Met-ALD and Liver Transplantation: Navigating Treatment Options

Met-ALD and Liver Transplantation: Navigating Treatment Options

Summary of CME Lecture by Juan Pablo Arab, MD

1. Main Clinical Topics Discussed

• Global burden of steatotic liver disease (SLD), including metabolic dysfunction-associated steatotic liver disease (MASLD) and alcohol-associated liver disease (ALD)
• New nomenclature and definition of MetALD — a novel, distinct clinical entity representing the overlap of metabolic dysfunction and significant alcohol consumption
• Pathophysiology of dual-etiology liver disease
• Risk stratification, natural history, and disease progression in MetALD vs. MASLD vs. ALD
• Clinical assessment and management framework, including liver transplantation considerations

2. Key Learning Points, Guidelines, and Recommendations

New Disease Classification

• Steatotic Liver Disease (SLD) serves as the overarching umbrella term encompassing MASLD, ALD, and MetALD
• MetALD is defined by the coexistence of metabolic dysfunction criteria (aligned with metabolic syndrome definitions used in endocrinology) and significant alcohol consumption that does not meet full ALD diagnostic thresholds
• Clinicians receiving a referral for "fatty liver" must systematically work up all contributing etiologies before assigning a diagnosis

Alcohol Consumption Thresholds (Revised Guidance)

• Low risk: <2 drinks per week (for both males and females) — a dramatic revision from prior guidance of ≤1/day for females, ≤2/day for males
• High risk: >7 drinks per week (both sexes)
• Moderate risk: Between low and high thresholds
• Zero risk = zero alcohol; no truly "safe" level has been established, particularly for individuals >60 years of age
• Canada updated national guidelines in 2023 to reflect this substantially lower threshold

Clinical Assessment Recommendations

• Quantify alcohol intake precisely — terms such as "social drinker" or "occasional drinker" are clinically insufficient and should be avoided
• Screen all patients with suspected SLD for hepatic fibrosis
• Assess for metabolic risk factors using established metabolic syndrome criteria

3. Specific Clinical Data, Statistics, and Study Results Cited

Disease Burden

• MASLD prevalence: ~32–38% globally (consistent across multiple large studies)
• ALD prevalence: ~1.1% (likely underestimated; alcohol use disorder affects ~6% of the U.S. population)
• MetALD prevalence: ~2.2–2.6% (two recent studies using similar but slightly differing criteria)
• MASLD is the #1 cause of liver transplantation in females; ALD is #1 in males — both indications are increasing
• Obesity rates (USA): ~10% in 1975 → ~35% currently (>3-fold increase), with parallel rise in MASLD prevalence (Lasso et al., 2008)
• Cirrhosis is among the leading causes of potential years of working life lost in every global region, including the Americas (WHO data)

Alcohol Consumption Data

• Global average: 6.4 liters of pure alcohol per capita/year
• Europe: highest at 12 liters/capita/year
• Americas: ~8 liters; USA specifically: 9.8 liters/capita/year (data from 2016, published 2018)
• *Lancet* 2018 publication: risk begins with 1 drink/day, no safe threshold
• *Lancet* 2022 follow-up: individuals <60 years may have marginal protection at very low intake; those >60 have no safe threshold

Natural History and Progression Rates

• Heavy alcohol use → 90–95% develop steatosis; steatosis can develop within 1 week of heavy drinking in healthy individuals
• 20–40% of heavy drinkers develop fibrosis; 8–20% progress to cirrhosis
• 5-year decompensation risk by fibrosis stage:

- MASLD, F0: ~1%

- MASLD, F4: 5–15%

- ALD, F0: 2–15%

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