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.
