尽管证据表明在内镜检查活检结果为阴性（即正常黏膜）的个体中，结肠和直肠癌的风险可持续降低10年，但仍有人担心这些人在其他长期健康结果方面的影响。本研究旨在探讨内镜检查活检结果为正常黏膜后炎症性肠病（IBD）的长期风险。 在这项全国性队列研究中，我们确定了瑞典所有在1965年至2016年期间进行下消化道或上消化道正常黏膜活检的个体（暴露组，下消化道和上消化道活检人数分别为200495和257,192），与其配对的人口群体参照（下位组别人数为989,484和1,268,897），以及未暴露的兄弟姐妹（人数分别为221,179和274,529）。采用柔性参数模型估计风险比（HR）来衡量内镜检查活检结果为正常黏液膜和IBD之间的关联，估计IBD的累积发生率，同时估计95％置信区间（CI）。为避免检测偏差、监测偏差或逆因果效应，第一次内镜检查后6个月被排除在外。在约10年的中位随访时间内，下消化道正常黏膜活检的4,853个个体发展为IBD（2.4％），而人口参照组为0.4％。这相当于每10,000人年的患病率（IR）分别为20.39和3.39，或者是每37个检查正常内镜暴露的个体中，有1个额外的IBD病例在活检后30年内估计发生。暴露组患者的总体IBD风险持续较高（平均HR = 5.56；95％CI： 5.28至5.85），而溃疡性结肠炎（UC）(平均HR = 5.20；95％CI：4.85至5.59)和克罗恩病（CD）（平均HR = 6.99；95％CI：6.38至7.66）的风险也持续较高。在兄弟比较中，总体IBD的平均HR分别为3.27（3.05至3.51）、UC为3.27（2.96至3.61）和CD为3.77（3.34至4.26）。对于上消化道正常黏膜活检的个体，CD的平均HR分别为2.93（2.68至3.21）和2.39（2.10至2.73），与人口参照组和未暴露的兄弟姐妹相比。增加的IBD风险持续至少30年，研究结论受到检查指征数据的缺乏和IBD风险或保护因素的未测量残余混杂因素的影响。结束检查结果为正常黏膜的内镜活检与IBD发病率的升高相关，持续至少30年。这可能表明了IBD症状的可观察期和早期IBD患者的不完整诊断。版权所有：©2023 Sun等。本文是一篇开放获取文章，在注明原作者和来源的情况下，允许任何媒介进行无限制的使用、下载和再使用。

Although evidence suggests a persistently decreased risk of colorectal cancer for up to 10 years among individuals with a negative endoscopic biopsy result (i.e., normal mucosa), concerns have been raised about other long-term health outcomes among these individuals. In this study, we aimed to explore the long-term risk of inflammatory bowel disease (IBD) after an endoscopic biopsy with normal mucosa.In the present nationwide cohort study, we identified all individuals in Sweden with a lower or upper gastrointestinal (GI) biopsy of normal mucosa during 1965 to 2016 (exposed, n = 200,495 and 257,192 for lower and upper GI biopsy, respectively), their individually matched population references (n = 989,484 and 1,268,897), and unexposed full siblings (n = 221,179 and 274,529). Flexible parametric model estimated hazard ratio (HR) as an estimate of the association between a GI biopsy of normal mucosa and IBD as well as cumulative incidence of IBD, with 95% confidence interval (CI). The first 6 months after GI biopsy were excluded to avoid detection bias, surveillance bias, or reverse causation. During a median follow-up time of approximately 10 years, 4,853 individuals with a lower GI biopsy of normal mucosa developed IBD (2.4%) compared to 0.4% of the population references. This corresponded to an incidence rate (IR) of 20.39 and 3.39 per 10,000 person-years in the respective groups or 1 extra estimated IBD case among 37 exposed individuals during the 30 years after normal GI biopsy. The exposed individuals had a persistently higher risk of overall IBD (average HR = 5.56; 95% CI: 5.28 to 5.85), ulcerative colitis (UC, average HR = 5.20; 95% CI: 4.85 to 5.59) and Crohn's disease (CD, average HR = 6.99; 95% CI: 6.38 to 7.66) than their matched population references. In the sibling comparison, average HRs were 3.27 (3.05 to 3.51) for overall IBD, 3.27 (2.96 to 3.61) for UC, and 3.77 (3.34 to 4.26) for CD. For individuals with an upper GI biopsy of normal mucosa, the average HR of CD was 2.93 (2.68 to 3.21) and 2.39 (2.10 to 2.73), compared with population references and unexposed full siblings, respectively. The increased risk of IBD persisted at least 30 years after cohort entry. Study limitations include lack of data on indications for biopsy and potential residual confounding from unmeasured risk or protective factors for IBD.Endoscopic biopsy with normal mucosa was associated with an elevated IBD incidence for at least 30 years. This may suggest a substantial symptomatic period of IBD and incomplete diagnostic examinations in patients with early IBD.Copyright: © 2023 Sun et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.