Review
Dig Surg 1998;15:287–296
Maher Osman a
Susanne Bach Lausten a
Talaat El-Sefi b
Ibrahim Boghdadi c
M-Yousri Rashed d
Steen Lindkær Jensen a
a
b
c
d
Department of Surgery L, Århus University
Hospital, Århus University, Århus,
Denmark;
Department of Surgery, Liver Institute, and
Department of Internal Medicine, Faculty
of Medicine, Menoufiya University,
Shibin El Kom, and
Department of Internal Medicine, Faculty
of Medicine, Alexandria University,
Alexandria, Egypt
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Key Words
Biliary parasites
Epidemiology, biliary parasites
Parasitic disease, clinical
presentation and diagnosis
Biliary Parasites
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Abstract
Parasitic diseases of the biliary tract occur frequently in tropical and subtropical areas and cause high morbidity and mortality. In general, neither the clinical presentation nor the general laboratory findings are sufficiently unique to
raise the possibility of a parasitic biliary infestation in the mind of the surgeon.
Once considered, however, the presence of a parasitic biliary infestation is
easily confirmed. Most commonly this is accomplished by the identification of
the parasite in stools or duodenal contents. Ultrasonography, CT and MRI are
not only important in the diagnosis of parasitic biliary diseases but also in the
follow-up and surveillance. ERCP is an excellent diagnostic tool for demonstrating the presence of parasites in the biliary tree. Furthermore, ERCP is also
used in the therapy of biliary parasitic infestations and carries less morbidity
and mortality than the surgical approach. Surgery is only indicated in complicated cases. Mechanisms that may be effective against parasites include: antibodies; cytotoxic T cells; T-cell-induced activated macrophages; natural killer
cells, and a variety of cells that mediate antibody-dependent cell-mediated
cytotoxicity and modulators of the immune system such as cytokines. Future
research has to focus on the importance of these mechanisms for the immune
evasion by parasites.
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Introduction
Classification of Biliary Parasites
Helminthic invasion of the human biliary tract is a
prominent medical and surgical problem especially in
tropical and subtropical areas where these parasites are
endemic [1]. Parasitic infestations rarely occur in the temperate zones, although the incidence seems to be increasing gradually in such areas due to the increasing number
of tourists, immigrants and expatriates. Accordingly, it is
important for physicians and surgeons in the temperate
areas of the world to be aware of biliary parasites, their
clinical picture, diagnosis and treatment. The aim of the
present report is to review the present knowledge of biliary tract parasitic infestations.
ABC
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Helminthic infestation may affect the liver and/or the
biliary tract either during passage of worms through these
structures or because these organs serve as their natural
habitat. Table 1 shows the classification of parasitic infestations affecting the liver and/or the biliary tract. It should
be noted that some parasites such as schistosomes invade
the liver parenchyma but are not associated with biliary
conditions. Table 1 includes the scientific and common
names of the parasite or disease as well as the source from
which infection is most commonly derived. Among the
many parasites present, only nematodes and hermaphroditic trematodes affect the biliary system.
Maher Osman, MD
c/o Prof. Steen Lindkær Jensen, MD, DMSc, Department of Surgery
Århus University Hospital, Nørrebrogade 44
DK–8000 Århus C (Denmark)
Tel. +45 89493883; Fax +45 894938990
Table 1. Classification of biliary flukes
(Metazoa)
Table 2. Geographic distribution of
parasites affecting the biliary tree
Type
Species
Relationship
Common name
Source
Nematodes
Ascariasis
Intestinal pathogenic
Trematodes
Chlonorchis + Tissue pathogenic
relatives
Liver fluke
Raw fish
Fasciola
Sheep liver fluke
Freshwater
plants
Tissue pathogenic
Human feces
Fasciola hepatica
South America, Middle East, China, Russia, Poland, England,
France, Spain, Hungary, Algeria, Somalia, South Africa, Hawaii
Ascariasis lumbricoides
Worldwide, more common in warm, moist climates
Clonorchis sinensis
Japan, Korea, Taiwan, China, Vietnam
Episthorchis filineus
Southern, Central and Eastern Europe, North Vietnam, Korea,
Japan, Philippines
Dicrocoeliasis dendriticum Eastern Europe, Africa, North and South America
Table 3. Clinical presentation of biliary
flukes according to the literature
Presenting
symptom/signs
Ascariasis
Fascioliasis
Biliary pain
Fever/chills
Jaundice
Nausea
Hepatomegaly
Asymptomatic
Acute presentation1
Chronic presentation2
65/71 (91%)
93/125 (74%)
106/129 (82%)
48/100 (48%)
–
–
–
–
76/149 (51%)
11/203 (54%)
30/40 (75%)
–
23/32 (71%)
–
–
–
1
2
Table 2 demonstrates the geographic distribution of
parasites affecting the biliary tract.
Manifestations of Biliary Parasitic Infestations
Table 3 demonstrates the frequency of the different
symptoms in patients with biliary fluke infection according to the literature. Parasites in the biliary tree can cause
the syndrome commonly referred to as ‘Oriental cholan-
Dig Surg 1998;15:287–296
1,143/5,243 (21.8%)
5/79 (6.3%)
74/79 (93.7%)
Acute presentation consists of pain, fever, jaundice and loss of appetite.
Chronic presentation consists of malaise and jaundice.
