酒精性肝炎:翻译中的困境
Alcoholic Hepatitis: Lost in Translation.
作者信息
Woolbright Benjamin L, Jaeschke Hartmut
机构信息
Department of Pharmacology, Toxicology & Therapeutics, University of Kansas Medical Center, Kansas City, Kansas, USA.
出版信息
J Clin Transl Hepatol. 2018 Mar 28;6(1):89-96. doi: 10.14218/JCTH.2017.00054. Epub 2017 Dec 17.
Alcoholic hepatitis is the most severe and acute form of alcoholic liver disease. The mortality rate associated with alcoholic hepatitis is high, largely due to the lack of suitable pharmacological interventions. While there has been substantial research in the area, generating pharmacological interventions has been plagued by the lack of a robust mouse model both for testing and for understanding the underlying pathology. A number of major notable advances have been made in this area recently, with the goal of generating a mouse model of alcoholic hepatitis. The purpose of this article is to review recent advances in modeling alcoholic liver disease both and in the mouse, and place them in the context of the greater spectrum of alcoholic liver disease, with a focus on how we can translate current advances into a high-fidelity model of alcoholic hepatitis. In addition, we will review the basic mechanisms of alcoholic hepatitis as it is currently understood, focusing on recent advancements in diagnosis, prognosis and current pathophysiology, especially as it relates to the profound immune dysfunction present during alcoholic hepatitis.
酒精性肝炎是酒精性肝病最严重和急性的形式。与酒精性肝炎相关的死亡率很高,这主要是由于缺乏合适的药物干预措施。尽管该领域已经进行了大量研究,但由于缺乏用于测试和理解潜在病理的强大小鼠模型,开发药物干预措施一直受到困扰。最近在这一领域取得了一些重大进展,目标是建立酒精性肝炎的小鼠模型。本文的目的是回顾在小鼠中建模酒精性肝病的最新进展,并将其置于更广泛的酒精性肝病范围内,重点关注如何将当前进展转化为酒精性肝炎的高保真模型。此外,我们将回顾目前所理解的酒精性肝炎的基本机制,重点关注诊断、预后和当前病理生理学的最新进展,特别是与酒精性肝炎期间存在的严重免疫功能障碍相关的进展。