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RESEARCH PRODUCT

Hepassocin as a treatment for fulminant hepatic failure: will it translate from rats to human?

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Acute liver failure (ALF) is defined as the abrupt loss of hepatic cellular function in a patient without pre-existing liver disease, with the subsequent development of coagulopathy, jaundice and encephalopathy. It remains one of the most challenging medical emergencies, due to the multiorgan nature of the disease, the rapid evolution of the clinical condition and the need for multidisciplinary supportive interventions in order to assess the necessity for liver transplantation (LT) correctly.1 Despite different causes of ALF, the mode of cell death typically follows one of two patterns: necrosis or apoptosis; apoptosis is manifest by nuclear and cytoplasmic shrinkage without disturbance of cell membrane integrity or liberation of intracellular content. Consequently, secondary inflammation is not a feature. Necrosis involves depletion of ATP with resultant cell swelling and lysis, leading to release of cellular content and secondary inflammation. However, there is increasing evidence that they are alternative outcomes of the same initiating factors and signalling pathways, a process known as necroapoptosis.2 The main mechanism of liver cell death in ALF is the activation of cell membrane receptors. The cytokine, tumour necrosis factor α (TNFα), and the Fas ligand mediate hepatocellular death through interaction with structurally related cell membrane receptors. In addition to TNFα, other proinflammatory and anti-inflammatory cytokines may have a role in the pathogenesis of acute liver injury of various aetiologies, both experimentally and clinically. Although all the factors responsible for regeneration in the setting of such severe liver cell loss remain incompletely understood, it has been shown …