echinococcus multilocularis is one of the rare types of parasitic infestations in the northern hemisphere which can involve several organs , especially the liver .
however , there is not enough information about liver involvement related to this parasite in human beings ( hepatic alveolar echinococcosis ) ( 1 ) .
liver involvement of this parasite is a life - threatening infestation , especially when diagnosis is delayed , which itself can be life - threatening ( 2 ) . in this review ,
we discuss all of the published cases of hepatic ae from iran in regard to epidemiology , clinical presentation , diagnosis , and protocols of treatment .
the adult form of this tapeworm lives in the intestines of natural definitive hosts , which can be wild carnivores such as red fox or domestic dogs and cats .
the eggs released by the adult tapeworm are passed in the stool of the definitive hosts , which then is ingested by the intermediate hosts , such as small rodents or red foxes . however , there are other accidental intermediate hosts , such as humans .
ingestion of the eggs by humans usually occurs because of the contamination of food or water by the fecal material of definitive hosts .
after the ingestion of the eggs by humans , the larvae ( metacestodes ) travel to the liver , where they create alveolar small vesicles and alveolar cysts ( 3 - 5 ) .
as mentioned , hepatic ae is caused by the infestation of humans , as an accidental intermediate host , by the larval stage of e. multilocularis .
the echinococcal metacestodes grow in the liver and create an alveolar - like structure , which consists of several vesicles surrounded by large granuloma .
human ae is a severe and emerging disease which , with delayed diagnosis , can be life - threatening ( 2 ) .
ae is considered one of the most dangerous parasitic infestations of human beings in the northern hemisphere .
new ae cases in western and central europe have been estimated in the range of 170 - 200 per year .
the highest reported numbers of ae from europe were from france , germany , switzerland , lithuania , and poland , and it is extremely rare in the eastern and central parts of europe ( 6 ) .
high parasite prevalence is also reported in the middle east and arabic north africa . in the middle east , iran , iraq , and turkey are known as areas where ae is endemic ( 7 ) . however , from these regions , where the parasite is known to be present , there is a scarcity of information about recent distribution and frequency ( 8) .
the adult form of this tapeworm lives in the intestines of natural definitive hosts , which can be wild carnivores such as red fox or domestic dogs and cats .
the eggs released by the adult tapeworm are passed in the stool of the definitive hosts , which then is ingested by the intermediate hosts , such as small rodents or red foxes . however , there are other accidental intermediate hosts , such as humans .
ingestion of the eggs by humans usually occurs because of the contamination of food or water by the fecal material of definitive hosts . after the ingestion of the eggs by humans , the larvae ( metacestodes ) travel to the liver , where they create alveolar small vesicles and alveolar cysts ( 3 - 5 ) .
as mentioned , hepatic ae is caused by the infestation of humans , as an accidental intermediate host , by the larval stage of e. multilocularis .
the echinococcal metacestodes grow in the liver and create an alveolar - like structure , which consists of several vesicles surrounded by large granuloma .
human ae is a severe and emerging disease which , with delayed diagnosis , can be life - threatening ( 2 ) .
ae is considered one of the most dangerous parasitic infestations of human beings in the northern hemisphere .
new ae cases in western and central europe have been estimated in the range of 170 - 200 per year .
the highest reported numbers of ae from europe were from france , germany , switzerland , lithuania , and poland , and it is extremely rare in the eastern and central parts of europe ( 6 ) .
high parasite prevalence is also reported in the middle east and arabic north africa . in the middle east , iran , iraq , and turkey are known as areas where ae is endemic ( 7 ) . however , from these regions , where the parasite is known to be present , there is a scarcity of information about recent distribution and frequency ( 8) .
in this brief review , the published cases of hepatic ae from iran were retrieved for review via a search in pubmed , scopus , google scholar , iranmedex , scientific information database ( sid ) , magiran , and irandoc ( 1995 - 2015 ) , using the keywords echinococcus multilocularis and iran , alveolar hydatid cyst and iran , liver and alveolar hydatid cyst and iran , and hepatic alveolar hydatid cyst and iran .
the following inclusion criteria were employed : 1 , articles must be written in english or farsi ; 2 , articles must have been published between 1995 and 2015 ; 3 , cases must have been confirmed by pathologic examination .
during the 20 years between 1995 and 2015 , there were 24 published cases of hepatic ae from iran ( 9 - 14 ) .
