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Equine Winter 2006 (Vol 1, No 4)

Therapeutics in Practice: "Cholangiohepatitis, Suppurative Cholangitis, and Cholelithiasis"

by Samuel L. Jones, DVM, PhD, DACVIM


    Cholangiohepatitis is a suppurative inflammatory disease of the intrahepatic biliary tracts and surrounding hepatic parenchyma. It is likely that many, if not most, cases of cholangiohepatitis in horses begin as suppurative (neutrophilic) cholangitis involving only the bile ducts, and then the condition extends into the surrounding hepatic parenchyma. Cholangiohepatitis and suppurative cholangitis are usually attributed to an ascending bacterial infection of the biliary system from the gastrointestinal (GI) tract. Diseases associated with adynamic ileus or mechanical obstruction increase intraluminal pressure in the small intestine and can reduce bile outflow, cause bile stasis, and allow bacteria to ascend the common bile duct. GI diseases associated with cholangiohepatitis or suppurative cholangitis include proximal duodenitis-jejunitis,1 sand-induced enteritis,1 and duodenal obstruction.2 However, previous GI disease is not a requisite for the development of cholangiohepatitis or cholelithiasis.3,4 As expected, gram-negative bacteria commonly found in the GI tract (e.g., Escherichia coli and other enteric bacteria [ see box ]) are most frequently associated with cholangiohepatitis and suppurative cholangitis.1,3,5,6

    In chronic cases of cholangiohepatitis or suppurative cholangitis, intrahepatic or extrahepatic biliary calculi (choleliths) may form (Figure 1). Choleliths are concretions of the normal constituents of bile and are principally composed of calcium bilirubinate in horses.3 Most choleliths in horses are associated with bacterial infection of the biliary tracts, suggesting a cause-and-effect relationship. Biliary tract infection causes bile stasis and thus may have a key role in cholelith formation. Obstruction of the biliary ducts by choleliths can cause increased biliary pressure and marked dilation, resulting in compression of adjacent parenchyma and even rupture of bile into the parenchyma, which in itself is cytotoxic to hepatocytes and exacerbates inflammation. Dissemination of bacteria to the hepatic parenchyma may occur, resulting in abscess formation. Peritonitis may result either from rupture of distended biliary tracts or by extension of the infection through the capsule.

    Cholangiohepatitis may also be associated with so-called chronic active hepatitis, which is characterized by lymphocytic inflammation of the biliary tracts and periportal regions of the liver and is thus perhaps more appropriately called lymphocytic cholangitis. The type of inflammation suggests that lymphocytic cholangitis may be immune mediated. Some horses with histologic evidence of lymphocytic cholangitis also have features consistent with concurrent suppurative cholangiohepatitis. The relationship between lymphocytic cholangitis and suppurative cholangiohepatitis is unclear, but they may be interrelated.

    Suppurative periportal inflammation with or without actual bacterial infection can occur in the absence of ascending infection of the bile ducts. In this scenario, the source of the bacteria, bacterial products, or proinflammatory mediators triggering the suppurative periportal inflammation is likely the blood supply draining ulcerated, infected, or otherwise damaged areas of the GI tract.1,7 Biochemical evidence of hepatitis is frequently noted in horses with proximal enteritis or colitis. Although hepatitis associated with these diseases is often without clinical consequence, occasionally it is severe and results in liver dysfunction or failure.

    Clinical Signs and Diagnosis

    Common clinical signs of cholangiohepatitis and suppurative cholangitis are similar and include weight loss, colic, fever, and icterus. Other signs attributable to liver disease may also be noted, albeit less commonly (see box). In acute cases, systemic signs of sepsis (e.g., tachycardia, tachypnea, poor pulse quality, hyperemic mucous membranes, trembling, fever or hypothermia, prolonged capillary refill time, depression) may be noted. Signs of hepatoencephalopathy (see box) may be observed if liver failure occurs, but this is unusual. Obstructive cholelithiasis is often accompanied by colic, particularly if the obstruction is in the distal biliary tree. Concurrent peritonitis may cause ileus, diarrhea, colic, or weight loss and may be associated with signs of sepsis. Serum biochemical findings are typical of cholestatic disease (see box). Evidence of hepatocellular damage is variable, depending on the degree of parenchymal involvement surrounding the biliary tracts. Hyperbilirubinemia is usually characteristic of posthepatic obstruction, with more than 25% of total bilirubin consisting of the conjugated form. Serum bile acid concentration may also be high if liver function is altered. Hepatoencephalopathy is typically associated with a high serum ammonia concentration. An inflammatory leukogram, hyperfibrinogenemia, and anemia of chronic disease are expected findings. Clinical or clinicopathologic evidence of coagulopathy is uncommon and usually only a feature of very acute severe infections or chronic infections with end-stage liver failure.

