patients with acute and chronic hepatitis B.

    PubMed Central

    Eggink, H F; Houthoff, H J; Huitema, S; Wolters, G; Poppema, S; Gips, C H

    1984-01-01

    The characteristics and distribution of the inflammatory infiltrate in liver biopsies of 25 patients with hepatitis B viral (HBV) infection were studied in relation to the distribution and expression of HBV antigens. Mononuclear subsets were characterized with monoclonal (OKT, OKM, Leu) antibodies to surface antigens. For the demonstration of viral antigens directly conjugated antibodies to surface (HBsAg), core (HBcAg) and 'e' (HBeAg) antigen were used. For the study of mutual relations all methods were performed on serial cut tissue sections. In chronic active hepatitis B (CAH-B, n = 12) OKT8+ lymphocytes of T cell origin were the only cell type present in areas with liver cell degeneration and T cell cytotoxicity appears to be the only immune mechanism. In chronic persistent hepatitis B (CPH-B, n = 7) the only conspicuous feature was the presence of many Leu 3+ lymphocytes of the helper/inducer population in the portal tracts. In acute hepatitis B (AHB, n = 6) OKT8+ cells of non-T origin (OKT1-,3-) and Leu 7+ cells of presumed natural killer (NK) potential predominated in the areas with liver cell necrosis, and non-T cell cytotoxicity appears to be the predominant immune mechanism. In none of these disease entities a positive spatial relation could be established between the cytotoxic cells and the demonstrable expression of HBV antigens in hepatocytes. It is concluded that differences in immunological reaction pattern may explain the different course in the three forms of HBV infection studied. Images Fig. 1 Fig. 2 PMID:6713726

  18. Sustained viral response in a hepatitis C virus-infected chimpanzee via a combination of direct-acting antiviral agents.

    PubMed

    Olsen, David B; Davies, Mary-Ellen; Handt, Larry; Koeplinger, Kenneth; Zhang, Nanyan Rena; Ludmerer, Steven W; Graham, Donald; Liverton, Nigel; MacCoss, Malcolm; Hazuda, Daria; Carroll, Steven S

    2011-02-01

    Efforts to develop novel, interferon-sparing therapies for treatment of chronic hepatitis C (HCV) infection are contingent on the ability of combination therapies consisting of direct antiviral inhibitors to achieve a sustained virologic response. This work demonstrates a proof of concept that coadministration of the nucleoside analogue MK-0608 with the protease inhibitor MK-7009, both of which produced robust viral load declines as monotherapy, to an HCV-infected chimpanzee can achieve a cure of infection. PMID:21115793

  19. Liver function in acute viral hepatitis as determined by a hepatocyte-specific ligand: 99mTc-galactosyl-neoglycoalbumin.

    PubMed

    Virgolini, I; Müller, C; Höbart, J; Scheithauer, W; Angelberger, P; Bergmann, H; O'Grady, J; Sinzinger, H

    1992-04-01

    Twelve patients with recently diagnosed acute viral hepatitis underwent serial 99mTc-galactosyl neoglycoalbumin scanning of the liver (for up to 8 mo). Injection of 99mTc-galactosyl neoglycoalbumin (150 mBq) at a rate of 3.5 mg (50 nmol; 1 ml) revealed that the liver is the exclusive site of tracer uptake. Simulation of 99mTc-galactosyl neoglycoalbumin kinetics allowed quantification of galactosyl neoglycoalbumin binding to human hepatic binding protein. Return of liver function test scores to normal values was associated in two patients with hepatitis A, in four patients with hepatitis B and in two patients with non-A, non-B hepatitis virus infection, with increases in hepatic binding protein concentration (up to three times the initial concentration), binding rate constant and hepatic blood flow. In the other four patients (three patients with hepatitis B and one patient with cytomegalovirus infection) a prolonged course of disease was monitored. In the mean, hepatic binding protein increased from 0.41 +/- 0.11 mumol/L after onset of acute hepatitis (n = 12) to 0.78 +/- 0.21 mumol/L after 6 mo of follow-up (n = 10) (p less than 0.001). During this period, binding rate constant (72.4 +/- 12.6 vs. 82 +/- 11.5 mumol/L/sec; p less than 0.05) and hepatic blood flow (0.027 +/- 0.0051 vs. 0.031 +/- 0.0083 L/sec; p less than 0.05) increased. Hepatic binding protein concentration correlated highly with actual laboratory test results for liver function (r = 0.98; p = 0.0001). We conclude that scintigraphic evaluation of functional liver cell mass using the new receptor-tracer 99mTc-galactosyl neoglycoalbumin could provide an in vivo diagnostic means of quantifying liver function and assessing liver morphology. In addition, our findings suggest that changes in hepatic binding protein-receptor concentration are likely to occur in vivo. PMID:1551636

