Associations between the human MHC and sustained virologic response in the treatment of chronic hepatitis C virus infection.
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; approximately 30%) compared to Caucasian Americans (CA; approximately 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-alpha-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.
Rhodes
S L
SL
Cedars Sinai Medical Center, Los Angeles, CA, USA.
Erlich
H
H
Im
K A
KA
Wang
J
J
Li
J
J
Bugawan
T
T
Jeffers
L
L
Tong
X
X
Su
X
X
Rosen
H R
HR
Yee
L J
LJ
Liang
T J
TJ
Yang
H
H
D001741:Black or African American; D000483:Alleles; D000998:Antiviral Agents / Q000627:therapeutic use*; D015331:Cohort Studies; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D005805:Genes, MHC Class I; D005802:Genes, MHC Class II; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000208:ethnology / Q000821:virology; D006579:Heterozygote; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage; D008297:Male; D011092:Polyethylene Glycols / Q000008:administration & dosage; D012367:RNA, Viral / Q000235:genetics; D011994:Recombinant Proteins; D012254:Ribavirin / Q000008:administration & dosage; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States; D019562:Viral Load; D044465:White People
D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C100416:peginterferon alfa-2a