What are the causes of sudden transaminitis (elevated liver enzymes)?

Causes of Sudden Transaminitis

The most common causes of sudden transaminitis include medication-induced liver injury, viral hepatitis, alcohol-induced liver disease, and nonalcoholic fatty liver disease (NAFLD), with the specific etiology determined by the pattern and severity of enzyme elevation. 1

Classification of Transaminase Elevations

• Severity classification:
  • Mild: <5 times the upper limit of normal (ULN)
  • Moderate: 5-10 times ULN
  • Severe: >10 times ULN 2

Common Causes of Sudden Transaminitis

Medication-Induced Liver Injury

• Antimalarials: Chloroquine and hydroxychloroquine can cause rare but possible liver injury with elevated aminotransferases 2
• Antiretrovirals:
  • Remdesivir: Associated with elevated transaminases in 23% of patients 2
  • Lopinavir/ritonavir: Can cause moderate-to-severe elevations in 3-10% of patients 2
• Antipsychotics: Medications like olanzapine can cause transient elevations of liver enzymes, with risk increased in patients with underlying liver disease 3
• Other common hepatotoxic medications:
  • Antibiotics (amoxicillin-clavulanate, fluoroquinolones)
  • Statins
  • NSAIDs
  • Anti-tuberculosis drugs 4

Viral Causes

• Acute viral hepatitis (A, B, C, E)
  • Typically presents with ALT/LD ratio >1.5 (mean 4.65) 5
  • Hepatitis C can cause significant transaminitis, especially when combined with hepatotoxic medications 3

Metabolic Causes

• Nonalcoholic fatty liver disease (NAFLD):

  • Most common liver disease in developed countries (20-30% prevalence)
  • Prevalence increases to 70% with obesity and 90% with diabetes 2
  • AST:ALT ratio typically <1 2

• Alcohol-induced liver disease:

  • AST:ALT ratio generally >2 2
  • Can present with mild to severe transaminitis depending on consumption patterns

Vascular/Ischemic Causes

• Ischemic hepatitis:
  • Characterized by markedly elevated lactate dehydrogenase (LD)
  • ALT/LD ratio typically low (mean 0.87) 5
  • Often occurs in setting of cardiac failure or hypotension

Other Important Causes

• Biliary disease:

  • Chronic cholecystitis can present with acute severe transaminitis 6
  • Often accompanied by elevated alkaline phosphatase (ALP)

• Autoimmune hepatitis:

  • Can present with acute or chronic transaminitis
  • Often accompanied by elevated immunoglobulins

• Genetic/Metabolic disorders:

  • Hemochromatosis
  • Wilson's disease
  • Alpha-1 antitrypsin deficiency 2

• Glycogenic hepatopathy:

  • Underdiagnosed complication of uncontrolled Type 1 diabetes
  • Presents as acute relapsing hepatitis with reversible transaminase elevations 7

Diagnostic Approach

1. Initial laboratory evaluation:

   • Complete liver function panel (AST, ALT, ALP, bilirubin)
   • Complete blood count
   • Coagulation studies
   • Viral hepatitis serologies
   • Autoimmune markers if indicated

2. Imaging:

   • Ultrasound is the first-line investigation for mild increases in liver enzymes
   • Can detect steatosis with 84.8% sensitivity and 93.6% specificity when hepatic fat content >33% 2
   • Consider CT or MRI if ultrasound is inconclusive

3. Pattern recognition:

   • Hepatocellular pattern: Predominant elevation of aminotransferases (AST, ALT)
   • Cholestatic pattern: Predominant elevation of ALP
   • Mixed pattern: Elevations in both 2

4. Specialized testing:

   • ALT/LD ratio: >1.5 suggests viral hepatitis; <1.5 suggests ischemic or toxic injury 5
   • Drug levels when medication toxicity is suspected
   • Liver biopsy in unclear cases

Management Considerations

• Immediately discontinue suspected hepatotoxic medications for transaminases >3× ULN 1
• Monitor frequency based on severity:
  • Severe elevations: Every 2-3 days initially
  • Moderate elevations: Weekly until improving
  • Mild elevations: Every 2-4 weeks 1
• Avoid alcohol consumption and other hepatotoxic medications during recovery 1

Important Clinical Pitfalls

• Underlying liver disease significantly increases risk of drug-induced liver injury 3
• Multiple concurrent causes may be present (e.g., viral hepatitis plus medication toxicity)
• Non-hepatic causes of AST elevation (muscle injury, hemolysis, thyroid disease) should be considered 2
• Transaminitis in patients with HIV receiving antiretrovirals requires careful evaluation for drug toxicity versus opportunistic infections 2