Circulating bile acid concentrations and non‐alcoholic fatty liver disease in Guatemala

Abstract

Background: Non-alcoholic fatty liver disease (NAFLD) is a major liver disease worldwide. Bile acid dysregulation may be a key feature in its pathogenesis and progression. Aims:To characterise the relationship between bile acid levels and NAFLD at the population level Methods: We conducted a cross-sectional study in Guatemala in 2016 to examine the prevalence of NAFLD. Participants (n = 415) completed questionnaires, donated blood samples and had a brief medical exam. NAFLD was determined by calculation of the fatty liver index. The levels of 15 circulating bile acids were determined by LC-MS/MS. Adjusted prevalence odds ratios (POR adj ) and 95% CI were calculated to examine the relationships between bile acid levels (in tertiles) and NAFLD.Results: Persons with NAFLD had significantly higher levels of the conjugated primary bile acids glycocholic acid (GCA) (POR adj T3 vs T1 = 1.85), taurocholic acid (TCA) (POR adj T3 vs T1 = 2.45) and taurochenodeoxycholic acid (TCDCA) (POR adj T3 vs T1 = 2.10), as well as significantly higher levels the unconjugated secondary bile acid, deoxycholic acid (DCA) (POR adj T3 vs T1 = 1.78) and its conjugated form, taurodeoxycholic acid (TDCA) (POR adj T3 vs T1 = 1.81). Conclusions:The bile acid levels of persons with and without NAFLD differed significantly. Among persons with NAFLD, higher levels of the conjugated forms of CA (i.e. GCA, TCA) and the secondary bile acids that derive from CA (i.e. DCA, TDCA) may indicate there is hepatic overproduction of CA, which may affect the liver via aberrant signalling mediated by the bile acids.

Editorial: higher levels of certain serum bile acids in non‐alcoholic fatty liver disease—new insights from Guatemala

“…We believe that the findings of this study 1 add to an ever‐increasing body of literature on serum BA levels and NAFLD (as summarized in Table 1). It is the largest cross‐sectional study to date to examine serum BA profiles between subjects with and without NAFLD.…”

“…The authors have discussed in a balanced way the major strengths and limitations of the study, including the use of FLI for diagnosing NAFLD and the lack of any data on non-invasive tests of liver fibrosis. 1 We believe that the findings of this study 1 add to an everincreasing body of literature on serum BA levels and NAFLD (as summarized in Table 1). It is the largest cross-sectional study to date to examine serum BA profiles between subjects with and without NAFLD.…”

“…Collectively, the findings of this interesting cross‐sectional study from Guatemala 1 represent a further step in our understanding of the possible role played by serum BAs in NAFLD, although further efforts should be made.…”

“…present their findings from a cross‐sectional study involving 415 middle‐aged individuals from Guatemala (mean age 55.3 years; 60% women; 31.3% were obese; and 21.7% had type 2 diabetes mellitus [T2DM]), in whom NAFLD was detected by the fatty liver index (defined as FLI > 60; n = 251 [60.5%]), and the levels of 15 serum bile acids (BAs) were measured by liquid chromatography‐mass spectrometry 1 . Compared to those without NAFLD, patients with NAFLD had significantly higher adjusted levels of the conjugated primary BAs glycocholic acid, taurocholic acid (TCA) and taurochenodeoxycholic acid, as well as higher adjusted levels of the unconjugated secondary BAs, deoxycholic acid (DCA) and its conjugated form, taurodeoxycholic acid, even after adjusting for age, sex, residence, ethnicity, smoking, alcohol intake and pre‐existing T2DM 1 . However, if a Bonferroni correction to these p‐values was applied, only serum TCA levels would be considered a significant finding.…”

“…However, if a Bonferroni correction to these p‐values was applied, only serum TCA levels would be considered a significant finding. The authors have discussed in a balanced way the major strengths and limitations of the study, including the use of FLI for diagnosing NAFLD and the lack of any data on non‐invasive tests of liver fibrosis 1 …”