title: Liver transplantation for aHUS: still needed in the eculizumab era?
abstract: BACKGROUND
  The risk of disease recurrence after a kidney transplant is high in patients with atypical hemolytic uremic syndrome (aHUS) and mutations in the complement factor H (FH) gene (CFH). Since FH is mostly produced by the liver, a kidney transplant does not correct the genetic defect. The anti-C5 antibody eculizumab prevents post-transplant aHUS recurrence, but it does not cure the disease. Combined liver-kidney transplantation has been performed in few patients with CFH mutations based on the rationale that liver replacement provides a source of normal FH.
  
  
  METHODS
  We report the 9-year follow-up of a child with aHUS and a CFH mutation, including clinical data, extensive genetic characterization, and complement profile in the circulation and at endothelial level. The outcome of kidney and liver transplants performed separately 3 years apart are reported.
  
  
  RESULTS
  The patient showed incomplete response to plasma, with relapsing episodes, progression to end-stage renal disease, and endothelial-restricted complement dysregulation. Eculizumab prophylaxis post-kidney transplant did not achieve sustained remission, leaving the child at risk of disease recurrence. A liver graft given 3 years after the kidney transplant completely abrogated endothelial complement activation and allowed eculizumab withdrawal.
  
  
  CONCLUSIONS
  Liver transplant may definitely cure aHUS and represents an option for patients with suboptimal response to eculizumab.
authors.affiliation: Nephrology Dialysis and Transplantation, AOU Città della Salute e della Scienza di Torino, Turin and Fondazione Ricerca Molinette, Regina Margherita Hospital, Turin, Italy.
authors.forename: Rosanna
authors.initials: R
authors.lastname: Coppo
authors.affiliation: Nephrology Dialysis and Transplantation, AOU Città della Salute e della Scienza di Torino, Turin and Fondazione Ricerca Molinette, Regina Margherita Hospital, Turin, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Bonaudo
authors.affiliation: Nephrology Dialysis and Transplantation, AOU Città della Salute e della Scienza di Torino, Turin and Fondazione Ricerca Molinette, Regina Margherita Hospital, Turin, Italy.
authors.forename: R Licia
authors.initials: RL
authors.lastname: Peruzzi
authors.affiliation: Nephrology Dialysis and Transplantation, AOU Città della Salute e della Scienza di Torino, Turin and Fondazione Ricerca Molinette, Regina Margherita Hospital, Turin, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Amore
authors.affiliation: Liver Transplantation Center, General Surgery Unit 2U, AOU Città della Salute e della Scienza di Torino, Molinette Hospital, University of Turin , Turin, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Brunati
authors.affiliation: Liver Transplantation Center, General Surgery Unit 2U, AOU Città della Salute e della Scienza di Torino, Molinette Hospital, University of Turin , Turin, Italy.
authors.forename: Renato
authors.initials: R
authors.lastname: Romagnoli
authors.affiliation: Liver Transplantation Center, General Surgery Unit 2U, AOU Città della Salute e della Scienza di Torino, Molinette Hospital, University of Turin , Turin, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Salizzoni
authors.affiliation: Clinical Research Center for Rare Diseases "Aldo e Cele Daccò", IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri", Villa Camozzi, 3-24020, Ranica (Bergamo), Italy.|Centro Anna Maria Astori, IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri", Science and Technology Park Kilometro Rosso, Bergamo, Italy.
authors.forename: Miriam
authors.initials: M
authors.lastname: Galbusera
authors.affiliation: Unit of Nephrology and Dialysis, Azienda Ospedaliera Papa Giovanni XXIII, Bergamo, Italy.
authors.forename: Eliana
authors.initials: E
authors.lastname: Gotti
authors.affiliation: Clinical Research Center for Rare Diseases "Aldo e Cele Daccò", IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri", Villa Camozzi, 3-24020, Ranica (Bergamo), Italy.
authors.forename: Erica
authors.initials: E
authors.lastname: Daina
authors.affiliation: Clinical Research Center for Rare Diseases "Aldo e Cele Daccò", IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri", Villa Camozzi, 3-24020, Ranica (Bergamo), Italy. marina.noris@marionegri.it.
authors.forename: Marina
authors.initials: M
authors.lastname: Noris
authors.affiliation: Clinical Research Center for Rare Diseases "Aldo e Cele Daccò", IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri", Villa Camozzi, 3-24020, Ranica (Bergamo), Italy.|Centro Anna Maria Astori, IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri", Science and Technology Park Kilometro Rosso, Bergamo, Italy.|Unit of Nephrology and Dialysis, Azienda Ospedaliera Papa Giovanni XXIII, Bergamo, Italy.|Department of Biomedical Sciences of Health, University of Milan, Milan, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Remuzzi
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D065766:Atypical Hemolytic Uremic Syndrome / Q000175:diagnosis / Q000235:genetics / Q000628:therapy*; D002478:Cells, Cultured; D003167:Complement Activation / Q000187:drug effects* / Q000235:genetics; D017242:Complement Factor H / Q000235:genetics; D051056:Complement Inactivating Agents / Q000627:therapeutic use*; D004252:DNA Mutational Analysis; D020022:Genetic Predisposition to Disease; D040941:Heredity; D006801:Humans; D007223:Infant; D016030:Kidney Transplantation; D016031:Liver Transplantation; D008297:Male; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; C493495:CFH protein, human; D051056:Complement Inactivating Agents; D017242:Complement Factor H; C481642:eculizumab
keywords: Alternative; Atypical hemolytic uremic syndrome; Complement pathway; Eculizumab; Kidney transplantation; Liver transplantation; Rare diseases