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直接作用抗病毒药物的无干扰素慢性丙型肝炎治疗不会改变肝硬化患者新发肝细胞癌的短期风险。

Interferon-free therapy of chronic hepatitis C with direct-acting antivirals does not change the short-term risk for de novo hepatocellular carcinoma in patients with liver cirrhosis.

机构信息

Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.

Department of Transplantation Medicine, University of Muenster, Muenster, Germany.

出版信息

Aliment Pharmacol Ther. 2018 Feb;47(4):516-525. doi: 10.1111/apt.14427. Epub 2017 Dec 4.

Abstract

BACKGROUND

Hepatitis C virus (HCV) clearance with IFN-based therapies reduces the incidence of hepatocellular carcinoma (HCC). There has been some debate if IFN-free therapy with direct-acting antivirals alters the risk for HCC.

AIM

To investigate the HCC incidence in cirrhotic HCV patients who cleared HCV with direct-acting antivirals vs untreated controls.

METHODS

We prospectively monitored 373 patients with chronic hepatitis C who received IFN-free therapies with direct-acting antiviral after January 2014. A retrospective control cohort of untreated cirrhotic patients was recruited out of 3715 HCV patients who were followed at our centre between 2007 and 2013, with similar HCC screening protocols.

RESULTS

158 direct-acting antiviral-treated and 184 control patients with liver cirrhosis were included in this analysis. The groups did not differ in gender and genotype distribution, severity of liver disease and prevalence of diabetes mellitus. Patients were followed up for a median of 440 (range 91-908) and 592 (range 90-1000) days. HCCs developed in 6 and 14 patients during follow-up, resulting in an incidence of 2.90 vs 4.48 HCCs per 100 person-years. In the direct-acting antiviral-treated group, there was no new case of HCC later than 450 days after treatment initiation. In multivariate analysis, higher MELD-Scores and AFP-levels were independently associated with HCC development. Transplant-free patient survival was similar in both groups.

CONCLUSIONS

IFN-free direct-acting antiviral therapy of chronic hepatitis C does not alter the short-term risk for HCC in patients with liver cirrhosis. A reduced HCC incidence may become evident after more than 1.5 years of follow-up.

摘要

背景

基于干扰素的治疗清除丙型肝炎病毒 (HCV) 可降低肝细胞癌 (HCC) 的发病率。关于无干扰素的直接作用抗病毒药物治疗是否改变 HCC 的风险存在一些争议。

目的

研究通过直接作用抗病毒药物清除 HCV 的肝硬化丙型肝炎病毒患者与未治疗对照者 HCC 的发病率。

方法

我们前瞻性监测了 373 例于 2014 年 1 月后接受无干扰素直接作用抗病毒治疗的慢性丙型肝炎患者。从我们中心在 2007 年至 2013 年期间随访的 3715 例 HCV 患者中招募了未经治疗的肝硬化对照患者,采用相似的 HCC 筛查方案。

结果

158 例直接作用抗病毒药物治疗的肝硬化患者和 184 例对照患者纳入了本分析。两组在性别和基因型分布、肝病严重程度和糖尿病患病率方面无差异。患者中位随访 440(范围 91-908)和 592(范围 90-1000)天。随访期间,6 例和 14 例患者发生 HCC,导致每 100 人年 HCC 发生率分别为 2.90 和 4.48。在直接作用抗病毒药物治疗组中,治疗开始后 450 天以后没有新的 HCC 病例。多变量分析表明,较高的 MELD 评分和 AFP 水平与 HCC 发生独立相关。两组患者无移植生存率相似。

结论

无干扰素的直接作用抗病毒药物治疗慢性丙型肝炎不会改变肝硬化患者 HCC 的短期风险。随访超过 1.5 年后 HCC 发病率可能会降低。

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