Workup of Abnormal Liver Enzymes
The appropriate workup for abnormal liver enzymes should include a standard liver aetiology screen with abdominal ultrasound, viral hepatitis testing, autoimmune markers, and serum immunoglobulins, regardless of the level and duration of abnormality. 1
Initial Assessment
Clinical History
- Medication review (prescription, OTC, supplements, herbs)
- Alcohol consumption (AUDIT score)
- Risk factors for viral hepatitis (country of birth, injection drug use)
- Metabolic syndrome features (obesity, diabetes, hypertension, dyslipidemia)
- Family history of liver disease
- Autoimmune conditions
- Travel history
- Occupational exposures
Physical Examination
- BMI calculation
- Abdominal examination for hepatosplenomegaly
- Signs of chronic liver disease (jaundice, ascites, spider nevi)
Laboratory Testing
Core Panel (First-Line)
- Complete liver panel (ALT, AST, ALP, GGT, bilirubin, albumin)
- Hepatitis B surface antigen
- Hepatitis C antibody (with reflex PCR if positive)
- Autoimmune markers (anti-mitochondrial, anti-smooth muscle, antinuclear antibodies)
- Serum immunoglobulins (IgG, IgA, IgM)
- Ferritin and transferrin saturation
- Complete blood count
- INR/prothrombin time
Extended Panel (If Core Panel Negative)
- Hepatitis A, D, and E serology
- Ceruloplasmin (if age <40)
- Alpha-1 antitrypsin level
- Celiac disease antibodies
- HIV testing
Imaging
- Abdominal ultrasound (first-line) to assess:
- Liver morphology and echogenicity
- Biliary tract
- Presence of masses
- Signs of cirrhosis or portal hypertension
Pattern-Based Approach
Hepatocellular Pattern (Predominant ALT/AST Elevation)
Mild elevation (<3× ULN)
- Consider NAFLD, ARLD, medications, viral hepatitis
- For NAFLD: Calculate FIB-4 or NAFLD Fibrosis Score
Moderate elevation (3-5× ULN)
- Hold potentially hepatotoxic medications
- Monitor every 3 days until improving
- Consider steroid therapy (0.5-1 mg/kg/d prednisone) if no improvement after 3-5 days
Severe elevation (>5× ULN)
- Urgent referral to hepatology
- Consider viral hepatitis, autoimmune hepatitis, drug-induced liver injury
- Monitor for jaundice (Hy's Law: ALT ≥3× ULN plus bilirubin ≥2× ULN)
Cholestatic Pattern (Predominant ALP Elevation)
- Evaluate for biliary obstruction
- Consider primary biliary cholangitis, primary sclerosing cholangitis
- Additional imaging may be needed (MRCP, ERCP)
Management Approach
For NAFLD
- Risk stratification using FIB-4 or NAFLD Fibrosis Score 1
- Lifestyle modifications (Mediterranean diet, exercise, weight loss)
- Consider vitamin E (800 IU daily) for non-diabetic NASH patients 2
For ARLD
- AUDIT score assessment
- Referral to alcohol services if AUDIT score >19 1
- Fibroscan/elastography if available
- Refer to secondary care if evidence of advanced liver disease or Fibroscan >16 kPa 1
For Drug-Induced Liver Injury
- Discontinue suspected hepatotoxic medications
- Monitor liver enzymes every 2-3 days if ALT >3× ULN 2
Referral Criteria
- ALT/AST >5× ULN
- Persistent elevation >6 months despite interventions
- Evidence of advanced liver disease on imaging
- Elevated ALT with elevated bilirubin
- Diagnostic uncertainty
- Suspected autoimmune hepatitis requiring histological confirmation 2
Monitoring and Follow-up
- Repeat liver enzymes every 2-3 days for severe elevations until improving
- Monitor every 3 months for persistent mild-moderate elevations
- Refer to hepatology if enzymes remain elevated after 6 months despite interventions 2
Common Pitfalls to Avoid
- Assuming normal ALT excludes liver disease
- Delaying evaluation of significantly elevated ALT levels
- Repeatedly testing without diagnostic workup
- Missing medication-related causes
- Failing to assess alcohol consumption accurately
Remember that 75% of abnormal liver tests remain abnormal on retesting, so simply repeating tests without a diagnostic workup is not recommended 1. A systematic approach focusing on identifying the underlying cause is essential for appropriate management and improved outcomes.