Recurrence After Liver Transplantation for Hepatocellular Carcinoma: A New MORAL to the Story.
We sought to develop a "Model Of Recurrence After Liver transplant" (MORAL) for hepatocellular carcinoma (HCC).



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.



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



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.



The MORAL score provides a simple, highly accurate tool for predicting recurrence and risk-stratification pre- and postoperatively.
*Division of Liver Transplantation and Hepatobiliary Surgery, Department of Surgery, Weill Cornell Medical College, New York, NY †Center for Liver Disease and Transplantation, Columbia University Medical Center, New York Presbyterian Hospital, New York, NY ‡Division of Gastroenterology and Hepatology, Department of Medicine, Weill Cornell Medical College, New York, NY.
Karim J
KJ
Halazun
Marc
M
Najjar
Rita M
RM
Abdelmessih
Benjamin
B
Samstein
Adam D
AD
Griesemer
James V
JV
Guarrera
Tomoaki
T
Kato
Elizabeth C
EC
Verna
Jean C
JC
Emond
Robert S
RS
Brown
D000046:Academic Medical Centers; D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000401:mortality / Q000473:pathology / Q000601:surgery*; D015331:Cohort Studies; D016208:Databases, Factual; D018572:Disease-Free Survival; D005260:Female; D006084:Graft Rejection; D006085:Graft Survival; D006801:Humans; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000401:mortality / Q000473:pathology / Q000601:surgery*; D016031:Liver Transplantation / Q000009:adverse effects* / Q000379:methods / Q000401:mortality; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009361:Neoplasm Invasiveness / Q000473:pathology; D009364:Neoplasm Recurrence, Local / Q000401:mortality* / Q000473:pathology* / Q000628:therapy; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012372:ROC Curve; D018570:Risk Assessment; D016019:Survival Analysis