eMedicine Specialties > Radiology > Gastrointestinal

Caroli Disease

William J Romano, MD, FRCPC, Director, Interventional Radiology Research, Department of Radiology, William Beaumont Hospital; Clinical Assistant Professor, Department of Radiology, Wayne State University School of Medicine

Updated: Apr 6, 2009

Introduction

Background

Caroli disease is a nonobstructive dilatation of the intrahepatic bile ducts, which was first described in 1958 by the French physician Jacques Caroli. This is a rare congenital disorder that classically causes saccular ductal dilatation, which usually is segmental. Caroli disease is associated with recurrent bacterial cholangitis and stone formation.

Drawing shows the main right hepatic duct and the multiple segmental branch dilatations related to Caroli disease. Note the saccular dilatations that can occur, involving the right lobe of liver in this case.

Dilated intrahepatic biliary tree without presence of air or stones. Both lobes of the liver are involved

Presentation

Demographics

• Caroli disease is rare but most often affects females.
• Complications of Caroli disease often manifest in young adults, leading to the diagnosis. Caroli disease can occur in children. As imaging techniques improve, earlier diagnosis may be possible. Prenatal diagnosis with fetal ultrasound has been reported.¹  The average age of patients at diagnosis is 22 years. 
• Morbidity is common and is related to complications of the disease. These include cholangitis, sepsis, choledocholithiasis, and cholangiocarcinoma. These morbid conditions often prompt the diagnosis. Portal hypertension also may be present. These problems can severely affect the patient's quality of life.
• Mortality in Caroli disease is indirect and caused by complications. After cholangitis occurs, a large proportion of patients die within 5-10 years.

The names of the intrahepatic biliary radicles are based on the lobes and segments of the liver that they drain. The right and left main ducts and segmental branches from these main channels subtend their respective liver segments. Liver segments are typically named on the basis of divisions related to the blood supply and venous drainage.

The extrahepatic ductal anatomy includes the cystic duct and the common hepatic and common bile ducts.

Caroli disease involves congenital cystic dilatation of the intrahepatic biliary radicles of the liver. It is believed to have an autosomal recessive inheritance pattern. It may be associated with autosomal recessive polycystic kidney disease. The likely mechanism involves an in utero event that arrests ductal plate remodeling at the level of the larger intrahepatic bile ducts. Insufficient resorption of the ductal plates leads to the formation of multiple primitive bile ducts surrounding the central portal vein. These enlarge, dilate, and become ectatic. This effect may be segmental. In addition to the intrahepatic involvement, extrahepatic bile duct dilatation may occur — perhaps as a consequence of recurrent cholangitis and gallstone passage — as may choledochal cysts.²

Two forms of Caroli disease exist: a simple or classic type and a second type (termed Caroli syndrome) that is associated with congenital hepatic fibrosis .³

Signs and symptoms

Patients may have bilirubinemia and abdominal pain. They generally are febrile. Other complaints, such as nausea and vomiting, may be nonspecific. Liver function test results may be abnormal and include elevated alkaline phosphatase levels. On examination, patients may have hepatomegaly, especially if they have hepatic fibrosis. Portal hypertension related to this may cause variceal bleeding. Elevation in white blood cell counts and positive blood culture results suggest sepsis and cholangitis. Patients may have long symptom-free periods. Malignancy occurs in approximately 7% of patients.

Other etiologies for these symptoms should be excluded. The differential diagnosis can include sclerosing cholangitis, Oriental cholangitis, choledochal cyst, and hydatid disease.

Complications

The complications of Caroli disease, especially recurrent bouts of cholangitis, may be the first clinical manifestations of the disorder. Intrahepatic calculi and abscesses are common. Stone passage can cause pancreatitis.

Treatment

Treat any diagnosed complication. Therapy depends on the clinical manifestations and the location of the biliary abnormality. Antibiotic treatment with broad-spectrum agents is extremely important. Prophylactic antibiotics have had poor and unpredictable results. The addition of oral agents such as ursodeoxycholic acid has no definite benefit. Prevention of the complications is ideal, but no method has been proven effective.

The most common and often first interventional radiologic procedure is percutaneous transhepatic cholangiography (PTC), which reveals dilated segmental intrahepatic biliary radicles. No obstruction is present in the extrahepatic biliary tree. Bile samples can be used for culturing and sensitivity determinations.

