Cholangiopathy, HIV
PATHOGENS
CLINICAL
- Syndrome of biliary obstruction resulting from infection-associated strictures of the biliary tract (considered a secondary cause of sclerosing cholangitis). Typically occurs in pts with advanced HIV disease (CD4 < 50). Four sub-classifications:
- Papillary strictures/stenosis (10%)
- Sclerosing cholangitis-like (20%)
- Papillary stenosis with sclerosing cholangitis (50-60%)
- Extra-hepatic bile duct strictures (rare)
- Sx: RUQ pain (90%) often sharp and radiating to back (especially if strictures present). Fever (50%), low grade if present. Diarrhea common due to small bowel involvement with infectious agent.
- Signs: Labs suggest cholestasis with greater elevation in alkaline phosphatase compared to ALT and AST: mild increase in ALT, AST (2-3x ULN), total bili usually < 2x ULN (jaundice rare but can be present), alk phos 5-10x ULN (alk phos often markedly elevated in MAC -associated cholangiopathy).
- Large intrahepatic ducts most commonly involved; Cryptosporidium and CMV are usual pathogens in such cases.
- Recent case reports have more often been of intrahepatic cholestasis.
- Idiopathic in ~20% of cases.
DIAGNOSIS
- Established with ERCP or MRCP. Sensitivity of ultrasound (US) is 75-97%.
- Can be a clinical diagnosis.
- If US positive, MRCP or ERCP indicated to confirm Dx. ERCP can be used for therapy (stenting) or alternative diagnoses (brushings for cytology). If US negative, ERCP if abd. pain is severe or w/ known CMV or Cryptosporidium infection.
- DDx includes cholecytitis, vanishing bile duct syndrome (from TMP/SMX), autoimmune cholangiopathy, primary biliary cirrhosis, cholodocolithiasis, papilary obstruction, malignancy (KS, pancreatic, etc), sphincter of Oddi dysfunction.
- CMV viremia is common with advanced HIV disease; true diagnosis of CMV associated AIDS cholangiopathy requires histopathology findings.
TREATMENT
Papillary stenosis
- ERCP with sphincterotomy provides relief of Sx, but alk phos often remains high.
Isolated bile duct stricture
- Endoscopic stenting considered for pain management
Cholangiopathy without papillary stenosis
- Ursodeoxycholic acid (ursodiol 300 mg PO three times a day chronically) may improve laboratory values but does not relieve symptoms.
ART
- Overall survival improved by ART; unless there is an specific stricture or stenosis on imaging; ART is the primary therapy.
Pathogen-specific therapy
- Treatment directed against underlying pathogen does not influence Sx or cholangiographic abnormalities.
- Cryptosporidiosis
- Cyclospora cayetanensis
- CMV
- Microsporidiosis
- Mycobacterium avium complex
Differential Diagnosis
- Viral hepatitis (HAV, HBV, HCV, HDV)
- CMV, HSV, EBV infection
- Heptobiliary cryptococcosis
- Mycobacterial infection of the liver (TB, MAC)
- Fatty infiltration of liver
- Drug reaction (TMP-SMX, INH, rifampin, ketoconazole, pentamidine, pyrimethamine, dapsone)
- Lymphoma
- Vanishing bile duct syndrome (associated with high bilirubin in contrast to colangiopathy. Most commonly associated with TMP-SMX)
References
- Ahmed Y, Rahman MU, Khattak ZE, et al. Acquired Immune Deficiency Syndrome Cholangiopathy: Case Series of Three Patients and Literature Review. J Med Cases. 2022;13(9):462-470. [PMID:36258703]
Comment: Three intrahepatic cholangitis cases attributed to AIDS cholangiopathy and a review of the literature.
Rating: Important - Naseer M, Dailey FE, Juboori AA, et al. Epidemiology, determinants, and management of AIDS cholangiopathy: A review. World J Gastroenterol. 2018;24(7):767-774. [PMID:29467548]
Comment: Updated review of AIDS cholangiopathy.
Rating: Important - El Chaer F, Harris N, El Sahly H, et al. Mycobacterium avium complex-associated cholecystitis in AIDS patient: a case description and review of literature. Int J STD AIDS. 2016;27(13):1218-1222. [PMID:26023092]
Comment: Interesting case report.
