Alveolar Echinococcosis (AE) Workup

Updated: Nov 08, 2019
  • Author: Dominique A Vuitton, MD, PhD; Chief Editor: Burke A Cunha, MD  more...
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Approach Considerations

A diagnosis of alveolar echinococcosis (AE) is most often suspected based on imaging results (ultrasonography or CT scanning).

In endemic European areas, suspected alveolar echinococcosis lesions are increasingly discovered incidentally (56% of AE cases in the EurEchino registry in 2016; unpublished data), in asymptomatic subjects during routine imaging workup for another disease, especially in patients with immunosuppression-associated conditions (malignant disorders, chronic inflammatory diseases, allotransplantation, AIDS).

In western China, because of the national program against echinococcosis, mass ultrasonography screening is systematically performed in some highly endemic areas and thus may uncover asymptomatic cases, but patients referred to hospitals are most often symptomatic (73% were incident cases in Xinjiang, People’s Republic of China, in 2016, according to the AE registry of the WHO-Collaborating Centre for Prevention and Care Management of Echinococcosis, Urumqi, Xinjiang; unpublished data).

After a suspected alveolar echinococcosis lesion is found on initial imaging, complementary imaging is the second step, followed by serology.

A two-step approach for serology is recommended, first with a highly sensitive test (hemagglutination or enzyme-linked immunosorbent assay [ELISA] using heterologous crude antigen) and then, second, with Western blot. Western blot should be performed in all cases with a high level of suspicion based on imaging, especially in immunosuppressed patients. Definitive diagnosis relies on pathology or identification of the parasite larva via molecular biology.


Laboratory Studies

Blood cell count

Hypereosinophilia is a rare feature of disease (< 10%).

Lymphopenia develops in 45% of cases.

Immunoglobulin concentrations

Increase in levels of gammaglobulins is common, primarily resulting from an increase in immunoglobulin G (IgG) levels and, to a lesser degree, levels of immunoglobulin A (IgA) and immunoglobulin M (IgM).

Increased immunoglobulin E (IgE) levels are uncommon.

Inflammatory proteins

Tests usually show increased levels of haptoglobin, alpha1 acid glycoprotein, C3 and C4, and ceruloplasmin despite the absence of increased C-reactive protein (CRP) levels.

CRP levels increase in cases complicated by bacterial superinfection.

Hepatic function

Results may be normal in asymptomatic cases.

Gamma-glutamyl transferase (GGT) levels usually increase before the patient is symptomatic. GGT levels also increase if bile ducts are obstructed. GGT levels can reach 20 times the reference range.

Alkaline phosphatase levels increase later than GGT levels and are observed only in symptomatic patients.

Conjugated bilirubin levels increase in symptomatic patients who are diagnosed with jaundice.

Levels of aminotransferases increase only when associated with necrosis. Aspartate aminotransferase (AST) is equal to alanine aminotransferase (ALT).

Prothrombin time decreases because of cholestasis, which can usually be corrected with vitamin K supplementation.

Factor V levels decrease in rare cases of hepatic failure (eg, secondary biliary cirrhosis, Budd-Chiari syndrome).

Specific serology

Serology results usually confirm a diagnosis suspected based on ultrasonography or CT scanning findings obtained in a clinical setting. These studies are also used for mass screenings.

Results from routine tests using heterologous antigen (E granulosus cyst fluid) are positive for indirect hemagglutination in 75-80% of cases with a threshold value at 1/300 dilution and 94% of cases with a threshold value at 1/80 (with a very poor specificity, often positive in other helminth infections).

Immunofluorescence using protoscoleces as an antigen yields similar results but is no longer performed. Immunoelectrophoresis using Echinococcus crude extract yield low sensitivity and specificity; arc 5, considered typical of E granulosus, is observed in nearly 60% of patients with alveolar echinococcosis. This technique, as well as immunosyneresis, has inadequate sensitivity and is time-consuming so should be abandoned.

