Non-invasive assessment of liver fibrosis by serum metabolites in non-human primates and human patients

Tianhang Feng; Chunyou Lai; Qiuyun Yuan; Wanchun Yang; Yutong Yao; Mengze Du; Deyuan Zhong; Sijia Wang; Qinyan Yang; Jin Shang; Ying Shi; Xiaolun Huang

doi:10.1016/j.isci.2023.107538

Non-invasive assessment of liver fibrosis by serum metabolites in non-human primates and human patients

iScience. 2023 Aug 3;26(9):107538. doi: 10.1016/j.isci.2023.107538. eCollection 2023 Sep 15.

Authors

Tianhang Feng¹, Chunyou Lai¹, Qiuyun Yuan², Wanchun Yang³, Yutong Yao¹, Mengze Du³, Deyuan Zhong⁴, Sijia Wang¹, Qinyan Yang⁴, Jin Shang⁴, Ying Shi¹, Xiaolun Huang⁴

Affiliations

¹ Department of Hepatobiliary and Pancreatic Surgery, Sichuan Academy of Medical Sciences, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.
² State Key Laboratory of Oral Diseases, National Center of Stomatology, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China.
³ Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu, China.
⁴ Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.

Abstract

Liver fibrosis, a rising cause of chronic liver diseases, could eventually develop into cirrhosis and liver failure. Current diagnosis of liver fibrosis relies on pathological examination of hepatic tissues acquired from percutaneous biopsy, which may produce invasive injuries. Here, for non-invasive assessment of liver fibrosis, we applied comparative multi-omics in non-human primates (rhesus macaques) and subsequent serum biopsy in human patients. Global transcriptomics showed significant gene enrichment of metabolism process, in parallel with oxidative stress and immune responses in fibrotic primates. Targeted metabolomics were concordant with transcriptomic patterns, identifying elevated lipids and porphyrin metabolites during hepatic fibrosis. Importantly, liquid biopsy results validated that specific metabolites in the serum (e.g., biliverdin) were highly diagnostic to distinguish human patients from healthy controls. Findings describe the interconnected transcriptional and metabolic network in primate liver fibrosis and provide potential indices for non-invasive detection of liver fibrosis in humans.

Keywords: Diagnostic technique in health technology; Nonclinical topic.