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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*

    PubMed Central

    Deinhardt, F.; Gust, I. D.

    1982-01-01

    Three forms of viral hepatitis can be recognized: hepatitis A, hepatitis B, and hepatitis non-A, non-B. Hepatitis A is caused by a picornavirus, is transmitted by the faceal—oral route, does not become chronic, and no chronic virus carriers exist. The virus can be grown in cell cultures, and killed as well as live attenuated virus vaccines are under development. Hepatitis B is caused by an enveloped virus containing a circular, double-stranded form of DNA. The disease is transmitted parenterally through inoculation of blood or blood products containing virus or through close personal contact with a virus-positive person. Hepatitis B becomes chronic in a certain number of cases and can lead to cirrhosis and primary liver cell carcinoma. The blood and certain body secretions of individuals with a persistent or chronic infection may remain infectious for many years. The hepatitis B virus cannot be grown in cell cultures but the entire genome has been sequenced and cloned in bacterial and eukaryotic cells. An inactivated virus vaccine has been prepared from hepatitis B surface antigen present in the plasma of hepatitis B virus carriers and further vaccines are under development. The agents of hepatitis non-A, non-B have not been identified. It is possible to distinguish between a predominantly parenterally transmitted and an orally transmitted form of hepatitis non-A, non-B. The latter is reported to be caused by a picornavirus that does not, however, have any antigenic relationship with hepatitis A virus. PMID:6817933

  4. Viral Factors Induce Hedgehog Pathway Activation in Humans with Viral Hepatitis, Cirrhosis, and Hepatocellular Carcinoma

    PubMed Central

    Pereira, Thiago de Almeida; Witek, Rafal P.; Syn, Wing-Kin; Choi, Steve S.; Bradrick, Shelton; Karaca, Gamze F; Agboola, Kolade M.; Jung, Youngmi; Omenetti, Alessia; Moylan, Cynthia A.; Yang, Liu; Fernandez-Zapico, Martin E.; Jhaveri, Ravi; Shah, Vijay H.; Pereira, Fausto E.; Diehl, Anna Mae

    2010-01-01

    Hh pathway activation promotes many processes that occur during fibrogenic liver repair. Whether the Hh pathway modulates the outcomes of virally-mediated liver injury has never been examined. Gene-profiling studies of human hepatocellular carcinomas (HCC) demonstrate Hh pathway activation in HCCs related to chronic infection with hepatitis B virus (HBV) or hepatitis C virus (HCV). Because most HCC develop in cirrhotic livers, we hypothesized that Hh pathway activation occurs during fibrogenic repair of liver damage due to chronic viral hepatitis, and that Hh-responsive cells mediate disease progression and hepatocarciongenesis in chronic viral hepatitis. Immunohistochemistry and qRTPCR analysis were used to analyze Hh pathway activation and identify Hh-responsive cell types in liver biopsies from 45 patients with chronic HBV or HCV. Hh signaling was then manipulated in cultured liver cells to directly assess the impact of Hh activity in relevant cell types. We found increased hepatic expression of Hh ligands in all patients with chronic viral hepatitis, and demonstrated that infection with HCV stimulated cultured hepatocytes to produce Hh ligands. The major cell populations that expanded during cirrhosis and HCC (i.e., liver myofibroblasts, activated endothelial cells, and progenitors expressing markers of tumor stem/initiating cells) were Hh-responsive, and higher levels of Hh pathway activity associated with cirrhosis and HCC. Inhibiting pathway activity in Hh-responsive target cells reduced fibrogenesis, angiogenesis, and growth. Conclusions HBV/HCV infection increases hepatocyte production of Hh ligands and expands types of Hh-responsive cells that promote liver fibrosis and cancer. PMID:20697376

  5. 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

  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. 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.

  9. [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

  10. 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

  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. Hepatic sarcoidosis complicating treatment-naive viral hepatitis

    PubMed Central

    Aravinthan, Aloysious; Gelson, William; Limbu, Anita; Brais, Rebecca; Richardson, Paul

    2012-01-01

    Hepatic sarcoidosis is usually asymptomatic but rarely leads to adverse liver-related outcome. Co-existence of viral hepatitis and hepatic sarcoidosis is a rare, but recognised phenomenon. Obtaining a balance between immune suppression and anti-viral therapy may be problematic. Immunosuppression in the presence of viral hepatitis can lead to rapid deterioration of liver disease. Similarly, anti-viral therapy may exacerbate granulomatous hepatitis. Here we present two cases of viral hepatitis co-existing with sarcoidosis that illustrate successful management strategies. In one, hepatitis B replication was suppressed with oral anti-viral therapy before commencing prednisolone. In the second, remission of hepatic sarcoidosis was achieved with prednisolone, before treating hepatitis C and obtaining a sustained virological response with pegylated interferon and ribavirin therapy. PMID:23355920

  15. Problems in diagnosing viral hepatitis.

    PubMed Central

    Bonino, F; Colloredo Mels, G; Bellati, G; Ideo, G; Oliveri, F; Colombatto, P; Brunetto, M R

    1993-01-01

    The most reliable method of making a specific aetiological diagnosis of chronic viral hepatitis would be to identify virus specific cytotoxic T lymphocytes responsible for the killing of virus infected hepatocytes in each patient's liver. Unfortunately, this can not be proposed for routine diagnosis and surrogate tests are required. The detection of virus markers, and even of the virus itself, does not imply that liver damage is caused by virus infection. Indirect markers of the host's antiviral immunoresponse have to be used to confirm more specifically the diagnosis of viral hepatitis. IgM antibodies against viral antigens implicated in the elimination of the virus seem to be suitable alternative candidates. Significant changes in the serum values of viraemia and aminotransferases occur within a few days, while a significant variation in liver histology takes much longer. Only the kinetics of the highly variable parameters can be used for an appropriate study of the relationship between viraemia, antiviral immunoresponse, and liver cell necrosis. Quantitative and dynamic analyses of hepatitis virus markers seem the most suitable and reliable methods of monitoring the patients eligible for antiviral treatment and identifying the most appropriate time to start this. PMID:8314490

  16. Single-domain intrabodies against hepatitis C virus core inhibit viral propagation and core-induced NFκB activation.

    PubMed

    Suzuki, Ryosuke; Saito, Kenji; Matsuda, Mami; Sato, Mitsuru; Kanegae, Yumi; Shi, Guoli; Watashi, Koichi; Aizaki, Hideki; Chiba, Joe; Saito, Izumu; Wakita, Takaji; Suzuki, Tetsuro

    2016-04-01

    Hepatitis C virus (HCV) core plays a key role in viral particle formation and is involved in viral pathogenesis. Here, constructs for single-domain intrabodies consisting of variable regions derived from mouse mAbs against HCV core were established. Expressed single-domain intrabodies were shown to bind to HCV core, and inhibit the growth of cell culture-produced HCV derived from JFH-1 (genotype 2a) and a TH (genotype 1b)/JFH-1 chimera. Adenovirus vectors expressing intrabodies were also capable of reducing HCV propagation. Intrabody expression did not affect viral entry or genome replication of single-round infectious trans-complemented HCV particles. However, intrabody expression reduced intracellular and extracellular infectious titres in CD81-defective Huh7-25 cells transfected with the HCV genome, suggesting that these intrabodies impair HCV assembly. Furthermore, intrabody expression suppressed HCV core-induced NFκB promoter activity. These intrabodies may therefore serve as tools for elucidating the role of core in HCV pathogenesis. PMID:26861864

  17. Hepatitis C virus induced insulin resistance impairs response to anti viral therapy

    PubMed Central

    El-Zayadi, Abdel-Rahman; Anis, Mahmoud

    2012-01-01

    Hepatitis C virus (HCV) infection is an important risk factor for insulin resistance (IR). The latter is the pathogenic foundation underlying metabolic syndrome, steatosis and cirrhosis, and possibly hepatocellular carcinoma (HCC). The interplay between genetic and environmental risk factors ultimately leads to the development of IR. Obesity is considered a major risk factor, with dysregulation of levels of secreted adipokines from distended adipose tissue playing a major role in IR. HCV-induced IR may be due to the HCV core protein inducing proteasomal degradation of insulin receptor substrates 1 and 2, blocking intracellular insulin signaling. The latter is mediated by increased levels of both tumour necrosis factor-α (TNF-α) and suppressor of cytokine signaling 3 (SOC-3). IR, through different mechanisms, plays a role in the development of steatosis and its progression to steatohepatitis, cirrhosis and even HCC. In addition, IR has a role in impairing TNF signaling cascade, which in turn blocks STAT-1 translocation and interferon stimulated genes production avoiding the antiviral effect of interferon. PMID:22294824

  18. 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 ...

  19. The epidemiology of viral hepatitis in Qatar.

    PubMed

    Bener, Abdulbari; Al-Kaabi, Saad; Derbala, Moutaz; Al-Marri, Ajayeb; Rikabi, Ammar

    2009-03-01

    Viral hepatitis is a major public health problem in many countries all over the world and especially in Middle East, Asia, East-Europe, and Africa. The aim of our study was to assess the incidence of viral hepatitis A, B and C in Qatar and compare it with other countries. This is a retrospective cohort study, which was conducted at Hamad General Hospital, State of Qatar from 2002-2006. Patients who were screened and diagnosed with viral hepatitis were included in this study. The diagnostic classification of definite viral hepatitis was made in accordance with criteria based on the International Classification of Disease tenth revision (ICD-10). A total of 527 cases of hepatitis C, 396 cases of hepatitis B, 162 cases of hepatitis A and 108 cases of unspecified were reported during the year 2006. Reported incidence rate per 10,000 populations during the year 2006 for hepatitis A was 1.9, hepatitis B 4.7, and Hepatitis C 6.3. The proportion of hepatitis B and C was significantly higher in male population than females across the years (2002-2006). Hepatitis A was more prevalent in children below 15 years (72.3%), hepatitis B in adults aged above 15 years, and hepatitis C in the population above 35 years of age. The incidence of hepatitis A has been declining in Qataris and increasing in expatriates. There was a significant relationship in gender and age group of the patients with hepatitis A, B and C. We conclude that hepatitis has become a national health issue in Qatar. The incidence rate of hepatitis in Qatar is comparable to its neighboring countries, United Arab Emirates and Saudi Arabia. There is a need for further research on hepatitis and the associated risk factors.

  20. 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

  1. 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

  2. History and Global Burden of Viral Hepatitis.

    PubMed

    Blum, Hubert E

    2016-01-01

    Between 1963 and 1989, 5 hepatotropic viruses have been discovered that are the major causes of viral hepatitides worldwide: hepatitis A virus, hepatitis B virus (HBV), hepatitis C virus (HCV), hepatitis delta virus and hepatitis E virus. Their epidemiology and pathogenesis have been studied in great detail. Furthermore, the structure and genetic organization of their DNA or RNA genome including the viral life cycle have been elucidated and have been successfully translated into important clinical applications, such as the specific diagnosis, therapy and prevention of the associated liver diseases, including liver cirrhosis and hepatocellular carcinoma (HCC). The prevalence of acute and chronic viral hepatitis A-E shows distinct geographic differences. The global burden of disease (prevalence, incidence, death, disability-adjusted life years) has been analyzed in seminal studies that show that the worldwide prevalence of hepatitis A-E has significantly decreased between 1990 and 2013. During the same time, the incidence of HBV-related liver cirrhosis and HCC, respectively, also decreased or increased slightly, the incidence of the HCV-related liver cirrhosis remained stable and the incidence of HCV-related HCC showed a major increase. During the coming years, we expect to improve our ability to prevent and effectively treat viral hepatitis A-E, resulting in the control of these global infections and the elimination of their associated morbidities and mortalities. PMID:27170381

  3. [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

  4. [Viral hepatitis: from A to G viruses].

    PubMed

    Figueroa Barrios R, R

    1996-01-01

    Great advances has been achieved in the last 10 years in the study of acute and chronic viral hepatitis. The enigma of non-A non-B viral hepatitis was disclosed when C virus was identified and later when E virus was isolated. New viruses has been searched to explain non-A to non-E viral hepatitis, being reported recently G virus. Epidemiology and clinical aspects has been reviewed identifying unusual clinical forms: choletasic and relapsing hepatitis in HAV infection; escape mutants B virus hepatitis in HVB infection; and the silent evolution to chronicity in more than 70% of cases in HVC infection. Diagnostic techniques has been developed to asses serum antibodies and the virus itself. It is important to quantitate the viral particles in the serum before treatment. PCR technique has been used with good results. A and E virus do not remain in the host and permanent inmunity is obtained after infection is resolved. 10% of B and 80% of C viral hepatitis goes to chronicity. So far, the only drug used to treat chronic viral B, D and C hepatitis is interferon alfa, obtaining good response en 40%. Combinations with Rivabirin and increasing the dose, frequency and duration of interferon treatment are in study. lt is a recomendation to treat acute HCV infection with Interferon alfa to prevent chronicity. Vaccines against A and B virus are used, being included in childhood vaccination programs. No HVC vaccine has developed probably to constant virus mutancy. New chalenges are present in this field and in the identification of new hepatitis viruses. PMID:12165788

  5. 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

  6. 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

  7. 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

  8. Chronic viral hepatitis: the histology report.

    PubMed

    Guido, Maria; Mangia, Alessandra; Faa, Gavino

    2011-03-01

    In chronic viral hepatitis, the role of liver biopsy as a diagnostic test has seen a decline, paralleled by its increasing importance for prognostic purposes. Nowadays, the main indication for liver biopsy in chronic viral hepatitis is to assess the severity of the disease, in terms of both necro-inflammation (grade) and fibrosis (stage), which is important for prognosis and therapeutic management. Several scoring systems have been proposed for grading and staging chronic viral hepatitis and there is no a general consensus on the best system to be used in the daily practice. All scoring systems have their drawbacks and all may be affected by sampling and observer variability. Whatever the system used, a histological score is a reductive approach since damage in chronic viral hepatitis is a complex biological process. Thus, scoring systems are not intended to replace the detailed, descriptive, pathology report. In fact, lesions other than those scored for grading and staging may have clinical relevance and should be assessed and reported. This paper aims to provide a systematic approach to the interpretation of liver biopsies obtained in cases of chronic viral hepatitis, with the hope of helping general pathologists in their diagnostic practice.

  9. Viral hepatitis and liver cancer on the Island of Guam.

    PubMed

    Haddock, R L; Paulino, Y C; Bordallo, R

    2013-01-01

    Patient records from the Guam Cancer Registry were compared with patients listed in a health department viral hepatitis case registry and the numbers of liver cancer and viral hepatitis cases were compared by ethnicity. Hepatitis C was the form of viral hepatitis most common among liver cancer cases on Guam (63.3% of viral hepatitis-associated liver cancer cases). Since viral hepatitis is an important cause of liver cancer, studies such as the present one may provide the information necessary to establish programs (screening of populations at risk and infant vaccination in the case of hepatitis B, for example) that may lessen the impact of liver cancer in the future.

  10. Viral Hepatitis and Liver Cancer on the Island of Guam

    PubMed Central

    Haddock, RL; Paulino, YC; Bordallo, R

    2015-01-01

    Patient records from the Guam Cancer Registry were compared with patients listed in a health department viral hepatitis case registry. The number of liver cancer and viral hepatitis cases were compared by ethnicity. Hepatitis C was the form of viral hepatitis most common among liver cancer cases on Guam (63.3% of viral hepatitis-associated liver cancer cases). Since viral hepatitis is an important cause of liver cancer, studies such as the present one may provide the information necessary to establish programs (screening of populations at risk and infant vaccination in the case of hepatitis B, for example) that may lessen the impact of liver cancer in the future. PMID:23803099

  11. 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 ...

  12. [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

  13. Therapies for HIV and viral hepatitis coinfection.

    PubMed

    Cooper, Curtis L

    2005-02-01

    The natural history of chronic viral hepatitis is altered by HIV coinfection. Liver fibrosis rates and clinical features of liver disease develop more rapidly. Although HIV-hepatitis C virus coinfected subjects may progress more rapidly to AIDS, this is probably explained by comorbid illness, substance abuse and socioeconomic circumstances. Safe and virologically active treatment of HIV-hepatitis B virus coinfection can be concurrently achieved by the use of highly active antiretroviral therapy regimens containing lamivudine and/or tenofovir. In most cases, highly active antiretroviral therapy represents the most beneficial initial pharmaceutical intervention for HIV-hepatitisC virus coinfection. HepatitisC virus antiviral therapy should, in most cases, be reserved for those achieving HIV RNA suppression and immune restoration from highly active antiretroviral therapy or with nadir CD4 T-lymphocytes above 350 cells/microl. PMID:15757459

  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. Acute viral E hepatitis with chronic liver disease (autoimmune hepatitis).

    PubMed

    Desai, H G; Naik, A S

    2005-03-01

    A 36 years old male presented with anorexia, jaundice and ascites. He was suffering from acute viral E hepatitis. In view of ascites, he was investigated for associated asymptomatic chronic liver disease (CLD). The CLD was diagnosed as cirrhosis with autoimmune hepatitis and was treated with steroid with good response. He is maintaining good health with low dose steroid, on follow up for 1 year.

  16. 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 ...

  17. Acute viral hepatitis in California sea lions.

    PubMed

    Britt, J O; Nagy, A Z; Howard, E B

    1979-11-01

    Acute viral hepatitis was diagnosed in five California sea lions (Zalophus californianus) stranded along the Los Angeles coast. Light microscopy revealed large nuclear inclusion bodies in hepatocytes. Electron microscopy provided evidence that these inclusion bodies were composed of adenovirus-like virions. Attempts to grow the virus in cell culture systems were unsuccessful. PMID:521373

  18. 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

  19. 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

  20. Bupropion for interferon-alpha-induced depression in patients with hepatitis C viral infection: an open-label study.

    PubMed

    Chen, Wei-Chun; Lai, Hsueh-Chou; Su, Wen-Pang; Palani, Mahalakshmi; Su, Kuan-Pin

    2015-01-01

    Interferon (IFN)-α therapy for chronic hepatitis C virus (HCV) infection is frequently associated with major depressive episodes. Bupropion, a commonly used antidepressant agent, has recently found to have strong anti-inflammatory effects in animal models. Despite of the theoretical relevancy, the antidepressant effect of bupropion in IFN-alpha-induced depression has never been studied. Ten HCV patients with IFN-α-induced depression were recruited to receive 8-week bupropion treatment and were assessed every 2 weeks for depressive symptoms by the Hamilton rating scale for depression (HAMD) and somatic symptoms by the Neurotoxicity Rating Scale (NRS). Four of the 10 patients met the criteria for remission (total HAMD scores≤7), and 5 patients met the criteria for response (at least 50% reduction in total HAMD scores). In addition, 5 patients had 50% decreases in NRS for neuropsychiatric symptoms. This preliminary open-label study suggests that bupropion is effective in treating IFN-alpha-induced depressive and somatic symptoms.

  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. Ly6Chi monocytes regulate T cell responses in viral hepatitis

    PubMed Central

    Zhu, Jiangao; Chen, Huiyao; Huang, Xiaopei; Jiang, Songfu

    2016-01-01

    Viral hepatitis remains a global health challenge despite recent progress in the development of more effective therapies. Although virus-specific CD8+ and CD4+ T cell responses are essential for viral clearance, it remains largely unknown what regulates T cell–mediated viral clearance. Thus, a better understanding of the regulation of anti-viral T cell immunity would be critical for the design of more effective therapies for viral hepatitis. Using a model of adenovirus-induced hepatitis, here we showed that adenoviral infection induced recruitment of Ly6Chi monocytes to the liver in a CCR2-dependent manner. These recruited Ly6Chi monocytes suppressed CD8+ and CD4+ T cell responses to adenoviral infection, leading to a delay in viral clearance. In vivo depletion of Ly6Chi monocytes markedly enhanced anti-viral T cell responses and promoted viral clearance. Mechanistically, we showed that induction of iNOS and the production of NO by Ly6Chi monocytes are critical for the suppression of T cell responses. In addition, a contact-dependent mechanism mediated by PD-1 and PD-L1 interaction is also required for T cell suppression by Ly6Chi monocytes. These findings suggest a critical role for Ly6Chi monocytes in the regulation of T cell immunity in viral hepatitis and may provide new insights into development of more effective therapies for treating viral hepatitis based on targeting the immunosuppressing monocytes. PMID:27777980

  4. [Social determinants and risk of acute viral hepatitis].

    PubMed

    Malvasio, P; Russo, R; Zotti, C; Vigna, I; Ruggenini Moiraghi, A

    1998-01-01

    The authors examined the relationship between viral hepatitis risk and social determinants in Piedmont region population surveyed by SEIEVA (sistema epidemiologico integrato dell'epatite virale acuta). The education and the working position showed different correlation with incidence rates of different types of viral hepatitis A, B, non-A non-B. The hepatitis A risk is proportional to education and the probability of hepatitis B and non-A non-B is higher in low social classes. This situation is only apparently a balanced risk: the clinical seriousness and the strong probability of complications of hepatitis B and non-A non-B make the risks deeply unequal.

  5. 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

  6. Prevention and management of viral hepatitis in pregnancy.

    PubMed

    Rac, Martha W F; Sheffield, Jeanne S

    2014-12-01

    Of the 5 types of viral hepatitis (HAV-HEV), HBV and HCV are by far the most common causes of chronic hepatitis in both pregnant and nonpregnant populations, causing more than 50% of cirrhosis cases and 78% of cases of primary liver cancer. Infection during pregnancy can have adverse effects on both the mother and her fetus. For all 5 viral hepatitis syndromes, early identification allows appropriate measures to be taken to optimize pregnancy outcomes and minimize the risk of perinatal transmission. This article reviews the prevention and management of all 5 viral hepatitis syndromes during pregnancy. PMID:25454991

  7. Viral hepatitis: how to manage type C and D infections.

    PubMed

    Najm, W

    1997-05-01

    Hepatitis C and D are relative newcomers to the study of viral hepatitis. Their transmission is mainly parenteral. The 0.5 to 2.2% prevalence of hepatitis C in the United States does not vary by patient age. Often, hepatitis C is asymptomatic. In older patients, symptomatic infection has a cholesteatic appearance, and progress to chronic hepatitis and cirrhosis is more rapid than in younger adults. Hepatitis D virus is a defective single-stranded RNA that presents as a co-infection or superinfection of hepatitis B. Prevalence varies by geographic region. The rate of progression to chronic disease and cirrhosis is high in superinfection.

  8. Host - hepatitis C viral interactions: The role of genetics.

    PubMed

    Heim, Markus H; Bochud, Pierre-Yves; George, Jacob

    2016-10-01

    Hepatitis C virus (HCV) is a major cause of chronic viral hepatitis that can lead to cirrhosis and hepatocellular carcinoma. Only a minority of patients can clear the virus spontaneously. Elimination of HCV during acute infection correlates with a rapid induction of innate, especially interferon (IFN)-induced genes, and a delayed induction of adaptive immune responses. There is a strong association between genetic variants in the IFNλ (IL28B) locus with the rate of spontaneous clearance. Individuals with the ancestral IFNλ4 allele capable of producing a fully active IFNλ4 are paradoxically not able to clear HCV in the acute phase and develop chronic hepatitis C (CHC) with more than 90% probability. In the chronic phase of HCV infection, the wild-type IFNλ4 genotype is strongly associated with an induction of hundreds of classical type I/type III IFN stimulated genes in hepatocytes. However, the activation of the endogenous IFN system in the liver is ineffective in clearing HCV, and is even associated with impaired therapeutic responses to pegylated (Peg)IFNα containing treatments. While the role of genetic variation in the IFNλ locus to the outcome of CHC treatment has declined, it is clear that variation not only at this locus, but also at other loci, modulate clinically important liver phenotypes, including inflammation, fibrosis progression and the development of hepatocellular cancer. In this review, we summarize current knowledge about the role of genetics in the host response to viral hepatitis and the potential future evolution of knowledge in understanding host-viral interactions. PMID:27641986

  9. Viral dynamics in hepatitis B virus infection.

    PubMed Central

    Nowak, M A; Bonhoeffer, S; Hill, A M; Boehme, R; Thomas, H C; McDade, H

    1996-01-01

    Treatment of chronic hepatitis B virus (HBV) infections with the reverse transcriptase inhibitor lamivudine leads to a rapid decline in plasma viremia and provides estimates for crucial kinetic constants of HBV replication. We find that in persistently infected patients, HBV particles are cleared from the plasma with a half-life of approximately 1.0 day, which implies a 50% daily turnover of the free virus population. Total viral release into the periphery is approximately 10(11) virus particles per day. Although we have no direct measurement of the infected cell mass, we can estimate the turnover rate of these cells in two ways: (i) by comparing the rate of viral production before and after therapy or (ii) from the decline of hepatitis B antigen during treatment. These two independent methods give equivalent results: we find a wide distribution of half-lives for virus-producing cells, ranging from 10 to 100 days in different patients, which may reflect differences in rates of lysis of infected cells by immune responses. Our analysis provides a quantitative understanding of HBV replication dynamics in vivo and has implications for the optimal timing of drug treatment and immunotherapy in chronic HBV infection. This study also represents a comparison for recent findings on the dynamics of human immunodeficiency virus (HIV) infection. The total daily production of plasma virus is, on average, higher in chronic HBV carriers than in HIV-infected patients, but the half-life of virus-producing cells is much shorter in HIV. Most strikingly, there is no indication of drug resistance in HBV-infected patients treated for up to 24 weeks. PMID:8633078

  10. 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

  11. 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

  12. Inhibitor-Based Therapeutics for Treatment of Viral Hepatitis

    PubMed Central

    Dey, Debajit; Banerjee, Manidipa

    2016-01-01

    Abstract Viral hepatitis remains a significant worldwide threat, in spite of the availability of several successful therapeutic and vaccination strategies. Complications associated with acute and chronic infections, such as liver failure, cirrhosis and hepatocellular carcinoma, are the cause of considerable morbidity and mortality. Given the significant burden on the healthcare system caused by viral hepatitis, it is essential that novel, more effective therapeutics be developed. The present review attempts to summarize the current treatments against viral hepatitis, and provides an outline for upcoming, promising new therapeutics. Development of novel therapeutics requires an understanding of the viral life cycles and viral effectors in molecular detail. As such, this review also discusses virally-encoded effectors, found to be essential for virus survival and replication in the host milieu, which may be utilized as potential candidates for development of alternative therapies in the future. PMID:27777893

  13. Tickling the TLR7 to cure viral hepatitis

    PubMed Central

    2014-01-01

    Chronic hepatitis B and C are the leading causes of liver disease and liver transplantation worldwide. Ability to mount an effective immune response against both HBV and HCV is associated with spontaneous clearance of both infections, while an inability to do so leads to chronicity of both infections. To mount an effective immune response, both innate and adaptive immune responses must work in tandem. Hence, developing protective immunity to hepatitis viruses is an important goal in order to reduce the global burden of these two infections and prevent development of long-term complications. In this regard, the initial interactions between the pathogen and immune system are pivotal in determining the effectiveness of immune response and subsequent elimination of pathogens. Toll-like receptors (TLRs) are important regulators of innate and adaptive immune responses to various pathogens and are often involved in initiating and augmenting effective antiviral immunity. Immune-based therapeutic strategies that specifically induce type I interferon responses are associated with functional cure for both chronic HBV and HCV infections. Precisely, TLR7 stimulation mediates an endogenous type I interferon response, which is critical in development of a broad, effective and protective immunity against hepatitis viruses. This review focuses on anti-viral strategies that involve targeting TLR7 that may lead to development of protective immunity and eradication of hepatitis B. PMID:24884741

  14. Time for Action on Viral Hepatitis.

    PubMed

    Lim, Seng Gee

    2016-01-01

    The recent outbreak of hepatitis C virus (HCV) at Singapore General Hospital (SGH) has highlighted the dangers of viral hepatitis. In this case, infection control and environmental contamination were the culprits, particularly, a drop of blood containing 5 million IU HCV. From a broader perspective, there has been a revolution in HCV therapy with the recent rapid evolution of short-term (12 weeks) safe, all oral directly- acting antiviral (DAA) therapy leading to cure rates of 90% to 100%, even in previously difficult to treat patients with liver cirrhosis, previous treatment failure and those on immunosuppression. Consequently, treating HCV in risk groups such as renal dialysis and haemophiliacs can eliminate a pool of infected patients to prevent future outbreaks. A seroprevalence study is needed to identify a possible "birth cohort" effect that could aid screening. For HBV, vaccination has reduced prevalence to 3.8%, but these patients are prone to complications such as HBV flares. Since 2014, 13 patients developed liver failure and were listed for liver transplantation at National University Hospital (NUH) but 6 died beforehand. This avoidable catastrophe is due to undiagnosed HBV infection or patients who did not return for follow-up. Good antiviral therapy is available, but the issues are similar to HCV, identification of patients and linkage to care. A cure seems likely in the future as pharmaceutical companies are developing new agents. Singapore has joined in this initiative with a recent award of a national research translational grant to better understand the pathophysiology and the processes needed for a cure of HBV. PMID:27118226

  15. [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

  16. [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

  17. Viral hepatitis A, B, and C: grown-up issues.

    PubMed

    Sharapov, Umid M; Hu, Dale J

    2010-08-01

    Viral hepatitis is a major global health problem associated with significant morbidity and mortality. Although there are five major and distinct human hepatitis viruses characterized to date--referred to as hepatitis A, B, C, D, and E, respectively--only hepatitis A, B, and C are epidemiologically and clinically relevant for adolescents in North America. The clinical presentation of acute infection with each of these viruses is similar; thus, diagnosis depends on the use of specific serologic markers and viral nucleic acids. This review provides data on the epidemiology, clinical symptoms, diagnosis, treatment, and prevention of each of these three viral infections, along with points that are important or unique to adolescent patients.

  18. Zafirlukast-induced acute hepatitis.

    PubMed

    Su, Chien-Wei; Wu, Jaw-Ching; Huang, Yi-Hsiang; Huang, Yi-Shin; Chang, Full-Young; Lee, Shou-Dong

    2002-11-01

    Zafirlukast, a competitive cysteinyl leukotriene receptor antagonist, is a new class of asthma medications. It has shown an adverse event profile similar to that of placebo. Herein, we present a 69-year-old female patient who suffered from general malaise, poor appetite, nausea and jaundice after 3 months of zafirlukast therapy for asthma. She had no past history of liver disease, nor history of alcoholism, herb medication, blood transfusion, acupuncture, tattoo or recent traveling history. Liver biochemistries revealed elevated serum alanine aminotransferase and aspartase aminotransferase levels up to 481 U/L and 212 U/L, respectively. Moreover, peak serum total bilirubin level was elevated to 34.8 mg/dL during admission. Serum viral hepatitis marker, antinuclear antibody, anti-mitochondrial antibody and anti-smooth muscle antibody were all negative. Her general condition and liver biochemistries improved gradually after zafirlukast was discontinued. Roussel Uclaf causality assessment for adverse drug reaction confirmed the diagnosis of drug-induced liver injury. This case reminds us that zafirlukast is a potentially hepato-toxic drug. If clinical manifestations of hepatitis develop, patients should be managed cautiously and closely monitored for liver biochemistries. If drug-induced hepatitis is suspected, medication should be discontinued immediately to prevent further liver injury. PMID:12583521

  19. 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

  20. 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

  1. RNAi for Treating Hepatitis B Viral Infection

    PubMed Central

    Chen, Yong; Cheng, Guofeng

    2007-01-01

    Chronic hepatitis B virus (HBV) infection is one of the leading causes of liver cirrhosis and hepatocellular carcinoma (HCC). Current treatment strategies of HBV infection including the use of interferon (IFN)-α and nucleotide analogues such as lamivudine and adefovir have met with only partial success. Therefore, it is necessary to develop more effective antiviral therapies that can clear HBV infection with fewer side effects. RNA interference (RNAi), by which a small interfering RNA (siRNA) induces the gene silence at a post-transcriptional level, has the potential of treating HBV infection. The successful use of chemically synthesized siRNA, endogenous expression of small hairpin RNA (shRNA) or microRNA (miRNA) to silence the target gene make this technology towards a potentially rational therapeutics for HBV infection. However, several challenges including poor siRNA stability, inefficient cellular uptake, widespread biodistribution and non-specific effects need to be overcome. In this review, we discuss several strategies for improving the anti-HBV therapeutic efficacy of siRNAs, while avoiding their off-target effects and immunostimulation. There is an in-depth discussion on the (1) mechanisms of RNAi, (2) methods for siRNA/shRNA production, (3) barriers to RNAi-based therapies, and (4) delivery strategies of siRNA for treating HBV infection. PMID:18074201

  2. The three types of human viral hepatitis

    PubMed Central

    Zuckerman, A. J.

    1978-01-01

    Infections with hepatitis A and B viruses are common in all parts of the world and constitute a major public health problem. The identification of specific antigenic markers of these viruses has led to the development of sensitive laboratory tests. These, in turn, have resulted in a better understanding of the epidemiology, pathogenesis, immunology, and the nature of these common infections. In the case of hepatitis type B, laboratory tests revealed a persistent carrier state of the surface antigen in some 120-175 million people and established the significance of hepatitis B virus in the pathogenesis of serious chronic liver disease, including a strong association with primary hepatocellular carcinoma in tropical and some subtropical regions. In addition, the specific diagnosis of hepatitis types A and B has revealed a previously unrecognized form of hepatitis which is clearly unrelated to either type. This new form of infection of the liver is now the most common type of hepatitis after the transfusion of blood and blood products in some areas of the world and it also appears to be an important cause of sporadic hepatitis, particularly among adults. ImagesFig. 1Fig. 2 PMID:78770

  3. The Association of Viral Hepatitis and Acute Pancreatitis

    PubMed Central

    Geokas, Michael C.; Olsen, Harvey; Swanson, Virginia; Rinderknecht, Heinrich

    1972-01-01

    The histological features of 24 pancreases obtained from patients who died of causes other than hepatitis, pancreatitis or pancreatic tumors, included a variable degree of autolysis, rare foci of inflammatory reaction but no hemorrhagic fat necrosis or destruction of elastic tissue in vessel walls (elastolysis). Assays of elastase in extracts of these pancreases showed no free enzyme, but varying amounts of proelastase. A review of autopsy findings in 33 patients with fatal liver necrosis attributed to halothane anesthesia, demonstrated changes of acute pancreatitis only in two. On the other hand, a review of 16 cases of fulminant viral hepatitis revealed changes characteristic of acute pancreatitis in seven – interstitial edema, hemorrhagic fat necrosis, inflammatory reaction and frequently elastolysis in vessel walls. Determination of elastase in extracts of one pancreas showed the bulk of the enzyme in free form. Furthermore, assays of urinary amylase in 44 patients with viral hepatitis showed increased levels of this enzyme (2583 ± 398 mean value ± standard error, Somogyi units per 100 ml in 13, or 29.5 percent). The evidence suggests that acute pancreatitis may at times complicate viral hepatitis. Although direct proof of viral pancreatic involvement is not feasible at present, a rational hypothesis is advanced which underlines similar mechanisms of tissue involvement in both liver and pancreas that may be brought about by the hepatitis viruses. PMID:5070694

  4. [The problems of viral hepatitis B in hemodialysis units].

    PubMed

    Nazarov, Sh N; Akalaev, R N; Aripkhodzhaeva, F A; Mirkamalov, A A

    1993-01-01

    To study the spread of viral hepatitis B in hemodialysis departments, 92 patients and 52 members of the personnel were examined at such department. The presence of the complex of viral hepatitis B markers was determined with the use of such highly sensitive techniques as the radioimmunoassay and the enzyme immunoassay. All markers of hepatitis B virus infection were detected altogether in 50% of the patients and 79.1% of the personnel of the department. Clinico-laboratory studies revealed a considerable proportion of persons with chronic forms of the disease among these subjects. In patients with chronic renal insufficiency the latent course of the disease was mainly established, which probably ensured the continuity of the epidemic process at the department. Taking into account the present epidemiological situation, the main measures for the prophylaxis of viral hepatitis B at hemodialysis departments were recommended. The conclusions made on the basis of these studies emphasize that a wide complex of anti-epidemic measures for controlling viral hepatitis B was necessary at hemodialysis departments. PMID:8059578

  5. 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

  6. 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

  7. 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

  8. Screening for Viral Hepatitis and Hepatocellular Cancer.

    PubMed

    Cameron, Andrew M

    2015-10-01

    Accurate tests for at-risk populations are available for hepatitis B virus, hepatitis C virus (HCV), and hepatocellular carcinoma (HCC). Effective treatments for all three diseases exist if diagnosed early. New antivirals are making a significant impact on HCV. Liver transplant is curative for early HCC and is prioritized by the United Network for Organ Sharing in the United States. Screening and surveillance for deadly disease only makes sense if there are identifiable populations at risk for the condition, there are sensitive and specific low-cost tests available for the condition, and there are effective treatments for the condition.

  9. 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

  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. Bio-mathematical models of viral dynamics to tailor antiviral therapy in chronic viral hepatitis

    PubMed Central

    Brunetto, Maurizia Rossana; Colombatto, Piero; Bonino, Ferruccio

    2009-01-01

    The simulation of the dynamics of viral infections by mathematical equations has been applied successfully to the study of viral infections during antiviral therapy. Standard models applied to viral hepatitis describe the viral load decline in the first 2-4 wk of antiviral therapy, but do not adequately simulate the dynamics of viral infection for the following period. The hypothesis of a constant clearance rate of the infected cells provides an unrealistic estimation of the time necessary to reach the control or the clearance of hepatitis B virus (HBV)/hepatitis C virus (HCV) infection. To overcome the problem, we have developed a new multiphasic model in which the immune system activity is modulated by a negative feedback caused by the infected cells reduction, and alanine aminotransferase kinetics serve as a surrogate marker of infected-cell clearance. By this approach, we can compute the dynamics of infected cells during the whole treatment course, and find a good correlation between the number of infected cells at the end of therapy and the long-term virological response in patients with chronic hepatitis C. The new model successfully describes the HBV infection dynamics far beyond the third month of antiviral therapy under the assumption that the sum of infected and non-infected cells remains roughly constant during therapy, and both target and infected cells concur in the hepatocyte turnover. In clinical practice, these new models will allow the development of simulators of treatment response that will be used as an “automatic pilot” for tailoring antiviral therapy in chronic hepatitis B as well as chronic hepatitis C patients. PMID:19195054

  12. 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

  13. 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.

  14. 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

  15. CROI 2016: Viral Hepatitis and Liver Fibrosis.

    PubMed

    Luetkemeyer, Anne F; Wyles, David L

    2016-01-01

    At the 2016 Conference on Retroviruses and Opportunistic Infections (CROI) in Boston, Massachusetts, hepatitis C virus (HCV) infection remained a major theme in the context of HIV-associated liver disease, although other causes of liver disease garnered increased attention, including fatty liver disease, hepatitis B, and the impact of HIV disease itself on the liver. Although no data from phase III studies of HCV direct-acting antiviral (DAA) drugs for the treatment of HIV/HCV coinfection were presented at CROI 2016, a broad range of HCV DAA-related topics were presented, including accumulating experience with real-world performance of DAA-based regimens outside of clinical trials, drug interactions between DAA and antiretroviral drugs, treatment of acute HCV infection, and retreatment of individuals whose DAA-based regimens failed and those in whom resistance to DAA drugs emerged. A summary of select abstracts from CROI 2016 is presented, including discussion of clinical relevance where appropriate and areas for future research.

  16. 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

  17. The role played by gender in viral hepatitis.

    PubMed

    Bernabucci, Veronica; Villa, Erica

    2014-01-01

    Although not a classical target for estrogens, the liver is a target for their action and is sensitive to their deprivation. The occurrence of menopause is accompanied by a chain of events depending on the progressive estrogen deprivation that eventually leads to a shift from a low inflammatory to a high inflammatory state. This has a series of well-known consequences in many different organs and tissues (bone, heart, brain, body fat etc.) among which the liver is particularly interesting. The consequences are extremely evident in HCV-positive women in whom HCV infection and menopause cooperate to induce higher necro-inflammatory features, increased hepatic steatosis and eventually faster progression of fibrosis. In addition, menopause is the strongest negative factor for sustained viral response (SVR) in HCV-positive females, especially HCV genotype 1 (in whom menopause was the only independent factor for failure of antiviral therapy). This suggests that HCV-positive women should be treated early during fertile age to obtain maximal response to antiviral therapy.

  18. 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

  19. Viral (hepatitis C virus, hepatitis B virus, HIV) persistence and immune homeostasis

    PubMed Central

    Zhou, Yun; Zhang, Ying; Moorman, Jonathan P; Yao, Zhi Q; Jia, Zhan S

    2014-01-01

    Immune homeostasis is a host characteristic that maintains biological balance within a host. Humans have evolved many host defence mechanisms that ensure the survival of individuals upon encountering a pathogenic infection, with recovery or persistence from a viral infection being determined by both viral factors and host immunity. Chronic viral infections, such as hepatitis B virus, hepatitis C virus and HIV, often result in chronic fluctuating viraemia in the face of host cellular and humoral immune responses, which are dysregulated by multi-faceted mechanisms that are incompletely understood. This review attempts to illuminate the mechanisms involved in this process, focusing on immune homeostasis in the setting of persistent viral infection from the aspects of host defence mechanism, including interferon-stimulated genes, apolipoprotein B mRNA editing enzyme catalytic polypeptide 3 (APOBEC3), autophagy and interactions of various immune cells, cytokines and regulatory molecules. PMID:24965611

  20. Aqueous extract of the edible Gracilaria tenuistipitata inhibits hepatitis C viral replication via cyclooxygenase-2 suppression and reduces virus-induced inflammation.

    PubMed

    Chen, Kuan-Jen; Tseng, Chin-Kai; Chang, Fang-Rong; Yang, Jin-Iong; Yeh, Chi-Chen; Chen, Wei-Chun; Wu, Shou-Fang; Chang, Hsueh-Wei; Lee, Jin-Ching

    2013-01-01

    Hepatitis C virus (HCV) is an important human pathogen leading to hepatocellular carcinoma. Using an in vitro cell-based HCV replicon and JFH-1 infection system, we demonstrated that an aqueous extract of the seaweed Gracilaria tenuistipitata (AEGT) concentration-dependently inhibited HCV replication at nontoxic concentrations. AEGT synergistically enhanced interferon-α (IFN-α) anti-HCV activity in a combination treatment. We found that AEGT also significantly suppressed virus-induced cyclooxygenase-2 (COX-2) expression at promoter transactivation and protein levels. Notably, addition of exogenous COX-2 expression in AEGT-treated HCV replicon cells gradually abolished AEGT anti-HCV activity, suggesting that COX-2 down-regulation was responsible for AEGT antiviral effects. Furthermore, we highlighted the inhibitory effect of AEGT in HCV-induced pro-inflammatory gene expression such as the expression of tumour necrosis factor-α, interleukin-1β, inducible nitrite oxide synthase and COX-2 in a concentration-dependent manner to evaluate the potential therapeutic supplement in the management of patients with chronic HCV infections.

  1. 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

  2. Aggravation of viral hepatitis by platelet-derived serotonin.

    PubMed

    Lang, Philipp A; Contaldo, Claudio; Georgiev, Panco; El-Badry, Ashraf Mohammad; Recher, Mike; Kurrer, Michael; Cervantes-Barragan, Luisa; Ludewig, Burkhard; Calzascia, Thomas; Bolinger, Beatrice; Merkler, Doron; Odermatt, Bernhard; Bader, Michael; Graf, Rolf; Clavien, Pierre-Alain; Hegazy, Ahmed N; Löhning, Max; Harris, Nicola L; Ohashi, Pamela S; Hengartner, Hans; Zinkernagel, Rolf M; Lang, Karl S

    2008-07-01

    More than 500 million people worldwide are persistently infected with hepatitis B virus or hepatitis C virus. Although both viruses are poorly cytopathic, persistence of either virus carries a risk of chronic liver inflammation, potentially resulting in liver steatosis, liver cirrhosis, end-stage liver failure or hepatocellular carcinoma. Virus-specific T cells are a major determinant of the outcome of hepatitis, as they contribute to the early control of chronic hepatitis viruses, but they also mediate immunopathology during persistent virus infection. We have analyzed the role of platelet-derived vasoactive serotonin during virus-induced CD8(+) T cell-dependent immunopathological hepatitis in mice infected with the noncytopathic lymphocytic choriomeningitis virus. After virus infection, platelets were recruited to the liver, and their activation correlated with severely reduced sinusoidal microcirculation, delayed virus elimination and increased immunopathological liver cell damage. Lack of platelet-derived serotonin in serotonin-deficient mice normalized hepatic microcirculatory dysfunction, accelerated virus clearance in the liver and reduced CD8(+) T cell-dependent liver cell damage. In keeping with these observations, serotonin treatment of infected mice delayed entry of activated CD8(+) T cells into the liver, delayed virus control and aggravated immunopathological hepatitis. Thus, vasoactive serotonin supports virus persistence in the liver and aggravates virus-induced immunopathology.

  3. Effect of alpha 2b interferon on inducement of mIL-2R and treatment of HCV in PBMC from patients with chronic viral hepatitis C

    PubMed Central

    Wang, Jian; Xiang, Gui-Ju; Liu, Bing-Xiang

    2003-01-01

    AIM: To study the level of membrane interleukin-2 receptor (mIL-2R) on surface of peripheral blood mononuclear cells (PBMC) and the therapeutic efficacy of alpha 2b interferon on the treatment of HCV-RNA in PBMC of patients with chronic hepatitis C and to compare the negative rates of HCV-RNA in PBMC, HCV-RNA and anti-HCV in serum. METHODS: Before and after treatment of alpha 2b interferon, the level of mIL-2R of patients with chronic hepatitis C was detected by biotin-streptavidin (BSA). The therapeutic group (26 cases) was treated with alpha 2b interferon (3 MU/d) and control therapeutic group (22 cases) was treated with routine drugs (VitC, aspartic acid). The total course of treatment with alpha 2b interferon and routine drug was six months and per course of the treatment was three months. The levels of HCV-RNA in PBMC, HCV-RNA and anti-HCV in serum were detected before and after a course of the treatment. RESULTS: Before and after treatment of alpha 2b interferon and routine drugs, the levels of mIL-2R in silence stage were (3.44 ± 0.77)% and (2.95 ± 0.72)%, the levels of mIL-2R in inducement stage were (33.62 ± 3.95)% and (30.04 ± 3.73)%. There was a significant difference between two groups (P < 0.01-P < 0.05). After treatment of alpha 2b interferon with 3 MU/d for two courses of the treatment, the total negative rates of HCV-RNA in the PBMC and HCV-RNA, anti-HCV in serum were 42.31% (11/26), 57.69% (15/26), 65.38%(17/26) respectively. After the treatment of routine drug, the negative rates of HCV-RNA in PBMC and HCV-RNA, anti-HCV in serum were 13.64% (3/22), 22.73% (5/22), 27.27% (6/22) respectively. There was high significant difference in the group treated with alpha 2b interferon and the group treated with routine drugs (P < 0.01-P < 0.05). CONCLUSION: The mIL-2R can be induced by alpha 2b interferon during the treatment. The alpha 2b interferon has a definite effect on the treatment of HCV-RNA in PBMC. The curative effect of alpha 2b interferon is

  4. 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

  5. Treatment of type 2 diabetes mellitus by viral eradication in chronic hepatitis C: Myth or reality?

    PubMed

    Vanni, Ester; Bugianesi, Elisabetta; Saracco, Giorgio

    2016-02-01

    Chronic hepatitis C is a systemic disease inducing metabolic alterations leading to extrahepatic consequences. In particular, hepatitis C virus (HCV) infection seems to increase the risk of incident type 2 diabetes mellitus in predisposed individuals, independently of liver disease stage. The mechanisms through which hepatitis C induces T2DM involve direct viral effects, insulin resistance, pro-inflammatory cytokines and other immune-mediated processes. Many studies have reported the clinical consequences of type 2 diabetes mellitus on hepatitis C outcome, but very few studies have addressed the issue of microangiopathic complications among patients with hepatitis C only, who develop type 2 diabetes mellitus. Moreover, clinical trials in HCV-positive patients have reported improvement in glucose metabolism after antiviral treatment; recent studies have suggested that this metabolic amelioration might have a clinical impact on type 2 diabetes mellitus-related complications. These observations raise the question as to whether the HCV eradication may also have an impact on the future morbidity and mortality due to type 2 diabetes mellitus. The scope of this review is to summarise the current evidence linking successful antiviral treatment and the prevention of type 2 diabetes mellitus and its complications in hepatitis C-infected patients.

  6. Current Concepts of Viral Hepatitis and A Peek into the Future 1

    PubMed Central

    Koff, Raymond S.

    1974-01-01

    New information has prompted revision of the conceptual framework for considering the epidemiology and virology of viral hepatitis. The means are now at hand to identify infections due to either Hepatitis A or B, as well as to implicate other etiologic agents in hepatitis. Immunologic evidence of variation in the antigens associated with Hepatitis B, and possibly in Hepatitis A, may explain some well known epidemiologic phenomena and has important implications in immune serum globulin prophylaxis. The ambiguous relationship of antigenemia and viremia in Hepatitis B is explored in relation to the hepatitis hazard of blood products, to trials of immune serum globulin, and to the potential role of the carrier-health worker in hepatitis transmission. The emerging concept of non-parenteral transmission of Hepatitis B is reviewed and future developments in the production of hepatitis vaccines and in experimental viral hepatitis in non-human primates is briefly discussed. PMID:4376306

  7. 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.

  8. Evolution of hepatitis C viral quasispecies and hepatic injury in perinatally infected children followed prospectively.

    PubMed

    Farci, Patrizia; Quinti, Isabella; Farci, Stefania; Alter, Harvey J; Strazzera, Rita; Palomba, Elvia; Coiana, Alessandra; Cao, Daniele; Casadei, Anna Maria; Ledda, Ritarella; Iorio, Raffaele; Vegnente, Angela; Diaz, Giacomo; Tovo, Pier-Angelo

    2006-05-30

    Perinatal infection with hepatitis C virus (HCV) is characterized by a wide range of alanine aminotransferase (ALT) levels. The mechanisms responsible for this variability are unknown. We examined whether the evolution of the HCV quasispecies was associated with different ALT profiles in perinatally infected children. Sequences within HCV envelope 1 and 2 genes, inclusive of the hypervariable region 1, the viral load, and the nascent humoral immunity were analyzed in serial serum samples from 12 perinatally infected children prospectively followed for a median of 53 months. These patients were selected to represent two different ALT patterns during the first year of life: 6 had high levels (maximum values ranging from 4.2 to 30 times the normal upper limit), and 6 had normal or slightly elevated levels (< 2 times the normal upper limit). Two patterns of viral evolution were identified according to the ALT profiles. Biochemical evidence of hepatic injury was invariably associated with a mono- or oligoclonal viral population, whereas mild or no liver damage correlated with the early emergence of a heterogeneous viral quasispecies. Consistent with selective immune pressure, amino acid changes occurred almost exclusively within the hypervariable region 1 and were temporally associated with antibody seroconversion; at this time, the difference in genetic diversity between the two groups was highly significant (P = 0.002). The two patterns of viral evolution persisted over time and did not correlate with viral load or genotype. Our study demonstrates that, in perinatally infected children, the evolution of HCV quasispecies correlates with hepatic injury. The sequences reported in this paper have been deposited in the GenBank database (accession nos. DQ 504441-DQ 507112).

  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. [Evaluation of viral hepatitis in solid organ transplantation].

    PubMed

    Mikolašević, Ivana; Sladoje-Martinović, Branka; Orlić, Lidija; Milić, Sandra; Lukenda, Vesna; Župan, Željko; Štimac, Davor; Rački, Sanjin

    2014-04-01

    Renal transplantation has significantly improved survival of patients with end-stage renal disease (ESRD). Transplantation is the best treatment in this population of patients. Despite the introduction of various preventive measures, viral hepatitis, i.e. hepatitis B virus (HBV) and hepatitis C virus (HCV) infections, are still a major problem because they are common in patients on renal replacement therapy as well as in allograft recipients. They are a significant cause of morbidity and mortality in this patient population. In recent years, hepatitis E virus (HEV) infection has been added as an emergent cause of chronic hepatitis in solid organ transplantation, mainly in renal and liver allograft recipients. Most studies show higher mortality in renal transplant recipients (RTRs) infected with HBV, compared with RTRs without HBV infection, although this topic is still under debate. Furthermore, HCV infection in RTRs is associated with a significant reduction in patient and graft survival due to liver disease and septic complications related to cirrhosis and immunosuppressive therapy. The immunosuppressive therapy prescribed after transplantation modifies the natural history of chronic HCV infection. Given the high prevalence of HCV and HBV infections in RTRs, a growing incidence of hepatocellular carcinoma and the possible contribution of immunosuppression might be expected in these patients. Therefore, after renal transplantation, early screening with abdominal ultrasound (every 3 months in cirrhotic patients and every 6-12 months in non-cirrhotic RTRs) is necessary when the risk factors such as HBV and HCV are present. The European Association for the Study of the Liver (EASL) recommends that all HbsAg-positive patients who are candidates for solid organ transplantation should be treated with nucleoside analogs. The KDIGO guidelines recommend that all HbsAg-positive RTRs receive prophylaxis with tenofovir, entecavir or lamivudine; however, tenofovir and

  11. XTC-induced hepatitis.

    PubMed

    Oranje, W A; von Pol, P; vd Wurff, A; Zeijen, R N; Stockbrügger, R W; Arends, J W

    1994-02-01

    An increasing number of severe complications associated with the use of XTC is being reported. After 11 earlier case reports we describe an acute hepatitis due to occasional use of XTC in a 25-year-old woman.

  12. Progress in the control of viral hepatitis: Memorandum from a WHO Meeting*

    PubMed Central

    1988-01-01

    Viral hepatitis is a major public health problem in all parts of the world, with hepatitis B (HB) as the most important of all the viral hepatitides. It is estimated that worldwide there are nearly 300 million carriers of HB markers of active infection. More than 40% of persistently infected persons who survive into adult life will die of the consequences of HB, such as cirrhosis and hepatocellular carcinoma. The vaccines available against HB have an impressive record of safety and efficacy, and the best means of controlling the infection on a global scale, including the reduction of mortality due to its sequelae, will be by mass immunization of infants. In areas where most infections are acquired early in life the vaccine should be administered shortly after birth, and HB immunization should be integrated into the Expanded Programme on Immunization. Progress has been made also in developing hepatitis A vaccines and in isolating the agents that induce hepatitis non-A non-B. PMID:2971466

  13. [Knowledge about viral hepatitis in a sample of Brazilian students from Vale do Araguaia, Legal Amazonia].

    PubMed

    Ferrari, Carlos K B; Savazzi, Kamirri; Honorio-França, Adenilda C; Ferrari, Graziele S L; França, Eduardo L

    2012-06-01

    Viral and non-viral hepatitis are of great concern among developing nations because of their pathogenicity and virulence, and also their wide spreading by contaminated blood, food or water. The objective of this work was to evaluate the knowledge about hepatitis of academic students from three life/health sciences courses and also students from the last year of high school To measure the students' knowledge on hepatitis an instrument containing 22 questions was applied. Surprinsingly, it was verified that 41.9% of students had poor knowledge of viral hepatitis. Among the high school students, 31.8% ignored that viral hepatitis are infectious and transmissible diseases. Considering hepatitis symptomatology, just 18% of high school students declared knowledge of the symptons, but none of those cited the ictericia. Among the academic students, 75.9% of nursing students had adequate knowledge of hepatitis, followed by pharmacy (51.3%), and biology students (18.2%). Nursing students had also higher scores of right answers regarding viral hepatitis and chronic disease. On contrary, biology and high school students had poor knowledge of that matter (37% and 44.5%, respectively). Less than 15% of nursing and pharmacy students did not know that viral hepatitis are sexually transmissible, whereas 78.6% of the 3rd year and 52.4% of the 4th year biology course ignored the sexual transmission of viral hepatitis. Still considering the same question, 54.5% of the high school students also ignored that viral hepatitis are sexually transmitted diseases. Important conclusions can be drawn from this study, since the higher hepatitis knowledge scores were found among nursing students, followed by pharmacy academics. However, biology students, which will serve as high school teachers, had poor and insufficient knowledge on hepatitis. This finding could explain the same poor disease knowledge among high school pupils.

  14. 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.

  15. 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:...

  16. Significance of viral status on occurrence of hepatitis B-related hepatocellular carcinoma

    PubMed Central

    Qu, Li-Shuai; Zhou, Guo-Xiong

    2014-01-01

    Hepatitis B virus (HBV) infection remains a challenging global health problem, with more than 350 million people chronically infected and at risk of developing hepatocellular carcinoma (HCC). Interactions that occur among host, environmental, and viral factors determine the natural course and predict the prognosis of patients with chronic HBV infection. In the past decades, several important viral factors of predictive of HCC have been identified, such as high hepatitis B surface antigen level, seropositivity of hepatitis B e antigen, high viral load, viral genotype, and specific viral sequence mutations. Identification of certain viral risk factors for HCC development and stratification of patient risk are very important to perform future surveillance programs. In this article, we thus reviewed the risk of viral factors involved in hepatocarcinogenesis. PMID:24876722

  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. Drug-induced hepatic steatosis.

    PubMed

    Amacher, David E; Chalasani, Naga

    2014-05-01

    Several drugs have been associated with the potential for drug-induced hepatic steatosis (DIHS) and/or phospholipidosis (DIPL), a lysosomal storage disorder. Drug-induced hepatic steatosis is generally a chronic but reversible affliction and may involve drug accumulation in the liver. Fat accumulation may be either macrovesicular or microvesicular in nature. Commonly used medications associated with DIHS include amiodarone, valproate, tamoxifen, methotrexate, and some chemotherapeutic and antiretroviral agents. Two recently approved medications for the treatment of hereditary homozygous hypercholesterolemia have also been noted to cause hepatic steatosis. For some compounds such as methotrexate and tamoxifen, the underlying metabolic risk factors such as obesity and metabolic syndrome may exacerbate their potential to cause DIHS and its progression. In this article, the authors discuss the preclinical screening and mechanisms of DIHS and DIPL, and review specific examples of drugs commonly used in clinical practice that are known to cause DIHS. PMID:24879984

  19. Brief report: acute viral hepatitis and poor maternal and perinatal outcomes in pregnant Sudanese women.

    PubMed

    Ahmed, Rihab E; Karsany, Mubarak S; Adam, Ishag

    2008-10-01

    Sixteen pregnant women presented at the three main hospitals in Khartoum province, Sudan during the period of March-September 2007 with features of acute viral hepatitis. Their mean (SD) gestational age was 28.0(6.7) weeks. The etiology of acute viral hepatitis was hepatitis B virus in five women (31.3%), hepatitis C virus in one woman (6.3%), hepatitis E virus in eight women (50%), and hepatitis non-A-to-E virus in two women (12.5%). There were four (25%) maternal deaths and three (18.7%) intrauterine fetal deaths. Three of these maternal deaths were due to hepatitis E virus and the fourth was due to hepatitis B virus.

  20. The NLRP3 Inflammasome and IL-1β Accelerate Immunologically Mediated Pathology in Experimental Viral Fulminant Hepatitis.

