Caroli syndrome (CS) presents bile duct dilatation with hepatic fibrosis (4), and it is commonly associated with renal lesions (i.e., cysts and medullary fibrosis) (8). The failure of involution of ductal plates and large intrahepatic ducts is the ultimate cause of CS (9). The case reports of CS are rare in both canine and feline medical field. In this paper, we report a feline CS case and canine CS-suspicion case. The aim of this report is to emphasize the diagnostic importance of CS for young animals with hepatic cysts. To the best of our knowledge, this is the first case report to describe CS in Korea.

Case 1

A 1-year-old, intact female Munchkin breed cat was referred to Nowon-N animal hospital with icterus and multiple hepatic cysts. Physical examination revealed body weight 2.3 kg, elevated rectal temperature with 40.0°C, and icterus.

Laboratory investigations, including complete blood count (CBC), serum chemistry, and feline immunodeficiency virus antibody/feline leukemia virus antigen (FIV Ab/FeLV Ag) kit tests, were performed with blood samples from the jugular vein. CBC revealed leukocytosis (leukocytes: 35,700/µL; reference value: 5,500-19,500/µL) with neutrophilia (neutrophils: 31,900/µL; reference value: 2,800-13,000/µL), and non-regenerative anemia (hematocrit: 19.9%; reference value: 25.0-45%). Serum chemistry tests revealed low albumin (2.1 g/dL, reference value: 2.3-3.5 g/dL) and normal total protein (6.7 g/dL, reference value: 5.7-7.8 g/dL). Serum chemistry revealed high alanine transaminase (ALT) (287 U/L, reference value: 30-125 U/L), high aspartate aminotransferase (AST) (96 U/L, reference value: 15-62 U/L), normal alkaline phosphatase (ALP) (47 U/L, reference value: 16-100 U/L), and high total bilirubin (T-bil) (7.4 mg/dL, reference value: 0.1-0.5 mg/dL) levels. FIV Ab/FeLV Ag kit (SNAP FIV/FeLV Combo Test; IDEXX Laboratories Inc., ME, USA) tests were negative.

Abdominal radiography revealed loss of serosal detail in the upper abdomen. Abdominal ultrasonography (AUS) revealed small amount of abdominal effusion, multiple anechoic hepatic cysts, dilated intrahepatic ducts (maximum diameter 7.17 mm), and dilated pancreatic duct (maximum diameter 2.24 mm) (Fig. 1A-C). Further, computed tomography (CT) revealed multiple dilated intrahepatic bile ducts, which were communicating with biliary tree (Fig. 1D). Dilated pancreatic duct was also confirmed on CT (Fig. 1E). However, the entry of common bile duct to the major papilla could not be confirmed on CT images. The dilatations of the common bile duct and pancreatic duct were considered to occur owing to the obstruction of common bile duct. The etiologic agent of the obstruction could not be confirmed on CT images. The obstruction of common bile duct could induce dilatations of intrahepatic bile ducts (1). Therefore, we conducted trial surgery for stenting common bile duct and pertained liver biopsy samples (Fig. 2). The histopathologic examinations of this patient revealed bile duct ectasia, partial fibrosis with inflammation (Fig. 3). The jaundice completely resolved 4 days after surgery. The next day of surgery, the value of serum bilirubin decreased from 14 mg/dL to 4.6 mg/dL (reference value: 0.1-0.5 mg/dL). However, the dilatations of intrahepatic bile ducts persisted after surgery. Also, the liver-related hematologic values were mildly elevated except T-bil values until discharge. Therefore, we made the diagnosis of CS based on the histopathologic findings of hepatic fibrosis with cholangitis and images of dilated intrahepatic bile ducts (8,15). This patient had been treated with IV fluid (0.9% NS; JW Pharmaceutical Co, Korea), sulbactam/ampicillin sodium (Ubacillin injection; Whanin Pharmaceutical Co, Korea) 20 mg/kg IV tid, metronidazole (Metrinal injection; Daihan Pharmaceutical Co, Korea) 15 mg/kg IV bid, enrofloxacin (Bytril injection; Elanco Pharmaceutical Co, United States) 5 mg/kg SC sid, famotidine (Gaster injection; Donga-st Pharmaceutical Co, Korea) 0.5 mg/kg IV bid, prednisolone (Solone injection; Handong Pharmaceutical Co, Korea) 1 mg/kg PO bid, ursodeoxycholic acid (Ursa tablet; Daewoong Pharmaceutical Co, Korea) 10 mg/kg PO bid, silymarin (Silymarin tablet; Eltscience Pharmaceutical Co, Korea) 2 mg/kg PO bid, biphenyl dimethyl dicarboxylate (Lefotil tablet; CMG Pharmaceutical Co, Korea) 2 mg/kg PO bid. This patient was discharged at 12 days after surgery and managed at the local animal hospital. Until two years after surgery, this patient was followed-up at the local hospital and managed with liver protectant drugs.

