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World J Gastroenterol. Dec 7, 2006; 12(45): 7319-7325
Published online Dec 7, 2006. doi: 10.3748/wjg.v12.i45.7319
Role of immunosuppression and tumor differentiation in predicting recurrence after liver transplantation for hepatocellular carcinoma: A multicenter study of 412 patients
Thomas Decaens, Françoise Roudot-Thoraval, Solange Bresson-Hadni, Carole Meyer, Jean Gugenheim, Francois Durand, Pierre-Henri Bernard, Olivier Boillot, Philippe Compagnon, Yvon Calmus, Jean Hardwigsen, Christian Ducerf, Georges Philippe Pageaux, Sébastien Dharancy, Olivier Chazouillères, Daniel Cherqui, Christophe Duvoux
Thomas Decaens, Christophe Duvoux, Service d’Hépatologie et de Gastroentérologie, AP-HP, Hôpital Henri Mondor, Créteil, Unité INSERM 581, France
Françoise Roudot-Thoraval, Département de Santé Publique, AP-HP, Hôpital Henri Mondor, Créteil, France
Solange Bresson-Hadni, Service d’Hépatologie, Hôpital Jean Minjoz, Besançon, France
Carole Meyer, Service de Transplantation, Hôpital Hautefeuille, Strasbourg, France
Jean Gugenheim, Service de Chirurgie Digestive, Hôpital L’Archet 2, Nice, France
Francois Durand, Service d’Hépatologie, AP-HP, Hôpital Beaujon, Clichy, France
Pierre-Henri Bernard, Service d’Hépatologie et de Gastroentérologie, Hôpital Pellegrin, Bordeaux, France
Olivier Boillot, Service de Chirurgie Digestive, Hôpital Edouard Herriot, Lyon, France
Philippe Compagnon, Service de Chirurgie Digestive, Hôpital Ponchaillou, Rennes, France
Yvon Calmus, Service de Chirurgie Digestive, AP-HP, Hôpital Cochin, Paris, France
Jean Hardwigsen, Service de Chirurgie Digestive, Hôpital la Conception, Marseille, France
Christian Ducerf, Service de Chirurgie Digestive, Hôpital de la Croix Rousse, Lyon, France
Georges Philippe Pageaux, Fédération Médico-Chirurgicale des Maladies de l’Appareil Digestif, Hôpital Saint-Eloi, Montpellier, France
Sébastien Dharancy, Service d’Hépatologie et de Gastroentérologie, Hôpital Claude Huriez, Lille, France
Olivier Chazouillères, Service d’Hépatologie, AP-HP, Hôpital St Antoine, Paris, France
Daniel Cherqui, Service de Chirurgie Générale et Digestive, AP-HP, Hopital Henri Mondor, Créteil, France
Correspondence to: Dr. Thomas Decaens, Service d’Hépatologie et de Gastroentérologie, Unité de Transplantation Hépatique, Hôpital Henri Mondor, 51 Ave. Maréchal de Lattre de Tassigny, Créteil 94010, France. thomasdecaens@9online.fr
Telephone: +33-1-49812353 Fax: +33-1-49812352
Received: April 21, 2006
Revised: April 28, 2006
Accepted: July 18, 2006
Published online: December 7, 2006
Abstract

AIM: To assess pre-orthotopic liver transplantation (OLT) factors that could be evaluated pre-operatively or controlled post-operatively associated with hepatocellular carcinoma (HCC) recurrence and disease-free survival after liver transplantation (LT).

METHODS: Four hundred and twelve patients transplanted for HCC between 1988 and 1998 in 14 French centers, who survived the postoperative period were studied. Kaplan Meier estimates were calculated for 24 variables potentially associated with recurrence of HCC. Uni- and multivariate analyses were conducted to identify independent predictors of recurrence.

RESULTS: Overall 5-year disease-free survival was 57.1%. By univariate analysis, variables associated with disease-free survival were: presence of cirrhosis (P = 0.001), etiology of liver disease (P = 0.03), α fetoprotein level (< 200, 200 to 2000, or > 2000; P < 0.0001), γ-GT activity (N, N to 2N or > 2N; P = 0.02), the number of nodules (1, 2-3 or ≥ 4; P = 0.02), maximal diameter of the largest nodule (< 3 cm, 3 to 5 cm or > 5 cm; P < 0.0001), the sum of the diameter of the nodules (< 3 cm, 3 to 5 cm, 5 to 10 cm or >10 cm; P < 0.0001), bi-lobar location (P = 0.01), preoperative portal thrombosis (P < 0.0001), peri-operative treatment of the tumor (P = 0.002) and chemoembolization (P = 0.03), tumor differentiation (P = 0.01), initial type of calcineurin inhibitor (P = 0.003), the use of antilymphocyte antibodies (P = 0.02), rejection episodes (P = 0.003) and period of LT (P < 0.0001). By multivariate analysis, 6 variables were independently associated with HCC recurrence: maximal diameter of the largest nodule (P < 0.0001), time of LT (P < 0.0001), tumor differentiation (P < 0.0001), use of anti-lymphocyte antibody (ATG) or anti-CD3 antibody (OKT3) (P = 0.005), preoperative portal thrombosis (P = 0.06) and the number of nodules (P = 0.06).

CONCLUSION: This study identifies immunosuppression, through the use of ATG or OKT3, as a predictive factor of tumor recurrence, and confirms the prognostic value of tumor differentiation.

Keywords: Immunosuppression; Hepatocellular carcinoma; Tumor differentiation; Liver transplantation