Rating: Important - Imai K, Misawa K, Matsumura T, et al. Progressive HIV-associated Cholangiopathy in an HIV Patient Treated with Combination Antiretroviral Therapy. Intern Med. 2016;55(19):2881-2884. [PMID:27725553]
Comment: Interesting case report.
- Zuckerman MJ, Peters J, Fleming RV, et al. Cholangiopathy associated with giardiasis in a patient with human immunodeficiency virus infection. J Clin Gastroenterol. 2008;42(3):328-9. [PMID:18223486]
Comment: Report of cholangiopathy associated with Giardia infection
- Hindupur S, Yeung M, Shroff P, et al. Vanishing bile duct syndrome in a patient with advanced AIDS. HIV Med. 2007;8(1):70-2. [PMID:17305935]
Comment: Description of the vanishing bile duct sundrome in HIV
- Ko WF, Cello JP, Rogers SJ, et al. Prognostic factors for the survival of patients with AIDS cholangiopathy. Am J Gastroenterol. 2003;98(10):2176-81. [PMID:14572564]
Comment: HAART shown to improve survival in patients with AIDS and Cholangiopathy. Presence or history of any OIs is associated with a worse outcome.
- Castiella A, Iribarren JA, López P, et al. Ursodeoxycholic acid in the treatment of AIDS-associated cholangiopathy. Am J Med. 1997;103(2):170-1. [PMID:9274905]
Comment: Improvement with ursodeoxycholic acid reported in a small number of patients.
- Daly CA, Padley SP. Sonographic prediction of a normal or abnormal ERCP in suspected AIDS related sclerosing cholangitis. Clin Radiol. 1996;51(9):618-21. [PMID:8810689]
Comment: US 98% accurate in prediction of normal or abnormal ERCP, with sensitivity of 97% and specificity of 100%.
- Cello JP, Chan MF. Long-term follow-up of endoscopic retrograde cholangiopancreatography sphincterotomy for patients with acquired immune deficiency syndrome papillary stenosis. Am J Med. 1995;99(6):600-3. [PMID:7503081]
Comment: ERCP sphincterotomy provided significant reduction in pain in 25 pts with AIDS-associated papillary stenosis over 9 mos of follow-up.
- Ducreux M, Buffet C, Lamy P, et al. Diagnosis and prognosis of AIDS-related cholangitis. AIDS. 1995;9(8):875-80. [PMID:7576321]
Comment: Description of clinical, laboratory, and radiologic features based on 45 cases.
- Benhamou Y, Caumes E, Gerosa Y, et al. AIDS-related cholangiopathy. Critical analysis of a prospective series of 26 patients. Dig Dis Sci. 1993;38(6):1113-8. [PMID:8389687]
Comment: Demonstrates that large intrahepatic ducts most commonly involved.C. parvum and CMV are the usual pathogens in such cases.
- Forbes A, Blanshard C, Gazzard B. Natural history of AIDS related sclerosing cholangitis: a study of 20 cases. Gut. 1993;34(1):116-21. [PMID:8381757]
Comment: All 20 patients in this study had abd. pain; 11 had diarrhea. Alk. phos. was >2x normal in 13, but bilirubin raised in only 3. 13 had cryptosporidiosis, 6 had active CMV, 5 had no GI pathogen.
- Teixidor HS, Godwin TA, Ramirez EA. Cryptosporidiosis of the biliary tract in AIDS. Radiology. 1991;180(1):51-6. [PMID:2052722]
Comment: Describes US and cholangiographic findings seen in HIV Cholangiopathy.
- Cello JP. Acquired immunodeficiency syndrome cholangiopathy: spectrum of disease. Am J Med. 1989;86(5):539-46. [PMID:2712061]
Comment: 4 patterns of cholangiographic abnormalities identified in 20 patients: sclerosing cholangitis and papillary stenosis (10 pts), papillary stenosis alone (3), sclerosing cholangitis alone (4), and long extrahepatic bile duct strictures (3).
- Tonolini M, Bianco R. HIV-related/AIDS cholangiopathy: pictorial review with emphasis on MRCP findings and differential diagnosis. Clin Imaging. 2013;37(2):219-26. [PMID:23465971]
Comment: Updated description of imaging, especially the use of MRCP for diagnosis of AIDS cholangiopathy.
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