索磷布韦维帕他韦治疗慢性丙型肝炎患者疗效和安全性观察:一项单中心真实世界回顾性分析

doi:10.3969/j.issn.1672-5069.2022.01.008

摘要/Abstract

摘要： 目的回顾性分析索磷布韦维帕他韦(SOF/VEL)联合利巴韦林(RBV)治疗慢性丙型肝炎(CHC)患者真实世界研究(RWS)的疗效和安全。方法 2018年5月～2020年4月初治/PR经治的CHC患者32例和代偿期丙型肝炎肝硬化(CHC-CLC)患者36例,接受SOF/VEL治疗12 w,失代偿期丙型肝炎肝硬化(CHC-DLC)或合并肝细胞癌(HCC)患者31例,接受SOF/VEL联合利巴韦林(RBV)治疗12 w。部分患者合并存在高血压、糖尿病、肿瘤和慢性乙型肝炎。采用RT-PCR法检测HCV基因型(GTs)。结果本组HCV 感染患者以GT 2a(55.6%)和GT1b(34.3%)为主;CHC、CHC-CLC和CHC-DLC患者早期病毒学应答(EVR4)分别为90.6%、86.1%、83.9%,治疗结束病毒学应答(EOT)均为100.0%,CHC组和CHC-CLC组SVR12和SVR24均为100.0%,CHC-DLC组 SVR12和SVR24均为93.5%,三组间EVR4、EOT、SVR12、SVR24均无显著性差异(P>0.05);所有患者SVR12和SVR24均为97.8%,除GT3b型外其他GTs感染患者SVR12和SVR24均为100.0%;三组血生化学应答率分别为87.5%、83.3%和74.2%;本组总体不良反应(AE)发生率为12.1%,无严重AE或因AE停药和死亡事件发生。结论应用SOF/VEL或联合RBV治疗CHC或相关的肝硬化患者,无论何种基因型感染,均有良好的效果,且安全。

关键词: 慢性丙型肝炎, 索磷布韦/维帕他韦, 真实世界, 疗效, 安全性

Abstract: Objective The aim of this study was to investigate the efficacy and safety of sofosbuvir/velpatasvir (SOF/VEL) in treatment of patients with chronic hepatitis C (CHC) and hepatitis C precipitated liver cirrhosis in real-world study (RWS) in a single centre. Method This RWS included naïve or PR-treated patients with CHC, some concomitant with blood hypertension, diabetes, tumor or hepatitis, between May 2018 and April 2020. 32 patients with CHC and 36 patients with compensated hepatitis C -induced liver cirrhosis (CHC-CLC) received SOF/VEL for 12 weeks, and 31 patients with decompensated hepatitis C liver cirrhosis (CHC-DLC) or hepatocellular carcinoma received SOF/VEL and ribavirin (RBV) for 12 weeks. The HCV genotypes (GTs) were determined by RT-PCR. Results The prevalence of GT 2a(55.6%) and GT1b(34.3%) was dominant in our series; the early virological response (EVR4)in patients with CHC, CHC-CLC and CHC-DLC were 90.6%, 86.1% and 83.9%, the end of treatment (EOT) virologic response were 100.0% in the three groups, the sustained virological response (SVR) 12 and SVR24 in patients with CHC and CHC-CLC were 100.0% and 100.0% and both the SVR12 and SVR24 in patients with CHC-DLC were 93.5%, not significantly different among the three groups(P>0.05); both the SVR12 and SVR24 in our series was 97.8%, and they reached 100.0% when the patients with GT3b infection were excluded; the biochemical responses rates in the three groups were 87.5%, 83.3% and 74.2%, and the incidence of adverse event (AE) in our series was 12.1%, no severe AE or discontinuation of therapy owning to AE occurred. Conclusion The efficacy of SOF/VEL and/or with RBV in treating patients with CHC and CHC-precipitated liver diseases is good and promising, without severe untoward effects.

Key words: Hepatitis C, Sofosbuvir/velpatasvir, Real world, Efficacy, Safety

包飞云, 李彤, 王玉珊, 张亚萍, 李娟, 麻爱娣, 刘元元, 张岭漪. 索磷布韦维帕他韦治疗慢性丙型肝炎患者疗效和安全性观察:一项单中心真实世界回顾性分析[J]. 实用肝脏病杂志, 2022, 25(1): 30-33.

Bao Feiyun, Li Tong, Wang Yushan, et al. Real-world study of efficacy and safety of sofosbuvir/velpatasvir in treatment of patients with hepatitis C and hepatitis C precipitated liver cirrhosis in a single centre of western-north China[J]. Journal of Practical Hepatology, 2022, 25(1): 30-33.

