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（Crohn’s disease, CD）的小肠病变大多可超出回结肠镜的探查范围，且尚无金标准影像学检查手段用于其筛查，这提示亟需开发最优生物标志物。本研究旨在比较C反应蛋白（C-reactive protein, CRP）、粪便钙卫蛋白（faecal calprotectin, FC）以及富亮氨酸α2糖蛋白（leucine-rich alpha-2 glycoprotein, 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。前瞻性检测了临床实践中医师筛选的静止期克罗恩病患者的CRP、FC及LRG水平，这些患者均接受了影像学检查，包括胶囊或球囊辅助内镜、磁共振小肠造影或肠道超声。小肠黏膜愈合（mucosal healing, MH）定义为无溃疡形成。本研究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 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（area under the curve, AUC）分别为0.74（95%置信区间0.61~0.87）、0.69（0.52~0.81）以及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截断值取16μg/ml时，阳性预测值最高，达1.00，特异性亦为1.00；而当截断值取9μg/ml时，阴性预测值最高（0.71），灵敏度为0.89。

讨论/结论 LRG可通过两个截断值准确检测和/或排除小肠病变。