    PubMed

    Guo, Sheng; Yang, Chengying; Diao, Bo; Huang, Xiaoyong; Jin, Meihua; Chen, Lili; Yan, Weiming; Ning, Qin; Zheng, Lixin; Wu, Yuzhang; Chen, Yongwen

    2015-09-01

    Viral fulminant hepatitis (FH) is a severe disease with high mortality resulting from excessive inflammation in the infected liver. Clinical interventions have been inefficient due to the lack of knowledge for inflammatory pathogenesis in the virus-infected liver. We show that wild-type mice infected with murine hepatitis virus strain-3 (MHV-3), a model for viral FH, manifest with severe disease and high mortality in association with a significant elevation in IL-1β expression in the serum and liver. Whereas, the viral infection in IL-1β receptor-I deficient (IL-1R1-/-) or IL-1R antagonist (IL-1Ra) treated mice, show reductions in virus replication, disease progress and mortality. IL-1R1 deficiency appears to debilitate the virus-induced fibrinogen-like protein-2 (FGL2) production in macrophages and CD45+Gr-1high neutrophil infiltration in the liver. The quick release of reactive oxygen species (ROS) by the infected macrophages suggests a plausible viral initiation of NLRP3 inflammasome activation. Further experiments show that mice deficient of p47phox, a nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunit that controls acute ROS production, present with reductions in NLRP3 inflammasome activation and subsequent IL-1β secretion during viral infection, which appears to be responsible for acquiring resilience to viral FH. Moreover, viral infected animals in deficiencies of NLRP3 and Caspase-1, two essential components of the inflammasome complex, also have reduced IL-1β induction along with ameliorated hepatitis. Our results demonstrate that the ROS/NLRP3/IL-1β axis institutes an essential signaling pathway, which is over activated and directly causes the severe liver disease during viral infection, which sheds light on development of efficient treatments for human viral FH and other severe inflammatory diseases.

  1. PD-1 Blockage Reverses Immune Dysfunction and Hepatitis B Viral Persistence in a Mouse Animal Model

    PubMed Central

    Tzeng, Horng-Tay; Tsai, Hwei-Fang; Liao, Hsiu-Jung; Lin, Yi-Jiun; Chen, Lieping; Chen, Pei-Jer; Hsu, Ping-Ning

    2012-01-01

    Persistent hepatitis B viral (HBV) infection results in chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma (HCC). Recent studies in animal models of viral infection indicate that the interaction between the inhibitory receptor, programmed death (PD)-1, on lymphocytes and its ligand (PD-L1) play a critical role in T-cell exhaustion by inducing T-cell inactivation. High PD-1 expression levels by peripheral T-lymphocytes and the possibility of improving T-cell function by blocking PD-1-mediated signaling confirm the importance of this inhibitory pathway in inducing T-cell exhaustion. We studied T-cell exhaustion and the effects of PD-1 and PD-L1 blockade on intrahepatic infiltrating T-cells in our recently developed mouse model of HBV persistence. In this mouse animal model, we demonstrated that there were increased intrahepatic PD-1-expressing CD8+ and CD4+ T cells in mice with HBV persistence, but PD-1 upregulation was resolved in mice which had cleared HBV. The Intrahepatic CD8+ T-cells expressed higher levels of PD-1 and lower levels of CD127 in mice with HBV persistence. Blockade of PD-1/PD-L1 interactions increased HBcAg-specific interferon (IFN)-γ production in intrahepatic T lymphocytes. Furthermore, blocking the interaction of PD-1 with PD-L1 by an anti-PD-1 monoclonal antibody (mAb) reversed the exhausted phenotype in intrahepatic T lymphocytes and viral persistence to clearance of HBV in vivo. Our results indicated that PD-1 blockage reverses immune dysfunction and viral persistence of HBV infection in a mouse animal model, suggesting that the anti-PD-1 mAb might be a good therapeutic candidate for chronic HBV infection. PMID:22761734

  2. [Viral load survey from geographical areas within Argentina with high hepatitis B virus prevalence].

    PubMed

    Amegeiras, Beatriz; González, Jorge Enrique; Jotimliansky, Laura; Zingoni, Carolina; Vulcano, Cristina

    2013-03-01

    Several studies have demonstrated that viral load is a key factor to determine the development of HBV infection and to assess treatment options for the disease. There is a lack of studies analyzing viral load levels in chronic hepatitis B patients in Argentina and the epidemiologic information is limited. The aim of this study was to determine viral load levels and its distribution in patients diagnosed with chronic hepatitis B from geographical areas with high prevalence for HBV in Argentina. Fifty-one per cent of the study population had HBV DNA levels > or = 10(4) copies/ml and a median viral load of 11,910 copies/ml. The viral load was significantly higher in HBeAg seropositive patients compared with those seronegative for HBeAg (P < 0.05). Salta and Entre Ríos provinces showed low viral loads, while Chaco, Misiones and Formosa provinces had a median viral load ranging between 10(4) and 10(5) copies/ ml. This is the first study providing detailed information on viral load in chronic hepatitis B patients from Argentina. Availability of viral load levels in chronic hepatitis B enables evaluation of implementation of actions to analyze follow-up and/or treatment options for preventing disease complications, improving health care and diminishing the potential burden on the health care system. PMID:23650829

  3. [The state of cellular immunity in women with a history of viral hepatitis].

    PubMed

    Dyndar, O A

    1998-08-01

    Overall sixty puerperants were examined with a history of viral hepatitis before true pregnancy has set in, with 50 healthy puerperants being controls. In women with prior viral hepatitis, the B-cell link of immunity was found out to be disordered, especially so postpartum, as evidenced by investigations designed to study the chief classes of immunoglobulin G, A, M in parturient women's blood sera and the postpartum complications patterns.

  4. Mutagenic Effects of Ribavirin on Hepatitis E Virus—Viral Extinction versus Selection of Fitness-Enhancing Mutations

    PubMed Central

    Todt, Daniel; Walter, Stephanie; Brown, Richard J. P.; Steinmann, Eike

    2016-01-01

    Hepatitis E virus (HEV), an important agent of viral hepatitis worldwide, can cause severe courses of infection in pregnant women and immunosuppressed patients. To date, HEV infections can only be treated with ribavirin (RBV). Major drawbacks of this therapy are that RBV is not approved for administration to pregnant women and that the virus can acquire mutations, which render the intra-host population less sensitive or even resistant to RBV. One of the proposed modes of action of RBV is a direct mutagenic effect on viral genomes, inducing mismatches and subsequent nucleotide substitutions. These transition events can drive the already error-prone viral replication beyond an error threshold, causing viral population extinction. In contrast, the expanded heterogeneous viral population can facilitate selection of mutant viruses with enhanced replication fitness. Emergence of these mutant viruses can lead to therapeutic failure. Consequently, the onset of RBV treatment in chronically HEV-infected individuals can result in two divergent outcomes: viral extinction versus selection of fitness-enhanced viruses. Following an overview of RNA viruses treated with RBV in clinics and a summary of the different antiviral modes of action of this drug, we focus on the mutagenic effect of RBV on HEV intrahost populations, and how HEV is able to overcome lethal mutagenesis. PMID:27754363

  5. 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

  6. 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

  7. [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

  8. [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. [

  9. 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

  10. Viral hepatitis among drug users in methadone maintenance: Associated factors, vaccination outcomes, and interventions

    PubMed Central

    Perlman, David C.; Jordan, Ashly E.; McKnight, Courtney; Young, Christopher; Delucchi, Kevin L.; Sorensen, James L.; Des Jarlais, Don C.; Masson, Carmen L.

    2014-01-01

    Background Drug users (DUs) are at high risk of viral hepatitis A, B, and C (HAV, HBV, HCV). Methods We examined the prevalence of HAV, HBV, and HCV, associated factors, and vaccine seroconversion among drug treatment program participants in a randomized controlled trial of hepatitis care coordination. Results Of 489 participants, 44% and 47% required HAV/HBV vaccination, respectively; 59% were HCV positive requiring linkage to care. Factors associated with serologic statuses, and vaccine seroconversion are reported; implications for strategies in drug treatment settings are discussed. Conclusions Results suggest generalizable strategies for drug treatment programs to expand viral hepatitis screening, prevention, vaccination and linkage to care. PMID:25299236

  11. 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

  12. The incidence and significance of pattern-recognition receptors in chronic viral hepatitis types B and C in man.

    PubMed

    Mozer-Lisewska, Iwona; Sikora, Jan; Kowala-Piaskowska, Arleta; Kaczmarek, Mariusz; Dworacki, Grzegorz; Zeromski, Jan

    2010-08-01

    Chronic viral hepatitis B and C are among the most common and devastating liver diseases worldwide. Immune response plays a crucial role in the course of both diseases. In spite of the importance of the adaptive arm of the immune response, there is a growing role of innate immunity, the earliest confronted with viral attack. Pattern-recognition receptors (PRRs) and, in particular, Toll-like receptors (TLRs) are molecules which are able not only to recognize foreign invaders, but also quickly mount an antiviral defense. Activation of PRRs has been demonstrated in both hepatitis types, i.e. in situ in the liver and on while blood cells. Both viruses, HCV and HBV, are able to subvert the PRR-mediated antiviral response by means of various proteins and enzymes. HCV acts via the non-structural proteins NS2 and NS3/4A, while HBV HBeAg is inversely correlated with TLR activity. Viral counterattack is particularly directed toward dendritic cells, those creating the link with the adaptive immune response. Apart from TLRs, other PRRs such as RIG-1 and MDA-5 are also able to recognize viral infection and participate in the activation of type I interferon synthesis. TLRs manifest gene polymorphism, which was shown to affect several consequences associated with chronic viral hepatitis such as liver cirrhosis and the outcome of liver allotransplantation. There have been numerous attempts to take advantage of the existence and activity of PRRs for the patients' benefit. Several authors examined the role of TLR synthetic agonists as inducers of TLR activation. In hepatitis C the most promising agonists appear to be TLR3, 7, and 9 for potential antiviral therapy. PRRs may also act as potent adjuvants in HBV vaccines. Their baseline mRNA levels may have predictive value in the course of antiviral therapy.

  13. Establishment of a viral hepatitis surveillance system--Pakistan, 2009-2011.

    PubMed

    2011-10-14

    Hepatitis A is thought to infect almost all persons living in Pakistan by age 15 years, and hepatitis E is responsible for sporadic infections and outbreaks. The prevalence of hepatitis B virus (HBV) infection is estimated at 2.5% and the prevalence of hepatitis C virus (HCV) infection, estimated at 4.8%, is one of the highest rates in the world. Hepatitis surveillance in Pakistan has been syndromic, failing to confirm infection, distinguish among viruses, or collect information on risk factors. To understand the epidemiology of viral hepatitis in Pakistan more clearly, the Ministry of Health (MOH) asked the Pakistan Field Epidemiology and Laboratory Training Program (FELTP) to establish a hepatitis sentinel surveillance system in five large public hospitals in four provinces and Islamabad Capital Territory. This report describes the implementation of the viral hepatitis surveillance system in Pakistan and summarizes major findings from June 2010 through March 2011. A total of 712 cases of viral hepatitis were reported; newly reported HCV infection accounted for 53.2% of reported cases, followed by acute hepatitis A (19.8%), acute hepatitis E (12.2%), and newly reported HBV infection (10.8%). A history of health-care--related exposures, particularly receipt of therapeutic injections and infusions, commonly were reported by persons infected with HBV and HCV, and most patients reported drinking unboiled water. These findings point to the need for improved provider and community education about risks associated with unsafe injections, strengthening infection control practices in health facilities, increasing hepatitis B vaccination coverage, and improving access to clean drinking water in Pakistan.

  14. Early changes in hepatitis C viral quasispecies during interferon therapy predict the therapeutic outcome

    PubMed Central

    Farci, Patrizia; Strazzera, Rita; Alter, Harvey J.; Farci, Stefania; Degioannis, Daniela; Coiana, Alessandra; Peddis, Giovanna; Usai, Francesco; Serra, Giancarlo; Chessa, Luchino; Diaz, Giacomo; Balestrieri, Angelo; Purcell, Robert H.

    2002-01-01

    Despite recent treatment advances, the majority of patients with chronic hepatitis C fail to respond to antiviral therapy. Although the genetic basis for this resistance is unknown, accumulated evidence suggests that changes in the heterogeneous viral population (quasispecies) may be an important determinant of viral persistence and response to therapy. Sequences within hepatitis C virus (HCV) envelope 1 and envelope 2 genes, inclusive of the hypervariable region 1, were analyzed in parallel with the level of viral replication in serial serum samples obtained from 23 patients who exhibited different patterns of response to therapy and from untreated controls. Our study provides evidence that although the viral diversity before treatment does not predict the response to treatment, the early emergence and dominance of a single viral variant distinguishes patients who will have a sustained therapeutic response from those who subsequently will experience a breakthrough or relapse. A dramatic reduction in genetic diversity leading to an increasingly homogeneous viral population was a consistent feature associated with viral clearance in sustained responders and was independent of HCV genotype. The persistence of variants present before treatment in patients who fail to respond or who experience a breakthrough during therapy strongly suggests the preexistence of viral strains with inherent resistance to IFN. Thus, the study of the evolution of the HCV quasispecies provides prognostic information as early as the first 2 weeks after starting therapy and opens perspectives for elucidating the mechanisms of treatment failure in chronic hepatitis C. PMID:11880647

  15. Epidemiology of viral hepatitis among US Navy and Marine Corps personnel, 1984-85.

    PubMed Central

    Dembert, M L; Shaffer, R A; Baugh, N L; Berg, S W; Zajdowicz, T

    1987-01-01

    Six hundred and twenty-nine cases of viral hepatitis (A, B, and NonA-NonB) were reported among a total of 768,832 United States Navy and Marine Corps personnel during 1984 and 1985 via a passive surveillance system. Cumulative incidence for all three hepatitis types was higher than those reported for the general population at the same time. Hepatitis B was the most common diagnosis within all sex, rank, and race/ethnic description categories. Enlisted medical personnel (hospital corpsmen) had a disproportionately higher incidence of hepatitis B. PMID:3661799

  16. Hepatitis Due to Equine Abortion Virus. Comparison Between the Liver Histology in Human, Canine, Duckling, and Equine Viral Hepatitis1

    PubMed Central

    Corrêa, W. M.; Nilsson, M. R.

    1966-01-01

    Five livers of equine fetuses, aborted due to the action of equine abortion virus, five livers from men, two of whom died of epidemic hepatitis and three obtained by needle biopsies, 5 livers of dogs with infectious canine hepatitis and 7 livers of ducklings that had hepatitis, were studied histopathologically. The foals' livers were studied by several staining methods and the others by H. E. only. The results indicate that the lesions are quite similar in the four species with the appearance of nuclear inclusion bodies only in foals and dogs. The strong staining properties of the nuclear inclusion bodies in infectious canine hepatitis and the weak staining properties of the equine virus abortion reveal that the protein-DNA association is different resulting in a different electropolarity. The lesions in foals are of two main types, one a Necrotic-Mosaic Type in which the hepatocyte degeneration is irregularly distributed within the hepatic lobules and the other an Hyperplastic Type in which marked regeneration occurs. In the Hyperplastic Type the practical absence of plasmocytes in foals' livers might suggest that if the newborn is a female, abortions may occur later in life because the virus remained alive in colts which were born in an immune tolerance state. Histologically the picture in the livers of aborted foals assume features of a viral hepatitis similar to the viral hepatitis in men, dogs and ducklings. ImagesFig. 1.Fig. 2.Fig. 3.Fig. 4.Fig. 5.Fig. 6.Fig. 7.Fig. 8.Fig. 9. PMID:4225286

  17. 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

  18. 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.

  19. [Prevention of viral hepatitis B and C infections--jurisdiction and certification difficulties].

    PubMed

    Olesiak-Andryszczak, Małgorzata; Cnota, Wojciech; Sodowski, Krzysztof

    2004-01-01

    The number of the cases for payment because of viral hepatitis B and C inflammation is significant. Because of the greater patients' notice of the disease and portal of infection, lawyer's opinion accessibility and poor economical situation of society the claims for damages seems to be more popular. The lawyers specialize in medical law. This is the reason to pay more attention to prevention of infections. Besides the hospital infections there is problem of viral hepatitis B and C infection as the occupational disease with all health and juridical consequences. These problems concern specially operative specialties therefore gynecology and obstetrics among the others. The aim of our study was to analyze jurisdiction and certification difficulties in context of occupational disease and cases for payment because of viral hepatitis B and C infections. We also try to answer the question what are possibilities to prevent infections and to defence in law suits.

  20. 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

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

    PubMed

    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

  2. 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

  3. [The tocopherol acetate and splenin correction of the immunological disorders in patients with viral hepatitis B].

    PubMed

    Frolov, V M; Peresadin, N A; Dekaliuk, I V; Pshenichnyĭ, I Ia

    1992-04-01

    Inclusion of tocopherol acetate and splenin into complex treatment of viral hepatitis B (VHB) ensures a marked immunomodulating effect consisting in control of T-lymphopenia, normalization of helper-suppressor ratio, reduction of circulating immune complexes and a tendency to restoration of normal ratio between separate fractions of immune complexes, stimulation of phagocytic activity of monocytes of the peripheral blood. Splenin and tocopherol acetate are recommended in the complex treatment of hepatitis B.

  4. 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

    2016-08-22

    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.

  5. 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

  6. 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

  7. 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.…

  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. The cytotoxic T lymphocyte response to multiple hepatitis B virus polymerase epitopes during and after acute viral hepatitis

    PubMed Central

    1995-01-01

    Cytotoxic T lymphocytes (CTL) are thought to contribute to viral clearance and liver cell injury during hepatitis B virus (HBV) infection. Using a strategy involving the in vitro stimulation of peripheral blood mononuclear cells (PBMC) with HBV-derived synthetic peptides containing HLA-A2.1, -A31, and -Aw68 binding motifs, we have previously described CTL responses to several epitopes within the HBV nucleocapsid and envelope antigens in patients with acute hepatitis. In this study we define six HLA-A2-restricted CTL epitopes located in the highly conserved reverse transcriptase and RNase H domains of the viral polymerase protein, and we show that the CTL response to polymerase is polyclonal, multispecific, and mediated by CD8+ T cells in patients with acute viral hepatitis, but that it is not detectable in patients with chronic HBV infection or uninfected healthy blood donors. Importantly, the peptide-activated CTL recognize target cells that express endogenously synthesized polymerase protein, suggesting that these peptides represent naturally processed viral epitopes. DNA sequence analysis of the viruses in patients who did not respond to peptide stimulation indicated that CTL nonresponsiveness was not due to infection by viral variants that differed in sequences from the synthetic peptides. CTL specific for one of the epitopes were unable to recognize several naturally occurring viral variants, except at high peptide concentration, underlining the HBV subtype specificity of this response. Furthermore, CTL responses against polymerase, core, and envelope epitopes were detectable for more than a year after complete clinical recovery and seroconversion, reflecting either the persistence of trace amounts of virus or the presence of long lived memory CTL in the absence of viral antigen. Finally, we demonstrated that wild type viral DNA and RNA can persist indefinitely, in trace quantities, in the serum and PBMC after complete clinical and serological recovery

  10. 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

  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. [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

  13. Viral markers in the treatment of hepatitis B and C.

    PubMed Central

    Schmilovitz-Weiss, H; Levy, M; Thompson, N; Dusheiko, G

    1993-01-01

    Acute hepatitis B virus (HBV) infection is typically distinguished from chronic disease by a positive IgM anti-hepatitis B core antigen (anti-HBc) test. Patients with chronic hepatitis B remain hepatitis B surface antigen (HBsAg) positive, often with raised serum alanine aminotransferase (ALT) activities, for more than six months. The presence of hepatitis B e antigen (HBeAg) and HBV-DNA correlates with infectivity (although patients infected with the pre-core mutated virus may be HBeAg negative). Immunity after HBV infection is characterised by the presence of anti-HBs and anti-HBc antibodies. Patients who respond to interferon alfa treatment lose HBV-DNA and HBeAg from serum and their ALT values return to normal; some also lose HBsAg and acquire anti-HBs. Diagnosis of acute hepatitis C virus (HCV) infection remains largely dependent on history and exclusion, as anti-HCV antibodies may appear late or never at all, although HCV-RNA may be detectable on polymerase chain reaction (PCR) within days of infection. Second generation ELISAs detect a range of anti-HCV antibodies in chronic infections, and confirmatory RIBAs have reduced the incidence of false-positive results. Direct tests for HCV antigens in serum are not yet available, although PCR testing for HCV-RNA can be used to confirm viraemia. Patients who respond to interferon alfa treatment show continuous normalisation of serum ALT values, and some lose HCV-RNA. Relapse occurs in about half of all those who respond. PMID:7686114

  14. 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.

  15. Characteristics and TB treatment outcomes in TB patients with viral hepatitis, New York City, 2000-2010.

    PubMed

    Bushnell, G; Stennis, N L; Drobnik, A M; Proops, D C; Ahuja, S D; Bornschlegel, K; Fuld, J

    2015-07-01

    Literature surrounding the burden of and factors associated with hepatitis B virus (HBV) and hepatitis C virus (HCV) infection in persons with tuberculosis (TB) disease remains limited and focused on populations outside the USA. Cross-matched New York City (NYC) TB and viral hepatitis surveillance data were used to estimate the proportion of NYC adults diagnosed with TB from 2000 to 2010 with a report of viral hepatitis infection and to describe the impact of viral hepatitis infection on TB treatment completion and death. For 9512 TB patients, HCV infection was reported in 4.2% and HBV infection in 3.7%; <1% of TB patients had both HCV and HBV infection. The proportion of TB patients with HCV infection to die before TB treatment completion was larger than in TB patients without a viral hepatitis report (21% vs. 9%); this association remained when stratified by HIV status. There was no significant difference in death before treatment completion for TB patients with HBV infection compared to TB patients without a viral hepatitis report when stratified by HIV status. These findings reinforce the importance of hepatitis testing and providing additional support to TB patients with viral hepatitis infection.

  16. Hepatitis B Virus Protein X Induces Degradation of Talin-1

    PubMed Central

    van de Klundert, Maarten A. A.; van den Biggelaar, Maartje; Kootstra, Neeltje A.; Zaaijer, Hans L.

    2016-01-01

    In the infected human hepatocyte, expression of the hepatitis B virus (HBV) accessory protein X (HBx) is essential to maintain viral replication in vivo. HBx critically interacts with the host damaged DNA binding protein 1 (DDB1) and the associated ubiquitin ligase machinery, suggesting that HBx functions by inducing the degradation of host proteins. To identify such host proteins, we systematically analyzed the HBx interactome. One HBx interacting protein, talin-1 (TLN1), was proteasomally degraded upon HBx expression. Further analysis showed that TLN1 levels indeed modulate HBV transcriptional activity in an HBx-dependent manner. This indicates that HBx-mediated TLN1 degradation is essential and sufficient to stimulate HBV replication. Our data show that TLN1 can act as a viral restriction factor that suppresses HBV replication, and suggest that the HBx relieves this restriction by inducing TLN1 degradation. PMID:27775586

  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.

  18. Acute pancreatitis associated with acute viral hepatitis A (HAV) - a case report.

    PubMed

    Arafat, S M; Azad, A K; Basher, A; Ananna, M A; Islam, M S; Abdullah, S; Abdullah, A M; Islam, M A

    2013-01-01

    In this case report, a young woman had acute viral hepatitis (HAV) and acute pancreatitis together. She was admitted to our hospital with fever, jaundice and abdominal pain. Hepatic and pancreatic enzymes were elevated. Her serum alanine aminotransferase (ALT) level was high. An initial abdominal ultrasound was per-formed at hospital and revealed features of acute viral hepatitis. Spiral computed imaging revealed imaging features of an acute stage of pancreatitis and gallbladder wall thickness. HAV infection was diagnosed by the detection of immunoglobulin M (IgM) against HAV in the serum. She was closely monitored and treated conservatively. On 10th day of hospital admission she was discharge after an uneventful recovery. In the current literature HAV infections have rarely been reported as a cause of acute pancreatitis.

  19. Hepatitis C virus evasion of adaptive immune responses: a model for viral persistence.

    PubMed

    Burke, Kelly P; Cox, Andrea L

    2010-07-01

    Hepatitis C virus (HCV) infects over 170 million people worldwide and is a leading cause of cirrhosis and hepatocellular carcinoma. Approximately 20% [corrected] of those acutely infected clear the infection, whereas the remaining 80% [corrected] progress to chronic infection. Hepatitis C thus provides a model in which successful and unsuccessful responses can be compared to better understand the human response to viral infection. Our laboratory studies the strategies by which HCV evades the adaptive immune response. This review describes the impact of viral mutation on T cell recognition, the role of cell surface inhibitory receptors in recognition of HCV, and the development of antibodies that neutralize HCV infection. Understanding what constitutes an effective immune response in the control of HCV may enable the development of prophylactic and therapeutic vaccines for HCV and other chronic viral infections.

  20. The Dual Role of Exosomes in Hepatitis A and C Virus Transmission and Viral Immune Activation.

    PubMed

    Longatti, Andrea

    2015-12-17

    Exosomes are small nanovesicles of about 100 nm in diameter that act as intercellular messengers because they can shuttle RNA, proteins and lipids between different cells. Many studies have found that exosomes also play various roles in viral pathogenesis. Hepatitis A virus (HAV; a picornavirus) and Hepatitis C virus (HCV; a flavivirus) two single strand plus-sense RNA viruses, in particular, have been found to use exosomes for viral transmission thus evading antibody-mediated immune responses. Paradoxically, both viral exosomes can also be detected by plasmacytoid dendritic cells (pDCs) leading to innate immune activation and type I interferon production. This article will review recent findings regarding these two viruses and outline how exosomes are involved in their transmission and immune sensing.

  1. The Dual Role of Exosomes in Hepatitis A and C Virus Transmission and Viral Immune Activation

    PubMed Central

    Longatti, Andrea

    2015-01-01

    Exosomes are small nanovesicles of about 100 nm in diameter that act as intercellular messengers because they can shuttle RNA, proteins and lipids between different cells. Many studies have found that exosomes also play various roles in viral pathogenesis. Hepatitis A virus (HAV; a picornavirus) and Hepatitis C virus (HCV; a flavivirus) two single strand plus-sense RNA viruses, in particular, have been found to use exosomes for viral transmission thus evading antibody-mediated immune responses. Paradoxically, both viral exosomes can also be detected by plasmacytoid dendritic cells (pDCs) leading to innate immune activation and type I interferon production. This article will review recent findings regarding these two viruses and outline how exosomes are involved in their transmission and immune sensing. PMID:26694453

  2. 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

  3. Limonium sinense and gallic acid suppress hepatitis C virus infection by blocking early viral entry.

    PubMed

    Hsu, Wen-Chan; Chang, Shun-Pang; Lin, Lie-Chwen; Li, Chia-Lin; Richardson, Christopher D; Lin, Chun-Ching; Lin, Liang-Tzung

    2015-06-01

    A preventive vaccine against hepatitis C virus (HCV) infection remains unavailable and newly developed drugs against viral replication are complicated by potential drug-resistance and high cost. These issues justify the need to develop alternative antiviral agents and expand the scope of strategies for the treatment of hepatitis C, such as targeting viral entry. In this study, we explore the bioactivity of Limonium sinense (L. sinense) and its purified constituents against HCV life cycle using subgenomic replicon and infectious HCV culture systems. Data indicated that the water extract from the underground part of L. sinense (LS-UW) exhibited potent inhibitory activity against HCV at non-cytotoxic concentrations. LS-UW targeted early HCV infection without affecting viral replication, translation, and cell-to-cell transmission, and blocked viral attachment and post-attachment entry/fusion steps. Bioactivity analysis of major constituents from LS-UW through viral infectivity/entry assays revealed that gallic acid (GA) also inhibits HCV entry. Furthermore, both LS-UW and GA could suppress HCV infection of primary human hepatocytes. Due to their potency and ability to target HCV early viral entry, LS-UW and GA may be of value for further development as prospective antivirals against HCV.

  4. Limonium sinense and gallic acid suppress hepatitis C virus infection by blocking early viral entry.

    PubMed

    Hsu, Wen-Chan; Chang, Shun-Pang; Lin, Lie-Chwen; Li, Chia-Lin; Richardson, Christopher D; Lin, Chun-Ching; Lin, Liang-Tzung

    2015-06-01

    A preventive vaccine against hepatitis C virus (HCV) infection remains unavailable and newly developed drugs against viral replication are complicated by potential drug-resistance and high cost. These issues justify the need to develop alternative antiviral agents and expand the scope of strategies for the treatment of hepatitis C, such as targeting viral entry. In this study, we explore the bioactivity of Limonium sinense (L. sinense) and its purified constituents against HCV life cycle using subgenomic replicon and infectious HCV culture systems. Data indicated that the water extract from the underground part of L. sinense (LS-UW) exhibited potent inhibitory activity against HCV at non-cytotoxic concentrations. LS-UW targeted early HCV infection without affecting viral replication, translation, and cell-to-cell transmission, and blocked viral attachment and post-attachment entry/fusion steps. Bioactivity analysis of major constituents from LS-UW through viral infectivity/entry assays revealed that gallic acid (GA) also inhibits HCV entry. Furthermore, both LS-UW and GA could suppress HCV infection of primary human hepatocytes. Due to their potency and ability to target HCV early viral entry, LS-UW and GA may be of value for further development as prospective antivirals against HCV. PMID:25865056

  5. Hepatitis B viral clearance studies using duck virus model.

    PubMed

    Long, Z; Sun, C S; White, E M; Horowitz, B; Sito, A F

    1993-01-01

    We have shown data to suggest that the in vivo duck hepatitis B virus system represents an excellent animal model system for the study of hepatitis B virus. Because of the similarity of DHBV to human HBV (including comparable results in virus inactivation studies), the high level of sensitivity of the DHBV assay, and the rapidity, ease, and relative low cost of obtaining results, we propose that the in vivo DHBV titration system be used as a model for human HBV in process validation studies. Data generated in such validation studies have, in fact, been submitted by a number of blood products manufacturers to the U.S. F.D.A. in support of IND applications.

  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. Prophylactic managements of hepatitis B viral infection in liver transplantation

    PubMed Central

    Onoe, Takashi; Tahara, Hiroyuki; Tanaka, Yuka; Ohdan, Hideki

    2016-01-01

    Liver transplantation (LT) is a considerably effective treatment for patients with end-stage hepatitis B virus (HBV)-related liver disease. However, HBV infection often recurs after LT without prophylaxis. Since the 1990s, the treatment for preventing HBV reinfection after LT has greatly progressed with the introduction of hepatitis B immunoglobulin (HBIG) and nucleos(t)ide analogues (NAs), resulting in improved patient survival. The combination therapy consisting of high-dose HBIG and lamivudine is highly efficacious for preventing the recurrence of HBV infection after LT and became the standard prophylaxis for HBV recurrence. However, mainly due to the high cost of HBIG treatment, an alternative protocol for reducing the dose and duration of HBIG has been evaluated. Currently, combination therapy using low-dose HBIG and NAs is considered as the most efficacious and cost-effective prophylaxis for post-LT HBV reinfection. Recently, NA monotherapy and withdrawal of HBIG from combination therapy, along with the development of new, potent high genetic barrier NAs, have provided promising efficacy, especially for low-risk recipients. This review summarizes the prophylactic protocol and their efficacy including prophylaxis of de novo HBV infection from anti-HBc antibody-positive donors. In addition, challenging approaches such as discontinuation of all prophylaxis and active immunity through hepatitis B vaccination are discussed. PMID:26755868

  8. Sequential Bottlenecks Drive Viral Evolution in Early Acute Hepatitis C Virus Infection

    PubMed Central

    McElroy, Kerensa; Gaudieri, Silvana; Pham, Son T.; Chopra, Abha; Cameron, Barbara; Maher, Lisa; Dore, Gregory J.; White, Peter A.; Lloyd, Andrew R.

    2011-01-01

    Hepatitis C is a pandemic human RNA virus, which commonly causes chronic infection and liver disease. The characterization of viral populations that successfully initiate infection, and also those that drive progression to chronicity is instrumental for understanding pathogenesis and vaccine design. A comprehensive and longitudinal analysis of the viral population was conducted in four subjects followed from very early acute infection to resolution of disease outcome. By means of next generation sequencing (NGS) and standard cloning/Sanger sequencing, genetic diversity and viral variants were quantified over the course of the infection at frequencies as low as 0.1%. Phylogenetic analysis of reassembled viral variants revealed acute infection was dominated by two sequential bottleneck events, irrespective of subsequent chronicity or clearance. The first bottleneck was associated with transmission, with one to two viral variants successfully establishing infection. The second occurred approximately 100 days post-infection, and was characterized by a decline in viral diversity. In the two subjects who developed chronic infection, this second bottleneck was followed by the emergence of a new viral population, which evolved from the founder variants via a selective sweep with fixation in a small number of mutated sites. The diversity at sites with non-synonymous mutation was higher in predicted cytotoxic T cell epitopes, suggesting immune-driven evolution. These results provide the first detailed analysis of early within-host evolution of HCV, indicating strong selective forces limit viral evolution in the acute phase of infection. PMID:21912520

  9. [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.

  10. Chaparral-induced hepatic injury.

    PubMed

    Batchelor, W B; Heathcote, J; Wanless, I R

    1995-05-01

    Two patients with hepatic injury after ingestion of chaparral leaf are presented. The first patient, a 71-yr-old man, developed biopsy-proven hepatitis 3 months after ingesting chaparral leaf daily. His illness resolved with discontinuation of the herb and later recurred with rechallenge. The second patient is a 42-yr-old woman who developed hepatitis 2 months after chaparral leaf ingestion and recovered completely after discontinuation of the compound. Both patients have remained well with abstinence from chaparral. These reports provide evidence of the hepatotoxicity of this herb and stress the need for awareness of the potential harm from such nonprescription remedies.

  11. 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

  12. 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

  13. 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

  14. Viral hepatitis markers in liver tissue in relation to serostatus in hepatocellular carcinoma

    PubMed Central

    Hernandez, Brenda Y.; Zhu, Xuemei; Kwee, Sandi; Chan, Owen T. M.; Tsai, Naoky; Okimoto, Gordon; Horio, David; McGlynn, Katherine A.; Altekruse, Sean; Wong, Linda L.

    2013-01-01

    Background Hepatocellular carcinoma (HCC) incidence is rising in the United States. Hepatitis B virus (HBV) and hepatitis C virus (HCV) are major causes of HCC. Hepatitis infection in HCC patients is generally diagnosed by serology, which is not always consistent with the presence of HBV and HCV in the liver. The relationship of liver viral status to serostatus in hepatocarcinogenesis is not fully understood. Methods HBV and HCV were evaluated in formalin-fixed paraffin-embedded liver tissue specimens in a retrospective study of 61 U.S. HCC cases of known serologic status. HBV DNA and HCV RNA were detected by PCR, RT-PCR and pyrosequencing, and HBsAg and HBcAg were evaluated by immunohistochemistry. Results Viral markers were detected in the liver tissue of 25 of 61 (41%) HCC cases. Tissue viral and serologic status were discordant in 27 (44%) cases, including those with apparent “occult” infection. Specifically, HBV DNA was detected in tissue of 4 of 39 (10%) serum HBsAg (−) cases, including 1 anti-HCV(+) case; and HCV RNA was detected in tissue of 3 of 42 (7%) anti-HCV seronegative cases, including 2 with serologic evidence of HBV. Conclusions Viral hepatitis, including HBV-HCV coinfection, may be unrecognized in up to 17% of HCC patients when based on serology alone. Further research is needed to understand the clinical significance of viral makers in liver tissue of HCC patients in the absence of serologic indices. Impact The contribution of HBV and HCV to the rising incidence of HCC in the United States may be underestimated. PMID:23983238

  15. 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.

  16. A better regulation is required in viral hepatitis smartphone applications.

    PubMed

    Cantudo-Cuenca, Ma R; Robustillo-Cortés, Ma A; Cantudo-Cuenca, Ma D; Morillo-Verdugo, R

    2014-04-01

    Objetivo: describir las características y el contenido de aplicaciones móviles disponibles sobre hepatitis vírica, así como el nivel de participación de los profesionales médicos en su desarrollo. Métodos: Se realizó un estudio observacional descriptivo en septiembre de 2013. Buscamos en la tienda Google Play (Android) y en la tienda Apple App (iOS) aplicaciones para teléfonos inteligentes que se relacionasen específicamente con la hepatitis vírica empleando una búsqueda por palabras claves que incluía los siguientes términos: ‘hepatitis’, ‘hepatología’, “HBV” y ‘HCV’. Los datos recogidos incluían: nombre, plataforma, categoría, coste, puntuación del usuario por estrellas, número de descargas, fecha en la que el creador actualizó la aplicación y público objetivo. Analizamos el contenido de las aplicaciones y se distribuyeron en 3 categorías en función del tipo de hepatitis vírica. Realizamos un análisis en el que se examinó específicamente la autoría con el fin de evaluar la prevalencia de la participación de los profesionales sanitarios en su desarrollo. Resultados: Se incluyó un total de 33 aplicaciones (de 232 identificadas), de las cuales 10 estaban duplicadas. La mayoría de las aplicaciones se subían en la categoría médica. Tres tuvieron puntuaciones menores de 3,9 estrellas (de 5 posibles). Sólo 6 aplicaciones superaban las 1000 descargas. Un total de 12 aplicaciones estaban dirigidas a profesionales sanitarios mientras que 4 se centraban en los pacientes (7 para ambos colectivos). La participación de los profesionales sanitarios en el desarrollo de las aplicaciones fue del 56,6%. Conclusiones: Existen aplicaciones disponibles sobre hepatitis vírica tanto para profesionales sanitarios como para pacientes; sin embargo, la mayor parte de la información contenida en ellas a menudo no está validada. Deberían estar certificadas.

  17. 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

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

    PubMed

    Díez-Padrisa, Núria; Castellanos, Luis Gerardo

    2013-10-01

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

  19. Hydralazine-induced cholestatic hepatitis.

    PubMed

    Hassan, Ahad; Hammad, Raza; Cucco, Robert; Niranjan, Selva

    2009-01-01

    , mixed hepatocellular injury, acute hepatitis, cholestatic jaundice, or centrilobular necrosis. The Hydralazine-induced cholestatic liver injury seems to be fully reversible. Complete clinical and biochemical recovery occurs after discontinuation of the drug. Also, the differential diagnosis of any patient with hepatocellular injury should include medications. This will prevent unnecessary diagnostic tests.

  20. Viral hepatitis in resource-limited countries and access to antiviral therapies: current and future challenges

    PubMed Central

    Lemoine, Maud; Nayagam, Shevanthi; Thursz, Mark

    2013-01-01

    Chronic viral hepatitis is a major public health issue worldwide and mostly affects resource-limited countries. These regions combine a considerable set of barriers to containing the epidemic, including shortage of healthcare workers, poor medical infrastructures, insufficient screening and poor access to care and treatment. At a time when morbidity and mortality of chronic liver disease has been widely improved in wealthy countries by new innovative strategies and potent antiviral drugs, it is now urgent to face the challenges of better management of chronic hepatitis in resource-poor countries from the perspectives of global health and social justice. PMID:23662157

  1. 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).

  2. 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

  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: 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 ...

  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. Orlistat-induced fulminant hepatic failure.

    PubMed

    Sall, D; Wang, J; Rashkin, M; Welch, M; Droege, C; Schauer, D

    2014-12-01

    Orlistat was approved by the Food and Drug Administration in 1998 and has been shown to be superior to placebo in achieving weight loss. It is generally well tolerated. However, severe liver injury has been reported. We present a case of hepatic failure in a patient taking orlistat. A 54-year-old African-American woman with hypertension presented with hepatic failure. She had noticed increasing fatigue, jaundice and confusion. She used alcohol sparingly and denied tobacco or illicit drug use, but had been taking over-the-counter orlistat for the past two months. Physical examination revealed scleral icterus, jaundice, asterixis and slow speech. Laboratory testing showed markedly abnormal liver function tests with coagulopathy. Acute viral and autoimmune serologies were negative, as was toxicology screen. Liver biopsy showed necrotic hepatic parenchyma likely secondary to drug toxicity. Based upon her clinical presentation and time course, the pattern of liver injury seen on liver biopsy and lack of an alternative plausible explanation, her liver failure was most likely associated with orlistat use. She continued to deteriorate and ultimately underwent orthotopic liver transplantation. Fourteen cases of severe liver injury associated with orlistat use have been reported, four of which are detailed in the literature. This is the second published case of liver failure associated with over-the-counter orlistat usage. Clinicians should be aware of the growing number of cases associating liver injury and orlistat use and carefully monitor their patients on this medication for signs of hepatic dysfunction.

  9. Orlistat-induced fulminant hepatic failure.

    PubMed

    Sall, D; Wang, J; Rashkin, M; Welch, M; Droege, C; Schauer, D

    2014-12-01

    Orlistat was approved by the Food and Drug Administration in 1998 and has been shown to be superior to placebo in achieving weight loss. It is generally well tolerated. However, severe liver injury has been reported. We present a case of hepatic failure in a patient taking orlistat. A 54-year-old African-American woman with hypertension presented with hepatic failure. She had noticed increasing fatigue, jaundice and confusion. She used alcohol sparingly and denied tobacco or illicit drug use, but had been taking over-the-counter orlistat for the past two months. Physical examination revealed scleral icterus, jaundice, asterixis and slow speech. Laboratory testing showed markedly abnormal liver function tests with coagulopathy. Acute viral and autoimmune serologies were negative, as was toxicology screen. Liver biopsy showed necrotic hepatic parenchyma likely secondary to drug toxicity. Based upon her clinical presentation and time course, the pattern of liver injury seen on liver biopsy and lack of an alternative plausible explanation, her liver failure was most likely associated with orlistat use. She continued to deteriorate and ultimately underwent orthotopic liver transplantation. Fourteen cases of severe liver injury associated with orlistat use have been reported, four of which are detailed in the literature. This is the second published case of liver failure associated with over-the-counter orlistat usage. Clinicians should be aware of the growing number of cases associating liver injury and orlistat use and carefully monitor their patients on this medication for signs of hepatic dysfunction. PMID:25826164

  10. 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

  11. A probability cellular automaton model for hepatitis B viral infections.

    PubMed

    Xiao, Xuan; Shao, Shi-Huang; Chou, Kuo-Chen

    2006-04-01

    The existing models of hepatitis B virus (HBV) infection dynamics are based on the assumption that the populations of viruses and cells are uniformly mixed. However, the real virus infection system is actually not homogeneous and some spatial factors might play a nontrivial role in governing the development of HBV infection and its outcome. For instance, the localized populations of dead cells might adversely affect the spread of infection. To consider this kind of inhomogeneous feature, a simple 2D (dimensional) probability Cellular Automaton model was introduced to study the dynamic process of HBV infection. The model took into account the existence of different types of HBV infectious and non-infectious particles. The simulation results thus obtained showed that the Cellular Automaton model could successfully account for some important features of the disease, such as its wide variety in manifestation and its age dependency. Meanwhile, the effects of the model's parameters on the dynamical process of the infection were also investigated. It is anticipated that the Cellular Automaton model may be extended to serve as a useful vehicle for studying, among many other complicated dynamic biological systems, various persistent infections with replicating parasites.

  12. 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.

  13. 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.

  14. Occult hepatitis B viral infection among blood donors in South-Eastern Nigeria.

    PubMed

    Nna, Emmanuel; Mbamalu, Chinenye; Ekejindu, Ifeoma

    2014-07-01

    Hepatitis B virus infection is endemic in many parts of sub-Saharan Africa including Nigeria. Occult hepatitis B virus infection (OBI) is a challenging clinical problem characterized by the absence of Hepatitis B surface Antigen (HBsAg) and low viral DNA load. We aimed at determining the prevalence of OBI among repeat blood donors in Abakaliki, south-eastern Nigeria. Of 113 informed consented repeat blood donors enrolled into the study, 12 donors (10·6%) tested positive to both serological HBsAg screening, anti-HBc total and hepatitis B virus (HBV) DNA Nested PCR tests. One donor (0·9%) tested HBsAg positive, anti-HBC positive but Nested PCR negative. All donors were negative for HIV 1 and 2 and HCV infections. Of the 100 HbsAg negative repeat blood donors, 8·0% (eight donors) were HBV DNA positive by nested PCR method and anti-HBc total positive by ELISA. The median viral load, determined by real time PCR-Taqman chemistry, in the OBI blood samples was 51 IU/ml compared to 228 IU/ml of the HBsAg screen positive donors. The observed OBI prevalence of 8·0% corroborated with high endemicity of HBV infection in Abakaliki. We therefore recommend routine HBV DNA testing by real time PCR method on all sero-negative blood donations in Abakaliki and for a similar policy to be evaluated across the sub-Saharan Africa. PMID:24995918

  15. 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

  16. Role of T cell death in maintaining immune tolerance during persistent viral hepatitis

    PubMed Central

    Larrubia, Juan Ramón; Lokhande, Megha Uttam; García-Garzón, Silvia; Miquel, Joaquín; Subirá, Dolores; Sanz-de-Villalobos, Eduardo

    2013-01-01

    Virus-specific T cells play an important role in the resolution of hepatic infection. However, during chronic hepatitis infection these cells lack their effector functions and fail to control the virus. Hepatitis B virus and hepatitis C virus have developed several mechanisms to generate immune tolerance. One of these strategies is the depletion of virus-specific T cells by apoptosis. The immunotolerogenic liver has unique property to retain and activate naïve T cell to avoid the over reactivation of immune response against antigens which is exploited by hepatotropic viruses to persist. The deletion of the virus-specific T cells occurs by intrinsic (passive) apoptotic mechanism. The pro-apoptotic molecule Bcl-2 interacting mediator (Bim) has attracted increasing attention as a pivotal involvement in apoptosis, as a regulator of tissue homeostasis and an enhancer for the viral persistence. Here, we reviewed our current knowledge on the evidence showing critical role of Bim in viral-specific T cell death by apoptotic pathways and helps in the immune tolerance. PMID:23569333

  17. 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. PMID:27605882

  18. 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

  19. 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 ...

  20. Cost-Effectiveness of Testing Hepatitis B–Positive Pregnant Women for Hepatitis B e Antigen or Viral Load

    PubMed Central

    Fan, Lin; Owusu-Edusei, Kwame; Schillie, Sarah F.; Murphy, Trudy V.

    2015-01-01

    OBJECTIVE To estimate the cost-effectiveness of testing pregnant women with hepatitis B (hepatitis B surface antigen [HBsAg]-positive) for hepatitis B e antigen (HBeAg) or hepatitis B virus (HBV) DNA, and administering maternal antiviral prophylaxis if indicated, to decrease breakthrough perinatal HBV transmission from the U.S. health care perspective. METHODS A Markov decision model was constructed for a 2010 birth cohort of 4 million neonates to estimate the cost-effectiveness of two strategies: testing HBsAg-positive pregnant women for 1) HBeAg or 2) HBV load. Maternal antiviral prophylaxis is given from 28 weeks of gestation through 4 weeks postpartum when HBeAg is positive or HBV load is high (108 copies/mL or greater). These strategies were compared with the current recommendation. All neonates born to HBsAg-positive women received recommended active-passive immunoprophylaxis. Effects were measured in quality-adjusted life-years (QALYs) and all costs were in 2010 U.S. dollars. RESULTS The HBeAg testing strategy saved $3.3 million and 3,080 QALYs and prevented 486 chronic HBV infections compared with the current recommendation. The HBV load testing strategy cost $3 million more than current recommendation, saved 2,080 QALYs, and prevented 324 chronic infections with an incremental cost-effectiveness ratio of $1,583 per QALY saved compared with the current recommendations. The results remained robust over a wide range of assumptions. CONCLUSION Testing HBsAg-positive pregnant women for HBeAg or HBV load followed by maternal antiviral prophylaxis if HBeAg-positive or high viral load to reduce perinatal hepatitis B transmission in the United States is cost-effective. PMID:24785842

  1. Why is hepatocellular carcinoma less attributable to viral hepatitis in Yemen?

    PubMed

    Saeed, Nadeem Mohammed; Bawazir, Amen Ahmed; Al-Zuraiqi, Masuod; Al-Negri, Fadhel; Yunus, Faisel

    2012-01-01

    The hepatitis B virus (HBV) and the hepatitis C virus (HCV) are still public health problems in Yemen, with older individuals having much higher prevalence than younger generations. However, research on the prevalence of viral hepatitis in association with hepatocellular cancer (HCC) has not yet been undertaken in Yemen. The aim of this study was to determine the prevalence of HBV and HCV infection among HCC patients and to estimate the risk of these infections being associated with the development of HCC. A cross-sectional study was conducted on patients attending oncology outpatient in Sana'a, Yemen, through the period 2008-mid 2010 with confirmed diagnosis of HCC. A total of 88 cases were studied thoroughly with different investigations such as CT-scan, ultrasound, tumour marker, alpha-feto-protein and histopathological biopsy. A structured questionnaire was also applied and physical examination done to assess the general condition of the patients. Statistical package (SPSS version 16) was used for analysis of the data. The mean age of the cases was 61.2 years (± 12.6) with half over 60 years. There were fewer male patients (36%) compared to females and most (97%) only had basic /no formal education. Seventy nine (89%) were diagnosed as HCC cases with histopathological biopsy while the rest were diagnosed by ultrasound, CT scan, tumour marker, and alpha-feto-protein. Around one-third of the subjects were positive for HBsAg and HCV antibodies. Multivariate analysis showed infection with HCV and use of smoking was associated with HCC diagnosis. Although an association was observed between the occurrence of HCC and viral hepatitis (either HBV or HCV) and cigarette smoking, but the rate of viral infection was lower than what has been reported elsewhere.

  2. Novel artemisinin derivatives with potential usefulness against liver/colon cancer and viral hepatitis.

    PubMed

    Blazquez, Alba G; Fernandez-Dolon, Manuel; Sanchez-Vicente, Laura; Maestre, Alba D; Gomez-San Miguel, Ana B; Alvarez, Marcelino; Serrano, Maria A; Jansen, Herwig; Efferth, Thomas; Marin, Jose J G; Romero, Marta R

    2013-07-15

    Antitumor and antiviral properties of the antimalaria drug artemisinin from Artemisia annua have been reported. Novel artemisinin derivatives (AD1-AD8) have been synthesized and evaluated using in vitro models of liver/colon cancer and viral hepatitis B and C. Cell viability assays after treating human cell lines from hepatoblastoma (HepG2), hepatocarcinoma (SK-HEP-1), and colon adenocarcinoma (LS174T) with AD1-AD8 for a short (6h) and long (72h) period revealed that AD5 combined low acute toxicity together with high antiproliferative effect (IC50=1-5μM). Since iron-mediated activation of peroxide bond is involved in artemisinin antimalarial activity, the effect of iron(II)-glycine sulfate (ferrosanol) and iron(III)-containing protoporphyrin IX (hemin) was investigated. Ferrosanol, but not hemin, enhanced antiproliferative activity of AD5 if the cells were preloaded with AD5, but not if both compouds were added together. Five derivatives (AD1>AD2>AD7>AD3>AD8) were able to inhibit the cytopathic effect of bovine viral diarrhoea virus (BVDV), a surrogate in vitro model of hepatitis C virus (HCV), used here to evaluate the anti-Flaviviridae activity. Moreover, AD1 and AD2 inhibited the release of BVDV-RNA to the culture medium. Co-treatment with hemin or ferrosanol resulted in enhanced anti-Flaviviridae activity of AD1. In HepG2 cells permanently infected with hepatitis B virus (HBV), AD1 and AD4, at non-toxic concentrations for the host cells were able to reduce the release of HBV-DNA to the medium. In conclusion, high pharmacological interest deserving further evaluation in animal models has been identified for novel artemisinin-related drugs potentially useful for the treatment of liver cancer and viral hepatitis B and C. PMID:23685181

  3. 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

  4. [Humoral and cellular immune phenomena in an acute viral hepatitis (author's transl)].

    PubMed

    Sodomann, C P

    1975-08-01

    During the course of acute viral hepatitis A and B, several humoral and cellular immune phenomena have been observed, part of which is predominantly or even exclusively associated with hepatitis B: 1. Relative and absolute counts for T-lymphocytes depressed and for "null" -cells elevated; 2. mild elevation of serum globulin levels; 3. IgM augmentation occurring fastly, pronounced, and long lasting in typical cases; 4. IgG augmentation occurring later, less pronounced, and for a shorter period in typical cases; 5. autoantibodies to smooth muscles and mitochondria in low titers in some patients; 6. specific antibodies to "e" -antigen (early) and HB-Ag (later in the course) in part of the cases with hepatitis B; 7. immune complexes including HB-Ag, IgG and probably IgM (and IgA) as well as complement in some cases; 8. depressed levels of the fourth component of complement and - in cases complicated by "allergic" symptoms - of C3, C4, and total complement; 9. occurrence of activated lymphocytes ("virocytes") in peripheral blood; 10. enhanced spontaneous lymphocytic DNA-synthesis; 11. enchanced phytohaemagglutinin stimulation of lymphocytes; 12. mild lymphocyte proliferation to HB-Ag in part of the acute and convalescent cases of hepatitis B; 13. production of migration inhibition factor to liver specific protein (and HB-Ag) or lymphocytes in different percentages of patients with hepatitis B. Origin, diagnostic and prognostic importance, as well as pathogenetic revelance of the described immune phenomena are discussed.

  5. Increased risk of viral hepatitis in Taiwanese male conscriptees with tattoos.

    PubMed

    Shi, Ming-Der; Lee, Sheng-Yu; Lee, Yuan-Bing

    2007-05-01

    A number of previous literature reviews and research studies have found a correlation between viral hepatitis infections and tattoos. The 1897 subjects of the current study were young adult male military recruits in southern Taiwan (476 with tattoos and 1421 without tattoos) who underwent induction physical examinations before conscription. During the examination, blood samples were collected to screen for hepatitis B surface antigen, antibodies to hepatitis C virus (anti-hepatitis B HCV), syphilis, and human immunodeficiency virus. Approximately 25.1% had tattoos, 11.3% were positive for HBV surface antigen, 2.5% were positive for HCV antibody, and 2.1% were positive for HCV RNA. The odds ratios for positive hepatitis B virus and HCV infection status were 1.38 (95% confidence interval, 0.98-1.93) and 5.00 (95% confidence interval, 1.83-13.67), respectively, for those with tattoos, compared with those with no tattoos. All conscriptees were seronegative for syphilis and human immunodeficiency virus.

  6. 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

  7. 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

  8. Comparison of effects of hepatitis E or A viral superinfection in patients with chronic hepatitis B

    PubMed Central

    Ke, Weimin; Xie, Junqiang; Zhao, Zhixin; Xie, Dongying; Gao, Zhiliang

    2010-01-01

    Purpose To compare the demographics, liver function, and prognosis of Chinese patients infected with chronic hepatitis B (CHB) and superinfected with hepatitis E virus (HEV) or hepatitis A virus (HAV). Patients and methods Among 188 patients with CHB, 136 with HEV superinfection and 52 with HAV superinfection were treated at our hospital between March 1999 and October 2007 for clinical features suggestive of acute hepatitis. The patients’ age, sex, incidence of liver failure, and mortality were recorded. The tested biochemical indices and markers of liver function included serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBil), prothrombin activity (PTA), and the serum levels of HBeAg, HBeAb, and HBV DNA. Results There were significant differences between the age and sex distributions of the two groups (P < 0.05). More patients in the CHB + HEV group had complications (94.9 vs. 61.5%, P < 0.001), and hepatic failure (39.7 vs. 11.5%, P = 0.002). Additionally, the mortality among the CHB + HEV group was significantly higher (33.8 vs. 1.9%, P < 0.001). Conclusions The comparison of clinical outcomes revealed that patients with HBV + HEV had more advanced baseline liver disease and a poorer prognosis than those with HBV + HAV. Because there is no vaccine against HEV, patients with CHB should take appropriate precautions against superinfection with HEV, such as consumption of boiled water and well-cooked food, in regions where it is endemic. PMID:21063485

  9. Evaluation of viral load in saliva from patients with chronic hepatitis C infection.

    PubMed

    Xavier Santos, Renata L; de Deus, Dayse M V; de Almeida Lopes, Edmundo P; Duarte Coêlho, Maria R C; de Castro, Jurema F L

    2015-01-01

    Hepatitis C virus can be detected in blood and other bodily fluids, such as saliva. The aim of this study was to detect and quantify the HCV-RNA in saliva and plasma from patients with chronic hepatitis C infections, as well as check the level of viral load in sex groups (age, ethnicity and virus subtypes). Whole saliva and blood from 70 patients with chronic hepatitis C infections attended at the department of gastroenterology from University Hospital. The HCV-RNA load was performed by qRT-PCR using Sybr Green I master mix. HCV-RNA was detected in 80% (56/70) of patients in saliva and 92.85% (65/70) in plasma. The median of the viral load in the plasma was of 4.87 log10, and in saliva, it was 3.32log10, (p = 0.0005). Female patients and black patients exhibited a negative correlation between the HCV-RNA load in saliva vs. the HCV-RNA load in plasma (r = -0.3172, CI95% -0.6240 to -0.03736, p = 0.0491) and (r = -0.3141; IC95% -0.6069 to -0.05926; p = 0.0209), respectively. HCV-RNA was detected and quantified in saliva samples, and according to the quantification levels, saliva may be a possible transmission source of HCV, particularly in women and people of black ethnicity who develop chronic HCV infections.

  10. Dried blood spots, valid screening for viral hepatitis and human immunodeficiency virus in real-life

    PubMed Central

    Mössner, Belinda K; Staugaard, Benjamin; Jensen, Janne; Lillevang, Søren Thue; Christensen, Peer B; Holm, Dorte Kinggaard

    2016-01-01

    AIM To detect chronic hepatitis B (CHB), chronic hepatitis C (CHC) and human immunodeficiency virus (HIV) infections in dried blood spot (DBS) and compare these samples to venous blood sampling in real-life. METHODS We included prospective patients with known viral infections from drug treatment centers, a prison and outpatient clinics and included blood donors as negative controls. Five drops of finger capillary blood were spotted on filter paper, and a venous blood sample was obtained. The samples were analyzed for HBsAg, anti-HBc, anti-HBs, anti-HCV, and anti-HIV levels as well as subjected to a combined nucleic acid test (NAT) for HBV DNA, HCV RNA and HIV RNA. RESULTS Samples from 404 subjects were screened (85 CHB, 116 CHC, 114 HIV and 99 blood donors). DBS had a sensitivity of > 96% and a specificity of > 98% for the detection of all three infections. NAT testing did not improve sensitivity, but correctly classified 95% of the anti-HCV-positive patients with chronic and past infections. Anti-HBc and anti-HBS showed low sensitivity in DBS (68% and 42%). CONCLUSION DBS sampling, combined with an automated analysis system, is a feasible screening method to diagnose chronic viral hepatitis and HIV infections outside of the health care system. PMID:27672281

  11. 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. PMID:27630725

  12. Clinical course and management of acute and chronic viral hepatitis during pregnancy.

    PubMed

    Licata, A; Ingrassia, D; Serruto, A; Soresi, M; Giannitrapani, L; Montalto, G; Craxì, A; Almasio, P L

    2015-06-01

    Pregnancy is a para-physiologic condition, which usually evolves without any complications in the majority of women, even if in some circumstances moderate or severe clinical problems can also occur. Among complications occurring during the second and the third trimester very important are those considered as concurrent to pregnancy such as hyperemesis gravidarum, intrahepatic cholestasis of pregnancy, HELLP syndrome and acute fatty liver of pregnancy. The liver diseases concurrent to pregnancy typically occur at specific times during the gestation and they may lead to significant maternal and foetal morbidity and mortality. Commonly, delivery of the foetus, even preterm, usually terminates the progression of these disorders. All chronic liver diseases, such as chronic viral hepatitis, autoimmune hepatitis, Wilson's disease, and cirrhosis of different aetiologies may cause liver damage, independently from pregnancy. In this review we will also comment the clinical implications of pregnancies occurring in women who received a orthotopic liver transplantation (OLT) Therefore, the management of immunosuppressive therapy before and after the delivery in women who received liver transplant is becoming a relevant clinical issue. Finally, we will focus on acute and chronic viral hepatitis occurring during pregnancy, on management of advanced liver disease and we will review the literature on the challenging issue regarding pregnancy and OLT.

