Objective: To evaluate the efficacy and safety of DCV-based DAAs therapy for chronic HCV infected Chinese patients. Methods: An open-label, non-randomized, prospective study was designed. Fifty-two patients with chronic HCV infection were enrolled. Among them, there was one patient after liver transplantation, 2 patients after kidney transplantation, 3 patients with hepatocellular carcinoma, and 4 patients with HBV infection. Thirteen cases with chronic hepatitis C (one compensated cirrhosis) who were negative for resistance-related variants [NS5A RAS (-)] of gene 1b and NS5A were treated with daclatasvir (DCV) + asunaprevir (ASV) for 24 weeks. Twenty-five cases of CHC (six compensated cirrhosis) with GT 1b, 2a, 3a, 3b, 6a were treated with DCV + SOF ± RBV for 24 weeks. 8 cases with decompensated cirrhosis of gene 1b and NS5A RAS(-) were given DCV + SOF + RBV regimen for 12 weeks. Six cases with decompensated cirrhosis, of gene 2a, 1b, 2a, 3a, 3b, were given DCV + SOF + RBV regimen for 24 weeks. HCV RNA, blood routine test, liver and kidney function, and upper abdominal ultrasound/MRI were measured at baseline, 4 weeks of treatment, end of treatment, and 12 weeks of follow-up. The incidence of adverse events and laboratory abnormalities during treatment were recorded. A t-test was used to compare the measurement data between two groups, and analysis of variance was used to compare the measurement data between multiple groups. Results: Sixteen patients (100%) achieved SVR12 after treatment, with 0% recurrence rate. Rapid virological response (RVR) of the four treatment regimens were 76.92%, 54.17%, 87.50%, and 83.33%, respectively, and 32 patients achieved 100% virological response after the completion of treatment. The incidence of adverse events of chronic hepatitis C with cirrhosis and decompensated cirrhosis was 62.5% and 64.29%, respectively. The most common adverse event was fatigue in CHC (25.00%), and elevated indirect bilirubin in decompensated cirrhosis (42.86%). No serious adverse drug events, deaths or adverse reactions occurred. Conclusion: DCV-based DAAs regimen is promising option for the treatment of HCV genotypes, compensated cirrhosis, decompensated cirrhosis, hepatocellular carcinoma, and HCV infection after liver/kidney transplantation in china. Above all, it has high SVR12 with good tolerability and safety profile.
目的： 研究以达拉他韦（DCV）为基础直接抗病毒药物（DAAs）方案治疗中国慢性HCV感染者，评价其疗效及安全性。方法： 前瞻性、开放性、单中心、非随机临床研究。共纳入52例慢性HCV感染者，其中肝移植术后患者1例，肾移植术后患者2例，肝细胞癌患者3例，合并HBV感染患者4例。13例基因1b，NS5A耐药相关变异阴性 [NS5A RAS（-）]的慢性丙型肝炎患者（其中代偿期肝硬化1例）DCV+阿舒瑞韦（ASV）方案治疗24周；25例慢性丙型肝炎患者（其中代偿期肝硬化6例），包括基因型1a、1b、2a、3a、3b、6a，予DCV+索磷布韦（SOF）±利巴韦林（RBV）方案治疗24周；8例基因1b，NS5A RAS（-）的失代偿期肝硬化患者予DCV + SOF ± RBV方案12周；6例失代偿期肝硬化患者，包括基因2a、1b、2a、3a、3b，予DCV + SOF ± RBV 24周。检测患者基线、治疗4周、疗程结束和随访12周的HCV RNA、血常规、肝肾功能及上腹部彩超/MRI，记录治疗过程的不良事件和实验室异常。计量资料两组间比较采用t检验，多组间比较采用方差分析。结果： 16例患者达到持续病毒学应答（SVR12）（100％），复发率为0。本研究中4种治疗方案的快速病毒学应答（RVR）分别为76.92％、54.17％、87.50％、83.33％，32例患者在结束疗程时达到病毒学应答（100％）。慢性丙型肝炎及偿期肝硬化和失代偿肝硬化不良事件发生率分别为62.50％和64.29％，其中前者以乏力最多见（25.00％），后者以间接胆红素升高最多见（42.86％）。所有患者均无出现严重不良反应事件、死亡和因不良反应停用药物。结论： 以DCV为基础DAAs方案用于治疗中国各常见基因型初治和经治慢性丙型肝炎、代偿期肝硬化、失代偿期肝硬化、肝细胞癌及肝/肾移植后HCV感染者，均有较高SVR12，且耐受性和安全性良好。.
Keywords: Daclatasvir; Direct-acting antiviral agent; Hepatitis C, chronic; Safety; Therapy.