Abstract Background Metabolic dysfunction-associated steatotic liver disease (MASLD) is increasing in prevalence, affecting approximately 30% of the world population. MASLD elevates the risk of liver fibrosis and hepatocellular carcinoma, with risk factors including obesity and type 2 diabetes. Inflammatory bowel disease (IBD) is considered a separate risk factor for MASLD development, as IBD-patients have a higher prevalence of MASLD than the general population even with fewer associated risk factors. The Fibrosis-4 (FIB-4) score is a commonly used non-invasive tool to assess the risk of liver fibrosis based on age, blood AST, ALT and platelet count1. The aim of this study was to assess the longitudinal change of the FIB-4 score in IBD-patients undergoing therapy to evaluate the risk of liver fibrosis. Methods A retrospective analysis of 3685 longitudinal observations from 361 IBD-patients was performed based on previously published data2. We computed the FIB-4 score at each observation, with a mean follow-up of 39 months (±24.5). We applied a linear mixed effects model correcting for sex, body-mass-index (BMI), CRP, chronic inflammatory disease (CID) of the joints or skin, and use of prednisone, methotrexate, and advanced therapies (ATs). Patients were separated into those that had never received ATs, those who had always received the same AT (most likely responding to that therapy), and those who had undergone an AT escalation during their clinical follow-up. Results As expected under IBD treatment, BMI increased, while CRP decreased significantly in time, especially in those patients always receiving the same AT (p 0.01). FIB-4 scores increased significantly during follow-up. There was a strong positive association between FIB-4-score and BMI (p 0.001), and presence of other CIDs (p 0.05). Surprisingly, FIB-4 was negatively correlated with CRP as an inflammatory marker (p 0.001). Patients always receiving the same AT had a significant increase in FIB-4 over time compared to those who were never exposed to an AT (p 0.05). However, this could be driven by the significant decrease in thrombocytes observed in patients maintained on the same AT, likely reflecting reduced inflammation (p 0.05). As lower thrombocytes result in higher FIB-4 scores, the increase in FIB-4 in these patients could simply reflect lower inflammation rather than a higher steatosis risk. This interpretation aligns with the inverse correlation between FIB-4 and CRP. Conclusion Our data therefore indicates that FIB-4 may misclassify liver fibrosis risk in IBD, and a more granular analysis incorporating IBD-specific inflammation indices and comorbidity data (e.g., diabetes, hypertension) is needed to disentangle the relationship between IBD, MASLD, and liver fibrosis risk. References: 1. Sterling RK, Lissen E, Clumeck N, et al. Development of a simple noninvasive index to predict significant fibrosis in patients with HIV/HCV coinfection. Hepatology. 2006;43(6):1317-1325. doi:10.1002/hep.21178 EBioMedicine. 2024;102:105056. doi:10.1016/j.ebiom.2024.105056 2. Harris DMM, Szymczak S, Schuchardt S, et al. Tryptophan degradation as a systems phenomenon in inflammation - an analysis across 13 chronic inflammatory diseases. EBioMedicine. 2024;102:105056. doi:10.1016/j.ebiom.2024.105056 Conflict of interest: Mrs. Guggeis, Martina: No conflict of interest Harris, Danielle: No conflict of interest Szymczak, Silke: grant GUIDE-IBD from the German Ministry of Education and Research (BMBF, 031L0188A) Tran, Florian: Grant: Sanofi/Regeneron Personal Fees: Speaker’s fees: Abbvie, Bristol-Myers-Squibb, Celltrion Healthcare, Dr Falk Pharma, Eli Lilly, Ferring Pharmaceuticals, J & J, Sanofi, Takeda Consulting honoraria: AbbVie, J & J, Takeda Non-financial Support: Sanofi for statistical analysis Welz, Lina: Received support from Celltrion for independent reporting from scientific congresses. Schreiber, Stefan Wolfgang: Personal Fees: AbbVie, Alfasigma, Amgen, Arena, Biogen, Boehringer Ingelheim, Bristol Meyers Squibb, Celgene, Celltrion, Falk, Ferring, Fresenius Kabi, Galapagos, Gilead, IMAB, Janssen, Lilly, MSD, Mylan, Novartis, Pfizer, Protagonist, Provention Bio, Roche, Sandoz/Hexal, Shire, Takeda, Theravance Aden, Konrad: Personal Fees: Lecture fee: Takeda, Janssen, Lilly, Abbvie Consulting fee: Takeda, Jannsen, Lilly, Guidepoint Rosenstiel, Philip: stock ownership Gerion
Guggeis et al. (Thu,) studied this question.