Background: Echinococcosis also known as hydatid disease is a zoonotic parasitic disease caused by a tapeworm. It has a worldwide distribution. For long, it was thought to be a problem of the poorly sanitized “third world” and not given the importance it deserved. However, its occurrence in countries like Australia and New Zealand and recently in countries in Central Europe has meant that it is included in a WHO list of neglected diseases, has recently been the subject of extensive epidemiological studies, and has been the recipient of increased research funding. Summary: The diagnosis is still based on clinical presentation in an endemic area corroborated with typical findings on imaging which routinely include ultrasound and CT scan. Serological tests have been used in some centers to support the diagnosis. Treatment depends on the site of involvement and can vary from wait and watch to extensive radical surgical procedures. The common element of all treatments is the addition of albendazole which forms an essential cornerstone of all treatment protocols. Inspite having been used for a fairly long time, there is still no consensus on the dose, duration, and timing of therapy with albendazole. Key Message: Hydatid disease continues to be a significant global health problem inspite of a good understanding of its life cycle and rising standards of public sanitation. Though diagnosis is straightforward and not expensive, treatment can sometimes be complicated. The addition of albendazole to all treatment protocols is an important advance, but firm guidelines on duration of its use are still awaited.

Echinococcosis also known as hydatid disease has a worldwide distribution [1] (Fig. 1). Hydatid disease is a zoonotic parasitic disease caused by a small tapeworm of the genus Echinococcus. More than two dozen types and sub-types have been described. The clinically important ones are Echinococcus granulosus causing cystic echinococcosis (CE) and Echinococcus multilocularis causing alveolar echinococcosis. Research funding for hydatid disease has increased due to its inclusion in a WHO list of 17 neglected tropical diseases [2] and also due to the increasing frequency with which it is now being reported in the “developed” world including Central Europe.

Fig. 1.

Distribution of E. granulosus and CE worldwide (World Health Organization 2011).

Fig. 1.

Distribution of E. granulosus and CE worldwide (World Health Organization 2011).

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Data and Issue Guidelines

While guidelines on CE are now fairly comprehensive, the group met in October 2017 in Algiers to finalize recommendations for E. multilocularis and for preparing a technical manual on CE [3]. This review summarizes the current management options for liver hydatid cysts and briefly shares our experience of using these options for treating patients with liver hydatid disease in a tertiary care facility in northern India.

The adult worm inhabits the intestine of a canine species commonly the dog which is the definitive host [4] (Fig. 2). The gravid worm releases embryonated eggs in dog feces. These are ingested by the intermediate host, commonly sheep, swine, horses, camels, and men. Man is an accidental intermediate host as transmission to man is not conducive to the continuation of the species. The eggs hatch in the intestines of the intermediate host and release oncospheres which penetrate the host intestines to enter the portal circulation and travel to the liver. Once through the liver, oncospheres enter the general circulation and travel to other organs. The contaminated tissues of the intermediate host, mainly the sheep, are ingested by the dog, and the ingested protoscolices adhere to the mucosa in the dog intestine and develop into adult worms which reside in the intestine and release embryonated eggs in the dog feces, allowing the life cycle to continue.

Fig. 2.

Life cycle of Echinococcosis (World Health Organization) [4] (see text for details).

Fig. 2.

Life cycle of Echinococcosis (World Health Organization) [4] (see text for details).

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Echinococcus has a predilection for the liver. A large experience from India showed that the liver and lung were the common sites for developing hydatid cysts in 75% and 15%, respectively [5]. Here the cyst develops and grows, making its presence felt by the size of the cyst or by causing pressure effects on surrounding structures.

