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

作者：A‐Na Liu, Cuifang Xu, Ya‐Ru Liu, Dan‐Qin Sun, Ling Jiang, Liang‐Jie Tang, Pei‐Wu Zhu, Sui‐Dan Chen, Wen‐Yue Liu, Xiaodong Wang, Giovanni Targher, Christopher D. Byrne, Vincent Wai‐Sun Wong, Junfen Fu, Mingming Su, Rohit Loomba, Ming‐Hua Zheng, Yan Ni · 发表于：Alimentary Pharmacology & Therapeutics · 年份：2023 · DOI：10.1111/apt.17362 · 被引用次数：36 · 研究领域：Liver Disease Diagnosis and Treatment、Drug Transport and Resistance Mechanisms、Liver Diseases and Immunity

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...