CHARACTERIZATION OF THE RESOLUTION OF SEVERE CHOLESTASIS IN 11 CHILDREN WITH ALAGILLE SYNDROME

22 Alagille syndrome (AGS) and biliary atresia (BA) are the most common bile duct disorders leading to transplantation in children. The degree of cholestasis in severe AGS is more profound than in BA, but the implications for transplantation are different. A toddler with jaundice due to BA will require eventual transplantation, but the same may not be true for AGS, AIMS: To document the extent and the temporal progression of cholestasis in AGS. METHODS: Records of 11 older AGS pts (7M:4F, ages 4.0 to 21.9 yrs) with severe disease were analyzed for biochemical parameters of cholestasis and synthesis. The mean, median and range of peak and final values and age (in yrs) at peak were recorded for bilirubin (bili), bile salts (BS), ALT, AST, GGT, alkaline phosphatase (AP), albumin and PT. (Table)TABLEAlbumin and PT demonstrate stable synthetic function in all pts. CONCLUSIONS: Measures of cholestasis may continue to worsen until the 3rd or 4th year of life in AGS pts whose cholestasis will subsequently improve. Mean peak cholestasis occurs at 2.5 to 3.8 yrs of age, according to the biochemical parameter assessed. Serum bile salts (167×) and GGT (40×) are most elevated, followed by alkaline phosphatase (17×), bilirubin (9×) and cholesterol (5×) in pts with normal synthetic capability. SPECULATIONS: Cholestasis can dramatically improve in pts with severe AGS. Commitment to transplantation should not be based solely on the level of cholestasis, particularly in young children, as long term survival without transplantation is common. Further investigations into the mechanisms whereby cholestasis is emeliorated may provide information that will lead to effective therapy.