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Original Research |

Albumin Dialysis With a Noncell Artificial Liver Support Device in Patients With Acute Liver Failure: A Randomized, Controlled Trial

Faouzi Saliba, MD; Christophe Camus, MD; François Durand, MD; Philippe Mathurin, MD, PhD; Alexia Letierce, PhD; Bertrand Delafosse, MD; Karl Barange, MD; Pierre François Perrigault, MD; Magali Belnard; Philippe Ichaï, MD; and Didier Samuel, MD, PhD
[+] Article and Author Information

From Assistance Publique–Hôpitaux de Paris Hôpital Paul Brousse, Centre Hépato-Biliaire, Villejuif; Université Paris-Sud and Institut National de la Santé et de la Recherche Médicale 785, Paris; Hôpital Pontchaillou, Centre Hospitalier Universitaire, Rennes; Assistance Publique–Hôpitaux de Paris Hôpital Beaujon, Clichy; Hôpital Claude Huriez, Centre Hospitalier Universitaire, Lille; Assistance Publique–Hôpitaux de Paris Unité de Recherche Clinique Paris-Sud, Hôpital Bicêtre, Kremlin-Bicêtre; Hôpital Edouard Herriot, Centre Hospitalier Universitaire, Lyon; Hôpital Purpan, Centre Hospitalier Universitaire, Toulouse; and Hôpital Saint-Eloi, Centre Hospitalier Universitaire, Montpellier, France.

Acknowledgment: The authors acknowledge the contributions of the Fulminant Molecular Adsorbent Recirculating System Investigators (Appendix). They thank C. Jourdain, A. Souag, and N. Best from the Department of Clinical Research, Assistance Publique–Hôpitaux de Paris; L. Becquemont, J. Tartiere, M. Debette-Gratien, and P. Opolon from the data and safety monitoring board committee; and S. Bremont and L. Becquemont from the Assistance Publique–Hôpitaux de Paris Unité de Recherche Clinique Paris-Sud, Hôpital Bicêtre.

Financial Support: By Assistance Publique–Hôpitaux de Paris.

Potential Conflicts of Interest: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M11-1163.

Reproducible Research Statement: Study protocol: Available from Dr. Saliba (e-mail, faouzi.saliba@pbr.aphp.fr). Statistical code and data set: Not available.

Requests for Single Reprints: Faouzi Saliba, MD, Hôpital Paul Brousse, Centre Hépato-Biliaire, 12 avenue Paul-Vaillant-Couturier, 94804 Villejuif, France; e-mail, faouzi.saliba@pbr.aphp.fr.

Current Author Addresses: Drs. Saliba, Ichaï, and Samuel: Hôpital Paul Brousse, Centre Hépato-Biliaire, 12 avenue Paul-Vaillant-Couturier, 94804 Villejuif, France.

Dr. Camus: Hôpital Pontchaillou, Centre Hospitalier Universitaire, 2 rue Henri-Le-Guilloux, 35033 Rennes Cedex 9, France.

Dr. Durand: Assistance Publique–Hôpitaux de Paris Hôpital Beaujon, 100 boulevard du Général Leclerc, 92118 Clichy, France.

Dr. Mathurin: Hôpital Claude Huriez, Centre Hospitalier Universitaire, 1 Place de Verdun, 59037 Lille, France.

Dr. Letierce and Ms. Belnard: Assistance Publique–Hôpitaux de Paris Unité de Recherche Clinique Paris-Sud, Hôpital Bicétre, 78 rue du Général Leclerc, 94275 Kremlin-Bicêtre, France.

Dr. Delafosse: Hôpital Edouard Herriot, Centre Hospitalier Universitaire, 5 Place d’Arsonval, 69437 Lyon, France.

Dr. Barange: Hôpital Purpan, Centre Hospitalier Universitaire, Place du Docteur Baylac, 31059 Toulouse Cedex 9, France.

Dr. Perrigault: Hôpital Saint-Eloi, Centre Hospitalier Universitaire, 80 rue A. Fliche, BP 74103-34091 Montpellier Cedex 5, France.

Author Contributions: Conception and design: F. Saliba, C. Camus, F. Durand, D. Samuel.

Analysis and interpretation of the data: F. Saliba, P. Mathurin, A. Letierce, D. Samuel.

Drafting of the article: F. Saliba, A. Letierce, P. Ichaï, D. Samuel.

