Hepatic fascioliasis of emphasizing diagnostic difficulty and the need for high index of suspicion: Four case reports

Abstract

BACKGROUND

Fasciola hepatica (F. hepatica) (liver fluke) is a parasitic trematode that infects humans through the consumption of contaminated aquatic plants harboring the infective stage of the parasite. Despite being a neglected tropical disease, a World Health Organization report estimates that it affects approximately 2.4 million people worldwide, with high endemicity in regions characterized by poor sanitation and limited access to clean water. Clinical manifestations range from asymptomatic infection to severe complications such as liver abscess and multi-organ involvement.

CASE SUMMARY

We report 4 cases with varied and unusual presentations. Case 1: A 41-year-old woman with an initial presumptive clinical diagnosis of liver malignancy. Case 2: A 34-year-old woman who presented with urticaria and eosinophilia, initially suspected to be vasculitis. Case 3: A 67-year-old man who presented with dyspeptic symptoms, easy fatigability, headache, and fever. Case 4: A 60-year-old patient who presented with an eosinophilic liver abscess after prolonged antibiotic treatment failure.

CONCLUSION

Hepatic fascioliasis is frequently misdiagnosed due to its non-specific symptoms and limited diagnostic tools, especially in resource-limited settings. It is crucial to enhance awareness among healthcare professionals regarding its recognition and appropriate management. This case report aims to contribute to the growing body of literature on F. hepatica infection to facilitate timely diagnosis and empiric treatment with triclabendazole or nitazoxanide, as these are effective and reduce unnecessary interventions.

Key Words: Fasciola hepatica; Neglected tropical disease; Vasculitis; Liver abscess; Triclabendazole; Nitazoxanide; Eosinophilia; Ethiopia; Case report

Core Tip: Hepatic fascioliasis remains a significant yet under-recognized cause of morbidity, particularly in endemic regions. Its variable presentations, prolonged clinical course, and limited clinician awareness—coupled with constrained access to serologic testing—often lead to misdiagnosis (e.g., as malignancy or bacterial abscess). This results in unnecessary costs and delayed treatment. A high index of clinical suspicion, a thorough inquiry about exposure and travel history, recognition of characteristic imaging findings, and correlation with eosinophilia are critical for a timely diagnosis. Early empiric treatment, which is simple and cost-effective, can prevent invasive procedures and reduce the patient burden.

INTRODUCTION

Fasciola hepatica is a parasitic trematode and a significant cause of the snail-borne disease fascioliasis. While it primarily infects domestic ruminants like sheep and cattle, causing substantial economic losses, it has also emerged as an important neglected tropical disease in humans, who act as incidental hosts[1]. Globally, 180 million people are believed to be at risk of infection in more than 50 countries. It is endemic in many parts of the world including Central and South America, Asia, Africa and Middle East particularly in developing countries with poor sanitation and limited access to clean water sources[2,3].

The global distribution of fascioliasis is dependent on competent intermediate snail hosts. Fasciola hepatica (F. hepatica) is more common in temperate zones, while F. gigantica is found in tropical areas, including parts of Africa[4,5]. In Ethiopia, F. hepatica is the most prevalent liver fluke, typically found at higher altitudes, though mixed infections with F. gigantica can occur[6,7]. While animal fasciolasis is well-documented and highly prevalent in Ethiopia[8,9], data on human infection are more limited. Available studies indicate a significant disease burden, with prevalence among high-risk groups, such as school-aged children, ranging from 2.5%-9.8%[8].

Human infection is typically acquired by ingesting metacercariae on contaminated aquatic plants, such as watercress. Diagnosis can be challenging, relying on a combination of clinical suspicion, imaging, and diagnostic techniques like serology (e.g., antibody the enzyme-linked immunosorbent assay) or stool examination[10].

Given its status as a neglected tropical disease and its potential for unusual clinical presentations, fascioliasis is often misdiagnosed. This highlights a critical need for enhanced awareness among healthcare professionals. This case report aims to contribute to the clinical literature on human F. hepatica infection to facilitate timely diagnosis and appropriate management, thereby helping to reduce the associated morbidity.

