Caroli disease

Infobox_Disease
Name = PAGENAME


Caption = Figure 1 Bilary tract, system, or tree includes the gallbladder and the bile ducts.
DiseasesDB = 29874
ICD10 =
ICD9 =
ICDO =
OMIM = 263200
MedlinePlus =
eMedicineSubj = radio
eMedicineTopic = 131
MeshID = D016767

Caroli disease (kuh-ROH-leez duh-zeez) is a rare inherited disorder that dilates the bile ducts from the liver. There are two types of Caroli disease, the most common being the simple, or isolated case where the bile ducts are widened by ectasia. The second, more complex, case is commonly known as Caroli Syndrome. This complex form is also linked with portal hypertension and congenital hepatic fibrosis. [ [http://www.indianpediatrics.net/aug2004/848.pdf Karim, Bazlul. August 2007. Caroli’s Disease Case Reports. "Indian Pediatrics, Vol 41: 848-850".] ] The differences between the causes of the two cases have not yet been discovered. Caroli disease is also associated with liver failure and polycystic kidney disease. The disease affects about 1 in 1,000,000 people, with more reported cases of Caroli syndrome than of Caroli disease. [ [http://www.emedicine.com/radio/topic131.htm Romano, William J, MD. Oct 2002. Caroli Disease. eMedicine from WebMD.] ]

Caroli disease also is known as communicating cavernous ectasia, or congenital cystic dilatation of the intrahepatic biliary tree. Caroli disease is distinct from other diseases that cause ducal dilatation caused by obstruction, in that it is not one of the many choledochal cyst derivatives. [ [http://www.indianpediatrics.net/aug2004/848.pdf Karim, Bazlul. August 2007. Caroli’s Disease Case Reports. "Indian Pediatrics, Vol 41: 848-850".] ]

History

Jacques Caroli, a gastroenterologist, first described a rare congenital condition in 1958. [ [http://chorus.rad.mcw.edu/doc/00059.html Kahn, Charles E, Jr. January 2003. Collaborative Hypertext of Radiology. Medical College of Wisconsin.] ] [ [http://www.whonamedit.com/doctor.cfm/3078.html Constantin, Joseph; Wells, Chris. 2008. Jacques Caroli. Who Named It.] ] He described it as "nonobstructive saccular or fusiform multi-focal segmental dilatation of the intra-hepatic bile ducts"; basically, he observed cavernous ectasia in the biliary tree causing a chronic, often life-threatening hepatobiliary disease. [ [http://www.ncbi.nlm.nih.gov/pubmed/7618550?ordinalpos=8&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum Miller WJ, Sechtin AG, Campbell WL, Pieters PC. 1995 Aug. "Imaging findings in Caroli's disease. AJR Am J Roentgen, 165(2):333-7".] ] Caroli, born in France in 1902, learned and practiced medicine in Angers. After World War II he was chief of service for 30 years at Saint-Antoine in Paris. Before dying in 1979, he was honored with the rank of commander in the Legion of Honour in 1976. [ [http://www.whonamedit.com/doctor.cfm/3078.html Constantin, Joseph; Wells, Chris. 2008. Jacques Caroli. Who Named It.] ]

Detection

ymptoms

The first symptoms typically include fever, intermittent abdominal pain, and hepatomegaly. Occasionally jaundice occurs. [ [http://www.medcyclopaedia.com/library/topics/volume_iv_1/c/CAROLIS_DISEASE.aspx Caroli’s Disease- Gastrointestinal Imaging. 2008. "Medcyclopaedia", 4(1)] ] Caroli disease usually occurs in the presence of other diseases, such as autosomal recessive polycystic kidney disease, cholangitis, gallstones, bilary abscess, septicemia, liver cirrhosis, renal failure, and cholangiocarcinoma (only 7% infected). [ [http://www.indianpediatrics.net/aug2004/848.pdf Karim, Bazlul. August 2007. Caroli’s Disease Case Reports. "Indian Pediatrics, Vol 41: 848-850".] ] People with Caroli disease are 100 times more at risk for cholangiocarcinoma than the general population. [ [http://www.medcyclopaedia.com/library/topics/volume_iv_1/c/CAROLIS_DISEASE.aspx Caroli’s Disease- Gastrointestinal Imaging. 2008. "Medcyclopaedia", 4(1)] ] After recognizing symptoms of related diseases, Caroli disease can be diagnosed.

