Cholic acid for primary bile acid synthesis defects: a life-saving therapy allowing a favorable outcome in adulthood

BACKGROUND: Oral cholic acid (CA) replacement has been shown to be an effective therapy in children with primary bile acid synthesis defects, which are rare and severe genetic liver diseases. To date there has been no report of the effects of this therapy in children reaching adulthood. The aim of the study was to evaluate the long-term effectiveness and safety of CA therapy. METHODS: Fifteen patients with either 3β-hydroxy-Δ(5)-C(27)-steroid oxidoreductase (3β-HSD) (n = 13) or Δ(4)–3-oxosteroid 5β-reductase (Δ(4)–3-oxo-R) (n = 2) deficiency confirmed by mass spectrometry and gene sequencing received oral CA and were followed prospectively. RESULTS: The median age at last follow-up and the median time of follow-up with treatment were 24.3 years (range: 15.3–37.2) and 21.4 years (range: 14.6–24.1), respectively. At last evaluation, physical examination findings and blood laboratory test results were normal in all patients. Liver sonograms were normal in most patients. Mean daily CA dose was 6.9 mg/kg of body weight. Mass spectrometry analysis of urine showed that excretion of the atypical metabolites remained low or traces in amount with CA therapy. Liver fibrosis scored in liver biopsies or assessed by elastography in 14 patients, after 10 to 24 years with CA therapy, showed a marked improvement with disappearance of cirrhosis (median score < F1; range: F0-F2). CA was well tolerated in all patients, including five women having 10 uneventful pregnancies during treatment. CONCLUSIONS: Oral CA therapy is a safe and effective long-term treatment of 3β-HSD and Δ(4)–3-oxo-R deficiencies and allows affected children to reach adulthood in good health condition without the need for a liver transplantation.