Geographical Distribution of Biliary Parasites
288
Clonorchiasis
opisthorchiasis
giohepatitis’. Features of this syndrome include helminthiasis, choledocholithiasis, choledochal obstruction, recurrent cholangitis with stones and a propensity for stricture of the left hepatic duct. A parasite may act as a nidus
for stone formation or provoke the disease in the bile ducts
that leads to stone formation [2]. The stones associated
with ‘Oriental cholangiohepatitis’ are darkly pigmented,
soft and friable, different from gallstones seen in the Western part of the world. However, the relation between choledocholithiasis and parasites may be coincidental. Clinically, ‘Oriental cholangiohepatitis’ includes biliary colic,
jaundice, cholecystitis and/or cholangitis [3].
Osman/Bach Lausten/El-Sefi/Boghdadi/
Rashed/Jensen
Table 4. Complications of biliary flukes according to the literature
Table 5. Diagnosis of biliary flukes
Complication
Ascariasis
Fascioliasis
Clonorchiasis
Obstructive jaundice
Pyogenic cholangitis
Acute cholecystitis
Chronic cholecystitis
Acute pancreatitis
Intrahepatic stones
Liver abscesses
Mortality
Gallbladder perforation
Bile duct stricture
Cholaniocarcinoma
HCC
500/612 (82%)
167/574 (29%)
101/634 (16%)
16/68 (24%)
42/570 (7%)
21/517 (4%)
11/553 (2%)
4/521 (1%)
–
–
6/6 (100%)
–
34/42 (80%)
21/31 (67%)
21/28 (75%)
–
–
4/20 (20%)
73/89 (82%)
–
–
–
–
–
–
21/33 (64%)
–
–
9/13 (32%)
95/974 (10%)
4/27 (15%)
–
2/6 (33%)
3/20 (15%)
40/50 (80%)
5/26 (19%)
Table 4 lists the frequency of different complications
associated with biliary fluke infestation according to the
literature.
Acute pancreatitis is occasionally seen as a result of
parasites in the common bile duct either due to obstruction of the pancreatic duct or the terminal common bile
duct [4].
Liver cysts and abscesses occur secondary to ascariasis
and liver flukes, whereas hepatocellular carcinoma and
cholangiocarcinoma are seen in association with Clonorchis sinensis and opisthorchiasis [5, 6].
Biliary Parasites
+
+
+
++++
++
++
+++
++
++
++++
Table 6. Conservative treatment of parasitic biliary diseases
Parasite
Drug
Adult and pediatric dose
Fasciola hepatica
Bithionol
30–50 mg/kg on alternate
days, 10–15 doses
Niclofolan
Chloroquine
Metronidazole
Triclabendazole
Ascariasis
Diagnosis of Biliary Parasitic Infestations
The clinical picture of parasitic biliary infestations
often varies, impeding final diagnosis. Table 5 shows the
different diagnostic tools available for the diagnosis of biliary parasitic infestations. None of the tests are specific
except the demonstration of eggs in feces and/or duodenal
contents (fig. 1). ERCP is extremely helpful in defining
changes in the bile ducts as well as demonstrating the parasites directly, their location and movements (fig. 2, 3).
Ultrasonography, CT, MRI can be used to demonstrate
the flukes (fig. 4), dilatation of the biliary tree due to biliary obstruction caused by the parasites, the presence of
stones, cholangiocarcinoma, hepatoma, liver abscesses or
cysts [7]. Characteristic sonographic and CT features can
be found for ascaris and clonorchis worms in the biliary
tree [8, 9]. Ultrasonography, CT and MRI are useful in
the follow-up of patients with biliary parasitic infestations. Eosinophilia is often present but insignificant [7] as
well as leukocytosis.
History
Clinical examination
Clinical chemistry
Parasitology
Serology
Radioisotopes
Ultrasonography
CT
MRI
ERCP
Clornorchis sinensis
and relatives
Pyrantel
pamoate
or
Mebendazol
or
Piperazine
citrate
Single dose of 1 mg/kg
(maximum 1 g)
Praziquantel
25 mg/kg t.i.d. for 2 days
100 mg b.i.d. for 3 days
75 mg/kg (maximum
3–5 g/day) for 2 days
The presence of eosinophilia supports the suspicion of
the presence of parasites. Variable elevations in bilirubin,
transaminases, alkaline phosphatases and Á-glutamyltranspeptidase are seen in severe cases, whereas the level
of these liver tests may be normal in mild cases of biliary
parasitic infestations.
Treatment
Treatment modalities at hand for biliary fluke infection include conservative treatment, endoscopy and/or
surgery. Conservative treatment consists of antihelmin-
Dig Surg 1998;15:287–296
289
1
3
5
2
Fig. 1. Fasciola hepatica flukes from the duodenal content.
Fig. 2. Massive dilatation of the common bile duct caused by
Fasciola hepatica flukes demonstrated on ERC.
Fig. 3. ERC demonstration of Fasciola hepatica fluke in the common bile duct and of several flukes in the gallbladder.
Fig. 4. The appearance of Fasciola hepatica fluke on ultrasonographic examination of the gallbladder. During ultrasonography
movements of the fluke can be demonstrated.
Fig. 5. Ascariasis worm seen moving from the papilla of Vater
into the duodenum on ERC.
