Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard Medical School, Boston, MA 02129, USA; Department of Internal Medicine, University Hospital Basel, Basel, Switzerland; Department of Biomedicine, University Hospital Basel, Basel, Switzerland.
Genome-wide association studies have identified polymorphisms located near the gene encoding IL28B, which turned out to be the best predictor of response to pegylated interferon plus ribavirin for chronic hepatitis C virus (HCV) genotype 1 infection. This association was extended to spontaneous clearance of HCV, suggesting shared mechanisms of treatment and natural control of this virus. In addition to the biologic implications for innate immunity and HCV, a variety of clinical studies have suggested possible translation to a useful genetic test for practitioners. This article reviews the discovery, biology, and potential clinical applications that have stemmed from the seminal observation that IL28B polymorphisms are a main predictor of HCV clearance.