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直接抗病毒药物(DAA)清除丙型肝炎病毒后肝脏和心血管死亡率:RESIST-HCV 队列研究数据。

Liver and cardiovascular mortality after hepatitis C virus eradication by DAA: Data from RESIST-HCV cohort.

机构信息

Gastroenterology and Hepatology Unit, Department of Health Promotion Sciences Maternal and Infantile Care, Internal Medicine and Medical Specialities, PROMISE, University of Palermo, Palermo, Italy.

UOC Epatologia Clinica e Biomolecolare, Messina, Italy.

出版信息

J Viral Hepat. 2021 Aug;28(8):1190-1199. doi: 10.1111/jvh.13523. Epub 2021 May 7.

Abstract

Real-world evidence on the course of Hepatitis C Virus (HCV) chronic liver disease after Sustained Virologic Response (SVR) obtained with direct-acting antiviral drugs (DAAs) are still limited, and the effects on mortality remain unclear. We evaluated the post-treatment survival of 4307 patients in the RESIST-HCV cohort (mean age 66.3 ± 11.6 years, 56.9% males, 24.7% chronic hepatitis, 66.9% Child-Pugh A cirrhosis and 8.4% Child-Pugh B cirrhosis) treated with DAAs between March 2015 and December 2016 and followed for a median of 73 weeks (range 16-152). Proportional cause-specific hazard regression for competing risks was used to evaluate the survival and to assess the predictors of liver and cardiovascular death. Overall, 94.7% of patients achieved SVR while 5.3% were HCV RNA-positive at last follow-up. Sixty-three patients (1.4%) died during the observation period. SVR was associated with a decreased risk of liver mortality (hazard ratio,HR0.09, beta -2.37, p < .001). Also, platelet count (HR 0.99, beta-0.01, p = .007) and albumin value (HR 0.26, beta -1.36 p = .001) were associated with liver mortality by competing risk analysis. SVR was associated with a reduced risk of cardiovascular mortality regardless of presence of cirrhosis (HR 0.07, beta-2.67, p < .001). Presence of diabetes (HR 3.45, beta 1.24, p = .014) and chronic kidney disease class ≥3 (HR 3.60, beta 1.28, p = 0.016) were two factors independently associated with higher risk of cardiovascular mortality. Patients with SVR to a DAA therapy have a better liver and cardiovascular survival, and the effects of HCV eradication are most evident in patients with compensated liver disease.

摘要

使用直接作用抗病毒药物 (DAA) 获得的持续性病毒学应答 (SVR) 后丙型肝炎病毒 (HCV) 慢性肝病病程的真实世界证据仍然有限,其对死亡率的影响仍不清楚。我们评估了 2015 年 3 月至 2016 年 12 月间接受 DAA 治疗的 4307 名 RESIST-HCV 队列患者(平均年龄 66.3±11.6 岁,56.9%为男性,24.7%为慢性肝炎,66.9%为 Child-Pugh A 级肝硬化,8.4%为 Child-Pugh B 级肝硬化)的治疗后生存情况,中位随访时间为 73 周(范围 16-152 周)。使用竞争风险比例因果风险回归来评估生存情况,并评估肝和心血管死亡的预测因素。总体而言,94.7%的患者达到 SVR,而 5.3%的患者在最后一次随访时 HCV RNA 阳性。在观察期间,有 63 名患者(1.4%)死亡。SVR 与肝死亡率降低相关(风险比,HR0.09,β-2.37,p<.001)。此外,血小板计数(HR 0.99,β-0.01,p=0.007)和白蛋白值(HR 0.26,β-1.36,p=0.001)也通过竞争风险分析与肝死亡率相关。无论是否存在肝硬化,SVR 均与心血管死亡率降低相关(HR 0.07,β-2.67,p<.001)。存在糖尿病(HR 3.45,β 1.24,p=0.014)和慢性肾脏病 3 级以上(HR 3.60,β 1.28,p=0.016)是与心血管死亡率升高相关的两个独立因素。接受 DAA 治疗的 SVR 患者具有更好的肝和心血管生存情况,HCV 清除的效果在代偿性肝病患者中最为明显。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a5ec/8359835/5149d2dbcae9/JVH-28-1190-g002.jpg

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