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.
Bibliographical noteFunding Information:
The study was financed by Vital Therapies, Inc., San Diego, CA.
Jan Stange own stocks in and consults for Vital Therapies and Albutec GmbH. She owns Ja Stange GmbH. Parvez Mantry advises and received contracts from Gilead, Intercept, Merck, and Bristol-Myers Squibb. He advises Salix and Abbvie. He received grants from Genfit. David Reich and Brian Borg received grants from Vital Therapies, and David Reich consults for Vital Therapies, Inc., San Diego, CA. David Wolf is on the speakers’ bureau for Abbvie, Gilead, Intercept, Merck, and Salix. Julie Thompson, Robert Brown, and Lance Stein consult for Vital Therapies. Ram Subramanian consults for and received grants from Vital Therapies. Lee Landeen, William Frank, Robert Ashley, Alyssa Henry, and Patricia Bedard owns stocks in Vital Therapies. Andrés Duarte-Rojo advises Gilead and recieved grants from Ocera. Michael Millis owns stocks in and consults for Vital Therapies. Lewis Teperman and Michael Millis are members of the Clinical Advisory Board of Vital Therapies, Inc., San Diego, CA. Rajiv Jalan advises and received grants from Ocera. He is on the speakers’ bureau of and received grants from Grifols and Sequana. Tarek Hassanein advises, is on the speakers’ bureau of, and recieved grants from Abbvie and Bristol-Myers Squibb. He advises and recieved contracts from Merck and Trek. He is on the speakers’ bureau and received grants from Gilead, Salix, and Janssen. He also received grants from Eaisi, Madrigal, Intercept, NGM, Obalon, Ocera, Sund-ise, Shire, TaiGen, Vital Therapies, Novartis, Boston Biomedical, Cymabay, and Genfit. Alyssa Henry, Patricia Bedard, Lee Landeen, Robert Ashley, William Frank, and Andrew Henry are employees of Vital Therapies, Inc., San Diego, CA.