title: Impact of donor and recipient IL28B rs12979860 genotypes on hepatitis C virus liver graft reinfection.
abstract: OBJECTIVE
  Recent studies have described a major impact of genetic variations near the IL28B gene on the natural course and outcome of antiviral therapy in chronic hepatitis C. We therefore, aimed to explore the impact of donor and recipient genotypes of these polymorphisms on hepatitis C virus (HCV) liver graft reinfection.
  
  
  METHODS
  Donor and recipient genotypes of IL28B rs12979860C>T single nucleotide polymorphism were determined in 91 patients with HCV liver graft reinfection, 47 of whom were treated with pegylated interferon-α (PEG-IFN-α) and ribavirin. IL28B genetic polymorphisms were correlated with the natural course and treatment outcome of recurrent hepatitis C.
  
  
  RESULTS
  Patients requiring liver transplantation due to end-stage chronic hepatitis C appeared to be selected toward the adverse genotypes rs12979860 CT/TT compared to non-transplanted HCV-infected patients (p=0.046). Patients with the donor genotype rs12979860 CC had higher peak ALT and HCV RNA serum concentrations than those with CT/TT (p=0.04 and 0.06, respectively). No association was observed between ALT/HCV RNA serum concentrations and recipient genotypes (p>0.3). More important, donor IL28B rs12979860 CC vs. CT/TT genotypes were associated with rapid, complete early, and sustained virologic response (RVR, cEVR, SVR) to treatment with PEG-IFN-α and ribavirin (p=0.003, 0.0012, 0.008, respectively), but weaker associations of recipient genotypes with RVR, cEVR, and SVR were observed as well (p=0.0046, 0.115, 0.118, respectively).
  
  
  CONCLUSIONS
  We provide evidence for a dominant, but not exclusive impact of the donor rather than the recipient IL28B genetic background on the natural course and treatment outcome of HCV liver graft reinfection.
authors.affiliation: Medizinische Klinik 1, Klinikum der J.W. Goethe-Universität Frankfurt am Main, D-60590 Frankfurt am Main, Germany. Christian.Lange@chuv.ch
authors.forename: Christian M
authors.initials: CM
authors.lastname: Lange
authors.forename: Darius
authors.initials: D
authors.lastname: Moradpour
authors.forename: Alexandra
authors.initials: A
authors.lastname: Doehring
authors.forename: Hans-Anton
authors.initials: HA
authors.lastname: Lehr
authors.forename: Beat
authors.initials: B
authors.lastname: Müllhaupt
authors.forename: Stephanie
authors.initials: S
authors.lastname: Bibert
authors.forename: Pierre-Yves
authors.initials: PY
authors.lastname: Bochud
authors.forename: Anca T
authors.initials: AT
authors.lastname: Antonino
authors.forename: Manuel
authors.initials: M
authors.lastname: Pascual
authors.forename: Harald
authors.initials: H
authors.lastname: Farnik
authors.forename: Ying
authors.initials: Y
authors.lastname: Shi
authors.forename: Wolf Otto
authors.initials: WO
authors.lastname: Bechstein
authors.forename: Christian
authors.initials: C
authors.lastname: Moench
authors.forename: Martin-Leo
authors.initials: ML
authors.lastname: Hansmann
authors.forename: Christoph
authors.initials: C
authors.lastname: Sarrazin
authors.forename: Jörn
authors.initials: J
authors.lastname: Lötsch
authors.forename: Stefan
authors.initials: S
authors.lastname: Zeuzem
authors.forename: Wolf-Peter
authors.initials: WP
authors.lastname: Hofmann
mesh_terms: D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D000998:Antiviral Agents / Q000008:administration & dosage; D005260:Female; D005838:Genotype; D019698:Hepatitis C, Chronic / Q000188:drug therapy / Q000235:genetics* / Q000503:physiopathology / Q000601:surgery*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage; D007372:Interferons; D007378:Interleukins / Q000235:genetics*; D008103:Liver Cirrhosis / Q000209:etiology; D016031:Liver Transplantation / Q000009:adverse effects* / Q000502:physiology; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000008:administration & dosage; D020641:Polymorphism, Single Nucleotide; D012367:RNA, Viral / Q000097:blood; D011994:Recombinant Proteins / Q000008:administration & dosage; D012008:Recurrence; D012254:Ribavirin / Q000008:administration & dosage; D014019:Tissue Donors; D016896:Treatment Outcome; D000095022:Interferon Lambda
chemical_list: D000410:Alanine Transaminase; D000998:Antiviral Agents; D000077190:Interferon alpha-2; 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; C417083:peginterferon alfa-2b; C100416:peginterferon alfa-2a