Multiple liver abscesses in a dog secondary to the liver fluke Metorchis conjunctus treated by percutaneous transhepatic drainage and alcoholization

Abstract

A 1-year-old German shepherd × husky cross dog was diagnosed with multiple liver abscesses and severe cholangitis secondary to the liver fluke Metorchis conjunctus. The dog was successfully treated with 2 percutaneous transhepatic drainage and alcoholization procedures, and a prolonged course of antibiotics and praziquantel.

The North American liver fluke, Metorchis conjunctus, a trematode of the family Opisthorchiidae, infects various fish-eating animals and humans. Throughout its range, liver fluke infection is rare in dogs but the prevalence of infection is higher in dogs from northern Canada (where this dog originated) (1,2). Dogs become infected after eating raw fish, primarily the white sucker (Catostomus commersonii) that carry the parasite. In the definitive host, the adult trematodes migrate up the biliary tree. Most cases of parasitism with M. conjunctus in dogs are subclinical; however, if there is a large parasite burden, severe hepatic dysfunction with chronic clinical signs and eventually death can result (3). To the authors’ knowledge, this case represents the first case of multiple liver abscesses and severe cholangitis in a dog occurring secondary to infection with the liver fluke Metorchis conjunctus.

Case description

A 1-year-old, 20.1-kg, castrated male German shepherd × husky cross dog was referred to the Western College of Veterinary Medicine, Saskatoon, Saskatchewan, for evaluation following a history of acute anorexia, vomiting, and lethargy. On physical examination the dog was in good body condition, dehydrated (capillary refill time < 3 to 4 s) but cardiovascularly stable, icteric, and febrile at 40.6°C. Abdominal palpation and a rectal examination revealed pain and melena. The dog was born in Canada and had been rescued 3 mo earlier from a reserve in northern Saskatchewan. Nonspecific supportive treatments with IV fluids, pantoprazole (Partenaires Pharmaceutiques du Canada, Toronto, Ontario), 1 mg/kg body weight (BW), IV, q24h, hydromorphone (Sandoz Canada, Boucherville, Quebec), 0.005 to 0.01 mg/kg BW/h, IV, and sucralfate (Aptalis Pharma Canada, Montreal, Quebec), 1 g PO, q8h, were initiated.

A complete blood (cell) count (CBC) revealed a moderate neutrophilia [16.1 × 10⁹ cells/L, reference interval (RI): 3.0 to 10.0 × 10⁹ cells/L] with a severe left shift (6.8 × 10⁹ cells/L, RI: 0 to 0.1 × 10⁹ cells/L), 2+ toxic changes, marked monocytosis (4.2 × 10⁹ cells/L, RI: 0.08 to 1.0 × 10⁹ cells/L), and severe thrombocytopenia (36 × 10⁹ cells/L, RI: 200 to 900 × 10⁹ cells/L). Thrombocytopenia was confirmed by a manual platelet count. Agglutination and spherocytes suggested possible immune-mediated red blood cell destruction. A coagulation panel to evaluate for evidence of disseminated intravascular coagulation (DIC), showed a moderately elevated activated partial thromboplastin time (aPTT) (19.3 s, RI: 9.3 to 13.8 s) with a normal prothrombin time (8.8 s, RI: 7.5 to 9.9 s). The thrombocytopenia and concurrent elevation of aPTT suggested DIC but fibrinogen or D-dimers were not measured. Evans syndrome, consisting of concurrent immune-mediated hemolytic anemia (IMHA) and thrombocytopenia (ITP), secondary to an underlying inflammatory or neoplastic condition was also considered as a possible differential.

Results of a serum biochemistry profile revealed moderate hepatocellular injury and cholestasis as evidenced by elevations in alanine aminotransferase (ALT) (326 U/L, RI: 19 to 59 U/L), alkaline phosphatase (ALP) (1049 U/L, RI: 9 to 90 U/L), gamma glutamyl-transpeptidase (GGT) (13 U/L, RI: 0 to 8 U/L), bilirubin (15.4 mmol/L, RI: 1 to 4 mmol/L); and cholesterol (7.56 mmol/L, RI: 2.70 to 5.94 mmol/L). A moderate hypoalbuminemia (22 g/L, RI: 32 to 42 g/L), likely the result of a negative acute phase response, and a moderate hyperglobulinemia (44 g/L, RI: 20 to 34 g/L), likely indicative of antigenic stimulation, were also seen. On abdominal ultrasound, multiple hypoechoic cystic structures (> 12), ranging from a few mm to 2.5 cm in diameter, were seen throughout the hepatic parenchyma but predominantly within the right hepatic lobes (Figure 1). The gallbladder, cystic duct, and common bile duct (CBD) were also moderately to markedly distended and contained echogenic debris. The CBD was markedly dilated (8 to 9 mm diameter, normal CBD being < 3 mm diameter) up to its insertion at the duodenal papilla where it narrowed but had thickened walls and a lumen < 2 mm diameter, suggestive of a partial obstruction. Within the liver, some hepatic ducts were mildly dilated (> 2 mm) with prominent walls. Normal intrahepatic ducts are not visible on ultrasound. A moderate amount of anechoic peritoneal effusion and enlarged perihepatic lymph nodes were also evident.

