Immediate Listing for Liver Transplantation Versus Standard Care for Child–Pugh Stage B Alcoholic Cirrhosis

A Randomized Trial

  1. Claire Vanlemmens, MD;
  2. Vincent Di Martino, MD, PhD;
  3. Chantal Milan, PhD;
  4. Michel Messner, MD;
  5. Anne Minello, MD, PhD;
  6. Christophe Duvoux, MD, PhD;
  7. Thierry Poynard, MD, PhD;
  8. Jean-Marc Perarnau, MD;
  9. Marie-Anne Astrid Piquet, MD, PhD;
  10. Georges-Philippe Pageaux, MD, PhD;
  11. Sébastien Dharancy, MD;
  12. Christine Silvain, MD;
  13. Sophie Hillaire, MD, PhD;
  14. Gérard Thiefin, MD;
  15. Jean-Pierre Vinel, MD;
  16. Patrick Hillon, MD;
  17. Estelle Collin, MSc;
  18. Georges Mantion, MD;
  19. Jean-Philippe Miguet, MD; and
  20. the TRANSCIAL Study Group*
  1. From Centre Hosptialier Universitaire (CHU) Jean Minjoz, Besançon; Centre d'Epidémiologie de Population 106 and CHU du Bocage, Dijon; CHU de Pontchaillou, Rennes; CHU Henri Mondor, Créteil; CHU Pitié-Salpêtrière, Paris; Centre Hospitalier Régional Bon Secours, Metz; CHU de Caen, Caen, France; CHU Saint-Eloi, Montpellier; Centre Hospitalier Régional Universitaire Claude Huriez, Lille; CHU Jean Bernard, Poitiers; CHU Beaujon, Clichy; CHU Robert Debré, Reims; and CHU Purpan, Toulouse, France.

    Abstract

    Background: Liver transplantation improves survival of patients with end-stage (Child–Pugh stage C) alcoholic cirrhosis, but its benefit for patients with stage B disease is uncertain.

    Objective: To compare the outcomes of patients with Child–Pugh stage B alcoholic cirrhosis who are immediately listed for liver transplantation with those of patients assigned to standard treatment with delay of transplantation until progression to stage C disease.

    Design: Randomized, controlled trial.

    Setting: 13 liver transplantation programs in France.

    Patients: 120 patients with Child–Pugh stage B alcoholic cirrhosis and no viral hepatitis, cancer, or contraindication to transplantation.

    Interventions: Patients were randomly assigned to immediate listing for liver transplantation (60 patients) or standard care (60 patients).

    Measurements: Overall and cancer-free survival over 5 years.

    Results: Sixty-eight percent of patients assigned to immediate listing for liver transplantation and 25% of those assigned to standard care received a liver transplant. All-cause death and cirrhosis-related death did not statistically differ between the 2 groups: 5-year survival was 58% (95% CI, 43% to 70%) for those assigned to immediate listing versus 69% (CI, 54% to 80%) for those assigned to standard care. In multivariate analysis, independent predictors of long-term survival were absence of ongoing alcohol consumption (hazard ratio, 7.604 [CI, 2.395 to 24.154]), recovery from Child–Pugh stage C (hazard ratio, 7.633 [CI, 2.392 to 24.390]), and baseline Child–Pugh score less than 8 (hazard ratio, 2.664 [CI, 1.052 to 6.746]). Immediate listing for transplantation was associated with an increased risk for extrahepatic cancer: The 5-year cancer-free survival rate was 63% (CI, 43% to 77%) for patients who were immediately listed and 94% (CI, 81% to 98%) for those who received standard care.

    Limitation: Restriction of the study sample to alcoholic patients may limit the generalizability of results to other settings.

    Conclusion: Immediate listing for liver transplantation did not show a survival benefit compared with standard care for Child–Pugh stage B alcoholic cirrhosis. In addition, immediate listing for transplantation increased the risk for extrahepatic cancer.

    Funding: The French National Program for Clinical Research.

    Article and Author Information

    • Note: Drs. Vanlemmens and Di Martino contributed equally to this work.

    • Grant Support: By the French National Program for Clinical Research.

    • Potential Financial Conflicts of Interest: None disclosed.

    • Reproducible Research Statement: Study protocol: Available at http://www.clinicaltrials.gov (NCT00701792). Statistical code and data set: Not available.

