Do Colonic Mucosal Tumor Necrosis Factor Alpha Levels Play a Role in Diverticular Disease? A Systematic Review and Meta-Analysis

Diverticular disease (DD) is the most frequent condition in the Western world that affects the colon. Although chronic mild inflammatory processes have recently been proposed as a central factor in DD, limited information is currently available regarding the role of inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-a). Therefore, we conducted a systematic review and meta-analysis aiming to assess the mucosal TNF-a levels in DD. We conducted a systematic literature search using PubMed, Embase, and Scopus to identify observational studies assessing the TNF-a levels in DD. Full-text articles that satisfied our inclusion and exclusion criteria were included, and a quality assessment was performed using the Newcastle-Ottawa Scale (NOS). The principal summary outcome was the mean difference (MD). The results were reported as MD (95% confidence interval (CI)). A total of 12 articles involving 883 subjects were included in the qualitative synthesis, out of which 6 studies were included in our quantitative synthesis. We did not observe statistical significance related to the mucosal TNF-a levels in symptomatic uncomplicated diverticular disease (SUDD) vs. the controls (0.517 (95% CI -1.148-2.182)), and symptomatic vs. asymptomatic DD patients (0.657 (95% CI -0.883-2.196)). However, the TNF-a levels were found to be significantly increased in DD compared to irritable bowel disease (IBS) patients (27.368 (95% CI 23.744-30.992)), and segmental colitis associated with diverticulosis (SCAD) vs. IBS patients (25.303 (95% CI 19.823-30.784)). Between SUDD and the controls, as well as symptomatic and asymptomatic DD, there were no significant differences in the mucosal TNF-a levels. However, the TNF-a levels were considerably higher in DD and SCAD patients than IBS patients. Our findings suggest that TNF-a may play a key role in the pathogenesis of DD in specific subgroups and could potentially be a target for future therapies.