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Review
. 2018 Mar 28;6(1):89-96.
doi: 10.14218/JCTH.2017.00054. Epub 2017 Dec 17.

Alcoholic Hepatitis: Lost in Translation

Benjamin L Woolbright  1 , Hartmut Jaeschke  1
Affiliations
Review

Alcoholic Hepatitis: Lost in Translation

Benjamin L Woolbright et al. J Clin Transl Hepatol. .

Abstract

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 in vitro and in vivo 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.

Keywords: Alcohol; Alcoholic hepatitis; Cirrhosis; Keratin-18; Liver disease; Prognosis.

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Conflict of interest statement

The authors have no conflict of interests related to this publication.

Figures

Fig. 1.
Fig. 1.. Ratio of K18 (M65) to plasma alanine aminotransferase (ALT) activity compiled from multiple studies.
K18:ALT was calculated in a series of studies on different clinically relevant liver diseases. Acetaminophen (APAP) data are derived from Antoine et al.; obstructive cholestasis data are derived Woolbright et al.; alcoholic cirrhosis (AC) and alcoholic hepatitis data are derived from Woolbright et al.
Fig. 2.
Fig. 2.. Disease severity in patients versus alcohol model progression.
A majority of models fail to recapitulate the disease severity observed in AH patients.. Abbreviations: ACLF, acute-on-chronic liver failure; AH, alcoholic hepatitis; HCC, hepatocellular carcinoma.
See this image and copyright information in PMC

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