The effect of cholecystokinin-octapeptide on the hepatobiliary dysfunction caused by total parenteral nutrition

Purpose: Patients on total parenteral nutrition (TPN) commonly have hepatobiliary dysfunction. Interruption of the enterohepatic circulation (EHC) and gallbladder stasis are part of the pathogenesis. Cholecystokinin-octapeptide (CCK-OP), by emptying the gallbaldder, stimulates the EHC. This study was performed to determine whether daily CCK-OP infusions can ameliorate the hepatobiliary dysfunction caused by TPN. Methods: Rabbits maintained on a standard TPN for 12 days were divided into two groups. One group (n = 6) received daily intravenous doses of CCK-OP, and the other (n = 13) received TPN only. A lab-chow-fed (LCF) group (n = 8) served as controls. The authors studied bile flow and bile acid secretion rates, sulfobromophthalein (BSP) secretion, gallbladder emptying in response to CCK-OP, and liver histology. Results: The LCF group had a bile flow of 82.3 μL/kg/min; that for the TPN-only group was 45.7 μL/kg/min (P < .001). The daily CCK-OP group did not improve more than the TPN-only group, with a bile flow of 45.8 μL/kg/min (P = NS). Bile acid secretion was 0.64 μmol/kg/min for the LCF group, 0.46 for the TPN-only group (P = NS), and 0.46 for the daily CCK-OP group (P = NS). TPN impaired the ability of the gallbladder to empty, and this was restored with daily CCK-OP. In the LCF group, the mean BSP secretion was 81.7% of a 5-mg/kg bolus within 60 minutes, compared with 72.5% in the daily CCK-OP group (P = NS) and 63.5% in the TPN-only group (P < .01). Histological examination of the liver showed that daily CCK-OP produced less periportal inflammation and fibrosis, although all TPN groups had hepatocyte damage in the centrilobular area. Conclusion: Stimulation of the EHC with daily CCK-OP infusions during TPN decreased periportal inflammation and fibrosis, maintained gallbladder emptying capacity, and improved organic anion (BSP) secretion, although bile flow and bile acid secretion were not improved, and hepatocyte damage persisted.