INCREASED INTESTINAL PERMEABILITY AND ALTERED MUCOSAL IMMUNITY IN CHOLESTATIC JAUNDICE

Objective To examine the effects of cholestatic jaundice on gut barrie r function. Summary Background Data Gut barrier failure occurs in anim al models of jaundice. In humans, the presence of endotoxemia indirect ly implicates failure of this host defense, but this has not previousl y been investigated in jaundiced patients. Methods Twenty-seven patien ts with extrahepatic obstructive jaundice and 27 nonicteric subjects w ere studied. intestinal permeability was measured using the lactulose- mannitol test. Small intestinal morphology and the presence of mucosal immunologic activation were examined in endoscopic biopsies of the se cond pari of the duodenum. Systemic antiendotoxin core IgG antibodies and serum interleukin-6 and C-reactive protein were also quantified. i ntestinal permeability was remeasured in 9 patients 5 weeks after inte rnal biliary drainage. Results The median lactulose-mannitol ratio was significantly increased in the jaundiced patients. This was accompani ed by upregulation of HLA-DR expression on enterocytes and gut-associa ted lymphoid tissue, suggesting immune activation. A significant incre ase in the acute phase response and circulating antiendotoxin core ant ibodies was also observed in the jaundiced patients. After internal bi liary drainage, intestinal permeability returned toward normal levels. Conclusions A reversible impairment in gut barrier function occurs in patients with cholestatic jaundice. Increased intestinal permeability is associated with local immune cell and enterocyte activation. in vi ew of the role of gut defenses in the modern paradigm of sepsis, these data may directly identify an important underlying mechanism contribu ting to the high risk of sepsis in jaundiced patients.