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

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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 general US population, whereas AC in the US Veterans' population was estimated at 327 per 100,000 enrollees.7 In privately insured US patients, AC has been estimated at approximately 100 per 100,000 enrollees, and, overall, rates are projected to rise over time.3 Worldwide, AC deaths account for about 10% of all alcohol‐attributable deaths, and nearly half of those deaths are due to liver disease, resulting in the loss of 22.2 million disability‐adjusted life years annually.10 In the United States, ALD competes with chronic HCV as the leading indication for liver transplantation (LT).12 Medical costs are high for AC, driven in part by the higher number of admissions for these patients.9 In addition, deaths related to alcohol use are frequently underestimated due to the stigma of alcohol use and lack of candor in reporting.10 In women, AC prevalence may be increasing at a faster rate than in men, mirroring the rise in alcohol use in women in the United States.9 The incidence of AH has been difficult to estimate, as diagnostic accuracy of administrative coding is less reliable for AH.15 The incidence of AH varies worldwide. In the United States, admissions for AH were found to have increased to 0.83% of all admissions for 2010.13 In Denmark, the incidence of AH for the period 1999‐2008 rose from 37 to 46 per million persons per year in men and 24 to 34 per million persons per year for women.17 A similar study in Finland reported increased incidence rates for AH from 37 to 65 cases per million persons per year for men and from 13 to 27 cases per million persons per year for women.18 In both of these cases, estimates were based on diagnostic coding, which may be less accurate and highlights the difficulty in estimating the burden of AH. Accurate assessment of the full spectrum of ALD prevalence is challenging, particularly given the difficulty with identifying earlier, asymptomatic stages of ALD, such as ASH AH, that may be with use of steatosis and assessment and increased for the to disease. studies the prevalence and burden by as ALD those patients additional liver such as in of the that ALD rates are as high as in some patients with other liver in nonalcoholic and may 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 US increasing by and with reported among women, and those of The of alcohol and the prevalence of more more over the period with substantial for of and Worldwide, alcohol varies with the rates of reported per alcohol in and and for in the is in over a period than The of at of these an more is a to alcohol A 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 given 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 related such 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 be for patients, may a and and and of The of AUD and ALD may not be particularly in stages of The on and has published a for to alcohol use more and more cases to for on to general than patients with ALD is of alcohol for patients with the US has published its in and and The statement for alcohol use in in years including women, and persons in with to reduce alcohol to alcohol use are by the use of The a in the year have more in a more in a is the definition of in in women over the a the is The is and is by the on and alcohol‐associated with a than of alcohol use, and than of alcohol are (the as a more of for alcohol use, not on more alcohol use The is and than the and other in identifying alcohol of at may alcohol not a of to the for a formal The and to for the general a more of in general and has been shown to patients with ALD and by with a of the for liver disease, may be for alcohol alcohol use of and in the heavy ALD diagnosis, and to of use of such 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 e

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