Liver Transplantation

Abstract
Importance: Alcohol-related liver disease (ALD) is the leading cause of liver-related morbidity and mortality, and the most common indication for liver transplant in Europe and the US. In the US, ALD-related mortality increased from 6.7 deaths per 100 000 people in 1999 to 12.5 deaths per 100 000 people in 2022.

Observations: ALD can develop with long-term daily alcohol consumption of more than 20 g per day for women (1.4 standard drinks/d) and more than 30 g per day for men (2.1 standard drinks/d), with 1 standard drink containing 14 g of ethanol, equivalent to approximately 12 oz of beer, 5 oz of wine, or 1.5 oz of distilled spirits. ALD encompasses reversible steatosis; steatohepatitis, which can cause alcohol-associated hepatitis; and fibrosis, which can cause cirrhosis, portal hypertension, hepatic decompensation, and hepatocellular carcinoma. Risk factors for ALD progression include increased quantity and duration of alcohol use, female sex, older age, obesity, type 2 diabetes, metabolic syndrome, smoking, viral hepatitis, and specific genetic variants. Most patients with ALD (90%) are asymptomatic or have nonspecific symptoms, such as fatigue. Alcohol-associated hepatitis often causes fever, anorexia, nausea, vomiting, abdominal pain, and jaundice. Individuals with decompensated cirrhosis typically have ascites, variceal bleeding, jaundice, and/or hepatic encephalopathy. Noninvasive liver fibrosis tests, such as the Fibrosis-4 score (which includes alanine transaminase, aspartate aminotransferase, platelet count, and age), and more specific second-line tests, including liver stiffness measurement (vibration-controlled transient elastography) and blood-based fibrosis markers such as the enhanced liver fibrosis test and N-terminal propeptide of type III collagen, provide early diagnosis of ALD and assess liver fibrosis severity, which is the strongest predictor of liver-related outcomes. Alcohol cessation interventions such as motivational enhancement therapy, cognitive behavioral therapy, and pharmacologic therapy (eg, baclofen, naltrexone) are recommended to prevent disease progression. Because alcohol consumption is often underreported, screening tools, such as the Alcohol Use Disorders Identification Test, and sensitive biomarkers of recent alcohol intake (eg, blood phosphatidylethanol) may improve clinical accuracy. Sustained abstinence from alcohol is the primary treatment for ALD. Among patients with alcohol-related cirrhosis, alcohol abstinence over a median follow-up of 36 months was associated with reduced risk of liver-related mortality (adjusted hazard ratio, 0.43 [95% CI, 0.26-0.70]) and all-cause mortality (adjusted hazard ratio, 0.45 [95% CI, 0.30-0.67]). Liver transplant evaluation should be considered for patients with severe alcohol-associated hepatitis or decompensated cirrhosis.

Conclusions and Relevance: People with chronic daily heavy alcohol consumption should be assessed for ALD with noninvasive testing. The primary treatment goal is alcohol cessation. Patients with severe alcohol-associated hepatitis or decompensated cirrhosis should be considered for liver transplant.