Diagnosing alcohol-associated liver disease has two parts: recognising harmful drinking, and characterising the liver injury it has caused.
Recognising harmful drinking
The first step in the diagnosis of any alcohol-associated disorder, including alcohol-associated liver disease (ALD), is recognising harmful drinking. Asking directly is the most effective single step: “How many times during the last year have you had 5 or more drinks in a day, or 4 or more in the case of a woman?” A positive answer should prompt a structured questionnaire such as the Alcohol Use Disorders Identification Test (AUDIT) or its short form, AUDIT-C.
Laboratory tests are limited by how quickly alcohol and its metabolites are eliminated, so they detect only recent drinking. The classic biomarker is carbohydrate-deficient transferrin (CDT). Transferrin is made by the liver and heavily modified with carbohydrate residues, especially sialic acid; heavy drinking reduces this modification, so transferrin molecules that lack carbohydrate circulate, and they have a long half-life. These features make CDT specific for recent heavy drinking, but its sensitivity is low (about 25–50%), and it can be raised in severe liver disease without any drinking. Newer markers avoid some of these problems: urinary ethyl glucuronide detects drinking in the past 3 days, and blood phosphatidylethanol (PEth) detects drinking over 2–3 weeks and is not affected by liver disease. A combination of CDT with mean corpuscular erythrocyte volume (MCV) and serum gamma-glutamyl transpeptidase (GGTP) is more sensitive and specific than CDT alone.
Working definitions of alcohol-associated hepatitis
By consensus, alcohol-associated hepatitis can be described in three tiers:
- definite alcohol-associated hepatitis — when there is liver biopsy evidence
- probable alcohol-associated hepatitis — when laboratory and clinical features are present without any confounding cause
- possible alcohol-associated hepatitis — when laboratory and clinical features are present with a confounding cause
The syndrome itself, its severity scoring and its treatment are described in Alcohol-Associated Hepatitis.
Differential diagnosis
Although the clinical and histological signs of ALD are quite sensitive, they overlap with other liver disorders, which can make the differential difficult:
- NAFLD — the hardest condition to separate, because the histological and clinical findings are very similar; the key step is determining the patient’s alcohol use.
- hemochromatosis — severe ALD can mimic hereditary hemochromatosis, with elevated serum iron, elevated ferritin and increased hepatic iron deposition; the best test for separating the two is genetic testing for HFE.
- Budd-Chiari syndrome
Treatment
Abstinence from alcohol is the single most important factor for survival in ALD, and all patients should be advised to stop drinking completely. Because alcohol use is itself the cause, treating the alcohol use disorder is part of treating the liver disease. Integrated, multidisciplinary care with addiction specialists improves abstinence, and pharmacotherapy can help:
- acamprosate and baclofen can be considered in patients with ALD; baclofen is the only medication tested in a randomised trial in cirrhosis
- naltrexone is effective in general use but is metabolised by the liver and carries hepatotoxicity concerns; disulfiram is not recommended in ALD
Nutritional support matters because protein-calorie malnutrition is common and predicts worse outcomes. Enteral nutrition is preferred over parenteral, and thiamine and other micronutrients should be replaced.
For patients whose disease has reached cirrhosis, management follows that of cirrhosis in general, treating ascites, varices, hepatic encephalopathy and spontaneous bacterial peritonitis as they arise.
Liver transplantation is the definitive treatment for decompensated alcohol-associated cirrhosis. Referral should be considered for new decompensation, a Model for End-Stage Liver Disease (MELD) score of 21 or more, or Child-Pugh class C. A fixed six-month period of abstinence is no longer required to be considered for transplant; the assessment instead weighs addiction history, social support and insight into the illness. For patients with severe alcohol-associated hepatitis who do not respond to medical treatment, early liver transplantation is considered under the criteria described in Alcohol-Associated Hepatitis.