  13. 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

  14. Alverine citrate induced acute hepatitis.

    PubMed

    Arhan, Mehmet; Koklu, Seyfettin; Koksal, Aydln-S; Yolcu, Omer-F; Koruk, Senem; Koruk, Irfan; Kayacetin, Ertugrul

    2004-08-01

    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

  15. 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

  16. Viral hepatitis and tests for the Australia (hepatitis-associated) antigen and antibody*

    PubMed Central

    1970-01-01

    ”Australia” antigen has been shown to be closely associated with serum hepatitis. The presence of the antigen and its corresponding antiserum can be detected in human beings (and in certain primates) by a number of laboratory tests. This is of great potential importance to blood transfusion and similar services because detection and exclusion of blood donors carrying the antigen might significantly reduce the risk of hepatitis from transfusions and other procedures. In this paper the present state of knowledge of ”Australia” or ”hepatitis-associated” antigen is reviewed. The currently employed tests are described in detail and their use, interpretation and limitations are discussed. Though it appears from early studies that the application of routine screening tests to blood donors would only reduce the risk to recipients by less than 25%, the more sensitive tests becoming available may increase this percentage and it is recommended that where competent laboratory services are available steps should be taken to set up a scheme for testing donors—provided that the current limitations of such a scheme are clearly recognized. ImagesFIG. 2FIG. 3FIG. 1FIG. 6FIG. 7FIG. 8 PMID:4991606

  17. [Epidemiology of viral hepatitis B in the Iasi County in the interval 1990-2005].

    PubMed

    Duca, Elena; Manole, Alina; Hurmuzache, M; Ivan, A

    2006-01-01

    Viral hepatitis and especially hepatitis B (HVB) continue to represent major health problems. In Romania, the morbidity from HVB is still 3 to 5 times higher than in Western Europe and North America. In the Iasi County, the effectiveness of the preventive measures is proven by a curve of morbidity values close to or even below those recorded at national level. As a result of the preventive interventions, in the interval 1996-2005, the morbidity from HVB was lower in all age groups as compared to the interval 1990-1995. The significant decrease in morbidity following the introduction of a vaccination program and the preservation of a constantly descending trend reflect the favourable change in the epidemiological process of HVB. PMID:17438913

  18. The relationship between visfatin, liver inflammation, and acute phase reactants in chronic viral hepatitis B.

    PubMed

    Yüksel, Enver; Akbal, Erdem; Koçak, Erdem; Akyürek, Ömer; Köklü, Seyfettin; Ekiz, Fuat; Yılmaz, Barış

    2016-09-01

    Chronic viral hepatitis B (CHB) is an important cause of morbidity and mortality. Adipokine stimulation might play an important role in the pathogenesis of chronic inflammation. The aim of this study was to evaluate serum visfatin concentrations and the relationship between visfatin, fibrosis, liver inflammation, and acute phase reactants in CHB patients.The sampling universe of the study consisted of 41 CHB patients and 25 healthy controls. All patients had positive hepatitis B surface antigen (Hepatitis e antigen (HBeAg) positive n: 7, n: 34 HBeAg negative) for at least 6 months and detectable serum HBV DNA. Serum visfatin concentrations were significantly higher in the CHB patients [18.0 ± 10.9 ng dL(-1)] than in the healthy controls [9.4 ± 1.6 ng dL(-1)] [P < 0.001]. On the other hand, fibrinogen and haptoglobin concentrations were significantly lower in CHB patients. A strong negative correlation was observed between serum visfatin concentration, haptoglobin, and fibrinogen levels; however, there was no significant correlation between visfatin, glucose, alanine aminotransferase, aspartate aminotransferase, BMI, Knodell score, fibrosis score, hepatitis B virus DNA, sedimentation, and C-reactive protein. Visfatin concentrations were elevated and visfatin was negatively correlated with haptoglobin and fibrinogen levels in CHB patients.

  19. Peek-a-boo: membrane hijacking and the pathogenesis of viral hepatitis

    PubMed Central

    Feng, Zongdi; Lemon, Stanley M.

    2014-01-01

    Historically, animal viruses have been classified on the basis of the presence or absence of an envelope – an external lipid bilayer membrane typically carrying one or more viral glycoproteins. However, growing evidence indicates that some ‘non-enveloped’ viruses circulate in the blood of infected individuals enveloped in host-derived membranes that provide protection from neutralizing antibodies. In this opinion piece, we discuss this novel strategy for virus survival and consider how it contributes to the pathogenesis of acute viral hepatitis. The acquisition of an envelope by ‘non-enveloped’ viruses profoundly influences their interaction with the host at both the cellular and system level, and challenges how we think about vaccine protection against these infections. PMID:24268716

  20. 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

  1. [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

  2. Forgotten, not neglected: viral hepatitis in resource-limited settings, recall for action.

    PubMed

    Lemoine, Maud; Thursz, Mark; Njie, Ramou; Dusheiko, Geoffrey

    2014-01-01

    In 2010, the World Health Assembly adopted a resolution calling for interventions for the prevention and control of chronic viral hepatitis. These infectious diseases mostly affect resource-limited countries accounting for 80% of the world's population and facing numerous obstacles to contain the epidemic. At a time when morbidity and mortality of chronic liver disease have been considerably improved in wealthy countries by new innovative strategies and new potent antiviral drugs, it is now urgent to recall for concrete actions from stakeholders of global health policy to reduce the burden in resource-limited countries.

  3. Subviral Hepatitis B Virus Filaments, like Infectious Viral Particles, Are Released via Multivesicular Bodies

    PubMed Central

    Jiang, Bingfu; Himmelsbach, Kiyoshi; Ren, Huimei; Boller, Klaus

    2015-01-01

    ABSTRACT In addition to infectious viral particles, hepatitis B virus-replicating cells secrete large amounts of subviral particles assembled by the surface proteins, but lacking any capsid and genome. Subviral particles form spheres (22-nm particles) and filaments. Filaments contain a much larger amount of the large surface protein (LHBs) compared to spheres. Spheres are released via the constitutive secretory pathway, while viral particles are ESCRT-dependently released via multivesicular bodies (MVBs). The interaction of virions with the ESCRT machinery is mediated by α-taxilin that connects the viral surface protein LHBs with the ESCRT component tsg101. Since filaments in contrast to spheres contain a significant amount of LHBs, it is unclear whether filaments are released like spheres or like virions. To study the release of subviral particles in the absence of virion formation, a core-deficient HBV mutant was generated. Confocal microscopy, immune electron microscopy of ultrathin sections and isolation of MVBs revealed that filaments enter MVBs. Inhibition of MVB biogenesis by the small-molecule inhibitor U18666A or inhibition of ESCRT functionality by coexpression of transdominant negative mutants (Vps4A, Vps4B, and CHMP3) abolishes the release of filaments while the secretion of spheres is not affected. These data indicate that in contrast to spheres which are secreted via the secretory pathway, filaments are released via ESCRT/MVB pathway like infectious viral particles. IMPORTANCE This study revises the current model describing the release of subviral particles by showing that in contrast to spheres, which are secreted via the secretory pathway, filaments are released via the ESCRT/MVB pathway like infectious viral particles. These data significantly contribute to a better understanding of the viral morphogenesis and might be helpful for the design of novel antiviral strategies. PMID:26719264

  4. 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

  5. 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

  6. Butachlor-induced acute toxic hepatitis.

    PubMed

    Daryani, Nasser Ebrahimi; Hosseini, Parviz; Bashashati, Mohammad; Haidarali, Mona; Sayyah, Alireza

    2007-01-01

    Butachlor is a highly effective herbicidal substance widely used by farmers. We report a 60-year-old man with exfoliative dermatitis, jaundice, increase in liver enzymes and eosinophilia one day after accidental dermal exposure to butachlor toxin. The diagnostic workup showed no other cause and liver histology was consistent with substance-induced toxic hepatitis. Within two weeks of conservative therapy, his liver function tests returned to normal.

  7. 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

  8. Assessment of the Frequency of Autoantibodies in Chronic Viral Hepatitis

    PubMed Central

    Acay, Akif; Demir, Kasim; Asik, Gulsah; Tunay, Havva; Acarturk, Gursel

    2015-01-01

    Objective: To examine the occurrence frequency of auto-antibodies and autoimmune diseases in patients with chronic hepatitis B or C. Methods: A total of 67 patients diagnosed with chronic hepatitis B and 77 patients diagnosed with chronic hepatitis C infection based on HBs Ag, Anti HCV, HBe Ag, Anti HBe Ag, HBV DNA, HCV RNA, liver ultrasound, and liver biopsy results as well as 48 healthy individuals were included in this study. ANA, anti dsDNA, anti LKM, Anti-SMA, AMA, C-ANCA, P-ANCA, anti-SSA, anti-SSB, anti-Scl-70, anti Jo-1, anti-U1snRNP, anti-centromere, anti-Jo-1, anti tpo, and anti tg were studied in all individuals in each study group. Results: ANA positivity was detected in 8 (12%), 15 (19%) and 2 (4%) individuals in HBV, HCV and control groups, respectively. The difference between the groups was significant (P=0.04). Similarly, anti Tg was positive in one subject in HBV group, in 6 subjects (7%) in HCV group, and in one subject among controls, the difference being significant (P=0.04). There were no significant differences between the study groups in the frequency of other auto-antibodies. Conclusion: Similar to studies involving patients who received interferon and/or antiviral agents, an increased frequency of auto-antibodies was also detected in our patient group consisting of interferon and anti-viral naive subjects. The increase in the frequency of auto-antibodies reached statistical significance among individuals with HCV infection. Thus, pre-treatment assessment of auto-antibodies in newly diagnosed cases of chronic hepatitis B or hepatitis C infection may provide beneficial information on the future occurrence of auto-immune responses in these patients. PMID:25878633

  9. 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

  10. 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

  11. Human Choline Kinase-α Promotes Hepatitis C Virus RNA Replication through Modulation of Membranous Viral Replication Complex Formation

    PubMed Central

    Wong, Mun-Teng

    2016-01-01

    ABSTRACT Hepatitis C virus (HCV) infection reorganizes cellular membranes to create an active viral replication site named the membranous web (MW). The role that human choline kinase-α (hCKα) plays in HCV replication remains elusive. Here, we first showed that hCKα activity, not the CDP-choline pathway, promoted viral RNA replication. Confocal microscopy and subcellular fractionation of HCV-infected cells revealed that a small fraction of hCKα colocalized with the viral replication complex (RC) on the endoplasmic reticulum (ER) and that HCV infection increased hCKα localization to the ER. In the pTM-NS3-NS5B model, NS3-NS5B expression increased the localization of the wild-type, not the inactive D288A mutant, hCKα on the ER, and hCKα activity was required for effective trafficking of hCKα and NS5A to the ER. Coimmunoprecipitation showed that hCKα was recruited onto the viral RC presumably through its binding to NS5A domain 1 (D1). hCKα silencing or treatment with CK37, an hCKα activity inhibitor, abolished HCV-induced MW formation. In addition, hCKα depletion hindered NS5A localization on the ER, interfered with NS5A and NS5B colocalization, and mitigated NS5A-NS5B interactions but had no apparent effect on NS5A-NS4B and NS4B-NS5B interactions. Nevertheless, hCKα activity was not essential for the binding of NS5A to hCKα or NS5B. These findings demonstrate that hCKα forms a complex with NS5A and that hCKα activity enhances the targeting of the complex to the ER, where hCKα protein, not activity, mediates NS5A binding to NS5B, thereby promoting functional membranous viral RC assembly and viral RNA replication. IMPORTANCE HCV infection reorganizes the cellular membrane to create an active viral replication site named the membranous web (MW). Here, we report that human choline kinase-α (hCKα) acts as an essential host factor for HCV RNA replication. A fraction of hCKα colocalizes with the viral replication complex (RC) on the endoplasmic reticulum

  12. Liver stiffness is associated with monocyte activation in HIV-infected Ugandans without viral hepatitis.

    PubMed

    Redd, Andrew D; 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

    2013-07-01

    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.

  13. 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

  14. Global burden of HIV, viral hepatitis, and tuberculosis in prisoners and detainees.

    PubMed

    Dolan, Kate; Wirtz, Andrea L; Moazen, Babak; Ndeffo-Mbah, Martial; Galvani, Alison; Kinner, Stuart A; Courtney, Ryan; McKee, Martin; Amon, Joseph J; Maher, Lisa; Hellard, Margaret; Beyrer, Chris; Altice, Fredrick L

    2016-09-10

    The prison setting presents not only challenges, but also opportunities, for the prevention and treatment of HIV, viral hepatitis, and tuberculosis. We did a comprehensive literature search of data published between 2005 and 2015 to understand the global epidemiology of HIV, hepatitis C virus (HCV), hepatitis B virus (HBV), and tuberculosis in prisoners. We further modelled the contribution of imprisonment and the potential impact of prevention interventions on HIV transmission in this population. Of the estimated 10·2 million people incarcerated worldwide on any given day in 2014, we estimated that 3·8% have HIV (389 000 living with HIV), 15·1% have HCV (1 546 500), 4·8% have chronic HBV (491 500), and 2·8% have active tuberculosis (286 000). The few studies on incidence suggest that intraprison transmission is generally low, except for large-scale outbreaks. Our model indicates that decreasing the incarceration rate in people who inject drugs and providing opioid agonist therapy could reduce the burden of HIV in this population. The prevalence of HIV, HCV, HBV, and tuberculosis is higher in prison populations than in the general population, mainly because of the criminalisation of drug use and the detention of people who use drugs. The most effective way of controlling these infections in prisoners and the broader community is to reduce the incarceration of people who inject drugs. PMID:27427453

  15. [Natural history of viral hepatitis A in Chilean adults: clinical and laboratory aspects].

    PubMed

    Ibarra, H; Riedemann, S; Froesner, G; Reinhardt, G; Gómez, J C; Cornejo, A; Toledo, C; Soto, N; Ruiz, M

    1993-01-01

    In many countries, Hepatitis is mainly due to virus. A. When improving life condition in a given population, initially there is a tendency to increase the number of cases in adults. We report clinical and laboratory findings in 87 adults with acute viral Hepatitis A in Chile. The rate man/woman was 1.55/1. Mean age: 23.8 years. Clinical forms: icteric classical (77.01%), cholestatic (10.34%), anicteric (8.05%), biphasic (2.30%) and fulminant (2.30%). From 87 patients in consult 1, 64 were controlled at day 15 (consult 2) and 35 one year later (consult 3). Laboratory (means): ALT (UI/L): 856.8, 111.6 and 20.8 in consult 1, 2 and 3 respectively. Correlation between values of ALT and AST (p < 0.0001). Mean total bilirubin (mg%): 6.6, 2.5 and 0.8 respectively. The evolution of Hepatitis A was favorable with a rapid decrease of clinical signs and normalization of laboratory values within the 3 first weeks of disease.

  16. Viral hepatitis screening guideline before biological drug use in rheumatic patients

    PubMed Central

    Karadağ, Ömer; Kaşifoğlu, Timuçin; Özer, Birol; Kaymakoğlu, Sabahattin; Kuş, Yeşim; İnanç, Murat; Keser, Gökhan; Kiraz, Sedat

    2016-01-01

    Biological drugs (tumor necrosis factor inhibitors, rituximab, tocilizumab, abatacept, and tofacitinib) are important treatment alternatives in rheumatology, particularly for resistant patients. However, they may cause hepatitis B virus (HBV) and hepatitis C virus (HCV) reactivation; for instance, HBV reactivation may occur in a patient who is an inactive hepatitis B surface antigen (HBsAg) carrier or who has resolved HBV infection. Therefore, the screening of patients before biological treatment and the application of a prophylactic treatment, particularly with respect to latent HBV infections, are recommended when necessary. This guideline covers pre-treatment screening and follow-up recommendations, if required, with respect to viral hepatitides in rheumatology patients who are planned to be given biological drugs. Although this guideline is prepared for biological disease-modifying antirheumatic drugs (DMARDs), it is recommended to be used also for target-oriented DMARDS and medium–high dose corticosteroids (>7.5 mg prednisolone/day equivalent). It should be considered that the reactivation risk is higher when more than one immunosuppressive drug is used.

  17. [Viral hepatitis infection and response to the hepatitis B vaccine in hemodialyzed patients].

    PubMed

    Curciarello, J O; Corallini, O; Adrover, R E; Chiera, A O; Giammona, A M; Barbero, R; Apraiz, M; Belloni, P O; Neumann, M; Jmelnitzky, A C

    1994-01-01

    Data from 219 hemodyalized patients receiving attention in our Hospital and other private centers in our city are shown. Mean age was 46.9 (range: 14-85), and 132 were male; mean time under dialysis was 20 months, and subjects received an average of 5 transfusions per patient year. Serological reactivity to HBs Ag, Anti HBs and IgG anti HBc by ELISA were investigated in all of them, and anti HCV by second generation enzimo-immunoassay (EIA II) in 73 HBe Ag/anti HBe system were determined in HBs Ag positive patients and those reactive to anti HCV (EIA II) were confirmed by LIA (immunoblotting of synthetic peptides LIA-TEK Organos Teknica). Recombinant anti HBV vaccine 40 mcg at 0-1 and six month were received by 81 cases without HBV markers in their sera and a protective response was considered when anti HBs titration of 10 mU/ml or more were obtained two months later. Prevalence for anti HBc and anti HBs were 38.8% respectively and that for HBs Ag was 21% with 78% of them reactive for HBs Ag. True reactivity for anti HCV (confirmed by LIA) was present in 35.6%, but it was 9.7% in our Hospital and 54.8% in private units (p < 0.0002). Anti HBs titration was done in 69/81 patients who received anti HBV vaccine, and a protective response in 49% were obtained; the other 12 patients underwent acute hepatitis B during the vaccination period.(ABSTRACT TRUNCATED AT 250 WORDS)

  18. Risk and burden associated with the acquisition of viral hepatitis A and B in the corporate traveler.

    PubMed

    Bunn, William B

    2008-08-01

    As the number of international business travelers continues to grow, so does the list of destinations, many of which are endemic for both hepatitis A and B. Generally, travelers are unaware of the risks of acquiring viral hepatitis when traveling; many are unsure of modes of transmission and do not seek pretravel advice or do not follow the recommendations of travel health professionals. Infected employees can result in increased health care costs and reduced productivity in the workplace. Safe and efficacious monovalent vaccines and a combined hepatitis A and B vaccine are available. Successful corporate health and immunization programs can prevent hepatitis A and B when employees are abroad on business. This article examines the distribution, risks, costs, burden, and prevention of hepatitis A and B in the international business traveler.

  19. Vinyl chloride-induced hepatic angiosarcoma.

    PubMed

    Falk, H

    1987-01-01

    In early 1974, an alert plant physician reported the occurrence of several cases of the otherwise rare hepatic angiosarcoma (HAS) at a single polyvinyl chloride (PVC) production facility in Louisville, Kentucky (U.S.A.). Upon further investigation, the relative risk for HAS at this plant appeared to be approximately 5,000, strongly indicating a causal relationship with some factor at the plant. Epidemiologic studies at this and other PVC polymerization plants identified vinyl chloride monomer (VCM) as the causative agent. Experimental studies reported in early 1974 confirmed VCM as a hepatic carcinogen capable of producing HAS and other tumors. Follow-up epidemiologic studies revealed that: 1) HAS is the end stage of a progressive liver disease consisting of hepatocytic and sinusoidal cell hyperplasia, sinusoidal dilatation, and hepatic fibrosis; 2) over 100 cases of VCM-induced HAS have occurred worldwide; and 3) an increased risk of lung cancer has been reported in some cohort studies of PVC polymerization workers, although this outcome may be related to PVC dust or factors other than VCM. A national study of HAS in the United States identified 3 other causes of HAS: Thorotrast, inorganic arsenic, and androgenic-anabolic steroids. Of 168 cases found to occur during 1964 through 1974, 42 cases (25%) were associated with the 4 known etiologic agents, while 126 cases (75%) were of unknown etiology.

  20. Label Free Inhibitor Screening of Hepatitis C Virus (HCV) NS5B Viral Protein Using RNA Oligonucleotide

    PubMed Central

    Roh, Changhyun; Kim, Sang Eun; Jo, Sung-Kee

    2011-01-01

    Globally, over 170 million people (ca. 3% of the World’s population) are infected with the hepatitis C virus (HCV), which can cause serious liver diseases such as chronic hepatitis, evolving into subsequent health problems. Driven by the need to detect the presence of HCV, as an essential factor in diagnostic medicine, the monitoring of viral protein has been of great interest in developing simple and reliable HCV detection methods. Despite considerable advances in viral protein detection as an HCV disease marker, the current enzyme linked immunosorbent assay (ELISA) based detection methods using antibody treatment have several drawbacks. To overcome this bottleneck, an RNA aptamer become to be emerged as an antibody substitute in the application of biosensor for detection of viral protein. In this study, we demonstrated a streptavidin-biotin conjugation method, namely, the RNA aptamer sensor system that can quantify viral protein with detection level of 700 pg mL−1 using a biotinylated RNA oligonucleotide on an Octet optical biosensor. Also, we showed this method can be used to screen inhibitors of viral protein rapidly and simply on a biotinylated RNA oligonucleotide biosensor. Among the inhibitors screened, (−)-Epigallocatechin gallate showed high binding inhibition effect on HCV NS5B viral protein. The proposed method can be considered a real-time monitoring method for inhibitor screening of HCV viral protein and is expected to be applicable to other types of diseases. PMID:22163979

  1. 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

  2. Curcumin-induced recovery from hepatic injury involves induction of apoptosis of activated hepatic stellate cells.

    PubMed

    Priya, S; Sudhakaran, P R

    2008-10-01

    Hepatic stellate cells (HSCs) undergo activation and transdifferentiation to myofibroblast like cells in liver injury, leading to liver fibrosis. During recovery from injury, activated HSCs may either revert back to quiescent state or undergo apoptosis or both. In the present study, we have examined whether recovery from hepatic injury involves apoptosis of activated HSCs and tested whether curcumin (the yellow pigment from Curcuma longa Linn.) promotes recovery from hepatic injury by inducing apoptosis of these cells. Hepatic injury was induced by CCl4 and apoptosis was studied in HSCs isolated from liver by MTT assay, DNA fragmentation, and DAPI and annexin staining. Hepatic recovery was assessed by measuring hepatic marker activities, such as serum GOT, GPT and protein. Hepatic recovery occurred within 4 weeks after inducing injury in untreated control, whereas curcumin treatment caused hepatic recovery within 2 weeks, as evidenced by the reduction of hepatic marker activities to near normal levels. HSCs isolated from liver of animals treated with curcumin showed maximum apoptotic marker activities in 2nd week, whereas in HSCs from untreated control recovering from injury, maximum apoptosis was observed in 4th week. Induction of apoptosis in vivo during hepatic recovery was also suggested by increase in caspase-3 activity. Treatment of isolated HSCs in culture with curcumin caused apoptosis during later stages confirming that curcumin induced apoptosis of activated HSCs and not in unactivated quiescent HSCs. These results suggested that hepatoprotective effect of curcumin causing recovery from injury involved apoptosis of activated HSCs. PMID:19069843

  3. [Immunoallergic reaction with hepatitis induced by minocycline].

    PubMed

    Pavese, P; Sarrot-Reynauld, F; Bonadona, A; Massot, C

    1998-12-01

    We report the case of a 19-year old black West Indian woman who had been treated for acne for two years with oral minocycline (50 mg per day) and topical of benzoyle peroxide (5%). She was admitted for fatigue, arthralgia, myalgia and widespread pruritus. We observed several skin lesions of hyperpigmentation, biological signs of hepatitis, and significant levels of antinuclear, anti-mitochondrial and anti-smooth muscle antibodies. Minocycline was immediately stopped. Two months later, all of the biological abnormalities had disappeared but the skin lesions seemed to be irreversible. Minocycline is largely used for the treatment of acne and may induce severe immuno-allergic reactions. Several cases of induced lupus, autoimmune hepatitis, eosinophilic pneumonia, hypersensitivity syndrome, serum-sickness-like illness and Sweet's syndrome have already been described. These side effects are rare but may be life-threatening. So, minocycline should be used as a second-line treatment for acne and should be avoided in black people whom seem to be at risk of such reactions. If, despite those precautions, minocycline-induced immuno-allergic reactions occur, the treatment should be immediately stopped and never prescribed again.

  4. 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

  5. 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.

  6. Cholesterol-Enriched Domain Formation Induced by Viral-Encoded, Membrane-Active Amphipathic Peptide.

    PubMed

    Hanson, Joshua M; Gettel, Douglas L; Tabaei, Seyed R; Jackman, Joshua; Kim, Min Chul; Sasaki, Darryl Y; Groves, Jay T; Liedberg, Bo; Cho, Nam-Joon; Parikh, Atul N

    2016-01-01

    The α-helical (AH) domain of the hepatitis C virus nonstructural protein NS5A, anchored at the cytoplasmic leaflet of the endoplasmic reticulum, plays a role in viral replication. However, the peptides derived from this domain also exhibit remarkably broad-spectrum virocidal activity, raising questions about their modes of membrane association. Here, using giant lipid vesicles, we show that the AH peptide discriminates between membrane compositions. In cholesterol-containing membranes, peptide binding induces microdomain formation. By contrast, cholesterol-depleted membranes undergo global softening at elevated peptide concentrations. Furthermore, in mixed populations, the presence of ∼100 nm vesicles of viral dimensions suppresses these peptide-induced perturbations in giant unilamellar vesicles, suggesting size-dependent membrane association. These synergistic composition- and size-dependent interactions explain, in part, how the AH domain might on the one hand segregate molecules needed for viral assembly and on the other hand furnish peptides that exhibit broad-spectrum virocidal activity.

  7. WHO guidance on the prevention of viral hepatitis B and C among people who inject drugs.

    PubMed

    Walsh, Nick; Verster, Annette; Rodolph, Michelle; Akl, Elie A

    2014-05-01

    Viral hepatitis B and C (HBV, HCV) disproportionately affect people who inject drugs (PWID) across the world. To date there has been little global action focusing on prevention, care and treatment of HBV and HCV among PWID. Here we report on the development process and discuss the implications of evidence informed WHO Guidelines for the Prevention of HBV and HCV in PWID. The World Health Organization (WHO) convened a Guideline Development Panel to develop recommendations on the prevention of HBV and HCV among PWID. The process followed the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. It included the development of PICO (Population, Interventions, Comparator, Outcomes) questions and conducting systematic reviews. Quality of evidence was classified into 4 levels: high, moderate, low, and very low. In the process of moving from evidence to recommendations, the following were considered: quality of evidence, balance of benefits and harms, community values and preferences and resource use. The WHO recommendations include the following for working with PWID: offer the rapid HBV vaccination regimen; offer incentives to increase uptake and completion of the HBV vaccine schedule; needle and syringe programs should also provide low dead-space syringes for distribution; and offer peer interventions to reduce the incidence of viral hepatitis. This guideline complements other WHO documents regarding PWID, including HIV prevention initiatives such as needle and syringe programs and opioid substitution therapy. This guidance offers a first step in the prevention of HBV and HCV among PWID. However, the lack of high quality evidence in this area necessitates further research and resources for implementation.

  8. 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

  9. 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

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

    PubMed

    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

  11. 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

  12. Delayed Viral Clearance after 6-Week Treatment with Peginterferon Plus Ribavirin in a Patient with Chronic Hepatitis C Virus Genotype 1b

    PubMed Central

    Sato, Akira; Ishii, Toshiya; Adachi, Kayo; Takahashi, Hideaki; Sano, Fumiaki; Matsumoto, Nobuyuki

    2016-01-01

    Following interferon-based therapy for chronic hepatitis C, the negativity of hepatitis C virus RNA is essential to achieve viral clearance at the end of treatment. We report a case of clearance of chronic hepatitis C virus infection following early discontinuation (at 6 weeks) of peginterferon plus ribavirin therapy, without negativity for hepatitis C virus RNA during the treatment period. The patient was a 76-year-old Japanese male infected with hepatitis C virus genotype 1b and TT of IL28B rs8099917. Hepatitis C virus RNA remained positive at persistently low levels for more than 2 months after the cessation of therapy and became negative at 7 months after the discontinuation of therapy. Spontaneous clearance of hepatitis C virus RNA can occur following antiviral failure in patients with persistently low viral loads, and virological follow-up is therefore necessary in chronic hepatitis C virus infection, even after antiviral failure. PMID:27721727

  13. [Prevalence of viral hepatitis B markers in the region of Tataouine (southern Tunisia)].

    PubMed

    Gorgi, Y; Ayed, K; Jenhani, F; Pichoud, C; Trepo, C

    1989-01-01

    Tataouine (South Tunisia) has been subject to several viral hepatitis epidemics during these last years. Prospective study has been conducted to define the prevalence of HVB infection. It has examined 511 cases, the age of whom was between 1 month and 70 years, reported in groups through the OMS recommendations, taking into account the number of inhabitants in each area. The global prevalence was 6.2% for HBs Ag and 18.5% for HBs antibody. These results were not different from the frequencies observed within the Tunisian population in general. The analysis of this study according to these groups, shows that in three areas (Ras El Oued, Bir 30, Dhibet) 60 to 80% of cases have at least one of HVB marquers, whereas the prevalence in other areas (Rogba) was very weak. The geographic repartition of HVB infection corresponds approximatively to areas that have been the most infected by the last hepatitis epidemics. A second study has completed and confirmed the results of the first one, taking into consideration a more important number of cases from areas of strong and weak endemicity. 596 sera have been examined in Rogba which counts 2000 inhabitants and is a weak endemicity area. 528 sera have been examined in the three areas of strong endemicity: 199 in Bir 30, 201 in Dhibet and 128 in Ras El Oued, which count around 2000 inhabitants, too. The percentage of cases presenting at least one of HVB serological marquers reaches 84 in Dhibet, 70 in Ras El Oued, 50 in Bir 30 and 24 in Rogba. This HBs Ag frequency is 3.8% in Rogba, 15% in Bir 30, 24% in Ras El Oued and 26.3% in Dhibet. It seems that the HVB is the virus of hepatitis epidemics observed in Tataouine at least in the three strong endemicity areas. PMID:2488540

  14. 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

  15. Imino sugars inhibit the formation and secretion of bovine viral diarrhea virus, a pestivirus model of hepatitis C virus: Implications for the development of broad spectrum anti-hepatitis virus agents

    PubMed Central

    Zitzmann, Nicole; Mehta, Anand S.; Carrouée, Sandra; Butters, Terry D.; Platt, Frances M.; McCauley, John; Blumberg, Baruch S.; Dwek, Raymond A.; Block, Timothy M.

    1999-01-01

    One function of N-linked glycans is to assist in the folding of glycoproteins by mediating interactions of the lectin-like chaperone proteins calnexin and calreticulin with nascent glycoproteins. These interactions can be prevented by inhibitors of the α-glucosidases, such as N-butyl-deoxynojirimycin (NB-DNJ) and N-nonyl-DNJ (NN-DNJ), and this causes some proteins to be misfolded and retained within the endoplasmic reticulum (ER). We have shown previously that the NN-DNJ-induced misfolding of one of the hepatitis B virus (HBV) envelope glycoproteins prevents the formation and secretion of virus in vitro and that this inhibitor alters glycosylation and reduces the viral levels in an animal model of chronic HBV infection. This led us to investigate the effect of glucosidase inhibitors on another ER-budding virus, bovine viral diarrhea virus, a tissue culture surrogate of human hepatitis C virus (HCV). Here we show that in MDBK cells α-glucosidase inhibitors prevented the formation and secretion of infectious bovine viral diarrhea virus. Data also are presented showing that NN-DNJ, compared with NB-DNJ, exhibits a prolonged retention in liver in vivo. Because viral secretion is selectively hypersensitive to glucosidase inhibition relative to the secretion of cellular proteins, the possibility that glucosidase inhibitors could be used as broad-based antiviral hepatitis agents is discussed. A single drug against HBV, HCV, and, possibly, HDV, which together chronically infect more than 400 million people worldwide, would be of great therapeutic value. PMID:10518544

  16. The Role of Consensus Interferon in the Current Treatment of Chronic Hepatitis C Viral Infection

    PubMed Central

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

    2008-01-01

    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

  17. 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

  18. 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

  19. 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

  20. 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.

  1. RNA-HCV viral load in serum, peripheral blood mononuclear cells and liver in children with chronic hepatitis C.

    PubMed

    Kowala-Piaskowska, Arleta; Mozer-Lisewska, Iwona; Januszkiewicz-Lewandowska, Danuta; Michalak, Michał; Zeromski, Jan; Madaliński, Kazimierz; Słuzewski, Wojciech

    2012-01-01

    The liver is the major site of hepatitis C virus (HCV) infection and replication. However, HCV may infect and replicate in extrahepatic sites as well. Several investigators have demonstrated that peripheral blood mononuclear cells (PBMCs) are the major extrahepatic milieu of infection and viral replication. The aim of the study was to investigate the correlation between RNA-HCV level in serum. PBMCs and liver in children with chronic viral hepatitis C (CHC). The impact of RNA-HCV level on the sustained virological response (SVR) after therapy was also determined. Study was carried out in the group of 10 children with CHC, age 8 to 17 years. Antiviral therapy was implemented in all patients with pegylated interferon alpha (Peg-lFNalpha) 2a or 2b and ribavirin during 48 weeks. The following tests were performed prior the therapy: basic laboratory parameters, histology of liver biopsy, RNA-HCV viral load in serum, PBMCs and in liver. The behavior of HCV-RNA viral load in serum, PBMCs and liver in children with CHC did not present strict mutual relations. However, the positive correlation between serum and PBMCs viral load (r = 0.47) and negative correlation between PBMCs and liver viral load (r = -0.47) was demonstrated. Although no statistically significant results were found, some trends of relationship in viral load between various body compartments were present. Given the aforementioned results, it is clear that more data are needed, mostly more numerous groups of patients, especially those whose influence of RNA-HCV viral load had a major impact on the antiviral treatment.

  2. 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 ...

  3. [Periarteritis nodosa induced by hepatitis B virus].

    PubMed

    Mouthon, L

    1999-03-01

    Polyarteritis nodosa (PAN) induced by the hepatitis B virus (HBV) is a rare condition whose incidence has decreased markedly over the last decade. HBV-related PAN is an acute condition that occurs within six months of HVB infection and shares many features with classic PAN. Some manifestations, however, are more common in HBV-related PAN, such as abdominal signs, renal failure, malignant arterial hypertension, and orchitis. Tests for antineutrophil cytoplasmic antibody are usually negative. Management combines a short course of steroid therapy, plasma exchanges, and antiviral drugs. The ten-year disease-free survival rate is 80%. Over half the patients develop antibody to Hbe and 24.4% to HBs. PMID:10214615

  4. 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

  5. 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.

  6. Presence of lichen planus during a course of interferon alpha-2a therapy for a viral chronic C hepatitis.

    PubMed

    Guijarro Guijarro, B; López Sánchez, A F; Hernández Vallejo, G

    2001-01-01

    We present the case of a 66-year-old woman with a diagnosis of chronic active viral C hepatitis, for whom a course of interferon alpha-2A was prescribed at a dose of 4.5 MU per day for a 2 month period, followed by the same dose on alternate days for 4 months. After completion of a month of therapy, the patient presented with painful oral lesions that made normal oral food intake impossible. These lesions persisted, in spite of withdrawal of interferon therapy. Intraoral examination revealed erosive intraoral lesions in both yugal mucosae, the upper vestibular gum, the floor of the mouth, the ventral region of the tongue, and the lower lip. A diagnosis of erosive lichen planus induced by interferon therapy was established. The prescribed treatment was 0.1% triamcinolone acetonide in orabase applied 3 times a day for 4 weeks. Following the therapeutical course, the erosive lesions disappeared, and the symptoms stopped, although the reticular lesions remained visible.

  7. Development of viral disinfectant assays for duck hepatitis B virus using cell culture/PCR.

    PubMed

    Wang, Chi-Young J; Giambrone, Joseph J; Smith, Bruce F

    2002-10-01

    Human hepatitis B virus (HBV) is a worldwide public health problem with chronic carriers at risk for developing cirrhosis and hepatocellular carcinoma. Accidental nosocomial infections from inadequately disinfected equipment or exposure to blood and body fluids from patients are major routes. To solve such problems, disinfectants to inactivate HBV must be validated. Duck hepatitis B virus (DHBV) is accepted as a surrogate for HBV, due to their similar sensitivities to disinfectants and its safety. Ducklings are used for disinfectant efficacy assays; however, the same virus titer is obtained using duck embryonic hepatocytes. Viral titration in disinfectant efficacy assay is conducted using Southern hybridization of infected duck serum. However, this test requires radioisotopes. Therefore, disinfectant assessment protocols were developed using duck embryonic hepatocytes with polymerase chain reaction (PCR) or nested PCR. The ease of handling, lowered cost and enhanced sensitivity make PCR desirable. Chicken embryonic hepatocytes were applied to DHBV disinfectant efficacy assay. Results were consistent and could be used under certain conditions. The virucidal activities of two quaternary ammonium chloride disinfectants, n-alkyl dimethyl benzyl ammonium chloride and alkyl dimethyl benzyl ammonium chloride (10C-12C) were compared and effective concentrations were 1200 and 1800 ppm, respectively. Efficacies of these disinfectants were validated using real-time quantitative PCR. Results confirmed that the efficacy of n-alkyl dimethyl benzyl ammonium chloride was higher than alkyl dimethyl benzyl ammonium chloride (10C-12C). This assay was useful for rapid discrimination of killing potentials of disinfectants. In conclusion, these assays can be applied to other viruses that are unable to cause CPE in cell cultures and broadened the utility of DHBV as animal model for HBV.

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

    PubMed Central

    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

  9. Potential transmission of viral hepatitis through use of stored blood vessels as conduits in organ transplantation--Pennsylvania, 2009.

    PubMed

    2011-02-18

    Solid organ transplantation sometimes requires the use of blood vessels from a deceased donor as conduits to connect transplanted organ vessels to recipient vessels. Vessels not immediately used are sometimes stored for later use, including vessels collected from hepatitis B virus (HBV) and hepatitis C virus (HCV) seropositive donors; HBV and HCV seropositive vessels can be stored for use in seropositive recipients. In May 2009, HCV was transmitted when a transplant facility inadvertently used a blood vessel conduit from an HCV-seropositive donor in a seronegative recipient. In November 2009, a second transplant facility, the University of Pittsburgh Medical Center (UPMC), identified two cases of potential hepatitis virus transmission from vessel conduits. In December 2009, CDC was asked to assist the local health department in conducting an investigation at UPMC. This report summarizes the results of that investigation, which determined that, although neither recipient of the vessel conduits at UPMC contracted hepatitis, these represented "near miss" incidents in which transmission could have occurred. The storage of vessels from hepatitis-seropositive donors at UPMC and its affiliated Department of Veterans Affairs (VA) hospital was not necessary; vessels from seropositive donors were infrequently used because adequate supplies of vessels from seronegative donors were available. UPMC's prohibition of the storage of vessels from hepatitis-seropositive donors has removed a documented risk factor for viral transmission while not substantially affecting the transplant centers' vessel conduit supply. Evaluation of available national data supports this prohibition. Therefore, CDC recommends that transplant centers discontinue the practice of storing vessel from donors with markers for viral hepatitis, including HBV surface antigen (HBsAg), HCV antibody (anti-HCV), and HBV or HCV detectable by nucleic acid tests.

  10. 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 ...

  11. 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 ...

  12. 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

  13. Data harmonization process for creating the National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention Atlas.

    PubMed

    Elmore, Kim; Nelson, Rob; Gant, Zanetta; Jeffries, Carla; Broeker, Lance; Mirabito, Massimo; Roberts, Henry

    2014-01-01

    In 2009, the CDC National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention (NCHHSTP) initiated the online, interactive NCHHSTP Atlas. The goal of the Atlas is to strengthen the capacity to monitor the diseases overseen by NCHHSTP and to illustrate demographic, spatial, and temporal variation in disease patterns. The Atlas includes HIV, AIDS, viral hepatitis, sexually transmitted disease, and tuberculosis surveillance data, and aims to provide a single point of access to meet the analytical and data dissemination needs of NCHHSTP. To accomplish this goal, an NCHHSTP-wide Data Harmonization Workgroup reviewed surveillance data collected by each division to harmonize the data across diseases, allowing one to query data and generate comparable maps and tables via the same user interface. Although we were not able to harmonize all data elements, data standardization is necessary and work continues toward that goal.

  14. Data Harmonization Process for Creating the National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention Atlas

    PubMed Central

    Nelson, Rob; Gant, Zanetta; Jeffries, Carla; Broeker, Lance; Mirabito, Massimo; Roberts, Henry

    2014-01-01

    In 2009, the CDC National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention (NCHHSTP) initiated the online, interactive NCHHSTP Atlas. The goal of the Atlas is to strengthen the capacity to monitor the diseases overseen by NCHHSTP and to illustrate demographic, spatial, and temporal variation in disease patterns. The Atlas includes HIV, AIDS, viral hepatitis, sexually transmitted disease, and tuberculosis surveillance data, and aims to provide a single point of access to meet the analytical and data dissemination needs of NCHHSTP. To accomplish this goal, an NCHHSTP-wide Data Harmonization Workgroup reviewed surveillance data collected by each division to harmonize the data across diseases, allowing one to query data and generate comparable maps and tables via the same user interface. Although we were not able to harmonize all data elements, data standardization is necessary and work continues toward that goal. PMID:24385651

  15. Intrinsic Viral Factors Are the Dominant Determinants of the Hepatitis C Virus Response to Interferon Alpha Treatment in Chimeric Mice

    PubMed Central

    Chen, Ran; Kobewka, Michelle; Addison, William; Lachance, Gerald; Tyrrell, D. Lorne

    2016-01-01

    Background Hepatitis C virus infection is a global health problem. New direct-acting antiviral agents have been recently approved. However, due to their high cost and some genotypes remaining difficult to treat, interferon-based therapy with pegylated interferon and ribavirin likely may remain a component of hepatitis C virus treatment for some patients. Unfortunately, pegylated interferon / ribavirin treatment achieved favorable outcomes in less than 50% of patients. Factors determining the outcome to pegylated interferon / ribavirin include both host and viral factors. It has been a major challenge to separate the host and viral factors in most in vivo systems. Aims & Methods We used two hepatitis C virus strains from patients with different interferon-sensitivities and three hepatocyte donors, each with distinct interleukin 28B and interferon lambda 4 single nucleotide polymorphisms to investigate the contributions of viral and host factors to the response of hepatitis C virus to interferon treatment in chimeric mice. Results and Conclusions We found that viral factors were the dominant factors in determining the interferon treatment outcomes in chimeric mice. Host factors, such as pre-treatment liver interferon-stimulated gene expression and single nucleotide polymorphisms near interleukin 28B and interferon lambda 4 coding regions, were less important determinants of the response to interferon in the chimeric mice than they were in patients. Our results also suggest that a complete immune system as seen in patients may be required for host factors such as single nucleotide polymorphisms near interleukin 28B / interferon lambda 4 and pre-treatment liver interferon-stimulated gene upregulation to have an effect on the interferon response. PMID:26765841

  16. [Markers of viral hepatitis B and D and levels of alanine aminotransferase in military blood donors: a profile of 30,000 blood donations in 1989].

    PubMed

    Boulesteix, G; Bourin, P; Fabre, G; Blanchard de Vaucouleurs, A; Molinié, C; Denee, J M; Buisson, Y; Schill, H; Joussemet, M

    1990-01-01

    Serologic data for B and D viral hepatitis are studied on 30,000 military blood donors. Because of legal norms of blood products for transfusion 761 donations (2.53% have been destroyed). Exclusion criteria for viral B hepatitis and ALT are independent. In this study the prevalency of HBV infections is significantly lower than for other blood centers: probably in account of the young age of military blood donors.

  17. 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

  18. 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

  19. 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

  20. Polymorphism in the Human Major Histocompatibility Complex and Early Viral Decline during Treatment of Chronic Hepatitis C ▿ ‡

    PubMed Central

    Yee, Leland J.; Im, KyungAh; Wahed, Abdus S.; Bugawan, Teodorica; Li, Jia; Rhodes, Shannon L.; Erlich, Henry; Rosen, Hugo R.; Liang, T. Jake; Yang, Huiying

    2009-01-01

    The dynamics of the viral decline immediately after the start of therapy for chronic hepatitis C virus (HCV) infection may have prognostic potential for ultimate sustained virologic response. Considerable interindividual variability in the decline has been reported, including differences by race. The human major histocompatability complex (MHC) genes encode the human leukocyte antigens, which are important in the immune response to viral infections. We examined whether carriage of specific human MHC alleles are associated with the rate of the early viral decline. Longitudinal viral level data (baseline and days 1, 2, 7, 14, and 28 of treatment), medium resolution MHC genotyping, and random coefficients models were used to examine associations between MHC class I and class II allele carriage and the dynamics of the viral decline in 180 African-Americans (AAs) and 194 Caucasian Americans (CAs) with genotype-1 HCV infection over the first 28 days of treatment with peginterferon α2a plus ribavirin. Baseline viral levels were similar by race, irrespective of allele carriage. However, the rate of change in the viral decline was associated with both allele and race. Among the four subgroups defined by race and specific allele, the fastest rates of decline were observed (in terms of estimated mean viral declines log10 IU/ml during the first four weeks) in CA noncarriers for A*03 (2.75; P = 0.018), in CA carriers for Cw*03 (2.99; P = 0.046), and in CA noncarriers for DQA1*04 (2.66; P = 0.018) or DQB1*0402 (2.65; P = 0.018). MHC alleles are associated with the viral decline during the first 28 days of peginterferon therapy. PMID:18852273

  1. Effects of hemoperfusion adsorption and/or plasma exchange in treatment of severe viral hepatitis: A comparative study

    PubMed Central

    He, Nian-Hai; Wang, Ying-Jie; Wang, Ze-Wen; Liu, Jun; Li, Jia-Jia; Liu, Guo-Dong; Wang, Yu-Ming

    2004-01-01

    AIM: Non-bioartificial liver has been applied to clinic for quite a long time, but the reported efficacy has been very different. The aim of this study was to compare the efficacy and safety of hemoperfusion adsorption, plasma exchange and plasma exchange plus hemoperfusion adsorption in treatment of severe viral hepatitis. METHODS: Seventy-five patients with severe viral hepatitis were treated with hemoperfusion adsorption therapy (24 cases), plasma exchange therapy (17 cases) and plasma exchange plus hemoperfusion adsorption therapy (34 cases). The data of liver function, renal function, blood routine test, prothrombin time (PT) and prothrombin activity (PTa) pre-and post-therapy were analyzed. RESULTS: Clinical symptoms of patients improved after treatment. The levels of aminotransferase, total bilirubin, direct bilirubin decreased significantly after 3 therapies (P < 0.05 or P < 0.01). PT, the level of total serum protein decreased significantly and PTa increased significantly after plasma exchange therapy and plasma exchange plus hemoperfusion adsorption therapy (P < 0.05 or P < 0.01). The side effects were few and mild in all patients. CONCLUSION: Three therapies were effective in the treatment of severe viral hepatitis. Plasma exchange therapy and plasma exchange plus hemoperfusion adsorption therapy are better than hemoperfusion adsorption therapy. PMID:15069730

  2. 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

  3. Flexible and rapid construction of viral chimeras applied to hepatitis C virus.

    PubMed

    McClure, C Patrick; Urbanowicz, Richard A; King, Barnabas J; Cano-Crespo, Sara; Tarr, Alexander W; Ball, Jonathan K

    2016-09-01

    A novel and broadly applicable strategy combining site-directed mutagenesis and DNA assembly for constructing seamless viral chimeras is described using hepatitis C virus (HCV) as an exemplar. Full-length HCV genomic cloning cassettes, which contained flexibly situated restriction endonuclease sites, were prepared via a single, site-directed mutagenesis reaction and digested to receive PCR-amplified virus envelope genes by In-Fusion cloning. Using this method, we were able to construct gene-shuttle cassettes for generation of cell culture-infectious JFH-1-based chimeras containing genotype 1-3 E1E2 genes. Importantly, using this method we also show that E1E2 clones that were not able to support cell entry in the HCV pseudoparticle assay did confer entry when shuttled into the chimeric cell culture chimera system. This method can be easily applied to other genes of study and other viruses and, as such, will greatly simplify reverse genetics studies of variable viruses.

  4. Evaluation on anti-hepatitis viral activity of Vitis vinifer L.

    PubMed

    Liu, Tao; Zhao, Jun; Li, Haibo; Ma, Long

    2010-10-22

    Suosuo grape (Vitis vinifer L) is traditionally used as a therapeutic agent for measles and hepatitis by the ethnic Uighurs. This work aimed to investigate the anti-HBV effect of total triterpene (VTT), total flavonoids (VTF) and total polysaccharides (VTP) from Suosuo grape, and their synergistic effects were also tested. The viral antigens of cellular secretion, HBsAg and HBeAg, were determined by enzyme linked immunosorbent assay (ELISA).The quantity of HBV-DNA released in the supernatant was assayed by real-time PCR. It was found that it effectively suppressed the secretion of HBsAg and HBeAg from HepG2.2.15 cells in a dose-dependent manner, as well as the HBV DNA. The results of orthogonal design experiment showed that the combination of VTT 20 μg/mL, VTF 50 μg/mL and VTP 50 μg/mL had the best optimistic inhibitory effects on HBeAg secretion.

  5. Flexible and rapid construction of viral chimeras applied to hepatitis C virus.

    PubMed

    McClure, C Patrick; Urbanowicz, Richard A; King, Barnabas J; Cano-Crespo, Sara; Tarr, Alexander W; Ball, Jonathan K

    2016-09-01

    A novel and broadly applicable strategy combining site-directed mutagenesis and DNA assembly for constructing seamless viral chimeras is described using hepatitis C virus (HCV) as an exemplar. Full-length HCV genomic cloning cassettes, which contained flexibly situated restriction endonuclease sites, were prepared via a single, site-directed mutagenesis reaction and digested to receive PCR-amplified virus envelope genes by In-Fusion cloning. Using this method, we were able to construct gene-shuttle cassettes for generation of cell culture-infectious JFH-1-based chimeras containing genotype 1-3 E1E2 genes. Importantly, using this method we also show that E1E2 clones that were not able to support cell entry in the HCV pseudoparticle assay did confer entry when shuttled into the chimeric cell culture chimera system. This method can be easily applied to other genes of study and other viruses and, as such, will greatly simplify reverse genetics studies of variable viruses. PMID:27329374

  6. Electrostatics of capsid-induced viral RNA organization

    NASA Astrophysics Data System (ADS)

    Forrey, Christopher; Muthukumar, M.

    2009-09-01

    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

  7. 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

  8. Anti-viral therapy to reduce recurrence and improve survival in hepatitis B virus-related hepatocellular carcinoma

    PubMed Central

    Ishikawa, Toru

    2013-01-01

    Hepatocellular carcinoma (HCC) is the most common malignancy and the third leading cause of cancer death worldwide. Chronic infection with hepatitis B virus (HBV) and hepatitis C virus accounts for approximately 75%-80% of HCC cases worldwide. In particular, chronic HBV infection is a predominant risk factor for HCC in Asia and Africa. Hepatic resection and radiofrequency ablation are increasingly used for the curative treatment of HCC, and good local control can be achieved. However, the high rate of recurrence is a major obstacle to improving prognosis. A high viral load of HBV DNA is the most important correctable risk factor for recurrence. Furthermore, interferon and/or nucleotide analogues may decrease HBV DNA. Therefore, these drugs may decrease recurrence. In this article, treatment strategies for HBV-related HCC are described in order to reduce recurrence and improve survival. PMID:24379608

  9. [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

  10. [Inter-observes agreement of Ishak and Metavir scores in histological evaluation of chronic viral hepatitis B and C].

    PubMed

    Rammeh, Soumaya; Khadra, Hajer Ben; Znaidi, Nadia Sabbegh; Romdhane, Neila Attia; Najjar, Taoufik; Bouzaidi, Slim; Zermani, Rachida

    2014-01-01

    Many classification systems are currently used for histological evaluation of the severity of chronic viral hepatitis, including the Ishak and Metavir scores, but there is not a consensus classification. The objective of this work was to study the intra and inter-observers agreement of these two scores in the histopathological analysis of liver biopsies in patients with chronic viral hepatitis B or C. Fifty nine patients were included in the study, 26 had chronic hepatitis C and 33 had chronic hepatitis B. To investigate the inter-observers agreement, the liver biopsies were analyzed separately by two pathologists without prior consensus reading. The two pathologists conducted then a consensual reading before reviewing all cases independently. Cohen's kappa coefficient was calculated and in case of asymmetry Spearman's rho coefficient. Before the consensus reading, the agreement was moderate for the analysis of histological activity with both scores (Metavir: kappa=0.41, Ishak: rho=0.58). For the analysis of fibrosis, the agreement was good with both scores (Metavir: kappa=0.61, Ishak: rho=0.86). The consensus reading has improved the reproducibility of the activity that has become good with both scores (Metavir: kappa=0.77, Ishak: rho=0.76). For fibrosis improvement was observed with the Ishak score which agreement became excellent (kappa=0.81). In conclusion, we recommend in routine practice, a combined score: Metavir for activity and Ishak for fibrosis and to make a double reading for each biopsy.

  11. Severe viral hepatitis in a patient with chronic lymphocytic leukemia (CLL) complicated with autoimmune hemolytic anemia (AIHA), treated with steroids.

    PubMed

    Orvain, Corentin; Ducancelle, Alexandra; Eymerit-Morin, Caroline; Rousselet, Marie-Christine; Oberti, Frederic; Hunault-Berger, Mathilde; Tanguy-Schmidt, Aline

    2015-01-01

    Infectious complications are a major cause of morbidity and mortality in patients with chronic lymphocytic leukemia (CLL) due to impaired immunity secondary to the disease itself and to the immunosuppressive therapies administered to these patients. We report a 78-year-old woman with CLL who was treated with steroids for autoimmune hemolytic anemia (AIHA). A few weeks later, she was admitted for severe acute hepatitis with disseminated intravascular coagulation (DIC). Despite the symptomatic treatment of DIC, standard reanimation and probabilistic antibiotics, the patient died within 24h with severe hepatic failure. Autopsy was in favor of a disseminated viral infection with esophageal, hepatic and pulmonary cytopathologic lesions with acidophilic intranuclear inclusions suggestive of herpes virus, even though HSV 1 and 2, CMV and HHV6 PCRs were negative. This case of severe viral hepatitis with esophagitis occurring three weeks after the introduction of high-dose steroid treatment for AIHA in a CLL patient calls for anti-herpetic prophylaxis in such patients, immunodepressed by their diseases and the treatment they receive.

  12. 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

  13. 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

  14. IL-33 treatment attenuated diet-induced hepatic steatosis but aggravated hepatic fibrosis

    PubMed Central

    Gao, Yinjie; Liu, Yuan; Yang, Mei; Guo, Xiaodong; Zhang, Min; Li, Hanwei; Li, Jin; Zhao, Jingmin

    2016-01-01

    The aim of our work was to investigate the role of interleukin-33 (IL-33) and its receptor ST2 in the progression of diet-induced nonalcoholic steatohepatitis (NASH) in mice, and the characteristic expression in livers of patients with NASH. Mice were fed with high-fat diet (HFD) or methionine-choline 4-deficient diet (MCD) and injected intraperitoneally with IL-33. Both mRNA and protein expression levels of IL-33 and ST2 were up-regulated in the livers of mice fed with HFD or MCD. Treatment with IL-33 attenuated diet-induced hepatic steatosis and reduced activities of ALT in serum, as well as ameliorated HFD-induced systemic insulin resistance and glucose intolerance, while aggravated hepatic fibrosis in diet-induced NASH. Furthermore, treatment with IL-33 can also promote Th2 response and M2 macrophage activation and beneficial modulation on expression profiles of fatty acid metabolism genes in livers. ST2 deficiency did not affect hepatic steatosis and fibrosis when fed with controlling diet. IL-33 did not affect diet-induced hepatic steatosis and fibrosis in ST2 knockout mice. Meanwhile, in the livers of patients with NASH, IL-33 was mainly located in hepatic sinusoid, endothelial cells, and hepatic stellate cells. The mRNA expression level of IL-33 and ST2 was elevated with the progression of NASH. In conclusion, treatment with IL-33 attenuated diet-induced hepatic steatosis, but aggravated hepatic fibrosis, in a ST2-dependent manner. PMID:27172901

  15. Temperature-Induced Viral Resistance in Emiliania huxleyi (Prymnesiophyceae)

    PubMed Central

    Kendrick, B. Jacob; DiTullio, Giacomo R.; Cyronak, Tyler J.; Fulton, James M.; Van Mooy, Benjamin A. S.; Bidle, Kay D.

    2014-01-01

    Annual Emiliania huxleyi blooms (along with other coccolithophorid species) play important roles in the global carbon and sulfur cycles. E. huxleyi blooms are routinely terminated by large, host-specific dsDNA viruses, (Emiliania huxleyi Viruses; EhVs), making these host-virus interactions a driving force behind their potential impact on global biogeochemical cycles. Given projected increases in sea surface temperature due to climate change, it is imperative to understand the effects of temperature on E. huxleyi’s susceptibility to viral infection and its production of climatically active dimethylated sulfur species (DSS). Here we demonstrate that a 3°C increase in temperature induces EhV-resistant phenotypes in three E. huxleyi strains and that successful virus infection impacts DSS pool sizes. We also examined cellular polar lipids, given their documented roles in regulating host-virus interactions in this system, and propose that alterations to membrane-bound surface receptors are responsible for the observed temperature-induced resistance. Our findings have potential implications for global biogeochemical cycles in a warming climate and for deciphering the particular mechanism(s) by which some E. huxleyi strains exhibit viral resistance. PMID:25405345

  16. Temperature-induced viral resistance in Emiliania huxleyi (Prymnesiophyceae).

    PubMed

    Kendrick, B Jacob; DiTullio, Giacomo R; Cyronak, Tyler J; Fulton, James M; Van Mooy, Benjamin A S; Bidle, Kay D

    2014-01-01

    Annual Emiliania huxleyi blooms (along with other coccolithophorid species) play important roles in the global carbon and sulfur cycles. E. huxleyi blooms are routinely terminated by large, host-specific dsDNA viruses, (Emiliania huxleyi Viruses; EhVs), making these host-virus interactions a driving force behind their potential impact on global biogeochemical cycles. Given projected increases in sea surface temperature due to climate change, it is imperative to understand the effects of temperature on E. huxleyi's susceptibility to viral infection and its production of climatically active dimethylated sulfur species (DSS). Here we demonstrate that a 3°C increase in temperature induces EhV-resistant phenotypes in three E. huxleyi strains and that successful virus infection impacts DSS pool sizes. We also examined cellular polar lipids, given their documented roles in regulating host-virus interactions in this system, and propose that alterations to membrane-bound surface receptors are responsible for the observed temperature-induced resistance. Our findings have potential implications for global biogeochemical cycles in a warming climate and for deciphering the particular mechanism(s) by which some E. huxleyi strains exhibit viral resistance.