Figure 1.

Longitudinal gray-scale ultrasonographic image of the abdomen. Two cystic structures with anechoic center can be seen in the liver (white arrows).

Given the severe thrombocytopenia and suspicion for possible DIC, a fresh frozen plasma transfusion (18 mL/kg BW) and later a unit of fresh platelet were administered to the patient to permit fine-needle aspiration of the enlarged perihepatic lymph nodes, the liver and the cavitary lesions within the liver. A large amount of purulent exudate was collected from 2 of the cystic structures for cytology, aerobic, and anaerobic cultures. Cytology showed marked suppurative inflammation with intracellular and extracellular rods and cocci, as well as moderate number of oval ovae, consistent with M. conjunctus (Figure 2). Many bile casts were present, suggesting a biliary origin of the abscesses. The liver and lymph node cytology were consistent with neutrophilic inflammation.

Figure 2.

Ova of Metorchis conjunctus. Original magnification ×60. The egg was yellowish brown with a distinct operculum and measured 30 μm long × 17 μm wide.

Treatment with ampicillin (Novopharm, Toronto, Ontario), 22 mg/kg BW, IV, q6h, amikacin (Amiglyde-V; Wyeth Animal Health, Guelph, Ontario), 15 mg/kg BW, IV, q24h, and metronidazole (Baxter Corporation, Mississauga, Ontario), 15 mg/kg BW, IV, q12h, was initiated while the culture results were pending. Bacterial culture was positive for Escherichia coli and a Clostridium spp. The E. coli isolate was resistant to amoxicillin, penicillin, and clindamycin, but sensitive to gentamicin and all other antibiotics on the sensitivity panel.

Treatment with percutaneous drainage, lavage, and transhepatic alcoholization of the abscesses performed under general anesthesia was elected. Most abscesses were drained and flushed with 0.9% NaCl with ultrasound guidance, using a 22-gauge spinal needle. With drainage and flushing, many of the abscesses were noted to communicate with each other. A solution of 70% ethyl alcohol (WCVM Compounding Pharmacy, Saskatoon, Saskatchewan) was then injected 1 to 3 times into several of the emptied abscess cavities to attempt sterilization. After a dwell time of 30 to 60 s, the alcohol was re-aspirated. The total volume of alcohol injected was 18 mL with recovery of about 50% of the alcohol.

Post procedure, S-adenosyl methionine and silybin combination (Zentonil advanced; Vétoquinol, Lavatrie, Quebec), 20 mg/kg BW, PO, q24h, ursodeoxycholic acid (Ursodiol; Aptalis Pharma), 15.5 mg/kg BW per day, PO, divided into 2 doses and praziquantel (Biltricide; Bayer, Montreal, Quebec), 30 mg/kg BW, PO, q12h for 6 d were added to the treatment regimen. Fecal flotation, performed prior to administration of praziquantel and then 2 wk and 2 mo later, were all negative. Over the course of the next 4 d, the thrombocytopenia remained severe and a mild but stable anemia (Packed Cell Volume, PCV, of 0.36 L/L, RI: 0.39 to 0.56 L/L) developed with persisting signs of IMHA (spherocytes, positive saline agglutination, and increasing hyperbilirubinemia). This was despite improvement in the inflammatory leukogram seen on the CBC and improvement in the dog’s clinical demeanor, which suggested that Evans syndrome, possibly triggered from the parasitic or bacterial hepatic infection, was likely the main cause of the severe thrombocytopenia and anemia. Given the risk for sepsis and stability of the anemia, immunosuppressive medications were withheld in favor of aggressive treatment of the liver abscesses.