4
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Osman/Bach Lausten/El-Sefi/Boghdadi/
Rashed/Jensen
thics as demonstrated in table 6. Previously, surgical
treatment was necessary for the management of biliary
parasites and related stones. Nowadays, endoscopic
spincterotomy and extraction of the biliary parasites is a
good alternative to surgery, and carries less morbidity and
mortality than the surgical approach. Surgery is still indicated in cases with acute or chronic cholecystitis due to
parasitic infestation and related stones. Biliary parasites
causing recurrent pyogenic cholangitis due to biliary tree
invasion and obstruction is treated endoscopically by
spincterotomy, parasite extraction and nasobiliary drainage. The nasobiliary tube is also used for instillation of
antihelminthics.
Nematodes
Among the nematodes only Ascariasis lumbricoides is
able to migrate into the biliary tract.
non-obstructive cases and also to follow the exit of worms
from the bile ducts [16–18]. ERCP is helpful during the
active phase and sometimes worms may be seen moving
actively into the biliary tree from the duodenum (fig. 5)
[19–21]. The worms migrate from the bile duct within
24 h up to 2 weeks. Serology is available for the diagnosis of
ascariasis but the diagnostic usefulness is only marginal.
Treatment. More than 95% of patients with uncomplicated biliary ascariasis respond to conservative treatment
[22]. Table 6 demonstrates the antihelminthics commonly used. The reinfection rate is high in endemic areas and
prolonged antihelminthic therapy is recommended. The
indications for surgery are persistent severe right upper
quadrant colic and signs of peritonitis or clinical evidence
of other complications which cannot be treated endoscopically [22].
Prognosis. The prognosis is excellent in uncomplicated
cases. It has been demonstrated that after treatment continuous monitoring of the patient during follow-up shows
disappearance of the symptoms; the biochemical tests
return to normal, and control ultrasonography and ERCP
show no worms left within the biliary tree [11]. Complications occur in 15% of operated patients; the most frequent
being biliary fistulae.
Ascariasis lumbricoides
Ascariasis is one of the most common helminthic diseases in humans [10] and occurs mostly in countries with
low standards of public health and personal hygiene, making ascariasis highly endemic in developing countries
[11]. Ascariasis is, however, worldwide in distribution
and is probably second only to gallstones as the cause of
acute biliary symptoms. It is estimated that around 25%
of the world’s population are infected with A. lumbricoides [12].
Clinical Presentations. All patients with biliary ascariasis have intestinal ascariasis. Many suffer from vomiting,
intestinal colic and/or a palpable mass of intestinal
worms. In advanced cases with massive biliary ascariasis
the patients complain of severe intermittent right upper
quadrant abdominal pain and vomiting. Fever accompanied by persistent pain is seen in many patients and suggests the presence of cholangitis and/or pyogenic liver
abscess [12]. On examination enlargement of the liver,
tenderness and guarding of the right upper quadrant can
be found in up to 30% of the cases. Around 10–20% of the
patients suffer from jaundice and about 20% of a palpable
gallbladder [12, 13].
Diagnosis. Diagnosis of ascariasis migration to the biliary tract is difficult and usually made at laparotomy [14].
Biliary ascariasis sould be suspected in cases of biliary colics and a history of vomiting of worms. The diagnosis is
made by demonstration of ascariasis ova in vomit or in a
fecal smear [15]. Ultrasonography is the first choice in
order to detect biliary ascariasis in obstructive as well as
Clonorchiasis
C. sinensis is a small fluke measuring only 10–25 mm
long, 3–5 ! 1 mm. The fluke may live for up to 50 years
in the biliary tree of its host. Occasionally the flukes also
live in the pancreatic duct and the gallbladder, where they
lay eggs [23]. Operculated eggs are passed into the feces
and when reaching fresh water the eggs are ingested by
snails. From the snails cercariae are released and penetrate freshwater fish. Human infections originate from
ingestion of the raw, dried, salted or pickled flesh or freshwater fish containing encysted metacercariae. The larva is
released in the duodenum from where it enters the common bile duct and migrates to the second-order bile ducts.
Besides humans, dogs, pigs, cats, and rats serve as disease
reservoirs [23]. The disease may be acquired in the West-
Biliary Parasites
Dig Surg 1998;15:287–296
Hermaphroditic Trematode Infections
The trematodes of humans are long-lived parasites that
cause progressive damage to the tissue of their host. With
the exception of schistosomiasis, they are similar in morphology and life cycle. The adult flukes are flat, leaf-like
and hermaphroditic varying in length from a few millimeters to several centimeters.
291
ern world by ingestion of infected frozen or pickled fish
imported from the Far East.
Pathology. As a result of infestation with flukes, certain
morphological changes in the bile ducts can be seen such
as adenomatous hyperplasia and goblet cell metaplasia
[24, 25]. In chronic infections the process of adenomatous
tissue formation is gradually replaced by fibrous tissue
formation resulting in extensive thickening of the bile
ducts sometimes extending into the parenchyma, but never to the extent of forming nodular cirrhosis [26]. If the
infection becomes persistent, periductal fibrosis and eosinophilic infiltration may supervene [23]. Major pathological findings are also seen in the liver, and the bile
ducts proximal to the worm dilate due to partial obstruction. This can often be seen through the capsule of the
liver as bluish spots [25].
Clinical Presentation. The diagnosis should be suspected in patients coming from endemic areas who have
jaundice, hepatomegaly, enlarged gallbladder or obscure
liver disease. The clinical manifestations of biliary clonorchiasis are diverse and can, depending on the severity, be
divided into 3 groups: mild asymptomatic infestations;
moderate or heavy infestations, and mild infestations
with complications [23].