CASE PRESENTATION

Chief complaints

Case 1: A 41-year-old woman presented with dull aching right upper abdominal pain of 6 months duration.

Case 2: A 34-year-old female patient presented with urticaria for 1 month.

Case 3: A 67-year-old female patient from Addis Ababa presented with a 2-week history of dyspepsia.

Case 4: A 60-year-female presented with abdominal pain and vomiting of 2 weeks duration.

History of present illness

Case 1: She had nausea and intermittent vomiting of ingested matter associated with loss of appetite and fatigue of 6 months duration.

Case 2: She took different anti histamines for her presenting complaint but had poor response. She had new onset right side chest pain of 1 day duration with dyspepsia and difficulty of swallowing. On further inquiry, she had intermittent knee joint pain and flu like symptoms for the preceding few weeks.

Case 3: Associated with the above complaint she also has easy fatigability, headache, and high grade intermittent fever. She denied any right upper quadrant (RUQ) abdominal pain or vomiting.

Case 4: Associated with the above complaint she also has easy fatigability and loss of appetite. She had no history of jaundice, fever, anorexia or weight loss.

History of past illness

Cases 1 and 2: No pertinent history of hospitalization or known chronic illness.

Case 3: Associated with the above complaint she also has easy fatigability, headache, and high grade intermittent fever. She denied any RUQ abdominal pain or vomiting.

Case 4: Her past medical history was significant for well controlled bronchial asthma and remote cholecystectomy.

Personal and family history

Case 1: There is no additional personal or family history of diabetes, high blood pressure, or cardiac conditions.

Case 2: The patient’s personal and family history is negative for heart disease, hypertension, and diabetes.

Case 3: No history of cardiovascular illness, high blood pressure, or diabetes is known in the patient or their family.

Case 4: Beyond the presenting condition, the patient reports no personal or familial instances of diabetes, hypertensive disease, or heart disorders.

Physical examination

Case 1: Physical examination revealed normal vital signs and a mild right upper quadrant tenderness. Abdominal palpation did not reveal liver or spleen enlargement.

Case 2: Physical finding was non-revealing on the first presentation for the urticaria but on the second presentation, she had tachypnea and tachycardia. Chest and cardiovascular examinations were unremarkable.

Case 3: The patient had normal vital signs. Abdominal examination revealed no significant findings.

Case 4: Physical exam was remarkable for right upper quadrant tenderness. Otherwise normal findings.

Laboratory examinations

Case 1: Pertinent laboratory findings included leukocytosis with significant eosinophilia, accounting for 38% of the white cell population (absolute count 3990 cells/mL). Comprehensive metabolic panel assessing renal function, electrolytes, and liver enzymes was unremarkable. Serologic screening for blood-borne pathogens (hepatitis B, hepatitis C, syphilis, human immunodeficiency virus) returned negative results.

Case 2: Laboratory tests showed a white blood count of 10600 cells/mL (neutrophil count was 8480 cells/mL [80%]) eosinophil count was slightly elevated, 699 cells/mL (6.6%). Repeated complete blood count showed a white blood count of 6130 cells/mL with eosinophil count of 1240 cells/mL (20.2%). Further studies showed a normal serum Rheumatoid actor titer, complement 3 (C3), complement 4 (C4), and cytoplasmic and peri-nuclear anti-neutrophil cytoplasmic antibodies. A qualitative ANA serology was also non-reactive. A serologic test was not available but stool examination was done repeatedly and one exam showed egg of fasciola (Figure 1).

Figure 1 Microscopic visualization of a fasciola egg in a stool specimen. This light microscopic image shows a single, large oval shaped egg with a thin, smooth, yellowish shell visualized under non stained wet mount stool preparation.

Case 3: Laboratory tests showed a white blood count (WBC) of 19000 cells/mL (eosinophil count of 14630 cells/mL [77%]). Peripheral blood smear was consistent with eosinophilia and leukocytosis. Stool examination done repeatedly was negative for ova or parasites.

