应用索磷布韦/维帕他韦治疗门诊和住院筛查的丙型肝炎患者疗效研究

doi:10.3969/j.issn.1672-5069.2021.06.013

摘要/Abstract

摘要： 目的调查真实世界丙型肝炎病毒感染情况,并探讨应用索磷布韦/维帕他韦治疗慢性丙型肝炎(CHC)患者病毒学应答情况。方法 2017年9月～2019年9月行血清抗-HCV检测的3966例住院和门诊患者,应用索磷布韦/维帕他韦治疗CHC患者12 w。结果在3966例患者中,检出血清抗-HCV阳性80例(2.0%);在80例抗-HCV阳性者中,同期进行了血清HCV RNA检测者42例,结果40例(95.2%)血清HCV RNA阳性;在40例CHC患者中,12例无明显症状和体征,18例有腹胀、乏力、纳差,10例有蜘蛛痣、肝病面容、肝掌、脾肿大;35例血清AST＞90 U/L,4例AST轻度异常,1例AST正常;3例存在HBV/HCV混合感染;B超检查14例正常,26例提示肝内光点增粗;40例CHC患者接受索磷布韦/维帕他韦治疗,结果RVR、EVR、ETVR、SVR、NR和复发率分别为75.0%、80.0%、82.5%、72.5%、10.0%和10.0%;在治疗12 w末,血清TBIL水平为(30.7±4.3)μmol/L,显著低于治疗前【(80.4±15.6)μmol/L,P＜0.05】,血清AST水平为(72.5±18.6)U/L,显著低于治疗前【(247.7±110.4) U/L,P＜0.05】,血清ALB水平为(49.2±11.5)g/L,显著高于治疗前【(35.9±9.2)g/L,P＜0.05】;不良反应发生率为22.5%。结论真实世界丙型肝炎发病率较高,对患者进行HCV感染筛查很有必要。应用索磷布韦/维帕他韦治疗CHC患者疗效显著,血清病毒学应答率高,能显著改善肝功能,且具有一定的安全性。

关键词: 丙型肝炎, 索磷布韦/维帕他韦, 病毒学应答, 治疗

Abstract: Objective The aim of this study was to investigate the screening of patients with hepatitis C in the real world, and the efficacy of sofosbuvir and velpatasvir in patients with hepatitis C. Methods Serum anti-HCV screening was carried out in 3966 inpatients and outpatients in our hospital between September 2017 and September 2019, and the confirmed patients with chronic hepatitis C (CHC) received sofosbuvir and velpatasvir treatment for 12 weeks. Results Among the 3966 patients screened, serum anti-HCV positive was 2.0% (80/3966), and out of the 80 patients with anti-HCV positive, 42 cases had their serum HCV RNA loads tested and 40 cases (95.2%) were positive; in the 40 patients with CHC, there were 12 cases without any obvious symptoms and signs, 18 cases had abdominal distension, fatigue and anorexia, 10 cases had vascular spider, liver disease face, liver palms, and splenomegaly; there were 35 cases having serum AST level ＞90 U/L, 4 cases having mildly elevated serum AST level and 1 case having normal serum AST level; 3 cases had mixed HBV/HCV infection; the B-mode ultrasound examination showed normal liver in 14 cases, and increased intrahepatic light spots in 26 cases; in 40 patients with CHC treated with sofosbuvir and velpatasvir, the early virologic response, rapid virologic response, the end treatment virologic response, sustained virologic response, none response and recurrence rates were 75.0%, 80.0%, 82.5%, 72.5%, 10.0% and 10.0%, respectively; serum bilirubin level in patient after 12 weeks of treatment was (30.7±4.3) μmol/L, significantly lower than [(80.4±15.6) μmol/L, P＜0.05] before treatment, and serum AST level was (72.5±18.6) U/L, significantly lower than [(247.7±110.4) U/L, P＜0.05] before treatment; serum albumin level was (49.2±11.5) g/L, significantly higher than [(35.9±9.2) g/L, P＜0.05] before treatment; the incidence of adverse reactions was 22.5% in our series. Conclusion The prevalence of hepatitis C in the real world is relatively high, and the screening of infection is of great importance. The application of sofosbuvir and velpatasvir in the treatment of patients with hepatitis C has a promising clinical efficacy, with a good serum virological response and safety.

Key words: Hepatitis C, Screening, Sofosbuvir, Velpatasvir, Virological response, Therapy

黄飞虎, 薛建亚, 朱咏梅, 余姣, 王丽艳, 鲁琼. 应用索磷布韦/维帕他韦治疗门诊和住院筛查的丙型肝炎患者疗效研究[J]. 实用肝脏病杂志, 2021, 24(6): 819-822.

Huang Feihu, Xue Jianya, Zhu Yongmei, et al. Short-term efficacy of sofosbuvir and velpatasvir in the treatment of patients with hepatitis C[J]. Journal of Practical Hepatology, 2021, 24(6): 819-822.

