The effect of HLA alleles on response to interferon therapy in patients with chronic hepatitis C.
OBJECTIVE
To compare HLA alleles in the patients with chronic hepatitis C treated with interferon-alpha (IFN-alpha) between patients with response to IFN treatment and nonresponse.


METHODS
Sixty-seven Japanese patients with chronic hepatitis C were treated with daily intramuscular administration of IFN-alpha (6 million units) for 2 weeks followed by three times per week for 22 weeks. Viral loads of hepatitis virus C (HCV), HCV genotypes and HLA antigens were determined just before IFN-alpha treatment. Responders to IFN-alpha were defined as normalization of alanine aminotransferase at the end of treatment and during a follow-up period at least longer than 6 months. The patients who could not reach the above response criteria were defined as nonresponders.


RESULTS
There were 20 responders and 47 nonresponders to IFN treatment. The low viral load with less than 1 x 10(6) copy/ml (P< 0.05), and type 2a genotype (P< 0.05) were significantly increased in responders. Other clinical and biochemical parameters were not significant. There was no difference in HLA-A and C antigens between responders and nonresponders. In contrast, HLA-B54,DR4 and A24-B54-DR4 haplotype of nonresponders increased compared with responders or controls (Pc < 0.0001, Pc < 0.001, Pc < 0.0001, respectively). At multivariate analysis, viral loads, HLA-B54 and HLA-A24-B54-DR4 haplotype were significant (P=0.0002, P=0.0258, P=0.0378, respectively).


CONCLUSIONS
The low viral load is a good predictor. HLA-B54 and HLA-A24-B54-DR4 haplotype should be predictors for poor response to IFN therapy in patients with chronic hepatitis C.
Kikuchi
I
I
Department of Internal Medicine, Miyazaki Prefectural Hospital, Japan.
Ueda
A
A
Mihara
K
K
Miyanaga
O
O
Machidori
H
H
Ishikawa
E
E
Tamura
K
K
D000410:Alanine Transaminase / Q000097:blood; D000483:Alleles; D005260:Female; D006680:HLA Antigens / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000097:blood / Q000188:drug therapy* / Q000235:genetics*; D006801:Humans; D007273:Injections, Intramuscular; D016898:Interferon-alpha / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000097:blood; D016896:Treatment Outcome; D019562:Viral Load
D006680:HLA Antigens; D016898:Interferon-alpha; D012367:RNA, Viral; D000410:Alanine Transaminase