Moser Stephan, Kozbial Karin, Laferl Hermann, Schütz Angelika, Reiberger Thomas, Schwabl Philipp, Gutic Enisa, Schwanke Cornelia, Schubert Raphael, Luhn Julian, Lang Tobias, Schleicher Michael, Steindl-Munda Petra, Haltmayer Hans, Ferenci Peter, Gschwantler Michael
Department of Internal Medicine IV, Wilhelminenspital.
Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Medical University.
Eur J Gastroenterol Hepatol. 2018 Mar;30(3):291-295. doi: 10.1097/MEG.0000000000001027.
In the era of direct-acting antivirals, hepatitis C virus (HCV) genotype (GT) 3 remains as the most difficult-to-treat HCV-GT. Currently, data on the efficacy of ledipasvir/sofosbuvir plus ribavirin (SOF/LDV+RBV) in GT3-infected patients are limited. We investigated the efficacy of this regimen in a real-life cohort from Austria.
A total of 55 patients with HCV-GT3 and compensated liver disease (20% treatment-experienced, 33% with cirrhosis, 7% with HIV coinfection) from four Austrian hepatitis centers received treatment with SOF/LDV+RBV for 12 weeks. The primary endpoint was sustained virological response 12 weeks after end of therapy (SVR12).
In the modified intention-to-treat analysis - excluding patients lost to follow-up - the overall SVR12 rate was 94% (95% confidence interval: 84-99%). In treatment-naive and treatment-experienced patients, SVR12 rates were 95 and 89%, respectively. SVR12 rate was 91% in patients without cirrhosis and 100% in patients with cirrhosis. There were no serious adverse events. Viral sequencing did not show the presence of any resistance-associated substitutions in any of the three relapsed patients.
Despite a very weak antiviral activity of ledipasvir against HCV-GT3 in vitro, a 12-week course of SOF/LDV+RBV was highly effective, with a 94% SVR12 rate in our cohort of compensated HCV-GT3-infected patients. Thus, if pangenotypic NS5A inhibitors are not available or not reimbursed by insurances, SOF/LDV+RBV seems to be an effective alternative in patients with HCV-GT3 infection.
在直接抗病毒药物时代，丙型肝炎病毒（HCV）基因3型（GT3）仍然是最难治疗的HCV基因型。目前，关于来迪派韦/索磷布韦联合利巴韦林（SOF/LDV+RBV）治疗GT3感染患者疗效的数据有限。我们在来自奥地利的一个真实队列中研究了该方案的疗效。
来自奥地利四个肝炎中心的55例HCV-GT3且有代偿性肝病的患者（20%有治疗史，33%有肝硬化，7%合并HIV感染）接受了SOF/LDV+RBV治疗12周。主要终点是治疗结束后12周的持续病毒学应答（SVR12）。
在改良意向性分析中（排除失访患者），总体SVR12率为94%（95%置信区间：84-99%）。在初治和经治患者中，SVR12率分别为95%和89%。无肝硬化患者的SVR12率为91%，肝硬化患者为100%。未发生严重不良事件。病毒测序未显示3例复发患者中存在任何与耐药相关的替代突变。
尽管来迪派韦在体外对HCV-GT3的抗病毒活性非常弱，但SOF/LDV+RBV治疗12周疗程非常有效，在我们这组有代偿性HCV-GT3感染患者中SVR12率为94%。因此，如果泛基因型NS5A抑制剂不可用或未被保险报销，SOF/LDV+RBV似乎是HCV-GT3感染患者的一种有效替代方案。
