Acute liver failure: from bench to bedside

Acute liver failure constitutes a challenge to clinicians and scientists alike. The course of the disease, usually unpredictable and polarizing, is associated with a high mortality unless liver transplantation is feasible, but can end in a spontaneous restitution. It poses many scientific questions regarding the mechanisms of liver cell damage and regeneration and the possibility of new therapeutic approaches. However, the performance of clinical studies in patients in acute liver failure presents problems because of the varied etiology, the small number of cases, and furthermore due to ethical and logistical difficulties. For this reason experimental investigations have gained a special importance. Arising from the improved understanding of the mechanisms of liver cell damage in acute liver failure, which may be primarily due not to the initial noxious agent alone but may also be triggered secondarily by the release of proinflammatory mediators, there are numerous options for liver cell protection, some of which have already proved successful in experimental studies. New insights into the mechanisms of regulation of liver regeneration and the physiological liver mass, gathered in particular from experimental models of partial hepatectomy and by the use of gene-manipulated animals, have contributed to the development of new therapeutic approaches for the stimulation of liver cell regeneration. Temporary liver support systems have already been successfully employed in some cases under clinical conditions. Although the systematic experimental investigation of many of the questions of acute liver failure has significantly contributed to a better understanding of liver cell damage and regeneration, the application of this new knowledge to clinical practice is to some extent made difficult by the artificial simplification that experimental studies inevitably entail and needs to be validated by controlled clinical studies.