What tests should be ordered in a patient with deranged liver function?

Evaluation of Deranged Liver Function Tests

In patients with deranged liver function tests, a standard liver aetiology screen should include abdominal ultrasound, hepatitis B surface antigen, hepatitis C antibody (with PCR if positive), autoantibody panel, immunoglobulins, ferritin and transferrin saturation to identify the underlying cause and guide management. 1

Initial Liver Blood Test Panel

The initial investigation for potential liver disease should include:

• Bilirubin
• Albumin
• Alanine aminotransferase (ALT)
• Alkaline phosphatase (ALP)
• γ-glutamyltransferase (GGT)
• Full blood count (if not performed in the previous 12 months) 1

It's important to note that the extent of liver blood test abnormality is not necessarily a guide to clinical significance. This is determined by the specific analyte which is abnormal and the clinical context. 1

Comprehensive Liver Aetiology Screen

Core Panel (Standard for Adults)

• Abdominal ultrasound scan
• Hepatitis B surface antigen
• Hepatitis C antibody (with follow-on PCR if positive)
• Autoantibody panel:
  • Anti-mitochondrial antibody
  • Anti-smooth muscle antibody
  • Antinuclear antibody
• Serum immunoglobulins
• Ferritin and transferrin saturation (simultaneously) 1

Special Considerations for Children

• Autoantibody panel should include anti-liver kidney microsomal antibody and coeliac antibodies
• Alpha-1-antitrypsin level
• Caeruloplasmin (age >3 years)
• Ferritin and transferrin saturation may not be indicated 1

Pattern Recognition and Further Testing

Hepatocellular Pattern (Elevated ALT/AST)

For patients with more marked elevations in ALT (>1000 U/L), consider:

• Viral hepatitis (A, B, C, E)
• Cytomegalovirus
• Drug-induced liver injury
• Autoimmune hepatitis 1

Cholestatic Pattern (Elevated ALP/GGT)

For patients with cholestatic liver enzymes, consider:

• Primary biliary cholangitis (with positive anti-mitochondrial antibody)
• Primary sclerosing cholangitis (especially with history of inflammatory bowel disease)
• Biliary obstruction (requires urgent referral if suspected) 1

Isolated Unconjugated Hyperbilirubinemia

When only indirect bilirubin is elevated with normal liver enzymes:

• Evaluate for Gilbert's syndrome
• Consider hemolysis
• Review medications 2

Risk Stratification for Specific Conditions

For Non-alcoholic Fatty Liver Disease (NAFLD)

• Use fibrosis-4 (FIB-4) or NAFLD Fibrosis Score (NFS) for first-line testing
• AST:ALT ratio >1 suggests advanced fibrosis/cirrhosis 1

For Alcohol-related Liver Disease (ARLD)

• Clinical assessment and Fibroscan/ARFI elastography
• Refer to secondary care if evidence of advanced liver disease or Fibroscan reading >16 kPa
• Consider referral to alcohol services for patients with AUDIT score >19 1

Monitoring Recommendations

• Patients with abnormal liver tests should be monitored closely, especially when using potentially hepatotoxic medications
• For patients with COVID-19 on hepatotoxic medications, monitoring twice weekly is reasonable 1
• For isolated unconjugated hyperbilirubinemia, repeat liver tests in 1-2 months to confirm stability 2

Referral Criteria

Urgent referral to secondary care is indicated for:

• Marked derangement of liver blood tests
• Evidence of synthetic failure
• Suspicious clinical symptoms/signs
• Dilated bile ducts on imaging
• Evidence of advanced liver disease (features of cirrhosis or portal hypertension) 1

Common Pitfalls to Avoid

1. Simply repeating the same panel of tests without determining the cause when abnormalities are found
2. Overlooking synthetic function tests (albumin, INR, platelet count) which may indicate advanced disease even with mild enzyme elevations
3. Missing underlying chronic liver disease as normal values in baseline liver tests do not rule out advanced fibrosis or cirrhosis 3
4. Assuming high levels of liver enzymes indicate liver failure - they are markers of injury, not function 3
5. Failing to recognize that both AST and ALT can be normal even in the setting of cirrhosis 1

Remember that in the BALLETS study, less than 5% of people with abnormal liver blood test results had a specific disease affecting the liver, and only 1.3% had a specific liver disease requiring immediate treatment 1. However, proper evaluation is essential to identify these cases and guide appropriate management.