Caroli Disease

Published on 19/07/2015 by admin

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Last modified 22/04/2025

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 Variably distributed (diffuse, lobar, or segmental)

image Enhancing “dot” (portal radicles) at either center or periphery of dilated duct: Central dot sign on CECT
image Hepatolithiasis frequent
• MR: T1 hypointense, T2 hyperintense, nonenhancing cysts variably distributed in liver

image Communication with biliary tree well visualized on MRCP
image Central dot sign visible on T1WI C+
image Hepatolithiasis: Signal voids within dilated ducts
• ERCP: Dilatation (usually saccular) of large intrahepatic ducts with alternating biliary strictures

PATHOLOGY

• Pathogenesis not completely understood but likely due to arrest or derangement in remodeling of ductal plate

image Considered to be variant of fibropolycystic liver disease
image Typically autosomal recessive inheritance
• Frequently associated with polycystic hepatorenal syndrome (usually autosomal recessive), hepatic fibrosis, and medullary sponge kidney
• Presentation in childhood or young adulthood often due to cholangitis, cholestasis, or progressive hepatic fibrosis

CLINICAL ISSUES

• Supportive therapy (antibiotics, sphincterotomy, stone removal) for cholangitis and stone disease
• Surgery, including partial hepatectomy or liver transplant, may be option depending on distribution of involvement
image
(Left) Gross photograph of the liver shows clusters of dilated and cystic intrahepatic bile ducts image in a patient with Caroli disease. (Courtesy J. Misdraji, MD.)

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(Right) Frontal ERCP shows saccular dilatation of the large intrahepatic ducts as well as multiple ductal filling defects, representing biliary calculi image, a characteristic constellation of findings in Caroli disease.
image
(Left) Axial T2WI MR shows gross, irregular dilation of the intrahepatic bile ducts image.

image
(Right) Coronal MRCP in the same patient makes it easier to recognize the continuity of the cystic intrahepatic lesions image with the biliary tree, compatible with Caroli disease. The gallbladder is also seen image. This patient was treated with liver transplantation.

TERMINOLOGY

Synonyms

• Communicating cavernous biliary ectasia

Definitions

• Originally divided into 2 variants

image Caroli disease (“pure” form): Congenital multifocal saccular dilation of large intrahepatic bile ducts (IHBDs) in absence of other hepatic abnormalities
image Caroli syndrome (“complex” form) : More common variant characterized by cystic dilatation of large intrahepatic ducts, hepatic fibrosis, and portal hypertension

IMAGING

General Features

• Best diagnostic clue

image Multiple intrahepatic cysts of varying size that communicate with biliary tree
image Central dot sign: Enhancing tiny dots (portal radicles) within dilated intrahepatic bile ducts on CECT
• Location

image Saccular dilatation of intrahepatic ducts can be diffuse, lobar, or segmental

– Caroli syndrome usually involves entire liver diffusely
– Caroli disease occasionally can be lobar (usually left lobe) but usually predominates in 1 segment

image Number of cysts usually < 10 in cases with lobar distribution
• Size

image Cysts can be of variable size (mm to cm)
• Morphology

image Segmental saccular dilatation of large intrahepatic bile ducts separated by normal or dilated bile ducts

– Individual cysts are contiguous with biliary tree
image Size of common bile duct (CBD) is classically thought to be normal

– Extrahepatic duct may be dilated in up to 50%, possibly due to prior cholangitis, passage of stones, or concurrent choledochal cyst
image Caroli syndrome (more common variant) frequently associated with autosomal recessive polycystic kidney disease (ARPKD), medullary sponge kidney, medullary cystic disease
• Considered to be a variant of fibropolycystic liver disease

image Other variants include congenital hepatic fibrosis, autosomal dominant (ADPKD) and recessive (ARPKD) polycystic liver and kidney disease, biliary hamartomas, and choledochal cyst
• Todani classification of choledochal cysts

image Caroli disease is classified as type V choledochal cyst: Cystic dilation of intrahepatic bile ducts

Radiographic Findings

• Endoscopic retrograde cholangiopancreatogram (ERCP)

image Dilatation (saccular more often than fusiform) of large intrahepatic ducts (either diffuse, lobar, or segmental) with alternating sites of bile duct strictures/narrowing
image Hepatolithiasis and sludge are common and appear as filling defects
image In cases with cholangitis, ERCP may demonstrate communication of biliary tree with biliary abscesses

