Inflammatory disease is the second most common cause of hepatobiliary disease in cats. The histological classification of feline inflammatory liver disease is confusing. Terms used in the literature have included suppurative or acute cholangiohepatitis, chronic cholangiohepatitis, chronic lympocytic cholangitis, progressive lymphocytic cholangitis, sclerosing cholangitis, lymphoplasmacytic cholangitis/cholangiohepatitis, lymphocytic portal hepatitis, and biliary cirrhosis. This lack of consistency has made it difficult to compare reported cases. In 2004, the WSAVA Liver Disease and Pathology Standardization Research Group proposed a new classification scheme in order to provide consistency in terminology. Since the group felt that the inflammation was primarily centered on the biliary tree it defined three distinct histopathologic forms of feline cholangitis: 1.) neutrophilic cholangitis (acute and chronic) 2.) lymphocytic cholangitis and 3.) chronic cholangitis associated with biliary fluke infestation. Cats can get true chronic hepatitis but it is rare. Copper toxicity would be one to rule out.
Acute neutrophilic cholangitis (ANC) is marked by accumulation of neutrophils in the lumen and/or epithelium of the bile ducts with associated bile duct degeneration and necrosis. Edema and PMN’s may break through the limiting plate leading to cholangiohepatitis. Cats presenting with ANC are typically younger (<5 yrs old) than cats with other forms of cholangitis. Typically they have an acute onset of lethargy, anorexia, vomiting, +/- icterus, fever and abdominal pain. They may have a leukocytosis on CBC with a left shift or toxic changes and mild to moderate increases in ALT and GGT. ALP may be normal or mildly elevated. On diagnostic imaging choleliths, thickened GB or biliary duct walls may be present (Fig 1). ANC is almost always associated with bacterial infection. Culture of the liver or preferably bile should be part of the work up. Enteric aerobic and anaerobic organisms are isolated. E coli is the most common isolate. Most cats will have some predisposing cause for biliary tract infection (e.g. choleliths, inflammatory bowel disease, infectious nidus elsewhere in the body or concurrent chronic cholangitis). Treatment consists of antibiotics for 6-8 weeks +/- hepatoprotectants and choleretics.
Chronic neutrophilic cholangitis (CNC) is marked by a mixed inflammatory infiltrate (neutrophils, lymphocytes and plasma cells) in the bile ducts and periportal area with associated bile duct proliferation and varying degrees of peri-portal fibrosis which can bridge portal areas. Concurrent IBD (83%) and/or pancreatitis (50%) can occur. The clinical presentation is typically a middle- to senior-aged cat with a history of waxing and waning signs of vomiting and intermittent anorexia. Weight loss may be present. On physical examination the cats may have hepatomegaly and icterus. Typically all serum liver enzymes are increased. Some cats may have hyperglobulinemia. Ultrasound of the liver may be normal or may show hepatomegaly. The liver may be hyperechoic or hypoechoic with prominent markings. Ultrasound changes in the gallbladder and biliary ducts (wall thickening, mineralization, presence of biliary sludge) may be present. Concurrent changes in the pancreas and intestinal tract consistent with chronic inflammatory disease may be seen. Some cats present for bile duct obstruction from choleliths or inspissated bile. Many cats have evidence of secondary bacterial infection, and culture of a liver biopsy or bile aspirate should be done. Etiology of this disorder is unknown. It may be immune in origin or possibly a reaction to the presence of chronic bacterial infection or chronic exposure to bacterial products. Treatment usually consists of hepatoprotective agents (SAMe, ursodeoxycholate, vitamin E, silymarin) and a 6-week course of antibiotics. After antibiotic therapy many cats are prescribed an immunosuppressive course of prednisolone. Therapy should be directed at concurrent IBD if it is suspected. Hypoallergenic or novel ingredient diets along with parenteral supplementation with vitamin B12 is in order.
Lymphocytic cholangitis is marked by infiltration of small lymphocytes in the portal areas with lymphocytes centered around bile ducts or present in the biliary epithelium. Variable degrees of portal fibrosis and bile duct proliferation are present. There may be rare plasma cells and eosinophils. Based on H&E staining alone it may be very difficult to distinguish lymphocytic cholangitis from a small cell lymphoma. Ductopenia, peribiliary fibrosis, immunologic targeting of the bile ducts and lipogranulomas were more common with lymphocytic cholangitis than with small cell lymphoma. Immunophenotyping may be of some value in making the determination as most (but not all) cases of lymphocytic cholangitis are a mixture of B and T cells (often portal aggregates of B cells are present, while small cell lymphomas are either exclusively B or T cells). Tests for clonality can be done on biopsy material as well with most lymphomas being derived from one clone. Clinical presentation in cats with lymphocytic cholangitis is similar to that seen with CNC but these cats often have an even more insidious onset. Therapy for lymphocytic cholangitis is a combination of prednisolone with chlorambucil +/- vitamin B12 supplementation and hepatoprotectants.
Chronic cholangitis associated with biliary fluke infestation is characterized by dilated large bile ducts with papillary projections and associated marked periductal and periportal fibrosis. There are scant to moderate mixed inflammatory cell infiltrates within the bile ducts or periportal areas. There may or may not be eosinophils present. Treatment is with praziquantel. The intermediate hosts for the flukes are not present in New England.
It should be noted that some old cats get a progressive accumulation of lymphocytes in the portal regions of the liver. This appears to be reactive lesion and may not be associated with primary hepatobiliary disease. It has been called lymphocytic portal hepatitis in the literature. Over 80% of cats old than 10-years of age have this lesion.