Sofosbuvir-based regimens combined with ribavirin for recipients with genotype 1 hepatitis C after liver transplantation: a Meta-analysis
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摘要:
目的 通过系统评价和Meta分析评估以索非布韦(SOF)为基础的直接抗病毒药物(DAAs)联合利巴韦林(RBV)(联合RBV)治疗肝移植术后丙型肝炎病毒(HCV)基因1型(GT1)肝炎受者能否获益。 方法 系统检索国内外多个数据库,根据标准筛选文献,并进行文献质量评价,提取数据。将文献按肝移植术后HCV-GT1肝炎受者接受联合RBV或只用SOF的DAAs不联合RBV(不联合RBV)治疗分为两组。采用Rev Man 5.3和R3.4.3软件对数据进行Meta分析。对治疗结束后12周持续病毒学应答(SVR12)的发生率进行评估。 结果 检索文献2 195篇,按纳入标准筛选共纳入6篇英文文献。Meta分析结果表明联合RBV组和不联合RBV组两组间SVR12的发生率差异无统计学意义(P=0.28),但是联合RBV组贫血的发生率明显增高(P < 0.01)。联合RBV或不联合RBV治疗方案对肝移植术后HCV-GT1a和HCV-GT1b两个亚型同样有效,两基因亚型间疗效差异无统计学意义(P=0.33)。将肝移植术后HCV-GT1肝炎受者的疗程从12周延长至24周的SVR率差异无统计学意义(P=0.95)。 结论 采用基于SOF的DAAs方案治疗肝移植术后HCV-GT1肝炎受者时,联合RBV不仅不能提高病毒的清除率,反而增加了受者发生贫血的风险,不能从中获益。 Abstract:Objective To evaluate whether sofosbuvir (SOF)-based direct-acting antiviral agents (DAAs) combined with ribavirin (RBV) (combined RBV) can yield benefits to the recipients infected with hepatitis C virus (HCV) genotype 1 (GT1) after liver transplantation through systematic evaluation and Meta-analysis. Methods Multiple databases at home and abroad were systematically searched, the literature screening was conducted according to relevant standards, the quality of literatures was evaluated and data extraction was performed. The literature was divided into two groups according to the recipients with HCV-GT1 hepatitis after liver transplantation who received the treatment combined RBV or SOF-based DAAs alone without RBV (not combined RBV). Meta-analysis of the data was carried out using Rev Man 5.3 and R3.4.3 software. The incidence of sustained virological response 12 weeks (SVR12) after therapy was evaluated. Results A total of 2 195 articles were retrieved, and 6 articles published in English were eventually included according to the inclusion criteria. The Meta-analysis results demonstrated that the incidence of SVR12 did not significantly differ between the combined RBV and not combined RBV groups (P=0.28). However, the incidence of anemia in the combined RBV group was significantly higher than that in the other group (P < 0.01). Both combined RBV and not combined RBV therapies were efficacious in treating HCV-GT1a and HCV-GT1b subtypes after liver transplantation with similar clinical efficacy (P=0.33). The incidence of SVR in HCV-GT1 recipients did not significantly differ after receiving 12- and 24-weeks therapy after liver transplantation (P=0.95). Conclusions When SOF-based DAAs regimen is adopted to treat HCV-GT1 in recipients after liver transplantation, combination with RBV not only fails to improve the virus clearance rate and bring clinical benefits, but also increases the risk of anemia in the recipients. -
Key words:
- Liver transplantation /
- Sofosbuvir /
- Ribavirin /
- Meta-analysis /
- Hepatitis C virus /
- Infection /
- Anemia /
- Sustained virological response
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表 1 纳入文献的基本特征
Table 1. Basic characteristics of the included articles
