Recommended Laboratory Workup for MASLD (Metabolic Associated Steatotic Liver Disease)
The recommended laboratory workup for MASLD should follow a multi-step approach starting with blood-based fibrosis scores followed by specialized imaging or additional biomarker testing to accurately assess disease severity and guide management. 1
Initial Laboratory Assessment
Basic Laboratory Tests
- Complete blood count with platelets
- Comprehensive metabolic panel including:
- Liver enzymes (ALT, AST)
- Albumin
- Total bilirubin
- Fasting glucose
- Lipid profile (total cholesterol, LDL, HDL, triglycerides)
- Hemoglobin A1c
- Calculation of AST/ALT ratio
Fibrosis Assessment
- FIB-4 score calculation (using age, AST, ALT, and platelet count)
- FIB-4 <1.3 (or <2.0 if ≥65 years): Low risk
- FIB-4 1.3-2.67: Indeterminate risk
- FIB-4 >2.67: High risk 1
Exclusion of Alternative Liver Diseases
- Viral hepatitis serologies:
- HCV antibody + HCV RNA
- HBsAg, HBsAb, HBcAb
- Autoimmune markers:
- Antinuclear antibody (ANA)
- Anti-smooth muscle antibody (ASMA)
- Antimitochondrial antibody (AMA)
- Iron studies (ferritin, transferrin saturation)
- Immunoglobulins
- Alpha-1 antitrypsin level
- Alcohol consumption assessment (AUDIT-C questionnaire) 1, 2
Second-Line Testing Based on FIB-4 Results
For Indeterminate or High FIB-4 Scores
- Vibration-controlled transient elastography (VCTE/FibroScan) with:
- Liver stiffness measurement (LSM) for fibrosis assessment
- Controlled attenuation parameter (CAP) for steatosis quantification
- Interpretation thresholds:
- LSM <8.0 kPa: Low risk of advanced fibrosis
- LSM 8.0-12.0 kPa: Indeterminate risk
- LSM >12.0 kPa: High risk of advanced fibrosis
- LSM >15.0 kPa: Possible cirrhosis 1
Alternative Second-Line Tests
- Enhanced Liver Fibrosis (ELF) test
- <7.7: Low risk
- 7.7-9.8: Intermediate risk
9.8: High risk
11.3: Cirrhosis 1
- Magnetic resonance elastography (MRE)
- <2.6 kPa: Low risk
- 2.6-3.6 kPa: Intermediate risk
3.6 kPa: High risk
4.6 kPa: Cirrhosis 1
Assessment of Metabolic Comorbidities
- Insulin resistance assessment (HOMA-IR) in patients without established diabetes 1
- Blood pressure measurement
- Waist circumference measurement
- Screening for sleep apnea and other obesity-related conditions 1
Additional Testing in Specific Scenarios
For Suspected Advanced Disease
- Prothrombin time/INR
- Serum albumin
- Abdominal ultrasound to assess for signs of portal hypertension 1
For Patients with Strong Family History or Early Presentation
- Consider genetic testing for PNPLA3, TM6SF2, MBOAT7, and GCKR variants 1, 2
- Next-generation sequencing approaches for treatable genetic causes of liver disease 1
Follow-Up Testing Schedule
- Low risk patients (FIB-4 <1.3): Reassess FIB-4 every 1-3 years
- Intermediate risk patients (FIB-4 1.3-2.67 with VCTE <8.0 kPa): Reassess within 1 year
- High risk patients (FIB-4 >2.67 or VCTE ≥8.0 kPa): Refer to hepatology for further evaluation 1
Important Considerations
- FIB-4 has better negative predictive value (ruling out advanced fibrosis) while elastography has better positive predictive value (confirming advanced fibrosis) 1
- Non-invasive tests cannot assess microscopic features of MASLD such as ballooning or lobular inflammation 1
- Liver biopsy remains the gold standard for definitive diagnosis of steatohepatitis (MASH) but is not required for routine clinical management 1
- Test performance is highly dependent on the prevalence of the condition in the tested population 1
This laboratory workup algorithm provides a systematic approach to diagnosing MASLD, assessing fibrosis severity, and identifying patients who require specialist referral and more intensive monitoring.