索非布韦联合达卡他韦治疗丙肝肝硬化或PR治疗失败丙肝患者的有效性与安全性研究

Efficacy and safety of Sofosbuvir combined with Daclatasvir in treatment of hepatitis C cirrhosis patients and hepatitis C patients with treatment failure of peglated-interferon and Ribavirin regimen

目的评价索非布韦(SOF)联合达卡他韦(DCV)对初治丙型肝炎(丙肝)肝硬化或干扰素联合利巴韦林(RBV)方案(PR方案)治疗失败丙肝患者的疗效及安全性。方法选取2015年9月至2017年3月重庆医科大学第二临床学院感染病科门诊就诊的初治丙肝肝硬化患者或PR方案治疗失败丙肝患者为研究对象,均使用SOF+DCV治疗。丙肝肝硬化患者疗程24周,丙肝基因3型患者疗程24周且加用RBV,其余丙肝患者疗程12周。分别于治疗开始后的第2、4、12周和(或)24周检测肝功能、丙肝病毒定量(HCV-RNA定量)和血常规,其中治疗满4周后HCV-RNA定量采用高精度方法检测。记录患者不良反应情况。治疗结束后每12周随访1次肝功能、HCV-RNA定量等,共随访24周。结果共纳入70例初治丙肝肝硬化患者和29例PR方案治疗失败的慢性丙肝患者,治疗结束第12周随访时,有2例丙肝肝硬化患者病毒反跳,均为丙肝基因3型,有多年吸毒史,且2例患者均因个人因素停用RBV。随访24周无新增病毒反跳患者。治疗期间没有因为药物不良反应终止治疗的患者。主要不良反应有体重增加、轻度贫血等。部分服用RBV患者出现轻度贫血,停药后恢复,未见严重不良事件发生。结论 SOF联合DCV治疗丙肝肝硬化及PR治疗失败丙肝患者病毒持续应答率高,安全性高;联合使用RBV,特别是对于丙肝基因3型患者,有可能减少复发。

Objective To evaluate the efficacy and safety of Sofosbuvir(SOF)combined with Daclatasvir(DCV)in the initial treatment of the patients with hepatitis C cirrhosis or hepatitis C patients who failed in treatment with peglated-interferon combined with Ribavirin(RBV)regimen(PR regimen).Methods Patients who were previously untreated hepatitis C cirrhosis or hepatitis C with treatment failure of PR regimen in the Infection Clinic of the Second Clinical College of Chongqing Medical University from September 2015 to March 2017 as research objects,who all had used SOF+DCV treatment.Duration for patients with cirrhosis and genotype 3 were 24 weeks,and genotype 3 was simultaneously administered with RBV.Other patients were treated for 12 weeks.Liver function,HCV-RNA quantification,and blood routine were measured after the 2nd,4th,12th and 24th week after the start of treatment,respectively,and the HCV-RNA quantification was detected by the higher sensitive method at the 4th week of treatment.Meanwhile,the adverse reactions of patients were closely monitored and recorded.Liver function and HCV-RNA quantification were followed up every 12 weeks after treatment and were followed up for a total 24 weeks.Results Participants included 70 cases of simple patients with hepatitis C related cirrhosisand 29 cases of treated patients with chronic hepatitis C.Viral rebound was found in 2 patients in cirrhosis group during 12 weeks follow up after treatment.They were infected with genetype 3 virus and had a history of drug abuse for many years,and the two patients had stopped RBV during treatment.No new viral rebounded patients were founded in the followed up of 24 weeks.During the treatment period,there was no patient who was discontinued due to adverse drug reactions.The main adverse reactions included weight gain,mild anemia and so on.Some patients developed mild anemia owing to RBV use and recovered after discontinuation.No serious adverse events occurred.Conclusion The combination of SOF and DCV in the treatment of hepatitis C cirrhosis and PR failure treatment patients has a high rate of sustained viral response,high safety.In combination with RBV,it is possible to reduce relapse,especially for patients with genotype 3.