Parasitic Gallbladder Infection: Case Study of Biliary Clonorchiasis in a Non-Endemic Region

Introduction

Parasitic gallbladder infections are a prevalent challenge, especially in endemic regions where the prevalent trematode species vary by area. Multiple parasitic species affect the biliary tree, causing various hepatobiliary diseases [1]. Clonorchis sinensis is endemic in Northeast China, Korea, Taiwan, and Vietnam; Opisthorchis viverrini is endemic in Laos and Thailand; and Opisthorchis felineus is found in parts of Eastern Europe and Russia [2]. Diagnosing such diseases is particularly challenging due to the extensive clinical overlap between parasitic cholecystic diseases and typical cholecystitis, even though peripheral eosinophilia could be a clue in some patients [3]. Even though parasitic cholecystitis is usually acalculous, there is growing evidence that it can be a risk factor for stone formation since certain cases were found to have concomitant calculi [4].

The most common gallbladder flukes, Clonorchis and Opisthorchis, share a similar life cycle. After the ingestion of raw fish, metacercariae cysts are freed from the flesh. The larvae migrate from the duodenum through the ampulla of Vater into the bile duct, where they mature into adult worms in about 25 days [4,5].

Herein, we report a case of acute cholecystitis that was found to be caused by the inflammatory reaction to a parasitic infection consistent with Clonorchis in a non-endemic region in the Middle East.

Case Report

A 38-year-old woman with no relevant medical or surgical history came to the emergency department in King Abdullah University Hospital, Irbid, Jordan. She was complaining of abdominal pain in the right hypochondrium. The pain was sudden in onset and colicky, never returned to the baseline, radiated to the ipsilateral shoulder, and was aggravated by fatty food. The pain was accompanied by vomiting and did not improve after the intake of simple analgesics. She had a negative travel history outside the country. The patient reported no smoking or alcohol use, and she follows a regular meat- and chicken-based diet.

On physical examination, the patient had normal vital signs except for a temperature of 38.5 degrees Celsius. The abdominal exam revealed tenderness in the right upper quadrant with a positive Murphy’s sign. The remainder of the examination was normal.

Laboratory values were inconclusive. A complete blood count showed an elevated white blood cell count of 18 610 cells/μL (normal range: 4000–11 000 cells/μL), with a neutrophil count of 90% (normal range: 40–60%). Liver transaminases and biliary markers were in the normal range, but alkaline phosphatase showed a slight elevation (123 U/L) (normal range: 44–121 U/L). Stool ova and parasites were negative. Kidney function tests were within the normal range.

Diagnostic ultrasonography was done, which concluded that findings typical of cholecystitis were present, including a distended gallbladder with numerous tiny echogenic shadowing stones seen in its dependent part associated with minimal pericholecystic fluid. The findings were suggestive of acute cholecystitis. Additional findings included a diffuse fatty infiltration of an enlarged liver with no focal lesions seen, with the long axis of the liver measuring 17.9 centimeters, and no intrahepatic biliary dilation. The common bile duct was normal and measured about 6 millimeters.

A list of suggested differential diagnoses was considered, including infection, parasitic infestation, gallstones, and malignancy.

A computed tomography scan (CT) of the abdomen was ordered to confirm the diagnosis. Findings relevant to diagnosis included a distended gallbladder containing layering hyperdense material in its dependent part with a moderate amount of pericholecystic fluid as well as surrounding fat stranding. Multiple sub-centimeter-enhancing lymph nodes were seen in the portohepatic, aortocaval, precaval, and peripancreatic regions, the largest measuring about 0.7 centimeters in width. In addition, moderate amounts of free fluid were seen in the right subphrenic, subhepatic regions, and the right iliac fossa tracking to the pelvis. Other differential diagnoses of acute abdomen were excluded due to the scan showing normal abdominal organs.

The patient underwent a laparoscopic cholecystectomy, and the procedure went smoothly without complications. Preoperative management included pain medication and antibiotics (piperacillin and tazobactam, 2.25 grams intravenous every 6 hours). Postoperatively, the patient was placed on moxifloxacin, 400 milligrams intravenous every 24 hours.

