What are the differential diagnoses for a post‑cholecystectomy patient presenting with diffuse abdominal pain, leukocytosis, elevated aspartate aminotransferase, elevated lipase, and elevated alkaline phosphatase?

Differential Diagnosis for Post-Cholecystectomy Patient with Diffuse Abdominal Pain, Leukocytosis, Elevated AST, Lipase, and Alkaline Phosphatase

The combination of leukocytosis, elevated alkaline phosphatase, and elevated AST in a post-cholecystectomy patient with diffuse abdominal pain most strongly suggests bile duct injury with either retained choledocholithiasis or bile leak, and you must obtain urgent abdominal ultrasound followed by contrast-enhanced MRCP to differentiate these life-threatening complications. 1, 2

Primary Biliary Complications (Most Urgent)

Bile Duct Injury with Bile Leak

• This is your most critical diagnosis to exclude because unrecognized bile duct injury progresses to secondary biliary cirrhosis, portal hypertension, liver failure, and death within weeks to months. 2
• The leukocytosis reflects peritoneal irritation from bile accumulation, while the elevated ALP indicates biliary tree involvement. 1, 2
• Key distinguishing feature: Jaundice is typically absent or mild in bile leaks because peritoneal drainage decompresses the biliary tree, preventing cholestasis—this contrasts sharply with obstructive injuries where jaundice predominates. 2, 3
• Look specifically for persistent abdominal pain that fails to improve postoperatively, abdominal distension, nausea/vomiting, and visible bile drainage from drains or incision sites. 2
• The elevated AST likely reflects surgical manipulation rather than true hepatocellular injury in early leaks. 3

Retained Choledocholithiasis

• This presents with cholestatic pattern (elevated ALP) plus leukocytosis if cholangitis is developing. 1, 4
• The World Journal of Emergency Surgery recommends assessing for alarm symptoms including fever with chills, persistent worsening pain, jaundice with dark urine and pale stools. 1
• Unlike bile leak, retained stones typically cause more pronounced jaundice and cholestatic enzyme elevation (ALP >3× baseline with bilirubin >2× upper limit). 1

Biloma Formation with Secondary Infection

• Occurs when bile accumulates in the subhepatic region without adequate drainage, leading to intra-abdominal abscess. 2
• The leukocytosis and fever indicate infectious complications requiring urgent source control. 2
• Can progress rapidly to sepsis and multiorgan failure if not drained. 2

Secondary Consideration: Pancreatitis

Post-ERCP or Gallstone Pancreatitis

• The elevated lipase is your key laboratory finding pointing toward pancreatic involvement. 5
• However, isolated pancreatitis would not typically cause the elevated alkaline phosphatase pattern you're seeing—the combination suggests either:
  • Concurrent biliary obstruction with pancreatitis (choledocholithiasis causing both), or
  • Post-ERCP pancreatitis if the patient underwent preoperative stone extraction. 5
• Look for epigastric pain radiating to the back, nausea, and vomiting as distinguishing features.

Diagnostic Algorithm

Immediate First-Line Imaging

• Obtain abdominal ultrasound immediately to assess for biliary ductal dilation, retained stones, and fluid collections—this has high specificity for choledocholithiasis. 1
• If ultrasound shows fluid collections, proceed directly to triphasic CT to characterize them and assess for biloma versus other postoperative collections. 2

Definitive Second-Line Imaging

• If ultrasound is negative but ALP remains elevated and clinical suspicion persists, proceed to contrast-enhanced MRI with MRCP—this provides near-100% accuracy for detecting and localizing bile leaks and identifies bile duct injury classification. 1, 2
• Optimal hepatobiliary-phase imaging at 60-90 minutes after contrast shows direct extravasation into collections, confirming active leak. 2

Critical Laboratory Additions

• Obtain comprehensive cholestatic panel: direct/indirect bilirubin, AST, ALT, ALP, GGT, albumin, and complete blood count. 1
• In critically ill patients appearing septic, add CRP, procalcitonin, and serum lactate to assess sepsis severity and mortality risk. 1, 2
• If drain fluid is present, send for bilirubin measurement—drain fluid bilirubin ≥3× simultaneous serum bilirubin confirms bile leak. 3

Management Based on Findings

If Choledocholithiasis Identified

• Proceed directly to ERCP with sphincterotomy and stone extraction. 1
• Do not delay when ALP rises >3× baseline with bilirubin >2× upper limit or when cholangitis symptoms develop. 1

If Minor Bile Leak Confirmed (Strasberg A-D)

• Initial observation with drain management if surgical drain already present. 2
• If no drain exists, perform percutaneous drainage of collections. 2
• Escalate to ERCP with biliary sphincterotomy and stent placement if leak persists or worsens. 2

If Major Bile Duct Injury (Strasberg E1-E2)

• Within 72 hours of diagnosis: Immediate referral to hepatopancreatobiliary center for urgent Roux-en-Y hepaticojejunostomy. 2
• Between 72 hours and 3 weeks: Staged approach with percutaneous drainage, broad-spectrum antibiotics (piperacillin-tazobactam, imipenem-cilastatin, or meropenem within one hour), nutritional support, consider ERCP with sphincterotomy to lower biliary pressure, then definitive repair after 3 weeks. 2

If Diffuse Biliary Peritonitis

• Immediate abdominal lavage and drainage for source control before definitive repair. 2

Critical Pitfalls to Avoid

• Never be falsely reassured by normal or only mildly elevated bilirubin—this is typical in early bile leaks because peritoneal absorption prevents back-pressure and cholestasis. 3
• Do not rely on CT alone to exclude bile duct injury—it cannot differentiate bile from blood, pus, or serous fluid and may only show nonspecific "peri-portal tracking." 3
• Do not dismiss persistent postoperative symptoms as "normal recovery"—bile duct injuries can present with delayed symptoms requiring immediate investigation. 2
• Do not postpone definitive imaging while awaiting worsening symptoms—prompt HIDA scan or MRCP prevents progression to life-threatening complications. 3
• Jaundice, worsening leukocytosis, and longer operative times are associated with postoperative biliary complications and predict 30-day readmission risk. 5