Meta-Analysis of Genetic Variants Associated With HBV Infection Susceptibility and Hepatocellular Carcinoma Risk

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.