Therapeutic innovation

APACHE: Short-term survival of subjects with acute-on-chronic liver failure after plasma exchange with human serum albumin 5%

The issue

Patients with ACLF are at high risk of short-term mortality. The higher the number of organ failure, the lower the survival. Liver support systems were developed in the past to improve liver function allowing either the compensation of the patient or bridging him/her to liver transplantation. Bioartificial systems are no longer available and studies on albumin dialysis have not demonstrated that these systems improve survival in ACLF. On the contrary, high-volume plasma exchange improves transplant-free survival in patients with acute liver failure. A pilot study performed in the Hospital Clinic demonstrated that this treatment is safe in patients with ACLF.

The approach

The APACHE study is a phase III, multicenter, randomized, open-label trial in 380 patients with acute-on-chronic liver failure (ACLF) grade 1b, grade 2 or grade 3a aimed to determine whether plasma exchange with 5% albumin (from 4 to 9 plasma exchange sessions) improves 90-day survival in comparison with standard medical treatment. The study is being performed in 31 centers across Europe and North America.

The APACHE study is the largest randomized clinical trial evaluating a liver support system ever performed in patients with ACLF and is aimed to demonstrate that plasma exchange is able to improve 90-transplant-free survival in patient with 1 to 3 organ failures. Very severe patients (with 4 to 6 organ failures) are excluded from the study. If our hypothesis is confirmed, plasma exchange using 5% albumin as the main replacement fluid, will become the main liver support system to be used in patients with ACLF. This treatment would mainly act as a bridge for early liver transplantation in the most severe patients and for stabilization and standard liver transplantation in less severe patient. Plasma exchange is easy to perform and quite cheap in comparison to albumin dialysis systems. If the APACHE study is positive, we would have, for the first time, a liver support system capable to improve survival in these sick patients.

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