NATAP: Pegasys & RBV Post Transplant

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Pegasys + RBV & RBV Maintenance for Recurrent HCV Post Transplantation

"MULTICENTER RANDOMIZED TRIAL OF HCV TREATMENT WITH PEGINTERFERON-ALFA 2A (Pegasys) AND RIBAVIRIN AFTER LIVER TRANSPLANTATION:ONE-YEAR REPORT"

Reported by Jules Levin

AASLD

San Francisco, Nov 11, 2005

Yvon Calmus, Service de Chirurgie, Hopital Cochin, APHP, Paris, France; Christophe Duvoux, Hopital Henri Mondor, Cre´teil, France; Didier , Hopital Brousse, Villejuif, France; s P. Pageaux, Hopital Saint-Eloi, Montpellier, France; Michel Messner, Hopital Pontchaillou, Rennes, France; Philippe Wolf, Hopital Hautepierre, Strasbourg, France; Lionel Rostaing, Hopital

Rangueil, Toulouse, France; Vanlemmens, Hopital Minjoz, Besancon, France; Yves-Patrice LeTreut, Hopital Conception, Marseille, France; Sebastien Dharancy, Hopital Huriez, Lille, France; Guguenheim, Hopital de l'Archet, Nice, France; Francois Durand, Hopital Beaujon, Clichy, France; e Neau-Cransac, Hopital Pellegrin, Bordeaux, France; Olivier Boillot, Hopital Edouard Herriot, Lyon, France; ce Samelson, Laboratoires Roche, Neuilly, France; Karim Boudjema, Hopital Pontchaillou, Rennes, France

The aim of this randomized, double blind study was to determine whether maintenance therapy for one year with ribavirin (RBV) alone after a year of bitherapy with peginterferon-alfa 2a (PEG2A) and RBV, enhanced the eradication of HCV after liver transplantation (LT). Primary endpoints were the virological response at 12 (end of bitherapy) and 30 months (6 months after one year of maintenance therapy with RBV or placebo). We report here the results of the first year of treatment.

Methods: 97 patients were included, with recurrent HCV and a minimum of stage 1 fibrosis (METAVIR scoring) on a liver biopsy obtained 1 to 5 years after LT. 75% of patients received tacrolimus and 25% cyclosporine. PEG-2A was initiated at 90 ug/wk and RBV at 600 mg/d, then increased to 180 ug/wk and 1000 mg/d or adjusted as a function of hematological tolerance. Growth factor use was permitted. Therapy was stopped for intolerable side effects or cytopenia (hemoglobin <8g/dl, PMN <750/ul, platelets <30,000/ul).

Results:

At 52 weeks, HCV-PCR was negative in 62 % of patients(60/97), and in 75 % (58/77) of those who had completed 52 weeks of therapy (21% of patients did not complete the 52-week course of therapy). Viral response was 100 % in patients with genotype 2 or 3 and 65% in patients with genotype 1 or 4 (p=0.004).

There was no correlation between viral response and histological score, biological parameters at inclusion or the type of calcineurin inhibitor. ALT transaminases were 133 ± 120 IU/l (SD) before therapy, and 52 ± 38 IU/l after one year (p 0.001).

Histological activity was 1.68 ± 0.77 before, and 1.11 ± 0.767 after therapy (p=0.0001), whereas fibrosis remained unchanged (1.47 ± 0.71 and 1.61 ± 0.99,

respectively, p=0.06).

37% of patients required erythropoietin (EPO) support and 12% also required G-CSF. Globally, hemoglobin levels decreased from 13.7 ± 1.5 to 11.3 ± 1.5 g/dl.

Serious antiviral-related adverse effects were observed in 15 patients: acute rejection was observed in 2, severe cytopenia requiring the discontinuation of antiviral therapy in 7, acute renal failure in 2, ischemic cardiopathy in 2, psychiatric disorders in 2, diabetes in 2.

Conclusions: Using PEG-2A and RBV associated with a liberal use of EPO, a viral response was achieved in 74% of patients, with a low rate of side effects, including 2% of acute rejection and 2% of renal failure.