  20. Natural killer cells contribute to hepatic injury and help in viral persistence during progression of hepatitis B e-antigen-negative chronic hepatitis B virus infection.

    PubMed

    Ghosh, S; Nandi, M; Pal, S; Mukhopadhyay, D; Chakraborty, B C; Khatun, M; Bhowmick, D; Mondal, R K; Das, S; Das, K; Ghosh, R; Banerjee, S; Santra, A; Chatterjee, M; Chowdhury, A; Datta, S

    2016-08-01

    Hepatitis B e-antigen negative (e(-)) chronic HBV infection (CHI) encompasses a heterogeneous clinical spectrum ranging from inactive carrier (IC) state to e(-) chronic hepatitis B (CHB), cirrhosis and hepatic decompensation. In the backdrop of dysfunctional virus-specific T cells, natural killer (NK) cells are emerging as innate effectors in CHI. We characterized CD3(-) CD56(+) NK cells in clinically well-defined, treatment-naive e(-) patients in IC, e(-)CHB or decompensated liver cirrhosis (LC) phase to appraise their role in disease progression. The NK cell frequencies increased progressively with disease severity (IC 8.2%, e(-)CHB 13.2% and LC 14.4%). Higher proportion of NK cells from LC/e(-)CHB expressed CD69, NKp46, NKp44, TRAIL and perforin, the last two being prominent features of CD56(bright) and CD56(dim) NK subsets, respectively. The frequencies of CD3(-) CD56(+) NK cells together with TRAIL(+) CD56(bright) and Perforin(+) CD56(dim) NK cells correlated positively with serum alanine transaminase levels in e(-)CHB/LC. K562 cell-stimulated NK cells from e(-)CHB/LC exhibited significantly greater degranulation but diminished interferon-γ production than IC. Further, Perforin(+) NK cell frequency inversely correlated with autologous CD4(+) T-cell count in e(-) patients and ligands of NK receptors were over-expressed in CD4(+) T cells from e(-)CHB/LC relative to IC. Co-culture of sorted CD56(dim) NK cells and CD4(+) T cells from e(-)CHB showed enhanced CD4(+) T-cell apoptosis, which was reduced by perforin inhibitor, concanamycin A, suggesting a possible perforin-dependent NK cell-mediated CD4(+) T-cell depletion. Moreover, greater incidence of perforin-expressing NK cells and decline in CD4(+) T cells were noticed intrahepatically in e(-)CHB than IC. Collectively, NK cells contribute to the progression of e(-)CHI by enhanced TRAIL- and perforin-dependent cytolytic activity and by restraining anti-viral immunity through reduced interferon-γ secretion and

  1. Liver Enzymes in Children with beta-Thalassemia Major: Correlation with Iron Overload and Viral Hepatitis

    PubMed Central

    Salama, Khaled M.; Ibrahim, Ola M.; Kaddah, Ahmed M.; Boseila, Samia; Ismail, Leila Abu; Hamid, May M. Abdel

