Characterization of the clinical features, laboratory findings, and outcomes of human fascioliasis in a global network: a retrospective mutlicenter study

Abstract

Background:

Fascioliasis, caused by Fasciola hepatica and F. gigantica, is a neglected tropical disease that has significant medical and veterinary importance. This foodborne zoonotic trematodiases primarily affects poor rural populations in tropical and subtropical areas, where prevalence can be as high as 21%.

Objective:

This study aims to characterize the clinical features, laboratory findings, and outcomes of fascioliasis in a real-world cohort.

Design:

Retrospective study.

Methods:

Patients ⩾ 18 years old diagnosed with fascioliasis were identified from TriNetX, a global federated research network, on October 26, 2024. We used the International Classification of Diseases results to define fascioliasis (ICD-10 code B66.3) for the period 2021–2024. These data include demographics, diagnoses, comorbidities, procedures, clinical laboratory results, and medications. All variables except outcomes were not time-bound to the diagnosis date.

Results:

In a cohort of 174 predominantly middle-aged, female, and Caucasian patients, we found high rates of essential hypertension, neoplasms, heart disease, liver disease, and sleep disorders. Key symptoms included upper abdominal pain, skin complaints, dyspnea, and malaise/fatigue. Some outcomes were hepatomegaly, cholelithiasis, and cholangitis in 10% of patients, with hepatic cirrhosis being rare. Among hospitalized patients within 3 months of diagnosis, 63% experienced abdominal pain. Of the 13 patients who developed cholangitis or cholelithiasis, most were men, had abdominal pain, nausea/vomiting, dysphagia, and ascites with a history of liver or intrahepatic bile neoplasia. A total of 90-day mortality was low (less than 6%). Triclabendazole was reported in only 6% of these patients.

Conclusion:

In a large real-world case series of fascioliasis, we found a high frequency of comorbidities and typical gastrointestinal symptoms. The low use of triclabendazole may be due to limited access to the product in certain countries or its omission from the database if prescribed in the outpatient setting. Mortality was very low, but biliary and liver complications warrant characterization through additional prospective clinical studies.

Plain language summary

Clinical outcomes of fascioliasis

Fascioliasis is a parasitic disease, now seen worldwide. Here a summary of cases seen in a multinational database with the goal to report comorbidities and clinical outcomes

Introduction

Fascioliasis, caused by Fasciola hepatica and F. gigantica, is a neglected tropical disease with significant global public health implications, particularly in endemic regions. ¹ The foodborne zoonotic trematodiases primarily affect rural populations in tropical and subtropical areas, where prevalence in humans can reach 21%. ² Over 180 million people are estimated to be at risk of infection worldwide, particularly in areas with high infection rates among ruminant definitive hosts. ³ Human fascioliasis and the other foodborne trematodiases are responsible for 200,000 illnesses and more than 7000 deaths annually, translating to 1066 thousand disability-adjusted life years (DALYs) lost globally. ⁴ The burden is nevertheless underestimated, as the impact of chronic complications such as anemia, malnutrition, liver fibrosis, and biliary obstruction, which can impair quality of life and necessitate long-term medical care, is difficult to measure.^5,6

Fascioliasis is also a major veterinary problem, not only in terms of animal morbidity but also in economic losses in the agricultural sector, estimated to be over $3 billion worldwide annually.^7,8 Despite advancements in diagnosis and treatment, a considerable knowledge gap remains regarding long-term outcomes, especially in diverse populations and healthcare settings.

This gap highlights the need for more robust studies to understand the factors affecting disease progression and to inform more effective management strategies for fascioliasis. This study aims to characterize the clinical features, laboratory findings, and outcomes of fascioliasis in a real-world cohort.

Methods

Study design and inclusion criteria

Adult patients (⩾18 years) diagnosed with fascioliasis were identified from TriNetX, a global federated research network, on October 26, 2024. We used the International Classification of Diseases to define the fascioliasis (ICD-10 code B66.3) between 2021 and 2024.

Database

TriNetX aggregates anonymized data from approximately 100 million patients across more than 80 medical centers in the United States, Canada, Europe, Australia, Indonesia, and other countries. These data include demographics, diagnoses, procedures, clinical laboratory results, and medications. All variables, except outcomes, were not time-bound to the diagnosis event. Our group has published several large cohort studies using this database.^9–11

Statistical analysis

Frequency analyses (mean and standard deviations) were completed within the TriNetX platform. Any data displayed on the TriNetX platform in aggregate form, or any patient-level data provided in a data set generated by the TriNetX platform, only contains de-identified data as per the de-identification standard defined in Section 164.514(a) of the Health Insurance Portability and Accountability Act (HIPAA) Privacy Rule.

Ethical considerations

Not applicable. Research utilizing TriNetX does not require ethical approval because patient-identifiable information is inaccessible to users.

