• Please log in or register to access this feature.

Original Article

You have free access to this content

Cholestatic hepatitis C following liver transplantation: An outcome-based histological definition, clinical predictors, and prognosis

  1. Elizabeth C. Verna1,
  2. Rita Abdelmessih1,
  3. Marcela A. Salomao2,
  4. Jay Lefkowitch2,
  5. Roger K. Moreira2,†,*,
  6. Robert S. Brown Jr1,‡,*

Article first published online: 27 DEC 2012

DOI: 10.1002/lt.23559

Issue

Liver Transplantation

Liver Transplantation

Volume 19, Issue 1, pages 78–88, January 2013

Additional Information

How to Cite

Verna, E. C., Abdelmessih, R., Salomao, M. A., Lefkowitch, J., Moreira, R. K. and Brown, R. S. (2013), Cholestatic hepatitis C following liver transplantation: An outcome-based histological definition, clinical predictors, and prognosis. Liver Transpl, 19: 78–88. doi: 10.1002/lt.23559

Author Information

  1. 1

    Center for Liver Disease and Transplantation, Division of Digestive and Liver Diseases

  2. 2

    Department of Pathology and Cell Biology, Columbia University College of Physicians and Surgeons, New York, NY

  1. †

    Telephone: 212-305-7164; FAX: 212-305-6595;

  2. ‡

    Telephone: 212-305-0660; FAX: 212-305-9139;

*Department of Pathology and Cell Biology, Columbia University College of Physicians and Surgeons, 630 West 168th Street, VC 238B, New York, NY 10032-3784

  1. †

    Telephone: 212-305-7164; FAX: 212-305-6595;

  2. ‡

    Telephone: 212-305-0660; FAX: 212-305-9139;

Publication History

  1. Issue published online: 27 DEC 2012
  2. Article first published online: 27 DEC 2012
  3. Accepted manuscript online: 18 OCT 2012 11:29AM EST
  4. Manuscript Accepted: 10 JUL 2012
  5. Manuscript Received: 1 APR 2012

SEARCH

SEARCH BY CITATION

ARTICLE TOOLS

View Full Article (HTML) Get PDF (2950K)

