Histological Fibrosis Quantification in Chronic Hepatitis C
Histological Fibrosis Quantification in Chronic Hepatitis C
Hepatic fibrosis staging is based on semiquantitative scores. Digital imaging analysis (DIA) appears more accurate because fibrosis is quantified in a continuous scale. However, high cost, lack of standardization and worldwide unavailability restrict its use in clinical practice. We developed an inexpensive and widely available DIA technique for fibrosis quantification in hepatitis C, and here, we evaluate its reproducibility and correlation with semiquantitative scores, and determine the fibrosis percentage associated with septal fibrosis and cirrhosis. 282 needle biopsies staged by Ishak and METAVIR scores were included. Images of trichrome-stained sections were captured and processed using Adobe® Photoshop® CS3 and Adobe® Bridge® softwares. The percentage of fibrosis (fibrosis index) was determined by the ratio between the fibrosis area and the total sample area, expressed in pixels calculated in an automated way. An excellent correlation between DIA fibrosis index and Ishak and METAVIR scores was observed (Spearman's r = 0.95 and 0.92; P < 0.001, respectively). Excellent intra-observer reproducibility was observed in a randomly chosen subset of 39 biopsies with an intraclass correlation index of 0.99 (95% CI, 0.95–0.99). The best cut-offs associated with septal fibrosis and cirrhosis were 6% (AUROC 0.97, 95% CI, 0.95–0.99) and 27% (AUROC 1.0, 95% CI, 0.99–1), respectively. This new DIA technique had high correlation with semiquantitative scores in hepatitis C. This method is reproducible, inexpensive and available worldwide allowing its use in clinical practice. The incorporation of DIA technique provides a more complete evaluation of fibrosis adding the quantification to architectural patterns.
Chronic hepatitis C is a major public health problem and continues to be a leading cause of chronic liver disease and cirrhosis worldwide. Liver fibrosis staging is still essential in management of these patients. The accurate assessment of hepatic fibrosis plays a critical role determining antiviral treatment, screening strategies and prognosis. Furthermore, patients with advanced fibrosis and cirrhosis have a poor prognosis, presenting lower survival rate than mild fibrosis patients.
Currently, liver biopsy is still considered the gold standard for fibrosis staging. Traditional histological assessment is based on semiquantitative scoring systems (Ishak and METAVIR score). Although frequently used, these scoring systems do not allow a precise quantification of liver fibrosis. Moreover, they are subjective measurements with high rates of intra- and interobserver variability.
During the last years, methods to quantify liver fibrosis through computer software, called digital image analysis (DIA), have been developed. DIA allows quantitative assessment of fibrosis using pixel counting to estimate fibrosis area. The great advantage of this method over semiquantitative scores is that DIA is a truly quantitative method, not influenced by subjective visual interpretation of the observer. This new technology has been applied to estimate liver fibrosis in chronic viral hepatitis. However, the use of different softwares, high cost, lack of standardization of this method and worldwide unavailability restrained its use to a few numbers of specialized centres.
The primary aim of this study was to develop an inexpensive and worldwide available DIA technique for fibrosis quantification in liver biopsies of patients with chronic hepatitis C. Secondary aims were (i) to compare METAVIR and Ishak scoring systems with this new quantitative assessment of fibrosis, (ii) to determine the intra-observer reproducibility of the fibrosis index and (iii) to establish the most accurately cut-off associated to septal fibrosis and cirrhosis.
Abstract and Introduction
Abstract
Hepatic fibrosis staging is based on semiquantitative scores. Digital imaging analysis (DIA) appears more accurate because fibrosis is quantified in a continuous scale. However, high cost, lack of standardization and worldwide unavailability restrict its use in clinical practice. We developed an inexpensive and widely available DIA technique for fibrosis quantification in hepatitis C, and here, we evaluate its reproducibility and correlation with semiquantitative scores, and determine the fibrosis percentage associated with septal fibrosis and cirrhosis. 282 needle biopsies staged by Ishak and METAVIR scores were included. Images of trichrome-stained sections were captured and processed using Adobe® Photoshop® CS3 and Adobe® Bridge® softwares. The percentage of fibrosis (fibrosis index) was determined by the ratio between the fibrosis area and the total sample area, expressed in pixels calculated in an automated way. An excellent correlation between DIA fibrosis index and Ishak and METAVIR scores was observed (Spearman's r = 0.95 and 0.92; P < 0.001, respectively). Excellent intra-observer reproducibility was observed in a randomly chosen subset of 39 biopsies with an intraclass correlation index of 0.99 (95% CI, 0.95–0.99). The best cut-offs associated with septal fibrosis and cirrhosis were 6% (AUROC 0.97, 95% CI, 0.95–0.99) and 27% (AUROC 1.0, 95% CI, 0.99–1), respectively. This new DIA technique had high correlation with semiquantitative scores in hepatitis C. This method is reproducible, inexpensive and available worldwide allowing its use in clinical practice. The incorporation of DIA technique provides a more complete evaluation of fibrosis adding the quantification to architectural patterns.
Introduction
Chronic hepatitis C is a major public health problem and continues to be a leading cause of chronic liver disease and cirrhosis worldwide. Liver fibrosis staging is still essential in management of these patients. The accurate assessment of hepatic fibrosis plays a critical role determining antiviral treatment, screening strategies and prognosis. Furthermore, patients with advanced fibrosis and cirrhosis have a poor prognosis, presenting lower survival rate than mild fibrosis patients.
Currently, liver biopsy is still considered the gold standard for fibrosis staging. Traditional histological assessment is based on semiquantitative scoring systems (Ishak and METAVIR score). Although frequently used, these scoring systems do not allow a precise quantification of liver fibrosis. Moreover, they are subjective measurements with high rates of intra- and interobserver variability.
During the last years, methods to quantify liver fibrosis through computer software, called digital image analysis (DIA), have been developed. DIA allows quantitative assessment of fibrosis using pixel counting to estimate fibrosis area. The great advantage of this method over semiquantitative scores is that DIA is a truly quantitative method, not influenced by subjective visual interpretation of the observer. This new technology has been applied to estimate liver fibrosis in chronic viral hepatitis. However, the use of different softwares, high cost, lack of standardization of this method and worldwide unavailability restrained its use to a few numbers of specialized centres.
The primary aim of this study was to develop an inexpensive and worldwide available DIA technique for fibrosis quantification in liver biopsies of patients with chronic hepatitis C. Secondary aims were (i) to compare METAVIR and Ishak scoring systems with this new quantitative assessment of fibrosis, (ii) to determine the intra-observer reproducibility of the fibrosis index and (iii) to establish the most accurately cut-off associated to septal fibrosis and cirrhosis.
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