Systematic quantification of histological patterns shows accuracy in reflecting cirrhotic remodeling.

Abstract

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. 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. 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. QCP preliminarily demonstrates potential for quantitating cirrhotic remodeling with high resolution and accuracy. Further validation with in-study cohorts and multiple-etiologies is warranted.