REFERENCES

  • 1
    O'Grady JG, Smith HM, Davies SE, Daniels HM, Donaldson PT, Tan KC, etal. Hepatitis B virus reinfection after orthotopic liver transplantation. Serological and clinical implications. J Hepatol 1992; 14: 104–111.
  • 2
    Davies SE, Portmann BC, O'Grady JG, Aldis PM, Chaggar K, Alexander GJ, Williams R. Hepatic histological findings after transplantation for chronic hepatitis B virus infection, including a unique pattern of fibrosing cholestatic hepatitis. Hepatology 1991; 13: 150–157.
    Direct Link:
  • 3
    Saleh F, Ko HH, Davis JE, Apiratpracha W, Powell JJ, Erb SR, Yoshida EM. Fatal hepatitis C associated fibrosing cholestatic hepatitis as a complication of cyclophosphamide and corticosteroid treatment of active glomerulonephritis. Ann Hepatol 2007; 6: 186–189.
  • 4
    Ceballos-Viro J, López-Picazo JM, Pérez-Gracia JL, Sola JJ, Aisa G, Gil-Bazo I. Fibrosing cholestatic hepatitis following cytotoxic chemotherapy for small-cell lung cancer. World J Gastroenterol 2009; 15: 2290–2292.
  • 5
    Rosenberg PM, Farrell JJ, Abraczinskas DR, Graeme-Cook FM, Dienstag JL, Chung RT. Rapidly progressive fibrosing cholestatic hepatitis–hepatitis C virus in HIV coinfection. Am J Gastroenterol 2002; 97: 478–483.
    Direct Link:
  • 6
    Antonini TM, Sebagh M, Roque-Afonso AM, Teicher E, Roche B, Sobesky R, etal. Fibrosing cholestatic hepatitis in HIV/HCV co-infected transplant patients–usefulness of early markers after liver transplantation. Am J Transplant 2011; 11: 1686–1695.
    Direct Link:
  • 7
    Delladetsima JK, Boletis JN, Makris F, Psichogiou M, Kostakis A, Hatzakis A. Fibrosing cholestatic hepatitis in renal transplant recipients with hepatitis C virus infection. Liver Transpl Surg 1999; 5: 294–300.
    Direct Link:
  • 8
    Muñoz De Bustillo E, Ibarrola C, Colina F, Castellano G, Fuertes A, Andrés A, etal. Fibrosing cholestatic hepatitis in hepatitis C virus-infected renal transplant recipients. J Am Soc Nephrol 1998; 9: 1109–1113.
  • 9
    Delladetsima JK, Makris F, Psichogiou M, Kostakis A, Hatzakis A, Boletis JN. Cholestatic syndrome with bile duct damage and loss in renal transplant recipients with HCV infection. Liver 2001; 21: 81–88.
    Direct Link:
  • 10
    Zylberberg H, Carnot F, Mamzer MF, Blancho G, Legendre C, Pol S. Hepatitis C virus-related fibrosing cholestatic hepatitis after renal transplantation. Transplantation 1997; 63: 158–160.
  • 11
    Toth CM, Pascual M, Chung RT, Graeme-Cook F, Dienstag JL, Bhan AK, Cosimi AB. Hepatitis C virus-associated fibrosing cholestatic hepatitis after renal transplantation: response to interferon-alpha therapy. Transplantation 1998; 66: 1254–1258.
  • 12
    Lam PW, Wachs ME, Somberg KA, Vincenti F, Lake JR, Ferrell LD. Fibrosing cholestatic hepatitis in renal transplant recipients. Transplantation 1996; 61: 378–381.
  • 13
    Delgado J, Muñoz de Bustillo E, Ibarrola C, Colina F, Morales JM, Rodriguez E, etal. Hepatitis C virus-related fibrosing cholestatic hepatitis after cardiac transplantation: is azathioprine a contributory factor? J Heart Lung Transplant 1999; 18: 607–610.
  • 14
    Lim HL, Lau GK, Davis GL, Dolson DJ, Lau JY. Cholestatic hepatitis leading to hepatic failure in a patient with organ-transmitted hepatitis C virus infection. Gastroenterology 1994; 106: 248–251.
  • 15
    Satapathy SK, Sclair S, Fiel MI, Del Rio Martin J, Schiano T. Clinical characterization of patients developing histologically-proven fibrosing cholestatic hepatitis C post-liver transplantation. Hepatol Res 2011; 41: 328–339.
    Direct Link:
  • 16
    Schluger LK, Sheiner PA, Thung SN, Lau JY, Min A, Wolf DC, etal. Severe recurrent cholestatic hepatitis C following orthotopic liver transplantation. Hepatology 1996; 23: 971–976.
    Direct Link:
  • 17
    Dixon LR, Crawford JM. Early histologic changes in fibrosing cholestatic hepatitis C. Liver Transpl 2007; 13: 219–226.
    Direct Link:
  • 18
    Taga SA, Washington MK, Terrault N, Wright TL, Somberg KA, Ferrell LD. Cholestatic hepatitis C in liver allografts. Liver Transpl Surg 1998; 4: 304–310.
    Direct Link:
  • 19
    Takahashi T, Ashizawa S, Matsumoto H, Furuta K, Omura T, Sato K, Kakita A. Fibrosing cholestatic hepatitis developing after liver transplantation: case report of a patient with HCV-related cirrhosis. Transplant Proc 2003; 35: 392–393.
  • 20
    Troppmann C, Rossaro L, Perez RV, McVicar JP. Early, rapidly progressive cholestatic hepatitis C reinfection and graft loss after adult living donor liver transplantation. Am J Transplant 2003; 3: 239–240.
    Direct Link:
  • 21
    Fukuhara T, Morita K, Takeishi K, Toshima T, Umeda K, Nagata S, etal. Early diagnosis and treatment resolved cholestatic hepatitis C without fibrosis after living donor liver transplantation: report of a case. Surg Today 2010; 40: 982–985.
  • 22
    Furuta K, Takahashi T, Aso K, Hoshino H, Sato K, Kakita A. Fibrosing cholestatic hepatitis in a liver transplant recipient with hepatitis C virus infection: a case report. Transplant Proc 2003; 35: 389–391.
  • 23
    Cimsit B, Assis D, Caldwell C, Arvelakis A, Taddei T, Kulkarni S, etal. Successful treatment of fibrosing cholestatic hepatitis after liver transplantation. Transplant Proc 2011; 43: 905–908.
