Mancuso Maria Elisa, Linari Silvia, Aghemo Alessio, Bartolozzi Dario, Santagostino Elena, Rumi Maria Grazia, Fognani Elisa, Fasulo Maria Rosaria, Gragnani Laura, Bruno Raffaele, Morfini Massimo, Zignego Anna Linda, Colombo Massimo
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:
Thromb Haemost. 2014 Jun;111(6):1067-76. doi: 10.1160/TH13-11-897. Epub 2014 Feb 13.
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).
慢性丙型肝炎是接受非病毒灭活的血浆源性凝血因子浓缩物的成年血友病患者发病和死亡的主要原因。总体而言，病毒自发清除率为10%-25%，唯一能阻止疾病进展的方法是通过抗病毒治疗根除丙型肝炎病毒（HCV）。在非血友病患者中，干扰素λ3（IFNλ3）基因上游的一个单核苷酸多态性与病毒自发清除以及抗病毒治疗后的持续病毒学应答均相关。本研究的目的是评估rs12979860多态性是否为一大群HCV感染的血友病患者病毒自发清除以及抗病毒治疗后持续病毒学应答的预测指标。在342名血友病患者队列中检测了定义为CC基因型或T等位基因的rs12979860多态性，并将其评估为自发清除或抗病毒治疗应答的预测指标。通过多变量回归分析，IFNλ3 CC基因型是病毒自发清除的独立预测指标（比值比：3.7，95%置信区间：2.0-6.8）。CC基因型患者的持续病毒学应答率是T等位基因患者的两倍（78%对44%；p<0.001），尤其是在1型HCV患者中（67%对32%；p<0.001），并且在未实现快速病毒学应答的CC基因型患者中观察到更高的持续应答率（T等位基因患者中为61%对30%；p=0.006）。
