Systematic Quantitation of Histologic Patterns Shows Accuracy in Reflecting Cirrhotic Remodeling

Background and Aim 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 the potential relevance to clinical complications. We aimed to establish a new tool for quantify the cirrhotic patterns and test it for reflecting the cirrhotic remodeling. Methods We designed a computerized algorithm (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 (CHB) and a carbon tetrachloride-intoxicated rat model for simulating the bidirectional cirrhotic change. Results QCP can characterize 14 histologic cirrhosis parameters (HCPs) involving the nodules, septa, sinusoid and vessels. For CHB biopsies, the mean overall intra- 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 (CPA), septal (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 HCPs-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 CPA, SPA, and ND had strong correlations with both cirrhosis progression and regression and faithfully characterized the histologic 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.