Hydatid disease of the liver

Introduction

Hydatid disease, or cystic echinococcosis (CE), is a worldwide parasitic zoonosis, caused by the larval stages of the metacestode Echinococcus granulosus . Three more species of Echinococcus of public health concern have been recognized: Echinococcus multilocularis, causing alveolar echinococcosis, which will be discussed in the next section of this chapter; and Echinococcus vogeli and Echinococcus oligarthus, both causing polycystic echinococcosis. Hydatid disease is the most prevalent and accounts for more than 95% of the estimated 2 to 3 million cases of echinococcosis in the world. The definitive hosts of this parasite are usually members of the canid family, such as dogs, which develop the adult worm in the gut following ingestion of the larvae, present in the tissues of the intermediate hosts, usually sheep. When infected, humans develop visceral hydatid cysts, which are fluid-filled structures limited by a parasite-derived membrane that contain a germinal epithelium. Hydatid cysts usually affect the liver (50%–70%), followed by the lungs (20%–30%) and less frequently the spleen, kidney, heart, bones, central nervous system, and other organs. Cysts can remain asymptomatic for years, but as they increase in size symptoms and complications can arise. Up to a third of affected patients can develop complications such as secondary infection of the cyst cavity, biliary fistula, and rupture into the peritoneal and pleural cavity. Therefore it is important to strictly abide by treatment guidelines to decrease the rate of possible complications. The modern treatment of liver hydatid cyst (LHC) varies from surgical intervention to percutaneous drainage or medical therapy. Surgery remains the only definitive treatment for large, active, symptomatic, or complicated hydatid cysts. Surgical management has evolved from open surgery to an increase in the application of the laparoscopic approach. Percutaneous techniques can be a good alternative to surgery in selected patients with uncomplicated cysts or high-risk medical status performance. Medical therapy is used for inoperable cases, for disseminated systemic disease, or as a complementary therapeutic option in percutaneous or surgical approaches to prevent postoperative recurrence.

This zoonosis represents a major public and economic health problem due to the health costs generated for patient care; those affected by the disease may require prolonged hospitalizations with loss of quality of life, working days, and uprooting as they must move to urban centers for definitive care. Also, significant economic losses happen due to seized viscera or reduced production of wool or meat in infected animals. Prevention is the most effective and efficient way to control hydatid disease, and the development of health education and promotion activities in the community is essential.

Echinococcus granulosus

Echinococcus granulosus (EG), from a taxonomic perspective, is currently considered a multispecies complex referred to as EG sensu lato (s.l.). The species identified in this complex are EG sensu stricto (genotypes G1/G2/G3), Echinococcus equinus (genotype G4), Echinococcus ortleppi (genotype G5), Echinococcus canadensis (genotypes G6/G7/G8/G9/G10), and Echinococcus felidis (lion strain). Genotype 1 (G1) is the most widely distributed species at the global level and accounts for approximately 80% of human cases of hydatid disease. Genotypes G2, G5, G6, G7, G8, and G9 have also been documented to infect humans.

The adult worm of EG, 3 to 6 mm long, consists of scolex (head) bearing a rostellum with a double row of numerous hooks, four prominent suckers, a short neck region, and the strobilae (body) with three proglottids—usually one immature, one mature, and one gravid. The last is the largest and bears the mature eggs. On maturity each gravid proglottid can contain an average of 587 fertile eggs, which are eliminated with the dog’s feces. A complete life cycle of the EG requires two hosts, a carnivore and a herbivore, and takes 32 to 80 days ( Fig. 72.1 ). The adult tapeworm lives in the intestine of the dog, which is the most common definitive host. Gravid proglottids release microscopic ovoid eggs (30–40 μm) that are passed in the feces and are immediately infectious. Echinococcus eggs contain a hexacanth embryo (oncosphere or first larval stage) surrounded by a thick keratinized wall and are extremely resistant, enabling them to withstand a wide range of environmental temperatures for many months. After ingestion by a suitable intermediate host (sheep, goat, swine, cattle, horse, camel), eggs hatch in the small intestine and release six-hooked oncospheres that penetrate the intestinal wall and migrate through the circulatory system into various organs, especially the liver and lungs. In these organs, the oncosphere develops into a thick-walled hydatid cyst that enlarges gradually, producing protoscolices and daughter cysts that fill the cyst interior. The definitive host becomes infected by ingesting the cyst-containing organs of the infected intermediate host. After ingestion, the protoscolices evaginate, attach to the intestinal mucosa, and develop into adult stages. Humans are aberrant intermediate hosts; they become infected by ingesting eggs either from direct contact with a contaminated dog or by ingesting contaminated water, food, or soil. Oncospheres are released in the intestine, and hydatid cysts develop in a variety of organs. These cysts grow at a rate of 1 to 5 cm/year and may remain undetected for years, so they can reach very large sizes before becoming clinically evident. If cysts rupture, the liberated protoscolices may create secondary cysts in other sites within the body (secondary echinococcosis).