  17. Evasion of superinfection exclusion and elimination of primary viral RNA by an adapted strain of hepatitis C virus.

    PubMed

    Webster, Brian; Ott, Melanie; Greene, Warner C

    2013-12-01

    Cells that are productively infected by hepatitis C virus (HCV) are refractory to a second infection by HCV via a block in viral replication known as superinfection exclusion. The block occurs at a postentry step and likely involves translation or replication of the secondary viral RNA, but the mechanism is largely unknown. To characterize HCV superinfection exclusion, we selected for an HCV variant that could overcome the block. We produced a high-titer HC-J6/JFH1 (Jc1) viral genome with a fluorescent reporter inserted between NS5A and NS5B and used it to infect Huh7.5 cells containing a Jc1 replicon. With multiple passages of these infected cells, we isolated an HCV variant that can superinfect cells at high levels. Notably, the superinfectious virus rapidly cleared the primary replicon from superinfected cells. Viral competition experiments, using a novel strategy of sequence-barcoding viral strains, as well as superinfection of replicon cells demonstrated that mutations in E1, p7, NS5A, and the poly(U/UC) tract of the 3' untranslated region were important for superinfection. Furthermore, these mutations dramatically increased the infectivity of the virus in naive cells. Interestingly, viruses with a shorter poly(U/UC) and an NS5A domain II mutation were most effective in overcoming the postentry block. Neither of these changes affected viral RNA translation, indicating that the major barrier to postentry exclusion occurs at viral RNA replication. The evolution of the ability to superinfect after less than a month in culture and the concomitant exclusion of the primary replicon suggest that superinfection exclusion dramatically affects viral fitness and dynamics in vivo.

  18. Hepatic immunophenotyping for streptozotocin-induced hyperglycemia in mice

    PubMed Central

    Lee, Young-Sun; Eun, Hyuk Soo; Kim, So Yeon; Jeong, Jong-Min; Seo, Wonhyo; Byun, Jin-Seok; Jeong, Won-Il; Yi, Hyon-Seung

    2016-01-01

    Emerging evidence revealed that diabetes induces abnormal immune responses that result in serious complications in organs. However, the effect of hyperglycemia on hepatic immunity remains obscure. We evaluated the population and function of hepatic immune cells in streptozotocin (STZ)-induced hyperglycemic mice. CC chemokine receptor 2 (CCR2)-knockout mice and mice with a depletion of regulatory T cells (DEREG) were used to investigate the migration and role of regulatory T cells (Tregs) in hyperglycemic mice. The inflammatory cytokines and hepatic transaminase levels were significantly increased in the hyperglycemic mice. The population and number of infiltrating monocytes, granulocytes, and Tregs were enhanced in the livers of the hyperglycemic mice. Hepatic monocytes other than macrophages showed the increased expression of inflammatory cytokines and chemokines in the hyperglycemic mice. The CCR2 knockout and DEREG chimeric mice exhibited increased populations of activated T cells and neutrophils compared to the WT chimeric mice, which promoted hepatic inflammation in the hyperglycemic mice. The migration of CCR2 knockout Tregs into the liver was significantly reduced compared to the WT Tregs. We demonstrated that hyperglycemia contributes to increase in infiltrating monocytes and Tregs, which are associated with hepatic immune dysfunction in mice. CCR2-mediated migration of Tregs regulates hyperglycemia-induced hepatic inflammation. PMID:27464894

  19. Modeling chronic hepatitis B or C virus infection during antiviral therapy using an analogy to enzyme kinetics: long-term viral dynamics without rebound and oscillation.

    PubMed

    Takayanagi, Toshiaki

    2013-12-01

    The basic model for chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection during therapy enables us to analyze short-term viral kinetics. However, the model is not useful for analyzing long-term viral kinetics. Here, I suggest a new model that was obtained by introducing Michaelis-Menten kinetics into the basic model. The new model can exhibit long-term viral kinetics without rebound and oscillation, unlike the basic model. The value of the parameter K in the new model is analogous to the Michaelis constant Km and is predicted to be approximately less than 10(10)/ml.

  20. A Rapid Method for Viral Particle Detection in Viral-Induced Gastroenteritis: A TEM Study

    NASA Astrophysics Data System (ADS)

    Hicks, M. John; Barrish, James P.; Hayes, Elizabeth S.; Leer, Laurie C.; Estes, Mary K.; Cubitt, W. D.

    1995-10-01

    Infectious gastroenteritis is a common cause of hospitalization in the pediatric population. The most frequent cause of gastroenteritis is viral in origin. The purpose of this study was to compare a rapid modified negative-staining TEM method with the conventional pseudoreplica technique in detection of viral particles in fecal samples from children with viral gastroenteritis. The modified negative-staining method resulted in a significantly higher (2.5 ± 0.5, p = 0.02) viral rating score than that for the conventional pseudoreplica technique (1.7 ± 0.4). In addition, the preparation time for the negative-staining method was approximately one fifth that for the conventional pseudoreplica technique. Rapid diagnosis of viral gastroenteritis may be made by ultrastructural detection of viral particles in fecal samples using the negative staining technique.

  1. Dynamic metabolic change is indicative of inflammation-induced transformation of hepatic cells.

    PubMed

    Peng, Bo; Liu, Fan; Han, Rong; Luo, George; Cathopoulis, Terry; Lu, Kun; Li, Xiao; Yang, Ling; Liu, Guo-Yan; Cai, Jian-Chun; Shi, Song-Lin

    2015-09-01

    The observation that prolonged inflammation plays a causative role in cancer development has been well documented. However, an incremental process that leads from healthy to malignant phenotypes has not yet been described. Experimentally induced hepatocellular carcinoma is considered one of the representative laboratory models for studying this process. Hepatic exposure to viral infection or toxic reagents leads to chronic inflammation and gradual transformation into hepatocellular carcinoma. Here we present metabolomic profiles of hepatic cells at different stages during inflammation-induced cellular transformation by N-nitrosodiethylamine. Using gas chromatography-mass spectrometry, we quantitatively assessed the changes in cellular metabolites during the transformation process in hepatitis and liver cirrhosis. Further pathway analysis of the differentially expressed metabolites showed that carbohydrate metabolism and lipid metabolism were greatly altered in hepatitis and liver cirrhosis, respectively. Additionally, the enhanced inflammation in cirrhosis was associated with a shift from carbohydrate metabolism to lipid and amino acid metabolism. Among the differentially expressed metabolites found in diseased mouse livers, d-glucose and d-mannitol showed the most significant changes, highlighting them as potential early-diagnostic biomarkers of hepatocellular carcinoma development. Taken together, these investigations into the dynamic metabolic changes that occur during the precancerous stages of hepatocellular carcinoma add to and refine understanding of how chronic inflammation ultimately leads to cancer. Furthermore, the findings set the stage for identifying metabolites that may serve as early-diagnostic indicators of these unfolding events.

  2. Knowledge of viral hepatitis among Puerto Rican adults: implications for prevention.

    PubMed

    Soto-Salgado, Marievelisse; Suárez, Erick; Ortiz, Ana P; Adrovet, Sandra; Marrero, Edmir; Meléndez, Marytere; Colón, Héctor M; Albizu, Carmen; Del C Santos, María; Torres, Esther; Pérez, Cynthia M

    2011-08-01

    Although primary prevention of HAV and HBV can be achieved through vaccination, the burden of HCV can only be reduced through behavioral interventions to reduce its risk factors. This study evaluated knowledge regarding transmission, clinical manifestations and prevention of viral hepatitis in Puerto Rico. We assessed the level of knowledge about HAV (six questions), HBV (12 questions) and HCV (eight questions) among non-institutionalized Puerto Rican adults aged 21-64 years. Demographic characteristics and self-reported knowledge of these infections were determined through a face-to-face interview. A mean knowledge score was computed by summing correct responses to each scale. Mean knowledge scores according to demographics were compared using ANOVA or the Kruskal-Wallis test. Mean knowledge scores for HAV, HBV and HCV infections were 2.6 ± 1.5, 6.1 ± 2.4, and 3.6 ± 1.1, respectively. For HAV and HBV infections, the mean knowledge score significantly (P < 0.05) increased with age, level of counseling received and number of sources of information. However, for HCV infection the mean knowledge score significantly increased with decreasing age, increased educational level and increased annual family income. Contrary to HBV, a higher HAV and HCV knowledge score was observed among individuals with history of vaccination for HAV and HBV, seropositive status for HAV and HCV, and history of drug use. A sizeable proportion of adults in this study demonstrated an inadequate level of knowledge, especially about transmission routes. Health education must be focused on transmission and prevention methods, including the availability of a vaccine for HAV and HBV, especially among those with chronic liver disease. PMID:21125319

  3. Ebselen Inhibits Hepatitis C Virus NS3 Helicase Binding to Nucleic Acid and Prevents Viral Replication

    PubMed Central

    2015-01-01

    The hepatitis C virus (HCV) nonstructural protein 3 (NS3) is both a protease, which cleaves viral and host proteins, and a helicase that separates nucleic acid strands, using ATP hydrolysis to fuel the reaction. Many antiviral drugs, and compounds in clinical trials, target the NS3 protease, but few helicase inhibitors that function as antivirals have been reported. This study focuses on the analysis of the mechanism by which ebselen (2-phenyl-1,2-benzisoselenazol-3-one), a compound previously shown to be a HCV antiviral agent, inhibits the NS3 helicase. Ebselen inhibited the abilities of NS3 to unwind nucleic acids, to bind nucleic acids, and to hydrolyze ATP, and about 1 μM ebselen was sufficient to inhibit each of these activities by 50%. However, ebselen had no effect on the activity of the NS3 protease, even at 100 times higher ebselen concentrations. At concentrations below 10 μM, the ability of ebselen to inhibit HCV helicase was reversible, but prolonged incubation of HCV helicase with higher ebselen concentrations led to irreversible inhibition and the formation of covalent adducts between ebselen and all 14 cysteines present in HCV helicase. Ebselen analogues with sulfur replacing the selenium were just as potent HCV helicase inhibitors as ebselen, but the length of the linker between the phenyl and benzisoselenazol rings was critical. Modifications of the phenyl ring also affected compound potency over 30-fold, and ebselen was a far more potent helicase inhibitor than other, structurally unrelated, thiol-modifying agents. Ebselen analogues were also more effective antiviral agents, and they were less toxic to hepatocytes than ebselen. Although the above structure–activity relationship studies suggest that ebselen targets a specific site on NS3, we were unable to confirm binding to either the NS3 ATP binding site or nucleic acid binding cleft by examining the effects of ebselen on NS3 proteins lacking key cysteines. PMID:25126694

  4. Hepatitis B viral replication influences the expression of natural killer cell ligands

    PubMed Central

    Koumbi, Lemonica; Pollicino, Teresa; Raimondo, Giovanni; Kumar, Naveenta; Karayiannis, Peter; Khakoo, Salim I.

    2016-01-01

    Background Hepatitis B virus (HBV) is accounting for over one million deaths annually due to immune-mediated chronic liver damage. Natural killer (NK) cells are abundant in the liver and contribute in HBV persistence. NK cytotoxic effects are controlled by signals from activating and inhibitory receptors. HBV may circumvent host antiviral immunity via the regulation of NK receptors and their ligands. We investigated the effect of viral replication and HBeAg mutations on NK mediators expression in the livers of chronic HBV (CHB) patients and in cell cultures. Methods HBV monomers bearing hotspot mutations in the basal core promoter and precore region were transfected into HepG2 cells using a plasmid-free assay. Serum viremia and liver HBV RNA were measured in 19 CHB patients. The expression of HBV RNA and of NKG2D ligands, B7H6, DNAX accessory molecule-1, lectin-like transcript 1 (LLT1), LFA-1 and TRAIL was measured in the livers of CHB patients and transfected cells. Results In general, high HBV replication in CHB patients and cell lines upregulated the mRNA of all NK cell ligands and particularly the inhibitory NK cell ligand, LLT1. The exception was the NKG2D ligand, MICA, that was significantly decreased in patients with high serum viremia and intrahepatic HBV RNA levels. Conclusions HBV replication has differential effects on NK cell ligands suggesting a potential escape mechanisms through up-regulation of LLT1 and down-regulation of MICA. A general trend towards upregulating NK cell ligands can be counteracted by decreasing MICA and hence weakening NK surveillance. PMID:27366037

  5. ADVANCED LIVER INJURY IN PATIENTS WITH CHRONIC HEPATITIS B AND VIRAL LOAD BELOW 2,000 IU/mL

    PubMed Central

    de OLIVEIRA, Valter Oberdan Borges; OLIVEIRA, Juliana Passos Rocha; de FRANÇA, Eloy Vianey Carvalho; BRITO, Hugo Leite de Farias; NASCIMENTO, Tereza Virgínia; FRANÇA, Alex

    2016-01-01

    SUMMARY Introduction: According to the guidelines, the viral load of 2,000 IU/mL is considered the level to differentiate between inactive carriers and HBeAg(-) chronic hepatitis B patients. Even so, liver damage may be present in patients with lower viral load levels, mainly related to regional variations. This study aims to verify the presence of liver injury in patients with viral load below 2,000 IU/mL. Methods: Patients presenting HBsAg(+) for more than six months, Anti-HBe(+)/HBeAg(-), viral load below 2,000 IU/mL and serum ALT levels less than twice the upper limit of normality underwent liver biopsy. Clinical and laboratory characteristics were evaluated in relation to the degree of histologic alteration. Liver injury was considered advanced when F ≥ 2 and/or A ≥ 2 by the METAVIR classification. Results: 11/27 (40.7%) patients had advanced liver injury, with a mean viral load of 701.0 (± 653.7) IU/mL versus 482.8 (± 580.0) IU/mL in patients with mild injury. The comparison between the mean values of the two groups did not find a statistical difference (p = 0.37). The average of serum aminotransferases was not able to differentiate light liver injury from advanced injury. Conclusions: In this study, one evaluation of viral load did not exclude the presence of advanced liver damage. Pathologic assessment is an important tool to diagnose advanced liver damage and should be performed in patients with a low viral load to indicate early antiviral treatment. PMID:27680170

  6. Expression of inducible nitric oxide synthase in experimental viral myocarditis.

    PubMed

    Glück, B; Merkle, I; Dornberger, G; Stelzner, A

    2000-05-01

    Nitric oxide (NO) is an important bioactive molecule with regulatory, cytotoxic or cytoprotective properties. In virus-induced myocarditis, NO mediates host defense mechanisms against the infection or causes cardiac dysfunctions. NO is synthesized from L-arginine by the enzyme nitric oxide synthase (NOS). The expression of the inducible form of the nitric oxide synthase (iNOS) is regulated by cytokines, involved in the complex myocardial immune response to enterovirus infections. The present study was undertaken to characterize the role of iNOS and NO in the murine model of viral myocarditis induced by coxsackievirus B3 (CVB3). In response to CVB3 infection we investigated the time course of iNOS induction in correlation with cytokine mRNA expression (TNF-alpha, IL-1 alpha, IFN-gamma, TGF-beta) in the heart of NMRI mice by RT-PCR. Positive PCR signals for viral RNA were found in the acute and chronic stage of disease by seminested PCR, indicating the persistence of viral genome. We found distinct expression of iNOS at all time points (1, 2, 3, 4, 7, 14, 28, 56, 98 days post infection [p.i.]). Higher iNOS mRNA levels were identified between days 4 until 28 p.i. in comparison to day 56 and 98 p.i. using densitometric values. The mRNA of the inflammatory cytokines TNF-alpha, IL-1 alpha, IFN-gamma appeared at days 1, 4, and 7 p.i., peaked at day 7 p.i. and persisted until day 98 p.i. Similar like the iNOS mRNA pattern was the expression profile of TGF-beta. Using in situ hybridization and immunohistochemistry iNOS was localized in infiltrates, vascular endothelial cells, smooth muscle cells, myocytes and throughout the interstitial spaces between myocardial fibers in the heart sections of NMRI mice. Increased levels of NO were measured as total nitrate/nitrite concentration in the sera of mice from day 7 until day 28 p.i.

  7. Quantum dot-induced viral capsid assembling in dissociation buffer.

    PubMed

    Gao, Ding; Zhang, Zhi-Ping; Li, Feng; Men, Dong; Deng, Jiao-Yu; Wei, Hong-Ping; Zhang, Xian-En; Cui, Zong-Qiang

    2013-01-01

    Viruses encapsulating inorganic nanoparticles are a novel type of nanostructure with applications in biomedicine and biosensors. However, the encapsulation and assembly mechanisms of these hybridized virus-based nanoparticles (VNPs) are still unknown. In this article, it was found that quantum dots (QDs) can induce simian virus 40 (SV40) capsid assembly in dissociation buffer, where viral capsids should be disassembled. The analysis of the transmission electron microscope, dynamic light scattering, sucrose density gradient centrifugation, and cryo-electron microscopy single particle reconstruction experimental results showed that the SV40 major capsid protein 1 (VP1) can be assembled into ≈25 nm capsids in the dissociation buffer when QDs are present and that the QDs are encapsulated in the SV40 capsids. Moreover, it was determined that there is a strong affinity between QDs and the SV40 VP1 proteins (KD=2.19E-10 M), which should play an important role in QD encapsulation in the SV40 viral capsids. This study provides a new understanding of the assembly mechanism of SV40 virus-based nanoparticles with QDs, which may help in the design and construction of other similar virus-based nanoparticles.

  8. Quantum dot-induced viral capsid assembling in dissociation buffer

    PubMed Central

    Gao, Ding; Zhang, Zhi-Ping; Li, Feng; Men, Dong; Deng, Jiao-Yu; Wei, Hong-Ping; Zhang, Xian-En; Cui, Zong-Qiang

    2013-01-01

    Viruses encapsulating inorganic nanoparticles are a novel type of nanostructure with applications in biomedicine and biosensors. However, the encapsulation and assembly mechanisms of these hybridized virus-based nanoparticles (VNPs) are still unknown. In this article, it was found that quantum dots (QDs) can induce simian virus 40 (SV40) capsid assembly in dissociation buffer, where viral capsids should be disassembled. The analysis of the transmission electron microscope, dynamic light scattering, sucrose density gradient centrifugation, and cryo-electron microscopy single particle reconstruction experimental results showed that the SV40 major capsid protein 1 (VP1) can be assembled into ≈25 nm capsids in the dissociation buffer when QDs are present and that the QDs are encapsulated in the SV40 capsids. Moreover, it was determined that there is a strong affinity between QDs and the SV40 VP1 proteins (KD = 2.19E-10 M), which should play an important role in QD encapsulation in the SV40 viral capsids. This study provides a new understanding of the assembly mechanism of SV40 virus-based nanoparticles with QDs, which may help in the design and construction of other similar virus-based nanoparticles. PMID:23776332

  9. Generation of mouse induced pluripotent stem cells without viral vectors.

    PubMed

    Okita, Keisuke; Nakagawa, Masato; Hyenjong, Hong; Ichisaka, Tomoko; Yamanaka, Shinya

    2008-11-01

    Induced pluripotent stem (iPS) cells have been generated from mouse and human somatic cells by introducing Oct3/4 and Sox2 with either Klf4 and c-Myc or Nanog and Lin28 using retroviruses or lentiviruses. Patient-specific iPS cells could be useful in drug discovery and regenerative medicine. However, viral integration into the host genome increases the risk of tumorigenicity. Here, we report the generation of mouse iPS cells without viral vectors. Repeated transfection of two expression plasmids, one containing the complementary DNAs (cDNAs) of Oct3/4, Sox2, and Klf4 and the other containing the c-Myc cDNA, into mouse embryonic fibroblasts resulted in iPS cells without evidence of plasmid integration, which produced teratomas when transplanted into mice and contributed to adult chimeras. The production of virus-free iPS cells, albeit from embryonic fibroblasts, addresses a critical safety concern for potential use of iPS cells in regenerative medicine.

  10. Bovine viral diarrhea virus infection induces autophagy in MDBK cells.

    PubMed

    Fu, Qiang; Shi, Huijun; Ren, Yan; Guo, Fei; Ni, Wei; Qiao, Jun; Wang, Pengyan; Zhang, Hui; Chen, Chuangfu

    2014-07-01

    Bovine viral diarrhea virus (BVDV) is an enveloped, positive-sense, single-stranded RNA virus that belongs to the genus Pestivirus (Flaviviridae). The signaling pathways and levels of signaling molecules are altered in Madin-Darby Bovine Kidney (MDBK) cells infected with BVDV. Autophagy is a conservative biological degradation pathway that mainly eliminates and degrades damaged or superfluous organelles and macromolecular complexes for intracellular recycling in eukaryotic cells. Autophagy can also be induced as an effective response to maintain cellular homeostasis in response to different stresses, such as nutrient or growth factor deprivation, hypoxia, reactive oxygen species exposure and pathogen infection. However, the effects of BVDV infection on autophagy in MDBK cells remain unclear. Therefore, we performed an analysis of autophagic activity after BVDV NADL infection using real-time PCR, electron microscopy, laser confocal microscopy, and Western blotting analysis. The results demonstrated that BVDV NADL infection increased autophagic activity and significantly elevated the expression levels of the autophagy-related genes Beclin1 and ATG14 in MDBK cells. However, the knockdown of Beclin1 and ATG14 by RNA interference (RNAi) did not affect BVDV NADL infection-related autophagic activity. These findings provided a novel perspective to elaborate the effects of viral infection on the host cells.

  11. [Experience of biologically active supplements to food containing indoles and isothiocyanates in patients with chronic viral hepatitis].

    PubMed

    Gichev, Iu P; Gichev, Iu Iu; Grek, O R; Tolokonskaia, N P; Chernousova, N Ia; Tomilenko, T G; Makkosland, K

    2002-01-01

    We have studied the effect of dietary supplement "ExPress" on clinical and biochemical parameters and on the activity of detoxification enzymes of liver in patients with chronic viral hepatitis B and C. 24 patients (19 females and 5 males aged 16-39 years) were enrolled in the study. Patients in case group received dietary supplement "ExPress" in addition to basic treatment. Average indices of total bilirubin in cases after treatment were 26.98 +/- 2.85 mmol/l, while in controls--34.31 +/- 5.72 mmol/l (p > 0.05). Average indices of alanin-aminotransferase and aspartate-aminotransferase were 78.75 +/- 11.25 and 160.75 +/- 23.67 units while in controls--208.5 +/- 56.4 and 330.25 +/- 65.14 units respectively (p < 0.05). In case group we observed full normalization of thymol test--from 9.99 +/- 1.51 to 4.03 +/- 0.73 units (p = 0.001), while in controls--from 7.9 +/- 1.56 only to 5.2 +/- 1.15 units (p = 0.194). Contents of non-metabolized antipyrine in cases decreased from 9.76 +/- 1.2% (p = 0.0002) whilst in controls--from 9.38 +/- 1.28% only to 3.93 +/- 1.18% (p = 0.01). Results of the study show that dietary supplement "ExPress" induces the activity of detoxification enzymes of liver and increases the efficiency of basic treatment. PMID:12462952

  12. Induced pluripotent stem cells generated without viral integration.

    PubMed

    Stadtfeld, Matthias; Nagaya, Masaki; Utikal, Jochen; Weir, Gordon; Hochedlinger, Konrad

    2008-11-01

    Pluripotent stem cells have been generated from mouse and human somatic cells by viral expression of the transcription factors Oct4, Sox2, Klf4, and c-Myc. A major limitation of this technology is the use of potentially harmful genome-integrating viruses. We generated mouse induced pluripotent stem (iPS) cells from fibroblasts and liver cells by using nonintegrating adenoviruses transiently expressing Oct4, Sox2, Klf4, and c-Myc. These adenoviral iPS (adeno-iPS) cells show DNA demethylation characteristic of reprogrammed cells, express endogenous pluripotency genes, form teratomas, and contribute to multiple tissues, including the germ line, in chimeric mice. Our results provide strong evidence that insertional mutagenesis is not required for in vitro reprogramming. Adenoviral reprogramming may provide an improved method for generating and studying patient-specific stem cells and for comparing embryonic stem cells and iPS cells. PMID:18818365

  13. Hepatitis B virus x protein induces autophagy via activating death-associated protein kinase.

    PubMed

    Zhang, H-T; Chen, G G; Hu, B-G; Zhang, Z-Y; Yun, J-P; He, M-L; Lai, P B S

    2014-01-01

    Hepatitis B virus x protein (HBX), a product of hepatitis B virus (HBV), is a multifunctional protein that regulates viral replication and various cellular functions. Recently, HBX has been shown to induce autophagy; however, the responsible mechanism is not fully known. In this study, we established stable HBX-expressing epithelial Chang cells as the platform to study how HBX induced autophagy. The results showed that the overexpression of HBX resulted in starvation-induced autophagy. HBX-induced autophagy was related to its ability to dephosphorylate/activate death-associated protein kinase (DAPK). The block of DAPK by its siRNA significantly counteracted HBX-mediated autophagy, confirming the positive role of DAPK in this process. HBX also induced Beclin 1, which functions at the downstream of the DAPK-mediated autophagy pathway. Although HBX could activate JNK, a kinase known to participate in autophagy in certain conditions, the change in JNK failed to influence HBX-induced autophagy. In conclusion, HBX induces autophagy via activating DAPK in a pathway related to Beclin 1, but not JNK. This new finding should help us to understand the role of autophagy in HBX-mediated pathogenesis and thus may provide targets for intervening HBX-related disorders.

  14. RNA editing of hepatitis B virus transcripts by activation-induced cytidine deaminase.

    PubMed

    Liang, Guoxin; Kitamura, Kouichi; Wang, Zhe; Liu, Guangyan; Chowdhury, Sajeda; Fu, Weixin; Koura, Miki; Wakae, Kousho; Honjo, Tasuku; Muramatsu, Masamichi

    2013-02-01

    Activation-induced cytidine deaminase (AID) is essential for the somatic hypermutation (SHM) and class-switch recombination (CSR) of Ig genes. The mechanism by which AID triggers SHM and CSR has been explained by two distinct models. In the DNA deamination model, AID converts cytidine bases in DNA into uridine. The uridine is recognized by the DNA repair system, which produces DNA strand breakages and point mutations. In the alternative model, RNA edited by AID is responsible for triggering CSR and SHM. However, RNA deamination by AID has not been demonstrated. Here we found that C-to-T and G-to-A mutations accumulated in hepatitis B virus (HBV) nucleocapsid DNA when AID was expressed in HBV-replicating hepatic cell lines. AID expression caused C-to-T mutations in the nucleocapsid DNA of RNase H-defective HBV, which does not produce plus-strand viral DNA. Furthermore, the RT-PCR products of nucleocapsid viral RNA from AID-expressing cells exhibited significant C-to-T mutations, whereas viral RNAs outside the nucleocapsid did not accumulate C-to-U mutations. Moreover, AID was packaged within the nucleocapsid by forming a ribonucleoprotein complex with HBV RNA and the HBV polymerase protein. The encapsidation of the AID protein with viral RNA and DNA provides an efficient environment for evaluating AID's RNA and DNA deamination activities. A bona fide RNA-editing enzyme, apolipoprotein B mRNA editing catalytic polypeptide 1, induced a similar level of C-to-U mutations in nucleocapsid RNA as AID. Taken together, the results indicate that AID can deaminate the nucleocapsid RNA of HBV.

  15. Detection of hepatitis C viral RNA sequences in fresh and paraffin-embedded liver biopsy specimens of non-A, non-B hepatitis patients.

    PubMed

    Bresters, D; Cuypers, H T; Reesink, H W; Chamuleau, R A; Schipper, M E; Boeser-Nunnink, B D; Lelie, P N; Jansen, P L

    1992-07-01

    In this study methods of HCV-RNA detection in fresh frozen and formalin-fixed, paraffin-embedded liver biopsies are described. Of 22 untreated chronic non-A, non-B hepatitis patients and 6 control patients, a plasma sample and part of a liver biopsy were freshly frozen for hepatitis C virus (HCV) cDNA-PCR. From 16 of the same non-A, non-B hepatitis patients and from 5 of the same control patients formalin-fixed, paraffin-embedded liver tissue from the same biopsy was available also for HCV cDNA-PCR. In 13 of 22 non-A, non-B hepatitis patients HCV-RNA could be detected in plasma as well as in liver tissue. In the other 9 non-A, non-B hepatitis patients and in 6 control patients, no HCV-RNA was detectable in either plasma or liver tissue. The comparison between HCV cDNA-PCR results in fresh frozen versus formalin-fixed, paraffin-embedded liver biopsies showed that although detection of HCV-RNA in both correlated 100% the quantity of HCV-RNA was lower in the formalin-fixed, paraffin-embedded liver biopsies of 5 of 8 patients for whom end-point dilution titration of liver RNA was performed. We conclude that using the procedures described HCV-RNA can be reliably detected in both fresh-frozen and formalin-fixed, paraffin-embedded liver biopsies and that HCV cDNA-PCR in liver tissue may become an important assay, especially for monitoring anti-viral therapy.

  16. In vitro and ex vivo delivery of short hairpin RNAs for control of hepatitis C viral transcript expression.

    PubMed

    Lonze, Bonnie E; Holzer, Horatio T; Knabel, Matthew K; Locke, Jayme E; DiCamillo, Gregory A; Karhadkar, Sunil S; Montgomery, Robert A; Sun, Zhaoli; Warren, Daniel S; Cameron, Andrew M

    2012-04-01

    Recurrent hepatitis C virus (HCV) infection is the most common cause of graft loss and patient death after transplantation for HCV cirrhosis. Transplant surgeons have access to uninfected explanted livers before transplantation and an opportunity to deliver RNA interference-based protective gene therapy to uninfected grafts. Conserved HCV sequences were used to design short interfering RNAs and test their ability to knockdown HCV transcript expression in an in vitro model, both by transfection and when delivered via an adeno-associated viral vector. In a rodent model of liver transplantation, portal venous perfusion of explanted grafts with an adeno-associated viral vector before transplantation produced detectable short hairpin RNA transcript expression after transplantation. The ability to deliver anti-HCV short hairpin RNAs to uninfected livers before transplantation and subsequent exposure to HCV offers hope for the possibility of preventing the currently inevitable subsequent infection of liver grafts with HCV.

  17. Immune blot analysis of viral surface proteins in serum and liver of patients with chronic hepatitis B virus infection.

    PubMed

    Gerken, G; Manns, M; Gerlich, W H; Hess, G; Meyer zum Büschenfelde, K H

    1989-12-01

    The small and the middle surface proteins of hepatitis virus form either the virion or the 22 nm particle both of which are secreted. The large surface protein by itself remains cell bound in artificially transfected cell culture unless it is accompanied by an excess of the smaller protens. Its behavior in vivo is not yet well studied. Using specific monoclonal antibodies for immunoblotting, we found an abundance of small surface protein in the serum of chronic virus carriers and moderate amounts in the liver irrespective of viremia. The large surface protein was present in the serum and the liver of viremic carriers. In nonviremic carriers, the large protein was absent from serum, but in the liver a shorter form of the large protein was readily detectable. These findings suggest a complex regulatory mechanism of the viral surface protein depending on the expression of other viral gene products. PMID:2621452

  18. Serodiagnosis of viral hepatitis A: rise in antibody titre and evaluation of three methods for detecting early and late antibodies.

    PubMed

    Girardet, C; Peitrequin, R; Frei, P C

    1983-08-15

    A serological investigation was made on patients with viral hepatitis A and individuals with a past history of this disease. Titration of antibody in sequential samples was found to be of no help in diagnosis. Separation of early (IgM) from late (IgG) antibodies by protein A or by 2-mercaptoethanol did not prove to be convenient for the serodiagnosis. A chromatographic separation of late and early antibody was found to be satisfactory, and equivalent to a radioimmunoassay for IgM-antibodies.

  19. A Survey of Texas HIV, Sexually Transmitted Disease, Tuberculosis, and Viral Hepatitis Providers' Billing and Reimbursement Capabilities.

    PubMed

    Flynn, Matthew B; Atwood, Robin; Greenberg, Jennifer B; Ray, Tara; Harris, Karol Kaye

    2015-11-01

    The Affordable Care Act presents financial challenges and opportunities for publicly funded service providers. We assessed billing practices and anticipated barriers to third-party billing among organizations in Texas that provide publicly funded HIV, sexually transmitted diseases, tuberculosis, and viral hepatitis services. One third to one half of the organizations did not bill for medical services. The most common barrier to third-party billing was lack of staff knowledge about billing and coding. Future research must evaluate options for organizations and communities to maintain access to infectious disease services for vulnerable populations.

  20. Comparison of Next-Generation Sequencing Technologies for Comprehensive Assessment of Full-Length Hepatitis C Viral Genomes.

    PubMed

    Thomson, Emma; Ip, Camilla L C; Badhan, Anjna; Christiansen, Mette T; Adamson, Walt; Ansari, M Azim; Bibby, David; Breuer, Judith; Brown, Anthony; Bowden, Rory; Bryant, Josie; Bonsall, David; Da Silva Filipe, Ana; Hinds, Chris; Hudson, Emma; Klenerman, Paul; Lythgow, Kieren; Mbisa, Jean L; McLauchlan, John; Myers, Richard; Piazza, Paolo; Roy, Sunando; Trebes, Amy; Sreenu, Vattipally B; Witteveldt, Jeroen; Barnes, Eleanor; Simmonds, Peter

    2016-10-01

    Affordable next-generation sequencing (NGS) technologies for hepatitis C virus (HCV) may potentially identify both viral genotype and resistance genetic motifs in the era of directly acting antiviral (DAA) therapies. This study compared the ability of high-throughput NGS methods to generate full-length, deep, HCV sequence data sets and evaluated their utility for diagnostics and clinical assessment. NGS methods using (i) unselected HCV RNA (metagenomics), (ii) preenrichment of HCV RNA by probe capture, and (iii) HCV preamplification by PCR implemented in four United Kingdom centers were compared. Metrics of sequence coverage and depth, quasispecies diversity, and detection of DAA resistance-associated variants (RAVs), mixed HCV genotypes, and other coinfections were compared using a panel of samples with different viral loads, genotypes, and mixed HCV genotypes/subtypes [geno(sub)types]. Each NGS method generated near-complete genome sequences from more than 90% of samples. Enrichment methods and PCR preamplification generated greater sequence depth and were more effective for samples with low viral loads. All NGS methodologies accurately identified mixed HCV genotype infections. Consensus sequences generated by different NGS methods were generally concordant, and majority RAVs were consistently detected. However, methods differed in their ability to detect minor populations of RAVs. Metagenomic methods identified human pegivirus coinfections. NGS provided a rapid, inexpensive method for generating whole HCV genomes to define infecting genotypes, RAVs, comprehensive viral strain analysis, and quasispecies diversity. Enrichment methods are particularly suited for high-throughput analysis while providing the genotype and information on potential DAA resistance.

  1. Multiplex diagnosis of viral infectious diseases (AIDS, hepatitis C, and hepatitis A) based on point of care lateral flow assay using engineered proteinticles.

    PubMed

    Lee, Jong-Hwan; Seo, Hyuk Seong; Kwon, Jung-Hyuk; Kim, Hee-Tae; Kwon, Koo Chul; Sim, Sang Jun; Cha, Young Joo; Lee, Jeewon

    2015-07-15

    Lateral flow assay (LFA) is an attractive method for rapid, simple, and cost-effective point of care diagnosis. For LFA-based multiplex diagnosis of three viral intractable diseases (acquired immune deficiency syndrome and hepatitis C and A), here we developed proteinticle-based 7 different 3D probes that display different viral antigens on their surface, which were synthesized in Escherichia coli by self-assembly of human ferritin heavy chain that was already engineered by genetically linking viral antigens to its C-terminus. Each of the three test lines on LFA strip contains the proteinticle probes to detect disease-specific anti-viral antibodies. Compared to peptide probes, the proteinticle probes were evidently more sensitive, and the proteinticle probe-based LFA successfully diagnosed all the 20 patient sera per each disease without a false negative signal, whereas the diagnostic sensitivities in the peptide probe-based LFAs were 65-90%. Duplex and triplex assays performed with randomly mixed patient sera gave only true positive signals for all the 20 serum mixtures without any false positive signals, indicating 100% sensitivity and 100% specificity. It seems that on the proteinticle surface the antigenic peptides have homogeneous orientation and conformation without inter-peptide clustering and hence lead to the enhanced diagnostic performance with solving the problems of traditional diagnostic probes. Although the multiplex diagnosis of three viral diseases above was demonstrated as proof-of-concept here, the proposed LFA system can be applied to multiplex point of care diagnosis of other intractable diseases.

  2. Complementary Effects of Interleukin-15 and Alpha Interferon Induce Immunity in Hepatitis B Virus Transgenic Mice

    PubMed Central

    Di Scala, Marianna; Otano, Itziar; Gil-Fariña, Irene; Vanrell, Lucia; Hommel, Mirja; Olagüe, Cristina; Vales, Africa; Galarraga, Miguel; Guembe, Laura; Ortiz de Solorzano, Carlos; Ghosh, Indrajit; Maini, Mala K.; Prieto, Jesús

    2016-01-01

    ABSTRACT In chronic hepatitis B (CHB), failure to control hepatitis B virus (HBV) is associated with T cell dysfunction. HBV transgenic mice mirror many features of the human disease, including T cell unresponsiveness, and thus represent an appropriate model in which to test novel therapeutic strategies. To date, the tolerant state of CD8+ T cells in these animals could be altered only by strong immunogens or by immunization with HBV antigen-pulsed dendritic cells; however, the effectors induced were unable to suppress viral gene expression or replication. Because of the known stimulatory properties of alpha interferon (IFN-α) and interleukin-15 (IL-15), this study explored the therapeutic potential of liver-directed gene transfer of these cytokines in a murine model of CHB using adeno-associated virus (AAV) delivery. This combination not only resulted in a reduction in the viral load in the liver and the induction of an antibody response but also gave rise to functional and specific CD8+ immunity. Furthermore, when splenic and intrahepatic lymphocytes from IFN-α- and IL-15-treated animals were transferred to new HBV carriers, partial antiviral immunity was achieved. In contrast to previous observations made using either cytokine alone, markedly attenuated PD-L1 induction in hepatic tissue was observed upon coadministration. An initial study with CHB patient samples also gave promising results. Hence, we demonstrated synergy between two stimulating cytokines, IL-15 and IFN-α, which, given together, constitute a potent approach to significantly enhance the CD8+ T cell response in a state of immune hyporesponsiveness. Such an approach may be useful for treating chronic viral infections and neoplastic conditions. IMPORTANCE With 350 million people affected worldwide and 600,000 annual deaths due to HBV-induced liver cirrhosis and/or hepatocellular carcinoma, chronic hepatitis B (CHB) is a major health problem. However, current treatment options are costly and not

  3. Induced immunity against hepatitis B virus

    PubMed Central

    Said, Zeinab Nabil Ahmed; Abdelwahab, Kouka Saadeldin

    2015-01-01

    Prevention of hepatitis B virus (HBV) infection with its consequent development of HBV chronic liver disease and hepatocellular carcinoma is a global mandatory goal. Fortunately, safe and effective HBV vaccines are currently available. Universal hepatitis B surface antigen HBV vaccination coverage is almost done. Growing knowledge based upon monitoring and surveillance of HBV vaccination programs has accumulated and the policy of booster vaccination has been evaluated. This review article provides an overview of the natural history of HBV infection, immune responses and the future of HBV infection. It also summarizes the updated sources, types and uses of HBV vaccines, whether in the preclinical phase or in the post-field vaccination. PMID:26140085

  4. Liver-Specific Alpha 2 Interferon Gene Expression Results in Protection from Induced Hepatitis

    PubMed Central

    Aurisicchio, Luigi; Delmastro, Paola; Salucci, Valentina; Paz, Odalys Gonzalez; Rovere, Patrizia; Ciliberto, Gennaro; La Monica, Nicola; Palombo, Fabio

    2000-01-01

    The current therapy for hepatitis B and C is based on systemic administration of recombinant human alpha interferon (r-hIFN-α). However, systemic delivery of r-hIFN-α is associated with severe side effects, but more importantly, it is effective in only a small percentage of patients. In an effort to maximize IFN-α antiviral efficacy, we have explored the therapeutic potential of murine IFN-α2 (mIFNα2) selectively expressed in the liver. To this end, we have developed a helper-dependent adenovirus vector (HD) containing the mIFN-α2 gene under the control of the liver-specific transthyretin promoter (HD-IFN). Comparison with a first-generation adenovirus carrying the same mIFN-α2 expression cassette indicates that at certain HD-IFN doses, induction of antiviral genes can be achieved in the absence of detectable circulating mIFN-α2. Challenge of injected mice with mouse hepatitis virus type 3 showed that HD-IFN provides high liver protection. Moreover, liver protection was also observed in acute nonviral liver inflammation hepatitis induced by concanavalin A at 1 month postinfection. These results hold promise for the development of a gene therapy treatment for chronic viral hepatitis based on liver-restricted expression of IFN-α2. PMID:10775620

  5. Hepatitis B Infection, Viral Load and Resistance in HIV-Infected Patients in Mozambique and Zambia

    PubMed Central

    Wandeler, Gilles; Musukuma, Kalo; Zürcher, Samuel; Vinikoor, Michael J.; Llenas-García, Jara; Aly, Mussa M.; Mulenga, Lloyd; Chi, Benjamin H.; Ehmer, Jochen; Hobbins, Michael A.; Bolton-Moore, Carolyn; Hoffmann, Christopher J.; Egger, Matthias

    2016-01-01

    Background Few data on the virological determinants of hepatitis B virus (HBV) infection are available from southern Africa. Methods We enrolled consecutive HIV-infected adult patients initiating antiretroviral therapy (ART) at two urban clinics in Zambia and four rural clinics in Northern Mozambique between May 2013 and August 2014. HBsAg screening was performed using the Determine® rapid test. Quantitative real-time PCR and HBV sequencing were performed in HBsAg-positive patients. Risk factors for HBV infection were evaluated using Chi-square and Mann-Whitney tests and associations between baseline characteristics and high level HBV replication explored in multivariable logistic regression. Results Seventy-eight of 1,032 participants in Mozambique (7.6%, 95% confidence interval [CI]: 6.1–9.3) and 90 of 797 in Zambia (11.3%, 95% CI: 9.3–13.4) were HBsAg-positive. HBsAg-positive individuals were less likely to be female compared to HBsAg-negative ones (52.3% vs. 66.1%, p<0.001). Among 156 (92.9%) HBsAg-positive patients with an available measurement, median HBV viral load was 13,645 IU/mL (interquartile range: 192–8,617,488 IU/mL) and 77 (49.4%) had high values (>20,000 UI/mL). HBsAg-positive individuals had higher levels of ALT and AST compared to HBsAg-negative ones (both p<0.001). In multivariable analyses, male sex (adjusted odds ratio: 2.59, 95% CI: 1.22–5.53) and CD4 cell count below 200/μl (2.58, 1.20–5.54) were associated with high HBV DNA. HBV genotypes A1 (58.8%) and E (38.2%) were most prevalent. Four patients had probable resistance to lamivudine and/or entecavir. Conclusion One half of HBsAg-positive patients demonstrated high HBV viremia, supporting the early initiation of tenofovir-containing ART in HIV/HBV-coinfected adults. PMID:27032097

  6. Hepatitis C Virus Genotypes and Association With Viral Load in Yazd, Central Province of Iran

    PubMed Central

    Hadinedoushan, Hossein; Salmanroghani, Hasan; Amirbaigy, Mohammad Kazem; Akhondi-Meybodi, Mohsen

    2014-01-01

    Background: Hepatitis C virus (HCV) is a major cause of liver disease. Infection with HCV is a global public health problem. The virus is classified into 6 genotypes and more than 80 subtypes named as a, b, c, etc. HCV genotyping has been an important parameter for the treatment of HCV infection. Objectives: The main aim of this study was to estimate the prevalence of HCV genotypes in Yazd, central province of Iran. In addition, the study investigated whether there was any association between HCV load and genotypes. Patients and Methods: This descriptive cross-sectional study was performed on samples suspicious of HCV infection from March 2010 to June 2013. Peripheral blood sample was obtained and screened for anti-HCV antibodies using Enzyme-Linked Immunosorbent Assay (ELISA). Then sera of anti-HCV positive samples were analyzed using quantitative polymerase chain reaction method. Plasma samples were used to determine the HCV genotypes of 1a, 1b, 2, 3, and 4 in 191 infected patients. Results: One hundred fifty-two out of 191 (79.6%) samples were from male patients. The mean of the patients’ age was 40.7 ± 11.9 years (range 21-75 years old). Sixty- three (33%) patients were included in 31-40 years group. The mean number of HCV in infected patients was 2.92 × 106 ± 1.85 × 106 copies/mL (Min: 508; Max: 2.75 × 108 copies/mL). HCV genotype 3 was the predominant genotype (50.3%) followed by subtypes 1a (38.7%) and 1b (6.8%). The distribution of other HCV genotypes showed genotype 2 in 1.6% and mixed genotypes in 2.6% of positive samples. Genotype 3 was predominant in all age groups except 21-30 years of age group. We were unable to find any significant difference between mean viral load of the patients infected with genotype 3 and those infected with genotype 1 (1a and 1b). Conclusions: Findings of the present study showed that HCV genotype 3 was the predominant genotype followed by the subtypes 1a and 1b in Yazd, central province of Iran. In addition, there was

  7. A Dog Model for Acetaminophen-Induced Fulminant Hepatic Failure

    PubMed Central

    FRANCAVILLA, A.; MAKOWKA, L.; POLIMENO, L.; BARONE, M.; DEMETRIS, J.; PRELICH, J.; Van THIEL, D. H.; STARZL, T. E.

    2010-01-01

    The development of a large animal model of fulminant hepatic failure produced with acetaminophen that should be useful in the development and evaluation of potential medical therapies for the important clinical problem of fulminant hepatic failure is described. Acetaminophen in dimethyl sulfoxide (600 mg/ml) given as three subcutaneous injections, with the first dose (750 mg/kg body wt) being given at noon, the second dose (200 mg/kg body wt) being given 9 h later, and the third dose (200 mg/kg body wt) being given 24 h after the initial dose consistently produces fulminant hepatic failure in dogs. The dimethyl sulfoxide vehicle, injected intramuscularly, does not influence either animal survival or hepatic function in control-treated dogs. No deaths occur within the first 36 h. By 72 h after initial drug administration, the mortality is 90%. Histopathological and biochemical investigations demonstrate a high degree of hepatocellular necrosis in nonsurviving animals without appreciable damage to the kidneys, lungs, or heart. The drug schedule and preparation outlined avoids the administration of large volumes of vehicle and results in prolonged high levels of acetaminophen in the blood sufficient to induce severe hepatic injury. Ranitidine (120 mg/kg body wt i.m.) given 30 min before each acetaminophen dose significantly reduces the mortality and hepatic necrosis produced using this model. This model satisfies all criteria established by Miller et al. for the production of a suitable large animal model of fulminant acute hepatic failure. PMID:2910762

  8. Ultra-deep pyrosequencing analysis of the hepatitis B virus preCore region and main catalytic motif of the viral polymerase in the same viral genome.

    PubMed

    Homs, Maria; Buti, Maria; Quer, Josep; Jardí, Rosendo; Schaper, Melanie; Tabernero, David; Ortega, Israel; Sanchez, Alex; Esteban, Rafael; Rodriguez-Frias, Francisco

    2011-10-01

    Hepatitis B virus (HBV) pregenomic RNA contains a hairpin structure (ε) located in the preCore region, essential for viral replication. ε stability is enhanced by the presence of preCore variants and ε is recognized by the HBV polymerase (Pol). Mutations in the retrotranscriptase domain (YMDD) of Pol are associated with treatment resistance. The aim of this study was to analyze the preCore region and YMDD motif by ultra-deep pyrosequencing (UDPS). To evaluate the UDPS error rate, an internal control sequence was inserted in the amplicon. A newly developed technique enabled simultaneous analysis of the preCore region and Pol in the same viral genome, as well as the conserved sequence of the internal control. Nucleotide errors in HindIII yielded a UDPS error rate <0.05%. UDPS study confirmed the possibility of simultaneous detection of preCore and YMDD mutations, and demonstrated the complexity of the HBV quasispecies and cooperation between viruses. Thermodynamic stability of the ε signal was found to be the main constraint for selecting main preCore mutations. Analysis of ε-signal variability suggested the essential nature of the ε structural motif and that certain nucleotides may be involved in ε signal functions.

  9. Dipeptidyl peptidase-4 inhibition ameliorates Western diet-induced hepatic steatosis and insulin resistance through hepatic lipid remodeling and modulation of hepatic mitochondrial function.

    PubMed

    Aroor, Annayya R; Habibi, Javad; Ford, David A; Nistala, Ravi; Lastra, Guido; Manrique, Camila; Dunham, Merlow M; Ford, Kaitlin D; Thyfault, John P; Parks, Elizabeth J; Sowers, James R; Rector, R Scott

    2015-06-01

    Novel therapies are needed for treating the increasing prevalence of hepatic steatosis in Western populations. In this regard, dipeptidyl peptidase-4 (DPP-4) inhibitors have recently been reported to attenuate the development of hepatic steatosis, but the potential mechanisms remain poorly defined. In the current study, 4-week-old C57Bl/6 mice were fed a high-fat/high-fructose Western diet (WD) or a WD containing the DPP-4 inhibitor, MK0626, for 16 weeks. The DPP-4 inhibitor prevented WD-induced hepatic steatosis and reduced hepatic insulin resistance by enhancing insulin suppression of hepatic glucose output. WD-induced accumulation of hepatic triacylglycerol (TAG) and diacylglycerol (DAG) content was significantly attenuated with DPP-4 inhibitor treatment. In addition, MK0626 significantly reduced mitochondrial incomplete palmitate oxidation and increased indices of pyruvate dehydrogenase activity, TCA cycle flux, and hepatic TAG secretion. Furthermore, DPP-4 inhibition rescued WD-induced decreases in hepatic PGC-1α and CPT-1 mRNA expression and hepatic Sirt1 protein content. Moreover, plasma uric acid levels in mice fed the WD were decreased after MK0626 treatment. These studies suggest that DPP-4 inhibition ameliorates hepatic steatosis and insulin resistance by suppressing hepatic TAG and DAG accumulation through enhanced mitochondrial carbohydrate utilization and hepatic TAG secretion/export with a concomitant reduction of uric acid production.

  10. Hepatitis Information for the Public

    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 Information for the Public Recommend on Facebook Tweet ...

  11. Seroprevalence for Hepatitis E and Other Viral Hepatitides among Diverse Populations, Malawi.

    PubMed

    Taha, Taha E; Rusie, Laura K; Labrique, Alain; Nyirenda, Mulinda; Soko, Dean; Kamanga, Melvin; Kumwenda, Johnstone; Farazadegan, Homayoon; Nelson, Kenrad; Kumwenda, Newton

    2015-07-01

    Data on prevalence of hepatitis E virus (HEV) in Malawi is limited. We tested blood samples from HIV-uninfected and -infected populations of women and men enrolled in research studies in Malawi during 1989-2008 to determine the seroprevalence of HEV, hepatitis A virus (HAV), hepatitis B virus (HBV), and hepatitis C virus (HCV). Samples were tested for IgG against HEV, total antibodies against HAV and HCV, and presence of HBV surface antigens. Of 800 samples tested, 16.5% were positive for HEV IgG, 99.6% were positive for HAV antibodies, 7.5% were positive for HBV surface antigen, and 7.1% were positive for HCV antibodies. No clear trends over time were observed in the seroprevalence of HEV, and HIV status was not associated with hepatitis seroprevalence. These preliminary data suggest that the seroprevalence of HEV is high in Malawi; the clinical effects may be unrecognized or routinely misclassified.

  12. Seroprevalence for Hepatitis E and Other Viral Hepatitides among Diverse Populations, Malawi

    PubMed Central

    Rusie, Laura K.; Labrique, Alain; Nyirenda, Mulinda; Soko, Dean; Kamanga, Melvin; Kumwenda, Johnstone; Farazadegan, Homayoon; Nelson, Kenrad; Kumwenda, Newton

    2015-01-01

    Data on prevalence of hepatitis E virus (HEV) in Malawi is limited. We tested blood samples from HIV-uninfected and -infected populations of women and men enrolled in research studies in Malawi during 1989–2008 to determine the seroprevalence of HEV, hepatitis A virus (HAV), hepatitis B virus (HBV), and hepatitis C virus (HCV). Samples were tested for IgG against HEV, total antibodies against HAV and HCV, and presence of HBV surface antigens. Of 800 samples tested, 16.5% were positive for HEV IgG, 99.6% were positive for HAV antibodies, 7.5% were positive for HBV surface antigen, and 7.1% were positive for HCV antibodies. No clear trends over time were observed in the seroprevalence of HEV, and HIV status was not associated with hepatitis seroprevalence. These preliminary data suggest that the seroprevalence of HEV is high in Malawi; the clinical effects may be unrecognized or routinely misclassified. PMID:26079666

  13. Structural Basis for Host Membrane Remodeling Induced by Protein 2B of Hepatitis A Virus

    PubMed Central

    Vives-Adrián, Laia; Garriga, Damià; Buxaderas, Mònica; Fraga, Joana; Pereira, Pedro José Barbosa

    2015-01-01

    ABSTRACT The complexity of viral RNA synthesis and the numerous participating factors require a mechanism to topologically coordinate and concentrate these multiple viral and cellular components, ensuring a concerted function. Similarly to all other positive-strand RNA viruses, picornaviruses induce rearrangements of host intracellular membranes to create structures that act as functional scaffolds for genome replication. The membrane-targeting proteins 2B and 2C, their precursor 2BC, and protein 3A appear to be primarily involved in membrane remodeling. Little is known about the structure of these proteins and the mechanisms by which they induce massive membrane remodeling. Here we report the crystal structure of the soluble region of hepatitis A virus (HAV) protein 2B, consisting of two domains: a C-terminal helical bundle preceded by an N-terminally curved five-stranded antiparallel β-sheet that displays striking structural similarity to the β-barrel domain of enteroviral 2A proteins. Moreover, the helicoidal arrangement of the protein molecules in the crystal provides a model for 2B-induced host membrane remodeling during HAV infection. IMPORTANCE No structural information is currently available for the 2B protein of any picornavirus despite it being involved in a critical process in viral factory formation: the rearrangement of host intracellular membranes. Here we present the structure of the soluble domain of the 2B protein of hepatitis A virus (HAV). Its arrangement, both in crystals and in solution under physiological conditions, can help to understand its function and sheds some light on the membrane rearrangement process, a putative target of future antiviral drugs. Moreover, this first structure of a picornaviral 2B protein also unveils a closer evolutionary relationship between the hepatovirus and enterovirus genera within the Picornaviridae family. PMID:25589659

  14. TRC8-dependent degradation of hepatitis C virus immature core protein regulates viral propagation and pathogenesis

    PubMed Central

    Aizawa, Sayaka; Okamoto, Toru; Sugiyama, Yukari; Kouwaki, Takahisa; Ito, Ayano; Suzuki, Tatsuya; Ono, Chikako; Fukuhara, Takasuke; Yamamoto, Masahiro; Okochi, Masayasu; Hiraga, Nobuhiko; Imamura, Michio; Chayama, Kazuaki; Suzuki, Ryosuke; Shoji, Ikuo; Moriishi, Kohji; Moriya, Kyoji; Koike, Kazuhiko; Matsuura, Yoshiharu

    2016-01-01

    Signal-peptide peptidase (SPP) is an intramembrane protease that participates in the production of the mature core protein of hepatitis C virus (HCV). Here we show that SPP inhibition reduces the production of infectious HCV particles and pathogenesis. The immature core protein produced in SPP-knockout cells or by treatment with an SPP inhibitor is quickly degraded by the ubiquitin–proteasome pathway. Oral administration of the SPP inhibitor to transgenic mice expressing HCV core protein (CoreTg) reduces the expression of core protein and ameliorates insulin resistance and liver steatosis. Moreover, the haploinsufficiency of SPP in CoreTg has similar effects. TRC8, an E3 ubiquitin ligase, is required for the degradation of the immature core protein. The expression of the HCV core protein alters endoplasmic reticulum (ER) distribution and induces ER stress in SPP/TRC8 double-knockout cells. These data suggest that HCV utilizes SPP cleavage to circumvent the induction of ER stress in host cells. PMID:27142248

  15. Toxin-Induced Autoimmune Hepatitis Caused by Raw Cashew Nuts

    PubMed Central

    Stueck, Ashley; Bansal, Meena

    2016-01-01

    A 64-year-old man with no past medical history presented with abnormally elevated liver enzymes 1 year after developing a diffuse rash thought to be related to eating large quantities of raw cashew nuts. Liver biopsy was performed, which revealed features concerning for drug- or toxin-induced autoimmune hepatitis. The patient began treatment with azathioprine and prednisone, and liver enzymes normalized. We describe a unique case of a toxin-induced autoimmune hepatitis precipitated not by a drug or dietary supplement but by a food product. PMID:27807585

  16. Genotypes and viral load of hepatitis C virus among persons attending a voluntary counseling and testing center in Ethiopia.

    PubMed

    Abreha, Tesfay; Woldeamanuel, Yimtubezinash; Pietsch, Corinna; Maier, Melanie; Asrat, Daniel; Abebe, Almaz; Hailegiorgis, Bereket; Aseffa, Abraham; Liebert, Uwe Gerd

    2011-05-01

    The prevalence of different genotypes of hepatitis C virus (HCV) in Ethiopia is not known. HCV genotypes influence the response to therapy with alpha-interferon alone or in combination with ribavirin. A cross sectional study was conducted on attendees of voluntary counseling and testing center. Serum samples from 1,954 (734 HIV positive and 1,220 HIV negative) individuals were screened for HCV antibody. Active HCV infection was confirmed by quantitative PCR in 18 of the 71 samples with anti-HCV antibodies. The HCV viral load ranged from 39,650 to 9,878,341 IU/ml (median 1,589,631 IU/ml) with no significant difference [χ(2)(17) = 18.00, P = 0.389] between persons positive or negative for HIV. The viral load of HCV was, however, higher in older study subjects (r = 0.80, P = 0.000). HCV genotypes were determined using the VERSANT HCV Genotype Assay (LiPA) and sequence analysis of the NS5b region of the HCV genome. Diverse HCV genotypes were found including genotypes 1, 2, 4, and 5. There was no difference in the distribution regarding the HIV status. As in other parts of the world, genotyping of HCV must be considered whenever HCV is incriminated as a cause of hepatitis. PMID:21351106

  17. Identification, using sera from exposed animals, of putative viral antigens in livers of primates with callitrichid hepatitis.