    2015-01-01

    BACKGROUND: Beta Thalassemia is the most common chronic hemolytic anemia in Egypt (85.1%) with an estimated carrier rate of 9-10.2%. Injury to the liver, whether acute or chronic, eventually results in an increase in serum concentrations of Alanine transaminase (ALT) and Aspartate transaminase (AST). AIM: Evaluating the potentiating effect of iron overload & viral hepatitis infection on the liver enzymes. PATIENTS AND METHODS: Eighty (80) thalassemia major patients were studied with respect to liver enzymes, ferritin, transferrin saturation, HBsAg, anti-HCV antibody and HCV-PCR for anti-HCV positive patients. RESULTS: Fifty % of the patients were anti-HCV positive and 55% of them were HCV-PCR positive. Patients with elevated ALT and AST levels had significantly higher mean serum ferritin than those with normal levels. Anti-HCV positive patients had higher mean serum ferritin, serum ALT, AST and GGT levels and higher age and duration of blood transfusion than the negative group. HCV-PCR positive patients had higher mean serum ferritin and serum ALT and also higher age and duration of blood transfusion than the negative group. CONCLUSION: Iron overload is a main leading cause of elevated liver enzymes, and presence of HCV infection is significantly related to the increased iron overload. PMID:27275237

  2. Targeted transfection and expression of hepatitis B viral DNA in human hepatoma cells.

    PubMed Central

    Liang, T J; Makdisi, W J; Sun, S; Hasegawa, K; Zhang, Y; Wands, J R; Wu, C H; Wu, G Y

    1993-01-01

    A soluble DNA carrier system consisting of an asialoglycoprotein covalently linked to poly-L-lysine was used to bind DNA and deliver hepatitis B virus (HBV) DNA constructs to asialoglycoprotein receptor-positive human hepatoma cells. 4 d after transfection with surface or core gene expression constructs, HBsAg and HBeAg in the media were measured to be 16 ng/ml and 32 U/ml per 10(7) cells, respectively. Antigen production was completely inhibited by the addition of an excess of asialoorosomucoid. On the other hand, asialoglycoprotein receptor-negative human hepatoma cells, SK-Hep1, did not produce any viral antigens under identical conditions after incubation with HBV DNA complexed to a conjugate composed of asialoorosomucoid and poly-L-lysine. Using a complete HBV genome construct, HBsAg and HBeAg levels reached 16 ng/ml and 16 U/ml per 10(7) cells, respectively. Northern blots revealed characteristic HBV RNA transcripts including 3.5-, 2.4-, and 2.1-kb fragments. Intracellular and extracellular HBV DNA sequences including relaxed circular, linear and single stranded forms were detected by Southern blot hybridization. Finally, 42-nm Dane particles purified from the spent cultures medium were visualized by electron microscopy. This study demonstrates that a targetable DNA carrier system can transfect HBV DNA in vitro resulting in the production of complete HBV virions. Images PMID:8383700

  3. Differential viral kinetics in treated genotype 4 chronic hepatitis C patients according to ethnicity.

    PubMed

    Elefsiniotis, I S; Pavlidis, C; Dimitroulopoulos, D; Vezali, E; Mihas, C; Mariolis-Sapsakos, T; Koutsounas, S; Paraskevas, E; Saroglou, G

    2009-10-01

    Data concerning the efficacy of PEG-IFN alpha 2a plus ribavirin treatment in treatment-naive, genotype 4-infected chronic hepatitis C (CHC) patients from Europe are limited. Hence the aim of this study was to investigate the viral kinetics as well as the sustained virological response (SVR) rates and their predictors, in these patients. One hundred and twenty-three patients were retrospectively analysed. Early (EVR) and late virological response (LVR) was confirmed by undetectable (<50 IU/mL) serum HCV-RNA at week 12 and week 24 of treatment, respectively. SVR was confirmed by undetectable serum HCV-RNA at the end of treatment as well as 6 months later. Overall, 43.5% of patients exhibited SVR, 42.6% were nonresponders and 13.9% were relapsers. EVR was observed in 40.74% and LVR in 59.25% of them. The positive predictive values of EVR and LVR were 72.97% and 86.27% whereas their negative predictive values were 64.29% and 92.85%, respectively. EVR independently predicted SVR in Caucasian patients (P < 0.001) but not in Egyptian patients (P = 0.613), in whom the only independent predictor of SVR was the absence of cirrhosis (P = 0.004). LVR seems to be a better predictor of SVR than EVR in the vast majority of genotype 4-infected CHC patients, irrespective of ethnicity and all the other baseline parameters. PMID:19413697

