Blood Tests for Suspected Gallbladder Issues
For patients with suspected gallbladder disease, obtain liver function tests (LFTs) including alkaline phosphatase (ALP), gamma-glutamyl transpeptidase (GGT), bilirubin (total and direct), AST, and ALT, along with a complete blood count (FBC) and coagulation studies (INR/PT) if intervention is anticipated. 1
Essential Initial Blood Tests
Liver Function Tests Panel
The following tests should be ordered as part of the initial workup 1:
- Alkaline phosphatase (ALP) - Most sensitive marker for biliary obstruction, with 92% sensitivity at cut-off >125 IU/L 1
- Gamma-glutamyl transpeptidase (GGT) - Most reliable LFT for common bile duct stones (CBDS) with 80.6% sensitivity and 75.3% specificity at cut-off of 224 IU/L 1
- Total and direct bilirubin - Elevated in 60-77% of patients with CBDS; at cut-off >22.23 μmol/L has 84% sensitivity and 91% specificity 1
- AST and ALT - Elevated ALT is a predictor of CBDS with 90% of CBDS patients showing elevation 1
- Serum albumin - Assesses hepatic synthetic function and chronic disease 1
Hematologic Tests
- Complete blood count (FBC) - Required before any biliary intervention; leucocytosis combined with elevated bilirubin may predict gangrenous cholecystitis 1
- INR/PT - Mandatory prior to ERCP or biliary sphincterotomy 1
Critical Interpretation Caveats
LFTs Have Limited Predictive Value
Elevated LFTs alone are insufficient to diagnose common bile duct stones and should not be used as the sole method to identify CBDS. 1 Key limitations include:
- Normal LFTs have 97% negative predictive value but abnormal LFTs have only 15% positive predictive value for CBDS 1
- In acute cholecystitis, 15-50% of patients show elevated LFTs without CBDS due to inflammatory processes rather than obstruction 1
- Among patients with acute cholecystitis and elevated LFTs, only 58% actually have CBDS 1
- Approximately 30% of acute cholecystitis patients without CBDS have abnormal ALP/bilirubin, and 50% have abnormal ALT 1
When LFTs Are Most Useful
- Biliary colic setting: Total bilirubin has 85% positive predictive value for CBDS 2
- Serial monitoring: LFTs that fail to decrease within 4 days suggest persistent CBDS, whereas improvement suggests resolution 1
- Bilirubin >twice normal limit: Achieves 97% specificity but only 42% sensitivity for CBDS 1
Additional Tests in Specific Scenarios
If Cholangiocarcinoma Suspected
When intrahepatic ducts are dilated without extrahepatic dilation 1, 3:
- CA 19-9 - Elevated in up to 85% of cholangiocarcinoma; >100 U/ml has 75% sensitivity and 80% specificity 1, 3
- CEA - Elevated in approximately 30% of cases 1
- CA-125 - Elevated in 40-50% of cases 1
If Autoimmune Cholangiopathy Suspected
For chronic cholestasis with elevated ALP/GGT 1, 3:
- Anti-mitochondrial antibodies (AMA) - Diagnostic for primary biliary cholangitis with >95% specificity 1
- ANA (anti-Sp100, anti-gp210) - High specificity (>95%) for PBC when AMA negative 1
- IgG4 levels - For IgG4-related cholangitis 1, 3
- Immunoglobulin M - Typically elevated in PBC 1
If Sepsis or Cholangitis Suspected
- C-reactive protein (CRP) - Evaluates severity of inflammation 1
- Procalcitonin (PCT) - Predicts fatal progression in septic patients 1
- Serum lactate - Associated with poor outcomes and increased mortality 1
Algorithmic Approach
Initial presentation with suspected gallbladder disease: Order LFTs (ALP, GGT, bilirubin, AST, ALT, albumin) + FBC 1, 4
If LFTs normal: Does not exclude CBDS; proceed with imaging (ultrasound) if clinical suspicion remains high 1
If LFTs elevated: Add INR/PT if intervention anticipated 1; proceed to imaging (ultrasound first, then MRCP if intermediate probability of CBDS) 1, 3
If cholestatic pattern (elevated ALP/GGT) persists: Consider autoimmune workup (AMA, ANA, IgG4) and tumor markers (CA 19-9, CEA) 1, 3
If fever/sepsis present: Add CRP, PCT, lactate 1
Normal LFTs and ultrasound do not preclude further investigation if clinical suspicion remains high. 1