索磷布韦联合利巴韦林治疗初治基因2型慢性HCV感染者的有效性及安全性分析

Clinical efficacy and safety of sofosbuvir tablets combined with ribavirin in treatment of treatment-na■ve patients with genotype 2 chronic hepatitis C virus infection

目的评价索磷布韦联合利巴韦林对初治基因2型慢性HCV感染者的有效性和安全性。方法在全国16家研究中心筛选初治基因2型慢性HCV感染者,所有受试者接受索磷布韦(400 mg/片,1片/d)联合利巴韦林(体质量<75 kg,1000 mg/d;体质量≥75 kg,1200 mg/d)治疗12周,停药随访12周。主要的疗效指标为治疗结束停药随访12周时获得持续病毒学应答情况。次要疗效指标包括:治疗2、4、8、12周及停药后4周时HCV RNA低于定量下限的比率;治疗4、8、12周时病毒学反跳率;停药随访4、12周的复发率。并观察治疗期不良事件发生情况,以评价药物的安全性。结果共入组136例受试者,非肝硬化121例,代偿期肝硬化15例。停药12周获得的持续病毒学应答率为92.6%(95%可信区间:88.3%~97.0%);治疗第8周,有1例病毒学反跳;停药4周时,有8例病毒学复发;停药12周时,有10例病毒学复发。入组的136例受试者中,共有128(94.1%)例报告了549例次治疗期不良事件,研究用药相关治疗期不良事件243例次(99例受试者,72.8%),未出现导致索磷布韦调药或暂停用药的不良事件,6(4.4%)例受试者发生了7例次严重不良事件,仅1例考虑与研究用药可能有关(肝低回声区性质待查),未出现导致试验中止或受试者死亡的不良事件。结论索磷布韦联合利巴韦林治疗初治的基因2型慢性HCV感染可获得较高的持续病毒学应答,不良反应大多为轻度,安全性可接受。

Objective To investigate the clinical efficacy and safety of sofosbuvir combined with ribavirin in the treatment of treatment-naive patients with genotype 2 chronic hepatitis C virus(HCV)infection.Methods Treatment-naive patients with genotype 2 HCV infection were screened in sixteen research centers of China.All patients received sofosbuvir(400 mg/tablet,1 tablet/d)combined with ribavirin(1000 mg/d for patients with a body weight of<75 kg and 1200 mg/d for those with a body weight of≥75 kg)for 12 weeks and were followed up for 12 weeks after drug withdrawal.The primary outcome measure was sustained virologic response at week 12 of follow-up,and the secondary outcome measures included the proportion of patients with HCV RNA below the lower limit of quantitation at weeks 2,4,8,and 12 of treatment and after 4 weeks of drug withdrawal,virological rebound rate at weeks 4,8,and 12 of treatment,and recurrence rate at weeks 4 and 12 of follow-up.Adverse events were observed during treatment to evaluate drug safety.Results A total of 136 subjects were enrolled,among whom 121 had no liver cirrhosis and 15 had compensated liver cirrhosis.The sustained virologic response(SVR)ratewas 92.6%(95%confidence interval:88.3%-97.0%)after 12 weeks of drug withdrawal.At week 8 of treatment,1 patient experienced virological rebound;after 4 weeks of drug withdrawal,8 patients experienced virological rebound;after 12 weeks of drug withdrawal,10 patients experienced virological rebound.Among the 136 subjects,128(94.1%)reported 549 cases of treatment-emergent adverse events,among which 243 cases were associated with sofosbuvir and/or ribavirin and were reported in 99 subjects(72.8%).No adverse events leading to the adjustment or discontinuation of sofosbuvir were observed.A total of 7 serious adverse events were reported in 6 patients(4.4%),among which only one(a low echo area in the liver with unknown nature)was considered possibly associated with sofosbuvir and/or ribavirin.No adverse events leading to study discontinuation or death were observed.Conclusion Sofosbuvir combined with ribavirin can achieve a high SVR rate in treatment-na6 ve patients with genotype 2 chronic HCV infection,with mild adverse reactions and acceptable safety profile.