在初治和经治丙型肝炎病毒基因1b型慢性感染的代偿期肝硬化亚洲成年患者中评价奥比帕利和达塞布韦联合利巴韦林治疗的有效性和安全性  

Efficacy and safety of ombitasvir/paritaprevir/ritonavir and dasabuvir combined with ribavirin in Asian adult patients with chronic HCV genotype lb infection and compensated cirrhosis

作　　者：魏来[1] 王贵强[2] Sarah Kopecky-Bromberg 成军[4] 诩青 汪茂荣[6] 许敏[7] 段钟平[8] 侯金林[9] 张明香[10] 张跃新[11] 唐红[12] 赵伟[13] 蔺淑梅[14] 贾战生 牛俊奇[15] 高志良[16] 袁宏[17] 林明华[18] 周新民 Luo Yan Linda Fredrick Niloufar Mobashery Wang Ye 贾继东[21] Wei Lai;Wang Guiqiang;Sarah Kopecky-Bromberg;Cheng Jun;Xie Qing;Wang Maorong;Xu Min;Duan Zhongping;Hou Jinlin;Zhang Mingxiang;Zhang Yuexin;Tang Hong;Zhao Wei;Lin Shumei;Jia Zhansheng;Niu Junqi;Gao Zhiliang;Yuan Hong;Lin Minghua;Zhou Xinmin;Luo Yan;Linda Fredrick;Niloufar Mobashery;Wang Ye;Jia Jidong(Peking University People＇s Hospital, Beijing 100044, China;Peking University First Hospital, Beijing 100034, Chin;AbbVie Inc., North Chicago 60064, IL, US;Beijing Ditan Hospital Capital Medical University, Beijing 100015, Chin;Rui Jin Hospital Shanghai, Jiao Tong University School of Medicine, Shanghai 200025,China;81 Hospital The Chinese People＇s Liberation Army, Nanjing 210002, Chin;The 8th Hospital of Guangzhou, Guangzhou 510000, Chin;Beij＇ing You＇an Hospital Capital Medical University, Beijing 100069, Chin;Nan Fang Hospital Guangzhou 510515, Chin;Shengyang 6th People＇s Hospital Shenyang 110006, China;The 1st Hospital of Xinjiang Medical University, Urumqi 830011, China;est China School of Medicine, Chengdu 610041, Chin;anjing 2nd Hospital Nanjing 210028, Chin;he 1st Hospital of Xi＇an Jiaotong University, Xi＇an 710065, Chin;angdu Hospital Xi＇an 710038, Chin;he 1st Hospital of Jilin University, Changchun 130021, Chin;he 3rd Hospital Sun Yay-sen Hospital Guangzhou 510630, Chin;he 1st Hospital of Lanzhou University, Lanzhou 730000, Chin;he Infectious Hospital of Fuzhou, Fuzhou 350001, Chin;ijing Hospital of The 4th Military Medical University, Xi＇an 710032, Chin;bb Vie. Shanghai 200041, Chin;eijing Friendship Hospital Capital Medical University, Beo＇ing 100050, Chin)

机构地区：[1]北京大学人民医院,100044 [2]北京大学第一医院,100034 [3]AbbVie Inc.,North Chicago, IL, USA,60064 [4]首都医科大学附属北京地坛医院,北京100015 [5]上海交通大学医学院附属瑞金医院,200025 [6]解放军第八一医院,南京210002 [7]广州市第八人民医院,510000 [8]首都医科大学附属佑安医院,北京100069 [9]南方医科大学南方医院,广州510515 [10]沈阳市第六人民医院,110006 [11]新疆医科大学第一附属医院,乌鲁木齐830011 [12]四川大学华西医院,成都610041 [13]南京市第二医院,210028 [14]西安交通大学第一附属医院,710065 [15]吉林大学第一医院,长春130021 [16]中山大学附属第三医院,广州510630 [17]兰州大学第一医院,730000 [18]福州市传染病医院,350001 [19]第四军医大学第一附属医院,西安710032 [20]AbbVie.China. Shanghai 100004 [21]首都医科大学附属北京友谊医院,北京100050

