Current considerations for the management of liver echinococcosis

Abstract

Echinococcosis or hydatid disease is induced mainly by Echinococcus granulosus and occasionally by Echinococcus multilocularis (alveolaris) and affects the liver predominantly. Hepatic alveolar echinococcosis is similar to carcinoma in appearance, and without treatment, it can lead to death. Diagnosis is based on current imaging modalities. Surgical management is the cornerstone of treatment. Complete removal of the cyst (total pericystectomy or hepatectomy) ensures a permanent cure and should be the first-choice treatment for cystic disease. Cyst evacuation, partial cystectomy, and drainage or omentoplasty, may be alternative choices in difficult cases. Albendazole, mebendazole and praziquantel are options for treating small cysts and preventing recurrence after surgery. Despite the efforts, alveolar echinococcus is not usually amenable to surgical management, except in the early stage, which is less common, and management by albendazole is indicated. However, there are few recent reports of major operations (ex-vivo hepatectomy, autotransplantation and vascular reconstruction) in advanced stages.

Key Words: Hepatic echinococcosis; Hydatid disease; Echinococcus granulosus; Echinococcus alveolaris; Hepatectomy for parasite diseases; Pericystectomy

Core Tip: The most common cystic hepatic echinococcosis has a chronic course. Proper elective surgical management or emergency complications is mandatory to ensure good outcomes and a permanent cure. Attention must be given to the early diagnosis of alveolar echinococcosis as surgery can be successful at the initial stage. Otherwise, albendazole treatment is indicated in the final stage.

TO THE EDITOR

We read the paper by Tao et al[1] with great interest, and we would like to congratulate the authors for their excellent comprehensive work that reports precisely the role of ultrasonography as the first step in diagnosing liver echinococcus cysts.

Echinococcosis, otherwise known as hydatid disease, is a zoonotic disease that in the vast majority of individuals (95%) is induced by the tapeworm Echinococcus granulosus, which mainly parasitizes the gut of dogs, but in some instances, can also be caused by the tapeworm Echinococcus alveolaris (multilocularis), which is found mainly in the gut of foxes. Humans, sheep, cattle or pigs (intermediate hosts) are infected by the eggs of the parasite via food or water contaminated by the stool of dogs, wolves or foxes (the main hosts). The main hosts are infected by consuming the livers of the intermediate host containing echinococcus cysts[2-4].

Despite progress in reducing its incidence by improving sanitary conditions to stop the echinococcus cycle, it is still endemic in some countries (e.g., in the Mediterranean, Middle East, South America, Oceania, Africa, and Southeast Asia). Necessary preventive measures include thorough washing of fruits, adequate boiling of greens and vegetables, slaughter of animals in modern organized slaughterhouses and a sanitary burial of infected animals and their entrails. The liver is affected in most cases (70%-80%). The cysts are usually solitary (80%) and affect the right lobe. Other less common sites include the lungs (15%), spleen, kidneys, brain and other unusual locations in the body[3-5].

Typically, Echinococcus granulosus infection progresses through a long, usually asymptomatic course, and the cyst is discovered incidentally[6,7]; however, complications can sometimes occur as an emergency setting[8]. The most common complication is rupture into the biliary tree, which manifests as acute cholangitis[6], followed by rupture into the peritoneal cavity or occasionally the thoracic cavity, which manifest as anaphylactic shock[9]. Another complication is echinococcus cyst suppuration and abscess formation, which manifests as sepsis[10].

Alveolar echinococcus is an unusual infection that predominates in northern and central Europe, mainly in Switzerland, Russia, China, Alaska, Canada, and Japan, and without treatment, it can lead to portal hypertension, liver cirrhosis and ultimately, the death; there are reported instances of it being misdiagnosed as hepatocellular carcinoma[11-14]. When alveolar hepatic echinococcosis is accompanied by lymph node metastasis (8.5%), hepatectomy with lymph node clearance will be required if possible[15].

The following methods are used for diagnosis and follow-up: Ultrasound (US), with a diagnostic accuracy of up to 90%[11,16,17]; intraoperative US[18]; computed tomography (CT), with high sensitivity (94%) and specificity above 95%[19,20]; and magnetic resonance imaging (MRI)/cholangiopancreatography, with high sensitivity (96%) and specificity (98%)[17]. In ambitious cases, serum specific anti-echinococcal antibodies, i.e., IgG and IgM, may be valuable. US is the first step in detecting the disease in clinical practice[1]. Multidetector CT is the best tool for venous invasion assessment in alveolar echinococcus, which is common, as well as for assessing bile duct invasion[21]. MRI is used to evaluate the detailed characteristics and appearance of hydatid cysts, as well as any communication of the cyst with the biliary tree, which is a prerequisite for developing an operative plan[17]. US, CT or MRI may be used to evaluate the imaging characteristics of alveolar echinococcosis, contributing to the diagnosis, staging and follow-up; in addition, these methods can provide guidance for percutaneous palliative interventions in inoperable cases[22].

In biliary rupture, emergency endoscopic retrograde cholangiopancreatography with sphincterotomy and bile duct clearance is necessary[23,24]. Additionally, ERCP is valuable in the diagnosis and management of postoperative biliary fistulas, including occult[25,26] and bile leaks[24,27].

