HBsAg mutations in patients with chronic hepatitis B undergoing adefovir dipivoxil resistance

Abstract

Objective To investigate adefovir dipivoxil (ADV) resistant mutation related HBsAg mutation, vaccine escape mutation and T cell epitope mutations in Chinese patients with chronic hepatitis B (CHB) who underwent adefovir resistance. Methods Seventy CHB patients who underwent ADV resistance from December 2007 to September 2011 in Beijing Ditan Hospital, Capital Medical Unversity were enrolled. While 70 ADV treated patients without ADV resistance were randomly selected as control group. HBV Rt/S ORF were sequenced with PCR product Sanger sequencing and pyrosequencing. ADV resistant mutation related HBsAg mutation, vaccine escape mutation and T cell epitope mutations were compared between ADV treated CHB patients with and without ADV resistance. Results Total of 70 ADV resistant patients with CHB were enrolled, while 70 ADV treated CHB patients without ADV resistance were set as control. Baseline characteristics were comparable between the two groups. All 42 rtA181T mutations were related to sW172* mutations. Mean ratio of rtA181T/sW172* mutations in quasispecies was (42.6 ± 22.1)% (12.2%-100%). More patients in resistance group showed vaccine escape mutation (χ2 = 12.8736, P = 0.0003) and T cell epitope mutations (χ2 = 4.8344, P = 0.0279) than control group. Conclusions In Chinese patients with CHB, rtA181T is mainly related to sW172* mutations. ADV resistance is related to vaccine escape mutation and T cell epitope mutations. Further studies should focus on the possible mechanism. Key words: Chronic hepatitis B; Hepatitis B virus; Adefovir dipivoxil; Hepatitis B surface antigen