Impacts of the Percentage of Basal Core Promoter Mutation on the Progression of Liver Fibrosis After Hepatitis B e Antigen Seroconversion
Jia-Feng Wu, Kai-Chi Chang, Yen-Hsuan Ni, Hong-Yuan Hsu, Mei-Hwei Chang
The Journal of Infectious Diseases, Volume 223, Issue 8, 15 April 2021, Pages 1381–1389, https://doi.org/10.1093/infdis/jiaa545
Published:
29 August 2020
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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.
antiviral agents, hepatitis B virus, liver stiffness measurement, transient elastography
Topic:
mutation hepatic fibrosis antiviral agents hepatitis b e antigens interferons hepatitis b virus tenofovir entecavir human leukocyte interferon liver stiffness measurement programmed cell death 1 ligand 1 seroconversion