title: qFibrosis: a fully-quantitative innovative method incorporating histological features to facilitate accurate fibrosis scoring in animal model and chronic hepatitis B patients.
abstract: OBJECTIVE
  There is increasing need for accurate assessment of liver fibrosis/cirrhosis. We aimed to develop qFibrosis, a fully-automated assessment method combining quantification of histopathological architectural features, to address unmet needs in core biopsy evaluation of fibrosis in chronic hepatitis B (CHB) patients.
  
  
  METHODS
  qFibrosis was established as a combined index based on 87 parameters of architectural features. Images acquired from 25 Thioacetamide-treated rat samples and 162 CHB core biopsies were used to train and test qFibrosis and to demonstrate its reproducibility. qFibrosis scoring was analyzed employing Metavir and Ishak fibrosis staging as standard references, and collagen proportionate area (CPA) measurement for comparison.
  
  
  RESULTS
  qFibrosis faithfully and reliably recapitulates Metavir fibrosis scores, as it can identify differences between all stages in both animal samples (p<0.001) and human biopsies (p<0.05). It is robust to sampling size, allowing for discrimination of different stages in samples of different sizes (area under the curve (AUC): 0.93-0.99 for animal samples: 1-16 mm(2); AUC: 0.84-0.97 for biopsies: 10-44 mm in length). qFibrosis can significantly predict staging underestimation in suboptimal biopsies (<15 mm) and under- and over-scoring by different pathologists (p<0.001). qFibrosis can also differentiate between Ishak stages 5 and 6 (AUC: 0.73, p=0.008), suggesting the possibility of monitoring intra-stage cirrhosis changes. Best of all, qFibrosis demonstrates superior performance to CPA on all counts.
  
