title: S100A9: A Potential Biomarker for the Progression of Non-Alcoholic Fatty Liver Disease and the Diagnosis of Non-Alcoholic Steatohepatitis.
abstract: Non-alcoholic fatty liver (NAFL) has the potential to progress to non-alcoholic steatohepatitis (NASH) or to promote type 2 diabetes mellitus (T2DM). However, NASH and T2DM do not always develop coordinately. Additionally, there are no definite noninvasive methods for NASH diagnosis currently. We established rat models of NAFL, NASH, and NAFL + T2DM to recapitulate different phenotypes associated with non-alcoholic fatty liver disease (NAFLD) and its progression. Histologic features of rat livers were scored according to criteria established by the Nonalcoholic Steatohepatitis Clinical Research Network. Microarray was performed to assess gene expression changes in rat livers. We find that gene expression of s100a9 was higher in NAFL group compared with control, and was increased in NASH groups and decreased in NAFL + T2DM group compared with NAFL. In contrast, srebf1, tbx21, and gimap4 only showed limited discriminating abilities in different groups. There is a significant positive correlation between serum levels of S100A9 and NAFLD Activity Score (NAS), the severity of hepatic steatosis, and lobular inflammation (r = 0.80, 0.64 and 0.86, P < 0.001). These findings suggest that S100A9 may be extremely useful in the diagnosis of NASH (AUROC: 0.947, CI: 0.845-1.049). Additionally, serum S100A9 levels displayed a strong correlation with ALT, AST and TBil (r = 0.81, 0.89 and 0.91, P < 0.001) but a weak correlation with FBG, HOMA-IR, TG, and TC (r = -0.41, -0.40, 0.47 and 0.49, P < 0.05).
  
  
  CONCLUSIONS
  The results we provide here suggest that S100A9 may be useful as a biomarker for the hepatic and metabolic progression of NAFLD and the non-invasive diagnosis of NASH.
authors.affiliation: Division of Gastroenterology and Hepatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, Shanghai, China.
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Liu
authors.affiliation: Division of Gastroenterology and Hepatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, Shanghai, China.
authors.forename: Yongfeng
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Division of Gastroenterology and Hepatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, Shanghai, China.
authors.forename: Yanan
authors.initials: Y
authors.lastname: Ming
authors.affiliation: Department Biostatistics, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Song
authors.affiliation: Division of Gastroenterology and Hepatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, Shanghai, China.
authors.forename: Jingyi
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Division of Gastroenterology and Hepatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, Shanghai, China.
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Chen
authors.affiliation: Division of Gastroenterology and Hepatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, Shanghai, China.
authors.forename: Minde
authors.initials: M
authors.lastname: Zeng
authors.affiliation: Division of Gastroenterology and Hepatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, Shanghai, China.
authors.forename: Yimin
authors.initials: Y
authors.lastname: Mao
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism*; D040502:Calgranulin B / Q000378:metabolism*; D018450:Disease Progression; D065626:Non-alcoholic Fatty Liver Disease / Q000378:metabolism*; D051381:Rats
chemical_list: D015415:Biomarkers; D040502:Calgranulin B