HBV PreS Variants Significantly Decrease in Liver Tissues After 104 Weeks of Antiviral Therapy With Nucleos(t)ide...

Nucleos(t)ide analogues (NAs) are widely used in patients infected with hepatitis B virus (HBV). However, limited data are available on the changes of the HBV variants at 2 years (104 weeks, w) after therapy, largely due to the difficulty in detecting the viral genome in peripheral blood. In our study, fifteen HBV-infected patients (HBV e antigen positive) were enrolled, liver biopsy was performed at baseline and 104 w to evaluate liver fibrosis, and the clinically significant HBV variants related to hepatocellular carcinoma (HCC) and viral quasispecies diversity were also analyzed. PreS deletions were found in eight patients (53.3%) at baseline. All the eight patients showed a decrease in preS deletions after antiviral therapy (p < 0.05). Moreover, all the eight patients with the preS2 start codon mutations/deletions at baseline were decreased after NAs treatment. BCP/preC mutations did not significantly change among the patients, including the eight patients achieved HBeAg seroconversion (all p > 0.05). HBV quasispecies diversity did not show significant differences, and no NAs-related drug resistance mutations were found in the eight patients with low-level viremia. The reduction of HBV preS variants may represent one of the important mechanisms by which NAs therapy lowers the risk of progression to HCC.