Drainage procedures with endoscopic retrograde cholangiopancreatography (ERCP) or percutaneous transhepatic cholangiography (PTC) are important, and sphincterotomy can aid biliary drainage and stone removal or subsequent passage and may decrease bouts of cholangitis. ERCP reveals dilated segmental intrahepatic biliary radicles. No obstruction is present. Stones may be noted. If the process is confined to one lobe, lobectomy completely relieves the symptoms. Internal surgical bypass (choledochojejunostomy, Roux-en-Y, hepaticojejunostomy) is helpful in diffuse forms of the disease. No cure for the disease exists.

With PTC or ERCP, the diagnosis can be made with a high degree of confidence when the large intrahepatic branches have focal or segmental involvement with cystic outpouchings in which the contrast medium collects. False-positive findings are rare with these techniques, and false-negative findings are related to poor filling in the dilated ducts (especially possible with ERCP).

Percutaneous biliary drainage (PBD) with an external catheter or, ideally, an internal/external catheter placed with its distal tip in the duodenum, allows decompression of the biliary tree.

Extracorporeal shock-wave lithotripsy or intraductal electrohydraulic lithotripsy with biliary drainage, stent placement, and liberal sphincterotomy is advocated as an important but aggressive method to treat and prevent choledocholithiasis.

Ultimately, liver transplantation may be required.^4,5,6 This is the best alternative when recurrent cholangitis has not yet developed.

Often, drainage tube placement is indicated, especially if bilirubinemia or possible infection (cholangitis) is present. Internal stent placement may be indicated. Generally, plastic temporary stents are used in nonmalignant conditions; these can be placed percutaneously with fluoroscopic guidance.

Biopsy procedures with brushes or image-guided placement of transabdominal needles may be required to exclude malignant complications. Solid masses can be evaluated or core biopsy samples can be obtained for histologic evaluation.

Preferred Examination

Imaging studies play a major role in the diagnosis of Caroli disease.

• Ultrasonography is widely available and is often  used first in the diagnosis of any process involving the liver; therefore, it is commonly performed early in the workup of patients with Caroli disease. Demonstration of the continuity of the cystic lesions with the bile ducts is paramount in diagnosis.
• Nuclear scintigraphy also may be performed in the initial workup and can be valuable in excluding obstructive causes for intrahepatic duct dilatation that are depicted on cross-sectional images.
• CT imaging is excellent for screening patients.

Caroli disease. CT image in a patient with biliary dilatation.

Dilated intrahepatic biliary tree without presence of air or stones. Both lobes of the liver are involved

• MRI can aid in the diagnosis. Also, magnetic resonance cholangiopancreatography (MRCP) can be performed, and images show ductal anatomy well, with additional techniques.
• ERCP can be performed in patients with Caroli disease and can aid in diagnosis. Biliary interventions also can be performed but the intrahepatic ducts can be difficult to access.

Caroli disease. Endoscopic retrograde cholangiopancreatographic images obtained during stone removal from the hepatic ducts. The patient is prone.

• PTC is a more invasive technique that can allow direct visualization of the biliary tree and then therapy with transcutaneous interventions. Drainage catheters may be placed to divert bile. Stones can be removed, or balloon sphincter dilatation can be performed.

Caroli disease. Contrast-enhanced percutaneous transhepatic cholangiographic image shows the dilated ducts in the left lobe of the liver.

Laboratory examinations also are important and include bilirubin level analysis and liver function testing. Elevated white blood cell counts indicate infection, possibly cholangitis. Cultures of the blood, if findings are positive, support a diagnosis of sepsis.

Biopsy of solid liver masses may be performed to aid in the diagnosis of cholangiocarcinoma. Congenital hepatic fibrosis must be diagnosed at histologic examination; this diagnosis can help exclude cirrhosis.

Limitations of Techniques

• Ultrasonography can be limited by air in the adjacent bowel.
• The many reasons for false-positive scintigraphic results are well known, and if biliary obstruction from a complicating factor is present, nuclear scans may be nondiagnostic.
• Artifact can affect CT scans. Not all patients can receive iodinated intravenous (IV) contrast.
• ERCP and PTC are invasive. ERCP cannot be performed if a gastric outlet obstruction or a previous surgical anastomosis (eg, gastrojejunostomy) cannot be crossed. PTC can be difficult if the peripheral ducts are not dilated, or PTC may be contraindicated if the patient has a severe allergy to radiographic contrast media or an uncorrected coagulopathy.
• MRI and MRCP can be hampered by artifact as well as patient factors such as claustrophobia or excessive weight.

