Untitled Document




Role of Ursodeoxycholic Acid in Managing Gall Stone Disease and Fatty Liver

	Professor Salimur Rahman MBBS, FCPS Professor, Department of Hepatology Bangabandhu Sheikh Mujib Medical University Dhaka, Bangladesh	Dr. Mamun-Al-Mahtab MBBS, MSc (Gastroenterology, London), MD (Hepatology), FACG Assistant Professor Department of Hepatology Bangabandhu Sheikh Mujib Medical University Dhaka, Bangladesh
INTRODUCTION Background Ursodeoxycholic acid (UDCA) is a dihydroxy bile acid that contributes 3-4% to the human bile acid pool.1 It was first identified in 1902 in the bile of polar beer.2 This present name was given in 1927 by Shoda in Japan, who isolated it from Chinese black beer.3 Chemical structure of UDCA was first analyzed in 1936 by Iwasaki.`4` Structure UDCA is a 7b epimer of primary bile acid chenodeoxycholic acid. It originates in colon and not in the liver. The Japanese are leaders in introducing therapeutic administration of UDCA, although it was used by the Chinese for treatment of liver diseases many centuries back. Mechanism of Action UDCA has choleretic effect to increase hepatocellular bile acid excretion. It also has cytoprotective, anti-apoptotic and immunomodulatory properties. It has high first-pass metabolism approaching 70%. This is responsible for the low level of UDCA in systemic circulation. In bile, the peak concentration of UDCA is reached within 1-3 hours following oral administration. It has a half-life of 3.5-5.8 days. Oral absorption is facilitated by bile acid solubilization, the reason why UDCA is administered with meals. Concurrent administration with cholestyramine, activated charcoal and aluminum-containing antacid reduce intestinal uptake of UDCA by intra-luminal binding. It is therefore recommended that UDCA be taken at least 5 hours apart from these drugs.`5` Indication of Use UDCA is indicated primarily for treatment of primary biliary cirrhosis (PBC), a condition rather common in the West, butrarely seen in our part of the globe. In PBC patients, UDCA achieves symptomatic relief, improves biochemical parameters and liver histology and most importantly prolongs survival.`1`		Gall stone and fatty liver are two other important indications of UDCA, especially so in Bangladesh given the high incidence of these two hepato-biliary diseases in Bangladesh. UDCA is also indicated for a number of other liver diseases like primary sclerosing cholangitis`6`, intra-hepatic cholestasis of pregnancy,`7` liver disease in cystic fibrosis,`8` alcoholic liver disease`9` and paediatric cholestatic diseases.`10`


		Effects Result
		n	Decreases hydrophobic bile acids	Alteration of bile acid pool
		n	Increases hydrophilic bile acids
		n	Inhibits ileal bile acid absorption
		n	Preserves/stabilizes plasma membrane and mitochondria	Cytoprotection of hepatocytes and cholangiocytes
		n	Induces sub-cellular antiapoptotic pathways
		n	Decreases MHC class I and II expression	Immunomodulatory effect
		n	Corrects defective NK cell activity in PBC
		n	Decreases serum IgM against pyruvate dehydrogenase including AMA	-
		n	Reduces peripheral blood eosinophils	-
		n	Inhibits eosinophil activation and degradation
		n	Inhibits pro-apoptotic caspase 3, 8 and 9 activation	Protects against Th1 mediated liver injury
		n	Inhibits pro-inflammatory caspase IL-1, IL-18 and IFN- release
		n	Stimulates hepatocellular bile acid excretion	Choleresis and hypercholeresis
		n	Upregulates Cl--HCO3+ anion exchanger 2 in PBC
		n	Increases intra-cellular Ca++	Increases activity of whole-cell Cl channel in these cells
		Table 1: Mechanism of action of UDCA