中国南方地区基因3型慢性丙型肝炎抗病毒治疗的疗效和安全性分析

Efficacy and safety of antiviral therapy for genotype 3 chronic hepatitis C in Southern China

目的研究口服直接抗病毒药物(direct-acting antiviral,DAA)不同组合的抗病毒治疗方案,治疗中国南方地区GT3型丙型肝炎病毒感染患者的疗效及安全性。方法采用回顾性研究方法,纳入40例GT3型、初治、伴或不伴(失)代偿期肝硬化的慢性丙型肝炎患者,分别接受不同的DAA治疗方案联合利巴韦林进行抗病毒治疗,包括:利托那韦增强的达诺瑞韦+索磷布韦+利巴韦林(DNVr+SOF+RBV),索磷布韦+维帕他韦+利巴韦林(SOF+VEL+RBV),索磷布韦+达拉他韦+利巴韦林(SOF+DCV+RBV)治疗12/24周。评估患者12/24周治疗结束后获得的持续病毒学应答(SVR12)、治疗过程中安全性及随访过程中出现不良事件情况。结果本研究纳入了40例GT3型的慢丙肝患者,其中20%(8/40)存在代偿期肝硬化、5%(2/40)存在失代偿期肝硬化;5%(2/40)合并肾功能异常、5%(2/40)为肾移植术后、10%(4/40)合并乙型肝炎感染。40例患者接受12周或24周治疗方案,其中以SOF+DCV+RBV方案治疗失代偿性肝硬化患者,疗程为24周,非失代偿期肝硬化患者治疗疗程均为12周。在治疗的4、12周,DNVr+SOF+RBV组病毒学应答率分别93.3%、100%,与另外两组相比病毒学应答率差异无统计学意义(P=0.644,P=0.567),在治疗结束后第4、12周的随访时,DNVr+SOF+RBV组的病毒学应答率均为100%。与另外两组相比病毒学应答率差异无统计学意义(P=0.567)。各组治疗结束后肝癌发生率以及HCV RNA复阳率之间的比较均差异无统计学意义(P=0.567,P=0.285)。结论以DNVr为基础的DAA抗病毒治疗方案,SVR12可达到100%,且安全性较高、不良反应较少。但仍需进行更大规模的研究,进一步评估以DNVr为基础的方案治疗GT3型慢丙肝患者的疗效及安全性。

Objective To evaluate the efficacy and safety in patients with genotype 3 HCV infection treated with different direct-acting antivirals(DAA)in Southern China.Methods This was a retrospective study.Forty treatment-naive Genotype 3 HCV infected patients,with or without cirrhosis,were treated with three different DAA therapies combined with ribavirin for 12/24 weeks.The DAAs include ritonavir-boosted danoprevir+sofosbuvir+ribavirin(DNVr+SOF+RBV),sofosbuvir+velpatasvir+ribavirin(SOF+DCV+RBV),sofosbuvir+dacatasvir+ribavirin(SOF+DCV+RBV).DAA-induced SVR12,safety during treatment and adverse events were monitored during follow-up period.Results A total of 40 GT3 HCV patients were enrolled in this study.Among of these patients,20%were with compensatory cirrhosis(8/40);5%were with decompensated cirrhosis(2/40);5%patients had renal dysfunction(2/40);5%patients had received renal transplantation(2/40);and 10%combined with hepatitis B infection(4/40).40 patients received 12 or 24 weeks of treatment,patients with decompensated cirrhosis were treated with SOF+DCV+RBV regimen for 24 weeks,and patients with non-decompensated cirrhosis were treated with DAA for 12 weeks.At the end of 4 week and 12 week treatment,the virological response rates in the DNVr+SOF+RBV group were 93.3%and 100%,respectively.There was no significant difference in virus response rate between the other two groups(P=0.644,P=0.567).At the end of 4^(th) week and 12^(th) week of follow-up after treatment,both the sustained virological responses(SVR)in the DNVr+SOF+RBV group were 100%,which was not significantly different from the other two groups(P=0.567).There was no statistical significance in the incidence of liver cancer and HCV RNA responsive rate among the three groups after treatment.Conclusion The DAA therapies based on DNVr can reach 100%SVR12,and with high safety and less adverse reactions.However,more large scale studies are still needed to evaluate further the efficacy and safety of DNVr based regimen in patients with GT3 HCV infection.