Can cholelithiasis (gallstones) cause elevated Liver Function Tests (LFTs)?

Cholelithiasis and Elevated Liver Function Tests

Yes, cholelithiasis (gallstones) can cause elevated liver function tests (LFTs), particularly when stones migrate to the common bile duct or cause inflammation that affects the biliary system. 1

Patterns of LFT Elevation in Gallstone Disease

Uncomplicated Gallstones

• In uncomplicated symptomatic cholelithiasis (gallstones confined to the gallbladder):
  • LFTs are normal in approximately 85-87% of patients 2
  • When elevation occurs, it's typically mild and not clinically significant 3

Acute Cholecystitis

• In acute cholecystitis without common bile duct (CBD) stones:
  • 15-50% of patients show mild elevation of ALT/AST
  • Bilirubin is normal or slightly elevated
  • Mild to moderate elevation of alkaline phosphatase (ALP) and gamma-glutamyl transferase (GGT) 1

Choledocholithiasis (Common Bile Duct Stones)

• When gallstones migrate to the CBD, more significant LFT abnormalities occur:
  • Marked elevation of ALP (>3x normal)
  • Significant elevation of GGT (sensitivity 80.6%, specificity 75.3%)
  • Moderate to marked elevation of ALT/AST
  • Elevated bilirubin, especially direct (conjugated) bilirubin 1

Diagnostic Value of LFTs in Detecting CBD Stones

• GGT is the most reliable LFT for detecting CBD stones in acute cholecystitis:

  • Sensitivity: 80.6%
  • Specificity: 75.3%
  • Positive predictive value: 50%
  • Negative predictive value: 91.4% (at cut-off level of 224 IU/L) 1

• Using a cut-off point for GGT at 90 units/L:

  • Sensitivity: 86%
  • Specificity: 74.5%
  • Positive predictive value: 33%
  • Negative predictive value: 97.2% 4

• Normal LFTs have a high negative predictive value (97%) for CBD stones 1

Important Clinical Considerations

• Elevated LFTs alone are insufficient for diagnosis of CBD stones - the World Society of Emergency Surgery strongly recommends against using elevated LFTs or bilirubin as the only method to identify CBD stones in patients with acute cholecystitis 5

• LFT abnormalities in acute cholecystitis may be due to the inflammatory process affecting the gallbladder and biliary tree rather than direct biliary obstruction 5

• In patients with suspected CBD stones, further diagnostic tests should be performed, such as MRCP, EUS, or ERCP 5, 1

• LFT patterns can help risk-stratify patients for likelihood of CBD stones:

  • Low risk (<10% probability): Normal LFTs
  • Intermediate risk (10-50% probability): Mildly elevated LFTs
  • High risk (>50% probability): Significantly elevated LFTs, especially GGT and direct bilirubin 1

Pitfalls and Caveats

• False positives: Elevated LFTs in gallstone disease may be due to other conditions such as hepatitis, medication effects, or alcohol consumption

• False negatives: Up to 15% of patients with CBD stones may have normal LFTs 6

• Timing matters: LFTs may normalize within 3-4 days even with persistent CBD stones 7

• Acute cholecystitis can cause LFT elevation even without CBD stones, making interpretation challenging 6

• GGT and bilirubin levels, while relatively sensitive for CBD stones, are not reliable enough due to high false-positive and false-negative rates, especially in acute cholecystitis 6

When evaluating a patient with cholelithiasis and elevated LFTs, consider the pattern and degree of elevation to determine the likelihood of CBD stones, but always confirm with appropriate imaging studies rather than relying solely on laboratory values.