Abstract
Hepatobiliary fascioliasis is one of the rare but important parasitic infection in endemic areas such as Pakistan. Clinical manifestations overlap with common clinical conditions such as hepatitis and biliary stones causing common bile duct obstruction. Fascioliasis is a zoonotic infection caused by a leaf-shaped organism known as Fasciola Hepatica. Humans are accidentally infected by consuming contaminated water or food, especially undercooked cattle and sheep liver or raw green vegetables. We report three cases with similar clinical manifestations presenting in two different cities in Pakistan. After detailed clinical evaluation and laboratory investigations, the diagnosis was established by abdominal ultrasound and diagnostic and therapeutic cholangiography. Patients were followed till complete resolution of their symptoms and normalisation of liver function tests.
Introduction
Fasciola Hepatica is also known as a liver fluke. It belongs to the Trematoda class of flatworms and commonly infests cattle, goats and sheep 1 and is endemic in Africa and Asia as well as parts of Europe and South America. 1 Its journey of migration is complex: it lives in the biliary ducts of host animals, lays eggs that pass through faeces and contaminate water, where they hatch and form ciliated miracidia. Snails are intermediate hosts and are infected by miracidia, which later leave the snails and become metacercariae cysts. 2 After accidental human ingestion of these cysts, the organism leaves the cyst within the small intestine, crosses the intestinal mucosa and reaches the peritoneum, later entering into the hepatic parenchyma by penetrating through Glison's capsule. Finally, they reach the biliary system and mature into an adult form. 3
Clinical manifestations differ depending upon two different phases of the infection. A hepatic phase begins 4–12 weeks after ingestion of metacercerial cysts when they penetrate the hepatic parenchyma. During this phase, patients may have right upper abdominal pain, fever, weight loss, urticaria, pruritis, peripheral eosinophilia, and deranged liver function tests. In severe cases, hepatic necrosis and sub-capsular haemorrhage have been documented. A biliary phase may present with intermittent abdominal pain, fever, and jaundice and radiological evidence of biliary obstruction. 4 Prolonged biliary infection in humans may lead to cholangiocarcinoma. 5
Consent was taken from all the three cases for their data presentation and publication.
Case reports
Our first case was a 40-year old female from Chitral, who presented to the Prime Teaching Hospital Peshawar with a four-day history of epigastric pain and vomiting. On examination, she was jaundiced but afebrile and normotensive (BP: 138/74 mmHg), with normal pulse, and oxygen saturation. She had right upper abdominal tenderness without hepatomegaly. Laboratory evaluation showed Hb: 114 g/l, leucocytes: 11.5 × 109/l, eosinophils 5% and platelets: 276 × 109/l. Liver function revealed: total bilirubin: 68.4 μmol/l, direct bilirubin: 47.88 μmol/l, alanine transaminase: 430 IU/l, gamma-glutamyl transferase: 387 IU/l, alkaline phosphatase: 645 IU/l. Urea, and creatinine levels, electrolytes, and coagulation profile were all normal. The ultrasound of the abdomen showed a dilated common bile duct of 7 mm with a single small stone and multiple calculi in the gallbladder.
The patient was admitted with a diagnosis of obstructive jaundice secondary to choledocholithiasis. She was treated with intravenous Ceftriaxone and rehydrated with IV fluids before an endoscopic cholangio-pancreaticogram (ERCP) was performed; this showed a normal biliary system with a single curvilinear filling defect. After sphincterotomy, with a balloon sweep, a single live Fasciola Hepatica was retrieved and was removed with a rotation net. Biliary clearance was subsequently confirmed by cholangiography. Laboratory evaluation later confirmed the clinical diagnosis. The patient was kept under observation for 24 h, remained stable and was discharged with Nitazoxanide. After one week, she was asymptomatic with normalised liver function tests (Figures 1 and 2).
Cholangiogram image.
Endoscopic image.
