Surrogate markers of mucosal healing in inflammatory bowel disease: A systematic review

Abstract

BACKGROUND Mucosal healing (MH) has emerged as a key therapeutic target in inflammatory bowel disease (IBD), and achievement of this goal is documented by endoscopy with biopsy. However, colonoscopy is burdensome and invasive, and substitution with an accurate noninvasive biomarker is desirable. AIM To summarize published data regarding the performance of noninvasive biomarkers in assessing MH in IBD patients. METHODS We conducted a systematic review of studies that reported the performance of biomarkers in diagnosing MH in patients with IBD. The main outcome measure was to review the diagnostic accuracy of serum and fecal markers that showed promising utility in assessing MH. RESULTS We screened 1301 articles, retrieved 46 manuscripts and included 23 articles for full-text analysis. The majority of the included manuscripts referred to fecal markers (12/23), followed by circulatory markers (8/23); only 3/23 of the included manuscripts investigated combined markers (serum and/or fecal markers). Fecal calprotectin (FC) was the most investigated fecal marker for assessing MH. In ulcerative colitis, for cutoff levels ranging between 58 mcg/g and 490 mcg/g, the sensitivity was 89.7%-100% and the specificity was 62%-93.3%. For Crohn’s disease, the cutoff levels of FC ranged from 71 mcg/g to 918 mcg/g (sensitivity 50%-95.9% and specificity 52.3%-100%). The best performance for a serum marker was observed for the endoscopic healing index, which showed a comparable accuracy to the measurement of FC and a higher accuracy than the measurement of serum C-reactive protein. CONCLUSION Several promising biomarkers of MH are emerging but cannot yet substitute for endoscopy with biopsy due to issues with reproducibility and standardization.

Role of Biomarkers in the Diagnosis and Treatment of Inflammatory Bowel Disease

“…In CD, FCP cutoff levels for MH detection ranged from 71 mcg/g (sensitivity 95.9% and specificity 52.3%) to 918 mcg/g (sensitivity 50% and specificity 100%). Although inferior in UC, FCP is also found to be well associated with MH in CD [75].…”

Changes in Salivary Parameters of Oral Immunity after Biologic Therapy for Inflammatory Bowel Disease

“…Fecal calprotectin is commonly used for monitoring the response to treatment and healing of the intestinal mucosa [38,39]. In the only previous study examining the effect of biologic therapy for IBD on salivary parameters, Majster et al [40] compared calprotectin levels in saliva before and after therapy.…”

Colonocyte keratin 7 is expressed de novo in inflammatory bowel diseases and associated with pathological changes and drug-resistance

“…The diagnosis of chronic colon inflammatory conditions is based on symptoms, colonoscopy, pathological findings from biopsies and elevated levels of stool calprotectin. Nevertheless, due to heterogeneity especially in IBD, distinguishing between disease subtypes using current diagnostics methods is challenging, and findings do not fully indicate the prediction of the disease 14 , 15 . Calprotectin is produced by neutrophils and thus is an acute marker of inflammatory activity, and less related to pathological changes in the epithelium.…”