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重复进行肠内营养治疗小儿克罗恩病:疗效及预后的预测因素

Repeated exclusive enteral nutrition in the treatment of paediatric Crohn's disease: predictors of efficacy and outcome.

作者信息

Frivolt K, Schwerd T, Werkstetter K J, Schwarzer A, Schatz S B, Bufler P, Koletzko S

机构信息

Dr. von Hauner Children's Hospital, University of Munich Medical Center, Munich, Germany; 2nd Department of Pediatrics, Comenius University Medical School, Bratislava, Slovakia.

出版信息

Aliment Pharmacol Ther. 2014 Jun;39(12):1398-407. doi: 10.1111/apt.12770. Epub 2014 Apr 30.

Abstract

BACKGROUND

Exclusive enteral nutrition (EEN) induces remission and mucosal healing in children with active Crohn's disease (CD).

AIM

To compare short- and long-term outcomes of the first vs. second courses of EEN, and to identify predictors of sustained remission.

METHODS

Retrospective single centre analysis of all patients with CD (6-18 years) treated with EEN over 7.5 years. Patients were excluded if exposed to anti-TNFα or corticosteroids 3 months prior to EEN. Data included disease phenotype, activity, NOD2 genotype, laboratory indices and anthropometrics. Remission and relapse were defined by mathematically weighted Paediatric Crohn's Disease Activity Index (wPCDAI) with 1-year follow-up.

RESULTS

Of 94 patients treated with EEN, 52 fulfilled inclusion criteria (31 male, mean age 13.2 years). Azathioprine was started within the first month in 33/52 patients; 26/52 received a second EEN course. First compared to second EEN revealed higher wPCDAI at start (59 vs. 40, P < 0.0001), tended to higher remission rates after 3 months (92% vs. 77%, n.s.), but showed comparable 1-year relapse rates (67% vs. 70%, median time 231 vs. 145 days, n.s.). Disease activity, weight gain and inflammatory markers showed better improvement with first EEN. Faecal calprotectin >200 μg/g during EEN was associated with shorter remission (median time 157 vs. 287 days, n.s.). Certain NOD2 genotypes were related to higher relapse rates (92% R702W or G908R vs. 50% 1007fs vs. 60% wild-type, P < 0.01).

CONCLUSIONS

Exclusive enteral nutrition induces remission in active Crohn's disease, but efficacy tends to decrease with the second course. Despite early azathioprine use, 1-year relapse rates are high, but may be related to NOD2 genotype.

摘要

背景

全肠内营养(EEN)可诱导活动期克罗恩病(CD)患儿病情缓解并实现黏膜愈合。

目的

比较EEN首个疗程与第二个疗程的短期和长期结局,并确定持续缓解的预测因素。

方法

对7.5年间接受EEN治疗的所有CD(6 - 18岁)患者进行回顾性单中心分析。如果患者在EEN治疗前3个月内使用过抗TNFα或皮质类固醇,则将其排除。数据包括疾病表型、活动度、NOD2基因型、实验室指标和人体测量学数据。通过数学加权的儿童克罗恩病活动指数(wPCDAI)定义缓解和复发情况,并进行1年的随访。

结果

在94例接受EEN治疗的患者中,52例符合纳入标准(31例男性,平均年龄13.2岁)。33/52例患者在第一个月内开始使用硫唑嘌呤;26/52例接受了第二个EEN疗程。与第二个EEN疗程相比,首个疗程开始时的wPCDAI更高(59对40,P < 0.0001),3个月后的缓解率有升高趋势(92%对77%,无统计学差异),但1年复发率相当(67%对70%,中位时间231天对145天,无统计学差异)。疾病活动度、体重增加和炎症标志物在首个EEN疗程中改善更明显。EEN期间粪便钙卫蛋白>200μg/g与缓解期缩短有关(中位时间157天对287天,无统计学差异)。某些NOD2基因型与较高的复发率相关(R702W或G908R为92%,1007fs为50%,野生型为60%,P < 0.01)。

结论

全肠内营养可诱导活动期克罗恩病缓解,但第二个疗程的疗效往往会降低。尽管早期使用了硫唑嘌呤,1年复发率仍较高,但可能与NOD2基因型有关。

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