A repeat abdominal ultrasound 5 d later showed recollection of the fluid within the hepatic abscesses. The dog was anesthetized and percutaneous transhepatic drainage was performed again. The thrombocytopenia had improved to 95 × 10⁹/L (RI: 200 to 900 × 10⁹ cells/L); therefore, the potential for iatrogenic hemorrhage was considered less likely and a second platelet transfusion was not administered prior to re-aspiration of the liver abscess. Purulent material was again aspirated from multiple interconnected abscesses and was re-submitted for culture. Iohexol 240 (Omnipaque; GE Healthcare Canada, Mississauga, Ontario) was then injected in the emptied abscesses of the right lateral liver lobe (approximately 4 mL in each site) and a computed tomography scan of the abdomen was performed. Multifocal regions of cystic contrast enhancement were seen within the liver parenchyma (Figures 3, 4) that connected and drained into the cystic duct, gall bladder, and common bile duct. These intrahepatic cystic dilations were therefore diagnosed as focally dilated hepatic ducts. Dilation of hepatic ducts in the other hepatic lobes was variable. In the right liver, there were 5 irregularly marginated large cystic structures which communicated with the hepatic ducts. In the left liver, there were linear accumulations of contrast consistent with dilated hepatic ducts; however, cystic cavitations were not seen. Full patency of the CBD was confirmed (Figure 5).

Figure 3.

Post contrast transverse computed tomographic image of the abdominal cavity, soft-tissue algorithm. The contrast agent was injected into the emptied abscesses of the right lateral liver lobe. Multifocal regions of cystic contrast enhancement were seen in the liver parenchyma (asterisks *).

Figure 4.

Post contrast coronal computed tomographic image of the abdominal cavity, soft-tissue algorithm. The contrast agent was injected in the emptied abscesses of the right lateral liver lobe (asterisk *). Iodinated contrast material was seen in dilated hepatic ducts, indicating communication between the abscesses and the biliary system (black arrows). Contrast material was present within the small intestine, indicating patency of the common bile duct, CBD (black arrowheads).

Figure 5.

Post contrast transverse computed tomographic image of the abdominal cavity, soft-tissue algorithm. The contrast agent can be seen in focal dilation of hepatic ducts (asterisks *) and filling the full length of the common bile duct, indicating patency (black arrow).

An E. coli with intermediate sensitivity to amoxicillin/clavulanic acid, but which remained sensitive to doxycycline, was cultured from the second aspiration. The dog was discharged 7 d after initial hospitalization with 10 wk of amoxicillin/clavulanic acid (Clavamox; Pfizer Animal Health, Kirkland, Quebec), 18.6 mg/kg BW, PO, q8h, doxycycline (Sanis Health, Dieppe, New Brunswick), 5 mg/kg BW, PO, q12h, S-adenosyl methionine and silybin combination, 20 mg/kg BW, PO, q24h, and ursodeoxycholic acid, 15.5 mg/kg BW per day, PO, divided into 2 doses.

Repeat serum biochemistry profiles and CBCs showed progressive improvement and complete resolution of the previously described abnormalities including the anemia and thrombocytopenia. A follow-up ultrasound 1 mo later showed marked improvement of the intrahepatic cavitary lesions; however, multiple 1 cm thick-walled cysts and mild CBD dilation were still present, likely the result of irreversible scarring of these structures. At the time of writing, 1 y later, the dog continues to do well clinically.

Discussion

Acute and severe illness related to a partial obstruction of the CBD, upstream cystic dilatation of hepatic ducts, multi-bacterial abscessation, and suspected secondary Evans syndrome is a very unusual presentation for Metorchis conjunctus parasitism in the dog and to the authors’ knowledge has not been previously reported.

Based on the geographic location from which this dog originated, Northern Saskatchewan, the eggs observed on the bile cytology were suspected to be more consistent with Metorchis conjunctus. However less common opisthorchiid trematodes in this region, such as Parametorchis sp., could not be differentiated from M. conjunctus based on egg morphology alone and were other possibilities (4). Nevertheless, some authors do not differentiate Parametorchis sp. from Metorchis conjunctus and classify them as the same species (5–7).

Bacterial hepatic abscessation has been described in dogs, with single abscesses or abscesses restricted to 1 liver lobe being more common than multiple abscesses (8). Previously reported causes of hepatic abscessation in dogs include omphaloplebitis in puppies, ascending biliary tract infection, hepatic neoplasia, liver lobe torsion (8–11), and potentially Yersinia spp., Nocardia asteroids, and Actinomyces spp. infection (12). Liver abscess formation secondary to liver fluke migration has only been rarely described in humans with Fasciola hepatica, Opisthorchis felines, and Clonorchis sinensis (13–15), but has not been reported in dogs.

In humans, liver abscessation occurs most commonly secondary to an ascending biliary infection (16–18). Systemic diseases such as diabetes mellitus, or diseases and/or treatments leading to immunodeficiency may predispose patients to development of hepatic abscessation (19). Direct damage from the fluke migration within the biliary tract as well as from the ensuing inflammatory reaction was the likely cause of narrowing of the CBD, biliary stasis, and ascending biliary tract abscessation in this dog. Hyperplasia of the intrahepatic bile ducts and gall bladder mucosa, and cystic dilatation of the bile ducts have been previously described in chronic cases of M. conjunctus parasitism in the dog and were likely part of the pathology leading to the ultrasound findings in this case (5).

