Interferon lambda 3 rs12979860 polymorphism in patients with haemophilia and HCV infection: a predictor of spontaneous viral clearance and sustained virological response

Maria Elisa Mancuso; Silvia Linari; Alessio Aghemo; Dario Bartolozzi; Elena Santagostino; Maria Grazia Rumi; Elisa Fognani; Maria Rosaria Fasulo; Laura Gragnani; Raffaele Bruno; Massimo Morfini; Anna Linda Zignego; Massimo Colombo

doi:10.1160/TH13-11-897

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2014; 111(06): 1067-1076
DOI: 10.1160/TH13-11-897

Blood Coagulation, Fibrinolysis and Cellular Haemostasis

Schattauer GmbH

Interferon lambda 3 rs12979860 polymorphism in patients with haemophilia and HCV infection: a predictor of spontaneous viral clearance and sustained virological response

Maria Elisa Mancuso

¹Angelo Bianchi Bonomi Haemophilia and Thrombosis Center, Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico, Milan, Italy

,

Silvia Linari

²Haemophilia Center, A.O.U. Careggi, Florence, Italy

,

Alessio Aghemo

³A.M. Migliavacca Center for Liver Disease, First Division of Gastroenterology, Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico and University of Milan, Milan, Italy

,

Dario Bartolozzi

⁴Infectious Diseases Unit, University Hospital of Florence, Florence, Italy

,

Elena Santagostino

¹Angelo Bianchi Bonomi Haemophilia and Thrombosis Center, Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico, Milan, Italy

,

Maria Grazia Rumi

⁵Division of Hepatology, Ospedale San Giuseppe and University of Milan, Milan, Italy

,

Elisa Fognani

⁶Center for Systemic Manifestations of Hepatitis Viruses (MaSVE), Department of Experimental and Clinical Medicine, University of Florence, and Istituto Toscano Tumori (ITT), Florence, Italy

,

Maria Rosaria Fasulo

¹Angelo Bianchi Bonomi Haemophilia and Thrombosis Center, Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico, Milan, Italy

,

Laura Gragnani

⁶Center for Systemic Manifestations of Hepatitis Viruses (MaSVE), Department of Experimental and Clinical Medicine, University of Florence, and Istituto Toscano Tumori (ITT), Florence, Italy

,

Raffaele Bruno

⁷Department of Infectious and Tropical Diseases, Fondazione IRCCS Ospedale San Matteo and University of Pavia, Pavia, Italy

,

Massimo Morfini

²Haemophilia Center, A.O.U. Careggi, Florence, Italy

,

Anna Linda Zignego

⁶Center for Systemic Manifestations of Hepatitis Viruses (MaSVE), Department of Experimental and Clinical Medicine, University of Florence, and Istituto Toscano Tumori (ITT), Florence, Italy

,

Massimo Colombo

³A.M. Migliavacca Center for Liver Disease, First Division of Gastroenterology, Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico and University of Milan, Milan, Italy

› Author Affiliations

Abstract

Summary

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).

Keywords

Haemophilia - chronic hepatitis C - interferon lambda 3 - antiviral therapy - spontaneous clearance

Full Text

References

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