Figure 1. Ultrasonographic (A-C) and computed tomographic (D-E) images of Case 1. Dilated gallbladder (A) and intrahepatic bile ducts (B). Color Doppler image of dilated intrahepatic bile ducts (C). Owning to the absence of color flow Doppler signal, this structures are considered as intrahepatic biliary ducts. Transverse image of dilated intrahepatic bile ducts (arrow) communicating with dilated extrahepatic bile ducts or common bile ducts (arrow head) without obstruction (D). Transverse image of dilated pancreatic duct (arrow) (E).

Figure 2. Ultrasonographic image after stent placement in Case 1.

Figure 3. Histopathologic images of the liver tissue. The bile duct surrounded by necrotic liver (scale bar = 3 mm) (A). All bile ducts are markedly dilated and are full of suppurative exudate and mucoid fluid. The capsule is thickened by reactive fibroplasia, and fibrosis occasionally extends into the hepatic parenchyma (scale bar = 300 µm) (B). Stained with hematoxylin and eosin.

Case 2

A 1-year-old, intact female, mixed breed dog was admitted with anorexia, lethargy, and abdominal distention of 3 weeks’ duration. Although this patient was prescribed antibiotics and diuretics for 1 week at local animal hospital, there was no improvement in clinical signs. Physical examination revealed emaciated body condition score 2/9, abdominal distention without icterus. There were no remarkable findings, except depressed mental status.

Laboratory investigations, including CBC and serum chemistry tests, were performed with blood samples from the jugular vein. CBC revealed leukocytosis (leukocytes: 25,350/µL; reference value: 5,200-13,900/µL) with neutrophilia (neutrophils: 19,640/µL; reference value: 3,900-8,000/µL) and normal hematocrit value within lower range (hematocrit: 37.2%; reference value: 37.1-57%). Serum chemistry tests revealed low albumin (1.9 g/dL, reference value: 2.5-4.4 g/dL) and low total protein (4.6 g/dL, reference value: 5.4-8.2 g/dL). Serum chemistry tests revealed normal ALT (51 U/L, reference value: 10-118 U/L), high ALP (353 U/L, reference value: 20-150 U/L), and normal T-bil (0.3 mg/dL, reference value: 0.1-0.6 mg/dL) levels. Elevated ammonia of 120 µmol/L (reference value: 0-99 µmol/L) and C-reactive protein of 22.7 mg/dL (reference value: 0-22 mg/dL) were found.

Abdominal radiography revealed loss of serosal detail in the entire abdomen. Abdominal U/S revealed abdominal effusion, multiple anechoic hepatic cysts, and renal cysts (Fig. 4). Further CT or magnetic resonance imaging (MRI) was not performed because of the owner’s poor compliance.

Figure 4. Ultrasonographic images of Case 2. Multiple anechoic hepatic (A, B) and renal cysts (C).

Occasionally, multiple renal cysts are concurrent in CS (8). Hepatic cysts rarely induce ascites but CS usually presents with ascites, owing to portal hypertension (1). This patient had ascites without any other causes, except portal hypertension. Based on multiple intrahepatic cysts concurrent with renal cysts, ascites and patient’s young age, this patient was suspected to have CS. We prescribed hepatic protectant or L-aspartic acid L-ornithine hydrate (Hepamerz syrup; Hanhwa Pharmaceutical Co, Korea). However, this patient died at home after 7 days of visiting hospital.