Differential Diagnoses

Biliary Atresia

Other Problems to Be Considered

Choledochal cyst
Focal dilatation of the intrahepatic bile ducts
Hereditary ductal dilatation
Association with congenital hepatic fibrosis
Sclerosing cholangitis
Oriental cholangitis
Hydatid disease

Radiography

Findings

Plain abdominal radiographs are not helpful unless hepatic calculi are found. Barium examinations are not indicated. Traditional IV or oral cholangiography is not beneficial. However, ERCP is helpful.

Degree of Confidence

Confidence is poor because these are not appropriate studies.

Computed Tomography

Caroli disease. CT image in a patient with biliary dilatation.

Dilated intrahepatic biliary tree without presence of air or stones. Both lobes of the liver are involved

Findings

Dilated segmental intrahepatic biliary radicles are present without involvement of the extrahepatic biliary tree. Preinfused scans may show hyper-attenuating sludge and stones or debris.

Hypoattenuating, tubular branching structures are identified; these communicate and extend from the porta hepatis toward the periphery. CT scan with IV contrast enhancement can show tiny dots, representing intraluminal portal veins, within the dilated intrahepatic bile ducts. This is termed the central dot sign. Take 3D images with or without the CT cholangiographic technique to help prove the relationship of the dilated structure to the ductal system, although this is better accomplished with MRCP (see below). CT can help depict abscesses and guide percutaneous drainage.

Complications such as cholangitis, choledocholithiasis, or cholangiocarcinoma may be present and can be identified with CT imaging. Portal hypertension can be present and result in hepatosplenomegaly with varices. Contrast-enhanced images obtained through the kidneys can show associated multiple renal cysts.

Degree of Confidence

The diagnosis can be made confidently if irregular cystic lesions communicate with the dilated biliary tree. No obstruction is present without the usual peripheral tapering of intrahepatic ducts on the opposite side that extend from dilated central ducts and the dilated extrahepatic biliary tree. Liver cysts are round.

False Positives/Negatives

False-positive findings are unusual. Bilobar dilatation of the intrahepatic ducts from causes other than Caroli disease mimics obstruction and does not have the superior liver predominance characteristic of Caroli disease. Artifact can cause false-negative findings.

Magnetic Resonance Imaging

Findings

Dilated segmental intrahepatic biliary radicles can be identified with MRI, as with CT and ultrasonography. MRCP reveals similar findings and allows better review of the results, especially with a computer workstation. This noninvasive 3D technique is a good alternative to ERCP or direct cholangiography. This can confidently show the communication of the multiple cysts, which is mandatory for the differential diagnosis with cystic disease of the liver and multiple abscesses. In polycystic liver disease, the hepatic cysts rarely  communicate with the bile ducts and the bile ducts typically are intrinsically normal.² Complications of Caroli disease also can be identified with MRI.

Degree of Confidence

The confidence level is very high. MRI can be used to distinguish other forms of cystlike liver diseases. MRI plus MRCP has been proposed as the study of choice.^7,8

False Positives/Negatives

False-positive findings can occur with other cystic or cystlike lesions. Artifact can limit the evaluation and cause false-negative results.

Ultrasonography

Findings

Ultrasonography is currently the examination of choice. Dilated segmental intrahepatic biliary radicles are easily detected. No obstruction is present. The cystlike tubular anechoic spaces converge toward the porta hepatis. They are largest in the superior part of the liver. The intraluminal portal vein sign is related to the protrusion of the portal vein branches into the cyst wall. Color flow Doppler ultrasonography is helpful in showing blood flow in these branches but no flow is present in the bile-containing spaces. Portal branches bridge the cyst walls.

Ultrasonography can also help in the diagnosis of complications and in the follow-up of patients with Caroli disease. Intraductal calculi are echogenic with acoustic shadowing.

Ultrasonography-guided needle aspiration of bile from the cystlike lesions may be beneficial in the diagnosis of cholangitis and in confirming that the cysts communicate with the biliary tree. Congenital hepatic fibrosis in Caroli syndrome may be diagnosed with sonograms that show abnormal liver echogenicity. Ultrasonography-guided core biopsy may be performed, if necessary, to obtain liver samples for histologic evaluation to confirm this condition. In addition, polycystic renal disease, which is associated with Caroli disease, can be confirmed with sonography.

Degree of Confidence

Ultrasonography is an excellent tool. A positive result has good predictive value and permits diagnosis with a high level of confidence. Caroli disease is the only condition in which dilated ducts surround the portal radicles; this finding at ultrasonography may obviate other invasive diagnostic techniques.

False Positives/Negatives

Few variants affect diagnosis with ultrasonography. Choledochal cyst or other cystic diseases, including congenital or acquired cystic masses, may cause false-positive findings. These structures do not communicate with the biliary tree. False-negative results occur if the liver is not fully evaluated.

