What is the recommended medical workup for MAFLD (Metabolic Associated Fatty Liver Disease) de novo?

Medical Workup for MASLD De Novo

The recommended medical workup for MASLD (Metabolic dysfunction-associated steatotic liver disease) should follow a multi-step approach starting with blood-based fibrosis scores followed by liver elastography to assess fibrosis stage, which is the key determinant of prognosis and management. 1

Initial Assessment

Step 1: Risk Factor Identification

• Identify cardiometabolic risk factors:
  • Type 2 diabetes
  • Abdominal obesity with ≥1 additional metabolic risk factor
  • Abnormal liver function tests
  • Hypertension (>130/85 mmHg)
  • Dyslipidemia (elevated triglycerides, low HDL)

Step 2: Exclusion of Alternative Etiologies

• Alcohol consumption assessment:
  • Use validated instruments/biomarkers to quantify intake
  • MASLD definition: <140g/week for women, <210g/week for men 1
• Rule out other causes of hepatic steatosis:
  • Viral hepatitis (especially HCV)
  • Drug-induced liver injury
  • Genetic disorders (Wilson's disease, hypobetalipoproteinemia)
  • Malnutrition or rapid weight loss

Fibrosis Assessment

Step 3: First-Line Non-Invasive Testing

• Blood-based fibrosis scores 1:
  • FIB-4 index (first choice):
    • Low risk: <1.3
    • Indeterminate risk: 1.3-2.67
    • High risk: >2.67
  • APRI score:
    • F3 thresholds: 0.5 (sensitivity cutoff), 1.5 (specificity cutoff)
  • NAFLD Fibrosis Score (NFS):
    • F3 thresholds: -1.455 (sensitivity cutoff), 0.676 (specificity cutoff)

Step 4: Second-Line Testing

• Liver elastography for patients with indeterminate or high-risk blood test results 1:
  • Vibration-controlled transient elastography (VCTE/FibroScan):
    • F3 thresholds: 8 kPa (sensitivity cutoff), 12 kPa (specificity cutoff)
  • 2D-SWE (ultrasound-based shear wave elastography):
    • F3 thresholds: 8 kPa (sensitivity cutoff), 10.5 kPa (specificity cutoff)
  • MR elastography (if available):
    • F2: 3.14 kPa
    • F3: 3.53 kPa
    • F4: 4.45 kPa

Step 5: Advanced Fibrosis Markers (if available)

• Enhanced Liver Fibrosis (ELF) test 1, 2:
  • F3 thresholds: 7.7 (sensitivity cutoff), 9.8 (specificity cutoff)
• Other specialized tests:
  • FAST score (FibroScan-AST): thresholds 0.35-0.67
  • MAST score (MRI-AST): thresholds 0.165-0.242
  • Corrected T1: thresholds 825-875 ms

Imaging Assessment

Step 6: Steatosis Quantification

• Ultrasound (first-line) 2:
  • Sensitivity 84.8% and specificity 93.6% for moderate-severe steatosis
• Controlled Attenuation Parameter (CAP) with VCTE 1:
  • S1 (mild): 248 dB/m
  • S2 (moderate): 268 dB/m
  • S3 (severe): 280 dB/m
• MRI-PDFF (if available) 1:
  • S1: 5%
  • S2: 11-18%
  • S3: 16-23%

Additional Workup

Step 7: Comorbidity Assessment

• Laboratory tests for related comorbidities 1:
  • Fasting glucose, HbA1c
  • Lipid profile (total cholesterol, LDL, HDL, triglycerides)
  • Renal function (creatinine, eGFR)
  • Thyroid function
  • Insulin resistance assessment (HOMA-IR) in patients without established diabetes

Step 8: Portal Hypertension Assessment (for advanced fibrosis/cirrhosis)

• For patients with LSM ≥20 kPa and/or platelet count <150×10^9/l 1:
  • Upper gastrointestinal endoscopy to screen for varices
• For ruling out clinically significant portal hypertension 1:
  • LSM ≤15 kPa plus platelet count ≥150×10^9/l

Step 9: Hepatocellular Carcinoma (HCC) Surveillance

• For patients with cirrhosis 1:
  • Ultrasound with alpha-fetoprotein every 6 months
• For patients with F3 fibrosis 1:
  • Consider surveillance based on individual risk assessment

Liver Biopsy Indications

Liver biopsy is not required for routine clinical management but should be considered when 1:

• Diagnostic uncertainty persists after non-invasive testing
• Alternative or concurrent liver diseases are suspected
• Definitive diagnosis of steatohepatitis is required (e.g., for clinical trials)

Follow-up Recommendations

• Low risk patients (FIB-4 <1.3): Reassess every 1-3 years 2
• Intermediate risk patients (FIB-4 1.3-2.67 with VCTE <8.0 kPa): Reassess within 1 year 2
• High risk patients (FIB-4 >2.67 or VCTE ≥8.0 kPa): Refer to hepatology for further evaluation 2

Pitfalls and Caveats

• LSM can be confounded by obesity; the threshold of LSM ≥25 kPa to rule in clinically significant portal hypertension is only applicable to non-obese (BMI <30 kg/m²) adults 1
• Non-invasive tests cannot assess microscopic features like ballooning or lobular inflammation 1
• Ultrasound-based HCC surveillance has low sensitivity in obese patients; adding alpha-fetoprotein measurement is recommended 2
• Current recommended non-invasive tests may have insufficient accuracy (<80%) for advanced fibrosis diagnosis; newer tests like FIB-9 may provide improved accuracy 3

By following this systematic approach, clinicians can effectively diagnose MASLD, assess disease severity, identify complications, and guide appropriate management decisions.