Results

Demographics

A total of 174 patients (mean age of 57 ± 20 years) met the inclusion criteria. Among these patients, 95 were women (55%) and 79 were men (45%). Ethnic distribution revealed that the majority were non-Hispanic (62%), and a minority were Hispanic or Latino (8%). Most patients were Caucasian (54%), followed by African or African American (13%), with Asian, Native Hawaiian, or other Pacific Islander groups each representing under 10% (details are in Table 1).

Table 1.

Demographic data, clinical features, laboratory findings, and outcomes among patients diagnosed with fascioliasis.

Clinical features	N = 174
Age (mean ± SD)	57 ± 20
Sex (women)	95 (55%)
Ethnicity
Not Hispanic	107 (62%)
Unknown	53 (31%)
Hispanic or Latino	14 (8%)
Race
Caucasian	94 (54%)
Unknown Race	30 (17%)
African or African American	22 (13%)
Other Race	14 (8%)
Asian	13 (7%)
Native Hawaiian or Other Pacific Islander	10 (6%)
Comorbidities
Essential hypertension	72 (41%)
Neoplasm	62 (36%)
Heart disease	61 (35%)
Liver disease	52 (30%)
Sleep disorders	40 (23%)
Anemia	39 (22%)
Vitamin D deficiency	37 (21%)
DM2	35 (20%)
IBD	31 (18%)
Hypothyroidism	26 (15%)
Chronic kidney disease	21 (12%)
Eosinophilia	15 (9%)
HIV	<10 (<6%)
Symptoms
Upper abdominal pain	58 (33%)
Skin complaints	57 (33%)
Dyspnea	55 (32%)
Throat or Chest pain	53 (30%)
Malaise and Fatigue	50 (29%)
Headache	49 (28%)
Shortness of breath	47 (27%)
Diarrhea	44 (25%)
Nausea and vomiting	42 (24%)
Cough	41 (24%)
Dyspnea	40 (23%)
Labs (mean ± SD)
WBC (103/µL)	7.1 ± 3.4
Hemoglobin (mg/dL)	13.1 ± 2.0
Hematocrit (%)	39.7 ± 5.5
Eosinophils (%)	3.6 ± 5.9
Platelets (103/µL)	240.8 ± 76.5
ALT (U/L)	29.3 ± 23.7
AST (U/L)	30.1 ± 27.5
Creatinine (mg/dL)	0.9 ± 0.6
C-Reactive Protein (mg/L)	14.1 ± 27.6
ESR (mm/hour)	26.7 ± 28.2
Ferritin (ng/mL)	190.3 ± 278.7
LDH (U/L)	1.7 ± 0.9
Antiparasitics
Praziquantel	20 (11%)
Albendazole	19 (11%)
Ivermectin	11 (6%)
Triclabendazole	10 (6%)
Procedures
ERCP	12 (7%)
Outcomes
Hepatomegaly (±1 year)	16 (9%)
Cholangitis/cholelithiasis at 5 years	14 (8%)
Hepatic cirrhosis at 5 years	<10 (<6%)
Portal vein thrombosis at 5 years	<10 (<6%)
Hospitalization (90 days)	50 (29%)
90-day mortality	<10 (<6%)

ALT, alanine aminotransferase; AST, aspartate aminotransferase; CK, chronic kidney disease; DM2, diabetes mellitus type 2; ERCP, endoscopic retrograde cholangiopancreatography; ESR, erythrocyte sedimentation rate; HIV, human immunodeficiency virus; IBD, inflammatory bowel disease; LDH, lactate dehydrogenase.

Comorbidities

Common comorbidities included essential hypertension (41%), neoplasms (36%), heart disease (35%), liver disease (30%), and sleep disorders (23%). Key symptoms included upper abdominal pain and skin complaints (33% each), dyspnea (32%), and malaise/fatigue (29%).

Laboratory, treatment, and imaging results

Laboratory values showed white blood cells (WBC) of 7.1 ± 3.4 × 10³/µL with a mean of 3.6% eosinophils and platelets averaging 240.8 ± 76.5 × 10³/µL. There was a wide value range for the C-reactive protein (CRP), averaging 14.1 ± 27.6 mg/L, and the erythrocyte sedimentation rate (ESR) was 26.7 ± 28.2 mm/H. Antiparasitic treatments like praziquantel and albendazole were recorded in 11% of cases, with triclabendazole administered to 10 patients. Endoscopic retrograde cholangiopancreatography (ERCP) was only reported in 7% of the patients.

Twenty-nine percent of the patients were hospitalized. The 90-day mortality was low (<6%). Hepatomegaly, cholelithiasis, and cholangitis occurred in 10% of cases, while hepatic cirrhosis was uncommon. Among hospitalized patients within 3 months of diagnosis, 63% had abdominal pain. Of the 13 patients who developed cholangitis or cholelithiasis, 53% were men (47% women) with abdominal pain, nausea/vomiting, dysphagia, ascites, and liver or intrahepatic bile neoplasia.

