Hepatic Alveolar Echinococcosis

Description

Alveolar echinococcosis (AE) is a serious and potentially fatal zoonotic parasitic infection caused by the larval form of Echinococcus multilocularis. It primarily affects the liver, where it grows in a tumor-like and infiltrative manner, and can spread to other organs such as the lungs, brain, and bones. The disease develops as the parasite continuously proliferates within vesicle-like structures, eliciting a strong granulomatous and fibrous response from the host, which can result in severe damage to liver tissue and obstruction of bile ducts and blood vessels. Humans become infected accidentally by ingesting parasite eggs released into the environment by definitive hosts, mainly foxes. Over the past four decades, the prognosis for patients with AE has significantly improved due to earlier detection and advances in treatment strategies. However, alveolar echinococcosis remains underrecognized in many European countries, as it is an emerging disease in nearly every country where it has been detected, with two major epicentres identified in the Alpine and Baltic regions of Central, Northern, and Eastern Europe.

Genetics

So far no disease specific genetics have been reported that have a clinical relevance.

Clinical presentation

In immunocompetent individuals, alveolar echinococcosis (AE) typically progresses slowly, with an average incubation period of 5–15 years. Early stages are often asymptomatic, while advanced disease can present with diffuse abdominal pain, hepatomegaly, and jaundice, usually due to mass effect or bile duct invasion. Complications such as secondary biliary cirrhosis, liver dysfunction, and portal hypertension may develop. Nearly all primary AE lesions originate in the liver, from which the infection can spread locally or metastasize via lymphatic or hematogenous routes to distant organs. In advanced stages, metastatic lesions occur in approximately 20–35% of cases, most commonly affecting the lungs, brain, and bones. Imaging typically reveals heterogeneous, infiltrative hepatic lesions with irregular, scattered calcifications, often resembling malignant tumors. In Europe, the number of asymptomatic AE cases detected has increased in recent years. Concurrently, the incidence of AE in immunosuppressed individuals has risen, with these cases often demonstrating faster progression and posing greater diagnostic challenges.

Risk factors

AE is endemic to the Northern Hemisphere, with high-prevalence regions in Central Europe, parts of Asia, and North America. China reports the highest number of cases globally. Foxes are the primary definitive hosts, although domestic dogs can also play a significant role in transmission. Risk factors include occupational or recreational exposure to foxes, dogs, or their feces, as well as consumption of contaminated produce such as raw vegetables, berries, salads, or untreated water. The growing fox population in urban environments has contributed to an increasing incidence in previously non-endemic areas. Additionally, the number of AE cases among immunosuppressed individuals has increased, raising concerns due to the disease’s more aggressive progression and the greater challenge associated with diagnosis in this population.

Diagnosis

Diagnostic protocols for alveolar echinococcosis (AE) involve a combination of clinical assessment, imaging, and specific serological tests. Ultrasonography is the primary imaging modality, typically revealing heterogeneous, predominantly hyperechogenic lesions with irregular and poorly defined margins. Scattered calcifications are commonly observed. Computed tomography (CT) and magnetic resonance imaging (MRI) provide enhanced anatomical detail, which is especially valuable for surgical planning. In immunocompetent patients, serological assays such as Em2-ELISA and recEm18-ELISA offer high sensitivity and specificity and correlate well with parasite activity. Confirmatory testing using Echinococcus multilocularis immunoblot significantly improves diagnostic sensitivity. This second-line test is particularly useful in immunocompromised patients, in whom first-line serological tests may yield false-negative results. In uncertain cases, histopathological examination or PCR-based techniques may be necessary to establish a definitive diagnosis.

Management

Current therapeutic management of alveolar echinococcosis (AE) requires a multidisciplinary approach, with albendazole (ABZ), a benzimidazole derivative with parasitostatic effects, serving as the cornerstone of treatment. Therapy should be initiated promptly upon diagnosis.

Curative treatment involves complete surgical removal (R0 resection) of the parasitic lesion, although this is often difficult due to the infiltrative growth pattern and proximity to critical vascular and biliary structures. While WHO guidelines traditionally recommend wide surgical margins, recent studies suggest that margins as narrow as 1 mm may be acceptable. Postoperative albendazole therapy is currently still advised for two years to reduce the risk of recurrence. Long-term follow-up, including imaging and serological monitoring, is recommended for up to 10 years after surgery. Liver transplantation is an option for selected patients with end-stage liver disease and no evidence of extrahepatic spread, although the risk of recurrence is high due to the immunosuppression.

In unresectable cases, lifelong albendazole therapy is indicated In symptomatic patients, endoscopic biliary interventions can provide significant relief. Follow-up should include imaging and serological monitoring to assess disease activity and treatment response too. 

Complications

Complications in alveolar echinococcosis (AE) result from both disease progression and treatment-related factors. Locally, AE can lead to biliary obstruction, secondary biliary cirrhosis, and portal hypertension. Hepatic abscesses due to central parasitic necrosis and thrombosis of major vessels are rare but potentially life threatening. In advanced stages, metastatic spread most frequently involves the lungs and central nervous system. Despite improvements in imaging and therapeutic strategies, disease recurrence remains a major concern, with rates ranging from 2% to 16% even after curative resection. Therefore, lifelong surveillance using imaging and serological markers is recommended to monitor for relapse and assess disease activity.