Évaluation du traitement des déficits de synthèse des acides biliaires primaires ar l'acide cholique et/ou l'acide ursodésoxycholique dans le cadre d'un essai clinique en pédiatrie

Defects in enzymes involved in primary bile acid synthesis, 3β-hydroxy-C₂₇-steroid deshydrogenase/isomerase (3β-HSD) and Δ⁴-3 oxosteroid 5-reductase (Δ⁴3 oxo-R), represent a rare genetic autosomal recessive transmitted disease which leads to cholestasis and liver failure. Twelve children have been diagnosed in France and were included in a clinical trial to assess the effect of treatment with a primary bile acid, cholic acid (clinical trial AP-HP, N° 93-37). Cholic acid is not registered in the european pharmacopea and was supplied by Dr Falk GmbH (pharmaceutical company Germany). Hard capsules of cholic acid (70, 100, 250 mg) were prepared by the hospital pharmacist after identification of the active compound. Capsules were controlled and dispensed to the outpatients. Various clinical and biological parameters were recorded at inclusion and thereafter every 6 months. Children with 3β-HSD deficiency (n = 10) normalized their liver tests after ursodesoxycholic acid and/or cholic acid treatment. By contrast ursodesoxycholic acid alone did not succeed in normalizing liver tests in the two children with Δ⁴-3 oxo-R deficiency. When ursodesoxycholic acid was combined with cholic acid liver function improvement was noticed. Cholic acid tolerance was good in 11/12 children. Pruritus was observed in one children and disappeared with decreasing dosage. Cholic acid capsules allow to treat a rare metabolic disease and to avoid hepatic transplantation in the mean term. The long term tolerance needs to be evaluated.