University of Utah and Intermountain Primary Children's Hospital, Salt Lake City, UT.
University of Toronto, Toronto, Ontario, Canada.
J Pediatr Gastroenterol Nutr. 2020 Oct;71(4):459-464. doi: 10.1097/MPG.0000000000002855.
Most patients with primary sclerosing cholangitis (PSC) also have inflammatory bowel disease (IBD). The liver and colon express MAdCAM-1, a target of lymphocyte homing integrins. Vedolizumab (VDZ) is an α4β7 integrin antibody used to treat IBD. We investigated liver outcomes in children with PSC-IBD treated with VDZ.
Patients were identified within the Pediatric PSC Consortium, a multicenter research registry. Retrospective demographic, phenotypic, biochemical, radiological, histopathologic and IBD data for up to 1 year of VDZ therapy were collected. Liver biochemical and IBD responses were defined as: a 75% or greater reduction in initial γ-glutamyltransferase (GGT), or a GGT that fell to <50 IU/L and improved Mayo endoscopy grade or IBD activity scores after 9 to 12 months.
Thirty-seven patients were identified from 19 centers. VDZ was initiated at median age of 16 years [IQR 15-18], 69% were male, 65% had large duct involvement, 19% had (Metavir F3/F4) fibrosis and 59% had ulcerative colitis. Of 32 patients with abnormal GGT at baseline, 22% had a liver biochemical response after 9 to 12 months. For IBD, 32% achieved remission, 30% had a clinical response, and 38% had no response. Final GGT after 9 to 12 months was 51 [IQR 28-71] in IBD patients in remission versus 127 [IQR 63-226] in those with active IBD, (P = 0.066).
Liver biochemistry worsened over time in IBD unresponsive to VDZ but remained unchanged in IBD patients in remission. VDZ did not improve liver biochemistry in pediatric PSC-IBD. Progressive liver disease may be more common in patients with medically refractory IBD.
大多数原发性硬化性胆管炎（PSC）患者也患有炎症性肠病（IBD）。肝脏和结肠表达 MAdCAM-1，这是淋巴细胞归巢整合素的靶标。Vedolizumab（VDZ）是一种用于治疗 IBD 的α4β7 整合素抗体。我们研究了接受 VDZ 治疗的 PSC-IBD 儿童的肝脏结局。
在儿科 PSC 联盟（一个多中心研究注册中心）中确定了患者。收集了最多 1 年 VDZ 治疗的回顾性人口统计学、表型、生化、影像学、组织病理学和 IBD 数据。肝脏生化和 IBD 反应定义为：初始 γ-谷氨酰转移酶（GGT）降低 75%或更多，或 GGT 降至<50IU/L 以下，9 至 12 个月后梅奥内镜分级或 IBD 活动评分改善。
从 19 个中心确定了 37 名患者。VDZ 开始治疗时的中位年龄为 16 岁[IQR 15-18]，69%为男性，65%有大胆管受累，19%有（Metavir F3/F4）纤维化，59%有溃疡性结肠炎。32 名基线 GGT 异常的患者中，22%在 9 至 12 个月后出现肝脏生化反应。在 IBD 中，32%达到缓解，30%有临床反应，38%无反应。缓解的 IBD 患者 9 至 12 个月时的最终 GGT 为 51[IQR 28-71]，而活动性 IBD 患者为 127[IQR 63-226]，（P=0.066）。
对 VDZ 无反应的 IBD 患者的肝脏生化随时间恶化，但缓解的 IBD 患者的肝脏生化保持不变。VDZ 未改善儿科 PSC-IBD 的肝脏生化。对药物治疗无反应的 IBD 患者可能更常见进行性肝病。
