HBV genotype C strains with spontaneous YMDD mutations may be a risk factor for hepatocellular carcinoma.

HBV has a relatively high mutation rate in its genome and most of these mutations are associated with the curative effect of nucleoside analogs. In this study, 1,424 patients with HBV-related liver diseases not treated with antiviral drugs, including 197 asymptomatic HBV carriers, 769 chronic hepatitis B patients, 145 acute-on-chronic liver failure (ACLF) patients, 187 HBV-related liver cirrhosis patients, and 126 HBV-related HCC patients, were selected to investigate the distribution and clinical significance of spontaneous YMDD mutations in liver diseases at different stages. Spontaneous YMDD mutations were detected in all stages of liver diseases and the YIDD variant was the dominant mutation type. The mutation rate was higher in genotype C strains than in genotype B strains. The χ(2) subdivision method showed that the spontaneous YMDD mutation rate in HCC was higher than that in other liver diseases. The difference in spontaneous YMDD mutation rates in patients with liver diseases infected with genotype C strains at different stages was statistically significant. Spontaneous YMDD mutation rates in patients with liver diseases infected with genotype C strains at different stages were then compared one to one using the χ(2) subdivision method. The results showed that the spontaneous YMDD mutation rate in HCC was higher than that in other liver diseases. Taken together, these results indicated that spontaneous YMDD mutations are more likely to occur in patients infected with genotype C strains, and genotype C strains with spontaneous YMDD mutations may be a risk factor for HCC.