%0 Journal Article
%A Agarwal, Banwari
%A Bañares Cañizares, Rafael
%A Ibáñez Samaniego, Luis
%A Jalan, Rajiv
%T Randomized, controlled clinical trial of the DIALIVE liver dialysis device versus standard of care in patients with acute-on-chronic liver failure
%D 2023
%@ 0168-8278
%U https://hdl.handle.net/20.500.14352/97505
%X Background & Aims: Acute-on-chronic liver failure (ACLF) is characterized by severe systemic inflammation, multi-organ failureand high mortality rates. Its treatment is an urgent unmet need. DIALIVE is a novel liver dialysis device that aims to exchangedysfunctional albumin and remove damage- and pathogen-associated molecular patterns. This first-in-man randomizedcontrolledtrial was performed with the primary aim of assessing the safety of DIALIVE in patients with ACLF, with secondary aimsof 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 andend points were assessed at Day 10. Safety was assessed in all patients (n = 32). The secondary aims were assessed in a prespecifiedsubgroup 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-CACLF scores (p = 0.042) at Day 10. Time to resolution of ACLF was significantly faster in DIALIVE group (p = 0.036). Biomarkers ofsystemic inflammation such as IL-8 (p = 0.006), cell death [cytokeratin-18: M30 (p = 0.005) and M65 (p = 0.029)], endothelialfunction [asymmetric dimethylarginine (p = 0.002)] and, ligands for Toll-like receptor 4 (p = 0.030) and inflammasome (p = 0.002)improved significantly in the DIALIVE group.Conclusions: These data indicate that DIALIVE appears to be safe and impacts positively on prognostic scores and pathophysiologicallyrelevant biomarkers in patients with ACLF. Larger, adequately powered studies are warranted to further confirm itssafety and efficacy.Clinical trial number: NCT03065699.
%~