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Meta-analysis identifies genetic variants linked to HBV susceptibility and HCC risk

Meta-analysis identifies genetic variants linked to HBV susceptibility and HCC risk
Photo by MJH SHIKDER / Unsplash
Key Takeaway
Consider that genetic variants CD40 rs1883832 and C2 rs9267665 are strongly associated with HBV susceptibility, but causation is not established.

This meta-analysis pooled data from East Asian cohorts to evaluate associations between genetic variants and susceptibility to hepatitis B virus (HBV) infection as well as risk of hepatocellular carcinoma (HCC). The analysis focused on variants in immune-related genes and HLA regions.

For HBV infection susceptibility, the strongest associations were found for CD40 rs1883832 and C2 rs9267665, with no heterogeneity across studies. Additionally, HLA-DPA1 rs3077 and HLA-DQB1 rs2856718 were significantly associated with HBV susceptibility, though these findings showed considerable heterogeneity.

Regarding HCC risk, the authors report that certain risk variants are linked to specific causes including HBV, HCV, alcohol-related disease, and nonalcoholic fatty liver disease (NAFLD). However, no pooled effect sizes or specific variants were reported for HCC outcomes.

The meta-analysis does not report limitations, funding sources, or practice relevance. Importantly, the results represent associations, not causation, and the heterogeneity for some findings limits the strength of conclusions. Clinicians should interpret these genetic associations as preliminary and not yet ready for clinical application.

Study Details

Study typeMeta analysis
EvidenceLevel 1
PublishedMay 2026
View Original Abstract ↓
Hepatitis B virus (HBV) and hepatocellular carcinoma (HCC) are serious medical problems worldwide. Today, many researchers believe that genetic variations play a major role in how easily someone gets infected and how the disease progresses over time. Although many genetic association studies have suggested various susceptibility loci, lack of consistent results across studies has limited clinical utility. We performed a comprehensive meta-analysis primarily involving East Asian cohorts. We analysed eight SNPs related to HBV infection and 11 SNPs related to HCC across multiple etiologic subgroups. We found that CD40 rs1883832 and C2 rs9267665 exhibited the strongest associations with susceptibility to HBV infection, with no heterogeneity. We found that HLA-DPA1 rs3077 and HLA-DQB1 rs2856718 were significantly associated with HBV infection susceptibility, though with considerable heterogeneity. In our HCC analyses, we found that certain risk variants are linked to specific causes. These include HBV, HCV, alcohol-related disease, and non-alcoholic fatty liver disease (NAFLD). Each cause seems to have its own genetic factors. Based on these results, our meta-analysis brings together many studies to give a clearer picture of the genetic factors that influence HBV infection and HCC in different etiologic pathways. We found that immune-related genes and HLA class II variants seem to have roles in HBV persistence, while metabolic gene variants are major contributors to HCC risk.
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