    • Requests for Single Reprints: Vincent Di Martino, MD, PhD, Service d'hépatologie, CHU Jean Minjoz, 3 Boulevard A. Fleming, 25030 Besançon, France; e-mail, vdimartino{at}chu-besancon.fr.

    • Current Author Addresses: Drs. Vanlemmens, Di Martino, Mantion, and Miguet and Ms. Collin: Service d'hépatologie, CHU Jean Minjoz, 3 Boulevard A. Fleming, 25030 Besançon, France.

    • Dr. Milan: EPI INSERM 0106, Centre d'Epidémiologie de Population, Faculté de Médecine BP 87900, 21079 Dijon, France.

    • Dr. Messner: Hôpital Pontchaillou, 2 rue Henri Le Guilloux, 35033 Rennes Cedex 9, France.

    • Drs. Minello and Hillon: CHU Le Bocage, BP 1542, 21000 Dijon Cedex, France.

    • Dr. Duvoux: Hôpital Henri Mondor, 51 Avenue de Lattre de Tassigny, 94010 Créteil, France.

    • Dr. Poynard: Hôpital Pitié-Salpêtrière, 47-83 Boulevard de l'hôpital, 75013 Paris, France.

    • Dr. Perarnau: CHR Metz—Hôpital Bon Secours, 1 Place Philippe De Vigneulles, 57038 Metz Cedex 1, France.

    • Dr. Piquet: CHRU de Caen, 14033 Caen Cedex 9, France.

    • Dr. Pageaux: Hôpital Saint-Eloi, 2 Avenue Bertin Sans, 34295 Montpellier, France.

    • Dr. Dharancy: CHU Claude Huriez, 59037 Lille, France.

    • Dr. Silvain: CHU Hôpital Jean Bernard, 2 Rue de la Miletrie, 86000 Poitiers, France.

    • Dr. Hillaire: Hôpital Beaujon, 100 Boulevard Général Leclerc, 92110 Clichy Cedex, France.

    • Dr. Thiefin: Hôpital Robert Debré, Avenue du Général Koenig, 51092 Reims, France.

    • Dr. Vienel: Hôpital Purpan, Place du Docteur Baylac, 31059 Toulouse Cedex 9, France.

    • Author Contributions: Conception and design: C. Vanlemmens, G. Mantion, J.P. Miguet.

    • Analysis and interpretation of the data: V. Di Martino, C. Milan, E. Collin.

    • Drafting of the article: V. Di Martino, J.P. Miguet.

    • Critical revision of the article for important intellectual content: C. Milan, A. Minello, T. Poynard, J.M. Perarnau, G.P. Pageaux, S. Dharancy, C. Silvain, G. Thiefin, J.P. Vinel, G. Mantion, J.P. Miguet.

    • Final approval of the article: C. Vanlemmens, V. Di Martino, C. Milan, M. Messner, A. Minello, C. Duvoux, T. Poynard, J.M. Perarnau, M.A. Piquet, G.P. Pageaux, S. Dharancy, C. Silvain, S. Hillaire, G. Thiefin, J.P. Vinel, P. Hillon, G. Mantion, J.P. Miguet.

    • Provision of study materials or patients: C. Vanlemmens, V. Di Martino, M. Messner, A. Minello, C. Duvoux, T. Poynard, J.M. Perarnau, M.A. Piquet, G.P. Pageaux, S. Dharancy, C. Silvain, S. Hillaire, G. Thiefin, J.P. Vinel, P. Hillon, G. Mantion, J.P. Miguet.

    • Statistical expertise: V. Di Martino, C. Milan.

    • Obtaining of funding: J.P. Miguet.

    • Administrative, technical, or logistic support: C. Vanlemmens, E. Collin.

    • Collection and assembly of data: C. Milan, E. Collin.

    • ClinicalTrials.gov registration number: NCT00701792.

    • ↵* For a list of the members of the TRANSCIAL (TRANSplantation for CIrrhosis related to ALcohol consumption) Study Group, see the Appendix.

    Summary for Patients

    • Summaries for Patients:Immediate Versus Later Listing for Liver Transplantation for Alcoholic Cirrhosis Ann Intern Med February 3, 2009 150:I-18; doi:10.1059/0003-4819-150-3-200902030-00001
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    1. Ann Intern Med February 3, 2009 vol. 150 no. 3 153-161
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