Liver failure could be resolved by liver dialysis device
A clinical trial using DIALIVE, a liver dialysis device, to treat patients with liver failure demonstrated “significant improvements”, according to new research.
Acute-on-chronic liver failure (ACLF) occurs in 30% of hospitalised cirrhosis patients, and reportedly leads to over one million deaths worldwide each year.
ACLF is characterised clinically by multi-organ failure and high risk of short-term mortality, and pathophysiologically by the presence of systemic inflammation. The worldwide reported mortality rate according to the EASL-CLIF Consortium definition is between 30% and 50% at 28 days from presentation.
Currently the only potential treatment for this condition is liver transplantation, which is available to very few patients.
A first-in-human randomised controlled clinical trial using DIALIVE, a novel liver dialysis device, demonstrated its potential as a disease-modifying therapy. It resolved liver failure “significantly faster and in a greater proportion of patients compared with controls”, according to a study published in the Journal of Hepatology.
Treatment of ACLF patients resulted in improvements in all the main underlying pathophysiological mechanisms of ACLF.
“DIALIVE is a novel liver dialysis device invented at University College London (UCL) by Dr Nathan Davies and me,” explained study investigator Rajiv Jalan, PhD, UCL Institute for Liver & Digestive Health, based at the Royal Free Hospital, London, and European Foundation for the Study of Chronic Liver Failure (EF Clif), Barcelona.
“It is based on an understanding of the mechanisms underlying ACLF, which are what we are correcting with this machine by exchanging dysfunctional albumin and removing damage- and pathogen-associated molecular patterns.
“Two previous preclinical trials showed that this device saved the lives of animals with liver failure. These data were used to apply for an EU grant to conduct this clinical trial.”
In the multicentre, randomised clinical trial investigators evaluated 32 alcoholic cirrhosis patients with ACLF who were treated with either DIALIVE or standard care for up to five days. End points were assessed at Day 10.
The primary aim was to evaluate DIALIVE’s safety in acute ACLF patients, while secondary aims were to assess clinical effects, device performance and effect on pathophysiologically relevant biomarkers. Safety was assessed in all patients. The secondary aims were assessed in a pre-specified subgroup of 30 patients who had at least three treatment sessions with DIALIVE.
The study, which involved multiple centres across Europe, was led by clinical investigator Banwari Agarwal, MBBS, MD, consultant in liver ICU at the Royal Free Hospital.
The study concluded that the DIALIVE system is safe. In addition, patients experienced significant improvements in all the main underlying pathophysiological mechanisms of ACLF. This included improvement in albumin function, reduction in products of cell death and endotoxin, restoration of endothelial function and cell signalling.
Although the study was not powered for efficacy, it showed that the proportion of patients in which ACLF was resolved was greater with DIALIVE, and the time to resolution of ACLF was significantly reduced. It did not, however, reduce mortality. Larger clinical trials are needed to test DIALIVE’s efficacy and establish its safety.
“This is the first treatment that has shown such a rapid clinical effect in patients with ACLF,” said co-lead investigator Steffen Mitzner, MD, PhD, Fraunhofer IZI and Department of Medicine II, Division of Gastroenterology and Endocrinology, Rostock University Medical Center, Rostock, Germany.
“The patients that resolved ACLF remained free of ACLF for 28 days despite only being treated with the device for three days. The improvement in biomarkers underlying the pathophysiology of ACLF was sustained even five days after stopping therapy.”
“These data indicate that DIALIVE may be a disease-modifying therapy for ACLF patients and could impact the outcome of patients with ACLF, for which there is no available therapy except liver transplantation available to a very small minority of these patients,” Jalan concluded.
“The potential impact is huge if these data can be confirmed in larger clinical trials.”
“The positive results from this trial are great news for ACLF patients, and we are now preparing for a larger clinical trial,” added Carrie Morgan, Vice President, Clinical Operations, Yaqrit Discovery Ltd — a UCL spin-off company located in London, and producer of DIALIVE.
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