    PubMed Central

    Stephensen, C B; Montali, R J; Ramsay, E C; Holmes, K V

    1990-01-01

    Callitrichid hepatitis (CH) is an acute, frequently fatal viral hepatitis which affects members of the primate family Callitrichidae (R. J. Montali, E. C. Ramsay, C. B. Stephensen, M. Worley, J. A. Davis, and K. V. Holmes, J. Infect. Dis. 160:759-765, 1989; E. C. Ramsay, R. J. Montali, M. Worley, C. B. Stephensen, and K. V. Holmes, J. Zoo Wildlife Med. 20:178-183, 1989). Outbreaks of the disease occur in zoos and animal parks. In this study, CH-specific antigens were identified in the livers of infected animals by using immune sera from primates with CH and CH-exposed asymptomatic animals. Three CH-specific antigens with apparent molecular masses of 34, 54, and 65 kDa were identified. A polyclonal antiserum was raised against the 54-kDa antigen. These antigens were not found in the livers of uninfected animals and may be viral proteins. Our results suggest that at least five of the six outbreaks of CH considered here were caused by the same virus or by an antigenically related virus. Images PMID:2123012

  18. Integrated hepatitis B virus DNA sequences specifying the major viral core polypeptide are methylated in PLC/PRF/5 cells.

    PubMed

    Miller, R H; Robinson, W S

    1983-05-01

    The methylation of various hepatitis B virus (HBV) DNA sequences was examined using the restriction endonucleases Hpa II and Msp I. HBV DNA from virions (Dane particles) and virus-infected liver tissue was digested with Hpa II or Msp I and fractionated by electrophoresis in agarose gels, and the restriction enzyme cleavage pattern was examined by Southern blot analysis. No methylation of the 5' C-C-G-G 3' recognition sequence was detected in either virion DNA or HBV DNA from infected liver tissue. The tissue culture cell line PLC/PRF/5, derived from a human hepatoma, possesses HBV DNA exclusively integrated at several sites. Digestion of PLC/PRF/5 DNA with Hpa II and Msp I revealed that the integrated HBV DNA sequences were methylated. Further analysis using probes specific for various regions of the HBV genome showed that some of the hepatitis B viral DNA sequences, including those specifying the major surface antigen polypeptide, were methylated infrequently or not at all. In contrast, the viral DNA sequences coding for the major core polypeptide were extensively methylated. Because the surface antigen is expressed in these cells while the core antigen is not, our results suggest that DNA methylation could account for the selective expression of HBV genes in this hepatoma cell line.

  19. Phosphorylation of Hepatitis C Virus RNA Polymerases Ser29 and Ser42 by Protein Kinase C-Related Kinase 2 Regulates Viral RNA Replication

    PubMed Central

    Han, Song-Hee; Kim, Seong-Jun; Kim, Eun-Jung; Kim, Tae-Eun; Moon, Jae-Su; Kim, Geon-Woo; Lee, Seung-Hoon; Cho, Kun; Yoo, Jong Shin; Son, Woo Sung; Rhee, Jin-Kyu; Han, Seung Hyun

    2014-01-01

    ABSTRACT Hepatitis C virus (HCV) nonstructural protein 5B (NS5B), an RNA-dependent RNA polymerase (RdRp), is the key enzyme for HCV RNA replication. We previously showed that HCV RdRp is phosphorylated by protein kinase C-related kinase 2 (PRK2). In the present study, we used biochemical and reverse-genetics approaches to demonstrate that HCV NS5B phosphorylation is crucial for viral RNA replication in cell culture. Two-dimensional phosphoamino acid analysis revealed that PRK2 phosphorylates NS5B exclusively at its serine residues in vitro and in vivo. Using in vitro kinase assays and mass spectrometry, we identified two phosphorylation sites, Ser29 and Ser42, in the Δ1 finger loop region that interacts with the thumb subdomain of NS5B. Colony-forming assays using drug-selectable HCV subgenomic RNA replicons revealed that preventing phosphorylation by Ala substitution at either Ser29 or Ser42 impairs HCV RNA replication. Furthermore, reverse-genetics studies using HCV infectious clones encoding phosphorylation-defective NS5B confirmed the crucial role of these PRK2 phosphorylation sites in viral RNA replication. Molecular-modeling studies predicted that the phosphorylation of NS5B stabilizes the interactions between its Δ1 loop and thumb subdomain, which are required for the formation of the closed conformation of NS5B known to be important for de novo RNA synthesis. Collectively, our results provide evidence that HCV NS5B phosphorylation has a positive regulatory role in HCV RNA replication. IMPORTANCE While the role of RNA-dependent RNA polymerases (RdRps) in viral RNA replication is clear, little is known about their functional regulation by phosphorylation. In this study, we addressed several important questions about the function and structure of phosphorylated hepatitis C virus (HCV) nonstructural protein 5B (NS5B). Reverse-genetics studies with HCV replicons encoding phosphorylation-defective NS5B mutants and analysis of their RdRp activities revealed

  20. The nsp2 Replicase Proteins of Murine Hepatitis Virus and Severe Acute Respiratory Syndrome Coronavirus Are Dispensable for Viral Replication

    PubMed Central

    Graham, Rachel L.; Sims, Amy C.; Brockway, Sarah M.; Baric, Ralph S.; Denison, Mark R.

    2005-01-01

    The positive-stranded RNA genome of the coronaviruses is translated from ORF1 to yield polyproteins that are proteolytically processed into intermediate and mature nonstructural proteins (nsps). Murine hepatitis virus (MHV) and severe acute respiratory syndrome coronavirus (SARS-CoV) polyproteins incorporate 16 protein domains (nsps), with nsp1 and nsp2 being the most variable among the coronaviruses and having no experimentally confirmed or predicted functions in replication. To determine if nsp2 is essential for viral replication, MHV and SARS-CoV genome RNA was generated with deletions of the nsp2 coding sequence (MHVΔnsp2 and SARSΔnsp2, respectively). Infectious MHVΔnsp2 and SARSΔnsp2 viruses recovered from electroporated cells had 0.5 to 1 log10 reductions in peak titers in single-cycle growth assays, as well as a reduction in viral RNA synthesis that was not specific for any positive-stranded RNA species. The Δnsp2 mutant viruses lacked expression of both nsp2 and an nsp2-nsp3 precursor, but cleaved the engineered chimeric nsp1-nsp3 cleavage site as efficiently as the native nsp1-nsp2 cleavage site. Replication complexes in MHVΔnsp2-infected cells lacked nsp2 but were morphologically indistinguishable from those of wild-type MHV by immunofluorescence. nsp2 expressed in cells by stable retroviral transduction was specifically recruited to viral replication complexes upon infection with MHVΔnsp2. These results demonstrate that while nsp2 of MHV and SARS-CoV is dispensable for viral replication in cell culture, deletion of the nsp2 coding sequence attenuates viral growth and RNA synthesis. These findings also provide a system for the study of determinants of nsp targeting and function. PMID:16227261

  1. The nsp2 replicase proteins of murine hepatitis virus and severe acute respiratory syndrome coronavirus are dispensable for viral replication.

    PubMed

    Graham, Rachel L; Sims, Amy C; Brockway, Sarah M; Baric, Ralph S; Denison, Mark R

    2005-11-01

    The positive-stranded RNA genome of the coronaviruses is translated from ORF1 to yield polyproteins that are proteolytically processed into intermediate and mature nonstructural proteins (nsps). Murine hepatitis virus (MHV) and severe acute respiratory syndrome coronavirus (SARS-CoV) polyproteins incorporate 16 protein domains (nsps), with nsp1 and nsp2 being the most variable among the coronaviruses and having no experimentally confirmed or predicted functions in replication. To determine if nsp2 is essential for viral replication, MHV and SARS-CoV genome RNA was generated with deletions of the nsp2 coding sequence (MHVDeltansp2 and SARSDeltansp2, respectively). Infectious MHVDeltansp2 and SARSDeltansp2 viruses recovered from electroporated cells had 0.5 to 1 log10 reductions in peak titers in single-cycle growth assays, as well as a reduction in viral RNA synthesis that was not specific for any positive-stranded RNA species. The Deltansp2 mutant viruses lacked expression of both nsp2 and an nsp2-nsp3 precursor, but cleaved the engineered chimeric nsp1-nsp3 cleavage site as efficiently as the native nsp1-nsp2 cleavage site. Replication complexes in MHVDeltansp2-infected cells lacked nsp2 but were morphologically indistinguishable from those of wild-type MHV by immunofluorescence. nsp2 expressed in cells by stable retroviral transduction was specifically recruited to viral replication complexes upon infection with MHVDeltansp2. These results demonstrate that while nsp2 of MHV and SARS-CoV is dispensable for viral replication in cell culture, deletion of the nsp2 coding sequence attenuates viral growth and RNA synthesis. These findings also provide a system for the study of determinants of nsp targeting and function. PMID:16227261

  2. Hepatitis

    MedlinePlus

    ... Got Homework? Here's Help White House Lunch Recipes Hepatitis KidsHealth > For Kids > Hepatitis Print A A A ... an important digestive liquid called bile . What Is Hepatitis? Hepatitis is an inflammation (say: in-fluh-MAY- ...

  3. Prevalence of chronic viral hepatitis in people of south Asian ethnicity living in England: the prevalence cannot necessarily be predicted from the prevalence in the country of origin.

    PubMed

    Uddin, G; Shoeb, D; Solaiman, S; Marley, R; Gore, C; Ramsay, M; Harris, R; Ushiro-Lumb, I; Moreea, S; Alam, S; Thomas, H C; Khan, S; Watt, B; Pugh, R N; Ramaiah, S; Jervis, R; Hughes, A; Singhal, S; Cameron, S; Carman, W F; Foster, G R

    2010-05-01

    The prevalence of hepatitis B and hepatitis C in immigrant communities is unknown. Immigrants from south Asia are common in England and elsewhere, and the burden of viral hepatitis in these communities is unknown. We aimed to determine the prevalence of viral hepatitis in immigrants from south Asia living in England, and we therefore undertook a community-based testing project in such people at five sites in England. A total of 4998 people attending community centres were screened for viral hepatitis using oral fluid testing. The overall prevalence of anti-hepatitis C virus (HCV) in people of south Asian origin was 1.6% but varied by country of birth being 0.4%, 0.2%, 0.6% and 2.7% in people of this ethnic group born in the UK, India, Bangladesh and Pakistan, respectively. The prevalence of hepatitis B surface antigen was 1.2%-0.2%, 0.1%, 1.5% and 1.8% in people of this ethnic group born in the UK, India, Bangladesh and Pakistan, respectively. Analysis of risk factors for HCV infection shows that people from the Pakistani Punjab and those who have immigrated recently are at increased risk of infection. Our study suggests that migrants from Pakistan are at highest risk of viral hepatitis, with those from India at low risk. As prevalence varies both by country and region of origin and over time, the prevalence in migrant communities living in western countries cannot be easily predicted from studies in the country of origin.

  4. Hepatitis B and C viral infections among blood donors. A retrospective study from a rural community of Ghana

    PubMed Central

    2011-01-01

    Background Infection by Hepatitis B virus (HBV) and Hepatitis C virus (HCV) cause serious mortality, morbidity and financial burden and are thus a major global health problem. The study was conducted to investigate the prevalence of Hepatitis B and C infections and co-infections among blood donors in a rural community of Ghana. This was a retrospective study conducted at the Agogo Presbyterian Hospital in the Asanti Akim North District of Ghana to investigate the prevalence of these infections over a three year period among 2773 blood donors. Males constituted a larger proportion of the study population (92.2%). Majority of the study population (43.9%) were within 26-35 age group. The disease prevalence was calculated at a 95% confidence interval. Findings The prevalence of Hepatitis B viral (HBV) infection was highest in females- 21.4% (95% CI: 11.6-34.4) in 2006 than males in the same year- 13.2% (95% CI: 10.8-15.9). Hepatitis C viral (HCV) infection was highest among males- 11.6% (95% CI: 9.5-13.8) in 2007. HBV and HCV co-infection was higher in males- 2.6% (95% CI: 1.6-3.8) than females- 1.3% (95% CI: 0-7.0) in 2007. The overall prevalence of HBV and HCV was 13.8% (95% CI: 11.4- 16.4) and 9.4% (95% CI: 7.4-11.6) respectively in 2006. The rate of co-infection of HBV and HCV however increased from 1.6% (95% CI: 0.8-2.7) in 2006 to 2.2% (95% CI: 1.3-3.2) in 2008 in males and from 0% (95% CI: 0-6.4) in 2006 to 1.2% (95% CI: 0-6.5) in 2008 in females. Conclusion The single infections of HBV and HCV reduced but co-infection of these transfusion transmitted infections increased. Measures such as more sensitive techniques for effective diagnosis and sanitary education to enlighten the population must be implemented. PMID:22152159

  5. Boronic acid-modified lipid nanocapsules: a novel platform for the highly efficient inhibition of hepatitis C viral entry.

    PubMed

    Khanal, Manakamana; Barras, Alexandre; Vausselin, Thibaut; Fénéant, Lucie; Boukherroub, Rabah; Siriwardena, Aloysius; Dubuisson, Jean; Szunerits, Sabine

    2015-01-28

    The search for viral entry inhibitors that selectively target viral envelope glycoproteins has attracted increasing interest in recent years. Amongst the handful of molecules reported to show activity as hepatitis C virus (HCV) entry inhibitors are a variety of glycan-binding proteins including the lectins, cyanovirin-N (CV-N) and griffithsin. We recently demonstrated that boronic acid-modified nanoparticles are able to reduce HCV entry through a similar mechanism to that of lectins. A major obstacle to any further development of these nanostructures as viral entry inhibitors is their only moderate maximal inhibition potential. In the present study, we report that lipid nanocapsules (LNCs), surface-functionalized with amphiphilic boronic acid (BA) through their post-insertion into the semi-rigid shell of the LNCs, are indeed far superior as HCV entry inhibitors when compared with previously reported nanostructures. These 2(nd) generation particles (BA-LNCs) are shown to prevent HCV infection in the micromolar range (IC50 = 5.4 μM of BA moieties), whereas the corresponding BA monomers show no significant effects even at the highest analyzed concentration (20 μM). The new BA-LNCs are the most promising boronolectin-based HCV entry inhibitors reported to date and are thus observed to show great promise in the development of a pseudolectin-based therapeutic agent. PMID:25502878

  6. Obstructive jaundice due to radiation-induced hepatic duct stricture

    SciTech Connect

    Chandrasekhara, K.L.; Iyer, S.K.

    1984-10-01

    A case of obstructive jaundice due to radiation-induced hepatic duct stricture is reported. The patient received postoperative radiation for left adrenal carcinoma, seven years prior to this admission. The sequelae of hepatobiliary radiation and their management are discussed briefly.

  7. Cytosolic activation of aromatic and heterocyclic amines. Inhibition by dicoumarol and enhancement in viral hepatitis B.

    PubMed Central

    De Flora, S; Bennicelli, C; D'Agostini, F; Izzotti, A; Camoirano, A

    1994-01-01

    The aromatic amines 2-aminofluorene (2AF), 2-acetylaminofluorene, and 2-aminoanthracene, and the heterocyclic amines 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), 2-amino-3,4-dimethylimidazo[4,5-f]quinoline, and 3-amino-1-methyl-SH-pyrido[4,3-b]indole (Trp-P-2) were activated by rat liver cytosolic fractions to form mutagenic metabolites in Salmonella typhimurium strains TA98, TA98NR, and TA98/1,8-DNP6. In the case of the Trp-P-2, the cytosolic activation was even more potent than the microsomal activation, which is classically ascribed to N-hydroxylation and subsequent esterification. The cytosolic activation was a) NADPH-dependent, b) induced by pretreatment of rats with 3-methylcholanthrene and especially Aroclor 1254 but not by phenobarbital, and c) inhibited by dicoumarol. The hypothesis is that, following a preliminary oxidative step in the cytosol (pure cytosolic activation) or in microsomes via prostaglandin H synthase (mixed microsomal-cytosolic activation), an oxidized intermediate of amino compounds may serve as substrate for DT diaphorase activity and bielectronically reduced to the corresponding N-hydroxyamino derivative. Purified DT diaphorase, in the presence of either NADPH or NADH as electron donor, produced mutagenic derivatives from IQ and Trp-P-2. An NADPH-dependent activation of Trp-P-2 also occurred in the liver cytosol of woodchucks (Marmota monax), but was not inhibited by dicoumarol. As previously demonstrated with liver S-12 fractions in both humans and woodchucks, the cytosolic activation of Trp-P-2 was enhanced in animals affected by hepatitis B virus infection. This enhanced metabolism, which persisted even after appearance of primary hepatocellular carcinoma in virus carriers, is likely to be ascribed to mechanisms other than DT diaphorase induction, such as glutathione depletion. PMID:7534225

  8. Dynamics of lipid droplets induced by the hepatitis C virus core protein

    SciTech Connect

    Lyn, Rodney K.; Kennedy, David C.; Stolow, Albert; Ridsdale, Andrew; Pezacki, John Paul

    2010-09-03

    Research highlights: {yields} Hepatitis C virus uses lipid droplets (LD) onto which HCV core proteins bind. {yields} HCV core proteins on LDs facilitate viral particle assembly. {yields} We used a novel combination of CARS, two-photon fluorescence, and DIC microscopies. {yields} Particle tracking experiments show that core slowly affects LD localization. {yields} Particle tracking measured the change in speed and directionality of LD movement. -- Abstract: The hepatitis C virus (HCV) is a global health problem, with limited treatment options and no vaccine available. HCV uses components of the host cell to proliferate, including lipid droplets (LD) onto which HCV core proteins bind and facilitate viral particle assembly. We have measured the dynamics of HCV core protein-mediated changes in LDs and rates of LD movement on microtubules using a combination of coherent anti-Stokes Raman scattering (CARS), two-photon fluorescence (TPF), and differential interference contrast (DIC) microscopies. Results show that the HCV core protein induces rapid increases in LD size. Particle tracking experiments show that HCV core protein slowly affects LD localization by controlling the directionality of LD movement on microtubules. These dynamic processes ultimately aid HCV in propagating and the molecules and interactions involved represent novel targets for potential therapeutic intervention.

  9. Exceptional Heterogeneity in Viral Evolutionary Dynamics Characterises Chronic Hepatitis C Virus Infection

    PubMed Central

    Lemey, Philippe; Farci, Patrizia; Pybus, Oliver G.

    2016-01-01

    The treatment of HCV infection has seen significant progress, particularly since the approval of new direct-acting antiviral drugs. However these clinical achievements have been made despite an incomplete understanding of HCV replication and within-host evolution, especially compared with HIV-1. Here, we undertake a comprehensive analysis of HCV within-host evolution during chronic infection by investigating over 4000 viral sequences sampled longitudinally from 15 HCV-infected patients. We compare our HCV results to those from a well-studied HIV-1 cohort, revealing key differences in the evolutionary behaviour of these two chronic-infecting pathogens. Notably, we find an exceptional level of heterogeneity in the molecular evolution of HCV, both within and among infected individuals. Furthermore, these patterns are associated with the long-term maintenance of viral lineages within patients, which fluctuate in relative frequency in peripheral blood. Together, our findings demonstrate that HCV replication behavior is complex and likely comprises multiple viral subpopulations with distinct evolutionary dynamics. The presence of a structured viral population can explain apparent paradoxes in chronic HCV infection, such as rapid fluctuations in viral diversity and the reappearance of viral strains years after their initial detection. PMID:27631086

  10. Exceptional Heterogeneity in Viral Evolutionary Dynamics Characterises Chronic Hepatitis C Virus Infection.

    PubMed

    Raghwani, Jayna; Rose, Rebecca; Sheridan, Isabelle; Lemey, Philippe; Suchard, Marc A; Santantonio, Teresa; Farci, Patrizia; Klenerman, Paul; Pybus, Oliver G

    2016-09-01

    The treatment of HCV infection has seen significant progress, particularly since the approval of new direct-acting antiviral drugs. However these clinical achievements have been made despite an incomplete understanding of HCV replication and within-host evolution, especially compared with HIV-1. Here, we undertake a comprehensive analysis of HCV within-host evolution during chronic infection by investigating over 4000 viral sequences sampled longitudinally from 15 HCV-infected patients. We compare our HCV results to those from a well-studied HIV-1 cohort, revealing key differences in the evolutionary behaviour of these two chronic-infecting pathogens. Notably, we find an exceptional level of heterogeneity in the molecular evolution of HCV, both within and among infected individuals. Furthermore, these patterns are associated with the long-term maintenance of viral lineages within patients, which fluctuate in relative frequency in peripheral blood. Together, our findings demonstrate that HCV replication behavior is complex and likely comprises multiple viral subpopulations with distinct evolutionary dynamics. The presence of a structured viral population can explain apparent paradoxes in chronic HCV infection, such as rapid fluctuations in viral diversity and the reappearance of viral strains years after their initial detection. PMID:27631086

  11. Hepatic glutathione contributes to attenuation of thioacetamide-induced hepatic necrosis due to suppression of oxidative stress in diet-induced obese mice.

    PubMed

    Shirai, Makoto; Matsuoka, Miho; Makino, Toshihiko; Kai, Kiyonori; Teranishi, Munehiro; Takasaki, Wataru

    2015-08-01

    We previously reported that hepatic necrosis induced by thioacetamide (TA), a hepatotoxicant, was attenuated in mice fed a high-fat diet (HFD mice) in comparison with mice fed a normal rodent diet (ND mice). In this study, we focused on investigation of the mechanism of the attenuation. Hepatic content of thiobarbituric acid reactive substances (TBARS), an oxidative stress marker, significantly increased in ND mice at 24 and 48 hr after TA administration in comparison to that in vehicle-treated ND mice. At these time points, severe hepatic necrosis was observed in ND mice. Treatment with an established antioxidant, butylated hydroxyanisole, attenuated the TA-induced hepatic necrosis in ND mice. In contrast, in HFD mice, hepatic TBARS content did not increase, and hepatic necrosis was attenuated in comparison with ND mice at 24 and 48 hr after TA dosing. Metabolomics analysis regarding hepatic glutathione, a biological antioxidant, revealed decreased glutathione and changes in the amount of glutathione metabolism-related metabolites, such as increased ophtalmate and decreased cysteine, and this indicated activation of glutathione synthesis and usage in HFD mice. Finally, after treatment with L-buthionine-S,R-sulfoxinine, an inhibitor of glutathione synthesis, TA-induced hepatic necrosis was enhanced and hepatic TBARS contents increased after TA dosing in HFD mice. These results suggested that activated synthesis and usage of hepatic GSH, which suppresses hepatic oxidative stress, is one of the factors that attenuate TA-induced hepatic necrosis in HFD mice. PMID:26165648

  12. Hepatitis C Virus Deletion Mutants Are Found in Individuals Chronically Infected with Genotype 1 Hepatitis C Virus in Association with Age, High Viral Load and Liver Inflammatory Activity.

    PubMed

    Cheroni, Cristina; Donnici, Lorena; Aghemo, Alessio; Balistreri, Francesca; Bianco, Annalisa; Zanoni, Valeria; Pagani, Massimiliano; Soffredini, Roberta; D'Ambrosio, Roberta; Rumi, Maria Grazia; Colombo, Massimo; Abrignani, Sergio; Neddermann, Petra; De Francesco, Raffaele

    2015-01-01

    Hepatitis C virus (HCV) variants characterized by genomic deletions in the structural protein region have been sporadically detected in liver and serum of hepatitis C patients. These defective genomes are capable of autonomous RNA replication and are packaged into infectious viral particles in cells co-infected with the wild-type virus. The prevalence of such forms in the chronically HCV-infected population and the impact on the severity of liver disease or treatment outcome are currently unknown. In order to determine the prevalence of HCV defective variants and to study their association with clinical characteristics, a screening campaign was performed on pre-therapy serum samples from a well-characterized cohort of previously untreated genotype 1 HCV-infected patients who received treatment with PEG-IFNα and RBV. 132 subjects were successfully analyzed for the presence of defective species exploiting a long-distance nested PCR assay. HCV forms with deletions predominantly affecting E1, E2 and p7 proteins were found in a surprising high fraction of the subjects (25/132, 19%). Their presence was associated with patient older age, higher viral load and increased necroinflammatory activity in the liver. While the presence of circulating HCV carrying deletions in the E1-p7 region did not appear to significantly influence sustained virological response rates to PEG-IFNα/RBV, our study indicates that the presence of these subgenomic HCV mutants could be associated with virological relapse in patients who did not have detectable viremia at the end of the treatment.

  13. Hepatitis C Virus Deletion Mutants Are Found in Individuals Chronically Infected with Genotype 1 Hepatitis C Virus in Association with Age, High Viral Load and Liver Inflammatory Activity

    PubMed Central

    Aghemo, Alessio; Balistreri, Francesca; Bianco, Annalisa; Zanoni, Valeria; Pagani, Massimiliano; Soffredini, Roberta; D’Ambrosio, Roberta; Rumi, Maria Grazia; Colombo, Massimo; Abrignani, Sergio; Neddermann, Petra; De Francesco, Raffaele

    2015-01-01

    Hepatitis C virus (HCV) variants characterized by genomic deletions in the structural protein region have been sporadically detected in liver and serum of hepatitis C patients. These defective genomes are capable of autonomous RNA replication and are packaged into infectious viral particles in cells co-infected with the wild-type virus. The prevalence of such forms in the chronically HCV-infected population and the impact on the severity of liver disease or treatment outcome are currently unknown. In order to determine the prevalence of HCV defective variants and to study their association with clinical characteristics, a screening campaign was performed on pre-therapy serum samples from a well-characterized cohort of previously untreated genotype 1 HCV-infected patients who received treatment with PEG-IFNα and RBV. 132 subjects were successfully analyzed for the presence of defective species exploiting a long-distance nested PCR assay. HCV forms with deletions predominantly affecting E1, E2 and p7 proteins were found in a surprising high fraction of the subjects (25/132, 19%). Their presence was associated with patient older age, higher viral load and increased necroinflammatory activity in the liver. While the presence of circulating HCV carrying deletions in the E1-p7 region did not appear to significantly influence sustained virological response rates to PEG-IFNα/RBV, our study indicates that the presence of these subgenomic HCV mutants could be associated with virological relapse in patients who did not have detectable viremia at the end of the treatment. PMID:26405760

  14. Alginate hydrogel protects encapsulated hepatic HuH-7 cells against hepatitis C virus and other viral infections.

    PubMed

    Tran, Nhu-Mai; Dufresne, Murielle; Helle, François; Hoffmann, Thomas Walter; François, Catherine; Brochot, Etienne; Paullier, Patrick; Legallais, Cécile; Duverlie, Gilles; Castelain, Sandrine

    2014-01-01

    Cell microencapsulation in alginate hydrogel has shown interesting applications in regenerative medicine and the biomedical field through implantation of encapsulated tissue or for bioartificial organ development. Although alginate solution is known to have low antiviral activity, the same property regarding alginate gel has not yet been studied. The aim of this work is to investigate the potential protective effect of alginate encapsulation against hepatitis C virus (HCV) infection for a hepatic cell line (HuH-7) normally permissive to the virus. Our results showed that alginate hydrogel protects HuH-7 cells against HCV when the supernatant was loaded with HCV. In addition, alginate hydrogel blocked HCV particle release out of the beads when the HuH-7 cells were previously infected and encapsulated. There was evidence of interaction between the molecules of alginate hydrogel and HCV, which was dose- and incubation time-dependent. The protective efficiency of alginate hydrogel towards HCV infection was confirmed against a variety of viruses, whether or not they were enveloped. This promising interaction between an alginate matrix and viruses, whose chemical mechanisms are discussed, is of great interest for further medical therapeutic applications based on tissue engineering.

  15. Alginate Hydrogel Protects Encapsulated Hepatic HuH-7 Cells against Hepatitis C Virus and Other Viral Infections

    PubMed Central

    Tran, Nhu-Mai; Dufresne, Murielle; Helle, François; Hoffmann, Thomas Walter; François, Catherine; Brochot, Etienne; Paullier, Patrick; Legallais, Cécile; Duverlie, Gilles; Castelain, Sandrine

    2014-01-01

    Cell microencapsulation in alginate hydrogel has shown interesting applications in regenerative medicine and the biomedical field through implantation of encapsulated tissue or for bioartificial organ development. Although alginate solution is known to have low antiviral activity, the same property regarding alginate gel has not yet been studied. The aim of this work is to investigate the potential protective effect of alginate encapsulation against hepatitis C virus (HCV) infection for a hepatic cell line (HuH-7) normally permissive to the virus. Our results showed that alginate hydrogel protects HuH-7 cells against HCV when the supernatant was loaded with HCV. In addition, alginate hydrogel blocked HCV particle release out of the beads when the HuH-7 cells were previously infected and encapsulated. There was evidence of interaction between the molecules of alginate hydrogel and HCV, which was dose- and incubation time-dependent. The protective efficiency of alginate hydrogel towards HCV infection was confirmed against a variety of viruses, whether or not they were enveloped. This promising interaction between an alginate matrix and viruses, whose chemical mechanisms are discussed, is of great interest for further medical therapeutic applications based on tissue engineering. PMID:25310111

  16. Comparison of Next-Generation Sequencing Technologies for Comprehensive Assessment of Full-Length Hepatitis C Viral Genomes.

    PubMed

    Thomson, Emma; Ip, Camilla L C; Badhan, Anjna; Christiansen, Mette T; Adamson, Walt; Ansari, M Azim; Bibby, David; Breuer, Judith; Brown, Anthony; Bowden, Rory; Bryant, Josie; Bonsall, David; Da Silva Filipe, Ana; Hinds, Chris; Hudson, Emma; Klenerman, Paul; Lythgow, Kieren; Mbisa, Jean L; McLauchlan, John; Myers, Richard; Piazza, Paolo; Roy, Sunando; Trebes, Amy; Sreenu, Vattipally B; Witteveldt, Jeroen; Barnes, Eleanor; Simmonds, Peter

    2016-10-01

    Affordable next-generation sequencing (NGS) technologies for hepatitis C virus (HCV) may potentially identify both viral genotype and resistance genetic motifs in the era of directly acting antiviral (DAA) therapies. This study compared the ability of high-throughput NGS methods to generate full-length, deep, HCV sequence data sets and evaluated their utility for diagnostics and clinical assessment. NGS methods using (i) unselected HCV RNA (metagenomics), (ii) preenrichment of HCV RNA by probe capture, and (iii) HCV preamplification by PCR implemented in four United Kingdom centers were compared. Metrics of sequence coverage and depth, quasispecies diversity, and detection of DAA resistance-associated variants (RAVs), mixed HCV genotypes, and other coinfections were compared using a panel of samples with different viral loads, genotypes, and mixed HCV genotypes/subtypes [geno(sub)types]. Each NGS method generated near-complete genome sequences from more than 90% of samples. Enrichment methods and PCR preamplification generated greater sequence depth and were more effective for samples with low viral loads. All NGS methodologies accurately identified mixed HCV genotype infections. Consensus sequences generated by different NGS methods were generally concordant, and majority RAVs were consistently detected. However, methods differed in their ability to detect minor populations of RAVs. Metagenomic methods identified human pegivirus coinfections. NGS provided a rapid, inexpensive method for generating whole HCV genomes to define infecting genotypes, RAVs, comprehensive viral strain analysis, and quasispecies diversity. Enrichment methods are particularly suited for high-throughput analysis while providing the genotype and information on potential DAA resistance. PMID:27385709

  17. Comparison of Next-Generation Sequencing Technologies for Comprehensive Assessment of Full-Length Hepatitis C Viral Genomes

    PubMed Central

    Thomson, Emma; Ip, Camilla L. C.; Badhan, Anjna; Christiansen, Mette T.; Adamson, Walt; Ansari, M. Azim; Breuer, Judith; Brown, Anthony; Bowden, Rory; Bonsall, David; Da Silva Filipe, Ana; Hinds, Chris; Hudson, Emma; Klenerman, Paul; Lythgow, Kieren; Mbisa, Jean L.; McLauchlan, John; Myers, Richard; Piazza, Paolo; Roy, Sunando; Trebes, Amy; Sreenu, Vattipally B.; Witteveldt, Jeroen; Simmonds, Peter

    2016-01-01

    Affordable next-generation sequencing (NGS) technologies for hepatitis C virus (HCV) may potentially identify both viral genotype and resistance genetic motifs in the era of directly acting antiviral (DAA) therapies. This study compared the ability of high-throughput NGS methods to generate full-length, deep, HCV sequence data sets and evaluated their utility for diagnostics and clinical assessment. NGS methods using (i) unselected HCV RNA (metagenomics), (ii) preenrichment of HCV RNA by probe capture, and (iii) HCV preamplification by PCR implemented in four United Kingdom centers were compared. Metrics of sequence coverage and depth, quasispecies diversity, and detection of DAA resistance-associated variants (RAVs), mixed HCV genotypes, and other coinfections were compared using a panel of samples with different viral loads, genotypes, and mixed HCV genotypes/subtypes [geno(sub)types]. Each NGS method generated near-complete genome sequences from more than 90% of samples. Enrichment methods and PCR preamplification generated greater sequence depth and were more effective for samples with low viral loads. All NGS methodologies accurately identified mixed HCV genotype infections. Consensus sequences generated by different NGS methods were generally concordant, and majority RAVs were consistently detected. However, methods differed in their ability to detect minor populations of RAVs. Metagenomic methods identified human pegivirus coinfections. NGS provided a rapid, inexpensive method for generating whole HCV genomes to define infecting genotypes, RAVs, comprehensive viral strain analysis, and quasispecies diversity. Enrichment methods are particularly suited for high-throughput analysis while providing the genotype and information on potential DAA resistance. PMID:27385709

  18. Prevalence and severity of depression in chronic viral hepatitis in Iran

    PubMed Central

    Mirabdolhagh Hazaveh, Mojgan; Dormohammadi Toosi, Taraneh; Nasiri Toosi, Mohsen; Tavakoli, Amir; Shahbazi, Fatemeh

    2015-01-01

    Aim: The aim of this study was to compare the prevalence and severity of depression in chronic hepatitis B (CHB) patients, chronic hepatitis C (CHC) patients, and healthy participants. Methods: Two hundred and fifty-three persons participated in this cross-sectional study between 2011 and 2012 in Imam Khomeini Hospital. The prevalence and severity of depression were assessed using the Hamilton Scale. Results: There was significantly higher prevalence of depression in CHC patients (35.9%) than in healthy participants (11.3%) and CHB patients (19.8%) (both P < 0.01). However, CHB and CHC patients did not differ significantly in their depression prevalence after excluding inactive hepatitis B surface antigen (HBsAg) carriers (29.3% vs. 35.9%; P > 0.05). Inactive HBsAg carriers differed significantly from CHB patients—excluding inactive HBsAg carriers—in depression prevalence (10.0% vs. 29.3%; P < 0.05). No statistically significant difference was found in depression severity between all groups (P > 0.05). Conclusion: Depression screening in chronic hepatitis B and chronic hepatitis C patients may be beneficial in disease management. PMID:25663386

  19. Hepatitis A Test

    MedlinePlus

    ... be limited. Home Visit Global Sites Search Help? Hepatitis A Testing Share this page: Was this page ... HAV-Ab total; Anti-HAV Formal name: Viral Hepatitis A Antibody Related tests: Hepatitis B Testing ; Hepatitis ...

  20. Autologous blood donor screening indicated a lower prevalence of viral hepatitis in East vs West Germany: epidemiological benefit from established health resources.

    PubMed

    Wiegand, J; Luz, B; Mengelkamp, A-K; Moog, R; Koscielny, J; Halm-Heinrich, I; Susemihl, C; Bentzien, F; Diekmann, J; Wernet, D; Karger, R; Angert, K; Schmitt-Thomssen, A; Kiefel, V; Lutter, K; Hesse, R; Kätzel, R; Opitz, A; Luhm, J; Barz, D; Leib, U; Matthes, G; Tillmann, H L

    2009-10-01

    Prevalence data concerning viral hepatitis and human immunodeficiency virus (HIV) in the general population are usually scarce. We aimed for a large cohort representative of the general population that required little funding. Autologous blood donors are relatively representative of the general population, and are tested for viral hepatitis and HIV in many countries. However, frequently these data are not captured for epidemiologic purposes. We analysed data from well over 35,000 autologous blood donors as recorded in 21 different transfusion centres for anti-hepatitis C virus (HCV), HBsAg and anti-HIV, as well as TPHA if available. We found a lower prevalence of hepatitis B virus and HCV in East vs West Germany, 0.2%vs 0.32% and 0.16%vs 0.32% respectively, which confirms earlier data in smaller cohorts, thus supporting the value of our approach. HIV was too rare to disclose significant differences, 0.01%vs 0.02%. TPHA was higher in East (0.34%) vs West Germany (0.29%) without significant differences. HCV was more frequent in women vs men. Transfusion institutes managing autologous blood donations should be used as a resource for epidemiological data relating to viral hepatitis and HIV, if such testing is performed routinely. This approach generates data relating to the general population with special emphasis on undiagnosed cases.

  1. [A system for the mass combined vaccination of the adult population against influenza, viral hepatitis, typhoid, meningitis and diphtheria].

    PubMed

    Gapochko, K G; Titova, T S; Kharitonova, V A; Misnikov, O P; Savel'ev, A P; Stepanov, A V; Alliluev, A P; Bichurina, M A; Maksimova, N M; Ozeretskovskiĭ, N A

    1993-01-01

    A safe, moderately reactogenic and immunologically effective scheme of complex (combined) immunization against meningitis A, diphtheria, typhoid fever, viral hepatitis A and influenza has been developed as the result of experimental and clinico-immunological studies. Depending on the epidemiological situation, the newly developed scheme can be used in two variants. According to the first variant of this scheme, the following preparations are injected subcutaneously into three different sites: a mixture of group A meningococcal vaccine and diphtheria toxoid, typhoid vaccine and influenza vaccine. The second variant of the scheme differs from its first variant in using intramuscular injection of normal human immunoglobulin instead of injection of influenza vaccine. Moreover, in practical realization these variants may be altered by excluding vaccines, unnecessary under present conditions. The newly developed scheme of vaccinal prophylaxis is recommended for practical use. PMID:8067144

  2. Inhibition of bovine viral diarrhea virus in vitro by xanthohumol: comparisons with ribavirin and interferon-alpha and implications for the development of anti-hepatitis C virus agents.

    PubMed

    Zhang, Ni; Liu, Zhengwen; Han, Qunying; Chen, Jinghong; Lou, Sai; Qiu, Jianming; Zhang, Guoyu

    2009-11-01

    Xanthohumol (XN) is a natural compound with potential antiviral activity. In this study, the ability of XN to inhibit bovine viral diarrhea virus (BVDV), a surrogate model of hepatitis C virus (HCV), was investigated. The antiviral activity of XN was compared with that of ribavirin (RBV) and interferon (IFN)-alpha. The results showed that XN could inhibit BVDV induced cytopathic effects (CPE). At 1000 TCID(50) and 100 TCID(50), the values of 50% effective concentration (EC(50)) were 3.24+/-0.02 mg/l and 2.77+/-0.19 mg/l, respectively, and the therapeutic indices were >7.72 and >9.03, respectively. XN inhibited BVDV E2 expression and viral RNA levels in a dose-dependent manner. At 6.25mg/l, XN decreased the viral RNA from released virus by 3.83 log 10 at 1000 TCID(50) and to an undetectable level at 100 TCID(50), and decreased the viral RNA level in whole cell culture by 3.36 log 10 and 2.88 log 10 at 1000 TCID(50) and 100 TCID(50), respectively. The inhibitory activity of XN on CPE, BVDV E2 expression and viral RNA levels was stronger than that of RBV and weaker than that of IFN-alpha. These results indicate the need to investigate the anti-HCV potential of XN. PMID:19720145

  3. Cost-effectiveness of entecavir versus lamivudine for the suppression of viral replication in chronic hepatitis B patients in Brazil.

    PubMed

    Costa, Anna Maria N; L 'italien, Gilbert; Nita, Marcelo Eidi; Araujo, Evaldo Stanislau A

    2008-10-01

    Hepatitis B virus infection is an important public-health issue. Chronic patients have a higher risk of death due to complications, which increases health-care expenses in. Cost-effectiveness analysis of entecavir (ETV) versus lamivudine (LVD) for treatment of chronic hepatitis B, in e antigen (AgHBe)-positive and negative patients, based on two phase 3, controlled and randomized studies. A decision analysis model was developed, using the following endpoints: cost per patient with undetectable viral load and cost per quality life year (QALY) gained. Risks for complications (compensated or decompensated cirrhosis and hepatocellular carcinoma) were based on the cohort study REVEAL, published in 2006. The REVEAL parameters were applied to the results of the viral load levels obtained from the clinical assay data. The complication costs were based on a study of the disease cost conducted in Brazil, in 2005. The cost data were obtained predominantly from Sistema Unico de Saúde [SUS - Brazilian public health system] payment tables and drug price lists. The utility data were obtained from literature and life expectancy information was based on IBGE data. The analysis perspective was that of SUS. A discount rate of 3% per year was used. For the horizon of time of 10 years, the ETV had an incremental cost of approximately two million Brazilian Reais (R$) compared to LVD. Reducing the number of complications, ETV treatment reduced costs by around 3 million, reducing final costs by 1 million, for AgHBe-positive patients. ETV also reduced the incremental cost per QALY gained. ETV was found to be the most cost-effective alternative for AgHBe-positive and negative patients. PMID:19219274

  4. Insulin Resistance Induces Posttranslational Hepatic Sortilin 1 Degradation in Mice*

    PubMed Central

    Li, Jibiao; Matye, David J.; Li, Tiangang

    2015-01-01

    Insulin promotes hepatic apolipoprotein B100 (apoB100) degradation, whereas insulin resistance is a major cause of hepatic apoB100/triglyceride overproduction in type 2 diabetes. The cellular trafficking receptor sortilin 1 (Sort1) was recently identified to transport apoB100 to the lysosome for degradation in the liver and thus regulate plasma cholesterol and triglyceride levels. Genetic variation of SORT1 was strongly associated with cardiovascular disease risk in humans. The major goal of this study is to investigate the effect and molecular mechanism of insulin regulation of Sort1. Results showed that insulin induced Sort1 protein, but not mRNA, in AML12 cells. Treatment of PI3K or AKT inhibitors decreased Sort1 protein, whereas expression of constitutively active AKT induced Sort1 protein in AML12 cells. Consistently, hepatic Sort1 was down-regulated in diabetic mice, which was partially restored after the administration of the insulin sensitizer metformin. LC-MS/MS analysis further revealed that serine phosphorylation of Sort1 protein was required for insulin induction of Sort1 in a casein kinase 2-dependent manner and that inhibition of PI3K signaling or prevention of Sort1 phosphorylation accelerated proteasome-dependent Sort1 degradation. Administration of a PI3K inhibitor to mice decreased hepatic Sort1 protein and increased plasma cholesterol and triglyceride levels. Adenovirus-mediated overexpression of Sort1 in the liver prevented PI3K inhibitor-induced Sort1 down-regulation and decreased plasma triglyceride but had no effect on plasma cholesterol in mice. This study identified Sort1 as a novel target of insulin signaling and suggests that Sort1 may play a role in altered hepatic apoB100 metabolism in insulin-resistant conditions. PMID:25805502

  5. Microglia retard dengue virus-induced acute viral encephalitis

    PubMed Central

    Tsai, Tsung-Ting; Chen, Chia-Ling; Lin, Yee-Shin; Chang, Chih-Peng; Tsai, Cheng-Chieh; Cheng, Yi-Lin; Huang, Chao-Ching; Ho, Chien-Jung; Lee, Yi-Chao; Lin, Liang-Tzung; Jhan, Ming-Kai; Lin, Chiou-Feng

    2016-01-01

    Patients with dengue virus (DENV) infection may also present acute viral encephalitis through an unknown mechanism. Here, we report that encephalitic DENV-infected mice exhibited progressive hunchback posture, limbic seizures, limbic weakness, paralysis, and lethality 7 days post-infection. These symptoms were accompanied by CNS inflammation, neurotoxicity, and blood-brain barrier destruction. Microglial cells surrounding the blood vessels and injured hippocampus regions were activated by DENV infection. Pharmacologically depleting microglia unexpectedly increased viral replication, neuropathy, and mortality in DENV-infected mice. In microglia-depleted mice, the DENV infection-mediated expression of antiviral cytokines and the infiltration of CD8-positive cytotoxic T lymphocytes (CTLs) was abolished. DENV infection prompted the antigen-presenting cell-like differentiation of microglia, which in turn stimulated CTL proliferation and activation. These results suggest that microglial cells play a key role in facilitating antiviral immune responses against DENV infection and acute viral encephalitis. PMID:27279150

  6. Microglia retard dengue virus-induced acute viral encephalitis.

    PubMed

    Tsai, Tsung-Ting; Chen, Chia-Ling; Lin, Yee-Shin; Chang, Chih-Peng; Tsai, Cheng-Chieh; Cheng, Yi-Lin; Huang, Chao-Ching; Ho, Chien-Jung; Lee, Yi-Chao; Lin, Liang-Tzung; Jhan, Ming-Kai; Lin, Chiou-Feng

    2016-01-01

    Patients with dengue virus (DENV) infection may also present acute viral encephalitis through an unknown mechanism. Here, we report that encephalitic DENV-infected mice exhibited progressive hunchback posture, limbic seizures, limbic weakness, paralysis, and lethality 7 days post-infection. These symptoms were accompanied by CNS inflammation, neurotoxicity, and blood-brain barrier destruction. Microglial cells surrounding the blood vessels and injured hippocampus regions were activated by DENV infection. Pharmacologically depleting microglia unexpectedly increased viral replication, neuropathy, and mortality in DENV-infected mice. In microglia-depleted mice, the DENV infection-mediated expression of antiviral cytokines and the infiltration of CD8-positive cytotoxic T lymphocytes (CTLs) was abolished. DENV infection prompted the antigen-presenting cell-like differentiation of microglia, which in turn stimulated CTL proliferation and activation. These results suggest that microglial cells play a key role in facilitating antiviral immune responses against DENV infection and acute viral encephalitis. PMID:27279150

  7. Evidence of viral adaptation to HLA class I-restricted immune pressure in chronic hepatitis C virus infection.

    PubMed

    Gaudieri, Silvana; Rauch, Andri; Park, Lawrence P; Freitas, Elizabeth; Herrmann, Susan; Jeffrey, Gary; Cheng, Wendy; Pfafferott, Katja; Naidoo, Kiloshni; Chapman, Russell; Battegay, Manuel; Weber, Rainer; Telenti, Amalio; Furrer, Hansjakob; James, Ian; Lucas, Michaela; Mallal, Simon A

    2006-11-01

    Cellular immune responses are an important correlate of hepatitis C virus (HCV) infection outcome. These responses are governed by the host's human leukocyte antigen (HLA) type, and HLA-restricted viral escape mutants are a critical aspect of this host-virus interaction. We examined the driving forces of HCV evolution by characterizing the in vivo selective pressure(s) exerted on single amino acid residues within nonstructural protein 3 (NS3) by the HLA types present in two host populations. Associations between polymorphisms within NS3 and HLA class I alleles were assessed in 118 individuals from Western Australia and Switzerland with chronic hepatitis C infection, of whom 82 (69%) were coinfected with human immunodeficiency virus. The levels and locations of amino acid polymorphisms exhibited within NS3 were remarkably similar between the two cohorts and revealed regions under functional constraint and selective pressures. We identified specific HCV mutations within and flanking published epitopes with the correct HLA restriction and predicted escaped amino acid. Additional HLA-restricted mutations were identified that mark putative epitopes targeted by cell-mediated immune responses. This analysis of host-virus interaction reveals evidence of HCV adaptation to HLA class I-restricted immune pressure and identifies in vivo targets of cellular immune responses at the population level. PMID:17071929

  8. Efficient Inhibition of Hepatitis B Virus Infection by Acylated Peptides Derived from the Large Viral Surface Protein†

    PubMed Central

    Gripon, Philippe; Cannie, Isabelle; Urban, Stephan

    2005-01-01

    The lack of an appropriate in vitro infection system for the major human pathogen hepatitis B virus (HBV) has prevented a molecular understanding of the early infection events of HBV. We used the novel HBV-infectible cell line HepaRG and primary human hepatocytes to investigate the interference of infection by HBV envelope protein-derived peptides. We found that a peptide consisting of the authentically myristoylated N-terminal 47 amino acids of the pre-S1 domain of the large viral envelope protein (L protein) specifically prevented HBV infection, with a 50% inhibitory concentration (IC50) of 8 nM. The replacement of myristic acid with other hydrophobic moieties resulted in changes in the inhibitory activity, most notably by a decrease in the IC50 to picomolar concentrations for longer unbranched fatty acids. The obstruction of HepaRG cell susceptibility to HBV infection after short preincubation times with the peptides suggested that the peptides efficiently target and inactivate a receptor at the hepatocyte surface. Our data both shed light on the molecular mechanism of HBV entry into hepatocytes and provide a basis for the development of potent hepadnaviral entry inhibitors as a novel therapeutic concept for the treatment of hepatitis Β. PMID:15650187

  9. Viral RNA but no evidence of replication can be detected in the peripheral blood mononuclear cells of hepatitis E virus infected patients

    PubMed Central

    Ippagunta, Sirish Kumar; Naik, Sita; Jameel, Shahid; KN, Sudha Ramana; Aggarwal, Rakesh

    2010-01-01

    SUMMARY Hepatitis E virus (HEV) infection is an important cause of acute viral hepatitis in several developing countries, but has recently been shown to cause chronic hepatitis in immunosuppressed persons. Other hepatotropic viruses that cause chronic infection have been shown to infect peripheral blood mononuclear cells (PBMCs) and to persist in those cells. We therefore decided to look for evidence of replication of HEV in PBMCs obtained from patients with acute hepatitis E, using strand-specific assays for positive and negative HEV RNA. Of the 44 patients with acute hepatitis E during an outbreak in India, including 27 with detectable IgM anti-HEV and 19 with detectable serum HEV RNA, 11 had detectable HEV RNA in their PBMCs. However, of the six PBMC specimens with strong HEV RNA signal, none had detectable negative-strand-HEV RNA, a marker of viral replication. These findings indicate the presence of HEV RNA but the absence of its replication in PBMCs from patients with acute hepatitis E. PMID:20659304

  10. Stable cytotoxic T cell escape mutation in hepatitis C virus is linked to maintenance of viral fitness.

    PubMed

    Uebelhoer, Luke; Han, Jin-Hwan; Callendret, Benoit; Mateu, Guaniri; Shoukry, Naglaa H; Hanson, Holly L; Rice, Charles M; Walker, Christopher M; Grakoui, Arash

    2008-01-01

    Mechanisms by which hepatitis C virus (HCV) evades cellular immunity to establish persistence in chronically infected individuals are not clear. Mutations in human leukocyte antigen (HLA) class I-restricted epitopes targeted by CD8(+) T cells are associated with persistence, but the extent to which these mutations affect viral fitness is not fully understood. Previous work showed that the HCV quasispecies in a persistently infected chimpanzee accumulated multiple mutations in numerous class I epitopes over a period of 7 years. During the acute phase of infection, one representative epitope in the C-terminal region of the NS3/4A helicase, NS3(1629-1637), displayed multiple serial amino acid substitutions in major histocompatibility complex (MHC) anchor and T cell receptor (TCR) contact residues. Only one of these amino acid substitutions at position 9 (P9) of the epitope was stable in the quasispecies. We therefore assessed the effect of each mutation observed during in vivo infection on viral fitness and T cell responses using an HCV subgenomic replicon system and a recently developed in vitro infectious virus cell culture model. Mutation of a position 7 (P7) TCR-contact residue, I1635T, expectedly ablated the T cell response without affecting viral RNA replication or virion production. In contrast, two mutations at the P9 MHC-anchor residue abrogated antigen-specific T cell responses, but additionally decreased viral RNA replication and virion production. The first escape mutation, L1637P, detected in vivo only transiently at 3 mo after infection, decreased viral production, and reverted to the parental sequence in vitro. The second P9 variant, L1637S, which was stable in vivo through 7 years of follow-up, evaded the antigen-specific T cell response and did not revert in vitro despite being less optimal in virion production compared to the parental virus. These studies suggest that HCV escape mutants emerging early in infection are not necessarily stable, but are

  11. Transmission of Hepatitis C Virus Among People Who Inject Drugs: Viral Stability and Association With Drug Preparation Equipment

    PubMed Central

    Doerrbecker, Juliane; Behrendt, Patrick; Mateu-Gelabert, Pedro; Ciesek, Sandra; Riebesehl, Nina; Wilhelm, Corinne; Steinmann, Joerg; Pietschmann, Thomas; Steinmann, Eike

    2013-01-01

    Background. Hepatitis C virus (HCV) transmission among people who inject drugs remains a challenging public health problem. We investigated the risk of HCV transmission by analyzing the direct association of HCV with filters, water to dilute drugs, and water containers. Methods. Experiments were designed to replicate practices by people who inject drugs and include routinely used injection equipment. HCV stability in water was assessed by inoculation of bottled water with HCV. Viral association with containers was investigated by filling the containers with water, inoculating the water with HCV, emptying the water, and refilling the container with fresh water. Transmission risk associated with drug preparation filters was determined after drawing virus through a filter and incubating the filter to release infectious particles. Results. HCV can survive for up to 3 weeks in bottled water. Water containers present a risk for HCV transmission, as infectious virions remained associated with water containers after washing. Physical properties of the water containers determined the degree of HCV contamination after containers were refilled with water. HCV was also associated with filter material, in which around 10% of the viral inoculum was detectable. Conclusions. This study demonstrates the potential risk of HCV transmission among injection drug users who share water, filters, and water containers and will help to define public health interventions to reduce HCV transmission. PMID:23129759

  12. Molecular Mechanisms of Viral and Host Cell Substrate Recognition by Hepatitis C Virus NS3/4A Protease

    SciTech Connect

    Romano, Keith P.; Laine, Jennifer M.; Deveau, Laura M.; Cao, Hong; Massi, Francesca; Schiffer, Celia A.

    2011-08-16

    Hepatitis C NS3/4A protease is a prime therapeutic target that is responsible for cleaving the viral polyprotein at junctions 3-4A, 4A4B, 4B5A, and 5A5B and two host cell adaptor proteins of the innate immune response, TRIF and MAVS. In this study, NS3/4A crystal structures of both host cell cleavage sites were determined and compared to the crystal structures of viral substrates. Two distinct protease conformations were observed and correlated with substrate specificity: (i) 3-4A, 4A4B, 5A5B, and MAVS, which are processed more efficiently by the protease, form extensive electrostatic networks when in complex with the protease, and (ii) TRIF and 4B5A, which contain polyproline motifs in their full-length sequences, do not form electrostatic networks in their crystal complexes. These findings provide mechanistic insights into NS3/4A substrate recognition, which may assist in a more rational approach to inhibitor design in the face of the rapid acquisition of resistance.

  13. Boronic acid-modified lipid nanocapsules: a novel platform for the highly efficient inhibition of hepatitis C viral entry

    NASA Astrophysics Data System (ADS)

    Khanal, Manakamana; Barras, Alexandre; Vausselin, Thibaut; Fénéant, Lucie; Boukherroub, Rabah; Siriwardena, Aloysius; Dubuisson, Jean; Szunerits, Sabine

    2015-01-01

    The search for viral entry inhibitors that selectively target viral envelope glycoproteins has attracted increasing interest in recent years. Amongst the handful of molecules reported to show activity as hepatitis C virus (HCV) entry inhibitors are a variety of glycan-binding proteins including the lectins, cyanovirin-N (CV-N) and griffithsin. We recently demonstrated that boronic acid-modified nanoparticles are able to reduce HCV entry through a similar mechanism to that of lectins. A major obstacle to any further development of these nanostructures as viral entry inhibitors is their only moderate maximal inhibition potential. In the present study, we report that lipid nanocapsules (LNCs), surface-functionalized with amphiphilic boronic acid (BA) through their post-insertion into the semi-rigid shell of the LNCs, are indeed far superior as HCV entry inhibitors when compared with previously reported nanostructures. These 2nd generation particles (BA-LNCs) are shown to prevent HCV infection in the micromolar range (IC50 = 5.4 μM of BA moieties), whereas the corresponding BA monomers show no significant effects even at the highest analyzed concentration (20 μM). The new BA-LNCs are the most promising boronolectin-based HCV entry inhibitors reported to date and are thus observed to show great promise in the development of a pseudolectin-based therapeutic agent.The search for viral entry inhibitors that selectively target viral envelope glycoproteins has attracted increasing interest in recent years. Amongst the handful of molecules reported to show activity as hepatitis C virus (HCV) entry inhibitors are a variety of glycan-binding proteins including the lectins, cyanovirin-N (CV-N) and griffithsin. We recently demonstrated that boronic acid-modified nanoparticles are able to reduce HCV entry through a similar mechanism to that of lectins. A major obstacle to any further development of these nanostructures as viral entry inhibitors is their only moderate maximal

  14. Hepatitis C: Questions to Ask Your Doctor about Your Diagnosis

    MedlinePlus

    ... to Ask Your Doctor about Your Diagnosis Viral Hepatitis Menu Menu Viral Hepatitis Viral Hepatitis Home For ... me? Other questions you want to ask: ______________________________________________________ ______________________________________________________ ______________________________________________________ ______________________________________________________ ______________________________________________________ ______________________________________________________ Search Hepatitis Search this website Submit Share this page Related ...

  15. Hepatitis C: Questions to Ask Your Doctor about Treatment

    MedlinePlus

    ... Questions to Ask Your Doctor about Treatment Viral Hepatitis Menu Menu Viral Hepatitis Viral Hepatitis Home For ... treatment? Other questions you want to ask: _______________________________________ _______________________________________ _______________________________________ Search Hepatitis Search this website Submit Share this page Related ...

