title: Systematic quantification of histological patterns shows accuracy in reflecting cirrhotic remodeling.
abstract: OBJECTIVE
  There still lacks a tool for precisely evaluating cirrhotic remodeling. Histologic distortion characterized in cirrhosis (i.e. cirrhotic patterns) has a validated pathophysiological meaning and potential relevance to clinical complications. We aimed to establish a new tool to quantify the cirrhotic patterns and test it for reflecting the cirrhotic remodeling.
  
  
  METHODS
  We designed a computerized algorithm, named qCP, dedicated for the analysis of liver images acquired by second harmonic microscopy. We evaluated its measurement by using a cohort of 95 biopsies (Ishak staging F4/5/6 = 33/35/27) of chronic hepatitis B and a carbon tetrachloride-intoxicated rat model for simulating the bidirectional cirrhotic change.
  
  
  RESULTS
  QCP can characterize 14 histological cirrhosis parameters involving the nodules, septa, sinusoid, and vessels. For chronic hepatitis B biopsies, the mean overall intra-observer and inter-observer agreement was 0.94 ± 0.08 and 0.93 ± 0.09, respectively. The robustness in resisting sample adequacy-related scoring error was demonstrated. The proportionate areas of total (collagen proportionate area), septal (septal collagen proportionate area [SPA]), sinusoidal, and vessel collagen, nodule area, and nodule density (ND) were associated with Ishak staging (P < 0.01 for all). But only ND and SPA were independently associated (P ≤ 0.001 for both). A histological cirrhosis parameters-composed qCP-index demonstrated an excellent accuracy in quantitatively diagnosing evolving cirrhosis (areas under receiver operating characteristic curves 0.95-0.92; sensitivity 0.93-0.82; specificity 0.94-0.85). In the rat model, changes in collagen proportionate area, SPA, and ND had strong correlations with both cirrhosis progression and regression and faithfully characterized the histological evolution.
  
  
  CONCLUSIONS
  QCP preliminarily demonstrates potential for quantitating cirrhotic remodeling with high resolution and accuracy. Further validation with in-study cohorts and multiple-etiologies is warranted.
authors.affiliation: State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research; Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou, China.|Biomedical Research Center, Southern Medical University, Guangzhou, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: School of Biomedical Engineering, Southern Medical University, Guangzhou, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Huang
authors.affiliation: Biomedical Research Center, Southern Medical University, Guangzhou, China.
authors.forename: Ruhua
authors.initials: R
authors.lastname: Li
authors.affiliation: School of Biomedical Engineering, Southern Medical University, Guangzhou, China.
authors.forename: Zhaoqiang
authors.initials: Z
authors.lastname: Yun
authors.affiliation: State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research; Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Youfu
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Biomedical Research Center, Southern Medical University, Guangzhou, China.
authors.forename: Jinlian
authors.initials: J
authors.lastname: Yang
authors.affiliation: School of Clinical Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Hailin
authors.initials: H
authors.lastname: Liu
authors.affiliation: School of Clinical Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Zhipeng
authors.initials: Z
authors.lastname: Liu
authors.affiliation: School of Biomedical Engineering, Southern Medical University, Guangzhou, China.
authors.forename: Qianjin
authors.initials: Q
authors.lastname: Feng
authors.affiliation: State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research; Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Jinlin
authors.initials: J
authors.lastname: Hou
mesh_terms: D000465:Algorithms; D000818:Animals; D002251:Carbon Tetrachloride; D003952:Diagnostic Imaging / Q000379:methods*; D004195:Disease Models, Animal; D018450:Disease Progression; D007091:Image Processing, Computer-Assisted / Q000379:methods*; D008099:Liver / Q000000981:diagnostic imaging* / Q000473:pathology*; D008103:Liver Cirrhosis / Q000000981:diagnostic imaging* / Q000473:pathology*; D008297:Male; D008853:Microscopy; D017207:Rats, Sprague-Dawley; D012680:Sensitivity and Specificity
chemical_list: D002251:Carbon Tetrachloride
keywords: animal model; biopsy; chronic hepatitis B; fibrosis change; liver cirrhosis; liver fibrosis; quantitative image analysis