Abstract:
Objective Analysis of the association between hepatitis B surface antigen (HBsAg) clearance and amino acid mutations in the pre-S/S region of the hepatitis B virus (HBV) in a cohort from Wuwei city, Gansu province.
Methods A cohort of chronic hepatitis B (CHB) infected individuals was established at the Wuwei City Tumor Hospital in Gansu province during August 2018 and December 2022. Follow-up continued until December 31, 2022, with individuals who cleared HBsAg designated as the case group and those with persistent HBsAg positivity as the control group. Serum samples collected at baseline were subjected to next-generation sequencing (NGS) of the HBV pre-S/S region. Amino acid mutation rates and complexity were calculated. A sparse logistic regression (SLR) model was constructed to analyze the association between HBsAg clearance and amino acid mutations in the HBV pre-S/S region.
Results A total of 171 patients with complete genotype C sequences were included, with 23 in the HBsAg clearance group and 148 in the persistent positive group. The average mutation frequency (Z = 2.881) and complexity (Z = 3.255) in the S region were significantly higher in the HBsAg persistent positive group than in the clearance group (P < 0.05). Mutations at 121 amino acid sites showed statistically significant differences between the two groups (P < 0.05), with 20 sites identified as effective mutation sites. Except for site H132, all other sites showed higher mutation rates in the HBsAg persistent positive group than in the clearance group (P < 0.05). An SLR model identified six characteristic indicators significantly associated with HBsAg clearance: HBV DNA, Sn_271, Sn_399, Sn_194, P_121, and Sn_397, with HBV DNA having the highest contribution.
Conclusions Changes in amino acid sites in the HBV pre-S/S region may influence HBsAg clearance. The application of the SLR model provides new insights for precision treatment of CHB.
下载: