URSODEOXYCHOLIC ACID THERAPY IN PEDIATRIC-PATIENTS WITH PROGRESSIVE FAMILIAL INTRAHEPATIC CHOLESTASIS

Progressive familial intrahepatic cholestasis (PFIC) is a lethal inher ited childhood cholestasis of hepatocellular origin. Different subtype s of PFIC have been described according to serum gamma-glutamyl transp eptidase (GGT) activity. There is currently no effective medical thera py available for children with PFIC. We report on 39 patients with PFI C who received ursodeoxycholic acid (UDCA) orally (20-30 mg/kg b.w./da y) for a period of 2 to 4 years. Group 1 (n = 26) consisted of childre n with normal GGT activity, and group 2 (n = 13) of children with high GGT activity. Within group 1, liver tests normalized in 11 children, improved in 5, and stabilized or worsened in 10. Within group 2, liver tests normalized in six children, improved in four, and stabilized or worsened in three. Improvement of parameters was associated with an e nrichment of the circulating pool of bile acids with UDCA. Hepatosplen omegaly and pruritus disappeared or diminished in children in whom liv er tests normalized. In nine of these children, liver tests worsened a nd normalized again after stopping and restarting UDCA. Liver histolog y assessed in four children after normalization of liver tests and 2 y ears of treatment showed a decrease in fibrosis. We conclude that UDCA should be considered in the initial therapeutic management of childre n with PFIC, because it appears effective in resolving or improving th e liver function and the clinical status of a fair proportion of child ren. Chronic UDCA therapy might thus avoid the need for liver transpla ntation in some children with PFIC.