Case 4: Laboratory tests shows WBC of 9700 cells/mL (eosinophil count of 2000 cells/mL [21.2%]). Liver enzymes were elevated (aspartate transaminase 137 U/L [< 8-48 IU], alanine transaminase 252 U/L [4-36 IU/L], alkaline phosphatase 375 U/L [44-147 U/L]). Fine needle aspiration cytology from liver lesions reported a necrotic background with sheets of mixed inflammatory cells and scattered Charcot-Leyden crystals, suggesting eosinophilic liver abscess (Figure 2).

Figure 2 Histopathology of eosinophilic liver abscess. Photomicrographs demonstrate a necrotic background with sheets of mixed inflammatory cells and scattered Charcot-Leyden crystals.

Imaging examinations

Case 1: Abdominal ultrasonography demonstrated a normal gallbladder; however, numerous hypoechoic heterogeneous lesions in the liver parenchyma were seen. Abdominal computed tomography (CT) scan showed an enlarged liver with multiple ill-defined hypodense lesions in the right lobe having minimal arterial enhancement and slight filling in delayed phase with the underlying hepatic parenchyma having internal attenuation more around the periportal area (Figure 3).

Figure 3 Abdominal computed tomography scan. A: Abdominal computed tomography scan showed an enlarged liver; B: Shows multiple ill-defined hypodense lesions in the right lobe; C: Shows the largest lesion, a 5.3 cm × 3.3 cm measuring hypodense lesion having minimal arterial enhancement; D: Shows the delayed portal venous phase; E: Shows a slight filling in the delayed phase with the underlying hepatic parenchyma having internal attenuation more around the periportal area, which was consistent with fascioliasis.

Case 2: Abdominal ultrasound and chest X-ray showed focal lesions on liver and right kidney, and multiple lesions on the lung with minimal effusion respectively. Abdominal CT scan showed hepatic segment 6 small subcapsular hypodense lesion with peripheral enhancement (Figure 4).

Figure 4 Abdominal computed tomography scan consistent with hepatic and kidney fasciola involvement. A and B: The above computed tomography image showed hepatic segment 6 small subcapsular hypodense lesion with peripheral enhancement likely Fasciola hepatica (the hepatic lesions on segment 6 were clusters of oval hypodense nodules with peripheral enhancement where there is also mild biliary tree dilatation) (A). Multiple hyperdense lesions were also seen on both kidney’s (B).

Case 3: Abdominal CT scan showed an enlarged liver with heterogeneous echo reflectivity. Multiple patchy confluent nodules were seen, predominantly iso-echoic to liver parenchyma, with scattered calcifications (Figure 5A and B).

Figure 5 Abdominal computed tomography, magnetic resonance imaging, and magnetic resonance cholangiopancreatography images. A and B: Shows arterial phase axial abdominal computed tomography (CT) can showing ill defined, confluent hypodense right lobe liver lesions (A). Delayed phase abdominal axial CT scan showing progressive central enhancement of the right lobe hypodense lesion (B); C: Showing dilated complete blood count and edematous gallbladder wall; D: Abdominal magnetic resonance imaging diffusion weighted imaging and apparent diffusion coefficient image showing focal right lobe capsular retraction with adjacent mildly restricting right lobe liver lesion.

Magnetic resonance cholangiopancreatography (MRCP) study, the liver showed an ill-defined, T1 hypointense and T2 intermediate/hyperintense lesion predominantly in segments 5, 6, and 7, with moderate diffusion restriction (Figure 5C and D).

Case 4: MRCP showed dilated common bile duct with suspicious ampullary stricture and small focal liver lesions to rule out abscesses. Abdominal CT scan showed normal sized liver with segment VI 6 cm × 5.4 cm hypodense, poorly defined lesion with heterogeneous enhancement (Figure 6).

Figure 6 Abdominal computed tomography scan. A-C: Showed normal sized liver with segment VI 6 cm × 5.4 cm hypodense, poorly defined lesion with heterogeneous enhancement. Segment VII multiple smaller (1-1.5 cm) satellite nodules with similar characteristics. There was also a central intrahepatic duct dilatation with normal common hepatic duct size.

