Literature DB >> 25815091

Immunological dysfunction during or after antiviral therapy for recurrent hepatitis C reduces graft survival.

Pratima Sharma1, Amy Hosmer1, Henry Appelman2, Barbara McKenna2, Mohammad S Jafri1, Patricia Sullivan1, Robert J Fontana1, Anna S Lok1.   

Abstract

INTRODUCTION: Pegylated interferon and ribavirin (PEGIFN/RBV) therapy for recurrent hepatitis C after liver transplantation (LT) is associated with a lower sustained virological response (SVR) rate as well as more frequent side effects compared to non-transplant patients. We aimed to determine the incidence and clinical characteristics of LT recipients with recurrent hepatitis C who developed immunological dysfunction (ID) during or after PEG-IFN/RBV therapy and to assess its impact on patient and graft survival.
METHODS: Seventy-four deceased donor LT recipients with histological recurrence of hepatitis C were treated with PEG-IFN/RBV from 1/00 to 12/08. ID was defined as biopsy-proven rejection or moderate plasma cell hepatitis. Patients were followed up until death, re-LT or 30 September 2011.
RESULTS: Twelve patients (16 %) had ID, 8 (10.7 %) had cholestasis without ID, while 54 had no ID/cholestasis during or after discontinuation of PEG-IFN/RBV therapy. Biopsy-proven acute cellular rejection prior to (hazard ratio = 4.87, p = 0.009) and type of immunosuppression at the time of initiation of PEG-IFN/RBV were the only independent predictors of ID. Patients who were on tacrolimus at the time of initiation of PEG-IFN/RBV had a significantly lower risk of ID compared to those who were on cyclosporine (HR 0.254, p = 0.023). Patients with ID had a trend toward a lower SVR rate (25 vs. 54 %, p = 0.18) and a significantly higher rate of graft failure (33 vs. 4 %, p = 0.004) compared to patients with no ID/cholestasis.
CONCLUSIONS: ID is common during or after PEG-IFN/RBV therapy for recurrent hepatitis C and frequently associated with decreased graft survival, trending toward low rates of SVR. Careful monitoring of liver biochemistries during or after PEG-IFN/RBV therapy with a low threshold to biopsy patients and particularly those receiving cyclosporine-based immunosuppression may improve outcomes in these patients.

Entities:  

Keywords:  Immunological dysfunction; Liver transplantation; Recurrent hepatitis C

Year:  2013        PMID: 25815091      PMCID: PMC4371864          DOI: 10.1007/s12072-013-9436-1

Source DB:  PubMed          Journal:  Hepatol Int        ISSN: 1936-0533            Impact factor:   6.047


  32 in total

1.  Spanish society of liver transplantation (SETH) consensus recommendations on hepatitis C virus and liver transplantation.

Authors:  Marina Berenguer; Ramón Charco; Juan Manuel Pascasio; Jose Ignacio Herrero
Journal:  Liver Int       Date:  2012-01-04       Impact factor: 5.828

Review 2.  Viral hepatitis and liver transplantation.

Authors:  Pratima Sharma; Anna Lok
Journal:  Semin Liver Dis       Date:  2006-08       Impact factor: 6.115

3.  Incidence, risk factors, and outcome of chronic rejection during antiviral therapy for posttransplant recurrent hepatitis C.

Authors:  Inmaculada Fernández; Esperanza Ulloa; Francisco Colina; Manuel Abradelo; Carlos Jiménez; Alberto Gimeno; Juan Carlos Meneu; Carlos Lumbreras; José Antonio Solís-Herruzo; Enrique Moreno
Journal:  Liver Transpl       Date:  2009-08       Impact factor: 5.799

4.  Benefit of sustained virological response to combination therapy on graft survival of liver transplanted patients with recurrent chronic hepatitis C.

Authors:  Thierry Bizollon; Pierre Pradat; Jean-Yves Mabrut; Michelle Chevallier; Mustapha Adham; Sylvie Radenne; Jean-Christophe Souquet; Christian Ducerf; Jacques Baulieux; Fabien Zoulim; Christian Trepo
Journal:  Am J Transplant       Date:  2005-08       Impact factor: 8.086

5.  Sustained virologic response to therapy of recurrent hepatitis C after liver transplantation is related to early virologic response and dose adherence.

Authors:  Pratima Sharma; Jorge A Marrero; Robert J Fontana; Joel K Greenson; Hari Conjeevaram; Grace L Su; Frederick Askari; Patricia Sullivan; Anna S Lok
Journal:  Liver Transpl       Date:  2007-08       Impact factor: 5.799

6.  HCV-related fibrosis progression following liver transplantation: increase in recent years.

Authors:  M Berenguer; L Ferrell; J Watson; M Prieto; M Kim; M Rayón; J Córdoba; A Herola; N Ascher; J Mir; J Berenguer; T L Wright
Journal:  J Hepatol       Date:  2000-04       Impact factor: 25.083

7.  Posttransplant plasma cell hepatitis (de novo autoimmune hepatitis) is a variant of rejection and may lead to a negative outcome in patients with hepatitis C virus.

Authors:  M Isabel Fiel; Kaushik Agarwal; Carmen Stanca; Nassim Elhajj; Nikolas Kontorinis; Swan N Thung; Thomas D Schiano
Journal:  Liver Transpl       Date:  2008-06       Impact factor: 5.799

8.  Long-term outcome of hepatitis C infection after liver transplantation.

Authors:  E J Gane; B C Portmann; N V Naoumov; H M Smith; J A Underhill; P T Donaldson; G Maertens; R Williams
Journal:  N Engl J Med       Date:  1996-03-28       Impact factor: 91.245

Review 9.  Cyclosporin versus tacrolimus for liver transplanted patients.

Authors:  E M Haddad; V C McAlister; E Renouf; R Malthaner; M S Kjaer; L L Gluud
Journal:  Cochrane Database Syst Rev       Date:  2006-10-18

10.  Altered thymic function during interferon therapy in HCV-infected patients.

Authors:  Stephanie Beq; Sandra Rozlan; Sandy Pelletier; Bernard Willems; Julie Bruneau; Jean-Daniel Lelievre; Yves Levy; Naglaa H Shoukry; Rémi Cheynier
Journal:  PLoS One       Date:  2012-04-16       Impact factor: 3.240

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  3 in total

Review 1.  Drug-drug interactions with oral anti-HCV agents and idiosyncratic hepatotoxicity in the liver transplant setting.

Authors:  Sarah Tischer; Robert J Fontana
Journal:  J Hepatol       Date:  2013-11-23       Impact factor: 25.083

2.  The prediction of immunological dysfunction during antiviral therapy for HCV after liver transplantation: can we improve outcomes?

Authors:  Ji-Yuan Zhang; Yuan-Yuan Li; Zheng Zhang; Fu-Sheng Wang
Journal:  Hepatol Int       Date:  2013-10-17       Impact factor: 6.047

3.  Impact of direct-acting antivirals for hepatitis C virus therapy on tacrolimus dosing in liver transplant recipients.

Authors:  Alexandra L Bixby; Linda Fitzgerald; Rachael Leek; Jessica Mellinger; Pratima Sharma; Sarah Tischer
Journal:  Transpl Infect Dis       Date:  2019-04-01       Impact factor: 2.228

  3 in total

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