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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    • "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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