Are faecal markers good indicators of mucosal healing in inflammatory bowel disease?

AIM: To review the published literature concerning the accuracy of faecal inflammatory markers for identifying mucosal healing. METHODS: Bibliographical searches were performed in MEDLINE electronic database up to February 2015, using the following terms: inflammatory bowel disease, Crohn's disease, ulcerative colitis, faecal markers, calprotectin, lactoferrin, S100A12, endoscop*, mucosal healing, remission. In addition, relevant references from these studies were also included. Data were extracted from the published papers including odds ratios with 95% CI, P values and correlation coefficients. Data were grouped together according to each faecal marker, Crohn's disease or ulcerative colitis, and paediatric compared with adult study populations. Studies included in this review assessed mucosal inflammation by endoscopic and/or histological means and compared these findings to faecal marker concentrations in inflammatory bowel diseases (IBD) patient cohorts. Articles had to be published between 1990 and February 2015 and written in English. Papers excluded from the review were those where the faecal biomarker concentration was compared between patients with IBD and controls or other disease groups, those where serum biomarkers were used, those with a heterogeneous study population and those only assessing post-operative disease. RESULTS: The available studies show that faecal markers, such as calprotectin and lactoferrin, are promising non-invasive indicators of mucosal healing. However, due to wide variability in study design, especially with regard to the definition of mucosal healing and evaluation of marker cut offs, the available data do not yet indicate the optimal roles of these markers. Thirty-six studies published between 1990 and 2014 were included. Studies comprised variable numbers of study participants, considered CD (15-164 participants) or UC (12-152 participants) separately or as a combined group (11-252 participants). Eight reports included paediatric patients. Several indices were used to document mucosal inflammation, encompassing eleven endoscopic and eight histologic grading systems. The majority of the available reports focused on faecal calprotectin (33 studies), whilst others assessed faecal lactoferrin (13 studies) and one study assessed S100A12. Across all of the biomarkers, there is a wide range of correlation describing the association between faecal markers and endoscopic disease activity (r values ranging from 0.32 to 0.87, P values ranging from < 0.0001 to 0.7815). Correlation coefficients are described in almost all studies and are used more commonly than outcome measures such as sensitivity, specificity, PPV and/or NPV. Overall, the studies that have evaluated faecal calprotectin and/or faecal lactoferrin and their relationship with endoscopic disease activity show inconsistent results. CONCLUSION: Future studies should report the results of faecal inflammatory markers in the context of mucosal healing with clear validated cut offs.