Treatments in Chronic Cholestasis in Children

Abstract

Few specific treatments for children with chronic cholestasis are available. Most therapy strategies relieve bile component retention or palliate some of the consequences of chronic cholestasis. Ursodeoxycholic acid is the most frequently used pharmacological agent in children with chronic cholestasis. This bile acid is administered at dosages between 10 and 30 mg/kg/day to patients with cystic fibrosis, inborn errors of bile acid metabolism, progressive familial intrahepatic cholestasis, sclerosing cholangitis, biliary atresia, Alagille syndrome, or those receiving total parenteral nutrition. Ursodeoxycholic acid mainly increases bile flow and has a membrane-stabilizing effect, reducing the toxicity of more hydrophobic bile acids. Rifampicin, an antibiotic, at dosages between 10 and 20 mg/kg/day is very efficient in relieving pruritus. Similar effects are obtained using nonabsorbable ion exchange resins. In addition, these molecules decrease the serum cholesterol levels contributing to reduce xanthomas. Replacement of some deficiencies created by total parenteral nutrition by administration of essential fatty acids or cysteine can prevent or contribute to improve the associated liver disorders. In some cholestatic diseases, surgical procedures can help to relieve the obstacle to the bile flow, as it is the case for portoenterostomy in patients with biliary atresia. In cases of intrahepatic cholestasis, a clinical and biochemical improvement can be recorded after bile diversion or other procedure (ileum exclusion) limiting the absorption of bile acids by the intestine. In the future, the association of these different pharmacological agents, increasing the bile flow, protecting cell membranes, or restoring nutritional deficiencies, could contribute to an improvement in quality of life in children with chronic cholestasis and eventually delay the need of a more drastic therapy such as liver transplantation. Advances in gene therapy and hepatocyte transplantation could also be of great help; however, many years of intense research are still necessary before even a pilot study using one of these therapies can be considered on liver diseases resulting in chronic cholestasis.

Ion Exchange Resins for Clinical Applications

“…Bile acid in turn dissociates quickly and is absorbed in the ileum. Cholestyramine is an orange-flavored granule that can be employed for improving pruritus [48]. Cholestyramine has been used for a long time owing to its proven safety and effectiveness, however, it has poor palatability which limits the tolerance of the drug.…”