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клинические
A RARE PARASITIC DISEASE OF THE LIVER — ALVEOLAR ECHINOCOCCOSIS
Tomás Kupka1, Peter Bala1, Lubomíra Hozáková2, Jaroslav Havelka3, Martina Bojková1, Bohdana Bregová1, Arnost Martínek1, Petr Díte1 University Hospital Ostrava
1 Clinic of Internal Medicine of the Faculty of Medicine of Ostrava University and University Hospital of Ostrava, Head Physician doc. MUDr. Arnost Martínek, CSc
2 Clinic of Infectious Medicine of the Faculty of Medicine of Ostrava University and University Hospital of Ostrava, Head Physician doc. MUDr. Ludek Roznovsky,
CSc
3 Department of Radiology of the Faculty of Medicine of Ostrava University and University Hospital of Ostrava, Head Physician doc. MUDr. Petr Krupa, CSc
РЕДКОЕ ПАРАЗИТАРНОЕ ЗАБОЛЕВАНИЕ ПЕЧЕНИ — АЛЬВЕОЛЯРНЫЙ ЭХИНОКОККОЗ
Купка Т.1, Бала П.1, Хозакова Л.2, Гавелка Я.3, Бойкова М.1, Брегова Б.1, Мартинек Э.1, Дитэ П.1 Университетская больница Остравы
1 Клиника внутренней медицины медицинского факультета университета Остравы и Университетская больница Остравы, главный врач док. MUDr. Arnost Martínek, CSc
2 Клиника инфекционной медицины медицинского факультета университета Остравы и Университетская больница Остравы, главный врач док. MUDr. Людек Roznovsky, CSc
3 Отдел радиологии медицинского факультета университета Остравы и Университетская больница Остравы, главный врач док. MUDr. Петр Крупа, CSc
Summary
Alveolar echinococcosis is a rare parasitic disease, especially of the liver, caused by the larval stage of the tapeworm Echinococcus multilocularis. At the end of the last century France, Germany, Austria and Switzerland were the regions where this disease most often manifested itself, these days this infection is diagnosed also in our territory. We describe the case of the disease of a twenty-five-year-old male with nonspecific signs and hepatomegaly, who was diagnosed on the basis of imaging and laboratory sampling. Due to inoperability the patient is now in infectologist follow-up on long-term treatment with Albendazole. He is clinically stable, included on the waiting list for liver transplantation.
Keywords: alveolar echinococcosis — benzimidazols — Echinococcus multilocularis — parasitic disease of the liver
Eksperimental'naya i Klinicheskaya Gastroenterologiya 2016; 135 (11): 119-122
Резюме
Альвеолярный эхинококкоз-редкое паразитарное заболевание, чаще всего печени, вызванный личинкой ленточного червя Echinococcus multilocularis
В конце прошлого века во Франции, Германии, Австрии и Швейцарии были регионы, где это заболевание отмечалось достаточно часть. В наши дни эта инфекция диагностируется иногда на территории современной Чехии. Мы описываем случай заболевания двадцатипятилетнего мужчины с неспецифическими признаками и гепатомегалией, у которого эхинококкоз был диагностирован на основе визуализации и лабораторных исследований. Из-за неработоспособности пациент сейчас находится в инфекционной больнице, где проходит курс длительного лечения Альбендазолом. Пациент клинически стабилен, включен в лист ожидания трансплантации печени.
Ключевые слова: альвеолярный эхинококкоз, бензимидазолы, Эхинококк аотвеолярный, паразитарное заболевание печени
Экспериментальная и клиническая гастроэнтерология 2016; 135 (11): 119-122
Introduction
Interest in both human and animal alveolar echino- cases of affected people [1]. Human alveolar echinococcosis has continued to increase over the past three coccosis is caused by the larval stage of the tapeworm decades, in particular, due to a major increase in noted Echinococcus multilocularis that ranges at least in 42
Tomás Kupka
Купка Томас tomas.kupka@fno.cz
countries ofthe northern hemisphere. The latest studies conducted in Europe and Asia show that expansion of this parasite is larger than originally expected and that infected foxes have moved from rural to urban areas [2]. Domestic dogs which can freely move in nature, eat infected rodents and spread the infection close to the human may also play an important role. In the second half of the 20th century, most cases of human alveolar echinococcosis in Europe were noted in France, Germany, Switzerland and Austria [2, 3]. At the present, most cases are reported from China [4].
Three strains of Echinococcus multilocularis have been defined based on epidemiologic characteristics: the European strain, besides European countries also covering China, the Alaskan and North American strains, with rodents being the intermediate hosts. The fourth, so far insufficiently differentiated strain is the Hokkaido strain [5]. Adult tapeworms live in the small intestine of carnivores — foxes, dogs and cats, small rodents are the intermediate hosts. A human can become infected by incidentally eating the eggs. Having been
eaten, the eggs release an embryo in the stomach and small intestine which penetrates the intestinal wall and then the bloodstream delivers it to the internal organs, in particular to the liver, where it is transformed into a cyst [6-8].
