title: A novel immunosuppressive strategy combined with preemptive antiviral therapy improves the eighteen-month mortality in HCV recipients transplanted with aged livers.
abstract: BACKGROUND
  Donor's age and immunosuppression influence the severity of hepatitis C virus (HCV) recurrence. We analyzed the 18-month mortality in 302 consecutive HCV recipients, divided into three groups, with homogeneous immunosuppression and preemptive antiviral therapy in the last group.
  
  
  METHODS
  Group 1: one hundred thirty-three patients (1996-2000) mainly received a triple therapy (steroids- cyclosporine A [CyA]-azathioprine); first line treatment of biopsy-proven acute rejection (BPAR) was with steroid boluses; second-line with OKT3. Group 2: ninety-one patients (2001-2003) mainly received a double therapy (steroids-CyA) and induction with anti-CD25 antibody; first-line BPAR treatment was increased dose/switch of the calcineurin inhibitor; second-line steroid boluses; third-line extracorporeal photopheresis (ECP). Group 3: seventy-eight patients (2004-June 2006) mainly received a monotherapy (CyA) associated with ECP and induction with anti-CD25 antibody; first-line BPAR treatment was increased dose/switch of calcineurin inhibitor with increased ECP frequency, second-line steroid boluses, and third-line retransplantation.
  
  
  RESULTS
  Median donor's age increased from 54 (13-84) years in group 1 to 60 (10-93) years in group 2 and 66 (17-84) years in group 3 (P<0.001). Overall mortality in groups 1, 2, and 3 decreased from 28.6% to 22% and 10.2% respectively (P = 0.003); HCV-related mortality from 7.5% and 12.1% to 1.3%, respectively (P = 0.029). BPAR were 33.8% in group 1 and 9.0% in group 3. Applicability of the preemptive antiviral therapy in group 3 was 69.2%. Sustained viral clearance occurred in 38.9% of 36 patients who completed the protocol. At multivariate analysis, a single-drug immunosuppressive regimen was the only variable independently associated with survival (P=0.05).
  
  
  CONCLUSIONS
  Low and steady immunosuppression combined with preemptive antiviral therapy significantly improved the short-term mortality of HCV recipients transplanted with aged organs. Prolonged follow-up will assess whether this benefit is maintained in the long run.
authors.affiliation: Department of Liver Transplantation, General Surgery and Liver Transplantation Unit, Azienda Ospedaliero-Universitaria Pisana, Cisanello Hospital, Pisa, Italy. l.urbani@ao-pisa.toscana.it
authors.forename: Lucio
authors.initials: L
authors.lastname: Urbani
authors.forename: Alessandro
authors.initials: A
authors.lastname: Mazzoni
authors.forename: Piero
authors.initials: P
authors.lastname: Colombatto
authors.forename: Lucia
authors.initials: L
authors.lastname: Bindi
authors.forename: Gianni
authors.initials: G
authors.lastname: Biancofiore
authors.forename: Carlo
authors.initials: C
authors.lastname: Tascini
authors.forename: Francesco
authors.initials: F
authors.lastname: Menichetti
authors.forename: Maurizia Rossana
authors.initials: MR
authors.lastname: Brunetto
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Scatena
authors.forename: Franco
authors.initials: F
authors.lastname: Filipponi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000998:Antiviral Agents / Q000627:therapeutic use*; D002648:Child; D004359:Drug Therapy, Combination; D006084:Graft Rejection / Q000473:pathology; D006526:Hepatitis C / Q000188:drug therapy / Q000601:surgery*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007558:Italy; D016031:Liver Transplantation / Q000276:immunology / Q000401:mortality / Q000502:physiology*; D008875:Middle Aged; D012189:Retrospective Studies; D015996:Survival Rate; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D007166:Immunosuppressive Agents