What are the diagnostic criteria for Metabolic Associated Steatohepatitis Liver Disease (MASLD)?

Diagnostic Criteria for Metabolic Associated Steatotic Liver Disease (MASLD)

The diagnosis of MASLD requires evidence of hepatic steatosis plus at least one metabolic risk factor, with no requirement to exclude other liver diseases as was previously necessary under the NAFLD definition. 1, 2

Primary Diagnostic Criteria

MASLD is diagnosed when the following criteria are met:

1. Evidence of hepatic steatosis detected by:

   • Imaging techniques (ultrasound, CT, MRI) 1
   • Controlled attenuation parameter (CAP) measurements 1
   • MRI-proton density fat fraction (MRI-PDFF) 1
   • Liver biopsy (if performed for other reasons) 1

2. PLUS at least one of the following metabolic risk factors:

   • Type 2 diabetes 1
   • Abdominal obesity 1
   • Presence of metabolic dysfunction (≥2 metabolic risk abnormalities) 1

Metabolic Risk Abnormalities

Metabolic dysfunction is defined by the presence of at least two of the following:

• Elevated waist circumference (population and country-specific definitions) 1
• Elevated blood pressure (>130/85 mmHg) or treatment for hypertension 1
• Elevated fasting triglycerides (≥1.70 mmol/L or ≥150 mg/dL) or treatment for hypertriglyceridemia 1
• Low HDL cholesterol (<1.0 mmol/L or <39 mg/dL in men; <1.3 mmol/L or <50 mg/dL in women) or lipid-lowering treatment 1
• Pre-diabetes (fasting glucose 5.6-6.9 mmol/L or 100-125 mg/dL, or 2-hour post-load glucose 7.8-11.0 mmol/L or 140-199 mg/dL, or HbA1c 5.7-6.4%) 1
• Insulin resistance assessment (e.g., HOMA-IR) 1

Diagnostic Algorithm

1. Initial Assessment:

   • Screen individuals with:
     • Type 2 diabetes OR
     • Abdominal obesity with ≥1 additional cardiometabolic risk factor OR
     • Persistently elevated liver enzymes 1

2. Multi-Step Diagnostic Approach:

   • First step: Use established non-patented blood-based score (e.g., FIB-4) 1
   • Second step: If FIB-4 is indeterminate (1.3-2.67) or high (>2.67), proceed with liver elastography (e.g., VCTE/FibroScan) or alternative tests 1
   • Alternative second step: Tests of specific collagen-related blood constituents (e.g., ELF) 1

3. Fibrosis Assessment Thresholds:

   • FIB-4: <1.3 (rule out advanced fibrosis); >2.67 (rule in advanced fibrosis) 1
   • VCTE: <8.0 kPa (rule out advanced fibrosis); >12 kPa (rule in advanced fibrosis) 1, 3
   • ELF: <7.7 (rule out advanced fibrosis); >9.8 (rule in advanced fibrosis) 1

Exclusion of Other Causes

Unlike the previous NAFLD definition, MASLD can coexist with other liver diseases. However, clinicians should still consider and evaluate for other causes of steatotic liver disease (SLD) when appropriate 1, 2:

• Hepatitis C virus (especially genotype 3) 1
• Drug-induced liver disease 1
• Hypobetalipoproteinaemia 1
• Lipodystrophy 1
• Lysosomal acid lipase deficiency 1
• Wilson disease 1
• Endocrine diseases (hypothyroidism, PCOS, GH deficiency) 1

Important Clinical Considerations

• Liver biopsy is not required for routine clinical management of MASLD but remains the gold standard for definitive diagnosis of steatohepatitis (MASH) and fibrosis staging 1

• Non-invasive tests cannot assess microscopic features like ballooning or lobular inflammation that define MASH 1

• Genetic testing may be considered in specialized centers for personalized risk stratification, especially for individuals with:

  • Strong family history of severe liver disease in first-degree relatives 1
  • Early presentation with severe phenotype 1
  • Normal body weight without obvious metabolic triggers 1

• Assessment of comorbidities (T2DM, dyslipidemia, hypertension, kidney disease, sleep apnea, PCOS) and cardiovascular risk is essential in all adults with MASLD 1

Pitfalls to Avoid

• Do not rely solely on liver enzymes for diagnosis, as they can be normal in MASLD 3
• FIB-4 thresholds need adjustment for age (for patients >65 years, lower FIB-4 cut-off is 2.0) 1
• Elastography techniques have limitations in patients with ascites, obesity, narrow intercostal spaces, acute hepatitis, or extrahepatic biliary obstruction 3
• Remember that 18-43% of patients with normal ALT levels may have significant fibrosis, particularly those older than 35-40 years 3
• Sequential testing using FIB-4 followed by elastography is more accurate than using either test alone 3