What is the initial workup for a patient presenting with transaminitis (elevated liver enzymes)?

Initial Workup for Transaminitis (Elevated Liver Enzymes)

The initial workup for transaminitis should include discontinuation of all potentially hepatotoxic medications, assessment of liver synthetic function (INR, albumin, bilirubin), complete blood count with platelets, comprehensive metabolic panel, fasting lipid profile and glucose, and serum iron studies. 1

Step 1: Immediate Management

• Discontinue potentially hepatotoxic medications (including acetaminophen, NSAIDs, statins) 1, 2
• Assess severity by checking:
  • Liver synthetic function (INR, albumin, bilirubin)
  • Complete blood count with platelets
  • Comprehensive metabolic panel
  • Fasting lipid profile and glucose
  • Serum iron, ferritin, and total iron-binding capacity 1

Step 2: Pattern Recognition

Identify pattern of liver enzyme elevation to guide further workup:

1. Hepatocellular pattern (predominant AST/ALT elevation):

   • Viral hepatitis serologies (HAV, HBV, HCV)
   • Autoimmune markers (ANA, anti-smooth muscle antibody, IgG levels)
   • Ceruloplasmin (Wilson's disease) if age <40
   • Alpha-1 antitrypsin level

2. Cholestatic pattern (predominant alkaline phosphatase/GGT elevation):

   • Ultrasound of liver/biliary system
   • Anti-mitochondrial antibody (primary biliary cholangitis)
   • MRCP if obstruction suspected

3. Mixed pattern:

   • Consider drug-induced liver injury
   • Consider overlap syndromes

Step 3: Risk Factor Assessment

• Metabolic factors: Check BMI, assess for metabolic syndrome, diabetes 3
• Alcohol use: Detailed alcohol history
• Medication review: Prescription, OTC, and supplements
• Viral risk factors: IV drug use, sexual history, travel history
• Autoimmune history: Personal or family history of autoimmune disorders

Step 4: Initial Testing

Based on the American Gastroenterological Association and European Association for the Study of the Liver recommendations 1:

• Viral hepatitis screening: HBsAg, anti-HBc, anti-HBs, anti-HCV
• Autoimmune workup: ANA, ASMA, IgG levels
• Metabolic workup: Fasting lipid panel, HbA1c, ferritin, transferrin saturation
• Imaging: Right upper quadrant ultrasound

Step 5: Monitoring and Follow-up

• Monitor liver function tests every 2-4 weeks initially 1
• More frequent monitoring (every 1-2 weeks) for patients with:
  • History of hepatotoxic medication use
  • High risk of liver disease 1

Special Considerations

• Acute severe transaminitis (ALT/AST >10x ULN): Consider acute viral hepatitis, ischemic injury, or toxin-induced injury 4
• Mild persistent transaminitis (ALT/AST <5x ULN): Don't dismiss as NAFLD without proper screening for viral hepatitis, as chronic hepatitis B/C can present with fluctuating mild elevations 2
• Immune checkpoint inhibitor therapy: Consider immune-related hepatitis in patients on these medications 5, 1

Common Pitfalls to Avoid

1. Assuming NAFLD in overweight patients without proper screening - This can miss viral hepatitis and other causes 2
2. Delaying hepatitis screening - The "wait and see" approach can delay diagnosis of treatable conditions 2
3. Overlooking medications and supplements - Many OTC products can cause transaminitis
4. Missing autoimmune hepatitis - Can present with varying degrees of transaminitis and may require liver biopsy for diagnosis 5, 6

By following this systematic approach, most causes of transaminitis can be identified and appropriately managed, leading to better patient outcomes and prevention of progression to chronic liver disease.