What tests do I order for hepatocellular liver enzyme elevation?

Laboratory Testing for Hepatocellular Liver Enzyme Elevation

Order a core liver aetiology panel including hepatitis B surface antigen (HBsAg), hepatitis C antibody, immunoglobulin G (IgG), autoantibodies (ANA, ASMA, anti-LKM), ferritin with transferrin saturation, and fasting glucose/lipid panel to identify treatable causes of hepatocellular injury. 1

Initial Core Laboratory Panel

The British Society of Gastroenterology recommends a standardized core panel as the first-line investigation for hepatocellular enzyme elevation 1:

• Viral hepatitis serologies: HBsAg, hepatitis B core IgM, and HCV antibody to identify viral causes 1, 2
• Autoimmune markers: Serum IgG and autoantibodies (antinuclear antibody, anti-smooth muscle antibody, anti-liver-kidney microsomal antibody) to detect autoimmune hepatitis 1
• Iron studies: Ferritin and transferrin saturation (>45% suggests hemochromatosis) 1
• Metabolic parameters: Fasting glucose, lipid panel, and assessment for metabolic syndrome components (obesity, diabetes, hypertension) to evaluate for nonalcoholic fatty liver disease 2
• Complete liver panel: AST, ALT, alkaline phosphatase, total and direct bilirubin, albumin, and prothrombin time to assess synthetic function 2

Additional Testing Based on Clinical Context

For Marked Elevations (ALT >1000 U/L)

Consider additional viral serologies including hepatitis A, hepatitis E, and cytomegalovirus 1

Extended Panel for Unclear Etiology

Reserve extended testing for patients without a clear cause after core panel 1:

• Thyroid function tests to rule out thyroid disorders as a cause of transaminase elevations 2
• Creatine kinase to exclude muscle disorders as a source of AST elevation 2
• Ceruloplasmin and 24-hour urinary copper if Wilson's disease is suspected (particularly in patients <40 years)

Key Diagnostic Considerations

Do not simply repeat the same liver enzyme panel without investigating the underlying cause, as 84% of abnormal tests remain elevated at 1 month and 75% at 2 years 1. The goal is etiologic diagnosis, not monitoring alone.

Pattern Recognition

• AST:ALT ratio <1 suggests NAFLD, viral hepatitis, or medication-induced injury 2
• AST:ALT ratio >2 suggests alcoholic liver disease 2
• Normal albumin, bilirubin, and PT/INR indicates preserved synthetic function despite hepatocellular injury 2

Common Pitfalls to Avoid

• Isolated elevated ferritin does not indicate hemochromatosis; it commonly occurs in dysmetabolic iron overload syndrome associated with alcohol excess and NAFLD 1. Transferrin saturation >45% is required for hemochromatosis diagnosis 1
• AST is less liver-specific than ALT and can be elevated in cardiac, skeletal muscle, kidney, and red blood cell disorders 2
• Normal ALT ranges differ by sex: 29-33 IU/L for males and 19-25 IU/L for females 2

Clinical History Requirements

Obtain specific details on 1:

• Alcohol consumption: Current and past intake in average units per week (consider AUDIT-C questionnaire) 1
• Comprehensive medication review: Prescribed, over-the-counter, herbal supplements, and illicit drug use 1, 2
• Metabolic syndrome features: Central obesity, hypertension, diabetes/insulin resistance, dyslipidemia 1
• Risk factors for viral hepatitis: Country of birth (strongest predictor of viral hepatitis), ethnicity, travel history, occupational exposure 1
• Symptoms: Jaundice, abdominal pain, weight loss, pruritus, fatigue 1

Imaging Recommendations

Abdominal ultrasound with Doppler is the initial imaging modality of choice for hepatocellular enzyme elevation 1, 2:

• Sensitivity of 84.8% and specificity of 93.6% for detecting moderate to severe hepatic steatosis 2
• Identifies structural causes including focal lesions, vascular abnormalities, and hepatosplenomegaly 2
• Doppler provides hemodynamic information when vascular abnormalities are suspected 1

For mild aminotransferase elevations, ultrasound and Doppler are complementary procedures that should be ordered together 1. For moderate to severe elevations, consider adding CT abdomen/pelvis with IV contrast 1.

Referral Criteria

Immediate specialist referral is warranted for 1:

• Unexplained clinical jaundice
• Suspicion of hepatic or biliary malignancy
• Evidence of hepatitis B (HBsAg positive), HCV (antibody and PCR positive), autoimmune hepatitis (raised IgG with positive autoantibodies), or hemochromatosis (ferritin elevated with transferrin saturation >45%)
• Dilated bile ducts on imaging requiring urgent assessment

Consider hepatology referral if transaminases remain elevated for ≥6 months without identified cause or if there is evidence of synthetic dysfunction 2.