Management is stratified on the basis of the etiological agent (E. granulosus vs E. multilocularis), and the options include surgery, percutaneous methods and conservative oral drug therapy (albendazole, mebendazole and praziquantel). The World Health Organization classification may be useful for choosing the best treatment and follow-up methods[2,14,28]. Surgical resection may provide permanent treatment and is the most preferable option worldwide, whereas the use of interventional percutaneous methods is limited since they are accompanied by more complications and recurrences than excision surgery is. However, these methods are a good alternative choice for high-risk patients who are not amenable to surgery[2,14].

Surgery is the cornerstone of any therapeutic effort in cystic echinococcosis, particularly in solitary large cysts[3,17,29,30], even in the elderly[31]. Operative management concerns include the need for more complicated radical operations preferably, such as total pericystectomy[32-34] and hepatectomy[4,33,35,36], or the need for simpler, classical operations, e.g., cyst evacuation, partial cystectomy, and drainage or omentoplasty[6,17,33]. Intact cyst excision, despite the difficulty of the procedure, ensures a permanent cure and preservation of the hepatic parenchyma along with the avoidance of residual cavity complications; thus, it should be the first choice[32]. Laparoscopic or robotic surgery has gained popularity in recent years because of the advantages of minimally invasive surgery[6,7,33,37,38]. The use of indocyanine green fluorescence ensures better robotic imaging[39].

Percutaneous methods, including the puncture, aspiration, injection, reaspiration (PAIR) method combined with intracystic scolicocidal agent injection of alcohol or hypertonic saline[6,32,37,40,41] of equivalent efficacy[42] and its modification (Örmeci technique) by injection of alcohol and polidocanol[43], have been used as an alternative to surgery for cystic echinococcosis. Percutaneous drainage in combination with oral albendazole and praziquantel has been proposed to avoid PAIR-related toxic alcohol cholangitis if an occult cysto-biliary fistula exists or if life-threatening hypernatremia from hypertonic saline use occurs[44]. The complications of PAIR include cyst rupture, anaphylactic reactions, recurrence[6,32,40,43], toxic cholangitis, life-threatening hypernatremia[44], and residual cavity[37] or abscess formation[41]. Standard catheterization is recommended for treating cysto-biliary fistulas or avoiding abscess formation[41]. The recurrence rate was reported to be between 4.5%[40] and 20%[32]. The complication rate was reported to be 19.5% for ethanol injection and 13.5% for hypertonic saline injection[42].

Hepatectomy is the main management method for early-stage alveolar echinococcosis. Surgical resection, preferably in combination with the newest drug therapy, albendazole, or the older drug therapy, mebendazole, is recommended, but a disadvantage of drug therapy is hepatotoxicity[11,12]. Unfortunately, the disease is usually diagnosed at a late stage in patients with final portal hypertension and cirrhosis; thus, therapeutic excision is not possible[11]. However, for advanced-stage liver alveolar echinococcosis, hepatectomy accompanied by two-step vascular exclusion and in situ hypothermic portal perfusion has recently been performed in some very difficult cases. Although this major operation includes resection and reconstruction of the portal vein, inferior vena cava and hepatic veins, it has been proposed to be safe and effective[45]. Similarly, ex vivo hepatectomy and autotransplantation have recently been performed[46,47] in combination with inferior vena cava reconstruction[48].

Microwave ablation under US guidance has been used recently with promising results for the management of alveolar echinococcosis in some difficult cases[49] or in early-stage patients in combination with albendazole[50] as an alternative to surgery.

There are new drugs that can be combined with albendazole for treating alveolar echinococcosis, i.e., inhibitors of leucine aminopeptidase (ubenimex) antibiotics (clarithromycin, intraconazole, amphotericin b), immunosuppressants (interferon, cyclosporine), antineoplastics (imatinib, 5-fluorouracil, bortezomib, paclitaxel, tamoxifen) and antiangiogenic factors (sorafenib, anacardic acid), all of which have been tested in in vitro studies, with limited data from clinical trials but promising results from preliminary research[11].

Albendazole, which has almost completely replaced mebendazole, is recommended for patients with small cysts (less than 5 cm in size) or multiple cysts but without calcification. Treatment with albendazole prevents the need for surgical intervention as well as recurrence after surgery. It is required in the management of most cases of alveolar echinococcosis[4]. However, prolonged drug use is related to hepatotoxicity and bone marrow suppression[11].

Percutaneous drainage and oral albendazole may improve the quality of life in patients with alveolar echinococcosis who are not amenable to surgery[51]. The dose of albendazole is 10 mg/kg body weight/day per oral. The scheme usually includes one 400 mg tablet twice daily for a period of four weeks, followed by a two-week break, and then this cycle is repeated until 3 to 6 cycles are completed[52]. The addition of a single dose of praziquantel at 40 mg/kg body weight/day per oral twice a week for 4 weeks, followed by a break and then restarting, similar to the protocol for albendazole, increases the therapeutic efficacy of albendazole[28]. Liver function tests and blood white cell count monitoring are necessary during therapy to avoid potential toxicity[11].

In conclusion, surgery is the main management option for hepatic echinococcosis. Radical operations such as total pericystectomy or hepatectomy offer a permanent cure and should be the first choice for the most common type of cystic echinococcosis. Hepatectomy is recommended for early-stage alveolar disease, but it has also been attempted recently for advanced-stage alveolar disease. Albendazole has an important role in conservative management.