In modern history, the first case of alveolar echinococcosis ("AE") in the Czech Republic was noted by Dr. Slais in a 1978 post mortem of a 78-year-old woman from the Klatovy District, more than 16 cases have been noted in the Czech Republic since 2007, however, it is not mandatory in the Czech Republic to report and record AE.
With respect to the recent increase in the fox population all over Europe, associated with vaccination of these animals against hydrophobia which significantly reduced their population in the past, we can assume higher risk of this disease [7]. The biggest prevalence of foxes infected by Echinococcus multilocularis is in the Karlovy Vary Region, followed by the Liberec Region, Plzen Region, South-Bohemian Region, with the lowest occurrence in the South-Moravian Region [9].
Case Report
A 25-year-old patient was sent by his general practitioner to the Clinic of Internal Medicine of the University Hospital of Ostrava for additional examination of the parasitic disease of the liver indicated by abdominal ultrasonography (USG). The patient reported non-specific symptoms lasting for six months, such as progressing tiredness, breathless-ness with minimum exertion and backache on the right-hand side. He did not complain about fevers, shivering or high temperatures, he did not suffer from any digestive troubles. The anamnesis details indicate that the patient has no family burden, he has been healthy so far. He works as a motor vehicle mechanic, but his hobbies include hunting, he was not abroad, the last time in Slovakia 15 years ago. The objective finding indicates an enlarged liver 3 cm below the costal arch and palpable spleen, otherwise no anomalies.
The laboratory findings indicate microcytic anaemia with haemoglobin (Hb) 76 g per litre, slight thrombocytopenia 85 x 109/l, without leucocytosis, coagulation parameters within standard limits, biochemistry shows slightly higher alkaline phosphatise (ALP) 4.75 |icat per litre, glutamyl transferase (GMT) 2.11 |icat per litre, albumin 31.4 g per litre and C-reac-tive protein (CRP) 44 mg per litre. At the beginning of hospitalization, the conducted ultrasonographic examination of the abdomen proved parasitic disease of the liver (Figure 1), which was also confirmed by subsequent computed tomography (CT) of the abdomen which revealed finding of extensive multifocal disease of the liver with central necrosis and minor calcifications around with the size of 7 x 5 x 5 cm and splenomegaly of 17 cm along the long axis (Figure 2), differential diagnostics by the radiologist included liver granuloma, changes in the case of leukaemia or cholangiogenic carcinoma, although the focus did not saturate after contrastive substance administering.
In order to exclude haematologic malignity, ultrasonography of the peripheral nodes was conducted
and ^-microglobulin was taken, both without proof of pathology. The manual differential number of leukocytes was added, identifying a higher number of eosinophils 0.560 per |l. The digestive tract examination was conducted, while gastroscopy and coloscopy did not prove pathological changes. The infectologist expressed suspicion of alveolar echinococcosis and amoebiasis and the serological surveys in the National Reference Laboratory for Tissue Parasitosis proved highly positive Western blot of echinococcosis. The total immunoglobulins E (IgE) were higher (678 U per ml). The patient was treated by Mebendazole and Metronidazole with partial CRP decrease down to the value of 12 mg per litre and then was transferred to the infectologists for treatment and outpatient monitoring.
At present, the patient has been followed up at the Clinic of Infectious Medicine, with long-term administration of Albendazole in the dose of 400 mg twice a day, but his treatment compliance is poor, the patient does not arrive for examination on a periodical basis and does not take the prescribed medicines. The patient's PET CT was additionally conducted with demonstrable hypermetabolism of glucose at the border of cystic focuses in the right liver flap, demonstrating activity of the diseases. The patient was also discussed at the multi-disciplinary conference where the surgeons decided on inoper-ability of the focus due to its extension. As a result, the patient was examined in the Cardiovascular and Transplantation Surgery Centre of Brno for the purposes of considering liver transplantation; he is on the waiting list. According to the latest abdomen ultrasonography (Figure 3), the finding on the liver is in slight regression, stable, the cystic focus in the right liver flap with the diameter of 4 cm persists. The laboratory finding continues to show light-degree microcytic anaemia, eosinophilia 0.420 per |l, CRP within standard limits and total IgE has a decreasing trend (382 U per ml).
a rare parasitic disease of the liver — alveolar echinococcosis | редкое паразитарное заболевание печени — альвеолярный эхинококкоз
Figure 1.
Initial abdomen USG. Created and kindly provided by the Radiology Institute of the University Hospital of Ostrava.