  16. Geneticin Stabilizes the Open Conformation of the 5′ Region of Hepatitis C Virus RNA and Inhibits Viral Replication

    PubMed Central

    Ariza-Mateos, Ascensión; Díaz-Toledano, Rosa; Block, Timothy M.; Prieto-Vega, Samuel

    2015-01-01

    The aminoglycoside Geneticin (G418) is known to inhibit cell culture proliferation, via virus-specific mechanisms, of two different virus genera from the family Flaviviridae. Here, we tried to determine whether Geneticin can selectively alter the switching of the nucleotide 1 to 570 RNA region of hepatitis C virus (HCV) and, if so, whether this inhibits viral growth. Two structure-dependent RNases known to specifically cleave HCV RNA were tested in the presence or absence of the drug. One was the Synechocystis sp. RNase P ribozyme, which cleaves the tRNA-like domain around the AUG start codon under high-salt buffer conditions; the second was Escherichia coli RNase III, which recognizes a double-helical RNA switch element that changes the internal ribosome entry site (IRES) from a closed (C) conformation to an open (O) one. While the drug did not affect RNase P activity, it did inhibit RNase III in the micromolar range. Kinetic studies indicated that the drug favors the switch from the C to the O conformation of the IRES by stabilizing the distal double-stranded element and inhibiting further processing of the O form. We demonstrate that, because the RNA in this region is highly conserved and essential for virus survival, Geneticin inhibits HCV Jc1 NS3 expression, the release of the viral genomic RNA, and the propagation of HCV in Huh 7.5 cells. Our study highlights the crucial role of riboswitches in HCV replication and suggests the therapeutic potential of viral-RNA-targeted antivirals. PMID:26621620

  17. Evidence of recombination in quasispecies populations of a Hepatitis C Virus patient undergoing anti-viral therapy

    PubMed Central

    Moreno, María P; Casane, Didier; López, Lilia; Cristina, Juan

    2006-01-01

    Background/Aim Hepatitis C virus (HCV) has been the subject of intense research and clinical investigation as its major role in human disease has emerged. HCV circulates in vivo as a complex population of different but closely related viral variants, commonly referred to as a quasispecies. The extent to which recombination plays a role in the evolution of HCV quasispecies when patients are undergoing anti-viral therapy is currently unknown. In order to gain insight into these matters, we have performed a phylogenetic analysis of HCV quasispecies populations from six patients undergoing anti-viral therapy. Methods Putative recombinant sequences were identified with the use of SimPlot program. Recombination events were confirmed by bootscaning, using putative recombinant sequence as a query. Statistical support for the presence of a recombination event was done by the use of LARD program. Results A crossing-over event in the NS5A gene in a HCV strain recovered after four weeks of treatment was identified in quasispecies from a patient with sustained response. Putative parental-like strains were identified as strains circulating in previous weeks on the same patient. Conclusion Only one recombinant strain was detected in all patient quasispecies populations studied. The recombination break-point is situated on the PKR-binding region of NS5A. Although recombination may not appeared to be extensive in NS5A genes of HCV quasispecies populations of patients undergoing antiviral therapy, this possibility should be taken into account as a mechanism of genetic variation for HCV. PMID:17062150

  18. Rabies Virus Infection Induces the Formation of Stress Granules Closely Connected to the Viral Factories

    PubMed Central

    Nikolic, Jovan; Civas, Ahmet; Lagaudrière-Gesbert, Cécile; Blondel, Danielle

    2016-01-01

    Stress granules (SGs) are membrane-less dynamic structures consisting of mRNA and protein aggregates that form rapidly in response to a wide range of environmental cellular stresses and viral infections. They act as storage sites for translationally silenced mRNAs under stress conditions. During viral infection, SG formation results in the modulation of innate antiviral immune responses, and several viruses have the ability to either promote or prevent SG assembly. Here, we show that rabies virus (RABV) induces SG formation in infected cells, as revealed by the detection of SG-marker proteins Ras GTPase-activating protein-binding protein 1 (G3BP1), T-cell intracellular antigen 1 (TIA-1) and poly(A)-binding protein (PABP) in the RNA granules formed during viral infection. As shown by live cell imaging, RABV-induced SGs are highly dynamic structures that increase in number, grow in size by fusion events, and undergo assembly/disassembly cycles. Some SGs localize in close proximity to cytoplasmic viral factories, known as Negri bodies (NBs). Three dimensional reconstructions reveal that both structures remain distinct even when they are in close contact. In addition, viral mRNAs synthesized in NBs accumulate in the SGs during viral infection, revealing material exchange between both compartments. Although RABV-induced SG formation is not affected in MEFs lacking TIA-1, TIA-1 depletion promotes viral translation which results in an increase of viral replication indicating that TIA-1 has an antiviral effect. Inhibition of PKR expression significantly prevents RABV-SG formation and favors viral replication by increasing viral translation. This is correlated with a drastic inhibition of IFN-B gene expression indicating that SGs likely mediate an antiviral response which is however not sufficient to fully counteract RABV infection. PMID:27749929

  19. Update on the Development of Anti-Viral Agents Against Hepatitis C

    PubMed Central

    Macarthur, Kristin L.; Smolic, Robert; Smolic, Martina V.; Wu, Catherine H.

    2013-01-01

    Hepatitis C virus (HCV) infects nearly 170 million people worldwide and causes chronic hepatitis, cirrhosis, and hepatocellular carcinoma. The search for a drug regimen that maximizes efficacy and minimizes side effects is quickly evolving. This review will discuss a wide range of drug targets currently in all phases of development for the treatment of HCV. Direct data from agents in phase III/IV clinical trials will be presented, along with reported side-effect profiles. The mechanism of action of all treatments and resistance issues are highlighted. Special attention is given to available trial data supporting interferon-free treatment regimens. HCV has become an increasingly important public health concern, and it is important for physicians to stay up to date on the rapidly growing novel therapeutic options. PMID:26357602

  20. [VIRAL HEPATITIS C: EVOLUTION OF THE EPIDEMIOLOGIC PROCESS, EVOLUTION OF THE VIRUS].

    PubMed

    Zhebrun, A B; Kalinina, O V

    2016-01-01

    Periodization of the evolution of epidemic process of hepatitis C is given based on the results of phylodynamic, phylogeographic, historic and demographic studies: invasion of the virus into European and North-American population in 1700-1850; primary activation of the epidemic process in the years of the World War 1; expansive giowth of prevalence in 40--60s of the 20th century due to mass parenteral interventions; new rise due to heroine drug abuse in 60--80s of the 20th century; manifold reduction of incidence of acute hepatitis C in industrial countries for the last 10-15 years as a result of general medical measures of prevention of hemocontact infec-tions. A problem of possibility of hepatitis C management and necessity of evaluation of effectiveness of existing prophylaxis measures involving quantitative analytical methods of epidemiology is discussed. Data from phylogenetic studies on stages of hepatitis C virus evolution (HCV) are provided: division of its root genetic lineage with homologous hepaciviruses of animals 985--2013 years ago; division of HCV into genotypes 500--2000 years ago; division of genotypes into subtypes 70--300 years ago. Contribution of mutations and genetic recombinations into HCV evolution is discussed. Genotyping is stated as an inefficient approach for determination of pathogenicity determinants, immune evasion, non-responsiveness to therapy, as well as search for predictors of infection outcome. A necessity of genomic approach for these aims is justified, as well as for risk monitoring, ensuing from continuing evolution and biodiversity of HCV and other hepaciviruses. PMID:27029124

  1. [VIRAL HEPATITIS C: EVOLUTION OF THE EPIDEMIOLOGIC PROCESS, EVOLUTION OF THE VIRUS].

    PubMed

    Zhebrun, A B; Kalinina, O V

    2016-01-01

    Periodization of the evolution of epidemic process of hepatitis C is given based on the results of phylodynamic, phylogeographic, historic and demographic studies: invasion of the virus into European and North-American population in 1700-1850; primary activation of the epidemic process in the years of the World War 1; expansive giowth of prevalence in 40--60s of the 20th century due to mass parenteral interventions; new rise due to heroine drug abuse in 60--80s of the 20th century; manifold reduction of incidence of acute hepatitis C in industrial countries for the last 10-15 years as a result of general medical measures of prevention of hemocontact infec-tions. A problem of possibility of hepatitis C management and necessity of evaluation of effectiveness of existing prophylaxis measures involving quantitative analytical methods of epidemiology is discussed. Data from phylogenetic studies on stages of hepatitis C virus evolution (HCV) are provided: division of its root genetic lineage with homologous hepaciviruses of animals 985--2013 years ago; division of HCV into genotypes 500--2000 years ago; division of genotypes into subtypes 70--300 years ago. Contribution of mutations and genetic recombinations into HCV evolution is discussed. Genotyping is stated as an inefficient approach for determination of pathogenicity determinants, immune evasion, non-responsiveness to therapy, as well as search for predictors of infection outcome. A necessity of genomic approach for these aims is justified, as well as for risk monitoring, ensuing from continuing evolution and biodiversity of HCV and other hepaciviruses.

  2. Prevalence, Correlates, and Viral Dynamics of Hepatitis Delta Among Injection Drug Users

    PubMed Central

    Kucirka, Lauren M; Farzadegan, Homayoon; Feld, Jordan J.; Mehta, Shruti H.; Winters, Mark; Glenn, Jeffrey S; Kirk, Gregory D.; Segev, Dorry L.; Nelson, Kenrad E.; Marks, Morgan; Heller, Theo; Golub, Elizabeth T.

    2010-01-01

    Background Most hepatitis delta virus(HDV) prevalence estimates from the United States are over 10 years old, and HDV has shown significant temporal variation in other populations. HDV/hepatitis B(HBV) dual infection progresses rapidly, has more complications, and a different treatment regimen than HBV infection alone. Accurate estimates of prevalence and risk factors are important to help clinicians decide who to screen. Methods Injection drug users(IDUs) in Baltimore, MD positive for HBV serologic markers were tested for hepatitis delta antibody(HDAb) at two time periods: 1988-1989(n= 194) and 2005-2006(n=258). Those HDAb+ in 2005-2006 plus a random sample of HDAb-, HBV+ participants were tested for HDV-RNA, HBV-DNA, and HCV-RNA. Characteristics associated with HDV exposure and viremia were identified. Results HDV prevalence declined from 15% in 1988-1989 to 11% in 2005-2006. Among those with chronic HBV infection, prevalence increased from 29%(n=15/48) to 50%(n=19/38), p = 0.05. Visiting a shooting gallery was a strong correlate of HDAb positivity (relative risk=3.08, p=0.01). 8(32%) of those HDAb+ were HDV viremic. Viremic participants had elevated liver enzymes and more ER visits. Conclusions The temporal increase in HDV prevalence among those with chronic HBV infection is concerning; understanding this change should be a priority to prevent the burden from increasing. PMID:20701536

  3. A neurotoxic alcohol exposure paradigm does not induce hepatic encephalopathy.

    PubMed

    Hashimoto, Joel G; Wiren, Kristine M; Wilhelm, Clare J

    2016-01-01

    Alcohol abuse is associated with neurological dysfunction, brain morphological deficits and frank neurotoxicity. Although these disruptions may be a secondary effect due to hepatic encephalopathy, no clear evidence of causality is available. This study examined whether a 72h period of alcohol intoxication known to induce physical dependence, followed by a single withdrawal, was sufficient to induce signs of hepatic encephalopathy in male and female mice. Animals were continuously intoxicated via alcohol vapor inhalation, a procedure previously shown to induce significant neurotoxicity in female mice. At peak synchronized withdrawal (8h following the end of alcohol exposure), blood samples were taken and levels of several liver-regulated markers and brain swelling were characterized. Glutathione levels were also determined in the medial frontal cortex (mFC) and hippocampus. Results revealed elevated levels of cholesterol, albumin, alkaline phosphatase (ALP), alanine aminotransferase (ALT) and decreased levels of blood urea nitrogen and total bilirubin in alcohol-exposed male and female groups compared to controls. Brain water weight was not affected by alcohol exposure, though males tended to have slightly more water weight overall. Alcohol exposure led to reductions in tissue levels of glutathione in both the hippocampus and mFC which may indicate increased oxidative stress. Combined, these results suggest that hepatic encephalopathy does not appear to play a significant role in the neurotoxicity observed following alcohol exposure in this model. PMID:27268733

  4. Cross‐reactivity of hepatitis C virus specific vaccine‐induced T cells at immunodominant epitopes

    PubMed Central

    Kelly, Christabel; Swadling, Leo; Brown, Anthony; Capone, Stefania; Folgori, Antonella; Salio, Mariolina; Klenerman, Paul

    2014-01-01

    Viral diversity is a challenge to the development of a hepatitis C virus (HCV) vaccine. Following vaccination of humans with adenoviral vectors, we determined the capacity of T cells to target common viral variants at immundominant epitopes ex vivo. We identified two major variants for epitopes NS31073 and NS31446, and multiple variants for epitope NS31406 that occurred in >5% of genotype 1 and 3 sequences at a population level. Cross‐reactivity of vaccine‐induced T cells was determined using variant peptides in IFN‐γ ELISPOT assays. Vaccine‐induced T cells targeted approximately 90% of NS31073 genotype 1 sequences and 50% of NS31446 genotype 1 and 3 sequences. For NS31406, 62% of subtype‐1b sequences were targeted. Next, we assessed whether an in vitro priming system, using dendritic cells and T cells from healthy donors, could identify a variant of NS31406 that was maximally cross‐reactive. In vitro priming assays showed that of those tested the NS31406 vaccine variant was the most immunogenic. T cells primed with genotype 1 variants from subtype 1a or 1b were broadly cross‐reactive with other variants from the same subtype. We conclude that immunization with candidate HCV adenoviral vaccines generates cross‐reactive T cells at immunodominant epitopes. The degree of cross‐reactivity varies between epitopes and may be HCV‐subtype specific. PMID:25263407

  5. Delineating liver events in trichloroethylene-induced autoimmune hepatitis.

    PubMed

    Gilbert, Kathleen M; Przybyla, Beata; Pumford, Neil R; Han, Tao; Fuscoe, James; Schnackenberg, Laura K; Holland, Ricky D; Doss, Jason C; Macmillan-Crow, Lee Ann; Blossom, Sarah J

    2009-04-01

    Exposure to the environmental pollutant trichloroethylene (TCE) has been linked to autoimmune disease development in humans. Chronic (32-week) low-level exposure to TCE has been shown to promote autoimmune hepatitis in association with CD4(+) T cell activation in autoimmune-prone MRL+/+ mice. MRL+/+ mice are usually thought of as a model of systemic lupus rather than an organ-specific disease such as autoimmune hepatitis. Consequently, the present study examined gene expression and metabolites to delineate the liver events that skewed the autoimmune response toward that organ in TCE-treated mice. Female MRL+/+ mice were treated with 0.5 mg/mL TCE in their drinking water. The results showed that TCE-induced autoimmune hepatitis could be detected in as little as 26 weeks. TCE exposure also generated a time-dependent increase in the number of antibodies specific for liver proteins. The gene expression correlated with the metabolite analysis to show that TCE upregulated the methionine/homocysteine pathway in the liver after 26 weeks of exposure. The results also showed that TCE exposure altered the expression of selective hepatic genes associated with immunity and inflammation. On the basis of these results, future mechanistic studies will focus on how alterations in genes associated with immunity and inflammation, in conjunction with protein alterations in the liver, promote liver immunogenicity in TCE-treated MRL+/+ mice.

  6. Alcohol induced hepatic degeneration in a hepatitis C virus core protein transgenic mouse model.

    PubMed

    Noh, Dong-Hyung; Lee, Eun-Joo; Kim, Ah-Young; Lee, Eun-Mi; Min, Chang-Woo; Kang, Kyung-Ku; Lee, Myeong-Mi; Kim, Sang-Hyeob; Sung, Soo-Eun; Hwang, Meeyul; Yu, Dae-Yeul; Jeong, Kyu-Shik

    2014-01-01

    Hepatitis C virus (HCV) has become a major public health issue. It is prevalent in most countries. HCV infection frequently begins without clinical symptoms, before progressing to persistent viremia, chronic hepatitis, cirrhosis and hepatocellular carcinoma (HCC) in the majority of patients (70% to 80%). Alcohol is an independent cofactor that accelerates the development of HCC in chronic hepatitis C patients. The purpose of the current study was to evaluate ethanol-induced hepatic changes in HCV core-Tg mice and mutant core Tg mice. Wild type (NTG), core wild-Tg mice (TG-K), mutant core 116-Tg mice (TG-116) and mutant core 99-Tg mice (TG-99) were used in this investigation. All groups were given drinking water with 10% ethanol and 5% sucrose for 13 weeks. To observe liver morphological changes, we performed histopathological and immunohistochemical examinations. Histopathologically, NTG, TG-K and TG-116 mice showed moderate centrilobular necrosis, while severe centrilobular necrosis and hepatocyte dissociation were observed in TG-99 mice with increasing lymphocyte infiltration and piecemeal necrosis. In all groups, a small amount of collagen fiber was found, principally in portal areas. None of the mice were found to have myofibroblasts based on immunohistochemical staining specific for α-SMA. CYP2E1-positive cells were clearly detected in the centrilobular area in all groups. In the TG-99 mice, we also observed cells positive for CK8/18, TGF-β1 and phosphorylated (p)-Smad2/3 and p21 around the necrotic hepatocytes in the centrilobular area (p < 0.01). Based on our data, alcohol intake induced piecemeal necrosis and hepatocyte dissociation in the TG-99 mice. These phenomena involved activation of the TGF-β1/p-Smad2/3/p21 signaling pathway in hepatocytes. Data from this study will be useful for elucidating the association between alcohol intake and HCV infection.

  7. Development and assessment of a novel real-time PCR assay for quantitation of hepatitis D virus RNA to study viral kinetics in chronic hepatitis D.

    PubMed

    Katsoulidou, A; Manesis, E; Rokka, C; Issaris, C; Pagoni, A; Sypsa, V; Hatzakis, A

    2013-04-01

    Hepatitis delta virus (HDV) infection is a usually severe type of viral hepatitis associated with increased mortality and rapid evolution to cirrhosis. Currently, treatment is limited to extended interferon administration and measurement of HDV RNA blood levels is essential to judge the response. The aim of this study was to develop a highly sensitive and reproducible real-time reverse transcriptase-polymerase chain reaction (real-time RT-PCR) for the quantitation of circulating HDV RNA of all clades (1-8), and assess its usefulness in the follow-up of patients. The amplification was combined with molecular beacon technology using the LightCycler 2.0 system. The assay was specific and showed linearity over a wide range from 13 to 13 × 10(10) copies/mL. The 95% detection limit was 43.2 copies/mL. Intra-assay reproducibility, as expressed by the coefficient of variation, ranged from 1.84 to 18.61%, whereas the corresponding estimates for the inter-assay variability ranged from 0.57 to 10.18%. Finally, the dynamic profiles of six patients regarding virological (HDV RNA, HBV DNA), biochemical and serological data were constructed. We were able to observe that most patients who were treated with an interferon-based regime showed a significant reduction in delta viremia. In conclusion, our real-time RT-PCR for HDV RNA quantification combines high sensitivity and reproducibility in a high dynamic range, can provide important information for patient management and can be a useful tool for monitoring the response to antiviral therapies.

  8. [A case report of alverine-citrate-induced acute hepatitis].

    PubMed

    Han, Jee Young; Lee, Jin Woo; Kim, Joon Mee; Joo, Kowoon; Chon, Ung; Lee, Jung Il; Jeong, Seok; Lee, Don Haeng; Kim, Young Soo; Min, Kyung Sun

    2010-03-01

    Alverine citrate is one of the most commonly used antispasmodic drugs for patients with irritable bowel syndrome. Alverine-citrate-induced hepatotoxicity is extremely rare, with only a few cases having been reported worldwide. We present a case of a 75-year-old female patient who experienced complicated jaundice and abdominal discomfort after taking alverine citrate. Other causes of hepatitis were ruled out and the results of the liver function test returned to normal after ceasing the drug. This is the first case report in Korea of alverine-citrate-induced hepatotoxicity. PMID:20375645

  9. Intrahepatic endothelial and Kupffer cells involved in immunosuppressive cytokines and natural killer (NK)/NK T cell disorders in viral acute hepatitis

    PubMed Central

    Jacques, A; Bleau, C; Martin, J-P; Lamontagne, L

    2008-01-01

    During acute viral hepatitis, the intrahepatic tolerance sustained by immunosuppressive cytokines such as interleukin (IL)-4, IL-10, transforming growth factor (TGF)-β and prostaglandin E2 (PGE2), produced by Kupffer cells (KC), liver sinusoidal endothelial cells (LSEC), natural killer (NK) T cells and natural regulatory T cells may be disturbed. NK cells are recruited normally in the liver and produce interferon (IFN)-γ to control viral replication. The use of mouse hepatitis virus type 3 (MHV3) attenuated variants showing selected tropisms for KC or LSEC have allowed determining their roles in the disturbances of immune tolerance during viral hepatitis. Groups of C57BL/6 mice were infected with the pathogenic L2-MHV3 (KC+, LSEC+), low attenuated 51·6-MHV3 (KC+, LSEC−) or high attenuated CL12-MHV3 (KC−, LSEC−) variants for the first 3 days. Results showed that IL-10, TGF-β and PGE2 production in the liver decreased in L2-MHV3-infected mice and increased in 51·6-MHV3- and CL12-MHV3-infected mice. The ratio of IFN-γ/IL-4 in liver decreased in L2-MHV3-infected mice, while it was not (or low) altered in mice infected with the attenuated MHV3 variant mice. Phenotypic analysis of intrahepatic mononuclear cells revealed that apoptotic NK and NK T cells increased in mice infected with the L2-MHV3, but were minor in 51·6-MHV3- and CL12-MHV3-infected mice. The numbers of CD4+ forkhead box P3+ cells increased in the livers from low pathogenic CL12-MHV3 and YAC-MHV3-infected mice. These results indicate that viral permissivity of KC and LSEC is involved in the decrease of IL-10 and PGE2, while KC may play an additional role in the apoptosis of NK and NK T cells during acute viral hepatitis. PMID:18336588

  10. Apolipoprotein E Likely Contributes to a Maturation Step of Infectious Hepatitis C Virus Particles and Interacts with Viral Envelope Glycoproteins

    PubMed Central

    Lee, Ji-Young; Acosta, Eliana G.; Stoeck, Ina Karen; Long, Gang; Hiet, Marie-Sophie; Mueller, Birthe; Fackler, Oliver T.; Kallis, Stephanie

    2014-01-01

    ABSTRACT The assembly of infectious hepatitis C virus (HCV) particles is tightly linked to components of the very-low-density lipoprotein (VLDL) pathway. We and others have shown that apolipoprotein E (ApoE) plays a major role in production of infectious HCV particles. However, the mechanism by which ApoE contributes to virion assembly/release and how it gets associated with the HCV particle is poorly understood. We found that knockdown of ApoE reduces titers of infectious intra- and extracellular HCV but not of the related dengue virus. ApoE depletion also reduced amounts of extracellular HCV core protein without affecting intracellular core amounts. Moreover, we found that ApoE depletion affected neither formation of nucleocapsids nor their envelopment, suggesting that ApoE acts at a late step of assembly, such as particle maturation and infectivity. Importantly, we demonstrate that ApoE interacts with the HCV envelope glycoproteins, most notably E2. This interaction did not require any other viral proteins and depended on the transmembrane domain of E2 that also was required for recruitment of HCV envelope glycoproteins to detergent-resistant membrane fractions. These results suggest that ApoE plays an important role in HCV particle maturation, presumably by direct interaction with viral envelope glycoproteins. IMPORTANCE The HCV replication cycle is tightly linked to host cell lipid pathways and components. This is best illustrated by the dependency of HCV assembly on lipid droplets and the VLDL component ApoE. Although the role of ApoE for production of infectious HCV particles is well established, it is still poorly understood how ApoE contributes to virion formation and how it gets associated with HCV particles. Here, we provide experimental evidence that ApoE likely is required for an intracellular maturation step of HCV particles. Moreover, we demonstrate that ApoE associates with the viral envelope glycoproteins. This interaction appears to be dispensable

  11. Prevalence of hepatitis A viral RNA and antibodies among Chinese blood donors.

    PubMed

    Sun, P; Su, N; Lin, F Z; Ma, L; Wang, H J; Rong, X; Dai, Y D; Li, J; Jian, Z W; Tang, L H; Xiao, W; Li, C Q

    2015-12-09

    Like other developing countries, China was reported to have a relatively high seroprevalence of anti-hepatitis A antibodies (anti-HAV). However, no studies have evaluated the prevalence of anti-HAV and HAV RNA among voluntary blood donors with or without elevated serum alanine transaminase (ALT) levels. Anti-HAV antibodies were detected using an enzyme-linked immunosorbent assay, and reverse transcription quantitative polymerase chain reaction was carried out for detection of HAV RNA. In the current study, we analyzed a total of 450 serum samples with elevated ALT levels (≥40 U/L) and 278 serum samples with non-elevated ALT levels. Seroprevalence rates of anti-HAV were 51.6% in donors with elevated ALT and 41.4% in donors with non-elevated ALT; however, none of the samples was positive for HAV RNA. The results of our study showed lower seroprevalence rates of anti-HAV in blood donors (irrespective of ALT levels) than those in published data on Chinese populations. Although donors with elevated ALT had statistically higher prevalence rates of anti- HAV than did those with non-elevated ALT, none of the serum samples had detectable levels of the active virus. In conclusion, our results demonstrate that the transmission of hepatitis A by blood transfusion will occur rarely.

  12. Pharmacogenetics of ribavirin-induced anemia in hepatitis C.

    PubMed

    Ampuero, Javier; Romero-Gómez, Manuel

    2016-09-01

    Pharmacogenetics assesses inherited genetic differences in drug metabolic pathways and its role in medicine is growing. Ribavirin (RBV) and peginterferon were the standard of care therapy in hepatitis C virus infection during 15 years, with the addition of first-generation protease inhibitors at the beginning of 2010s. New direct-acting agents are the new standard of care, but RBV remains important in some scenarios. The main adverse effect of RBV is anemia, which requires dose reduction and even stopping treatment in some patients. Pharmacogenetics has identified ITPA and SLC28/29 genes to be closely related to RBV-induced anemia. The routine evaluation of these genes could help to identify those patients at risk of developing anemia during the hepatitis C virus treatment. PMID:27547881

  13. Drug-induced acute autoimmune hepatitis during combination therapy with atorvastatin and ezetimibe.

    PubMed

    van Heyningen, Charles

    2005-09-01

    A case is presented of a patient who developed acute hepatitis during cholesterol-lowering treatment with atorvastatin and ezetimibe. Further investigations reveal a probable drug-induced autoimmune hepatitis, and ezetimibe is considered to be the most likely causal agent. This case is the first report of an autoimmune hepatitis associated with ezetimibe therapy.

  14. Influenza Virus Induces Inflammatory Response in Mouse Primary Cortical Neurons with Limited Viral Replication

    PubMed Central

    Jiang, Zhiwu; Gu, Liming; Chen, Yanxia

    2016-01-01

    Unlike stereotypical neurotropic viruses, influenza A viruses have been detected in the brain tissues of human and animal models. To investigate the interaction between neurons and influenza A viruses, mouse cortical neurons were isolated, infected with human H1N1 influenza virus, and then examined for the production of various inflammatory molecules involved in immune response. We found that replication of the influenza virus in neurons was limited, although early viral transcription was not affected. Virus-induced neuron viability decreased at 6 h postinfection (p.i.) but increased at 24 h p.i. depending upon the viral strain. Virus-induced apoptosis and cytopathy in primary cortical neurons were not apparent at 24 h p.i. The mRNA levels of inflammatory cytokines, chemokines, and type I interferons were upregulated at 6 h and 24 h p.i. These results indicate that the influenza virus induces inflammatory response in mouse primary cortical neurons with limited viral replication. The cytokines released in viral infection-induced neuroinflammation might play critical roles in influenza encephalopathy, rather than in viral replication-induced cytopathy. PMID:27525278

  15. Influenza Virus Induces Inflammatory Response in Mouse Primary Cortical Neurons with Limited Viral Replication.

    PubMed

    Wang, Gefei; Li, Rui; Jiang, Zhiwu; Gu, Liming; Chen, Yanxia; Dai, Jianping; Li, Kangsheng

    2016-01-01

    Unlike stereotypical neurotropic viruses, influenza A viruses have been detected in the brain tissues of human and animal models. To investigate the interaction between neurons and influenza A viruses, mouse cortical neurons were isolated, infected with human H1N1 influenza virus, and then examined for the production of various inflammatory molecules involved in immune response. We found that replication of the influenza virus in neurons was limited, although early viral transcription was not affected. Virus-induced neuron viability decreased at 6 h postinfection (p.i.) but increased at 24 h p.i. depending upon the viral strain. Virus-induced apoptosis and cytopathy in primary cortical neurons were not apparent at 24 h p.i. The mRNA levels of inflammatory cytokines, chemokines, and type I interferons were upregulated at 6 h and 24 h p.i. These results indicate that the influenza virus induces inflammatory response in mouse primary cortical neurons with limited viral replication. The cytokines released in viral infection-induced neuroinflammation might play critical roles in influenza encephalopathy, rather than in viral replication-induced cytopathy. PMID:27525278

  16. Azithromycin induces anti-viral effects in cultured bronchial epithelial cells from COPD patients

    PubMed Central

    Menzel, Mandy; Akbarshahi, Hamid; Bjermer, Leif; Uller, Lena

    2016-01-01

    Rhinovirus infection is a major cause of chronic obstructive pulmonary disease (COPD) exacerbations and may contribute to the development into severe stages of COPD. The macrolide antibiotic azithromycin may exert anti-viral actions and has been reported to reduce exacerbations in COPD. However, little is known about its anti-viral actions on bronchial epithelial cells at clinically relevant concentrations. Primary bronchial epithelial cells from COPD donors and healthy individuals were treated continuously with azithromycin starting 24 h before infection with rhinovirus RV16. Expression of interferons, RIG-I like helicases, pro-inflammatory cytokines and viral load were analysed. Azithromycin transiently increased expression of IFNβ and IFNλ1 and RIG-I like helicases in un-infected COPD cells. Further, azithromycin augmented RV16-induced expression of interferons and RIG-I like helicases in COPD cells but not in healthy epithelial cells. Azithromycin also decreased viral load. However, it only modestly altered RV16-induced pro-inflammatory cytokine expression. Adding budesonide did not reduce interferon-inducing effects of azithromycin. Possibly by inducing expression of RIG-I like helicases, azithromycin increased rhinovirus-induced expression of interferons in COPD but not in healthy bronchial epithelium. These effects would reduce bronchial viral load, supporting azithromycin’s emerging role in prevention of exacerbations of COPD. PMID:27350308

  17. Antioxidant and Anti-Hepatitis C Viral Activities of Commercial Milk Thistle Food Supplements.

    PubMed

    Anthony, Kevin; Subramanya, Gitanjali; Uprichard, Susan; Hammouda, Faiza; Saleh, Mahmoud

    2013-01-01

    Milk thistle dietary supplements that contain silymarin are widely marketed and used in the USA and other countries for liver enhancement and recovery. More recently, silymarin has also been identified as a possible antiviral for the treatment of hepatitis C virus (HCV) infection. To assess different brands of commercially sold silymarin, 45 products were collected from local stores and analyzed for their silymarin content, antioxidant activities, and antiviral activity against HCV. Antioxidant activity was measured as radical scavenging activity using DPPH and by estimating their antioxidant capacity as trolox equivalent. Anti-HCV activity was measured in an HCV genotype 1b replication inhibition assay. Samples were found to vary widely in their silymarin content, with some samples having none or very low concentrations while silymarin represented higher than 80% of other samples. Both antioxidant and anti-HCV activity correlated with the overall level of silymarin.

  18. Hepatic and extra-hepatic sequelae, and prevalence of viral hepatitis C infection estimated from routine data in at-risk groups

    PubMed Central

    2010-01-01

    Background Concerns about the hepatitis C virus (HCV) are due to the high risk of chronic liver disease and poor treatment efficacy. Synthesizing evidence from multiple data sources is becoming widely used to estimate HCV-infection prevalence. This paper aims to estimate the prevalence of HCV infection, and the hepatic and extrahepatic sequelae in at-risk groups, using routinely collected data in the Lazio region, Italy. Methods HCV laboratory surveillance and dialysis, hospital discharge, and drug-user registers were used as information sources to identify at-risk groups and to estimate HCV prevalence and sequelae. Full name and birth date were used as linkage keys for the various health registries. Prevalence was estimated as the percentage of cases within the general population and the at-risk groups, with 95% confidence intervals (95% CI) from 1997 to 2001. The risk of sequelae was estimated through a follow-up of hospital discharges up to December 31, 2004 and calculated as the prevalence ratio in HCV-positive and HCV-negative people, within each at-risk group, with 95% CI. Results There were 65,127 HCV-infected people in the study period; the prevalence was 1.24% (95%CI = 1.23%-1.25%) in the whole population, higher in males and older adults. Drug users (35.1%; 95%CI = 34.6-35.7) and dialysis patients (21.1%; 95%CI = 20.2%-22.0%) showed the highest values. Medical procedures with little exposure to blood resulted in higher estimates, ranging between 1.3% and 3.4%, which was not conclusively attributable to the surgical procedures. Cirrhosis, hepatocellular carcinoma and encephalopathy were the most frequent hepatic sequelae; cryoglobulinaemia and non-Hodgkin's lymphoma were the most frequent extrahepatic sequelae. Conclusions Synthesising data from multiple routine sources improved estimates of HCV prevalence and sequelae in dialysis patients and drug users, although prevalence validity should be assessed in survey and sequelae need a well

  19. Modulation of Bcl-x Alternative Splicing Induces Apoptosis of Human Hepatic Stellate Cells.

    PubMed

    Wu, Lin; Mao, Chengqiong; Ming, Xin

    2016-01-01

    Liver fibrosis is a major cause of morbidity and mortality worldwide due to chronic viral hepatitis and, more recently, from fatty liver diseases. Activation and proliferation of hepatic stellate cells (HSCs) represent a key aspect of fibrogenesis and are associated with progressive reduction of HSC apoptosis. Bcl-x, an antiapoptotic member of Bcl-2 gene family, plays a role in apoptosis regulation in mammalian cells. Through alternative splicing, the Bcl-x gene yields two major protein isoforms with opposing functions, antiapoptotic Bcl-xL and proapoptotic Bcl-xS. This study aimed to investigate the role of Bcl-x and its alternate splicing in HSC apoptosis. The results indicated that the expression of Bcl-xL was dramatically higher than Bcl-2 in activated human HSCs. The relative expression of Bcl-xL over Bcl-xS increased gradually when HSCs were activated in cell culture, which was consistent with the increase in apoptosis resistance of activated HSCs. Redirection of Bcl-x splicing by an antisense oligonucleotide from the antiapoptotic isoform to the proapoptotic isoform induced death of HSCs without other apoptosis stimuli. We conclude that Bcl-x plays a role in regulation of HSC apoptosis and modulation of Bcl-x alternative splicing may become a novel molecular therapy for liver fibrosis. PMID:27579319

  20. Modulation of Bcl-x Alternative Splicing Induces Apoptosis of Human Hepatic Stellate Cells

    PubMed Central

    Wu, Lin; Mao, Chengqiong

    2016-01-01

    Liver fibrosis is a major cause of morbidity and mortality worldwide due to chronic viral hepatitis and, more recently, from fatty liver diseases. Activation and proliferation of hepatic stellate cells (HSCs) represent a key aspect of fibrogenesis and are associated with progressive reduction of HSC apoptosis. Bcl-x, an antiapoptotic member of Bcl-2 gene family, plays a role in apoptosis regulation in mammalian cells. Through alternative splicing, the Bcl-x gene yields two major protein isoforms with opposing functions, antiapoptotic Bcl-xL and proapoptotic Bcl-xS. This study aimed to investigate the role of Bcl-x and its alternate splicing in HSC apoptosis. The results indicated that the expression of Bcl-xL was dramatically higher than Bcl-2 in activated human HSCs. The relative expression of Bcl-xL over Bcl-xS increased gradually when HSCs were activated in cell culture, which was consistent with the increase in apoptosis resistance of activated HSCs. Redirection of Bcl-x splicing by an antisense oligonucleotide from the antiapoptotic isoform to the proapoptotic isoform induced death of HSCs without other apoptosis stimuli. We conclude that Bcl-x plays a role in regulation of HSC apoptosis and modulation of Bcl-x alternative splicing may become a novel molecular therapy for liver fibrosis. PMID:27579319

  1. The mode of action of interferons in viral infections and their possible role in the control of hepatitis B.

    PubMed

    Billiau, A

    1986-01-01

    Interferons can alter the course of virus infections by inhibiting virus replication at the intracellular level and by modifying the aspecific and specific immune response to viral antigens in body fluids and on cellular surfaces. Treatment of isolated cells with interferon renders them resistant to infections by viruses belonging to virtually any family. Knowledge of the mechanism of this effect is derived from studies employing both DNA (especially vaccinia virus and SV40) and RNA-viruses (especially picorna-, toga-, rhabdo-, reo- and retroviruses). Interferon induces multiple alterations in the level and state of intracellular regulatory molecules, leading to inhibition of virus replication at several possible steps. In the case of certain DNA viruses, transcription of viral DNA seems to be inhibited. In the case of RNA viruses the target for interferon action is mainly translation. The retroviridae constitute a special case and, in view of their analogy with the hepadnaviridae, are of particular relevance to the possible effects of interferon on the replication of HBV. Interferon inhibits one or more initial stages of primary infection of cells by transforming or nontransforming retroviruses, thereby preventing or delaying the synthesis and/or integration of viral DNA. In cells that already contain an integrated and fully expressed retrovirus genome, interferon treatment results in a reduced release of viral particles as well as a downward shift of the ratios between the numbers of infectious vs noninfectious particles. Immuno-modulatory properties of interferon which might alter the course of HBV-infection include: potentiation of cytotoxic activity of lymphocytes and macrophages; direct anti-inflammatory effects; enhancement or depression in antibody formation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2439572

  2. Hepatitis

    MedlinePlus

    ... has been associated with drinking contaminated water. Hepatitis Viruses Type Transmission Prognosis A Fecal-oral (stool to ... risk for severe disease. Others A variety of viruses can affect the liver Signs and Symptoms Hepatitis ...

  3. A Cell-Permeable Hairpin Peptide Inhibits Hepatitis C Viral Nonstructural Protein 5A Mediated Translation and Virus Production

    PubMed Central

    Khachatoorian, Ronik; Arumugaswami, Vaithilingaraja; Ruchala, Piotr; Raychaudhuri, Santanu; Maloney, Eden M.; Miao, Edna; Dasgupta, Asim; French, Samuel W.

    2012-01-01

    NS5A is a key regulator of hepatitis C virus (HCV) life cycle including RNA replication, assembly, and translation. We and others have shown NS5A to augment HCV IRES-mediated translation. Further, Quercetin treatment and heat shock protein (HSP) 70 knockdown inhibit NS5A-driven augmentation of IRES-mediated translation and infectious virus production. We have also co-immunoprecipitated HSP70 with NS5A and demonstrated cellular colocalization leading to the hypothesis that the NS5A/HSP70 complex formation is important for IRES-mediated translation. Here, we have identified the NS5A region responsible for complex formation through in vitro deletion analyses. Deletion of NS5A domains II and III failed to reduce HSP70 binding, whereas domain I deletion eliminated complex formation. NS5A domain I alone also bound HSP70. Deletion mapping of domain I identified the C-terminal 34 amino acids (C34) to be the interaction site. Further, addition of C34 to domains II and III restored complex formation. C34 expression significantly reduced intracellular viral protein levels, in contrast to same size control peptides from other NS5A domains. C34 also competitively inhibited NS5A-augmented IRES-mediated translation, while controls did not. Triple-alanine scan mutagenesis identified an exposed beta-sheet hairpin in C34 to be primarily responsible for NS5A-augmented IRES-mediated translation. Moreover, treatment with a 10 amino acid peptide derivative of C34 suppressed NS5A-augmented IRES-mediated translation and significantly inhibited intracellular viral protein synthesis, with no associated cytotoxicity. Conclusion: These results support the hypothesis that the NS5A/HSP70 complex augments viral IRES-mediated translation, identify a sequence-specific hairpin element in NS5A responsible for complex formation, and demonstrate the functional significance of C34 hairpin-mediated NS5A/HSP70 interaction. Identification of this element may allow for further interrogation of NS5A

  4. [Analysis of characteristics of traditional Chinese medicine and western medicine clinical use in patients with viral hepatitis based on real world hospital information system data].

    PubMed

    Ma, Kun; Xie, Yan-Ming; Yang, Wei; Wang, Yong-Yan; Yi, Dan-Hui; Zhuang, Yan

    2014-09-01

    Viral hepatitis is clinical multiple strong infectious disease, to know characteristics of traditional Chinese medicine and western medicine clinical use in patients with viral hepatitis, the research object of this study is 41 180 cases of hospitalized patients with viral hepatitis in hospital information system from 17 grade A hospitals, using frequency statistics and association rules method to analyze the traditional Chinese medicine and western medicine clinical use information, the drug kinds analysis results: western medicine of reduced glutathione tablets use frequency is highest, 14 079 cases (34.61%), traditional Chinese medicine of diammonium glycyrrhizinateuse frequency is highest, 14 058 cases (34.56%); traditional Chinese medicine and western medicine drug combination in diammonium glycyrrhizinate combined with reduced glutathione tabletsuse frequency is highest, 8 607 cases (25.09%). The mechanism of drug classification results :both traditional Chinese medicine and western medicine are the sort of educed enzyme medicine that has the highest percentage of drug use, traditional Chinese medicine 10 983 cases (27.01%), western medicine, 9 595 cases (23.59%); traditional Chinese medicine and western medicine combination in a kind of medicine to clear heat and promote diuresis combined with educed enzyme drug use frequency is highest, 5 621 cases (13.82%). Through the analysis above, combine traditional Chinese and western medicine therapy for the treatment of viral hepatitis should be given priority. Traditional Chinese medicine to clear heat and promote diuresis combined with western medicine of educed enzyme drug is the most commonly appear in clinical two drug combination scheme, traditional Chinese medicine to clear heat and promote diuresis combined with western medicine of educed enzyme drug and nucleustide analogsis the most commonly appear in clinical three drug combination scheme.

  5. Acute viral hepatitis E presenting with haemolytic anaemia and acute renal failure in a patient with glucose-6-phosphate dehydrogenase deficiency.

    PubMed

    Tomar, Laxmikant Ramkumarsingh; Aggarwal, Amitesh; Jain, Piyush; Rajpal, Surender; Agarwal, Mukul P

    2015-10-01

    The association of acute hepatitis E viral (HEV) infection with glucose-6-phosphate dehydrogenase (G6PD) deficiency leading to extensive intravascular haemolysis is a very rare clinical entity. Here we discuss such a patient, who presented with acute HEV illness, developed severe intravascular haemolysis and unusually high levels of bilirubin, complicated by acute renal failure (ARF), and was later on found to have a deficiency of G6PD. The patient recovered completely with haemodialysis and supportive management. PMID:25500531

  6. Hepatic histological alterations and biochemical changes induced by sildenafil overdoses.

    PubMed

    Jarrar, Bashir Mahmoud; Almansour, Mansour Ibrahim

    2015-11-01

    Sildenafil is used for the treatment of erectile dysfunction and is helping millions of men around the world to achieve and maintain a long lasting erection. Fifty healthy male rabbits (Oryctolagus cuniculus) were used in the present study and exposed daily to sildenafil (0, 1, 3, 6, 9 mg/kg) for 5 days per week for 7 weeks to investigate the biochemical changes and alterations in the hepatic tissues induced by this drug overdosing. In comparison with respective control rabbits, sildenafil overdoses elevated significantly (p-value<0.05, ANOVA test) alanine aminotransferase (ALT), aspartate aminotransferase (AST), testosterone, follicular stimulating hormone and total protein, while creatinine and urea were lowered with no significant alteration was observed in uric acid and luteinizing hormone concentration. Also sildenafil provoked hepatocytes nuclear alterations, necrosis, hydropic degeneration, bile duct hyperplasia, Kupffer cells hyperplasia, inflammatory cells infiltration, hepatic vessels congestion and evident partial depletion of glycogen content. The results show that subchronic exposure to sildenafil overdoses exhibits significant biochemical and alterations in the hepatic tissues that might affect the functions of the liver and other vital organs. PMID:26639481

  7. ACUTE HEPATIC NECROSIS INDUCED BY BRUCELLA INFECTION IN HYPERTHYROID MICE

    PubMed Central

    Bradley, G. Mary; Spink, Wesley W.

    1959-01-01

    When small numbers of Brucella melitensis were inoculated into ABC mice, occasional hepatic granulomas without necrosis were demonstrated. The greatest multiplication of brucellae was detected in the spleens. Because it had been previously observed that ACTH or cortisone markedly accelerated the multiplication of brucellae in the livers of infected mice with destruction of liver cells, it was considered that triiodothyronine might likewise exaggerate a brucella infection by stimulating endogenous adrenal secretion. Although adrenal hypertrophy was produced, infection of mice treated with triiodothyronine resulted in severe hepatic necrosis or infarcts without the multiplication of brucellae in either the livers or spleens. The lesions were not encountered in untreated infected mice or in control mice treated with triiodothyronine. The necrosis was associated with minimal inflammatory reaction. The necrosis was not induced in mice treated with triiodothyronine and given brucella endotoxin. The precise genesis of the acute hepatic necrosis cited in these experiments remains undefined. Triiodothyronine did not cause deaths in mice infected with Br. melitensis. The infection was neither enhanced nor suppressed. PMID:13803714

  8. Systematic review and meta-analysis of hepatitis C virus infection and HIV viral load: new insights into epidemiologic synergy

    PubMed Central

    Petersdorf, Nicholas; Ross, Jennifer M; Weiss, Helen A; Barnabas, Ruanne V; Wasserheit, Judith N

    2016-01-01

    Introduction Hepatitis C virus (HCV) and HIV infection frequently co-occur due to shared transmission routes. Co-infection is associated with higher HCV viral load (VL), but less is known about the effect of HCV infection on HIV VL and risk of onward transmission. Methods We undertook a systematic review comparing 1) HIV VL among ART-naïve, HCV co-infected individuals versus HIV mono-infected individuals and 2) HIV VL among treated versus untreated HCV co-infected individuals. We performed a random-effects meta-analysis and quantified heterogeneity using the I2 statistic. We followed Cochrane Collaboration guidelines in conducting our review and PRISMA guidelines in reporting results. Results and discussion We screened 3925 articles and identified 17 relevant publications. A meta-analysis found no evidence of increased HIV VL associated with HCV co-infection or between HIV VL and HCV treatment with pegylated interferon-alpha-2a/b and ribavirin. Conclusions This finding is in contrast to the substantial increases in HIV VL observed with several other systemic infections. It presents opportunities to elucidate the biological pathways that underpin epidemiological synergy in HIV co-infections and may enable prediction of which co-infections are most important to epidemic control. PMID:27649908

  9. Improvement in the Amino Acid Imbalance in Hepatitis C Virus Infected Patients After Viral Eradication by Interferon Treatment

    PubMed Central

    Enomoto, Hirayuki; Nishikawa, Hiroki; Ikeda, Naoto; Aizawa, Nobuhiro; Sakai, Yoshiyuki; Yoh, Kazunori; Takata, Ryo; Hasegawa, Kunihiro; Nakano, Chikage; Nishimura, Takashi; Ishii, Akio; Takashima, Tomoyuki; Iwata, Yoshinori; Iijima, Hiroko; Nishiguchi, Shuhei

    2016-01-01

    Background In patients with chronic liver diseases (CLDs), hepatitis C virus (HCV) infection in particular may cause various metabolic disorders. We previously reported that the value of the ratio of branched-chain amino acids to tyrosine (BTR) decreased with the progression of liver fibrosis. Objectives We investigated the changes in clinical variables during interferon (IFN) treatment and assessed whether HCV eradication improved the amino acid imbalance in HCV infected patients. Patients and Methods We retrospectively collected the clinical data of HCV-related CLD patients whose BTR values had been measured both pre- and post-IFN treatment. A total of 17 patients with a sustained viral response (SVR) (mean observational period: 1085.0 days) and 19 patients without an SVR (Non-SVR) (mean observational period: 1002.5 days) were studied. Results In patients with an SVR, the serum levels of aminotransferases were decreased after HCV eradication. Although general liver functional tests (albumin and total bilirubin) did not significantly change, the BTR values significantly increased. However, in patients without an SVR, an improvement in the BTR value was not observed after IFN treatment. Conclusions HCV eradication can improve the amino acid imbalance in HCV infected patients. PMID:27630724

  10. Systematic review and meta-analysis of hepatitis C virus infection and HIV viral load: new insights into epidemiologic synergy

    PubMed Central

    Petersdorf, Nicholas; Ross, Jennifer M; Weiss, Helen A; Barnabas, Ruanne V; Wasserheit, Judith N

    2016-01-01

    Introduction Hepatitis C virus (HCV) and HIV infection frequently co-occur due to shared transmission routes. Co-infection is associated with higher HCV viral load (VL), but less is known about the effect of HCV infection on HIV VL and risk of onward transmission. Methods We undertook a systematic review comparing 1) HIV VL among ART-naïve, HCV co-infected individuals versus HIV mono-infected individuals and 2) HIV VL among treated versus untreated HCV co-infected individuals. We performed a random-effects meta-analysis and quantified heterogeneity using the I2 statistic. We followed Cochrane Collaboration guidelines in conducting our review and PRISMA guidelines in reporting results. Results and discussion We screened 3925 articles and identified 17 relevant publications. A meta-analysis found no evidence of increased HIV VL associated with HCV co-infection or between HIV VL and HCV treatment with pegylated interferon-alpha-2a/b and ribavirin. Conclusions This finding is in contrast to the substantial increases in HIV VL observed with several other systemic infections. It presents opportunities to elucidate the biological pathways that underpin epidemiological synergy in HIV co-infections and may enable prediction of which co-infections are most important to epidemic control.

  11. Drug-induced fulminant hepatic failure in pregnancy.

    PubMed

    Firoz, Tabassum; Webber, Douglas; Rowe, Hilary

    2015-12-01

    Liver disease in pregnancy can be classified as predating, co-incidental or unique to pregnancy. Medications are often overlooked as a significant cause of liver disease. We present the case of a 39-year-old patient who presented at 20 weeks with jaundice, elevated liver enzymes, and abnormal liver function progressing eventually to fulminant hepatic failure. The patient was on methyldopa and labetalol from 12 weeks' gestational age. Liver biopsy was consistent with drug-induced liver injury. Both methyldopa and labetalol have been associated with hepatotoxicity including liver failure. This case highlights the importance of including medications as a cause of liver failure in pregnant patients.

  12. Evolution of nanoparticle-induced distortion on viral polyhedra.

    PubMed

    Das, Sumistha; Datta, Alokmay; Mukherjee, Smita; Biswas, Nupur; Goswami, Arunava

    2013-03-01

    Morphological changes in the polyhedra of the Bombyx mori L. nuclear polyhedrosis virus (BmNPV), a baculovirus causing the deadly grasserie disease in silkworms, brought about by mixing with lipophilically capped amorphous silica nanoparticles (LASN, average size 10 ± 2 nm) were studied with scanning electron microscopy (SEM) and Fourier transform infrared (FTIR) spectroscopy. SEM shows that the regular octagonal polyhedra facets are replaced by a larger number of newly formed irregular ones. The average number of facets reveals a nonlinear growth pattern with nanoparticle (NP) concentration, where an initial linear region ends in a plateau. IR bands corresponding to vibration modes of the capping show (a) a saturation of the area under the band with NP concentration, indicating a correlation with attachment to viral polyhedra and (b) a narrowing of the band per NP from the linear to the plateau portions of the distortion curve, suggesting non-equilibrium and equilibrium situations, respectively. PMID:23860867

  13. Management of viral hepatitis in patients with haematological malignancy and in patients undergoing haemopoietic stem cell transplantation: recommendations of the 5th European Conference on Infections in Leukaemia (ECIL-5).

    PubMed

    Mallet, Vincent; van Bömmel, Florian; Doerig, Christopher; Pischke, Sven; Hermine, Olivier; Locasciulli, Anna; Cordonnier, Catherine; Berg, Thomas; Moradpour, Darius; Wedemeyer, Heiner; Ljungman, Per

    2016-05-01

    Viral hepatitis affects millions of people worldwide, and host immunity is the key determinant of patient outcome. Viral hepatitis can be life threatening in patients with haematological malignancy, including haemopoietic stem cell transplant recipients, because of the virus itself, or through a need to decrease the dose of chemotherapy. A past or currently infected haemopoietic stem cell donor could also transmit viral hepatitis. The burden of viral hepatitis in patients with haematological malignancies and the weak evidence on which previous guidelines are based has prompted the European Conference on Infection in Leukaemia (ECIL-5) to convene a group of experts in the fields of viral hepatitis and of haematological malignancy to specifically address previously unconsidered issues and grade the available quality of evidence according to the Infectious Diseases Society of America grading system. The group recommends that all patients should be screened for hepatotropic viruses before haematological treatment and that patients or haemopoietic stem cell donors with markers of past or current viral hepatitis should be assessed by an expert. Screening, vaccination, and treatment rules are reported in this Review. PMID:27599653

  14. Clinical care of incarcerated people with HIV, viral hepatitis, or tuberculosis.

    PubMed

    Rich, Josiah D; Beckwith, Curt G; Macmadu, Alexandria; Marshall, Brandon D L; Brinkley-Rubinstein, Lauren; Amon, Joseph J; Milloy, M-J; King, Maximilian R F; Sanchez, Jorge; Atwoli, Lukoye; Altice, Frederick L

    2016-09-10

    The burden of HIV/AIDS and other transmissible diseases is higher in prison and jail settings than in the non-incarcerated communities that surround them. In this comprehensive review, we discuss available literature on the topic of clinical management of people infected with HIV, hepatitis B and C viruses, and tuberculosis in incarcerated settings in addition to co-occurrence of one or more of these infections. Methods such as screening practices and provision of treatment during detainment periods are reviewed to identify the effect of community-based treatment when returning inmates into the general population. Where data are available, we describe differences in the provision of medical care in the prison and jail settings of low-income and middle-income countries compared with high-income countries. Structural barriers impede the optimal delivery of clinical care for prisoners, and substance use, mental illness, and infectious disease further complicate the delivery of care. For prison health care to reach the standards of community-based health care, political will and financial investment are required from governmental, medical, and humanitarian organisations worldwide. In this review, we highlight challenges, gaps in knowledge, and priorities for future research to improve health-care in institutions for prisoners. PMID:27427452

  15. Using the Hepatitis C Virus RNA-Dependent RNA Polymerase as a Model to Understand Viral Polymerase Structure, Function and Dynamics

    PubMed Central

    Sesmero, Ester; Thorpe, Ian F.

    2015-01-01

    Viral polymerases replicate and transcribe the genomes of several viruses of global health concern such as Hepatitis C virus (HCV), human immunodeficiency virus (HIV) and Ebola virus. For this reason they are key targets for therapies to treat viral infections. Although there is little sequence similarity across the different types of viral polymerases, all of them present a right-hand shape and certain structural motifs that are highly conserved. These features allow their functional properties to be compared, with the goal of broadly applying the knowledge acquired from studying specific viral polymerases to other viral polymerases about which less is known. Here we review the structural and functional properties of the HCV RNA-dependent RNA polymerase (NS5B) in order to understand the fundamental processes underlying the replication of viral genomes. We discuss recent insights into the process by which RNA replication occurs in NS5B as well as the role that conformational changes play in this process. PMID:26193306

  16. Roles of bovine viral diarrhea virus envelope glycoproteins in inducing autophagy in MDBK cells.

    PubMed

    Fu, Qiang; Shi, Huijun; Shi, Mengting; Meng, Luping; Bao, Haiyang; Zhang, Guoqi; Ren, Yan; Zhang, Hui; Guo, Fei; Qiao, Jun; Jia, Bin; Wang, Pengyan; Ni, Wei; Sheng, Jinliang; Chen, Chuangfu

    2014-11-01

    Macroautophagy (autophagy) is an evolutionarily conserved control process that maintains cellular homeostasis in eukaryotic cells. Autophagy principally serves an adaptive role to degrade dysfunctional proteins and to clean damaged organelles in response to pathogenic, viral, or microbial infection, nutrient deprivation and endoplasmic reticulum (ER) stress. In previous study, we showed bovine viral diarrhea virus (BVDV) NADL infection induced autophagy and significantly elevated the expression levels of autophagy-related genes, Beclin1 and ATG14, at 12 h post-infection in MDBK cells. However, the specific mechanisms involved in controlling autophagic activity remain unclear. Here, we investigate the effects of BVDV NADL envelope glycoproteins overexpression on inducing autophagy. The results show that viral envelope glycoproteins E(rns) and E2 overexpression mediated by lentivirus increase the formation of autophagosome, the percentage of GFP-LC3 puncta-positive cells and the expression levels of Beclin1 and ATG14. Whereas E1 overexpression doesn't affect autophagic activity. Collectively, these findings suggest that the viral envelope glycoproteins E(rns) and E2 are involved in inducing autophagy, and provide a mechanistic insight into the regulation of autophagy in viral infected cells.

