Controversies in Alcohol-Associated Liver Disease

Overview

This lecture by Prof. Gene Im provides a comprehensive review of alcohol-associated liver disease (ALD), covering its epidemiology, diagnosis, management of alcohol use disorder (AUD), and emerging therapeutic strategies, with emphasis on reducing stigma and improving clinical outcomes.

Key Clinical Topics

• Epidemiology and rising mortality trends in ALD
• Definitions, stigma reduction, and diagnostic criteria for AUD
• Diagnosis and fibrosis assessment in ALD
• Pharmacological and behavioral treatment of AUD
• Management of alcohol-associated hepatitis (AH)
• Emerging therapies and future directions

Key Learning Points

• Alcohol use disorder (AUD): Diagnosed using DSM-5 criteria, classified as mild, moderate, or severe; terminology has shifted away from "alcoholic" to reduce patient stigma
• AUDIT-C and SASQ: Validated screening tools for identifying harmful alcohol use in clinical settings
• PEth testing: Standard biomarker for objectively assessing alcohol use in ALD diagnosis and monitoring
• Liver fibrosis assessment: Evaluated using blood-based tests and imaging; accuracy may be reduced in the presence of inflammation or obesity
• Alcohol-associated hepatitis (AH): Presents with jaundice, coagulopathy, and characteristic laboratory findings; often requires inpatient admission
• Corticosteroids: Remain the mainstay of treatment for severe AH; response is assessed using the Lille score
• Infections, AKI, and ACLF: Key complications requiring close monitoring during AH management and influencing prognosis
• Naltrexone and acamprosate: FDA-approved pharmacotherapies for AUD; no liver-specific drugs are currently approved for ALD
• GLP-1 receptor agonists (e.g., semaglutide): Emerging agents showing promise in reducing heavy alcohol consumption
• Liver transplantation: An option for carefully selected patients with severe AH, with recent evidence supporting early transplantation
• Integrated multidisciplinary care: Associated with reduced relapse rates and improved mortality in ALD patients
• Hidden alcohol use in MASLD: Many cases of suspected metabolic-associated steatotic liver disease (MASLD) may involve underestimated alcohol consumption

Clinical Data & Study Results

• ALD and liver transplantation: ALD is cited as the primary indication for liver transplantation in the US
• AUD treatment utilization: Only a small percentage of eligible patients receive pharmacological therapy or formal behavioral treatment
• GLP-1 receptor agonists: Preliminary data suggest semaglutide reduces heavy drinking episodes, though large-scale ALD-specific trials are ongoing
• Cirrhosis mortality: Deaths from cirrhosis in the US have risen significantly, correlating with increasing alcohol consumption trends
• Risk stratification: Women and older adults are at disproportionately higher risk of ALD at equivalent levels of alcohol intake

Practical Takeaways

• Screen all patients with liver disease for AUD using AUDIT-C or SASQ, and consider PEth for objective alcohol use confirmation
• Offer naltrexone or acamprosate to eligible ALD patients with AUD, as these therapies remain underutilized despite established efficacy
• Monitor patients with severe AH on corticosteroids closely using the Lille score at day 7 to guide continuation or discontinuation
• Implement antibiotic prophylaxis and vigilant surveillance for infection, AKI, and ACLF in hospitalized AH patients
• Consider referral for early liver transplantation in select severe AH patients who fail medical therapy
• Adopt person-first, non-stigmatizing language and pursue multidisciplinary team-based care to improve engagement and long-term outcomes