A method for establishing allocation equity among patients with and without hepatocellular carcinoma on a common liver transplant waiting list

Abstract

Background & aims: 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.

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.