Savino Bruno1, Alex J Thompson2, Rosina Critelli3, Andrea Crosignani4, Sonia Rossi5, Stefania De Lisi5, Elisabetta Cariani6, Paola Zermiani4, Valentina Vaira7, Vincenzo Boccaccio5, Patrick Maisonneuve8, Erica Villa3. 1. Department of Internal Medicine, A.O. Fatebenefratelli e Oftalmico, Milan, Italy. Electronic address: savino.bruno@fbf.milano.it. 2. 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. 3. Department of Gastroenterology, University of Modena and Reggio Emilia, Modena, Italy. 4. Department of Internal Medicine, A.O. San Paolo, University of Milan, Italy. 5. Department of Internal Medicine, A.O. Fatebenefratelli e Oftalmico, Milan, Italy. 6. Clinical Pathology-Toxicology, Ospedale Civile S. Agostino-Estense, Modena, Italy. 7. Division of Pathology, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy. 8. Division of Epidemiology and Biostatistics, European Institute of Oncology, Milan, Italy.
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. CONCLUSION: 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.
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. CONCLUSION: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: Alexander Gutwerk; Thomas Wex; Kerstin Stein; Cosima Langner; Ali Canbay; Peter Malfertheiner; Alexander Link Journal: J Clin Med Date: 2018-03-05 Impact factor: 4.241