What causes transaminitis?

Causes of Transaminitis

Transaminitis is most commonly caused by non-alcoholic fatty liver disease (NAFLD) and alcoholic liver disease, followed by drug-induced liver injury, viral hepatitis, and other less common etiologies. 1

Common Causes

Metabolic and Lifestyle-Related Causes

• Non-alcoholic fatty liver disease (NAFLD): Most common cause in developed countries, associated with:
  • Obesity
  • Type 2 diabetes
  • Hypercholesterolemia
  • Metabolic syndrome 2
• Alcoholic liver disease: Second most common cause 1

Medication-Related Causes

• Drug-induced liver injury (DILI):
  • Statins: Can cause mild transaminase elevations (0.5-2.0% of cases), rarely severe hepatotoxicity 2
  • Acetaminophen: Most common cause of severe acute liver failure requiring transplantation (22% in France) 2
  • Methotrexate: Can cause transaminitis, especially in patients with risk factors for NAFLD 3
  • Other medications:
    • Antimicrobial agents
    • Antiepileptic drugs
    • NSAIDs
    • Amiodarone
    • Tamoxifen
    • Antiretrovirals 2

Infectious Causes

• Viral hepatitis:
  • Hepatitis B and C (14.6% of acute liver failure cases) 2
  • Hepatitis A 2

Less Common Causes

Autoimmune and Genetic Disorders

• Autoimmune hepatitis 2, 1
• Hereditary hemochromatosis 1
• Wilson's disease 2, 1
• Alpha-1 antitrypsin deficiency 1

Vascular and Ischemic Causes

• Ischemic hepatitis: Often in critically ill patients with cardiac or circulatory failure 2
• Budd-Chiari syndrome 2

Toxic Causes

• Herbal supplements 2
• Recreational drugs (cocaine, ecstasy) 2
• Mushroom poisoning 2

Biliary Causes

• Cholecystitis: Can present with transaminitis 4
• Biliary obstruction 2

Extrahepatic Causes

• Thyroid disorders
• Celiac disease
• Hemolysis
• Muscle disorders (can elevate AST) 1
• Malignancy: Primary liver tumors or hepatic metastases 2

Evaluation Algorithm

1. Initial assessment:

   • Assess for metabolic syndrome risk factors (waist circumference, blood pressure, fasting lipids, glucose/A1C)
   • Complete medication review including over-the-counter and herbal supplements
   • Alcohol consumption history
   • Complete blood count with platelets
   • Serum albumin, iron studies (iron, TIBC, ferritin)
   • Hepatitis C antibody and hepatitis B surface antigen 1

2. For mild elevations (less than 3x ULN):

   • Consider NAFLD if metabolic risk factors present
   • Calculate NAFLD fibrosis score
   • Consider trial of lifestyle modification if common causes identified 1

3. For moderate elevations (3-5x ULN):

   • More urgent evaluation needed
   • Consider drug-induced causes and discontinue potential hepatotoxic medications
   • Abdominal ultrasound to assess liver morphology and rule out biliary obstruction 2

4. For severe elevations (>10x ULN):

   • Urgent evaluation needed
   • Consider acetaminophen toxicity and initiate N-acetylcysteine without waiting for acetaminophen levels 2
   • Assess for acute viral hepatitis, ischemic injury, or severe DILI

5. If initial evaluation inconclusive:

   • Consider less common causes
   • Evaluate for autoimmune hepatitis, Wilson's disease, hemochromatosis
   • Consider liver biopsy in selected cases 2

Important Clinical Pearls

• Up to 25% of acute liver failure cases remain of unknown etiology despite extensive investigation 2
• Mild elevations of transaminases (1-3x ULN) may be transient and resolve spontaneously, a phenomenon called "adaptation" 2
• Patients with NAFLD risk factors (obesity, diabetes, hyperlipidemia) are at higher risk for drug-induced transaminitis, particularly with medications like methotrexate 3
• N-acetylcysteine therapy is beneficial not only for acetaminophen-induced liver injury but may improve outcomes in non-acetaminophen acute liver failure as well 2
• The AST:ALT ratio can provide diagnostic clues - a ratio <1 is typical in early NAFLD, while a ratio >1 may suggest alcoholic liver disease or advanced fibrosis 2

By systematically evaluating patients with transaminitis using this approach, clinicians can efficiently identify and manage the underlying cause, potentially preventing progression to more severe liver disease.