What causes transient elevated liver function tests (LFTs)?

Causes of Transient Elevated Liver Function Tests

The most common causes of transient elevated liver function tests (LFTs) include nonalcoholic fatty liver disease (NAFLD), alcohol-induced liver disease, drug-induced liver injury, viral hepatitis, and occupational chemical exposures. 1

Common Patterns of LFT Elevation

Hepatocellular Pattern (Predominantly Elevated Aminotransferases)

• Common causes:

  • Nonalcoholic fatty liver disease (NAFLD) - most common in first world countries (20-30% prevalence) 1
  • Alcohol-induced liver disease 1
  • Drug-induced liver injury 1
  • Viral hepatitis (B and C) 1
  • Ischemic hepatitis/shock liver 1

• Pattern identification:

  • ALT > AST: Suggests NAFLD, viral hepatitis 1
  • AST > ALT (ratio >2): Suggests alcohol-induced liver disease 1
  • AST predominance may also indicate non-hepatic causes (hemolysis, myopathy, thyroid disease, exercise) 1

Cholestatic Pattern (Predominantly Elevated ALP)

• Common causes:
  • Extrahepatic biliary obstruction (choledocholithiasis, malignancy, strictures) 2
  • Intrahepatic cholestasis (primary biliary cholangitis, primary sclerosing cholangitis) 2
  • Drug-induced cholestasis 2
  • Infiltrative liver diseases 2
  • Sepsis (can cause extremely high ALP) 2

Mixed Pattern (Both Aminotransferases and ALP Elevated)

• Common causes:
  • Infiltrative diseases 2
  • Mixed injury patterns 2
  • Advanced liver disease 3

Transient Causes of LFT Elevation

1. Medication-related causes:

   • Antimalarials (chloroquine, hydroxychloroquine) 1
   • Antiretroviral medications (particularly in HIV/HCV co-infection) 4
   • Various other hepatotoxic medications 1, 2

2. Infectious causes:

   • Acute viral hepatitis 1
   • COVID-19 (15% of hospitalized patients) 1
   • Other systemic infections 2

3. Metabolic/physiologic causes:

   • Exercise-induced transaminase elevation 1
   • Steatosis without inflammation 1
   • Transient ischemic injury 1

4. Environmental/occupational causes:

   • Chemical hepatotoxin exposure 2
   • Alcohol consumption (even short-term) 1, 2

5. Other transient causes:

   • Hemolysis (causing AST elevation) 1
   • Systemic inflammatory response syndrome 1
   • Cytokine storm 1

Important Clinical Considerations

• Don't ignore mild elevations - they may be the first sign of significant disease, particularly in cholestatic processes 2

• Genetic factors - Variation in LFTs has a significant heritable basis (h² ranging from 20% to 77%) 5

• Pattern recognition is key - The R-ratio (ALT/ALP ratio) can help categorize the type of liver injury and guide further investigation 3, 6

• Monitoring approach:

  • Repeat testing to confirm persistent abnormalities 2
  • For drug-induced elevations, monthly monitoring is recommended 4
  • Consider GGT testing to confirm hepatic origin of ALP elevation 2

• Common pitfalls:

  • Attributing elevations solely to medications without ruling out more serious underlying causes 2
  • Failing to consider occupational exposures 2
  • Overlooking sepsis as a cause of extremely high ALP 2
  • Not evaluating for advanced fibrosis in patients with cholestatic pattern LFTs (31.3% have advanced fibrosis) 3

Diagnostic Algorithm for Transient LFT Elevations

1. Confirm elevation with repeat testing to rule out laboratory error
2. Determine pattern of elevation (hepatocellular, cholestatic, or mixed)
3. Review medication history thoroughly for potential drug-induced causes
4. Assess alcohol consumption (AST:ALT ratio >2 suggests alcohol-related)
5. Consider viral etiologies (test for hepatitis A, B, C as appropriate)
6. Evaluate for metabolic factors (diabetes, obesity, metabolic syndrome)
7. Consider occupational/environmental exposures
8. If cholestatic pattern, check GGT to confirm hepatic origin
9. If persistent, consider imaging and further specialized testing

Automated investigation algorithms like intelligent liver function testing (iLFT) have been shown to increase liver disease diagnoses by 43% and are cost-effective in evaluating abnormal LFTs 7.