title: Abnormal intestinal permeability in primary biliary cirrhosis.
abstract: Antimitochondrial antibodies (AMAs) found in patients with primary biliary cirrhosis (PBC) cross-react with bacterial proteins and hence molecular mimicry has been proposed as a mechanism for AMA development. Alterations in gastrointestinal permeability would provide a potential route for increased exposure of gut flora to the immune system. In this study we aimed to compare the measured gastrointestinal permeability in patients with PBC to that in patients with liver disease (hepatitis C) and healthy control populations. Subjects drank a mixture of sucrose, lactulose, and mannitol dissolved in water. Eight-hour urinary excretion of the sugars was measured to assess intestinal permeability. Antiendomysial antibody testing was performed to exclude subclinical celiac disease. Eighty-six patients with PBC were evaluated and compared to 69 hepatitis C patients and 155 healthy controls. The mean urinary excretion of sucrose in the PBC patients (133.89 +/- 72.56 mg) was significantly higher than that in hepatitis C patients (101.07+/-63.35) or healthy controls (89.46+/-41.76) (P=0.0001), suggesting abnormal gastric or proximal small intestinal permeability. Sucrose excretion was not increased among patients with hepatitis C compared to healthy controls. The ratio of lactulose:mannitol excretion, reflecting small bowel permeability, was also elevated in the PBC group (0.017+/-0.012) compared to healthy controls (0.012+/-0.007) (P=0.0001) but was equal to that found among patients with hepatitis C (0.016+/-0.011) (P=NS). We conclude that the permeability of both the stomach and the small bowel is increased in patients with PBC, however, it is unclear if it is a cause, consequence, or manifestation of the disease.
authors.affiliation: Division of Gastroenterology, University of Toronto, Toronto, Ontario, Canada. feldj@niddk.nih.gov
authors.forename: Jordan J
authors.initials: JJ
authors.lastname: Feld
authors.forename: Jonathan
authors.initials: J
authors.lastname: Meddings
authors.forename: E Jenny
authors.initials: EJ
authors.lastname: Heathcote
mesh_terms: D000328:Adult; D000368:Aged; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007408:Intestinal Absorption / Q000502:physiology; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000503:physiopathology; D007422:Intestines / Q000503:physiopathology; D007792:Lactulose / Q000493:pharmacokinetics; D008105:Liver Cirrhosis, Biliary / Q000378:metabolism* / Q000503:physiopathology; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged; D010539:Permeability; D012720:Severity of Illness Index; D013395:Sucrose / Q000493:pharmacokinetics
chemical_list: D007792:Lactulose; D013395:Sucrose