Gender-Specific Bile Acid Profiles in Non-Alcoholic Fatty Liver Disease

Area of Science:

• Hepatology
• Metabolomics
• Biochemistry

Background:

• Non-alcoholic fatty liver disease (NAFLD) is a growing global health concern, often linked to Western lifestyles.
• Early detection of aggressive NAFLD subtypes is crucial for patient outcomes, yet non-invasive diagnostic tools remain limited.
• Understanding the complex interplay of insulin resistance, inflammation, microbiome, and genetics in NAFLD pathogenesis is vital, with metabolomics offering potential insights.

Purpose of the Study:

• To investigate gender-specific bile acid (BA) profiles in patients with non-alcoholic fatty liver disease (NAFLD) and alcohol-associated liver disease (ALD).
• To explore the relationship between bile acid alterations and liver fibrosis severity (ELF score) in NAFLD and ALD.
• To identify potential gender-based differences in the metabolic pathways underlying NAFLD and ALD.

Main Methods:

• Targeted mass spectrometry was employed to quantify bile acids in plasma samples from adult NAFLD and ALD patients and healthy controls.
• Analysis focused on differentiating bile acid profiles between genders within the NAFLD and ALD cohorts.
• Correlations between specific bile acid fractions and the Enhanced Liver Fibrosis (ELF) score were assessed.

Main Results:

• Women with NAFLD exhibited significantly higher levels of total bile acids, primary bile acids, cholic acid, chenodeoxycholic acid, and glycine-conjugated bile acids compared to controls.
• Men with NAFLD showed altered levels of specific bile acid subtypes, including elevated glycodeoxycholic acid and decreased cholic acid.
• In NAFLD, most bile acid fractions positively correlated with the ELF score, indicating a link between bile acid dysregulation and liver fibrosis severity.

Conclusions:

• Distinct gender-specific bile acid profiles were observed in NAFLD and ALD, suggesting different pathogenic mechanisms.
• Women with NAFLD appear to experience more severe cholestasis, while men may exhibit compensatory mechanisms related to fat metabolism.
• Taurine-conjugated bile acids, elevated in men with NAFLD, are associated with potentially beneficial metabolic functions.