Nuclear Imaging

Findings

Hepatobiliary scintigraphy with technetium-99m iminodiacetic acid (^99mTc IDA) agents reveals large, irregular, multifocal collections of the radiotracer in the liver. A beaded appearance in the dilated ducts, if present, is somewhat pathognomonic. These collections correspond to the segmental dilatations, and no extrahepatic obstruction is present, although bile stasis and stone formation may result in atypical obstruction.

On early images, if the ducts are dilated enough, they appear as photopenic branching areas within the liver. Single photon emission computed tomography (SPECT) may better outline the ductal pattern but it is most helpful in the evaluation of focal disease.

Degree of Confidence

The confidence level is moderate to high when focal or segmental involvement is present in the large intrahepatic branches without obstruction. Overall, scintigraphy is not helpful compared with cross-sectional imaging techniques.

False Positives/Negatives

False-positive findings may be related to other cystic lesions of the biliary tree. False-negative findings are related to problems with the technique. Cholangitis can impair hepatic uptake of radiotracers. Obstruction related to stones or debris from the ducts may cause misdiagnosis.

Angiography

Findings

Intervention

Medicolegal Pitfalls

• Iatrogenic complications from interventional radiology procedures such as PTC, stone removal, tube drainage, and stent placement can be serious. These include, but are not limited to, bleeding, hemobilia, infection, sepsis, reactions to the contrast medium, pneumothorax, bile ascites, allergic reactions to other procedural medications, renal failure, liver injury, and liver infarction. Surgical correction may be required.
• Misdiagnosis of Caroli disease is not uncommon because the diagnosis is largely one of exclusion. Abnormal findings on cross-sectional images are typical but their cause may be mistaken. Misinterpretation of the imaging results may delay diagnosis of the disease or its complications.
• Misdiagnosis of cancer related to cholangiocarcinoma in a patient with Caroli disease is possible. Once Caroli disease is diagnosed, related complications should be excluded. If changes (eg, development of a mass) occur with subsequent studies, cholangiocarcinoma should be suspected.

Special Concerns

• Pediatric patients require tailored examinations.

Multimedia

Media file 1: Percutaneous transhepatic cholangiographic image of Caroli disease. During catheter placement, contrast material previously injected outlines the irregular, dilated saccular ductal branches.

Media file 2: Drawing shows the main right hepatic duct and the multiple segmental branch dilatations related to Caroli disease. Note the saccular dilatations that can occur, involving the right lobe of liver in this case.

Media file 3: Caroli disease. CT image in a patient with biliary dilatation.

Media file 4: Caroli disease. Endoscopic retrograde cholangiopancreatographic images obtained during stone removal from the hepatic ducts. The patient is prone.

Media file 5: Caroli disease. Contrast-enhanced percutaneous transhepatic cholangiographic image shows the dilated ducts in the left lobe of the liver.

Media file 6: Caroli disease. Image obtained after percutaneous transhepatic cholangiography shows the percutaneous biliary drainage tube in place.

Media file 7: Dilated intrahepatic biliary tree without presence of air or stones. Both lobes of the liver are involved

References

1. Sgro M, Rossetti S, Barozzino T, Toi A, Langer J, Harris PC, et al. Caroli's disease: prenatal diagnosis, postnatal outcome and genetic analysis. Ultrasound Obstet Gynecol. Jan 2004;23(1):73-6. [Medline].

2. Levy AD, Rohrmann CA Jr, Murakata LA, Lonergan GJ. Caroli's disease: radiologic spectrum with pathologic correlation. AJR Am J Roentgenol. Oct 2002;179(4):1053-7. [Medline]. [Full Text].

3. Ananthakrishnan AN, Saeian K. Caroli's disease: identification and treatment strategy. Curr Gastroenterol Rep. Apr 2007;9(2):151-5. [Medline].

4. Wang ZX, Yan LN, Li B, Zeng Y, Wen TF, Wang WT. Orthotopic liver transplantation for patients with Caroli's disease. Hepatobiliary Pancreat Dis Int. Feb 2008;7(1):97-100. [Medline].

5. Ulrich F, Pratschke J, Pascher A, Neumann UP, Lopez-Hänninen E, Jonas S, et al. Long-term outcome of liver resection and transplantation for Caroli disease and syndrome. Ann Surg. Feb 2008;247(2):357-64. [Medline].

6. Millwala F, Segev DL, Thuluvath PJ. Caroli's disease and outcomes after liver transplantation. Liver Transpl. Jan 2008;14(1):11-7. [Medline].