there were 20 female patients and 4 male ( f / m = 5/1 ) .
the age range of these patients was 21 - 74 years ( 42.6  12.2 ) .
twenty - two patients were from the northeast part of the country , i.e. , khorasan razavi province , one patient was from ardebil province , and one case was reported from the south , i.e. , khuzestan province .
clinical presentation of the patients was mostly right upper quadrant ( ruq ) pain in 20 ( 83% ) patients , anorexia and weight loss in 2 ( 8.3% ) patients , jaundice in 5 ( 20.8% ) patients , and fever in 4 ( 16.6% ) patients .
the most common sign in physical examination was hepatomegaly and liver mass in all 24 patients , which was tender in two of them ( 8.3% ) .
one patient presented with cough , bloody sputum , and fatigue , secondary to lung metastasis ( 13 ) .
duration of the disease at the time of diagnosis was from 20 days to 5 years ( 35.6  27.5 months ) .
in all of the cases , sonographic findings were described as large ( from 10 - 30 cm ) solid or cystic liver masses with heterogeneous echogenicity and irregular margins . magnetic resonance image ( mri ) and
ct scan , used in a few cases , revealed large multiloculated liver masses with heterogeneous density and irregular and infiltrative margin .
fifteen cases had a mass in the right lobe of the liver , seven cases in the left lobe , and in two patients , there were multiple liver masses in both liver lobes . in most of the published cases ,
however , in four reported cases , wbc was increased in two of the patients ( 5,200 - 15,500/ml ) .
liver enzymes , including alanine aminotransferase ( alt ) , aspartate aminotransferase ( ast ) , and alkaline phosphatase ( alp ) were mostly abnormal .
alt was 10 - 268 iu / l ( 74.9  78.6 ) ( normal < 28
iu / l ) , ast was 18 - 262 iu / l ( 79.83  80.4 ) ( normal < 28 iu / l ) , and alp was 90 - 1919 iu / l ( 578.7  595 ) ( normal < 150
bilirubin level was reported in 21 patients as between 0.3 to 29.3 mg / dl ( 6.5  8.7 ) with a normal of < 1.2 mg / dl .
table 1 shows the primary characteristics of the 24 patients with hepatic ae published from iran .
iu / l ) ; * * * alp , alkaline phosphatase ( normal < 150
the gold standard for final diagnosis in all of the cases of hepatic ae from iran was tissue biopsy and pathologic diagnosis , either with a wedge biopsy or needle biopsy .
most of the cases were treated by a combination of surgery and antiparasitic medical therapy , i.e. , albendazole , for six months to two years .
nine cases had large , unresectable liver masses , one of which was scheduled for liver transplantation , but the patient did not accept it .
however , she responded to medical therapy and , after six months follow - up , she remained alive ( 9 , 10 ) . postoperative complications for patients who underwent resection included postsurgical abscess , cholangitis , and biliopulmonary fistula ( 13 , 14 ) . death was reported in three patients , secondary to lung metastasis , infection , and fistula ( 13 ) .
the larval form rapidly proliferates and produces an alveolar - like pattern of microvesicles in different tissues of the body , especially the liver ( 15 ) . therefore , the characteristic feature of ae is its tumor - like pattern of growth .
the liver is the first and most common organ to be affected by larval infestation .
hepatic ae is a rare and life - threatening parasitic disease , which develops as a result of intrahepatic growth of the echinococcus multilocularis ( 4 ) .
liver involvement related to echinococcus multilocularis was first observed by virchow in 1855 , who published an article entitled echinococcus - tumor of the liver ( 16 ) .
the who - iwge pnm classification system was established in 2001 , based on imaging findings , as an international standardization for evaluation of diagnostic and therapeutic modalities .
p is the degree of extension of the parasite , n indicates the involvement of nearby organs , and m is considered metastasis .
this classification was developed to evaluate the extension of the disease and therapeutic approaches ( 15 ) .
ae is characterized by primary lesions in the liver , producing tumor - like , multi - vesicular , infiltrating structures .
early diagnosis of ae by characteristic signs and symptoms , imaging modalities , immunologic tests ( such as elisa ) , histopathological examination , or molecular analysis of tissue materials can be life - saving and will significantly improve the prognosis of ae patients .
recently developed and improved serological and molecular tests for ae have been shown to be reliable ( 17 ) . however , in most patients , characteristic symptoms are not present , and in most geographic areas of world , as in many parts of iran , these tests are not available .
