What are the diagnostic criteria for Metabolic Associated Fatty Liver Disease (MAFLD)?

MAFLD Diagnostic Criteria

MAFLD (Metabolic dysfunction-Associated Fatty Liver Disease) is diagnosed when hepatic steatosis is present PLUS at least one of three metabolic criteria: overweight/obesity (BMI ≥25 kg/m²), type 2 diabetes mellitus, or evidence of metabolic dysregulation (defined as ≥2 metabolic risk abnormalities). 1

Core Diagnostic Framework

The diagnosis of MAFLD represents a paradigm shift from the older NAFLD terminology by using positive inclusion criteria rather than exclusion criteria, meaning you do not need to rule out other liver diseases or quantify alcohol consumption to make the diagnosis. 1, 2

Step 1: Demonstrate Hepatic Steatosis

Evidence of hepatic steatosis can be established through:

• Imaging modalities: Ultrasound, CT, or MRI are acceptable first-line methods 2
• Advanced quantitative techniques:
  • Controlled attenuation parameter (CAP) via FibroScan 2
  • MRI-proton density fat fraction (MRI-PDFF) 2
• Liver biopsy: Remains the gold standard but reserved for cases where performed for other clinical indications 2

Step 2: Confirm Metabolic Dysfunction

You must document at least ONE of the following three criteria: 1, 2

Criterion A: Overweight or Obesity

• BMI ≥25 kg/m² in Caucasians
• BMI ≥23 kg/m² in Asians (population-specific thresholds apply) 2

Criterion B: Type 2 Diabetes Mellitus

• Established diagnosis of type 2 diabetes 1

Criterion C: Evidence of Metabolic Dysregulation

Requires ≥2 of the following metabolic risk abnormalities: 2

• Elevated waist circumference: Population and country-specific definitions (e.g., >102 cm in men, >88 cm in women for Caucasians) 2
• Elevated blood pressure: ≥130/85 mmHg or on antihypertensive treatment 2
• Elevated fasting triglycerides: ≥150 mg/dL or on lipid-lowering therapy 2
• Low HDL cholesterol: <40 mg/dL in men, <50 mg/dL in women, or on treatment 2
• Prediabetes: Fasting glucose 100-125 mg/dL or HbA1c 5.7-6.4% 2
• Insulin resistance: HOMA-IR ≥2.5 or other validated measures 2

Critical Distinction from NAFLD

MAFLD does NOT require exclusion of: 1, 3

• Concurrent alcohol consumption (unless meeting criteria for alcohol-associated liver disease)
• Viral hepatitis
• Other coexisting liver diseases

This represents a fundamental departure from NAFLD criteria, which mandated exclusion of "significant" alcohol intake and other liver diseases. 4, 3

Practical Clinical Algorithm

For case-finding in clinical practice: 5

1. Screen high-risk populations: Individuals with type 2 diabetes, obesity (BMI ≥30 kg/m²), or metabolic syndrome 2

2. Initial assessment: Check for hepatic steatosis via ultrasound or CAP in patients with ≥1 cardiometabolic risk factor 5

3. Confirm metabolic criteria: Document which of the three main criteria (A, B, or C above) are present 1

4. Assess fibrosis risk: Use FIB-4 score as initial non-invasive test 2

   • FIB-4 <1.3: Low risk, routine follow-up
   • FIB-4 1.3-2.67: Indeterminate, proceed to elastography
   • FIB-4 >2.67: High risk, refer to hepatology 2

5. Secondary fibrosis assessment (if FIB-4 indeterminate/elevated): 2

   • Vibration-controlled transient elastography (VCTE): <8 kPa rules out, >12 kPa rules in advanced fibrosis
   • MR elastography: Most accurate non-invasive method 4

Essential Comorbidity Assessment

At initial diagnosis and regular intervals, evaluate: 4

• Type 2 diabetes screening (HbA1c, fasting glucose, OGTT if indicated) 4
• Lipid panel (total cholesterol, LDL, HDL, triglycerides) 4
• Blood pressure measurement 4
• Renal function (eGFR, urinalysis for proteinuria) 4
• Obstructive sleep apnea screening (STOP-BANG questionnaire) 4
• Polycystic ovary syndrome assessment in women of reproductive age 4
• 10-year cardiovascular risk calculation 4

Common Pitfalls to Avoid

• Do not exclude MAFLD diagnosis based on alcohol consumption alone; the new criteria allow for concurrent modest alcohol use unless ALD criteria are met 3
• Do not rely solely on ALT/AST levels: Normal transaminases do not exclude MAFLD or advanced fibrosis 5
• Do not assume lean patients cannot have MAFLD: Approximately 5% of MAFLD patients have normal BMI but meet metabolic dysregulation criteria 1, 6
• Do not use MAFLD diagnosis as a prognostic marker alone: The presence of metabolic comorbidities (especially diabetes) and fibrosis stage drive outcomes more than the MAFLD label itself 7

Terminology Note

MAFLD has replaced the older term "NAFLD" in most international guidelines as of 2020, though evidence from NAFLD studies remains applicable since 99.8% of NAFLD patients meet MAFLD criteria. 3 The term MASLD (Metabolic dysfunction-Associated Steatotic Liver Disease) is now preferred by some societies including EASL and AASLD as of 2023-2024, but uses identical diagnostic criteria. 4, 3