出　　处：《中华肝脏病杂志》2018年第5期353-358,共6页Chinese Journal of Hepatology

摘　　要：目的 评估奥比帕利（奥比他韦/帕立瑞韦/利托那韦）25/150/100mg,1次/d和达塞布韦（DSV） 250 mg,2次/d联合利巴韦林在丙型肝炎病毒基因1b型感染的代偿期肝硬化中国大陆成年患者中的有效性和安全性. 方法 采用开放标签、多中心Ⅲ期临床试验,在中国大陆、中国台湾地区和韩国开展,纳入初治和经治基因1b型丙型肝炎病毒感染的代偿期肝硬化（Metavir 评分纤维化分期=F4）成年患者,接受奥比他韦/帕立瑞韦/利托那韦和达塞布韦联合利巴韦林治疗12周.评估患者停药12周获得的持续病毒学应答（SVR）及24周获得的SVR率,并在接受至少1次研究药物的患者中评估有效性和安全性. 结果 共纳入63例中国大陆患者,其中62例（98.4％）患者基线Child-Pugh评分为5分.患者总体SVR12率及SVR24率为100％ （95％ CI：94.3％ ～ 100.0％）.发生的大多数不良事件为轻度.常见（发生率≥10％）所有级别不良事件和实验室异常包括总胆红素升高（36.5％）、乏力（19.0％）、非结合胆红素升高（19.0％）、结合胆红素升高（17.5％）和贫血（14.3％）.3例（4.8％）患者发生≥3级不良事件,均被研究者判定为与研究药物无关.无患者出现导致提前停药的不良事件. 结论 丙型肝炎病毒基因1b型感染的代偿期肝硬化中国大陆患者接受奥比他韦/帕立瑞韦/利托那韦和达塞布韦联合利巴韦林治疗12周,停药12周和24周的SVR均为100％.耐受性及安全性良好,大多数不良事件为轻度.Objective To evaluate the efficacy and safety of ombitasvir/paritaprevir/ritonavir （OBV/PTV/r） 25/150/100 mg once daily and dasabuvir （DSV） 250 mg twice daily combined with ribavirin in adult patients of China's Mainland with chronic HCV genotype 1b infection and compensated cirrhosis.Methods An open-label,multicenter,phase 3 clinical trial study was conducted in China's Mainland,Taiwan,and South Korea.Adult patients with compensated cirrhosis （Metavir score =F4） who were newly diagnosed and treated for hepatitis C virus genotype lb infection with ombitasvir/paritaprevir/ritonavir and dasabuvir combined with ribavirin for 12 weeks were included.Assessed SVR rate of patients obtained at 12 and 24 weeks after drug withdrawal.Efficacy and safety were evaluated in patients who received at least one time study drugs.Results A total of 63 patients from China's Mainland were enrolled,62 of whom （98.4%） had a baseline Child-Pugh score of 5 points.The overall rate of SVR12 and SVR24 in patients was 100% （95% CI：94.3% to 100.0%）.Most of the adverse events that occurred were mild.The incidence of common （≥ 10%） adverse events and laboratory abnormalities included elevated total bilirubin （36.5%）,weakness （19.0%）,elevated unconjugated bilirubin （19.0%） and conjugated bilirubin （17.5%）,and anemia （14.3%）.Three cases （4.8%） of patients experienced Grade ≥ 3 adverse events that were considered by the investigators to be unrelated to the study drug.None patients had adverse events leading to premature drug withdrawal.Conclusion Mainland Chinese patients with chronic HCV genotype lb infection and compensated cirrhosis who were treated with OBV/PTV/r plus DSV combined with RBV for 12 weeks achieved 100 % SVR at 12 and 24 weeks after drug withdrawal.Tolerability and safety were good,and majority of adverse events were mild.

关 键 词：肝炎 丙型 慢性 肝硬化 直接抗病毒药物 

分 类 号：R512.63[医药卫生—内科学]