Hydatid cysts are usually unilocular and can range anywhere from 1 to 20 cm in diameter. Cystic growth is expansive by concentric enlargement. They tend to affect the right lobe more frequently than the left lobe due to the nature of the portal blood flow. There are three layers in a hydatid cyst: pericyst, ectocyst, and endocyst ( Fig. 72.2 ). The pericyst or adventitial layer is the outermost layer, which is entirely made up of host tissues in response to the expanding parasite. The host cellular inflammatory reaction is initiated in the early stages of postoncospheral development, and the initial intensity of this reaction varies between hosts and governs the fate of the developing metacestode. If too intense it will cause the degeneration and eventual death of the parasite, whereas in suitable intermediate hosts the initial reaction resolves, leaving a fibrous capsule. With time, the adventitial layer may calcify, either partially or totally. The ectocyst is the middle acellular layer, which is the elastic, laminated membrane resembling egg white that protects the cyst. It provides a physiochemical barrier with apparent multifunctionality, allows passage of nutrients, and is easily separable from the adventitia. Finally, the endocyst or the germinal epithelium is the innermost layer, which is the only living component, being responsible for the formation of the other layers as well as the hydatid fluid and brood capsules (see Fig. 72.2 ). Undifferentiated cells in the germinal layer produce invaginations into the cyst cavity, forming the brood capsules. It surrounds a cavity filled with hydatid fluid. Hydatid fluid is clear and contains electrolytes and proteins. Cyst fluid is clear or pale yellow, has a neutral pH, and contains sodium chloride, proteins, glucose, ions, lipids, and polysaccharides. The fluid is antigenic and may also contain protoscolices and hooklets. When vesicles rupture within the cyst, protoscolices pass into the cyst fluid and form a white sediment known as hydatid sand. Daughter cysts have a structure similar to the mother cysts, including a laminated and germinative membrane, cyst fluid, brood capsules, and protoscolices. The only difference is the absence of an adventitial layer.

