Assessment of metabolic biomarkers associated with hepatic steatosis in Crohn’s disease

Abstract

BACKGROUND

Steatotic liver disease (SLD) is the most frequent hepatic manifestation in inflammatory bowel disease. The contribution of intestinal inflammatory activity and hepatokines to steatosis development in Crohn’s disease (CD) remains unclear. We aimed to evaluate the prevalence of steatosis according to CD activity, analyze metabolic and hepatokine profiles, and assess the performance of non-invasive imaging techniques.

AIM

To investigate SLD, associated biomarkers, and diagnostic imaging accuracy in CD.

METHODS

Seventy-two subjects were included: Active CD (n = 19), CD in sustained deep remission (n = 24), and healthy controls (n = 29). Patients with diabetes mellitus, chronic liver disease, or significant alcohol consumption were excluded. CD activity was assessed using, among other parameters, intestinal ultrasound. SLD was assessed by ultrasound and controlled attenuation parameter (CAP). Liver stiffness was measured by transient elastography and two-dimensional shear wave elastography. Serum angiopoietin-like protein 3 (ANGPTL3), ANGPTL6, fibroblast growth factor 19 (FGF19), and FGF21 levels were determined. Metabolic assessment included lipid profile, homeostasis model assessment of insulin resistance, and glycated hemoglobin (HbA1c).

RESULTS

Overall prevalence of SLD was 33% (24/72): 53% in active CD, 30% in CD remission, and 21% in controls (P = 0.04). Among patients with SLD, HbA1c levels were significantly higher in active CD (31.4 mmol/mol) compared to CD in remission (17.8 mmol/mol) and controls (5.8 mmol/mol) (P = 0.007). No significant differences in liver enzymes were observed among groups with steatosis. Patients with steatosis showed higher levels of ANGPTL6 (124.5 ng/mL vs 112.8 ng/mL; P = 0.04) and FGF21 (0.12 ng/mL vs 0.06 ng/mL; P = 0.01) compared to subjects without steatosis, although no differences were observed among the different cohorts. No significant differences were found in ANGPTL3, ANGPTL4, or FGF19, either according to the presence of steatosis or between cohorts. CAP values were significantly higher in ultrasound-detected SLD (P = 0.0001), with area under the curve (AUC) ranging. CAP values were higher in patients with active CD compared to remission CD and controls; however, CAP demonstrated adequate diagnostic accuracy for steatosis across all three groups, with AUC values (0.76-0.82).

CONCLUSION

Inflammatory activity in CD is associated with a higher prevalence of SLD and subclinical metabolic alterations. ANGPTL6 and FGF21 may serve as potential biomarkers of SLD in CD. CAP appears to be a reliable non-invasive tool, although inflammatory status should be considered.

Keywords: Crohn’s disease; Metabolic dysfunction-associated steatotic liver disease; Hepatic steatosis; Hepatokines; Angiopoietin-like protein 6; Fibroblast growth factor 21; Controlled attenuation parameter; Intestinal inflammation

Core Tip: Active Crohn’s disease is associated with a higher prevalence of steatosis and increased angiopoietin-like protein 6 and fibroblast growth factor 21 levels, suggesting inflammation-related metabolic alterations. Controlled attenuation parameter may serve as a reliable non-invasive tool for steatosis detection in Crohn’s disease, although inflammatory activity should be considered in its interpretation.