The compression of the liver due to the growing cyst and the inflammatory response elicited from the presence of the cyst result in the formation of the pericyst which is entirely host tissue entrapping within its biliary ducts which first stretch over the growing cyst and later become encased by it and sometimes fistulate through into the biliary ducts, setting up a cystobiliary communication. The tough fibrotic pericyst prevents complete collapse of the residual cystic cavity after therapeutic evacuation. Interestingly, the pericyst formation is seen only in the liver and spleen and does not form in other tissues like the lung and brain. The inner layer is the lamellar layer of the hydatid cyst proper [6] (Fig.3). On the inside, it is covered with the germinal layer, producing the daughter cysts which can get detached or burrow through the wall to fistulate into surrounding body structures. Separating the pericyst from the lamellar layer is a layer of loose areolar tissue. The lamellar layer is held against the pericyst by the pressure within the cyst which is around 35 mm of Hg. If the pressure is released by a leak or rupture or by therapeutic intervention, the lamellar layer readily separates from the pericyst and falls into the cyst cavity. The intracystic contents degenerate in older long-standing cysts to a pultaceous gelatinous amber-colored structure called the “matrix.” The appearance is often referred to as a pseudotumor and needs differentiation from a pyogenic abscess. Endocyst calcification when seen is indicative of a dead cyst. Pericyst calcification alone is commonly detected by imaging techniques in a third of cases and does not necessarily indicate a dead cyst [7].

Fig. 3.

Pathoanatomy of a hydatid cyst.

Fig. 3.

Pathoanatomy of a hydatid cyst.

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In our approach to the cyst, we need to confirm the diagnosis and exclude other cystic lesions of the liver. In endemic areas, an ultrasound examination of a liver cyst will be sufficient to clinch a diagnosis.

Liver hydatid cysts may present in three ways:

  • 1. Asymptomatic: these get picked up incidentally on imaging done for surveillance in endemic areas or during imaging for an unrelated indication.

  • 2. Uncomplicated cysts: presenting due to size and location.

  • 3. Complicated cysts: due to infection and or rupture into bile ducts, surrounding organs, or cavity.

A rupture into the peritoneal cavity can present with pain, shock, and features of anaphylaxis. In addition to rupture into the biliary system and peritoneal cavity, cysts can become infected and then behave like a liver abscess and need treatment accordingly. Pressure on the portal vein can cause features of extrahepatic portal vein obstruction with splenomegaly and enlarged collaterals and varices [8]. Though pressure on all hepatic veins at one time is unlikely, caval compression directly by a large cyst can cause features of IVC obstruction with dependent edema and dilated flank veins [9].

Serum Tests for Hydatid Disease

Serological tests for antibody detection and assay using ELISA are widely available, and even though sensitivity for liver hydatid is reported between 85 and 98%, the specificity is limited due to cross-reaction with presence of other parasites, cirrhosis, and even tumors [10]. Presently, there are no serological tests which can differentiate sub-species of Echinococcus. In a Swiss study, ELISA positivity in Echinococcus had a sensitivity of 81–97% for CE and >99.9% for AE. The specificity for the tests was in the same range of 92 and >99.9%, respectively [11]. The high sensitivity and specificity of ELISA in this European study is attributed to the fact that all cases had advanced disease. ELISA positivity increases with duration of the infestation and with age.

Imaging

Ultrasound provides a very effective means of diagnosing hydatid cysts. Gharbi et al. [12] proposed a classification system for hydatid cysts based on ultrasound findings alone, and this has been found to correlate well with CT-MR imaging [13, 14]. (Table 1; Fig. 4). Imaging with CT and MRI is needed to further define the location of the cyst for therapeutic planning as also to look for complications, the most important being the presence of cyst-biliary communication. WHO-IWGE has modified Gharbi’s original classification and proposed a classification which is used to guide treatment [3].

Table 1.

Hydatid cyst classification by ultrasound (World Health Organization – Informal Working Group on Echinococcus [WHO-IWGE])

Classification typeClassifying featuresStage
GharbiWHO-IWGE
CE-1 Univesicular fluid collection/simple cyst Active 
III CE-2 Multivesicular fluid collection with multiple daughter cysts or septae (honeycomb) Active 
II CE-3A Fluid collection with membrane detached (water lily sign) Transitional 
III CE-3B Daughter cysts in solid matrix Transitional 
IV CE-4 Cysts with heterogenous matrix, no daughter cysts Inactive/degenerative 
CE-5 Solid cystic wall Inactive/degenerative 
Classification typeClassifying featuresStage
GharbiWHO-IWGE
CE-1 Univesicular fluid collection/simple cyst Active 
III CE-2 Multivesicular fluid collection with multiple daughter cysts or septae (honeycomb) Active 
II CE-3A Fluid collection with membrane detached (water lily sign) Transitional 
III CE-3B Daughter cysts in solid matrix Transitional 
IV CE-4 Cysts with heterogenous matrix, no daughter cysts Inactive/degenerative 
CE-5 Solid cystic wall Inactive/degenerative 
Fig. 4.

