Acute-on-chronic liver failure: the liver and portal haemodynamics

Abstract

During acute-on-chronic liver failure (ACLF), the marked systemic inflammatory response and rapid deterioration in liver function are associated with a significant deterioration in organ perfusion and an appreciable rise in portal pressure. Indeed, the development of sepsis and multiorgan dysfunction that commonly follows presentation in these patients is intricately related to the severity of portal hypertension. It follows that understanding the drivers for rising portal pressure in ACLF will inform new therapies. As this review aims to highlight, there has been a paradigm shift in understanding of the drivers of portal hypertension, from a prior focus on splanchnic vasodilatation and therapies targeting portal inflow, toward appreciation of increasing intrahepatic resistance as the trigger for further vascular derangement, especially in the context of systemic inflammatory responses. By elaborating on those mechanisms that are especially perturbed by inflammatory responses, this article aims to show how this understanding has helped inform the identification of potential new targets for therapy in ACLF. Particular emphasis is given to agents with data supporting their progression toward clinical trials and those currently undergoing validation in clinical studies.