Mild Infestation. The patients harbor less than 100
flukes, are often asymptomatic and the diagnosis is established by the discovery of the characteristic operculate
ova on routine stool examination [27]. Asymptomatic
infestation may exist for up to 35 years [1].
Moderate and Heavy Infestations. Moderate infection
with up to 1,000 flukes may present with uncharacteristic
dyspeptic symptoms such as anorexia, nausea, diarrhea,
and epigastric discomfort [27]. Infections with up to
20,000 flukes are usually characterized by acute, intermittent right upper quadrant pain and tenderness, hepatomegaly, anorexia and weight loss [23, 27].
Mild Infestation with Complication. The most common complication of biliary clonorchiasis, recurrent pyogenic cholangitis, is due to secondary obstruction of the
bile ducts which are obscured by flukes, usually accompanied by intrahepatic biliary stones [25]. Pancreatic involvement occurs in 30% of the cases and includes acute
pancreatitis and pancreaticolithiasis [28, 29]. The pathology includes adenomatous hyperplasia of the ductal epithelium, but frequently squamous cell metaplasia is seen
[30, 31]. Other complications include jaundice, cirrhosis,
portal hypertension, ascites, cholecystitis and cholelithiasis, while liver abscesses, retention cysts and malignancy
[30] are the most serious sequelae of biliary clonorchiasis.
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Dig Surg 1998;15:287–296
Epidemiological studies have demonstrated that
chronic infection is associated with an increased incidence of biliary tract malignancies [30, 31]. The association between this type of cancer and the helminthic infection is also supported by the fact that cholangiocarcinoma
usually develops in second-order intrahepatic bile ducts
where clonorchis is located and that adenomatous proliferation of the ductal epithelium can be seen together with
malignant changes in the bile duct [26]. The precise
sequence of events leading to cholangiocarcinoma is unclear. It has been suggested that mechanical irritation by
flukes, chemical alteration of the bile by the flukes or carcinogenic products of the parasites are responsible for the
development of malignant changes [6, 26, 27].
Diagnosis. The diagnosis rests on a high index of suspicion [31]. The definitive diagnosis is made by identification of eggs in the feces or in the duodenal aspirate (table 5). ERCP is useful in the diagnosis [32, 33]. Four
ERCP patterns have been observed: (a) diffuse tapering of
the intrahepatic ducts with dilatation of the intra- and
extrahepatic ducts; (b) a solitary cyst similar to a liver
abscess cavity or retention cysts; (c) multiple cystic dilatations of the intrahepatic ducts, producing a mulberry-like
appearance that is characteristic of liver fluke infestation,
and (d) a combination of these findings, with extensive
cystic dilatation in some areas of the liver and biliary duct
ectasia in others. Ultrasonography and CT should also be
performed [34, 35].
Treatment. Principles in medical treatment is shown in
table 6. Complicated cases are treated surgically or endoscopically depending on the complication. The interventional procedures are combined with an appropriate vermifuge [36] because these procedures cannot free the biliary system from infection. In patients with obstructive
jaundice a modified Longmire bypass operation may be
used for palliation. There is no indication for prophylactic
surgery including partial liver resection in preventing the
development of cholangiocarcinoma.
Prognosis. The cure after medical treatment has ranged
between 73 and 100% in patients not developing cholangiocarcinoma. The intensity of infection has been greatly
reduced in those not cured. If the biliary fluke infestations
are complicated by intrahepatic cholangiocarcinoma arising in the bile ducts near the hilum, the prognosis is bad. If
unresected the 3-year survival is about 10%. Average survival after resection is longer, making it essential that, in
clonorchis patients fit for surgery, proper assessment is
made.
Osman/Bach Lausten/El-Sefi/Boghdadi/
Rashed/Jensen
Opisthorchiasis and Dicrocoeliasis
C. sinensis has three relatives: (a) Opisthorchis felineus;
(b) Opisthorchis viverrini, and (c) Dicrocoeliasis dendriticum. These relatives are very much akin to C. sinensis.
Table 2 demonstrates the endemic distribution of these
flukes worldwide. The flukes have also been sporadically
reported from nonendemic areas [37].
Humans acquire opisthorchiasis by eating raw fish
containing infective metacercariae. The flukes reside inside the small bile ducts and gallbladder and do not
undergo systemic migration. The flukes are occasionally
found in the pancreatic duct [36]. As in C. sinensis the
pathological changes include: (a) dilated bile ducts with
thickened walls; (b) desquamation of bile duct epithelium
followed by proliferative hyperplasia, fibrosis and goblet
cell metaplasia [38], and (c) development of cholangiocarcinoma [38]. Cholangiocarcinoma is the leading type of
cancer in Northern Thailand but is rare in areas where the
fluke is absent [39]. Recent molecular biological studies
have revealed that mutations of ras oncogenes in intrahepatic cholangiocarcinomas are evident more frequently in
cases without any liver fluke association [40].
D. dendriticum is an unusual fluke in the human biliary tract [12]. The small parasite is seen especially in Eastern Europe and Russia [41]. There are two intermediate
hosts: (a) different types of land snails, and (b) small field
ants. Humans may accidentally ingest the infected ants
[42]. The fluke produces marked changes in the portal
tract and gives rise to a lump in the liver.
