What are the management guidelines for patients with liver disease according to MASLD (Model for End-Stage Liver Disease)?

Management Guidelines for Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)

The management of patients with MASLD requires a structured approach focused on risk stratification, lifestyle modifications, and targeted pharmacological interventions based on disease severity and comorbidities to reduce morbidity and mortality.

Diagnosis and Risk Assessment

Initial Evaluation

• Screening Tools:
  • Ultrasound is the first-line investigation for hepatic steatosis (sensitivity 84.8%, specificity 93.6% for moderate-severe steatosis) 1
  • Blood-based fibrosis scores (FIB-4) should be used for initial risk stratification 1
    • FIB-4 <1.3: Low risk
    • FIB-4 1.3-2.67: Indeterminate risk
    • FIB-4 >2.67: High risk

Advanced Assessment

• For indeterminate/high risk patients:
  • Vibration-controlled transient elastography (VCTE/FibroScan) 2, 1
    • <8.0 kPa: Low risk
    • 8.0-12.0 kPa: Indeterminate risk

    • 12.0 kPa: High risk

  • Enhanced Liver Fibrosis (ELF) test or other specialized biomarkers 1

Comorbidity Assessment

• Mandatory evaluation for all MASLD patients 2:
  • Type 2 diabetes
  • Dyslipidemia
  • Hypertension
  • Kidney disease
  • Sleep apnea
  • Polycystic ovary syndrome
  • Cardiovascular risk assessment

Management Strategy Based on Fibrosis Stage

Non-Cirrhotic MASLD (F0-F3)

Lifestyle Interventions (First-line for all patients)

• Diet: Mediterranean diet pattern 3
• Weight loss targets:
  • 7-10% weight reduction for overweight/obese patients 3
  • Sustained weight loss is associated with histological improvement 2
• Physical activity:
  • 150-300 minutes/week of moderate-intensity exercise 2
  • Both aerobic and resistance training are beneficial

Pharmacological Management

• For patients with F2-F3 fibrosis:

  • Resmetirom if locally approved 2

• For patients with comorbid type 2 diabetes:

  • GLP-1 receptor agonists (semaglutide, liraglutide, dulaglutide) 2
  • GLP-1/GIP co-agonists (tirzepatide) 2
  • SGLT2 inhibitors (empagliflozin, dapagliflozin) 2

• For dyslipidemia:

  • Statins are safe and recommended according to cardiovascular risk guidelines 2, 4

Bariatric Surgery

• Should be considered for patients with approved indications as it induces long-term beneficial effects on the liver and metabolic parameters 2

Compensated Cirrhosis (F4)

Lifestyle Interventions

• Moderate weight reduction with emphasis on high protein intake (1.2-1.5 g/kg/day) and physical activity to maintain muscle mass 2
• Recommended caloric intake: At least 35 kcal/kg body weight/day 2
• Late evening snack to prevent catabolism 2

Pharmacological Management

• For diabetes management:

  • Metformin can be used in compensated cirrhosis with preserved renal function 2
  • GLP-1 receptor agonists can be used in Child-Pugh class A cirrhosis 2
  • SGLT2 inhibitors can be used in Child-Pugh class A and B cirrhosis 2
  • Avoid sulfonylureas due to hypoglycemia risk 2

• For cardiovascular risk reduction:

  • Statins are safe and recommended in compensated cirrhosis 2

Portal Hypertension Management

• For ruling out clinically significant portal hypertension (CSPH):

  • LSM by VCTE <15 kPa plus platelet count >150×10⁹/L 2

• If CSPH is present:

  • Non-selective beta-blockers unless contraindicated 2

• For patients with LSM >20 kPa and/or platelet count <150×10⁹/L:

  • Upper gastrointestinal endoscopy to screen for varices 2

Decompensated Cirrhosis

Medication Adjustments

• Avoid metformin due to risk of lactic acidosis 2
• Avoid sulfonylureas due to hypoglycemia risk 2
• Insulin is the preferred agent for diabetes management 2

Nutritional Management

• High-protein diet and late evening snack 2
• Avoid bariatric surgery as it is contraindicated 2

Transplant Evaluation

• Multidisciplinary assessment for transplant candidacy 2
• Cardiovascular work-up using a stepwise approach 2

Surveillance Recommendations

Hepatocellular Carcinoma (HCC) Surveillance

• For patients with cirrhosis:

  • Regular HCC surveillance is strongly recommended 2
  • Ultrasound with alpha-fetoprotein every 6 months 2

• For patients with F3 fibrosis:

  • Consider surveillance based on individual risk assessment 2

• For patients with F0-F2 fibrosis:

  • Routine surveillance not recommended 2

Follow-up Intervals

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

Special Considerations

Liver Transplantation

• Pre-transplant weight management:
  • Target BMI <40 kg/m² (ideally <35 kg/m²) through dietary modification and supervised exercise 2
  • Pharmacological weight-loss strategies may be considered after risk-benefit assessment 2
  • In compensated cirrhosis without CSPH, sleeve gastrectomy may be considered 2

Post-Transplant Management

• High risk of MASLD recurrence after transplantation 2
• Therapeutic interventions to control obesity and cardiometabolic complications are strongly recommended 2
• Standard non-pharmacological dietary and lifestyle interventions should be universally implemented 2

Pitfalls and Caveats

• LSM thresholds to rule in CSPH (>25 kPa) are only applicable to non-obese patients (BMI <30 kg/m²) 2
• Ultrasound-based HCC surveillance has low sensitivity in obese patients; consider adding AFP measurement 2
• Bariatric surgery is contraindicated in decompensated cirrhosis 2
• Metformin should not be used in patients with decompensated cirrhosis or renal impairment 2