What is the evaluation and management approach for a patient with elevated Liver Function Tests (LFTs)?

Evaluation and Management of Elevated Liver Function Tests

The initial approach to a patient with elevated liver function tests (LFTs) should include a thorough clinical history, targeted physical examination, and a standard liver aetiology screen to identify the cause of liver damage and exclude additional pathologies. 1

Initial Assessment

Core Diagnostic Panel

• ALT, AST, ALP, total bilirubin, direct bilirubin
• Complete blood count with platelets
• Albumin, prothrombin time/INR
• Hepatitis B surface antigen (HBsAg)
• Hepatitis C antibody (with reflex PCR if positive)
• Autoimmune markers (ANA, anti-smooth muscle antibody, IgG)
• Ferritin and transferrin saturation
• Abdominal ultrasound

Pattern Recognition

1. Hepatocellular pattern: Predominant elevation of aminotransferases (ALT, AST)
2. Cholestatic pattern: Predominant elevation of ALP and bilirubin
3. Mixed pattern: Elevations in both aminotransferases and cholestatic markers

Management Algorithm Based on Pattern and Severity

For Hepatocellular Pattern (Elevated ALT/AST)

Mild Elevations (<5× ULN)

• Evaluate for common causes:
  • Medications/supplements (statins, antibiotics, herbal products)
  • Alcohol use
  • Non-alcoholic fatty liver disease (metabolic syndrome features)
  • Viral hepatitis (A, B, C, E)
  • Autoimmune hepatitis
  • Hemochromatosis

Moderate to Severe Elevations (>5× ULN)

• More expeditious evaluation required
• Consider additional testing:
  • Hepatitis A, B, C, E serology
  • CMV, EBV serology
  • Ceruloplasmin (Wilson's disease)
  • Drug toxicity evaluation
  • Liver imaging (CT or MRI)

For Cholestatic Pattern (Elevated ALP/Bilirubin)

• Confirm hepatic origin of ALP elevation with GGT
• Distinguish between extrahepatic and intrahepatic cholestasis:
  • Abdominal ultrasound to evaluate biliary system
  • If dilated bile ducts: consider MRCP, ERCP, or urgent referral
  • If normal bile ducts: consider:
    • Primary biliary cholangitis (anti-mitochondrial antibody)
    • Primary sclerosing cholangitis (MRCP)
    • Drug-induced cholestasis
    • Infiltrative diseases

For Isolated Hyperbilirubinemia

• Determine if unconjugated (indirect) or conjugated (direct):
  • Unconjugated: Consider Gilbert's syndrome, hemolysis
  • Conjugated: Evaluate for biliary obstruction, hepatocellular disease

Special Considerations

For Persistent Abnormalities (>6 months)

• Extended evaluation with additional serologic testing
• Consider liver biopsy if diagnosis remains unclear

For Patients with Abnormal Baseline LFTs

• Adjust thresholds for action based on baseline values
• For patients with baseline ALT <1.5× ULN, consider withholding suspected medications when ALT rises above 5× ULN 1
• For patients with abnormal baseline ALT (1.5-5× ULN), use mapped thresholds rather than simple multiples of baseline 1

For Critically Ill Patients

• Consider secondary causes of liver injury:
  • Sepsis
  • Ischemic/hypoxic hepatitis (shock, heart failure)
  • Parenteral nutrition-related injury
  • Drug-induced liver injury
  • Secondary sclerosing cholangitis in critically ill patients 2

When to Refer to a Specialist

• Jaundice or clinical suspicion of hepatic/biliary malignancy (immediate referral) 1
• Evidence of chronic liver disease or hepatic decompensation
• Markedly elevated and/or persistent LFT abnormalities
• Positive tests for viral hepatitis, autoimmune hepatitis, or hemochromatosis
• Abnormal synthetic function (low albumin, prolonged INR)

Pitfalls and Caveats

• Do not simply repeat the same panel of tests when abnormalities are found; determine the cause unless there is high suspicion of a transient finding 1
• Isolated elevated serum ferritin is commonly seen in dysmetabolic iron overload syndrome and does not necessarily reflect hemochromatosis 1
• In the BALLETS study, <5% of people with abnormal liver blood test results had a specific disease affecting the liver 1
• The magnitude of ALT elevation does not always correlate with the severity of liver injury 1
• Medications containing ursodeoxycholic acid may actually decrease liver enzyme levels in liver disease, but patients should still have AST and ALT monitored at initiation of therapy 3
• Transient LFT abnormalities may be due to decreased liver perfusion, particularly in patients with vascular disease 4

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