ELISA results using heterologous antigen (E granulosus cyst fluid) are positive in 97% of cases, positive in abortive cases, and positive before species-specific tests in cases that recur after radical surgery or transplantation. ELISA results may also be positive in other types of cestode infections, especially cysticercosis (Taenia solium infection in humans) and, although less frequently, in other helminth infections. Considerations are as follows:

  • ELISA results using homologous antigen ( E multilocularis extract) are positive in 95% of cases but may be positive in other cestode infections.
  • ELISA results using recombinant and purified antigens of E multilocularis (Em2+, which combines Em2 and recombinant Em18, or recombinant Em18 alone) are positive in 95% of cases and have better specificity. Both are commercially available. Em18 is more suitable for follow-up of EA.
  • Dot immunogold filtration assay (DIGFA) for the diagnosis of echinococcosis and discrimination between E granulosus and E multilocularis, as a rapid test that does not require laboratory facilities, is commercially available in the People's Republic of China.
  • ELISA using the purified alkaline phosphatase of E multilocularis is both highly sensitive and specific (nearly 100%) but is not commercially available.

Western blot tests using combined extracts of E granulosus and E multilocularis or E multilocularis alone result in patterns specific for alveolar echinococcosis. Two narrow bands at 18 kDa are associated with 1 band at 26-27 kDa or only 1 band at 26-28 kDa. A pattern consisting of 1 band at 7 kDa and 1 band at 26-28 kDa without an intermediate band cannot differentiate E multilocularis infection from that of E granulosus. Western blot tests are highly sensitive (97%), and cross-reactions resulting in a similar pattern are observed only with sera from patients with neurocysticercosis. Western blot tests are commercially available. Specific Western blot using Em18 antigen or Em18 recombinant protein has comparable diagnostic value; in addition, they may be used for follow-up. A test kit using Em18 recombinant antigen is now commercially available (CE registration: CH-201708-0010).

Specific IgE is present in the serum of 50% of patients, more frequently in patients with progressive and advanced cases, and cannot be used for diagnosis.

Cellular immunology

These tests are used primarily for research purposes. None of them is applicable to diagnosis.

Specific histamine release by basophils, using a homologous antigen, is observed in all cases.

Specific proliferation of peripheral blood lymphocytes can be induced using specific homologous extracts but is not routinely used.

Spontaneous secretion of IL-10 by peripheral lymphocytes in culture is observed in most patients with a progressive form of the disease.


Imaging Studies

Aspect and location of alveolar echinococcosis lesions in the liver

In 50% of cases, lesions are located in a single hepatic lobe (right liver, 75%; left liver, 15%). Involvement of both right and left liver lobes by a single lesion is observed in 50% of cases.

The infiltrative lesions may be larger than 10 cm in diameter and invade or surround vascular and/or biliary structures. Some lesions are more nodular, 3-6 cm in diameter, and more calcified.

Two or more distinct parasitic foci may be observed.

Thoroughly investigate ultrasonographic evidence of bile duct dilation, portal hypertension, ascites, and splenomegaly. Doppler studies are a useful complement to better characterize hepatic and portal vessels and blood flow.

Diagnostic and prognostic value of contrast-enhanced ultrasonography and functional CT scanning and MRI need further evaluation. [16]

Classifications of sonograms and computed tomography (CT) scans, based on the morphological aspect of the lesions (eg, solid, pseudocystic, hemangiomalike, metastasislike) and the type of associated calcifications were recently proposed. [17, 18] Before being fully standardized and adopted at the international level, these classifications are currently being evaluated in a multicenter German/French/Chinese study.


Ultrasonographic examination (see image below) is used to assess the morphology of alveolar echinococcosis both for diagnosis in hospital settings and in mass field screenings. It should be used as a first-line imaging technique.

Sonogram of a typical form of alveolar echinococco Sonogram of a typical form of alveolar echinococcosis of the liver, discovered at a screening in China. Courtesy of Dominique A. Vuitton, MD, PhD; Brigitte Bartholomot, MD; and Philip S. Craig, PhD.

In most cases, ultrasonographic images show a pseudoneoplastic intrahepatic mass with a heterogeneous ultrasonographic structure that is mainly hyperechoic and contains scattered calcifications and irregular, poorly defined edges.

A central necrotic cavity with a hypoechoic pseudoliquid structure and anfractuous borders may be observed.

