Hepatitis: Post JJ

Lloyd AR, Jagger E, Post JJ, Crooks LA, Rawlinson WD, Hahn YS, Ffrench RA. · Centre for Infection and Inflammation Research, School of Medical Sciences, University of New South Wales, Sydney, New South Wales, Australia. · Immunol Cell Biol. · Pubmed #17130897 No free full text.

Abstract: Individuals infected with hepatitis C virus (HCV) have two possible outcomes of infection, clearance or persistent infection. The focus of this review is the host mechanisms that facilitate clearance. The interaction between HCV viral components and the immune system ultimately determines the balance between the virus and host. Strong evidence points to the aspects of cellular immune response as the key determinants of outcome. The recent discovery of viral evasion strategies targeting innate immunity suggests that the interferon-alpha/beta induction pathways are also critical. A growing body of evidence has implicated polymorphisms in both innate and adaptive immune response genes as determinants of viral clearance in individuals infected with HCV.

Freeman AJ, Ffrench RA, Post JJ, Harvey CE, Gilmour SJ, White PA, Marinos G, van Beek I, Rawlinson WD, Lloyd AR. · Department of Pathology, School of Medical Sciences, The University of New South Wales, Sydney, New South Wales, Australia. · J Infect Dis. · Pubmed #15319859 No free full text.

Abstract: This report describes subjects who were highly likely to have been repeatedly exposed to hepatitis C virus (HCV) through injection drug use and who remained negative for anti-HCV antibody. Production of virus-specific interferon- gamma by peripheral blood mononuclear cells was seen in the majority of subjects (72%) and was associated with higher-risk behavior. For 92% of the subjects, results of recombinant immunoblot assays demonstrated faint bands against nonstructural proteins. The immune responses described are likely to have been primed and maintained by episodes of subclinical infection without classic seroconversion and may indicate a hepatitis C-resistant phenotype. Vaccine strategies to mimic this response may provide protection against persistent HCV infection.

Gates JA, Post JJ, Kaldor JM, Pan Y, Haber PS, Lloyd AR, Dolan KA, Anonymous00249. · National Drug and Alcohol Research Centre, UNSW, Sydney, 2052, Australia. · J Urban Health. · Pubmed #15273267 No free full text.

Abstract: The objective of this study was to compare the prevalence of risk factors for hepatitis C virus (HCV) infection among male prison inmates enrolling into a prospective cohort in Australia. We tested 121 inmates who were previously untested or were previously known to be anti-HCV antibody negative for anti-HCV antibodies by enzyme-linked immunosorbent assay. HCV-positive inmates were classified as cases (n = 25) and HCV-negative inmates as controls (n = 96). The study found that cases were less educated than controls and confirmed that prior imprisonment, drug injection, and a longer duration of injecting were risk factors for HCV infection. More than half of those who tested HCV positive perceived that they did not have HCV infection, and 44% were unsure of their HCV status. Those inmates who were incorrect about their HCV status tended to be less educated and were more likely to have been previously imprisoned than those who were correct about their HCV status. Inmates who were unsure of their HCV status were less likely to have been tested for HCV than those who had a clear perception of their HCV status, even if incorrect. Three (12%) inmates who tested positive denied injecting drug use, but reported other risk factors. Prisons are likely to remain an important site for the diagnosis of HCV infection and targeted interventions aimed at risk reduction among inmates with low education levels and a previous imprisonment history.

Post JJ, Pan Y, Freeman AJ, Harvey CE, White PA, Palladinetti P, Haber PS, Marinos G, Levy MH, Kaldor JM, Dolan KA, Ffrench RA, Lloyd AR, Rawlinson WD, Anonymous00131. · Department of Pathology, School of Medical Sciences, University of New South Wales, Sydney, New South Wales, Australia. · J Infect Dis. · Pubmed #15122521 No free full text.

Abstract: Understanding the earliest virological and immunological events in acute hepatitis C virus (HCV) infection may provide insight into the determinants of protective immunity. Four cases of HCV viremia with subsequent viral clearance, but without biochemical hepatitis or anti-HCV seroconversion, are reported from a prospective cohort study of prison inmates. Two of the subjects who developed sustained viremia were assessed for production of interferon (IFN)- gamma, by use of the enzyme-linked immunospot (ELISPOT) method and by assessment of HCV cytotoxic T lymphocyte (CTL) activity, CD4 lymphocyte proliferative responses, HCV load, and genotype. After 2-6 months of viremia, all 4 subjects cleared serum HCV RNA. Specific cellular responses were detected in both of the subjects who were assessed, and production of IFN- gamma was demonstrated in one subject. All subjects had weak, but consistent, serological reactivity against HCV nonstructural proteins on immunoblot testing, despite repeatedly nonreactive HCV ELISA tests. These cases highlight the potential for cellular immune responses against HCV to facilitate viral clearance, responses that may model those required for effective HCV vaccination.

