Immunohistochemical Evaluation of CD68, β-catenin, α-SMA and Ki67 Expression in Kupffer and Parenchymal Stellate Cells Associated With Bovine Liver Lesions Leading to Fibrosis.

Introduction: Liver fibrosis is a disorder resulting from numerous diseases that threaten animal life. Materials and Methods: Over two years (2021-2023), a total of 1,525 bovine livers were inspected, and common liver diseases leading to fibrosis -including fascioliasis, fatty change, hydatid cyst, and abscess -were diagnosed using various histochemical staining techniques. Results: The evaluation of serum enzymes indicated a significant increase in alanine aminotransferase (ALT) in fascioliasis, as well as aspartate transferase (AST) and gamma-glutamyl transferase (GGT) in fascioliasis and fatty change, compared to other groups (P<0.05). Immunohistochemical results demonstrated that the expression intensity and mean number of α-SMA-positive stellate cells and β-catenin-positive significantly increased (P<0.05) in fascioliasis, fatty change, abscess, and hydatid cyst lesions compared to normal liver. The expression pattern of α-SMA in lesions was observed in three states Perisinusoidal, periportal, and pericentral. Furthermore, in fatty liver change, nuclear expression of β-catenin was observed in parenchymal cells. Indeed, unlike the human liver -where β-catenin expression is present in bile duct cells under normal conditions -in cattle, only membranous-cytoplasmic expression of β-catenin was recorded in bile duct cells of livers affected by fascioliasis. The number of CD68-positive Kupffer cells (KCs) and Ki67-positive cells in liver lesions showed a significant increase compared to normal liver (P<0.05). Conclusion: Overall, considering the results, with increasing severity of liver fibrosis, the expression of CD68, β-catenin, α-SMA, and Ki67 markers also increases. In other words, with the onset and progression of inflammation in the bovine liver, simultaneous activation of stellate and KCs and increased collagen production contribute to the reconstruction of the damaged liver with connective tissue, thereby leading to liver fibrosis.