Year: 2019
Type: dissertation
Study design: Observational Study
Abstract: Background: Hepatobiliary pathologies, including primary sclerosing cholangitis (PSC) and drug-induced liver injury (DILI), are among the most clinically significant extraintestinal manifestations in inflammatory bowel disease (IBD), but paediatric data are scarce. We sought to 1) delineate the IBD phenotype of PSC-IBD in children; 2) investigate the disconnect between the increased colorectal cancer risk and mild clinical course described in PSC-IBD; and 3) examine the association between anti-TNFα exposure and liver injury. Methods: In Aim 1, a single-centre retrospective cohort study, children with PSC-IBD were each matched to two children with ulcerative colitis (UC) or IBD-unclassified (IBD-U). Longitudinal disease activity and anthropometrics were analyzed using mixed effects models, and time to event outcomes using Cox proportional hazards regression. In Aim 2, a single-centre cross-sectional study, correlations between symptoms, fecal calprotectin (FCP), endoscopy and histology were determined and compared between PSC-IBD and UC/IBD-U groups. Multivariable logistic regression and ROC analyses were used. In Aim 3, a large single-centre cohort of children receiving anti-TNFα for IBD was retrospectively reviewed, using multivariable Cox proportional hazards regression and RUCAM scores to assess causality. Results: In Aim 1 (74 PSC-IBD, 148 UC/IBD-U), paediatric PSC-IBD was associated with more pancolitis, rectal sparing and backwash ileitis, milder disease over time, including less frequent colectomy, and linear growth impairment. In Aim 2 (37 PSC-IBD, 50 UC/IBD-U), symptoms underestimated endoscopic and histologic activity in the PSC-IBD group, but FCP had excellent accuracy for mucosal healing. In Aim 3 (659 IBD patients), significant liver enzyme elevations occurred in 7.7% but, in the vast majority, alternate etiologies were identified, and biochemistry normalized spontaneously. There were only 9 patients in whom an alternate cause was not found, including one strongly suggestive case of DILI with autoimmune hepatitis (AIH) features that resolved with medication withdrawal. Conclusions: Paediatric PSC-IBD shares phenotypic features with adult PSC-IBD. We propose growth impairment as a novel, paediatric-specific element of the phenotype and subclinical inflammation as a possible mediator of the increased colorectal cancer risk. While liver enzyme elevations are fairly common in children with IBD receiving anti-TNFα, AIH-like DILI is rare, and most biochemical derangements resolve without medication cessation.
Source: TSpace (University of Toronto)
Author: Amanda Ricciuto
Language: English
Topic: Inflammatory Bowel Disease
Subfield: Gastroenterology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W3097883258