Gallbladder agenesis is a congenital anomaly rarely observed in humans, dogs, and cats. In humans, the prevalence of gallbladder agenesis ranges from 0.01 to 0.075% (11). Gallbladder agenesis in dogs has been reported primarily in small breeds, with Chihuahuas (58.8%; 10/17) being the most common (25). Breeds, such as Maltese (1,16), Toy poodle, Shiba, Jack Russell Terrier (25), Miniature Pinscher (13), French Bulldog (12), crossbreeds (27), and even larger breeds like German Shepherds (25) and Bull terriers (9) have also been reported to experience gallbladder agenesis. Gallbladder agenesis is extremely rare in cats, with only two cases reported (20,23).

The etiology of gallbladder agenesis in animals and humans is unclear, but it is believed to be an abnormal hepatobiliary development during embryogenesis (11). Almost half of the affected dogs were asymptomatic (47%), while the others exhibited symptoms such as vomiting, anorexia, and ascites (25). Until further cases with extended follow-up data are available, the prognosis for dogs with gallbladder agenesis remains uncertain (12). However, dogs solely affected by gallbladder agenesis typically live a normal lifespan, and the concurrent congenital conditions like DPM may affect prognosis (25). While asymptomatic cases generally do not require treatment, it is recommended to support liver function with medication and implement a low-fat diet as a preventive measure against hepatocyte damage (12).

This paper presents a case of a Golden Retriever diagnosed with gallbladder agenesis through CT imaging, which had initially been misinterpreted as a PSS during an ultrasound examination.

A two-year-old, 24 kg intact female Golden Retriever, smaller than her littermates, was presented with a tentative diagnosis of a PSS at a local animal hospital. The dog was alert and showed no clinical signs.

The laboratory tests revealed increased alanine transferase (216 U/L; reference range 19 to 70 U/L) and alkaline phosphatase levels (210 U/L; reference range 15 to 127). The fasting bile acids (22.3 μmol/L; reference range 0 to 7.9) and postprandial bile acids (83.4 μmol/L; reference range 0 to 7.9) were elevated. The blood ammonia concentrations and complete blood count were within the normal range.

Abdominal radiographs revealed mild microhepatica and a mild loss of serosal detail. Abdominal ultrasonography revealed a normal morphology and echogenicity of the liver. The gallbladder could not be found, and the CBD was dilated to 6.9 mm. Small amounts of anechoic free fluid were identified between the liver and spleen. Due to poor patient cooperation and an insufficient amount of fluid, abdominocentesis was not performed. An aberrant vessel entering CVC cranial to left renal vein was found with high-velocity blood flow (maximum 95.6 cm/s) on color and pulsed wave Doppler examination, which was suspected as a shunt vessel (Fig. 1). An abdominal CT (Alexion_TM, Canon Medical Systems, Japan) was performed under general anesthesia using a 32-slice CT scanner with the patient positioned in sternal recumbency. Data were obtained using the following parameters: 120 kilovoltage peak, 150 milliampere seconds, 2.0 mm slice thickness, 2.0 mm interval, 0.75 second rotation time, and 0.938 collimation beam pitch. Post-contrast CT images were acquired at 7, 30 and 90 seconds after intravenous injection of 600 mg iodine/kg iohexol (Omnipaque_TM; GE Healthcare, Ireland). The sagittal and dorsal reconstruction images in the soft tissue window were acquired. The CT study revealed the absence of a gallbladder at its normal location. Distended CBD exhibited a diameter of 8.3 mm, and the CBD to aorta ratio was 0.66 at the level of the porta hepatis. At the duodenal papilla level, the corresponding measurements were 8.5 mm and 0.72 (Fig. 2) with no evidence of obstruction or compression. The left intrahepatic bile duct next to the left portal vein branch was also dilated, reaching a maximum diameter of 3.4 mm and other branches of intrahepatic ducts were not visualized on CT images. The portal vein was tortuous and slightly dilated, but the portal vein to aorta ratio was within the normal range (0.97; normal range 0.71-1.20) (7). A dilated left phrenico-abdominal vein, 3.4 mm in size, entered the CVC, which had previously been misinterpreted as a PSS on ultrasound. Gastroduodenal, splenic, ovarian, colic veins (Fig. 2E), as well as hepatic and gastric arteries, were dilated and serpentine. Small tortuous varices were found craniomedial portion to left kidney, which is considered as gastrophrenic varices (Fig. 2D).