ultrasonography , ct scan , and mri are the most common imaging modalities for the diagnosis of ae in the liver .
large liver masses with mixed echogenicity and irregular margin are the most common sonographic findings ( 18 ) .
it is recommended to perform ct scans in cases where liver - involved ae is suspected , but in most of the published cases from iran , no ct report was mentioned .
ae in ct presents with a hypodense liver mass , very similar to a malignant infiltrative process with irregular borders .
ct scan has the capacity to determine the extension of the disease , as well as the number , size , and localization ( 12 ) . magnetic resonance imaging ( mri ) is also a good modality to diagnose the extension of the disease . in mri , the liver mass of ae presents as an irregular , solid - cystic mass , with honeycomb appearance in t2-weighted images ( 19 ) .
fluorodeoxyglucose positron emission tomography ( fdg - pet ) is a noninvasive modality for the detection of metabolic activity in ae .
delayed images would increase its sensitivity for the assessment of the metabolism of the lesion and its reliability for the continuation or withdrawal of antiparasitic treatment ( 20 ) .
pet - ct can be used to monitor suppression of periparasitic inflammatory activity and has an important role for excluding the metastatic spread .
however , expensive and sophisticated equipment is not widely available , which limits its use for a routine procedure ( 19 ) .
the most common presentation is extensive necrosis , with small vesicles and delicate membranes scattered in the necrosis . in our experience ,
the most common pitfall for the pathologist is missing the above - mentioned structures and calling the biopsy unsatisfactory , because of extensive necrosis ( 9 , 10 ) .
this places emphasis on the role of the pathologist in the diagnosis of ae in the liver , because delayed diagnosis of hepatic ae leads to advanced disease with unresectable masses and poor prognosis ( 21 ) . in these circumstances , for very large , unresectable masses , the only surgical therapeutic modality can be liver transplantation ( 22 ) .
in addition to surgical approaches , considering long - term ( six months to two years ) medical antiparasitic therapy ( e.g. , albendazole ) is very important to decrease the risk of recurrence and postsurgical complications ( 23 ) . according to the previous studies in the english literature ,
although liver hydatid cyst , secondary to echinococcus granulosus , is a very common disease in iran , very few cases of hepatic alveolar hydatid cyst have been published from iran ( 12 ) . despite the rarity of this disease ,
thus , it is very important to consider this disease in the differential diagnosis of patients with liver mass , especially those from endemic areas ( e.g. , northeast iran ) ( 9 , 10 ) .
 contextechinococcus multilocularis is the cause of alveolar hydatid disease , which most commonly involves the liver in more than 90% of cases . 
 this disease is endemic in northern iran . 
 however , there are very few published cases from iran . in this article , we will review all of the published cases of hepatic alveolar echinococcosis from iran regarding all aspects , including clinical , paraclinical , and treatment protocols.evidence acquisitionin this brief review , the published cases of hepatic alveolar echinococcosis ( ae ) from iran were retrieved for review via a search in pubmed , scopus , google scholar , iranmedex , scientific information database ( sid ) , magiran , and irandoc ( 1995 - 2015 ) using the keywords echinococcus multilocularis and iran , alveolar hydatid cyst and iran , liver and alveolar hydatid cyst and iran , and hepatic alveolar hydatid cyst and iran . 
 the following inclusion criteria were employed : 1 , articles must be written in english or farsi ; 2 , articles must have been published between 1995 and 2015 ; 3 ) cases must have been confirmed by pathological diagnosis.resultsthere were 24 published cases of liver - involved alveolar hydatid cyst from iran . 
 the disease was more common in young- to middle - aged women in northeast iran . 
 the most common presenting signs and symptoms were abdominal pain with hepatomegaly and liver mass . 
 most of the patients were treated by surgery and albendazole . 
 the few unresectable liver masses were treated by medical therapy . 
 no liver transplantation for this disease was reported from iran.conclusionshepatic alveolar hydatid cyst should be considered one of the important differential diagnoses of liver masses , especially in endemic areas of the world . 
1. Context
1.1. Echinococcus Multilocularis: Classification and Life Cycle
1.2. Hepatic Alveolar Cyst (Hepatic AE)
1.3. Epidemiology of Hepatic AE
2. Evidence Acquisition
3. Results
4. Discussion