The Role of Ursodeoxycholic Acid in Treatment of Gallstones in Hemolytic Disorders
Status:
Terminated
Trial end date:
2017-09-10
Target enrollment:
Participant gender:
Summary
It is well established that hemolytic diseases predispose patients to the development of
pigment gallstones. Gallstones are noted in at least 5% of children under the age of 10
years, increasing to 40-50% in the second to fifth decades. The co-inheritance of Gilbert's
syndrome increases the risk of cholelithiasis four to five-fold.
In patients with chronic hemolysis, total bile lipid concentration is decreased and the total
bilirubin to total lipid ratio is increased. This suggests that the conjugating capacity of
hepatocytes is surpassed by the excessive amount of bilirubin resulting from hemolysis.
Increased bilirubin monoconjugate and unconjugated bilirubin can precipitate in bile and form
complexes with inorganic ions, mostly calcium, and develop into stones.
Patients with hemolytic disorders can also develop biliary sludge, a suspension of
precipitated particulate matter in bile dispersed in a viscous, mucin-rich liquid phase . The
chemical composition of the precipitates correlates well with the composition of the
associated stone and sludge often stands as a harbinger of future stone development.
There is strong data suggesting a benefit in treating cholelithiasis with UDCA and also in
preventing gallstone development in various high risk scenarios.
There are several proposed mechanisms for the positive effect of UDCA in primary prevention
of pigment stones. Mucoglycoproteins are present in significant amounts in black pigment
stones and contribute to the matrix of gallstones. UDCA suppresses the secretion of protein
and decreases the levels of various proteins in bile . It has also been suggested that
increased colonic bile salt may solubilize unconjugated bilirubin and may prevent calcium
complexing.
There is no published data at present on the role of UDCA in prevention and treatment of
cholelithiasis in hemolytic diseases. The investigators hypothesise that UDCA can be of
benefit to patients with hemolytic disorders in the primary prevention of pigment stones,
possible resolution of biliary sludge and existent stones, and reduction of symptomatic
episodes of cholelithiasis.