Figure 1. Ultrasonography scan of the abdomen revealed the liver and CVC. Note the distension of the CBD (A) and the absence of a gallbladder (B). A vessel suspected as an extrahepatic shunt to the CVC was observed (C), exhibiting continuous high blood flow velocity (D) using color and pulsed wave Doppler.

Figure 2. Post-contrast transverse (A, B), dorsal (C, D), and 3D reconstructed (E) abdominal CT images. (A) Note the absence of the gallbladder and mildly dilated left intrahepatic bile duct (arrow) as a hypoattenuating tubular structure. (B) Mildly dilated left phrenico-abdominal vein (arrowhead) entering the CVC was observed. (C) The portal vein appears slightly dilated and tortuous. (C, D) Moderately distended CBD (asterisk) and small tortuous varices craniomedial to the left kidney were shown (circle). (E) Dilated and tortuous portal vein with gastroduodenal, splenic, ovarian, colic veins were observed. C, caudal vena cava; P, portal vein.

In the arterial phase, generalized hepatic parenchyma shows heterogenous, patchy transient arterial hyperperfusion and it fades in the porto-delayed phase. Mean density of the hepatic parenchyma was 70 HU on pre-contrast, 150 HU on artery phase, 135 HU on portal phase and 125 HU on delayed phase. All intrahepatic portal vein branches were intact; thus, liver lobe agenesis was ruled out. Liver biopsy for histopathologic evaluations was not performed per the owner’s request.

The dog was prescribed S-adenosylmethionine (200 mg, PO, BID, for four weeks) and has remained asymptomatic for seven months following the investigations. However, no further laboratory or imaging tests were performed.

During embryogenesis, the hepatic diverticulum originates from the embryonic foregut and subsequently divides into two components: the pars hepatica and the pars cystica (11,25). The pars hepatica gives rise to the liver and intrahepatic bile duct, while the pars cystica gradually forms a vacuole that expands to become the gallbladder, with its stalk eventually developing into the cystic duct (11,25). The etiology of gallbladder agenesis in humans and dogs is unknown, but it has been suggested that gallbladder agenesis with cystic duct agenesis may be associated with the failed recanalization of the cystic duct and gallbladder (24). Other possible hypotheses for gallbladder agenesis include failed hepatic diverticulum development into the pars hepatica and pars cystica (11,24,25). Hence, gallbladder agenesis is often accompanied by additional hepatobiliary developmental disorders in dogs, such as liver lobe agenesis (35%; 6/17), hypoplasia (24%; 4/17), or ductal plate malformation (DPM) (94%; 16/17) (25).

In a previous study on gallbladder agenesis in dogs, most cases were asymptomatic, accounting for 47% (8/17) with clinical signs including vomiting (29%; 5/17), anorexia (12%; 2/17), ascites (12%; 2/17), diarrhea (6%; 1/17), and seizures (6%; 1/17) (25). In human patients, gallbladder agenesis is classified into three groups: symptomatic, asymptomatic, and those with multiple fetal anomalies (26). The most frequently reported clinical symptoms in humans are right upper quadrant abdominal pain, nausea, vomiting, intolerance to high-fat foods, and dyspepsia (2,21). Biliary dyskinesia and choledocholithiasis have been suspected as potential contributors to abdominal pain (17,21).

All of the dogs had increased serum activity of at least one liver enzyme (25). The cause of elevated enzyme concentrations in dogs is unclear, but it is believed to be related to conditions such as cholangiohepatitis, cholestasis resulting from bile, and intestinal content reflux into the CBD (16) or other concurrent congenital anomalies like ductal plate malformation (DPM) (25). Elevated hepatic enzyme activity in DPM may include a variety of causes, such as focal inflammation associated with bile duct dilation, biliary proliferation, dynamic extracellular matrix expansion of portal tracts and the accumulation of hepatocellular copper (22).

In our study, there was a significant dilation of CBD at both the porta hepatis and duodenal papilla levels when compared to established reference ranges for CBD diameter and CBD to aorta ratio (porta hepatis level; 2.79 ± 0.49 mm, 0.34 ± 0.05 and duodenal papilla level; 3.83 ± 0.50 mm, 0.47 ± 0.06) (14). Moreover, distension of the left intrahepatic bile duct was observed, with a diameter of 3.4 mm. A previous investigation on healthy Labrador Retrievers reported a median diameter of the left intrahepatic bile duct as 2.3 mm (19). In cases of gallbladder agenesis, the hepatic bile duct may compensate for the absence of the gallbladder by dilating and taking on the role of bile storage (10). Under these conditions, the occurrence of dyskinesia in the bile tract, an elevation in the basal pressure of the Oddi sphincter, cholestasis, or infection of the bile ducts due to increased retrograde propagation of phasic muscular contractions with regurgitation of contents can trigger the onset of a clinical condition and lead to lithiasis of the CBD (3).