Hyperechoic nodular homogenous hemangiomalike lesions, 1-2 cm diameter, may be associated with typical lesions and observed as a recurrence after surgery or observed in patients who are asymptomatic at screening. These lesions represent an early stage of development. They are more often observed in patients with immune suppression. Cancer metastasislike and abscesslike lesions may also be observed in such patients. [14]

Disclosure of nodular or scattered calcified lesions in the liver is common in mass surveys and can be observed in hospital settings in endemic areas (see image below). If the calcifications are associated with a positive result on specific serology, they may represent aborted forms of the disease. A 2019 study showed that microcalcifications on CT scans were strongly correlated with hypermetabolic activity of AE hepatic lesions on FDG-PET/CT, regardless of the presence of macrocalcifications. [19]

Sonogram of an abortive form of alveolar echinococ Sonogram of an abortive form of alveolar echinococcosis of the liver, discovered at a screening in China. Courtesy of Dominique A. Vuitton, MD, PhD; Brigitte Bartholomot, MD; and Philip S. Craig, PhD.

CT scanning

Abdominal CT scanning reveals the morphologic aspect of the lesions (see image below). This is the best examination to show the typical calcifications inside the lesions and is particularly useful for very calcified lesions that are difficult to delineate with ultrasonography because of the induced shadow.

Ultrasonographic, CT scan, and perioperative aspec Ultrasonographic, CT scan, and perioperative aspect of a typical lesion of alveolar echinococcosis with central necrosis. Courtesy of Jean-Philippe Miguet, MD.

Abdominal CT scanning is also useful for preoperative evaluation to assess vascular involvement and extension to adjacent organs and tissues (eg, diaphragm and lungs, stomach, spleen, left kidney, adrenal gland).

Perform thoracic and cerebral CT scanning before any radical surgery, especially liver transplantation. Metastatic lesions appear as tumorlike structures, single or multiple, in the lungs and/or brain.

Magnetic resonance imaging

The cancerlike intrahepatic lesions appear as low signal intensity with a possible isointense component on T2-weighted images, and they produce variable signals on T2-weighted images, including necrotic areas in high signal intensity and some areas in low signal intensity.

MRI demonstrates a pathognomonic image of alveolar echinococcosis lesions (microcysts) that resembles bunches of grapes or a honeycomb. These lesions are more commonly observed on high-intensity T2-weighted images and are composed of many rounded cavities smaller than 1 cm in diameter (see images below).MRI description of the lesions may use Kodama classification. [20]

Pathognomonic aspect of alveolar echinococcosis le Pathognomonic aspect of alveolar echinococcosis lesions invading the adrenal gland (resembling a honeycomb) that shows a necrotic area in the contiguous left liver lesion; MRI showing multiple parasitic cysts smaller than 1 cm in diameter appearing in high signal intensity on T2-weighted sequence. Courtesy of Brigitte Bartholomot, MD.
Pathognomonic image of alveolar echinococcosis. Mu Pathognomonic image of alveolar echinococcosis. Multiple microcysts of alveolar echinococcosis, better seen at MRI on T2-weighted sequence. Courtesy of Prof. Eric Delabrousse and Dr. Amel Azizi, Department of Radiology, University Hospital, Besançon, France.


T2-weighted MRI. Typical aspect of an advanced liv T2-weighted MRI. Typical aspect of an advanced liver alveolar echinococcosis case in a young adult presenting with cholestasis. Central necrotic area surrounded by multiple hyperdense microcysts; the lesion invades bile ducts and liver vessels. Courtesy of Laurianne Plastaras, MD, Hôpital Louis Pasteur, Colmar, France, and Stéphane Koch, MD, Centre Hospitalier Régional Universitaire, France.
Video of T2-weighted MRI. Typical aspect of an advanced liver alveolar echinococcosis case in a young adult presenting with cholestasis. Central necrotic area surrounded by multiple hyperdense microcysts; the lesion invades bile ducts and liver vessels. Courtesy of Laurianne Plastaras, MD, Hôpital Louis Pasteur, Colmar, France, and Stéphane Koch, MD, Centre Hospitalier Régional Universitaire, France.

Gadolinium reveals an absence of contrast enhancement of the focus and the perilesional area in 60% of the cases.

