Animal models applied to acute-on-chronic liver failure: Are new models required to understand the human condition?

Abstract

The liver is a multifaceted organ; its location and detoxifying function expose this organ to countless injuries. Acute-on-chronic failure liver (ACLF) is a severe syndrome that affects the liver due to acute decompensation in patients with chronic liver disease. An infection environment, ascites, increased liver enzymes and prothrombin time, encephalopathy and fast-evolving multiorgan failure, leading to death, usually accompany this. The pathophysiology remains poorly understand. In this context, animal models become a very useful tool in this regard, as understanding; the disease may be helpful in developing novel therapeutic methodologies for ACLF. However, although animal models display several similarities to the human condition, they do not represent all ACLF manifestations, resulting in significant challenges. An initial liver cirrhosis framework followed by the induction of an acute decompensation by administering lipopolysaccharide and D-GaIN, potentiating liver damage supports the methodologies applied to induce experimental ACLF. The entire methodology has been described mostly for rats. Nevertheless, a quick PubMed database search indicates about 30 studies concerning ACFL models and over 1000 regarding acute liver failure models. These findings demonstrate the clear need to establish easily reproducible ACFL models to elucidate questions about this quickly established and often fatal syndrome.

Therapeutic potentials of mesenchymal stromal cells-derived extracellular vesicles in liver failure and marginal liver graft rehabilitation: a scoping review

“…Preclinical ACLF models typically include the first hit of chronic injury followed by a second hit of acute liver injury. For example, some authors described the ACLF model using CCl 4induced fibrosis followed by multiple injections of lipopolysaccharide (LPS)/D-GalN to trigger acute liver injury or even the combination of bile duct ligature for fibrosis with LPS to trigger acute liver injury 26 . In serum porcine, LPS/D-GalN mice ACLF models, intravenous administration of human umbilical cord-derived MSCs (UCMSCs) promoted liver repair, fibrosis resolution, and improved liver function 27 .…”

Gut Microbiota and Metabolomics Correlation in a Mouse Model of Acute-on-Chronic Liver Failure

“…In this study, based on the development of chronic liver injury induced by carbon tetrachloride (CCl 4 ) in mice, we constructed an ACLF mouse model by combining lipopolysaccharide (LPS) with D-Gal [10] . Subsequently, a comprehensive metabolomics approach utilizing liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-mass spectrometry (GC-MS) was employed to analyze the metabolites in ACLF mice.…”