Liver transplantation in acute liver failure: Dilemmas and challenges

Acute liver failure (ALF) refers to a state of severe hepatic injury that leads to altered coagulation and sensorium in the absence of pre-existing liver disease. ALF has different causes, but the clinical characteristics are strikingly similar. In clinical practice, however, inconsistency in the definition of ALF worldwide and confusion regarding the existence of pre-existing liver disease raise diagnostic dilemmas. ALF mortality rates used to be over 80% in the past; however, survival rates on medical treatment have significantly improved in recent years due to a greater understanding of pathophysiology and advances in critical care management. The survival rates in acetaminophen-associated ALF have become close to the post-transplant survival rates. Given that liver transplantation (LT) is an expensive treatment that involves a major surgical operation in critically ill patients and lifelong immunosuppression, it is very important to select accurate patients who may benefit from it. Still, emergency LT remains a lifesaving procedure for many ALF patients. However, there is a lack of consistency in current prognostic models that hampers the selection of transplant candidates in a timely and precise manner. The other problems associated with LT in ALF are the shortage of graft, development of contraindications on the waiting list, vaguely defined delisting criteria, time constraints for pre-transplant evaluation, ethical concerns, and comparatively poor post-transplant outcomes in ALF. Therefore, there is a desperate need to establish accurate prognostic models and explore the roles of evolving adjunctive and alternative therapies, such as liver support systems, plasma exchange, stem cells, auxiliary LT, and so on, to enhance transplant-free survival and to fill the void created by the graft shortage.