In 40% of cases, an abnormal and delayed contrast enhancement is observed on the flash 2D sequences after contrast medium enhancement, especially on delayed T1-weighted images. They may correspond to the active neovascularized granuloma surrounding the parasitic lesions.

MRI is not effective for showing typical calcifications, but it is the best technique, when available, to differentiate an early homogenous hyperechoic parasitic lesion and a more common hemangioma.

When available, use MRI to confirm the diagnosis, especially when serology results are negative (eg, in immunosuppressed patients). Use MRI for preoperative evaluation, especially to disclose invasion of vessels and neighboring organs and tissues (see image above). Use magnetic resonance (MR) cholangiopancreatography to study the relationship between the alveolar echinococcosis lesion and the biliary tree.


Cholangiography may show the precise level of bile duct obstruction and/or may be used to assess communication between bile ducts and the central necrotic area of the lesions and/or demonstrate communication between bile ducts and bronchi.

Percutaneous transhepatic cholangiography may be the first stage of an interventional procedure. [21]

Endoscopic retrograde cholangiopancreatography may also be used as the first stage of intrabiliary stent insertion. [21]


MRI, ultrasonography with Doppler, and CT scanning have replaced angiographic procedures in most cases, but angiographic procedures may be indicated in rare cases before surgery.

Angiography may reveal invasion of hepatic arteries, portal vein obstruction or thrombosis, portocaval anastomoses, and obstruction or thrombosis of hepatic veins and vena cava.

Chest radiography

Chest radiography is the initial examination to assess the presence of lung metastases.

Lung metastases may be unique or multiple and appear as nodular images that resemble primary or metastatic tumors.

Complement radiography with lung CT scanning is indicated before any surgical intervention is planned, especially liver transplantation.


Other Tests

Fluorodeoxyglucose (FDG)–positron emission tomography (PET) scanning: PET scanning, and especially morpho-PET scanning (PET combined with CT scanning, using image fusion), may be used to assess the viability of the parasitic lesions and the level of periparasitic cellular inflammation.

FDG is actively metabolized by the cell immune response surrounding parasitic lesions; thus, lesional or perilesional enhancement ("hot spots") may be seen if the lesions are metabolically active. This technique may be used for the follow-up of patients treated with chemotherapy. Inactive lesions and calcified lesions do not uptake fluorodeoxyglucose.

Delayed acquisition of PET images (3 hours after FDG injection) increases the sensitivity of the procedure and is recommended before any decision of medical treatment withdrawal is made. [22]

The presence of microcysts on MRI, as assessed in Kodama classification, well correlates with metabolic activity on PET. [23] ; the correlation between diffusion-weighted MRI and the metabolic status of the lesions should be confirmed in larger series of patients. [16]

Fluorodeoxyglucose (FDG) positron emission tomogra Fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT scan aspect of active alveolar echinococcosis. White-yellow colors show a very high FDG uptake due to the periparasitic granulomatous infiltration and/or active germinal layer of Echinococcus multilocularis, and green-gray colors show the absence of the FDG uptake by inactive parasitic lesions (mostly necrotic). Courtesy of Solange Bresson-Hadni, MD, PhD, and Oleg Blagosklonov, MD, PhD.
Fluorodeoxyglucose (FDG) positron emission tomogra Fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT scan aspect of inactive alveolar echinococcosis. No abnormal FDG uptake by the parasitic lesions after several years of albendazole treatment. Courtesy of Solange Bresson-Hadni, MD, PhD, and Oleg Blagosklonov, MD, PhD.


Esophagogastroduodenoscopy may show esophageal varices in cases that involve portal hypertension; it may be used as the first step of retrograde cholangiography and perendoscopic intervention (drainage and/or stenting) to relieve bile duct obstruction.

Bronchoscopy may be useful in cases of lung invasion or metastases.

Avoid needle liver biopsy if the diagnosis has been assessed on epidemiologic grounds using ultrasonography and/or CT scanning/MRI and confirmed with serology. Needle liver biopsy carries the risk of dissemination and subsequent growth of parasitic cells and should be followed by albendazole treatment if alveolar echinococcosis is confirmed.

