Recurrence after liver transplantation for hepatocellular carcinoma

Karim J. Halazun, Marc Najjar, Rita M. Abdelmessih, Benjamin Samstein, Adam D. Griesemer, James Guarrera, Tomoaki Kato, Elizabeth C. Verna, Jean C. Emond, Robert S. Brown

Research output: Contribution to journalArticle

51 Citations (Scopus)

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 >3cm (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 >3cm (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.

Original languageEnglish (US)
Pages (from-to)557-564
Number of pages8
JournalAnnals of Surgery
Volume265
Issue number3
DOIs
StatePublished - Mar 1 2017
Externally publishedYes

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Liver Transplantation
Hepatocellular Carcinoma
Recurrence
Liver
Transplants
Neutrophils
Lymphocytes
alpha-Fetoproteins
Cohort Studies
Biomarkers
Regression Analysis
Prospective Studies
Survival

All Science Journal Classification (ASJC) codes

  • Surgery

Cite this

Halazun, K. J., Najjar, M., Abdelmessih, R. M., Samstein, B., Griesemer, A. D., Guarrera, J., ... Brown, R. S. (2017). Recurrence after liver transplantation for hepatocellular carcinoma. Annals of Surgery, 265(3), 557-564. https://doi.org/10.1097/SLA.0000000000001966
Halazun, Karim J. ; Najjar, Marc ; Abdelmessih, Rita M. ; Samstein, Benjamin ; Griesemer, Adam D. ; Guarrera, James ; Kato, Tomoaki ; Verna, Elizabeth C. ; Emond, Jean C. ; Brown, Robert S. / Recurrence after liver transplantation for hepatocellular carcinoma. In: Annals of Surgery. 2017 ; Vol. 265, No. 3. pp. 557-564.
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Halazun, KJ, Najjar, M, Abdelmessih, RM, Samstein, B, Griesemer, AD, Guarrera, J, Kato, T, Verna, EC, Emond, JC & Brown, RS 2017, 'Recurrence after liver transplantation for hepatocellular carcinoma', Annals of Surgery, vol. 265, no. 3, pp. 557-564. https://doi.org/10.1097/SLA.0000000000001966

Recurrence after liver transplantation for hepatocellular carcinoma. / Halazun, Karim J.; Najjar, Marc; Abdelmessih, Rita M.; Samstein, Benjamin; Griesemer, Adam D.; Guarrera, James; Kato, Tomoaki; Verna, Elizabeth C.; Emond, Jean C.; Brown, Robert S.

In: Annals of Surgery, Vol. 265, No. 3, 01.03.2017, p. 557-564.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Recurrence after liver transplantation for hepatocellular carcinoma

AU - Halazun, Karim J.

AU - Najjar, Marc

AU - Abdelmessih, Rita M.

AU - Samstein, Benjamin

AU - Griesemer, Adam D.

AU - Guarrera, James

AU - Kato, Tomoaki

AU - Verna, Elizabeth C.

AU - Emond, Jean C.

AU - Brown, Robert S.

PY - 2017/3/1

Y1 - 2017/3/1

N2 - 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 >3cm (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 >3cm (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.

AB - 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 >3cm (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 >3cm (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.

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Halazun KJ, Najjar M, Abdelmessih RM, Samstein B, Griesemer AD, Guarrera J et al. Recurrence after liver transplantation for hepatocellular carcinoma. Annals of Surgery. 2017 Mar 1;265(3):557-564. https://doi.org/10.1097/SLA.0000000000001966