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Importance of Host Genetic Factors HLA and IL28B as Predictors of Response to Pegylated Interferon and Ribavirin
- Source :
- American Journal of Gastroenterology. 106:1246-1254
- Publication Year :
- 2011
- Publisher :
- Ovid Technologies (Wolters Kluwer Health), 2011.
-
Abstract
- Viral factors are considered the best predictors of response to treatment for chronic hepatitis C (CHC), but genetic factors are known to have an important role in this respect. This paper investigates the relationships among the host genetic factors HLA and IL28B, viral factors, and the outcome of combination therapy.A multicenter retrospective cohort of 428 previously untreated CHC patients was treated with pegylated interferon/ribavirin (pegIFN/RBV) for 48 weeks. In all, 378 (88%) of these patients were genotype 1 or 4, and 50 (12%) were genotype 2 or 3.Multivariate logistic regression showed the rs12979860 CC genotype (adjusted odds ratio (aOR)=4.3, 95% confidence interval (95% CI): 2.6-7), the HLA-DQB1*0301 allele (aOR=2.08, 95% CI: 1.2-3.5) and age, viral genotype, and viral load levels to be significantly associated with sustained virological response (SVR). When the variable rs12979860 was eliminated, the area under the receiver operating characteristic (ROC) curve (AUC) decreased significantly (0.76 vs. 0.69; P=0.03). AUC values derived from viral factors were lower than those corresponding to host genetic factors (0.67 vs. 0.72, respectively; P=0.04). The HLA-DQB1*0301 and A*0201 alleles were associated with rs12979860 CC genotype and SVR (P0.0001).The HLA-DQB1*0301 allele and IL28B genotype are factors that are associated independently with SVR. There is a synergism between the HLA-DQB1*0301 and HLA-A*0201 alleles with polymorphism rs12979860 CC, which increases the SVR rate. IL28B genotype is the best predictor of SVR.
- Subjects :
- Adult
Male
Genotype
viruses
Genes, MHC Class II
Genes, MHC Class I
Human leukocyte antigen
Interferon alpha-2
Antiviral Agents
Polyethylene Glycols
chemistry.chemical_compound
Pegylated interferon
Ribavirin
medicine
Humans
Alleles
Retrospective Studies
Hepatology
business.industry
Host (biology)
Interleukins
Gastroenterology
Interferon-alpha
virus diseases
Hepatitis C, Chronic
Viral Load
biochemical phenomena, metabolism, and nutrition
Virology
Recombinant Proteins
digestive system diseases
Logistic Models
ROC Curve
chemistry
Area Under Curve
Immunology
Drug Therapy, Combination
Female
Interferons
business
medicine.drug
Subjects
Details
- ISSN :
- 00029270
- Volume :
- 106
- Database :
- OpenAIRE
- Journal :
- American Journal of Gastroenterology
- Accession number :
- edsair.doi.dedup.....6a2c625ad3b15cafa901758a99ad9635