| Chronic liver disease is a common diagnosis in dogs, but aside from well-described breed-specific copper storage hepatopathy, little is known about the underlying etiologies or pathogenesis of most forms of canine chronic liver injury. This study uses a modification of Ishak's grading and staging scheme to establish a standardized method of histologic examination of H&E-stained liver biopsy specimens from 45 case dogs with chronic liver disease and 55 healthy control dogs. Intraobserver repeatability and interobserver agreement of the grading/staging scheme were substantial.;The Ishak score for grade of necroinflammatory activity was strongly correlated (using Spearman correlation coefficients) with total serum bilirubin (SCC=0.58), an index of Ki-67 immunoreactivity (SCC=0.57), an index of cleaved caspase-3 immunoreactivity (SCC=0.51), iron staining (SCC=0.61), scoring for hepatic eNOS immunoreactivity (SCC=0.64) (in hepatocytes, lobular, portal and septal stroma cells), scoring for iNOS imunoreactivity (SCC=0.64) (particularly in lobular, portal, and septal stromal cells), and diffuse hepatocellular malondialdehyde-protein adduct immunoreactivity (SCC=0.65). Weak positive correlation was found with Perl's staining for copper (SCC=0.39), and weak negative correlation with alpha-smooth muscle actin immunoreactivity within perisinusoidal hepatic stellate cells (SCC=-0.34).;The Ishak score for stage of fibrosis was strongly correlated with Masson's trichrome collagen staining (SCC=0.90), and upregulated von Willebrand's factor immunoreactivity (vWF) within lobular sinusoidal endothelial cells (SCC=0.57); a weak correlation was identified with malondialdehyde-protein adducts within Kupffer cells (SCC=0.29). No significant correlations were noted between malondialdehyde-protein adduct immunoreactivity and histochemically detected iron or copper.;These findings indicate that a modification of a standardized histologic evaluation scheme for assessing chronic liver disease in humans can be applied to liver biopsies of dogs, although clinical utility requires further investigation. The scheme may have utility in further research. These studies also demonstrate changes in sinusoidal endothelial vWF immunoreactivity, oxidative stress and nitric oxide synthase isoform expression in chronic liver disease of dogs. |
