Caroli syndrome . Report of five pediatric cases

S.Mazigh Mrad , I.Selmi , L.Bouzidi , S.Yahyaoui , O.Bouyahia , S.Boukthir , A.Sammoud

Service de pédiatrie infantile C , Hôpital d’enfants de tunis

PED17

Caroli disease and caroli syndrome are congenital disorders to the intarhepatic bile ducts . They are both characterized by dilatation of the intrahepatic biliary tree .

The term Caroli disease is limited to ectasia or segmental dilatation of the large intrahepatic ducts . This form is less common than caroli syndrome , in which malformations of small bile ducts and congenital hepatic fibrosis are also present . This process can be either diffuse or segmental and may be limited to one lobe of the liver .

Introduction :

Data on five patients with the diagnosis of Caroli’s syndrome were entered into the archives of our institution from Junuary 1990 to December 2000 .

It was composed of three girls and two boys .

Material and methods :

Case sex Age of diagnosis

Cosanguineous marriage

1 F 3 years No2 F 9 months First degree3 F 8 years First degree4 M 17

monthsNo

5 M 2 years First degree

In our cases , childs were diagnosed at a relatively young age

The physical examination findings of hard hepatomegaly and firm splenomegaly made us suspect the diagnosis which was then confirmed by ultrasound abdomen or liver biopsy .

Patients with caroli syndrome may have recurrent episodes of cholangitis and are also at risk for associated bacteremia and sepsis (4M/5) .

They may also have complications of portal hypertension as is observed in congenital hepatic fibrosis ( hematemesis or melena secondary to bleedingvarices and ascites 3M/5 )

Associated cystic dilatation of kidneys was seen in 4 cases of our 5 patients ( renal tubular ectasia , medullary sponge kidney , cortical cyst , recessive polycystic kidney disease or rarely autosomal dominant polycystic kidney disease was discrebed ) . These patients are usually asymptomatic but may develop renal stone disease and infections .

It is also associated with a risk of cholangiocarcinoma at a rate of 100 times that of the general population .

Ultrasonography is the initial investigation of choice ; the pure form shows diverticulum like sacculi of intrahepatic biliary tree , more pronounced towards the center and can be segmental or generalized . It consists of portal vein radicles surrounded by the dilated bile ducts .

Kidney may be normal or of variable echogenicity .

Radiologic characteristics of caroli’s syndrome :

Hepatomegaly with bile ducts

Polycystic kidney

Polycystic kidney disease associated to Caroli’s syndrome

Scan is an invaluable adjunct that complements ultrasound . It can identify cholangiocarcinoma and hepatic masses not identified by ultrasound .

In the diagnosis of Caroli syndrome , the liver biopsy is not conclusive in all cases ; therefore the rapports of radiology above all the ultrasound scan .

The diagnosis is more difficult to establish in the case of fusiform dilatations of the biliary tracts and endoscopic retrograde cholangiopancreatography is the gold standard in this situation . In our cases , this investigation was not required .

Multiple hypodense rounded areas Dilated intrahepatic bile ducts

Saccular bile duct dilatation in caroli disease

Contrast-enhanced CT scan shows marked intrahepatic ductal dilatationInvolving entire liver . Enhancing central fibrovascular buddles are identified in many of dilated ducts ( central dot sign ) Enlarged spleen is partially visible

Contrast –enhanced CT scan shows intra and extrahepatic bile duct dilatation .Many intrahepatic ducts contain peripherally enhancing fibrovascular bundles .

Varices in caroli’s syndrome associated to ARPKDAxial contrast-enhanced CT scan shows enlarged and tortuous splenic veins , indicating portal hypertension

MRI : Caroli disease and autosomal polycystic kidney disease ( T2 )

Ultrasonography is widely available and is often used first in the diagnosis .

CT imaging is excellent for screening patients .

MRI can aid in the diagnosis . Also magnetic resonance cholangiopancreatography can be performed , and images show ductal anatomy well .

ERCP can be also performed in patients with Caroli disease .

In conclusion : imaging studies play a major role in the diagnosis of Caroli disease

Congenital fibrosis is a histopathological diagnosis

Histopathological intrahepatic bile duct ectasia and proliferation are associated with severe periportal fibrosis and confirm the congenital hepatic fibrosis componenet of Caroli’s syndrome .

Periductal fibrosis and stones were visible macroscopically in 3 patients .

histopathology :

Portal bile duct surrounded by chronic inflammation Fibrous portal expansion with bile ductules alongsepta is consistent with congenital hepatic fibrosis

The cause appears to be genetic . The simple form in an autosomal dominant trait while the complex form is an autosomal recessive trait .

Females are more prone to caroli disease than males .

Family history may include kidney and liver disease due to the link between caroli disease and ARPKD ( autosomal recessive polycystic kidney disease ) .

Causes :

PKHD 1 , the gene linked to ARPKD , has been found mutated in patients with Caroli syndrome .

The genetic basis for the difference between Caroli disease and Caroli’s syndrome has not be defined .

Location of the PKHD 1 gene on chromosome 6

The treatment depends on clinical features and the location of the biliary abnormality .

Antibiotics are used to treat the inflammation of the bile duct and ursoeoxycholic acid for hepatolithiasis (Ursodiol ) .

In diffuse cases of Caroli disease , treatment options include conservative or endoscopic therapy , internal biliary bypass procedures and liver transplantation in carefully selected cases .

Treatment :

Caroli’s syndrome is a rare congenital anomaly , it should be included in differential diagnosis in children presenting with abdominal pain and hepatomegaly .

Caroli’s syndrome and its complications have overlapping radiologic appearances that reflect the underlying pathology of fibrosis , ductal dilatation , cholangitis , stone formation , malignancy and renal cysts when they are associated .

In a genetic level , unbalanced translocation between the chromosome 3 and 8 seems to be responsible . This explains the familial clustering and its association with polycystic kidney disease. The natural history of caroli’s disease diagnosed antenatally is unclear .

Conclusion :

Thank you

Rdte Inès Selmi