Blood Tests for Liver Toxicity Assessment
The standard panel for assessing liver toxicity includes ALT, AST, ALP, GGT, total and direct bilirubin, and albumin, which should be monitored regularly when liver toxicity is suspected. 1
Primary Liver Function Tests
Core Panel
- Alanine aminotransferase (ALT) - Primary marker of hepatocellular injury
- Aspartate aminotransferase (AST) - Marker of hepatocellular injury, less liver-specific than ALT
- Alkaline phosphatase (ALP) - Marker of cholestatic injury
- Gamma-glutamyl transferase (GGT) - Confirms hepatic origin of ALP elevation
- Bilirubin (total and direct) - Assesses liver's ability to process and excrete bilirubin
- Albumin - Reflects synthetic function of the liver
Additional Tests
- Prothrombin time (PT)/International Normalized Ratio (INR) - Assesses liver's synthetic function
- Complete blood count (CBC) - Particularly platelet count, which may decrease in advanced liver disease
Pattern Recognition
Hepatocellular Injury Pattern
- Predominant elevation of ALT and AST (ALT often > AST)
- R value ≥5 (R = [ALT/ALT ULN]/[ALP/ALP ULN]) 1
Cholestatic Injury Pattern
- Predominant elevation of ALP and GGT
- R value ≤2 1
Mixed Pattern
- Elevations in both transaminases and cholestatic enzymes
- R value >2 and <5 1
Etiological Workup for Abnormal Liver Tests
When liver toxicity is suspected, additional tests should be performed to determine the underlying cause:
Viral Hepatitis Panel
- Hepatitis B surface antigen (HBsAg)
- Hepatitis C antibody (with PCR confirmation if positive)
- Consider testing for hepatitis A, D, and E in appropriate clinical contexts 1
Autoimmune Markers
- Anti-nuclear antibody (ANA)
- Anti-smooth muscle antibody (ASMA)
- Anti-mitochondrial antibody (AMA)
- Serum immunoglobulins 1
Metabolic Disease Markers
- Ferritin and transferrin saturation (for hemochromatosis)
- Ceruloplasmin (for Wilson's disease in patients <40 years)
- Alpha-1-antitrypsin level 1
Drug-Induced Liver Injury Assessment
- Thorough medication history (prescription, over-the-counter, supplements)
- Pattern of injury can help identify drug-related toxicity 1
Monitoring Recommendations
Frequency of Testing
- For suspected drug-induced liver toxicity: Monitor ALT, AST, ALP, and bilirubin before each treatment cycle or at least monthly 1
- For Phase 1 clinical trials: Weekly monitoring for first 2 cycles or 6-8 weeks, then every 2-4 weeks 1
Grading of Liver Test Abnormalities
- Grade 1: ALT/AST >ULN to 3× ULN
- Grade 2: ALT/AST >3× to 5× ULN
- Grade 3: ALT/AST >5× to 20× ULN
- Grade 4: ALT/AST >20× ULN 1
Special Considerations
Baseline Abnormalities
- For patients with abnormal baseline liver tests, use multiples of baseline rather than ULN for grading 1
Imaging
- Abdominal ultrasound is recommended as first-line imaging when liver test abnormalities are detected 2
Liver Biopsy
- Consider when serologic testing and imaging fail to establish a diagnosis
- Useful for assessing drug-induced liver injury when other causes have been excluded 3
Common Pitfalls to Avoid
Relying solely on ALT/AST: GGT and ALP provide crucial information about cholestatic patterns of injury that may be missed by focusing only on transaminases 1
Ignoring mild elevations: Even mild elevations (1-3× ULN) can indicate significant liver disease and should not be dismissed 2, 3
Failing to calculate R values: The pattern of liver enzyme elevation (hepatocellular, cholestatic, or mixed) provides important diagnostic clues 1
Not considering medication history: Always obtain a comprehensive medication history, including over-the-counter drugs and supplements 1
Inadequate follow-up: Persistent abnormalities require continued monitoring and potentially specialist referral 2
By systematically evaluating these liver function tests and understanding their patterns, clinicians can effectively assess and monitor liver toxicity, leading to improved patient outcomes through early detection and intervention.