Experimental Models of Acute Liver Failure in Mice: From Pathogenesis and Inflammatory Cascades to the Role of...

Acute liver failure (ALF) is a severe pathological condition with high mortality, arising from diverse etiologies and involving multiple pathogenetic mechanisms. ALF is often accompanied by multi-organ failure due to infectious complications. Because of disease's rapid progression, clinical studies of ALF remain limited, making the search for novel therapeutic strategies targeting specific molecular pathways and biochemical cascades a pressing task. Preclinical in vivo models are unique tools for reproducing individual aspects of ALF development. However, there is still no consensus on the gold-standard experimental animal model that fully captures ALF pathogenesis. This review systematically categorizes existing mouse models of ALF, outlining their advantages and with respect to the translational applicability of the data obtained. Among these models, we highlight the LPS/D-GalN model as the most reliable in reproducing key stages of ALF development complicated by bacterial infection. Using this model as an example, we describe the known stages of pathogenesis, supported by the experiments with pharmacologically active substances and the use of various genetically modified mouse lines. Finally, special attention is given to the intestine as an organ that sustains significant damage during ALF progression in both clinical cases and most animal models.