title: Interferon lambda-3 is not associated with clinical outcome in patients with HCV-induced compensated cirrhosis: a long-term cohort study.
abstract: BACKGROUND
  Interferon Lambda-3 (IFN-λ3) gene polymorphism is associated with spontaneous clearance of hepatitis C virus (HCV) and response to IFN-based therapy (IFN). However, very few data are available about its value in predicting sustained virologic response (SVR) in patients with cirrhosis, and whether IFN-λ3 genotype influences liver disease progression remains unclear.
  
  
  METHODS
  We determined IFN-λ3 genotype by PCR in a cohort of patients with compensated HCV-related cirrhosis, enrolled between 1989 and 1992. Person-years follow-up was calculated for each individual from the date of enrolment to the development of first episode of decompensation, HCC, liver transplant, death or end of follow-up. The follow-up of patients who achieved SVR was censored at the time of IFN initiation. Kaplan-Meier curves and Cox regression analyses were used to assess the association between IFN-λ3 genotype and clinical outcome.
  
  
  RESULTS
  IFN-λ3 was determined in 264 patients (52% males, mean age 57±8 years, 67% HCV genotype (G)1, while CC, CT and TT genotypes were 36%, 50% and 14%, respectively. During a median follow-up of 14.8 years, 149 (56%) patients received IFN. Overall, SVR was achieved in 31 (21%) patients, 40% among those with CC genotype (22% in G1 and 61% in G2, respectively) compared to 10% and 13% among patients with CT and TT genotypes (p<0.0001). Univariate and multivariate analyses found no association between IFN-λ3 (CC vs. non-CC genotype) and disease progression.
  
  
  CONCLUSIONS
  IFN-λ3 determination is fundamental for allocating cirrhotic patients to be treated with IFN, while it has no value in predicting the outcome of the disease.
authors.affiliation: Department of Internal Medicine, A.O. Fatebenefratelli e Oftalmico, Milan, Italy. Electronic address: savino.bruno@fbf.milano.it.
authors.forename: Savino
authors.initials: S
authors.lastname: Bruno
authors.affiliation: Department of Gastroenterology, St Vincent's Hospital, The University of Melbourne, VIC, Australia; Department of Medicine, St Vincent's Hospital, The University of Melbourne, VIC, Australia; Duke Clinical Research Institute and Department of Gastroenterology, Duke University, Durham, NC, USA.
authors.forename: Alex J
authors.initials: AJ
authors.lastname: Thompson
authors.affiliation: Department of Gastroenterology, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Rosina
authors.initials: R
authors.lastname: Critelli
authors.affiliation: Department of Internal Medicine, A.O. San Paolo, University of Milan, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Crosignani
authors.affiliation: Department of Internal Medicine, A.O. Fatebenefratelli e Oftalmico, Milan, Italy.
authors.forename: Sonia
authors.initials: S
authors.lastname: Rossi
authors.affiliation: Department of Internal Medicine, A.O. Fatebenefratelli e Oftalmico, Milan, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: De Lisi
authors.affiliation: Clinical Pathology-Toxicology, Ospedale Civile S. Agostino-Estense, Modena, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Cariani
authors.affiliation: Department of Internal Medicine, A.O. San Paolo, University of Milan, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Zermiani
authors.affiliation: Division of Pathology, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Vaira
authors.affiliation: Department of Internal Medicine, A.O. Fatebenefratelli e Oftalmico, Milan, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Boccaccio
authors.affiliation: Division of Epidemiology and Biostatistics, European Institute of Oncology, Milan, Italy.
authors.forename: Patrick
authors.initials: P
authors.lastname: Maisonneuve
authors.affiliation: Department of Gastroenterology, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Erica
authors.initials: E
authors.lastname: Villa
mesh_terms: D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000187:drug effects; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D006801:Humans; D007372:Interferons / Q000627:therapeutic use*; D007378:Interleukins / Q000235:genetics*; D008103:Liver Cirrhosis / Q000188:drug therapy* / Q000235:genetics / Q000821:virology; D016031:Liver Transplantation; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D016896:Treatment Outcome; D000095022:Interferon Lambda
chemical_list: D000998:Antiviral Agents; D007372:Interferons; D007378:Interleukins; C000624353:interferon-lambda, human; D000095022:Interferon Lambda
keywords: IFN-based therapy; IFN-λ3 polymorphism; Outcome of compensated cirrhosis