Epidemiology

EG sensu lato has a worldwide geographic distribution with endemic foci present on every inhabited continent ( Fig. 72.3 ). Some areas, such as Central Asia, present a high prevalence of both EG and Echinococcus multilocularis. In regions where CE is endemic, incidence rates in humans can exceed 50 per 100,000 person-years. The global burden of hydatid disease is estimated at 1 million at any one time. The greatest prevalence of hydatid disease in human and animal hosts is found in countries of the temperate zones, including several parts of Eurasia (the Mediterranean regions, southern and central parts of Russia, central Asia, China), Australia, some parts of the Americas (especially South America), and north and east Africa. The distinct genetic types of EG, based on morphology, host specificity, and molecular characteristics, include two sheep strains (G1 and G2), two bovid strains (G3 and G5), a horse strain (G4), a camelid strain (G6), a pig strain (G7), and a cervid strain (G8). A ninth genotype (G9) has been described in swine in Poland and a tenth strain (G10) in reindeer in Eurasia. The most frequent strain associated with human hydatid disease appears to be the common sheep strain (G1). This strain appears to be widely distributed in all continents ( Fig. 72.4 ). Highest rates of infection are recorded in communities involved in extensive sheep farming, and epidemiologic studies suggest that this genetic variant is the principal strain infecting humans. In Europe, EG is present in most countries. Annual incidence rates of 4 to 8 per 10 ⁵ population have been reported in the Mediterranean regions. ^, Fourteen countries reported 412 confirmed cases of CE in 2017. This was an 11% decrease compared with 2016, when 465 confirmed cases were reported. Bulgaria accounted for 53% of the cases in 2017 and Germany for 18%. The majority (35%) of CE cases were observed in the age group 25 to 44 years, followed by the age group 45 to 64 years (25%). Increasing country-specific trends were observed in Austria, Germany, Lithuania, and Poland, and decreasing trends in Slovakia and Spain. Hydatid disease is a serious health problem in Turkey with 5.7 per 10 ⁵ population and a high prevalence in regions of the Anatolian peninsula. In central Asia and western China at least 270 million people (58% of the total population) are at risk for hydatid disease. The infection rate of females in China has been assessed to be considerable higher than that of males because of their role in the home activities, including feeding dogs, collecting yak dung for fuel, and milking livestock. This nomadic or seminomadic pastoral lifestyle is one of the most important risk factors for hydatid disease in China. In Australia, where EG established viable reservoirs in native wallabies and kangaroos, the highest rates recorded have been in rural northeast and southeast New South Wales with 23.5 per 10 ⁵ population. In South America, the disease is endemic or hyperendemic in Argentina, Uruguay, Chile, Southern Brazil, and mountain regions of Perú and Bolivia. In a 5-year period, 29,556 cases of CE were reported to official authorities in the five countries belonging to the Sub-Regional Initiative for the control of EG (Argentina, Brazil, Chile, Peru, and Uruguay), with an incidence rate range between 0.012 and 13 per 100,000 inhabitants according to the country. Argentina shows three high-incidence areas: the Patagonia region, in the south of the country (where the provinces of Neuquén and Chubut show the highest national rates), the Northwest region (including the provinces of Catamarca, Santiago del Estero, and Salta), and the province of Entre Ríos in the East. Neuquén is one of the provinces with higher hydatid disease endemicity in Argentina, despite the fact that provincial sanitary authorities have carried out a control program of EG since 1970; the mean annual incidence of human EG in Neuquén is 8.9 per 10 ⁵ inhabitants. In selected areas of other South American countries, hydatid disease has been recorded as 6 to 20 per 10 ⁵ , such as in the south of Chile. The global burden of hydatid disease has been calculated to be of approximately 1 to 3 million disability-adjusted life years (DALYs) annually. In addition, the economic burden of this disease to the global livestock industry has been estimated at over $3 billion per annum. Despite the substantial socioeconomic impact, echinococcosis remains a neglected zoonosis in certain countries. A study performed in Salamanca Province, Spain, demonstrated a diminished incidence of hydatid disease in recent years, although active transmission remains in pediatric and young patients. Continuous education and training for the relevant health professionals is still needed because hydatid disease is endemic in many countries.

Complications

The natural history of hydatid cyst can be divided into two phases. In the first phase of cyst growth, rupture can occur when the pressure of the hydatid liquid becomes greater than the resistance of the hydatid wall (pericyst). The second phase is of ageing and progressive involution as a consequence of the overproduction of scolices and daughter cysts. During this phase the hydatid cyst will be full of scolices and membranes that replace the hydatid liquid, and calcifications occur in the pericyst. Hydatid cyst in the liver may cause symptoms resulting from compression, distortion of neighboring structures or viscera, infection, and erosion into the bile duct, the pleural space, or the peritoneal cavity. Less frequently the cyst may communicate with the digestive tract and the bronchial tree. Complications are usually observed in one third of patients with hydatid disease of the liver (HDL).

Compressive effects

Liver hydatid cyst (LHC) growth may lead to significant mass effect to adjacent structures, including biliary tree, portal vein, hepatic veins, right diaphragm, stomach, and kidney. Enlargement of the cyst tends to occur toward the surface of the liver and is commonly seen in the presence of atrophied lobes or segments containing hydatid cysts with enlargement of the residual hepatic parenchyma due to compensatory regeneration ( Fig. 72.5 ). Depending on the location, large cysts can cause compression of the bile ducts and obstructive jaundice ( Fig. 72.6 ). Compression and displacement of hepatic veins and inferior vena cava (IVC) may lead to secondary Budd-Chiari syndrome (see Chapter 86 ). Clinical manifestations include abdominal pain, jaundice, and swelling of the lower limbs. Ascites and venous thrombosis may also develop in these patients. Portal vein obstruction is a rare complication, more commonly reported in hydatid cysts located around the hilum; it is generated by a decreased portal vein inflow and thrombosis with cavernous transformation and is commonly associated with presinusoidal portal hypertension.

