# Quantification of Liver Fibrosis--A Comparative Study
## 4 Results and Discussion
### Results from Earlier Works Employing DIA and HAI Systems

Table 5: Recent publications building intelligent systems for automated CPA detection. observed between the percentage of fibrosis estimated histomorphometrically and the amount of collagen measured colorimetrically (r = 0.77, \(p<0.001\)). [PERSON] et al. [12] observed a regression of liver collagen in patients treated with interferon, whereas conventional histological evaluation (Knodell's HAI) did not detect any significant improvement in fibrosis. Moreover, the colorimetric and morphometric measurements of total collagen and the collagen content in the Disse space correlated significantly (r = 0.774, \(p<0.005\) and r = 0.709, \(p<0.01\)). A highly significant correlation (r = 0.778) was also observed between the collagen content measured colorimetrically and the percentage of fibrosis assessed histomorphometrically. [PERSON] et al. [13] noted that the collagen index of the liver tissue (ratio of the stained fibrotic area to the total tissue area) correlated well with the biochemically measured hydroxyproline content in biopsy specimens as well as with the fibrosis percentage retrieved from samples colored with SR and Fast green double stain (r = 0.887). [PERSON] et al. [14] proved that the microscopy histological image analysis was better related to morphometric measurement of fibrosis as well as with four main fibrotic deposit sites embedded in the developed by the researchers' semi-quantitative scoring system (SSS). In particular, the estimation of the total fibrosis score was expressed by the following formula:  
\[\text{SSS}=\text{CLV}+\text{PS}+\text{PT}+2(\text{WS}+\text{NS}), \tag{11}\]  
where CLV refers to centrilobular vein, PS to the perisinusoidal space, PT to the portal tract, while WS and NS stand for the width and the number of the septa, respectively. The results showed that the correlations between the novel SSS and the surface density of total collagen (SDTC) were (r = 0.73, \(p\leq 10^{-5}\)). Each one of the above five individual histological variables, except fibrosis in the CLV, presented an excellent intra-observer and inter-observer agreement. Several studies were based on microscopy image analysis to examine differences in liver collagen content at several stages of chronic hepatitis. In [PERSON] et al. [15], the total collagen index (CI) was correlated well with the one quantified by biochemical analysis (r = 0.88, \(p<0.0001\)). [PERSON] et al. [16] observed a strong and significant Scheuer correlation between the stage and the area of fibrosis in both hepatitis B (r = 0.67, \(p<0.001\)) and hepatitis C patients (r = 0.75, \(p<0.001\)). Specifically, the area of the collagen fiber in the initial biopsy was related significantly to the period of evolution from chronic hepatitis C to cirrhosis. Also, the results proved to be well correlated and the increase in the rate of fibrosis in hepatitis C patients was noticeably higher than in hepatitis B patients. [PERSON] et al. [17] showed that the area of fibrosis determined by microscopy image analysis and the semi-quantitative scores were well correlated (r = 0.84, \(p<10^{-4}\)). When serum markers of fibrosis were taken into account, the correlation was higher when the area of fibrosis was used as reference compared to a semi-quantitative score. In conclusion, most markers were not correlated with major fibrotic histological findings, meaning that they lack accuracy over the quantitative measurement of liver fibrosis. Thus, the merits of microscopy image analysis motivated the researchers to focus on designing and developing image analysis tools, such as the FibroQuant application, to quantify the percentage of the glomerular porto-periportal and septal fibrosis areas. [PERSON] et al. [18] showed significant correlations (0.72 \(<\) r \(<\) 0.83, \(p<0.0001\)) between the microscopy image analysis based on FibroQuant application and the Knodell, Scheuer histologic evaluations of liver fibrosis. [PERSON] et al.