    Diagnosis is aided by ultrasonographic examination of the liver.8 The overall echogenicity of the liver is usually greater than normal. In particular, the portal regions are typically hyperechoic, reflecting inflammation and fibrosis. Bile ducts may be mildly or markedly dilated or thickened and may contain choleliths (identified as discrete hyperechoic structures that cast an acoustic shadow). The most definitive diagnostic test is liver biopsy. At least two samples should be obtained—one for histopathologic examination and one for culture and sensitivity testing. A sample of peritoneal fluid should also be obtained to determine whether concurrent peritonitis is present and may also be submitted for culture and sensitivity testing.


    Treatment is guided by histopathologic findings, culture and sensitivity results, and clinical response. If the principal histo­pathologic feature is neutrophilic inflammation (rather than predominantly lymphocytic inflammation characteristic of lymphocytic cho­langitis), antibiotic therapy is indicated. The choice of antibiotic is ideally aided by culture and sensitivity results; however, anti­biotics (e.g., enro­floxacin, tetracycline, chlor­am­phen­i­col, ceftiofur, trimethoprim-sulfonamide, ampicillin) that obtain a high concentration in bile and have a good spec­trum of activity against gram-negative bacteria are usually recommended. Other broad-spectrum antibiotic (e.g., penicillin-gentamicin) regimens may also be used. Of these options, enro­flox­acin, chloramphenicol, and trimethoprim-sulfonamide are available in oral formulations, which are desirable for long-term administration. It is worth noting that some bacterial isolates from horses with cholangiohepatitis have reportedly been resistant to trimethoprim-sulfonamide.6 Care should be taken in horses with bile duct obstruction or liver dysfunction or failure because these complications may significantly affect the disposition kinetics of antibiotics eliminated by the liver. Treatment is recommended for 4 to 6 weeks or until clinical signs and laboratory evidence of inflammation resolve. Some au­thors4 suggest that treatment should be continued until serum hepatic enzyme activities (particularly g-glutamyltransferase activity) return to normal.

    Supportive care consisting of in­travenous fluid administration (crystalloid solutions, colloidal solutions, and/or fresh-frozen plasma) may be indicated in patients that are septic or endotoxemic to restore circulating blood volume, increase blood pressure, and replenish albumin and consumed coagulation proteins. NSAID therapy (i.e., flunixin meglumine [0.25 mg/kg IV tid or qid; 1 mg/kg IV bid]) may be useful to control fever, reduce systemic inflammation, and control abdominal pain. Polymyxin B (6,000 IU IV bid for 3 days) or J-5 plasma (2 to 4 L IV sid) may also be antiinflammatory if endotoxemia is suspected. Persistent abdominal pain that is not controlled by flunixin administration may respond to butorphanol administered either intramuscularly (0.01 to 0.1 mg/kg q4-6h) or as a constant-rate infusion (13 µg/kg/hr).

    Medical management of cholelithiasis is often successful.4 However, obstruction of the common bile duct by one or more choleliths may require surgery. Although several reports9-11 have described successful removal of choleliths from the common bile duct, no discrete criteria indicate when surgical intervention is necessary. The location of the common bile duct precludes ultrasonographic imaging to localize choleliths. Colic is a cardinal sign of common bile duct obstruction, but it may also be a feature of intrahepatic obstruction. Although fever and abdominal pain may be more persistent and the bile acid concentrations may be higher in horses with choleliths obstructing the common bile duct than in horses with only cholangiohepatitis,6 it is unclear how this information can be used on a per-case basis to decide whether surgical intervention is necessary. The severity and persistence of abdominal pain may be the most useful parameters in making this decision.

    Successful surgical resolution of obstruction of the common bile duct has been described in horses with cholelithiasis and may be quite successful. Choleliths may be surgically removed from the common bile duct via cholelithotripsy,9 manual massage of the cholelith into the duodenum,10 or choledochotomy.11 Cholelitho­tripsy requires specialized equipment to fragment the cholelith within the bile duct. Regardless of the technique used to resolve the obstruction, the procedure requires ventral midline laparotomy. Intrahepatic choleliths cannot be removed surgically. There is evidence that dimethyl sulfoxide may dissolve calcium bilirubinate bile stones in humans12 and may be useful to reduce or eliminate small intrahepatic choleliths in horses. It is important to remember that chronic liver disease may alter phospholipid composition of erythrocyte membranes, rendering them more fragile and susceptible to hemolysis. Thus dimethyl sulfoxide should be administered intravenously as a 1% to 2% solution to prevent unwanted erythrocyte hemolysis.

