Ratio of Conjugated Chenodeoxycholic to Muricholic Acids is Associated with Severity of Nonalcoholic Steatohepatitis

Obesity (Silver Spring). 2019 Dec;27(12):2055-2066. doi: 10.1002/oby.22627. Epub 2019 Oct 27.

Abstract

Objective: Bile acids (BAs) are important molecules in the progression of nonalcoholic fatty liver disease. This study aimed to investigate BA profile alterations in Chinese nonalcoholic steatohepatitis (NASH) patients.

Methods: BA profiles in serum and liver tissues were determined by ultraperformance liquid chromatography coupled to tandem mass spectrometry in patients from two different clinical centers.

Results: A total of 134 participants were enrolled in this study to serve as the training (n = 87) and validation (n = 47) cohorts. The ratio of circulating conjugated chenodeoxycholic acids to muricholic acids (P = 0.001) was elevated from healthy controls to non-NASH individuals to NASH individuals in a stepwise manner in the training cohort and was positively associated with the histological severity of NASH: steatosis (R2 = 0.12), lobular inflammation (R2 = 0.12), ballooning (R2 = 0.11), and fibrosis stage (R2 = 0.18). The ratio was elevated in the validation cohort of NASH patients (P < 0.001), and it was able to predict NASH (area under the receiver operating characteristic curve: 75%) and significant fibrosis (area under the receiver operating characteristic curve: 71%) in these two cohorts. Moreover, this elevated ratio and impaired farnesoid X receptor signaling were found in the NASH liver.

Conclusions: Altered BA profile in NASH is closely associated with the severity of liver lesions, and it has the potential for predicting NASH development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Bile Acids and Salts / blood*
  • Chenodeoxycholic Acid / blood*
  • Cholic Acids / blood*
  • Cohort Studies
  • Disease Progression
  • Female
  • Humans
  • Liver / pathology*
  • Male
  • Middle Aged
  • Non-alcoholic Fatty Liver Disease / blood*
  • Non-alcoholic Fatty Liver Disease / pathology
  • Risk Factors

Substances

  • Bile Acids and Salts
  • Cholic Acids
  • Chenodeoxycholic Acid
  • muricholic acid