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

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Abstract

Introduction

Pegylated interferon and ribavirin (PEG-IFN/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.

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Abbreviations

AIH:

Autoimmune hepatitis

HCV:

Hepatitis C virus

ID:

Immunological dysfunction

LT:

Liver transplantation

PEG-IFN:

Pegylated interferon

RBV:

Ribavirin

SVR:

Sustained virological response

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Acknowledgments

This research was presented in part as a free communication at the American Transplant Congress, 2011, held in Philadelphia, PA. Dr. Sharma is supported by National Institutes of Health (NIH) grant KO8 DK-088946 and a research award from American College of Gastroenterology.

Conflict of interest

None.

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Authors and Affiliations

  1. Division of Gastroenterology, Department of Internal Medicine, University of Michigan Health System, 3912, Taubman Center, SPC 5362, Ann Arbor, MI, 48109, USA

    Pratima Sharma, Amy Hosmer, Mohammad S. Jafri, Patricia Sullivan, Robert J. Fontana & Anna S. Lok

  2. Department of Pathology, University of Michigan, Medical Science Building-1, 1301, Catherine Road, Ann Arbor, MI, USA

    Henry Appelman & Barbara McKenna

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  1. Pratima Sharma
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Correspondence to Pratima Sharma.

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Sharma, P., Hosmer, A., Appelman, H. et al. Immunological dysfunction during or after antiviral therapy for recurrent hepatitis C reduces graft survival. Hepatol Int 7, 990–999 (2013). https://doi.org/10.1007/s12072-013-9436-1

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  • DOI: https://doi.org/10.1007/s12072-013-9436-1

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