    Treatment with corticosteroids may be indicated in cases with evidence of lymphocytic cholangitis and concomitant suppurative cholangitis or cholangiohepatitis. Because suppurative inflammation indicates that bacterial infection is likely, it is wise to first administer antibiotics, even if bacteria have not been isolated from biopsy cultures. Once the bacterial infection has been adequately resolved, corticosteroid treatment can be initiated. Ideally, examination and culture of biopsy samples collected after 4 to 6 weeks of antibiotic therapy can be used to guide therapy. As an alternative, treatment with antibiotics may be continued until clinical signs and laboratory evidence of inflammation have resolved. However, this endpoint may not be reached if the lymphocytic component of the liver inflammation is significant. Dexamethasone (0.05 to 0.1 mg/kg/day PO, IM, or IV) is the usual initial corticosteroid used to treat lymphocytic inflammation. If a satisfactory response is achieved with this initial regimen of dexamethasone, the dose can be gradually decreased over 2 to 3 weeks. Treatment should be continued until clinical signs and biochemical evidence of hepatic inflammation have resolved. Some cases improve but do not resolve with the use of dexamethasone. In these cases, continued therapy with prednisolone (1 to 2 mg/kg/day PO, IM, or IV) should be considered. Like many diseases in which an immune-mediated cause is suspected, continued therapy with corticosteroids (either continuous or intermittent treatment) may be required to control the disease without ever curing it.

    In many cases of cholangiohepatitis or suppurative cholangitis, the prognosis is determined by the degree of fibrosis resulting from chronic cholestasis and inflammation. The best antifibrotic therapy is treatment of the underlying disease. Relief of the biliary obstruction to reestablish bile flow and treatment of the infection often reduce fibrosis or at least prevent progression. It may be possible to reverse or prevent progression of fibrosis with colchicine or corticosteroid therapy, but there is no evidence documenting the efficacy of either approach in horses with cholangiohepatitis or suppurative cholangitis.

    1. Davis JL, Jones SL: Suppurative cholangiohepatitis and enteritis in adult horses. J Vet Intern Med 17(4):583-587, 2003.

    2. Schulz KS, Simmons TR, Johnson R: Primary cholangiohepatitis in a horse. Cornell Vet 80(1):35-40, 1990.

    3. Johnston JK, Divers TJ, Reef VB, et al: Cholelithiasis in horses: Ten cases (1982-1986). JAVMA 194(3):405-409, 1989.

    4. Peek SF, Divers TJ: Medical treatment of cholangiohepatitis and cholelithiasis in mature horses: 9 cases (1991-1998). Equine Vet J 32(4):301-306, 2000.

    5. Clabough DL, Duckett W: Septic cholangitis and peritonitis in a gelding. JAVMA 200(10):1521-1524, 1992.

    6. Barton MH: Cholelithiasis in horses. Proc 17th Annu Am Coll Vet Intern Med Forum 17:159-161, 1999.

    7. Davis JL, Blikslager AT, Catto K, et al: A retrospective analysis of hepatic injury in horses with proximal enteritis (1984-2002). J Vet Intern Med 17(6):896-901, 2003.

    8. Reef VB, Johnston JK, Divers TJ, et al: Ultrasonographic findings in horses with cholelithiasis: Eight cases (1985-1987). JAVMA 196(11):1836-1840, 1990.

    9. Tulleners EP, Becht JL, Richardson DW, Divers TJ: Choledocholithotripsy in a mare. JAVMA 186(12):1317-1319, 1985.

    10. Roussel Jr AJ, Becht JL, Adams SB: Choledocholithiasis in a horse. Cornell Vet 74:166-171, 1984.

    11. Traub JL, Grant BD, Rantanan NW, et al: Surgical removal of choleliths in a horse. JAVMA 182(7):714-716, 1983.

    12. Igimi H, Asakawa S, Tamura R, et al: DMSO preparation as a direct solubilizer of calcium bilirubinate stones. Hepatogastroenterology 41(1):65-69, 1994.

    References »

    NEXT: Abstract Thoughts—Are You Probiotic or Antibiotic?


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