Supplementary Material for: Optimal use of serum leucine-rich alpha-2 glycoprotein as a biomarker for small bowel lesions of Crohn's disease

Introduction A large proportion of small bowel lesions in Crohn’s disease (CD) may exist beyond the reach of ileocolonoscopy and there is no gold standard imaging modality to screen them, suggesting the need for optimal biomarkers. We aimed to compare the usefulness of C-reactive protein (CRP), faecal calprotectin (FC), and leucine-rich alpha-2 glycoprotein (LRG) in determining small bowel lesions of CD. Methods This was a cross-sectional observational study. CRP, FC, and LRG were prospectively measured in patients with quiescent CD who underwent imaging examinations (capsule or balloon-assisted endoscopy, magnetic resonance enterography, or intestinal ultrasound) selected by the physician in clinical practice. Mucosal healing (MH) of the small bowel was defined as a lack of ulcers. Patients with a Crohn’s disease activity index > 150 and active colonic lesions were excluded. Results A total of 65 patients (27, MH; 38, small bowel inflammation) were analysed. The area under the curve (AUC) of CRP, FC, and LRG was 0.74 (95% confidence interval 0.61-0.87), 0.69 (0.52-0.81), and 0.77 (0.59-0.85), respectively. The AUC of FC and LRG in a subgroup of 61 patients with CRP < 3 mg/l (26, MH; 32, small bowel inflammation) was 0.68 (0.50-0.81), and 0.74 (0.54-0.84), respectively. The cut-off of 16 μg/ml of LRG showed the highest positive predictive value of 1.00 with specificity of 1.00 while negative predictive value was highest (0.71) with sensitivity of 0.89 at the cut-off of 9 μg/ml. Discussion/Conclusion LRG can accurately detect and/or exclude the small bowel lesions by two cut-off values.

引言
克罗恩病（CD）的小肠病变中，有相当比例的病灶超出回结肠镜的检查范围，且目前尚无金标准影像学检查手段用于此类病变的筛查，这提示亟需开发最优的生物标志物。本研究旨在比较C反应蛋白（CRP）、粪便钙卫蛋白（FC）以及富亮氨酸α2糖蛋白（LRG）在诊断克罗恩病小肠病变中的应用价值。

方法
本研究为横断面观察性研究。对临床实践中医师筛选的、接受影像学检查（胶囊内镜或球囊辅助小肠内镜、磁共振小肠造影或肠道超声）的静止期克罗恩病患者，前瞻性检测其CRP、FC及LRG水平。将小肠黏膜愈合（MH）定义为无溃疡形成。排除克罗恩病活动指数＞150以及存在活动性结肠病变的患者。

结果
本研究共纳入65例患者进行分析，其中27例达到小肠黏膜愈合标准，38例存在小肠炎症。CRP、FC及LRG的受试者工作特征曲线下面积（AUC）分别为0.74（95%置信区间0.61~0.87）、0.69（0.52~0.81）及0.77（0.59~0.85）。在61例CRP＜3mg/L的亚组患者（26例黏膜愈合，32例小肠炎症）中，FC与LRG的AUC分别为0.68（0.50~0.81）与0.74（0.54~0.84）。当LRG截断值为16μg/ml时，其阳性预测值最高，达1.00，特异性为1.00；而当截断值为9μg/ml时，其阴性预测值最高（0.71），灵敏度为0.89。

讨论与结论
LRG可通过两个截断值准确检测和/或排除克罗恩病的小肠病变。