Abstract Background Liver steatosis (LS) is a common extraintestinal manifestation of inflammatory bowel disease (IBD), but the impact of advanced therapies on hepatic health is still unclear. This study aimed to evaluate the dynamics of LS following the initiation of advanced therapies, including anti-tumor necrosis factor (anti-TNF) agents, anti-integrin therapy, anti-interleukin-12/23 blockade, and Janus kinase inhibition in treatment-naïve IBD patients. Methods In this prospective single-center cohort study, adults with IBD who were starting advanced therapy and had baseline LS—defined as an attenuation coefficient (ATT) of ≥ 0.63 dB/cm/MHz and alanine aminotransferase (ALT) levels 40 IU/L—were followed for 26 weeks. Shear-wave elastography and laboratory testing were conducted at baseline and at week 26. Endoscopic remission and trough concentrations of the therapies were assessed. Each patient served as their own control. The primary outcome was the change in ATT, while secondary outcomes included changes in ALT levels and the effects of remission and drug exposure. Results Out of 174 patients initiating advanced therapies, 68 (39%) had LS (49 with ulcerative colitis and 19 with Crohn’s disease). Anti-TNF agents significantly improved LS: infliximab reduced ATT from 0.76 to 0.73 dB/cm/MHz (p = 0.041) and ALT from 50.2 to 45.6 IU/L (p = 0.035), while adalimumab reduced ATT from 0.83 to 0.79 (p = 0.009) and ALT from 56.3 to 50.9 IU/L (p = 0.010). Vedolizumab did not show an overall effect (ATT changed from 0.80 to 0.79, p = 0.268), but patients with both adequate trough levels and endoscopic remission showed improvement (ATT changed from 0.79 to 0.77, p = 0.031). In contrast, non-responders experienced worsening (ATT changed from 0.81 to 0.84, p = 0.033). Ustekinumab (n = 14) exhibited a neutral effect, with no significant changes in ATT (0.80 to 0.82, p = 0.217) or ALT (49.8 to 50.3, p = 0.421), regardless of remission status. Tofacitinib (n = 9) was associated with an increase in ALT (44.8 to 59.7, p = 0.004) and a borderline increase in ATT (0.74 to 0.80, p = 0.051), suggesting progression of LS. Overall, the most favorable LS outcomes were observed in patients achieving both endoscopic remission and adequate drug exposure across treatment classes. Conclusion Anti-TNF agents significantly improve LS in IBD, while vedolizumab benefits only those with both pharmacokinetic adequacy and endoscopic remission. Ustekinumab appears metabolically neutral, and tofacitinib may worsen LS. When selecting advanced therapy, hepatic comorbidities should be considered, and longer-term follow-up is needed to elucidate the hepatic impact of different therapeutic mechanisms. References: Papaefthymiou A, Potamianos S, Goulas A, Doulberis M, Kountouras J, Polyzos SA. Inflammatory bowel disease–associated fatty liver disease: the potential effect of advanced therapies. J Crohns Colitis. 2022;16(6):852–862. Fazel Y, Koenig AB, Sayiner M, Goodman ZD, Younossi ZM. Epidemiology and natural history of non-alcoholic fatty liver disease. Metabolism. 2016;65(8):1017–1025. Rodriguez-Duque JC, Calleja JL, Iruzubieta P, Hernández-Conde M, Rivas-Rivas C, Vera MI, et al. Increased risk of metabolic dysfunction–associated fatty liver disease and liver fibrosis in inflammatory bowel disease independent of classic metabolic risk factors. Clin Gastroenterol Hepatol. 2023;21(2):406–414.e7. Conflict of interest: Dr. Mitrovic, Milos: No conflict of interest Knezevic, Tamara: No conflict of interest Odanovic, Olga: No conflict of interest Andrej, Stupar: No conflict of interest Kalaba, Ana: No conflict of interest Kralj, Djordje: No conflict of interest Markovic, Srdjan: No conflict of interest
Mitrovic et al. (Thu,) studied this question.