Mutations in reverse transcriptase region of HBV affect Hepatitis B surface antigen titers and its correlation with HBV DNA

The impact of mutations in the reverse transcriptase region of HBV on serum HBsAg titer and its correlation with HBV DNA is largely unknown. A total of 644 patients, with a history of lamivudine or adefovir dipivoxil resistance who underwent genotypic resistance tests, were enrolled in this study. Serum HBsAg, hepatitis B e antigen and HBV DNA were quantified, and the HBV RT region was sequenced and analyzed. Then, the patients were divided into five sub-groups, including M204I/V, L180M+M204I/V, A181T/V, N236T and A181T/V+N236T according to the mutation spectra. HBsAg was lower in the wild-type and A181T/V+N236T groups as compared to the M204I/V, L180M+M204I/V and N236T groups. HBsAg was positively correlated with HBV DNA levels in the wild-type group (r = 0.322, p < 0.01), as well as in the M204I/V, L180M+M204I/V, A181T/V, and N236T subgroups, while no correlation was found in the A181T/V+N236T subgroup (r = 0.159, p = 0.217). Moreover, for patients with N236T mutation, HBsAg was positively correlated with HBV DNA level in the HBeAg negative group (r = 0.435, p = 0.016), but not in the HBeAg positive group (r = 0.105, p = 0.594). For patients with A181T/V or N236T mutation, HBsAg was positively correlated with HBV DNA in older patients (≥ 40 years), but not in younger patients (< 40 years). Serum HBsAg titer and its correlation with HBV DNA may be affected by mutations in the reverse transcriptase region of HBV, that should be re-evaluated in patients with antiviral resistance.