What labs are recommended for a Non-Alcoholic Steatohepatitis (NASH) workup?

Laboratory Workup for NASH

For a NASH workup, obtain a baseline liver evaluation including complete blood count, comprehensive liver panel (AST, ALT, bilirubin, alkaline phosphatase), INR, creatinine, fasting glucose or hemoglobin A1c, and lipid profile, followed by serologic testing to exclude other liver diseases including hepatitis B and C, autoimmune markers, iron studies, and alpha-1 antitrypsin level. 1, 2

Core Laboratory Panel

Initial Liver Chemistry Assessment

• AST and ALT: Most readily available tests for asymptomatic liver disease, though 50% of NAFLD patients have normal transaminases 1, 2
• Alkaline phosphatase: Usually normal, though mild elevations (<2× ULN) may occur 1
• Total bilirubin: Typically normal until advanced disease develops 1
• Gamma-glutamyltransferase (GGT): May range from low normal to >400 U/L, though isolated GGT elevation is insufficient for diagnosis 1
• Albumin: Assess synthetic function; hypoalbuminemia suggests cirrhosis 1
• INR: Elevated values indicate advanced disease or cirrhosis 1

Hematologic Assessment

• Complete blood count with platelets: Thrombocytopenia suggests portal hypertension or cirrhosis 1, 2

Metabolic Evaluation

• Fasting glucose or hemoglobin A1c: Essential for identifying diabetes, a major risk factor for NASH progression 1, 2
• Lipid profile: Including triglycerides and HDL cholesterol for cardiovascular risk assessment 1, 2
• Waist circumference and BMI: Document metabolic syndrome components 1

Renal Function

• Creatinine: Baseline assessment required 1, 2

Exclusion of Alternative Diagnoses

Viral Hepatitis Screening

• Hepatitis B surface antigen: Mandatory to exclude chronic hepatitis B 1, 2
• Hepatitis C antibody: Required for all patients 1, 2

Autoimmune and Metabolic Disorders

• Iron studies (serum iron, total iron-binding capacity, ferritin): Exclude hemochromatosis 1, 2
• Autoimmune markers (antinuclear antibody, smooth muscle antibody): Consider if ALT >5× ULN or elevated globulins 1, 2
• Alpha-1 antitrypsin level and phenotype: Screen for deficiency 1, 2
• Ceruloplasmin: If Wilson disease suspected, particularly in younger patients 1, 2
• Anti-mitochondrial antibody: Consider based on clinical presentation 1

Noninvasive Fibrosis Assessment

Calculate FIB-4 index as the first-line fibrosis assessment tool, as it offers 77.8% sensitivity and 71.2% specificity for excluding advanced fibrosis with a cutoff <1.3. 2

FIB-4 Index

• Formula components: Age, platelet count, AST, ALT 2
• Interpretation: <1.3 excludes advanced fibrosis; >2.67 suggests advanced fibrosis 2

NAFLD Fibrosis Score (NFS)

• Six parameters: Age, BMI, hyperglycemia, platelet count, albumin, AST/ALT ratio 2
• Performance: Cutoff of -1.455 shows 72.9% sensitivity and 73.8% specificity 2

Enhanced Liver Fibrosis (ELF) Panel

• Components: Hyaluronic acid, tissue inhibitor of metalloproteinase 1, N-terminal procollagen III-peptide 2
• Performance: AUROC 0.90 with 80% sensitivity and 90% specificity for advanced fibrosis 2

Critical Laboratory Interpretation Pitfalls

AST/ALT Ratio Patterns

• Early NASH: AST:ALT ratio typically <1 1, 2
• Advanced fibrosis: Ratio may reverse to >1, but this does not exclude NAFLD 1, 2
• AST:ALT >2: Suggests alcoholic liver disease rather than NAFLD; obtain detailed alcohol history 2

Normal Transaminases Do Not Exclude Disease

• Critical caveat: Normal ALT does not exclude NASH—this is a common diagnostic pitfall 1, 2
• Up to 80% of NASH patients may still be identified through elevated transaminases, but 50% of NAFLD patients have completely normal liver chemistries 1, 2

Typical NASH Laboratory Ranges

• ALT at diagnosis: Usually ranges from low normal to 250 IU/L, typically <5× ULN 1
• ALT >300 U/L: Occurs rarely in NASH and should prompt consideration of alternative diagnoses 1
• AST values: Typically lower than ALT in early disease, but may exceed ALT with advanced fibrosis 1

Indications for Liver Biopsy Consideration

Refer patients for liver biopsy consideration if they have diabetes and/or metabolic syndrome (risk factors for NASH and advanced fibrosis), findings concerning for cirrhosis (thrombocytopenia, AST>ALT, hypoalbuminemia), or indeterminate noninvasive test results. 1, 2

• High-risk patients: Those with diabetes, metabolic syndrome, or multiple cardiovascular risk factors 1, 2
• Cirrhosis indicators: Thrombocytopenia, AST>ALT ratio, hypoalbuminemia 1, 2
• Discordant results: When noninvasive tests provide conflicting information 2
• Competing diagnoses: When other liver diseases cannot be excluded serologically 2