title: CHI3L1 Is a Liver-Enriched, Noninvasive Biomarker That Can Be Used to Stage and Diagnose Substantial Hepatic Fibrosis.
abstract: Liver fibrosis is a major disease that is primarily caused by hepatitis virus infections, toxins, and alcohol abuse. Diagnosing and staging liver fibrosis are critical in guiding the treatment of chronic liver diseases, according to several international and Chinese guidelines. Liver biopsy is the gold standard for diagnosing and staging liver fibrosis, but it is invasive and suffers from several limitations. Consequently, much research has focused on the search for a noninvasive serum biomarker of fibrosis. In this study, we determined that Chitinase 3-like 1 (CHI3L1) is an abundantly expressed liver gene whose expression is highly enriched in the liver. We then compared serum levels of CHI3L1 among patients with various stages of liver fibrosis, as determined by liver biopsies, and found that the CHI3L1 levels were able to differentiate early stages of liver fibrosis (S0-S2) from late stages of liver fibrosis (S3-S4). We further showed that CHI3L1 is a good marker of substantial fibrosis, with areas under the ROC curves (AUCs) of 0.94 for substantial (S2, S3, S4) fibrosis and 0.96 for advanced (S3, S4) fibrosis. Finally, we showed that CHI3L1 is superior to hyaluronic acid (HA), type III procollagen (PCIII), laminin (LN), and type IV collagen (CIV), which are also serum biomarkers of liver fibrosis, in identifying advanced liver fibrosis in patients with HBV-related liver fibrosis in China.
authors.affiliation: 1 Department of Infectious Diseases, Zhejiang Provincial People's Hospital , Hangzhou, Zhejiang, China .
authors.forename: Haijun
authors.initials: H
authors.lastname: Huang
authors.affiliation: 2 System Biology Division, Zhejiang-California International Nanosystem Institute (ZCNI), Zhejiang University , Hangzhou, Zhejiang, China .
authors.forename: Tiangang
authors.initials: T
authors.lastname: Wu
authors.affiliation: 2 System Biology Division, Zhejiang-California International Nanosystem Institute (ZCNI), Zhejiang University , Hangzhou, Zhejiang, China .
authors.forename: Jian
authors.initials: J
authors.lastname: Mao
authors.affiliation: 2 System Biology Division, Zhejiang-California International Nanosystem Institute (ZCNI), Zhejiang University , Hangzhou, Zhejiang, China .
authors.forename: Yongxing
authors.initials: Y
authors.lastname: Fang
authors.affiliation: 1 Department of Infectious Diseases, Zhejiang Provincial People's Hospital , Hangzhou, Zhejiang, China .
authors.forename: Jiajie
authors.initials: J
authors.lastname: Zhang
authors.affiliation: 3 The Research Center for Clinical Pharmacy, State Key Laboratory for Diagnosis and Treatment of Infectious Disease, The First Affiliated Hospital of Zhejiang University , Hangzhou, Zhejiang, China .
authors.forename: Lihua
authors.initials: L
authors.lastname: Wu
authors.affiliation: 4 The Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education), The Second Affiliated Hospital, Zhejiang University School of Medicine , Hangzhou, Zhejiang, China .
authors.forename: Shu
authors.initials: S
authors.lastname: Zheng
authors.affiliation: 2 System Biology Division, Zhejiang-California International Nanosystem Institute (ZCNI), Zhejiang University , Hangzhou, Zhejiang, China .|4 The Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education), The Second Affiliated Hospital, Zhejiang University School of Medicine , Hangzhou, Zhejiang, China .|5 Department of Urology, University of Washington , Seattle, Washington.
authors.forename: Biaoyang
authors.initials: B
authors.lastname: Lin
authors.affiliation: 1 Department of Infectious Diseases, Zhejiang Provincial People's Hospital , Hangzhou, Zhejiang, China .
authors.forename: Hongying
authors.initials: H
authors.lastname: Pan
mesh_terms: D054392:Adipokines / Q000097:blood / Q000235:genetics* / Q000378:metabolism*; D015415:Biomarkers / Q000097:blood / Q000378:metabolism*; D000071451:Chitinase-3-Like Protein 1; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D037102:Lectins / Q000097:blood / Q000235:genetics* / Q000378:metabolism*; D008099:Liver / Q000378:metabolism* / Q000473:pathology*; D008103:Liver Cirrhosis / Q000175:diagnosis* / Q000235:genetics*
chemical_list: D054392:Adipokines; D015415:Biomarkers; C084533:CHI3L1 protein, human; D000071451:Chitinase-3-Like Protein 1; D037102:Lectins