The histologic spectrum of
nonalcoholic fatty liver disease (
NAFLD) includes
fatty liver (NAFL) and
steatohepatitis (NASH), which can progress to
cirrhosis in up to 20% of NASH patients.
Bile acids (BA) are linked to the pathogenesis and
therapy of NASH. We (1) characterized the plasma BA profile in biopsy-proven NAFL and NASH and compared to controls and (2) related the plasma BA profile to liver histologic features, disease activity, and
fibrosis. Liquid chromatography/mass spectrometry quantified BAs. Descriptive statistics, paired and multiple group comparisons, and regression analyses were performed. Of 86 patients (24 controls, 25 NAFL, and 37 NASH; mean age 51.8 years and body mass index 31.9 kg/m2 ), 66% were women. Increased total primary BAs and decreased secondary BAs (both P < 0.05) characterized NASH. Total conjugated primary BAs were significantly higher in NASH versus NAFL (P = 0.047) and versus controls (P < 0.0001). NASH had higher conjugated to unconjugated
chenodeoxycholate (P = 0.04),
cholate (P = 0.0004), and total primary BAs (P < 0.0001). The total
cholate to
chenodeoxycholate ratio was significantly higher in
NAFLD without (P = 0.005) and with (P = 0.02) diabetes. Increased key BAs were associated with higher grades of steatosis (
taurocholate), lobular (
glycocholate) and portal
inflammation (
taurolithocholate), and hepatocyte ballooning (
taurocholate). Conjugated
cholate and
taurocholate directly and secondary to primary BA ratio inversely correlated to
NAFLD activity score. A higher ratio of total secondary to primary BA decreased (odds ratio, 0.57; P = 0.004) and higher conjugated
cholate increased the likelihood of significant
fibrosis (F≥2) (P = 0.007). Conclusion:
NAFLD is associated with significantly altered circulating BA composition, likely unaffected by
type 2 diabetes, and correlated with histological features of NASH; these observations provide the foundation for future hypothesis-driven studies of specific effects of BAs on specific aspects of NASH. (Hepatology 2018;67:534-548).