157 INTESTINAL ABSORPTION OF SULPHATED GLYCOLITHOCHOLIC ACID F. Kuipers, H. Hzslinga, R. Havinga, C.M.A. Bijleveld, R.J. Vonk Department of Paediatrics, State University of Groningen~ Groningen, The Netherlands. Sulphated glycolithocholic acid (SGLC) causes intrahepatic eholestasis in experimental animals, despite its sulphated form. Elevated serum concentrations of this bile acid were found during symptom-fPee periods in patients with intermittent cholestasis. In these patients a marked postprandial rise in serum SGLC was observed, which could be prevented by adding cholestyramine to the testmeal. This suggests an intestinal origin of SGLC. Sulphation has been claimed to prevent intestinal bile acid absorption, however, quantitative data are scarce. Therefore, we studied intestinal SGLC absorption in rats. l<ats were provided with permanent catheters in bile duct, duodenum and heart. Intraduodenal infusions of 14C-radiolabeled SGLC (3 ml/h,4h) were started after at least 4 days of biliary drainag4, i.e. after exhaustion of the endogenous bile acid pool. Excretion of SGLC in bile, faeces and urine was measured during 24 hours. Intestinal absorption of SGLC was dose-dependent: at an infusion rate of 3 ~mol/h, recovery in bile was 104 + 5% (mean ~ SEM), but decreased to 50 + 1% when 15 ~mol/h was infused. SGLC absorption ~as not significantly altered by co-infUsion of rat bile or tauro- cholic acid. SGLC excretion in urine was less than 2%. No hepatic metabolism of SGLC occurred. It is concluded that the hepatotoxic agent SGLC can be absorbed relatively efficient from the intestine. Enhanced formation of this compound could therefore lead to its accumulation in the enterohepatic circulation and finally to cholestasis. Supported by grant 13-53-44 from HGO-TNO. 158 SYNDROMATIC PAUCITY OF INTRAHEPATIC BILE DUCTS - A RARE DIFFERENTIAL DIAGNOSIS OF INTRAHEPATIC CHOLESTASIS. W.Kurtz, U.Leuschner, W.D.Strohm, E.Lambrech~, M.Classen Department of Gastroenterology, Center of Internal Medicine, University Clinics, Frankfurt/Main, Germany *Center of Pathology, University Clinics, Frankfurt/Main, Germany In 1969 Alagille (J.Par. P~d. 1969,301) described a hereditary syndrome of intrahepatic cholestasis with patent extrahepatic bile ducts. The mode of inheritance is still disputed. We observed two families with this syndrome. An 18y. old woman presented the full picture of the disease with characteristic facies, developmental retardation, elevated liver enzymes, infundibular pulmonary stenosis, multiple peripheral pulmonary stenoses, kidney hypoplasia, and hypertension. In liver histology bile ducts were missing in the portal triads. ERC showed a highly rarified intrahepatic bile duct system. One sister had died from cardiac malformation at 10 days, one sister had unilateral kidney aplasia, four siblings had the "characteristic" facies. In a 31y. old man elevated liver enzymes had been observed for 6 years. Indocyanine green elimination was reduced to 9,9%/min.,the endogenous bile acid load test ( 0, 60, 120, 180 mlns. ) was 11,83, 6,84, 4,83, 11,19 ~mol/l for glycocholic acid, 1,13, 1,04, 0,57, 0,89 ~mol/l for sulfoglycolithocholic acid. Both children ( ly. old girl, 6y. old boy ) showed the typical facies and an intrahepatic cholestasis. Conclusions: In Alagille's syndrome, routine laboratory tests are noncharacteristic. The endogenous bile acid load test points to impaired hepatic bile acid uptake. Liver sections must be carefully scrutinized for absence of bile ducts in the portal triads. ERC validates the diagnosis. Our observations agree with dominant inheritance with variable expression. $79

Syndromatic paucity of intrahepatic bile ducts — A rare differential diagnosis of intrahepatic cholestasis

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Page 1: Syndromatic paucity of intrahepatic bile ducts — A rare differential diagnosis of intrahepatic cholestasis

157 INTESTINAL ABSORPTION OF SULPHATED GLYCOLITHOCHOLIC ACID

F. Kuipers, H. Hzslinga, R. Havinga, C.M.A. Bijleveld, R.J. Vonk Department of Paediatrics, State University of Groningen~ Groningen, The Netherlands.