Contrary to older reports in which liver abscesses were preferably managed surgically in humans, minimally invasive percutaneous drainage has become the treatment of choice. Surgical drainage is now only reserved for patients who also require surgery to address another problem, if the location of the abscess is inaccessible for percutaneous drainage, if the purulent material is too viscous to allow complete evacuation of the cavity, or for patients who have already failed percutaneous drainage (16,18,20). The presence of severe thrombocytopenia, as seen in this case, or a bleeding tendency may also be considered contraindications for surgery. The presence of complex, multi-septated abscesses has also been reported as an indication for surgical drainage but a recent report has demonstrated that percutaneous drainage can also be effective in this situation (17). In humans in whom abscesses exceed 10 cm in diameter, percutaneous placement of a pigtail catheter to allow repeated lavage and drainage is preferable to needle aspiration (21). In our case, all abscesses measured < 2.5 cm so percutaneous drainage was feasible and the interconnected abscesses facilitated drainage and lavage. Percutaneous drainage is considered a safe and effective procedure with a reported success rate between 70% and 98% in humans (18). Possible complications include rupture of an abscess leading to peritonitis and bleeding in cases of concurrent coagulopathy. Despite the presence of severe thrombocytopenia in our case, no excessive bleeding was seen with percutaneous drainage. Provision of platelets and clotting factors from the transfusions may have helped prevent bleeding associated with the procedure in this case.

Successful percutaneous drainage using needle aspiration was described in 4 dogs with hepatic abscessation. In 2 of these cases, as in our case, more than 1 needle aspiration procedure was required for effective control (8). Management by percutaneous drainage of liver abscesses which communicate with the biliary system as seen in this dog has, however, been associated with higher rate of treatment failure in humans, particularly when biliary obstruction is present (22). In such cases, continuous output of bile into the abscess cavity via the communicating tract has been speculated to prevent the tract from closing and healing, leading to treatment failure.

Alcoholization following drainage of the abscesses can enhance sterilization and promote healing by providing sclerotherapy compared with drainage alone. Ethanol concentrations higher (95% to 99%) than the 70% ethyl alcohol solution used in our case are usually recommended for ethanol sclerotherapy of cysts and abscesses (23–26). One study, however, used 70% ethyl alcohol with success for the sclerotherapy of bleeding dilated esophageal veins in children (27). Given that the alcohol was further diluted by the remaining bile and possibly by some of the previously injected saline, it is possible that we did not perform an effective sclerotherapy using a 70% ethyl alcohol solution. Since 2 percutaneous drainage and alcoholization procedures were required and high numbers of E. coli continued to be cultured prior to the second procedure, it is possible that we would have had better success using a higher concentration of ethanol. Percutaneous transhepatic alcoholization using 95% ethanol for the treatment of liver abscesses has been successfully used in veterinary patients with no complications or relapses noted in 5 dogs and a cat, each with a single hepatic abscess (25).

A mixed infection with E. coli and Clostridium spp. from the liver abscesses is consistent with previous reports in dogs in which these 2 bacteria were often isolated from hepatic abscesses (8,10,25). Polymicrobial infection is common, suggesting ascending biliary tract infection is the most likely route of infection (8,10). A prolonged course of antibiotics for 4 to 6 wk in addition to drainage is recommended in humans and this was used as a guide in this case (18). The recommended length of treatment with praziquantel for treatment of M. conjunctus is unclear. While a dose of 30 mg/kg BW of praziquantel given once is probably sufficient to kill the liver fluke in most cases (28), a prolonged course of antiparasitic medications, ranging from 7 to 60 d, has been prescribed in human patients with liver abscesses secondary to fascioliasis and clonorchiasis (15,29). A 6-day course of 30 mg/kg BW of praziquantel given twice a day was arbitrarily chosen in our case. Since the fecal flotations were negative in this dog on all occasions, resolution of clinical signs, laboratory abnormalities, and hepatic lesions seen on ultrasound were relied on to monitor response to therapy.

In conclusion, this report describes an unusual case of M. conjunctus parasitism in a dog associated with partial biliary obstruction, multiple liver abscesses with biliary communication, and presumed secondary Evans syndrome. The dog was successfully treated with medical management including 2 percutaneous transhepatic drainage and alcoholization procedures and a prolonged course of antibiotics and praziquantel. The dog was regularly followed for 50 d and repeat blood work showed complete resolution of the abnormalities. Repeat abdominal ultrasound a month after diagnosis showed marked improvement with persistence of only small cysts and mild dilation of the CBD likely from irreversible damage to the biliary tree. One year later, the dog continues to do well clinically. CVJ