(CSEMP014) PROFILE OF PLASMATIC AND FECAL BILE ACIDS ACCORDING TO STAGES OF METABOLIC-ASSOCIATED FATTY LIVER DISEASE.

Background: Type 2 diabetes (T2D) is a major risk factor for advanced stages of Metabolic-associated fatty liver disease (MAFLD) (advanced fibrosis and cirrhosis). Since bile acids are involved in the regulation of hepatic carbohydrates and lipid metabolism, they are increasingly studied in relation to MAFLD and T2D. Cholic (CA), chenodeoxycholic (CDCA), deoxycholic (DCA), or lithocholic (LCA) acids, take part in the activation of Farnesoid X receptor (FXR) or Takeda G-protein-coupled receptor (TGR5), involved in carbohydrate and lipid metabolism. The specific plasma profile of bile acid may influence activation of these receptors. The objective of this study was to establish the bile acid profile according to MAFLD stage and relation with T2D.

METHODS AND RESULTS: Participants with MAFLD from a specialized clinic at CHU de Québec – Université Laval were recruited and classified by stage: initial (IF: F0, F1, F2) and advanced fibrosis (AF: F3, F4). Fibrosis stage was established by clinical standard care; biopsy, Fibroscan® or elastography by ultrasound. BA profiles were analysed in fasting plasma and stool samples on LC-MS. Non-parametric Mann-Whitney tests (Median ± IQR) were performed.
44 participants were recruited: 29 in the IF group and 15 in the AF group. There were no statistical differences between the IF and AF groups for median sex (58 vs 47% of men, p>0.99), age (55 vs 54 years old, p=0.8784), and BMI (32 vs 33kg/m2, p=0.3873). There were also no statistical differences in fasting glucose or HbA1c (6.10 vs 6.80 mmol/L of glucose, p=0.52 and 5.50 vs 5.80% HbA1c, p=0.57) and proportion of participants with diabetes (48 vs 60% diabetes). In plasma, AF group had a higher concentration of total (p < 0.01), and primary BA (p=0.05), without change in secondary BA concentration. CA, CDCA and DCA family plasma concentration was higher in AF group (p < 0.05; p< 0.03; p=0.053) due to the increase of their tauro- and gluco-conjugated forms. Conversely, in stools, there was a lower concentration of total (p=0.12) and secondary BA (p=0.02) AF group.
There was no change in bile acid profile in participants with or without diabetes within the same group of fibrosis.

Conclusion: Our results show a plasmatic increase and a stool decrease of BA concentration in the advanced stage of fibrosis, suggesting an increase of BA intestinal reabsorption. Increased hepatic bile acid may promote inflammation and contribute to fibrosis, FXR activation and metabolic pathways need to be assessed to study impact of the specific BA profile found in this sample.