=Detection

Modern imaging techniques allow the diagnosis to be made more easily and without invasive imaging of the biliary tree. [ [http://www.ncbi.nlm.nih.gov/pubmed/17418061?ordinalpos=4&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum Ananthakrishnan AN, Saeian K. 2007 Apr. Caroli's disease: identification and treatment strategy. "Curr Gastroenterol Rep", 9(2): 151-5.] ] Commonly the disease is limited to the left lobe of the liver. Images taken by CT-scan, X-ray, or MRI will show enlarged intrahepatic (in the liver) bile ducts due to ectasia. Using an ultrasound, tubular dilation of the bile ducts can be seen. On a CT-Scan, Caroli disease can be observed by noting the many fluid-filled, tubular structures extending to the liver. [ [http://www.medcyclopaedia.com/library/topics/volume_iv_1/c/CAROLIS_DISEASE.aspx Caroli’s Disease- Gastrointestinal Imaging. 2008. "Medcyclopaedia", 4(1)] ] A high contrast CT must be used to distinguish the difference between stones and widened ducts. Bowel gas and digestive habits make it difficult to obtain a clear sonogram, therefore, a CT scan is a good substitution. When the intrahepatic bile duct wall has protrusions, it is clearly seen as central dots or a linear streak. [ [http://www.springerlink.com/content/1gptbh2y011a292j/fulltext.pdf Chiba, Tetsuhiro; Shinozaki,Masami; Kato, Shintaro; Goto, Nobuaki; Fujimoto, Hajime; Kondo, Fukuo.2002. Caroli's disease: central dot sign re-examined by CT arteriography and CT during arterial portography. "European Radiology, 12"(3): 701-702.] ] Caroli disease is commonly diagnosed after this “central dot sign” is detected on a CT scan or ultrasound. [ [http://www.springerlink.com/content/1gptbh2y011a292j/fulltext.pdf Chiba, Tetsuhiro; Shinozaki,Masami; Kato, Shintaro; Goto, Nobuaki; Fujimoto, Hajime; Kondo, Fukuo.2002. Caroli's disease: central dot sign re-examined by CT arteriography and CT during arterial portography. "European Radiology, 12"(3): 701-702.] ] However, cholangiography is the best, and final, approach to show the enlarged bile ducts as a result of Caroli disease.

Morbidity

Caroli disease is typically found in Asia and diagnosed in children under the age of 22. [ [http://www.indianpediatrics.net/aug2004/848.pdf Karim, Bazlul. August 2007. Caroli’s Disease Case Reports. "Indian Pediatrics, Vol 41: 848-850".] ] Cases have also been found in both infants and adults. As medical imaging technology improves, diagnostic age decreases. Morbidity is common and is caused by complications of cholangitis, sepsis, choledocholithiasis, and cholangiocarcinoma. [ [http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2215397 Lendoire, Javier; Schelotto, Pablo Barros; Rodríguez, Juan Alvarez; Duek, Fernando; Quarin, Carlos; Garay, Verónica; Amante, Marcelo; Cassini, Eduardo; Imventarza, Oscar. 2007. Bile duct cyst type V (Caroli's disease): surgical strategy and results. "HPB: official journal of the International Hepato Pancreat Biliary Association, 9(4): 281-284".] ] These morbid conditions often prompt the diagnosis. Portal hypertension may be present, resulting in other conditions including splenomegaly, hematemesis and melena. [ [http://www.emedicine.com/PED/topic325.htm Friedman, Joshua Richard, MD, PhD. Sep 2007. Caroli Disease. eMedicine from WebMD.] ] These problems can severely effect the patient's quality of life. In a ten year period between 1995 and 2005, only ten patients were surgically treated for Caroli disease, with an average patient age of 45.8 years. [ [http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2215397 Lendoire, Javier; Schelotto, Pablo Barros; Rodríguez, Juan Alvarez; Duek, Fernando; Quarin, Carlos; Garay, Verónica; Amante, Marcelo; Cassini, Eduardo; Imventarza, Oscar. 2007. Bile duct cyst type V (Caroli's disease): surgical strategy and results. "HPB: official journal of the International Hepato Pancreat Biliary Association, 9(4): 281-284".] ]

After reviewing 46 cases of Caroli disease before 1990, it was found that 21.7% of the cases were the result of an intraheptic cyst or non-obstructive biliary tree dilation, 34.7% were linked with congenital hepatic fibrosis, 13% were isolated choledochal cystic dilation, and the remaining 24.6% had a combination of all three. [ [http://radiology.rsnajnls.org/cgi/reprint/174/1/161.pdf Byung Ihn Choi, MD, Kyung Mo Yeon, MD , Seung Hyup Kim, MD, Man Chung Han, MD. Caroli Disease: Central Dot Sign in CT. "Radiology 174"(1):161-163, 1990.] ]

Mortality is indirect and caused by complications. After cholangitis occurs, patients typically die within approximately 5-10 years. [ [http://www.emedicine.com/radio/topic131.htm Romano, William J, MD. Oct 2002. Caroli Disease. eMedicine from WebMD.] ]

Causes

[
Figure 2 Location of the PKHD1 gene on chromosome 6, short (p) arm.]