  • 24
    Bolkhir A, Brunt EM, Solomon HS, Hayashi PH. Sustained resolution of fibrosing cholestatic hepatitis C despite viremic relapse after stopping pegylated interferon and ribavirin therapy. Liver Transpl 2007; 13: 309–311.
    Direct Link:
  • 25
    Gopal DV, Rosen HR. Duration of antiviral therapy for cholestatic HCV recurrence may need to be indefinite. Liver Transpl 2003; 9: 348–353.
    Direct Link:
  • 26
    Tolan DJ, Davies MH, Millson CE. Fibrosing cholestatic hepatitis after liver transplantation in a patient with hepatitis C and HIV infection. N Engl J Med 2001; 345: 1781.
  • 27
    Rosen HR, Gretch DR, Oehlke M, Flora KD, Benner KG, Rabkin JM, Corless CL. Timing and severity of initial hepatitis C recurrence as predictors of long-term liver allograft injury. Transplantation 1998; 65: 1178–1182.
  • 28
    Cotler SJ, Taylor SL, Gretch DR, Bronner MP, Rizk R, Perkins JD, Carithers RL Jr. Hyperbilirubinemia and cholestatic liver injury in hepatitis C-infected liver transplant recipients. Am J Gastroenterol 2000; 95: 753–759.
    Direct Link:
  • 29
    Ong JP, Younossi ZM, Gramlich T, Goodman Z, Mayes J, Sarbah S, Yen-Lieberman B. Interferon alpha 2B and ribavirin in severe recurrent cholestatic hepatitis C. Transplantation 2001; 71: 1486–1487.
  • 30
    Deshpande V, Burd E, Aardema KL, Ma CK, Moonka DK, Brown KA, etal. High levels of hepatitis C virus RNA in native livers correlate with the development of cholestatic hepatitis in liver allografts and a poor outcome. Liver Transpl 2001; 7: 118–124.
    Direct Link:
  • 31
    Neff GW, Shire N, Ruiz P, O'Brien C, Garcia M, Dela Garza J, etal. The importance of clinical parameters when differentiating cholestatic hepatitis C virus from allograft rejection. Transplant Proc 2005; 37: 4397–4402.
  • 32
    Gaglio PJ, Malireddy S, Levitt BS, Lapointe-Rudow D, Lefkowitch J, Kinkhabwala M, etal. Increased risk of cholestatic hepatitis C in recipients of grafts from living versus cadaveric liver donors. Liver Transpl 2003; 9: 1028–1035.
    Direct Link:
  • 33
    McCaughan GW, Bowen DG. Pathogenesis of cholestatic hepatitis C. J Hepatol 2011; 54: 392–394.
  • 34
    Xiao SY, Lu L, Wang HL. Fibrosing cholestatic hepatitis: clinicopathologic spectrum, diagnosis and pathogenesis. Int J Clin Exp Pathol 2008; 1: 396–402.
  • 35
    Wiesner RH, Sorrell M, Villamil F; for International Liver Transplantation Society Expert Panel. Report of the first International Liver Transplantation Society expert panel consensus conference on liver transplantation and hepatitis C. Liver Transpl 2003; 9: S1–S9.
    Direct Link:
  • 36
    Narang TK, Ahrens W, Russo MW. Post-liver transplant cholestatic hepatitis C: a systematic review of clinical and pathological findings and application of consensus criteria. Liver Transpl 2010; 16: 1228–1235.
    Direct Link:
  • 37
    Batts KP, Ludwig J. Chronic hepatitis. An update on terminology and reporting. Am J Surg Pathol 1995; 19: 1409–1417.
  • 38
    Costes V, Durand L, Pageaux GP, Ducos J, Mondain AM, Picot MC, etal. Hepatitis C virus genotypes and quantification of serum hepatitis C RNA in liver transplant recipients. Relationship with histologic outcome of recurrent hepatitis C. Am J Clin Pathol 1999; 111: 252–258.
  • 39
    Doughty AL, Spencer JD, Cossart YE, McCaughan GW. Cholestatic hepatitis after liver transplantation is associated with persistently high serum hepatitis C virus RNA levels. Liver Transpl Surg 1998; 4: 15–21.
    Direct Link:
  • 40
    Wali M, Harrison RF, Gow PJ, Mutimer D. Advancing donor liver age and rapid fibrosis progression following transplantation for hepatitis C. Gut 2002; 51: 248–252.
  • 41
    Berenguer M. Host and donor risk factors before and after liver transplantation that impact HCV recurrence. Liver Transpl 2003; 9: S44–S47.
    Direct Link:
  • 42
    Berenguer M, Crippin J, Gish R, Bass N, Bostrom A, Netto G, etal. A model to predict severe HCV-related disease following liver transplantation. Hepatology 2003; 38: 34–41.
    Direct Link:
  • 43
    Verna EC, Brown RS Jr. Hepatitis C and liver transplantation: enhancing outcomes and should patients be retransplanted. Clin Liver Dis 2008; 12: 637–659.
  • 44
    Verna EC, De Martin E, Burra P, Neri D, Gaglio PJ, Emond JC, Brown RS Jr. The impact of hepatitis C and biliary complications on patient and graft survival following liver transplantation. Am J Transplant 2009; 9: 1398–1405.
    Direct Link:
  • 45
    Mutimer DJ, Gunson B, Chen J, Berenguer J, Neuhaus P, Castaing D, etal. Impact of donor age and year of transplantation on graft and patient survival following liver transplantation for hepatitis C virus. Transplantation 2006; 81: 7–14.
  • 46
    Lai JC, Verna EC, Brown RS Jr, O'Leary JG, Trotter JF, Forman LM, etal.; for Consortium to Study Health Outcomes in HCV Liver Transplant Recipients (CRUSH-C). Hepatitis C virus-infected women have ahigher risk of advanced fibrosis and graft loss afterliver transplantation than men. Hepatology 2011; 54: 418–424.
    Direct Link:
View Full Article (HTML) Get PDF (2950K)