In a patient living with HIV who has refractory vomiting, elevated bilirubin, and a thickened gallbladder wall on ultrasound, what is the most likely cause and the next line of management?

AIDS-Related Cholangiopathy: Diagnosis and Management in HIV Patients

Most Likely Cause

The most likely diagnosis in this HIV patient with refractory vomiting, elevated bilirubin, and thickened gallbladder wall is AIDS-related cholangiopathy, specifically acalculous cholecystitis or papillary stenosis, caused by opportunistic infections such as Cryptosporidium, Cytomegalovirus (CMV), or Mycobacterium avium complex (MAC). 1, 2, 3

This diagnosis is particularly likely if the patient has:

• CD4+ count <100-200 cells/μL 4, 3, 5
• Elevated alkaline phosphatase (ALP) disproportionate to transaminases 1, 5
• Right upper quadrant pain with fever 5
• Conjugated hyperbilirubinemia 6

Immediate Diagnostic Workup

Laboratory Evaluation

• Complete hepatic profile including ALT, AST, ALP, GGT, total and direct bilirubin, and prothrombin time to characterize the pattern of liver injury 6, 7
• CD4+ count and HIV viral load to assess degree of immunosuppression 4, 3
• Blood cultures for MAC infection, which commonly causes disseminated disease in AIDS patients with CD4 <50 cells/μL 1, 2
• Stool examination specifically requesting Cryptosporidium and Cyclospora testing, as standard ova and parasite examination does not include these 1

Imaging Studies

• Abdominal ultrasound is the initial imaging modality of choice with sensitivity of 65-95% for detecting gallbladder wall thickening, biliary dilatation, and acalculous cholecystitis 1, 6
• Look specifically for: gallbladder wall thickening >3mm, pericholecystic fluid, bile duct dilatation, and absence of gallstones 1, 3
• If ultrasound is non-diagnostic but clinical suspicion remains high, proceed to MRCP to evaluate the biliary tree for strictures, dilatation, and beading characteristic of AIDS cholangiopathy 1, 8

Next Line of Management

Endoscopic Intervention

Endoscopic retrograde cholangiopancreatography (ERCP) is both diagnostic and therapeutic and should be performed urgently in patients with:

• Conjugated hyperbilirubinemia with biliary obstruction 6, 8
• Clinical signs of cholangitis (fever, jaundice, right upper quadrant pain) 4
• Papillary stenosis on imaging 5

ERCP findings in AIDS cholangiopathy typically show: 1, 5

• Stricture of the distal common bile duct
• Papillitis with papillary stenosis
• Diffuse sclerosing cholangitis pattern
• Intrahepatic bile duct irregularities

Endoscopic sphincterotomy of the papilla of Vater provides symptomatic relief in patients with papillary stenosis, though it does not alter overall prognosis 9, 5

Biliary stent placement may be required for complex strictures causing obstruction 4

Surgical Considerations

If acalculous cholecystitis is confirmed and the patient fails to improve with medical management, cholecystectomy is indicated: 3, 9

• Laparoscopic cholecystectomy is strongly preferred over open cholecystectomy, as it has zero mortality compared to 18% thirty-day mortality with open approach in AIDS patients with CD4 <200 3
• Gallbladder specimens should be sent for: acid-fast bacilli staining (MAC, tuberculosis), CMV immunohistochemistry, fungal cultures, and Cryptosporidium staining 2, 3

Antimicrobial Therapy

Initiate empiric antimicrobial therapy targeting the most common opportunistic pathogens while awaiting culture results: 1, 2

• For Cryptosporidium: The primary treatment is immune reconstitution with antiretroviral therapy; nitazoxanide may provide symptomatic benefit 1
• For CMV: Ganciclovir or foscarnet if CMV is suspected based on clinical presentation 1, 3
• For MAC: Clarithromycin plus ethambutol if disseminated MAC is suspected (fever, weight loss, CD4 <50) 1, 2

Antiretroviral Therapy

Initiate or optimize highly active antiretroviral therapy (HAART) immediately, as immune reconstitution is the most important protective factor and improves prognosis in AIDS cholangiopathy 5

Monitor for immune reconstitution inflammatory syndrome (IRIS), which can cause paradoxical worsening of symptoms including fever, lymphadenopathy, and worsening biliary inflammation 1

Monitoring and Supportive Care

Symptomatic Management

• Aggressive antiemetic therapy for refractory vomiting
• Intravenous hydration to prevent acute kidney injury, especially important as ceftriaxone (if used) can cause biliary precipitation 10
• Avoid ceftriaxone in this patient due to risk of ceftriaxone-calcium precipitates in the gallbladder and biliary tree, which can worsen biliary obstruction 10

Laboratory Monitoring

• Monitor ALP levels closely, as persistently elevated ALP (especially >3× ULN) is associated with worse prognosis in AIDS cholangiopathy 5
• Repeat liver function tests every 2-5 days initially to assess response to intervention 6, 7
• Monitor prothrombin time if biliary obstruction persists, as vitamin K malabsorption can occur 10

Common Pitfalls to Avoid

1. Do not assume calculous cholecystitis: 52% of AIDS patients with CD4 <200 have acalculous cholecystitis, which requires different management 3

2. Do not delay ERCP if biliary obstruction is present: Early endoscopic decompression improves outcomes and provides tissue diagnosis 4

3. Do not use standard ova and parasite examination alone: Specifically request Cryptosporidium testing, as it requires special staining 1

4. Do not overlook disseminated MAC: Blood cultures are essential, as MAC commonly causes both disseminated disease and biliary involvement 1, 2

5. Do not use ceftriaxone empirically: This antibiotic causes biliary precipitation and can worsen gallbladder disease in this clinical scenario 10

6. Do not perform open cholecystectomy if surgery is needed: Laparoscopic approach has significantly lower mortality in immunosuppressed patients 3