Baseline metabolites could predict responders with hepatitis B virus-related liver fibrosis for entecavir or combined with FuzhengHuayu tablet

Yun-Kai Dai; Hai-Na Fan; Kai Huang; Xin Sun; Zhi-Min Zhao; Cheng-Hai Liu

doi:10.4254/wjh.v15.i9.1043

Baseline metabolites could predict responders with hepatitis B virus-related liver fibrosis for entecavir or combined with FuzhengHuayu tablet

World J Hepatol. 2023 Sep 27;15(9):1043-1059. doi: 10.4254/wjh.v15.i9.1043.

Authors

Yun-Kai Dai¹, Hai-Na Fan¹, Kai Huang², Xin Sun^{1

2}, Zhi-Min Zhao^{1

2}, Cheng-Hai Liu^{1

2

3}

Affiliations

¹ Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Institute of Liver Diseases, Shanghai 201203, China.
² Shanghai Key Laboratory of Traditional Chinese Clinical Medicine, Institute of Liver Diseases, Shanghai 201203, China.
³ Key Laboratory of Liver and Kidney Diseases, Institute of Liver Diseases, Shanghai 201203, China. chenghai.liu@shutcm.edu.cn.

Abstract

Background: After receiving entecavir or combined with FuzhengHuayu tablet (FZHY) treatment, some sufferers with hepatitis B virus (HBV)-related liver fibrosis could achieve a histological improvement while the others may fail to improve even worsen. Serum metabolomics at baseline in these patients who were effective in treatment remain unclear.

Aim: To explore baseline serum metabolites characteristics in responders.

Methods: A total of 132 patients with HBV-related liver fibrosis and 18 volunteers as healthy controls were recruited. First, all subjects were divided into training set and validation set. Second, the included patients were subdivided into entecavir responders (E-R), entecavir no-responders (E-N), FZHY + entecavir responders (F-R), and FZHY + entecavir no-responders (F-N) following the pathological histological changes after 48 wk' treatments. Then, Serum samples of all subjects before treatment were tested by high performance liquid chromatography-tandem mass spectrometry (LC-MS) high-performance LC-MS. Data processing was conducted using multivariate principal component analysis and orthogonal partial least squares discriminant analysis. Diagnostic tests of selected differential metabolites were used for Boruta analyses and logistic regression.

Results: As for the intersection about differential metabolic pathways between the groups E-R vs E-N and F-R vs F-N, results showed that 4 pathways including linoleic acid metabolism, aminoacyl-tRNA biosynthesis, cyanoamino acid metabolism, alanine, aspartate and glutamate metabolism were screened out. As for the differential metabolites, these 7 intersected metabolites including hydroxypropionic acid, tyrosine, citric acid, taurochenodeoxycholic acid, benzoic acid, 2-Furoic acid, and propionic acid were selected.

Conclusion: Our findings showed that 4 metabolic pathways and 7 differential metabolites had potential usefulness in clinical prediction of the response of entecavir or combined with FZHY on HBV fibrotic liver.

Keywords: Differential metabolites; Entecavir; FuzhengHuayu tablet; Hepatitis B virus-related liver fibrosis; Serum metabolomics; Therapeutic responders.