Sulphated glycolithocholic acid (SGLC) causes intrahepatic eholestasis in experimental animals, despite its sulphated form. Elevated serum concentrations of this bile acid were found during symptom-fPee periods in patients with intermittent cholestasis. In these patients a marked postprandial rise in serum SGLC was observed, which could be prevented by adding cholestyramine to the testmeal. This suggests an intestinal origin of SGLC. Sulphation has been claimed to prevent intestinal bile acid absorption, however, quantitative data are scarce. Therefore, we studied intestinal SGLC absorption in rats.

l<ats were provided with permanent catheters in bile duct, duodenum and heart. Intraduodenal infusions of 14C-radiolabeled SGLC (3 ml/h,4h) were started after at least 4 days of biliary drainag4, i.e. after exhaustion of the endogenous bile acid pool. Excretion of SGLC in bile, faeces and urine was measured during 24 hours.

Intestinal absorption of SGLC was dose-dependent: at an infusion rate of 3 ~mol/h, recovery in bile was 104 + 5% (mean ~ SEM), but decreased to 50 + 1% when 15 ~mol/h was infused. SGLC absorption ~as not significantly altered by co-infUsion of rat bile or tauro- cholic acid. SGLC excretion in urine was less than 2%. No hepatic metabolism of SGLC occurred.

It is concluded that the hepatotoxic agent SGLC can be absorbed relatively efficient from the intestine. Enhanced formation of this compound could therefore lead to its accumulation in the enterohepatic circulation and finally to cholestasis.

Supported by grant 13-53-44 from HGO-TNO.

158 SYNDROMATIC PAUCITY OF INTRAHEPATIC BILE DUCTS - A RARE DIFFERENTIAL DIAGNOSIS OF INTRAHEPATIC CHOLESTASIS. W.Kurtz, U.Leuschner, W.D.Strohm, E.Lambrech~, M.Classen Department of Gastroenterology, Center of Internal Medicine, University Clinics, Frankfurt/Main, Germany *Center of Pathology, University Clinics, Frankfurt/Main, Germany

In 1969 Alagille (J.Par. P~d. 1969,301) described a hereditary syndrome of intrahepatic cholestasis with patent extrahepatic bile ducts. The mode of inheritance is still disputed. We observed two families with this syndrome. An 18y. old woman presented the full picture of the disease with characteristic facies, developmental retardation, elevated liver enzymes, infundibular pulmonary stenosis, multiple peripheral pulmonary stenoses, kidney hypoplasia, and hypertension. In liver histology bile ducts were missing in the portal triads. ERC showed a highly rarified intrahepatic bile duct system. One sister had died from cardiac malformation at 10 days, one sister had unilateral kidney aplasia, four siblings had the "characteristic" facies. In a 31y. old man elevated liver enzymes had been observed for 6 years. Indocyanine green elimination was reduced to 9,9%/min.,the endogenous bile acid load test ( 0, 60, 120, 180 mlns. ) was 11,83, 6,84, 4,83, 11,19 ~mol/l for glycocholic acid, 1,13, 1,04, 0,57, 0,89 ~mol/l for sulfoglycolithocholic acid. Both children ( ly. old girl, 6y. old boy ) showed the typical facies and an intrahepatic cholestasis. Conclusions: In Alagille's syndrome, routine laboratory tests are noncharacteristic. The endogenous bile acid load test points to impaired hepatic bile acid uptake. Liver sections must be carefully scrutinized for absence of bile ducts in the portal triads. ERC validates the diagnosis. Our observations agree with dominant

inheritance with variable expression.

$79