The importance of intestinal endotoxins in liver disease

The development and wider use of the Limulus amoebocyte lysate assay (LAL) for the detection of endotoxin, has led to renewed interest in the link between gut-derived endotoxin, liver injury and the extra-hepatic manifestations of clinical liver disease. The concept that endotoxemia may occur and be harmful in clinical states without the concomitant presence of Gram-negative bacteria is a relatively recent one and has been most intensively studied in the context of liver injury. Since the liver stands between the gut and the systemic circulation, it has been postulated that failure to detoxify endotoxins absorbed into the portal circulation after hepatic injury might lead to further liver damage and escape of this toxic material into the general circulation. The present review will update the status of this hypothesis, discuss mechanisms proposed for the damage and present evidence for the association in animal models. Finally, studies both positive and negative, will be cited that have used the LAL to detect endotoxemia and its consequences in human liver disease.