A morphological and immunohistochemical study of the effects of prednisolone or ursodeoxycholic acid on liver histology in feline lymphocytic cholangitis

Abstract

Feline lymphocytic cholangitis (LC) has been commonly treated with prednisolone, and more recently with ursodeoxycholic acid (UDCA). Previously, we found that prednisolone treatment resulted in a statistically longer survival time than treatment with UDCA. In order to explain this difference, we compared the effects of prednisolone and UDCA treatment on hepatic tissue by evaluating consecutive liver biopsies. Archival serial biopsy materials from cats with LC treated with prednisolone (n = 5) or UDCA (n = 4) were evaluated. We employed haematoxylin and eosin staining to evaluate inflammation, and reticulin staining for fibrosis. Immunohistochemical stainings for Ki-67, K19 (Cytokeratin 19) and α-smooth muscle actin were used to evaluate cell type-specific proliferation and activation of hepatic stellate cells. Inflammation decreased more in the group treated with prednisolone, while the number of cholangiocytes, progenitor cells and fibroblasts did not differ between the treatment groups. Additionally, no difference was found for the amount of fibrosis in both treatment groups.

Figure 1

Histological examples of feline lymphocytic cholangitis. (a) Large infiltrates of small lymphocytes are present in portal areas (asterisk) extending to portal–portal bridging inflammation. Haematoxylin and eosin (HE) staining. (b) Portal areas are infiltrated by moderate numbers of small lymphocytes with moderate bile duct proliferation. HE staining. (c) Concentric bands of collagen surround the bile duct (asterisk). Collagen stain according to Gordon and Sweet. (d) Positive staining against α-smooth muscle actin is present around the bile ducts, in the arterial tunica media and in the wall of the portal veins. In addition, the perisinusoidal spaces throughout the parenchyma are moderately stained, which is most likely due to activated stellate cells. Immunohistochemistry (IHC). (e) Positive staining for K19 is present in the cytoplasm of bile duct (arrowhead) cells and other cells (most likely liver progenitor cells) located in the periportal parenchyma (arrow). IHC. (f) Positive Ki-67 staining is present in nuclei of proliferating lymphocytes (arrow), fibroblasts (arrowhead) in portal areas and in hepatocytes (asterisk). IHC