What is the appropriate workup for abnormal Liver Function Tests (LFTs)?

Appropriate Workup for Abnormal Liver Function Tests

The appropriate workup for abnormal liver function tests (LFTs) should include a standard liver aetiology screen with abdominal ultrasound and serological testing, regardless of the level or duration of abnormality. 1

Initial Evaluation

Step 1: Basic LFT Panel

• Initial investigation should include:
  • Bilirubin
  • Albumin
  • Alanine aminotransferase (ALT)
  • Alkaline phosphatase (ALP)
  • γ-glutamyltransferase (GGT)
  • Full blood count (if not performed within previous 12 months) 1

Step 2: Clinical Assessment

• Review previous LFT results and medical history
• Assess for:
  • Medications (prescribed, over-the-counter, herbal)
  • Alcohol consumption (current and past intake)
  • Features of metabolic syndrome
  • Travel history
  • Occupational exposures
  • Family history of liver disease 1

Diagnostic Algorithm

For All Patients with Abnormal LFTs:

1. Standard Liver Aetiology Screen should include:

   • Abdominal ultrasound scan
   • Hepatitis B surface antigen
   • Hepatitis C antibody (with PCR follow-up if positive)
   • Anti-mitochondrial antibody
   • Anti-smooth muscle antibody
   • Antinuclear antibody
   • Serum immunoglobulins
   • Serum ferritin and transferrin saturation 1

2. For Suspected NAFLD (patients with metabolic risk factors):

   • Perform risk stratification using fibrosis-4 (FIB-4) or NAFLD Fibrosis Score (NFS) 1

3. For Suspected Alcoholic Liver Disease:

   • Look for AST/ALT ratio >2 (highly suggestive of alcoholic liver disease) 2
   • Consider referral to alcohol services 1

4. For Marked Derangement of LFTs, Synthetic Failure, or Suspicious Clinical Symptoms:

   • Urgent referral to secondary care 1

Special Considerations:

For Children:

• Include additional testing:
  • Anti-liver kidney microsomal antibody
  • Coeliac antibodies
  • Alpha-1-antitrypsin level
  • Caeruloplasmin (age >3 years) 1

For Immune Checkpoint Inhibitor Therapy:

• Monitor AST, ALT, and bilirubin before each infusion
• Consider weekly monitoring if grade 1 LFT elevations
• For grade ≥2 abnormalities, workup for other causes:
  • Viral hepatitis
  • Alcohol history
  • Iron studies
  • Thromboembolic events
  • Potential liver metastasis 1

Interpretation of Results

Pattern Recognition:

• Hepatocellular pattern (predominant elevation of ALT/AST):

  • Consider viral hepatitis, NAFLD, alcohol-related liver disease, drug-induced liver injury 2

• Cholestatic pattern (predominant elevation of ALP/GGT):

  • Consider biliary obstruction, primary biliary cholangitis, primary sclerosing cholangitis, drug-induced cholestasis 2

• Mixed pattern (elevation of both transaminases and cholestatic enzymes):

  • Consider infiltrative diseases, drug-induced liver injury, alcoholic hepatitis 2

Important Caveats:

1. The extent of LFT abnormality is not necessarily a guide to clinical significance 1
2. Normal LFTs do not exclude significant liver disease 2
3. 84% of abnormal tests remain abnormal on retesting after 1 month 1
4. Simply repeating abnormal tests without investigating the etiology is not recommended 1

Follow-up and Referral

• For mild LFT elevation (<3x upper limit of normal) with normal imaging:

  • Monitor LFTs every 3-6 months
  • Address modifiable risk factors 2

• Consider referral to hepatology for:

  • Persistent elevation >6 months despite interventions
  • Suspected autoimmune hepatitis
  • Conflicting clinical, laboratory, and imaging findings
  • Development of jaundice, ALT elevation >5× ULN, or signs of hepatic decompensation 2

Management Principles

• Lifestyle modifications are essential for managing mild liver enzyme elevation:

  • Mediterranean diet
  • Regular exercise
  • Weight loss if overweight/obese
  • Complete alcohol cessation 2

• For confirmed viral hepatitis:

  • Refer to hepatology for antiviral therapy 2

• For drug-induced liver injury:

  • Consider medication review and possible discontinuation of hepatotoxic drugs 2

The workup for abnormal LFTs should be systematic and thorough, as early diagnosis of liver disease can significantly impact morbidity and mortality outcomes.