Artificial Liver Helps Acute Liver Failure Patients Stay Alive

A human liver-cell based system could provide support for patients with severe liver failure by processing toxins and synthesizing proteins and metabolites important to normal human liver function.

The Extracorporeal Liver Assist Device (ELAD) is intended to treat patients with acute liver failure (ALF), providing important metabolic support for the regeneration of a patient's native liver, or maintaining sufficient liver function until a transplant organ is available (bridge to transplant). The central components of the system are four cartridges containing 440 grams each of a proprietary immortalized human hepatocyte cell line (C3A). The system works by continuously separating plasma from cellular components via an ultrafiltrate generator; while the cellular components are returned to the patient via the venous access, the ultrafiltrate is circulated through the ELAD cartridges containing the C3A cells and 32,000 hollow fibers. The fibers, made of a semi-permeable membrane, permit passage--from the C3A cells to the patient's ultrafiltrate--of macromolecules and other cellular products such as albumin, Factor V, transferrin, antithrombin III, C3 complement, α1-antitrypsin, α-fetoprotein, and others. The fibers also simultaneously permit a counterflow of toxins and nutrients such as glucose and oxygen from the ultrafiltrate to the C3A cells. After circulating through the cartridges, the ultrafiltrate then flows through additional filters prior to recombining with the cellular components of the patient's blood and returning to the patient. This circulation is maintained continuously, utilizing the same set of cartridges for up to 12 days. The ELAD system is under development by Vital Therapies (VTI, San Diego, CA, USA), and is currently undergoing patient enrollment for a randomized, controlled, multi-center, Phase 2 clinical trial that will study the device under three different protocols.


"With the continuing shortage of donor livers for transplantation and the large number of patients unlisted for transplant, patients are dying who do not have access to a donor liver or a living donor transplant," said Terry Winters, Ph.D., chairman and CEO of VTI. "Our goal is to get ELAD to market as soon as possible so patients with ALF may have another treatment option."

Most liver disease is chronic, originating from diseases such as hepatitis, cirrhosis, and cancer. With the onset of liver disease, hepatocyte cells are injured or die. If the injury is mild, the cells may regenerate and the patient may recover to a normal liver. However, when the injury is sustained or more severe, loss of liver function, even when temporary or partial, can result in serious complications and the disruption of essential bodily functions due to metabolic instability such as energy supply, acid-base balance, and blood coagulation. If not treated effectively and promptly, patients often become comatose and experience uncontrolled bleeding and sepsis, contributing to multiple organ failure and death. The only current treatment option for liver failure is transplantation.

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