qFibrosis: A fully-quantitative innovative method incorporating histological features to facilitate accurate fibrosis scoring in animal model and chronic hepatitis B patients

被引:150
作者
Xu, Shuoyu [1 ,2 ,3 ]
Wang, Yan [4 ,5 ,6 ,7 ]
Tai, Dean C. S. [1 ]
Wang, Shi [8 ]
Cheng, Chee Leong [8 ]
Peng, Qiwen [1 ,2 ]
Yan, Jie [1 ,3 ]
Chen, Yongpeng [4 ]
Sun, Jian [4 ]
Liang, Xieer [4 ]
Zhu, Youfu [4 ]
Rajapakse, Jagath C. [2 ,3 ,9 ,12 ]
Welsch, Roy E. [2 ,10 ]
So, Peter T. C. [2 ,3 ,11 ,12 ]
Wee, Aileen [8 ,13 ]
Hou, Jinlin [4 ]
Yu, Hanry [1 ,2 ,3 ,7 ,12 ,14 ]
机构
[1] Inst Bioengn & Nanotechnol, Singapore 138669, Singapore
[2] Singapore MIT Alliance, Computat & Syst Biol Program, Singapore 117576, Singapore
[3] Singapore MIT Alliance Res & Technol, Biosyst & Micromech IRG, Singapore 138602, Singapore
[4] Southern Med Univ, Nanfang Hosp, Dept Infect Dis, Inst Hepatol, Guangzhou 510515, Guangdong, Peoples R China
[5] Southern Med Univ, Zhujiang Hosp, Dept Hepatobiliary Surg, Guangzhou 510280, Guangdong, Peoples R China
[6] Southern Med Univ, Zhujiang Hosp, Dept Pathol, Guangzhou 510280, Guangdong, Peoples R China
[7] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Physiol, Singapore 117597, Singapore
[8] Natl Univ Singapore Hosp, Dept Pathol, Singapore 119074, Singapore
[9] Nanyang Technol Univ, Sch Comp Engn, Bioinformat Res Ctr, Singapore 639798, Singapore
[10] MIT, Sloan Sch Management, Cambridge, MA 02139 USA
[11] MIT, Dept Mech Engn, Cambridge, MA 02139 USA
[12] MIT, Dept Biol Engn, Cambridge, MA 02139 USA
[13] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Pathol, Singapore 119074, Singapore
[14] Mechanobiol Inst, T Lab 0501, Singapore 117411, Singapore
基金
中国国家自然科学基金;
关键词
Liver fibrosis assessment; qFibrosis; Chronic hepatitis B; Liver biopsy; Image analysis; CHRONIC VIRAL-HEPATITIS; LIVER FIBROSIS; DIAGNOSTIC-ACCURACY; IMAGE-ANALYSIS; CIRRHOSIS; BIOPSY; PROGRESSION; REGRESSION;
D O I
10.1016/j.jhep.2014.02.015
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Background & Aims: 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. (C) 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
引用
收藏
页码:260 / 269
页数:10
相关论文
共 33 条
[1]   Principal component analysis [J].
Abdi, Herve ;
Williams, Lynne J. .
WILEY INTERDISCIPLINARY REVIEWS-COMPUTATIONAL STATISTICS, 2010, 2 (04) :433-459
[2]  
[Anonymous], LIVER BIOPSY
[3]   Liver fibrosis [J].
Bataller, R ;
Brenner, DA .
JOURNAL OF CLINICAL INVESTIGATION, 2005, 115 (02) :209-218
[4]   Sampling variability of liver fibrosis in chronic hepatitis C [J].
Bedossa, P ;
Dargère, D ;
Paradis, V .
HEPATOLOGY, 2003, 38 (06) :1449-1457
[5]  
BEDOSSA P, 1994, HEPATOLOGY, V20, P15
[6]   Liver biopsy: The best, not the gold standard [J].
Bedossa, Pierre ;
Carrat, Fabrice .
JOURNAL OF HEPATOLOGY, 2009, 50 (01) :1-3
[7]   Computer-Assisted Image Analysis of Liver Collagen: Relationship to Ishak Scoring and Hepatic Venous Pressure Gradient [J].
Calvaruso, Vincenza ;
Burroughs, Andrew Kenneth ;
Standish, Richard ;
Manousou, Pinelopi ;
Grillo, Federica ;
Leandro, Gioacchino ;
Maimone, Sergio ;
Pleguezuelo, Maria ;
Xirouchakis, Ilias ;
Guerrini, Gian Piero ;
Patch, David ;
Yu, Dominic ;
O'Beirne, James ;
Dhillon, Amar Paul .
HEPATOLOGY, 2009, 49 (04) :1236-1244
[8]   Larger biopsies evaluation of transient elastography for detecting advanced fibrosis in patients with compensated chronic hepatitis B [J].
Chen, Yong Peng ;
Liang, Xie Er ;
Zhang, Qi ;
Peng, Jie ;
Zhu, You Fu ;
Wen, Wei Qun ;
Hou, Jin Lin .
JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, 2012, 27 (07) :1219-+
[9]   A systematic review of the quality of liver biopsy specimens [J].
Cholongitas, E ;
Senzolo, M ;
Standish, R ;
Marelli, L ;
Quaglia, A ;
Patch, D ;
Dhillon, AP ;
Burroughs, AK .
AMERICAN JOURNAL OF CLINICAL PATHOLOGY, 2006, 125 (05) :710-721
[10]   Impact of liver biopsy size on histological evaluation of chronic viral hepatitis: the smaller the sample, the milder the disease [J].
Colloredo, G ;
Guido, M ;
Sonzogni, A ;
Leandro, G .
JOURNAL OF HEPATOLOGY, 2003, 39 (02) :239-244