Cyst rupture

Intrabiliary rupture

Cistobiliary communication is the most common complication of HDL and one of the most serious, occurring in up to 42% of patients in some series. Two theories have been postulated about its pathogenesis: the first asserts that the compression of the LHC on the wall of the bile duct causes progressive necrosis and finally a communication between the cysts and the biliary tree; the second hypothesis states that after the trapping of small biliary radicals in the pericystic wall, high intracystic pressure (35 cm H ₂ O) causes atrophy first and then subsequently the rupture of biliary radicals. ^, It has been reported that up to 90% of the liver hydatid cysts have some kind of communication during their evolution. Clinical manifestations depend mainly on the size of the biliocystic communication. Minor communications (<5 mm) lead to cystic fluid drainage, whereas major ruptures (3%–17%) allow the passage of the cyst contents (hydatid membrane and daughter cysts) into the bile duct. The classic triad of biliary rupture in cystic hydatid disease (biliary colic, jaundice, and urticaria), eventually associated with fever (in case of cholangitis), is more frequent in patients with major communications ( Fig. 72.7 ). In cases of intrabiliary rupture smaller than 5 mm, it is exceptional to find hydatid material in the bile duct. In some patients, jaundice can be temporarily relieved following biliary communication due to reduction of intracystic pressure. Migration of daughter cysts through the biliocystic communication can lead to a secondary obstruction at the level of the duodenal papilla. Minor leaks of the cyst can produce flushing and urticaria, and major rupture can lead to potentially fatal anaphylactic reaction.

Communication between the cysts and the biliary tree occurs more frequently in those cysts located in the center of the liver, near the hilum, most commonly in the right hemiliver (see Fig. 72.7 ). From 114 cases of cystobiliary ruptures reported in three studies, 65% were located in the right hemiliver, 21% in the left hemiliver, and 14% presented a bilateral distribution. ^{, ,} Because cystobiliary rupture is a major risk factor for morbidity, preoperative and intraoperative identification of predictive factors is a relevant issue. ^, Size of the cyst has always been reported as an important predictor for the presence of cystobiliary communications. A cutoff value in size from 7.5 cm to 14.5 cm was demonstrated in different studies, but the most commonly reported was 10 cm. ^{, , ,} Other predictors described are a fibrotic or calcified pericystic wall, the number of cysts, cyst Gharbi type IV, and preoperative laboratory findings such as leukocytosis, eosinophilia, hyperbilirubinemia, and elevated alkaline phosphatase (ALP) and gamma glutamyl transpeptidase (GGT). ^{, , , ,}

Peritoneal rupture

Intraperitoneal rupture of a hydatid cyst may result from trauma or spontaneously when the intracystic pressure increases more than 50 cm H ₂ O. It is the third most common complication (1%–16%) after intrabiliary rupture and allergic reactions. The main risk factors predisposing to peritoneal rupture include young age, cyst diameter greater than 10 cm, and superficial cyst location. Young age is a risk factor because of the greater frequency of traumatic events in this population. Clinical signs and symptoms of intraperitoneal cyst ruptures may vary widely among patients. The most frequent symptoms are mild or severe abdominal pain, nausea, vomiting, and some allergic reactions that span a wide range. Antigenic fluid released into the peritoneal cavity and absorbed into the circulation is the cause of the acute allergic manifestations. If the content of the rupture is purulent or associated with the biliary tract, it may cause peritoneal irritation, and acute abdominal pain may occur. ^, Approximately 16.7% to 25% of patients with hydatid cyst rupture develop minor allergic reactions, such as urticaria and macular eruption, and 1% to 12.5% of patients develop more severe allergic reactions such as peripheral edema, syncope, or anaphylaxis. If the rupture is insidious, the release of brood capsules, scolices, and even daughter cysts from a ruptured hydatid cyst into the peritoneal cavity leads to multiple cysts in the peritoneal cavity. This phenomenon is called secondary echinococcosis .

