Signalment:  

13 years-old, female, Freiberger horse (Equus caballus) The horse had colic since 6 days. The horse showed obstipation at the flexura pelvis. Its colon was displaced to the right at the flexura pelvis. The horse shoed slight icterus. With ultrasound examination the liver was inconspicuous. The clinicians suspected a primary or secondary hepatopathy.

Gross Description:  

The liver showed severe atrophy of the Lobus hepatis dexter; the whole liver was mildly more friable and was marbled dark and pale brown; on cut section pus was coming out of the bile ducts; several small (up to 0.5 cm in diameter) white, hard superficial nodules were present (calcifications). In the stomach few Gasterophilus intestinalis were present on the Pars non-glandularis. The wall of the Ileum was mildly thickened (up to 1 cm thick). The left colon ascendens ventralis contained large amount of dry, dark green, fibrous content (impaction); the mucosa was mildly oedematous. 

Histopathologic Description:

Liver: Multifocally in the lumen of the bile ducts, in the portal triads and in the surrounding liver parenchyma there are many degenerate neutrophils and cell debris. The bile ducts are surrounded by moderate to large amounts of connective tissue and many lymphocytes, macrophages, plasma cells and degenerate neutrophils. Multifocally the bile ducts are increased in size and in number (bile duct hyperplasia). They are lined by columnar to cuboidal epithelial cells. Epithelial cells show rarely pyknotic nuclei or karyorrhexis and karyolysis. Many epithelial cells are plump and contain large amount of amphophilic cytoplasm and plump, vesiculated, pale basophilic nuclei. Multifocally there are a lot of bile plugs. There is mild lymphangiectasia and periportal edema. Multifocally there is a mild infiltration of the liver capsule with few lymphocytes and plasma cells.

Morphologic Diagnosis:  

Liver: Cholangiohepatitis, suppurative, multifocal to coalescing, severe, chronic Atrophy of the Lobus hepatis dexter
Colon ascendens ventralis left: Impaction

Lab Results:  

The blood values showed elevated liver enzymes. 
In the liver, a high content of Pasteurella sp. and of a mixed flora were isolated (Institut f+�-+r Veterin+�-�r-Bakteriologie of the University of Bern). 

Condition:  

Cholangiohepatitis

Contributor Comment:  

Cholangiohepatitis is a sporadic, but common disease of adult horses. Generally, the disease process is initiated by an ascending biliary tract infection due to a gram negative rod. In the chronic state choleliths can develop, causing obstruction of the biliary tree and leading to icterus and colic. Cholangiohepatitis may also occur secondary to cholelithiasis.⁴

The exact etiology and pathogenesis of cholangiohepatitis in large animals is unknown. The early stages of the disease are often associated with periportal inflammation as well as inflammation in the bile ducts. In suppurative cholangiohepatitis, the bacterial infection may be distributed through portal circulation or extend through the bile ducts. In non-suppurative cholangiohepatitis, disease progression is more likely due to an immune-mediated processes.⁷

Because the hepatocytes are being destroyed more rapidly than they can be replaced, fibrosis begins to bridge the affected areas of the liver. As the fibrosis becomes more extensive, cholestasis and failure of hepatic function may occur. The bile ducts and bile duct epithelium undergo proliferation, which may impair bile excretion.

On necropsy, the liver will appear firm, pale brown to green, with prominent irregular markings on the cut surface.

Histopathologically two forms are described. A suppurative form in which there is extensive neutrophilia in the periportal area. The neutrophils often contain bacteria. Biliary hyperplasia, loss of hepatocytes, and fibrosis are also evident in the periportal areas. A non-suppurative form in which the primary cellular infiltrate is composed of mononuclear cells, primarily lymphocytes, and plasma cells.^2,6

Early in the disease, clinical signs are referable to the inflammatory processes occurring in the liver. These inflammatory signs include fever and hepatomegaly, and may lead to colic and biliary obstruction. Anorexia follows in cases which present for colic. Biliary obstruction may then lead to icterus and hepatic photosensitization. Hepatic encephalopathy and related signs are rare except in cases of chronic hepatic fibrosis. 

