A 9-year-old spayed female 9.1 kg American Eskimo was referred for further evaluation of elevated liver enzymes. She was initially seen by her primary care veterinarian with an acute history of vomiting and diarrhea, and was found to be febrile on examination with a rectal temperature of 104.9F. A chemistry panel was performed and revealed the following abnormalities: ALT >1000 U/L, ALP 739 U/L, GGT 42 U/L, and total bilirubin 2.2 mg/dL. A complete blood count revealed a white cell count of 12,040 with possible bands. She had no known exposure to any toxins. She had been fed a new kind of jerky treat within the last few days (manufactured in the USA). No previous health history was reported, and she was current on vaccinations.
On presentation to DoveLewis, the dog was found to have a rectal temperature of 102.5F, a heart rate of 130bpm, and a mean arterial blood pressure of 136 mm/Hg. Abdominal palpation revealed suspected cranial organomegaly, but she was not assessed to be painful. She appeared adequately hydrated. No other significant abnormalities were appreciated.
Following sedation with butorphanol 2mg given intravenously, an abdominal ultrasound was performed which revealed a moderate quantity of mineralized sediment within the gallbladder but no obvious evidence of obstruction. A moderately distended common bile duct with echogenic material was also noted (Figure 1), which was thought to be most consistent with cholangitis (neoplasia felt to be less likely). No evidence of acute pancreatitis was noted. The liver was found to be mildly enlarged with hypoechoic nodules, for which the main differentials included cholangiohepatitis, nodular hyperplasia, and neoplasia. No intra-abdominal lymphadenopathy was noted and no peritoneal effusion was seen.
An IV catheter was placed and the dog was titrated propofol to effect (40 mg) to provide sedation for ultrasound guided hepatic fine needle aspirates, as well as cholecystocentesis to obtain a bile sample for aerobic and anaerobic culture and sensitivity. Both samples were submitted to an outside reference laboratory and the dog was hospitalized in the intensive care unit (ICU) for supportive therapy. Her initial treatment plan included a balanced electrolyte solution (Normasol-R) at 40 mL/hr, ampicillin-sulbactam 200mg IV q8 hours, metronidazole 60mg IV q8 hours, S-Adeosylmethionine + silybin 225mg PO q24 hours, and ursodeoxycholic acid 50mg PO q24 hours.
On day two of hospitalization, the dog’s vital signs were within normal limits, but she remained inappetant and she developed regurgitation which led to initiation of gastroprotective medications (sucralfate 500mg PO q8 hours and ranitidine 20mg IV q12 hours) as well as placement of a nasogastric tube for gastric suctioning and enteral nutritional support. She was initially started on a liquid diet at ½ her resting energy requirement to evaluate for tolerance of feedings. Recheck chemistries performed that afternoon revealed worsening of her liver values: ALP 1784 U/L (23-212), ALT 1671 U/L (10-100), GGT 48 U/L (0-7), and total bilirubin 3.3 mg/dL (0-0.9). Her blood glucose was noted to be 52 g/dL (70-143), but the sample had not been run immediately after it was drawn, and this was thought to be an artifactual finding.
On day three of hospitalization, no further regurgitation was noted and the dog had inadvertently removed her nasogastric tube overnight. She began eating small amounts of food voluntarily, and she was transitioned to oral medications – amoxicillin-clavulonic acid 125mg PO q12 hours and metronidazole 62.5mg PO q12 hours. A recheck partial chemistry panel revealed significant improvement in her hepatic values (ALT 816 U/L, total bilirubin 0.9 mg/dL) and she was discharged home pending her culture and cytology results. Medications prescribed at discharge included sucralfate 500mg PO q8 hours for six days, ursodeoxycholic 50mg PO q24 hours, S-Adeosylmethionine + silybin 225mg PO q24 hours, metronidazole 62.5mg PO q12 hours and amoxicillin-clavulonic acid 125mg PO q12 hours pending bile culture results.