Hydatid cyst classification (see text and Table 1 for details).

Fig. 4.

Hydatid cyst classification (see text and Table 1 for details).

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Current treatment options include one or more of the following modalities:

  • 1. Drug treatment

  • 2. Puncture aspiration injection reaspiration (PAIR)

  • 3. Surgery

  • 4. Wait and watch

Consensus on treatment of hydatid cyst is lacking due to the relatively low number of patients presenting to any given referral hospital with availability of all modalities required for managing hydatid disease [15] (Fig. 5).

Fig. 5.

Liver-tissue-preserving endocystectomy. First pivotal steps to prevent spillage and to secure decontamination. The cyst is decompressed via a 12-mm trocar followed by instillation of 20% saline solution, as depicted here, avoiding excess pressure within the cyst. The cloths positioned around the cyst are soaked with 20% saline to shield the abdominal cavity. (Dept. of Surgery, University Medical Center Rostock, Germany).

Fig. 5.

Liver-tissue-preserving endocystectomy. First pivotal steps to prevent spillage and to secure decontamination. The cyst is decompressed via a 12-mm trocar followed by instillation of 20% saline solution, as depicted here, avoiding excess pressure within the cyst. The cloths positioned around the cyst are soaked with 20% saline to shield the abdominal cavity. (Dept. of Surgery, University Medical Center Rostock, Germany).

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The benzimidazole drug albendazole is the current drug of choice for management of hydatid cyst. It is not recommended for primary treatment alone unless the patient is unwilling or unfit for surgery. The key issue in the use of albendazole is the intracystic concentration of albendazole. There is no correlation between plasma level and intracystic level of albendazole. Drug levels are found to be higher in smaller cysts and calcified cysts. Larger the cyst lower the drug level, possibly making the drug less efficacious in large cysts [16]. The addition of praziquantel does not increase intracystic albendazole levels. Drug treatment is currently recommended for small cysts CE-1 in a dose of 10–15 mg/kg in divided doses daily for 8–12 weeks. Drug bioavailability is increased by taking the drug with a fatty meal [17] and avoiding a high intragastric pH, e.g., due to use of proton pumps inhibitors while on albendazole therapy [18, 19]. Liposomal albendazole and nano-particulated albendazole hold the promise of increasing intracystic drug levels [20, 21]. Safety profile of the drug is good, and even prolonged use is free from serious side effects. The common side effects are transient increase in liver enzymes and leukopenia [22]. Complete hair loss is a very rare occurrence and fortunately reversible [22].

PAIR was first proposed by a Tunisian group [12]. Percutaneous drainage has been widely used for treatment of hepatic hydatid disease, and studies comparing results of percutaneous drainage with surgery have helped to identify a group of patients who are most suitable for PAIR [23, 24]. The WHO has a manual dedicated to PAIR which describes the procedure in great detail [25].

What is PAIR? PAIR is an acronym for Puncuture of cyst wall, Aspiration of contents, Instillation of scolicidal agent, Reaspiration of scolicidal agent.

Very simply, PAIR refers to image-guided, usually ultrasound-guided percutaneous drainage of the intra-abdominal hydatid cysts of the liver by a fine needle which is also used for injection of a scolicidal solution to kill live elements of the cyst. Large cysts more than 5 cm may require a drainage tube to be left in the cyst cavity, in which case the procedure is known as PAIR-D.

Indications for PAIR

  • • WHO cyst classification types CE-1, -2, and -3

  • • Multiple cysts if accessible to puncture

  • • Infected cysts

  • • Pregnant women and patients who are not fit for or refuse surgery

  • • Patients who recur after surgery or who do not respond to chemotherapy alone

Contraindications for PAIR

Non-co-operative patients, non-accessible cyst location, mature calcified cysts, cysts with biliary communication, and cysts opening into body cavities are considered unsuitable for PAIR.