7. Asselah T, Ernst O, Sergent G. Caroli''s disease: a magnetic resonance cholangiopancreatography diagnosis. Am J Gastroenterol. Jan 1998;93(1):109-10. [Medline].

8. Guy F, Cognet F, Dranssart M, Cercueil JP, Conciatori L, Krausé D. Caroli's disease: magnetic resonance imaging features. Eur Radiol. Nov 2002;12(11):2730-6. [Medline].

9. Caroli-Bosc FX, Demarquay JF, Conio M. The role of therapeutic endoscopy associated with extracorporeal shock- wave lithotripsy and bile acid treatment in the management of Caroli''s disease. Endoscopy. Aug 1998;30(6):559-63. [Medline].

10. Ciambotti GF, Ravi J, Abrol RP. Right-sided monolobar Caroli''s disease with intrahepatic stones: nonsurgical management with ERCP. Gastrointest Endosc. Nov-Dec 1994;40(6):761-4. [Medline].

11. Gold DM, Stark B, Pettei MJ. Successful use of an internal biliary stent in Caroli''s disease. Gastrointest Endosc. Dec 1995;42(6):589-92. [Medline].

12. Kaiser JA, Mall JC, Salmen BJ. Diagnosis of Caroli disease by computed tomography: report of two cases. Radiology. Sep 1979;132(3):661-4. [Medline].

13. Marchal GJ, Desmet VJ, Proesmans WC. Caroli disease: high-frequency US and pathologic findings. Radiology. Feb 1986;158(2):507-11. [Medline].

14. Mittelstaedt CA, Volberg FM, Fischer GJ. Caroli''s disease: sonographic findings. AJR Am J Roentgenol. Mar 1980;134(3):585-7. [Medline].

15. Sgro M, Rossetti S, Barozzino T, Toi A, Langer J, Harris PC, et al. Caroli's disease: prenatal diagnosis, postnatal outcome and genetic analysis. Ultrasound Obstet Gynecol. Jan 2004;23(1):73-6. [Medline].

16. Toma P, Lucigrai G, Pelizza A. Sonographic patterns of Caroli''s disease: report of 5 new cases. J Clin Ultrasound. Mar-Apr 1991;19(3):155-61. [Medline].

Keywords

Caroli disease, Caroli's disease, communicating cavernous ectasia, congenital cystic dilatation of the intrahepatic biliary tree

Contributor Information and Disclosures

Author

William J Romano, MD, FRCPC, Director, Interventional Radiology Research, Department of Radiology, William Beaumont Hospital; Clinical Assistant Professor, Department of Radiology, Wayne State University School of Medicine
William J Romano, MD, FRCPC is a member of the following medical societies: Royal College of Physicians and Surgeons of Canada
Disclosure: Nothing to disclose.

Medical Editor

Zahir Amin, MD, MBBS, MRCP, FRCR, Consulting Staff, Department of Imaging, University College Hospital, UK
Zahir Amin, MD, MBBS, MRCP, FRCR is a member of the following medical societies: British Institute of Radiology, British Medical Association, and Royal College of Radiologists
Disclosure: Nothing to disclose.

Pharmacy Editor

Bernard D Coombs, MB, ChB, PhD, Consulting Staff, Department of Specialist Rehabilitation Services, Hutt Valley District Health Board, New Zealand
Disclosure: Nothing to disclose.

Managing Editor

Abraham H Dachman, MD, FACR, Professor, Department of Radiology, The University of Chicago School of Medicine; Director of CT, Department of Radiology, The University of Chicago Hospitals
Abraham H Dachman, MD, FACR is a member of the following medical societies: Radiological Society of North America
Disclosure: iCAD, Inc. Consulting fee Consulting; iCAD, Inc. Grant/research funds Other; GE Healtcare, Inc. Honoraria Speaking and teaching

CME Editor

Robert M Krasny, MD, Consulting Staff, Department of Radiology, Resolution Imaging Medical Corporation
Robert M Krasny, MD is a member of the following medical societies: American Roentgen Ray Society and Radiological Society of North America
Disclosure: Nothing to disclose.

Chief Editor

John Karani, MBBS, FRCR, Clinical Director of Radiology and Consultant Radiologist, Department of Radiology, King's College Hospital, London
John Karani, MBBS, FRCR is a member of the following medical societies: British Institute of Radiology, British Society of Interventional Radiology, Cardiovascular and Interventional Radiological Society of Europe, European Society of Gastrointestinal and Abdominal Radiology, European Society of Radiology, Radiological Society of North America, and Royal College of Radiologists
Disclosure: Nothing to disclose.

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