索磷布韦维帕他韦治疗慢性丙型肝炎的真实世界研究

摘要/Abstract

摘要： 目的评价索磷布韦维帕他韦(SOF/VEL)治疗慢性丙型肝炎(CHC)患者的疗效和安全性。方法回顾性分析2018年8月至2019年12月广州市第八人民医院门诊诊治的48例接受SOF/VEL治疗的CHC患者,疗程为12周,随访12周,观察其疗效及停药12周持续病毒学应答率(SVR12)及药物-药物间相互作用(DDI)。结果 48例CHC患者治疗1、2、4、8、12周时血清HCV RNA转阴率分别为39.6％(19/48)、72.9％(35/48)、93.8％(45/48)、100.0％(48/48)和100.0％(48/48); SVR12为95.8%(46/48)。在治疗12周及停药12周时血清丙氨酸氨基转移酶(ALT)复常率分别为97.9%(47/48)、93.8%(45/48)、天冬氨酸氨基转移酶(AST)复常率分别为95.8%(46/48)、95.8%(46/48)。2例基线估算的肾小球滤过率(eGFR)<90 mL/(min·1.73 m²)患者未调整SOF/VEL剂量并完成疗程;1例基线eGFR正常患者在治疗8周及12周时出现eGFR下降,未调整SOF/VEL剂量并完成疗程,停药12周eGFR恢复正常;48例CHC患者中有16例同时合并其他疾病,占33.3%,其中10例患者有联合用药,联合1种药物3例,2种药物4例,3种药物1例,7种药物1例,9种药物1例,治疗期间无DDI发生。结论采用SOF/VEL治疗CHC患者可获得较高的SVR12和生化学应答,且安全性良好。

关键词: 慢性丙型肝炎, 索磷布韦, 维帕他韦, 疗效, 药物-药物间相互作用

Abstract: Objective To evaluate the efficacy and safety of Sofosbuvir/Velpatasvir (SOF/VEL) treatment on patients with chronic hepatitis C (CHC).Methods Forty-eight CHC patients who had received SOF/VEL treatment for 12 weeks and followed-up for 12 weeks were retrospectively analyzed. Sustained virological response (SVR) and drug-drug interactions (DDI) in these patients were observed during the 12-week’s follow-up period after drug withdrawal.Results Of the 48 patients, 24 patients (50%) were HCV genotype 6a,14 (29.2%) were genotype 3a, 5 (10.4%) were genotype 1b, 4 (8.3%) were genotype 3b and 1 (2.1%) was genotype 2a. Four (8.3%) of the 8 patients (16.7%) with liver cirrhosis were HCV genotype 6a, 2 (4.2%) were genotype 3a, 2 (4.2%) were genotype 1b. The negative conversion rate of serum HCV RNA was 39.6％ (19/48), 72.9％ (35/48), 93.8％ (45/48), 100.0％ (48/48) and 100.0％ (48/48) respectively at 1, 2, 4, 8 and 12 weeks of therapy. The overall SVR12 was 95.8% (46/48). The normalization rates of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) was 97.9% (47/48) and 95.8 (46/48) at 12 weeks of therapy, and 93.8% (45/48) and 95.8 (46/48) at the 12-week’s follow-up period after drug withdrawal. Two patients whose estimated glomerular filtration rate (eGFR) less than 90 mL·min^-1·1.73 m² at baseline had completed the treatment without adjustment of SOF/VEL dosage; One patient who had a decreased eGFR at 8, 12 weeks therapy had completed the treatment without adjustment of SOF/VEL dosage, and the eGFR level returned to normal at the 12-week’s follow-up period after drug withdrawal. Among the 48 patients with CHC, 16 cases were complicated with other diseases, accounting for 33.3%. Among these 16 cases, 10 patients had combined medication, 3 cases with 1, 4 cases with 2, 1 case with 3 , 1 case with 7, 1 case with 9 kinds of drugs, without occurring DDI during their treatments.Conclusion CHC patients who received SOF/VEL treatment had a very high SVR12 and biochemical responses, and the therapy is safe.

Key words: Chronic hepatitis C, Sofosbuvir, Velpatasvir , Efficacy, Drug-drug interactions

冯倩嫦, 张春兰, 李凌华, 张健珍, 许敏, 蔡卫平. 索磷布韦维帕他韦治疗慢性丙型肝炎的真实世界研究[J]. 肝脏, 2021, 26(6): 606-610.

FENG Qian-chang, ZHANG Chun-lan, LI Ling-hua, ZHANG Jian-zhen, XU Min, Cai Wei-ping. A real-world study on the treatment of chronic hepatitis C patients with Sofosbuvir/Velpatasvir[J]. Chinese Hepatolgy, 2021, 26(6): 606-610.

