Involvement of bile acid in diarrhoea and therapeutic effect of colestimide in hereditary ATTR amyloidosis.

IF 5.2 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Amyloid-Journal of Protein Folding Disorders Pub Date : 2024-11-20 DOI:10.1080/13506129.2024.2430554

Yusuke Mochizuki, Nagaaki Katoh, Akira Matsushima, Masahide Yazaki, Naoko Kuwabara, Saori Nakagawa, Yoshiki Sekijima

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Abstract

Background: Diarrhoea is one of the most serious complications in hereditary ATTR (ATTRv) amyloidosis. However, its precise pathomechanism remains unknown. The present study investigated the involvement of bile acid in diarrhoea along with the therapeutic effect of colestimide, a bile acid sequestrant, in ATTRv amyloidosis.

Methods: We prospectively enrolled 19 ATTRv amyloidosis patients (9 with refractory diarrhoea and 10 without diarrhoea) and 20 healthy individuals for measurements of serum 7a-hydroxy-4-cholesten-3-one (C4) levels. The patients with diarrhoea were then treated with oral colestimide (1.5 g twice daily) for 28 days. The frequency of diarrhoea and C4 level were evaluated before and after colestimide treatment.

Results: Mean serum C4 level was significantly higher in ATTRv patients with diarrhoea (62.3 ng/mL) than in ATTRv patients without diarrhoea (24.0 ng/mL, p = 0.03). Colestimide treatment significantly decreased mean diarrhoea frequency (pre-treatment period: 9.1 times/week, colestimide treatment period, 6.6 times/week, p = 0.04) and increased mean C4 level (before treatment: 66.2 ng/mL, after treatment: 187.1 ng/mL, p = 0.02).

Conclusions: Bile acid status was significantly associated with diarrhoea in ATTRv amyloidosis. Colestimide and other bile acid sequestrants may reduce diarrhoea frequency in afflicted patients.

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胆汁酸对遗传性 ATTR 淀粉样变性病腹泻的影响及可乐定的治疗效果。

背景：腹泻是遗传性 ATTR（ATTRv）淀粉样变性最严重的并发症之一。然而，其确切的病理机制仍不清楚。本研究调查了胆汁酸参与腹泻的情况，以及胆汁酸螯合剂考来替米在ATTRv淀粉样变性中的治疗效果：我们前瞻性地招募了19名ATTRv淀粉样变性患者（9名难治性腹泻患者和10名无腹泻患者）和20名健康人，测量他们的血清7a-羟基-4-胆甾烯-3-酮（C4）水平。腹泻患者随后接受口服考来替米（1.5 克，每天两次）治疗 28 天。结果显示：腹泻患者的平均血清 C4 含量高于非腹泻患者，而腹泻患者的平均血清 C4 含量低于非腹泻患者：结果：有腹泻的 ATTRv 患者的平均血清 C4 水平（62.3 纳克/毫升）明显高于无腹泻的 ATTRv 患者（24.0 纳克/毫升，P = 0.03）。可乐定治疗可明显减少平均腹泻次数（治疗前：9.1次/周，治疗后：9.1次/周）：结论：胆汁酸状态与腹泻密切相关：结论：胆汁酸状态与ATTRv淀粉样变性患者的腹泻密切相关。结论：胆汁酸状态与ATTRv淀粉样变性患者的腹泻密切相关，可乐定和其他胆汁酸螯合剂可减少患者的腹泻次数。

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

Amyloid-Journal of Protein Folding Disorders 生物-生化与分子生物学

CiteScore

10.60

自引率

10.90%

发文量

审稿时长

6-12 weeks

期刊介绍： Amyloid: the Journal of Protein Folding Disorders is dedicated to the study of all aspects of the protein groups and associated disorders that are classified as the amyloidoses as well as other disorders associated with abnormal protein folding. The journals major focus points are: etiology, pathogenesis, histopathology, chemical structure, nature of fibrillogenesis; whilst also publishing papers on the basic and chemical genetic aspects of many of these disorders. Amyloid is recognised as one of the leading publications on amyloid protein classifications and the associated disorders, as well as clinical studies on all aspects of amyloid related neurodegenerative diseases and major clinical studies on inherited amyloidosis, especially those related to transthyretin. The Journal also publishes book reviews, meeting reports, editorials, thesis abstracts, review articles and symposia in the various areas listed above.