MULTIDISCIPLINARY EXPERT CONSULTATION

Case 1

This patient’s care was managed by a multidisciplinary team comprising specialists in general internal medicine, gastroenterology, infectious disease, and oncology.

Case 2

A collaborative medical team, including experts from general internal medicine, rheumatology, pulmonary medicine, and infectious disease, oversaw the management of this patient.

Case 3

The patient’s treatment was guided by a consortium of specialists, including a general internist, a gastroenterologist, and an infectious disease expert.

Case 4

Management of this case was conducted through a coordinated effort between general internal medicine, gastroenterology, and infectious disease specialists.

FINAL DIAGNOSIS

Case 1

The diagnosis of hepatic fasciolasis mimicking hepatocellular carcinoma was made.

Case 2

The diagnosis of autoimmune vasculitis related to hepatic fasciolasis was made.

Case 3

Differentials considered were F. hepatica infection, chronic ascending cholangitis, hepatic granulomas or abscesses with reactive adenitis. The final impression of the disease was F. hepatica infection which was highly suspected based on initial eosinophilia, hepatic lesion appearance, and recent travel history to an endemic area.

Case 4

With the given evidence a diagnosis of F. hepatica presenting as hepatic abscess was considered.

TREATMENT

Case 1

After careful evaluation of the clinical presentation, laboratory and imaging findings, the diagnosis was changed to F. hepatica. She was started on triclabendazole 10 mg/kg/dose which was taken for two doses 12 hours apart.

Case 2

She was started on short term high dose oral steroid with pantoprazole. She was also given triclabendazole 10 mg/kg/dose which was taken for two doses 12 hours apart.

Case 3

Treatment for fascioliasis was initiated with nitazoxanide for 2 weeks.

Case 4

Nitazoxanide was administered at a dosage of 500 mg twice per day via the oral route for 2 weeks.

OUTCOME AND FOLLOW-UP

Case 1

After 2 months of treatment, her abdominal pain resolved, appetite improved, eosinophilia normalized, and subsequent abdominal ultrasound showed resolved liver lesions. Evaluation during the third- and six-month follow-up showed normal findings.

Case 2

After 1 month of treatment, hypereosinophilia, lung consolidation and effusion subsided; however she had right lung middle lobe peripheral atelectasis that persisted. Repeated abdominal ultrasound showed no focal lesions on the liver and kidney (Figure 7).

Figure 7 Serial computed tomography imaging depicting radiographic changes with treatment. A-C: Abdominal computed tomography (CT) images of the liver showing changes with treatment; D-F: Abdominal CT images of the kidneys showing improvement with treatment; G-I: Abdominal CT scans demonstrating the progression of hepatic and renal lesions throughout the clinical course, from initial presentation to post-treatment follow-up.

Case 3

On subsequent visit 2 weeks later, she had significant clinical and laboratory improvement. Subsequent imaging with abdominal ultrasound and abdominal CT was unremarkable.

Case 4

On a subsequent visit 2 weeks later, she had significant improvement as all her symptoms and laboratory parameters normalized. Abdominal ultrasound was also normal.

DISCUSSION

This case series illustrates the broad and often misleading clinical spectrum of hepatic fascioliasis, which frequently leads to diagnostic delays and misdiagnosis. Our patients presented with manifestations initially attributed to hepatic malignancy (Case 1), autoimmune vasculitis (Case 2), ascending cholangitis (Case 3), and pyogenic liver abscess (Case 4). These cases underscore that a high index of suspicion, anchored by consistent clinical clues, is paramount for accurate diagnosis, particularly in resource-limited settings. F. hepatica infection exhibits a broad spectrum of clinical manifestations, ranging from asymptomatic carriage to severe complications including liver abscesses, biliary obstruction, subcapsular hematoma, pancreatitis, and acute liver failure[10,11].

The most critical laboratory finding across all our cases was marked peripheral eosinophilia, which serves as a key differentiator from purely bacterial or amoebic abscesses. This was definitively demonstrated in Case 4, where the initial diagnosis of a bacterial abscess was revised after antibiotic failure and the subsequent finding of an eosinophilic abscess on fine-needle aspiration. This hematologic hallmark, when combined with a careful exposure history (including travel to or residence in endemic areas and dietary habits), provides a powerful diagnostic clue.

