Progression of fibrosis in advanced chronic hepatitis C: Evaluation by morphometric image analysis

Abstract

Fibrosis progression in chronic liver disease has usually been evaluated by liver biopsy using insensitive semiquantitative numerical scores. An alternative to this is to measure fibrous tissue quantitatively using morphometric image analysis. The aim of this study was to quantify fibrosis progression in a cohort of patients with treatment-refractory chronic hepatitis C enrolled in a placebo-controlled clinical trial of interferon gamma-1b (IFN-␥ 1b) for the treatment of advanced hepatic fibrosis. We used morphometry to quantify the amount of fibrous tissue in liver biopsies performed at baseline and after 48 weeks in 245 patients who had paired unfragmented, adequate-sized specimens and correlated the results with clinical and laboratory parameters. Eighty-seven patients were treated with placebo and 158 with IFN-␥ 1b. No effect of the drug on fibrosis was found in the trial, and so data from all 245 patients were combined for analysis. At baseline, 78% had cirrhosis; 22%, bridging fibrosis. The mean morphometrically determined collagen content increased by 58% between baseline and 48 weeks. There were statistically significant but weak correlations of fibrosis with platelet count, albumin, bilirubin, INR, and hyaluronic acid; however, changes in these did not correlate with or predict changes in fibrosis in the liver biopsy. Conclusion: In advanced chronic hepatitis C, fibrosis increases at a rapid pace that can only be detected by morphometry. This technique can be used in future therapeutic trials of agents to inhibit fibrosis progression. (HEPATOLOGY 2007;45:886-894.)

Mechanisms of Hepatic Fibrogenesis

“…Indeed, a key lesson from antifibrotic trials to date is that fibrosis may continue to accrue rapidly even in patients with cirrhosis when therapy is not effective. 216 Based on this lesson, it is clear that trials in such cirrhotic patients will need to be lengthy, with the use of more sensitive and specific biomarkers that do not rely on biopsy alone. 217 Further progress in understanding, diagnosing, and treating hepatic fibrosis will continue to rely on the exploration of fundamental mechanisms of fibrogenesis, which is certain to lead to a meaningful impact on the prognosis of patients with chronic liver disease.…”

Fibrosis 4 Score Versus Hyaluronic Acid as Non-Invasive Tools for Assessment of HCV-Related Hepatic Fibrosis: Correlation with Quantitative Morphometric Analysis of Liver Biopsy

“…In addition, morphometry could be considered a good, sensitive tool in quantitation of advanced liver fibrosis with high sensitivity and specificity (83% and 91%, respectively). Accurate morphometric studies require high quality specimens which are not fragmented and of adequate size, because fibrous tissue is under represented in small, fragmented specimens of fibrotic livers [23]. Therefore, biopsy specimen that did not meet these criteria was excluded.…”

What is the benefit of computer-assisted image analysis of liver fibrosis area?

“…Computer-assisted image analysis of the stained fibrosis area in liver biopsy specimens is a method for quantitatively measuring the amount of liver fibrosis [4]. It is not used for the clinical assessment of liver fibrosis in general, but is often used in the assessment of fibrosis in animal models.…”