Karemera Manon, Verce Marko, Roumain Martin, Muccioli Giulio G, Cani Patrice D, Everard Amandine, Stephenne Xavier, Sokal Etienne
From the Department of Pediatrics, Division of Pediatric Gastroenterology and Hepatology, Cliniques universitaires Saint-Luc, Brussels, Belgium.
Metabolism and Nutrition Research Group, Louvain Drug Research Institute, Walloon Excellence in Life Sciences and Biotechnology (WELBIO), UCLouvain, Université catholique de Louvain, Brussels, Belgium.
JPGN Rep. 2023 Jul 17;4(3):e334. doi: 10.1097/PG9.0000000000000334. eCollection 2023 Aug.
Autoimmune hepatitis and primary sclerosing cholangitis (PSC) can both be present, resulting in autoimmune sclerosing cholangitis (ASC). PSC physiopathology could be based on the cross-talk between gut microbiota and bile acids (BAs); antibiotics are an innovative therapy. This pilot study assesses metronidazole (MTZ)'s effectiveness in ASC or PSC patients according to the stage of the disease, and its effects on biochemical parameters, BA profiles, and gut microbiota.
ASC or PSC patients from Cliniques universitaires Saint-Luc's pediatric hepato-gastroenterology division were enrolled retrospectively and prospectively; both datasets were merged. MTZ was administered over at least 14 days on top of standard treatment (ursodeoxycholic acid, azathioprine, and steroids). Fecal and blood samples were collected before (T0) and at MTZ day 14 (T14). Sustained biochemical remission was defined by the reduction of transaminases (AST and ALT), gamma-glutamyl transferase (GGT), and CRP until 12 months post-MTZ.
A total of 18 patients (mean age, 13.2 ± 4.5 years) were enrolled (13 ASC and 5 PSC), and divided in remission or relapse patients. CRP, AST, ALT, and GGT levels decreased post-MTZ in both groups (excepting GGT in relapse patients), with decreases between T0 and T14 being significant for AST and ALT. Relapse patients were older ( = 0.0351) and in late-disease stage, with mainly large-duct PSC ( = 0.0466). In remission patients, the mean plasma relative abundance of hydrophilic BA increased by +6.3% ( = 0.0391) after MTZ. Neither at baseline nor T14, there were significant differences in gut microbiota recorded.
These data are likely indicative of long-term benefits following MTZ therapy at early-stage ASC or PSC, with increased hydrophilic BA abundance. Multicenter prospective studies are needed.
自身免疫性肝炎和原发性硬化性胆管炎（PSC）可能同时存在，导致自身免疫性硬化性胆管炎（ASC）。PSC的病理生理学可能基于肠道微生物群与胆汁酸（BAs）之间的相互作用；抗生素是一种创新疗法。这项前瞻性研究根据疾病阶段评估甲硝唑（MTZ）对ASC或PSC患者的疗效，及其对生化参数、BA谱和肠道微生物群的影响。
回顾性和前瞻性纳入了圣卢克大学医院儿科肝胃肠病科的ASC或PSC患者；将两个数据集合并。在标准治疗（熊去氧胆酸、硫唑嘌呤和类固醇）基础上，MTZ至少给药14天。在MTZ治疗前（T0）和第14天（T14）采集粪便和血液样本。持续生化缓解定义为转氨酶（AST和ALT）、γ-谷氨酰转移酶（GGT）和CRP在MTZ治疗后12个月内降低。
共纳入18例患者（平均年龄13.2±4.5岁）（13例ASC和5例PSC），分为缓解期或复发期患者。两组患者MTZ治疗后CRP、AST、ALT和GGT水平均下降（复发期患者GGT除外），T0至T14期间AST和ALT下降显著。复发期患者年龄较大（P = 0.0351）且处于疾病晚期，主要为大胆管PSC（P = 0.0466）。在缓解期患者中，MTZ治疗后亲水性BA的平均血浆相对丰度增加了+6.3%（P = 0.0391）。在基线期和T14时，肠道微生物群均无显著差异。
这些数据可能表明早期ASC或PSC患者接受MTZ治疗后具有长期益处，亲水性BA丰度增加。需要进行多中心前瞻性研究。
