Supplementary Material for: Mucosal healing of ulcerative colitis based on endoscopic diagnosis, histopathology, and mucosal inflammatory mediators

Mucosal healing is necessary to maintain the long-term remission of ulcerative colitis (UC). Currently, the gold standard for assessing mucosal healing is endoscopic diagnosis. The Mayo Endoscopic Subscore (MES) is the most commonly used index for evaluating endoscopic mucosal healing; however, a certain number of patients may experience relapse during the clinical course of the disease, even at MES 0, where the mucosa appears to be in a state of healing. Therefore, the usefulness of image-enhanced endoscopy, such as Narrow-Band Imaging, Linked Color Imaging, Autofluorescence Imaging, Red Dichromatic Imaging, Texture and Color Enhancement Imaging, and i-Scan, has been increasingly reported in recent years for the diagnosis of complete mucosal healing without recurrence. The importance of histological healing has also been emphasized in recent years. The three main histological scoring systems currently used are the Geboes score, Nancy Histological Index, and Robarts Histologic Index. When combined with MES, these histological assessments have been reported to considerably predict UC relapse. However, the relevance of diagnosing histological activity in patients with MES 0 and endoscopically confirmed mucosal healing remains debatable. Cytokines play an important role in UC pathogenesis, as evidenced by the effectiveness of biologics and small molecules that target specific cytokines in treating refractory cases. Therefore, the concept of “molecular healing” has recently been proposed to describe the regulation of cytokine profiles during mucosal healing in patients with UC. Specific mucosal cytokine expression correlates with endoscopic severity, predicts UC relapse, and indicates the therapeutic efficacy of biologics. This highlights the growing interest in understanding UC pathogenesis based on cytokine expression. Defining mucosal healing in UC based on mucosal cytokine expression is expected to evolve as a next-generation diagnostic approach. Therefore, accurate diagnosis of mucosal healing in patients with UC is essential. In this review, we describe mucosal healing from the perspective of mucosal gene expression, which has recently gained attention alongside advances in conventional endoscopic and histological diagnostics.