Clinical Presentation. The clinical picture of opisthorchiasis falls into three stages: (a) asymptomatic mild infestations with proliferation of the biliary tract epithelium;
(b) progressive infestations with involvement of the liver
parenchyma characterized by irregular appetite, diarrhea
and edema, and (c) severe infestations with cirrhosis and
portal hypertension [43]. Dicrocoeliasis produces limited
flatulence and diarrhea in mild cases and can simulate
C. sinensis with cholangitis in severe cases [12].
Diagnosis and Treatment. Diagnosis depends on the
demonstrations of eggs in stools. The eggs can only be
demonstrated by an experienced technician [44]. The
patients are treated as if they were infected with C. sinensis (table 6). The indication for surgical or endoscopical
treatment is the same as for other liver flukes. Dicrocoeliasis is treated with thymol and fuadin.
Prognosis. The prognosis is the same as that for patients infected with clonorchis.
Fascioliasis
Although fascioliasis is mainly a disease of herbivorous
animals, it occurs incidentally in man. Human fascioliasis
is caused mainly by two species, Fasciola hepatica and
Fasciola gigantica. Clinical cases of F. hepatica have been
reported from more than 40 countries in Europe, America, Asia, Africa and the Western Pacific. Human disease
due to F. gigantica infection has only been reported in
comparatively limited geographical areas, mainly in Africa, the Western Pacific and Hawaii. The pathology and
the clinical presentation of F. gigantica and F. hepatica
infections in man are similar. F. hepatica is a large trematode, 30 ! 13 mm residing in the intrahepatic biliary tree.
Fasciola infests the liver and biliary tree of cattle, sheep
and goat, inflicting severe often fatal disease. In endemic
countries almost 100% of sheep and 20% of cattle are
infected. Man is accidentally infected by eating watercress
contaminated with encysted metacercariae of the worm,
hereby making human fascioliasis uncommon [45]. The
adult worm lives in the bile ducts of the definitive host
[46]. The eggs are laid in the biliary duct and proceed with
the bile to the intestine and are evacuated in the feces in
an immature state. The eggs hatch a free-living miracidium which escapes from the egg and penetrates the first
intermediate host, the snail, where they mature. Once the
metacercariae are ingested, they exist in the duodenum.
The metacercariae migrate through the duodenal wall
into the peritoneal cavity. From the peritoneal cavity,
they penetrate the liver through the capsule of Glisson
and transverse the parenchyma producing numerous
tracts. The flukes become lodged in the bile ducts, where
they become large [47, 48]. Aberrant migration of fasciola
larvae can lead to ectopic fascioliasis with abscess formation involving almost any organ [49, 50]. This ectopic
migration is not seen in other liver fluke diseases [51].
Pathology. Fascioliasis can be characterized by three
distinct phases: (a) invasive (acute) phase; (b) latent
phase, and (c) chronic phase. The invasive phase corresponds to the penetration and migration of the juvenile,
immature parasites through the liver parenchyma with
the production of tissue necrosis, acute inflammation and
hemorrhages [50, 51], at times leading to severe anemia.
Fasciola can cause acute hemobilia and/or upper gastrointestinal bleeding. The invasive phase occurs during the
first 3 months after ingestion of the encysted metacercariae. After a period, healing takes place and evidence of
tissue destruction disappears completely [46]. The
chronic phase is established when the flukes gain access to
the biliary system. The fasciola produces biliary epithelial
hyperplasia. Thickening and dilatation of the ducts and
Biliary Parasites
Dig Surg 1998;15:287–296
293
the gallbladder wall occur (fig. 6). Other complications of
long-standing fascioliasis in humans have been reported,
including portal and biliary fibrosis, cirrhosis and portal
hypertension [52, 53]. However, the etiological relationship between fasciola infection and cirrhosis is not clear
[51].
Diagnosis. Clinical manifestations of F. hepatica have
different presentations, according to the phase of infection [50]. The acute phase may be severe but more commonly it passes without significant symptoms. In symptomatic patients the invasive phase usually begins with a
transitory period of dyspepsia, followed by high temperature (39–40 ° C), abdominal pain and tenderness. The
clinical symptoms can also include urticaria and respiratory symptoms. Marked eosinophilia (140%) may be
present [54, 55]. There may also be marked leukocytosis
and hypergammaglobulinemia [55]. No ova are present in
the stool, making the diagnosis of acute fascioliasis difficult. The diagnosis depends on clinical inference [45] and
various serological tests (table 5). On physical examination the following signs may appear: hepatomegaly and
splenomegaly; ascites; chest signs and jaundice. In the
latent phase patients may have gastrointestinal complaints or one or more relapses of the acute symptoms.
The chronic phase is characterized by intermittent biliary
obstruction and is due to the presence of the adult flukes
in the main bile ducts [56]. There are often fluctuating
elevations of alkaline phosphatases, bilirubin and transaminases. The patients may suffer from upper abdominal
pain (biliary colic), dyspepsia, fat intolerance, pruritus,
nausea and episodes of jaundice and fever simulating
acute cholangitis or cholecystitis with gallstones [57]. On
physical examination the liver is usually enlarged with or
without pain on palpation. Ascites may appear in advanced cases. The diagnosis in this phase is made by demonstrating the ova in the feces or duodenal contents
(fig. 1). ERCP is useful in the diagnosis of fascioliasis in
the chronic phase by visualizing the flukes directly
(fig. 2, 3) [58, 59]. Laparoscopy may reveal raised vermiform nodules at the surface of the liver [60]. Ultrasonography is important because it is often possible to show
mobile vermiform structures (fig. 4), duct dilatation and
irregular wall thickening [61, 62]. CT can demonstrate
peripheral tortuous lesions of the liver diagnostic of
hepatic fascioliasis [63].
