Initial Workup and Management of Elevated Liver Function Tests (LFTs)
The initial workup for elevated liver function tests should include a comprehensive laboratory evaluation to determine the pattern of liver injury, followed by targeted testing based on this pattern to identify the underlying cause. 1
Initial Assessment
- Obtain a complete laboratory panel including ALT, AST, ALP, GGT, total and direct bilirubin, albumin, and prothrombin time/INR to determine the pattern and severity of liver injury 1
- Classify the pattern as hepatocellular (predominant ALT/AST elevation), cholestatic (predominant ALP/GGT elevation), or mixed 1
- Categorize severity of aminotransferase elevations as mild (<5× ULN), moderate (5-10× ULN), severe (>10× ULN), or life-threatening (>20× ULN) 1
- Check serum creatine kinase (CK) to rule out muscle injury as a cause of elevated AST 1
- Review medication history, including prescription drugs, over-the-counter medications, and supplements 2
- Assess alcohol consumption history using validated tools such as AUDIT-C 2
Pattern-Based Investigation
For Hepatocellular Pattern (Elevated ALT/AST):
- Test for viral hepatitis: anti-HAV IgM, HBsAg, anti-HBc IgM, and anti-HCV 1
- Screen for NAFLD risk factors: obesity, type 2 diabetes, dyslipidemia, and hypertension 2
- For patients with NAFLD risk factors, perform risk stratification using FIB-4 or NAFLD Fibrosis Score 2
- Consider autoimmune hepatitis: ANA, ASMA, ANCA if clinical suspicion is high 2
- For isolated transaminase elevations, check CK to rule out muscle origin 2
For Cholestatic Pattern (Elevated ALP/GGT):
- Confirm hepatic origin of elevated ALP by checking GGT 2
- Perform abdominal ultrasound to evaluate for biliary obstruction 2
- If ALP is elevated alone, check GGT to confirm hepatic origin 2
Management Based on Severity
Mild Elevations (<5× ULN):
- Monitor liver enzymes weekly until normalization 1
- Discontinue potentially hepatotoxic medications and alcohol 2
- For Grade 1 LFT abnormality in patients on immune checkpoint inhibitors, continue treatment with close monitoring 2
Moderate Elevations (5-10× ULN):
- Monitor liver enzymes every 2-3 days until stable or improving 1
- For Grade 2 hepatic toxicity in patients on immune checkpoint inhibitors (AST/ALT >3.0 to ≤5.0× ULN), hold treatment temporarily and consider steroids (0.5-1 mg/kg/d prednisone) if no improvement after 3-5 days 2
- Increase monitoring frequency to every 3 days 2
Severe Elevations (>10× ULN):
- Monitor liver enzymes every 1-2 days 1
- For Grade 3 hepatic toxicity in patients on immune checkpoint inhibitors (AST/ALT 5-20× ULN), consider permanently discontinuing treatment and immediately start steroids (1-2 mg/kg methylprednisolone) 2
- Consider hepatology consultation 2
Life-Threatening Elevations (>20× ULN):
- Immediate hospitalization for intensive monitoring and supportive care 1
- For Grade 4 hepatic toxicity in patients on immune checkpoint inhibitors, permanently discontinue treatment 2
Special Considerations
- For harmful alcohol drinkers (>50 units/week for men, >35 units/week for women), perform risk stratification with Fibroscan/ARFI elastography 2
- Refer to alcohol services for adults with evidence of alcohol dependency (AUDIT score >19) 2
- For patients on immune checkpoint inhibitors with hepatitis, infliximab is contraindicated 2
- For patients with abnormal liver tests despite negative extended liver etiology screen and no risk factors for NAFLD, refer to a gastroenterologist with interest in liver disease/hepatologist 2
Follow-up Recommendations
- Repeat testing frequency should be based on the severity of elevation and clinical context 1
- Consider liver biopsy if the patient is steroid-refractory or if there is concern for differential diagnoses that would alter management 2
- Refer to hepatology for persistent unexplained elevations, evidence of advanced fibrosis, or ALT >5× ULN 1