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直接作用抗病毒药物清除丙型肝炎病毒后肝硬化患者的肝功能:来自 PITER 队列的数据。

Liver function following hepatitis C virus eradication by direct acting antivirals in patients with liver cirrhosis: data from the PITER cohort.

机构信息

Center for Global Health, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161, Rome, Italy.

University of Tor Vergata, Nostra Signora del Buon Consiglio di Tirana, Tirana, Albania.

出版信息

BMC Infect Dis. 2021 May 4;21(1):413. doi: 10.1186/s12879-021-06053-3.

Abstract

BACKGROUND

The development of direct-acting antivirals (DAA) for HCV has revolutionized the treatment of HCV, including its treatment in patients with HIV coinfection. The aim of this study was to compare the changes in liver function between coinfected and monoinfected patients with cirrhosis who achieved HCV eradication by DAA.

METHODS

Patients with pre-treatment diagnosis of HCV liver cirrhosis, consecutively enrolled in the multicenter PITER cohort, who achieved a sustained virological response 12 weeks after treatment cessation (SVR12) were analysed. Changes in Child-Pugh (C-P) class and the occurrence of a decompensating event was prospectively evaluated after the end of DAA treatment. Cox regression analysis was used to evaluate factors independently associated with changes in liver function following viral eradication.

RESULTS

We evaluated 1350 patients, of whom 1242 HCV monoinfected (median follow-up 24.7, range 6.8-47.5 months after viral eradication) and 108 (8%) HCV/HIV coinfected (median follow-up 27.1, range 6.0-44.6). After adjusting for age, sex, HCV-genotype, HBsAg positivity and alcohol use, HIV was independently associated with a more advanced liver disease before treatment (C-P class B/C vs A) (OR: 3.73, 95% CI:2.00-6.98). Following HCV eradication, C-P class improved in 17/20 (85%) coinfected patients (from B to A and from C to B) and in 53/82 (64.6%) monoinfected patients (from B to A) (p = 0.08). C-P class worsened in 3/56 coinfected (5.3%) (from A to B) and in 84/1024 (8.2%) monoinfected patients (p = 0.45) (from A to B or C and from B to C). Baseline factors independently associated with C-P class worsening were male sex (HR = 2.00; 95% CI = 1.18-3.36), platelet count < 100,000/μl (HR = 1.75; 95% CI 1.08-2.85) and increased INR (HR = 2.41; 95% CI 1.51-3.84). Following viral eradication, in 7 of 15 coinfected (46.6%) and in 61 of 133 (45.8%) monoinfected patients with previous history of decompensation, a new decompensating event occurred. A first decompensating event was recorded in 4 of 93 (4.3%) coinfected and in 53 of 1109 (4.8%) monoinfected patients (p = 0.83).

CONCLUSIONS

Improvement of liver function was observed following HCV eradication in the majority of patients with cirrhosis; however viral eradication did not always mean cure of liver disease in both monoinfected and coinfected patients with advanced liver disease.

摘要

背景

直接作用抗病毒药物(DAA)的发展彻底改变了 HCV 的治疗方法,包括对 HIV 合并感染患者的治疗。本研究旨在比较通过 DAA 实现 HCV 清除的合并感染和单纯感染肝硬化患者的肝功能变化。

方法

分析了连续入组多中心 PITER 队列、治疗结束后 12 周达到持续病毒学应答(SVR12)的 HCV 肝硬化患者。在 DAA 治疗结束后,前瞻性评估 Child-Pugh(C-P)分级的变化和失代偿事件的发生。使用 Cox 回归分析评估病毒清除后与肝功能变化相关的独立因素。

结果

我们评估了 1350 例患者,其中 1242 例 HCV 单纯感染(中位随访时间为病毒清除后 24.7 个月,范围为 6.8-47.5 个月)和 108 例(8%) HCV/HIV 合并感染(中位随访时间为 27.1 个月,范围为 6.0-44.6 个月)。调整年龄、性别、HCV 基因型、HBsAg 阳性和饮酒因素后,HIV 独立与治疗前更严重的肝病相关(C-P 分级 B/C 与 A)(OR:3.73,95%CI:2.00-6.98)。在 HCV 清除后,20 例合并感染患者中的 17 例(85%)(从 B 级到 A 级和从 C 级到 B 级)和 82 例单纯感染患者中的 53 例(64.6%)(从 B 级到 A 级)(p=0.08)的 C-P 分级得到改善。56 例合并感染患者中有 3 例(5.3%)(从 A 级到 B 级)和 1024 例单纯感染患者中有 84 例(8.2%)(从 A 级到 B 级或 C 级和从 B 级到 C 级)的 C-P 分级恶化(p=0.45)。C-P 分级恶化的独立预测因素包括男性(HR=2.00;95%CI=1.18-3.36)、血小板计数<100,000/μl(HR=1.75;95%CI 1.08-2.85)和国际标准化比值(INR)升高(HR=2.41;95%CI 1.51-3.84)。在 HCV 清除后,在 15 例合并感染患者中的 7 例(46.6%)和在 133 例单纯感染患者中的 61 例(45.8%)有既往失代偿病史的患者中,发生了新的失代偿事件。在 93 例合并感染患者中有 4 例(4.3%)和在 1109 例单纯感染患者中有 53 例(4.8%)记录了首次失代偿事件(p=0.83)。

结论

在大多数肝硬化患者中,HCV 清除后肝功能得到改善;然而,在合并感染和单纯感染的晚期肝病患者中,病毒清除并不总是意味着肝脏疾病的治愈。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea07/8094561/10f3303376d9/12879_2021_6053_Fig1_HTML.jpg

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