  4. A Novel Approach to Identify Candidate Prognostic Factors for Hepatitis C Treatment Response Integrating Clinical and Viral Genetic Data

    PubMed Central

    Amadoz, Alicia; González-Candelas, Fernando

    2015-01-01

    The combined therapy of pegylated interferon (IFN) plus ribavirin (RBV) has been for a long time the standard treatment for patients infected with hepatitis C virus (HCV). In the case of genotype 1, only 38%–48% of patients have a positive response to the combined treatment. In previous studies, viral genetic information has been occasionally included as a predictor. Here, we consider viral genetic variation in addition to 11 clinical and 19 viral populations and evolutionary parameters to identify candidate baseline prognostic factors that could be involved in the treatment outcome. We obtained potential prognostic models for HCV subtypes la and lb in combination as well as separately. We also found that viral genetic information is relevant for the combined treatment assessment of patients, as the potential prognostic model of joint subtypes includes 9 viral-related variables out of 11. Our proposed methodology fully characterizes viral genetic information and finds a combination of positions that modulate inter-patient variability. PMID:25780333

  5. Viral Determinants of miR-122-Independent Hepatitis C Virus Replication

    PubMed Central

    Hopcraft, Sharon E.; Azarm, Kristopher D.; Israelow, Benjamin; Lévêque, Nicolas; Schwarz, Megan C.; Hsu, Tien-Huei; Chambers, Matthew T.; Sourisseau, Marion; Semler, Bert L.

    2015-01-01

    ABSTRACT Hepatitis C virus (HCV) replication requires binding of the liver-specific microRNA (miRNA) miR-122 to two sites in the HCV 5′ untranslated region (UTR). Although we and others have shown that viral genetics impact the amount of active miR-122 required for replication, it is unclear if HCV can replicate in the complete absence of this miRNA. To probe the absolute requirements for miR-122 and the genetic basis for those requirements, we used clustered regularly interspaced short palindromic repeat (CRISPR) technology to knock out miR-122 in Huh-7.5 cells and reconstituted these knockout (KO) cells with either wild-type miR-122 or a mutated version of this miRNA. We then characterized the replication of the wild-type virus, as well as a mutated HCV bearing 5′ UTR substitutions to restore binding to the mutated miR-122, in miR-122 KO Huh-7.5 cells expressing no, wild-type, or mutated miR-122. We found that while replication was most efficient when wild-type or mutated HCV was provided with the matched miR-122, inefficient replication could be observed in cells expressing the mismatched miR-122 or no miR-122. We then selected viruses capable of replicating in cells expressing noncognate miR-122 RNAs. Unexpectedly, these viruses contained multiple mutations throughout their first 42 nucleotides that would not be predicted to enhance binding of the provided miR-122. These mutations increased HCV RNA replication in cells expressing either the mismatched miR-122 or no miR-122. These data provide new evidence that HCV replication can occur independently of miR-122 and provide unexpected insights into how HCV genetics influence miR-122 requirements. IMPORTANCE Hepatitis C virus (HCV) is the leading cause of liver cancer in the Western Hemisphere. HCV infection requires miR-122, which is expressed only in liver cells, and thus is one reason that replication of this virus occurs efficiently only in cells of hepatic origin. To understand how HCV genetics impact mi

  6. [Hepatitis C: diagnosis, anti-viral therapy, after-care. Hungarian consensus guideline].

    PubMed

    Hunyady, Béla; Gerlei, Zsuzsanna; Gervain, Judit; Horváth, Gábor; Lengyel, Gabriella; Pár, Alajos; Rókusz, László; Szalay, Ferenc; Telegdy, László; Tornai, István; Werling, Klára; Makara, Mihály

