What tests and treatments are recommended for a patient with suspected liver fibrosis or abnormal liver function?

Evaluation and Management of Suspected Liver Fibrosis and Abnormal Liver Function

For patients with suspected liver fibrosis or abnormal liver function, a systematic approach using validated non-invasive tests should be implemented to assess fibrosis severity, with referral to hepatology for those with evidence of advanced fibrosis or cirrhosis. 1

Initial Assessment

Standard Liver Blood Tests

• Complete liver panel including:
  • Bilirubin (total and direct)
  • Albumin
  • ALT (alanine aminotransferase)
  • AST (aspartate aminotransferase)
  • ALP (alkaline phosphatase)
  • GGT (gamma-glutamyl transferase)
  • Platelet count 1, 2

Important Considerations

• Normal liver blood tests do not rule out advanced fibrosis or cirrhosis 1
• ALT levels typically fall as liver fibrosis progresses 1
• Patients with cirrhosis frequently have normal ALT levels 1
• GGT is the most sensitive test for detecting liver disease with fewest false negatives 2

Comprehensive Liver Etiology Screen

Required Tests

1. Abdominal ultrasound scan
2. Viral hepatitis panel:
   • Hepatitis B surface antigen
   • Hepatitis C antibody (with PCR if positive)
3. Autoimmune markers:
   • Anti-mitochondrial antibody
   • Anti-smooth muscle antibody
   • Antinuclear antibody
4. Serum immunoglobulins
5. Iron studies:
   • Serum ferritin
   • Transferrin saturation 1, 2

Additional Tests (Based on Clinical Suspicion)

• Alpha-1-antitrypsin level
• Ceruloplasmin (if age >3 years)
• Coeliac antibodies 1, 2

Fibrosis Assessment Algorithm

First-Line Non-Invasive Tests

For patients with NAFLD or liver disease of unknown etiology:

1. FIB-4 Score: (age × AST)/(platelets × √ALT)

   • Low risk: <1.3 (if age <65 years) or <2.0 (if age >65 years)
   • Indeterminate risk: 1.3-3.25
   • High risk: >3.25 1

2. NAFLD Fibrosis Score: -1.675 + 0.037 × age + 0.094 × BMI + 1.13 × diabetes (yes=1, no=0) + 0.99 × AST/ALT ratio - 0.013 × platelet count - 0.66 × albumin

   • Low risk: <-1.455 (if age <65 years) or <0.12 (if age >65 years)
   • Indeterminate risk: -1.455 to 0.675
   • High risk: >0.675 1

Second-Line Tests (For Indeterminate or High Risk)

1. Transient Elastography (FibroScan):

   • <8 kPa: Minimal fibrosis
   • 8-16 kPa: Possible advanced fibrosis

   • 16 kPa: Possible cirrhosis 1, 2

2. Enhanced Liver Fibrosis (ELF) Test:

   • <9.8: Low risk of advanced fibrosis
   • 9.8-10.4: Intermediate risk

   • 10.5: High risk (caution needed to exclude cirrhosis) 1

3. Magnetic Resonance Elastography (MRE) (if available):

   • <3.0 kPa: Minimal fibrosis
   • 3.0-4.3 kPa: Significant/advanced fibrosis

   • 4.4 kPa: Possible cirrhosis 1

Management Based on Risk Stratification

Low Risk of Advanced Fibrosis

• Manage in primary care
• Address underlying causes:
  • For NAFLD: Weight loss, increased physical activity, diabetes management
  • For ARLD: Alcohol reduction/cessation
• Repeat fibrosis assessment in 3-5 years if risk factors persist 1

Indeterminate Risk

• Proceed to second-line testing (FibroScan/ARFI elastography or ELF test)
• If second-line tests suggest low risk, manage as above
• If second-line tests suggest high risk, refer to hepatology 1

High Risk of Advanced Fibrosis or Cirrhosis

• Refer to hepatologist or gastroenterologist with interest in liver disease
• Further evaluation may include:
  • Additional imaging
  • Consideration of liver biopsy
  • Screening for complications of portal hypertension 1

Special Considerations

Alcohol-Related Liver Disease

• For harmful drinkers (≥35 units/week women, ≥50 units/week men):
  • Risk stratification with clinical assessment and FibroScan/ARFI
  • Refer to alcohol services if AUDIT score >19
  • Refer to hepatology if FibroScan >16 kPa 1

Cystic Fibrosis-Related Liver Disease

• Annual liver blood tests should be performed at a time of clinical stability
• Transient elevation of liver enzymes during systemic inflammation or antibiotic treatment is common
• CFHBI (CF hepatobiliary involvement) is characterized by persistent liver test abnormalities 1

Common Pitfalls to Avoid

1. Relying solely on ALT levels - ALT may be normal even in advanced fibrosis 1
2. Failing to calculate fibrosis scores for patients with NAFLD 2
3. Missing advanced liver disease due to normal or minimally elevated transaminases 2
4. Not recognizing that the extent of liver test abnormality is not necessarily a guide to clinical significance 2
5. Delaying referral for patients with evidence of advanced liver disease 1

By following this systematic approach, clinicians can effectively identify patients with significant liver fibrosis who require specialist care, while appropriately managing those with lower risk in primary care settings.