Liver support systems and liver transplantation in acute liver failure

Abstract

Acute liver failure (ALF) results in a multitude of complications that result in multi-organ failure. This review focuses on the pathophysiological processes and how to manage with these with artificial liver support and liver transplantation (LT). The pathophysiological sequence of events behind clinical deterioration in ALF comes down to two profound consequences of the failing liver. The first is the development of hyperammonemia, as the liver can no longer synthesize urea. The result is that the splanchnic system instead of removing ammonia becomes an ammonia-producing organ system that causes hepatic encephalopathy (HE) and cerebral oedema. The second complication is caused by the necrotic liver cells that release large molecules that originate from degrading proteins, that is damage associated molecular patterns (DAMPs) which causes inflammatory activation of intrahepatic macrophages and an overflow of DAMPs molecules into the systemic circulation resulting in a clinical picture that resembles septic shock. In this context the combined use of continuous renal replacement therapy (CRRT) and plasma exchange are rational and simple ways to remove ammonia and DAMPS molecules. This combination improve survival for ALF patients deemed not appropriate for LT, despite poor prognostic criteria, but also ensure a better stability of vital organs while awaiting LT. The combination of CRRT with albumin dialysis tends to have a similar effect. Currently, the selection criteria for LT for non-paracetamol cases appear robust while the criteria for paracetamol-intoxicated patients have become more unreliable and now consist of more dynamic prognostic systems. For patients that need LT for survival, a tremendous improvement in the post-LT results has been achieved during the last decade with a survival that now reach merely 90% which is mirroring the results seen after LT for chronic liver disease.

Keywords: acute liver failure; albumin dialysis; ammonia; hepatic encephalopathy; liver support; liver transplantation; plasma exchange.

FIGURE 1

Liver damage result in release of ammonia (NH3) and DAMPs molecules from the failing liver into the systemic circulation which causes hepatic encephalopathy (HE), cerebral swelling and systemic inflammatory response syndrome (SIRS) with a subsequent development of multiorgan failure (MOF). High‐volume plasmapheresis (HVP) removes DAMPs, NH3 and glutamine (Gln) from the systemic circulation and turn the innate immune system towards an anti‐inflammation direction which may allow liver regeneration. Continuous renal replacement therapy (CRRT) will further decrease the circulating concentrations of NH3 and Gln (and perhaps some cytokines).

FIGURE 2

Patient survival at 10 years after liver transplantation according to primary disease. Data from the European Liver Transplant Registry considering of patients transplanted during the last 15 years. (From http://www.eltr.org).

FIGURE 3

Patient survival at 5 years after liver transplantation among adult deceased donor liver transplant recipients, 2014–2016, by diagnosis. From the OPTN/SRTR US registry (OPTN/SRTR 2021 annual report).