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抗TNFα治疗儿童及青少年炎症性肠病合并自身免疫性肝病

Anti-TNFα Treatment in Children and Adolescents With Combined Inflammatory Bowel Disease and Autoimmune Liver Disease.

作者信息

Nedelkopoulou Natalia, Vadamalayan Babu, Vergani Diego, Mieli-Vergani Giorgina

机构信息

Paediatric Liver, GI and Nutrition Centre, Mowat Labs and Institute of Liver Studies, King's College Hospital, London, UK.

出版信息

J Pediatr Gastroenterol Nutr. 2018 Jan;66(1):100-105. doi: 10.1097/MPG.0000000000001759.

Abstract

OBJECTIVES

Inflammatory bowel disease (IBD) and autoimmune liver disease (AILD) are closely associated, the former often dictating progression of the latter. Antibodies to tumor necrosis factor alpha (anti-TNFα) are effective in the management of IBD, but may cause liver injury.

METHODS

Retrospective review of medical records of patients with juvenile AILD who received anti-TNFα for IBD to evaluate the safety and efficacy of anti-TNFα.

RESULTS

Eleven patients (6 boys), ages 9 to 15 years (median 13 years) were identified. Ten had ulcerative colitis and 1 Crohn disease; 2 had autoimmune hepatitis type 1 and 9 autoimmune hepatitis-sclerosing cholangitis variant. All patients were started on infliximab (IFX, 5 mg/kg) and 2 required dose increase (10 mg/kg); 3 of 11 switched to adalimumab due to allergic reaction or nonresponse. Three received adalimumab after losing response or developing antibodies to IFX. Liver function tests (LFTs) improved in 5, 1 continued to have stably abnormal LFTs and 2 maintained normal LFTs. Patients on adalimumab showed stable or improved liver function compared to pretreatment status. Six of 8 treated with a full course of IFX maintained clinical remission of IBD for 6 months to 2.5 years; of the 6 patients treated with adalimumab, 1 sustained IBD clinical remission for 24 months, 2 achieved remission only after tacrolimus addition and 3 did not respond.

CONCLUSIONS

IBD in patients with AILD can be aggressive, requiring escalation to anti-TNFα or switching to other biologics. In this series, anti-TNFα did not impair liver function and improved gut disease in most of the patients, indicating that it can be beneficial and safe.

摘要

目的

炎症性肠病(IBD)与自身免疫性肝病(AILD)密切相关,前者常决定后者的进展。肿瘤坏死因子α抗体(抗TNFα)对IBD的治疗有效,但可能导致肝损伤。

方法

回顾性分析接受抗TNFα治疗IBD的青少年AILD患者的病历,以评估抗TNFα的安全性和有效性。

结果

共纳入11例患者(6例男孩),年龄9至15岁(中位年龄13岁)。其中10例患有溃疡性结肠炎,1例患有克罗恩病;2例为1型自身免疫性肝炎,9例为自身免疫性肝炎-硬化性胆管炎变异型。所有患者均开始使用英夫利昔单抗(IFX,5mg/kg),2例需要增加剂量(10mg/kg);11例中有3例因过敏反应或无反应而改用阿达木单抗。3例在失去反应或产生抗IFX抗体后改用阿达木单抗。5例患者的肝功能检查(LFTs)有所改善,1例LFTs持续异常,2例LFTs维持正常。与治疗前相比,使用阿达木单抗的患者肝功能稳定或改善。8例接受完整疗程IFX治疗的患者中有6例IBD临床缓解持续6个月至2.5年;在6例接受阿达木单抗治疗的患者中,1例IBD临床缓解持续24个月,2例仅在加用他克莫司后实现缓解,3例无反应。

结论

AILD患者的IBD可能较为严重,需要升级使用抗TNFα或改用其他生物制剂。在本系列研究中,抗TNFα并未损害肝功能,且在大多数患者中改善了肠道疾病,表明其有益且安全。

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