Correspondence
Fibrosing Cholestatic Hepatitis after Liver Transplantation in a Patient with Hepatitis C and HIV Infection
N Engl J Med 2001; 345:1781December 13, 2001
- Article
To the Editor:
A small but growing number of patients with human immunodeficiency virus (HIV) infection undergo orthotopic liver transplantation for complications of intercurrent infection with hepatitis B virus (HBV), hepatitis C virus (HCV), or both. HCV invariably reinfects liver allografts, typically causing a lobular hepatitis, and is reasonably well tolerated in the short term. If hepatitis B recurs after transplantation, it frequently causes devastating disease characterized by a rapidly progressive pathological process termed fibrosing cholestatic hepatitis, resulting in liver failure.1 The postulated mechanism of this process is unimpeded viral replication mediated by immunosuppression in the transplant recipient. HIV has been shown to cause fibrosing cholestatic hepatitis in combination with HBV infection.2,3 We report on a patient with HIV in whom fibrosing cholestatic hepatitis developed after liver transplantation for HCV infection, in the absence of HBV coinfection.
In 1999, a 40-year-old man was referred for liver transplantation because of decompensated HCV cirrhosis. HCV infection and HIV infection had been acquired from transfusions of infected factor VIII. Before transplantation, the HIV viral load (determined by polymerase-chain-reaction assay) was less than 50 copies per milliliter, and the CD4 count was 150 per cubic millimeter. A preoperative test for antibodies to hepatitis B surface antigen was negative; the donor also had a negative test for antibodies to hepatitis B surface antigen. Liver transplantation was complicated by hemorrhage on day 2 and by small-bowel obstruction on day 11; both required laparotomy. Liver biopsy on day 10 showed no evidence of acute rejection, but there was marked perivenular cholestasis with ballooning of hepatocytes — findings that were consistent with preservation injury. The patient recovered well from surgery. Because of a persistently elevated bilirubin level (84 μmol per liter), liver biopsy was repeated on day 25, but the findings were unchanged. The HIV viral load was less than 50 copies per milliliter, and the CD4 count was 80 per cubic millimeter. Immunosuppressive therapy consisted of tacrolimus and prednisolone. Antiretroviral therapy, comprising stavudine, lamivudine, nevirapine, and abacavir, was reintroduced three weeks after surgery.
The cholestasis worsened after the patient's discharge. A biliary stent inserted at endoscopic retrograde cholangiopancreatography did not improve liver function. Another biopsy, performed after four months, showed severe liver disease, with cirrhosis, intense cholestasis, and cytopathic changes in hepatocytes; the findings were consistent with the presence of fibrosing cholestatic hepatitis. The patient received treatment for 24 days with ribavirin and interferon alfa,4 with no clinical or biochemical improvement. He declined another liver graft and died 223 days after transplantation.
4 ReferencesDamian J.M. Tolan, M.B., Ch.B.
Mervyn H. Davies, M.D.
Charles E. Millson, M.D.
St. James University Hospital, Leeds LS9 7TF, United Kingdom
djmtolan@netscapeonline.co. uk 1
Harrison RF ,Davies MH ,Goldin RD ,Hubscher SG . Recurrent hepatitis B in liver allografts: a distinctive form of rapidly developing cirrhosis. Histopathology 1993;23:21-28
CrossRef | Web of Science | Medline2
Fang JW ,Wright TL ,Lau JY . Fibrosing cholestatic hepatitis in patient with HIV and hepatitis B. Lancet 1993;342:1175-1175
CrossRef | Web of Science | Medline3
Poulet B ,Chapel F ,Deny P , et al. Fibrosing cholestatic hepatitis by B virus reactivation in AIDS. Ann Pathol 1996;16:188-191
Web of Science | Medline4
Toth CM ,Pascual M ,Chung RT , et al. Hepatitis C virus-associated fibrosing cholestatic hepatitis after renal transplantation: response to interferon-alpha therapy. Transplantation 1998;66:1254-1258
CrossRef | Web of Science | Medline
- Citing Articles (21)
Citing Articles
1
Neil D. Theise, Henry C. Bodenheimer, Linda D. Ferrell. 2012. Acute and chronic viral hepatitis. , 361-401.
