Published online Oct 7, 2021. doi: 10.3748/wjg.v27.i37.6262
Peer-review started: April 8, 2021
First decision: June 26, 2021
Revised: July 6, 2021
Accepted: September 1, 2021
Article in press: September 1, 2021
Published online: October 7, 2021
Processing time: 174 Days and 0.1 Hours
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.
To examine genetic and nongenetic factors with persistent HBV infection and viral load in families with hepatocellular carcinoma (HCC).
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.
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).
In these east Asian adults, the mechanism of persistent HBV infection-related SNPs was a prolonged viral replication phase.
Core Tip: Hepatitis B virus (HBV)-related single nucleotide polymorphisms (SNPs) have been identified in East Asians. We evaluated five SNPs and nongenetic factors associated with HBV infection in a hepatocellular carcinoma family cohort. The factors were correlated with hepatitis B surface antigen (HBsAg) in the first-stage and with HBV viral load in the second-stage. The SNPs, sex, generation, and index case HBsAg contributed to persistent HBV infection. Neonatal tolerance and SNPs in the HLA loci were both independently associated with persistent HBV infection. A prolonged HBV replication phase in parents could be the main mechanism of persistent HBV infection in children in East Asia.