What labs are needed for the initial inpatient workup of Non-Alcoholic Steatohepatitis (NASH)?

Initial Inpatient Laboratory Workup for NASH

For hospitalized patients with suspected NASH, obtain a comprehensive metabolic panel, complete blood count, lipid panel, HbA1c, hepatitis B and C serologies, iron studies (ferritin and transferrin saturation), and calculate FIB-4 score to assess fibrosis risk—this forms the essential baseline assessment while excluding competing liver disease etiologies. 1

Core Laboratory Tests

Essential Initial Labs

• Liver enzymes: AST, ALT, alkaline phosphatase, and gamma-glutamyl-transpeptidase (GGT) to establish baseline hepatic injury pattern 1
• Fasting glucose and HbA1c: Critical for identifying diabetes or prediabetes, present in the majority of NASH patients 1
• Complete blood count: Platelet count is essential for calculating fibrosis scores and may reveal thrombocytopenia suggesting advanced disease 1
• Lipid panel: Total cholesterol, HDL-cholesterol, and triglycerides to assess metabolic syndrome components 1
• Comprehensive metabolic panel: Including albumin, total protein, and bilirubin to assess synthetic function 1

Exclusion of Competing Etiologies

• Hepatitis B surface antigen and hepatitis C antibody: Mandatory to exclude viral hepatitis as a coexisting or alternative diagnosis 1
• Iron studies: Ferritin and transferrin saturation, as elevated ferritin is common in NAFLD but persistently high levels with increased iron saturation warrant further evaluation 1
• Autoimmune markers: ANA and anti-smooth muscle antibodies (ASMA), though low titers (ANA ≥1:160 or ASMA ≥1:40) occur in 21% of NAFLD patients without autoimmune hepatitis 1

Important caveat: High serum titers of autoantibodies (>5× upper limit of normal aminotransferases) with elevated globulins or high total protein-to-albumin ratio should prompt workup for autoimmune liver disease, but isolated low-titer positivity is an epiphenomenon in NASH 1

Extended Laboratory Evaluation

Additional Tests Based on Clinical Context

• Thyroid function tests: To evaluate for hypothyroidism, a common comorbidity 1
• Uric acid: Component of metabolic syndrome assessment 1
• Creatine phosphokinase (CK): If AST/ALT elevation could be from muscle injury (exercise, statins) rather than liver disease 1
• Tests for celiac disease: In appropriate clinical context 1

Rare Liver Disease Exclusion (if indicated)

• Ceruloplasmin and 24-hour urine copper: For Wilson disease in younger patients 1
• Alpha-1 antitrypsin level and phenotype: If family history or early-onset disease 1

Fibrosis Risk Stratification

Calculate Non-Invasive Fibrosis Scores

• FIB-4 score: Using age, AST, ALT, and platelet count—this is the recommended initial screening tool 1, 2

  • FIB-4 ≥1.3 indicates need for further fibrosis assessment 1, 2
  • FIB-4 >3.25 suggests high risk for advanced fibrosis and warrants hepatology referral 1

• NAFLD Fibrosis Score (NFS): Alternative validated tool using age, BMI, platelet count, albumin, AST/ALT ratio, and presence of diabetes 1

These scores should be calculated for every NAFLD patient to rule out significant fibrosis (≥F2) and guide the need for imaging-based assessment like transient elastography. 1

Critical Pitfalls to Avoid

• Do not assume elevated ferritin indicates hemochromatosis: Ferritin elevation is common in NASH as an acute phase reactant; only pursue iron overload workup if transferrin saturation is also elevated 1

• Do not over-interpret low-titer autoantibodies: ANA ≥1:160 or ASMA ≥1:40 occur in 21% of NAFLD patients without autoimmune hepatitis and should not automatically trigger extensive autoimmune workup unless accompanied by very high aminotransferases or hypergammaglobulinemia 1

• Do not order cross-sectional imaging for HCC screening initially: Contrast-enhanced CT is not indicated for initial HCC screening in NASH patients without cirrhosis 1

• Measure baseline autoantibodies before enrollment in clinical trials: This provides comparison if drug-induced liver injury is suspected later 1

Assessment of Metabolic Comorbidities

All NASH patients require comprehensive cardiovascular disease workup given that CVD is the leading cause of death in this population, exceeding liver-related mortality. 1

• Document BMI, waist circumference, and blood pressure for metabolic syndrome criteria 1
• Screen for obstructive sleep apnea in obese patients 1
• Evaluate for polycystic ovary syndrome in women with appropriate clinical features 1

Monitoring Considerations

• For hospitalized patients with acute liver enzyme elevation: If ALT rises to ≥5× ULN in previously normal patients, or ≥3× baseline (or ≥300 U/L) in those with elevated baseline, evaluate for alternative etiologies including drug-induced liver injury rather than assuming NASH progression 1

• Emergence of ALP ≥2× ULN is not typical of NASH and should prompt evaluation for alternative cholestatic etiologies 1