  
  CONCLUSIONS
  qFibrosis can improve fibrosis scoring accuracy and throughput, thus allowing for reproducible and reliable analysis of efficacies of anti-fibrotic therapies in clinical research and practice.
authors.affiliation: Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, #04-01, Singapore 138669, Singapore.|Computation and System Biology Program, Singapore-MIT Alliance, 4 Engineering Drive 3, E4-04-10, Singapore 117576, Singapore.|Biosystems and Micromechanics IRG, Singapore-MIT Alliance for Research and Technology, 1 CREATE Way, #04-13/14 Enterprise Wing, Singapore 138602, Singapore.
authors.forename: Shuoyu
authors.initials: S
authors.lastname: Xu
authors.affiliation: Institute of Hepatology, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, 1838 North Guangzhou Avenue, Guangzhou 510515, China.|Departments of Hepatobiliary Surgery and Pathology, Zhujiang Hospital, Southern Medical University, 253 Gongye Dadao Avenue, Guangzhou 510280, China.|Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, 2 Medical Drive, MD9 #04-01, Singapore 117597, Singapore.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, #04-01, Singapore 138669, Singapore.
authors.forename: Dean C S
authors.initials: DCS
authors.lastname: Tai
authors.affiliation: Department of Pathology, National University Hospital, 5 Lower Kent Ridge Road, Singapore 119074, Singapore.
authors.forename: Shi
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Pathology, National University Hospital, 5 Lower Kent Ridge Road, Singapore 119074, Singapore.
authors.forename: Chee Leong
authors.initials: CL
authors.lastname: Cheng
authors.affiliation: Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, #04-01, Singapore 138669, Singapore.|Computation and System Biology Program, Singapore-MIT Alliance, 4 Engineering Drive 3, E4-04-10, Singapore 117576, Singapore.
authors.forename: Qiwen
authors.initials: Q
authors.lastname: Peng
authors.affiliation: Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, #04-01, Singapore 138669, Singapore.|Biosystems and Micromechanics IRG, Singapore-MIT Alliance for Research and Technology, 1 CREATE Way, #04-13/14 Enterprise Wing, Singapore 138602, Singapore.
authors.forename: Jie
authors.initials: J
authors.lastname: Yan
authors.affiliation: Institute of Hepatology, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, 1838 North Guangzhou Avenue, Guangzhou 510515, China.
authors.forename: Yongpeng
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Institute of Hepatology, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, 1838 North Guangzhou Avenue, Guangzhou 510515, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Sun
authors.affiliation: Institute of Hepatology, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, 1838 North Guangzhou Avenue, Guangzhou 510515, China.
authors.forename: Xieer
authors.initials: X
authors.lastname: Liang
authors.affiliation: Institute of Hepatology, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, 1838 North Guangzhou Avenue, Guangzhou 510515, China.
authors.forename: Youfu
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Computation and System Biology Program, Singapore-MIT Alliance, 4 Engineering Drive 3, E4-04-10, Singapore 117576, Singapore.|Biosystems and Micromechanics IRG, Singapore-MIT Alliance for Research and Technology, 1 CREATE Way, #04-13/14 Enterprise Wing, Singapore 138602, Singapore.|Bioinformatics Research Center, School of Computer Engineering, Nanyang Technological University, 50 Nanyang Avenue, Singapore 639798, Singapore.|Department of Biological Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
authors.forename: Jagath C
authors.initials: JC
authors.lastname: Rajapakse
authors.affiliation: Computation and System Biology Program, Singapore-MIT Alliance, 4 Engineering Drive 3, E4-04-10, Singapore 117576, Singapore.|Sloan School of Management, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
authors.forename: Roy E
authors.initials: RE
authors.lastname: Welsch
authors.affiliation: Computation and System Biology Program, Singapore-MIT Alliance, 4 Engineering Drive 3, E4-04-10, Singapore 117576, Singapore.|Biosystems and Micromechanics IRG, Singapore-MIT Alliance for Research and Technology, 1 CREATE Way, #04-13/14 Enterprise Wing, Singapore 138602, Singapore.|Department of Mechanical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.|Department of Biological Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
authors.forename: Peter T C
authors.initials: PTC
authors.lastname: So
authors.affiliation: Department of Pathology, National University Hospital, 5 Lower Kent Ridge Road, Singapore 119074, Singapore.|Department of Pathology, Yong Loo Lin School of Medicine, National University of Singapore, 5 Lower Kent Ridge Road, Singapore 119074, Singapore.
authors.forename: Aileen
authors.initials: A
authors.lastname: Wee
authors.affiliation: Institute of Hepatology, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, 1838 North Guangzhou Avenue, Guangzhou 510515, China.
authors.forename: Jinlin
authors.initials: J
authors.lastname: Hou
authors.affiliation: Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, #04-01, Singapore 138669, Singapore.|Computation and System Biology Program, Singapore-MIT Alliance, 4 Engineering Drive 3, E4-04-10, Singapore 117576, Singapore.|Biosystems and Micromechanics IRG, Singapore-MIT Alliance for Research and Technology, 1 CREATE Way, #04-13/14 Enterprise Wing, Singapore 138602, Singapore.|Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, 2 Medical Drive, MD9 #04-01, Singapore 117597, Singapore.|Department of Biological Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.|The Mechanobiology Institute, 5A Engineering Drive 1, T-Lab #05-01, Singapore 117411, Singapore.
authors.forename: Hanry
authors.initials: H
authors.lastname: Yu
mesh_terms: D000818:Animals; D001706:Biopsy; D003094:Collagen / Q000032:analysis; D004195:Disease Models, Animal; D019694:Hepatitis B, Chronic / Q000150:complications*; D006801:Humans; D008099:Liver / Q000473:pathology; D008106:Liver Cirrhosis, Experimental / Q000175:diagnosis* / Q000473:pathology; D051381:Rats
chemical_list: D003094:Collagen
keywords: Chronic hepatitis B; Image analysis; Liver biopsy; Liver fibrosis assessment; qFibrosis