Gonzales Emmanuel, Gerhardt Marie F, Fabre Monique, Setchell Kenneth D R, Davit-Spraul Anne, Vincent Isabelle, Heubi James E, Bernard Olivier, Jacquemin Emmanuel
Pediatric Hepatology Unit, Hôpital Bicêtre, Assistance Publique - Hôpitaux de Paris, Paris, France.
Gastroenterology. 2009 Oct;137(4):1310-1320.e1-3. doi: 10.1053/j.gastro.2009.07.043. Epub 2009 Jul 19.
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.
Fifteen patients with either 3beta-hydroxy-Delta(5)-C(27)-steroid oxidoreductase (3beta-HSD) (n = 13) or Delta(4)-3-oxosteroid 5beta-reductase (Delta(4)-3-oxo-R) (n = 2) deficiency confirmed by mass spectrometry and gene sequencing received oral CA and were followed up prospectively.
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 3beta-HSD and Delta(4)-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 3beta-HSD deficiency. CA was well tolerated with all children developing normally, including 2 women having 4 normal pregnancies during treatment.
Oral CA therapy is a safe and effective long-term treatment of the most common primary bile acid synthesis defects.
口服胆汁酸替代疗法已被证明是治疗原发性胆汁酸合成缺陷的有效方法，但迄今为止，尚无关于该疗法长期效果的报道。本研究的目的是评估胆酸（CA）治疗的长期有效性和安全性。
15例经质谱分析和基因测序确诊为3β-羟基-Δ⁵-C₂₇-类固醇氧化还原酶（3β-HSD）缺乏（n = 13）或Δ⁴-3-氧代类固醇5β-还原酶（Δ⁴-3-氧代-R）缺乏（n = 2）的患者接受口服CA治疗，并进行前瞻性随访。
CA治疗开始时的中位年龄为3.9岁（范围0.3 - 13.1岁）。治疗后的中位随访时间为12.4年（范围5.6 - 15年）。CA的初始平均日剂量为13 mg/kg，最后一次评估时为6 mg/kg。在CA治疗期间，体格检查结果、实验室检查结果和超声检查结果均恢复正常。尿液的质谱分析显示，在3β-HSD和Δ⁴-3-氧代-R缺乏症患者中，非典型代谢产物的排泄分别减少了500倍和30倍，总尿胆汁酸排泄量显著下降。14例患者在接受至少5年的CA治疗后进行肝脏活检，结果显示有明显改善，尤其是3β-HSD缺乏症患者。CA耐受性良好，所有儿童发育正常，包括2名女性在治疗期间有4次正常妊娠。
口服CA疗法是治疗最常见的原发性胆汁酸合成缺陷的一种安全有效的长期治疗方法。