Technique of PAIR

In addition to risks associated with needle puncture of the liver, the avoidance of spillage must be pointed out as specific challenge of the procedure. The critical point is the angle of puncture. Normal liver parenchyma must be present between the puncture point and the surface of the cyst to avoid leakage of cyst fluid and to prevent anaphylactic reactions and protoscolex dissemination in the abdominal cavity, resulting in uncontrollable disease. For instillation, the recommended scolicidal agent is 20% hypertonic saline, achieving at least 15% concentration within the cyst for a contact period of at least 20 min. Outcome of PAIR treatment in uncomplicated cysts types CE-1, -2, and -3 is similar to that of surgery [25].

Albendazole and PAIR

WHO recommends pre-PAIR treatment with albendazole for at least 4 h to 1 week and continuation of drug treatment for at least 1 month or more after the procedure [25]. The duration of treatment depends on the size of the cyst and continues till the cyst appears almost solid in follow-up ultrasound examinations. The optimum duration of treatment with albendazole has not yet been fully studied and may vary from a few weeks to several months.

Surgery still remains the treatment of choice for complicated cysts and was considered the only curative option for hepatic hydatid disease for many years. Its place in the management of hepatic hydatid disease is now better defined due to agreement on cyst classification, widespread availability of PAIR and a better understanding of the pharmacokinetics of albendazole and its importance as an adjunct to surgery [26].

Indication for Surgery

  • • Cyst classified as CE-2 and CE-3b with size >5–6 cm and any cyst with size >10 cms

  • • Complicated and recurrent cysts after previous surgery or PAIR

Aims of Surgery

These include total removal of live infected components, prevention of spillage, and management of residual cavity and cystobiliary communication.

Types of Surgery

Surgery for hydatid cyst may be “conservative” (i.e., parenchyma-preserving) or radical. Parenchym-preserving procedures include evacuation, deroofing of the cyst, and management of the residual cavity. Endocystectomy represents the basic procedure of preserving surgery which means leaving the pericyst intact and working within it. This is feasible for peripherally placed lesions and has one main challenge: avoiding the spillage of vital cyst content. We advocate the placement of a 12-mm trocar into the cyst after covering the surroundings with abdominal cloths that are soaked with a solution of 20% saline (Fig. 5). After inserting the trocar, the cyst is decompressed and filled with 20% saline without building up pressure to prevent drainage into the biliary system via inadvertent cystobiliary connections. This procedure is repeated twice for 10 min each. The cyst is unroofed, and endocystectomy is performed thereafter. The edge of the cyst is secured with a PDS 3/0 running suture to prevent biliary leakage.

High recurrence rate of 8–20% is a criticism of conservative surgery [27]. The requirement of perioperative albendazole has been quoted as a disadvantage of the conservative approach. However, in practice, almost all surgeons use perioperative albendazole whatever the type of surgery. The residual cavity after conservative surgery has been managed by marsupialization, capitonnage, simple drainage, or omental packing known as omentopexy. Omentopexy is associated with less biliary leak and infective complications [27].

Radical surgery involves liver resection. This may be a non-anatomical resection like cystopericystectomy or formal segmentectomy. With modern energy devices, cystopericystectomy can be quite safely performed without blood transfusion in most cases. Cystopericystectomy is of two types – with the cyst open when the content is aspirated prior to resection and closed when the resection is done without violating the contents. The advantages of radical surgery are a significant reduction of local recurrence, reduced incidence of biliary leaks, and no residual cavity to manage [28‒30].

Laparoscopic surgery for hydatid disease has been successfully applied to the management of hydatid cysts with results comparable to conventional surgery [31, 32]. Many innovative systems have been developed to prevent spillage in the open as well as laparoscopic procedures. Palanivelu et al. [31] have developed a novel system with double suction ports which allows spillage-free aspiration during minimally invasive surgery. They have reported impressive results using the same with no recurrences in 66 cases followed up for a mean of 5.8 years [32] (Fig. 6).

Fig. 6.

Palanivelu-Hydatid System allows for aspiration of cyst content during minimally invasive surgery [33].

Fig. 6.

Palanivelu-Hydatid System allows for aspiration of cyst content during minimally invasive surgery [33].