CT Findings

• Nonenhancing cysts of varying size that communicate with biliary tree

image Variably distributed (diffuse, lobar, or segmental)
• Enhancing portal radicles surrounded by saccular dilated ducts yields central dot sign on CECT

image Enhancing “dot” can be either at center or periphery of dilated duct
• Hyperdense hepatolithiasis may be easier to perceive on NECT
• Other findings related to concurrent hepatic fibrosis

image Hypertrophic lateral segment, atrophic right lobe (similar to other causes of cirrhosis)
image Normal or hypertrophied medial segment (distinct feature not usually seen in other causes of cirrhosis)
• Other findings related to frequently associated renal abnormalities

image Findings of ARPKD, ADPKD, medullary sponge kidney, medullary cystic disease

MR Findings

• T1 hypointense, T2 hyperintense, nonenhancing cysts variably distributed in liver

image Communication with biliary tree most evident on MRCP
image Due to communication with biliary tree, cysts fill with contrast in hepatobiliary phase when using hepatobiliary contrast agent (e.g., gadoxetate [Eovist])
image Central dot sign visible on T1WI C+: Enhancement of portal radicles within dilated IHBD 

– Portal radicles may appear as signal void at center of dilated ducts on T2W or MRCP images
image Hepatolithiasis appears as nonenhancing signal voids within dilated ducts
• Other findings related to concurrent hepatic fibrosis, with involved areas appearing T1 and T2 hypointense with volume loss
• Other findings related to frequently associated renal abnormalities, including polycystic disease, medullary sponge kidney, or fibrotic small kidneys

Ultrasonographic Findings

• Dilated intrahepatic bile ducts: Communication between cysts and biliary tree may be difficult to demonstrate on US
• Echogenic septa may completely or incompletely traverse dilated lumen of bile ducts (intraductal bridging sign)
• Small portal venous branches may be partially or completely surrounded by dilated IHBD (US correlate of central dot sign

image Visible as focus on color Doppler vascularity within (center or periphery) dilated bile duct
• Intraductal calculi common and appear as echogenic nodules with dense posterior acoustic shadowing
• Areas of hepatic fibrosis associated with areas of heterogeneous echotexture (and variable echogenicity)

Nuclear Medicine Findings

• Hepatobiliary scan: Unusual pattern of retained radiotracer activity throughout liver within dilated ducts

Imaging Recommendations

• Best imaging tool

image MRCP
• Protocol advice

image  

DIFFERENTIAL DIAGNOSIS

AD Polycystic Hepatic Disease

• Numerous (> 10 but usually hundreds) hepatic cysts
• No biliary dilatation or communication between cysts and biliary tree

image Cysts do not opacify on cholangiography
• Frequent association with renal cysts

Biliary Hamartomas

• Ductal plate malformation involving small-sized intrahepatic ducts (variant of fibropolycystic disease)
• Rare, benign, congenital malformation of bile ducts
• Location: Intraparenchymal
• Innumerable subcentimeter nodules in liver, which can be completely cystic or have solid components which enhance and become isodense with liver
• Biliary hamartomas do not communicate with biliary tree

Primary Sclerosing Cholangitis

• Strictures of intra- and extrahepatic bile ducts with alternating strictures, normal ducts, and dilated ducts
• Ductal dilatation much less severe compared to Caroli disease, and dilated ducts do not appear saccular
• Often progresses to cirrhosis and liver failure

Ascending Cholangitis

• Infection of biliary tree secondary to biliary obstruction (usually due to choledocholithiasis)
• May result in development of intrahepatic biliary abscesses that communicate with bile ducts
• Unlike Caroli disease, margins of abscesses are thick and irregular with surrounding parenchymal edema

image Bile duct walls may be thickened and hyperenhancing due to inflammation

Recurrent Pyogenic Cholangitis

• Disease characterized by formation of pigment stones throughout biliary tree, with resultant biliary strictures and repeated bouts of cholangitis 

image Biliary calculi may be cast-like and expand ductal lumen
• Dilatation of both intra- and extrahepatic bile ducts, usually of cylindrical morphology (not saccular)
• Almost always in patients from southeast Asia, and may be associated with parasitic and bacterial biliary infections
• Associated with parasitic and bacterial biliary infection

image Liver flukes (Clonorchis sinensis, Opisthorchis species, Fasciola hepatica)

PATHOLOGY

General Features

• Etiology

image Pathogenesis not completely understood, but likely due to arrest or derangement in remodeling of ductal plate

– Caroli disease: Malformation of large-sized ducts
– Caroli syndrome: Malformation of large and small-sized ducts

image Ductal plate anomaly of small-sized ducts is responsible for hepatic fibrosis
• Genetics

image Typically autosomal recessive inheritance (rare instances of autosomal dominant inheritance reported)
image Believed to be caused by mutation in PKHD1 (polycystic kidney and hepatic disease) gene on chromosome 6 (encoding fibrocystin)