参考文献

[1] Forns X,Lee SS,Valdes J, et al. Glecaprevir plus pibrentasvir for chronic hepatitis C virus genotype 1, 2, 4, 5, or 6 infection in adults with compensated cirrhosis (EXPEDITION-1): a single-arm, open-label, multicentre phase 3 trial. Lancet Infect Dis,2017,17(10):1062-1068.
[2] Sadeghi F,Salehi-Vaziri M,Almasi-Hashiani A,et al.Prevalence of hepatitis C virus genotypes among patients in countries of the eastern mediterranean regional office of WHO (EMRO): A systematic review and Meta-Analysis. Hepat Mon,2016,16(4):e35558.
[3] 张红.慢性丙型病毒性肝炎抗病毒治疗的临床疗效分析.中国冶金工业医学杂志,2019,36(3):280-281.
[4] 马亦林.直接抗病毒药物(DAAs)治疗丙型肝炎的研究现状.中华临床感染病杂志,2017,10(1):8-13.
[5] Schnell G,Tripathi R,Krishnan P,et al.Resistance characterization of hepatitis C virus genotype 2 from Japanese patients treated with ombitasvir and paritaprevir/ritonavir.J Med Virol,2017,90(1):109-119.
[6] 韩杰,郝竟琳,田姗,等.直接抗病毒药物(DAA)在丙肝治疗中的临床应用进展.首都食品与医药,2018,25(17):42-43.
[7] 张立新,王磊,薛艳,等.索磷布韦联合达拉他韦治疗肾移植合并丙肝的疗效与安全性.中华实验和临床病毒学杂志,2019,33(1):64-69.
[8] Ohya K,Akuta N,Suzuki F,et al.Predictors of treatment efficacy and liver stiffness changes following therapy with sofosbuvir plus ribavirin in patients infected with HCV genotype 2.J Med Virol,2018,90(5):919-925.
[9] Isakov V,Paduta D,Viani RM,et al.Ombitasvir/paritaprevir/ritonavir+dasabuvir+ribavirin for chronic hepatitis C virus genotype 1b-infected cirrhotics (TURQUOISE-IV).Eur J Gastroenterol Hepatol,2018,30(9):1073-1076.
[10] 徐杰,赵亚楠,乔桂芳,等.干扰素诱导蛋白10对早期HCV感染病情进展预测价值的研究.中国实验诊断学,2020,24(2):290-293.
[11] Bersoffmatcha SJ,Cao K,Jason M,et al.Hepatitis B virus reactivation associated with direct-acting antiviral therapy for chronic hepatitis C virus: A review of cases reported to the U.S. Food and Drug Administration Adverse Event Reporting System. Ann Intern Med,2017,166(11):792-798.
[12] 常青燕,朱杰,张晓慧,等.慢性丙型肝炎抗病毒治疗过程中CD4⁺的Treg细胞与Th17细胞动态变化.贵州医药,2018,42(4):406-408,封3.
[13] 贾因棠,段晓红,杨中鑫,等.IL-28B、IFNL4基因多态性与慢性丙型肝炎患者聚乙二醇干扰素联合利巴韦林抗病毒疗效相关性的研究.中华肝脏病杂志,2017,25(7):529-532.
[14] Cholankeril G,Joseph-Talreja M,Perumpail BJ,et al.Timing of hepatitis C virus treatment in liver transplant candidates in the era of direct-acting antiviral agents.J Clin Transl Hepatol,2017,5(4):363-367.
[15] 陈平钰,谢青.艾尔巴韦格拉瑞韦与索磷布韦维帕他韦治疗丙型肝炎的成本-效果分析.中国药物经济学,2019,14(7):14-18,26.
[16] Miller MM.Sofosbuvir-velpatasvir:A single-tablet treatment for hepatitis C infection of all genotypes. Am J Health Syst Pharm,2017,75(14):1045-1052.
[17] 张琼方,张大志.基于索磷布韦的丙型肝炎治疗方案在中国的价值和应用潜力.中华肝脏病杂志,2018,26(3):233-237.
[18] 卢捷,周惠娟,谢青.达拉他韦联合索磷布韦治疗丙型肝炎的临床研究进展.中华肝脏病杂志,2018,26(2):147-150.
[19] 米色日黎,白浪.索磷布韦/维帕他韦在丙型肝炎抗病毒治疗中的应用进展.国际流行病学传染病学杂志,2018,45(5):289.
[20] Aqarwal K,Castells L,Mullhaupt B,et al.Sofosbuvir/velpatasvir for 12 weeks in genotype 1-4 HCV-infected liver transplant recipients. J Hepatol,2018,69(3):603-607.
[21] Nehra V,Rizza SA,Temesgen Z.Sofosbuvir/velpatasvir fixed-dose combination for the treatment of chronic hepatitis C virus infection.Drugs Today(Brac),2017,53(3):177-189.