Human Leukocyte Antigen Polymorphism HLA-A*24:02 is Associated with Acute Liver Disease in HBV-Infected Han Chinese Adults

Immunol Invest. 2023 Nov;52(6):767-778. doi: 10.1080/08820139.2023.2232409. Epub 2023 Jul 7.

Abstract

Background: Whether polymorphic Human Leukocyte Antigen (HLA)-A, HLA-B and HLA-DRB1 alleles were associated with acute liver disease after hepatitis B virus (HBV) infections was investigated.

Methods: In this study, from initially 100 participants in each group, HLA-A, HLA-B and HLA-DRB1 sequences were available from 86 acute hepatitis B (AHB) patients and from 84 HBV-resistant individuals (controls), using sequencing-based typing allele groups and alleles that exhibited differences in distribution between the case and control groups were subjected to chi-squared and logistic regression analyses to identify those associated with AHB. A dose response analysis was also performed on the effect of HLA-A*24:02 allele number on acute liver disease following HBV infection.

Results: The frequency distribution of HLA-B and HLA-DRB1 alleles in the control group were in Hardy-Weinberg Equilibrium (P > .05). HLA-A*24:02 (χ2 = 6.949, P = .008) occurred most frequently in the AHB and HLA-DRB1*12:02 (χ2 = 7.768, P = .005) in the control group. With adjustment for sex, the logistic regression model showed that the HLA-A*24:02 allele was significantly associated with AHB liver injury (P = .0326, OR = 2.270, 95% CI: 1.070-4.816), whereas the other HLA-A, HLA-B, and HLA-DRB1 alleles were not (P > .05). A linear response was observed for the association between HLA-A*24:02 allele number and acute liver disease after HBV infections (χ2 = 4.428, P = .025).

Conclusion: The HLA-A*24:02 allele may influence the severity of the cellular response to HBV infection, increasing the elimination of HBV-infected hepatocytes. The HLA-A*24:02 allele may be a potential screening marker for identifying people or regional populations in China at higher risk of acute liver disease following HBV infection.

Keywords: Acute liver disease; HLA-A; HLA-B; hepatitis B virus; human leukocyte antigen.

MeSH terms

  • Adult
  • Alleles
  • China
  • East Asian People
  • Gene Frequency
  • Genetic Predisposition to Disease
  • HLA-A Antigens* / genetics
  • HLA-B Antigens
  • HLA-DRB1 Chains / genetics
  • Hepatitis B virus
  • Hepatitis B* / genetics
  • Humans

Substances

  • HLA-A Antigens
  • HLA-A*24:02 antigen
  • HLA-B Antigens
  • HLA-DRB1 Chains