TY - JOUR
T1 - Oral Cholic Acid for Hereditary Defects of Primary Bile Acid Synthesis
T2 - A Safe and Effective Long-term Therapy
AU - Gonzales, Emmanuel
AU - Gerhardt, Marie F.
AU - Fabre, Monique
AU - Setchell, Kenneth D.R.
AU - Davit-Spraul, Anne
AU - Vincent, Isabelle
AU - Heubi, James E.
AU - Bernard, Olivier
AU - Jacquemin, Emmanuel
PY - 2009/1/1
Y1 - 2009/1/1
N2 - Background & Aims: Oral bile acid replacement has been shown to be an effective therapy in primary bile acid synthesis defects, but to date there have been no reports of the long-term effects of this therapy. The aim of the study was to evaluate the long-term effectiveness and safety of cholic acid (CA) therapy. Methods: Fifteen patients with either 3β-hydroxy-Δ5-C27-steroid oxidoreductase (3β-HSD) (n = 13) or Δ4-3-oxosteroid 5β-reductase (Δ4-3-oxo-R) (n = 2) deficiency confirmed by mass spectrometry and gene sequencing received oral CA and were followed up prospectively. Results: CA therapy was started at a median age of 3.9 years (range, 0.3-13.1 years). The median follow-up with treatment was 12.4 years (range, 5.6-15 years). The mean daily dose of CA was initially 13 mg/kg and was 6 mg/kg at last evaluation. During CA therapy, physical examination findings, laboratory test results, and findings on sonography normalized. Mass spectrometry analysis of urine showed that excretion of the atypical metabolites was reduced by 500-fold and 30-fold in 3β-HSD and Δ4-3-oxo-R deficiency, respectively, and total urinary bile acid excretion decreased dramatically. Liver biopsies performed in 14 patients after at least 5 years of CA therapy showed marked improvement, especially in patients with the 3β-HSD deficiency. CA was well tolerated with all children developing normally, including 2 women having 4 normal pregnancies during treatment. Conclusions: Oral CA therapy is a safe and effective long-term treatment of the most common primary bile acid synthesis defects.
AB - Background & Aims: Oral bile acid replacement has been shown to be an effective therapy in primary bile acid synthesis defects, but to date there have been no reports of the long-term effects of this therapy. The aim of the study was to evaluate the long-term effectiveness and safety of cholic acid (CA) therapy. Methods: Fifteen patients with either 3β-hydroxy-Δ5-C27-steroid oxidoreductase (3β-HSD) (n = 13) or Δ4-3-oxosteroid 5β-reductase (Δ4-3-oxo-R) (n = 2) deficiency confirmed by mass spectrometry and gene sequencing received oral CA and were followed up prospectively. Results: CA therapy was started at a median age of 3.9 years (range, 0.3-13.1 years). The median follow-up with treatment was 12.4 years (range, 5.6-15 years). The mean daily dose of CA was initially 13 mg/kg and was 6 mg/kg at last evaluation. During CA therapy, physical examination findings, laboratory test results, and findings on sonography normalized. Mass spectrometry analysis of urine showed that excretion of the atypical metabolites was reduced by 500-fold and 30-fold in 3β-HSD and Δ4-3-oxo-R deficiency, respectively, and total urinary bile acid excretion decreased dramatically. Liver biopsies performed in 14 patients after at least 5 years of CA therapy showed marked improvement, especially in patients with the 3β-HSD deficiency. CA was well tolerated with all children developing normally, including 2 women having 4 normal pregnancies during treatment. Conclusions: Oral CA therapy is a safe and effective long-term treatment of the most common primary bile acid synthesis defects.
UR - http://www.scopus.com/inward/record.url?scp=70349414388&partnerID=8YFLogxK
U2 - 10.1053/j.gastro.2009.07.043
DO - 10.1053/j.gastro.2009.07.043
M3 - Article
C2 - 19622360
AN - SCOPUS:70349414388
SN - 0016-5085
VL - 137
SP - 1310-1320.e3
JO - Gastroenterology
JF - Gastroenterology
IS - 4
ER -