Efficacy and safety of switching therapy from chenodeoxycholic acid to cholic acid in Japanese patients with bile acid synthesis disorders

IF 1.8 4区医学 Q3 GENETICS & HEREDITY Molecular Genetics and Metabolism Reports Pub Date : 2024-11-22 DOI:10.1016/j.ymgmr.2024.101166

Mitsuyoshi Suzuki , Hajime Takei , Hiromi Suzuki , Jun Mori , Satoru Sugimoto , Tatsuki Mizuochi , Akira Ohtake , Hisamitsu Hayashi , Akihiko Kimura , Hiroshi Nittono

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Abstract

Objectives

This study aimed to assess the safety and efficacy of cholic acid (CA) treatment over 74 weeks in Japanese patients with inherited enzymatic bile acid synthesis disorders (BASD).

Methods

This phase 3, open-label, single-arm study enrolled four Japanese patients diagnosed with BASD, including two with 3β-hydroxy-Δ⁵-C₂₇-steroid dehydrogenase/isomerase (HSD3B7) deficiency and two with Δ⁴–3-oxosteroid 5β-reductase (SRD5B1) deficiency. The patients had received chenodeoxycholic acid (CDCA) treatment but were switched to CA treatment. Treatment efficacy was evaluated by measuring serum and urinary bile acid levels and liver-related biomarkers, and adverse events were evaluated to monitor safety.

Results

The daily CA doses ranged from 3.8 to 13.7 mg/kg/day. Laboratory values of liver-related biomarkers were maintained within normal ranges or improved. Bile acid analysis revealed CDCA replacement with CA in serum within the initial few weeks of CA treatment. Urinary concentrations of toxic bile acid metabolites associated with liver damage were higher than serum. Adverse effects from CA treatment were mild to moderate, and no treatment discontinuations were due to adverse events.

Conclusions

CA treatment over 74 weeks resulted in favorable efficacy and safety outcomes in Japanese patients with BASD, consistent with previous studies. These results support the utility of CA as a therapeutic option for Japanese patients with BASD.

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日本胆汁酸合成障碍患者从苯去氧胆酸转用胆酸治疗的有效性和安全性

目的本研究旨在评估胆酸（CA）治疗遗传性酶胆汁酸合成障碍（BASD）日本患者 74 周的安全性和有效性。方法这项 3 期、开放标签、单臂研究招募了四名确诊为 BASD 的日本患者，其中两名患有 3β-hydroxy-Δ5-C27-steroid dehydrogenase/isomerase (HSD3B7) 缺乏症，两名患有 Δ4-3-oxosteroid 5β-reductase (SRD5B1) 缺乏症。这些患者曾接受过酚类脱氧胆酸（CDCA）治疗，但后来改用CA治疗。通过测量血清和尿液中胆汁酸水平以及肝脏相关生物标志物来评估疗效，并评估不良事件以监测安全性。肝脏相关生物标志物的实验室值保持在正常范围内或有所改善。胆汁酸分析显示，在CA治疗的最初几周内，血清中的CDCA被CA取代。尿液中与肝损伤相关的有毒胆汁酸代谢物浓度高于血清。结论 CA 治疗 74 周后，日本 BASD 患者获得了良好的疗效和安全性，这与之前的研究结果一致。这些结果支持将 CA 作为日本 BASD 患者的一种治疗选择。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Molecular Genetics and Metabolism Reports Biochemistry, Genetics and Molecular Biology-Endocrinology

CiteScore

4.00

自引率

5.30%

发文量

105

审稿时长

33 days

期刊介绍： Molecular Genetics and Metabolism Reports is an open access journal that publishes molecular and metabolic reports describing investigations that use the tools of biochemistry and molecular biology for studies of normal and diseased states. In addition to original research articles, sequence reports, brief communication reports and letters to the editor are considered.