Cross-sectional imaging is pivotal. The characteristic radiological pattern consists of multiple, small, tortuous, branching hypodense lesions, often in a subcapsular location, showing peripheral enhancement[12]. These migratory tracks, evident in Cases 1, 2, and 4, were crucial in re-directing the diagnosis away from hepatocellular carcinoma in Case 1. Furthermore, while biliary complications can mimic ascending cholangitis, as in Case 3, the concomitant presence of these parenchymal lesions and intense eosinophilia points toward the correct parasitic etiology.

Diagnostic confirmation relies on a multi-modal strategy. Direct parasitological methods, such as identifying Fasciola eggs in stool or duodenal/jejunal aspirates, are definitive but lack sensitivity, particularly in the acute phase before the parasites mature and lay eggs. For this reason, serological tests are crucial. Antibody detection assays, like the enzyme-linked immunosorbent assay using excretory-secretory antigens, offer high sensitivity during the acute and invasive stages of the disease A significant limitation of these tests, however, is their inability to reliably distinguish between past and current infections due to persistent antibodies. To address this, copro-antigen detection assays, which identify active parasite antigens in stool, are promising for confirming active infection and monitoring treatment response[6,7]. In resource-limited settings where specific tests are unavailable, a pragmatic diagnostic strategy combines strong clinical suspicion, marked eosinophilia, characteristic imaging findings, and a response to empiric anthelminthic therapy. However, in resource-limited settings where such tests are unavailable, the clinical triad of eosinophilia, suggestive imaging, and relevant exposure history becomes the de facto diagnostic algorithm, effectively employed in Cases 1 and 3.

The presentation may be complicated by extra-hepatic manifestations attributed to an allergic or immunologic response[7]. Case 2 exemplifies this, with pleural effusion, pulmonary lesions, and urticaria. Some patients develop a chronic form of the disease, persisting for over 6 months, as seen in Case 1. Other organs like the heart, eyes, skin, genitourinary tract, brain, and muscle can also be involved[13-15].

Once a diagnosis of fascioliasis is established, management primarily consists of anthelminthic therapy. Common pharmacological options include triclabendazole and nitazoxanide[16]. Oral triclabendazole is highly effective, with cure rates typically exceeding 90%[17]. Standard regimens involve two doses of 10 mg/kg, though single-dose regimens have also demonstrated success[18-21]. While treatment failures occur, a repeated course can often achieve a cure[22,23]. Nitazoxanide serves as a well-tolerated alternative, with a recommended dosage of 500 mg twice daily for 7 days[24,25]. The dramatic response to empiric anti-helminthic therapy in all our patients, even without definitive parasitological proof in some, further supports the diagnosis and underscores the value of timely treatment.

CONCLUSION

Based on the comprehensive case series presented, hepatic fascioliasis represents a formidable diagnostic challenge, particularly in endemic regions with limited resources. This series of four cases underscores the protean clinical manifestations of F. hepatica infection, which can mimic a wide spectrum of conditions including hepatic malignancy, bacterial or amoebic abscess, autoimmune vasculitis, and ascending cholangitis. The cornerstone of accurate diagnosis rests upon a high index of suspicion, triggered by the consistent finding of marked peripheral eosinophilia and corroborated by a meticulous exposure history and characteristic imaging findings on ultrasound, CT, or magnetic resonance imaging. In settings where specific serologic testing is unavailable, these clinical and radiological clues become paramount. The documented successful outcomes with both triclabendazole and nitazoxanide affirm that timely empiric anti-parasitic therapy is highly effective, can prevent unnecessary and invasive diagnostic procedures, and significantly reduces morbidity. Therefore, enhancing clinician awareness of this neglected tropical disease is critical to improving patient outcomes and mitigating the risk of misdiagnosis.

ACKNOWLEDGEMENTS

We would like to acknowledge the patients for providing us consent to share their case history and image.