A liver dialysis device has been demonstrated as safe and effective for treating severe liver failure in the first in-patient trial.
It is estimated that globally there are around 100 million people living with cirrhosis of the liver and 10 million who have cirrhosis plus an additional complication. Around three million of those individuals have acute-on-chronic liver failure (ACLF), a condition that can cause liver function to suddenly decline, placing individuals at high risk of short-term death, said researchers.
The UK sees around 15,000 ACLF patients each year whose treatment costs the NHS in the region of £100,000 per patient, "without improving their mortality risk", alerted the authors of a new study, published in the Journal of Hepatology. Characterised by severe systemic inflammation, multi-organ failure, and high mortality rates, the treatment of ACLF was an "urgent unmet need", they said.
Faster Reversal of ACLF
The DIALIVE device, invented by Institute for Liver and Digestive Health researchers at University College London (UCL), was designed to exchange dysfunctional albumin and remove damage- and pathogen-associated molecular patterns.
For the "first-in-human" randomised, controlled clinical trial of a novel liver dialysis device the researchers set out to assess its safety while treating ACLF patients, to observe its clinical effects, and check the device's performance on pathophysiologically relevant biomarkers.
A total of 32 patients with alcohol-related ACLF were recruited from eight European hospitals in six countries, between July 2017 and January 2020 – 17 were treated with the device, and 15 with current standard of care, for up to 5 days. Outcomes were recorded at days 10 and 28, with safety assessed in all 32 patients. The secondary aims were assessed in a pre-specified subgroup of 30 patients that had had at least three treatment sessions with the device.
Mean age of the patients was 49 years, and approximately 75% of patients were male. All had clinical, radiological, or histological evidence of underlying alcohol-related cirrhosis.
The researchers found that treatment with the device was safe and associated with "significantly faster" reversal of ACLF compared with standard of care – with a substantial reduction in endotoxins and improved albumin function, highlighted the authors.
"ACLF resolved in about twice the number of patients when compared with patients receiving standard of care," according to the authors, who noted that "clinical improvement was associated with significant impact on the mechanisms underlying the development of ACLF".
They added: "Despite receiving as little as 3 days' treatment, patients whose ACLF resolved remained in remission for 28 days afterwards."
Filling an 'Unmet' Treatment Need
Chief investigator Dr Banwari Agarwal, from UCL and London's Royal Free Hospital, said he felt "enormous pleasure" having witnessed the device's performance.
He remarked that the intervention had the potential to "transform" the care provided to an ever-increasing number of patients and their families who suffered from the effects of what was "essentially a terminal illness" for many.
"It has the potential to transform the therapeutic options available to clinicians across the world for patients with ACLF," he claimed.
The authors explained how kidney dialysis patients must undergo treatment for several hours each day in order to live. However, because of the liver's "regenerative qualities", they expected that liver dialysis would be able to provide longer term benefits after a short stint of treatment lasting several days.
UCL's Professor Rajiv Jalan, who invented DIALIVE, said that the results of the trial had gifted him an "emotional moment".
The next step was to conduct a larger trial with more patients to confirm the device's safety and effectiveness, the researchers pointed out. One of the additional metrics that would be assessed was the "impact on patient mortality" of the device versus standard of care, as in the current small study, treatment with the device did not reduce mortality.
If successful, the authors postulated that the device could be approved for clinical use within 3 years.
Professor Jalan hoped that soon "we will start to fulfil the urgent unmet need for treating acute-on-chronic liver failure and improve outcomes for patients".
Funding was provided by the European Union's Horizon 2020 research and innovation program. RJ is the inventor of OPA, which has been patented by UCL and licensed to Mallinckrodt Pharma. He is also the founder of Yaqrit Discovery (the company that holds the intellectual property for DIALIVE), a spin out company from University College London, Hepyx Ltd, and Cyberliver. He had research collaborations with Yaqrit Discovery. ND, PL, RPM, and DG are shareholders in Yagrit Discovery. CM is employed by Yagrit Discovery. KW is employed by MedInnovation. JS is the founder of Albutech GmBh. JM is employed by Fakkel. MS is employed by IBM. The rest of the authors declared no conflicts of interest.