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丙型慢性肝炎患者持续的肝脏炎症与持续病毒学应答

Ongoing liver inflammation in patients with chronic hepatitis C and sustained virological response.

作者信息

Welsch Christoph, Efinger Mira, von Wagner Michael, Herrmann Eva, Zeuzem Stefan, Welzel Tania M, Lange Christian M

机构信息

Department of Internal Medicine 1, JW Goethe-University Hospital, Frankfurt/Main, Germany.

Institute of Biostatistics and Mathematical Modelling, Faculty of Medicine, Goethe-University, Frankfurt/Main, Germany.

出版信息

PLoS One. 2017 Feb 14;12(2):e0171755. doi: 10.1371/journal.pone.0171755. eCollection 2017.

Abstract

BACKGROUND

Novel direct-acting antiviral DAA combination therapies tremendously improved sustained virologic response (SVR) rates in patients with chronic HCV infection. SVR is typically accompanied by normalization of liver enzymes, however, hepatic inflammation, i.e. persistently elevated aminotransferase levels may persist despite HCV eradication. Aim: To investigate prevalence and risk factors for ongoing hepatic inflammation after SVR in two large patient cohorts.

METHODS

This post-hoc analysis was based on prospectively collected demographic and clinical data from 834 patients with SVR after HCV treatment with either PegIFN- or DAA-based treatment regimens from the PRAMA trial (n = 341) or patients treated at our outpatient clinic (n = 493).

RESULTS

We observed an unexpected high prevalence of post-SVR inflammation, including patients who received novel IFN-free DAA-based therapies. Up to 10% of patients had ongoing elevation of aminotransferase levels and another 25% showed aminotransferase activity above the so-called healthy range. Several baseline factors were independently associated with post-SVR aminotransferase elevation. Among those, particularly male gender, advanced liver disease and markers for liver steatosis were strongly predictive for persistent ALT elevation. The use of IFN-based antiviral treatment was independently correlated with post-SVR inflammation, further supporting the overall benefit of IFN-free combination regimens.

CONCLUSION

This is the first comprehensive study on a large patient cohort investigating the prevalence and risk factors for ongoing liver inflammation after eradication of HCV. Our data show a high proportion of patients with ongoing hepatic inflammation despite HCV eradication with potential implications for the management of approximately one third of all patients upon SVR.

摘要

背景

新型直接抗病毒药物(DAA)联合疗法极大地提高了慢性丙型肝炎病毒(HCV)感染患者的持续病毒学应答(SVR)率。SVR通常伴随着肝酶正常化,然而,即使HCV被根除,肝脏炎症,即转氨酶水平持续升高仍可能持续存在。目的:调查两个大型患者队列中SVR后持续肝脏炎症的患病率及危险因素。

方法

这项事后分析基于前瞻性收集的834例HCV治疗后获得SVR患者的人口统计学和临床数据,这些患者来自PRAMA试验中接受基于聚乙二醇干扰素(PegIFN)或DAA治疗方案治疗的患者(n = 341),或来自我们门诊治疗的患者(n = 493)。

结果

我们观察到SVR后炎症的患病率意外地高,包括接受新型无干扰素DAA疗法的患者。高达10%的患者转氨酶水平持续升高,另外25%的患者转氨酶活性高于所谓的健康范围。几个基线因素与SVR后转氨酶升高独立相关。其中,特别是男性、晚期肝病和肝脂肪变性标志物对ALT持续升高有很强的预测性。基于干扰素的抗病毒治疗的使用与SVR后炎症独立相关,进一步支持了无干扰素联合方案的总体益处。

结论

这是第一项对大型患者队列进行的全面研究,调查HCV根除后持续肝脏炎症的患病率及危险因素。我们的数据显示,尽管HCV已被根除,但仍有很大比例的患者存在持续肝脏炎症,这对SVR后约三分之一患者的管理可能有潜在影响。

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