Dataset Information

Replicated association between an IL28B gene variant and a sustained response to pegylated interferon and ribavirin.

ABSTRACT: BACKGROUND & AIMS:Patients with chronic hepatitis C virus (HCV) infections are treated with pegylated interferon and ribavirin (PEG-IFN/RBV), which is effective in less than 50% of those infected with HCV genotype 1. Genome-wide association studies have linked response to PEG-IFN/RBV with common single nucleotide polymorphisms in the vicinity of interferon (IFN)-lambda genes on chromosome 19. We investigated the association between the polymorphism rs12979860 and treatment response in a diverse cohort of chronic HCV patients. METHODS:A cross-sectional study of 1021 consecutive patients enrolled in the Duke Hepatology Clinic Research Database and Biorepository. We analyzed DNA, clinical and demographic data, along with validated data of the response of 231 subjects to PEG-IFN/RBV. The study included Caucasians (n = 178), African Americans (n = 53), and HCV genotypes 1 (n = 186) and 2/3 (n = 45). The rs12979860 genotype was tested for an association with sustained virologic response, defined as undetectable levels of HCV RNA 24 weeks after treatment ended. RESULTS:The rs12979860 CC genotype (found in approximately 40% of Caucasians) predicted a sustained virologic response to therapy among Caucasians (odds ratio, 5.79; 95% confidence interval, 2.67-12.57; P = 9.0 x 10(-6)), independent of HCV genotype and other covariates. Rs12979860 CC predicted a sustained response with 78% specificity and 65% sensitivity in patients infected with HCV genotype 1). CONCLUSIONS:rs12979860 genotype is a significant independent predictor of response to PEG-IFN/RBV in patients with chronic HCV infection; tests for this genotype might be used to determine the best course of treatment for patients considering antiviral therapy.

SUBMITTER: McCarthy JJ

PROVIDER: S-EPMC2883666 | biostudies-literature | 2010 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Replicated association between an IL28B gene variant and a sustained response to pegylated interferon and ribavirin.

McCarthy Jeanette J JJ Li Josephine H JH Thompson Alexander A Suchindran Sunil S Lao Xiang Qian XQ Patel Keyur K Tillmann Hans L HL Muir Andrew J AJ McHutchison John G JG

Gastroenterology 20100219 7

<h4>Background & aims</h4>Patients with chronic hepatitis C virus (HCV) infections are treated with pegylated interferon and ribavirin (PEG-IFN/RBV), which is effective in less than 50% of those infected with HCV genotype 1. Genome-wide association studies have linked response to PEG-IFN/RBV with common single nucleotide polymorphisms in the vicinity of interferon (IFN)-lambda genes on chromosome 19. We investigated the association between the polymorphism rs12979860 and treatment response in a ...[more]

PMID: 20176026

Similar Datasets

Project description:Background and aim: Conventional hepatitis C treatment using pegylated interferon (PEG-IFN) and ribavirin is associated with significant side effects. IL28B polymorphism can predict response to treatment, with CC genotype having a better response. ITPA gene deficiency protects against clinically significant anaemia induced by treatment. The purpose of this study was to determine IL28B polymorphism and ITPA variation among hepatitis C genotype 1 patients who have undergone therapy with PEG-IFN and ribavirin and their association with sustained viral response (SVR). Methods: All hepatitis C genotype 1 patients who had been treated with PEG-IFN and ribavirin over the past 10 years were identified by available medical records and were contacted by letter of invitation to participate in the study. Blood samples for IL28B and ITPA genotyping were obtained. Medical records were reviewed for verification of treatment response, development of anaemia and if treatment reduction was required during the treatment. Results: A total of 61 patients with hepatitis C genotype 1 were treated with PEG-IFN and ribavirin, of whom 42 agreed to participate in the study. Mean age was 45.6±12.9 years at time of treatment, and 83.3% of patients were males. Thirty-three (78.6%) had IL28B CC genotype, of whom 25 (75.8%) obtained SVR compared with only 3 of 9 (33.3%) non C/C genotype patients who achieved SVR (P=0.041). Eleven (26.1%) patients had ITPA AC genotype, and 30 (71.4%) had CC genotype. There was no statistically significant difference between ITPA AC and CC genotypes in predicting clinically significant anaemia (45.5% vs 63.3%, P=0.302). Even among patients who developed anaemia, 70.8% still managed to achieve SVR. Treatment reduction also had no impact on SVR. Conclusion: Hepatitis C genotype 1 patients should be informed of the response rate for treatment with PEG-IFN and ribavirin in a population with favourable IL28B genotype before consideration of newer therapeutic options.

Project description:BackgroundHepatitis C is a global health problem and represents a major cause of liver disease and socioeconomic burden. Effective antiviral therapy may prevent these complications, but the current treatment for patients with chronic hepatitis C virus (HCV) infection does not produce sustained virologic response. Therefore, identification of the determinants of response to treatment is a high priority. A number of host and viral factors have been associated with treatment outcomes.ObjectivesTo assess the associations of single nucleotide polymorphisms (SNP) of the IL28B and sustained virologic response (SVR) of patients with chronic hepatitis C to PEG-interferon/ribavirin therapy.Materials and methodsWe searched PubMed, Medline and Cochrane Library, and found 7 eligible papers involved in this study. Then we performed a meta-analysis comparing the SVR rate at SNP of the IL28B in individuals with PEG-interferon/ribavirin therapy. Meanwhile, the SVR rate between different races and HCV genotypes was studied.ResultsThe sustained virologic response rate was higher in patients with the rs12979860 CC and rs8099917 TT alleles in the IL28B SNP, comparing with the rs12979860 CT, or TT and rs8099917 TG or GG. Furthermore, a higher SVR was observed in the Caucasians than in Afro-Americans (OR = 3.85, 95% CI: 3.06-4.83); the percentage of rs12979860 TT genotype was lower in Caucasians (OR = 0.25, 95% CI: 0.20-0.31) and the percentage of rs12979860 CC genotype was higher in Caucasians than that of Afro-Americans (OR = 3.45, 95% CI = 2.68-4.44). Between different HCV genotypes, the SVR was much lower in those with HCV genotype 1 than those with genotype 2/3 (OR = 0.16, 95% CI: 0.11-0.24).ConclusionsIL28B is significantly associated with response to PEG-interferon/ribavirin therapy of patients with chronic HCV infection. Both the rs12979860 and rs8099917 alleles could be used as independent predictors of the treatment response. The rs12979860 allele in particular, is more important from our study. The polymorphism even explains part the difference in response rate between different ethnic groups and HCV genotypes.

Dataset Information

Replicated association between an IL28B gene variant and a sustained response to pegylated interferon and ribavirin.

Publications

Replicated association between an IL28B gene variant and a sustained response to pegylated interferon and ribavirin.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets