March 15, 2014

Image analysis of liver biopsy samples measures fibrosis and predicts clinical outcome

Journal of Hepatology

Article in Press

Yi Huang, W. Bastiaan de Boer, Leon A. Adams, Gerry MacQuillan, Max K. Bulsara, Gary P. Jeffrey 

Received 19 September 2013; received in revised form 20 January 2014; accepted 22 February 2014. published online 07 March 2014.
Accepted Manuscript


Background & Aims

Histopathological scoring of liver fibrosis mainly measures architectural abnormalities and requires a minimum biopsy size (greater than or equal to 10mm). Liver collagen quantification may allow use of small size biopsies and improve the prediction of clinical outcomes. This study evaluated the ability of the collagen proportional area (CPA) measurement to predict clinical outcomes.


Clinical outcomes were determined using population based data-linkage for chronic hepatitis C (CHC) patients from 1992-2012. Quantitative digital image analysis of liver biopsies was used for CPA measurement.


533 patients with a biopsy size greater than or equal to 5 mm were included. Median follow up was 10.5 years. 26 developed hepatocellular carcinoma (HCC), 39 developed liver decompensation and 33 had liver related death. 453 had Metavir F0-F2 and 80 had F3-F4. CPA ranged from 1.3%-44.6%. CPA and Metavir stage were independently associated with liver related death. Metavir stage, CPA stage and age were independently associated with HCC. CPA stage (C1: 0%-5%, C2: 5%-10%, C3: 10%-20%, C4: >20%) stratified risk and a significant difference in outcomes was present between all CPA stages for HCC and between C2-C3 and C3-C4 for decompensation and liver related death. The 15 year composite endpoint-free survival was 97% for C1, 89% for C2, 60% for C3, 7% for C4. C4 had significantly worse survival than ⩽C3 (p<0.001) in cirrhotic patients.


CPA stage gave additional information regarding risk stratification for adverse clinical outcomes independent of Metavir stage.

Abbreviations: CPA, collagen proportional area, CHC, chronic hepatitis C, HCC, hepatocellular carcinoma, HCV, hepatitis C virus, AUROC, area under receiver operating characteristic curves, HR, hazard ratio

Keywords: Collagen proportional area, Chronic hepatitis C, Histological stage, Liver complication, Liver related death

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