What are the causes of transaminitis?

Common Causes of Transaminitis

The most common causes of transaminitis include nonalcoholic fatty liver disease (NAFLD), alcoholic liver disease, medication-induced liver injury, viral hepatitis, and autoimmune hepatitis, with NAFLD affecting up to 30% of the general population 1.

Definition and Classification

Transaminitis refers to elevated serum levels of liver enzymes alanine aminotransferase (ALT) and aspartate aminotransferase (AST). The pattern and degree of elevation can help guide the diagnostic approach:

• Mild elevation: Less than 5 times the upper limit of normal (ULN)
• Moderate elevation: 5-10 times ULN
• Severe elevation: Greater than 10 times ULN

Common Causes

1. Metabolic Causes

• Nonalcoholic Fatty Liver Disease (NAFLD)

  • Most common cause of transaminitis in developed countries 2
  • Associated with metabolic syndrome, obesity, diabetes, and hyperlipidemia 3
  • Usually presents with mild to moderate ALT/AST elevation with AST:ALT ratio <1

• Nonalcoholic Steatohepatitis (NASH)

  • Progressive form of NAFLD with inflammation and potential fibrosis
  • May progress to cirrhosis in some patients

2. Toxic/Drug-Induced Causes

• Alcoholic Liver Disease

  • Typically shows AST:ALT ratio >2
  • May present with mild to severe transaminitis depending on consumption patterns

• Medication-Induced Liver Injury

  • Common medications include statins, antibiotics (particularly fluoroquinolones), methotrexate, and acetaminophen 4, 5
  • Immune checkpoint inhibitors can cause immune-mediated liver injury (ILICI) 3
  • Presentation varies from asymptomatic transaminitis to acute liver failure

3. Infectious Causes

• Viral Hepatitis

  • Hepatitis A, B, C, D, and E
  • Acute viral hepatitis can cause marked transaminitis (>1000 U/L)
  • Chronic hepatitis B and C typically cause mild to moderate elevations 3

• Other Infections

  • Cytomegalovirus, Epstein-Barr virus, herpes simplex virus
  • Bacterial infections with sepsis

4. Autoimmune Causes

• Autoimmune Hepatitis

  • More common in women
  • Often associated with other autoimmune conditions
  • May present with acute or chronic transaminitis 3

• Primary Biliary Cholangitis

• Primary Sclerosing Cholangitis

5. Genetic/Hereditary Causes

• Hemochromatosis
• Wilson's Disease
• Alpha-1 Antitrypsin Deficiency 3

6. Other Hepatic Causes

• Ischemic Hepatitis (shock liver)

  • Dramatic elevation of transaminases (often >1000 U/L)
  • Rapid improvement with restoration of blood flow

• Biliary Obstruction

  • Usually presents with predominant alkaline phosphatase elevation

7. Extrahepatic Causes

• Muscle Disorders

  • Rhabdomyolysis, muscular dystrophy, strenuous exercise
  • Usually affects AST more than ALT

• Thyroid Disorders

• Celiac Disease

• Adrenal Insufficiency

Diagnostic Approach

Initial Evaluation

1. Detailed history:

   • Alcohol consumption
   • Medication use (prescription, OTC, supplements)
   • Risk factors for viral hepatitis
   • Family history of liver disease

2. Initial laboratory testing:

   • Complete blood count with platelets
   • Comprehensive metabolic panel
   • Fasting lipid profile and glucose
   • Hepatitis B surface antigen and hepatitis C antibody
   • Serum iron, ferritin, and total iron-binding capacity 2, 6

Further Evaluation Based on Clinical Suspicion

1. For suspected NAFLD/NASH:

   • Assess for metabolic syndrome
   • Consider NAFLD fibrosis score
   • Liver ultrasound 3

2. For suspected autoimmune hepatitis:

   • Antinuclear antibody, smooth muscle antibody
   • Immunoglobulin levels
   • Consider liver biopsy 3

3. For suspected genetic disorders:

   • Alpha-1 antitrypsin level
   • Ceruloplasmin and 24-hour urinary copper (Wilson's disease)
   • Genetic testing for hemochromatosis

Management Principles

1. Treat the underlying cause:

   • Lifestyle modifications for NAFLD (weight loss, exercise)
   • Alcohol cessation for alcoholic liver disease
   • Discontinuation of hepatotoxic medications 2
   • Antiviral therapy for viral hepatitis
   • Immunosuppression for autoimmune hepatitis

2. Monitoring:

   • Follow liver enzymes every 2-4 weeks initially
   • More frequent monitoring (every 1-2 weeks) for high-risk patients 2

Common Pitfalls to Avoid

1. Assuming NAFLD in overweight patients without proper screening for other causes
2. Overlooking medications and supplements as potential causes
3. Missing autoimmune hepatitis, which may require liver biopsy for diagnosis
4. Dismissing mild persistent transaminitis without proper evaluation
5. Failing to assess liver synthetic function (INR, albumin, bilirubin) in patients with transaminitis

Remember that normal transaminase levels do not exclude significant liver disease, particularly in NASH where ALT may be normal or near normal despite significant pathology 3.