title: Steroid-free induction and preemptive antiviral therapy for liver transplant recipients with hepatitis C: a preliminary report from a prospective randomized study.
abstract: Recurrence of hepatitis C (HepC) has been a most difficult dilemma in liver transplantation (OLT) because the effects of immunosuppression with steroid, mycophenolate mofetil (MMF) calcineurin antagonists, and anti-interleukin-2 antibody as well as the role of preemptive antiviral therapy are uncertain. In this study, we randomized OLT recipients with HepC into two treatment arms: tacrolimus+daclizumab+MMF (study arm) versus tacrolimus+steroids+MMF (control arm). The study arm only received steroids for the treatment of biopsy-proven rejection episodes. Both arms received preemptive anti-viral therapy with Pegasys and ribavirin. The 39 enrolled patients (among 50 to be enrolled) have median follow-up of 458 days with 23 patients (8 in study arm, 15 in control arm) having reached 1 year. The incidences of rejection episodes within 0 to 3 months, 3 to 6 months, and 6 to 12 months were (study vs control): 0% vs 28%; 0% vs 6%; and 13% vs 20%; respectively (P = NS). The 1-year protocol biopsies showed advanced fibrosis (stage 3 or greater) in 20% (3 of 15) of the control arm, but none (0 of 7) of the study arm (P = NS). We compared anticipated side effects of steroids in the first 3 months (study vs control): hypertension (36% vs 58%, P = NS), PTDM (7% vs 43%, P = .02), and wound infections (14% vs 37%, P = NS). In conclusion, liver transplant recipients with HepC tolerate a steroid-free protocol. There was a trend toward reduced steroid side effects and a lower incidence of advanced fibrosis in 1-year biopsy samples among patients receiving the steroid-free protocol.
authors.affiliation: Division of Transplant, University of Miami, Miami, Florida 33136, USA. tkato@med.miami.edu
authors.forename: T
authors.initials: T
authors.lastname: Kato
authors.forename: H
authors.initials: H
authors.lastname: Yoshida
authors.forename: K
authors.initials: K
authors.lastname: Sadfar
authors.forename: E
authors.initials: E
authors.lastname: Martinez
authors.forename: S
authors.initials: S
authors.lastname: Nishida
authors.forename: J
authors.initials: J
authors.lastname: Moon
authors.forename: J
authors.initials: J
authors.lastname: Madariaga
authors.forename: G
authors.initials: G
authors.lastname: Selvaggi
authors.forename: D
authors.initials: D
authors.lastname: Levi
authors.forename: P
authors.initials: P
authors.lastname: Ruiz
authors.forename: E
authors.initials: E
authors.lastname: Schiff
authors.forename: A
authors.initials: A
authors.lastname: Tzakis
mesh_terms: D000305:Adrenal Cortex Hormones / Q000009:adverse effects / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000998:Antiviral Agents / Q000627:therapeutic use*; D000077561:Daclizumab; D004359:Drug Therapy, Combination; D005260:Female; D006084:Graft Rejection / Q000453:epidemiology; D006526:Hepatitis C / Q000175:diagnosis* / Q000517:prevention & control / Q000601:surgery*; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use*; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use; D016031:Liver Transplantation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000627:therapeutic use; D011994:Recombinant Proteins; D012008:Recurrence; D012254:Ribavirin / Q000627:therapeutic use; D016559:Tacrolimus / Q000627:therapeutic use*; D019562:Viral Load
chemical_list: D000305:Adrenal Cortex Hormones; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000998:Antiviral Agents; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; D000077561:Daclizumab; C100416:peginterferon alfa-2a; D016559:Tacrolimus