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

Workup for Elevated Liver Function Tests (LFTs)

The initial workup for elevated LFTs should include a standard liver etiology screen with abdominal ultrasound and serological testing, regardless of the level or duration of abnormality. 1

Initial Assessment

History and Physical Examination

• Medication review (including prescription, over-the-counter, and herbal supplements)
• Alcohol consumption assessment
• Features of metabolic syndrome (obesity, diabetes, hypertension)
• Travel history and occupational exposures
• Family history of liver disease
• Review of previous LFT results

Laboratory Studies

1. Initial panel:

   • Complete blood count with platelets
   • Comprehensive metabolic panel
   • Liver enzymes (ALT, AST, ALP, GGT)
   • Bilirubin (total and direct)
   • Albumin
   • Prothrombin time/INR

2. Standard liver etiology screen: 1

   • 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

Imaging

• Abdominal ultrasound is mandatory in all cases of abnormal LFTs 2, 1

Pattern Recognition and Further Workup

1. Hepatocellular Pattern (Elevated ALT/AST)

• Mild elevation (<5× upper limit of normal): 2

  • Most common causes: NAFLD, alcohol-related liver disease, medications
  • Consider viral hepatitis, hemochromatosis, autoimmune hepatitis
  • For suspected NAFLD: Calculate FIB-4 or NAFLD Fibrosis Score
  • AST/ALT ratio >2 suggests alcoholic liver disease, >3 is highly suggestive 1

• Moderate to severe elevation (>5× upper limit of normal): 2

  • Consider acute viral hepatitis, drug-induced liver injury, autoimmune hepatitis
  • Urgent referral to hepatology is recommended

2. Cholestatic Pattern (Elevated ALP/GGT)

• Initial imaging: Abdominal ultrasound to assess for biliary obstruction 2, 1
• If ultrasound normal but ALP remains elevated: Consider MRI abdomen with MRCP 2
• Common causes: Biliary obstruction, primary biliary cholangitis, primary sclerosing cholangitis, drug-induced cholestasis, infiltrative liver diseases

3. Mixed Pattern

• Evaluate for causes of both hepatocellular and cholestatic patterns
• Mixed patterns may indicate more advanced disease in NAFLD patients 3

Risk Stratification for NAFLD

1. Calculate non-invasive fibrosis scores:

   • FIB-4 or NAFLD Fibrosis Score
   • Low risk: FIB-4 <1.3 or NFS ≤1.455 (use higher cutoffs for patients >65 years: <2.0 and <0.12) 2

2. Second-line tests for intermediate/high risk:

   • Transient elastography (FibroScan)
   • Enhanced liver fibrosis (ELF) test
   • Consider referral to hepatology for advanced fibrosis 2, 1

Monitoring and Follow-up

• Normal or mildly abnormal LFTs with identified cause and low fibrosis risk:

  • Lifestyle modifications (Mediterranean diet, regular exercise, weight loss if overweight/obese)
  • Complete alcohol cessation if alcohol-related
  • Monitor LFTs every 6-12 months 1

• Persistently abnormal LFTs (>6 months):

  • Refer to hepatology for further evaluation 1

• Confirmed viral hepatitis:

  • Refer to hepatology for antiviral therapy
  • Repeat liver enzymes every 3-6 months 1

Indications for Urgent Referral to Hepatology

• Marked derangement of LFTs (ALT >5× ULN)
• Evidence of synthetic dysfunction (elevated INR, low albumin)
• Elevated bilirubin with elevated transaminases
• Signs of hepatic decompensation
• Suspected autoimmune hepatitis
• Conflicting clinical, laboratory, and imaging findings 1

Common Pitfalls to Avoid

1. Simply repeating abnormal tests without investigating etiology - 84% of abnormal tests remain abnormal on retesting after 1 month 1

2. Assuming normal LFTs exclude significant liver disease - Normal values do not exclude chronic hepatitis or cirrhosis 1

3. Focusing solely on ALT/AST without considering patterns - Different patterns suggest different etiologies 1

4. Premature discontinuation of medications for mild, asymptomatic elevations without proper evaluation 1

5. Overlooking non-hepatic causes of enzyme elevation - AST can be elevated in cardiac, skeletal muscle, and other disorders 2

By following this systematic approach to abnormal LFTs, clinicians can effectively diagnose liver disease at an early stage, potentially improving patient outcomes through timely intervention and management.