What is the diagnostic approach for Metabolic Associated Steatohepatitis Liver Disease (MASLD)?

Diagnosis of MASLD

MASLD diagnosis requires documented hepatic steatosis (by imaging or biopsy) plus at least one cardiometabolic risk factor, using a structured two-step approach: initial FIB-4 scoring followed by liver elastography for fibrosis assessment in those at intermediate or high risk. 1, 2

Who Should Undergo Case-Finding

Healthcare providers should actively look for MASLD with liver fibrosis in three specific populations: 1

• All patients with type 2 diabetes 1
• Patients with abdominal obesity plus ≥1 additional metabolic risk factor (hypertension, dyslipidemia, prediabetes, elevated triglycerides, low HDL) 1
• Patients with persistently abnormal liver function tests 1

Additional case-finding may be considered in patients with radiological signs of hepatic steatosis or other cardiometabolic risk factors, though this is a weaker recommendation. 1

Step 1: Establishing Steatosis

Hepatic steatosis can be detected by: 2, 3

• Ultrasound - most widely available screening modality for high-risk populations 3
• CT or MRI - with MRI-PDFF (proton density fat fraction) being superior for accurate quantification 2, 3
• Controlled attenuation parameter (CAP) via transient elastography 2, 3
• Liver biopsy - if performed for other clinical reasons 2

Critical caveat: Ultrasound cannot distinguish simple steatosis from steatohepatitis, cannot assess microscopic features like ballooning or inflammation, and has poor sensitivity when steatosis is <30%. 3 It also cannot assess fibrosis, which is the most critical prognostic factor. 3

Step 2: Confirming Metabolic Dysfunction

At least one of the following cardiometabolic criteria must be present: 2

• Elevated waist circumference (population-specific definitions)
• Elevated blood pressure (>130/85 mmHg or on treatment)
• Elevated fasting triglycerides
• Low HDL cholesterol
• Prediabetes, type 2 diabetes, or insulin resistance

Step 3: Multi-Step Fibrosis Assessment

The recommended algorithmic approach is: 1, 2

Initial Blood-Based Scoring

• Calculate FIB-4 score first (uses age, AST, ALT, platelet count) 1, 2
  • FIB-4 <1.3: Low risk - intensify comorbidity management, reassess FIB-4 every 1-3 years 1, 2
  • FIB-4 1.3-2.67: Indeterminate - proceed to elastography 1, 2
  • FIB-4 >2.67: High risk - proceed to elastography and consider hepatology referral 1, 2

Second-Line Imaging Assessment

• Vibration-controlled transient elastography (VCTE) or alternative elastography 1, 2
  • <8.0 kPa: Low risk - intensify comorbidity management, reassess FIB-4 at ≤1 year 1, 2
  • ≥8.0 kPa: Significant fibrosis likely - hepatology referral for diagnostic work-up 1, 2
  • ≥12 kPa: Advanced fibrosis likely - urgent hepatology referral 2

Alternative to Imaging

• Enhanced liver fibrosis (ELF) test - collagen-related blood biomarkers may substitute for elastography to identify advanced fibrosis 1

Key principle: Blood biomarker-derived scores and elastography should be used to exclude advanced fibrosis, while elastography is better suited to predict advanced fibrosis. 1

Role of Liver Biopsy

Liver biopsy is NOT required for routine clinical management but remains the only definitive method for: 1, 2

• Confirming steatohepatitis (MASH) diagnosis
• Assessing hepatocyte ballooning and lobular inflammation
• Ruling out alternative causes of liver disease
• Staging fibrosis when non-invasive tests are inconclusive

Important limitation: Non-invasive methods cannot assess microscopic features like ballooning or lobular inflammation that define steatohepatitis. 1

Critical Pitfalls to Avoid

Do not rely on ALT/AST alone - standard liver enzyme testing has lower diagnostic accuracy than combined blood-based scores and imaging. 1 Many patients with advanced fibrosis have ALT in the "normal" range; lowering the ALT threshold to >30 U/L identifies 33% more MASLD patients with advanced fibrosis who would be missed using conventional ranges. 4

Document alcohol consumption carefully - the amount, pattern, and history must be assessed using validated instruments and/or biomarkers to distinguish MASLD from MetALD (20-50 g/day women, 30-60 g/day men) or alcohol-related liver disease. 1

Essential Comorbidity Assessment

At initial diagnosis and regular follow-up, assess for: 1, 2

• Type 2 diabetes, dyslipidemia, hypertension
• Chronic kidney disease
• Sleep apnea, polycystic ovary syndrome
• Cardiovascular risk stratification
• Extrahepatic cancer screening (obesity and diabetes increase risk)

Consider genetic testing in specialized centers for patients with strong family history of severe liver disease, early severe presentation, or normal body weight without typical metabolic triggers. 1, 2