Alveolar Echinococcosis (AE) Treatment & Management

Updated: Nov 28, 2017
  • Author: Dominique A Vuitton, MD, PhD; Chief Editor: Burke A Cunha, MD  more...
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Treatment

Approach Considerations

A multidisciplinary approach and long-term follow-up are essential for optimal treatment of alveolar echinococcosis (AE). The first step consists of positive and differential diagnosis, as well as evaluation of the metabolic activity of lesions; the second step concerns the possibility of a complete resection of lesions (ie, radical or curative surgery). In 2016, a comprehensive review was published on the interventional strategy in alveolar echinococcosis. [18]

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Medical Care

Alveolar echinococcosis is rare and can be severe. All cases merit prolonged follow-up. Refer patients to reference centers to confirm their diagnosis and to obtain advice on therapeutic strategy.

Antiparasitic chemotherapy

The basic medical treatment is chemotherapy with benzimidazoles (eg, mebendazole, albendazole) at high doses.

According to the 1996 WHO Informal Working Group on Echinococcosis and updated consensus recommendations in 2010, [19] long-term chemotherapy, for several years (and possibly for life), is mandatory in inoperable patients. The decision to withdraw treatment is particularly difficult without objective and irrefutable proof of definitive cure. An attempt at withdrawing benzimidazole treatment may rely on negative FDG-PET scanning findings, including delayed images and negative EM2+ or Em18 serology results. Follow-up with careful PET scanning and serology should be performed first 3 months after treatment interruption and then yearly for 10 years.

Complementary and continuous chemotherapy with, preferably, albendazole is mandatory for at least 2 years following surgery. Careful follow-up examinations in these patients must continue for at least 10 years. In all cases of palliative operations, either surgical or ultrasonographically guided, chemotherapy is mandatory and follows the same therapeutic schedule as for patients who have not undergone surgery.

Intravenous amphotericin B (preferably as lipid emulsion) may be used as a rescue chemotherapy in patients resistant or intolerant to benzimidazoles. Pilot trials with interferon-gamma and nitazoxanide were unsuccessful. Interferon-alpha has yet to be tested in a pilot trial.

Other medication

Additional medical treatment includes antibiotics and antifungal agents for bacterial and fungal superinfection of the lesions, cholangitis and/or septicemia (mostly gram-negative bacteria, antibiotic-resistant Streptococcus faecalis, Pseudomonas aeruginosa, and Candida species after surgical interventions), and chronic cholestasis (including vitamin K and D supplementation).

Use propranolol to prevent digestive bleeding related to portal hypertension.

Ursodeoxycholic acid may be used in patients with chronic cholestasis and/or biliary stenting; its use has not been evaluated by specific studies.

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Surgical Care

Except in cases of limited lesions located in the left liver lobe, attempt surgical procedures only if the team is trained and equipped for major liver surgery.

Radical surgery

If operation is feasible and if resection of the entire parasitic lesion from other affected organs is possible, surgery is the first treatment choice.

Recurrence has been observed after liver resections judged radical by the surgeon based on macroscopic evidence, which supports the systematic prescription of albendazole for at least 2 years.

Recent retrospective studies of surgical series confirm the efficacy of the procedure if microscopic examination of the resected lesion confirms complete resection when the ”safety margin” is limited at least to 1 mm. [20, 21]

Palliative surgery

When radical surgery is impossible, one option is nonradical liver resection to reduce the parasitic mass and to increase the chances of effective chemotherapy. These palliative resections, as well as other types of palliative surgery performed to treat complications of disease (especially biliary obstruction), may generate specific complications (eg, recurrent biliary obstruction with cholangitis, septicemia, intrahepatic gallstones leading to secondary biliary cirrhosis). The current recommendation is to avoid palliative surgical procedures because of the relative efficacy of medical treatment, the use of interventional radiology and/or endoscopy, and a possible further indication of liver transplantation in patients with severe disease.

