BILIARY-TRACT DISEASE IN RATS WITH EXPERIMENTAL SMALL-BOWEL BACTERIAL OVERGROWTH

Small bowel bacterial overgrowth, which develops in surgically created jejunal self-filling blind loops, is associated with hepatic injury in susceptible rat strains. The histological findings are portal tract inflammation and bile duct proliferation and destruction. In this study, evidence of injury to the extrahepatic and intrahepatic bile ducts in susceptible and resistant inbred rats with self-filling blind loops was determined by bile flow rates, histological appearance of cross-sections of bile ducts and cholangiography. Lewis and Wistar rats with self-filling blind loops had thickening of the cross-sectional area of the extrahepatic bile ducts compared with controls and nonsusceptible Buffalo rats (p < 0.001). Daily metronidazole therapy significantly reduced thickening of bile ducts in Lewis and Wistar rats with self-filling blind loops. Bile flow was increased in Lewis and Wistar rats with blind loops compared with controls (p < 0.05). Cholangiograms of Lewis and Wistar rats with self-filling blind loops demonstrated extrahepatic ductal dilatation and ectasia with irregular, beaded, rapidly tapering and tortuous intrahepatic ducts. Blinded cholangiographical scores of susceptible rat strains with self-filling blind loops were higher (score = 5.9 +/- 2.3) than those of controls (1.2 +/- 0.4), rats with blind loops treated with metronidazole (0.8 +/- 1.3) and nonsusceptible Buffalo rats with blind loops (0.6 +/- 0.9) (p < 0.01). Biliary histological and cholangiographical abnormalities found in this rat model resemble features of primary sclerosing cholangitis. This animal model will be useful in exploring mechanisms of the association of hepatobiliary inflammation with intestinal injury and investigating potential therapeutic agents.