– Same genetic basis as ARPKD, but different manifestation of same genetic disease
• Associated abnormalities

image Medullary sponge kidney and renal fibrosis
image Autosomal recessive polycystic liver and kidney disease (rarely associated with ADKPD)
image Hepatic fibrosis, hepatic cysts, biliary hamartomas
image Choledochal cysts
• Embryological anatomy

image Ductal plate malformation: Incomplete remodeling of ductal plate leading to persistence of embryonic biliary ductal structures
image Varying spectrum of “adult” and “juvenile” manifestations of ductal malformations
image Dependent upon timing/stage of biliary involution-remodeling

– Congenital hepatic fibrosis and bile duct hamartomas: Malformation of small interlobular bile ducts

image Varying degrees of hepatic fibrosis with autosomal recessive polycystic disease: Progressive liver fibrosis if liver involvement is predominant
– Autosomal dominant polycystic disease: Malformation of medium-sized intrahepatic ducts
– Caroli disease: Ductal plate malformation of large intrahepatic bile ducts
– Choledochal cyst: Malformation of extrahepatic bile duct

Staging, Grading, & Classification

• Caroli disease/syndrome is considered Todani type V choledochal cyst

Gross Pathologic & Surgical Features

• Saccular dilatations of large intrahepatic bile ducts
• Diffuse, lobar, or segmental distribution
• Caroli syndrome is almost always a diffuse process
• Caroli disease can have lobar distribution (usually in left lobe)

image Segmental predominance

Microscopic Features

• Caroli disease

image Segmental saccular dilatation of large IHBD
image Dilated ducts lined by hyperplastic or ulcerated biliary epithelium
image Normal hepatic parenchyma
• Caroli syndrome

image Segmental saccular dilatation of IHBD
image Proliferation of bile ductules and fibrosis
image Fibrosis and enlargement of portal triads
image Hypoplastic portal vein branches

CLINICAL ISSUES

Presentation

• Most common signs/symptoms

image Usually asymptomatic in early stage, but often symptomatic in childhood or early adulthood
image Patients with both Caroli syndrome and Caroli disease may experience symptoms related to biliary disease, most often fever and abdominal pain due to recurrent bouts of cholangitis

– Biliary obstruction may result in symptoms of cholestasis (jaundice, pruritus, etc.)
image Caroli syndrome may present with symptoms related to hepatic fibrosis (i.e., portal hypertension)

– Hepatomegaly
• Other signs/symptoms

image Enlarged kidneys (due to associated ARPKD)
• Clinical profile

image Several modes of presentation based on age of onset
• Lab data

image ↑ alkaline phosphatase, ↑ GGT, ↑ bilirubin (direct)
image ↑ WBC
image May have ↑ AST/ALT due to cholangitis and hepatic microabscesses
image Coagulopathy due to fat-soluble vitamin malabsorption (vitamin K)
• Diagnosis is almost always based on imaging findings (especially MRCP and ERCP), and biopsy is not typically indicated

Demographics

• Age

image Condition is present at birth, although patients can be asymptomatic for years

– 80% become symptomatic before age of 30
image Caroli disease: Symptoms usually by 2nd/3rd decades
image Caroli syndrome: Symptoms can present during infancy or childhood

– Concurrent renal anomalies present early in life
• Gender

image M:F = 1:1
• Epidemiology

image Rare disease

Natural History & Prognosis

• Complications

image Recurrent bouts of cholangitis ± hepatic abscesses

– Biliary dilatation → stagnation of bile → intraductal sludge/stone formation → cholangitis
image Stone formation (95%) (usually calcium bilirubinate)
image Secondary biliary cirrhosis ± portal hypertension
image Cholangiocarcinoma (up to 7% risk)
• Prognosis

image Depends on severity of disease and coexisting renal disease
image Long-term prognosis for Caroli disease is usually poor

Treatment

• Supportive therapy for cholangitis/sepsis and stone disease

image Antibiotics for cholangitis
image Sphincterotomy/stone extraction for extrahepatic stones
image Intrahepatic stones may be treated with lithotripsy  

– Lithotripsy may be intraductal or extracorporeal
image Oral bile salts may be an option, especially for intractable intrahepatic stones (e.g., ursodeoxycholic acid [UDCA])

– Rationale: ↑ bile flow and ↓ stasis
• Decompression of biliary tract can be performed via external drainage or biliary-enteric anastomosis
• Surgery is an option in select patients

image Hepatic lobectomy or segmentectomy possible if dilated ducts confined to lobe or segment
image Liver transplantation possible for diffuse involvement of entire liver