Treatment. Uncomplicated biliary fascioliasis may be
managed by medical therapy as shown in table 6 [64–68].
Complicated biliary fascioliasis is treated surgically or
endoscopically depending on the complication. Cholecystectomy is performed if acute or chronic cholecystitis is
294
Dig Surg 1998;15:287–296
Fig. 6. Removed gallbladder of a patient with Fasciola hepatica
infection in its chronic phase. Marked thickening of the gallbladder
wall is seen together with three flukes.
present (fig. 6). Obstructive cholangitis caused by fasciola
is treated by ERCP with endoscopic sphincterotomy and
removal of the flukes.
Prognosis. The overall prognosis of uncomplicated fascioliasis is excellent. The prognosis of complicated fascioliasis depends among other things on the complication, the
presence of complicating diseases and the age of the
patient. Hepatic lesions heals completely.
Future Research
Human infections with biliary flukes have been reported from all over the world during the last two decades.
Most publications have described small series of hospital
patients with clinical symptoms. Only a few communitybased or epidemiological surveys have detected larger
numbers of infected persons [69, 70]. As human infections with biliary flukes may be asymptomatic and the
symptoms and signs are not pathognomonic, the actual
number of human cases is undoubtedly much greater than
reported. Accordingly, epidemiological studies have to be
carried out in endemic countries in order to try to establish the true incidence of infections with biliary flukes and
the sources of infection, so that appropriate measures to
eradicate the infections can be taken.
The mechanism of the immunity, i.e. cell- and/or antibody-mediated response to the flukes, varies from host to
host and, in the same host, according to the phase of the
infection. Little is known about the immunological re-
Osman/Bach Lausten/El-Sefi/Boghdadi/
Rashed/Jensen
sponse to human infection with biliary flukes. Future
research must focus on T-cell subpopulations, natural killer cells and inflammatory mediators in response to infection with biliary flukes at different phases.
The challenge to the control of these endemic diseases
is mainly its wide distribution in domestic animals and
the intermediate hosts. Available control measures are
aimed at chemotherapy and vector control, i.e. regular
chemical drenching of parasitized animals and eradication of intermediate hosts with molluscicides [71]. This
aspect has not received enough attention from public
health officials since these are the only measures that will
significantly eliminate the diseases. Recently, glutathione
S-transferase was used successfully as a vaccine against
liver fluke infection in ruminants [72].
Changing the dietary habits of the population may be
useful in controlling human infection. Thus, the addition
of a potassium permanganate solution (dilution of 24 mg/
l) to the water while washing raw leafy vegetables before
consumption allows removal of the sticky infective encysted metacercariae from the leaves of the vegetables. It
also may make these infective cysts perish [Farag H, personal commun., 73].
Studies on preventive measures are needed in order to
improve the control of these disease entities.
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References
1 Philips RD, Yung YH: Surgical helminthiasis
of the biliary tract. Ann Surg 1960;152:905–
910.
2 Yellin AE, Donovan AJ: Biliary lithiasis and
helminthiasis. Am J Surg 1981;142:128–136.
3 Shulman A: Non-Western patterns of biliary
stones and the role of ascariasis. Radiology
1987;161:425–430.
4 Choi TK, Wong U: Severe acute pancreatitis
caused by parasites in the common bile duct. J
Trop Med Hyg 1984;87:211–214.
5 Van Severen M, Lengel B, Dureuil J, Shapiro
M, Dire C: Hepatic ascaridiasis. Endoscopy
1987;19:140–142.
6 Purtilo DT: Clonorchiasis and hepatic neoplasms. Trop Geogr Med 1976;28:21–27.
7 El Sheikh ARM, Al-Karawi MA, Yasawy MI:
Modern techniques in the diagnosis and treatment of gastrointestinal and biliary tree parasites. Hepatogastroenterology 1991;38:180–
188.
8 Khuroo MS, Mahajan R, Zargar SA, Javid G,
Sapru S: Prevalence of biliary tract disease in
India: A sonographic study in adult population
in Kashmir. Gut 1989;30:201–205.
9 Choi BI, Kim HJ, Han MC, Do YS, Idan MH,
Lee SH: CT findings of clonorchiasis. AJR
1989;152:281–284.
10 Pfefferman R: Ascariasis of the biliary system.
Arch Surg 1972;195:118.
11 Khuroo MS, Zargar SA: Biliary Ascariasis: A
common cause of biliary and pancreatic disease in an endemic area. Gastroenterology
1985;88:418–423.
12 Ong GB: Helminthic diseases of the liver and
biliary tract; in Wright R, Alberti KGMM,
Karran S, Millward-Sadler GH (eds): Liver and
Biliary Disease. Philadelphia, Saunders, 1979,
pp 1267–1303.
13 Lloyd DA: Massive hepatobiliary ascariasis in
childhood. Br J Surg 1981;68:468–473.
14 Yang SCH, Laube PJ: Biliary ascariasis: Report
of 19 cases. Ann Surg 1946;123:299–303.
Biliary Parasites
15 Pillay SP, Baker LW, Angorn TB: Ascariasis
lumbricoides producing obstructive jaundice.
Ann R Coll Surg Edinb 1978;23:25–29.
