HLA-Cw*04 and hepatitis C virus persistence.

In studies of acute hepatitis C virus (HCV) infection, the early host immune response is one of the determinants of viral persistence. The class I human leukocyte antigens (HLA), which present foreign antigen to cytolytic T cells, are integral components of this response. We hypothesized that the highly polymorphic HLA genes affect the outcome of an HCV infection. To test this hypothesis, we molecularly typed 231 persons with well-documented clearance of an HCV infection and 444 matched persistently infected persons. HLA-A1101 (odds ratio [OR], 0.49; 95% confidence interval [95% CI], 0.27 to 0.89), HLA-B57 (OR, 0.62; 95% CI, 0.39 to 1.00), and HLA-Cw0102 (OR, 0.43; 95% CI, 0.21 to 0.89) were associated with viral clearance, whereas HLA-A2301 (OR, 1.78; 95% CI, 1.01 to 3.11) and HLA-Cw04 (OR, 1.78; 95% CI, 1.21 to 2.59) were associated with viral persistence. HLA-Cw04 is in strong linkage disequilibrium with HLA-B53 and HLA-B35, but only HLA-B53 (OR, 1.70; 95% CI, 0.95 to 3.06) and the Cw04-B53 haplotype (OR, 1.76; 95% CI, 0.94 to 3.26) were weakly associated with viral persistence. HLA-B53 has similar, but not necessarily identical, binding specificity to some HLA-B35 subtypes (B35-Px group). The association with the B35-Px group was less strong than with HLA-B53 alone. The association of HLA-Cw04 with HCV persistence was codominant (two copies of the gene were more strongly associated with persistence than one copy). However, HLA-Cw04 was not associated with HCV RNA levels among the persistently infected individuals. Since Cw*04 is a ligand for the killer immunoglobulin-like receptors on natural killer cells, these cells may be involved in recovery from HCV infection. Further investigation is needed to understand the relationship between class I alleles and HCV clearance.