Cholelithiasis, Choledocholithiasis, and Hepatolithiasis in Large Animals

Cholelithiasis in horses may cause biliary obstruction and concurrent liver disease or may be an incidental finding on ultrasonography or at necropsy. It most commonly affects middle-aged horses, with no sex or breed predilection. Solitary or multiple calculi may be present in ruminants in the bile duct or gallbladder (cholelithiasis), common bile duct (choledocholithiasis), or intrahepatic bile ducts (hepatolithiasis). Choledocholithiasis is the most common cause of biliary obstruction in large animals, with horses more frequently affected than other species. The cause of cholelith formation in horses is not known. Choleliths in horses are usually calcium bilirubinate but can include calcium phosphate. Ascending biliary tract inflammation (cholangiohepatitis), intestinal bacterial infection resulting in bile stasis, and a change in bile composition or cholesterol concentration have been proposed. Choleliths that form around a foreign body, such as ascending plant material or parasites, may occlude the common bile duct. Cholelithiasis and hepatolithiasis reportedly are not well recognized as a clinical problem in sheep and goats. Incidence in camelids is unknown.

Clinical signs commonly observed in horses with choleliths or cholangiohepatitis include weight loss, abdominal pain, icterus, depression, and intermittent fever. Signs of hepatic failure, including encephalopathy, photosensitivity, and coagulopathy, occur less frequently. Clinical signs are often intermittent. Complete obstruction of the common bile duct often is accompanied by persistent abdominal pain.

Laboratory abnormalities include increased plasma or serum bilirubin (direct or conjugated), gamma-glutamyl transferase (GGT), alkaline phosphatase (AP), and total bile acid concentrations. Increases in sorbitol dehydrogenase (SDH) and aspartate aminotransferase (AST) activities are observed; however, the increases are not as dramatic as those of the primary biliary enzymes. BUN, glucose, and potassium concentrations may be decreased in cases with greater chronicity or anorexia. Metabolic tests indicate decreased hepatic function. Prothrombin time (PT) and partial thromboplastin time (PTT) may be prolonged. Leukocytosis, anemia of chronic disease, and increases in total protein, globulins, fibrinogen, and serum amyloid A (SAA) concentrations may be present because of inflammation. Histologic changes include periportal and intralobular fibrosis, moderate bile duct dilatation and proliferation, and cholestasis. Culture of the liver may reveal a bacterial infection.

• Increases in plasma GGT and AP activities, as well as lesser increases in hepatocellular enzymes

• The presence of one or more hyperechoic focal "liths" on ultrasonography, with acoustic shadowing deep to the stones

Cholelithiasis should be considered in horses with a history of fever, icterus, and/or recurrent abdominal pain. Other clinical signs of hepatic failure (encephalopathy, photodermatitis, weight loss) are less consistently observed with cholelithiasis. A marked increase in plasma GGT activity with hyperbilirubinemia (direct bilirubin > 25%) also supports a diagnosis of cholelithiasis. Increases in SDH, AST, and AP activity are often also present; when they are absent despite increased serum GGT activity, however, the presumptive diagnosis of biliary stasis is more justified. Neutrophilic leukocytosis is often present, with inconsistent increases in globulin, fibrinogen, and SAA concentrations.

Ultrasonographic examination may reveal hepatomegaly with increased echogenicity of the liver, thickened distended bile ducts, and hyperechoic regions suggestive of choleliths. Choleliths in horses are typically visualized in the most cranioventral portion of the right lobe of the liver, especially in the sixth to eighth intercostal spaces. Choleliths may be hyperechoic, casting an acoustic shadow or sonolucent tract deep to the stone. Stones may be evident as discrete calculi or less discrete sludge deposits within the biliary tract. The thickened distended bile ducts may appear as dilated channels adjacent to portal veins. In horses, the acoustic shadowing caused by the large lung field may obscure choleliths on ultrasonograms.

• Surgery or lithotripsy

Although biliary obstruction in horses is often fatal, choledocholithotripsy and choledocholithotomy have been performed successfully. The prognosis in cases requiring choledocholithotomy depends on the severity of concurrent cholangiohepatitis and on the size of the horse. The procedure is difficult because of limited exposure and poor visibility of the common hepatic duct. Complications include bile contamination, bile peritonitis, dehiscence, bile duct stricture, cholelith re-formation, and enterocolitis. The prognosis is better if the obstruction is corrected by choledocholithotripsy.

Small calculi or less discrete sludge deposits may be successfully resolved by medical treatment. In addition, dissolution of bilirubinate stones may be facilitated by concurrent administration of dimethyl sulfoxide (DMSO: < 20% solution at 0.5–1 g/kg, IV). DMSO should be used cautiously or avoided in horses with coagulopathies or clinical signs of hemolysis; it is rapidly cardiotoxic if given in its original undiluted form. Anti-inflammatory agents are administered to decrease inflammation and provide analgesia. Because cholangitis is often present, longterm broad-spectrum antimicrobial treatment is indicated. The choice of antimicrobial is best guided by culture and sensitivity of the bacteria from a liver biopsy, from a bile duct aspirate, or from the cholelith. Supportive care is provided to manage any amount of accompanying hepatic insufficiency.