Fine-needle aspiration (or needle biopsy, if necessary) to characterize E multilocularis using polymerase chain reaction (PCR) may be used if all other techniques have failed to confirm alveolar echinococcosis.


Histologic Findings

Surgical liver biopsy results show parasitic vesicles delineated by a periodic acid-Schiff–positive laminated layer and surrounded by granulomatous infiltrate, either cellular in younger lesions or mostly fibrotic and acellular in older lesions. Protoscoleces are observed in 15% of lesions.

From the center to the periphery, the periparasitic granuloma (see image below) is composed of epithelioid cells lining the parasitic vesicles, macrophages, fibroblasts and myofibroblasts, giant multinucleated cells, and various cells of the nonspecific immune response. Collagen and other extracellular matrix protein deposits are present. The granuloma is usually surrounded by lymphocytes (mainly of the CD8+ subpopulation).

Histologic features of alveolar echinococcosis ves Histologic features of alveolar echinococcosis vesicles and periparasitic granuloma in humans, periodic acid-Schiff staining of the laminated layer. Courtesy of Bernadette Kantelip, MD.

E multilocularis may be identified with PCR using specific probes; however, a negative result on a thin needle aspiration sample does not rule out disease.

A specific immunostaining using anti-Em2G11 monoclonal antibody may be used to better characterize the presence of E multilocularis metacestode materials. [24]



Staging the disease is essential to allow comparisons between series of patients and to perform multicenter trials. The World Health Organization (WHO) Informal Working Group on Echinococcosis has developed such staging. The PNM (parasite, neighboring organ and tissue invasion, metastases) staging system has been evaluated prospectively in 220 cases from 4 centers in France, Germany, China, and Japan.

The currently proposed imaging classifications based on pure description of ultrasonography, CT scanning, and MRI images have no application to staging. [20, 17, 18] No studies have been specifically performed with the intent of associating the various morphological aspects of the lesions and/or the calcification in the lesions with therapeutic decisions or prognosis. They are being evaluated for this purpose on a larger collective of alveolar echinococcosis cases.

PNM classification and staging

Hepatic localization of the parasite

For classification, the plane that projects between the bed of the gallbladder and the inferior vena cava divides the liver into 2 lobes.

Staging is as follows:

  • PX - Primary tumor cannot be assessed

  • P0 - No detectable tumor in the liver

  • P1 - Peripheral lesions without proximal vascular or biliary involvement

  • P3 - Central lesions with hilar vascular or biliary involvement of both lobes or involvement of 2 hepatic veins

  • P4 - Any liver lesion with extension along the vessels (vessels meaning inferior vena cava, portal vein, and arteries) and the biliary tree

Extrahepatic involvement of neighboring organs

Neighboring organs include the diaphragm, lung, pleura, pericardium, heart, gastric and duodenal wall, adrenal glands, peritoneum, retroperitoneum, parietal wall (muscles, skin, bone), pancreas, regional lymph nodes, liver ligaments, and kidney.

Staging is as follows:

  • NX - Cannot be evaluated

  • N0 - No regional involvement

  • N1 - Regional involvement of contiguous organs or tissues

The absence or presence of distant metastasis

Locations include the lung, distant lymph nodes, spleen, CNS, orbital, bone, skin, muscle, kidney, and distant peritoneum and retroperitoneum.

Staging is as follows:

  • MX - Not completely evaluated

  • M0 - No metastasis (negative findings on chest radiograph and cerebral CT scan)

  • M1 - Metastasis

Determining stage

Once the parasite (P), neighboring organ and tissue invasion (N), and metastases (M) are determined, they are combined, and an overall stage of I, II, III, or IV is assigned. Stage III is subdivided using letters such as A and B. The formal stage of alveolar echinococcosis does not change over time, even if the disease progresses. Alveolar echinococcosis that regresses or spreads is still referred to by the stage it was given when it was first diagnosed.

The following is the PNM stage grouping of alveolar echinococcosis:

  • Stage I - P1, N0, M0

  • Stage II - P2, N0, M0

  • Stage IIIa - P3, N0, M0

  • Stage IIIb - P1-3, N1, M0 or P4, N0, M0

  • Stage IV - P4, N1, M0 or any P, any N, M