Specific Human Leukocyte Antigen Class I and II Alleles Associated With Hepatitis C Virus Viremia

Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Hepatology (Impact Factor: 11.06). 05/2010; 51(5):1514-22. DOI: 10.1002/hep.23515
Source: PubMed


Studies of human leukocyte antigen (HLA) alleles and their relation with hepatitis C virus (HCV) viremia have had conflicting results. However, these studies have varied in size and methods, and few large studies assessed HLA class I alleles. Only one study conducted high-resolution class I genotyping. The current investigation therefore involved high-resolution HLA class I and II genotyping of a large multiracial cohort of U.S. women with a high prevalence of HCV and HIV. Our primary analyses evaluated associations between 12 HLA alleles identified through a critical review of the literature and HCV viremia in 758 HCV-seropositive women. Other alleles with >5% prevalence were also assessed; previously unreported associations were corrected for multiple comparisons. DRB1*0101 (prevalence ratio [PR] = 1.7; 95% confidence interval [CI] = 1.1-2.6), B*5701 (PR=2.0; 95% CI = 1.0-3.1), B*5703 (PR = 1.7; 95% CI = 1.0-2.5), and Cw*0102 (PR = 1.9; 95% CI = 1.0-3.0) were associated with the absence of HCV RNA (i.e., HCV clearance), whereas DRB1*0301 (PR = 0.4; 95% CI = 0.2-0.7) was associated with HCV RNA positivity. DQB1*0301 was also associated with the absence of HCV RNA but only among HIV-seronegative women (PR = 3.4; 95% CI = 1.2-11.8). Each of these associations was among those predicted. We additionally studied the relation of HLA alleles with HCV infection (serostatus) in women at high risk of HCV from injection drug use (N = 838), but no significant relationships were observed. CONCLUSION: HLA genotype influences the host capacity to clear HCV viremia. The specific HLA associations observed in the current study are unlikely to be due to chance because they were a priori hypothesized.

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Available from: Stephen Gange, Sep 19, 2014
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    • "may increase the likelihood of spontaneous HCV clearance (Kim et al., 2011; Kuniholm et al., 2010; McKiernan et al., 2004). In a single-source HCV outbreak the strongest association with HCV clearance was identified for HLA-B ⁄ 2701 (McKiernan et al., 2004), an allele that also been associated with Fig. 1. "
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    ABSTRACT: Hepatitis C virus (HCV)-specific T cells are key factors in the outcome of acute HCV infection and in protective immunity. This review recapitulates the steps that immunologists have taken in the past 25 years to dissect the role of T cell responses in HCV infection. It describes technical as well as disease-specific challenges that were caused by the inapparent onset of acute HCV infection, the difficulty to identify subjects who spontaneously clear HCV infection, the low frequency of HCV-specific T cells in the blood of chronically infected patients, and the lack of small animal models with intact immune systems to study virus-host interaction. The review provides a historical perspective on techniques and key findings, and identifies areas for future research.
    Full-text · Article · Nov 2014 · Antiviral Research
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    • "evidence comes from T cell depletion experiments in the chimpanzee model, where a lack of either CD4 or CD8 T cells during exposure and early infection was associated with persistent viraemia [18] [26]. The importance of CD4 and CD8 cells for the outcome of HCV is further supported by human population studies that identified strong associations between disease resolution and certain human leukocyte antigen (HLA) class I and II alleles in various ethnic populations [29] [30] [31] [32] [33] [34]. "
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    ABSTRACT: Hepatitis C virus (HCV) infects an estimated more than 150 million people and is a leading cause of liver disease worldwide. The development of direct-acting antivirals (DAAs) will markedly improve the outcome of antiviral treatment with cure of the majority of treated patients. However, several hurdles remain before HCV infection can be considered a menace of the past: High treatment costs will most likely result in absent or limited access in middle and low resource countries and will lead to selective use even in wealthier countries. The limited efficacy of current HCV screening programs leads to a majority of cases being undiagnosed or diagnosed at a late stage and DAAs will not cure virus-induced end-stage liver disease such as hepatocellular carcinoma. Certain patient subgroups may not respond or not be eligible for DAA-based treatment strategies. Finally, reinfection remains possible, making control of HCV infection in people with ongoing infection risk difficult. The unmet medical needs justify continued efforts to develop an effective vaccine, protecting from chronic HCV infection as a mean to impact the epidemic on a global scale. Recent progress in the understanding of virus–host interactions provides new perspectives for vaccine development, but many critical questions remain unanswered. In this review, we focus on what is known about the immune correlates of HCV control, highlight key mechanisms of viral evasion that pose challenges for vaccine development and suggest areas of further investigation that could enable a rational approach to vaccine design. Within this context we also discuss insights from recent HCV vaccination studies and what they suggest about the best way to go forward.
    Preview · Article · Nov 2014 · Journal of Hepatology
    • "Persistent HCV infection is associated with a wide clinical spectrum ranging from mild hepatic injury to cirrhosis, chronic hepatitis, and hepatocellular carcinoma (HCC).[1] Worldwide, 170 million people were reported to have been infected with HCV.[23] Prevalence of HCV infection has been found to be significantly higher in patients receiving hemodialysis (HD) for end-stage renal disease (ESRD) compared to the general population.[45] Prevalence of anti-HCV positivity in HD centers has been reported to be between 8.5% and 75%.[6] "
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    ABSTRACT: Background/Aims: The efficacy of immune response against hepatitis C virus (HCV) is determined by human leukocyte antigen (HLA) molecules of the host which present HCV antigens to CD4 + and CD8 + T lymphocytes. In this study, we aimed to investigate the possible relationship between the frequencies of certain HLA class I-II alleles and the natural history of HCV in patients with end-stage renal disease (ESRD). Settings and Design: This is a retrospective cohort study conducted in a university hospital. Patients and Methods: The present study comprised 189 ESRD patients (candidates for renal transplantation) who had positive anti-HCV antibody test. The results concerning HCV and HLA status were gathered from patients' files. The viral persistence was compared between the groups that were determined by HLA sub-typing. Statistical Analysis: Statistical evaluation was performed using Mann-Whitney U-test, Chi-square test, and Fisher's exact test. Level of error was set at 0.05 for all statistical evaluations, and P values < 0.05 were considered statistically significant. Results: We found possible association between the course of HCV infection and specific HLA alleles. HLA class I CwFNx016 and HLA class II DRBFNx0110 alleles were observed more frequently in the viral clearance group (P < 0.05). The HLA class I BFNx0138 allele group was more prone to develop chronic hepatitis C (P < 0.01). Conclusions: These findings suggest that HLA class I CwFNx016 and HLA class II DRBFNx0110 alleles may be associated with immunological elimination of HCV in Turkish patients on hemodialysis. HLA sub-typing could help predict the prognosis of HCV infection.
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