What lab tests are used to diagnose fatty liver disease?

Laboratory Tests for Diagnosing Fatty Liver Disease

The diagnosis of fatty liver disease relies primarily on liver transaminases (ALT and AST), followed by a comprehensive metabolic panel, complete blood count, and exclusion of other liver diseases through specific serologic testing. 1

Initial Laboratory Evaluation

Core Liver Chemistry Panel

• ALT and AST are the most readily available and commonly used tests, with NAFLD typically showing mildly elevated levels (AST and/or ALT) with an AST:ALT ratio <1 in early disease 1
• The AST:ALT ratio may reverse to >1 in advanced fibrosis or cirrhosis, but this does not exclude NAFLD 1
• Critical caveat: 50% of patients with NAFLD have completely normal liver chemistries, and up to 80% of NASH patients may still be identified through elevated transaminases alone 1
• Normal ALT does not exclude NASH - this is a common pitfall that leads to missed diagnoses 1

Additional Baseline Tests

• Alkaline phosphatase and gamma-glutamyltransferase (GGT) may be mildly elevated, but bilirubin typically remains normal unless advanced disease is present 1
• Complete blood count to assess for thrombocytopenia (suggests portal hypertension) 1
• International normalized ratio (INR) and albumin - abnormalities indicate cirrhosis or advanced disease 1
• Fasting glucose or hemoglobin A1c to assess for diabetes 1
• Fasting lipid profile including triglycerides and HDL 1
• Creatinine for baseline renal function 1

Excluding Alternative Diagnoses

A critical step is ruling out other causes of liver disease through specific testing:

• Hepatitis B surface antigen and hepatitis C antibody to exclude viral hepatitis 1
• Serum iron, total iron-binding capacity, and ferritin to exclude hemochromatosis 1
• Autoimmune markers (antinuclear antibody, smooth muscle antibody) if high aminotransferases (>5x upper limit normal) or elevated globulins suggest autoimmune hepatitis 1
• Alpha-1 antitrypsin level for suspected deficiency 1
• Ceruloplasmin if Wilson disease is suspected (particularly in younger patients) 1
• TSH to exclude thyroid disorders as an extrahepatic cause 1

Noninvasive Fibrosis Assessment

Since fibrosis stage determines prognosis and mortality risk, assessing for advanced fibrosis is essential:

First-Line Fibrosis Scores

• FIB-4 index (calculated from age, platelet count, AST, ALT) is the most validated initial test with a cutoff <1.3 offering 77.8% sensitivity and 71.2% specificity to exclude advanced fibrosis 2
• NAFLD Fibrosis Score (NFS) uses 6 parameters (age, BMI, hyperglycemia, platelet count, albumin, AST/ALT ratio) with a cutoff of -1.455 showing 72.9% sensitivity and 73.8% specificity 1, 2
• Important limitation: 20-58% of patients fall into indeterminate zones with these scores, requiring additional testing 2

Second-Line Fibrosis Tests

• Enhanced Liver Fibrosis (ELF) panel (hyaluronic acid, tissue inhibitor of metalloproteinase 1, N-terminal procollagen III-peptide) has AUROC 0.90 with 80% sensitivity and 90% specificity for advanced fibrosis 1
• Transient elastography (FibroScan) measures liver stiffness and is FDA-approved for clinical use 1

Algorithmic Approach

1. Initial screening in high-risk patients (metabolic syndrome, diabetes): Obtain ALT and AST 1

2. If transaminases elevated or high clinical suspicion: Order comprehensive panel including:

   • Full liver chemistry panel (ALT, AST, alkaline phosphatase, GGT, bilirubin) 1
   • CBC with platelets 1
   • INR, albumin, creatinine 1
   • Metabolic assessment (fasting glucose/A1c, lipid panel) 1
   • Viral hepatitis serologies 1
   • Iron studies 1

3. Calculate FIB-4 as first-line fibrosis assessment 2

   • If FIB-4 <1.3: Low probability of advanced fibrosis 2
   • If FIB-4 >1.3: Proceed to second-line testing (elastography or ELF panel) 2

4. Consider liver biopsy if:

   • Indeterminate noninvasive test results 1
   • Suspicion of competing liver disease 1
   • Risk factors for NASH with advanced fibrosis (diabetes, metabolic syndrome) 1
   • Findings suggesting cirrhosis (thrombocytopenia, AST>ALT, hypoalbuminemia) 1

Critical Pitfalls to Avoid

• Do not rely on normal ALT to exclude NAFLD or NASH - half of NAFLD patients have normal transaminases 1
• Do not assume AST:ALT >1 excludes NAFLD - this ratio reverses in advanced disease 1
• Do not use aminotransferases alone to distinguish NASH from simple steatosis - they perform poorly (AUC 0.59 for ALT, 0.55 for AST) 3
• Do not skip fibrosis assessment - fibrosis stage, not steatosis or inflammation, determines mortality risk 1, 2
• Do not forget to exclude alcohol use - obtain detailed alcohol history as AST:ALT >2 suggests alcoholic liver disease rather than NAFLD 1