Recurrence After Liver Transplantation for Hepatocellular Carcinoma: A New MORAL to the Story

Ann Surg. 2017 Mar;265(3):557-564. doi: 10.1097/SLA.0000000000001966.

Abstract

Objective: We sought to develop a "Model Of Recurrence After Liver transplant" (MORAL) for hepatocellular carcinoma (HCC).

Background: The Milan criteria are used to allocate livers to patients with HCC requiring liver transplantation (LT) but do not include objective measures of tumor biology. Biological markers including the neutrophil-lymphocyte ratio (NLR) and alpha-fetoprotein (AFP) have been associated with recurrence risk.

Methods: Prospective cohort study of adults undergoing LT for HCC between January 2001 and December 2012.

Results: A total of 339 patients were included. On multivariable Cox regression analysis, 3 preoperatively available factors were independent predictors of worse recurrence-free survival (RFS), namely, an NLR ≥ 5 (P < 0.0001, hazard ratio, HR: 6.2), AFP > 200 (P < 0.0001, HR: 3.8), and Size >3 cm (P < 0.001, HR: 3.2). The Pre-MORAL score was constructed from the hazard ratios and assigning patients points in an additive fashion, with a minimum of 0 points (no factors) and a maximum of 13 points (all 3 factors). The highest risk patients in the Pre-MORAL had a 5-year RFS of 17.9% compared with 98.6% for the low risk group (P < 0.0001). The post-MORAL was constructed similarly using the 4 postoperatively available independent predictors of worse RFS, grade 4 HCC's (P < 0.0001, HR: 5.6), vascular invasion (P = 0.019, HR: 2.0), size >3 cm (P < 0.0001, HR: 3.2) and number >3 (P = 0.048, HR: 1.8). The pre- and post-MORAL were superior to Milan at predicting recurrence with c-statistics of 0.82 and 0.87, compared with 0.63, respectively. We then combined the scores to produce a combo-MORAL, with a c-statistic of 0.91 for predicting recurrence.

Conclusions: The MORAL score provides a simple, highly accurate tool for predicting recurrence and risk-stratification pre- and postoperatively.

MeSH terms

  • Academic Medical Centers
  • Adult
  • Aged
  • Carcinoma, Hepatocellular / mortality
  • Carcinoma, Hepatocellular / pathology
  • Carcinoma, Hepatocellular / surgery*
  • Cohort Studies
  • Databases, Factual
  • Disease-Free Survival
  • Female
  • Graft Rejection
  • Graft Survival
  • Humans
  • Kaplan-Meier Estimate
  • Liver Neoplasms / mortality
  • Liver Neoplasms / pathology
  • Liver Neoplasms / surgery*
  • Liver Transplantation / adverse effects*
  • Liver Transplantation / methods
  • Liver Transplantation / mortality
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Neoplasm Invasiveness / pathology
  • Neoplasm Recurrence, Local / mortality*
  • Neoplasm Recurrence, Local / pathology*
  • Neoplasm Recurrence, Local / therapy
  • Neoplasm Staging
  • Predictive Value of Tests
  • Prognosis
  • Proportional Hazards Models
  • Prospective Studies
  • ROC Curve
  • Risk Assessment
  • Survival Analysis