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原发性硬化性胆管炎及相关溃疡性结肠炎对口服万古霉素的成功反应可能取决于品牌和个性化剂量:一名青少年病例报告

Successful response of primary sclerosing cholangitis and associated ulcerative colitis to oral vancomycin may depend on brand and personalized dose: report in an adolescent.

作者信息

Buness Cynthia W, Johnson Kevin M, Ali Ahmad Hassan, Alrabadi Leina, Lindor Keith D, Miloh Tamir, Cox Kenneth L

机构信息

National Patient Advocate Foundation, Arizona State University, Phoenix, AZ, USA.

Department of Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, CT, USA.

出版信息

Clin J Gastroenterol. 2021 Apr;14(2):684-689. doi: 10.1007/s12328-020-01296-0. Epub 2020 Nov 24.

Abstract

Primary sclerosing cholangitis (PSC) is a rare, progressive liver disease characterized by cholestasis and bile duct fibrosis that has no accepted therapy known to delay or arrest its progression. We report a 23-year-old female patient who at age 14 was diagnosed with moderate pancolonic ulcerative colitis (UC) and at age 15 with small-duct PSC unresponsive to conventional therapy. The patient began single drug therapy with the antibiotic oral vancomycin (OVT) and achieved normalization of liver enzymes and resolution of UC symptoms with colonic mucosal healing. These improvements have persisted over 8 years. There has been no colon dysplasia, liver fibrosis or failure, bile duct stricture, or cancer. Of note, the patient's response was dependent on the brand of oral vancomycin capsule, as well as dose. This raised the questions of possible differences in bioequivalence of different commercial versions of the drug and whether this factor might play into the variability of efficacy seen in published trials. Evidence suggests that oral vancomycin both alters the intestinal microbiome and has immunomodulatory effects. Its striking effectiveness in this and other patients supports further investigation in randomized trials, with careful attention to its bioavailability profile in the gut.

摘要

原发性硬化性胆管炎(PSC)是一种罕见的进行性肝病,其特征为胆汁淤积和胆管纤维化,目前尚无已知可延缓或阻止其进展的治疗方法。我们报告一名23岁女性患者,她14岁时被诊断为中度全结肠溃疡性结肠炎(UC),15岁时被诊断为小胆管PSC,对传统治疗无反应。该患者开始使用抗生素口服万古霉素(OVT)进行单一药物治疗,实现了肝酶正常化,并使UC症状得到缓解,结肠黏膜愈合。这些改善持续了8年。未出现结肠发育异常、肝纤维化或衰竭、胆管狭窄或癌症。值得注意的是,患者的反应取决于口服万古霉素胶囊的品牌以及剂量。这就引发了不同商业版本药物生物等效性可能存在差异的问题,以及该因素是否可能影响已发表试验中观察到的疗效差异。有证据表明,口服万古霉素既能改变肠道微生物群,又具有免疫调节作用。它在该患者及其他患者中的显著疗效支持在随机试验中进一步研究,同时要密切关注其在肠道中的生物利用度情况。

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