Genetic Testing for Hepatitis C Virus Genotype 2 or 3 Infection

IL28B genotype was an independent predictor of sustained virologic response to HCV therapy.

Polymorphisms in the IL28B gene have been shown to play an important role in how patients infected with hepatitis C virus (HCV) genotype 1 develop chronic infection and respond to treatment (JW Gastroenterol Oct 16 2009). Now, researchers have evaluated the potential role of IL28B polymorphisms in patients infected with HCV genotype 2 or 3.

The study was a secondary analysis of a randomized trial in which 283 white patients with HCV genotype 2 or 3 received 12 or 24 weeks of peginterferon alfa-2b (1.0 µg/kg weekly) plus ribavirin (1000–1200 mg daily), depending on whether they had achieved rapid virologic response (RVR; undetectable viral load at 4 weeks; JW Gastroenterol Jul 26 2005). For the present analysis, 268 patients had available clinical, laboratory, and genetic data (IL28B genotyping of the rs12979860 single nucleotide polymorphism).

Of the 268 patients, 37% had IL28B genotype CC, 48% had genotype CT, and 15% had genotype TT. Sustained virologic response (SVR) was achieved by more genotype CC patients (82%) than genotype CT (75%) or TT (58%) patients (P=0.0046). However, this difference was evident only among patients who had not initially achieved RVR (87% SVR for CC vs. 67% for CT and 29% for TT; P=0.0002). In a multivariate analysis, IL28B genotype was a significant, independent predictor of SVR.

Comment: This analysis of previously well-characterized clinical-trial participants demonstrates the potential relevance of IL28B polymorphisms in HCV genotype 2 or 3 patients. The clinical value of genetic testing in HCV genotype 2 or 3 patients who achieve RVR is questionable, but it might be useful in patients who do not achieve RVR. Among non-RVR patients, the SVR rate was much lower for those with genotype TT than for patients with genotype CC or CT. Genotype TT patients might benefit from extended HCV therapy, possibly for 48 weeks. These preliminary, but clinically relevant, findings need to be validated in large prospective studies.

— Atif Zaman, MD, MPH

Published in Journal Watch Gastroenterology November 5, 2010

Citation(s):

Mangia A et al. An IL28B polymorphism determines treatment response of hepatitis C virus genotype 2 or 3 patients who do not achieve a rapid virologic response. Gastroenterology 2010 Sep; 139:821.

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