16 Khoroo MS, Zargar SA, Mahajan R, Bhat LR,
Javid G: Sonographic appearances in biliary
ascariasis. Gastroenterology 1987;93:267–272.
17 Schulman A, Loston AJ, Heyenrych JJ, Abdurahman KE: Sonographic diagnosis of biliary
ascariasis. AJR 1982;139:485–489.
18 Cremin BJ: Ultrasonic diagnosis of biliary ascariasis. (A bull’s eye in thee triple O). Br J
Radiol 1982;55:683.
19 Kamath PSDC, Joseph R, Chandran SR, Rao
ML, Prakash AJ D’Cruz: Biliary ascariasis: Ultrasonography, endoscopic retrograde cholangiography and biliary drainage. Gastroenterology 1986;91:730–732.
20 Jessen K, Al-Mofleh I, Al-Mofarreh M: Endoscopic treatment of ascariasis causing acute obstructive cholangitis. Hepatogastroenterology
1986;33:275–277.
21 Manialawi MS, Khattar NY, Helmy MM, Burcharth F: Endoscopic diagnosis and extraction
of biliary ascariasis. Endoscopy 1986;18:204–
205.
22 Khuroo MS, Zargar SA, Mahajan R: Hepatobiliary and pancreatic ascariasis in India. Lancet 1990;335:1503–1506.
23 Ona FV, Dytoc JNT: Clonorchis-associated
cholangiocarcinoma: A report of two cases
with unusual manifestations. Gastroenterology
1991;101:831–839.
24 Chow CW, Allen PW: Clonorchis sinensis infestation of liver associated with cholangiocarcinoma. Pathology 1978;10:174–175.
25 Hou PC: The pathology of Clonorchis sinensis
infestation of the liver. J Pathol Bacteriol 1955;
70:53–64.
26 Hou PC: The relationship between primary
carcinoma of the liver and infestation with
Clonorchis sinensis. J Pathol Bacteriol 1956;72:
239–246.
Dig Surg 1998;15:287–296
27 Schwartz DA: Cholangiocarcinoma associated
with liver fluke infection: A preventable source
of morbidity in Asian immigrants. Am J Gastroenterol 1986;81:76–79.
28 Lim JH, Ko YT: Clonorchiasis of the pancreas.
Clin Radiol 1990;41:195–198.
29 Shugar RA, Ryan JJ: Clonorchis sinensis and
pancreatitis. Am J Gastroenterol 1975;64:400–
403.
30 Schwartz DA: Helminths in the induction of
cancer: Opisthorchis viverrini, Clonorchis sinensis and cholangiocarcinoma. Trop Geogr Med
1980;32:95–100.
31 Attwood HD, Chou ST: The longevity of Clonorchiasis sinensis. Pathology 1978;10:153–
156.
32 Choi TK, Wong KP, Wong J: Cholangiographic appearance in clonorchiasis. Br J Radiol 1984;57:681–684.
33 Leung J, Sung JY, Ling T, Chung S, Metreweli
C: Filamentous filling defects on ERCP is pathognomonic of hepatic clonorchiasis (abstract). Gastrointest Endosc 1988;34:189–190.
34 Lim JH: Radiologic findings of clonorchiasis.
AJR 1990;155:1001–1008.
35 Choi BI, Park JH, Kim YI, Ye ES, Kim SH,
Kim WH, Kim CY, Han MC: Peripheral cholangiocarcinoma and clonorchiasis: CT findings. Radiology 1988;169:149–153.
36 Ming-gang C, Yiang-Jiu H, Zhan-ru W, Yuequi W, Chen MG, Hua XJ, Wan ZR, Weng
YO, Wang MJ, Zhu PJ, He BZ, Yu MY: Praziquantel in 237 cases of clonorchis sinensis.
Chin Med J 1983;96:935–940.
37 Nodgaard H, Kristensen B: Dicrocoelium dendriticum eggs in faeces of 2 Somali boys in Denmark: Transitory elimination after arrival to
Denmark. Ugeskr Laeger 1995;157:4140.
38 Upatham ES, Brokleman WY, Viyanant V, et
al: Indidence of endemic Opisthorchis viverrini
infection in a village in Northeast Thailand.
Am J Trop Med Hyg 1985;34:903–906.
295
39 Vatanaspt V, Uttaravichien T, Mairiang EO,
Pairojkul C, Chartbanchachai W, Haswell-Elkins M: Cholangiocarcinoma in Northeast
Thailand. Lancet 1990;335:116–117.
40 Shirai T, Pairojkul C, Ogawa K, Naito H, Thamavit B, Bhundhisawat W, Ito N: Histopathological characteristics of cholangiocellular carcinoma in Northeast Thailand, where a region
infection with the liver fluke, Opisthorchis viverrini is endemic. Acta Pathol Jpn 1992;42:
734–739.
41 Krull WH, Mapes CR: Studies on the biology
of Dicrocoelium dendriticum including its relation to the intermediate host, Cidmella lubrica
(Mylleu). IX. Notes on cyst metacercaria, and
infection in the ant, Formica fusca. Cornell Vet
1953;43:389.
42 Mapes CR: Studies on the biology of Dicrocoelium dendriticum including its relation to the
intermediate host, Cionella lubrica. I. A study
of Dicrocoelium dendriticum and dicrocoelium
infection. Cornell Vet 1951;41:383.
43 Wykoff DE, Chittayasothorn K, Winn M: Clinical manifestation of O. viverrini infection in
Thailand. Am J Trop Med Hyg 1966;15:914–
918.
