HBV mutations in EnhII/BCP/PC region contribute to the prognosis of hepatocellular carcinoma

Accompanied by HBV infection, HBV mutations gradually occur because HBV polymerase appears proofread deficiencies. In our previous study, we have identified that EnhII/BCP/PC mutations and genotype C of HBV DNA were associated with hepatocellular carcinoma (HCC) risk. In this study, we extend our research to explore HCC prognosis associated genotype and mutations in EnhII/BCP/PC regions.

We designed a case-cohort study of 331 HCC patients to evaluate the effects of the HBV genotypes and mutations on HCC survival. Log-rank test and Cox proportional hazard models were used for the analyses.

Results showed that genotype C, which was more frequent in HBV-related HCC (77.4%), presented a negative signal with HCC survival. Interestingly, we detected a significant association between EnhII/BCP/PC mutation nt1753 and HCC prognosis (Log-rank P = 0.034). Subgroup analysis revealed that this risk effect was more pronounced in non-B genotype (P = 0.090 for heterogeneity test). We also detected a borderline multiplicative interaction between genotypes of nt1753 and HBV genotype on HCC survival (P for interaction = 0.069).

These findings indicated that, in Chinese population, nt1753 in EnhII/BCP/PC region might be a novel marker for HCC prognosis.