Rare Daily Staff

While oral cholic acid replacement therapy has been shown to be an effective treatment for children with primary bile acid synthesis disorders due to single enzyme defects, to date no study had shown the effects of this therapy when these children reached adulthood.

Individuals with these rare disorders lack the enzymes needed to synthesize cholic acid, a primary bile acid normally produced in the liver from cholesterol. The absence of cholic acid in these patients leads to reduced bile flow, accumulation of potentially toxic bile acid intermediates in the liver (cholestasis), and malabsorption of fats and fat-soluble vitamins in the diet. If untreated, patients fail to grow and can develop life-threatening liver injury.

A recent study published in Orphanet Journal of Rare Diseases found that oral cholic acid replacement therapy for children with these rare and severe genetic liver defects allows them to reach adulthood in good health without the need for liver transplantation.

The study evaluated the long-term effectiveness and safety of cholic acid replacement therapy, which has been used in the United States and Europe for the past 20 years. Fifteen patients with 3β-HSD and Δ4–3-oxo-R deficiencies who were initially treated between 1993 and 2007 were examined.

The 15 children with a genetic defect in primary bile acid synthesis received oral cholic acid treatment for a median period of 21.4 years. With cholic acid therapy, the long-term outcome and the biochemical control of the patients were excellent. All patients are alive with their native liver, with normal findings on physical examination, except for hypo/areflexia in four patients being the irreversible consequence of prolonged vitamin E deficiency before disease diagnosis. Also, all patients had normal serum liver biochemistry tests and the excretion of the atypical metabolites of bile acids remained low or traces in amount, signaling good metabolic control of the primary bile acid synthesis defects with the therapy.

The primary authors of the study, Emmanuel Gonzales, a liver transplantation specialist at the Hôpitaux Universitaires Paris-Sud, and Lorenza Matarazzo, Department of Medicine, Surgery and Health Sciences at the University of Trieste, concluded that oral cholic acid replacement therapy is a safe and effective long-term treatment of the most common primary bile acid synthesis defects and allows affected children to reach adulthood in good health condition without the need for a liver transplantation.

October 30, 2018