研究作者 年份 研究机构 国家 样本量(n) 男性[n(%)] 年龄(岁) MINORS评分 HCV肝炎治疗史[n(%)] 治疗方案 疗程(周) O'Leary JG, et al[12] 2016 多中心 美国 46 34(74) 60(49~68)a — 0(0) SOF+SMV±RBV 12或24 Brown RS JR, et al[13] 2016 多中心 美国 151 112(74) 61(46~78)b 19 85(56) SOF+SMV±RBV 12或24 Crittenden NE, et al[14] 2016 多中心 美国 56 42(75) 61(7)c 20 41(73) SOF+SMV±RBV 12 Nair S, et al[15] 2017 单中心 美国 50 34(68) 56±7 18 30(60) SOF+SMV±RBV 12 Saab S, et al[16] 2017 单中心 美国 85 57 (67) 63±9 19 39(46) SOF+LDV±RBV 12或24 Pillai AA, et al[17] 2016 单中心 美国 57 43 (75) 58±6 19 24(42) SOF+SMV±RBV 12 a中位数(极差),b均数(极差),c中位数(四分位数间距),SMV为西咪匹韦,LDV为雷迪帕韦,—表示无 -
[1] WRIGHT TL, DONEGAN E, HSU HH, et al. Recurrent and acquired hepatitis C viral infection in liver transplant recipients[J]. Gastroenterology, 1992, 103(1):317-322. doi: 10.1016/0016-5085(92)91129-R [2] KALAMBOKIS G, MANOUSOU P, SAMONAKIS D, et al. Clinical outcome of HCV-related graft cirrhosis and prognostic value of hepatic venous pressure gradient[J]. Transpl Int, 2009, 22(2):172-181. DOI: 10.1111/j.1432-2277.2008.00744.x. [3] BERENGUER M, PRIETO M, RAYÓN JM, et al. Natural history of clinically compensated hepatitis C virus-related graft cirrhosis after liver transplantation[J]. Hepatology, 2000, 32(4 Pt 1):852-858. [4] COILLY A, ROCHE B, DUCLOS-VALLÉE JC, et al. Management of HCV transplant patients with triple therapy[J]. Liver Int, 2014, 34(Suppl 1):46-52. DOI: 10.1111/liv.12406. [5] ANGELICO M, PETROLATI A, LIONETTI R, et al. A randomized study on peg-interferon alfa-2a with or without ribavirin in liver transplant recipients with recurrent hepatitis C[J]. J Hepatol, 2007, 46(6):1009-1017. doi: 10.1016/j.jhep.2006.12.017 [6] DUMORTIER J, SCOAZEC JY, CHEVALLIER P, et al. Treatment of recurrent hepatitis C after liver transplantation: a pilot study of peginterferon alfa-2b and ribavirin combination[J]. J Hepatol, 2004, 40(4):669-674. doi: 10.1016/j.jhep.2003.12.015 [7] European Association for the Study of the Liver. EASL recommendations on treatment of hepatitis C 2018[J]. J Hepatol, 2018, 69(2):461-511. DOI: 10.1016/j.jhep.2018.03.026. [8] ELFEKI MA, ABOU MRAD R, MODARESI ESFEH J, et al. Sofosbuvir/ledipasvir without ribavirin achieved high sustained virologic response for hepatitis C recurrence after liver transplantation: two-center experience[J]. Transplantation, 2017, 101(5):996-1000. DOI: 10.1097/TP.0000000000001467. [9] ZHANG X. Direct anti-HCV agents[J]. Acta Pharm Sin B, 2016, 6(1):26-31. DOI: 10.1016/j.apsb.2015.09.008. [10] AASLD-IDSA HCV Guidance Panel. Hepatitis C guidance 2018 update: AASLD-IDSA recommendations for testing, managing, and treating hepatitis C virus infection[J]. Clin Infect Dis, 2018, 67(10):1477-1492. DOI: 10.1093/cid/ciy585. [11] PETRUZZIELLO A, MARIGLIANO S, LOQUERCIO G, et al. Global epidemiology of hepatitis C virus infection: an up-date of the distribution and circulation of hepatitis C virus genotypes[J]. World J Gastroenterol, 2016, 22(34):7824-7840. DOI: 10.3748/wjg.v22.i34.7824. [12] O'LEARY JG, FONTANA RJ, BROWN K, et al. Efficacy and safety of simeprevir and sofosbuvir with and without ribavirin in subjects with recurrent genotype 1 hepatitis C postorthotopic liver