Common Causes of Transaminitis
Transaminitis (elevated liver enzymes) is most commonly caused by non-alcoholic fatty liver disease (NAFLD), alcoholic liver disease, viral hepatitis, and medication-induced liver injury. 1
Primary Causes of Transaminitis
Metabolic Causes
- Non-alcoholic fatty liver disease (NAFLD): The most common cause of mildly elevated transaminases in developed countries 2, 1
- Associated with obesity, type 2 diabetes, hyperlipidemia, and metabolic syndrome
- Typically presents with AST:ALT ratio <1 in early stages 1
Alcohol-Related
- Alcoholic liver disease: Characterized by AST:ALT ratio >2 1
- Even moderate alcohol consumption can exacerbate other liver conditions
- Can potentiate hepatotoxicity of medications like acetaminophen 3
Viral Causes
- Viral hepatitis (B and C): Important infectious causes 2
- Hepatitis B and C can cause acute or chronic transaminitis
- Genotype 3 strains of hepatitis C are associated with increased rates of steatosis 2
Medication-Induced Liver Injury
- Drug-induced liver injury (DILI): Common cause of transaminitis 2, 1
- Common hepatotoxic medications include:
- Immune checkpoint inhibitors: Can cause immune-mediated liver injury (ILICI) 2
Less Common Causes
Autoimmune and Genetic
- Autoimmune hepatitis: Rare cause of transaminitis 5
- Hereditary conditions:
- Hemochromatosis (iron overload)
- Alpha-1 antitrypsin deficiency
- Wilson's disease 5
Endocrine and Metabolic
- Glycogen hepatopathy: Seen in poorly controlled diabetes with insulin therapy 6
- Hyperthyroidism: Can cause mild transaminitis 5
- Celiac disease: An extrahepatic cause of transaminitis 5
Other Causes
- Chronic cholecystitis: Rarely presents with severe transaminitis 7
- Rhabdomyolysis: Can cause elevated AST and ALT 5
- Pregnancy-associated liver disease: Including HELLP syndrome and acute fatty liver of pregnancy 5
Diagnostic Approach
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 1, 5
Imaging
- Ultrasound is the first-line investigation (84.8% sensitivity and 93.6% specificity for detecting steatosis when hepatic fat content >33%) 1
- Consider CT or MRI if ultrasound is inconclusive
Severity Classification
- Mild: <3× upper limit of normal (ULN)
- Moderate: 3-5× ULN
- Severe: >5× ULN
- Life-threatening: >20× ULN 1
Management Considerations
- Identify and address the underlying cause: This is the cornerstone of management
- Lifestyle modifications: For NAFLD, weight loss (7-10% of body weight), regular exercise, and Mediterranean diet 1
- Medication review: Discontinue or modify potentially hepatotoxic medications 2
- Alcohol cessation: Particularly important in those with existing liver disease 5
- Monitor transaminase levels: Every 3-6 months for mild transaminitis, every 1-3 months for moderate transaminitis, and every 2-4 weeks for severe transaminitis until improvement 1
Special Considerations
- Immune checkpoint inhibitor therapy: May require corticosteroids for immune-mediated hepatitis 2, 1
- Viral hepatitis treatment: Consider antiviral therapy for hepatitis B or C 2, 1
- Diabetes management: Monitor for glycogen hepatopathy in poorly controlled diabetes 6
Remember that mild asymptomatic increases in ALT or AST (>1× to <3× ULN) without elevated bilirubin may be related to non-specific causes like NAFLD, dietary changes, or vigorous exercise 2.