综述文章:功能性下消化道疾病中的生物标志物与个性化治疗

Review article: biomarkers and personalised therapy in functional lower gastrointestinal disorders.

作者信息

Camilleri M

机构信息

Clinical Enteric Neuroscience Translational and Epidemiological Research (C.E.N.T.E.R.), Mayo Clinic, Rochester, MN, USA.

出版信息

Aliment Pharmacol Ther. 2015 Oct;42(7):818-28. doi: 10.1111/apt.13351. Epub 2015 Aug 11.

Abstract

BACKGROUND

Treatment of IBS and functional lower gastrointestinal disorders is still based predominantly on symptoms; biomarkers that reflect the mechanism or pathophysiology have been identified. Given the diverse mechanisms that result in the same clinical phenotype of IBS, it is hypothesised that identification of biomarkers may lead to individualisation of medical therapy.

AIM

To review the biomarkers that have been appraised in IBS.

METHODS

A single author reviewed the published literature on biomarkers appraised in IBS.

RESULTS

The current literature suggests that these biomarkers are insufficiently sensitive or specific to differentiate IBS from health or from other diseases causing similar symptoms, such as coeliac disease or inflammatory bowel disease. Most of the proposed biomarkers are not actionable, that is, they do not lead to an efficacious therapy based on the biological inference of the biomarker itself. However, among proposed biomarkers in IBS, some are actionable, as they specifically reflect a quantitative difference in a mediator of dysfunction or result in a quantifiable disturbance of function that can be specifically treated. Such biomarkers may potentially identify relevant subgroups that respond to specific therapy. The most promising actionable biomarkers are measurement of colonic transit (leading to treatments that reverse the abnormal transit) and measurements of bile acid diarrhoea to identify responders to bile acid sequestrants.

CONCLUSIONS

Therefore, although biomarkers are not ready for prime time as diagnostic tests in IBS, some biomarkers could identify subgroups of patients with IBS for inclusion in clinical trials that target specific dysfunctions. Such an approach may enhance treatment efficacy, and may ultimately help reduce costs in drug development and in the management of patients in clinical practice.

摘要

背景

肠易激综合征(IBS)和功能性下消化道疾病的治疗仍主要基于症状;已鉴定出反映其机制或病理生理学的生物标志物。鉴于导致IBS相同临床表型的机制多样,推测生物标志物的鉴定可能会使药物治疗个体化。

目的

综述在IBS中评估过的生物标志物。

方法

由一位作者查阅已发表的关于IBS中评估生物标志物的文献。

结果

当前文献表明,这些生物标志物在区分IBS与健康状态或与其他引起类似症状的疾病(如乳糜泻或炎症性肠病)时,敏感性或特异性不足。大多数提出的生物标志物无法指导治疗,也就是说,基于生物标志物本身的生物学推断,它们无法带来有效的治疗。然而,在IBS中提出的生物标志物中,有些是可以指导治疗的,因为它们能特异性反映功能障碍介质的定量差异,或导致可特异性治疗的功能定量紊乱。此类生物标志物可能潜在地识别出对特定治疗有反应的相关亚组。最有前景的可指导治疗的生物标志物是结肠转运的测量(从而带来逆转异常转运的治疗)以及胆汁酸腹泻的测量,以识别对胆汁酸螯合剂有反应的患者。

结论

因此,尽管生物标志物作为IBS的诊断测试尚未成熟,但一些生物标志物可识别IBS患者亚组,以纳入针对特定功能障碍的临床试验。这种方法可能会提高治疗效果,并最终有助于降低药物研发成本以及临床实践中患者管理的成本。

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