Liver transplantation

Consider liver transplantation in very advanced cases. Since 1986, more than 50 liver transplantations have been performed in patients with alveolar echinococcosis. The overall associated survival rate is lower than that of other indications for liver transplantation but is acceptable. Survival periods of more than 20 years have been observed in patients with alveolar echinococcosis who have undergone liver transplantation, even in those with residual or recurrent lesions.

Recurrences and metastases are common after transplantation (even those judged radical) in immunosuppressed patients. Benzimidazole treatment is mandatory as soon as possible after transplantation in all patients; such therapy can stop the progression of residual or recurrent lesions.

To avoid prolonged therapeutic immune suppression and make major hepatectomy possible, “bench-hepatectomy” (also called ”ex-vivo liver resection”) followed by autotransplantation has been performed in very advanced cases of alveolar echinococcosis by Chinese surgeons since 2011, with reasonable success. [22, 23]

Interventional radiology or endoscopy

Consider ultrasonographically guided percutaneous procedures (eg, internal/external biliary drainage, abscess drainage, stenting) to alleviate intrahepatic complications.

Consider perendoscopic stenting of the bile duct in patients with biliary obstruction. Retrospective evaluation of the technique in 19 European centers shows that it is efficient and safe and makes recalibration of the bile duct stricture possible by using iterative stenting with multiple plastic stents. [14, 24] )

When performing perendoscopic drainage and stenting, be careful to perform intensive lavage of bile ducts with saline, remove all stones and debris, and give appropriate antibiotics after the procedure. [24]

Consider using endoscopic sclerosis of esophageal varices to prevent hemorrhages due to portal hypertension.

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Consultations

Before any therapeutic decision, especially if major hepatectomy or liver transplantation is considered, carefully assess for distant metastasis (ie, brain, lung, bone localizations). Include appropriate morphologic examinations and consultations. Discuss the case with liver and infectious disease specialists, radiologists, and all involved surgeons.

Neurosurgery and thoracic surgery may be indicated if brain or lung metastasis is complicated and/or accessible to surgery. These decisions and procedures require appropriate consultations.

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Diet

Patients require no special diet, except those with chronic cholestasis.

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Activity

Activity modification is not indicated, but chronic inflammation and cytokine production usually result in fatigue, which typically limits activity and may greatly impair quality of life.

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Complications

Any type of complication that may be seen at presentation may also be observed after treatment initiation. The accepted time frame for late complications (especially regarding late biliary complications, which are most common) is 3 years after diagnosis and treatment initiation.

Other types of complications are directly associated with therapeutic procedures, as follows:

  • Complications of liver resection
  • Complications of palliative liver surgery: Iterative bile duct stenosis
  • Complications of anti-infective treatment with benzimidazoles (eg, hepatic toxicity, leucopenia, alopecia, abdominal discomfort, possibly weight gain)
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Prevention

Alveolar echinococcosis is a zoonosis; thus, prevention should be considered both directly for humans and indirectly for the animal hosts.

Prevention in humans

No known drug prophylaxis for echinococcosis exists.

Prevention is hampered by incomplete knowledge of the actual mode of contamination in most endemic areas, but basic advice is to avoid touching foxes and to avoid eating uncooked fruits or vegetables collected from fields.

A better approach to environmental infection pressure is now made available through new molecular tools. Real-time PCR techniques well adapted to the identification and quantification of E multilocularis in environmental samples, including soil samples, [25, 26] and combined tests that identify both the parasite and the species of the definitive host’s feces have been developed. [27] Further evaluation is currently performed at a large scale and confirms the presence of E multilocularis eggs in gardens and in zoos/wildlife parks. [28, 29, 30] Global comparison of specific markers, such as the EmsB microsatellite, is now facilitated on a worldwide scale through a common website/database for data collection and phylogenetic studies. [31]

A vaccine prepared using a recombinant antigen protein has been successfully used to prevent larval infection by E granulosus in sheep. [32] The potential efficacy of this vaccine, demonstrated in a murine experimental model of E multilocularis infection [33] is questionable in humans, but it may be considered in endemic areas. [34]

Prevention in animal hosts

Regularly treating dogs and baiting of foxes with praziquantel in areas of Europe with demonstrated E multilocularis infection of urban areas showed encouraging results. However, this strategy fails when the prevalence of fox infection in the surrounding countryside is high. [35, 36]

Repeated and prolonged treatment is required, leading to logistic and financial concerns.