Intrathoracic rupture

LHC located at the dome of the liver can grow and erode through the diaphragm to involve the thoracic cavity. Intrathoracic rupture is a serious complication that can damage the pleura, pulmonary parenchyma, and bronchi. Its frequency appears to decline from 16% to 2.5% of the reported cases. Intrathoracic evolution of a hydatid cyst depends on several factors: the intimate contact of the hepatic dome with the diaphragm; the thoracoabdominal pressure gradient, which tends to aspirate the contents of the liver cyst toward the thoracic cavity; the erosion of the diaphragm by ischemia-necrosis caused by eventual inflammation and superinfection of the cyst; and the corrosion of all tissues in contact with the bile ( Fig. 72.8 ). The cyst, after having passed through the diaphragm, can be fistulized in the bronchi, generally of the lower and/or middle lobe. Initially, a hydatid pneumonia is generated that is followed by an intraparenchymal cavity where bronchi will eventually become fistulized constituting a biliobronchial fistula, the ultimate stage of this severe complication. The clinical presentation is predominantly pulmonary (cough, expectoration, and dyspnea) with abdominal symptoms being less frequent. Hemoptysis, hydatid vomica, and bilioptysis are clinical manifestations of the biliobronchial fistulization. Bilioptysis, a pathognomonic sign, is clinically evident in 28.6% to 40.6% of the cases.

Cutaneous fistulization and other complications

Spontaneous cyst-cutaneous fistula is an extremely rare complication of LHC, usually occurring silently, in elderly people. Spontaneous cyst rupture in the gastrointestinal tract also is infrequent, in only 0.5%; patients can present with hydatidemesis (hydatid cysts and membranes in the vomitus) and/or hydatidenteria (passage of hydatid membranes in the stools).

Exceptionally, a subacute chronic fistula may be created between the cyst and the IVC, with transit of daughter cyst or membranes into the bloodstream and then to the right atrium, causing a pulmonary embolism. The most severe complication of the cysto-venous communication is acute exsanguinating hemorrhage or anaphylactic shock, which may have a high mortality. The fact that the intracystic pressure is higher than the central venous pressure may facilitate the passage of material into the IVC.

Diagnosis

Humans are usually asymptomatic for an infection with EG for a long time. The growth of the cyst in the liver is variable, ranging from 1 to 5 mm in diameter per year. Most primary infections consist of a single cyst, but up to 20% to 40% of infected people have multiple cysts. The symptoms depend not only on the size and number of cysts, but also on the mass effect within the organ and on neighboring structures. HDL diagnosis is based on a combination of clinical findings, imaging techniques, and serology, usually in conjunction with a history of exposure or immigration from an endemic area. Proof of the presence of protoscolices may be given by microscopic examination of the fluid and histology. False-positive reactions may occur in persons with other tapeworm infections, cancer, or chronic immune disorders. Whether the patient has detectable antibodies depends on the physical location, integrity, and viability of the cyst. Patients with senescent, calcified, or dead cysts usually are seronegative.

The introduction of ultrasound for the diagnosis of human abdominal echinococcosis in the early 1970s was of special relevance for mass screening of populations. Mass screening has proven a reliable and relatively cheap method for demonstrating the true extent of human hydatid disease. Ultrasound examination is the basis of hydatid cyst diagnosis in abdominal locations, at both the individual and population level. In 1995, the World Health Organization–Informal Working Group on Echinococcosis (WHO-IWGE) developed a standardized classification that could be applied in all settings to replace the plethora of previous classifications and allow a natural grouping of six cyst types into three relevant groups (active, transition, inactive). An expert consensus on the clinical management of patients with CE established that the diagnosis may be defined according to three situations:

• Possible case: Any patient with a clinical or epidemiologic history, and imaging findings or serology positive for CE.

• Probable case: Any patient with the combination of clinical history, epidemiologic history, imaging findings, and serology positive for CE on two tests.

• Confirmed case: The above, plus either (1) demonstration of protoscolices or their components, using direct microscopy or molecular biology, in the cyst contents aspirated by percutaneous puncture or at surgery, or (2) changes in ultrasound appearance.

In most cases, the diagnosis is incidental, when ultrasonography or a computed tomography (CT) scan is indicated for investigation of other pathology or in patients with abdominal pain or anomalies of liver blood tests. The most common symptom, when it occurs, is right upper quadrant or epigastric pain, and the most common findings on examination are an enlarged liver and a palpable mass. Pressure effects are initially vague and may include nonspecific pain, cough, low-grade fever, and the sensation of abdominal fullness. As the mass grows, the symptoms become more specific because the mass impinges on or obstructs specific organs.