Analysis of clinical characteristics and S gene sequences in chronic asymptomatic HBV carriers with low-level HBsAg

作者:Wang, Tong; Cui, Dawei; Chen, Shaoming; Xu, Xujian; Sun, Changgui; Dai, Yuzhu*; Cheng, Jun*
来源:Clinics and Research in Hepatology and Gastroenterology, 2019, 43(2): 179-189.
DOI:10.1016/j.clinre.2018.08.015

摘要

Background: During the natural hepatitis B virus (HBV) infection process, some infected subjects are characterized by a sustained low serum HBV surface antigen (HBsAg) expression level. Most members in this population are chronic asymptomatic HBV carriers (ASCs). To elucidate the mechanism underlying low-level HBsAg expression in ASCs, we sequenced the HBV S gene in these patients to reveal specific sequence characteristics. @@@ Methods: Overall, 1308 cases of chronic ASCs were grouped according to their HBsAg serum expression levels (10 IU/mL). The clinical characteristics of the population were analysed in detail. The HBV S gene was sequenced from 276 ASC cases with low-level HBsAg expression. Additionally, 100 of 1032 ASC cases with high-level HBsAg expression were randomly selected for HBV S gene sequencing based on age matching according to the low-level HBsAg group. A comparative analysis was conducted with the HBV S gene sequences from ASCs with low HBsAg expression and the HBV reference S gene sequences from ASCs with high HBsAg expression. @@@ Results: The population with low-level HBsAg expression displayed the following primary clinical characteristics: mostly chronic asymptomatic HBV carriers, older age (mean age 55.09 years), HBsAg/anti-HBe/anti-HBc (core) positivity as the main serological pattern (97.1%), low HBV DNA replication (1.32 +/- 1.60 log(10) IU/mL), a low HBV-DNA positive rate (45.65%) and primarily genotype B (82.54%) and serotype adw (84.13%). The comparative analysis of the HBV S gene sequences from ASCs with low-level HBsAg showed significant mutations (including co-mutations) on both sides of the main hydrophilic region (MHR). @@@ Conclusion: Significant mutations in multiple regions and at multiple sites (including comutations) on both sides of the MHR may be one cause of the low HBsAg expression level in this population.