The cause appears to be genetic; the simple form is an autosomal dominant trait while the complex from is an autosomal recessive trait. [ [http://www.indianpediatrics.net/aug2004/848.pdf Karim, Bazlul. August 2007. Caroli disease Case Reports. "Indian Pediatrics, Vol 41: 848-850".] ] Females are more prone to Caroli disease than males. [ [http://chorus.rad.mcw.edu/doc/00059.html Kahn, Charles E, Jr. January 2003. Collaborative Hypertext of Radiology. Medical College of Wisconsin.] ] Family history may include kidney and liver disease due to the link between Caroli Disease and ARPKD. [ [http://www.emedicine.com/PED/topic325.htm Friedman, Joshua Richard, MD, PhD. Sep 2007. Caroli Disease. eMedicine from WebMD.] ] PKHD1, the gene linked to ARPKD, has been found mutated in patients with Caroli syndrome. PKHD1 is expressed primarily in the kidneys with lower levels in the liver, pancreas, and lungs, a pattern consistent with phenotype of the disease, which primarily affects the liver and kidneys. [ [http://www.emedicine.com/PED/topic325.htm Friedman, Joshua Richard, MD, PhD. Sep 2007. Caroli Disease. eMedicine from WebMD.] ] [ [http://www.indianpediatrics.net/aug2004/848.pdf Karim, Bazlul. August 2007. Caroli’s Disease Case Reports. "Indian Pediatrics, Vol 41: 848-850".] ] The genetic basis for the difference between Caroli disease and Caroli syndrome has not been defined.

Treatment

The treatment depends on clinical features and the location of the biliary abnormality. When the disease is localized to one hepatic lobe, hepatectomy relieves symptoms and appears to remove the risk of malignancy. [ [http://www.ncbi.nlm.nih.gov/pubmed/9581983?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum Taylor, AC, Palmer KR. 1998 Feb. Eur J Gastroenterol Hepatol, 10(2):105-8.] ] Sometimes, if the disease is isolated in one specific area, a lobectomy may be performed to remove the infected lobe, relieving symptoms and removing the risk of malignancy. [ [http://www.indianpediatrics.net/aug2004/848.pdf Karim, Bazlul. August 2007. Caroli disease Case Reports. "Indian Pediatrics, Vol 41: 848-850".] ] There is good evidence that malignancy complicates Caroli disease in approximately 7% of cases. [ [http://www.ncbi.nlm.nih.gov/pubmed/9581983?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum Taylor, AC, Palmer KR. 1998 Feb. Eur J Gastroenterol Hepatol, 10(2):105-8.] ]

Antibiotics are used to treat the inflammation of the bile duct, and ursodeoxycholic acid for hepatolithiasis. [ [http://www.ncbi.nlm.nih.gov/pubmed/17418061?ordinalpos=4&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum Ananthakrishnan AN, Saeian K. 2007 Apr. Caroli's disease: identification and treatment strategy. "Curr Gastroenterol Rep", 9(2): 151-5.] ] Ursodiol is given to treat cholelithiasis. In diffuse cases of Caroli disease, treatment options include conservative or endoscopic therapy, internal biliary bypass procedures and liver transplantation in carefully selected cases. [ [http://www.ncbi.nlm.nih.gov/pubmed/9581983?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum Taylor, AC, Palmer KR. 1998 Feb. Eur J Gastroenterol Hepatol, 10(2):105-8.] ] Surgical resection has been used successfully in patients with monolobar disease. [ [http://www.ncbi.nlm.nih.gov/pubmed/17418061?ordinalpos=4&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum Ananthakrishnan AN, Saeian K. 2007 Apr. Caroli's disease: identification and treatment strategy. "Curr Gastroenterol Rep", 9(2): 151-5.] ] An orthotopic liver transplant is another option, used only when antibiotics have no effect, in combination with recurring cholangitis. With a liver transplant, cholangiocarcinoma is usually avoided in the long run. [ [http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6VJ0-46SNFPR-40&_user=209810&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_acct=C000014439&_version=1&_urlVersion=0&_userid=209810&md5=cba471e8d086c5f18dcd1d9469df4966#toc7 Ulrich, F., T. Steinmüller, U. Settmacher, A. R. Müller, S. Jonas, S. G. Tullius and P. Neuhaus. Sept. 2007. Therapy of Caroli’s disease by orthotopic liver transplantation. Transplantation Proceedings, 34(6): 2279-80.] ]

Family studies are necessary to determine if Caroli disease is due to inheritable causes. Regular follow-ups, including ultrasounds and liver biopsies, are performed.

Notes

External links

*eMedicine
** [http://www.emedicine.com/ped/topic325.htm Caroli disease, by Joshua Richard Friedman, MD, PhD]
** [http://www.emedicine.com/radio/topic131.htm Caroli disease, by William J Romano, MD, FRCPC0]
*Medcyclopaedia
** [http://www.medcyclopaedia.com/library/topics/volume_iv_1/c/CAROLIS_DISEASE.aspx Caroli's disease-Gastrointestinal Imaging]