The ductal plate is a transient structure during embryonic development, originating from hepatoblasts surrounding portal vein branches (18). Biliary ducts are formed from remodeling and partial involution of these cylindric ductal plates and the alteration of this process can result in DPM (18). Involvement of various biliary duct parts result in choledocal cysts, biliary atresia, Caroli disease, polycystic liver disease, biliary hamartomas and congenital hepatic fibrosis in humans (18). Histopathologically, 16 of 17 gallbladder agenesis dogs (94%) were diagnosed with DPM (25) and 8 of 30 Boxers (27%) with DPM were identified gallbladder agenesis (22).

Concurrent portal hypertension was reported in 29% of the dogs diagnosed gallbladder agenesis in a previous study (25). Portal hypertension caused by congenital hepatic fibrosis results in a difficulty in the outflow of blood from portal to hepatic venous system (18,22). To bypass this blockage or increased resistance, a rearrangement of the portal venous network occurs, dilating preexistent vessels and activating angiogenesis, leading to the development of collaterals (5). Several patterns of acquired portal collaterals have been described in dogs, which presented as small tortuous vessels in the renal region or a tortuous vessel between splenic and left renal vein (4). In our case, small tortuous varices were seen around the left kidney and other abdominal veins (ovarian, splenic, colic and phrenico-abdominal veins) suggesting that acquired portal collaterals had developed due to concurrent portal hypertension although the exact shunt site of the portal collaterals not be visualized.

The liver features a unique dual blood supply, with 70% from portal vein and 30% from the hepatic artery, and these two inflows exhibit compensatory relationships (6). Congenital hepatic fibrosis, belongs to DPM, is characterized by a variable degree of periportal fibrosis (18) and resistance caused by fibrosis leads to portal hypertension, hepatofugal circulation and portal venous hypoperfusion (22). Portal hypertension results in an increased diameter and tortuosity of both portal and splanchnic veins (5). In response to the diminished portal flow, the hepatic arterial buffer response promotes the dilation of hepatic and splanchnic arteries, accompanied by the formation of arterial twigs and the development of vascular coiling (5,15,22). Also, transient hepatic attenuation differences observed in our case could potentially be attributed to hepatic arterialization resulting from decreased portal vein flow (8).

In humans, possible diagnostic methods for gallbladder agenesis include hepatobiliary scintigraphy, cholangiography, CT scans, endoscopic retrograde cholangiopancreatography, and magnetic resonance cholangiography (23). Retrograde cholangiography (1,3) and abdominal CT scans (12,13) have been used for confirmation in dogs suspected of gallbladder agenesis based on the ultrasonography findings. Unlike in small breed dogs, ultrasonographic scanning in large breed dogs with deep chests is often challenging when confirming the presence of gallbladder, PSS or portal hypertension. Furthermore, in the present case, the dilation of abdominal veins caused confusion, with dilated vessels being misinterpreted as PSS during ultrasonographic scanning. Notably, abdominal CT offers the advantage of assessing the presence of the gallbladder, dilation of bile ducts, and evidence of portal hypertension in both small and large breed dogs.

Given the close association between dogs with gallbladder agenesis and DPM, and DPM-associated portal hypertension had shorter survival time compared to dogs without portal hypertension (25), the main limitations of our case are the absence of histopathologic result from liver biopsy and relatively brief duration of the monitoring.

Gallbladder agenesis was diagnosed in a young, asymptomatic Golden Retriever with dilated CBD, elevated liver enzymes and acquired portal collaterals. To the best of the authors’ knowledge, this case represents the first documented instance of gallbladder agenesis in a Golden Retriever. When the gallbladder is not found during ultrasound examination in large breed dogs with a deep chest, CT scan may be very useful to diagnose gallbladder agenesis. Additionally, CT examination can provide information on biliary abnormalities, portal hypertension, portal collaterals, and liver lobe agenesis that may occur concurrently with gallbladder agenesis.

The authors have no conflicting interests.