Effects of sex and generation on hepatitis B viral load in families with hepatocellular carcinoma

AIM To explore factors associated with persistent hepatitis B virus(HBV) infection in a cohort of hepatocellular carcinoma(HCC)-affected families and then investigate factors that correlate with individual viral load among hepatitis B surface antigen(HBsA g)-positive relatives. METHODS We evaluated non-genetic factors associated with HBV replication in relatives of patients with HCC. Relatives of 355 HCC cases were interviewed using a structuredquestionnaire. Demographics, relationship to index case, HBs Ag status of mothers and index cases were evaluated for association with the HBV persistent infection or viral load by generalized estimating equation analysis. RESULTS Among 729 relatives enrolled, parent generation(P = 0.0076), index generation(P = 0.0044), mothers positive for HBs Ag(P = 0.0007), and HBs Ag-positive index cases(P = 5.98 × 10-8) were associated with persistent HBV infection. Factors associated with HBV viral load were evaluated among 303 HBs Ag-positive relatives. Parent generation(P = 0.0359) and sex(P = 0.0007) were independent factors associated with HBV viral load. The intra-family HBV viral load was evaluated in families clustered with HBs Ag-positive siblings. An intra-family trend of similar HBV viral load was found for 27 of 46(58.7%) families. Male offspring of HBsA gpositive mothers(P = 0.024) and older siblings were associated with high viral load.CONCLUSION Sex and generation play important roles on HBV viral load. Maternal birth age and nutritional changes could be the reasons of viral load difference between generations.

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 105 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.