title: Immunological dysfunction during or after antiviral therapy for recurrent hepatitis C reduces graft survival.
abstract: BACKGROUND
  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.
authors: Division of Gastroenterology, Department of Internal Medicine, University of Michigan Health System, 3912, Taubman Center, SPC 5362, Ann Arbor, MI 48109, USA.
authors: Pratima
authors: P
authors: Sharma
authors: Division of Gastroenterology, Department of Internal Medicine, University of Michigan Health System, 3912, Taubman Center, SPC 5362, Ann Arbor, MI 48109, USA.
authors: Amy
authors: A
authors: Hosmer
authors: Department of Pathology, University of Michigan, Medical Science Building-1, 1301, Catherine Road, Ann Arbor, MI, USA.
authors: Henry
authors: H
authors: Appelman
authors: Department of Pathology, University of Michigan, Medical Science Building-1, 1301, Catherine Road, Ann Arbor, MI, USA.
authors: Barbara
authors: B
authors: McKenna
authors: Division of Gastroenterology, Department of Internal Medicine, University of Michigan Health System, 3912, Taubman Center, SPC 5362, Ann Arbor, MI 48109, USA.
authors: Mohammad S
authors: MS
authors: Jafri
authors: Division of Gastroenterology, Department of Internal Medicine, University of Michigan Health System, 3912, Taubman Center, SPC 5362, Ann Arbor, MI 48109, USA.
authors: Patricia
authors: P
authors: Sullivan
authors: Division of Gastroenterology, Department of Internal Medicine, University of Michigan Health System, 3912, Taubman Center, SPC 5362, Ann Arbor, MI 48109, USA.
authors: Robert J
authors: RJ
authors: Fontana
authors: Division of Gastroenterology, Department of Internal Medicine, University of Michigan Health System, 3912, Taubman Center, SPC 5362, Ann Arbor, MI 48109, USA.
authors: Anna S
authors: AS
authors: Lok
keywords: Immunological dysfunction; Liver transplantation; Recurrent hepatitis C