  17. An outbreak of refrigerant-induced acute hepatitis in Hong Kong.

    PubMed

    Kan, Y M; Lau, C F; Chan, W C; Chan, W S; Tung, Y M; Loo, C K

    2014-12-01

    We report a cluster of acute hepatitis in five air-conditioning maintenance workers following accidental exposure to 2,2-dichloro-1,1,1-trifluoroethane (HCFC-123). They presented to us with complaints of feverishness, generalised malaise, and epigastric discomfort. Their blood biochemistry tests were compatible with acute hepatitis. Viral hepatitis serology, tests for autoimmune hepatitis, and analyses for drugs and alcohol consumption were all negative. No focal hepatic lesion was detected by ultrasound imaging. Percutaneous liver biopsy samples were taken from two of them. The patients were managed with supportive treatment. All had spontaneous, but slow, recovery. Their liver function tests returned to normal after 4 months and their outcomes were favourable. Physicians should be aware of this occupational disease entity. PMID:25488036

  18. Phenylbutyric acid protects against carbon tetrachloride-induced hepatic fibrogenesis in mice

    SciTech Connect

    Wang, Jian-Qing; Chen, Xi; Zhang, Cheng; Tao, Li; Zhang, Zhi-Hui; Liu, Xiao-Qian; Xu, Yuan-Bao; Wang, Hua; Li, Jun; Xu, De-Xiang

    2013-01-15

    A recent report showed that the unfolded protein response (UPR) signaling was activated in the pathogenesis of carbon tetrachloride (CCl{sub 4})-induced hepatic fibrosis. Phenylbutyric acid (PBA) is a well-known chemical chaperone that inhibits endoplasmic reticulum (ER) stress and unfolded protein response (UPR) signaling. In the present study, we investigated the effects of PBA on CCl{sub 4}-induced hepatic fibrosis in mice. All mice were intraperitoneally (i.p.) injected with CCl{sub 4} (0.15 ml/kg BW, twice per week) for 8 weeks. In CCl{sub 4} + PBA group, mice were i.p. injected with PBA (150 mg/kg, twice per day) from the beginning of CCl{sub 4} injection to the end. As expected, PBA significantly attenuated CCl{sub 4}-induced hepatic ER stress and UPR activation. Although PBA alleviated, only to a less extent, hepatic necrosis, it obviously inhibited CCl{sub 4}-induced tumor necrosis factor alpha (TNF-α) and transforming growth factor beta (TGF-β). Moreover, PBA inhibited CCl{sub 4}-induced hepatic nuclear factor kappa B (NF-κB) p65 translocation and extracellular signal-regulated kinase (ERK) and c-Jun N-terminal Kinase (JNK) phosphorylation. Interestingly, CCl{sub 4}-induced α-smooth muscle actin (α-SMA), a marker for the initiation phase of HSC activation, was significantly attenuated in mice pretreated with PBA. Correspondingly, CCl{sub 4}-induced hepatic collagen (Col)1α1 and Col1α2, markers for the perpetuation phase of HSC activation, were inhibited in PBA-treated mice. Importantly, CCl{sub 4}-induced hepatic fibrosis, as determined using Sirius red staining, was obviously attenuated by PBA. In conclusion, PBA prevents CCl{sub 4}-induced hepatic fibrosis through inhibiting hepatic inflammatory response and HSC activation. Highlights: ► CCl{sub 4} induces hepatic ER stress, inflammation, HSC activation and hepatic fibrosis. ► PBA alleviates CCl{sub 4}-induced hepatic ER stress and UPR signaling activation. ► PBA inhibits CCl{sub 4}-induced

  19. Interaction of vinyl chloride monomer exposure and hepatitis B viral infection on liver cancer.

    PubMed

    Wong, Ruey-Hong; Chen, Pau-Chung; Wang, Jung-Der; Du, Chung-Li; Cheng, Tsun-Jen

    2003-04-01

    Vinyl-chloride monomer (VCM), a human carcinogen, has caused angiosarcoma of the liver. Recent studies have shown that VCM exposure is associated with hepatocellular cancer. In Taiwanese studies, the majority of VCM-exposed workers with liver cancer had history of hepatitis B virus (HBV) infection. To determine the role of HBV on the development of liver cancer in the VCM-exposed workers, we conducted a case-control study from a previously established polyvinyl chloride (PVC) cohort consisting of 4096 male workers from six PVC polymerization plants. A total of 18 patients with liver cancer, and 68 control subjects matched for age and specific plant of employment were selected. Detailed history of the participants that included alcohol consumption status, cigarette use, occupation, and family history of chronic liver disease were obtained using an interviewer-administered questionnaire. When the HBV surface antigen (HBsAg)-negative subjects without history of tank-cleaning were used as the reference, the HBsAg-negative subjects with history of tank-cleaning demonstrated a 4.0-fold greater risk of liver cancer (95% confidence interval: 95% CI = 0.2-69.1). The HBsAg carriers without history of tank-cleaning revealed a 25.7-fold greater risk of liver cancer (95% CI = 2.9-229.4). Whereas the HBsAg carriers with history of tank-cleaning revealed the greatest risk (matched odds ratio (ORm) 396.0, 95% CI = 22.6 -infinity) of developing liver cancer among subjects with different VCM-exposure status and HBsAg status categories. Further analysis showed the interaction term was significant (P < .01). Therefore, our results suggest an interaction between occupational VCM exposure and HBV infection for the development of liver cancer.

  20. Investigation of intestine function during acute viral hepatitis using combined sugar oral loads.

    PubMed Central

    Parrilli, G; Cuomo, R; Nardone, G; Maio, G; Izzo, C M; Budillon, G

    1987-01-01

    One fifth of all cases of A virus hepatitis (AVH) have symptoms of gastroenteritis at the onset. This study investigated the mediated intestinal absorption of D-xylose (D-xyl) and 3-o-methyl-D-glucose (3-omG) and the non-mediated permeation of lactulose (Lacl, mol wt 342) and L-rhamnose (L-rh, mol wt 164) during acute and remission phases of AVH. Ten patients with AVH were given an oral load containing these sugars (5 g D-xyl: 2.5 g 3-omG, 1 g L-rh, 5 g lacl in 250 ml water) once during the acute phase and again during remission. The same load was given once to a group of 22 healthy controls. The mean concentration of D-xyl in urine and the ratio of D-xyl to 3-omG in plasma and urine were normal in both the AVH phases, ruling out intestinal malabsorption even in the acute phase. This study showed a significant increase in non-mediated permeation to Lacl, but not to L-rh, during the acute phase. These data indicate that the barrier function of the intestine is compromised in AVH infection while the absorptive function is not. An abnormally low concentration of D-xyl and 3-omG in plasma at one hour was found in all patients during the acute phase. This finding cannot be explained by alterations in intestinal absorption, but could be accounted for by increased space distribution of the sugars because of increased diffusion into tissue cells and/or expansion of the extracellular space by fluid retention. PMID:3428669

  1. Acute hepatitis C in a chronically HIV-infected patient: Evolution of different viral genomic regions

    PubMed Central

    Flichman, Diego; Kott, Veronica; Sookoian, Silvia; Campos, Rodolfo

    2003-01-01

    AIM: To analyze the molecular evolution of different viral genomic regions of HCV in an acute HCV infected patient chronically infected with HIV through a 42-month follow-up. METHODS: Serum samples of a chronically HIV infected patient that seroconverted to anti HCV antibodies were sequenced, from the event of superinfection through a period of 17 mo and in a late sample (42nd month). Hypervariable genomic regions of HIV (V3 loop of the gp120) and HCV (HVR-1 on the E2 glycoprotein gene) were studied. In order to analyze genomic regions involved in different biological functions and with the cellular immune response, HCV core and NS5A were also chosen to be sequenced. Amplification of the different regions was done by RT-PCR and directly sequenced. Confirmation of sequences was done on reamplified material. Nucleotide sequences of the different time points were aligned with CLUSTAL W 1.5, and the corresponding amino acid ones were deduced. RESULTS: Hypervariable genomic regions of both viruses (HVR1 and gp120 V3 loop) presented several nonsynonymous changes but, while in the gp120 V3 loop mutations were detected in the sample obtained right after HCV superinfection and maintained throughout, they occurred following a sequential and cumulative pattern in the HVR1. In the NS5A region of HCV, two amino acid changes were detected during the follow-up period, whereas the core region presented several amino acid replacements, once the HCV chronic infection had been established. CONCLUSION: During the HIV-HCV superinfection, each genomic region analyzed shows a different evolutionary pattern. Most of the nucleotide substitutions observed are non-synonymous and clustered in previously described epitopes, thus suggesting an immune-driven evolutionary process. PMID:12854149

  2. Melatonin inhibits the sphingosine kinase 1/sphingosine-1-phosphate signaling pathway in rabbits with fulminant hepatitis of viral origin.

    PubMed

    Crespo, Irene; San-Miguel, Beatriz; Sánchez, Diana I; González-Fernández, Bárbara; Álvarez, Marcelino; González-Gallego, Javier; Tuñón, María J

    2016-09-01

    The sphingosine kinase (SphK)1/sphingosine-1-phosphate (S1P) pathway is involved in multiple biological processes, including liver diseases. This study investigate whether modulation of the SphK1/S1P system associates to the beneficial effects of melatonin in an animal model of acute liver failure (ALF) induced by the rabbit hemorrhagic disease virus (RHDV). Rabbits were experimentally infected with 2 × 10(4) hemagglutination units of a RHDV isolate and received 20 mg/kg of melatonin at 0, 12, and 24 hr postinfection. Liver mRNA levels, protein concentration, and immunohistochemical labeling for SphK1 increased in RHDV-infected rabbits. S1P production and protein expression of the S1PR1 receptor were significantly elevated following RHDV infection. These effects were significantly reduced by melatonin. Rabbits also exhibited increased expression of toll-like receptor (TLR)4, tumor necrosis factor alpha (TNF-α), interleukin (IL)-6, nuclear factor-kappa B (NF-κB) p50 and p65 subunits, and phosphorylated inhibitor of kappa B (IκB)α. Melatonin administration significantly inhibited those changes and induced a decreased immunoreactivity for RHDV viral VP60 antigen in the liver. Results obtained indicate that the SphK1/S1P system activates in parallel to viral replication and the inflammatory process induced by the virus. Inhibition of the lipid signaling pathway by the indole reveals novel molecular pathways that may account for the protective effect of melatonin in this animal model of ALF, and supports the potential of melatonin as an antiviral agent. PMID:27101794

  3. Clinical evaluation of a new enzyme immunoassay for hepatitis B virus core-related antigen; a marker distinct from viral DNA for monitoring lamivudine treatment.

    PubMed

    Rokuhara, A; Tanaka, E; Matsumoto, A; Kimura, T; Yamaura, T; Orii, K; Sun, X; Yagi, S; Maki, N; Kiyosawa, K

    2003-07-01

    We aimed to assess the clinical performance of a newly developed chemiluminescence enzyme immunoassay (CLEIA) for the detection of hepatitis B virus (HBV) core-related antigen (HBcrAg) in patients with chronic HBV infection. A total of 82 patients with chronic HBV infection and 167 HBV-negative controls were studied. HBcrAg was measured by CLEIA with monoclonal antibodies to hepatitis B e antigen (HBeAg) and hepatitis B core antigen (HBcAg), and HBV DNA was measured by transcription-mediated amplification assay (TMA) and in-house real-time detection polymerase chain reaction (RTD-PCR). The HBcrAg assay detected viremia in 189 of 216 samples (88%) collected from 72 patients whilst the TMA assay detected viremia in 178 of the 216 samples (82%) (P = 0.019). The HBcrAg concentration correlated linearly with the HBV DNA concentration (P < 0.001) over a range which varied 100 000-fold. The accuracy in the measurement of the patients' HBV load obtained using the HBcrAg assay was not affected by the absence of hepatitis B e antigen from the serum or the presence of precore mutations in the HBV genome. In patients without anti-viral drugs, changes in their serum HBcrAg concentration over time corresponded to their HBV DNA concentration. In six additional patients who were later treated with lamivudine, HBV DNA concentration declined more rapidly than their HBcrAg concentration. Three months after treatment commenced, the ratio of HBcrAg: HBV DNA had increased in all six patients (P = 0.031). The HBcrAg assay is a sensitive and useful test for the assessment of a patient's HBV load. When monitoring the anti-viral effect of lamivudine, HBcrAg provides a viral marker which is independent of HBV DNA.

  4. Amplification of GB virus-C/hepatitis G virus RNA with primers from different regions of the viral genome.

    PubMed

    Kao, J H; Chen, P J; Chen, W; Hsiang, S C; Lai, M Y; Chen, D S

    1997-04-01

    GB virus-C/hepatitis G virus (GBV-C/HGV) is a newly identified RNA virus. The aim of the study was to compare three primer pairs from the 5' untranslated region (5'UTR), envelope region 2 (E 2) and nonstructural region 3 (NS 3) of GBV-C/HGV genome for their ability to detect GBV-C/HGV RNA by polymerase chain reaction (PCR) assays. By using PCR with primers from different regions of the viral genome, serum GBV-C/HGV RNA was assayed in 200 at-risk individuals. The sensitivity of this assay was assessed by a titration experiment, and nucleotide sequences of the amplified products were determined directly. Of 200 serum samples, 43 (21.5%) were positive for GBV-C/HGV RNA with at least one of the primer pairs. The positive rates by 5'UTR, NS 3, and E 2 primers were 100%, 98%, and 84%, respectively, and the sensitivity of PCR assays using 5'UTR primers was 10 to 100 times more likely to detect GBV-C/HGV RNA than that of NS 3 and E 2 primers. The average homology of amplified targets to the prototype HGV genome was 89%, 80%, and 85% and the similarity between each amplified target was up to 100%, 90%, and 92% in the 5'UTR, E 2, and NS 3 regions, respectively. Therefore, the 5'UTR of GBV-C/HGV genome is highly conserved and primers deduced from this region can provideva sensitive and specific PCR assay for GBV-C/HGV RNA.

  5. Patterns of viral load in chronic hepatitis B patients in Brazil and their association with ALT levels and HBeAg status.

    PubMed

    Nita, Marcelo Eidi; Gaburo, Nelson; Cheinquer, Hugo; L'Italien, Gilbert; Affonso de Araujo, Evaldo Stanislau; Mantilla, Patricia; Cure-Bolt, Nancy; Lotufo, Paulo A

    2009-01-01

    Serum hepatitis B virus (HBV) DNA level is a predictor of the development of cirrhosis and hepatocellular carcinoma in chronic hepatitis B patients. Nevertheless, the distribution of viral load levels in chronic HBV patients in Brazil has yet to be described. This cross-sectional study included 564 participants selected in nine Brazilian cities located in four of the five regions of the country using the database of a medical diagnostics company. Admission criteria included hepatitis B surface antigen seropositivity, availability of HBV viral load samples and age >or=18 years. Males comprised 64.5% of the study population. Mean age was 43.7 years. Most individuals (62.1%) were seronegative for the hepatitis B e antigen (HBeAg). Median serum ALT level was 34 U/L. In 58.5% of the patients HBV-DNA levels ranged from 300 to 99,999 copies/mL; however, in 21.6% levels were undetectable. Median HBV-DNA level was 2,351 copies/mL. Over 60% of the patients who tested negative for HBeAg and in whom ALT level was less than 1.5 times the upper limit of the normal range had HBV-DNA levels > 2,000 IU/mL, which has been considered a cut-off point for indicating a liver biopsy and/or treatment. In conclusion, HBV-DNA level identified a significant proportion of Brazilian individuals with chronic hepatitis B at risk of disease progression. Furthermore, this tool enables those individuals with high HBV-DNA levels who are susceptible to disease progression to be identified among patients with normal or slightly elevated ALT. PMID:20009133

  6. Policy responses to viral hepatitis B and C among people who inject drugs in Member States of the WHO European region: a sub-analysis of the WHO 2013 global hepatitis policy survey

    PubMed Central

    2014-01-01

    Background Unsafe injections, through infectious bodily fluids, are a major route of transmission for hepatitis B and C. Viral hepatitis burden among people who inject drugs is particularly high in many Member States of central and Eastern Europe while national capacity and willingness to address it varies greatly. In 2013, the World Health Organization conducted a survey assessing national viral hepatitis efforts of 194 national governments. Here, we present a sub-analysis of this global survey focusing on questions relating to people who inject drugs in the WHO European Region. Methods The initial survey included 43 questions covering awareness, data, prevention, and screening and treatment. It was sent in five languages to identified national focal points. This sub-analysis included 11 questions and 53 Member States in the WHO European Region. Descriptive analyses of national activities are presented. As a secondary outcome bivariate analyses of differences between Member States of the European Union (EU) and European Free Trade Association (EFTA) compared to those not in said grouping are presented. Results Forty-four of the 53 Member States responded to the survey (response rate of 83%). More than three-quarters reported offering publicly-funded treatment for HBV or HCV (82% and 80%, respectively), with a significantly higher proportion of EU/EFTA Member States (P=0.004 and P=0.010, respectively). Half of Member States (53%) reported the existence of a national policy for hepatitis prevention and control; however less than one-third (27%) reported having written national strategies. Under half of the responding Member States reported holding events for World Hepatitis Day 2012. One-fifth reported offering hepatitis B and C testing free of charge, with less than one-third reportedly conducting regular serosurveys among people who inject drugs. Conclusions Findings highlight key gaps requiring attention in order to improve national policies and programmes in the

  7. Secondhand smoke induces hepatic apoptosis and fibrosis in hamster fetus.

    PubMed

    Huang, Chien-Wei; Horng, Chi-Ting; Huang, Chih-Yang; Cho, Ta-Hsiung; Tsai, Yi-Chang; Chen, Li-Jeng; Hsu, Tsai-Ching; Tzang, Bor-Show

    2016-09-01

    Secondhand smoke (SHS) is an important health issue worldwide. Inhaling SHS during pregnancy could cause abnormalities in the internal tissues of newborns, which may then impair fetal development and even cause severe intrauterine damage and perinatal death. However, the understanding of cytopathic mechanisms of SHS by maternal passive smoking on fetus liver during pregnancy is still limited. This study analyzed the effects of high-dose SHS (SHSH) on fetus liver using a maternal passive smoking animal model. Experiments showed that hepatic matrix metalloproteinase-9 activity and terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick-end labeling-positive cells were significantly increased in livers from fetuses of hamsters treated with SHSH. Similarly, expressions of both extrinsic and intrinsic apoptotic molecules were significantly higher in livers from fetuses of hamsters exposed to SHSH. Additionally, significantly increased inflammatory proteins, including transforming growth factor β, inducible nitric oxide synthase, and interleukin 1β, and fibrotic signaling molecules, including phosphorylated Smad2/3, SP1, and α-smooth muscle actin, were observed in the fetus livers from hamsters treated with SHSH. This study revealed that SHSH not only increased apoptosis through intrinsic and extrinsic pathways in the livers of fetuses from hamsters exposed to SHSH but also augmented hepatic fibrosis via Smad2/3 signaling.

  8. Bile acids induce hepatic differentiation of mesenchymal stem cells

    PubMed Central

    Sawitza, Iris; Kordes, Claus; Götze, Silke; Herebian, Diran; Häussinger, Dieter

    2015-01-01

    Mesenchymal stem cells (MSC) have the potential to differentiate into multiple cell lineages and their therapeutic potential has become obvious. In the liver, MSC are represented by stellate cells which have the potential to differentiate into hepatocytes after stimulation with growth factors. Since bile acids can promote liver regeneration, their influence on liver-resident and bone marrow-derived MSC was investigated. Physiological concentrations of bile acids such as tauroursodeoxycholic acid were able to initiate hepatic differentiation of MSC via the farnesoid X receptor and transmembrane G-protein-coupled bile acid receptor 5 as investigated with knockout mice. Notch, hedgehog, transforming growth factor-β/bone morphogenic protein family and non-canonical Wnt signalling were also essential for bile acid-mediated differentiation, whereas β-catenin-dependent Wnt signalling was able to attenuate this process. Our findings reveal bile acid-mediated signalling as an alternative way to induce hepatic differentiaion of stem cells and highlight bile acids as important signalling molecules during liver regeneration. PMID:26304833

  9. Efficient generation of rat induced pluripotent stem cells using a non-viral inducible vector.

    PubMed

    Merkl, Claudia; Saalfrank, Anja; Riesen, Nathalie; Kühn, Ralf; Pertek, Anna; Eser, Stefan; Hardt, Markus Sebastian; Kind, Alexander; Saur, Dieter; Wurst, Wolfgang; Iglesias, Antonio; Schnieke, Angelika

    2013-01-01

    Current methods of generating rat induced pluripotent stem cells are based on viral transduction of pluripotency inducing genes (Oct4, Sox2, c-myc and Klf4) into somatic cells. These activate endogenous pluripotency genes and reprogram the identity of the cell to an undifferentiated state. Epigenetic silencing of exogenous genes has to occur to allow normal iPS cell differentiation. To gain more control over the expression of exogenous reprogramming factors, we used a novel doxycycline-inducible plasmid vector encoding Oct4, Sox2, c-Myc and Klf4. To ensure efficient and controlled generation of iPS cells by plasmid transfection we equipped the reprogramming vector with a bacteriophage φC31 attB site and used a φC31 integrase expression vector to enhance vector integration. A series of doxycycline-independent rat iPS cell lines were established. These were characterized by immunocytochemical detection of Oct4, SSEA1 and SSEA4, alkaline phosphatase staining, methylation analysis of the endogenous Oct4 promoter and RT-PCR analysis of endogenous rat pluripotency genes. We also determined the number of vector integrations and the extent to which reprogramming factor gene expression was controlled. Protocols were developed to generate embryoid bodies and rat iPS cells demonstrated as pluripotent by generating derivatives of all three embryonic germ layers in vitro, and teratoma formation in vivo. All data suggest that our rat iPS cells, generated by plasmid based reprogramming, are similar to rat ES cells. Methods of DNA transfection, protein transduction and feeder-free monolayer culture of rat iPS cells were established to enable future applications. PMID:23383095

  10. Viral Inhibition of the IFN-Induced JAK/STAT Signalling Pathway: Development of Live Attenuated Vaccines by Mutation of Viral-Encoded IFN-Antagonists.

    PubMed

    Fleming, Stephen B

    2016-01-01

    The interferon (IFN) induced anti-viral response is amongst the earliest and most potent of the innate responses to fight viral infection. The induction of the Janus kinase/signal transducer and activation of transcription (JAK/STAT) signalling pathway by IFNs leads to the upregulation of hundreds of interferon stimulated genes (ISGs) for which, many have the ability to rapidly kill viruses within infected cells. During the long course of evolution, viruses have evolved an extraordinary range of strategies to counteract the host immune responses in particular by targeting the JAK/STAT signalling pathway. Understanding how the IFN system is inhibited has provided critical insights into viral virulence and pathogenesis. Moreover, identification of factors encoded by viruses that modulate the JAK/STAT pathway has opened up opportunities to create new anti-viral drugs and rationally attenuated new generation vaccines, particularly for RNA viruses, by reverse genetics. PMID:27367734

  11. Viral Inhibition of the IFN-Induced JAK/STAT Signalling Pathway: Development of Live Attenuated Vaccines by Mutation of Viral-Encoded IFN-Antagonists

    PubMed Central

    Fleming, Stephen B.

    2016-01-01

    The interferon (IFN) induced anti-viral response is amongst the earliest and most potent of the innate responses to fight viral infection. The induction of the Janus kinase/signal transducer and activation of transcription (JAK/STAT) signalling pathway by IFNs leads to the upregulation of hundreds of interferon stimulated genes (ISGs) for which, many have the ability to rapidly kill viruses within infected cells. During the long course of evolution, viruses have evolved an extraordinary range of strategies to counteract the host immune responses in particular by targeting the JAK/STAT signalling pathway. Understanding how the IFN system is inhibited has provided critical insights into viral virulence and pathogenesis. Moreover, identification of factors encoded by viruses that modulate the JAK/STAT pathway has opened up opportunities to create new anti-viral drugs and rationally attenuated new generation vaccines, particularly for RNA viruses, by reverse genetics. PMID:27367734

  12. Hydrogen/Deuterium Exchange Kinetics Demonstrate Long Range Allosteric Effects of Thumb Site 2 Inhibitors of Hepatitis C Viral RNA-dependent RNA Polymerase.

    PubMed

    Deredge, Daniel; Li, Jiawen; Johnson, Kenneth A; Wintrode, Patrick L

    2016-05-01

    New nonnucleoside analogs are being developed as part of a multi-drug regimen to treat hepatitis C viral infections. Particularly promising are inhibitors that bind to the surface of the thumb domain of the viral RNA-dependent RNA polymerase (NS5B). Numerous crystal structures have been solved showing small molecule non-nucleoside inhibitors bound to the hepatitis C viral polymerase, but these structures alone do not define the mechanism of inhibition. Our prior kinetic analysis showed that nonnucleoside inhibitors binding to thumb site-2 (NNI2) do not block initiation or elongation of RNA synthesis; rather, they block the transition from the initiation to elongation, which is thought to proceed with significant structural rearrangement of the enzyme-RNA complex. Here we have mapped the effect of three NNI2 inhibitors on the conformational dynamics of the enzyme using hydrogen/deuterium exchange kinetics. All three inhibitors rigidify an extensive allosteric network extending >40 Å from the binding site, thus providing a structural rationale for the observed disruption of the transition from distributive initiation to processive elongation. The two more potent inhibitors also suppress slow cooperative unfolding in the fingers extension-thumb interface and primer grip, which may contribute their stronger inhibition. These results establish that NNI2 inhibitors act through long range allosteric effects, reveal important conformational changes underlying normal polymerase function, and point the way to the design of more effective allosteric inhibitors that exploit this new information. PMID:27006396

  13. IL-9 Inhibits Viral Replication in Coxsackievirus B3-Induced Myocarditis

    PubMed Central

    Yu, Miao; Long, Qi; Li, Huan-Huan; Liang, Wei; Liao, Yu-Hua; Yuan, Jing; Cheng, Xiang

    2016-01-01

    Myocardial injuries in viral myocarditis (VMC) are caused by viral infection and related autoimmune disorders. Recent studies suggest that IL-9 mediated both antimicrobial immune and autoimmune responses in addition to allergic diseases. However, the role of IL-9 in viral infection and VMC remains controversial and uncertain. In this study, we infected Balb/c mice with Coxsackievirus B3 (CVB3), and found that IL-9 was enriched in the blood and hearts of VMC mice on days 5 and 7 after virus infection. Most of IL-9 was secreted by CD8+ T cells on day 5 and CD4+ T cells on day 7 in the myocardium. Further, IL-9 knockout exacerbated cardiac damage following CVB3 infection, along with a sharp increase in viral replication and IL-17a expression, as well as a decrease in TGF-β. In contrast, the repletion of IL-9 in Balb/c mice with CVB infection induced the opposite effect. Studies in vitro further revealed that IL-9 directly inhibited viral replication in cardiomyocytes by reducing coxsackie and adenovirus receptor expression, which might be associated with upregulation of TGF-β autocrine effect in these cells. However, IL-9 had no direct effect on apoptosis in cardiomyocytes. Our data indicated that IL-9 played a protective role in disease progression by inhibiting CVB3 replication in the early stages of VMC. PMID:27766098

  14. Immunoactivation induced by chronic viral infection inhibits viral replication and drives immunosuppression through sustained IFN-I responses.

    PubMed

    Honke, Nadine; Shaabani, Namir; Merches, Katja; Gassa, Asmae; Kraft, Anke; Ehrhardt, Katrin; Häussinger, Dieter; Löhning, Max; Dittmer, Ulf; Hengel, Hartmut; Recher, Mike; Lang, Philipp A; Lang, Karl S

    2016-02-01

    Acute or chronic viral infections can lead to generalized immunosuppression. Several mechanisms, such as immunopathology of CD8(+) T cells, inhibitory receptors, or regulatory T (Treg) cells, contribute to immune dysfunction. Moreover, patients with chronic viral infections usually do not respond to vaccination, a finding that has not been previously explained. Recently, we reported that CD169(+) macrophages enforce viral replication, which is essential for guaranteeing antigen synthesis and efficient adaptive immune responses. In the present study, we used a chronic lymphocytic choriomeningitis virus infection mouse model to determine whether this mechanism is affected by chronic viral infection, which may impair the activation of adaptive immunity. We found that enforced viral replication of a superinfecting virus is completely blunted in chronically infected mice. This absence of enforced viral replication in CD169(+) macrophages is not explained by CD8(+) T-cell-mediated immunopathology but rather by prolonged IFN-I responses. Consequently, the absence of viral replication impairs both antigen production and the adaptive immune response against the superinfecting virus. These findings indicate that chronic infection leads to sustained IFN-I action, which is responsible for the absence of an antiviral immune response against a secondary viral infection. PMID:26507703

  15. Immunoactivation induced by chronic viral infection inhibits viral replication and drives immunosuppression through sustained IFN‐I responses

    PubMed Central

    Honke, Nadine; Shaabani, Namir; Merches, Katja; Gassa, Asmae; Kraft, Anke; Ehrhardt, Katrin; Häussinger, Dieter; Löhning, Max; Dittmer, Ulf; Hengel, Hartmut; Recher, Mike; Lang, Philipp A.

    2015-01-01

    Acute or chronic viral infections can lead to generalized immunosuppression. Several mechanisms, such as immunopathology of CD8+ T cells, inhibitory receptors, or regulatory T (Treg) cells, contribute to immune dysfunction. Moreover, patients with chronic viral infections usually do not respond to vaccination, a finding that has not been previously explained. Recently, we reported that CD169+ macrophages enforce viral replication, which is essential for guaranteeing antigen synthesis and efficient adaptive immune responses. In the present study, we used a chronic lymphocytic choriomeningitis virus infection mouse model to determine whether this mechanism is affected by chronic viral infection, which may impair the activation of adaptive immunity. We found that enforced viral replication of a superinfecting virus is completely blunted in chronically infected mice. This absence of enforced viral replication in CD169+ macrophages is not explained by CD8+ T‐cell‐mediated immunopathology but rather by prolonged IFN‐I responses. Consequently, the absence of viral replication impairs both antigen production and the adaptive immune response against the superinfecting virus. These findings indicate that chronic infection leads to sustained IFN‐I action, which is responsible for the absence of an antiviral immune response against a secondary viral infection. PMID:26507703

  16. The Characteristics Variation of Hepatic Progenitors after TGF-β1-Induced Transition and EGF-Induced Reversion.

    PubMed

    Wang, Ping; Cong, Min; Liu, Tianhui; Yang, Aiting; Sun, Guangyong; Zhang, Dong; Huang, Jian; Sun, Shujie; Mao, Jia; Ma, Hong; Jia, Jidong; You, Hong

    2016-01-01

    Profibrogenesis cytokine, transforming growth factor- (TGF-) β1, induces hepatic progenitors experiencing epithelial to mesenchymal transition (EMT) to matrix synthesis cells, even tumor initiating cells. Our previous data found that epidermal growth factor (EGF) blocks and reverses TGF-β1-induced transition. The aim of this study is to determine the characteristic changes of hepatic progenitors after TGF-β1-induced transition and EGF-induced reversion. Hepatic oval cells, rat hepatic progenitors, were isolated from rats fed a choline-deficient diet supplemented with ethionine. TGF-β1-containing medium was used for inducing EMT, while EGF-containing medium was used for reversing EMT. During TGF-β1-induced transition and EGF-induced reversion, hepatic oval cells sustained their progenitor cell marker expression, including α-fetoprotein, albumin, and cytokeratin-19. The proliferation ability and differentiation potential of these cells were suppressed by TGF-β1, while EGF resumed these capacities to the level similar to the control cells. RNA microarray analysis showed that most of the genes with significant changes after TGF-β1 incubation were recovered by EGF. Signal pathway analysis revealed that TGF-β1 impaired the pathways of cell cycle and cytochrome P450 detoxification, and EGF reverted TGF-β1 effects through activating MAPK and PI3K-Akt pathway. EGF reverses the characteristics impaired by TGF-β1 in hepatic oval cells, serving as a protective cytokine to hepatic progenitors. PMID:26955393

  17. BML-11, a lipoxin receptor agonist, protected carbon tetrachloride-induced hepatic fibrosis in rats.

    PubMed

    Zhou, Xiao-Yan; Yu, Zhong-Jian; Yan, Dan; Wang, Hong-Mei; Huang, Yong-Hong; Sha, Juan; Xu, Fang-Yun; Cai, Zhen-Yu; Min, Wei-Ping

    2013-10-01

    Inflammation plays an important role in the occurrence and development of fibrosis. Lipoxins (LXs) and BML-111 (lipoxin A4 agonist) have been approved for potent anti-inflammatory properties. Previously, we and others had showed LXs and BML-111 could protect acute hepatic injury, inhibit the growth and invasion of hepatic tumor. However, there are few reports dealing with their effects on hepatic fibrosis. To explore whether LXs and the analog could interrupt the process of hepatic fibrosis, the effects of BML-111 on tetrachloride-induced hepatic fibrosis were observed and the possible mechanism were discussed. Sprague-Dawley rats were induced liver fibrosis by carbon tetrachloride (CCl4) for 10 weeks with or without BML-111, and the histopathology and collagen content were employed to quantify hepatic necro-inflammation and fibrosis. Moreover, the expression levels of α-smooth muscle actin (α-SMA), transforming growth factor-β1 (TGF-β1), and platelet-derived growth factor (PDGF) were examined via Western blot or ELISA. Rats treated with BML-111 improved hepatic necro-inflammation and inhibited hepatic fibrosis in association with reduction of α-SMA expression and decreased collagen deposition. Furthermore, BML-111 could downregulate the expressions of TGF-β1 and PDGF significantly. BML-111 played a critical protective role in CCl4-induced hepatic fibrosis through inhibiting the levels of TGF-β1 and PDGF in rats.

  18. Naltrexone attenuates endoplasmic reticulum stress induced hepatic injury in mice.

    PubMed

    Moslehi, A; Nabavizadeh, F; Nabavizadeh, Fatemeh; Dehpour, A R; Dehpou, A R; Tavanga, S M; Hassanzadeh, G; Zekri, A; Nahrevanian, H; Sohanaki, H

    2014-09-01

    Endoplasmic reticulum (ER) stress provides abnormalities in insulin action, inflammatory responses, lipoprotein B100 degradation and hepatic lipogenesis. Excess accumulation of triglyceride in hepatocytes may also lead to disorders such as non-alcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). Opioid peptides are involved in triglyceride and cholesterol dysregulation, inflammation and cell death. In this study, we evaluated Naltrexone effects on ER stress induced liver injury. To do so, C57/BL6 mice received saline, DMSO and Naltrexone, as control groups. ER stress was induced by tunicamycin (TM) injection. Naltrexone was given before TM administration. Liver blood flow and biochemical serum analysis were measured. Histopathological evaluations, TNF-α measurement and Real-time RT-PCR were also performed. TM challenge provokes steatosis, cellular ballooning and lobular inflammation which significantly reduced in Naltrexone treated animals. ALT, AST and TNF-α increased in the TM group and improved in the Naltrexone plus TM group. Triglyceride and cholesterol levels decreased in TM treated mice with no increase in Naltrexone treated animals. In the Naltrexone plus TM group, gene expression of Bax/Bcl-2 ratio and caspase3 significantly lowered compared with the TM group. In this study, we found that Naltrexone had a notable alleviating role in ER stress induced steatosis and liver injury.

  19. High-resolution crystal structure of a hepatitis B virus replication inhibitor bound to the viral core protein.

    PubMed

    Klumpp, Klaus; Lam, Angela M; Lukacs, Christine; Vogel, Robert; Ren, Suping; Espiritu, Christine; Baydo, Ruth; Atkins, Kateri; Abendroth, Jan; Liao, Guochun; Efimov, Andrey; Hartman, George; Flores, Osvaldo A

    2015-12-01

    The hepatitis B virus (HBV) core protein is essential for HBV replication and an important target for antiviral drug discovery. We report the first, to our knowledge, high-resolution crystal structure of an antiviral compound bound to the HBV core protein. The compound NVR-010-001-E2 can induce assembly of the HBV core wild-type and Y132A mutant proteins and thermostabilize the proteins with a Tm increase of more than 10 °C. NVR-010-001-E2 binds at the dimer-dimer interface of the core proteins, forms a new interaction surface promoting protein-protein interaction, induces protein assembly, and increases stability. The impact of naturally occurring core protein mutations on antiviral activity correlates with NVR-010-001-E2 binding interactions determined by crystallography. The crystal structure provides understanding of a drug efficacy mechanism related to the induction and stabilization of protein-protein interactions and enables structure-guided design to improve antiviral potency and drug-like properties.

  20. High-resolution crystal structure of a hepatitis B virus replication inhibitor bound to the viral core protein

    PubMed Central

    Klumpp, Klaus; Lam, Angela M.; Lukacs, Christine; Vogel, Robert; Ren, Suping; Espiritu, Christine; Baydo, Ruth; Atkins, Kateri; Abendroth, Jan; Liao, Guochun; Efimov, Andrey; Hartman, George; Flores, Osvaldo A.

    2015-01-01

    The hepatitis B virus (HBV) core protein is essential for HBV replication and an important target for antiviral drug discovery. We report the first, to our knowledge, high-resolution crystal structure of an antiviral compound bound to the HBV core protein. The compound NVR-010–001-E2 can induce assembly of the HBV core wild-type and Y132A mutant proteins and thermostabilize the proteins with a Tm increase of more than 10 °C. NVR-010–001-E2 binds at the dimer–dimer interface of the core proteins, forms a new interaction surface promoting protein–protein interaction, induces protein assembly, and increases stability. The impact of naturally occurring core protein mutations on antiviral activity correlates with NVR-010–001-E2 binding interactions determined by crystallography. The crystal structure provides understanding of a drug efficacy mechanism related to the induction and stabilization of protein–protein interactions and enables structure-guided design to improve antiviral potency and drug-like properties. PMID:26598693

  1. High-resolution crystal structure of a hepatitis B virus replication inhibitor bound to the viral core protein.

    PubMed

    Klumpp, Klaus; Lam, Angela M; Lukacs, Christine; Vogel, Robert; Ren, Suping; Espiritu, Christine; Baydo, Ruth; Atkins, Kateri; Abendroth, Jan; Liao, Guochun; Efimov, Andrey; Hartman, George; Flores, Osvaldo A

    2015-12-01

    The hepatitis B virus (HBV) core protein is essential for HBV replication and an important target for antiviral drug discovery. We report the first, to our knowledge, high-resolution crystal structure of an antiviral compound bound to the HBV core protein. The compound NVR-010-001-E2 can induce assembly of the HBV core wild-type and Y132A mutant proteins and thermostabilize the proteins with a Tm increase of more than 10 °C. NVR-010-001-E2 binds at the dimer-dimer interface of the core proteins, forms a new interaction surface promoting protein-protein interaction, induces protein assembly, and increases stability. The impact of naturally occurring core protein mutations on antiviral activity correlates with NVR-010-001-E2 binding interactions determined by crystallography. The crystal structure provides understanding of a drug efficacy mechanism related to the induction and stabilization of protein-protein interactions and enables structure-guided design to improve antiviral potency and drug-like properties. PMID:26598693

  2. Hepatitis C Virus, Cholesterol and Lipoproteins — Impact for the Viral Life Cycle and Pathogenesis of Liver Disease

    PubMed Central

    Felmlee, Daniel J.; Hafirassou, Mohamed Lamine; Lefevre, Mathieu; Baumert, Thomas F.; Schuster, Catherine

    2013-01-01

    Hepatitis C virus (HCV) is a leading cause of chronic liver disease, including chronic hepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma. Hepatitis C infection associates with lipid and lipoprotein metabolism disorders such as hepatic steatosis, hypobetalipoproteinemia, and hypocholesterolemia. Furthermore, virus production is dependent on hepatic very-low-density lipoprotein (VLDL) assembly, and circulating virions are physically associated with lipoproteins in complexes termed lipoviral particles. Evidence has indicated several functional roles for the formation of these complexes, including co-opting of lipoprotein receptors for attachment and entry, concealing epitopes to facilitate immune escape, and hijacking host factors for HCV maturation and secretion. Here, we review the evidence surrounding pathogenesis of the hepatitis C infection regarding lipoprotein engagement, cholesterol and triglyceride regulation, and the molecular mechanisms underlying these effects. PMID:23698400

  3. [Influence of immunotropic preparation cycloferon and phytopreparations of Cynara scolimus L. on blood cytokines profile of the patients with chronic viral hepatitis C in medical rehabilitation period].

    PubMed

    Frolov, V M; Sotskaia, Ia A; Kruglova, O V

    2012-01-01

    The effect of the immunotropic drug cycloferon and herbal medicine resources on the basis of Cynara scolimus L. on the blood cytokine profile in the patients with chronic viral hepatitis C (CVHC) in medical rehabilitation (MR) period. Established that prior to MR period in the patients with CVHC was noted significantly increased levels of proinflammatory cytokines (CK) at the blood serum, and the level of antiinflammatory CK changed significantly. The use of cycloferon and herbal medicine resources on the basis of Cynara scolimus L. in the MR complex provided to normalize the studied CK concentration in the serum of the patients with CVHC.

  4. [Influence of immunotropic preparation cycloferon and phytopreparations of Cynara scolimus L. on blood cytokines profile of the patients with chronic viral hepatitis C in medical rehabilitation period].

    PubMed

    Frolov, V M; Sotskaia, Ia A; Kruglova, O V

    2012-01-01

    The effect of the immunotropic drug cycloferon and herbal medicine resources on the basis of Cynara scolimus L. on the blood cytokine profile in the patients with chronic viral hepatitis C (CVHC) in medical rehabilitation (MR) period. Established that prior to MR period in the patients with CVHC was noted significantly increased levels of proinflammatory cytokines (CK) at the blood serum, and the level of antiinflammatory CK changed significantly. The use of cycloferon and herbal medicine resources on the basis of Cynara scolimus L. in the MR complex provided to normalize the studied CK concentration in the serum of the patients with CVHC. PMID:23035608

  5. Specific primer sets used to amplify by PCR the hepatitis B virus overlapping S/Pol region select different viral variants.

    PubMed

    Cuestas, M L; Mathet, V L; Oubiña, J R

    2012-10-01

    PCR detection of viral genomes has provided new insights into viral diagnosis. Nowadays, it is the most frequently used nucleic acid testing (qualitative and quantitative) technique. The aim of this study was to analyse the major circulating hepatitis B virus (HBV) variants PCR-amplified by three sets of primers in a patient infected with genotype E. The HBV S/Pol overlapping genomic region was amplified from the serum of an infected child using three primer sets previously described. Sequence analysis corresponding to the HBV S/Pol region revealed the presence of different viral populations depending on the set of primers used. D144A S-escape mutant was detected with two of the primer sets, while the rtL217R mutant within the Pol - conferring resistance to Adefovir - could be picked up with a different pair of primer sets. This study undoubtedly implies that the description of viral polymorphisms should be stated together with the sequence of the primers used for PCR amplification when studies of escape and/or antiviral-resistant HBV mutants are carried out.

  6. Specific primer sets used to amplify by PCR the hepatitis B virus overlapping S/Pol region select different viral variants.

    PubMed

    Cuestas, M L; Mathet, V L; Oubiña, J R

    2012-10-01

    PCR detection of viral genomes has provided new insights into viral diagnosis. Nowadays, it is the most frequently used nucleic acid testing (qualitative and quantitative) technique. The aim of this study was to analyse the major circulating hepatitis B virus (HBV) variants PCR-amplified by three sets of primers in a patient infected with genotype E. The HBV S/Pol overlapping genomic region was amplified from the serum of an infected child using three primer sets previously described. Sequence analysis corresponding to the HBV S/Pol region revealed the presence of different viral populations depending on the set of primers used. D144A S-escape mutant was detected with two of the primer sets, while the rtL217R mutant within the Pol - conferring resistance to Adefovir - could be picked up with a different pair of primer sets. This study undoubtedly implies that the description of viral polymorphisms should be stated together with the sequence of the primers used for PCR amplification when studies of escape and/or antiviral-resistant HBV mutants are carried out. PMID:22967107

  7. The cis-acting replication element of the Hepatitis C virus genome recruits host factors that influence viral replication and translation

    PubMed Central

    Ríos-Marco, Pablo; Romero-López, Cristina; Berzal-Herranz, Alfredo

    2016-01-01

    The cis-acting replication element (CRE) of the hepatitis C virus (HCV) RNA genome is a region of conserved sequence and structure at the 3′ end of the open reading frame. It participates in a complex and dynamic RNA-RNA interaction network involving, among others, essential functional domains of the 3′ untranslated region and the internal ribosome entry site located at the 5′ terminus of the viral genome. A proper balance between all these contacts is critical for the control of viral replication and translation, and is likely dependent on host factors. Proteomic analyses identified a collection of proteins from a hepatoma cell line as CRE-interacting candidates. A large fraction of these were RNA-binding proteins sharing highly conserved RNA recognition motifs. The vast majority of these proteins were validated by bioinformatics tools that consider RNA-protein secondary structure. Further characterization of representative proteins indicated that hnRNPA1 and HMGB1 exerted negative effects on viral replication in a subgenomic HCV replication system. Furthermore DDX5 and PARP1 knockdown reduced the HCV IRES activity, suggesting an involvement of these proteins in HCV translation. The identification of all these host factors provides new clues regarding the function of the CRE during viral cycle progression. PMID:27165399

  8. The cis-acting replication element of the Hepatitis C virus genome recruits host factors that influence viral replication and translation.

    PubMed

    Ríos-Marco, Pablo; Romero-López, Cristina; Berzal-Herranz, Alfredo

    2016-01-01

    The cis-acting replication element (CRE) of the hepatitis C virus (HCV) RNA genome is a region of conserved sequence and structure at the 3' end of the open reading frame. It participates in a complex and dynamic RNA-RNA interaction network involving, among others, essential functional domains of the 3' untranslated region and the internal ribosome entry site located at the 5' terminus of the viral genome. A proper balance between all these contacts is critical for the control of viral replication and translation, and is likely dependent on host factors. Proteomic analyses identified a collection of proteins from a hepatoma cell line as CRE-interacting candidates. A large fraction of these were RNA-binding proteins sharing highly conserved RNA recognition motifs. The vast majority of these proteins were validated by bioinformatics tools that consider RNA-protein secondary structure. Further characterization of representative proteins indicated that hnRNPA1 and HMGB1 exerted negative effects on viral replication in a subgenomic HCV replication system. Furthermore DDX5 and PARP1 knockdown reduced the HCV IRES activity, suggesting an involvement of these proteins in HCV translation. The identification of all these host factors provides new clues regarding the function of the CRE during viral cycle progression. PMID:27165399

  9. Dominance of hepatitis C virus (HCV) is associated with lower quantitative hepatitis B surface antigen and higher serum interferon-γ-induced protein 10 levels in HBV/HCV-coinfected patients.

    PubMed

    Wiegand, S B; Jaroszewicz, J; Potthoff, A; Höner Zu Siederdissen, C; Maasoumy, B; Deterding, K; Manns, M P; Wedemeyer, H; Cornberg, M

    2015-07-01

    Different viral dominance patterns have been documented in coinfection with hepatitis B virus (HBV) and hepatitis C virus (HCV) based on HBV DNA and HCV RNA quantification. In most cases, HCV is dominant and suppresses HBV replication. In vitro studies revealed that there is most probably no direct interference between HBV and HCV replication. We hypothesized that indirect mechanisms mediated by host immune responses might be responsible for the different dominance patterns. In this study we analysed quantitative hepatitis B surface antigen (HBsAg) as a marker for immune control of HBV and interferon γ-induced protein 10 (IP-10) as host marker for the endogenous interferon in 85 patients with HBV/HCV coinfection. Levels of HBsAg were closely associated with viral dominance patterns in 85 HBV/HCV-coinfected patients. HBsAg levels were lowest in patients with HCV dominance, even lower compared with HBV-monoinfected patients undergoing treatment with nucleos(t)ide analogues (NA) but comparable to low replicative HBsAg carriers. An increase in HCV RNA during follow up was associated with HBsAg decline. Patients with HCV dominance had significantly higher serum IP-10 levels compared with HBV-dominant patients or HBV-monoinfected patients treated with NA. Lower HBsAg and higher IP-10 levels in HCV-dominant HBV/HCV-coinfected patients suggest that HCV suppresses HBV DNA replication and also HBsAg production by immune mechanisms.

  10. Liver Transplantation in Antituberculosis Drugs-Induced Fulminant Hepatic Failure

    PubMed Central

    Li, Xiaoyan; Liu, Yujie; Zhang, Erhong; He, Qiong; Tang, Yong-Bo

    2015-01-01

    Abstract The antituberculosis drugs isoniazid (INH), rifampicin (RMP), pyrazinamide (PZA), and ethambutol (EMB) usually expose patients to the risk of fulminant hepatic failure (FHF). This report presents a case of liver transplantation in antituberculosis drugs-induced FHF and reviews the relevant literature. A 39-year-old woman with pelvic and salpinx tuberculosis experienced complex pelvic exenteration. After the operation, she was administrated INH, RMP, PZA, and EMB to prevent tuberculosis. Two months later, examination revealed severe FHF and the antituberculosis therapy regimen was changed to ciprofloxacin and streptomycin. Subsequently, urgent orthotopic liver transplantation was performed. Posttransplantation, her serum transaminases improved gradually, but her total bilirubin level and direct bilirubin level continued to worsen, which may have been related to the rejection. However, irreversible damage from antituberulosis drugs was note excluded. Two liver biopsies and histological examinations were performed. One year after transplantation, she died as a consequence of ischemic cholangitis and pulmonary infection. A literature review revealed 9 other published cases of antituberculosis drugs-associated FHF with liver transplantation. This report suggests that, in most cases of antituberculosis drugs-induced FHF, discontinuation of toxic drugs and orthotopic liver transplantation are always sufficient treatment. PMID:26656321

  11. Polybrominated Diphenyl Ether (PBDE)-Induced Suppression of Phosphoenolpyruvate Carboxykinase (PEPCK) Decreases Hepatic Glyceroneogenesis and Disrupts Hepatic Lipid Homeostasis.

    PubMed

    Cowens, Kylie R; Simpson, Stephen; Thomas, W Kelley; Carey, Gale B

    2015-01-01

    Polybrominated diphenyl ethers (PBDE) are a class of flame-retardant chemicals that leach into the environment and enter the human body. PBDE have been shown to suppress activity of phosphoenolpyruvate carboxykinase (PEPCK), a key enzyme in fatty acid esterification via hepatic glyceroneogenesis. The objective of this investigation was to assess hepatic glyceroneogenesis and lipid metabolism in PBDE-treated rats. Male, weanling Wistar rats were gavaged daily for 28 d with 14 mg/kg body weight of either DE-71, a commercial PBDE mixture (treated), or corn oil (control). After a 48-h fast, rats were euthanized, blood was obtained, and livers were excised. Suppression of hepatic PEPCK activity by 40% was noted. Serum ketone bodies were elevated by 27% in treated rats compared to controls, while hepatic glyceroneogenesis as measured by (14)C-pyruvate incorporation into triglycerides was 41% lower in explants from treated rats compared to controls. Liver lipid content was 29% lower in treated animals compared to controls. Taken together, these findings suggest that DE-71-induced inhibition of hepatic PEPCK activity alters lipid metabolism by redirecting fatty acids away from esterification and storage toward ketone synthesis. PMID:26692069

  12. Direct hepatic differentiation of mouse embryonic stem cells induced by valproic acid and cytokines

    PubMed Central

    Dong, Xue-Jun; Zhang, Guo-Rong; Zhou, Qing-Jun; Pan, Ruo-Lang; Chen, Ye; Xiang, Li-Xin; Shao, Jian-Zhong

    2009-01-01

    AIM: To develop a protocol for direct hepatic lineage differentiation from early developmental progenitors to a population of mature hepatocytes. METHODS: Hepatic progenitor cells and then mature hepatocytes from mouse embryonic stem (ES) cells were obtained in a sequential manner, induced by valproic acid (VPA) and cytokines (hepatocyte growth factor, epidermal growth factor and insulin). Morphological changes of the differentiated cells were examined by phase-contrast microscopy and electron microscopy. Reverse transcription polymerase chain reaction and immunocytochemical analyses were used to evaluate the gene expression profiles of the VPA-induced hepatic progenitors and the hepatic progenitor-derived hepatocytes. Glycogen storage, cytochrome P450 activity, transplantation assay, differentiation of bile duct-like structures and tumorigenic analyses were performed for the functional identification of the differentiated cells. Furthermore, FACS and electron microscopy were used for the analyses of cell cycle profile and apoptosis in VPA-induced hepatic differentiated cells. RESULTS: Based on the combination of VPA and cytokines, mouse ES cells differentiated into a uniform and homogeneous cell population of hepatic progenitor cells and then matured into functional hepatocytes. The progenitor population shared several characteristics with ES cells and hepatic stem/progenitor cells, and represented a novel progenitor cell between ES and hepatic oval cells in embryonic development. The differentiated hepatocytes from progenitor cells shared typical characteristics with mature hepatocytes, including the patterns of gene expression, immunological markers, in vitro hepatocyte functions and in vivo capacity to restore acute-damaged liver function. In addition, the differentiation of hepatic progenitor cells from ES cells was accompanied by significant cell cycle arrest and selective survival of differentiating cells towards hepatic lineages. CONCLUSION: Hepatic cells

  13. Hepatitis C Virus Attenuates Interferon-Induced MHC Class I Expression and Decreases CD8+ T-Cell Effector Functions

    PubMed Central

    Kang, Wonseok; Sung, Pil Soo; Park, Su-Hyung; Yoon, Sarah; Chang, Dong-Yeop; Kim, Seungtaek; Han, Kwang Hyub; Kim, Ja Kyung; Rehermann, Barbara; Chwae, Yong-Joon; Shin, Eui-Cheol

    2015-01-01

    BACKGROUND & AIMS MHC class I-restricted CD8+ T cells are required for clearance of hepatitis C virus (HCV) infection. MHC class I expression is upregulated by type I and II interferons (IFNs). However, little is known about the effects of HCV infection on IFN-induced expression of MHC class I. METHODS We used the HCV cell culture system (HCVcc) with the genotype 2a Japanese Fulminant Hepatitis-1 strain to investigate IFN-induced expression of MHC class I and its regulatory mechanisms. HCVcc-infected Huh-7.5 cells were analyzed by flow cytometry, metabolic labeling, immunoprecipitation, and immunoblotting analyses. Protein kinase R (PKR) was knocked-down with lentiviruses that express small hairpin (sh)RNAs. The functional effects of MHC class I regulation by HCV were demonstrated in co-culture studies, using HCV-specific CD8+ T cells. RESULTS Although the baseline level of MHC class I was not affected by HCV infection, IFN-induced expression of MHC class I was notably attenuated in HCV-infected cells. This was associated with replicating HCV RNA, not with viral protein. HCV infection reduced IFN-induced synthesis of MHC class I protein and induced phosphorylation of PKR and eIF2α. IFN-induced MHC class I expression was restored by shRNA-mediated knockdown of PKR in HCV-infected cells. Co-culture of HCV-specific CD8+ T cells and HCV-infected cells that expressed HLA-A2 demonstrated that HCV infection reduced the effector functions of HCV-specific CD8+ T cells; these functions were restored by shRNA-mediated knockdown of PKR. CONCLUSIONS IFN-induced expression of MHC class I is attenuated in HCV-infected cells by activation of PKR, which reduces the effector functions of HCV-specific CD8+ T cells. This appears to be an important mechanism by which HCV circumvents antiviral adaptive immune responses. PMID:24486950

  14. [Fulminant hepatitis induced by disulfiram in a patient with alcoholic cirrhosis. Survival after liver transplantation].

    PubMed

    Vanjak, D; Samuel, D; Gosset, F; Derrida, S; Moreau, R; Soupison, T; Soulier, A; Bismuth, H; Sicot, C

    1989-12-01

    Fulminant hepatitis was observed in a 44-year-old patient with cirrhosis, 38 days after the beginning of a treatment by disulfiram. Hepatitis was associated with fever and hypereosinophilia. Liver transplantation was performed with success. We reviewed 15 previously published cases of disulfiram-induced hepatitis. They occurred from 10 to 180 days after the beginning of the treatment by disulfiram, aminotransferases were increased whereas alkaline phosphatases were not markedly changed; there was either focal or widespread necrosis. Fulminant hepatitis was observed mainly in patients with alcoholic chronic liver disease or in patients who continued to ingest disulfiram while jaundice was already present. An immunoallergic mechanism is thought to be responsible for disulfiram-induced hepatitis. PMID:2625187

  15. [A case of allopurinol-induced granulomatous hepatitis with ductopenia and cholestasis].

    PubMed

    Yoon, Jae Young; Min, Sun Yang; Park, Ju Yee; Hong, Seung Goun; Park, Sang Jong; Paik, So Ya; Park, Young Min

    2008-03-01

    Allopurinol-induced hypersensitivity syndrome is characterized by an idiosyncratic reaction involving multiple-organs, which usually begins 2 to 6 weeks after starting allopurinol. In rare cases, the adverse reactions to allopurinol are accompanied by a variety of liver injury, such as reactive hepatitis, granulomatous hepatitis, vanishing bile duct syndrome, or fulminant hepatic failure. Here we report a case with granulomatous hepatitis and ductopenia. A 69-year-old man with chronic renal failure, hyperuricemia, and previously normal liver function presented with jaundice, skin rash, and fever 2 weeks after taking allopurinol (200 mg/day). In histopathology, a liver biopsy specimen showed mild spotty necrosis of hepatocytes, marked cholestasis in parenchyma, and some granulomas in the portal area. There were vacuolar degeneration in the interlobular bile ducts and ductopenia in the portal tracts. Pathologic criteria strongly suggested the presence of allopurinol-induced granulomatous hepatitis with ductopenia and cholestasis. The patient fully recovered following the early administration of systemic corticosteroid therapy.

  16. Atherogenic diet-induced hepatitis is partially dependent on murine TLR4

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Diets high in cholesterol and cholate such as the Paigen diet have been used to study atherogenesis, lithogenesis, and proinflammatory microvascular changes induced by nutritional hypercholesterolemia. Although these diets lead to chronic hepatic inflammation and fibrosis, the early inflammatory cha...

  17. Bronchoscopic Investigation of Atypical Drug-induced Hypersensitivity Syndrome Showing Viral Lung Involvement.

    PubMed

    Hase, Isano; Arakawa, Hiroaki; Sakuma, Hideo; Kaneko, Fumio; Watanabe, Yuzuru; Fujiu, Koichi; Miyamoto, Hideaki; Ishii, Yoshiki

    2016-01-01

    We herein report a case of atypical drug-induced hypersensitivity syndrome (DIHS) involving serological reactivation of cytomegalovirus induced by carbamazepine with pulmonary and skin manifestations. These lesions were not present on admission, but developed on virus reactivation as indicated by the presence of inclusion bodies and multinucleated giant cells in alveolar cells with CD8(+) T lymphocyte infiltration on a transbronchial lung biopsy. Although the precise mechanism of DIHS remains unknown, this case suggests the crucial role of viral reactivation in pulmonary lesions in DIHS. PMID:27629969

  18. Identification of critical residues in Hepatitis E virus macro domain involved in its interaction with viral methyltransferase and ORF3 proteins

    PubMed Central

    Anang, Saumya; Subramani, Chandru; Nair, Vidya P.; Kaul, Sheetal; Kaushik, Nidhi; Sharma, Chandresh; Tiwari, Ashutosh; Ranjith-Kumar, CT; Surjit, Milan

    2016-01-01

    Hepatitis E virus (HEV) is a major cause of hepatitis in normal and organ transplant individuals. HEV open reading frame-1 encodes a polypeptide comprising of the viral nonstructural proteins as well as domains of unknown function such as the macro domain (X-domain), V, DUF3729 and Y. The macro domain proteins are ubiquitously present from prokaryotes to human and in many positive-strand RNA viruses, playing important roles in multiple cellular processes. Towards understanding the function of the HEV macro domain, we characterized its interaction partners among other HEV encoded proteins. Here, we report that the HEV X-domain directly interacts with the viral methyltransferase and the ORF3 proteins. ORF3 association with the X-domain was mediated through two independent motifs, located within its N-terminal 35aa (amino acids) and C-terminal 63-123aa. Methyltransferase interaction domain was mapped to N-terminal 30-90aa. The X-domain interacted with both ORF3 and methyltransferase through its C-terminal region, involving 66th,67th isoleucine and 101st,102nd leucine, conserved across HEV genotypes. Furthermore, ORF3 and methyltransferase competed with each other for associating with the X-domain. These findings provide molecular understanding of the interaction between the HEV macro domain, methyltransferase and ORF3, suggesting an important role of the macro domain in the life cycle of HEV. PMID:27113483

  19. Identification of critical residues in Hepatitis E virus macro domain involved in its interaction with viral methyltransferase and ORF3 proteins.

    PubMed

    Anang, Saumya; Subramani, Chandru; Nair, Vidya P; Kaul, Sheetal; Kaushik, Nidhi; Sharma, Chandresh; Tiwari, Ashutosh; Ranjith-Kumar, C T; Surjit, Milan

    2016-04-26

    Hepatitis E virus (HEV) is a major cause of hepatitis in normal and organ transplant individuals. HEV open reading frame-1 encodes a polypeptide comprising of the viral nonstructural proteins as well as domains of unknown function such as the macro domain (X-domain), V, DUF3729 and Y. The macro domain proteins are ubiquitously present from prokaryotes to human and in many positive-strand RNA viruses, playing important roles in multiple cellular processes. Towards understanding the function of the HEV macro domain, we characterized its interaction partners among other HEV encoded proteins. Here, we report that the HEV X-domain directly interacts with the viral methyltransferase and the ORF3 proteins. ORF3 association with the X-domain was mediated through two independent motifs, located within its N-terminal 35aa (amino acids) and C-terminal 63-123aa. Methyltransferase interaction domain was mapped to N-terminal 30-90aa. The X-domain interacted with both ORF3 and methyltransferase through its C-terminal region, involving 66(th),67(th) isoleucine and 101(st),102(nd) leucine, conserved across HEV genotypes. Furthermore, ORF3 and methyltransferase competed with each other for associating with the X-domain. These findings provide molecular understanding of the interaction between the HEV macro domain, methyltransferase and ORF3, suggesting an important role of the macro domain in the life cycle of HEV.

