Tabibian James H, Gossard Andrea, El-Youssef Mounif, Eaton John E, Petz Jan, Jorgensen Roberta, Enders Felicity B, Tabibian Anilga, Lindor Keith D
1Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN; 2Center for Clinical and Translational Sciences, Mayo Graduate School, Rochester, MN; 3Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN; 4Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN; and 5College of Health Solutions, Arizona State University, Phoenix, AZ.
Am J Ther. 2017 Jan/Feb;24(1):e56-e63. doi: 10.1097/MJT.0000000000000102.
Primary sclerosing cholangitis (PSC) is a rare, chronic, cholestatic liver disease in which emerging data suggest that oral antibiotics may offer therapeutic effects. We enrolled patients with PSC in a 12-week, open-label pilot study to investigate the efficacy and safety of 550 mg of oral rifaximin twice daily. The primary end point was serum alkaline phosphatase (ALK) at 12 weeks. Secondary end points included (1) serum bilirubin, gamma-glutamyl transpeptidase, and Mayo PSC risk score; (2) fatigue impact scale, chronic liver disease questionnaire, and short form health survey (SF-36) scores; and (3) adverse effects (AEs). Analyses were performed with nonparametric tests. Sixteen patients were enrolled, among whom the median age was 40 years; 13 (81%) were male, 13 had inflammatory bowel disease, and baseline ALK was 342 IU/mL (interquartile range, 275-520 IU/mL). After 12 weeks of treatment, there were no significant changes in ALK (median increase of 0.9% to 345 IU/mL; P = 0.47) or any of the secondary biochemical end points (all P > 0.05). Similarly, there were no significant changes in fatigue impact scale, chronic liver disease questionnaire, or SF-36 scores (all P > 0.05). Three patients withdrew from the study due to AEs; 4 others reported mild AEs but completed the study. In conclusion, although some antibiotics may have promise in treating PSC, oral rifaximin, based on the results herein, seems inefficacious for this indication. Future studies are needed to understand how the antimicrobial spectra and other properties of antibiotics might determine their utility in treating PSC.
原发性硬化性胆管炎（PSC）是一种罕见的慢性胆汁淤积性肝病，新出现的数据表明口服抗生素可能具有治疗作用。我们开展了一项为期12周的开放标签试验性研究，纳入PSC患者，以调查每日两次口服550 mg利福昔明的疗效和安全性。主要终点为12周时的血清碱性磷酸酶（ALK）。次要终点包括：（1）血清胆红素、γ-谷氨酰转肽酶和梅奥PSC风险评分；（2）疲劳影响量表、慢性肝病问卷和简短健康调查问卷（SF-36）评分；（3）不良反应（AE）。采用非参数检验进行分析。共纳入16例患者，其中位年龄为40岁；13例（81%）为男性，13例患有炎症性肠病，基线ALK为342 IU/mL（四分位间距为275 - 520 IU/mL）。治疗12周后，ALK无显著变化（中位升高0.9%至345 IU/mL；P = 0.47），其他次要生化终点也均无显著变化（所有P > 0.05）。同样，疲劳影响量表、慢性肝病问卷或SF-36评分也无显著变化（所有P > 0.05）。3例患者因AE退出研究；另外4例报告有轻度AE，但完成了研究。总之，尽管一些抗生素可能有望用于治疗PSC，但基于本文结果，口服利福昔明在该适应证上似乎无效。需要进一步研究以了解抗生素的抗菌谱和其他特性如何决定其在治疗PSC中的效用。