Clinical pathologic changes include significantly elevated GGT (600-2500 U/L), slight elevations in AST and SDH relative to the GGT levels, elevated Bile Acids, leukocytosis with neutrophilia, hyperfibrinogenemia and hyperproteinemia and coagulation parameters should be within normal range.^1,5

JPC Diagnosis:  

Liver: Cholangiohepatitis, chronic-active, diffuse, severe, with bile duct hyperplasia, diffuse bridging fibrosis, and cholestasis, Freiberger horse (Equus caballus), equine.

Conference Comment:  

The contributor gives an excellent overview of cholangiohepatitis in horses. Cholangiohepatitis in horses has been reported to occur as a primary disease, or secondarily due to cholelithiasis, duodenal inflammation, intestinal obstruction, neoplasia, parasitism, and certain toxins such as pyrrolizidine alkaloid and those of Trifolium hybridum (alsike clover).^3,7,8

Suppurative cholangiohepatitis in horses is most commonly associated with cholelithiasis, which is thought to result from ascending infections from the small intestine.² Cholangiohepatitis and/or pancreatitis secondary to reflux of duodenal contents may occur acutely as in cases of duodenal obstruction or more chronically, due to either intermittent outflow obstruction or spasm of the major duodenal papilla secondary to inflammation.¹ It has also been found that bacteria, bacterial products, and endotoxins may enter the liver through the portal circulation resulting in periportal inflammation.² The bacteria most commonly associated with cholelithiasis and cholangiohepatitis in horses are Escherichia coli, Salmonella sp, Aeromonas sp, and Citrobacter sp.²

Whether choleliths occur prior to or following the development of cholangiohepatitis has not been determined.⁴ The pathogenesis of cholelith formation is not clear, although most choleliths are reported to contain a mixed amount of bilirubin, bile pigments, cholesterol esters, esters of cholic and carboxylic acid, calcium phosphate, and sodium taurodeoxycholate.³

In cattle and sheep, cholangiohepatitis has been reported to occur due to sporidesmin, a fungal toxin produced by Pithomyces chartarum³, and liver flukes such as Fasciola hepatica.

References:

1 Buote M: Cholangiohepatitis and pancreatitis secondary to severe gastroduodenal ulceration in a foal. Can Vet J 44: 746-748, 2003
2 Davis JL, Jones SL: Suppurative cholangiohepatitis and enteritis in adult horses. J Vet Intern Med 17: 583-587, 2003
3. Gerros TC: Gallbladder and biliary tract disease. In: Large Animal Internal Medicine, ed. Smith BP, 2nd ed., pp. 946-948. Mosby-Year Book Inc., New York, NY, 1996
4. Peek SF, Divers TJ: Medical treatment of cholangiohepatitis and cholelithiasis in mature horses: 9 cases (1991-1998). Equine Vet J 32:301-306, 2000
5. Ryu SH, Bak UB, Lee CW, Lee YL: Cholelithiasis associated with recurrent colic in a Thoroughbred mare. J Vet Sci 5:79-82, 2004
6. Schulz KS, Simmons TR, Johnson R: Primary cholangiohepatitis in a horse. Cornell Vet 80:35-40, 1990
7. Smith MR, Stevens KB, Durham AE, Marr CM: Equine hepatic disease: The effect of patient- and case-specific variables on risk and prognosis. Equine Vet J 35:549-552, 2003
8. Stalker MJ, Hayes MA: Liver and biliary system. In: Jubb, Kennedy, and Palmers Pathology of Domestic Animals, ed. Maxie MG, 5th ed., vol. 2, pp. 345-348. Elsevier Limited, St. Louis, MO, 2007

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