title: Serum hepatocyte apoptosis biomarker predicts the presence of significant histological lesion in chronic hepatitis B virus infection.
abstract: BACKGROUND
  Hepatocyte death, either apoptosis or necrosis, is closely associated with hepatic inflammation and fibrosis.
  
  
  OBJECTIVE
  To investigate the potential values of hepatocytes death biomarker, M30 (apoptosis) and M65 (total death) in predicting histological lesions in chronic hepatitis B virus (HBV) infection.
  
  
  METHODS
  Total 201 treatment-naïve patients were prospectively recruited. Liver biopsies were performed prior to antiviral treatments for treatments starting evaluation. Sera were collected on the day of liver biopsy for biomarker measurements. Sera from 200 age-matched healthy volunteers served as healthy controls (HCs).
  
  
  RESULTS
  Significant histological lesions (SHL, i.e. significant inflammation and/or significant fibrosis) were confirmed in 150 (74.63%) patients. There were significantly higher serum M30 and M65 in patients with SHL than those without SHL (p<0.001) or than HCs (p<0.001). Serum M30, but not M65, independently predicted SHL [odds ratio:3.4 (95% CI, 1.8-6.2) per increase of 50U/L, p<0.001] after adjusting other potential confounding factors. A novel model based on M30 provided good diagnostic performance in predicting SHL [AUC, 0.87 (0.81-0.92)]. Cut-off value of >0 to confirm or ≤-0.5 to exclude SHL has ∼12% misclassification rate.
  
  
  CONCLUSIONS
  Hepatocyte apoptosis biomarker, M30 is a promising non-invasive alternative to liver biopsy in chronic HBV infection upon treatment evaluation.
authors: Department of Infectious Diseases, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors: Zhu-Jun
authors: ZJ
authors: Cao
authors: Department of Infectious Diseases, Huai-An Fourth People's Hospital, Jiangsu 223002, China.
authors: Jing
authors: J
authors: Li
authors: Department of Infectious Diseases, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors: Yun
authors: Y
authors: Wang
authors: Discipline of Anatomy and Histology, School of Medical Sciences and Bosch Institute, University of Sydney, Sydney, NSW 2006, Australia.
authors: Rebecca
authors: R
authors: Bao
authors: Department of Infectious Diseases, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors: Yu-Han
authors: YH
authors: Liu
authors: Department of Infectious Diseases, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors: Xiao-Gang
authors: XG
authors: Xiang
authors: Department of Infectious Diseases, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors: Lan-Yi
authors: LY
authors: Lin
authors: Department of Ophthalmology, Shanghai First People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China.
authors: Fu-Xiang
authors: FX
authors: Ye
authors: Department of Infectious Diseases, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors: Jie
authors: J
authors: Lu
authors: Department of Infectious Diseases, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China. Electronic address: xieqingrjh@163.com.
authors: Qing
authors: Q
authors: Xie
authors: Discipline of Pathology, School of Medical Sciences and Bosch Institute, University of Sydney, Sydney, NSW 2006, Australia. Electronic address: bob.bao@sydney.edu.au.
authors: Shi-San
authors: SS
authors: Bao
authors: Department of Infectious Diseases, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China. Electronic address: wanghuirj@163.com.
authors: Hui
authors: H
authors: Wang
mesh_terms: D000328:Adult; D017209:Apoptosis; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D002681:China; D003430:Cross-Sectional Studies; D005260:Female; D005355:Fibrosis; D019694:Hepatitis B, Chronic / Q000097:blood / Q000473:pathology*; D022781:Hepatocytes / Q000166:cytology / Q000473:pathology*; D006801:Humans; D007249:Inflammation / Q000097:blood; D053538:Keratin-18 / Q000097:blood*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009336:Necrosis / Q000097:blood*; D010446:Peptide Fragments / Q000097:blood*
chemical_list: D015415:Biomarkers; D053538:Keratin-18; C561463:M30 cytokeratin-18 peptide, human; C577325:M65 antigen, human; D010446:Peptide Fragments
keywords: Chronic hepatitis B; Fibrosis; Hepatocyte death; Inflammation