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