参考文献

[1] Polaris observatory HCV collaborators. Global prevalence and genotype distribution of hepatitisC virus infection in 2015: a modelling study. Lancet Gastroenterol Hepatol, 2017,2:161-176.
[2] Everson GT, Towner WJ, Davis MN, et al. Sofosbuvir with velpatasvir in treatment-naïve noncirrhotic patients with genotype 1 to 6 hepatitis C virus infection: a randomized trial. Ann Intern Med,2015,163:818-826.
[3] Pianko S, Flamm SL, Shiffman ML, et al. Sofosbuvir plus velpatasvir combination therapy for treatment-experienced patients with genotype 1 or 3 hepatitis C virus infection: a randomized trial. Ann Intern Med,2015,163:809-817.
[4] Curry MP, O'Leary JG,Bzowej N, et al. ASTRAL-4 Investigators. Sofosbuvir and velpatasvir for HCV in patients with decompensated cirrhosis. N Engl J Med,2015, 373:2618-2628.
[5] VonFelden J, Vermehren J, Ingiliz P, et al. High efficacy of sofosbuvir/velpatasvir and impact of baseline resistance-associated substitutions in hepatitis C genotype 3 infection. Aliment Pharmacol Ther,2018,47:1288-1295.
[6] Foster GR,Afdhal N, Roberts SK, et al. ASTRAL-2 investigators.ASTRAL-3 investigators. Sofosbuvir and velpatasvir for HCV genotype 2 and 3 infection. N Engl J Med,2015,373:2608-2617.
[7] 魏来,段钟平,王贵强.丙型肝炎防治指南(2019年版).实用肝脏病杂志,2020,23(01):33-52.
[8] 瞬时弹性成像技术诊断肝纤维化专家共识(2018年更新版).中华肝脏病杂志,2019,28(3):182-191.
[9] Freeman AJ, Dore GJ, Law MG, et al. Estimating progression to cirrhosis in chronic hepatitis C virus infection.Hepatolgy,2001,34(4 P1):809-816.
[10] Bennett H, Waser N, Johnston K, et al. A review of the burden of hepatitis C virus infection in China, Japan, South Korea and Taiwan of China. Hepatol Int,2015,9(3):378-390.
[11] European Association for the Study of the Liver. EASL recommendations on treatment of hepatitis C 2018.J Hepatol,2018,69(2):461 -511.
[12] John-Baptiste AA, Tomlinson G, Hsu PC, et al. Sustained responders have better quality of life and productivity compared with treatment failures long after antiviral therapy for hepatitis C. Am J Gastroenterol, 2009,104(10):2439-2448.
[13] Buggisch P, Wursthorn K, Stoehr A, et al. Real-world effectiveness and safety of sofosbuvir/velpatasvir and ledipasvir/sofosbuvir hepatitis C treatment in a single centre in Germany. PLoS One,2019,14(4):e0214795.
[14] Wilton J, Wong S, Yu A, et al. Real-world effectiveness of sofosbuvir/velpatasvir for treatment of chronic cepatitis C in British Columbia, Canada: a population-based cohort study.Open Forum Infect Dis,2020,29,7(3):ofaa055.
[15] Asselah T, Bourgeois S, Pianko S, et al. Sofosbuvir/velpatasvir in patients with hepatitis C virus genotypes 1-6 and compensated cirrhosis or advanced fibrosis. Liver Int,2018,38(3):443-450.
[16] Bwa AH, Nangia G, Win STS, et al. Strategy and efficacy of generic and pan-genotypic sofosbuvir/velpatasvir in chronic hepatitis C virus: a Myanmar experience. J Clin Exp Hepatol,2019,9(3):283-293.
[17] Mei YY, Chen YM, Wu YK, et al.Efficacy and safety of sofosbuvir-based direct-acting antiviral agents treatment for patients with genotype 3/6 hepatitis C virus infection.Can J Gastroenterol Hepatol,2020,2020:8872120.
[18] Chen Yi Mei SLG, Thompson AJ, et al. Sustained virological response halts fibrosis progression: a long-term follow-up study of people with chronic hepatitis C infection.PLoS One,2017,12:e0185609.
[19] Rao HY, Li H, Chen H, et al. Real-world treatment patterns and clinical outcomes of HCV treatment-naive patients in China: an interim analysis from the ccgenos study. J Gastroenterol Hepatol,2017,32:244-252.
[20] Tao YC, Deng R, Wang ML, et al. Satisfactory virological response and fibrosis improvement of sofosbuvir-based regimens for chinese patients with hepatitis C virus genotype 3 infection: results of a real-world cohort study.Virol J,2018 Oct 1,15(1):150.