Bachofner Jacqueline, Valli Piero V, Bergamin Irina, Kröger Arne, Künzler Patrizia, Baserga Adriana, Braun Dominique L, Seifert Burkhardt, Moncsek Anja, Fehr Jan, Semela David, Magenta Lorenzo, Müllhaupt Beat, Terziroli Beretta-Piccoli Benedetta, Mertens Joachim
Division of Gastroenterology and Hepatology, University Hospital Zürich, Switzerland and Swiss HPB Centre.
Division of Gastroenterology and Hepatology, Hospital St Gallen, Switzerland.
Swiss Med Wkly. 2018 Jan 18;148:w14560. doi: 10.4414/smw.2018.14560. eCollection 2018.
The introduction of direct acting antivirals (DAAs) for the therapy of chronic hepatitis C (CHC) has revolutionised treatment and marks a paradigm shift in the approach to this disease, rendering interferon-based therapies obsolete.
We retrospectively and prospectively evaluated treatment results after the introduction of DAA in Switzerland in a cohort of patients with CHC.
We examined 565 patients who received DAA treatment for CHC between November 2013 and June 2016 with regard to HCV genotype, fibrosis stadium, treatment and outcome. In addition, outcome of re-treatment and resistance-associated substitutions (RAS) in patients that did not achieve sustained virological response (SVR) were evaluated. The majority of patients participate in the Swiss Hepatitis C Cohort Study. Data were evaluated in an intention-to-treat and a modified intention-to-treat analysis.
Overall SVR rate for all patients was 94% (530 of 565, 95% CI 92-96%). Of 350 patients with HCV genotype 1 CHC, 335 achieved SVR, resulting in an SVR rate of 96% (335 of 350, 95% CI 94-98%). Patients with HCV genotype 2 achieved SVR in 94% (48 of 51, 95% CI 87-100%). Patients with HCV genotype 3 showed SVR of 92% (98 of 107, 95% CI 87-97%). In patients with HCV genotype 4, the SVR rate was substantially lower at 85% (49 of 57, 95% CI 76-94%). The rate of advanced liver fibrosis (Metavir F3/F4) assessed by means of liver biopsy or Fibroscan® in the entire patient population was 71% (404 of 565). Out of 35 patients that did not achieve SVR after DAA treatment, 32 had a relapse and 3 patients showed viral breakthrough. In 17 of 35 cases (49%) patients were treatment naïve and 21 of 35 patients (60%) were cirrhotic. RAS genotyping of HCV was performed in 14 patients. Nine of these 14 patients (60%) carried mutations in the NS5A region of the virus genome. Twenty-seven percent of patients who experienced treatment failure were not treated with recommended regimens as a result of drug availability and reimbursement limitations.
In Switzerland, novel DAA treatments for CHC reflect the positive results from registration trials. Genotypes 2 and 4 remained more difficult to treat between 2014 and 2016. Patients who experienced a relapse after DAA treatment in Switzerland predominantly showed mutations in the NS5A region of the virus genome. DAA treatment limitations in Switzerland did prevent optimal treatment regimens in some patients.
直接作用抗病毒药物（DAAs）用于慢性丙型肝炎（CHC）治疗的引入彻底改变了治疗方式，标志着该疾病治疗方法的范式转变，使基于干扰素的疗法过时。
我们回顾性和前瞻性地评估了瑞士引入DAA后一组CHC患者的治疗结果。
我们检查了2013年11月至2016年6月期间接受DAA治疗CHC的565例患者的HCV基因型、纤维化分期、治疗及结果。此外，还评估了未实现持续病毒学应答（SVR）患者的再治疗结果及耐药相关置换（RAS）情况。大多数患者参与了瑞士丙型肝炎队列研究。数据在意向性治疗和改良意向性治疗分析中进行评估。
所有患者的总体SVR率为94%（565例中的530例，95%置信区间92 - 96%）。在350例HCV基因型1型CHC患者中，335例实现了SVR，SVR率为96%（350例中的335例，95%置信区间94 - 98%）。HCV基因型2型患者的SVR率为94%（51例中的48例，95%置信区间87 - 100%）。HCV基因型3型患者的SVR率为92%（107例中的98例，95%置信区间87 - 97%）。在HCV基因型4型患者中，SVR率显著较低，为85%（57例中的49例，95%置信区间76 - 94%）。通过肝活检或Fibroscan®评估的整个患者群体中晚期肝纤维化（Metavir F3/F4）率为71%（565例中的404例）。在DAA治疗后未实现SVR的35例患者中，32例复发，3例出现病毒突破。35例中有17例（49%）患者未接受过治疗，35例中有21例（60%）患者为肝硬化患者。对14例患者进行了HCV的RAS基因分型。这14例患者中有9例（60%）在病毒基因组的NS5A区域携带突变。由于药物可及性和报销限制，27%经历治疗失败的患者未接受推荐方案治疗。
在瑞士，新型DAA治疗CHC反映了注册试验的阳性结果。在2014年至2016年期间，基因型2型和4型治疗起来仍更困难。在瑞士，DAA治疗后复发的患者主要在病毒基因组的NS5A区域出现突变。瑞士的DAA治疗限制确实在一些患者中妨碍了最佳治疗方案的实施。