Discussion
Alveolar echinococcosis needs to be considered in the case of multicystic liver diseases. In the case of AE infection, the liver is affected in 98% of cases. In immunocompetent persons, the disease has a long incubation period that is symptom-free and lasts for 5-15 years. The initial symptoms can be unspecific, with development of tiredness, pain in the epigastrium and weight loss, icterus may occur or the disease does not become evident until hepatomegaly identified — the size ofliver cysts may reach as much as 5-90 cm [8].
We will determine diagnosis based on the clinical symptoms, results of imaging methods and laboratory results. The laboratory findings may show slight increase in liver tests, mainly GMT and ALP, the value of total IgE antibodies is often higher, eosionophilia is not too frequent.
The serological survey is conducted by an indirect haemagglutination test and proof of IgG antibodies by
an ELISA test. In the case of echinococcosis, we usually survey the presence of antibodies in both tests. The presence of antibodies can also be unspecific, cross-reacting to other antigen, and therefore, it is required to examine the patient's serum for the presence of antibodies even against other parasites. The ELISA reaction is very sensitive, but it is not able to distinguish active lesions from inactive ones, which is very important for eventual application of radical treatment. Cross-reaction and falsely positive results can also be obtained in the case of non-parasitic infections, in particular, in the case of various types of malignity, liver cirrhosis and others [5]. In the case of negative serological results with persisting suspicion of the disease, we can conduct the polymerase chain reaction (PCR) which detects parasitary deoxyribonucleic acid (DNA) from biological material obtained by diagnostic puncture.
Figure 2.
Abdomen CT with finding of multifocal disease of the liver with central necrosis and calcifications around. Created and kindly provided by the Radiology Institute of the University Hospital of Ostrava.
Figure 3.
Control USG of the abdomen after treatment. Created and kindly provided by the Radiology Institute of the University Hospital of Ostrava.
Out of the imaging methods, an important role is played by ultrasonographic or CT examination of the abdomen where we find inexactly bounded hypoechoic focus with central necrosis and calcifications. The imaging methods are significant not only for determining the diagnosis, but also for evaluation of treatment efficiency. The most important one is the positron emission tomography (PET): in the case of successful treatment, we identify lower fluorodeoxyglucose uptake, which
demonstrates lower activity of the parasitary focus. Control PET is conducted after 12-18 months.
In the differential diagnosis, we should distinguish benign liver cysts without the presence of necrosis and calcification, liver polycystosis that is often associated also with polycystic change of the kidney, Caroli disease, which is a rare inherited disease with formation of cystic exaginations of the biliary tract, other congenital anomalies, as well as primary or metastatic
liver tumour. We also need to distinguish cystic echi-nococcosis (CE) that is induced by infection of the larval stage of the tapeworm Echinococcus granulosus and that causes unilocular disease when the imaging methods exactly demarcate the cyst with apparent septa, serological survey then proves Echinococcus granulosus.
CE therapy is also surgical, supported with pre-sur-gery and post-surgery therapy by Albendazole, solitary and uncomplicated cysts enable the PAIR method (puncture, aspiration, instillation, respiration) when Albendazole administration is followed by the focus puncture with a thin needle under USG or CT control, a part of the content is aspired, scolicide solution is installed and respiration is conducted after 30-minute action. The Albendazole treatment lasts for 3 months as a minimum, often even more than one year.
The basic therapy is surgical removal of the parasi-tary focuses, supported by pre-surgery and post-surgery chemotherapy by Benzimidazoles, most often Albendazole, less often by Mebendazole, that become absorbed inconstantly from the intestine and it is required to check its level in the blood. Experimentally tested Praziquantel does not have better results. The major adverse effects of these medicines include headache,
nausea and vomiting or convulsive fit. During the surgery, it is important to avoid contamination of the surgery field by the cyst content, which would result in infection dispersion. In the case of inoperable diseases, the Benzimidazole treatment takes a long time, even the whole life. Both Albendazole and Mebendazole are best absorbed after a fatty meal. During the treatment period, the liver tests, urine and blood count are conducted once a month. Higher Alanin-aminotransferase (ALT) and eosinophilia after the treatment starts may indicate a curing effect rather than a toxic reaction [7, 8, 10, 11]. Patients after successful radical surgery, supported by pre-surgery and post-surgery Albendazole therapy, have the best prognosis. In inoperable cases, it depends on the patient's compliance with long-term, sometimes life-long chemotherapy with the use of Albendazole. Without treatment, 70% of sick people die within 5 years and 90% within 10 years from diagnosis determination.
With respect to the increasing number of infected foxes all over Europe, the risk of human infection is also most likely higher. When finding unclear cystic focus in the liver, we should, therefore, also take into account this unusual diagnosis and include methods of clarification thereof in the examination procedure.
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