Controversies in clinical trials for alcoholic hepatitis
Controversies in clinical trials for alcoholic hepatitis
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DOI：
10.1016/j.jhep.2017.09.013
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发表时间：
2018-03-01
影响因子：
25.7
通讯作者：
Bataller, Ramon
中科院分区：
文献类型：
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作者：
Lieber, Sarah R.;Rice, John P.;Bataller, Ramon
酒精性肝炎(AH)是酒精性肝病中最严重的一种，导致严重的发病率和死亡率。然而，唯一可以提高存活率的治疗方法是皮质类固醇和肝移植，几十年来一直没有成功开发出新药。本文简要描述了急性呼吸窘迫综合征治疗的现状，并探讨了在重度急性呼吸窘迫综合征患者中进行对照试验所面临的实际和伦理挑战。虽然强的松龙被认为是重症急性肝炎的标准治疗方法，但考虑到类固醇的边际益处和可疑的长期安全性，这一建议仍然存在争议。没有类固醇的安慰剂对照试验在某些没有得到充分研究的急性肝炎患者中可能是必要的，而且在伦理上是合理的。最终，我们建议该领域将随着真实急性肝炎可信动物模型的发展，在不完全依赖死亡率的复合临床终点上达成共识，以及采纳NIAAA酒精性肝炎联合会关于标准定义和何时在研究进入之前请求肝脏活检的建议。(C)2017年欧洲肝脏研究协会。爱思唯尔出版，版权所有。
Alcoholic hepatitis (AH) is the most severe form of alcoholic liver disease, contributing to significant morbidity and mortality. Yet, the only available therapies that improve survival are corticosteroids and liver transplantation, with no new drugs successfully developed for decades. This article briefly describes the current state of affairs in AH therapy and examines the practical and ethical challenges of conducting controlled trials in patients with severe AH. While prednisolone is considered standard of care in severe AH, this recommendation remains controversial given the marginal benefits and questionable long-term safety of steroids. Placebo-controlled trials without steroids may be necessary and ethically justified in certain populations with AH who have not been adequately investigated. Ultimately, we suggest that the field will advance with the development of a plausible animal model of true AH, a consensus on a composite clinical endpoint that does not rely solely on mortality, as well as the adoption of the NIAAA Alcoholic Hepatitis Consortia recommendations regarding standard definitions and when to request a liver biopsy prior to study entry. (C) 2017 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.