HLA class II associated with outcomes of hepatitis B and C infections

Abstract

Several factors influence the clinical course of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection. The human leukocyte antigen (HLA) system, the major histocompatibility complex (MHC) in humans, has been considered one of the most important host factors with respect to outcomes. To date, conventional genotyping studies have shown that HLA class II loci are mainly associated with spontaneous clearance of HBV and HCV. However, the specific HLA locus associated with the outcomes of hepatitis virus infection remains unclear. A recent genome-wide association study (GWAS) using a comprehensive approach for human genotyping demonstrated single nucleotide polymorphisms (SNPs) associated with the outcomes of hepatitis virus infection. Examination of large numbers of cohorts revealed that several SNPs in both HLA-DPA1 and HLA-DPB1 loci are associated with persistent HBV infection in Asian populations. To date, however, few studies have focused on HLA-DP because polymorphisms of HLA-DP haplotype do not vary greatly as compared with other loci of HLA. There are not enough studies to reveal the function of HLA-DP. GWAS additionally detected candidate SNPs within HLA loci associated with chronic HBV or HCV hepatitis, hepatic fibrosis, and the development of hepatocellular carcinoma. The results of one cohort were not always consistent with those of other cohorts. To solve several controversial issues, it is necessary to validate reported SNPs on HLA loci in global populations and to elucidate the HLA-allele-regulated molecular response to hepatitis virus infection.

Keywords: Hepatitis B virus, Hepatitis C virus, Hepatocarcinogenesis, Human leukocyte antigen, Genome-wide association studies, Genotyping, Persistent infection

Core tip: Conventional genotyping studies have shown that human leukocyte antigen (HLA) typing was one of the most important host factors with respect to outcomes of hepatitis B and C virus infections. However, the specific HLA locus associated with the outcomes remains unclear. Recently a genome-wide association study for human genotyping demonstrated single nucleotide polymorphisms associated with the outcomes of hepatitis virus infection. Now it has been confirmed that several single nucleotide polymorphisms in both HLA-DP loci were associated with persistent hepatitis B virus infection in Asian populations.