    2015-03-01

    Approximately 70,000 people are infected with hepatitis C virus in Hungary, and more than half of them are not aware of their infection. From the point of infected individuals early recognition and effective treatment of related liver injury may prevent consequent advanced liver diseases and complications (liver cirrhosis, liver failure and liver cancer) and can increase work productivity and life expectancy. Furthermore, these could from prevent further spread of the virus as well as reduce substantially long term financial burden of related morbidity, as a socioeconomic aspect. Pegylated interferon + ribavirin dual therapy, which is available in Hungary since 2003, can clear the virus in 40-45% of previously not treated (naïve), and in 5-21% of previous treatment-failure patients. Addition of a direct acting first generation protease inhibitor drug (boceprevir or telaprevir) to the dual therapy increases the chance of sustained viral response to 63-75% and 59-66%, respectively. These two protease inhibitors are available and financed for a segment of Hungarian patients since May 2013. Between 2013 and February 2015, other direct acting antivirals and interferon-free combination therapies have been registered for the treatment of chronic hepatitis C with a potential efficacy over 90% and typically with a short duration of 8-12 weeks. Indication of therapy includes exclusion of contraindications to the drugs and demonstration of viral replication with consequent liver injury, i.e., inflammation and/or fibrosis in the liver. Non-invasive methods (elastography and biochemical methods) are accepted and preferred for staging liver damage (fibrosis). For initiation of treatment accurate and timely molecular biology tests are mandatory. Eligibility for treatment is a subject of individual central medical review. Due to budget limitations therapy is covered only for a proportion of patients by the National Health Insurance Fund. Priority is given to those with urgent

  7. Hepatitis C virus-induced hepatocellular carcinoma

    PubMed Central

    Goossens, Nicolas

    2015-01-01

    Hepatitis C virus (HCV) is a leading etiology of hepatocellular carcinoma (HCC). The interaction of HCV with its human host is complex and multilayered; stemming in part from the fact that HCV is a RNA virus with no ability to integrate in the host's genome. Direct and indirect mechanisms of HCV-induced HCC include activation of multiple host pathways such as liver fibrogenic pathways, cellular and survival pathways, interaction with the immune and metabolic systems. Host factors also play a major role in HCV-induced HCC as evidenced by genomic studies identifying polymorphisms in immune, metabolic, and growth signaling systems associated with increased risk of HCC. Despite highly effective direct-acting antiviral agents, the morbidity and incidence of liver-related complications of HCV, including HCC, is likely to persist in the near future. Clinical markers to selectively identify HCV subjects at higher risk of developing HCC have been reported however they require further validation, especially in subjects who have experienced sustained virological response. Molecular biomarkers allowing further refinement of HCC risk are starting to be implemented in clinical platforms, allowing objective stratification of risk and leading to individualized therapy and surveillance for HCV individuals. Another role for molecular biomarker-based stratification could be enrichment of HCC chemoprevention clinical trials leading to smaller sample size, shorter trial duration, and reduced costs. PMID:26157746

  8. Recurrent Acute Liver Failure Because of Acute Hepatitis Induced by Organic Solvents: A Case Report.

    PubMed

    Ito, Daisuke; Tanaka, Tomohiro; Akamatsu, Nobuhisa; Ito, Kyoji; Hasegawa, Kiyoshi; Sakamoto, Yoshihiro; Nakagawa, Hayato; Fujinaga, Hidetaka; Kokudo, Norihiro

    2016-01-01

    The authors present a case of recurrent acute liver failure because of occupational exposure to organic solvents. A 35-year-old man with a 3-week history of worsening jaundice and flu-like symptoms was admitted to our hospital. Viral hepatitis serology and autoimmune factors were negative. The authors considered liver transplantation, but the patient's liver function spontaneously recovered. Liver biopsy revealed massive infiltration of neutrophils, but the cause of the acute hepatitis was not identified. Four months after discharge, the patient's liver function worsened again. The authors considered the possibility of antinuclear antibody-negative autoimmune hepatitis and initiated steroid treatment, which was effective. Four months after discharge, the patient was admitted for repeated liver injury. The authors started him on steroid pulse therapy, but this time it was not effective. Just before the first admission, he had started his own construction company where he was highly exposed to organic solvents, and thus the authors considered organic solvent-induced hepatitis. Although urine test results for organic solvents were negative, a second liver biopsy revealed severe infiltration of neutrophils, compatible with toxic hepatitis. Again, his liver function spontaneously improved. Based on the pathology and detailed clinical course, including the patient's high exposure to organic solvents since just before the first admission, and the spontaneous recovery of his liver damage in the absence of the exposure, he was diagnosed with toxic hepatitis. The authors strongly advised him to avoid organic solvents. Since then, he has been in good health without recurrence. This is the first report of recurrent acute liver failure because of exposure to organic solvents, which was eventually diagnosed through a meticulous medical history and successfully recovered by avoiding the causative agents. In acute liver failure with an undetermined etiology, clinicians should rule

