title: A method for establishing allocation equity among patients with and without hepatocellular carcinoma on a common liver transplant waiting list.
abstract: OBJECTIVE
  The current organ allocation system for liver transplantation (LT) creates an imbalance between patients with and without hepatocellular carcinoma (HCC). We describe a model designed to re-establish allocation equity among patient groups using transplant benefit as the common endpoint.
  
  
  METHODS
  We enrolled consecutive adult patients entering the waiting list (WL group, n=2697) and undergoing LT (LT group, n=1702) during the period 2004-2009 in the North Italy Transplant program area. Independent multivariable regressions (WL and LT models) were created for patients without HCC and for those with stage T2 HCC. Monte Carlo simulation was used to create distributions of transplant benefit, and covariates such as Model for End-stage Liver Disease (MELD) and alpha-fetoprotein (AFP) were combined in regression equations. These equations were then calibrated to create an "MELD equivalent" which matches HCC patients to non-HCC patients having the same numerical MELD score.
  
  
  RESULTS
  Median 5 year transplant benefit was 15.12 months (8.75-25.35) for the non-HCC patients, and 28.18 months (15.11-36.38) for the T2-HCC patients (p<0.001). Independent predictors of transplant benefit were MELD score (estimate=0.89, p<0.001) among non-HCC patients, and MELD (estimate=1.14, p<0.001) and logAFP (estimate=-0.46, p<0.001) among HCC patients. The equation "HCC-MELD"=1.27∗MELD - 0.51∗logAFP+4.59 calculates a numerical score for HCC patients, whereby their transplant benefit is equal to that of non-HCC patients with the same numerical value for MELD.
  
  
  CONCLUSIONS
  We describe a method for calibrating HCC and non-HCC patients according to survival benefit, and propose that this method has the potential, if externally validated, to restore equity to the organ allocation system.
authors.affiliation: University Hospital of Padua, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Vitale
authors.affiliation: Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, USA.
authors.forename: Michael L
authors.initials: ML
authors.lastname: Volk
authors.affiliation: Organs and Tissue Transplant Immunology Unit, Fond. IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
authors.forename: Tullia Maria
authors.initials: TM
authors.lastname: De Feo
authors.affiliation: University Hospital of Padua, Italy. Electronic address: burra@unipd.it.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Burra
authors.affiliation: University Hospital of Padua, Italy.
authors.forename: Anna Chiara
authors.initials: AC
authors.lastname: Frigo
authors.affiliation: Veneto Institute of Oncology IOV - IRCCS, Padua, Italy.
authors.forename: Rafael
authors.initials: R
authors.lastname: Ramirez Morales
authors.affiliation: Surgery and Transplantation, Ospedale Niguarda Ca' Granda, Milan, Italy.
authors.forename: Luciano
authors.initials: L
authors.lastname: De Carlis
authors.affiliation: Hepatology and Gastroenterology, Ospedale Niguarda Ca' Granda, Milan, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Belli
authors.affiliation: Gastroenterology and Transplantation Hepatology, Ospedali Riuniti, Bergamo, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Colledan
authors.affiliation: Gastroenterology and Transplantation Hepatology, Ospedali Riuniti, Bergamo, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Fagiuoli
authors.affiliation: Liver Transplantation Unit, Fond. IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Rossi
authors.affiliation: IRCCS San Martino, Genoa, Italy.
authors.forename: Enzo
authors.initials: E
authors.lastname: Andorno
authors.affiliation: Medical Liver Transplant Unit, University of Udine, Italy.
authors.forename: Umberto
authors.initials: U
authors.lastname: Baccarani
authors.affiliation: Liver Transplantation, IRCCS INT, Milan, Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Regalia
authors.affiliation: Liver Transplantation Unit, Ancona Hospital, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Vivarelli
authors.affiliation: Liver Transplantation Unit, Verona Hospital, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Donataccio
authors.affiliation: University Hospital of Padua, Italy.
authors.forename: Umberto
authors.initials: U
authors.lastname: Cillo
mesh_terms: D000328:Adult; D006528:Carcinoma, Hepatocellular / Q000150:complications* / Q000401:mortality / Q000601:surgery*; D058625:End Stage Liver Disease / Q000150:complications* / Q000401:mortality / Q000601:surgery*; D005260:Female; D006801:Humans; D007558:Italy / Q000453:epidemiology; D008113:Liver Neoplasms / Q000150:complications* / Q000401:mortality / Q000601:surgery*; D016031:Liver Transplantation; D008297:Male; D008390:Markov Chains; D008875:Middle Aged; D009010:Monte Carlo Method; D016016:Proportional Hazards Models; D012720:Severity of Illness Index; D009927:Tissue and Organ Procurement / Q000379:methods* / Q000706:statistics & numerical data; D014850:Waiting Lists
keywords: AFP; CI; CR; Cirrhosis; Clinical decision making; HBV; HCC; HCV; HR; Hepatocellular carcinoma; INR; IQR; LT; Liver Transplantation; Liver transplantation; MELD; NITp; North Italy Transplant program; Surgical oncology; WL; alpha-fetoprotein; competing risk; confidence interval; hazard ratio; hepatitis B virus; hepatitis C virus; hepatocellular carcinoma; international normalized ratio; interquartile range; model for end-stage liver disease; waiting list