What labs should be ordered for elevated liver enzymes?

Laboratory Workup for Elevated Liver Enzymes

For this patient with AST 213 and ALT 105 (hepatocellular pattern with AST:ALT ratio >2), order a comprehensive liver etiology screen immediately including: hepatitis B surface antigen, hepatitis B core antibody, hepatitis C antibody, autoimmune markers (ANA, anti-smooth muscle antibody, anti-mitochondrial antibody), serum immunoglobulins, simultaneous ferritin and transferrin saturation, complete blood count with platelets, hepatic panel with bilirubin (total and direct), prothrombin time/INR, and abdominal ultrasound. 1, 2, 3

Pattern Recognition

This AST:ALT ratio >2 (213:105 = 2.0) strongly suggests alcohol-induced liver disease, where AST:ALT ratios typically exceed 2:1 with AST levels 2-6 times the upper limit of normal. 4 However, you must exclude other causes systematically. 1

Core Laboratory Panel (Order These Now)

Viral Hepatitis Serologies

• Hepatitis B surface antigen (HBsAg) 1, 3
• Hepatitis B core antibody (anti-HBc) 1, 3
• Hepatitis C antibody (with reflex HCV RNA/PCR if positive) 1, 3
• Consider hepatitis A IgM and hepatitis E serology if ALT were >1000 U/L, but less urgent here 4, 3

Autoimmune Markers

• Anti-nuclear antibody (ANA) 1, 3
• Anti-smooth muscle antibody 1, 3
• Anti-mitochondrial antibody 1, 3
• Serum immunoglobulins (elevated IgG suggests autoimmune hepatitis) 1, 2

Iron Studies

• Serum ferritin and transferrin saturation simultaneously 1, 2, 3
• Transferrin saturation >45% with elevated ferritin suggests hemochromatosis 1
• Important caveat: Isolated elevated ferritin commonly reflects dysmetabolic iron overload syndrome (seen with alcohol excess, NAFLD) rather than true hemochromatosis 4

Hepatic Function and Synthetic Markers

• Complete blood count with platelets (cytopenias suggest advanced disease or portal hypertension) 3
• Total and direct bilirubin 3
• Prothrombin time/INR (assesses synthetic liver function) 3
• Albumin (if not already included in hepatic panel) 1

Imaging

• Abdominal ultrasound to evaluate liver parenchyma, rule out biliary obstruction, assess for fatty liver, cirrhosis, or hepatosplenomegaly 1, 3

Additional Tests Based on Clinical Context

Metabolic Syndrome Assessment

• Hemoglobin A1c 3
• Lipid panel 3
• These are critical since NAFLD affects 20-30% of the general population and up to 90% of diabetic patients 4

Alcohol Assessment

• AUDIT-C screening questionnaire 2
• Full 10-item AUDIT if AUDIT-C positive 2
• Document current and past alcohol intake in average units per week 1

If Initial Workup Inconclusive, Consider:

• Alpha-1-antitrypsin level (especially if younger patient or emphysema) 3
• Ceruloplasmin (to rule out Wilson's disease, particularly in patients <40 years) 3
• Cytomegalovirus and Epstein-Barr virus serology (if marked transaminase elevation) 3

Fibrosis Risk Stratification

Calculate FIB-4 score using age, ALT, AST, and platelet count once you have the CBC results. 2

• FIB-4 >2.67 indicates high risk of advanced fibrosis and warrants hepatology referral 2
• Alternative: NAFLD Fibrosis Score can be used for first-line risk stratification 2
• If FIB-4 is elevated or intermediate, second-line assessment with serum ELF test or FibroScan/ARFI elastography is recommended 2

Critical Pitfalls to Avoid

• Don't simply repeat the same liver enzyme panel without investigating the cause—84% of abnormal tests remain abnormal at 1 month, and 75% remain abnormal even at 2 years 1, 3
• Don't overlook extrahepatic causes: Check for muscle injury (order CK if rhabdomyolysis suspected), thyroid disease (TSH), or hemolysis 4, 3
• Don't forget medication review: Document all prescription, over-the-counter, herbal supplements, and illicit drugs, as drug-induced liver injury is common 1, 3
• Don't attribute elevated ferritin to hemochromatosis without confirming transferrin saturation >45%, as isolated ferritin elevation is common in metabolic syndrome and alcohol excess 4

Referral Criteria

Refer to hepatology/gastroenterology if: 2

• Extended liver etiology screen is negative and no risk factors for NAFLD identified
• FIB-4 score >2.67 or other evidence of advanced fibrosis
• Evidence of hepatitis B (HBsAg positive), HCV (antibody then PCR positive), autoimmune hepatitis (raised IgG ± positive autoantibodies), primary biliary cholangitis (cholestatic enzymes + positive anti-mitochondrial antibody), or hemochromatosis (raised ferritin and transferrin saturation >45%) 1

Monitoring Strategy

For patients not meeting immediate referral criteria, repeat liver enzymes every 3-6 months initially, address modifiable risk factors including complete alcohol cessation, and implement lifestyle modifications for metabolic syndrome. 2