Liver pathophysiology

ALADDIN: Pathogenesis of acute-on-chronic liver failure and mechanisms of action of plasma exchange with human serum albumin 5% in decompensated cirrhotic subjects with systemic inflammation and acute-on-chronic liver failure

The issue

Several studies indicate that systemic inflammation plays a causal role in the development of ACLF. In parallel, important progresses have been made in the characterization of albumin pleiotropic properties (i.e. oncotic, antioxidative, anti-inflammatory) to propose that albumin can ameliorate systemic inflammation in patients with high risk of developing ACLF.

The approach

The ALADDIN study is a translational research project currently being performed in European centers participating in the APACHE trial, a phase III, multicenter, randomized, open-label trial involving intensive care units with expertise in the management of critically ill cirrhotic patients. The ALADDIN study is an agnostic investigation aimed to assess the mechanisms of systemic inflammation and acute-on-chronic liver failure (ACLF) in a large series of patients with and without ACLF. Protein expression, kinomic and genotyping will be determined using high-throughput molecular biology techniques in patients with ACLF from the APACHE study. Since patients included in the APACHE study will be investigated before, during and after treatment, the study will also assess the mechanism of action of plasma exchange and predictors of response in patients with ACLF.

The ALADDIN study is a unique investigation that could prove for the first time that plasma exchange using human serum albumin as the main replacement fluid can be effective and safe in the treatment of patients with decompensated cirrhosis with systemic inflammation and ACLF.