Workup for Elevated AST, ALT, and Lipase
The workup for a patient with elevated AST, ALT, and lipase should begin with a comprehensive evaluation for drug-induced liver injury (DILI), biliary obstruction, viral hepatitis, and pancreatitis, with specific laboratory and imaging studies based on the pattern and severity of enzyme elevations. 1, 2
Initial Laboratory Evaluation
First-line Tests
- Complete blood count
- Comprehensive metabolic panel (including bilirubin, albumin, total protein)
- Coagulation profile (PT/INR)
- Viral hepatitis panel:
- Hepatitis B (HBsAg, anti-HBc IgG/IgM, HBV DNA)
- Hepatitis C (anti-HCV, HCV RNA)
- Hepatitis E (anti-HEV IgG/IgM, HEV RNA if indicated)
- Autoimmune markers:
- ANA, ASMA, ANCA, p-ANCA, AMA
- Quantitative immunoglobulins (IgG, IgM, IgA)
- Lipid profile and HbA1c (to assess for metabolic syndrome)
- Blood gas analysis (if hypoxemia suspected)
- Serum acetaminophen level
- Alcohol markers (urinary ethyl-glucuronide, serum phosphatidylethanol)
Specific Tests for Elevated Lipase
- Amylase
- Lipase/amylase ratio (helpful in identifying biliary pancreatitis) 3
- Triglycerides
- Calcium levels
Imaging Studies
First-line Imaging
- Abdominal ultrasonography with Doppler studies to evaluate:
- Liver parenchyma and size
- Biliary tract (for obstruction or gallstones)
- Pancreatic structure
- Portal and hepatic vein patency
Second-line Imaging (if indicated)
- CT scan with contrast
- MRI with contrast
- MRCP (if cholestatic pattern or suspected biliary obstruction)
- Endoscopic ultrasound (if pancreatic pathology suspected)
Pattern Recognition
Calculate R Value
- R = (ALT/ALT ULN)/(ALP/ALP ULN)
- R ≥5: Hepatocellular injury pattern
- R ≤2: Cholestatic injury pattern
- R >2 and <5: Mixed injury pattern 1
Calculate AST/ALT Ratio
- Ratio >2: Strongly suggests alcoholic liver disease
- Ratio ≥1: High specificity for cirrhosis in chronic HCV
- Ratio <1: Common in NAFLD/NASH 2
- AST/ALT ratio provides valuable diagnostic information even when values are within normal range 2
Special Considerations
For Suspected Drug-Induced Liver Injury
- Complete medication history (prescription, OTC, supplements)
- Discontinue potential hepatotoxic medications
- Consider withholding immune checkpoint inhibitors if relevant 2
For Suspected Pancreatitis with Biliary Etiology
- ALT >150 U/L is highly diagnostic of biliary pancreatitis 3
- Lipase/amylase ratio provides additional diagnostic information for biliary obstruction 3
Second-line Testing (if initial workup inconclusive)
- Serological tests for EBV, CMV, HSV, VZV
- Blood ceruloplasmin and serum copper (Wilson's disease)
- Ferritin, iron, TIBC (hemochromatosis)
- Alpha-1 antitrypsin levels
- Thyroid function tests
- Urine toxicology screen
When to Consider Liver Biopsy
- Persistent unexplained elevation of liver enzymes >6 months
- Suspected autoimmune hepatitis
- Conflicting clinical, laboratory, and imaging findings
- To determine pattern and severity of DILI versus other etiologies 1, 2
Monitoring
- Follow-up laboratory testing at 3-6 month intervals
- Repeat imaging based on clinical course
- FIB-4 score calculation to assess for fibrosis
- Consider elastography if fibrosis is suspected 2
Referral Indications
- ALT elevation >5× ULN
- Persistent elevation >6 months despite interventions
- Signs of hepatic decompensation
- Suspected autoimmune hepatitis
- Conflicting clinical, laboratory, and imaging findings 2
The combination of elevated AST, ALT, and lipase requires careful evaluation as it may indicate several serious conditions including pancreatobiliary disease, which has been reported in 13% of patients with marked transaminase elevations 4. This pattern may also be seen in severe malnutrition states like anorexia nervosa, which can lead to critical complications 5.