The role of endotoxin in liver injury.

Evidence is present that a common pathway for hepatic injury by a variety of agents may result from impairment of the liver's ability to detoxify bacterial endotoxins from the gastrointestinal tract. Many factors may structurally, metabolically, or hormonally alter the normal liver's ability to render innocuous the small amounts of lipopolysaccharide ordinarily presented to it. This impairment may accentuate existing hepatic damage by allowing toxic levels of endotoxin to develop in the liver tissue, and by allowing endotoxin entry into the systemic circulation, may also lead to extrahepatic effects. Studies are cited that: (1) support a role for intraintestinal endotoxin in the development of experimental cirrhosis. (2) demonstrate how liver injury alters endotoxin detoxification, (3) examine the role of intestinal production and absorption of bacterial lipopolysaccharides in liver disease, and (4) point to a role for endotoxemia in extrahepatic manifestations of liver injury as well. Studies are also reviewed that suggest possible mechanisms for modifying endotoxicity in hepatic damage.