What lab tests are recommended for a patient with a new diagnosis of Non-Alcoholic Fatty Liver Disease (NAFLD) who has not had an initial lab workup?

Initial Laboratory Workup for Newly Diagnosed NAFLD

For a patient with newly diagnosed NAFLD who has not had initial lab work, you should order a comprehensive metabolic and liver evaluation including: complete liver panel (AST, ALT, alkaline phosphatase, total and direct bilirubin, albumin, PT/INR), complete blood count with platelets, fasting glucose and HbA1c, lipid profile, viral hepatitis serologies (HBsAg, anti-HBc, anti-HCV), and iron studies (ferritin, transferrin saturation). 1, 2

Core Laboratory Testing

Liver Function and Synthetic Assessment

• Complete liver chemistry panel is essential and must include AST, ALT, alkaline phosphatase, total and direct bilirubin, albumin, and prothrombin time/INR to assess hepatic synthetic function and identify cholestatic patterns 1, 2
• Complete blood count with platelet count is necessary for fibrosis risk stratification, as thrombocytopenia can indicate advanced fibrosis 2
• Note that up to 50% of NAFLD patients have normal liver enzymes, so normal values do not exclude disease 2, 3

Metabolic Parameters

• Fasting blood glucose and HbA1c are mandatory to screen for diabetes, as T2DM patients are at high risk for NAFLD progression regardless of liver enzyme levels 1, 2
• Complete lipid profile (total cholesterol, LDL, HDL, triglycerides) should be obtained to assess dyslipidemia, a core component of metabolic syndrome 1, 2
• Consider oral glucose tolerance test (OGTT) in high-risk groups with prediabetes markers (HbA1c 5.7-6.4%) 1

Exclusion of Competing Liver Diseases

• Viral hepatitis serologies including HBsAg, anti-HBc, and anti-HCV are essential to exclude viral causes of liver disease 1, 2
• Iron studies (serum ferritin and transferrin saturation) must be checked to screen for hemochromatosis 1, 2
  • If ferritin and transferrin saturation are persistently elevated, HFE genetic testing should be performed 1
  • Liver biopsy should be considered if homozygote or compound heterozygote C282Y HFE mutation is present 1
• Autoimmune markers (ANA, ASMA) should be checked if clinically indicated, though low-titer autoantibodies (ANA >1:160 or ASMA >1:40) are common in NAFLD and generally not clinically significant 1, 2
  • Only pursue autoimmune workup if aminotransferases are >5x upper limit of normal with high globulins or elevated total protein to albumin ratio 1

Fibrosis Risk Stratification

Non-Invasive Fibrosis Scores

After obtaining initial labs, calculate NAFLD Fibrosis Score (NFS) or FIB-4 index to stratify fibrosis risk 1, 2:

• NFS uses age, BMI, diabetes/impaired fasting glucose, AST/ALT ratio, platelet count, and albumin
  • NFS <-1.455 indicates low risk of advanced fibrosis
  • NFS >0.676 indicates high risk of advanced fibrosis 2
• FIB-4 uses age, AST, ALT, and platelet count
  • FIB-4 <1.45 indicates low risk
  • FIB-4 >3.25 indicates high risk 2

Advanced Testing Considerations

• Patients with indeterminate or high-risk fibrosis scores should be referred for vibration-controlled transient elastography (FibroScan) or magnetic resonance elastography 1
• Liver biopsy remains the gold standard but is reserved for patients with uncertain diagnosis, high risk of advanced fibrosis by non-invasive testing, or when competing diagnoses need exclusion 2, 3, 4

Assessment of Metabolic Comorbidities

Beyond laboratory testing, the initial evaluation must include 1, 2:

• Detailed alcohol history: <20 g/day for women, <30 g/day for men to confirm NAFLD diagnosis 1, 5
• Medication review: assess for steatosis-inducing drugs (corticosteroids, amiodarone, methotrexate, tamoxifen) 5, 2
• Screen for associated conditions: hypothyroidism, polycystic ovary syndrome, obstructive sleep apnea 1, 2
• Cardiovascular risk assessment: CVD is the leading cause of death in NAFLD patients 5

Common Pitfalls to Avoid

• Do not rely solely on liver enzymes for diagnosis or risk stratification, as normal ALT/AST does not exclude NASH or advanced fibrosis 2, 3
• Do not misinterpret mildly elevated ferritin as hemochromatosis without checking transferrin saturation and considering it may be an acute phase reactant in NAFLD 1
• Do not pursue extensive autoimmune workup for low-titer autoantibodies in the absence of other features suggesting autoimmune hepatitis 1, 2
• Do not order cross-sectional imaging (CT/MRI) for hepatocellular carcinoma screening at initial evaluation unless advanced fibrosis or cirrhosis is already established 1

Follow-Up Laboratory Monitoring

• Repeat liver enzymes every 3-6 months to monitor disease activity 2
• Periodic reassessment of fibrosis scores to detect progression 2
• Annual monitoring is recommended for patients with NASH and/or fibrosis 5
• 2-3 year intervals may be sufficient for simple steatosis without metabolic risk factor progression 5