Higher proportion of quasispecies mutations introduced by preS2 deletion in HBeAg-positive chronic hepatitis B patients with low HBsAg levels

HBeAg-positive chronic hepatitis B (CHB) with low HBsAg levels is a relatively rare serological pattern and associated with the severity of liver disease. However, the mechanisms in these patients are still unclear. In present we found that treatment-naïve HBeAg-positive CHB patients with low HBsAg levels (research group) was mainly of HBV-C genotype and had a higher proportion of quasispecies mutations introduced by preS2 deletion than patients with positive HBeAg and high HBsAg levels (control group). In vitro cell experiments showed the mutation did not affect HBV replication while significantly reduced the viral infectivity. The fibrosis scores in CHB patients with mutations were significantly higher than those in wild-type patients and the control group. Compared to the patients with the wild-type strain, the mutation group had higher levels of ALT, sPD-1, and sPD-L1. The number of viral-specific IFN-γ secretory cells induced by the mutant was significantly lower than that of the wild-type strain. The protein structure analysis also showed that the deletion regions had complex alpha helices and Epitope Assay Counts. Taken together, HBeAg-positive CHB patients with low HBsAg levels had a higher quasispecies variant rate introduced by preS2 deletion. The mutant virus could persist in patients due to its better ability to escape host immunity, which may be associated with the progression of liver disease.