  20. Application of dual-cloud point extraction for the trace levels of copper in serum of different viral hepatitis patients by flame atomic absorption spectrometry: A multivariate study

    NASA Astrophysics Data System (ADS)

    Arain, Salma Aslam; Kazi, Tasneem G.; Afridi, Hassan Imran; Abbasi, Abdul Rasool; Panhwar, Abdul Haleem; Naeemullah; Shanker, Bhawani; Arain, Mohammad Balal

    2014-12-01

    An efficient, innovative preconcentration method, dual-cloud point extraction (d-CPE) has been developed for the extraction and preconcentration of copper (Cu2+) in serum samples of different viral hepatitis patients prior to couple with flame atomic absorption spectrometry (FAAS). The d-CPE procedure was based on forming complexes of elemental ions with complexing reagent 1-(2-pyridylazo)-2-naphthol (PAN), and subsequent entrapping the complexes in nonionic surfactant (Triton X-114). Then the surfactant rich phase containing the metal complexes was treated with aqueous nitric acid solution, and metal ions were back extracted into the aqueous phase, as second cloud point extraction stage, and finally determined by flame atomic absorption spectrometry using conventional nebulization. The multivariate strategy was applied to estimate the optimum values of experimental variables for the recovery of Cu2+ using d-CPE. In optimum experimental conditions, the limit of detection and the enrichment factor were 0.046 μg L-1 and 78, respectively. The validity and accuracy of proposed method were checked by analysis of Cu2+ in certified sample of serum (CRM) by d-CPE and conventional CPE procedure on same CRM. The proposed method was successfully applied to the determination of Cu2+ in serum samples of different viral hepatitis patients and healthy controls.

  1. Application of dual-cloud point extraction for the trace levels of copper in serum of different viral hepatitis patients by flame atomic absorption spectrometry: a multivariate study.

    PubMed

    Arain, Salma Aslam; Kazi, Tasneem G; Afridi, Hassan Imran; Abbasi, Abdul Rasool; Panhwar, Abdul Haleem; Naeemullah; Shanker, Bhawani; Arain, Mohammad Balal

    2014-12-10

    An efficient, innovative preconcentration method, dual-cloud point extraction (d-CPE) has been developed for the extraction and preconcentration of copper (Cu(2+)) in serum samples of different viral hepatitis patients prior to couple with flame atomic absorption spectrometry (FAAS). The d-CPE procedure was based on forming complexes of elemental ions with complexing reagent 1-(2-pyridylazo)-2-naphthol (PAN), and subsequent entrapping the complexes in nonionic surfactant (Triton X-114). Then the surfactant rich phase containing the metal complexes was treated with aqueous nitric acid solution, and metal ions were back extracted into the aqueous phase, as second cloud point extraction stage, and finally determined by flame atomic absorption spectrometry using conventional nebulization. The multivariate strategy was applied to estimate the optimum values of experimental variables for the recovery of Cu(2+) using d-CPE. In optimum experimental conditions, the limit of detection and the enrichment factor were 0.046μgL(-1) and 78, respectively. The validity and accuracy of proposed method were checked by analysis of Cu(2+) in certified sample of serum (CRM) by d-CPE and conventional CPE procedure on same CRM. The proposed method was successfully applied to the determination of Cu(2+) in serum samples of different viral hepatitis patients and healthy controls.

  2. Tropism of human pegivirus (formerly known as GB virus C/hepatitis G virus) and host immunomodulation: insights into a highly successful viral infection.

    PubMed

    Chivero, Ernest T; Stapleton, Jack T

    2015-07-01

    Human pegivirus (HPgV; originally called GB virus C/hepatitis G virus) is an RNA virus within the genus Pegivirus of the family Flaviviridae that commonly causes persistent infection. Worldwide, ~750 million people are actively infected (viraemic) and an estimated 0.75-1.5 billion people have evidence of prior HPgV infection. No causal association between HPgV and disease has been identified; however, several studies described a beneficial relationship between persistent HPgV infection and survival in individuals infected with human immunodeficiency virus. The beneficial effect appeared to be related to a reduction in host immune activation. HPgV replicates well in vivo (mean plasma viral loads typically >1×107 genome copies ml-1); however, the virus grows poorly in vitro and systems to study this virus are limited. Consequently, mechanisms of viral persistence and host immune modulation remain poorly characterized, and the primary permissive cell type(s) has not yet been identified. HPgV RNA is found in liver, spleen, bone marrow and PBMCs, including T- and B-lymphocytes, NK-cells, and monocytes, although the mechanism of cell-to-cell transmission is unclear. HPgV RNA is also present in serum microvesicles with properties of exosomes. These microvesicles are able to transmit viral RNA to PBMCs in vitro, resulting in productive infection. This review summarizes existing data on HPgV cellular tropism and the effect of HPgV on immune activation in various PBMCs, and discusses how this may influence viral persistence. We conclude that an increased understanding of HPgV replication and immune modulation may provide insights into persistent RNA viral infection of humans.

  3. The risk of human T cell leukemia virus and viral hepatitis infection among US Marines stationed in Okinawa, Japan.

    PubMed

    Brodine, S K; Hyams, K C; Molgaard, C A; Ito, S I; Thomas, R J; Roberts, C R; Golbeck, A L; Oldfield, E C; Blattner, W A

    1995-03-01

    The prevalence and incidence of human T cell leukemia virus type I/II (HTLV-I/II) and hepatitis A, B, and C virus infection were determined among US Marines stationed in Okinawa, Japan. Of 2875 personnel, 2 (0.07%) had antibody to HTLV-I/II. After 1-3 years, no HTLV seroconversions were observed, although 23% reported sexual contact with Okinawans. Of 1010 hepatitis-tested marines, 121 (12%) had antibody to hepatitis A virus (anti-HAV), 26 (2.6%) had antibody to hepatitis B core antigen (anti-HBc), and 2 (0.2%) had antibody to hepatitis C virus (anti-HCV). On follow-up, 1 subject seroconverted to anti-HAV, 8 to anti-HBc, and none to anti-HCV. Most marines with recent hepatitis B infection were young, single, and enlisted and had been on short deployments to other countries in Southeast Asia. Marines stationed in Okinawa are not at high risk for HTLV infection but are at increased risk for hepatitis B infection and should be considered for vaccination. PMID:7876620

  4. Hydrogen sulfide protects against cognitive impairment induced by hepatic ischemia and reperfusion via attenuating neuroinflammation.

    PubMed

    Tu, Faping; Li, Jingdong; Wang, Ji; Li, Qiang; Chu, Weihua

    2016-03-01

    Previously, hepatic ischemia followed by reperfusion (hepatic I/R) has been found to cause cognitive impairment. Hydrogen sulfide (H2S) attenuates hepatectomy induced cognitive deficits and also protects against cognitive dysfunction induced by neurodegenerative diseases. In this study, we aim to determine whether sodium hydrosulfide (NaHS), a H2S donor, could alleviate hepatic I/R-induced cognitive impairment and the underlying mechanisms. Rats were injected intraperitoneally with NaHS (5 mg/kg/d) for 11 days. A segmental hepatic I/R model was established on the fourth day. Cognitive function, proinflammatory cytokines levels, and hippocampal ionized calcium-binding adaptor molecule 1 (Iba1) expression was analyzed. We found hepatic I/R increased proinflammatory cytokines levels in serum and hippocampus, up-regulated Iba1 expression, leading to cognitive impairment in rats. However, treatment with NaHS alleviated hepatic I/R induced these neuroinflammatory changes and effectively improved cognitive function. Thus, NaHS appears to protect against cognitive impairment in rats undergoing hepatic I/R by attenuating neuroinflammation in the hippocampus.

  5. Hydrogen sulfide protects against cognitive impairment induced by hepatic ischemia and reperfusion via attenuating neuroinflammation

    PubMed Central

    Tu, Faping; Li, Jingdong; Wang, Ji; Li, Qiang

    2016-01-01

    Previously, hepatic ischemia followed by reperfusion (hepatic I/R) has been found to cause cognitive impairment. Hydrogen sulfide (H2S) attenuates hepatectomy induced cognitive deficits and also protects against cognitive dysfunction induced by neurodegenerative diseases. In this study, we aim to determine whether sodium hydrosulfide (NaHS), a H2S donor, could alleviate hepatic I/R-induced cognitive impairment and the underlying mechanisms. Rats were injected intraperitoneally with NaHS (5 mg/kg/d) for 11 days. A segmental hepatic I/R model was established on the fourth day. Cognitive function, proinflammatory cytokines levels, and hippocampal ionized calcium-binding adaptor molecule 1 (Iba1) expression was analyzed. We found hepatic I/R increased proinflammatory cytokines levels in serum and hippocampus, up-regulated Iba1 expression, leading to cognitive impairment in rats. However, treatment with NaHS alleviated hepatic I/R induced these neuroinflammatory changes and effectively improved cognitive function. Thus, NaHS appears to protect against cognitive impairment in rats undergoing hepatic I/R by attenuating neuroinflammation in the hippocampus. PMID:26811101

  6. HMGB1 Promotes Hepatitis C Virus Replication by Interaction with Stem-Loop 4 in the Viral 5′ Untranslated Region

    PubMed Central

    Yu, Rong; Yang, Darong; Lei, Shaohua; Wang, Xiaohong; Meng, Xianghe; Xue, Binbin

    2015-01-01

    ABSTRACT High-mobility group box 1 (HMGB1) protein is a highly conserved nuclear protein involved in multiple human diseases, including infectious diseases, immune disorders, metabolic disorders, and cancer. HMGB1 is comprised of two tandem HMG boxes (the A box and the B box) containing DNA-binding domains and an acidic C-terminal peptide. It has been reported that HMGB1 enhances viral replication by binding to viral proteins. However, its role in hepatitis C virus (HCV) replication is unknown. Here, we show that HMGB1 promoted HCV replication but had no effect on HCV translation. RNA immunoprecipitation experiments indicated that the positive strand, not the negative strand, of HCV RNA interacted with HMGB1. HCV infection triggered HMGB1 protein translocation from the nucleus to the cytoplasm, in which it interacted with the HCV genome. Moreover, the A box of HMGB1 is the pivotal domain to interact with stem-loop 4 (SL4) of the HCV 5′ untranslated region. Deletion of the HMGB1 A box abrogated the enhancement of HCV replication by HMGB1. Our data suggested that HMGB1 serves as a proviral factor of HCV to facilitate viral replication in hepatocytes by interaction with the HCV genome. IMPORTANCE Hepatitis C virus (HCV) is a major global health threat, affecting more than 170 million people infection worldwide. These patients are at high risk of developing severe liver diseases such as chronic hepatitis, cirrhosis, and hepatocellular carcinoma. Currently, no vaccine is available. Many host factors may be implicated in the pathogenesis of HCV-related diseases. In this study, we found a novel HCV RNA-binding protein, HMGB1, that promotes HCV RNA replication. Moreover, SL4 in the 5′ untranslated region of the HCV genome is the key region for HMGB1 binding, and the A box of HMGB1 protein is the functional domain to interact with HCV RNA and enhance viral replication. HMGB1 appears to play an important role in HCV-related diseases, and further investigation is

  7. Hepatitis B

    MedlinePlus

    ... and Change Plan Wallet card for patients to record their alcohol use over a 4-week period as a way to monitor and reduce their drinking behavior. Glossary Definitions of terms commonly used with viral hepatitis and ...

  8. Genetic analysis of hepatitis A virus strains that induced epidemics in Korea during 2007-2009.

    PubMed

    Lee, Hyeokjin; Jeong, Hyesook; Yun, Heasun; Kim, Kisang; Kim, Jong-Hyun; Yang, Jai Myung; Cheon, Doo-Sung

    2012-04-01

    Hepatitis A virus is one of the most prominent causes of fecally transmitted acute hepatitis worldwide. In order to characterize the viral agents causing an outbreak in Korea (comprising North and South Korea) from June 2007 to May 2009, we collected specimens and performed genotyping of the VP1/P2A and VP3/VP1 regions of hepatitis A virus. We then used a multiple-alignment algorithm to compare the nucleotide sequences of the 2 regions with those of reference strains. Hepatitis A virus antibodies were detected in 64 patients from 5 reported outbreaks (North Korea, June 2007 [n = 11]; Jeonnam, April 2008 [n = 15]; Daegu, May 2008 [n = 13]; Seoul, May 2009 [n = 22]; and Incheon, May 2009 [n = 3]). We found 100% homology between strains isolated from the Kaesong Industrial Region and Jeonnam. While those strains were classified as genotype IA strains, strains from Seoul and Incheon were identified as genotype IIIA strains and showed 98.9 to 100% homology. Genotype IIIA was also dominant in Daegu, where strains were 95.7 to 100% homologous. All hepatitis A virus strains isolated from the Kaesong Industrial Region, Jeonnam, Seoul, and Incheon belonged to a single cluster. However, strains from Daegu could be classified into 2 clusters, suggesting that the outbreak had multiple sources. This study indicates that hepatitis A virus strains of 2 different genotypes are currently cocirculating in Korea. Moreover, it documents an increasing prevalence of genotype IIIA strains in the country. PMID:22238447

  9. HCV Infection and Interferon-Based Treatment Induce p53 Gene Transcription in Chronic Hepatitis C Patients.

    PubMed

    Świątek-Kościelna, Bogna; Kałużna, Ewelina Maria; Januszkiewicz-Lewandowska, Danuta; Rembowska, Jolanta; Mozer-Lisewska, Iwona; Bereszyńska, Iwona; Czubała, Katarzyna; Dziechciowska, Katarzyna; Wysocka-Leszczyńska, Joanna; Barcińska, Dominika; Wysocki, Jacek; Nowak, Jerzy Stanisław

    2015-10-01

    It is suggested that the tumor suppressor p53 gene, classified as an interferon-stimulated gene, is implicated in the interferon (IFN)-mediated innate immunity against viruses. This study aimed to examine the transcriptional response of the p53 gene to hepatitis C virus (HCV) infection and IFN-based therapy in chronic hepatitis C (CHC) patients. The study included 65 CHC patients (HCV genotype 1), treated with pegylated IFN-α and ribavirin, and 51 healthy individuals. p53 gene expression was quantified by real-time polymerase chain reaction in peripheral blood mononuclear cells (PBMCs). Analyses were performed before and at weeks 4 and 12 of treatment. p53 gene expression was significantly upregulated in CHC patients compared with healthy controls and at week 4 of therapy. No significant differences in p53 mRNA expression between rapid virologic responders, complete early virologic responders, and nonresponders were observed. No significant correlation was found between p53 gene expression and viral load. The results obtained indicate that HCV infection and IFN-based treatment induces p53 gene transcription in PBMCs. The p53 gene may therefore play a role in HCV infection but is not directly involved in treatment-induced HCV elimination. Moreover, variations in p53 gene expression do not determine on-treatment response in patients with chronic HCV genotype 1 infection.

  10. Prevalence of HBsAg, knowledge, and vaccination practice against viral hepatitis B infection among doctors and nurses in a secondary health care facility in Lagos state, South-western Nigeria

    PubMed Central

    Abiola, Abdul-Hakeem Olatunji; Agunbiade, Adebukola Bola; Badmos, Kabir Bolarinwa; Lesi, Adenike Olufunmilayo; Lawal, Abdulrazzaq Oluwagbemiga; Alli, Quadri Olatunji

    2016-01-01

    Introduction Hepatitis B Virus, a highly infectious blood-borne virus poses a major threat to public health globally due to its high prevalence rate and grave consequence in causing liver cirrhosis and hepatocelullar carcinoma, the third cause of cancer death worldwide. The aim is determine the prevalence of HBsAg, knowledge, and vaccination practices against viral hepatitis B infection among doctors and nurses in a health care facility. Methods Study design was a descriptive cross-sectional study among all the doctors and nurses in the health care facility. Data was collected using pre-tested, structured, self-administered questionnaire and blood samples were taken from respondents and tested using commercial enzyme-linked immunosorbent assay (ELIZA) test kit to determine prevalence of hepatitis B surface antigen after informed consent. Ethical approval was obtained from Health Research and Ethics Committee of the Lagos University Teaching Hospital. Responses of the respondents to the knowledge and vaccination practices against viral hepatitis B infection were scored and graded as poor (<50%), fair (50-74%) and good (≥75%). The study was carried out in January, 2014. Results A total of 134 out of the 143 recruited respondents participated in the study. Prevalence of HBsAg was 1.5%. Among the respondents, 56.7% had good knowledge and 94.8% reported poor practice of vaccination against viral hepatitis B infection. Mean knowledge and vaccination practices scores (%) were 72.54+7.60 and 29.44+14.37 respectively. Only 29% of the respondents did post vaccination testing for anti HBsAg. Conclusion Prevalence of HBsAg was low. Knowledge of viral hepatitis B was fair, and practice of post hepatitis B vaccination testing was poor. It is therefore recommended that the state ministry of health should organise further health education programme, institute compulsory occupational hepatitis B vaccination programme and post vaccination anti-HBS testing to ensure adequate

  11. Green tea phenolic epicatechins inhibit hepatitis C virus replication via cycloxygenase-2 and attenuate virus-induced inflammation.

    PubMed

    Lin, Ying-Ting; Wu, Yu-Hsuan; Tseng, Chin-Kai; Lin, Chun-Kuang; Chen, Wei-Chun; Hsu, Yao-Chin; Lee, Jin-Ching

    2013-01-01

    Chronic hepatitis C virus (HCV) infection is the leading risk factor for hepatocellular carcinoma (HCC) and chronic liver disease worldwide. Green tea, in addition to being consumed as a healthy beverage, contains phenolic catechins that have been used as medicinal substances. In the present study, we illustrated that the epicatechin isomers (+)-epicatechin and (-)-epicatechin concentration-dependently inhibited HCV replication at nontoxic concentrations by using in vitro cell-based HCV replicon and JFH-1 infectious systems. In addition to significantly suppressing virus-induced cyclooxygenase-2 (COX-2) expression, our results revealed that the anti-HCV activity of the epicatechin isomers occurred through the down-regulation of COX-2. Furthermore, both the epicatechin isomers additively inhibited HCV replication in combination with either interferon-α or viral enzyme inhibitors [2'-C-methylcytidine (NM-107) or telaprevir]. They also had prominent anti-inflammatory effects by inhibiting the gene expression of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and inducible nitrite oxide synthase as well as the COX-2 in viral protein-expressing hepatoma Huh-7 cells. Collectively, (+)-epicatechin and (-)-epicatechin may serve as therapeutic supplements for treating HCV-related diseases.

  12. Manifestation of psychiatric behaviors in a mouse model of griseofulvin-induced hepatic porphyria.

    PubMed

    Satoh, Yoko; Iwadate, Reiko; Watanabe, Yukino; Kawai, Hiroshi; Kudo, Naomi; Kawashima, Yoichi; Mitsumoto, Atsushi

    2008-12-01

    Most patients with hepatic porphyria exhibit neuropsychiatric symptoms, including abdominal pain, peripheral neuropathy, confusion, insomnia and mental disturbances such as anxiety and depression. Although heme deficiency and accumulation of heme precursors are thought to be responsible for neuropsychiatric manifestations in patients with acute porphyria, the pathogenetic mechanisms remain poorly understood. In the present study, we observed psychiatric behaviors in mice with hepatic porphyria induced by the ingestion of a griseofulvin (GF)-containing diet over a period of 12 weeks. GF ingestion by the mice caused an accumulation of porphyrins in the feces and a decrease in heme in the liver; these effects were observed throughout the entire duration of the experiment, with maximum levels observed after circa 1 week of ingestion of this diet. In addition, the mice developed enlargement of the liver, hepatocyte injury, and cholestasis. Mice with hepatic porphyria manifested an anxiety-like behavior by the long-term treatment (over 5 weeks) in a GF-dose and duration dependent manner. The hepatic porphyria mice also manifested depression-like behaviors by the short-term treatment (3 weeks) of GF2.0, which was reversed by administration of anti-depressant, imipramine. In conclusion, this study for the first time demonstrated psychiatric manifestations in GF-induced hepatic porphyria mice. The present results suggest that model animals could be useful for elucidating the mechanisms underlying psychiatric manifestations in syndromes such as hepatic porphyria and hepatic encephalopathy that are associated with the impairment of hepatic function.

  13. Silencing of hepatitis C virus replication by a non-viral vector based on solid lipid nanoparticles containing a shRNA targeted to the internal ribosome entry site (IRES).

    PubMed

    Torrecilla, Josune; Del Pozo-Rodríguez, Ana; Solinís, María Ángeles; Apaolaza, Paola S; Berzal-Herranz, Beatriz; Romero-López, Cristina; Berzal-Herranz, Alfredo; Rodríguez-Gascón, Alicia

    2016-10-01

    Gene silencing mediated by RNAi has gained increasing interest as an alternative for the treatment of infectious diseases such as refractory hepatitis C virus (HCV) infection. In this work we have designed and evaluated a non-viral vector based on solid lipid nanoparticles (SLN) bearing hyaluronic acid, protamine and a short hairpin RNA (shRNA74) targeted to the Internal Ribosome Entry Site (IRES) of the HCV. The vector was able to inhibit the expression of the HCV IRES in Huh-7 cells, with the inhibition level dependent on the shRNA74 to SLN ratio and on the shRNA74 dose added to the culture cells. The nanocarrier was also able to inhibit the replication in human hepatoma cells supporting a subgenomic HCV replicon (Huh-7 NS3-3'). The vector was quickly and efficiently internalized by the cells, and endocytosis was the most productive uptake mechanism for silencing. Clathrin-mediated endocytosis and to a lesser extent caveolae/lipid raft-mediated endocytosis were identified as endocytic mechanisms involved in the cell uptake. Internalization via the CD44 receptor was also involved, although this entry route seems to be less productive for silencing than endocytosis. The vector did not induce either hemolysis or agglutination of red cells in vitro, which was indicative of good biocompatibility. In summary, we have shown for the first time the ability of a non-viral SLN-based vector to silence a HCV replicon.

  14. Silencing of hepatitis C virus replication by a non-viral vector based on solid lipid nanoparticles containing a shRNA targeted to the internal ribosome entry site (IRES).

    PubMed

    Torrecilla, Josune; Del Pozo-Rodríguez, Ana; Solinís, María Ángeles; Apaolaza, Paola S; Berzal-Herranz, Beatriz; Romero-López, Cristina; Berzal-Herranz, Alfredo; Rodríguez-Gascón, Alicia

    2016-10-01

    Gene silencing mediated by RNAi has gained increasing interest as an alternative for the treatment of infectious diseases such as refractory hepatitis C virus (HCV) infection. In this work we have designed and evaluated a non-viral vector based on solid lipid nanoparticles (SLN) bearing hyaluronic acid, protamine and a short hairpin RNA (shRNA74) targeted to the Internal Ribosome Entry Site (IRES) of the HCV. The vector was able to inhibit the expression of the HCV IRES in Huh-7 cells, with the inhibition level dependent on the shRNA74 to SLN ratio and on the shRNA74 dose added to the culture cells. The nanocarrier was also able to inhibit the replication in human hepatoma cells supporting a subgenomic HCV replicon (Huh-7 NS3-3'). The vector was quickly and efficiently internalized by the cells, and endocytosis was the most productive uptake mechanism for silencing. Clathrin-mediated endocytosis and to a lesser extent caveolae/lipid raft-mediated endocytosis were identified as endocytic mechanisms involved in the cell uptake. Internalization via the CD44 receptor was also involved, although this entry route seems to be less productive for silencing than endocytosis. The vector did not induce either hemolysis or agglutination of red cells in vitro, which was indicative of good biocompatibility. In summary, we have shown for the first time the ability of a non-viral SLN-based vector to silence a HCV replicon. PMID:27451369

  15. Comparative analysis of viral genomes from acute and chronic hepatitis B reveals novel variants associated with a lower rate of chronicity.

    PubMed

    Chook, Jack Bee; Ngeow, Yun Fong; Khang, Tsung Fei; Ng, Kee Peng; Tiang, Yee Peng; Mohamed, Rosmawati

    2013-03-01

    Infection with the hepatitis B virus (HBV) may lead to an acute or chronic infection. It is generally accepted that the clinical outcome of infection depends on the balance between host immunity and viral survival strategies. In order to persist, the virus needs to have a high rate of replication and some immune-escape capabilities. Hence, HBVs lacking these properties are likely to be eliminated more rapidly by the host, leading to a lower rate of chronicity. To test this hypothesis, 177 HBV genomes from acute non-fulminant cases and 1,149 from chronic cases were retrieved from GenBank for comparative analysis. Selection of candidate nucleotides associated with the disease state was done using random guess cut-off and the Bonferroni correction. Five significant nucleotides were detected using this filtering step. Their predictive values were assessed using the support vector machine classification with five-fold cross-validation. The average prediction accuracy was 61% ± 1%, with a sensitivity of 24% ± 1%, specificity of 98% ± 1%, positive predictive value of 92% ± 4% and negative predictive value of 56% ± 1%. BCP/X, enhancer I and surface/polymerase variants were found to be associated almost exclusively with acute hepatitis. These HBV variants are novel potential markers for non-progression to chronic hepatitis. PMID:23297244

  16. Hepatitis B Virus X Protein Induces Hepatic Steatosis by Enhancing the Expression of Liver Fatty Acid Binding Protein

    PubMed Central

    Wu, Yun-li; Peng, Xian-e; Zhu, Yi-bing; Yan, Xiao-li; Chen, Wan-nan

    2015-01-01

    ABSTRACT Hepatitis B virus (HBV) has been implicated as a potential trigger of hepatic steatosis although molecular mechanisms involved in the pathogenesis of HBV-associated hepatic steatosis still remain elusive. Our prior work has revealed that the expression level of liver fatty acid binding protein 1 (FABP1), a key regulator of hepatic lipid metabolism, was elevated in HBV-producing hepatoma cells. In this study, the effects of HBV X protein (HBx) mediated FABP1 regulation on hepatic steatosis and the underlying mechanism were determined. mRNA and protein levels of FABP1 were measured by quantitative RT-PCR (qPCR) and Western blotting. HBx-mediated FABP1 regulation was evaluated by luciferase assay, coimmunoprecipitation, and chromatin immunoprecipitation. Hepatic lipid accumulation was measured by using Oil-Red-O staining and the triglyceride level. It was found that expression of FABP1 was increased in HBV-producing hepatoma cells, the sera of HBV-infected patients, and the sera and liver tissues of HBV-transgenic mice. Ectopic overexpression of HBx resulted in upregulation of FABP1 in HBx-expressing hepatoma cells, whereas HBx abolishment reduced FABP1 expression. Mechanistically, HBx activated the FABP1 promoter in an HNF3β-, C/EBPα-, and PPARα-dependent manner, in which HBx increased the gene expression of HNF3β and physically interacted with C/EBPα and PPARα. On the other hand, knockdown of FABP1 remarkably blocked lipid accumulation both in long-chain free fatty acids treated HBx-expressing HepG2 cells and in a high-fat diet-fed HBx-transgenic mice. Therefore, FABP1 is a key driver gene in HBx-induced hepatic lipid accumulation via regulation of HNF3β, C/EBPα, and PPARα. FABP1 may represent a novel target for treatment of HBV-associated hepatic steatosis. IMPORTANCE Accumulating evidence from epidemiological and experimental studies has indicated that chronic HBV infection is associated with hepatic steatosis. However, the molecular mechanism

  17. Hydroxychloroquine-induced toxic hepatitis in a patient with systemic lupus erythematosus: a case report.

    PubMed

    Abdel Galil, S M

    2015-05-01

    Increased serum level of liver enzymes is a common finding in patients with systemic lupus erythematosus (SLE). Hepatotoxic drugs, viral hepatitis and fatty liver are thought to be the main causes of hepatic lesion in these patients. Our aim was to determine the cause of strikingly elevated liver enzymes in a case with systemic lupus presenting with acute abdomen. Liver enzyme abnormality was defined as a 10-fold or greater increase in aspartate aminotransferase and alanine aminotransferase. Acute toxic hepatitis was diagnosed, which rapidly returned to normal after cessation of the suspected causative medication, hydroxychloroquine, and subsequent administration of mycophenolate mofetil. Elevated liver enzymes are a major concern and should be well investigated in SLE patients.

  18. Chemotherapy-induced fatal hepatitis B virus reactivation in a small-cell lung cancer patient

    PubMed Central

    Qin, Lei; Wang, Fang; Zou, Bing-Wen; Ding, Zhen-Yu

    2016-01-01

    Hepatitis B virus (HBV) reactivation during chemotherapy is a major concern and is widely reported, particularly in association with hematological malignancies and lymphomas. While lung cancer ranks first in incidence and mortality worldwide, HBV reactivation has been largely overlooked in this disease. As regards small-cell lung cancer (SCLC), HBV reactivation has rarely been reported. We herein report the case of a hepatitis B surface antigen-seropositive SCLC patient in whom HBV was reactivated during the course of chemotherapy, despite preemptive use of lamivudine. The patient developed fulminant viral hepatitis and succumbed to liver failure. The aim of this report was to highlight the major but overlooked issue of HBV reactivation in SCLC, and suggest that agents more potent than lamivudine may be more efficacious in high-risk patients. PMID:27699030

  19. Chemotherapy-induced fatal hepatitis B virus reactivation in a small-cell lung cancer patient

    PubMed Central

    Qin, Lei; Wang, Fang; Zou, Bing-Wen; Ding, Zhen-Yu

    2016-01-01

    Hepatitis B virus (HBV) reactivation during chemotherapy is a major concern and is widely reported, particularly in association with hematological malignancies and lymphomas. While lung cancer ranks first in incidence and mortality worldwide, HBV reactivation has been largely overlooked in this disease. As regards small-cell lung cancer (SCLC), HBV reactivation has rarely been reported. We herein report the case of a hepatitis B surface antigen-seropositive SCLC patient in whom HBV was reactivated during the course of chemotherapy, despite preemptive use of lamivudine. The patient developed fulminant viral hepatitis and succumbed to liver failure. The aim of this report was to highlight the major but overlooked issue of HBV reactivation in SCLC, and suggest that agents more potent than lamivudine may be more efficacious in high-risk patients.

  20. Lecithin:Cholesterol Acyltransferase Deficiency Protects against Cholesterol-induced Hepatic Endoplasmic Reticulum Stress in Mice*

    PubMed Central

    Hager, Lauren; Li, Lixin; Pun, Henry; Liu, Lu; Hossain, Mohammad A.; Maguire, Graham F.; Naples, Mark; Baker, Chris; Magomedova, Lilia; Tam, Jonathan; Adeli, Khosrow; Cummins, Carolyn L.; Connelly, Philip W.; Ng, Dominic S.

    2012-01-01

    We recently reported that lecithin:cholesterol acyltransferase (LCAT) knock-out mice, particularly in the LDL receptor knock-out background, are hypersensitive to insulin and resistant to high fat diet-induced insulin resistance (IR) and obesity. We demonstrated that chow-fed Ldlr−/−xLcat+/+ mice have elevated hepatic endoplasmic reticulum (ER) stress, which promotes IR, compared with wild-type controls, and this effect is normalized in Ldlr−/−xLcat−/− mice. In the present study, we tested the hypothesis that hepatic ER cholesterol metabolism differentially regulates ER stress using these models. We observed that the Ldlr−/−xLcat+/+ mice accumulate excess hepatic total and ER cholesterol primarily attributed to increased reuptake of biliary cholesterol as we observed reduced biliary cholesterol in conjunction with decreased hepatic Abcg5/g8 mRNA, increased Npc1l1 mRNA, and decreased Hmgr mRNA and nuclear SREBP2 protein. Intestinal NPC1L1 protein was induced. Expression of these genes was reversed in the Ldlr−/−xLcat−/− mice, accounting for the normalization of total and ER cholesterol and ER stress. Upon feeding a 2% high cholesterol diet (HCD), Ldlr−/−xLcat−/− mice accumulated a similar amount of total hepatic cholesterol compared with the Ldlr−/−xLcat+/+ mice, but the hepatic ER cholesterol levels remained low in conjunction with being protected from HCD-induced ER stress and IR. Hepatic ER stress correlates strongly with hepatic ER free cholesterol but poorly with hepatic tissue free cholesterol. The unexpectedly low ER cholesterol seen in HCD-fed Ldlr−/−xLcat−/− mice was attributable to a coordinated marked up-regulation of ACAT2 and suppressed SREBP2 processing. Thus, factors influencing the accumulation of ER cholesterol may be important for the development of hepatic insulin resistance. PMID:22500017

  1. Identification of peptides that bind hepatitis C virus envelope protein E2 and inhibit viral cellular entry from a phage-display peptide library.

    PubMed

    Lü, Xin; Yao, Min; Zhang, Jian-Min; Yang, Jing; Lei, Ying-Feng; Huang, Xiao-Jun; Jia, Zhan-Sheng; Ma, Li; Lan, Hai-Yun; Xu, Zhi-Kai; Yin, Wen

    2014-05-01

    Hepatitis C virus (HCV) envelope protein E2 is required for the entry of HCV into cells. Viral envelope proteins interact with cell receptors in a multistep process, which may be a promising target for the development of novel antiviral agents. In this study, a heptapeptide M13 phage-display library was screened for peptides that bind specifically to prokaryotically expressed, purified truncated HCV envelope protein E2. ELISA assay was used to quantify the binding of the peptides to HCV E2 protein. Flow cytometry, quantitative reverse-transcription PCR and western blotting were used to investigate the inhibition effect of one peptide on HCV infection in hepatoma cells (Huh7.5) in vitro. Four peptides capable of binding specifically to HCV E2 protein were obtained after three rounds of biopanning. Peptide C18 (WPWHNHR), with the highest affinity for binding HCV E2 protein, was synthesized. The results showed that peptide C18 inhibited the viral infectivity of both HCV pseudotype particles (HCVpp) harboring HCV envelope glycoproteins and cell-culture produced HCV (HCVcc). Thus, this study demonstrated that peptide C18 is a potential candidate for anti-HCV therapy as a novel viral entry inhibitor.

  2. miR-122 Stimulates Hepatitis C Virus RNA Synthesis by Altering the Balance of Viral RNAs Engaged in Replication Versus Translation

    PubMed Central

    Masaki, Takahiro; Arend, Kyle C.; Li, You; Yamane, Daisuke; McGivern, David R.; Kato, Takanobu; Wakita, Takaji; Moorman, Nathaniel J.; Lemon, Stanley M.

    2015-01-01

    SUMMARY The liver-specific microRNA, miR-122, stabilizes hepatitis C virus (HCV) RNA genomes by recruiting host argonaute 2 (AGO2) to the 5′ end and preventing decay mediated by exonuclease Xrn1. However, HCV replication requires miR-122 in Xrn1-depleted cells, indicating additional function s. We show that miR-122 enhances HCV RNA levels by altering the fraction of HCV genomes available for RNA synthesis. Exogenous miR-122 increases viral RNA and protein levels in Xrn1-depleted cells, with enhanced RNA synthesis occurring before heightened protein synthesis. Inhibiting protein translation blocks miR-122-mediated increases in RNA synthesis, but independently enhances RNA synthesis by releasing ribosomes from viral genomes. Additionally, miR-122 reduces the fraction of viral genomes engaged in protein translation. Depleting AGO2 or PCBP2, which binds HCV RNA in competition with miR-122 and promotes translation, eliminates miR-122 stimulation of RNA synthesis. Thus, by displacing PCBP2, miR-122 reduces HCV genomes engaged in translation while increasing the fraction available for RNA synthesis. PMID:25662750

  3. Protective Effects of N-Acetylcysteine in Concanavalin A-Induced Hepatitis in Mice

    PubMed Central

    Wang, Chengfen; Xia, Yujing; Dai, Weiqi; Wang, Fan; Chen, Kan; Li, Jingjing; Li, Sainan; Zhu, Rong; Yang, Jing; Yin, Qin; Zhang, Huawei; Wang, Junshan; Lu, Jie; Zhou, Yingqun; Guo, Chuanyong

    2015-01-01

    This study was designed to study the protective effects and mechanisms of N-acetylcysteine (NAC) in concanavalin A-induced hepatitis in mice. In this study, pretreatment with NAC ameliorated the histopathological changes and suppressed inflammatory cytokines in ConA-induced hepatitis. The expression of IL-2, IL-6, TNF-α, and IFN-γ was significantly reduced in the NAC-treated groups. NAC activated PI3K/Akt pathway and inhibited the activation of NF-κB. Additionally, NAC reduced autophagosome formation, as assessed by detecting the expression of LC3 and Beclin 1. Our results demonstrate that NAC can alleviate ConA-induced hepatitis by regulating the PI3K/Akt pathway and reducing the late stages of autophagy. Our results described a new pharmaceutical to provide more effective therapies for immune hepatitis. PMID:25821351

  4. Curcumin attenuates diet-induced hepatic steatosis by activating AMP-activated protein kinase.

    PubMed

    Um, Min Young; Hwang, Kwang Hyun; Ahn, Jiyun; Ha, Tae Youl

    2013-09-01

    Curcumin is a well-known component of traditional turmeric (Curcuma longa), which has been reported to prevent obesity and diabetes. However, the effect of curcumin on hepatic lipid metabolism remains unclear. The aim of this study was to examine the effects of curcumin on hepatic steatosis in high-fat/cholesterol diet (HFD)-induced obese mice. Male C57BL/6J mice were fed a normal diet (ND), HFD or HFD with 0.15% curcumin (HFD+C) for 11 weeks. We found that curcumin significantly lowered the body-weight and adipose tissue weight of mice in the HFD+C group compared with the findings for the HFD group (p < 0.05). The levels of total cholesterol, fasting glucose and insulin in serum were decreased, and HFD-induced impairment of insulin sensitivity was improved by curcumin supplementation (p < 0.05). Curcumin protected against the development of hepatic steatosis by reducing hepatic fat accumulation. Moreover, curcumin activated AMP-activated protein kinase (AMPK) and elevated the gene expression of peroxisome proliferator-activated receptor alpha. By contrast, curcumin suppressed the HFD-mediated increases in sterol regulatory element-binding protein-1, acetyl-CoA carboxylase 1, fatty acid synthase and cluster of differentiation 36 expression. Taken together, these findings indicate that curcumin attenuates HFD-induced hepatic steatosis by regulating hepatic lipid metabolism via AMPK activation, suggesting its use as a therapeutic for hepatic steatosis.

  5. Enterovirus 71-induced autophagy increases viral replication and pathogenesis in a suckling mouse model

    PubMed Central

    2014-01-01

    Background We previously reported that Enterovirus 71 (EV71) infection activates autophagy, which promotes viral replication both in vitro and in vivo. In the present study we further investigated whether EV71 infection of neuronal SK-N-SH cells induces an autophagic flux. Furthermore, the effects of autophagy on EV71-related pathogenesis and viral load were evaluated after intracranial inoculation of mouse-adapted EV71 (MP4 strain) into 6-day-old ICR suckling mice. Results We demonstrated that in EV71-infected SK-N-SH cells, EV71 structural protein VP1 and nonstructural protein 2C co-localized with LC3 and mannose-6-phosphate receptor (MPR, endosome marker) proteins by immunofluorescence staining, indicating amphisome formation. Together with amphisome formation, EV71 induced an autophagic flux, which could be blocked by NH4Cl (inhibitor of acidification) and vinblastine (inhibitor of fusion), as demonstrated by Western blotting. Suckling mice intracranially inoculated with EV71 showed EV71 VP1 protein expression (representing EV71 infection) in the cerebellum, medulla, and pons by immunohistochemical staining. Accompanied with these infected brain tissues, increased expression of LC3-II protein as well as formation of LC3 aggregates, autophagosomes and amphisomes were detected. Amphisome formation, which was confirmed by colocalization of EV71-VP1 protein or LC3 puncta and the endosome marker protein MPR. Thus, EV71-infected suckling mice (similar to EV71-infected SK-N-SH cells) also show an autophagic flux. The physiopathological parameters of EV71-MP4 infected mice, including body weight loss, disease symptoms, and mortality were increased compared to those of the uninfected mice. We further blocked EV71-induced autophagy with the inhibitor 3-methyladenine (3-MA), which attenuated the disease symptoms and decreased the viral load in the brain tissues of the infected mice. Conclusions In this study, we reveal that EV71 infection of suckling mice induces an

  6. Glycogen synthase kinase-3 facilitates con a-induced IFN-γ-- mediated immune hepatic injury.

    PubMed

    Tsai, Cheng-Chieh; Huang, Wei-Ching; Chen, Chia-Ling; Hsieh, Chia-Yuan; Lin, Yee-Shin; Chen, Shun-Hua; Yang, Kao-Chi; Lin, Chiou-Feng

    2011-10-01

    Immune hepatic injury induced by Con A results primarily from IFN-γ-mediated inflammation, followed by hepatic cell death. Glycogen synthase kinase (GSK)-3, which acts proapoptotically and is proinflammatory, is also important for facilitating IFN-γ signaling. We hypothesized a pathogenic role for GSK-3 in Con A hepatic injury. Con A stimulation caused GSK-3 activation in the livers of C57BL/6 mice. Inhibiting GSK-3 reduced Con A hepatic injury, including hepatic necrosis and apoptosis, inflammation, infiltration of T cells and granulocytes, and deregulated expression of adhesion molecule CD54. Con A induced hepatic injury in an IFN-γ receptor 1-dependent manner. Con A/IFN-γ induced activation and expression of STAT1 in a GSK-3-dependent manner. GSK-3 facilitated IFN-γ-induced inducible NO synthase, but had limited effects on CD95 upregulation and CD95-mediated hepatocyte apoptosis in vitro. Notably, inhibiting GSK-3 decreased Con A-induced IFN-γ production in both wild-type and IFN-γ receptor 1-deficient C57BL/6 mice. In Con A-activated NKT cells, GSK-3 was also activated and was required for nuclear translocation of T-box transcription factor Tbx21, a transcription factor of IFN-γ, but it was not required for CD95 ligand expression or activation-induced cell death. These results demonstrate the dual and indispensable role of GSK-3 in Con A hepatic injury by facilitating IFN-γ-induced hepatopathy.

  7. Viral infection of the marine alga Emiliania huxleyi triggers lipidome remodeling and induces the production of highly saturated triacylglycerol.

    PubMed

    Malitsky, Sergey; Ziv, Carmit; Rosenwasser, Shilo; Zheng, Shuning; Schatz, Daniella; Porat, Ziv; Ben-Dor, Shifra; Aharoni, Asaph; Vardi, Assaf

    2016-04-01

    Viruses that infect marine photosynthetic microorganisms are major ecological and evolutionary drivers of microbial food webs, estimated to turn over more than a quarter of the total photosynthetically fixed carbon. Viral infection of the bloom-forming microalga Emiliania huxleyi induces the rapid remodeling of host primary metabolism, targeted towards fatty acid metabolism. We applied a liquid chromatography-mass spectrometry (LC-MS)-based lipidomics approach combined with imaging flow cytometry and gene expression profiling to explore the impact of viral-induced metabolic reprogramming on lipid composition. Lytic viral infection led to remodeling of the cellular lipidome, by predominantly inducing the biosynthesis of highly saturated triacylglycerols (TAGs), coupled with a significant accumulation of neutral lipids within lipid droplets. Furthermore, TAGs were found to be a major component (77%) of the lipidome of isolated virions. Interestingly, viral-induced TAGs were significantly more saturated than TAGs produced under nitrogen starvation. This study highlights TAGs as major products of the viral-induced metabolic reprogramming during the host-virus interaction and indicates a selective mode of membrane recruitment during viral assembly, possibly by budding of the virus from specialized subcellular compartments. These findings provide novel insights into the role of viruses infecting microalgae in regulating metabolism and energy transfer in the marine environment and suggest their possible biotechnological application in biofuel production. PMID:26856244

  8. Woodchuck hepatitis virus core gene deletions and proliferative responses of peripheral blood mononuclear cells stimulated by an immunodominant epitope: a viral immune escape in the woodchuck model of chronic hepatitis B?

    PubMed

    Taffon, Stefania; Kondili, Loreta A; Giuseppetti, Roberto; Ciccaglione, Anna Rita; Pulimanti, Barbara; Attili, Adolfo F; Rapicetta, Maria; D'Ugo, Emilio

    2015-04-01

    Marmota monax and its natural infection by woodchuck hepatitis virus (WHV) could be used as a predictive model for evaluating mechanisms of viral persistence during chronic hepatitis B virus (HBV) infection. The aim of this study was to investigate the presence of viral variants in the core gene of chronically WHV-infected woodchucks that showed two different patterns of peripheral blood mononuclear cells' (PBMCs') responses after stimulation with a specific WHV core peptide. Sequences' analysis of the WHV core region from eight WHV chronically infected woodchucks have been performed after in vitro stimulation with an immunodominant epitope of the WHV core protein (amino acids [aa] 96-110). Following this stimulation, positive PBMC responses at each point of follow-up were observed for four animals (group A), and weak immune responses at one or a few points of follow-up were observed for the remaining four animals (group B). The WHV core gene sequences contained amino acid deletions (aa 84-126, aa 84-113) in three of four group A animals and in none of group B animals. In the group A animals, the same deletions were observed in liver specimens and in two of four tumor specimens. Hepatocellular carcinoma (HCC) was diagnosed in all group A animals and in one group B animal. In conclusion, internal deletions in the core region correlated with a sustained PBMC response to the immunogenic peptide (96-110) of the core protein. A possible role of this relationship in hepatocarcinogenesis could be hypothesized; however, this needs to be investigated in patients with chronic HBV infection. The evaluation of virus-specific T-cell responses and T-cell epitopes that are possibly related to the mechanisms of viral evasion should be further investigated in order to design combined antiviral and immune approaches to control chronic HBV infection. PMID:25666197

  9. Differential Effect of Viral Hepatitis Infection on Mortality among Korean Maintenance Dialysis Patients: A Prospective Multicenter Cohort Study

    PubMed Central

    Jang, Hye Min; Kim, Yon Su; Kang, Shin-Wook; Yang, Chul Woo; Kim, Nam-Ho; Kim, Hyun-Ji; Park, Jeung-Min; Lee, Ji-Eun; Jung, Hee-Yeon; Choi, Ji-Young; Park, Sun-Hee; Kim, Chan-Duck; Kim, Yong-Lim

    2015-01-01

    The role of infection with hepatitis B virus (HBV) and hepatitis C virus (HCV) in terms of survival among dialysis patients remains incompletely understood. In the present multicenter prospective cohort study, we investigated the prevalences of HBV and HCV infection among 3,321 patients receiving maintenance dialysis in Korea, and assessed the impacts of these infections on survival. All included patients underwent hepatitis B antigen (HBsAg) and HCV antibody (Ab) testing, which revealed that 236 patients (7.1%) were HBsAg-positive, and 123 patients (3.7%) were HCV Ab-positive. HBsAg-positive and HCV Ab-positive patients were matched to hepatitis virus-negative patients using a propensity score at a ratio of 1:2. The prevalences of HBV and HCV infection did not significantly differ according to dialysis modality. Linear-by-linear association analysis revealed that hepatitis B prevalence significantly increased with increasing dialysis vintage (p = 0.001), and hepatitis C prevalence tended to be higher with increasing dialysis vintage (p = 0.074). We compared the survival of HBsAg-positive and HCV Ab-positive patients to that of hepatitis virus-negative patients. After propensity score matching, cumulative survival did not differ between HBsAg-positive and HBsAg-negative patients (p = 0.37), while HCV Ab-positive patients showed significantly lower survival than HCV Ab-negative patients (p = 0.03). The main conclusions of the present study are that HBV infection prevalence increased with longer dialysis vintage, and that both HBV and HCV infections were most prevalent among patients with the longest dialysis vintage. Additionally, HCV infection among maintenance dialysis patients is associated with an increased risk of mortality. PMID:26263373

  10. Differential Effect of Viral Hepatitis Infection on Mortality among Korean Maintenance Dialysis Patients: A Prospective Multicenter Cohort Study.

    PubMed

    Kwon, Eugene; Cho, Jang-Hee; Jang, Hye Min; Kim, Yon Su; Kang, Shin-Wook; Yang, Chul Woo; Kim, Nam-Ho; Kim, Hyun-Ji; Park, Jeung-Min; Lee, Ji-Eun; Jung, Hee-Yeon; Choi, Ji-Young; Park, Sun-Hee; Kim, Chan-Duck; Kim, Yong-Lim

    2015-01-01

    The role of infection with hepatitis B virus (HBV) and hepatitis C virus (HCV) in terms of survival among dialysis patients remains incompletely understood. In the present multicenter prospective cohort study, we investigated the prevalences of HBV and HCV infection among 3,321 patients receiving maintenance dialysis in Korea, and assessed the impacts of these infections on survival. All included patients underwent hepatitis B antigen (HBsAg) and HCV antibody (Ab) testing, which revealed that 236 patients (7.1%) were HBsAg-positive, and 123 patients (3.7%) were HCV Ab-positive. HBsAg-positive and HCV Ab-positive patients were matched to hepatitis virus-negative patients using a propensity score at a ratio of 1:2. The prevalences of HBV and HCV infection did not significantly differ according to dialysis modality. Linear-by-linear association analysis revealed that hepatitis B prevalence significantly increased with increasing dialysis vintage (p = 0.001), and hepatitis C prevalence tended to be higher with increasing dialysis vintage (p = 0.074). We compared the survival of HBsAg-positive and HCV Ab-positive patients to that of hepatitis virus-negative patients. After propensity score matching, cumulative survival did not differ between HBsAg-positive and HBsAg-negative patients (p = 0.37), while HCV Ab-positive patients showed significantly lower survival than HCV Ab-negative patients (p = 0.03). The main conclusions of the present study are that HBV infection prevalence increased with longer dialysis vintage, and that both HBV and HCV infections were most prevalent among patients with the longest dialysis vintage. Additionally, HCV infection among maintenance dialysis patients is associated with an increased risk of mortality.

  11. Interleukin-28B polymorphisms and interferon gamma inducible protein-10 serum levels in seronegative occult hepatitis C virus infection.

    PubMed

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

    2016-02-01

    Polymorphisms upstream interleukin (IL)-28B gene and serum levels of interferon gamma inducible protein-10 (IP-10) are associated with spontaneous and treatment-induced hepatitis C virus (HCV) clearance. Patients with seronegative occult HCV infection are anti-HCV and serum HCV-RNA negative but have viral RNA in liver and abnormal values of liver enzymes. We examined if the rs12979860 polymorphism of IL-28B and serum IP-10 levels differ between chronic and seronegative occult CV infection. IL-28B polymorphism was determined with allele specific TaqMan probes in total DNA isolated from peripheral blood mononuclear cells and IP-10 by an enzyme-linked immunosorbent assay in serum from 99 patients with seronegative occult HCV infection and 130 untreated patients with chronic hepatitis C. IL-28B genotypes were also determined in 54 healthy volunteers. Prevalence of the IL-28B CC genotype was significantly higher in seronegative occult HCV infection (52/99; 52.5%) than in chronic hepatitis C (32/130; 24.6%, P < 0.0001) or healthy controls (19/54: 32.5%, P = 0.039). Among patients with seronegative occult HCV infection, HCV-RNA load in liver was significantly lower in those with the IL-28B CC genotype than in those with CT + TT genotypes (2.8 × 10(5)  ± 5.8 × 10(4) vs. 4.1 × 10(5)  ± 5.9 × 10(4)  copies/μg of total RNA respectively; P = 0.023). Mean serum IP-10 levels were significantly lower in patients with seronegative occult HCV infection than in patients with chronic hepatitis C (160.8 ± 17.9 vs. 288.7 ± 13.3 pg/ml respectively; P < 0.0001). These findings suggest that the host immune response plays an important role in seronegative occult HCV infection in comparison with chronic hepatitis C.

  12. Characterization of feline glomerulonephritis associated with viral-induced hematopoietic neoplasms.

    PubMed

    Glick, A D; Horn, R G; Holscher, M

    1978-08-01

    Light, electron, and immunofluorescence microscopy on tissues from 63 domestic cats revealed that glomerulonephritis occurred in almost one third of cats with hematopoietic neoplasms of the type linked with feline leukemia virus (FeLV). Glomerular lesions were of the immune complex type with subepithelial, subendothelial, and mesangial dense deposits and reticular aggregates, similar to the nephropathy associated with systemic lupus erythematosus in humans. Evidence that the glomerular lesions may be viral-induced raises the possibility of similar pathogenetic mechanisms in human disease. PMID:677265

  13. Resveratrol improves hepatic insulin signaling and reduces the inflammatory response in streptozotocin-induced diabetes.

    PubMed

    Sadi, Gökhan; Pektaş, Mehmet Bilgehan; Koca, Halit Bugra; Tosun, Murat; Koca, Tulay

    2015-10-10

    Diabetes mellitus is a heterogeneous metabolic disorder essentially characterized by deficiency of insulin secretion, insulin receptor or post-receptor events. This study aims to investigate the effects of resveratrol administration on the metabolic characteristics, hepatic functions, histopathological features and insulin signaling pathway components in streptozotocin induced diabetes. Male Wistar rats were randomly divided into four groups: (1) control/vehicle; (2) control/20mg/kg resveratrol; (3) diabetic/vehicle; and (4) diabetic/20mg/kg resveratrol. Histopathological examinations were carried out to reveal hepatic tissue damage and inflammation. In addition to hepatic glucose, lipid, insulin, ALT, AST, resistin and XOD contents, gene and protein expressions of insulin signaling pathway components such as insulin Rβ, IRS-1, IRS-2, eNOS, PI3K, Akt, and FOXO3a were analyzed by qRT-PCR and Western blot. The rats in the diabetes group had significantly lower terminal body weight and hepatic insulin level, but significantly higher hepatic glucose, total cholesterol, triglyceride and resistin concentrations. Diabetes triggered the inflammatory process in the liver tissues that was evidenced by histopathological deformations and increase in the hepatic ALT and AST levels. Hepatic inflammation was considerably associated with insulin signaling pathway ever since a significant down-regulation of insulin signaling components; IRS-1, IRS-2, PI3K, Akt and mTOR have been identified in the diabetic group. To some extent, resveratrol treatment reversed the diabetes-induced changes in the liver tissues. Taken together, resveratrol partly improved hepatic dysfunction induced by diabetes. This may be due to the healing activity of resveratrol on insulin signaling pathway, resistin levels and hepatic glucose-lipid contents.

  14. In vivo evidence for ribavirin-induced mutagenesis of the hepatitis E virus genome

    PubMed Central

    Todt, Daniel; Gisa, Anett; Radonic, Aleksandar; Nitsche, Andreas; Behrendt, Patrick; Suneetha, Pothakamuri Venkata; Pischke, Sven; Bremer, Birgit; Brown, Richard J P; Manns, Michael P; Cornberg, Markus; Bock, C Thomas; Steinmann, Eike; Wedemeyer, Heiner

    2016-01-01

    Objective Hepatitis E virus (HEV) infection can take chronic courses in immunocompromised patients potentially leading to liver cirrhosis and liver failure. Ribavirin (RBV) is currently the only treatment option for many patients, but treatment failure can occur which has been associated with the appearance of a distinct HEV polymerase mutant (G1634R). Here, we performed a detailed analysis of HEV viral intrahost evolution during chronic hepatitis E infections. Design Illumina deep sequencing was performed for the detection of intrahost variation in the HEV genome of chronically infected patients. Novel polymerase mutants were investigated in vitro using state-of-the-art HEV cell culture models. Results Together, these data revealed that (1) viral diversity differed markedly between patients but did not show major intraindividual short-term variations in untreated patients with chronic hepatitis E, (2) RBV therapy was associated with an increase in viral heterogeneity which was reversible when treatment was stopped, (3) the G1634R mutant was detectable as a minor population prior to therapy in patients who subsequently failed to achieve a sustained virological response to RBV therapy and (4) in addition to G1634R further dominant variants in the polymerase region emerged, impacting HEV replication efficiency in vitro. Conclusions In summary, this first investigation of intrahost HEV population evolution indicates that RBV causes HEV mutagenesis in treated patients and that an emergence of distinct mutants within the viral population occurs during RBV therapy. We also suggest that next-generation sequencing could be useful to guide personalised antiviral strategies. PMID:27222534

  15. Durability of response to vaccination against viral hepatitis A in HIV-infected patients: a 5-year observation.

    PubMed

    Jabłonowska, E; Kuydowicz, J

    2014-09-01

    The aim of this study was to estimate the prevalence of total antibodies to hepatitis A virus (anti-HAV-T) in the group of HIV-positive adults in Lodz region of Poland, and to evaluate the response and long-term immunity after vaccination against hepatitis A virus. In the group of 234 HIV-infected patients, 72 persons (30.8%) were anti-HAV-T positive (>20 IU/L). In multivariate analysis, two independent factors associated with the presence of anti-HAV-T were identified: the age of patients (OR = 1.07) and the presence of antibodies to hepatitis C virus (OR = 2.87). Vaccination was completed in 83 patients. Good response (anti-HAV-T >20 IU/L one month after the booster dose) was obtained in 79.5% of patients. In patients with CD4 >200 cells/µL in multivariate analysis only presence of antibodies to hepatitis C virus was a prognostic factor for the response to vaccination (OR = 0.13). Among responders available for the follow-up, 82% (50 out of 61) had detectable anti-HAV-T at 1 year and 75.5% (37 out of 49) at 5 years. Our results demonstrate that most of the studied HIV-positive patients were susceptible to hepatitis A virus infection. Most HIV-infected adults with high CD4 counts had a durable response even up to 5 years after vaccination. Patients with a HIV/hepatitis C virus coinfection displayed a worse response to vaccination.

  16. Mouse hepatitis virus type 4 (JHM strains). induced fatal central nervous system disease. I. genetic control and murine neuron as the susceptible site of disease

    PubMed Central

    1981-01-01

    Mouse hepatitis virus (JHM strain) type 4 induces acute encephalitis followed by death in many strains of laboratory mice. Immunohistochemical study in vivo and analysis of mouse neuronal cells in vitro both indicate that the target cells in this infection is the neuron. Further, examination of several inbred mouse strains and neuronal cells from them shows that disease expression is controlled by a single autosomal gene action at the level of the neuronal cell. Susceptibility is dominant but not H-2 linked. However, cultured neuronal cells and macrophages from SJL/J mice, which are resistant to this infection, fail to make significant amounts of infectious virus after an appropriate viral inoculation. Apparently the defect is not at the level of the virus-cell receptor, because these cells, in part, express viral antigens. PMID:6265583

  17. Hepatitis B Test

    MedlinePlus

    ... IgM; anti-HBe; Hepatitis B e Antibody; HBV DNA Formal name: Hepatitis