Critical revision of the article for important intellectual content: F. Saliba, P. Mathurin, D. Samuel.

Final approval of the article: F. Saliba, C. Camus, F. Durand, P. Mathurin, A. Letierce, B. Delafosse, K. Barrange, P. Ichaï, D. Samuel.

Provision of study materials or patients: C. Camus, F. Durand, P. Mathurin, B. Delafosse, K. Barrange, P.F. Perrigault, M. Belnard, P. Ichaï, D. Samuel.

Statistical expertise: A. Letierce.

Obtaining of funding: F. Saliba, D. Samuel.

Administrative, technical, or logistic support: F. Saliba, P. Mathurin, M. Belnard, D. Samuel.

Collection and assembly of data: C. Camus, F. Durand, P. Mathurin, A. Letierce, M. Belnard, P. Ichaï.


Ann Intern Med. 2013;159(8): 522-531. doi:10.7326/0003-4819-159-8-201310150-00005
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Chinese translation

Background: Albumin dialysis with the Molecular Adsorbent Recirculating System (MARS) (Gambro, Lund, Sweden), a noncell artificial liver support device, may be beneficial in acute liver failure (ALF).

Objective: To determine whether MARS improves survival in ALF.

Design: Randomized, controlled trial. (ClinicalTrials.gov: NCT00224705)

Setting: 16 French liver transplantation centers.

Patients: 102 patients with ALF.

Intervention: Conventional treatment (n = 49) or MARS with conventional treatment (n = 53), stratified according to whether paracetamol caused ALF.

Measurements: 6-month survival and secondary end points, including adverse events.

Results: 102 patients (mean age, 40.4 years [SD, 13]) were in the modified intention-to-treat (mITT) population. The per-protocol analysis (49 conventional, 39 MARS) included patients with at least 1 session of MARS of 5 hours or more. Six-month survival was 75.5% (95% CI, 60.8% to 86.2%) with conventional treatment and 84.9% (CI, 71.9% to 92.8%) with MARS (P = 0.28) in the mITT population and 75.5% (CI, 60.8% to 86.2%) with conventional treatment and 82.9% (CI, 65.9% to 91.9%) with MARS (P = 0.50) in the per-protocol population. In patients with paracetamol-related ALF, the 6-month survival rate was 68.4% (CI, 43.5% to 86.4%) with conventional treatment and 85.0% (CI, 61.1% to 96.0%) with MARS (P = 0.46) in the mITT population. Sixty-six of 102 patients had transplantation (41.0% among paracetamol-induced ALF; 79.4% among non–paracetamol-induced ALF) (P < 0.001). Adverse events did not significantly differ between groups.

Limitation: The short delay from randomization to liver transplantation (median, 16.2 hours) precludes definitive efficacy or safety evaluations.

Conclusion: This randomized trial of MARS in patients with ALF was unable to provide definitive efficacy or safety conclusions because many patients had transplantation before administration of the intervention. Acute liver failure not caused by paracetamol was associated with greater 6-month patient survival.

Primary Funding Source: Assistance Publique–Hôpitaux de Paris.

Figures

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Figure 1.

The MARS dialysis machine.

The MARS (Gambro, Lund, Sweden) connected to a continuous renal replacement machine and to the patient with a double-lumen femoral vein catheter. Blood passes through a hollow-fiber, high-flux dialysis membrane (MARS FLUX) that is impermeable to albumin. The 500-mL albumin dialysate solution is regenerated online by passing through nonspecific adsorbents (an anion-exchange column and an uncoated charcoal column), which remove toxins bound to albumin. The system is connected to a conventional dialysis machine. MARS = Molecular Adsorbent Recirculating System.

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Figure 2.

Study flow diagram.

mITT = modified intention to treat; MARS = Molecular Adsorbent Recirculating System.

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Figure 3.

Cumulative probability of transplantation.

Log-rank test, P = 0.04. MARS = Molecular Adsorbent Recirculating System.

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Figure 4.

Primary end point: 6-month patient survival (intention-to-treat analysis).

Log-rank test, P = 0.28. MARS = Molecular Adsorbent Recirculating System.

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Appendix Figure.

Six-month patient survival according to whether paracetamol caused the acute liver failure (intention-to-treat analysis).

MARS = Molecular Adsorbent Recirculating System. Top. Log-rank test, P = 0.45. Bottom. Log-rank test, P = 0.46.

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