Bile salt toxicity aggravates cold ischemic injury of bile ducts after liver transplantation in Mdr2+/??? mice

Primary sclerosing cholangitis (PSC) is a progressive, cholestatic disease of the liver that is marked by inflammation of the bile ducts and damage to the hepatic biliary tree. Approximately 60–70% of patients also have inflammatory bowel disease and progression of PSC can lead to ulcerative colitis and cirrhosis of the liver. Due to limited understanding of the etiology and mechanism of PSC, the only existing treatment option is orthotopic liver transplantation (OLT); however, recurrence of PSC, after OLT is estimated to be between 5% and 35%. We discuss the successful treatment of a pediatric patient, with recurrent PSC, after OLT with oral Vancomycin.

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Paucity of Interlobular Bile Ducts in Multidrug-Resistant P-Glycoprotein 3 (MDR3) Deficiency

International Journal of Surgical Pathology ◽

10.1177/1066896918799941 ◽

2018 ◽

Vol 27 (3) ◽

pp. 343-347 ◽

Cited By ~ 1

Author(s):

Mukul Vij ◽

Joseph Valamparampil ◽

Naresh Shanmugum ◽

Srinivas Mettu Reddy ◽

Shaman Rajindrajith ◽

...

Keyword(s):

Liver Transplantation ◽

Bile Ducts ◽

Multidrug Resistant ◽

Homozygous Deletion ◽

Second Child ◽

Donor Liver Transplantation ◽

P Glycoprotein ◽

Explanted Liver ◽

Base Pair Deletion ◽

Abcb4 Gene

Multidrug-resistant P-glycoprotein 3 (MDR3) is a phospholipid translocator encoded by the ABCB4 gene located on chromosome 7. MDR3 mediates the translocation of phosphatidylcholine across the canalicular membrane of the hepatocyte into bile. Severe MDR3 deficiency typically occurs during childhood with progressive cholestasis evolving to cirrhosis and liver failure, requiring liver transplantation. In this article, we report 2 pediatric cases of severe MDR3 deficiency with paucity of interlobular bile ducts. Both underwent living donor liver transplantation at our center for decompensated liver disease and portal hypertension. We diagnosed severe MDR3 deficiency in both the cases with negative MDR3 immunostaining in the explanted liver. Genetic studies revealed homozygous deletion single base pair deletion in exon 24 of the ABCB4 gene in the second child. The patients are on regular follow-up after liver transplant and are doing well. Our report highlights that cholangiopathy in MDR3 deficiency can lead to ductopenia in pediatric livers.

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EFFECTS OF PHENOBARBITAL ON BILE SALT METABOLISM IN CHOLESTASIS DUE TO INTRAHEPATIC BILE DUCT HYPOPLASIA

PEDIATRICS ◽

10.1542/peds.51.6.992 ◽

1973 ◽

Vol 51 (6) ◽

pp. 992-997

Author(s):

Adolf Stiehl ◽

M. Thaler ◽

William H. Admirand

Keyword(s):

Bile Duct ◽

Bile Salt ◽

Peripheral Blood ◽

Bile Salts ◽

Bile Ducts ◽

Enterohepatic Circulation ◽

Control Period ◽

Intrahepatic Bile Duct ◽

Total Serum ◽

Salt Excretion

The effects of phenobarbital (PB) on bile salt metabolism in a patient with severe cholestasis due to congenital paucity of perilobular bile ducts were studied with 14C-cholate and 3H-chenodeoxycholate. During the control period (without PB) cholate was the predominant bile salt in the peripheral blood, whereas chenodeoxycholate was predominant in the total bile salt pool. This difference in the distribution of the two primary bile salts appeared to be caused by relatively greater impairment of excretion of cholate from the liver cell into the bile. PB administration caused a decrease in the total serum bile salt concentration (from 132 to 62µg/ml), in the total bile salt pool (from 412 to 304 mg) and in the biologic half-life (cholate from 106 to 34 hours; chenodeoxycholate from 77 to 42 hours). The proportion of the total bile salt pool present in the peripheral blood decreased from 16.8% to 11.7%. In addition, PB markedly increased the fecal bile salt excretion. These data suggest the PB improves pruritus in this type of intrahepatic cholestasis by reducing serum bile salt concentrations. This is accomplished by a shift in bile salts from the peripheral blood into the enterohepatic circulation and by enhancing fecal bile salt excretion.

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