About this item:

265 Views | 156 Downloads

Author Notes:

Jan Stange, M.D., Center for Internal Medicine, University of Rostock, E‐Heydemann Strasse 06, Rostock 18055, Germany. E‐mail: E-mail address:jan.stange@med.uni-rostock.de

This article was written by Julie Thompson, Ram Subramanian, and Jan Stange.

Major contributions were provided by Ali Al‐Khafaji, Shahid Malik, David Reich, Santiago Munoz, Ross MacNicholas, Tarek Hassanein, Lewis Teperman, and Natasha Jones.

Major subject recruitment and additional contributions were provided by Lance Stein, Andrés Duarte‐Rojo, Raza Malik, Talal Adhami, Sumeet Asrani, Nikunj Shah, Paul Gaglio, Anupama Duddempudi, Brian Borg, Rajiv Jalan, Robert Brown, Heather Patton, Rohit Satoskar, Simona Rossi, Amay Parikh, Ahmed ElSharkawy, Parvez Mantry, Linda Sher, David Wolf, Marquis Hart, Charles Landis, Alan Wigg, Shahid Habib, Geoffrey McCaughan, Steven Colquhoun, and the VTI‐208 Study Group.

The statistical analysis was carried out according to a prespecified statistical plan, submitted to the FDA before the end of the study by Sara Rhee from Synteract, Inc. Carlsbad, CA.

The article was also reviewed and edited by Michael Millis, Robert Ashley, William Frank, and Andrew Henry, who were all material in the operational aspects of the study.

Clinical trial number: NCT01471028

See publication for full list of disclosures.

Subjects:

Research Funding:

The study was financed by Vital Therapies, Inc., San Diego, CA.

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Gastroenterology & Hepatology
  • Surgery
  • Transplantation
  • LIVER-DISEASE
  • CLINICAL-TRIALS
  • C3A CELLS
  • TRANSPLANTATION
  • PENTOXIFYLLINE
  • PREDNISOLONE
  • MORTALITY
  • STRATEGY
  • FAILURE

Extracorporeal cellular therapy (ELAD) in severe alcoholic hepatitis: A multinational, prospective, controlled, randomized trial

Show all authors Show less authors

Tools:

Journal Title:

Liver Transplantation

Volume:

Volume 24, Number 3

Publisher:

, Pages 380-393

Type of Work:

Article | Final Publisher PDF

Abstract:

Liver Transplantation published by Wiley Periodicals, Inc. on behalf of American Association for the Study of Liver Diseases. Severe alcoholic hepatitis (sAH) is associated with a poor prognosis. There is no proven effective treatment for sAH, which is why early transplantation has been increasingly discussed. Hepatoblastoma-derived C3A cells express anti-inflammatory proteins and growth factors and were tested in an extracorporeal cellular therapy (ELAD) study to establish their effect on survival for subjects with sAH. Adults with sAH, bilirubin ≥8 mg/dL, Maddrey's discriminant function ≥ 32, and Model for End-Stage Liver Disease (MELD) score ≤ 35 were randomized to receive standard of care (SOC) only or 3-5 days of continuous ELAD treatment plus SOC. After a minimum follow-up of 91 days, overall survival (OS) was assessed by using a Kaplan-Meier survival analysis. A total of 203 subjects were enrolled (96 ELAD and 107 SOC) at 40 sites worldwide. Comparison of baseline characteristics showed no significant differences between groups and within subgroups. There was no significant difference in serious adverse events between the 2 groups. In an analysis of the intent-to-treat population, there was no difference in OS (51.0% versus 49.5%). The study failed its primary and secondary end point in a population with sAH and with a MELD ranging from 18 to 35 and no upper age limit. In the prespecified analysis of subjects with MELD < 28 (n = 120), ELAD was associated with a trend toward higher OS at 91 days (68.6% versus 53.6%; P =.08). Regression analysis identified high creatinine and international normalized ratio, but not bilirubin, as the MELD components predicting negative outcomes with ELAD. A new trial investigating a potential benefit of ELAD in younger subjects with sufficient renal function and less severe coagulopathy has been initiated. Liver Transplantation 24 380–393 2018 AASLD.

Copyright information:

© 2017 The Authors.

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/).

Creative Commons License

Export to EndNote