The postoperative shattered specimen was sent to histopathology. Gross examination revealed a gallbladder measuring 8.0×6.5×3.0 centimeters in height, length, and width, respectively, containing multiple small, pigmented stones, and no focal lesions were identified. The gallbladder showed a wall thickness of 1 centimeter and smooth mucosa.

Microscopically, sections of the gallbladder wall showed mixed acute and inflammatory cells infiltrating the wall, including lymphocytes, plasma cells, neutrophils, and eosinophils. Wall edema and hemorrhage were identified. The histopathology confirmed the diagnosis of acute-on-top-of-chronic cholecystitis (Figure 1). In addition, 1 section identified a fluke-shaped egg-containing parasite measuring 2.0×1.0 millimeters in the viewed field. The type of parasite could not be determined definitively, but its appearance mimicked immature Clonorchis sinensis (Figure 2).

Based on those findings, the patient was placed on secnidazole (1 packet/2 grams of granules administered once, orally) as an anti-helminthic medicine. The postoperative course went smoothly, and the patient was followed up in the outpatient clinic after a few weeks without any complications reported.

Discussion

Multiple parasitic diseases can invade the human hepatobiliary system, including Clonorchis sinensis. Chen et al reported significant biliary microbiota changes in patients infected with Clonorchis, identified down to the genus level [6].

Signs and symptoms of clonorchiasis are typically related to worm burden, with most infections being of low burden and asymptomatic [2]. The clinical picture arises from multiple mechanisms. Although rare, inflammation of the bile ducts caused by the parasite’s presence disrupts normal function [7].

Additionally, the worms can intermittently block the ducts, further impacting the bile flow. Mechanical injury occurs as the worms feed on the lining of the ducts [7]. The worms’ waste products can also be toxic, contributing to symptoms of hepatic and biliary injury. Studies also showed an increased risk of development of gallbladder calculi, where Clonorchis eggs or adult worms function as nuclei, aiding in the genesis of the stones [4]. Finally, secondary bacterial infections can develop, worsening the situation [8].

In Jordan, the main endemic parasitic infections have been identified as cryptosporidiosis, amoebiasis, giardiasis, schistosomiasis, and toxocariasis. Those are all waterborne infections, and more prevalent in rural areas [9].

Radiological examinations are essential in diagnosing biliary tree diseases such as clonorchiasis. Clonorchiasis is primarily detected by screening ultrasonography of the liver, according to its pathognomonic findings of diffuse dilation of the intrahepatic bile ducts, periductal echogenicity, and floating materials in the gallbladder.

In this local case in a non-endemic area in the Middle East (Irbid, Jordan), the patient presented with the typical picture of cholecystitis. Later investigations and postoperative histopathology revealed multiple small stones and parasitic trematodes. The non-endemic geographic area where the case occurred made the parasitic infection a less obvious diagnosis; however, Clonorchis infection is associated with an increased risk of the formation of gallstones, and the gallstones led the patient to develop symptoms. The patient could not remember a significant fish-based diet; however, we believe that she developed the infection from consuming green legumes contaminated with parasite eggs or improper fish-containing food preparation (with fish that might have been imported from endemic countries).

Conclusions

Clonorchis sinensis remains a challenging diagnosis even in endemic areas due to the overlap of symptoms with typical cholecystitis, but this challenge is escalated in non-endemic areas. Our case report presents a patient with clonorchiasis diagnosed with acute calculus cholecystitis. Although the patient lacked a travel history to endemic regions, a high index of suspicion for parasitic infection should have been maintained, especially when eosinophilia or tissue eosinophils were identified.

Histopathological examination remains the gold standard for definitive diagnosis, demonstrating the parasite itself or eggs. In addition, suspicion should increase upon identifying eosinophils in the tissue. Early diagnosis and prompt treatment with anthelmintic medications alongside cholecystectomy, when indicated, can improve patient outcomes. Further studies are needed to investigate the mechanisms of local transmission and identify underdiagnosed cases in non-endemic areas.