transplant: the randomized GALAXY study[J]. Transpl Int, 2017, 30(2):196-208. DOI: 10.1111/tri.12896. [13] BROWN RS JR, O'LEARY JG, REDDY KR, et al. Interferon-free therapy for genotype 1 hepatitis C in liver transplant recipients: real-world experience from the hepatitis C therapeutic registry and research network[J]. Liver Transpl, 2016, 22(1):24-33. DOI: 10.1002/lt.24366. [14] CRITTENDEN NE, BUCHANAN LA, PINKSTON CM, et al. Simeprevir and sofosbuvir with or without ribavirin to treat recurrent genotype 1 hepatitis C virus infection after orthotopic liver transplantation[J]. Liver Transpl, 2016, 22(5):635-643. DOI: 10.1002/lt.24422. [15] NAIR S, SATAPATHY SK, GONZALEZ HC. Sofosbuvir and simeprevir for treatment of recurrent hepatitis C infection after liver transplant[J]. Exp Clin Transplant, 2017, 15(3):314-319. DOI: 10.6002/ect.2015.0289. [16] SAAB S, RHEEM J, JIMENEZ MA, et al. Effectiveness of ledipasvir/sofosbuvir with/without ribavarin in liver transplant recipients with hepatitis C[J]. J Clin Transl Hepatol, 2017, 5(2):101-108. DOI: 10.14218/JCTH.2016.00070. [17] PILLAI AA, WEDD J, NORVELL JP, et al. Simeprevir and sofosbuvir (SMV-SOF) for 12 weeks for the treatment of chronic hepatitis C genotype 1 infection: a real world (transplant) hepatology practice experience[J]. Am J Gastroenterol, 2016, 111(2):250-260. DOI: 10.1038/ajg.2015.422. [18] TERRAULT NA, SHIFFMAN ML, LOK AS, et al. Outcomes in hepatitis C virus-infected recipients of living donor vs. deceased donor liver transplantation[J]. Liver Transpl, 2007, 13(1):122-129. doi: 10.1002/lt.20995 [19] LIAO HT, TAN P, HUANG JW, et al. Ledipasvir + sofosbuvir for liver transplant recipients with recurrent hepatitis C: a systematic review and Meta-analysis[J]. Transplant Proc, 2017, 49(8):1855-1863. DOI: 10.1016/j.transproceed.2017.04.014. [20] LIAO H, TAN P, ZHU Z, et al. Sofosbuvir in combination with daclatasvir in liver transplant recipients with HCV infection: a systematic review and Meta-analysis[J]. Clin Res Hepatol Gastroenterol, 2017, 41(3):262-271. DOI: 10.1016/j.clinre.2016.12.001. [21] LIONETTI R, CALVARUSO V, PICCOLO P, et al. Sofosbuvir plus daclatasvir with or without ribavirin is safe and effective for post-transplant hepatitis C recurrence and severe fibrosis and cirrhosis: a prospective study[J]. Clin Transplant, 2018, 32(2). DOI: 10.1111/ctr.13165. [22] PUNGPAPONG S, AQEL B, LEISE M, et al. Multicenter experience using simeprevir and sofosbuvir with or without ribavirin to treat hepatitis C genotype 1 after liver transplant[J]. Hepatology, 2015, 61(6):1880-1886. DOI: 10.1002/hep.27770. [23] FONTANA RJ, BROWN RS JR, MORENO-ZAMORA A, et al. Daclatasvir combined with sofosbuvir or simeprevir in liver transplant recipients with severe recurrent hepatitis C infection[J]. Liver Transpl, 2016, 22(4):446-458. DOI: 10.1002/lt.24416. [24] CARDONA-GONZALEZ MG, GOLDMAN JD, NARAYAN L, et al. Sofosbuvir, velpatasvir, and voxilaprevir for treatment of recurrent hepatitis C virus infection after liver transplantation[J]. Hepatol Commun, 2018, 2(12):1446-1450. DOI: 10.1002/hep4.1280.