Elevated serum bile acids in NASH patients with fibrosis in the context of their cholestatic genetic predisposition

Background Current drug development in NAFLD show promising results for FXR-agonists against NAFLD progression, but bile acid (BA) retention could also promote liver injury. Genetic variant c.1331T>C of the bile-salt export pump (ABCB11) as the most frequent pro-cholestatic polymorphism represents a predisposition factor for bile salt retention under pathologic condition.

To analyze whether the relationship between serum BAs and NAFLD depends on c.1331T>C variant.

Method 70 NAFL, 124 NASH and 165 clinically diagnosed NAFLD patients were included in this study. The c.1331T>C variant was genotyped using TaqMan assays. Serum BAs were analyzed by mass-spectrometry in 33 NAFL, 58 NASH, and 146 NAFLD patients.

Results 69% of NAFLD patients presented a cholestatic pattern of serum enzymes with (ALT/ALTULN)/(AP/APULN) < 2. Total serum BAs were significantly higher in NASH compared to NAFL (2.6±2.2 vs. 1.8±1.6µM p=0.02). No significant association between overall BAs and steatosis, inflammation, or ballooning in histology was found. Histology proved NAFLD patients with F3/F4 had highest BAs, and F1/F2 patients still had higher BAs compared to F0. All NAFLD patients with cholestasis (BAs > 10µM) had significantly higher liver stiffness compared to non-cholestatic NAFLD. No significant elevation in serum BAs was observed in TT carriers compared to CT+CC. A significant correlation between liver stiffness and BAs was observed for CT+CC patients.

Conclusion NASH patients are characterized by higher serum BAs, and BAs are associated with advanced fibrotic disease. The c.1331T>C variant might be a co-factor for cholestasis in NAFLD, but no significant impact was found in the present cohort.

 

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Publication History

Article published online:
26 January 2022