What laboratory studies should be obtained to evaluate a patient for gallbladder disease?

Laboratory Testing for Gallbladder Disease

For patients with suspected gallbladder disease, obtain a complete liver biochemistry panel including ALT, AST, alkaline phosphatase (ALP), GGT, total and direct bilirubin, along with a complete blood count as the initial laboratory workup. 1, 2

Essential Initial Laboratory Tests

The following tests should be ordered as first-line investigations:

• Liver function tests: ALT, AST, bilirubin (total and direct), alkaline phosphatase, and GGT 1, 2
• Complete blood count (CBC): To assess for leukocytosis suggesting inflammation or infection 2
• Additional tests if intervention planned: Albumin and prothrombin time/INR should be obtained if endoscopic or surgical intervention is being considered 2

Diagnostic Value and Interpretation

For Acute Cholecystitis

The combination of clinical findings, laboratory abnormalities, and imaging provides the best diagnostic approach:

• Elevated C-reactive protein and elevated white blood cell count are useful laboratory markers 3
• GGT has the highest specificity among liver function tests for predicting common bile duct (CBD) stones in acute cholecystitis, with a cut-off of 90 units/L producing 86% sensitivity and 74.5% specificity 4
• A GGT >90 units/L indicates a 1 in 3 chance of CBD stones, while <90 units/L indicates only a 1 in 30 chance 4

For Gallstone Pancreatitis

When acute pancreatitis is suspected in the context of gallbladder disease:

• Add serum amylase or lipase, triglyceride level, and calcium level to confirm pancreatitis and identify alternative causes 3, 2
• ALT is the most clinically useful parameter for distinguishing gallstone from non-gallstone pancreatitis 5
• ALT ≥150 IU/L (approximately 3-fold elevation) has a 95% positive predictive value for gallstone pancreatitis 5

For Cholangitis

When cholangitis is suspected:

• Cholestatic pattern with elevated ALP and GGT is the most common biochemical abnormality 6
• Leukocytosis and elevated C-reactive protein are major diagnostic criteria 6
• The classic Charcot triad (fever/chills, right upper quadrant pain, jaundice) combined with laboratory cholestasis supports the diagnosis 6

Risk Stratification for Common Bile Duct Stones

Laboratory values help stratify risk for CBD stones, which guides further management:

Strong Predictors

• Bilirubin >4 mg/dL 1

Moderate Predictors

• Any abnormal liver function tests 1
• Age >55 years and clinical gallstone pancreatitis 1

Negative Predictive Value

• Normal liver biochemical tests have a 97% negative predictive value for CBD stones, making them highly useful for ruling out choledocholithiasis 1, 2
• However, the positive predictive value of any single abnormal test is only 15%, so abnormal results require correlation with imaging 1

Important Caveats and Pitfalls

• ALT is more liver-specific than AST and should be prioritized when assessing hepatocellular injury, as AST can be elevated in cardiac, skeletal muscle, kidney, and red blood cell disorders 2
• Bilirubin and alkaline phosphatase alone are not useful for diagnosing gallstone pancreatitis 5
• In acute cholecystitis, elevated LFTs are less predictive of CBD stones compared to biliary colic, with positive predictive values often <40% 7
• CA 19-9 should not be interpreted during active bacterial cholangitis, as infection can cause false elevation 3, 6
• Serial testing may be necessary if initial workup is equivocal, as initial labs may not capture the full extent of disease 2

Clinical Algorithm

1. Order initial labs: Complete liver panel (ALT, AST, ALP, GGT, total and direct bilirubin), CBC 1, 2
2. Add coagulation studies and albumin if intervention is planned 2
3. If pancreatitis suspected: Add amylase/lipase, triglycerides, and calcium 3, 2
4. Interpret results in context:
   • ALT ≥150 IU/L strongly suggests gallstone pancreatitis 5
   • GGT >90 units/L in acute cholecystitis warrants further imaging for CBD stones 4
   • Bilirubin >4 mg/dL is a strong predictor of choledocholithiasis 1
5. Repeat labs in 2-4 weeks if initial workup is equivocal or to establish trends 2