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
Affiliations
Tianhang Feng
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
Chunyou Lai
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
Qiuyun Yuan
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
Wanchun Yang
Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu, China; Corresponding author
Yutong Yao
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
Mengze Du
Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu, China
Deyuan Zhong
Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
Sijia Wang
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
Qinyan Yang
Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
Jin Shang
Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
Ying Shi
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
Xiaolun Huang
Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China; Corresponding author
Summary: 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.
