12周索磷布韦/维帕他韦方案治疗西北地区慢性丙型肝炎患者:一项真实世界多中心临床研究  

Twelve-week of sofosbuvir/velpatasvir therapeutic regimen for chronic hepatitis C patients in northwest region of China:a real-world niulticenter clinical study

作　　者：徐强[1] 张伟 马玉秀 贺彩妮 张立婷[5] 依力哈木·阿不力提甫 李彧[7] 王楠[8] 王宏利 赵蕴玉 高旭 高培根 粟兴洋 李慎[10] 刘媛媛 郭峰[1] 陈章乾 刘海玲 高晓琴 付建军[8] 于国英 王晓忠[1] 王九萍 张永萍[6] 纪泛扑[4,13,14] Xu Qiang;Zhang Wei;Ma Yiai;He Caini;Zhang Liting;Abulitifu Yilihamu;Li Yu;Wang Nan;Wang Hongli;Zhao Yunyu;Gao Xu;Gao Peigen;Su Xingyang;Li Shen;Liu Yuanyuan;Guo Feng;Chen Zhangqian;Liu Hailing;Gao Xiaoqin;Fu Jianjun;Yu Guoying;Wang Xiaozhong;Wang Jiuping;Zhang Yongping;Ji Fanpu(Hospital of Traditional Chinese Medicine Affiliated to Xinjiang Medical University,Urumqi 830000,China;Xijing Hospital of Air Force Medical University,Xi'an 710032,China;The Fourth People's Hospital of Qinghai Province,Xining 810000,China;The Second Affiliated Hospital of Xi'an,Xi'an Jiaotong University,Xi'an 710004,China;First Hospital of Lanzhou University,Lanzhou 730000,China;People's Hospital of Xinjiang Uygur Autonomous Region,Urumqi 830001,China;Shaanxi Provincial Peoples Hospital Xi'an 710068,China;The Affiliated Xi'an Central Hospital of Xi'an Jiaotong University,Xi'an 710003,China;The Eighth hospital of Xi'an City,Xi'an 710061,China;Shaanxi Provincial Centre for Disease Control and Prevention,Xi'an 710054,China;Central Hospital of Xianyang City,Xianyang 712000,China;Shaanxi Provincial Shenmu Hospital,Yulin 719300,China;National&Local Joint Engineering Research Center of Biodiagnosis and Biothenipy,the Second Affiliated Hospital,Xi’an Jiaotong University,Xi’an 710004,China;Shaanxi Provincial Clinical Medical Research Center of Infectious Diseases,Xi'an 710049,China)

机构地区：[1]新疆医科大学附属中医医院,乌鲁木齐830000 [2]空军军医大学西京医院,西安710032 [3]青海省第四人民医院,西宁810000 [4]西安交通大学第二附属医院,710004 [5]兰州大学第一医院,730000 [6]新疆维吾尔自治区人民医院,乌鲁木齐830001 [7]陕西省人民医院,西安710068 [8]西安市中心医院,710003 [9]西安市第八医院,710061 [10]陕西省疾病预防控制中心病毒所,西安710054 [11]咸阳市中心医院,712000 [12]陕西省神木市医院,719300 [13]生物诊断治疗国家地方联合工程研究中心,西安710004 [14]陕西省感染性疾病临床医学研究中心,西安710049

出　　处：《中华肝脏病杂志》2021年第11期1046-1052,共7页Chinese Journal of Hepatology

基　　金：国家自然科学基金(81300322);西安交通大学医学部国家级后备人选菁英计划(305);西安交通大学大学生创新创业训练计划项目(SJ202010698269)。

摘　　要：目的探讨索磷布韦/维帕他韦(SOF/VEL)治疗西北地区慢性丙型肝炎(CHC)患者的疗效和安全性。方法该项多中心、前瞻性、真实世界研究纳入中国西北地区10个研究中心CHC任何基因型接受SOF(400 mg)/VEL(100 mg)治疗12周患者,基因3型肝硬化和任何基因型失代偿期肝硬化患者联合利巴韦林(RBV)900~1 200 mg治疗。主要终点为治疗结束12周持续病毒学应答(SVR12)和安全性。次要终点是获得SVR12对肝脏生化指标的影响。结果共纳入143例患者, 4例失访, 1例治疗结束随访期间死亡, 最终138例纳入符合研究方案分析。中位年龄53岁, 53.6%肝硬化, 10.1% HBsAg阳性, 6.5%合并肾损害, 5.1%经治, 16.7%患者联合RBV治疗。基因型分布:1型35.5%, 2型42.8%, 3型15.9%, 5.8%未检测基因型。意向治疗分析, SVR12率为96.5% (138/143, 95%CI: 93.5%~99.6%);PP分析, 138例患者均获得SVR12(100%)。与基线相比治疗结束后12周血清总胆红素、ALT和AFP水平明显降低(P值均< 0.05), 血清白蛋白、血小板计数明显升高(P值均< 0.001)。任何不良事件发生率为29.0%, 贫血(14.5%)和乏力(8.0%)最常见。2例患者出现严重不良反应(水肿和乏力), 其中1例需要短暂中断治疗。结论 12周SOF/VEL单用或联合RBV治疗西北地区CHC患者可获得高的SVR12(96.5%~100%), 抗病毒治疗安全性良好, 获得SVR12患者肝脏生化指标明显改善。Objective To study the real-world outcome of China FDA-approved Sofosbuvir(SOF)/Velpatasvir(VEL)in Northwest China.Methods In this multicenter,prospective,real-world cohort study,we recruited patients from 10 sites from Northwest China,who were chronically infected with HCV GTs 1-6 from 06/2018 to 09/2019.Patients received SOF(400mg)/VEL(100mg)for 12 weeks,and with ribavirin 900-1200 mg for GT3 cirrhosis and for any genotype decompensated cirrhosis.The primary endpoint was sustained virological response at 12-weeks post-treatment(SVR12)and safety.The secondary endpoint was the change of liver function after the achievement of SVR12.Results Totally,143 patients were enrolled in the study,four patients were lost to follow-up and one died during the follow-up,138 patients were included in per-protocol analysis.Of the 138 patients,the mean age 53 years,53.6%male,94.2%Han nationality,53.6%liver cirrhosis,10.1%HBsAg,6.5%renal dysfunction,5.1%treatment-experienced,and 16.7%patients received ribavirin treatment.The genotype distribution was as follows:35.5%GT1,42.8%GT2,15.9%GT3,and 5.8%un-typed.The SVR12 rate was 96.5%(138/143,95% CI:93.5%-99.6%)for intention-to-treat analysis,and in per-protocol analysis,all 138 patients obtained SVR12(100%).Compared with baseline,the serum total bilirubin,ALT and AFP levels decreased(all P<0.05),as well as increased ALB and platelet count(all P<0.001)at post-treatment 12-weeks.Overall adverse events(AEs)rate is 29.0%,and the most common AEs were anemia(14.5%)and fatigue(8.0%).Severe side effects(edema and fatigue)occurred in 2 patients,one of whom needed a shortterm interruption of treatment due to fatigue.Conclusion In this real-world cohort study,12-week SOF/VEL regimen with or without ribavirin achieved high SVR12 rates(96.5%-100%overall)with excellent safety profile among patients with HCV GT1/2/3 infection including patients with GT3 and cirrhosis,and led to improvement of liver function.

关 键 词：慢性丙型肝炎 索磷布韦 维帕他韦 疗效 真实世界 基因3型 肝硬化 利巴韦林 

分 类 号：R512.63[医药卫生—内科学]