Progression of fibrosis in advanced chronic hepatitis C: evaluation by morphometric image analysis.
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-gamma 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-gamma 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.


CONCLUSIONS
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.
Goodman
Zachary D
ZD
Armed Forces Institute of Pathology, Division of Hepatic Pathology, Veterans Administration Special Reference Laboratory for Pathology, Washington, DC, USA. Goodman@afip.osd.mil
Becker
Robert L
RL
Pockros
Paul J
PJ
Afdhal
Nezam H
NH
D001706:Biopsy; D019698:Hepatitis C, Chronic / Q000150:complications / Q000473:pathology*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008099:Liver / Q000473:pathology*; D008103:Liver Cirrhosis / Q000209:etiology / Q000473:pathology*; D008111:Liver Function Tests