What is the initial workup for a patient with elevated Liver Function Tests (LFTs)?

Initial Workup for Elevated Liver Function Tests (LFTs)

The initial workup for a patient with elevated LFTs should include a comprehensive laboratory evaluation with complete blood count, urinalysis, serum electrolytes (including calcium and magnesium), blood urea nitrogen, serum creatinine, fasting blood glucose, lipid profile, liver function tests, and thyroid-stimulating hormone, followed by appropriate imaging studies. 1

Step 1: Laboratory Assessment

Basic Laboratory Panel:

• Complete blood count (CBC)
• Comprehensive metabolic panel including:
  • Liver enzymes (AST, ALT, alkaline phosphatase, GGT)
  • Bilirubin (total and direct)
  • Albumin and total protein
  • Electrolytes including calcium and magnesium
  • Blood urea nitrogen (BUN) and creatinine
  • Fasting blood glucose or glycohemoglobin
• Prothrombin time (PT/INR)
• Lipid profile
• Thyroid-stimulating hormone (TSH)

Pattern Recognition:

Categorize the LFT abnormality based on pattern:

• Hepatocellular pattern: Predominant elevation of AST/ALT
• Cholestatic pattern: Predominant elevation of alkaline phosphatase/GGT
• Mixed pattern: Elevation of both transaminases and cholestatic enzymes

Additional Testing Based on Pattern:

• For cholestatic pattern: Confirm hepatic origin of alkaline phosphatase with GGT and/or alkaline phosphatase isoenzyme fractionation 1
• For elevated bilirubin: Fractionation to confirm direct bilirubin percentage 1

Step 2: Viral Hepatitis and Autoimmune Workup

Viral Hepatitis Panel:

• Hepatitis B surface antigen (HBsAg)
• Hepatitis B core antibody (anti-HBc)
• Hepatitis B surface antibody (anti-HBs)
• Hepatitis C antibody (with reflex RNA testing if positive)
• Consider Hepatitis A IgM in acute presentations 1

Autoimmune Markers:

• Antinuclear antibody (ANA)
• Anti-smooth muscle antibody (ASMA)
• Immunoglobulin levels (IgG, IgM, IgA) 1

Step 3: Metabolic and Other Etiologies

Iron Studies:

• Serum iron
• Total iron binding capacity
• Transferrin saturation
• Ferritin (HFE gene testing if transferrin saturation ≥45% and/or ferritin is elevated) 1

Additional Tests:

• Alpha-1 antitrypsin level
• Ceruloplasmin (in patients <40 years with unexplained liver disease)
• HIV testing (recommended as part of evaluation for patients with elevated liver enzymes) 1

Step 4: Imaging Studies

First-line Imaging:

• Abdominal ultrasound (to assess liver parenchyma, biliary tract, and rule out obstruction) 1

Additional Imaging Based on Clinical Scenario:

• Magnetic resonance cholangiopancreatography (MRCP) for unexplained cholestasis
• Endoscopic ultrasound (EUS) as an alternative for evaluation of distal biliary tract obstruction
• CT abdomen with contrast if mass lesion suspected 1

Step 5: Non-invasive Fibrosis Assessment

• Calculate non-invasive fibrosis scores (FIB-4, NAFLD fibrosis score)
• Consider transient elastography (FibroScan) if available
  • Cut-offs: <8-10 kPa (advanced fibrosis unlikely), >12-15 kPa (advanced fibrosis suspected) 1

Step 6: Liver Biopsy Consideration

Consider liver biopsy if:

• Diagnostic uncertainty persists
• Ferritin >1000 μg/L with elevated liver enzymes
• Suspected autoimmune hepatitis requiring histological confirmation
• Conflicting clinical, laboratory, and imaging findings 1

Special Considerations

Alcohol-Related Liver Disease:

• Obtain detailed alcohol consumption history
• GGT is particularly sensitive to alcohol consumption
• If alcohol use is identified, recommend immediate abstinence and repeat LFTs after at least 1 week of abstinence 1

Medication-Induced Liver Injury:

• Review all medications and supplements
• Consider medication adjustment or discontinuation if:
  • ALT/AST >3× ULN: adjust dose or discontinue medication
  • ALT/AST >5× ULN: discontinue medication and consider referral to hepatology 1

Criteria for Hepatology Referral

Expedite evaluation or consider referral to hepatology if:

• ALT/AST increases to >5× ULN
• ALT/AST >3× ULN with total bilirubin ≥2× ULN
• Persistent elevation >6 months despite interventions
• Development of symptoms such as jaundice, abdominal pain, or fatigue
• Suspected autoimmune hepatitis
• Evidence of advanced fibrosis or cirrhosis 1

Monitoring Recommendations

• For mild elevation (ALT <5× ULN): Continue monitoring liver enzymes every 2-5 days and investigate potential causes
• If ALT increases to >5× ULN: Consider interruption of suspected hepatotoxic medications and expedite diagnostic evaluation
• If ALT >3× ULN with total bilirubin ≥2× ULN: Interrupt suspected hepatotoxic medications immediately and consider referral to hepatology 1

By following this systematic approach to the workup of elevated LFTs, clinicians can efficiently identify the underlying cause and initiate appropriate management to improve patient outcomes.