Cytology results returned consistent with moderate suppurative (neutrophilic) hepatitis and cholestasis. The bile culture grew two different strains of Escherichia coli, both sensitive to all tested antibiotics. A recheck chemistry profile performed with the primary care veterinarian one week after discharge revealed continued improvement in the liver values.
While cholangiohepatitis complex is a widely recognized clinical syndrome in cats, the incidence of bacterial cholangiohepatitis in dogs is not as well known. The condition most likely develops secondary to an ascending infection from the gastrointestinal tract, but can also occur via hematogenous spread from hepatic portal venous blood. Certain patients may be predisposed to cholangiohepatitis, including those with impeded bile flow, impaired hepatic perfusion, oxidant injury, immunocompromise, or underlying intestinal or pancreatic disease. Clinical signs are frequently non-specific and may include fever, lethargy, inappetance, abdominal pain, vomiting, diarrhea, and jaundice. Clinicopathologic findings typically include elevations in liver enzymes and bilirubin, as well as a variable neutrophilic leukocytosis. Confirmation of the diagnosis requires ultrasonographic evaluation and liver sampling, as well as culture of hepatic tissue and/or bile. These samples can be obtained percutaneously or via surgical exploratory. Bile cultures have been shown to be higher yield than hepatic cultures, and a variety of bacteria have been isolated (most commonly Escherichia coli, but also Enterococcus, Bacteroides, Streptococcus, and Clostridium spp.)
Treatment for cholangiohepatitis includes appropriate supportive care as dictated by patient condition, such as fluid therapy, anti-emetics, analgesics, nutritional support, and hepatic support (S-Adenosylmethionine, silymarin, vitamin E), as well as specific antibacterial therapy ideally guided by culture results. Good empiric antibiotic choices include amoxicillin-clavulanic acid, cephalosporins, and fluoroquinolones. Metronidazole may be used to provide anaerobic coverage, but is not recommended for use as the sole antibiotic. Antibiotic therapy should continue for a minimum of 6-8 weeks, and response monitored with serial chemistry panels. An additional medication that can be considered is ursodeoxycholic acid, which may be beneficial in patients with cholestatic hepatobiliary disease. This medication can increase bile flow and reduce hepatocellular inflammatory changes. It should not be used in patients that have a gallbladder obstruction.
For patients that fail to respond to the above therapies, repeat liver sampling (ideally a wedge biopsy sample for histopathology) should be considered to evaluate for persistent inflammation and/or fibrosis. These findings may necessitate additional therapies such as corticosteroids or colchicine, and may also alter the prognosis. While liver biopsy is more invasive than fine needle aspiration, studies have shown a much higher diagnostic yield with histopathology as this allows for evaluation of hepatic architecture.
While bacterial cholangiohepatitis is typically a medically managed disease, surgical intervention should be considered in some cases. Gallbladder obstruction is a clear indication for surgery, but exploratory laparotomy may also be indicated for cases of chronic or relapsing cholangitis, patients with focal pain elicited during gallbladder ultrasound, or patients with certain ultrasonographic changes including development of a gallbladder mucocele, free fluid in the cranial abdomen, or a thinning/hypoechoic gallbladder wall suspicious for focal ischemia or necrosis. Surgery may also be required to obtain hepatic biopsy samples and/or for feeding tube placement. If surgery is elected, gastrointestinal biopsies may also be indicated to evaluate for underlying enteric disease. Coagulation times should always be evaluated prior to surgical intervention, and vitamin K and/or plasma transfusions may be required for patient stabilization.
Additional differentials that should be considered in the canine patient presenting with an acute hepatopathy include a toxic insult (mushrooms, acetaminophen, blue-green algae, xylitol, iron, cycad palm, and alpha lipoic acid), leptospirosis, primary inflammatory disease, copper-associated hepatopathy, and neoplasia. In most cases, imaging and sampling should be strongly encouraged to guide therapy and prognosis. If evidence of hepatic failure develops (including decreases in albumin, glucose, cholesterol, or BUN, the presence of coagulopathy and/or signs of hepatic encephalopathy), the prognosis is considered poor regardless of the initial cause of the hepatic insult.