– Comparable results to liver transplantation for other indications

DIAGNOSTIC CHECKLIST

Consider

• Distinguish Caroli disease from other liver diseases that are associated with either hepatic cysts or dilated bile ducts

Image Interpretation Pearls

• Cholangiography

image Bulbous dilatations of peripheral intrahepatic bile ducts
• ERCP

image Saccular dilatations show communication with IHBD, which differentiates Caroli from other variants of fibropolycystic disease
image
(Left) Axial CECT shows massive dilatation of the intrahepatic bile ducts. Note the “central” or “eccentric” dot within many of the cystic structures, representing portal radicles image, a classic imaging finding in Caroli disease.

image
(Right) Axial CECT shows Caroli syndrome in a 40-year-old woman with hepatic and renal failure. Note the cystic dilations of the bile ducts and central dot sign image. Hepatic and renal fibrosis was the cause of liver and renal failure and portal hypertension in this patient.
image
(Left) Color Doppler ultrasound of a patient with Caroli disease shows saccular dilatation of the branches of the left bile duct image. Note eccentric color Doppler “dot” within the medial segmental branch of the left duct image, similar to the central dot sign more commonly described on CT or MR.

image
(Right) Axial T2WI MR shows saccular dilatation of the intrahepatic bile ducts, many of which contain large hypointense calculi image.
image
(Left) Coronal T2 MR demonstrates multiple cysts image predominantly in the right hepatic lobe which communicate with the biliary tree, compatible with Caroli syndrome.

image
(Right) Coronal CECT in the same patient again demonstrates saccular dilatation image of multiple ducts in the right hepatic lobe. Note the diffusely low attenuation of the parenchyma in the involved portions of the liver, likely on the basis of hepatic fibrosis and edema from cholangitis.
image
Sagittal sonogram shows cystic lesions in the liver, some with hyperechoic calculi image.

image
Axial CT shows marked saccular dilation of the intrahepatic biliary ducts in the right liver lobe. Within some of the cystic biliary spaces, small calculi are evident image.
image
Coronal MRCP MIP reconstruction shows cystic dilation image of many intrahepatic ducts, many of which contain low signal intensity calculi image in this patient with Caroli disease.
image
Axial CECT shows a dysmorphic (scarred and deformed) liver, with hepatic fibrosis confirmed on biopsy. Intrahepatic bile ducts image are irregularly dilated and contain calculi image.
image
ERCP in the same patient demonstrates cystic dilation image of the intrahepatic ducts (Caroli disease) with distortion and displacement of the ducts, probably due to the congenital hepatic fibrosis.
image
Coronal T2 HASTE MR image demonstrates several cysts image clustered in the left hepatic lobe in a patient with Caroli syndrome. Note the cystic replacement of the kidneys due to concurrent autosomal dominant polycystic kidney syndrome.
image
Axial T2WI FSE MR of a 35-year-old woman with Caroli syndrome shows saccular dilatation of posterior segmental ducts image and innumerable, coalescent hyperintense biliary hamartomas image.
image
Axial T2WI FSE MR of young male with Caroli syndrome (saccular biliary ductal dilatation and hepatic fibrosis) shows marked right lobe predominant intrahepatic biliary ductal dilatation.
image
Axial T2WI FSE MR of a 14-year-old boy shows massive saccular intrahepatic biliary ductal dilatation and a stone within the distal left bile duct image. Ductal dilatation extends to the periphery of the liver.
image
Axial NECT in the same patient shows signs of portal hypertension, including splenomegaly, ascites, and varices image. Note the end-stage kidneys image, all findings are due to congenital fibropolycystic disease of the liver and kidneys.
image
Axial NECT shows Caroli syndrome in a 20-year-old woman with hepatic and renal insufficiency. Note the dysmorphic liver and multiple cysts with the characteristic “central dot” sign image, representing the portal triads.
image
Axial CECT shows curvilinear and saccular dilations of the intrahepatic biliary tree. Some of the cystic collections contain gas image, and others exhibit the “central dot” sign image.
image
Coronal CECT demonstrates an enhancing portal vein radicle image within 1 of the cystic spaces noted in the right lobe. This is the “central dot” sign, with dilated bile ducts wrapped around. Also note the enlarged spleen and renal allograft image.
image
Percutaneous transhepatic cholangiogram shows generalized saccular dilatation of the intrahepatic and extrahepatic bile ducts. There is a spectrum of hepatic parenchymal and biliary abnormalities that may be associated with congenital defects of the biliary ductal plate.
image
Coronal MRCP of a 22-year-old male liver transplant candidate with Caroli syndrome shows marked bilobar intrahepatic biliary ductal dilatation (right > left) and a normal-appearing gallbladder image.

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