Liver disease is a growing and lethal problem, with about 170K patients dying from liver failure each year in Europe alone. When a liver fails, toxins accumulate and the patient is increasingly susceptible to infection, multi-organ failure and early death. Liver transplantation is the only treatment known to prolong life but is limited by the availability of organs, and the financial cost of transplantation is high. Therefore there is a need for an effective ICU intervention for patients with advanced liver disease. The ALIVER Consortium has developed and optimised a novel ‘liver dialysis device”, called DIALIVE based upon discoveries that (i) albumin, a circulating protein involved in detoxification, is damaged irreversibly in these patients and (ii) endotoxemia (circulating toxins) contributes to increased risk of infection in liver failure. DIALIVE removes and replaces albumin and removes endotoxin. In animal models of liver failure, Dialive prolonged survival and was shown to be safe. It reduced endotoxemia and improved albumin and immune function.
The ALIVER Consortium, which comprises experts in liver failure, SMEs and charities, was created to test Dialive for the first time in humans. The ALIVER funding delivered a completed randomised controlled clinical trial in patients with acute on chronic liver failure (ACLF). The result of this trial was that DIALIVE met its primary endpoints and many secondary endpoints with statistical significance, an unexpectedly encouraging result. This means that DIALIVE has moved from TLR5 to TLR7/8 during the course of the ALIVER program.
Now that potential health benefits of DIALIVE have been identified, the groundwork has been laid for manufacturing, further trials, distribution and reimbursement. At the time of grant submission, it was considered that during the grant period a CE-mark would be obtainable. Since then, the rules on CE Marking have changed, leading to delays in the CE Marking process for all medical device companies, and it is now anticipated that a CE Mark will be secured after the end of the grant period. It is worth noting that during the grant period the only other innovative “liver dialysis system” in development (the US system called ELAD) was unsuccessful in clinical trials. This means that Dialive has established a substantial technical lead in extra-corporeal liver support. Additionally, the ALIVER Consortium have identified that DIALIVE could benefit a wider patient group. A patent has been filed.