  9. Recurrent Acute Liver Failure Because of Acute Hepatitis Induced by Organic Solvents

    PubMed Central

    Ito, Daisuke; Tanaka, Tomohiro; Akamatsu, Nobuhisa; Ito, Kyoji; Hasegawa, Kiyoshi; Sakamoto, Yoshihiro; Nakagawa, Hayato; Fujinaga, Hidetaka; Kokudo, Norihiro

    2016-01-01

    Abstract The authors present a case of recurrent acute liver failure because of occupational exposure to organic solvents. A 35-year-old man with a 3-week history of worsening jaundice and flu-like symptoms was admitted to our hospital. Viral hepatitis serology and autoimmune factors were negative. The authors considered liver transplantation, but the patient's liver function spontaneously recovered. Liver biopsy revealed massive infiltration of neutrophils, but the cause of the acute hepatitis was not identified. Four months after discharge, the patient's liver function worsened again. The authors considered the possibility of antinuclear antibody-negative autoimmune hepatitis and initiated steroid treatment, which was effective. Four months after discharge, the patient was admitted for repeated liver injury. The authors started him on steroid pulse therapy, but this time it was not effective. Just before the first admission, he had started his own construction company where he was highly exposed to organic solvents, and thus the authors considered organic solvent-induced hepatitis. Although urine test results for organic solvents were negative, a second liver biopsy revealed severe infiltration of neutrophils, compatible with toxic hepatitis. Again, his liver function spontaneously improved. Based on the pathology and detailed clinical course, including the patient's high exposure to organic solvents since just before the first admission, and the spontaneous recovery of his liver damage in the absence of the exposure, he was diagnosed with toxic hepatitis. The authors strongly advised him to avoid organic solvents. Since then, he has been in good health without recurrence. This is the first report of recurrent acute liver failure because of exposure to organic solvents, which was eventually diagnosed through a meticulous medical history and successfully recovered by avoiding the causative agents. In acute liver failure with an undetermined etiology, clinicians

  10. Electrostatics of capsid-induced viral RNA organization

    PubMed Central

    Forrey, Christopher; Muthukumar, M.

    2009-01-01

    We have addressed the role of electrostatics in the formation of genome structure in the Pariacoto virus, where substantial experimental data are available. We have used Langevin dynamics simulation of a coarse-grained model, based on the published crystal structure of the rigid portion of the Pariacoto capsid and including flexible N-terminal protein arms, attached to the rigid capsid at the appropriate locations. The inclusion of charged residues in our model was dictated solely by the location of charges inherent in the Pariacoto sequence itself. Although the viral genome and other exogenous RNA sequences used in experimental studies can assume secondary structures, we have intentionally used uniformly charged flexible polyelectrolyte lacking predetermined secondary structures as the substitute for the viral genome, in order to see whether the same final assembled genome structure emerges without invoking secondary RNA structures. The intent of our study was to investigate the internal environment presented by the capsid proteins of Pariacoto virus, specifically whether the topological features and electrostatic potential at the inner capsid surface can induce complexation of generic negatively charged polyelectrolyte into structures similar to those observed experimentally with packaged RNA. We find that the charge decoration on the interior of the capsid templates the assembly of the flexible polyelectrolyte, allowing hybridizationlike folding of similarly charged strands, and eventually organizing dodecahedral assembly of the polymer. Our results from a generic flexible polyelectrolyte for the assembled structure and bimodal monomer distribution are remarkably matched to that of the viral RNA found experimentally. Results of our work can be interpreted primarily as a consequence of electrostatics, as consideration of base-pairing has been omitted. We propose that our work supports the growing body of evidence that electrostatic interactions play a crucial