Secondary bile acids improve risk prediction for non‐invasive identification of mild liver fibrosis in nonalcoholic fatty liver disease

• Published in: Alimentary pharmacology & therapeutics 2023-04, Vol.57 (8), p.872-885
• Main Authors: Liu, A‐Na, Xu, Cui‐Fang, Liu, Ya‐Ru, Sun, Dan‐Qin, Jiang, Ling, Tang, Liang‐Jie, Zhu, Pei‐Wu, Chen, Sui‐Dan, Liu, Wen‐Yue, Wang, Xiao‐Dong, Targher, Giovanni, Byrne, Christopher D., Wong, Vincent Wai‐Sun, Fu, Junfen, Su, Ming‐Ming, Loomba, Rohit, Zheng, Ming‐Hua, Ni, Yan
• Format: Article
• Language: English
• Subjects: Adult; Alanine transaminase; Bile acids; Bile Acids and Salts; Biomarkers; Biopsy; Blood pressure; Body mass index; Fatty liver; Female; Fibrosis; Humans; Inflammation - complications; Insulin; Insulin resistance; Liquid chromatography; Liver - pathology; Liver Cirrhosis - complications; Liver diseases; liver fibrosis; Male; Mass spectroscopy; Non-alcoholic Fatty Liver Disease - complications; nonalcoholic fatty liver disease; Obesity; Obesity - complications; risk prediction; secondary bile acids; Steatosis
• ISSN: 0269-2813; 1365-2036
• DOI: 10.1111/apt.17362

Background Dysregulated bile acid (BA) metabolism has been linked to steatosis, inflammation, and fibrosis in nonalcoholic fatty liver disease (NAFLD). Aim To determine whether circulating BA levels accurately stage liver fibrosis in NAFLD. Methods We recruited 550 Chinese adults with biopsy‐proven NAFLD and varying levels of fibrosis. Ultra‐performance liquid chromatography coupled with tandem mass spectrometry was performed to quantify 38 serum BAs. Results Compared to those without fibrosis, patients with mild fibrosis (stage F1) had significantly higher levels of secondary BAs, and increased diastolic blood pressure (DBP), alanine aminotransferase (ALT), body mass index, and waist circumstance (WC). The combination of serum BAs with WC, DBP, ALT, or Homeostatic Model Assessment for Insulin Resistance performed well in identifying mild fibrosis, in men and women, and in those with/without obesity, with AUROCs 0.80, 0.88, 0.75 and 0.78 in the training set (n = 385), and 0.69, 0.80, 0.61 and 0.69 in the testing set (n = 165), respectively. In comparison, the combination of BAs and clinical/biochemical biomarkers performed less well in identifying significant fibrosis (F2‐4). In women and in non‐obese subjects, AUROCs were 0.75 and 0.71 in the training set, 0.65 and 0.66 in the validation set, respectively. However, these AUROCs were higher than those observed for the fibrosis‐4 index, NAFLD fibrosis score, and Hepamet fibrosis score. Conclusions Secondary BA levels were significantly increased in NAFLD, especially in those with mild fibrosis. The combination of serum BAs and clinical/biochemical biomarkers for identifying mild fibrosis merits further assessment. Secondary bile acids were significantly increased in NAFLD, especially in those with mild fibrosis. The combination of serum bile acids and clinical/biochemical biomarkers for identifying mild fibrosis is worthy of further assessment.