How to differentiate Metabolic Associated Liver Disease (MetALD) from Metabolic Associated Steatohepatitis Liver Disease (MASLD)?

Differentiating MetALD from MASLD

The key distinction between MetALD and MASLD is based solely on alcohol consumption thresholds: MetALD is diagnosed when patients have hepatic steatosis with at least one cardiometabolic risk factor AND consume 20-50 g/day of alcohol in females or 30-60 g/day in males, whereas MASLD requires alcohol consumption below these thresholds (≤20 g/day in females, ≤30 g/day in males). 1

Diagnostic Algorithm

Step 1: Confirm Hepatic Steatosis

• Document hepatic steatosis by imaging (ultrasound, CT, MRI) or liver biopsy 1

Step 2: Assess Cardiometabolic Risk Factors

Both MetALD and MASLD require at least one of the following cardiometabolic criteria 1:

• Overweight/Obesity: BMI >25 kg/m² (>23 kg/m² in Asians) or elevated waist circumference 1
• Dysglycemia/Type 2 Diabetes: HbA1c ≥5.7%, fasting glucose ≥100 mg/dL, or 2-hour OGTT ≥140 mg/dL 1
• Hypertriglyceridemia: >150 mg/dL or on lipid-lowering treatment 1
• Low HDL-cholesterol: <39 mg/dL (men) or <50 mg/dL (women) or on treatment 1
• Hypertension: BP >130/85 mmHg or on antihypertensive treatment 1

Step 3: Quantify Alcohol Consumption (The Critical Differentiator)

Use detailed medical history, validated psychometric instruments, and/or biomarkers to assess current AND historical alcohol consumption patterns 1:

• MASLD: ≤20 g/day (females) or ≤30 g/day (males) 1
• MetALD: 20-50 g/day (females) or 30-60 g/day (males) 1
• ALD: >50 g/day (females) or >60 g/day (males) 1

Step 4: Exclude Other Causes

Rule out alternative etiologies of steatotic liver disease 1:

• Hepatitis C (especially genotype 3)
• Drug-induced liver disease (corticosteroids, tamoxifen, amiodarone, methotrexate, valproate)
• Monogenic diseases (hypobetalipoproteinemia, lipodystrophy, Wilson disease)
• Celiac disease, hypothyroidism, PCOS

Clinical Significance of the Distinction

Prognostic Differences

MetALD represents a distinct subclass with worse prognosis than MASLD despite sharing identical cardiometabolic risk factor prevalence 1:

• MetALD is associated with higher all-cause mortality compared to MASLD 1
• Alcohol-predominant MetALD patients have significantly higher risks of cirrhosis and mortality compared to cardiometabolic-predominant MetALD 2
• MetALD patients show intermediate infection rates (68.7%) between MASLD (87.3%) and ALD (56.1%) in decompensated cirrhosis 3

Treatment Implications

Diagnostic and treatment recommendations for MASLD cannot be directly extended to MetALD 1:

• MetALD requires alcohol cessation strategies, including medications for alcohol use disorder 4
• Most MASLD therapeutics have not been studied in patients with significant ongoing alcohol use 4
• Biopsychosocial interventions are essential for MetALD management 4

Practical Tools for Differentiation

Alcoholic Liver Disease/NAFLD Index (ANI)

The ANI can help distinguish between disease categories 5:

• MASLD: ANI <-3.5 (median -3.7) 5
• MetALD: ANI between -3.5 and -1.49 (median -1.45) 5
• ALD: ANI >-1.49 (median 0.71) 5
• ANI outperforms AST/ALT ratio (AUC 0.79-0.80 vs 0.75) and GGT (AUC 0.74) 5

Proteomic Profiling

A 10-protein model can differentiate alcohol-predominant from cardiometabolic-predominant MetALD with AUC 0.93, identifying patients at higher risk for cirrhosis and mortality 2

Common Pitfalls to Avoid

• Failing to quantify alcohol consumption accurately: Current drinking patterns may not reflect previous behavior; always obtain detailed lifetime alcohol history 1
• Relying solely on patient self-report: Use validated questionnaires (AUDIT-C) and consider biomarkers when available 1
• Assuming identical management: MetALD requires specific alcohol-focused interventions that differ from pure MASLD management 1, 4
• Ignoring the overlap: Approximately 40% of patients with steatotic liver disease consume some alcohol; careful categorization is essential 5