参考文献

[1] 陈若蝉,刘振国,范学工. DAA与HCC——丙肝治疗新时代的挑战. 中国感染控制杂志,2018,17:369-372.
[2] 中华医学会肝病学分会,感染病学分会.丙型肝炎防治指南(2019年版).中华肝脏病杂志,2019,27:962-979.
[3] Sarah B, Srefan Z, Michael M, et al. Global prevalence and genotype distribution of hepatitis C virus infection in 2015:a modelling study. Lancet Gastroenterol Hepatol,2017,2:161-176.
[4] Mohd HK, Groeger J, Flaxman Ad, et al. Global epidemiology of hepatitis C virus infection: new estimates of age-specific antibody to HCV seroprevalence. Hepatology,2013, 57:1333-1342.
[5] 窦晓光,魏来,任红,等. 聚乙二醇干扰素在中国丙型肝炎治疗中的地位. 中华肝脏病杂志,2015,23:641-643.
[6] 陈凤娟,郭凤霞,邵晓琼,等. 应答为指导的干扰素方案治疗6a型慢性丙型肝炎. 热带医学杂志,2017,17:751-754.
[7] 饶慧瑛. 丙型肝炎直接抗病毒治疗研究进展. 实用肝脏病杂志, 2016,19:390-393.
[8] 罗碧芬, 魏来. 丙型肝炎抗病毒治疗:口服药物改变了什么. 实用肝脏病杂志,2016,19: 385-389.
[9] Susser S, Dietz J, Vermehren J, et al.European RAVs database:frequency and characteristics of RAVs in treatment-naïve and DAA-experienced patients. J Hepatol,2016,64:s139.
[10] 魏来, 王琴. 直接抗病毒药物时代慢性丙型肝炎的治疗:不同方案选择的考虑. 中华传染病杂志, 2018, 36:577-586.
[11] 屈慧新,王玉泽,王彩霞,等. 新型抗丙型肝炎病毒药索非布韦的研究进展. 沈阳药科大学学报,2016,33:334-338.
[12] Cheng G, Yu M, Peng B, et al. 1191 GS-5816, A Second Generation HCV NS5A inhibitor with potent antiviral activity,broad genotypic coverage and a high resistance barrier. J Hepatol,2013,58:484-485.
[13] Lawitz E, Freilich B, Link J,et al. A phase 1, randomized, dose-ranging study of GS-5816,a once-daily NS5A inhibitor,in patients with genotype 1-4 hepatitis C virus. J Viral Hepat,2015,22:1011-1019.
[14] Ira MJ, Eric L, Edward JG, et al. Efficacy of 8 weeks of Sofosbuvir, Velpatasvir, and Voxilaprevir in patients with chronic HCV infection: 2 phase 3 randomized trials. Gastroenterology, 2017,153:113-122
[15] David W, Norbert B, Shyam K,et al. Sofosbuvir and Velpatasvir for the treatment of hepatitis C virus in patients coinfected with human immunodeficiency virus type 1: an open-label, phase 3 study. Clin Infect Dis,2017,65:6-12.
[16] Jason G, Olav D, Brian C, et al. Sofosbuvir and Velpatasvir for hepatitis C virus infection in people with recent injection drug use (SIMPLIFY): an open-label, single-arm, phase 4,multicentre trial. Lancet Gastroenterol Hepatol,2018,3:153-161.
[17] 汤伟亮,谢青.基因3型丙型肝炎病毒感染及其抗病毒治疗.实用肝脏病杂志,2016,19:394-397.
[18] Kirby BJ, Symonds WT, Kearney BP, et al. Pharmacokinetic, Pharmacodynamic, and drug-Interaction profile of the hepatitis C virus NS5B Polymerase Inhibitor Sofosbuvir. Clin Pharmacokinet, 2015, 54:677-690.
[19] Sergio MB, Janet D, Eric MY, et al. Sofosbuvir/velpatasvir for 12 weeks in hepatitis C virus-infected patients with end-stage renal disease undergoing dialysis. J Hepatol, 2019,71: 660-665.
[20] Ji F, Wang W, Dang S, et al. Outcomes after sofosbuvir-containing regimens for hepatitis C virus in patients with decompensated cirrhosis: a real-world study.Infect Agent Cancer, 2017,12:48.
[21] Michelle CMC, Alex JW, Benjamin EH, et al. Outcomes after successful direct-acting antiviral therapy for patients with chronic hepatitis C and decompensated cirrhosis. J hepatol,2016, 65: 741-747.
[22] Hanafy AS, Bassiony MA, Basha MAA. Management of HCV-related decompensated cirrhosis with direct-acting antiviral agents: who should be treated?.Hepatol Int, 2019,13: 165-172.
[23] 嵇小琴, 龚健. 老年CHC临床特点及抗病毒治疗策略研究进展. 实用肝脏病杂志, 2018, 21:995-998.
[24] Curry MP, O'Leary JG, Bzowej N ,et al. Sofosbuvir and velpatasvir for HCV in patients with decompensated cirrhosis. N Engl J Med, 2015,373: 2618-2628.
[25] Viola K, Stefan M,Tobias G,et al. Dynamics of liver stiffness by transient elastography in patients with chronic hepatitis C virus infection receiving direct-acting antiviral therapy—results from the german hepatitis C-registry. J Viral hepat,2020,27:690-698.