Clinical Advances in Liver, Pancreas, and Biliary TractAn IL28B Polymorphism Determines Treatment Response of Hepatitis C Virus Genotype 2 or 3 Patients Who Do Not Achieve a Rapid Virologic Response
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Patient and Control Populations
The primary study was a multicenter randomized controlled trial that recruited patients from 13 clinical sites in Italy.5 In the original study, 70 patients were randomized to standard treatment duration (24 wk; standard duration [SD], 24) and 213 to variable duration (VD) according to week 4 response: patients achieving RVR were treated for 12 weeks (VD12); while those not achieving RVR were treated for 24 weeks (VD24). Patients received pegIFN-alfa-2b (PEG-Intron; Schering-Plough, Kenilworth,
Patients
A total of 268 patients were included in this analysis. All patients were Caucasian, 213 patients were infected with genotype 2 HCV, and 55 patients were infected with genotype 3 HCV. Baseline demographic, biochemical, and virologic characteristics of the patients are reported in Table 1. Sixty-eight patients were randomized to 24 weeks of standard therapy, and 200 patients were randomized to variable duration therapy (Supplementary Figure 1). There were no significant differences in baseline
Discussion
We report on the role and relevance of the recently described IL-28B genetic polymorphism to PegIFN and RBV treatment outcome in the setting of chronic infection with genotype 2 or 3 HCV. This unique cohort, from a prospectively performed landmark clinical trial,5 has allowed us to carefully evaluate the interaction between this genetic determinant and treatment response in patients who received a variable duration of therapy based on week 4 virologic response.
The data indicate that the IL-28B
References (19)
- et al.
Peginterferon-alpha-2a (40KD) and ribavirin for 16 or 24 weeks in patients with genotype 2 or 3 chronic hepatitis C
Gastroenterology
(2005) Classification of chronic viral hepatitis: a need for reassessment
J Hepatol
(1991)- et al.
Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance
Nature
(2009) - et al.
Genome-wide association of IL28B with response to pegylated interferon-alpha and ribavirin therapy for chronic hepatitis C
Nat Genet
(2009) - et al.
IL28B is associated with response to chronic hepatitis C interferon-alpha and ribavirin therapy
Nat Genet
(2009) - et al.
Diagnosis, management, and treatment of hepatitis C: an update
Hepatology
(2009) - et al.
Peginterferon alfa-2b and ribavirin for 12 vs. 24 weeks in HCV genotype 2 or 3
N Engl J Med
(2005) - et al.
Pegylated interferon alfa and ribavirin for 14 versus 24 weeks in patients with hepatitis C virus genotype 2 or 3 and rapid virological response
Hepatology
(2008) - et al.
Peginterferon alfa-2a and ribavirin for 16 or 24 weeks in HCV genotype 2 or 3
N Engl J Med
(2007)
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2017, Kaohsiung Journal of Medical SciencesSofosbuvir and ribavirin for genotype 2 HCV infected patients with cirrhosis: A real life experience
2017, Journal of HepatologyComparison of Three Different Methods for Detection of IL28 rs12979860 Polymorphisms as a Predictor of Treatment Outcome in Patients with Hepatitis C Virus
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View this article's video abstract atwww.gastrojournal.org
Conflicts of interest These authors disclose the following: Alexander Thompson, Kevin Shianna, David Goldstein, and John McHutchison are co-inventors of a patent application based on the interleukin-28B discovery. The remaining authors disclose no conflicts.
Funding Supported by funding 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, the Gastroenterology Society of Australia, and the Royal Australasian College of Physicians (A.J.T.).