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A phase II study of human allogeneic liver-derived progenitor cell therapy for acute-on-chronic liver failure and acute decompensation Nevens, Frederik Gustot, Thierry Lasser, Luc L. Haralampiev, Lyudmil E. Vargas Blasco, Victor Manuel Laterre, Pierre-François Institut Català de la Salut [Nevens F] Department of Gastroenterology and Hepatology, University Hospitals, KU Leuven, Belgium. [Gustot T] Department of Gastroenterology and Hepato-Pancreatology, C.U.B. Erasme Hospital, Université Libre de Bruxelles, Brussels, Belgium. [Laterre PF] Intensive Care Unit, Cliniques Universitaires Saint-Luc, UCLouvain, Brussels, Belgium. [Lasser LL] Gastroenterology Clinic, CHU Brugmann, Brussels, Belgium. Department of Hepatogastroenterology, CHU Brugmann, Brussels, Belgium. [Haralampiev LE] Department of Internal Diseases, Multiprofile Hospital for Active Treatment (MEDICA), Ruse, Bulgaria. [Vargas V] Unitat del Fetge, Vall d'Hebron Hospital Universitari, Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. CIBERehd, Barcelona, Spain Vall d'Hebron Barcelona Hospital Campus Insuficiència hepàtica - Tractament Cèl·lules mare - Ús terapèutic - Eficàcia Avaluació de resultats (Assistència sanitària) DISEASES::Digestive System Diseases::Liver Diseases::Hepatic Insufficiency::Liver Failure::Liver Failure, Acute::Acute-On-Chronic Liver Failure Other subheadings::Other subheadings::/therapy ANATOMY::Cells::Stem Cells DISEASES::Pathological Conditions, Signs and Symptoms::Pathologic Processes::Disease Attributes::Disease Progression ENFERMEDADES::enfermedades del sistema digestivo::enfermedades hepáticas::insuficiencia hepática::fracaso hepático::fracaso hepático agudo::insuficiencia hepática crónica agudizada Otros calificadores::Otros calificadores::/terapia ANATOMÍA::células::células madre ENFERMEDADES::afecciones patológicas, signos y síntomas::procesos patológicos::atributos de la enfermedad::progresión de la enfermedad Malaltia hepàtica alcohòlica; Cèl·lules mare; Medicina regenerativa del fetge Enfermedad hepática alcohólica; Células madre; Medicina regenerativa del higado Alcoholic liver disease; Stem cell; Liver regenerative medicine Background & Aims Human allogeneic liver-derived progenitor cells (HALPC, HepaStem®; Promethera Biosciences, Mont-Saint-Guibert, Belgium) are an advanced therapy medicinal product that could potentially alleviate systemic inflammation and ameliorate liver function in patients with acute-on-chronic liver failure (ACLF) or acute decompensation of cirrhosis (AD). Methods This open-label phase II study was conducted in 9 centres in Belgium, Spain, and Bulgaria between 2016 and 2019. The primary objective was to assess the safety of HALPC therapy up to Day 28 and the secondary objectives were to assess its safety and preliminary efficacy up to Month 3. Results The 24 treated patients (mean age: 51 years) were mostly male with an alcoholic cirrhosis. On pre-infusion Day 1, 15 patients had ACLF and 9 patients had AD. Two of the 3 initial patients treated with high HALPC doses (∼5×106 cells/kg body weight [BW]) had severe adverse bleeding events attributed to treatment. In 21 patients subsequently treated with lower HALPC doses (0.6 or 1.2×106 cells/kg BW, 1 or 2 times 7 days apart), no serious adverse events were related to treatment, and the other adverse events were in line with those expected in patients with ACLF and AD. Overall, markers of systemic inflammation and altered liver function decreased gradually for the surviving patients. The Day-28 and Month-3 survival rates were 83% (20/24) and 71% (17/24), and at Month 3, no patient had ACLF. Conclusions The treatment of patients with ACLF or AD with up to 2 doses of 1.2×106 HALPC/kg BW appeared safe. The results of this study support the initiation of a proof-of-concept study in a larger cohort of patients with ACLF to further confirm the safety and evaluate the efficacy of HALPC therapy. 2022-03-25T07:02:10Z 2022-03-25T07:02:10Z 2021-08 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Nevens F, Gustot T, Laterre PF, Lasser LL, Haralampiev LE, Vargas V, et al. A phase II study of human allogeneic liver-derived progenitor cell therapy for acute-on-chronic liver failure and acute decompensation. JHEP Reports. 2021 Aug;3(4):100291. 2589-5559 https://hdl.handle.net/11351/7263 10.1016/j.jhepr.2021.100291 34169246 000687283500019 http://hdl.handle.net/11351/7263 eng JHEP Reports;3(4) https://doi.org/10.1016/j.jhepr.2021.100291 Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/openAccess application/pdf application/pdf application/pdf application/pdf application/pdf Elsevier Scientia