Impacts of the Percentage of Basal Core Promoter Mutation on the Progression of Liver Fibrosis After Hepatitis B e Antigen Seroconversion

• Published in: The Journal of infectious diseases Vol. 223; no. 8; pp. 1381 - 1389
• Main Authors: Wu, Jia-Feng, Chang, Kai-Chi, Ni, Yen-Hsuan, Hsu, Hong-Yuan, Chang, Mei-Hwei
• Format: Journal Article
• Language: English
• Published: US Oxford University Press 23.04.2021
• Subjects: Antibodies, Viral - blood; Antigens; Antiretroviral drugs; Antiviral agents; Antiviral Agents - therapeutic use; Antiviral drugs; B7-H1 Antigen; Fibrosis; Hepatitis B; Hepatitis B e antigen; Hepatitis B e Antigens - immunology; Hepatitis B virus - genetics; Hepatitis B, Chronic - drug therapy; Hepatocytes; Humans; Inflammation; Liver; Liver cirrhosis; Liver Cirrhosis - drug therapy; Liver Cirrhosis - virology; Mutation; PD-L1 protein; Promoter Regions, Genetic; Seroconversion; Tenofovir; transient elastography; liver stiffness measurement; antiviral agents; hepatitis B virus
• ISSN: 0022-1899; 1537-6613; 1537-6613
• DOI: 10.1093/infdis/jiaa545

Abstract Background We investigated the relationships among the percentage of hepatitis B virus (HBV) mutations and liver fibrosis after hepatitis B e antigen (HBeAg) seroconversion. Methods We quantified the percentage of HBV mutants by pyrosequencing using serum samples obtained at inflammatory phase and after HBeAg seroconversion in 160 initially HBeAg-positive chronic HBV-infected patients. The relationships between antiviral agents, percentages of HBV mutations, and liver stiffness measurements (LSMs) were analyzed. Results We demonstrated that the percentages of A1762T/G1764A mutation are significantly higher in subjects with an LSM >7 kPa than in those with an LSM ≤7 kPa after HBeAg seroconversion. Hepatitis B e antigen seroconversion age is positively correlated with the percentages of A1762T/G1764A mutation at inflammatory phase before HBeAg seroconversion. Subjects who underwent interferon, entecavir, or tenofovir disoproxil fumarate therapy before HBeAg seroconversion possessed a lower percentage of A1762T/G1764A mutation after HBeAg seroconversion. The percentage of A1762T/G1764A ≥20% after HBeAg seroconversion was predictive of an LSM >7 kPa (hazard ratio = 6.37, P = .001). The presence of A1762T/G1764A led to downregulated messenger ribonucleic acid and protein levels of programmed-death ligand-1 (PD-L1) in hepatocytes. Conclusions The percentage of A1762T/G1764A mutations after HBeAg seroconversion was associated with liver fibrosis. The A1762T/G1764A mutation may evoke hepatic inflammation by suppressing PD-L1 in hepatocytes. HBeAg-seroconversion age is associated with the percentage of A1762T/G1764A mutation. Interferon, entecavir, and TDF may decrease A1762T/G1764A mutations. The percentage of A1762T/G1764A after HBeAg seroconversion was predictive of LSM >7 kPa. A1762T/G1764A mutation may downregulate PD-L1 in hepatocytes.