Discussion

This cohort of 174 patients with fascioliasis was represented by predominantly middle-aged, female, and Caucasian patients, with a notable Hispanic representation (8%). Fascioliasis is geographically distributed in all continents except Antarctica. ¹² Most of these cases may have been diagnosed with fascioliasis in Asia, Africa, or represent imported cases from immigrants in North America, given that most patients were not Hispanic. Diagnosis of fascioliasis remains a challenge since tests for acute fascioliasis are limited in most countries where this disease is endemic. ¹³ Although coprological studies are widely available, eggs are not usually visualized during the acute phase of the disease because the larvae are still migrating through the peritoneal cavity or liver parenchyma and have not yet matured in the biliary ducts to release eggs. Thus, a point-of-care serological test to detect IgM/IgG for fascioliasis is urgently needed since clinicians in countries where the disease is endemic must still rely on research/outside laboratories to diagnose the disease.^14,15

The burden of comorbid conditions is not commonly reported for patients with fascioliasis, and is limited to only case reports of hypothyroidism and heart failure in two imported US cases. ¹⁶ We found high rates of essential hypertension, neoplasms, heart disease, liver disease, and sleep disorders in this cohort of patients with fasciolasis. Hypertension has been reported as a common comorbidity among cohorts of other neglected tropical diseases like chronic Chagas disease, with a prevalence of over 60%.^17,18 The increasing burden of chronic noninfectious disease is well recognized worldwide; thus, comorbid conditions in this and other cohorts are likely to represent conditions affecting the overall age-matched population and may not be related to their risk of infection. However, whether true associations exist and whether potential interactions of these conditions with neglected tropical diseases are plausible, warrants further investigation.

Symptoms during acute infection include right upper quadrant pain, fever, and hepatosplenomegaly, although many infections can be asymptomatic. ¹⁹ Key symptoms in this cohort included upper abdominal pain, skin complaints, dyspnea, and malaise/fatigue. Because we did not necessarily capture symptoms at the time of diagnosis, these may represent acute, residual, and perhaps even unrelated symptoms. For the same reason, although the eosinophilia is a routine finding during acute infection, its duration and magnitude could not be captured. Likewise, antiparasitic treatments and ERCP procedures were infrequent and likely related to limitations of the electronic medical records.

Although up to one-third of patients required hospitalization, the 90-day mortality and complication rates were low. Chronic infection complications usually develop after 6 months and up to 10 years or more after infection ²⁰ and include biliary colic, cholangitis, cholelithiasis, and obstructive jaundice.^21,22 Hepatomegaly, cholelithiasis, and cholangitis were infrequent complications in this, as in other cohorts. Cholangitis and/or cholelithiasis mainly presented with abdominal pain, nausea, and ascites in men with liver or bile duct neoplasia. Although case series and case reports have reported secondary pancreatitis ²³ as a complication in up to 38% of patients, we did not find any cases in our cohort. Liver cirrhosis and cancer are plausible, yet undocumented, complications of chronic liver infections, including fasciolasis, especially since there may be a link with fibrosis. ²⁴ However, rates of cirrhosis and portal vein thrombosis were also infrequent in this cohort. Exploring such long-term associations warrants further studies.

Our study has several limitations. The retrospective design and use of ICD codes for diagnosis may introduce selection bias and the potential for misclassification. We did not have access to microbiology or histology data to confirm cases clinically, identify the parasite species, or determine treatment courses. Other relevant data could not be obtained due to the ICD-10 limitations (e.g., acute vs chronic infection or subcapsular hematoma). However, this is one of the most extensive case series of fascioliasis patients ever described, with close to 200 subjects. In addition, treatment with triclabendazole, the only drug highly effective against this liver fluke, was reported only for a few patients and was surpassed by the frequency with which praziquantel, an ineffective drug against fascioliasis, was prescribed. The limited use of triclabendazole may be attributed to its lack of registration in certain countries. Alternatively, it could be due to insufficient data capture through our federal network, especially if treatment was administered outside the scope of the electronic medical record system. Documentation of treatment response to triclabendazole is of importance because of the increasing reports of drug resistance.^25,26

In conclusion, in a large real-world case series of fascioliasis, we found a high frequency of comorbidities and typical gastrointestinal symptoms characteristic of this infection. Mortality was low, as were complication rates. However, the role of chronic biliary and liver complications in the development of liver fibrosis and cancer warrants additional clinical prospective studies. Use of triclabendazole in this report was low (6%). Identifying cases of fascioliasis in large clinical networks may uncover new trends in the incidence of this re-emerging zoonotic disease that affects the poorest people on the planet.^27–33