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丙型肝炎病毒(HCV)相关肝硬化患者接受直接抗病毒药物(DAA)治疗后的临床结局取决于疾病的严重程度。

Clinical outcomes following DAA therapy in patients with HCV-related cirrhosis depend on disease severity.

作者信息

Krassenburg Lisette A P, Maan Raoel, Ramji Alnoor, Manns Michael P, Cornberg Markus, Wedemeyer Heiner, de Knegt Robert J, Hansen Bettina E, Janssen Harry L A, de Man Robert A, Feld Jordan J, van der Meer Adriaan J

机构信息

Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, Rotterdam, the Netherlands; Toronto Centre for Liver Disease, Toronto General Hospital, University Health Network, Toronto, Canada.

Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, Rotterdam, the Netherlands.

出版信息

J Hepatol. 2021 May;74(5):1053-1063. doi: 10.1016/j.jhep.2020.11.021. Epub 2020 Nov 23.

Abstract

BACKGROUND & AIMS: HCV-infected patients with cirrhosis achieve high sustained virological response (SVR) rates with direct-acting antivirals (DAAs) even after hepatic decompensation. We aimed to assess the clinical outcome following DAAs among patients with compensated and decompensated cirrhosis in relation to SVR and changes in model for end-stage liver disease (MELD) score.

METHODS

Consecutive DAA-treated chronic HCV-infected patients with cirrhosis from 4 hepatology clinics were included. The primary endpoint in survival analyses was clinical disease progression, defined as liver failure, hepatocellular carcinoma, liver transplantation or death.

RESULTS

In total, 868 patients were included with a median age of 59 (IQR 54-65) years; 719 (83%) with Child-Pugh A cirrhosis and 149 (17%) with Child-Pugh B/C cirrhosis. SVR was attained by 647 (90%) Child-Pugh A patients and 120 (81%) Child-Pugh B/C patients. During a median follow-up of 28 (IQR 20-36) months, 102 (14%) Child-Pugh A patients and 96 (64%) Child-Pugh B/C patients experienced clinical disease progression. SVR was independently associated with an improved event-free survival in patients with Child-Pugh A cirrhosis (adjusted hazard ratio [HR] 0.47; 95% CI 0.27-0.82, p = 0.007), but not in patients with Child-Pugh B/C cirrhosis (adjusted HR 1.23; 95% CI 0.67-2.26; p = 0.51). Twelve weeks post-DAAs, 28 (19%) patients with Child-Pugh B/C cirrhosis had ≥2-point MELD decline, but their 2-year event-free survival did not differ from those with a stable MELD (47.9%; 95% CI 28.7-67.1 vs. 48.9%; 95% CI 38.1-59.7, respectively, p = 0.99).

CONCLUSIONS

Among patients with chronic HCV infection, DAA-induced SVR was associated with a reduced risk of clinical disease progression in patients with Child-Pugh A cirrhosis but not in patients with Child-Pugh B/C cirrhosis. In Child-Pugh B/C cirrhosis, a ≥2-point MELD decline did not translate into improved clinical outcome.

LAY SUMMARY

Chronic HCV infection can be cured with antiviral therapy. In this study, we evaluated the long-term effects of antiviral therapy on liver-related complications in patients with cirrhosis. Our results suggest that patients with compensated cirrhosis who were cured of their HCV infection have a lower rate of complications. In contrast, the rate of complications was not related to virological cure among those with decompensated cirrhosis. While these patients seem to remain in need of liver transplantation, antiviral therapy may lower their priority on the liver transplantation waiting list.

摘要

背景与目的

即使在发生肝失代偿后,感染丙型肝炎病毒(HCV)的肝硬化患者使用直接抗病毒药物(DAA)也能获得较高的持续病毒学应答(SVR)率。我们旨在评估DAA治疗后,代偿期和失代偿期肝硬化患者的临床结局与SVR以及终末期肝病模型(MELD)评分变化之间的关系。

方法

纳入了来自4家肝病诊所接受DAA治疗的连续性慢性HCV感染肝硬化患者。生存分析的主要终点是临床疾病进展,定义为肝衰竭、肝细胞癌、肝移植或死亡。

结果

共纳入868例患者,中位年龄59(四分位间距54 - 65)岁;719例(83%)为Child-Pugh A级肝硬化,149例(17%)为Child-Pugh B/C级肝硬化。647例(90%)Child-Pugh A级患者和120例(81%)Child-Pugh B/C级患者实现了SVR。在中位随访28(四分位间距20 - 36)个月期间,102例(14%)Child-Pugh A级患者和96例(64%)Child-Pugh B/C级患者出现临床疾病进展。SVR与Child-Pugh A级肝硬化患者无事件生存期的改善独立相关(调整后风险比[HR] 0.47;95%置信区间0.27 - 0.82,p = 0.007),但与Child-Pugh B/C级肝硬化患者无关(调整后HR 1.23;95%置信区间0.67 - 2.26;p = 0.51)。DAA治疗12周后,28例(19%)Child-Pugh B/C级肝硬化患者的MELD评分下降≥2分,但其2年无事件生存期与MELD评分稳定的患者无差异(分别为47.9%;95%置信区间28.7 - 67.1 vs. 48.9%;95%置信区间38.1 - 59.7,p = 0.99)。

结论

在慢性HCV感染患者中,DAA诱导的SVR与Child-Pugh A级肝硬化患者临床疾病进展风险降低相关,但与Child-Pugh B/C级肝硬化患者无关。在Child-Pugh B/C级肝硬化患者中,MELD评分下降≥2分并未转化为更好的临床结局。

简要概述

慢性HCV感染可用抗病毒疗法治愈。在本研究中,我们评估了抗病毒疗法对肝硬化患者肝脏相关并发症的长期影响。我们的结果表明,HCV感染治愈的代偿期肝硬化患者并发症发生率较低。相比之下,失代偿期肝硬化患者的并发症发生率与病毒学治愈无关。虽然这些患者似乎仍需要肝移植,但抗病毒疗法可能会降低他们在肝移植等待名单上的优先级。

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