A potential role for bile acid signalling in celiac disease-associated fatty liver

Background Recently, liver injury emerged as a severe but rare extraintestinal manifestation of celiac disease. The spectrum ranges from simple steatosis with or without hepatic inflammation to liver failure. However, the mechanisms of celiac disease-associated steatosis and liver injury are not entirely understood. We and others have previously identified alterations in bile acid (BA) metabolism and gut-liver interactions as pivotal players in the pathogenesis of hepatic steatosis and its complications. Therefore, we here aimed to investigate the role of the gut-liver-axis with a focus on BA metabolism, hepatic steatosis, and liver damage in celiac disease.

Methods We included 20 patients with known celiac disease and 20 healthy volunteers. We analyzed liver function tests, cell death markers, and markers of BA and fatty acid metabolism (GLP1, FGF19, FGF21, Serum BAs). Hepatic steatosis was determined using a controlled attenuated parameter (CAP) via Fibroscan®​ and MRI-HFF. Findings: FGF19 levels were suppressed in celiac disease patients compared to controls, although all patients were in clinical remission. Intriguingly, an inverse association of FGF19 with the degree of steatosis was found in the celiac cohort. Subgroup analysis was performed comparing patients with measurable serum levels of anti-tTG to those without detectable anti-tTG levels. Correlation analyses of the subgroups indicated that especially patients with transglutaminase antibody levels > 1U/ml present an invert association between FGF19 and the extent of steatosis.

Conclusion FGF19 is repressed in celiac disease. Low levels of FGF19 are associated with higher grades of steatosis, especially in patients with increased levels of anti-tTG antibodies.

Publication History

Article published online:
26 January 2022