Endotoxin-induced defenestration of the hepatic sinusoidal endothelium: a factor in the pathogenesis of cirrhosis?

Defenestration and capillarisation of the hepatic sinusoidal endothelium occurs early in the pathogenesis of cirrhosis, both in patients suffering from alcohol abuse and in animal models. It is possible also that alcohol abuse promotes the absorption of bacterial endotoxins from the gastrointestinal tract. In this study we have investigated the effects of a single intravenous injection of endotoxin on the hepatic sinusoidal endothelium of rats. Seven days after the dose of endotoxin, the porosity of the sinusoidal endothelium was reduced to 40% of that of controls, due to a decrease in both diameter and number of fenestrae. The livers examined 14 days after dosing exhibited normal porosity. We postulate that bacterial endotoxins play a role in the pathogenesis of cirrhosis by modulating the fenestrated sinusoidal endothelium (liver sieve).