What labs should be ordered for a patient with suspected nonalcoholic cirrhosis of the liver?

Laboratory Evaluation for Suspected Nonalcoholic Cirrhosis

For patients with suspected nonalcoholic cirrhosis, obtain a baseline liver evaluation including: complete blood count (CBC), comprehensive liver panel (AST, ALT, bilirubin, alkaline phosphatase), INR, creatinine, albumin, and prothrombin time, along with tests to exclude alternative causes of liver disease. 1

Core Laboratory Panel

Essential Hepatic Function Tests

• Complete metabolic panel with liver enzymes: AST, ALT, bilirubin, alkaline phosphatase 1
• Synthetic function markers: Serum albumin, prothrombin time or INR 1
• Complete blood count (CBC): Evaluate for thrombocytopenia (suggests portal hypertension) and white blood cell count 1
• Serum creatinine: Assess renal function 1

Pattern Recognition for Cirrhosis

• AST > ALT ratio: When AST exceeds ALT, this suggests more advanced fibrosis or cirrhosis 1
• Thrombocytopenia: Platelet count <150,000 indicates portal hypertension and likely cirrhosis 1
• Hypoalbuminemia: Low albumin suggests decreased synthetic function and advanced disease 1
• Elevated INR or prolonged prothrombin time: Indicates impaired hepatic synthetic capacity 1

Metabolic and Cardiovascular Risk Assessment

Required Metabolic Screening

• Fasting glucose and/or hemoglobin A1c: Assess for diabetes, a major risk factor for NASH and advanced fibrosis 1
• Lipid profile: Evaluate dyslipidemia as part of metabolic syndrome 1
• Body mass index (BMI) and waist circumference: Document obesity parameters 1

These metabolic parameters are critical because diabetes and metabolic syndrome are major risk factors for progression to advanced fibrosis and cirrhosis in NAFLD. 1

Exclusion of Alternative Liver Disease Etiologies

Viral Hepatitis Screening

• Hepatitis B surface antigen (HBsAg): Exclude chronic hepatitis B 1, 2
• Hepatitis C antibody: Screen for hepatitis C infection 1, 2

Autoimmune and Metabolic Disorders

• Autoimmune markers: Consider antinuclear antibody (ANA), anti-smooth muscle antibody, anti-mitochondrial antibody to exclude autoimmune hepatitis and primary biliary cholangitis 1
• Iron studies: Transferrin saturation and ferritin to exclude hemochromatosis 1
• Alpha-1 antitrypsin level: Consider in appropriate clinical context 1
• Ceruloplasmin: Consider if Wilson disease is suspected (particularly in younger patients) 1

Alcohol Assessment

• Detailed alcohol consumption history: Document intake to distinguish NAFLD from alcoholic liver disease 1
• Mean corpuscular volume (MCV): Elevated MCV may suggest alcohol use 1
• Gamma-glutamyl transpeptidase (GGT): While nonspecific, markedly elevated GGT may suggest alcohol contribution 1

The distinction between alcoholic and nonalcoholic liver disease is critical, as approximately 20% of patients with suspected single-etiology liver disease have coexisting causes. 1

Fibrosis Assessment

Non-Invasive Fibrosis Markers

• FIB-4 index calculation: Use age, AST, ALT, and platelet count to estimate fibrosis stage 3, 2
  • High FIB-4 scores warrant gastroenterology referral and consideration for liver biopsy 3
  • This is a critical screening tool to identify patients with advanced fibrosis who need more intensive evaluation

Clinical Indicators Suggesting Cirrhosis

The following laboratory findings should prompt consideration of liver biopsy or advanced imaging: 1

• Thrombocytopenia (platelets <150,000)
• AST > ALT ratio
• Hypoalbuminemia
• Elevated INR or prolonged prothrombin time
• Elevated bilirubin

Common Pitfalls to Avoid

Critical Considerations

• Normal liver enzymes do not exclude cirrhosis: Advanced fibrosis may present with normal ALT and AST, making CBC (for platelets) and synthetic function tests essential 1
• Isolated GGT elevation is insufficient: GGT alone is a poor indicator of liver injury and should not be used as the sole marker 1
• ALT levels in NAFLD: Typical NAFLD shows ALT levels between normal and 250 IU/L, usually <5× upper limit of normal, with ALT typically higher than AST until advanced disease 1
• Exclude medication-induced steatosis: Review for hepatotoxic medications including corticosteroids, amiodarone, methotrexate, tamoxifen, estrogens, tetracyclines, and valproic acid 1

When to Pursue Liver Biopsy

Consider referral for liver biopsy when: 1

• Patient has diabetes and/or metabolic syndrome (high risk for NASH and advanced fibrosis)
• Laboratory findings suggest cirrhosis (thrombocytopenia, AST>ALT, hypoalbuminemia)
• Non-invasive tests are discordant or inconclusive
• Suspicion of competing or coexisting liver disease exists