The relation of HLA genotype to hepatitis C viral load and markers of liver fibrosis in HIV-infected and HIV-uninfected women

J Infect Dis. 2011 Jun 15;203(12):1807-14. doi: 10.1093/infdis/jir192.

Abstract

Background: Human leukocyte antigen (HLA) class I and II genotype is associated with clearance of hepatitis C virus (HCV) infection, but little is known regarding its relation with HCV viral load or risk of liver disease in patients with persistent HCV infection.

Methods: High-resolution HLA class I and II genotyping was conducted in a prospective cohort of 519 human immunodeficiency virus (HIV)-seropositive and 100 HIV-seronegative women with persistent HCV infection. The end points were baseline HCV viral load and 2 noninvasive indexes of liver disease, fibrosis-4 (FIB-4), and the aspartate aminotransferase to platelet ratio index (APRI), measured at baseline and prospectively.

Results: DQB1*0301 was associated with low baseline HCV load (β = -.4; 95% confidence interval [CI], -.6 to -.3; P < .00001), as well as with low odds of FIB-4-defined (odds ratio [OR], .5; 95% CI, .2-.9; P = .02) and APRI-defined liver fibrosis (OR, .5; 95% CI, .3-1.0; P = .06) at baseline and/or during follow-up. Most additional associations with HCV viral load also involved HLA class II alleles. Additional associations with FIB-4 and APRI primarily involved class I alleles, for example, the relation of B*1503 with APRI-defined fibrosis had an OR of 2.0 (95% CI, 1.0-3.7; P = .04).

Conclusions: HLA genotype may influence HCV viral load and risk of liver disease, including DQB1*0301, which was associated with HCV clearance in prior studies.

Publication types

  • Multicenter Study

MeSH terms

  • Adult
  • Alanine Transaminase / blood
  • Alleles
  • Aspartate Aminotransferases / blood
  • Cohort Studies
  • Female
  • Genotype
  • HIV Infections / complications*
  • HLA Antigens / genetics*
  • HLA-DQ Antigens / genetics
  • Hepacivirus / pathogenicity*
  • Hepatitis C, Chronic / complications
  • Hepatitis C, Chronic / virology*
  • Humans
  • Liver Cirrhosis / blood
  • Liver Cirrhosis / genetics*
  • Liver Cirrhosis / virology
  • Logistic Models
  • Platelet Count
  • Prospective Studies
  • United States
  • Viral Load / genetics*

Substances

  • HLA Antigens
  • HLA-DQ Antigens
  • Aspartate Aminotransferases
  • Alanine Transaminase