 |
|
|
| |
African-American Peg/RBV Response May Be Genetically Impaired: Polymorphism in the Human MHC and the Early Viral Decline During Treatment of HCV
|
| |
| |
Reported by Jules Levin
DDW, May 17-22, 2008
San Diego, CA
Leland J Yee1, KyungAh Im1, Abdus S Wahed1, Teodorica Bugawan2, Jia Li2, Shannon L Rhodes3, Henry Erlich2, Hugo R Rosen4, T. Jake Liang5, HuiYing Yang3
1. Department of Epidemiology, University of Pittsburgh, Pittsburgh, PA, USA, 2. Roche Molecular Systems, Inc., Alameda, CA, USA, 3. Division of Medical Genetics, Cedars Sinai Medical Center, Los Angeles, CA, USA, 4. Gastroenterology, University of Colorado Health Sciences Center, Denver, CO, USA, 5. Division of Digestive Diseases, NIDDK, Bethesda, MD, USA
ABSTRACT from program book
Background: The early viral response, or the rapidity of the viral decline during the first 4 weeks immediately following the start of therapy for chronic hepatitis C virus (HCV) infection, may have prognostic potential for ultimate sustained virologic response (SVR). Considerable inter-individual variability has been reported among patients treated peginterferon+ribavirin. Additionally, African Americans (AA) have been reported to have slower rates of viral decline than Caucasian Americans (CA). The human major histocompatability complex (MHC) genes encode the human leukocyte antigens (HLA), which are important in the immune response to viral infections, and may play an important role in the response to anti-HCV therapy. We examined whether carriage of specific human MHC alleles are associated with the early viral response.
Methods: We utilized a random coefficients model, longitudinal viral level data (baseline and days 0, 1, 2, 7, 14 and 28 of treatment), and medium resolution MHC genotyping to examine associations between MHC class I and class II allele carriage and the early viral response in 180 AA and 194 CA patients with genotype-1 HCV infection over the first 28 days of treatment with peginterferon-_-2a + ribavirin.
Results:
Baseline viral levels were similar irrespective of allele carriage, and race, but the rate of the viral decline was dependent upon both allele carriage and race. Fastest declines were observed for CA non-carriers of A*03, followed by CA carriers, AA carriers, and AA non-carriers, respectively (p=0.0179). For Cw*03, CA carriers had the fastest decline, followed by CA non-carriers, AA non-carriers, and AA carriers, respectively (p=0.0459). For DQA1*04, CA non-carriers had the fastest viral decline, followed by AA non-carriers, AA carriers, and CA carriers, respectively (p=0.0179). For DQB1*0402, CA non-carriers had the fastest decline, followed by AA non-carriers, AA carriers, and CA carriers, respectively (p=0.0178).
Conclusions:
MHC class I and class II alleles are associated with the dynamics of the viral decline during the 28 days following the start of peginterferon therapy. There are differential distributions of these alleles by race and may contribute to observed population differences in response by race. Our findings highlight the potential role of human genetic diversity in the response to peginterferon therapy for HCV. Funding provided by NIDDK and Roche Laboratories.
|
| |
|
|
|
|
|
