title: Interaction between calcineurin inhibitors and IL-28B rs12979860 C>T polymorphism and response to treatment for post-transplant recurrent hepatitis C.
abstract: BACKGROUND
  The impact of calcineurin inhibitors on achievement of sustained virological response to antiviral therapy for post-transplant recurrent hepatitis C is controversial. This study aimed at investigating the interactions between calcineurin inhibitors and interleukin-28B (IL-28B) gene polymorphisms and sustained virological response.
  
  
  METHODS
  Retrospective study of 147 liver transplant recipients with recurrent hepatitis C, who received 48 weeks of peg-interferon-α (N=113) or standard interferon (N=34), in association with ribavirin. Cyclosporine and tacrolimus were administered in 68 and 79 patients, respectively. IL-28B rs12979860 allele frequency was assessed in both donors and recipients.
  
  
  RESULTS
  Overall, 57 patients (38.8%) obtained sustained virological response; no difference was found between cyclosporine and tacrolimus-treated patients (42.6% vs. 35.4%, p=0.371). Recipient and donor IL-28B genotypic frequencies were C/C=30.6%, C/T=51.7%, T/T=17.7% and C/C=44.9%, C/T=50.3%, T/T=4.8%, respectively. Combining donor and recipient alleles, response rates decreased from cyclosporine-treated patients carrying ≤ 1 T allele (56.1%) to tacrolimus-treated patients carrying ≤ 1 T allele (44.7%) to patients carrying ≥ 2 T alleles (25.0%, p=0.0009).
  
  
  CONCLUSIONS
  Donor and recipient rs12979860 alleles synergistically influence sustained virological response rate to antiviral treatment for recurrent hepatitis C. In patients carrying <2 T alleles cyclosporine favours a better response than tacrolimus, while no difference was found in the presence of ≥ 2 T alleles.
authors.affiliation: Medical Liver Transplant Unit, Department of Medical Sciences Experimental and Clinical, University of Udine, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Bitetto
authors.forename: Tullia
authors.initials: T
authors.lastname: De Feo
authors.forename: Martina
authors.initials: M
authors.lastname: Mantovani
authors.forename: Edmondo
authors.initials: E
authors.lastname: Falleti
authors.forename: Carlo
authors.initials: C
authors.lastname: Fabris
authors.forename: Luca Saverio
authors.initials: LS
authors.lastname: Belli
authors.forename: Stefano
authors.initials: S
authors.lastname: Fagiuoli
authors.forename: Patrizia
authors.initials: P
authors.lastname: Burra
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Piccolo
authors.forename: Maria Francesca
authors.initials: MF
authors.lastname: Donato
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Toniutto
authors.forename: Sara
authors.initials: S
authors.lastname: Cmet
authors.forename: Annarosa
authors.initials: A
authors.lastname: Cussigh
authors.forename: Raffaella
authors.initials: R
authors.lastname: Viganò
authors.forename: Aldo
authors.initials: A
authors.lastname: Airoldi
authors.forename: Luisa
authors.initials: L
authors.lastname: Pasulo
authors.forename: Maria
authors.initials: M
authors.lastname: Colpanij
authors.forename: Eleonora
authors.initials: E
authors.lastname: De Martin
authors.forename: Martina
authors.initials: M
authors.lastname: Gambato
authors.forename: Cristina
authors.initials: C
authors.lastname: Rigamonti
mesh_terms: D000483:Alleles; D000998:Antiviral Agents / Q000627:therapeutic use; D065095:Calcineurin Inhibitors; D004247:DNA / Q000235:genetics*; D004359:Drug Therapy, Combination; D005500:Follow-Up Studies; D005838:Genotype; D016174:Hepacivirus / Q000187:drug effects / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000209:etiology / Q000235:genetics / Q000628:therapy*; D016898:Interferon-alpha / Q000627:therapeutic use*; D007372:Interferons; D007378:Interleukins / Q000235:genetics* / Q000378:metabolism; D016031:Liver Transplantation / Q000009:adverse effects*; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D011110:Polymorphism, Genetic; D012367:RNA, Viral / Q000235:genetics; D011994:Recombinant Proteins / Q000627:therapeutic use; D012008:Recurrence; D012189:Retrospective Studies; D012254:Ribavirin / Q000627:therapeutic use; D016896:Treatment Outcome; D019562:Viral Load / Q000187:drug effects; D000095022:Interferon Lambda
chemical_list: D000998:Antiviral Agents; D065095:Calcineurin Inhibitors; D004247:DNA; D016898:Interferon-alpha; D007372:Interferons; D007378:Interleukins; D011092:Polyethylene Glycols; D012367:RNA, Viral; D011994:Recombinant Proteins; D012254:Ribavirin; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C100416:peginterferon alfa-2a
keywords: Antiviral therapy; Calcineurin inhibitors; Chronic hepatitis; Interleukin-28B polymorphisms; Liver transplantation