INFECTIOUS COMPLICATIONS IN PATIENTS WITH PRIMARY SCLEROSING CHOLANGITIS AND INFLAMMATORY BOWEL DISEASE: A SYSTEMATIC REVIEW AND META-ANALYSIS

Abstract

Abstract BACKGROUND Primary sclerosing cholangitis (PSC) is a cholestatic immune-mediated liver disease that can be associated with inflammatory bowel disease (IBD) in up to 80% of patients. Those with concurrent PSC-IBD exhibit a distinct disease phenotype with increased risk of complications such as malignancy and pouchitis; however, the risk of infections is not yet clearly defined in this population. AIMS The aims of this systematic review and meta-analysis are (1) to determine the incidence of infections in patients with PSC-IBD and (2) to identify risk factors for infections in this population. METHODS MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials were searched from inception to March 24, 2022 for primary studies that reported incidence or risk factors for infection in adult and pediatric patients with PSC and IBD. Case reports and case series with less than five patients were excluded, as were any studies where infection rates in PSC-IBD patients could not be separated from those with PSC or IBD alone. The primary outcome of this study was incidence of all-cause infections including bacterial, viral, or fungal infections, and sepsis. The secondary outcomes included incidence of site-specific infections and mortality due to infection. A random-effects model was used to calculate pooled odds ratios (OR) with 95% confidence intervals (CI) comparing incidence of all-cause infections in PSC-IBD to those with PSC alone or IBD alone. RESULTS Seventy-one studies were included. The pooled incidence of all-cause infections in patients with PSC-IBD was 21.8% (95% CI 0.17-0.26, I2=95.9%), 31.1% (95% CI 0.16-0.46, I2=93.4%) in those with PSC alone, and 4.4% (95% CI -0.01-0.10, I2=99.2%) in those with IBD alone. Patients with PSC-IBD had an over three-fold increased odds of all-cause infection compared to those with isolated IBD (OR 3.67, 95% CI 2.07-6.50). Patients with PSC-IBD were more likely to develop sepsis (OR 3.35, 95% CI 2.29-4.90) and have infections resulting in mortality (OR 11.25, 95% CI 2.03-62.37) compared to those with IBD. The most common infections in the PSC-IBD group were sepsis followed by clostridioides difficile infection. There was no significant difference in the odds of infection between patients with PSC-IBD and those with PSC alone (OR 1.21, 95% CI 0.68-2.18). However, on sub-group analysis, patients with PSC-IBD undergoing liver transplantation (LT) were more likely to develop infection post-LT compared to those with PSC alone (OR 4.86, 95% CI, 2.32-10.17), with cytomegalovirus (CMV) being the most commonly reported infection. CONCLUSION Compared to those with IBD, patients with PSC-IBD appear to be at a higher risk of infection and resultant complications such as sepsis and death. Future studies are needed to elucidate specific risk factors such as immunosuppressive therapy and disease activity.