BILE ACID-INDEPENDENT BILE-FLOW IS DIFFERENTLY REGULATED BY GLUCAGON AND SECRETIN IN HUMANS AFTER ORTHOTOPIC LIVER-TRANSPLANTATION

The present study characterizes recovery of bile secretion after ortho topic liver transplantation (OLT) in humans with special regard to hor monal regulation of bile acid-independent bile flow by glucagon and se cretin. Sixty-seven patients with an uncomplicated postoperative cours e were studied during the first 3 weeks after OLT to determine normali zation of bile flow, A group of 7 and 10 patients, respectively, under went a biliary stimulation test by either glucagon at days 7, 14, and 21 after OLT or by secretin at days 2, 10, and 21 after OLT. Secretin tests were similarly performed in patients with acute severe rejection during the first 10 days after OLT, while glucagon tests were perform ed in patients with acute allograft rejection occurring 2 weeks after OLT. Furthermore, hormone effects were studied in nontransplanted pati ents after cholecystectomy with indwelling biliary T tube. After OLT, bile secretory function recovered and stabilized within 14 days after surgery by reconstitution of both bile acid-dependent and -independent bile flow, Two weeks after OLT, bile secretion was comparable with no ntransplanted patients after cholecystectomy. Glucagon and secretin st imulated bile acid-independent bile flow in transplanted and nontransp lanted patients significantly, yet secretin choleresis, unlike glucago n choleresis, had already occurred during the first days after OLT and was unaffected by acute allograft rejection. These results allow the speculation that, in humans, glucagon and secretin exert their cholere tic activity by different mechanisms and/or at different anatomical si tes in the liver. Assuming that secretin acts at the bile duct cells, its secretory capacity was not altered by the transplantation procedur e and during moderate or severe rejection episodes, as opposed to gluc agon choleresis, which most likely originates in the hepatocytes and r equires an entirely reconstituted canalicular transport system after O LT.