Severe Cholestatic Liver Disease Secondary to Liver Fluke (Platynosomum concinnum) Infection in Three Cats
Three middle-aged domestic cats were presented for vomiting, lethargy, anorexia, and jaundice. Complete blood counts, serum biochemical profiles, and abdominal ultrasounds were suggestive of extrahepatic biliary obstruction in all of the cats. Infection with the liver fluke Platynosomum concinnum was confirmed by intraoperative bile cytology in three cases and by histopathology in two cases. All three cats were euthanized in the postoperative period because of complications. These cases illustrate the severity of signs and complications that can occur with liver fluke infection in cats.
Introduction
The liver fluke, Platynosomum concinnum (P. concinnum), is a trematode that parasitizes the hepatobiliary tract of domestic cats. The known intermediate hosts are found only in tropical and subtropical climates.3–6 Within the continental United States, P. concinnum has been reported in cats in Florida, Illinois, and Ohio.2,6,7 The infected cats in Illinois and Ohio were either known or suspected to have lived in endemic areas previously.7,8 Platynosomum concinnum is also routinely found in cats in Hawaii, Puerto Rico, the Bahamas, and Brazil.3–6,9,10
The life cycle of this parasite includes two intermediate hosts. The first intermediate host is a land snail (i.e., Subulina octona). The second intermediate hosts in Florida include a variety of lizards (e.g., Anolis carolinensis, Anolis equestris, Anolis sagrei, Eumeces inexpectadus) and the marine toad Bufo marinus.3,11 Cats often acquire the infection by ingestion of lizards. The infective stage to the cat is the cercariae in the lizard, which cats acquire by ingestion. The infective stages then migrate into the gallbladder and bile ducts of cats, where they develop into adult liver flukes.3 Approximately 8 weeks are required from the time of infection until the fluke eggs can be found in the feces.3
Infection with P. concinnum is generally subclinical.1 However, severe hepatobiliary disease may develop in selected individuals and may necessitate surgical intervention.2 The purpose of this report is to describe three cases of severe liver fluke infection and the complications associated with this disease.
Case Reports
Case No. 1
A 5-year-old, castrated male, domestic shorthaired cat was presented with a 3-day history of vomiting, lethargy, and jaundice. The cat lived both indoors and outdoors. Since the onset of clinical signs, the cat had been treated with subcutaneous (SC) fluid therapy, famotidinea (0.5 mg/kg per os [PO] q 24 hours), amoxicillinb (10 mg/kg PO q 12 hours), and enrofloxacinc (2.5 mg/kg PO q 24 hours) with no response.
Significant clinical pathology abnormalities were hyperbilirubinemia (7.9 mg/dL; reference range <0.8 mg/dL) and elevated alkaline phosphatase (ALP, 123 U/L; reference range <101 U/L), alanine aminotransferase (ALT, 664 U/L; reference range <100 U/L), and aspartate aminotransferase (AST, 111 U/L; reference range <66 U/L). Total bilirubin was repeated 3 days later and had increased to >27.9 mg/dL.
Abdominal ultrasonography revealed moderate gallbladder distention, dilatation of the common bile duct, and mild pancreatic thickening. Extrahepatic biliary obstruction was suspected, and an exploratory laparotomy was recommended. At surgery, the gallbladder was distended, and the cystic duct appeared thickened and tortuous. The common bile duct and duodenum appeared within normal limits. Duodenotomy was performed, and the common bile duct was catheterized and found to be patent. Cholecystectomy was performed because of suspected cystic duct obstruction and bile inspissation. A jejunostomy tube was placed for postoperative nutritional support.
Bile samples were submitted for culture and examined for evidence of parasites. Liver fluke eggs consistent with P. concinnum infection were identified on microscopic examination of the bile. Liver tissue was submitted for histopathology. Histopathological findings included severe sclerosing cholangiohepatitis with eosinophils and fluke eggs, as well as ulcerative cholecystitis. Intrahepatic bile ducts were surrounded by neutrophils, lymphocytes, plasma cells, and eosinophils. The ducts were dilated and filled with debris. Sclerosis around the bile ducts was seen and extended into the hepatic parenchyma. One of the bile ducts was surrounded by numerous fluke eggs [Figure 1]. Culture results were negative for bacterial infection.