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Long-Term Monitoring

Long-term monitoring (at least 10 years) is an essential component of the treatment plan for alveolar echinococcosis, even in patients who undergo radical surgery and receive appropriate 2-year albendazole therapy.

Long-term monitoring includes at least a yearly visit and, at the minimum, ultrasonography examination, blood count, transaminases and alkaline phosphatase measurements, and Em18 ELISA. Whenever available, FDG-PET and CT (with delayed acquisition of images) should be performed every 2 years. The decision to withdraw albendazole treatment should be made only if FDG-PET and Em18 serology results are negative.

Follow-up schedule

Because of the risk of recurrence, regular follow-up examinations are mandatory (eg, ultrasonographic examination, drug adverse effect monitoring), even after radical surgery.

Depending on the severity of the case, an experienced physician (with a permanent link to a reference center) must observe the patient every 3, 6, or 12 months. The WHO-Collaborating Center for the Prevention and Treatment of Human Echinococcosis and the WHO-Informal Working Group on Echinococcosis (in France) may be contacted at ccoms@chu-besancon.fr; the WHO-Collaborating Center for Prevention and Care Management of Echinococcosis (in western China) may be contacted at renyong_lin@sina.com

Drug availability and monitoring

Depending on the country, MBZ and/or ABZ at the recommended dosage may or may not be authorized or easily available. See regulations for availability.

In view of the large individual variations in the systemic availability of benzimidazole drugs, measure patients' plasma concentrations. If the techniques are available locally, measure concentrations at the beginning of treatment (after 4 wk of continuous treatment) and every 6 months during long-term treatment, especially in patients with cholestasis or hepatocellular disturbances.

Measuring MBZ and ABZ sulfoxide may be difficult because this test is performed only in highly specialized pharmacology laboratories; their list is available through ccoms@chu-besancon.fr. In western China/Central Asia, ANZ sulfoxide measurement is also available at the WHO-Collaborating Center for Prevention and Care Management of Echinococcosis (Jian Hua Wang: jhw716@163.com)

Decision to stop chemotherapy

After several years of treatment, if serology findings using very specific antigens (eg, Em2+ or, preferably, Em18) have become negative and CT scanning shows massive calcification of the lesions, the decision of drug withdrawal may be made. The final decision is based on the morpho-PET (PET-CT or PET-RMI) images; absence of any FDG uptake 3 hours after injection supports withdrawal. Careful follow-up is necessary because recurrence may occur despite apparently inactive lesions. Persistently negative PET findings should be confirmed 3 months after withdrawal, then yearly for 10 years.

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Further Inpatient Care

Follow the usual rules for postoperative management of liver surgery (or of any other indicated surgical or interventional radiology procedures).

If perendoscopic procedures are indicated, perform extensive lavage of the bile ducts and use systematic antibiotic treatment before and after procedure.

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Inpatient & Outpatient Medications

Prescription includes MBZ or ABZ at the recommended dosage and blood sampling at recommended intervals to monitor adverse effects.

In cases that involve bacterial or fungal superinfection, administer antimicrobial drugs according to the usual rules of treatment for cholangitis, liver abscess, or septicemia.

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Transfer

Transfer the patient to a hospital with expertise in major hepatic surgery and, preferably, to a reference center familiar with this rare disease. Any physician under the guidance of a reference center specialist may institute follow-up care. Information on specialized centers in endemic countries and their addresses/contacts may be obtained by contacting the WHO Collaborating Center in Besançon, France: ccoms@chu-fcomte.fr. 

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