1. ¹Cedars Sinai Medical Center, Los Angeles, CA, USA
2. ²Roche Molecular Systems, Inc., Alameda, CA, USA
3. ³Department of Biostatistics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA
4. ⁴Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA
5. ⁵Department of Medicine, Center for Liver Diseases, Veterans Affairs Medical Center, Miami, FL, USA
6. ⁶Division of Gastroenterology and Hepatology, University of Colorado Health Sciences Center, Denver, CO, USA
7. ⁷Division of Infectious Diseases, Department of Medicine, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA
8. ⁸Liver Diseases Branch, NIDDK, National Institutes of Health, Bethesda, MD, USA
9. ⁹Department of Discovery, Medicine and Epidemiology, AstraZeneca Pharmaceuticals LP, Wilmington, DE, USA

Correspondence: Dr LJ Yee, University of Pittsburgh, A511 Crabtree Hall, 130 DeSoto Street, Pittsburgh, PA 15261, USA. E-mail: YeeL@edc.pitt.edu

Received 21 January 2008; Revised 27 February 2008; Accepted 28 February 2008; Published online 17 April 2008.

Abstract

The human major histocompatability complex (MHC) genes encode the human leukocyte antigens, which are important in antigen presentation and regulation of CD8+ and CD4+ T cells. Response to therapies in hepatitis C virus (HCV) infection is highly variable (30–80% ) and lower response rates have been reported among African Americans (AA; 30% ) compared to Caucasian Americans (CA; 50% ) infected with genotype-1 viruses. We evaluated whether MHC gene variants were associated with response to therapy and racial differences in AA and CA sustained virologic response (SVR) rates. We genotyped alleles at 8 MHC loci: 3 class I (A, B and C) and 5 class II (DRB1, DQA1, DQB1, DPA1 and DPB1) loci in 373 individuals (179 AA and 194 CA) with genotype-1 HCV infections, who were treated with peginterferon--2a and ribavirin. We observed carriage of A^*02 (RR=1.33(1.08–1.64); P=0.008), B^*58 (RR=1.84(1.24-2.73); P=0.002) and DPB1^*1701 (RR=1.57(1.09-2.26); P=0.015) to be associated with SVR after adjustment for other predictors of response. In analysis of AA and CA subgroups separately, we observed potential, though not statistically significant, differences in these MHC associations. Variation in the immunogenetic background of HCV-infected individuals might account for some observed variation in viral-specific immunity and courses of disease. In this regard, future studies examining broader patient populations are warranted.