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Cystobiliary Communication

Management of cystobiliary communication is a challenge. 90% of the liver cysts are believed to leak into the biliary system [34]. Rupture into larger bile ducts is clinically significant, resulting in jaundice and cholangitis. It happens in 10–15% of all patients with hepatic hydatid cysts. Size of the cyst may predict cystobiliary communication. In a series of 24 patients with cystobiliary communication, 20 (83.3%) had a cyst size of more than 7.5 cm [35]. When dealing with a large cyst and features of possible biliary obstruction, good imaging with CT or MRI can pick up the cystobiliary communication. Daughter cysts in the bile duct can be cleared during ERCP and the CBD stented. Pre-op ERCP is essential in patients with a clinical suspicion of rupture or high probability of the same. It can help to confirm diagnosis of cystobiliary communication, clear the common bile duct of Hydatid “material,” and allow stenting of the CBD in preparation for surgery [36]. Generally, if cystobiliary communication is diagnosed, intraluminal decontamination of the hydatid cyst must be strictly avoided, regardless the applied technique. Hyperoncotic solutions would damage the biliary epithelium, leading to sclerosing cholangitis. For this reason, no excess pressure should be built up in any case during instillation, even if no cystobiliary communication is expected since it can exist inadvertently.

Intraoperative detection of the site of leak due to cystobiliary communications can be elusive. The aspiration of bile-tinged cyst fluid confirms communication. Diligent examination of the cyst wall will usually make the leak quite obvious. Intraoperative cholangiography with dye can aid in locating the site of leak. The fistula site is sutured with absorbable sutures, and the residual cyst cavity is managed with omentopexy and drainage. CBD stenting is done later, if required.

Cyst types CE-4 and -5 remain inactive and dormant for prolonged periods, sometimes indefinitely. These can be safely followed up by ultrasound examination. In these cases, intervention is only indicated when complications occur (e.g., pain).

In our own experience, 53 patients were seen with abdominal hydatid cysts over the last 13 years. They were distributed as follows:

  • • Liver – 45

  • • Spleen – 04

  • • Peritoneal – 03

  • • Retroperitoneal – 01

Eighteen of these patients had a previous procedure, with 7 having had more than one procedure. Cystobiliary communication was encountered in 13 patients. All required ERCP and CBD stenting at different times in their management. Surgery remained the preferred modality of treatment with 16 patients having conservative surgery with the majority 15/16 having a laparoscopic procedure. 21 patients had a radical procedure in the form of a cystopericystectomy. Eight patients had a PAIR procedure. The preferred scolicidal agent is 20% hypertonic saline. 45/53 patients had already been on albendazole for periods ranging from 3 weeks to 3 years before coming to our center. We prefer pre-op albendazole for at least 1 week or longer which can be started even as patients take time to make up their minds for surgery. Post-surgery albendazole is continued for 3 months for simple cysts and 6 months for complex cysts and for situations where the operating surgeon feels that “uncontrolled spillage” cannot be excluded.

Hydatid disease is an important “neglected” global parasitic disease. The liver is the commonest site of predilection. An ideal drug with predictable pharmacokinetics is elusive, but nano-particulated liposomal albendazole holds immense promise. PAIR is an adequate treatment for selected patients and a backup procedure if access to surgery is limited. Endocystectomy should be performed in superficial cysts. Radical surgery under the cover of albendazole is associated with the least recurrence. Results of laparoscopic surgery for liver hydatid cysts are comparable with those of conventional surgery.

Perhaps the most significant change in our practice and approach to hydatid disease is that no single modality of treatment on its own can claim to be the best treatment option, and to that extent, controlled trials pitting one modality against another may actually be reluctant. The current management of liver hydatid disease is multimodal, combining albendazole with PAIR and/or surgery.

The article is based on a presentation made at the SSAT International symposium during DDW 2017 at Chicago, USA.

The authors have no conflicts of interest to declare.

No funding sources were required for this review and no sources to declare.

The review was conceived and presented at DDW by Drs. V.P. Bhalla and Ernst Klar. Both contributed to the writing and proofreading of the final document. Dr. Souvik Paul did the reference checks, organized the references, and helped with final compilation of data and the writing of the article.

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