The cat did poorly postoperatively and developed apnea, tachycardia, and hypotension. Euthanasia was performed after several hours of unsuccessful resuscitative efforts.
Case No. 2
An 11-year-old, castrated male, domestic shorthaired cat was presented for lethargy, anorexia, and jaundice. The cat lived primarily outdoors. The owners had not seen the cat for 2 weeks prior to presentation. The cat had no previous known medical problems. On presentation, the cat was jaundiced and dehydrated. A biochemical panel showed elevated ALP (368 U/L), ALT (300 U/L), and hyperbilirubinemia (43.39 mg/dL). The cat was negative for feline leukemia virus (FeLV) and feline immunodeficiency virus (FIV) infection.
Initial treatment included intravenous (IV) fluid therapy, enrofloxacin (2.5 mg/kg IV q 12 hours), ampicillind (22 mg/kg IV q 8 hours), praziquantele (10 mg/kg SC q 24 hours), and vitamin Kf (1 mg/kg SC q 12 hours). Abdominal ultrasonography revealed marked dilatation of the intrahepatic and common bile ducts, dilatation of the gallbladder with bile sludging, and bilaterally irregular kidneys. Extrahepatic biliary obstruction was suspected.
During laparotomy, the gallbladder was distended. Both the cystic duct and common bile duct were severely thickened and distended. Cholecystotomy was performed, and attempts to catheterize the cystic duct were unsuccessful. Duodenotomy was performed, and attempts to catheterize the common bile duct were also unsuccessful. No surgical procedure to relieve both obstructions was possible. Euthanasia was recommended but declined by the owner. A jejunostomy tube was inserted for nutritional support.
Inspissated bile was removed from the gallbladder and submitted for culture and cytology. Biliary cytology revealed liver fluke eggs of the species P. concinnum. Culture of the bile was negative for bacterial infection. Histopathology was not performed.
Postoperative treatment included praziquantel (10 mg/kg SC q 24 hours) for the liver flukes, ampicillin (22 mg/kg IV q 8 hours), enrofloxacin (2.5 mg/kg IV q 12 hours), hydromorphoneg (0.05 mg/kg intramuscularly [IM] q 4 to 6 hours) for pain, and famotidineh (0.5 mg/kg IV q 12 hours) and metoclopramidei (0.08 mg/kg per hour IV constantrate infusion [CRI]) to control nausea and vomiting. A whole blood transfusion was given 2 days postoperatively when the packed cell volume (PCV) dropped from 24% to 20% (reference range 25% to 45%). Anemia from chronic disease may have become evident with rehydration and aggressive fluid therapy during and after surgery. Enteral feeding through the jejunostomy tube was initiated 24 hours postoperatively.
Corticosteroid therapy with prednisolonej (1 mg/kg PO q 24 hours) to reduce inflammation in the liver, and ursodiolk (10 mg/kg PO q 24 hours) to thin the bile, were initiated 6 days postoperatively. Anorexia, vomiting, and icterus persisted, and the cat was euthanized 9 days after surgery.
Case No. 3
A 10-year-old, spayed female, domestic longhaired cat was presented for a 4-day history of vomiting, anorexia, and jaundice. The cat lived indoors in a multi-cat household. Several cats in the household were infected with FIV. None of the other cats were ill. The cat had been treated symptomatically for 3 days with IV fluids, famotidine, and ampicillin. A biochemical panel showed an elevated ALT (568 U/L), AST (283 U/L), and hyperbilirubinemia (4.1 mg/dL). Total bilirubin was repeated 2 days later and had increased to 8.39 mg/dL.
At referral, the cat was mentally dull and severely jaundiced. Physical examination revealed a grade II/VI left, parasternal heart murmur and a tense, painful abdomen. Biochemical panel showed an elevated ALP (128 U/L), elevated ALT (690 U/L), and elevated total bilirubin (9.33 mg/dL). Tests for FeLV and FIV were negative. Abdominal ultrasonography showed a slightly distended and mildly tortuous common bile duct. The kidneys were slightly irregular. Echocardiography showed mild concentric left ventricular hypertrophy, mild mitral regurgitation, and slight left atrial enlargement compatible with hypertrophic cardiomyopathy.
