一项评估索磷布韦联合利巴韦林治疗基因2型慢性丙型肝炎病毒感染受试者的有效性和安全性的单臂、开放、多中心Ⅱ期临床研究

目的评估索磷布韦(南京正大天晴制药有限公司)联合利巴韦林治疗基因2型慢性丙型肝炎病毒感染的受试者的有效性和安全性。方法在全国16家研究中心筛选初治或经治的基因2型慢性丙型肝炎病毒感染者,所有受试者接受每日一次的索磷布韦(400mg)联合利巴韦林(体质量<75kg,1000mg/d,早上400mg,晚上600mg;体质量≥75kg,1200mg/d,早晚各600mg)治疗12周,停药后随访12周。连续变量采用均值±标准差表示,不同随访时间点病毒学应答的受试者比例及95%置信区间采用极大似然比点估计及Clopper-Pearson区间估计。结果全国16家研究中心共入组132例基因2型慢性丙型肝炎病毒感染的受试者,其中12例受试者伴有肝硬化,其余120例受试者不伴有肝硬化。131例受试者完成了本研究,1例受试者在完成停药后第4周访视后失访。停药12周获得的持续病毒学应答率为96.2%(95%可信区间:92.37%~99.16%)。4例受试者发生病毒学复发。入组的132例受试者中,119例(90.2%)受试者共报告了617例次治疗期不良事件(TEAE),其中与索磷布韦和/或利巴韦林相关TEAE359例次(76.5%)。其中3级及3级以上TEAE9例次,共有6例(4.5%)受试者发生了6例次严重不良事件,仅1例严重不良事件与索磷布韦和利巴韦林相关(不稳定型心绞痛)。无导致停药的不良事件。无导致死亡的不良事件。结论索磷布韦联合利巴韦林治疗基因2型慢性丙型肝炎病毒感染具有较高的SVR率,发生的不良反应大多为轻度,安全性可接受。

应答为指导的干扰素方案治疗6a型慢性丙型肝炎

目的探讨以应答为指导(RGT)的聚乙二醇干扰素α-2a联合利巴韦林(Peg-IFNα-2a+RBV)方案在基因6a型慢性丙型肝炎(CHC)中的效果。方法 2014年1月至2015年12月间连续入组基因6a型CHC患者共60例(优化组),接受Peg-IFNα-2a+RBV抗病毒治疗,其中达到快速病毒学应答(RVR)的患者疗程缩短至24周,未达到RVR者疗程为48周。同时以2012年1月至2013年12月期间,接受48周固定疗程的Peg-IFNα-2a+RBV治疗的所有基因6a型CHC患者为对照组(56例)。结果优化组患者快速病毒学应答(RVR)、治疗终点病毒学应答(ETR)、持续病毒性应答(SVR)、停药后复发发生率分别为67.2%、87.9%、82.8%和5.2%,与对照组的71.4%、82.1%、80.4%、1.8%比较,差异均无统计学意义(P>0.05)。优化组与对照组获得RVR患者的最终SVR率(92.3%vs 87.5%,),差异亦无统计学意义(P=0.479)。优化组除血象异常发生率低于对照组外,其他差异均无统计学意义。结论获得RVR的基因6a型CHC患者,其接受24周与48周疗程Peg-IFNα-2a+RBV治疗均能取得较高的SVR率。

Real world experience with Pegylated Interferon and ribavirin in Hepatitis C Genotype 1 population with favourable IL28B polymorphism

Background and aim:Conventional hepatitis C treatment using pegylated interferon(PEG-IFN)and ribavirin is associated with significant side effects.IL28B polymorphism can predict response to treatment,with CC genotype having a better response.ITPA gene deficiency protects against clinically significant anaemia induced by treatment.The purpose of this study was to determine IL28B polymorphismand ITPA variation among hepatitis C genotype 1 patients who have undergone therapy with PEG-IFN and ribavirin and their association with sustained viral response(SVR).Methods:All hepatitis C genotype 1 patients who had been treated with PEG-IFN and ribavirin over the past 10 years were identified by available medical records and were contacted by letter of invitation to participate in the study.Blood samples for IL28B and ITPA genotyping were obtained.Medical records were reviewed for verification of treatment response,development of anaemia and if treatment reduction was required during the treatment.Results:A total of 61 patients with hepatitis C genotype 1 were treated with PEG-IFN and ribavirin,of whom 42 agreed to participate in the study.Mean age was 45.6±12.9 years at time of treatment,and 83.3%of patients weremales.Thirty-three(78.6%)had IL28B CC genotype,of whom 25(75.8%)obtained SVR compared with only 3 of 9(33.3%)non C/C genotype patients who achieved SVR(P=0.041).Eleven(26.1%)patients had ITPA AC genotype,and 30(71.4%)had CC genotype.There was no statistically significant difference between ITPA AC and CC genotypes in predicting clinically significant anaemia(45.5%vs 63.3%,P=0.302).Even among patients who developed anaemia,70.8%stillmanaged to achieve SVR.Treatment reduction also had no impact on SVR.Conclusion:Hepatitis C genotype 1 patients should be informed of the response rate for treatment with PEG-IFN and ribavirin in a population with favourable IL28B genotype before consideration of newer therapeutic options.