Hepatic steatosis in Crohn's disease: associations with anti-TNFα treatment, dysbiosis, and FGF-19.

Question:

Non-alcoholic fatty liver disease (NAFLD) is found in up to 33.6% of patients with inflammatory bowel disease (IBD), even in the absence of metabolic risk factors. We and others have shown that NASH in patients with Crohn"s disease (CD) is associated with an increased susceptibility for acute-on-chronic liver failure. Multivariate logistic regression analyses have shown that ongoing anti-Tumor Necrosis Factor-alpha (anti-TNFα) therapy was the only independent protective factor. To date, little is known about the mechanisms leading to hepatic steatosis in IBD nor how anti-TNFα affects steatosis. Therefore, we aimed to analyze and compare non-invasive predictors of liver disease paying special attention to the role of the gut-liver axis and bile-acid metabolism.

Methods:

We included patients with established CD with and without anti-TNFα treatment and analyzed serum markers of liver injury, transient elastography as well as controlled attenuation parameter (CAP) and MRI proton density fat fraction to assess hepatic steatosis. In addition, we compared gut microbiota and mediators of bile acid (BA) signaling in the absence or presence of treatment with biologicals through analysis of stool and serum from patients and compared it between groups.

Results:

Patients on treatment with TNFα antibodies expressed lower hepatic steatosis as assessed by CAP and MRI. Serum FGF-19 levels were higher in patients on anti-TNFα treatment and associated with steatosis as well as lower LFT-levels. Group-specific alterations in gut microbiome were found for several bacteria involved in BA metabolism and FGF-19 regulation, including Bacteroides and Firmicutes.

Conclusion:

Treatment with biologicals protects CD patients from hepatic steatosis. In this cohort, FGF-19 is associated with less steatosis, reduced circulating FGF19 levels and specific alterations in the composition of gut microbiota and BA metabolism.