Exploratory laparotomy revealed that the gallbladder was severely distended and thickened, with a thin, discolored area at the apex, suggestive of necrosis. The bile duct was thickened and tortuous. Duodenotomy was performed, and the common bile duct was catheterized with a small-gauge catheter. Bile was inspissated and could not be expressed. After partial cholecystectomy, cholecystoje-junostomy was performed to bypass the common bile duct. A 2-cm stoma was created along the entire length of the gallbladder. A gastrotomy tube was inserted for postoperative nutritional support.
Samples of bile and liver were collected for histopathology, culture, and cytology. Cytology of the bile showed numerous liver fluke ova of the species P. concinnum. Histopathology of the liver showed severe inflammation consisting of marked infiltrates of eosinophils with lesser numbers of lymphocytes, plasma cells, and neutrophils around the portal areas. Marked fibroplasia was noted around the portal areas. Fluke ova were found within these areas of inflammation [Figure 2]. Aerobic culture of the bile revealed light growth of Escherichia coli (E. coli).
The cat was treated postoperatively with ampicillin (22 mg/kg IV q 8 hours), enrofloxacin (2.5 mg/kg IV q 12 hours), famotidine (0.5 mg/kg IV q 12 hours), ursodiol (10 mg/kg PO q 24 hours), vitamin K (1 mg/kg SC q 12 hours), and praziquantel (25 mg/kg SC q 24 hours). Hydromorphone (0.05 mg/kg IM q 4 to 6 hours) was given for postoperative pain. A single dose of dexamethasone sodium phosphatel (0.25 mg/kg SC) was administered postoperatively to reduce hepatic inflammation. Enteral feeding was initiated through the gastrostomy tube 24 hours after surgery. A whole blood transfusion was given 2 days postoperatively when the PCV dropped to 23%. Hypotension diagnosed 3 days postoperatively by Doppler was treated with hydroxyethyl starchm (20 mg/kg per day IV as a CRI).
Three days after surgery, the cat became febrile (104.3°F), abdominal pain increased, and abdominocentesis yielded a thick, yellow abdominal effusion. Cytology of the effusion showed macrophages, occasional neutrophils, and red blood cells. Peritonitis was suspected, and the cat was euthanized. Postmortem examination was not performed.
Discussion
In the current case series, all cats were middle-aged. Two of the cats had access to the outdoors, and the risk of acquiring liver flukes may be higher for outdoor cats. Cats in two previous reports were 1 and 9 years of age, and both had lived outdoors as strays.7,8
Previous studies have reported that most cats experimentally infected with P. concinnum remain asymptomatic, even with large fluke burdens.1,12 Of those cats showing clinical signs (e.g., lethargy, weight loss, inappetance, and abdominal tenderness), all recovered by the 24th week after infection without treatment.1 Recovery may have occurred from the development of fibrous tissue, forming a barrier between the infected canals and the liver tissue, thus sequestering the infection. Cats that were experimentally infected did show extensive histopathological changes in the livers, including enlargement of the bile ducts, eosinophilic infiltrates 6 weeks after infection, periductal inflammation 4 months after infection, and fibrosis around the bile ducts 6 months after infection.1,12 The experimental infection study only followed cats for 21 months.1
It is likely with natural infection that clinical signs may develop after longer periods of infection or because of repeated infection. In one case report of a cat from Ohio, the cat was found as a stray in south Florida 6 years earlier and had remained in Ohio since that time.7 It is also possible that infection in the cats reported here was cumulative or repetitive rather than from an isolated exposure, as in the experimental infection. Continuous exposure to the source of infection, such as continued predation of lizards, may result in a high burden of parasites over a greater period of time or stimulate an increased inflammatory response, thus creating a more clinically significant infection than could be created experimentally.
In previous reports, the duration of clinical signs ranged from weeks to months.2,7,8 It is interesting that the cats in this report had an acute onset of clinical signs. It is possible that case no. 2 had a longer duration of signs, since the owners had not seen the cat for 2 weeks. Case no. 3 may also have had signs for longer than reported, as there were 15 other cats in the household. Possible explanations for the seemingly acute onset of clinical disease included superimposed bacterial cholangiohepatitis (positive culture for E. coli in case no. 3), pancreatitis (pancreatic thickening in case no. 1), hepatic encephalopathy or failure (lethargy, jaundice, and coagulopathy in case no. 2), and hypertrophic cardiomyopathy (case no. 3).
