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

VTI-208 Study Group, Julie Thompson, Natasha Jones, Ali Al-Khafaji, Shahid Malik, David Reich, Santiago Munoz, Ross MacNicholas, Tarek Hassanein, Lewis Teperman, Lance Stein, Andrés Duarte-Rojo, Raza Malik, Talal Adhami, Sumeet Asrani, Nikunj Shah, Paul Gaglio, Anupama Duddempudi, Brian Borg, Rajiv JalanRobert 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, Alyssa Henry, Patricia Bedard, Lee Landeen, Michael Millis, Robert Ashley, William Frank, Andrew Henry, Jan Stange, Ram Subramanian

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Abstract

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.

Original languageEnglish
Pages (from-to)380-393
Number of pages14
JournalLiver Transplantation
Volume24
Issue number3
DOIs
Publication statusPublished - Mar 2018
Externally publishedYes

Bibliographical note

This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

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  • Cite this

    VTI-208 Study Group, Thompson, J., Jones, N., Al-Khafaji, A., Malik, S., Reich, D., Munoz, S., MacNicholas, R., Hassanein, T., Teperman, L., Stein, L., Duarte-Rojo, A., Malik, R., Adhami, T., Asrani, S., Shah, N., Gaglio, P., Duddempudi, A., Borg, B., ... Subramanian, R. (2018). Extracorporeal cellular therapy (ELAD) in severe alcoholic hepatitis: A multinational, prospective, controlled, randomized trial. Liver Transplantation, 24(3), 380-393. https://doi.org/10.1002/lt.24986