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Systematic review with meta-analysis: proximal disease extension in limited ulcerative colitis.

ABSTRACT: BACKGROUND:Disease extent in ulcerative colitis is one of the major factors determining prognosis over the long-term. Disease extent is dynamic and a proportion of patients presenting with limited disease progress to more extensive forms of disease over time. AIM:To perform a systematic review and meta-analysis of epidemiological studies reporting on extension of ulcerative colitis to determine frequency of disease extension in patients with limited ulcerative colitis at diagnosis. METHODS:We performed a systematic literature search to identify studies on disease extension of ulcerative colitis (UC) and predictors of disease progression. RESULTS:Overall, 41 studies were eligible for systematic review but only 30 for meta-analysis. The overall pooled frequency of UC extension was 22.8% with colonic extension being 17.8% at 5 years and 31% at 10 years. Extension was 17.8% (95% CI 11.2-27.3) from E1 to E3, 27.5% (95% CI 7.6-45.6) from E2 to E3 and 20.8% (95% CI 11.4-26.8) from E1 to E2. Rate of extension was significantly higher in patients younger than 18 years (29.2% (CI 6.4-71.3) compared to older patients (20.2% (CI 13.0-30.1) (P<.0001). Risk of extension was significantly higher in patients from North America (37.8%) than from Europe (19.6%) (P<.0001). CONCLUSIONS:In this meta-analysis, approximately one quarter of patients with limited UC extend over time with most extension occurring during the first 10 years. Rate of extension depends on age at diagnosis and geographic origin. Predicting those at high risk of disease extension from diagnosis could lead to personalised therapeutic strategies.

SUBMITTER: Roda G

PROVIDER: S-EPMC6350510 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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Systematic review with meta-analysis: proximal disease extension in limited ulcerative colitis.

Roda G G Narula N N Pinotti R R Skamnelos A A Katsanos K H KH Ungaro R R Burisch J J Torres J J Colombel J-F JF

Alimentary pharmacology & therapeutics 20170427 12

<h4>Background</h4>Disease extent in ulcerative colitis is one of the major factors determining prognosis over the long-term. Disease extent is dynamic and a proportion of patients presenting with limited disease progress to more extensive forms of disease over time.<h4>Aim</h4>To perform a systematic review and meta-analysis of epidemiological studies reporting on extension of ulcerative colitis to determine frequency of disease extension in patients with limited ulcerative colitis at diagnosis ...[more]

PMID: 28449361

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Project description:Background and aimsDisease extent varies in ulcerative colitis (UC) from proctitis to left-sided colitis to pancolitis and is a major prognostic factor. When the extent of UC is limited there is often a sharp demarcation between macroscopically involved and uninvolved areas and what defines this or subsequent extension is unknown. We characterized the demarcation site molecularly and determined genes associated with subsequent disease extension.MethodsWe performed RNA sequence analysis of biopsy specimens from UC patients with endoscopically and histologically confirmed limited disease, of which a subset later extended. Biopsy specimens were obtained from the endoscopically inflamed upper (proximal) limit of disease, immediately adjacent to the uninvolved colon, as well as at more proximal, endoscopically uninflamed colonic segments.ResultsDifferentially expressed genes were identified in the endoscopically inflamed biopsy specimens taken at each patient's most proximal diseased site relative to healthy controls. Expression of these genes in the more proximal biopsy specimens transitioned back to control levels abruptly or gradually, the latter pattern supporting the concept that disease exists beyond the endoscopic disease demarcation site. The gradually transitioning genes were associated with inflammation, angiogenesis, glucuronidation, and homeodomain pathways. A subset of these genes in inflamed biopsy specimens was found to predict disease extension better than clinical features and were responsive to biologic therapies. Network analysis revealed critical roles for interferon signaling in UC inflammation and poly(ADP-ribose) polymerase 14 (PARP14) was a predicted key driver gene of extension. Higher PARP14 protein levels were found in inflamed biopsy specimens of patients with limited UC that subsequently extended.ConclusionMolecular predictors of disease extension reveal novel strategies for disease prognostication and potential therapeutic targeting.

Dataset Information

Systematic review with meta-analysis: proximal disease extension in limited ulcerative colitis.

Publications

Systematic review with meta-analysis: proximal disease extension in limited ulcerative colitis.

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