Indications for surgical intervention for cats with liver disease include ultrasonographic evidence of extrahepatic biliary obstruction or clinical deterioration in the face of medical management.13,14 A prior case of extrahepatic biliary obstruction associated with liver flukes, treated with cholecystoduodenostomy, had a successful outcome.2 Case no. 3 of the study reported here, where biliary diversion was attempted, had severe changes to the gallbladder wall that may have led to dehiscence of the anastomosis site and death of this cat. Biliary diversion surgery in cats has a high mortality rate, with <50% survival at 2 weeks regardless of the underlying problem.14 Prognosis may be worse in fluke-infected cats because of concurrent intrahepatic biliary obstruction that cannot be addressed surgically. If only the common bile duct is obstructed, it can be bypassed via cholecystoenterostomy. An alternative option may be insertion of a choledochal tube stent, which has recently been described in dogs.15 However, if the intrahepatic bile ducts are obstructed, extrahepatic biliary diversion is unrewarding.
Postoperative complications in cats with liver fluke infection are numerous, and close monitoring is needed. Concurrent problems may also have contributed to the poor outcomes in the cases reported here. Anemia that occurred after surgery in case nos. 2 and 3 may have arisen secondary to the dilutional effect of IV fluid therapy in the presence of anemia of chronic disease, which was not immediately apparent because of dehydration.
Prophylactic treatment of liver flukes has been previously suggested in one report.11 However, no studies have been done to show the efficacy of such treatment. Even in endemic regions, routine testing and preventative treatment of this parasite are rarely performed.
Conclusion
Three middle-aged domestic cats with vomiting, lethargy, anorexia, dehydration, and jaundice were diagnosed with P. concinnum infection on bile cytology in all cases and on histopathology in case nos. 1 and 3. Medical and surgical therapies were unsuccessful in alleviating the clinical signs, probably because of the severity of intrahepatic biliary obstruction and concurrent medical problems. One cat died and two cats were euthanized soon after diagnosis. Further investigation of prophylactic therapy is warranted in order to prevent life-threatening infections in high-risk cats.
Acknowledgments
The authors acknowledge Dr. Barbara Powers and the Colorado Veterinary Diagnostic Laboratory for providing the histopathology and photomicrographs.
Pepcid AC; Merck, Fort Washington, PA 19034
Amoxi Drop; GlaxoSmithKline, Research Triangle Park, NC 27701
Baytril; Bayer, Shawnee Mission, KS 66201
Ampicillin; American Pharmaceutical Partners, Schaumberg, IL 60173
Droncit; Bayer, Shawnee Mission, KS 66201
VEDA-K1; Phoenix Scientific, St. Joseph, MO 64503
Hydromorphone HCl Injection; Baxter, Deerfield, IL 60015
Famotidine Injection; Ben Venue Labs, Bedford, OH 44146
Metoclopramide Injection; Faulding Pharmaceutical, Paramus, NJ 07652
PrednisTab; Vet-A-Mix, Shenandoah, IA 51601
Actigall; Watson Laboratories, Inc., Corona, CA 92880
Dexamethasone Sodium Phosphate Injection; Phoenix Scientific, St. Joseph, MO 64503
Hetastarch; Abbott Laboratories, North Chicago, IL 60064
Citation: Journal of the American Animal Hospital Association 42, 3; 10.5326/0420234
Citation: Journal of the American Animal Hospital Association 42, 3; 10.5326/0420234
Photomicrograph of a liver biopsy taken from a 5-year-old, castrated male cat (case no.1) infected with Playtnosomum concinnum. Some bile ducts contain fluke eggs (arrows). A sclerosing reaction is evident around the bile ducts (Hematoxylin and eosin stain; bar=200 μm).
Photomicrograph of a liver biopsy taken from a 10-year-old, spayed female cat (case no. 3) showing a fluke egg (arrow) surrounded by inflammation and fibroplasia. Inflammatory infiltrates consisted primarily of eosinophils (Hematoxylin and eosin stain; bar=200 μm).
