Anti-TNFα treatment in Crohn’s disease: Impact on hepatic steatosis, gut-derived hormones and metabolic status
View/ Open
Date
2021-11Author
Manka, Paul
Sydor, Svenja
Wase, Nishikant
Best, Jan
Brandenburg, Malte
Hellbeck, Annika
Schänzer, Julia
Vilchez-Vargas, Ramiro
Link, Alexander
Figge, Anja
Jähnert, Andreas
Von Arnim, Ulrike
Coombes, Jason D.
Cubero, Francisco-Javier
Kahraman, Alisan
Kim, Moon-Sung
Kälsch, Julia
Kinner, Sonja
Faber, Klaas-Nico
Moshage, Han
Gerken, Guido
Syn, Wing-Kin
Friedman, Scott L.
Canbay, Ali
Bechmann, Lars P.
Metadata
Show full item record
Liver International 41(11) : 2646-2658 (2021)
Abstract
Background and Aims An association between Crohn's disease (CD) and hepatic steatosis has been reported. However, the underlying mechanisms of steatosis progression in CD are not clear. Among the most effective CD treatments are agents that inhibit Tumor-Necrosis-Factor (TNF) activity, yet it is unclear why anti-TNF alpha agents would affect steatosis in CD. Recent studies suggest that microbiome can affect both, CD and steatosis pathogenesis. Therefore, we here analysed a potential relationship between anti-TNF treatment and hepatic steatosis in CD, focusing on the gut-liver axis. Methods This cross-sectional study evaluated patients with established CD, with and without anti-TNF alpha treatment, analysing serum markers of liver injury, measurement of transient elastography, controlled attenuation parameter (CAP) and MRI for fat detection. Changes in lipid and metabolic profiles were assessed by serum and stool lipidomics and metabolimics. Additionally, we analysed gut microbiota composition and mediators of bile acid (BA) signalling via stool and serum analysis. Results Patients on anti-TNF alpha treatment had less hepatic steatosis as assessed by CAP and MRI. Serum FGF19 levels were significantly higher in patients on anti-TNF alpha therapy and associate with reduced steatosis and increased bowel motility. Neutral lipids including triglycerides were reduced in the serum of patients on anti-TNF treatment. Bacteria involved in BA metabolism and FGF19 regulation, including Firmicutes, showed group-specific alterations with low levels in patients without anti-TNF alpha treatment. Low abundance of Firmicutes was associated with higher triglyceride levels. Conclusions Anti-TNF alpha treatment is associated with reduced steatosis, lower triglyceride levels, alterations in FXR-signalling (eg FGF19) and microbiota composition in CD.
Collections
Except where otherwise noted, this item's license is described as This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.© 2021 The Authors. Liver International published by John Wiley & Sons Ltd.