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The effect of HLA alleles on response to interferon therapy in patients with chronic hepatitis C
Insights
Low hepatitis C viral load predicts treatment success. Certain HLA alleles, specifically HLA-B54 and the A24-B54-DR4 haplotype, indicate a poor response to interferon therapy in chronic hepatitis C patients.
Area of Science:
- Immunogenetics
- Hepatology
- Virology
Background:
- Chronic hepatitis C (HCV) is a significant global health concern.
- Interferon-alpha (IFN-alpha) therapy has been a cornerstone treatment for chronic hepatitis C.
- Predicting treatment response is crucial for optimizing patient outcomes.
Purpose of the Study:
- To investigate the association between Human Leukocyte Antigen (HLA) alleles and response to interferon-alpha (IFN-alpha) treatment in Japanese patients with chronic hepatitis C.
- To identify genetic markers that predict treatment efficacy or non-response.
Main Methods:
- A cohort of 67 Japanese patients with chronic hepatitis C received IFN-alpha treatment.
- Hepatitis C virus (HCV) viral loads, genotypes, and HLA antigens were assessed pre-treatment.
- Responders were defined by sustained normalization of alanine aminotransferase levels post-treatment.
Main Results:
- Low baseline HCV viral load (< 1 x 10(6) copies/ml) and genotype 2a were significantly associated with treatment response.
- No significant differences in HLA-A and HLA-C alleles were observed between responders and non-responders.
- Non-responders showed a significant increase in HLA-B54, DR4 alleles, and the A24-B54-DR4 haplotype compared to responders and controls.
Conclusions:
- Low viral load is a strong predictor of successful IFN-alpha therapy in chronic hepatitis C.
- Specific HLA alleles, namely HLA-B54 and the A24-B54-DR4 haplotype, are identified as significant predictors of poor response to IFN-alpha treatment.
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.
Method:
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).
Conclusion:
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.