44 Sirisinha S: Immunodiagnosis of human liver
fluke infestation. Asian Pac J Allergy Immunol
1986;4:81.
45 Hadden JW, Pascarelli EF: Diagnosis and
treatment of human fascioliasis. JAMA 1967;
202:149–151.
46 Dawes B: Fasciola hepatica: A tissue feeder.
Nature 1963;198:1011–1012.
47 Hardman EW, Jones RLH, Davies AH: Fascioliasis: A large outbreak. Br Med J 1970;29:
502–505.
48 Ashton WLG, Boardman PL, D’Sa CJ, Everall
PH, Houghton AWJ: Human fascioliasis in
Shropshire. Br Med J 1970;29:500.
49 Acuna-Soto R, Braun-Roth G: Bleeding ulcer
in the common bile duct due to Fasciola hepatica. Am J Gastroenterol 1987;82:560–562.
296
Dig Surg 1998;15:287–296
50 Kayabali I, Gokcora IH, Yerdel MA, Ormeci
N: Hepatic fascioliasis and biliary surgery. Int
Surg 1992;77:154–157.
51 Jones EA, Kay JM, Milligan HP, Owens D:
Massive infection with Fasciola hepatica in
man. Am J Med 1977;63:836.
52 Nicholas JL: Obstruction of the common bile
duct by Fasciola hepatica. Br J Surg 1970;57:
544–546.
53 Rivero MA, Marcial MA: Biliary tract disease
due to Fasciola hepatica: Report of a case (abstract). Bol Asoc Med P R 1989;81:272–274.
54 Balci S: Human fascioliasis: Gall bladder invasion by flukes in a five-year-old boy. Clin Pediatr 1975;14:1068–1069.
55 Espina AM, Dumenigo BE, Fernandez R, Finley CM: Immunodiagnosis of human fascioliasis by enzyme-linked immunosorbent assay using excretory-secretory products. Am J Trop
Med Hyg 1987;37:605–608.
56 Munro AI: Liver fluke in the common bile
duct. Br J Surg 1965;52:76–77.
57 Clay RC, Straight WM: Surgical removal of liver flukes from the common bile duct. JAMA
1961;177:786–788.
58 Hauser SC, Bynum TE: Abnormalities on
ERCP in a case of human fascioliasis. Gastrointest Endosc 1984;30:80–82.
59 Rashed MYT, El-Sefi T, Boughdadi I: Endoscopic retrograde cholangiographic patterns of
biliary fascioliasis. Proc Eur IHPBA Congr
Athens 95, 1995, pp 259–263.
60 Cosme A, Alzate L, Orive V, Recasens M, Torrado J, Ruiz I, Arenas J: Laparoscopic findings
in liver fascioliasis: study of 13 cases. Rev Esp
Enferm Dig 1990;78:359–362.
61 Han JK, Choi BI, Cho JM, Chung KB, Han
MC, Kim CW: Radiological findings of human
fascioliasis. Abdom Imaging 1993;18:261–
264.
62 Bears VB, Pringot J, Geubel A, Trigaux JP,
Bigugnon G, Dooms G: Hepatobiliary fascioliasis: Non-invasive imaging findings. Radiology 1990;174:809–810.
63 Miguel F, Garrasca J, Garcia N, Bustamanta V,
Beltran J: CT findings in human fascioliasis.
Gastrointest Radiol 1984;9:157–159.
64 Schiappacasse RH, Mohammadi D, Christia
AJ: Successful treatment of severe infection
with Fasciola hepatica with Praziquantel. J Infect Dis 1985;152:1339–1340.
65 Farid Z, Kamal M, Woody J: Treatment of
acute toxaemic Fascioliasis. Trans R Soc Trop
Med Hyg 1988;82:299.
66 Eckhardt T, Heckers H: Treatment of human
fascioliasis with Niclofolan. Gastroenterology
1981;81:795–798.
67 Loutan L, Bouvier M, Rajanawisut B, Stalder
H, Rouan MC, Buescher G, Poltera AA: Single
treatment of invasive fascioliasis with Triclabendazole. Lancet 1989;12:383.
68 Racq Y, Besnier JM, Duong TH, Pavie G, Metman EH, Choutet P: Successful treatment of
acute fascioliasis with Bithionol. Hepatology
1991;14:1066–1069.
69 Strok MG, Venables GS, Jennings SMF, Beesley JR: An investigation of endemic fascioliasis
in Peruvian village children. J Trop Med Hyg
1973;76:231–235.
70 Ripert C, Tribouley J, Luong Dinh Giap G,
Combes A, Laborde M, Bourianne C: Epidemiologie de la fasciolose humaine dans le sud
ouest de la France. Méd Chir Dig 1988;17:
355–355.
71 Chen MG, Kenneth EM: Progress in Assessment of morbidity due to Fasciola hepatica
infection. Trop Dis Bull 1990;87:R2–R37.
72 Sexton JL, Milner AR, Panaccio M, Waddington J: Glutathione S transferase. Novel vaccine
against Fasciola hepatica infection in sheen
sheep. J Immunol 1990;145:3905–3910.
73 Soliman MS, Hammam HM, Awad A: Prevention of Fascioliasis. Cairo, Egyptian Medical Syndicate, 1995, pp 22–26.
Osman/Bach Lausten/El-Sefi/Boghdadi/
Rashed/Jensen