DOP121Patients with IBD Are at Increased Risk of Metabolic Dysfunction–Associated Steatotic Liver Disease, Independent of Classic Metabolic Risk Factors

Abstract Background Metabolic dysfunction–associated steatotic liver disease (MASLD) is traditionally linked to metabolic risk factors such as insulin resistance, obesity and dyslipidemia, but emerging evidence suggests that patients with inflammatory bowel disease (IBD) may also be at risk. We aimed to evaluate the association between IBD and MASLD using a large, nationwide population-based cohort. Methods We analyzed data from the epi-IIRN cohort, covering 98% of Israel’s population. Patients with IBD were identified using validated diagnostic algorithms and matched 1:3 with non-IBD controls. MASLD was defined based on relevant ICD-9 codes. Adjusted prevalence rates were compared between groups. Time to MASLD diagnosis was assessed using Kaplan–Meier analysis, and predictors of MASLD were evaluated with Cox regression models. Results A total of 37,672 patients with IBD (56% Crohn’s disease CD) were compared with 83,303 matched controls. MASLD prevalence was significantly higher among patients with IBD (8.0% vs. 6.0%, P 0.001), in both the CD (8.3% vs. 5.5%) and ulcerative colitis (7.7% vs. 6.6%) subgroups (p 0.001 for all). MASLD rates were higher among patients with IBD before (3.7% vs. 2.7%) and after (4.3% vs. 3.3%) the IBD diagnosis, compared with non-IBD controls (P 0.001). In addition, time to MASLD development was shorter in patients with IBD vs. controls (P 0.001, Figure 1A). Patients with IBD and MASLD had lower BMI (29.7±5.7 vs. 31.3±6.2), LDL (102±41 vs. 109±46), ALT (29 20-49 vs. 35 22-56) and GGT (35 22-67 vs. 54 27-88), and lower rates of hypertension (36% vs 42%), compared to controls with MASLD (P 0.001 for all comparisons). Patients with IBD with MASLD had higher rates of mild disease activity (39% vs. 32%), and lower rates of steroid dependency (12% vs. 16%), immunomodulator exposure (26% vs. 34%), biologic exposure (18% vs. 31%) and surgeries (5% vs. 7%), compared to patients with IBD without MASLD (P 0.001 for all comparisons). Moreover, various features associated with mild IBD, including lack of steroid use, steroid dependency or biologic use were associated with shorter time to MASLD development (Figure 1B-E). Finally, mild disease activity was an independent predictor of MASLD development in patients with CD. Conclusion MASLD is more common in patients with IBD than in controls, and presents with a distinct profile characterized by lower metabolic and liver biomarkers and milder disease activity. These findings suggest a potentially novel, IBD-specific pathway for fatty liver disease that warrants further research. Conflict of interest: Shouval, Dror: Lecturing fee - Takeda SAB - Tracells Lujan, Rona: No conflict of interest Tal-Shifman, Noa: No conflict of interest Gepner, Yftach: No conflict of interest Ben-Tov, Amir: No conflict of interest Zacay, Galia: No conflict of interest Matz, Eran: No conflict of interest Zekaria, Shir: No conflict of interest Dotan, Iris: Grant: The Leona M. and Harry B. Helmsley Charitable Trust, Altman Research, Pfizer, BMS Personal Fees: Pfizer, Falk, Ferring, Abbvie, Janssen, Celltrion, Takeda, Celgene/BMS, Gilead, Galapagos, Materia Prima, Sandoz, Sublimity, Sangamo, Spyre, Eli-Lilly, Harp Diagnostics, Gutreat, Astra Zeneca Turner, Dan: Consultation fee: Janssen, Pfizer, Ferring, Abbvie, Takeda, Prometheus Biosciences, Lilly, SorrisoPharma, Boehringer Ingelheim, Galapagos, BMS, AlfaSigma, Merck, Gentech Research support: Janssen, Abbvie, Takeda, Pfizer Royalties: Shaare Zedek Medical Center, Hospital for Sick Children Shamir, Raanan: No conflict of interest