Contact Information: Email: firstname.lastname@example.org; Phone: 607-253-3060
Sponsor: Winn Feline Foundation
Grant Number: MT 10-004
Title: Investigation of the Role of Bacterial Cell Wall components, cytokine Signaling, and Myofibroblastic Fibrosis in Feline Nonsuppurative Cholangitis-Cholangiohepatitis Syndrome (CCHS) as an Aid to Improving Diagnostic Categorization and Treatment Modalities
Annual Direct Cost: $24,140
Project Period: 01/01/11-06/30/12
DESCRIPTION (provided by applicant): The feline cholangitis/cholangiohepatitis syndrome (CCHS) is the most common necroinflammatory liver disease in the cat and involves inflammation of the bile ducts and liver. Differentiation of CCHS from liver lymphoma (LSA) can be difficult even with special histologic and immunohistochemical stains, owing to overlap of microscopic features and possible evolution of LSA from CCHS. The cause of CCHS is uncertain, but destruction of bile ducts by the immune system and bacterial infection have been proposed as initiating mechanisms. This study aims to investigate the role of bacteria by determining the presence or absence of bacterial cell wall components in liver biopsies from cats with CCHS, cats with liver LSA, and cats with noninflammatory liver disease. Determining bacterial involvement in CCHS will enable clinicians to better target treatment to causal agents, rather than resorting only to immunomodulatory, antioxidant, and UDCA intervention. The expression of certain inflammatory mediators in bile duct epithelial cells and inflammatory infiltrates will also be investigated, as this has potential for differentiating CCHS and LSA. Finally, further investigations into bile duct fibrosis, and development of a grading system will help to quantify the severity of periductal fibrosis, investigate relevance to disease severity as indicated by clinical signs and liver biopsy microscopic features, and to assist with the differentiation of CCHS from LSA. We anticipate that findings will 1) identify cats that may derive benefit from chronic antimicrobial therapy, and 2) recommend additional stains :hat may be routinely used to assist in differentiation of nonsuppurative CCHS from hepatic LSA.