title: IFNL4-ΔG genotype is associated with slower viral clearance in hepatitis C, genotype-1 patients treated with sofosbuvir and ribavirin.
abstract: Response to pegylated interferon-alpha and ribavirin (IFN-α/RBV) treatment for chronic hepatitis C virus (HCV) infection is influenced by host genetic factors, but their role for IFN-α-free, direct-acting antiviral (DAA) regimens is unclear. An exonic deletion allele (IFNL4-ΔG) bolsters the established association with IFN-α/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-ΔG 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-λ4 in IFN-α-free DAA therapies.
authors.affiliation: Laboratory of Immunoregulation/National Institute of Allergy and Infectious Diseases/National Institutes of Health, Bethesda, Maryland.
authors.forename: Eric G
authors.initials: EG
authors.lastname: Meissner
authors.forename: Dimitra
authors.initials: D
authors.lastname: Bon
authors.forename: Ludmila
authors.initials: L
authors.lastname: Prokunina-Olsson
authors.forename: Wei
authors.initials: W
authors.lastname: Tang
authors.forename: Henry
authors.initials: H
authors.lastname: Masur
authors.forename: Thomas R
authors.initials: TR
authors.lastname: O'Brien
authors.forename: Eva
authors.initials: E
authors.lastname: Herrmann
authors.forename: Shyamasundaran
authors.initials: S
authors.lastname: Kottilil
authors.forename: Anuoluwapo
authors.initials: A
authors.lastname: Osinusi
mesh_terms: D000998:Antiviral Agents / Q000008:administration & dosage / Q000627:therapeutic use; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000235:genetics; D006801:Humans; D007378:Interleukins / Q000235:genetics / Q000378:metabolism*; D012254:Ribavirin / Q000008:administration & dosage / Q000627:therapeutic use*; D000069474:Sofosbuvir; D014542:Uridine Monophosphate / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000095022:Interferon Lambda
chemical_list: D000998:Antiviral Agents; D007378:Interleukins; D012254:Ribavirin; D000069474:Sofosbuvir; D014542:Uridine Monophosphate; C579163:IFNL4 protein, human; D000095022:Interferon Lambda
keywords: DAA therapy; IFNL4; IL28B; SVR; haplotype; hepatitis C virus; pharmacokinetics; relapse; viral kinetics