Our second case was a 17-year old boy from Hazara, who presented at the emergency department of Liaquat National Hospital, Karachi with a history of low-grade fever, undocumented weight loss, and progressive worsening jaundice of one month's duration. On examination, he was deeply jaundiced and febrile (temperature 39 °C, tachycardic (94 beats/min)), but normotensive with normal oxygen saturation. Abdominal examination revealed right upper abdominal tenderness. Laboratory evaluation showed anaemia (Hb: 95 g/l), leukocytosis (13.5 × 109/l), with normal platelet count (212 × 109/l). Total bilirubin: 188.1 μmol/l, direct bilirubin: 153.9 μmol/l, alanine transaminase: 59 IU/l, gamma-glutamyl transferase: 545 IU/l, alkaline phosphatase: 678 IU/l. Abdominal ultrasound showed a dilated common bile duct and intrahepatic ducts with echogenic material within and in the gallbladder. The patient was admitted with a diagnosis of obstructive jaundice. He was treated with intravenous Ceftriaxone and rehydrated. The following day, an ERCP was performed and by multiple balloon sweeps, two Fasciola Hepatica were removed, following which a cholangiogram showed clear ducts. Laboratory evaluation confirmed our clinical diagnosis. The patient remained stable and was discharged after 2 days on oral Nitazoxanide. Complete resolution of his symptoms and normalisation of liver function tests occurred after 12 days.
Our third case was a 20-year old boy (four months after the presentation of his younger brother as our second case above) presenting with a history of fever and upper abdominal pain for two weeks. On examination, he was febrile (temperature 98.5 °C) and pale but otherwise stable. He had right upper abdominal tenderness on palpation. Laboratory evaluation showed anaemia (Hb 75 g/l), leukocytosis (11.5 × 109/l) and thrombocythaemia (2190 × 109/l). Total bilirubin: 153.9 μmol/l, direct bilirubin: 51.3 μmol/l, alanine transaminase: 49 IU/l, gamma-glutamyl transferase: 214 IU/l, alkaline phosphatase: 328 IU/l. Abdominal ultrasound showed a normal distended gall bladder and echogenic material within the common bile duct causing proximal biliary dilation. The patient was admitted and treated as his brother. Few Fasciola Hepatica were retrieved, and the common bile duct lavaged with normal saline till the cholangiogram showed clear ducts. After the procedure, he remained stable and was discharged on oral Nitazoxanide.
The remaining family members were screened with liver function tests and abdominal ultrasound, which were normal, empirically dewormed, and given detailed counselling regarding general precautions and hygiene.
Discussion
Fascioliasis was considered to be a disease restricted to endemic countries but as a result of global traveling, immigration and the tremendous capability of Fasciola Hepatica to survive in many different climates, it has spread widely.6,7 Chronic obstruction of biliary ducts due to parasitic infestations may be asymptomatic but may lead to recurrent cholangitis, secondary fibrosis, biliary stricture or even cholangiocarinoma.5,6 Sometimes an overlap of hepatic and biliary symptoms may exist with chronic or recurrent infections, especially in endemic areas. 8 Rare presentations such as chronic hepatic abscess needing surgical resection have been reported; 9 this may even mimic a malignant mass or complex hydatid cyst. 10
Stool examination for the detection of eggs is the standard method for diagnosing Fasciola 11 but eggs will be absent in the acute hepatic phase of the disease. Furthermore, even mature parasites lay eggs in intervals, making a diagnosis based on stool samples only unreliable. Serological tests including FAST-ELISA, complement fixation, indirect immunofluorescence and counter-electrophoresis are useful, but these tests, though very sensitive, are not specific for Fasciola Hepatica and cross-react with echinococcus, for example. 11
Other possible diagnostic tools include microscopic examination of duodenal aspirate for parasitic eggs, and radiological imaging such as ultrasound, CT scan, or MRI. Owing to the lack of a single specific diagnostic test, clinician suspicion must remain high for early diagnosis and timely treatment, 12 even when gallstones are found.
Treatment depends upon clinical symptoms and stage of disease whether hepatic or biliary. The WHO recommendation for deworming is Triclabendazole. The effectiveness of this drug can be confirmed by assessing stool or duodenal contents c. 2–4 months after treatment. 12 In case of biliary obstruction, ERCP is the best diagnostic and therapeutic modality. Antibiotics for superimposed bacterial infections, anti-pruritic agents, and other symptomatic treatment are usually added. 12
In Pakistan, the prevalence of Hepatica Fasciola is likely to be underreported significantly. A study from Khyber Pakhtunkhwa showed significant prevalence in animals (20%, 57%, 20% and 20% prevalence in sheep, goats, cows and buffaloes, respectively). 11 Identified risk factors include poor education, active cattle handling, raw vegetable use, poor sanitary conditions and compromised water resources. 12
Conclusion
An important learning lesson in this case series is that parasitic infections can co-exist with biliary stones, or be the prime cause of biliary occlusion. Typical hepatobiliary symptoms, especially with peripheral eosinophilia, should alert the clinician irrespective of the duration of symptoms, especially in endemic countries.
Footnotes
Declaration of conflicting interests
The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding
The author(s) received no financial support for the research, authorship, and/or publication of this article.
