Diagnosis and Treatment of Alcohol‐Associated Liver Diseases: 2019 Practice Guidance From the American Association for the Study of Liver Diseases

Abstract

Supported by the American Association for the Study of Liver Diseases. Potential conflict of interest: Dr. Lucey received grants from Gilead, AbbVie and Pharmasolutions. Dr. Szabo consults and received grants from Allergan. She consults for Terra Firma, Glympse, Quest, Arrow, GLG, Salix and Tobira. She received grants from Gilead, Genfit, Intercept, Verlyx, Novartis, SignaBlok and Shire. She holds intellectual property rights with Up to Date. Purpose and Scope of the Guidance Alcohol‐associated liver disease (ALD) represents a spectrum of liver injury resulting from alcohol use, ranging from hepatic steatosis to more advanced forms including alcoholic hepatitis (AH), alcohol‐associated cirrhosis (AC), and acute AH presenting as acute‐on‐chronic liver failure. ALD is a major cause of liver disease worldwide, both on its own and as a co‐factor in the progression of chronic viral hepatitis, nonalcoholic fatty liver disease (NAFLD), iron overload, and other liver diseases. ALD develops through several stages, beginning with hepatic steatosis, and, in some individuals, gradually progressing through AH (the histological correlate of which is alcoholic steatohepatitis), culminating in cirrhosis (Fig. 1).1 Progression through these various stages is dependent on continued heavy alcohol use and other risk factors, including female sex, genetic susceptibility, diet, and comorbid liver disease. ALD carries a significant stigma in society. It is increasingly recognized by providers that patients and their families seek to reduce the stigma of ALD, and a change from the term “alcoholic” to “alcohol‐associated” will help; thus, alcohol‐associated liver disease, alcohol‐associated steatohepatitis, and alcohol‐associated cirrhosis are suggested, retaining the familiar abbreviations (ALD, ASH, and AC, respectively). Due to longstanding usage, the term “alcoholic hepatitis” will likely persist.Figure 1: Natural history of alcohol‐associated liver disease. Images courtesy of Dr. M. Isabel Fiel.This 2019 ALD Guidance provides a data‐supported approach to the prevalence, clinical spectrum, diagnosis, and clinical management of ALD and alcohol use disorders (AUDs). The Guidance was developed by consensus of an expert panel and provides guidance statements based on formal review and analysis of published literature on the topics. The quality (level) of the evidence and the strength of each guidance statement are not formally rated. Updates to the 2010 Guideline include an emphasis on AUD definition, screening, and treatment; new alcohol biomarkers; additional genetic and environmental susceptibility factors; a consensus definition of AH, and review of recent studies of corticosteroids and guidance on the role of transplantation in the management of AH. Prevalence and Burden of Alcohol‐Associated Liver Disease Alcohol‐associated liver disease includes a variety of clinical disorders: steatosis, ASH, AH of varying degrees of severity, AC, and AC complicated by hepatocellular carcinoma (HCC). ALD comprises a substantial portion of the overall cirrhosis burden, both in the United States and worldwide, and is responsible for rising rates of liver‐related mortality in the United States, especially among younger patients.3 In the United States, mortality due to all ALD was estimated at 5.5 per 100,000 in 2012; the relative contribution of ALD to all cirrhosis mortality is predicted to increase as the proportion of deaths due to hepatitis C virus (HCV) cirrhosis declines.3 More recently, AC mortality was shown to have increased from 2008 to 2016, particularly among patients ages 25‐34 years old.4 Cirrhotic and noncirrhotic ALD prevalence has been estimated at approximately 2% in the AC in the was estimated at per 100,000 In AC has been estimated at approximately per 100,000 and, rates are to AC deaths for of all and of deaths are due to liver disease, resulting in the of years In the United States, ALD with chronic as the for liver transplantation are for AC, in by the of for these In deaths to alcohol use are due to the stigma of alcohol use and of in In AC prevalence at a in the in alcohol use in in the United The of AH has been to as of is for The of AH In the United States, for AH to have increased to of all for In the of AH for the from to per per in and to per per for in increased rates for AH from to per per for and from to per per for In both of these based on which and the in the of AH. of the spectrum of ALD prevalence is particularly the with stages of ALD, as AH, that with use of steatosis and and increased for the to disease. studies the prevalence and by as ALD patients additional liver as in of the that ALD rates are as as in some patients with other liver in nonalcoholic and in as as a for of of the and the of alcohol and have been by the term use as based on the of and use is in the United States, with significant more forms of by alcohol to and the of alcohol are on the of AUD and have with the prevalence of AUD in of by and with among and of The of alcohol and the prevalence of more more the with substantial for of and alcohol with the rates of per alcohol in and and for in the is in a The of at of these an more is a to alcohol of is in to use from its a to use alcohol use resulting in a to major role at alcohol use by the of are of alcohol alcohol use in in which is use is continued of a that is likely to have been by as of the for increased of alcohol to with continued use of the of as by of the The alcohol a as a is to and to The approach to the of alcohol use is and to with for and the of alcohol of alcohol use for a and and and of The of AUD and ALD not particularly in stages of The on and has published a for to alcohol use more and more to for on to patients with ALD is of alcohol for patients with the has published its in and and The statement for alcohol use in in years including and in with to reduce alcohol to alcohol use are by the use of The a in the have more in a more in a is the definition of in in the a the is The is and is by the on and alcohol‐associated with a of alcohol use, and of alcohol are (the as a more of for alcohol use, not on more alcohol use The is and the and other in alcohol of at alcohol not a of to the for a formal The and to for the a more of in and has been shown to patients with ALD and by with a of the for liver disease, for alcohol alcohol use of and in the heavy ALD diagnosis, and to of use of as has been shown to as as the to clinical including for alcohol‐associated of of alcohol use to in which of alcohol use and an estimated of recent The American of and American Association the use of alcohol as an to diagnosis, to and as for with the as to of use include use with patients to and alcohol use of the alcohol has not on their own to alcohol use, with other other alcohol and the clinical evidence of alcohol use, on their own are to alcohol use in is an in the of several including liver and is in heavy and has is not for alcohol is as a of alcohol of as the of per to for in has a of The of is by its of in several studies and by in patients with liver disease in the of alcohol use of to more likely due to liver of alcohol is by and and are in the are in and and have been and of for of alcohol use and among patients with ALD and studies in patients with of liver disease, including of and for of the for and with of and and in resulting in a of alcohol in patients with disease. is a by the of with by in the has a of approximately with more heavy alcohol and not to by sex, disease, liver have for a of alcohol with are in has been in a of chronic liver disease patients not at a of for per more with a of and of of use in patients with ALD and a of and of for a of The of the for alcohol use are in and of of in Liver and of and and of significant to More all studies the that with alcohol studies on patients and of of in Liver of in with Liver Disease and Liver and Guidance patients in and and for alcohol use and to to patients in to in and and and 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with AH and In are several with some in that have not been for AUD include and a is the AUD that has been in an in patients with AC with AUD as as in In a of patients with both and AC, a of in rates of alcohol and with the of an patients with hepatic from as a that in more advanced liver disease. on and in the of an not to to the liver and is in Liver Disease and of ALD in patients with ALD in patients with ALD of through at in patients with ALD for and in patients with ALD in patients with ALD from for AUD is not on is not for use in patients with and per Guidance to AUD is for patients with advanced ALD to to the of AUD management of ALD and AUD is and rates of alcohol among patients with on the use of for the of AUD in patients with and for Alcohol‐Associated Liver Disease the of heavy alcohol use worldwide, is that a of heavy significant liver disease. 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