The MHC Is a Major Determinant of Viral Status, but Not Fibrotic Stage, in Individuals Infected With Hepatitis C

Gastroenterology. 2000 Jun;118(6):1124-30. doi: 10.1016/s0016-5085(00)70365-9.

Abstract

Background & aims: In hepatitis C infection, several studies have examined the role of the major histocompatibility complex (MHC) in determining outcome, with variable results. To clarify the importance of MHC, we examined class II DR and DQ antigens in a homogenous cohort of women exposed to hepatitis C genotype 1b from a single inoculum.

Methods: Of 243 participants, 95 had spontaneous viral clearance and 148 are chronically infected. The frequencies of HLA class II DR and DQ antigens were compared between the 2 groups and between liver biopsy findings of 145 chronically infected subjects.

Results: DRB1*0101 and DQB1*0501 alleles were more frequent in subjects who sustained viral clearance than in chronically infected subjects (32.3% and 36.8% vs. 8.8% and 14.2%, respectively; P = 0.002). DRB1*03011 and DQB1*0201 occurred more frequently in chronically infected subjects than in those who cleared the virus (41.5% and 42.6% vs. 16.7% and 15.8%, respectively; P = 0.001). Both DRB1*03011 and DQB1*0201 were significantly less frequent in those with higher inflammatory scores on liver biopsy.

Conclusions: We show that in a homogenous cohort of women infected with the same hepatitis C virus, several HLA antigens are associated with either viral clearance or persistence. This suggests a strong role for host immunogenetic factors in determining outcome in hepatitis C infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Alleles
  • Biomarkers
  • Biopsy
  • Cohort Studies
  • Female
  • Genetic Predisposition to Disease
  • HLA-DQ Antigens / analysis
  • HLA-DQ Antigens / genetics
  • HLA-DQ beta-Chains
  • HLA-DR Antigens / analysis
  • HLA-DR Antigens / genetics
  • HLA-DRB1 Chains
  • Haplotypes
  • Hepatitis C / genetics
  • Hepatitis C / immunology*
  • Hepatitis C / pathology*
  • Histocompatibility Antigens Class II / analysis*
  • Histocompatibility Antigens Class II / genetics
  • Histocompatibility Antigens Class II / immunology
  • Histocompatibility Testing
  • Humans
  • Immunophenotyping
  • Liver Cirrhosis / genetics
  • Liver Cirrhosis / immunology*
  • Liver Cirrhosis / pathology*
  • Middle Aged

Substances

  • Biomarkers
  • HLA-DQ Antigens
  • HLA-DQ beta-Chains
  • HLA-DQB1 antigen
  • HLA-DR Antigens
  • HLA-DRB1 Chains
  • Histocompatibility Antigens Class II