CrossRef2
Curtis Cooper, Steve Kanters, Marina Klein, Prosanto Chaudhury, Paul Marotta, Phil Wong, Norman Kneteman, Edward J Mills. (2011) Liver transplant outcomes in HIV-infected patients: a systematic review and meta-analysis with synthetic cohort. AIDS 25:6, 777-786
CrossRef3
Tarun K. Narang, Will Ahrens, Mark W. Russo. (2010) Post-liver transplant cholestatic hepatitis C: A systematic review of clinical and pathological findings and application of consensus criteria. Liver Transplantation 16:11, 1228-1235
CrossRef4
Takasuke Fukuhara, Kazutoyo Morita, Kazuki Takeishi, Takeo Toshima, Kenji Umeda, Shigeyuki Nagata, Keishi Sugimachi, Toru Ikegami, Tomonobu Gion, Yuji Soejima, Akinobu Taketomi, Yoshihiko Maehara. (2010) Early diagnosis and treatment resolved cholestatic hepatitis C without fibrosis after living donor liver transplantation: Report of a case. Surgery Today 40:10, 982-985
CrossRef5
Pierluigi Viale, Umberto Baccarani, Marcello Tavio. (2008) Liver transplant in patients with HIV: Infection risk associated with HIV and post-transplant immunosuppression. Current Infectious Disease Reports 10:1, 74-81
CrossRef6
Lydia M. Petrovic. (2007) HIV/HCV co-infection: histopathologic findings, natural history, fibrosis, and impact of antiretroviral treatment: a review article. Liver International 27:5, 598-606
CrossRef7
M. E. de Vera, I. Dvorchik, K. Tom, B. Eghtesad, N. Thai, O. Shakil, A. Marcos, A. Demetris, A. Jain, J. J. Fung, M. V. Ragni. (2006) Survival of Liver Transplant Patients Coinfected with HIV and HCV Is Adversely Impacted by Recurrent Hepatitis C. American Journal of Transplantation 6:12, 2983-2993
CrossRef8
Kenzo Hirose, Peter G Stock. (2006) Liver transplantation in the human immunodeficiency virus-positive patient. Current Opinion in Organ Transplantation 11:3, 241-246
CrossRef9
Michelle E. Roland, Peter G. Stock. (2005) Comprehensive guidelines translate research findings into clinical policy for HIV-infected transplant candidates and recipients. Enfermedades Infecciosas y Microbiología Clínica 23:6, 331-334
CrossRef10
Karen F. Murray, Robert L. Carithers. (2005) AASLD practice guidelines: Evaluation of the patient for liver transplantation. Hepatology 41:6, 1407-1432
CrossRef11
MATHIAS LICHTERFELD, SUSANNE HAAS, HANS-PETER FISCHER, ESTER VOIGT, JURGEN K ROCKSTROH, ULRICH SPENGLER. (2005) Liver histopathology in human immunodeficiency virus-hepatitis C virus co-infected patients with fatal liver disease. Journal of Gastroenterology and Hepatology 20:5, 739-745
CrossRef12
Klaus Radecke, Nils R. Fruhauf, Michael Miller, Birgit Ross, Roland Koditz, Massimo Malago, Christoph E. Broelsch, Guido Gerken, Ulrich Treichel. (2005) Outcome after orthotopic liver transplantation in five HIV-infected patients with virus hepatitis-induced cirrhosis. Liver International 25:1, 101-108
CrossRef13
Santiago Moreno, Jes
s Fort
CrossRef14
Kathy L Coffman. (2004) Evidence-based medicine: the dilemma of transplantation in patients with HIV infection. Current Opinion in Organ Transplantation 9:4, 422-427
CrossRef15
G. W. Neff, K. E. Sherman, B. Eghtesad, J. Fung. (2004) Review article: current status of liver transplantation in HIV-infected patients. Alimentary Pharmacology and Therapeutics 20:10, 993-1000
CrossRef16
John Fung, Bijan Eghtesad, Kusum Patel-Tom, Michael DeVera, Holly Chapman, Margaret Ragni. (2004) Liver transplantation in patients with HIV infection. Liver Transplantation 10:S10, S39-S53
CrossRef17
Jürgen Kurt Rockstroh, Ulrich Spengler. (2004) HIV and hepatitis C virus co-infection. The Lancet Infectious Diseases 4:7, 437-444
CrossRef18
Suzanne El Sayegh, Marla J. Keller, Shirish Huprikar, Barbara Murphy. (2004) Solid organ transplantation in HIV-infected recipients. Pediatric Transplantation 8:3, 214-221
CrossRef19
Stanislas Pol, Pascal Lebray, Anais Vallet‐Pichard. (2004) HIV Infection and Hepatic Enzyme Abnormalities: Intricacies of the Pathogenic Mechanisms. Clinical Infectious Diseases 38:s2, S65
CrossRef20
Christoph Troppmann, L. Rossaro, R.V. Perez, J.P. McVicar. (2003) Early, Rapidly Progressive Cholestatic Hepatitis C Reinfection and Graft Loss After Adult Living Donor Liver Transplantation. American Journal of Transplantation 3:2, 239-240
CrossRef21
H. Kojima, M. Abei, N. Takei, Y. Mukai, Y. Hasegawa, T. Iijima, T. Nagasawa. (2002) Fatal reactivation of hepatitis B virus following cytotoxic chemotherapy for acute myelogenous leukemia: fibrosing cholestatic hepatitis. European Journal of Haematology 69:2, 101-104
CrossRef
