Randomized, controlled clinical trial of the DIALIVE liver dialysis device versus standard of care in patients with acute-on- chronic liver failure

作者：Banwari Agarwal, Rafael Bañares, Faouzi Saliba, María Pilar Ballester, Dana Tomescu, Daniel Martín, Vanessa Stadlbauer, Gavin Wright, Mohammed Sheikh, Carrie Morgan, Carlos Alzola, Phillip Lavin, Daniel Green, Rahul Kumar, Sophie‐Caroline Sacleux, Gernot Schilcher, Sebastian Koball, Andrada Tudor, J. Minten, Gema Doménech, Juan Jose Aragones, Karl Oettl, Margret Paar, Katja Waterstradt, Stefanie M. Bode‐Böger, Luis Ibáñez, Amir Gander, Carolina Sesmero Ramos, Alexandru Chivu, Jan Stange, Georg Lamprecht, Moises Sanchez, Rajeshwar P. Mookerjee, Andrew Davenport, Nathan Davies, Marco Pavesi, Fausto Andreola, Agustı́n Albillos, Jeremy Cordingley, Hartmut Schmidt, Juan Antonio Carbonell‐Asins, Vicente Arroyo, Javier Fernández, Steffen Mitzner, Rajiv Jalan · 发表于：Journal of Hepatology · 年份：2023 · DOI：10.1016/j.jhep.2023.03.013 · 被引用次数：76 · 研究领域：Liver Disease and Transplantation、Acute Kidney Injury Research、Clinical Nutrition and Gastroenterology

BACKGROUND & AIMS: Acute-on-chronic liver failure (ACLF) is characterized by severe systemic inflammation, multi-organ failure and high mortality rates. Its treatment is an urgent unmet need. DIALIVE is a novel liver dialysis device that aims to exchange dysfunctional albumin and remove damage- and pathogen-associated molecular patterns. This first-in-man randomized-controlled trial was performed with the primary aim of assessing the safety of DIALIVE in patients with ACLF, with secondary aims of evaluating its clinical effects, device performance and effect on pathophysiologically relevant biomarkers. METHODS: Thirty-two patients with alcohol-related ACLF were included. Patients were treated with DIALIVE for up to 5 days and end points were assessed at Day 10. Safety was assessed in all patients (n = 32). The secondary aims were assessed in a pre-specified subgroup that had at least three treatment sessions with DIALIVE (n = 30). RESULTS: There were no significant differences in 28-day mortality or occurrence of serious adverse events between the groups. Significant reduction in the severity of endotoxemia and improvement in albumin function was observed in the DIALIVE group, which translated into a significant reduction in the CLIF-C (Chronic Liver Failure consortium) organ failure (p = 0.018) and CLIF-C ACLF scores (p = 0.042) at Day 10. Time to resolution of ACLF was significantly faster in DIALIVE group (p = 0.036). Biomarkers of systemic inflammation such as IL-8 (p = 0...