What laboratory tests should be ordered to evaluate hepatic steatosis?

Laboratory Workup for Hepatic Steatosis

All patients with suspected hepatic steatosis require a comprehensive metabolic panel with liver enzymes (AST, ALT, alkaline phosphatase, GGT, total and conjugated bilirubin), complete blood count with platelets, fasting glucose or HbA1c, lipid panel, and viral hepatitis serologies, followed immediately by calculation of a fibrosis risk score (FIB-4 or NAFLD Fibrosis Score) to stratify risk for advanced fibrosis. 1, 2

Initial Laboratory Panel

Essential Liver Biochemistries

• AST and ALT to assess hepatocellular injury and calculate fibrosis scores 1, 3

  • True healthy normal ALT ranges: 29-33 IU/L for males, 19-25 IU/L for females 3
  • Use age and sex-normative values rather than laboratory reference ranges 1
  • AST/ALT ratio >1 suggests more advanced disease or alcoholic etiology 1, 3

• Alkaline phosphatase and GGT to evaluate for cholestatic injury 1, 3

  • GGT is particularly useful for calculating the Fatty Liver Index 1

• Total and conjugated bilirubin to assess hepatic synthetic function 1, 3

  • Elevated conjugated bilirubin suggests advanced disease or biliary obstruction 1, 3

• Complete blood count with platelet count 1

  • Thrombocytopenia may indicate portal hypertension or advanced fibrosis 1
  • Essential for calculating FIB-4 and APRI scores 1, 2

Metabolic Assessment

• Fasting glucose and/or HbA1c to identify diabetes 1, 2
• Fasting insulin if calculating NAFLD Liver Fat Score 1
• Lipid panel (triglycerides, cholesterol) for metabolic syndrome assessment and FLI calculation 1, 2

Etiology Determination

• Viral hepatitis serologies (HBsAg, anti-HCV antibody) to exclude chronic viral hepatitis 2, 3

• Alcohol intake assessment using validated screening tools (AUDIT or AUDIT-C) 1

  • Threshold: <14 drinks/week for women, <21 drinks/week for men to diagnose NAFLD 2

• Autoimmune markers (ANA, anti-smooth muscle antibody) if clinically indicated 2, 3

• Iron studies, ceruloplasmin, alpha-1 antitrypsin for hereditary causes if initial workup is unrevealing 3

Mandatory Risk Stratification for Fibrosis

Calculate Non-Invasive Fibrosis Scores

Every patient requires immediate calculation of FIB-4 or NAFLD Fibrosis Score regardless of presumed etiology, as hepatic steatosis cannot exclude early cirrhosis. 1, 2

• FIB-4 Score (preferred): Age × AST / (Platelet count × √ALT) 1

  • <1.3 (or <2.0 if age >65): Low risk, repeat in 2-3 years 1
  • 1.3-2.67: Intermediate risk, proceed to elastography 1

  • 2.67: High risk for advanced fibrosis, refer to hepatology 1

• NAFLD Fibrosis Score: Incorporates age, BMI, diabetes, AST/ALT ratio, platelets, albumin 1

  • <-1.455: Low risk
  • -1.455 to 0.676: Indeterminate

  • 0.676: High risk 1

Optional Steatosis Quantification Panels

If imaging is not feasible, calculate validated steatosis scores: 1

Fatty Liver Index (FLI)

• Components: Triglycerides, GGT, BMI, waist circumference 1
• Interpretation:
  • <30: Excludes steatosis (NPV 85%) 1

  • 60: Diagnoses steatosis (PPV 99%) 1

• Performance: AUC 0.84-0.85, validated in Korean populations 1

NAFLD Liver Fat Score (NLFS)

• Components: Metabolic syndrome, diabetes, fasting insulin, AST, AST/ALT ratio 1
• Cutoff: >-0.64 suggests steatosis (sensitivity 86%, specificity 71%) 1
• Performance: AUC 0.86-0.87 1

Hepatic Steatosis Index (HSI)

• Formula: 8 × (ALT/AST) + BMI (+2 if diabetes, +2 if female) 1
• Interpretation:
  • <30: Excludes steatosis (sensitivity 93.1%) 1

  • 36: Diagnoses steatosis (specificity 92.4%) 1

• Performance: AUC 0.81, developed and validated in Korean populations 1

Critical Timing and Follow-Up

• Perform testing during clinical stability, not during acute illness or antibiotic treatment 1
• Annual screening recommended for all at-risk populations starting at diagnosis 1
• Persistent abnormalities (>3-6 months) warrant further evaluation even if initially mild 1
• Repeat FIB-4 every 2-3 years in low-risk patients to detect progression 1

Common Pitfalls to Avoid

• Do not use standard laboratory reference ranges for ALT; use sex-specific healthy normals 3
• Do not skip fibrosis risk stratification even if steatosis appears mild on imaging 2
• Do not rely on aminotransferases alone to exclude advanced disease; 60-80% of steatosis patients are asymptomatic with normal or minimally elevated enzymes 4
• Do not assume normal platelets exclude cirrhosis; baseline thrombocytosis in metabolic syndrome may mask relative thrombocytopenia 1
• Do not delay evaluation waiting for enzymes to reach 1.5-2× upper limit of normal; this contributes to delayed diagnosis 1