title: Interferon lambda 3 rs12979860 polymorphism in patients with haemophilia and HCV infection: a predictor of spontaneous viral clearance and sustained virological response.
abstract: Chronic hepatitis C is the main cause of morbidity and mortality in adult haemophilic patients who received non-virally inactivated plasma-derived clotting factor concentrates. Overall, spontaneous viral clearance rate is 10-25% and the only approach that can halt disease progression is hepatitis C virus (HCV) eradication by means of antiviral therapy. In non-haemophilic patients a single nucleotide polymorphism located upstream the gene of interferon lambda 3 (IFNλ3) has been associated with both spontaneous viral clearance and sustained virological response after antiviral treatment. The aim of this study was to assess whether the rs12979860 polymorphism was a predictor of spontaneous viral clearance and of sustained virological response after antiviral therapy in a large cohort of haemophilic patients with HCV infection. The rs12979860 polymorphism, defined as CC genotype or T allele, was tested in a cohort of 342 haemophilic patients and evaluated as predictor of spontaneous clearance or response to antiviral therapy. By multivariate regression analysis the IFNλ3 CC genotype was an independent predictor of spontaneous viral clearance (odds ratio: 3.7, 95% confidence interval: 2.0-6.8). Sustained virological response rates were doubled in patients with the CC genotype than in those with the T allele (78% vs 44%; p<0.001), especially in patients with HCV type 1 (67% vs 32%; p<0.001) and higher sustained response rates were observed in patients with the CC genotype who did not achieve rapid virological response (61% vs 30% in T allele patients; p=0.006).
authors: Maria Elisa Mancuso, MD, PhD, Angelo Bianchi Bonomi Haemophilia and Thrombosis Center, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Via Pace 9, 20122 Milan, Italy, Tel.: +39 02 5503 4072, Fax: +39 02 5503 2072, E-mail: elisamancuso@tiscali.it.
authors: Maria Elisa
authors: ME
authors: Mancuso
authors: Silvia
authors: S
authors: Linari
authors: Alessio
authors: A
authors: Aghemo
authors: Dario
authors: D
authors: Bartolozzi
authors: Elena
authors: E
authors: Santagostino
authors: Maria Grazia
authors: MG
authors: Rumi
authors: Elisa
authors: E
authors: Fognani
authors: Maria Rosaria
authors: MR
authors: Fasulo
authors: Laura
authors: L
authors: Gragnani
authors: Raffaele
authors: R
authors: Bruno
authors: Massimo
authors: M
authors: Morfini
authors: Anna Linda
authors: AL
authors: Zignego
authors: Massimo
authors: M
authors: Colombo
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use; D005260:Female; D005838:Genotype; D006467:Hemophilia A / Q000150:complications* / Q000235:genetics* / Q000276:immunology; D019698:Hepatitis C, Chronic / Q000150:complications* / Q000235:genetics* / Q000821:virology; D006801:Humans; D007372:Interferons; D007378:Interleukins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012008:Recurrence; D012189:Retrospective Studies; D016896:Treatment Outcome; D019562:Viral Load; D000095022:Interferon Lambda
chemical_list: D000998:Antiviral Agents; D007372:Interferons; D007378:Interleukins; C000624353:interferon-lambda, human; D000095022:Interferon Lambda
keywords: Haemophilia; antiviral therapy; chronic hepatitis C; interferon lambda 3; spontaneous clearance