Jin Chen1, Minghua Zheng2, Jun Liu3, Yan Luo4, Wenjun Yang5, Jing Yang4, Juan Liu5, Jingxing Zhou6, Chengfu Xu7, Faling Zhao6, Mingming Su8, Shufei Zang3, Junping Shi9. 1. Department of Gastroenterology, First People's Hospital of Yancheng City, Yancheng, Jiangsu, China. 2. Department of Hepatology, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China. 3. Department of Endocrinology, Fifth People's Hospital of Shanghai, Fudan University, Shanghai, China. 4. Department of Transformation Medical platform, Hangzhou Normal University Affiliated Hospital, Hangzhou, Zhejiang, China. 5. Department of Pathology, Hangzhou Normal University Affiliated Hospital, Hangzhou, Zhejiang, China. 6. Department of Statistics, Hangzhou Normal University, Hangzhou, Zhejiang, China. 7. Department of Gastroenterology, First Affiliated Hospital of Zhejiang University, Hangzhou, Zhejiang, China. 8. Metabo-profile Biotechnology, Shanghai, China. 9. Department of Liver Diseases, Hangzhou Normal University Affiliated Hospital, Hangzhou, Zhejiang, China.
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.
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 NASHpatients (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.