Risk stratification of IBD-associated liver disease using routinely collected biomarkers from a large-scale real-world dataset

Abstract

Objective: inflammatory bowel disease (IBD)-associated liver diseases (IBDALDs) are associated with hepatobiliary damage and malignancy, with diagnosis often delayed by heterogeneous presentation. We evaluated whether routinely collected biomarkers—at IBD diagnosis and during follow-up—can risk-stratify for IBDALD.

Methods: this observational retrospective longitudinal study included 1571 patients with IBD at University Hospital Southampton. Biomarkers including alanine aminotransferase (ALT), alkaline phosphatase (ALP) and erythrocyte sedimentation rate (ESR) (n=335 605 results) were summarised as patient-level medians within ±6 months of IBD diagnosis. Patients with pre-existing IBDALD were excluded. A 1:4 matched case-control design (age, sex, IBD subtype) was applied. Conditional logistic regression assessed associations with biomarkers (continuous values and binary—abnormal vs normal) and IBDALD. Longitudinal trends were evaluated using locally estimated scatterplot smoothing (LOESS) and linear mixed-effects models (LMMs).

Results: median age of IBD diagnosis was 18.0 years, median follow-up 11.5 years. Thirty-five IBDALD cases were identified (27 post-IBD); median time to IBDALD was 4.5 years. At IBD diagnosis, cases had elevated ALT, ALP and ESR (p<0.01). In case-control matching, ALT (OR=1.04 per U/L; 95% CI 1.01 to 1.07; p=0.012), ALP (OR=1.01; 95% CI 1.00 to 1.02; p=0.014) and ESR (OR=1.05; 95% CI 1.00 to 1.09; p=0.034) were associated with IBDALD. Any abnormal ALT (OR=5.10; 95% CI 1.57 to 16.59; p=0.0068) and ALP (OR=15.33; 95% CI 1.87 to 125.77; p=0.0110) were strongly associated. LOESS plots and LMMs demonstrated distinct biomarker trajectories (ALT, ALP) preceding IBDALD.

Conclusion : real-world biomarker data can support early risk stratification for IBDALD. Elevated ALT and ALP at IBD diagnosis and distinct longitudinal trajectories highlight the need for follow-up to biomarker normalisation, with persistent abnormalities prompting earlier hepatobiliary investigation to reduce diagnostic delay and improve outcomes.

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Identifiers

ORCID for Zachary Green: orcid.org/0000-0002-2907-5538

ORCID for Alex Z. Kadhim: orcid.org/0000-0001-5600-0411

ORCID for Lynn Kaythy Win: orcid.org/0000-0002-2624-0390

ORCID for Gabriela Czanner: orcid.org/0000-0002-1157-2093

ORCID for Sarah Ennis: orcid.org/0000-0003-2648-0869

ORCID for James John Ashton: orcid.org/0000-0003-0348-8198

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