To best of our knowledge, there are only 6 case reports of CS in both canine and feline medical journals and our case report is the first report of CS in Korea (3,6,7,10,13,14). CS is usually not suspected owning to its rarity. CD is characterized by multiple large intrahepatic biliary cysts, which are continuous with the biliary tract and can be diffuse or localized to a single liver lobe (8). CS is characterized by multiple hepatic cysts with congenital hepatic fibrosis and commonly associated with renal cysts (8). The ductal plate malformation in embryonic stage is considered to induce CD (9). CS is inherited in an autosomal recessive pattern in humans; however, limited information is available about etiopathogenesis in dogs and cats (8,15). The differential diagnosis of CS includes primary sclerosing cholangitis (PSC), recurrent pyogenic cholangitis, polycystic liver disease, choledochal cysts, and obstructive biliary dilatation (1,2). The hepatic cysts usually do not communicate with the normal bile ducts, and portal hypertension is rare in polycystic liver disease (1).

Diagnosis of CS is established based on intrahepatic bile duct dilatation with concomitant liver fibrosis and/or presence of polycystic kidney disease (9). Clinical signs of CS are vomiting, polyuria/polydipsia, ascites, anorexia, weight loss, and jaundice (5,6,10). In humans, additional clinical features are present, including recurrent cholangitis, abdominal pain, and ascites (1,12). Laboratory findings are non-specific in CS (15). U/S, CT, endoscopic retrograde cholangiopancreatography, or magnetic retrograde cholangiopancreatography are common diagnostic imaging tools (15). Furthermore, CT or MRI imaging of the central dot sign that is a dark cystic dilatation around a central bright spot marking the portal tract is a characteristic of CS (12,15). Finding of communication between hepatic cysts and the biliary tree is required to make a definitive diagnosis of CS (15). Liver biopsy is rarely performed, except in cases looking for evidence of hepatic fibrosis (1,15). CS might result in cholestasis, ascending cholangitis, cholelithiasis, and secondary hepatic fibrosis (11).

There are scarce canine or feline papers reporting CS treatment trials, including protein restricted diet (6,7). However, in humans, the treatment of CS is supportive and directed toward treating the biliary tract infections and complications of portal hypertension (1). Treatments of CS include antibiotics, liver protectant drugs, biliary drainage, liver lobectomy, and liver transplantation (1,15). Complications from human CS are cholangitis, sepsis, choledocholithiasis, hepatic abscess, cholangiocarcinoma, and portal hypertension (15). The prognosis of human CS is variable depending on the severity of the disease, presence of portal hypertension, and presence of coexisting renal disease (1). Recurrent cholangitis, complications related to biliary stones, and cholangiocarcinoma affect patient morbidity and survival (1).

Our case report emphasizes that the early diagnosis of CS, treatment of secondary cholangitis and life-long management of hepatic functions would make better prognosis. Also, the classic features of CS are well-described in our cases. In Case 1, the cat had dilated intrahepatic bile ducts, poor hepatic reserve capacity, common bile duct obstruction secondary to cholangitis, hepatic fibrosis and young age. In this case, we performed trial surgery for stenting obstructed common bile duct but the dilatation of intrahepatic bile ducts persisted. The obstruction of common bile duct was suspected to occur secondary to severe cholangitis. Liver biopsies are rarely required to make a definitive diagnosis for CS, but when performed show features of cholangitis and fibrosis (1,8). The fibrosis of CS is typically sequelae of cholangitis (1). We conducted histopathologic examinations to intensify our diagnosis. After confirming histopathologic cholangitis, we add anti-inflammatory treatments. Also, this patient had been treated with supportive therapy, including fluids, antibiotics and hepatic protectant drugs during hospitalization.

In Case 2, the dog had intrahepatic dilated cysts with renal cysts, poor hepatic reserve capacity, ascites and young age. The ascites was induced by portal hypertension. In this case, we performed supportive therapy using liver protectant drugs. The following limitation of this canine case must be addressed. No CT or MRI imaging was performed, which is necessary for definitive diagnosis, and no histopathology of hepatic tissues was conducted. Therefore, Case 2 is not a complete CS, but a CS-like case.

This paper is the first to report on suspected cases of CS in Korea, emphasizing the clinical importance of CS. CS should be considered a differential diagnosis for young dogs and cats with high liver-related hematologic values and intrahepatic cysts, with or without renal cysts.

This study was funded by the National Research Foundation (NRF) of Korea grant funded by the Korea government (MSIT) (RS-2023-00252033).

The author declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The dog and cat described in this report were client-owned patients. Informed owner consents were received for any possible research use of all diagnostic samples acquired from the patients.