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直接作用抗病毒药物的疗效:来自一个特征良好的主要为肝硬化 HCV 队列的英国真实世界数据。

Efficacy of direct-acting antivirals: UK real-world data from a well-characterised predominantly cirrhotic HCV cohort.

机构信息

Department of Clinical and Experimental Medicine, Brighton and Sussex Medical School (BSMS), Brighton, UK.

Department of Gastroenterology and Hepatology, Brighton and Sussex University Hospital (BSUH) NHS Trust, Brighton, UK.

出版信息

J Med Virol. 2019 Nov;91(11):1979-1988. doi: 10.1002/jmv.25552. Epub 2019 Aug 5.

Abstract

Direct-acting antivirals (DAAs) have revolutionised the management of chronic hepatitis C virus (HCV) infection. We describe UK real-world DAA experience. Individuals commencing HCV treatment containing a DAA regimen (Mar 2014-Nov 2016), participating in the National HCV Research UK (HCVRUK) Cohort Study were recruited from 33 UK HCV centers. The data were prospectively entered at sites onto a centralised database. The data were reported as median (Q1-Q3). Of the 1448 treated patients, 1054 (73%) were males, the median age being 54 years (47-60), 900 (62%) being genotype 1 and 455 (31%) genotype 3. The majority, 887 (61%) had cirrhosis, and 590 (41%) were treatment-experienced. DAA regimens utilised: genotype1 sofosbuvir (SOF)/Ledipasvir/±Ribavirin (625/900, 69%) and Ombitasvir/Paritaprevir/Dasabuvir/±RBV (220/900, 24%), and in genotype 3 SOF/Daclatasvir + RBV (256/455, 56%) and SOF/pegylated interferon/RBV (157/455, 35%). Overall, 1321 (91%) achieved sustained virological response (SVR12), genotype 1 vs 3, 93% vs 87%, P < .001. Prior treatment, presence of cirrhosis and treatment regimen did not impact SVR12. Predictors of treatment failure were genotype 3 infection, OR, 2.015 (95% CI: 1.279-3.176, P = .003), and male sex, OR, 1.878 (95% CI: 1.071-3.291, P = .028). Of those with hepatic decompensation at baseline (n = 39), 51% (n = 20) recompensated post-treatment, lower baseline serum creatinine being associated with recompensation (P = .029). There were two liver-related deaths, both having decompensated disease. This real-world UK data, comprising of a predominantly cirrhotic HCV genotype 1/3 cohort, confirms DAA efficacy with an overall 91% SVR12, with 51% recompensating post-treatment. Genotype 3 infection was a predictor of treatment failure.

摘要

直接作用抗病毒药物(DAAs)彻底改变了慢性丙型肝炎病毒(HCV)感染的治疗方式。我们描述了英国的真实世界 DAA 经验。2014 年 3 月至 2016 年 11 月,参加英国国家 HCV 研究 UK(HCVRUK)队列研究的 33 个英国 HCV 中心招募了开始接受包含 DAA 方案的 HCV 治疗的个体。数据前瞻性地在现场输入到集中数据库中。数据以中位数(Q1-Q3)报告。在 1448 名接受治疗的患者中,1054 名(73%)为男性,中位年龄为 54 岁(47-60 岁),900 名(62%)为基因型 1,455 名(31%)为基因型 3。大多数患者(887 名,61%)患有肝硬化,590 名(41%)为治疗经验丰富的患者。使用的 DAA 方案:基因型 1 的索非布韦(SOF)/雷迪帕韦/±利巴韦林(625/900,69%)和奥比他韦/帕利他韦/达卡他韦/±RBV(220/900,24%),以及基因型 3 的 SOF/达卡他韦+RBV(256/455,56%)和 SOF/聚乙二醇干扰素/RBV(157/455,35%)。总的来说,1321 名(91%)患者获得持续病毒学应答(SVR12),基因型 1 为 93%,基因型 3 为 87%,P<0.001。既往治疗、肝硬化的存在和治疗方案均未影响 SVR12。治疗失败的预测因素是基因型 3 感染,OR,2.015(95%CI:1.279-3.176,P=0.003),以及男性,OR,1.878(95%CI:1.071-3.291,P=0.028)。基线时有肝失代偿(n=39)的患者中,51%(n=20)在治疗后代偿,较低的基线血清肌酐与代偿相关(P=0.029)。有 2 例与肝脏相关的死亡,均为失代偿性疾病。该英国真实世界数据主要包含基因型 1/3 肝硬化 HCV 患者队列,证实 DAA 的疗效为总体 SVR12 为 91%,51%的患者在治疗后代偿。基因型 3 感染是治疗失败的预测因素。

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