IFNL4-ΔG Genotype Is Associated With Slower Viral Clearance in Hepatitis C, Genotype-1 Patients Treated With Sofosbuvir and Ribavirin

Response to pegylated interferon-alpha and ribavirin (IFN-alpha/RBV) treatment for chronic hepatitis C virus (HCV) infection is influenced by host genetic factors, but their role for IFN-alpha-free, direct-acting antiviral (DAA) regimens is unclear. An exonic deletion allele (IFNL4-Delta G) bolsters the established association with IFN-alpha/RBV therapy treatment outcome of another IFNL4 variant, rs12979860, which is located upstream of IFNL3 (IL28B). We report that in patients treated with the DAA sofosbuvir along with RBV, IFNL4-Delta G is associated with slower early viral decay, due to slower loss of free virus (P = .039) and decreased drug efficacy (P = .048), suggesting functional relevance of IFN-lambda 4 in IFN-alpha-free DAA therapies.