Cholangiopathy, HIV

Christopher J. Hoffmann, M.D., M.P.H.

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

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

  1. 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

  2. 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

  3. 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

  4. 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.

  5. 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

  6. 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

  7. 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.

  8. 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.

  9. 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%.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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).

  16. 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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Last updated: January 23, 2023