Harvey CE, Post JJ, Palladinetti P, Freeman AJ, Ffrench RA, Kumar RK, Marinos G, Lloyd AR. · Department of Gastroenterology, Prince of Wales Hospital, Sydney, New South Wales, Australia. · J Leukoc Biol. · Pubmed #12949239 links to  free full text

Abstract: The factors influencing lymphocyte trafficking to the liver lobule during chronic hepaititis C virus (HCV) infection are currently not well defined. Interferon-gamma-inducible protein 10 (IP-10), a chemokine that recruits activated T lymphocytes, has recently been shown by in situ hybridization to be expressed in the liver during chronic HCV infection. This study sought to define the cellular source of IP-10 in the liver by immunohistochemistry, to examine the expression of its receptor, CXCR3, on T lymphocytes isolated from blood and liver tissue, and to correlate IP-10 expression with the histological markers of inflammation and fibrosis. IP-10 was expressed by hepatocytes but not by other cell types within the liver, and the most intense immunoreactivity was evident in the areas of lobular inflammation. The IP-10 receptor was expressed on a significantly higher proportion of T lymphocytes in the liver compared with blood. CD8 T lymphocytes, which predominate in the liver lobule, were almost uniformly CXCR3-positive. The expression of IP-10 mRNA correlated with lobular necroinflammatory activity but not with inflammation or fibrosis in the portal tracts. These findings suggest that IP-10 may be induced by HCV within hepatocytes and may be important in the pathogenesis of chronic HCV infection, as recruitment of inflammatory cells into the lobule is an important predictor of disease progression.

O'Sullivan BG, Levy MH, Dolan KA, Post JJ, Barton SG, Dwyer DE, Kaldor JM, Grulich AE. · New South Wales Department of Health, Sydney, NSW, Australia. · Med J Aust. · Pubmed #12765501 links to  free full text

Abstract: OBJECTIVES: To determine whether infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV) occurred after two potential episodes of exposure through needle- and syringe-sharing in Australian prisons, and to examine use of post-exposure prophylaxis (PEP) against HIV infection in the prison setting. DESIGN: Cohort study of potential contacts of two prisoners infected with HIV, HBV and HCV followed up for up to 14 months. SETTING: Two Australian prisons between November 2000 (time of exposure) and December 2001. PARTICIPANTS: Two index patients (both infected with HIV and HCV; one also infectious for HBV) from two different prisons, and 104 inmates who shared needles and syringes. MAIN OUTCOME MEASURES: Seroconversions to HIV, HBV and HCV related to the high-risk exposure and uptake and completion of HIV PEP determined from medical records of inmates. RESULTS: There were four seroconversions to HCV within 14 months of the potential exposure (14% of those susceptible in the cohort), but no recorded HIV or HBV seroconversions. Forty-six inmates (82% of those eligible) were offered PEP, and 34 of these (74%) elected to receive it. Only eight (24% of the 34) completed the full PEP course. CONCLUSIONS: HCV transmission in the prison setting is related to high-risk needle- and syringe-sharing. Administering HIV PEP in the prison setting is complicated by challenging risk assessment and follow-up.

Freeman AJ, Pan Y, Harvey CE, Post JJ, Law MG, White PA, Rawlinson WD, Lloyd AR, Marinos G, Ffrench RA. · Viral Hepatitis Research, Gastrointestinal and Liver Unit, The Prince of Wales Hospital, Barker Street, Randwick, Sydney, NSW 2031, Australia. · J Hepatol. · Pubmed #12586302 No free full text.

Abstract: BACKGROUND/AIMS: The role of cytotoxic T lymphocytes (CTL) in limiting viral replication and producing hepatocellular injury in patients with chronic hepatitis C virus (HCV) infection is controversial. METHODS: Intrahepatic and peripheral blood HCV-specific CTL activity against the entire HCV polyprotein was assessed in 26 patients. CTL responses were assessed after effector lymphocytes were re-stimulated for 6 days in vitro using HCV-vaccinia virus-infected autologous cells expressing HCV antigens. Serum and hepatic viral loads were measured and immunohistochemistry for CD3 and CD8 was performed to localise and enumerate effector cells in liver. RESULTS: A positive CTL response was detected in 39/52 (75%) of assays conducted with intrahepatic mononuclear cells and 21/52 (40%) of peripheral blood assays (P<0.001). The presence of an intrahepatic CTL response was associated with low hepatic viral load (P=0.004). Hepatic lobular infiltration by CD8(+)T cells correlated weakly with serum alanine aminotransferase levels (r=0.42, P=0.04) and no relationship was demonstrated between CTL activity and histological evidence of liver damage. CONCLUSIONS: HCV-specific CTL activity is found more commonly in liver than in blood. An inverse relationship between CTL responses and viral load supports the hypothesis that HCV-specific CTL limit viral replication in patients with chronic HCV infection.

Post JJ, Dolan KA, Whybin LR, Carter IW, Haber PS, Lloyd AR. · Inflammation Research Unit, School of Pathology, University of NSW, Sydney. · Med J Aust. · Pubmed #11270759 links to  free full text

Abstract: Clinically apparent hepatitis C virus (HCV) infection developed in a prison inmate after two tattooing episodes within the recognised incubation period for HCV infection. Seroconversion and HCV viraemia with subsequent resolution of hepatitis and loss of plasma viraemia were documented. Introducing licensed tattooists, and thereby improving infection control practices, may reduce the risk of hepatitis C virus infection in prisons.

Post JJ, Freeman AJ, Harvey CE, Ffrench RA, Lloyd AR. · No affiliation provided · Lancet. · Pubmed #12383686 No free full text.

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