What are the monitoring guidelines for MAFLD (Metabolic Associated Fatty Liver Disease)?

Monitoring Guidelines for Metabolic Associated Fatty Liver Disease (MAFLD)

Patients with MAFLD should undergo regular monitoring with non-invasive tests to assess fibrosis progression, with frequency determined by disease severity: NAFL patients without worsening metabolic risk factors should be monitored every 2-3 years, NASH and/or fibrosis patients annually, and those with NASH cirrhosis every 6 months. 1

Initial Evaluation and Risk Stratification

Step 1: Multi-step Approach for Fibrosis Assessment

1. First-line screening: Use FIB-4 (fibrosis-4 index) as initial non-patented blood-based score 1

   • FIB-4 <1.3: Low risk, reassess in 1-3 years
   • FIB-4 1.3-2.67: Indeterminate risk, proceed to second-line testing
   • FIB-4 >2.67: High risk, refer to hepatology

2. Second-line testing: For indeterminate or high-risk patients, use:

   • Vibration-controlled transient elastography (VCTE) or alternative elastography
   • <8.0 kPa: Low risk, reassess in 1-3 years
   • ≥8.0 kPa: High risk, refer to hepatology 1

3. Alternative second-line testing: Enhanced liver fibrosis (ELF) test may serve as an alternative to imaging for identifying advanced liver fibrosis 1

Step 2: Comprehensive Metabolic Evaluation

• Complete blood count
• Liver enzymes (ALT, AST, GGT)
• Fasting blood glucose, HbA1c, OGTT
• Lipid profile (total cholesterol, HDL, triglycerides)
• Assessment of all components of metabolic syndrome 1

Monitoring Schedule Based on Disease Severity

For NAFL Patients Without Worsening Metabolic Risk Factors:

• Monitor every 2-3 years with:
  • Routine biochemistry
  • Assessment of comorbidities
  • Non-invasive monitoring of fibrosis (FIB-4) 1

For Patients with NASH and/or Fibrosis:

• Monitor annually with:
  • Routine biochemistry
  • Assessment of comorbidities
  • Non-invasive monitoring of fibrosis (FIB-4 and/or elastography)
  • Evaluation of metabolic parameters 1

For Patients with NASH Cirrhosis:

• Monitor every 6 months with:
  • Routine biochemistry
  • Assessment of comorbidities
  • Non-invasive monitoring of fibrosis
  • Hepatocellular carcinoma (HCC) surveillance 1

Special Monitoring Considerations

Patients with Advanced Fibrosis (F3) or Cirrhosis:

• HCC surveillance: Ultrasound-based surveillance combined with alpha-fetoprotein (AFP) measurement 1
• Portal hypertension assessment:
  • LSM ≤15 kPa plus platelet count ≥150×10⁹/l may rule out clinically significant portal hypertension
  • LSM ≥20 kPa and/or platelet count <150×10⁹/l: Perform upper GI endoscopy to screen for varices 1

Patients with NASH and Hypertension:

• Require closer monitoring due to higher risk of disease progression (fibrosis progression rate is doubled by arterial hypertension) 1

Monitoring Treatment Response

• Non-invasive tests may be repeatedly used to assess fibrosis progression but provide limited information about treatment response 1
• Changes in non-invasive markers that correlate with treatment response:
  • MRI-PDFF relative reduction by ≥30%
  • ALT reduction by ≥17 U/L 1

Weight Loss Targets to Monitor:

• ≥5% sustained weight reduction to reduce liver fat
• 7-10% to improve liver inflammation
• ≥10% to improve fibrosis 1

Cardiovascular Risk Assessment

• Regular assessment of cardiovascular risk factors is essential as CVD is a more common cause of death than liver disease in MAFLD patients 1
• Monitor:
  • Blood pressure
  • Lipid profile
  • Glycemic control
  • Inflammatory markers (high-sensitive CRP) 1

Important Caveats and Pitfalls

1. Liver biopsy limitations: Not suited for routine monitoring due to invasiveness and procedure-related limitations; should be reserved for specific cases where non-invasive tests are inconclusive 1

2. Obesity impact on elastography: LSM thresholds may be less accurate in obese patients (BMI >30 kg/m²), potentially leading to overestimation of fibrosis 1

3. Disease progression variability: While MAFLD is generally slowly progressive, fibrosis rapidly progresses in approximately 20% of cases, highlighting the importance of regular monitoring 1

4. Multidisciplinary approach: Given the connections between MAFLD and cardiometabolic comorbidities, a multidisciplinary approach is essential to target all components and improve both liver-related and extrahepatic outcomes 1

5. Monitoring limitations: Current evidence is insufficient to determine if treatment-induced histological changes translate into reduced risk of clinical outcomes, emphasizing the need for long-term follow-up studies 1