title: Tumor DNA Index and α-Fetoprotein Level Define Outcome following Liver Transplantation for Advanced Hepatocellular Carcinoma.
abstract: BACKGROUND
  Patients with hepatocellular carcinoma (HCC) beyond the Milan criteria are expected to have inferior outcome after liver transplantation (LT) and are therefore currently not considered for LT in many countries. The purpose of this study was to identify predictive factors for overall survival following LT for HCC that may support the Milan criteria in the selection of appropriate transplant candidates.
  
  
  METHODS
  Clinicopathological data on 364 patients with HCC who underwent LT between 1989 and 2010 were retrospectively evaluated. Predictors of overall survival in the entire cohort as well as in subsets of patients within (n = 214) and beyond (n = 150) the Milan criteria were analyzed.
  
  
  RESULTS
  Multivariate analysis in the entire cohort identified DNA index >1.5 (p < 0.0001), α-fetoprotein level (AFP) >200 ng/ml (p = 0.005), and HCC beyond the Milan criteria (p = 0.002) to be associated with worse overall survival. In patients within the Milan criteria (median survival: 170 months), DNA index >1.5 (p < 0.0001) was the only predictor of worse overall survival in multivariate analysis. In patients beyond the Milan criteria (median survival: 44 months), DNA index >1.5, AFP >200 ng/ml, microvascular invasion, patient age >60 years, and DNA index >1.5 concomitant with AFP >200 ng/ml were associated with worse overall survival in univariate analysis. Multivariate analysis identified DNA index >1.5 concomitant with AFP >200 ng/ml (p < 0.0001) as the only independent predictor of worse overall survival. Consequently, patients beyond the Milan criteria with a combined favorable DNA index ≤1.5 and AFP ≤200 ng/ml had a median survival (147 months) comparable to that of patients within the Milan criteria.
  
  
  CONCLUSIONS
  DNA index and AFP level predict overall survival following LT in patients with advanced HCC beyond the Milan criteria. A combined assessment of these markers during the evaluation of transplant candidates can contribute to the selection of patients with HCC who may benefit from LT independently of their tumor burden.
authors.affiliation: Department of General, Visceral and Transplant Surgery, Charitx00E9; - Universitx00E4;tsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Andreou
authors.forename: Marcus
authors.initials: M
authors.lastname: Bahra
authors.forename: Safak
authors.initials: S
authors.lastname: Guel
authors.forename: Benjamin
authors.initials: B
authors.lastname: Struecker
authors.forename: Igor M
authors.initials: IM
authors.lastname: Sauer
authors.forename: Fritz
authors.initials: F
authors.lastname: Klein
authors.forename: Andreas
authors.initials: A
authors.lastname: Pascher
authors.forename: Johann
authors.initials: J
authors.lastname: Pratschke
authors.forename: Daniel
authors.initials: D
authors.lastname: Seehofer