Analysis of hepatic fibrosis markers in the serum of chronic hepatitis B patients according to basal core promoter/precore mutants

Sci Rep. 2022 Jun 17;12(1):10261. doi: 10.1038/s41598-022-14285-9.

Abstract

The A1762T/G1764A double mutant in the basal core promoter (BCP) region of the hepatitis B virus (HBV) is associated with severe hepatic lesions while the G1899A mutation with the double mutant is associated with a significant reduction in the risk of severe fibrosis. This study aims to measure a number of markers in the serum of patients with chronic HBV infection and to assess relationships between these markers and BCP/precore mutants with consideration of the stage of fibrosis. The serum levels of resistin, TGF-β1, MMP-1, TIMP-1, collagen IA1 and PDGF-BB, which are markers that are known to be involved in the process of hepatic fibrosis, were assayed. The serum levels of PDGF-BB and TIMP-1, and the mutation profile were independently associated with advanced fibrosis. A higher level of TIMP-1 was associated with advanced fibrosis regardless of the mutation status, and a higher level of PDGF-BB was associated with nonsevere fibrosis in patients infected with viruses harboring the A1762T/G1764A or A1762T/G1764A/G1899A mutations. Our results suggest an impact of the A1762T/G1764A mutant on the biological pathway related to TGF-β1 and PDGF-BB. In vitro studies are needed to understand the impact of these mutants on the serum secretion of markers involved in fibrosis severity.

MeSH terms

  • Becaplermin / genetics
  • Biomarkers
  • DNA, Viral / genetics
  • Genotype
  • Hepatitis B virus / genetics
  • Hepatitis B*
  • Hepatitis B, Chronic* / complications
  • Humans
  • Liver Cirrhosis / complications
  • Mutation
  • Tissue Inhibitor of Metalloproteinase-1 / genetics
  • Transforming Growth Factor beta1 / genetics

Substances

  • Biomarkers
  • DNA, Viral
  • Tissue Inhibitor of Metalloproteinase-1
  • Transforming Growth Factor beta1
  • Becaplermin