Application of GWAS technology has revealed an unexpected role of IL28B in HCV infection. This finding could provide a strong rationale for developing novel therapeutic strategies for HCV infection as well as furthering basic studies on IFN-λs. The IL28B genotype could assist clinical decision-making for the treatment of acute HCV infection. In the context of PEG-IFN/RBV therapy for CHC, IL28B genotypes are strongly associated with treatment efficacy in patients infected with HCV genotype 1 or 4, with some effects on other HCV genotypes. IL28B genotyping is also useful for pretreatment prediction of the outcome of DAA plus PEG-IFN/RBV therapy, especially in treatment-naïve patients. Moreover, the IL28B genotype may affect responses to IFN-free regimens. Future more aggressive treatments, such as quadruple therapy or potent DAA combinations might obscure the influence of IL28B, but IL28B genotyping will remain useful for making decisions on suitable regimens and treatment duration in patients in the forthcoming era of DAAs. The mechanisms by which IFN-λs are active against HCV infection must be elucidated through the functional analyses of IFN-λs in future.
Conflicts of interests
Yasuhito Tanaka has research contracts with MSD (Merck Sharp & Dohme) and Chugai Pharmaceutical Co. Ltd. The remaining authors have no conflict of interests.
This work was supported in part by a grant-in-aid from the Ministry of Health, Labour and Welfare of Japan, and a grant-in-aid from the Ministry of Education, Culture, Sports, Science and Technology.
J Gastroenterol Hepatol. 2014;29(2):241-249. © 2014 Blackwell Publishing