Gastroenterology

Gastroenterology

Volume 138, Issue 7, June 2010, Pages 2307-2314
Gastroenterology

Clinical Advances in Liver, Pancreas, and Biliary Tract
Replicated Association Between an IL28B Gene Variant and a Sustained Response to Pegylated Interferon and Ribavirin

https://doi.org/10.1053/j.gastro.2010.02.009Get rights and content

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)-λ 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 ∼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 × 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.

Section snippets

Patient Population

The Duke Hepatology Clinical Research Database and Repository is an ongoing registry of HCV-infected subjects initiated in 1992, representing a large, well-phenotyped collection of North American chronic HCV patients.10 All subjects referred to the Duke Liver Clinic with a diagnosis of HCV infection are eligible to be included in this database. Patients are enrolled at the time of their initial clinic visit, and informed consent is obtained for the collection and storage of serum, liver tissue,

Association of rs12979860 Genotype With SVR to PEG-IFN/RBV by Race

A description of the cohort used in our analysis of response to PEG-IFN/RBV is shown in Table 1. Patients predominantly were Caucasian, infected with HCV genotype 1, and broadly representative of a tertiary care chronic HCV cohort. Among patients treated with PEG-IFN/RBV, those included in this analysis differed only slightly from those excluded, with more HCV genotype 2/3–infected subjects (20% vs 11%; P = .02). As expected, responders to standard-of-care PEG-IFN/RBV treatment were

Discussion

Treatment decisions in patients with chronic hepatitis C infection currently are based on clinical, demographic, and virologic characteristics of infected patients. Although these may be helpful from a population point of view, for any individual patient and provider, these baseline pretreatment characteristics are inaccurate in predicting treatment response in hepatitis C patients infected with genotype 1, the most common genotype found in the United States. We have confirmed in this study

Acknowledgments

The authors would like to thank all of the study participants who contributed their biospecimens and data to the Duke Hepatology Clinic Database and Biorepository, and the authors acknowledge Diane Uzarski, Crystal Cates, Chris Delionbach, and Melissa Austin for continued maintenance of this valuable resource.

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    Conflicts of interest These authors disclose the following: Drs Thompson and McHutchison are co-inventors with Schering Plough on a patent application on the original finding of rs12979860 association with pegylated interferon and ribavirin treatment response in HCV infection; Drs McHutchison and Muir have received research funding from and acted in an advisory capacity for Schering Plough. The remaining authors disclose no conflicts.

    Funding This study was funded in part by a generous grant from the David H. Murdock Institute for Business and Culture via the M.U.R.D.O.C.K. Study and award 1 UL1 RR024128-01 from the National Center for Research Resources, a component of the National Institutes of Health and National Institutes of Health Roadmap for Medical Research, and its contents are solely the responsibility of the authors and do not necessarily represent the official view of National Center for Research Resources or the National Institutes of Health. Dr Thompson received funding support from the Duke Clinical Research Institute, a generous research gift from the Richard B. Boebel Family Fund, the National Health and Medical Research Council of Australia, and the Gastroenterology Society of Australia.

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