Hepatitis B virus persistent infection-related single nucleotide polymorphisms in HLA regions are associated with viral load in hepatoma families

BACKGROUND Genome-wide association studies from Asia indicate that HLA-DP and HLA-DQ loci are important in persistent hepatitis B virus (HBV) infections. One of the key elements for HBV-related carcinogenesis is persistent viral replication and inflammation. AIM To examine genetic and nongenetic factors with persistent HBV infection and viral load in families with hepatocellular carcinoma (HCC). METHODS The HCC families included 301 hepatitis B surface antigen (HBsAg) carriers and 424 noncarriers born before the nationwide vaccination program was initiated in 1984. Five HBV-related single nucleotide polymorphisms (SNPs) - rs477515, rs9272105, rs9276370, rs7756516, and rs9277535 - were genotyped. Factors associated with persistent HBV infection and viral load were analyzed by a generalized estimating equation. RESULTS In the first-stage persistent HBV study, all SNPs except rs9272105 were associated with persistent infection. A significantly higher area under the reciprocal operating characteristic curve for nongenetic factors vs genetic factors (P < 0.001) suggests that the former play a major role in persistent HBV infection. In the second-stage viral load study, we added 8 HBsAg carriers born after 1984. The 309 HBsAg carriers were divided into low (n = 162) and high viral load (n = 147) groups with an HBV DNA cutoff of 10(5) cps/mL. Sex, relationship to the index case, rs477515, rs9272105, and rs7756516 were associated with viral load. Based on the receiver operating characteristic curve analysis, genetic and nongenetic factors affected viral load equally in the HCC family cohort (P = 0.3117). CONCLUSION In these east Asian adults, the mechanism of persistent HBV infection-related SNPs was a prolonged viral replication phase.

Automated summary

Genome-wide association studies have shown the importance of HLA-DP and HLA-DQ loci in persistent hepatitis B virus infections. In a study on families with hepatocellular carcinoma, non-genetic factors were found to play a major role in persistent HBV infection, while genetic factors affected viral load equally in the HCC family cohort. Sex, relationship to the index case, and certain genetic polymorphisms were associated with viral load in HBsAg carriers.