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Last updated: August 10, 2020
Years published: 1989, 1990, 1994, 1996, 1997, 2006, 2020
NORD gratefully acknowledges Brittany A. Hodge, MMSc, NORD Editorial Intern from the Emory University Genetic Counseling Training Program and Cecelia A. Bellcross, PhD, MS, CGC, Associate Professor, Director, Genetic Counseling Training Program, Emory University School of Medicine, for assistance in the preparation of this report.
Summary
Caroli disease is a rare genetic condition that causes the bile ducts in the liver to be wider than usual. Widening (dilation) of the bile ducts in the liver (intrahepatic bile ducts) can cause bile duct stones to form, which can lead to yellowing of the skin (jaundice) and flu-like symptoms. People with Caroli disease can have many episodes of these symptoms over their lifetime.
A different type of Caroli disease is called Caroli syndrome. It is common to group these two conditions together because they share features. People with Caroli syndrome have scarring on their liver (congenital hepatic fibrosis) which can cause high blood pressure in the veins in the liver (portal hypertension) as well as problems with the bile ducts in the liver. Sometimes, people with Caroli syndrome can develop cysts on their kidneys (polycystic kidney disease). Symptoms of Caroli syndrome are similar to Caroli disease, but can also include blood in the stools, frequent illnesses, and pain in the abdomen. Symptoms of these two conditions usually begin by the age of 30, but can happen at any age. Treatment may involve antibiotics or surgery to remove part of the liver, depending on symptoms and the parts of the liver that are damaged. Caroli disease and Caroli syndrome are thought to be genetic conditions.
Introduction
Caroli disease was first described in 1958 by a French physician named Dr. Jacques Caroli. He was a gastroenterologist who learned that some people had dilated bile ducts in their liver. He also noticed that some people had scarring on their liver in addition to having dilated bile ducts. Those who just had wider bile ducts were then known to have Caroli disease and those who had liver scarring would be known to have Caroli syndrome. Caroli disease is referred to as congenital dilation of intrahepatic bile duct, which means that somebody is born with wider than normal bile ducts in their liver.
Bile is made inside of the liver and sent to the digestive system through ducts to help break down fatty foods for the body to use as energy. These bile ducts are important because they need to be able to transport the bile to other parts of the body. If these bile ducts become too wide, bile will begin to collect and can make the bile ducts inside of the liver swollen (cholangitis). Cholangitis can cause pain in the stomach, fever, tiredness, and nausea and vomiting.
Caroli disease is usually diagnosed after a person first experiences the symptoms listed above. Having a diagnosis can help the medical team stop bile from collecting in the bile ducts in the future. Medication such as antibiotics can be used to prevent irritation, as well. Surgery is typically put off until symptoms start, since it is an invasive procedure. Surgery can be used to remove part of the liver where the bile ducts are too wide (hemi-hepatectomy) and if the patient is having too many episodes of cholangitis.
The other type of Caroli disease, Caroli syndrome, causes the tissue in the liver to scar (congenital hepatic fibrosis) which also causes the bile ducts to be wider than usual. This can also cause the blood pressure in the portal vein, which is blood vessels of the liver, to be high (portal hypertension). Medications such as beta-blockers can be added to help with portal hypertension. People with Caroli syndrome are at an increased risk to develop many cysts or growths on their kidneys (polycystic kidney disease), so they may need medication and surgery to help their kidneys work properly.
Bile needs to be able to move through the bile ducts without getting stuck. When these ducts become too wide, bile can collect easily. As bile collects over time, the build-up can cause small stones to form. These small stones usually do not cause symptoms unless they block the bile duct. When a bile duct is blocked due to stones, the bile ducts become swollen (cholangitis). This can cause pain on the right side of the body, vomiting, fever, and yellowing of the skin (jaundice). People with Caroli disease experience many episodes of cholangitis. Rarely, tumors called cholangiocarcinomas can form in the bile duct due to the build-up of bile. Usually, symptoms happen before the age of 30, but can happen at any age. Some people with Caroli disease may only have one episode of cholangitis, so it is important to understand how the disease impacts a personโs life.
The liver has its own bile ducts and its own blood vessels that make up the hepatic portal system. The portal system carries blood from the digestive organs to the liver in order for the liver to filter out waste. The liver needs to form correctly in order to work. Sometimes, people are born with a condition that causes their liver to have scarring and to be larger than normal (congenital hepatic fibrosis). This also changes the way their bile ducts in the liver are formed, putting them at a higher risk to have cholangitis. Since the hepatic portal system is also not formed correctly, blood pressure in these veins is higher than normal. People with Caroli syndrome have congenital hepatic fibrosis. Caroli syndrome is progressive meaning that damage to the liver is done over time. This condition can lead to liver failure and polycystic kidney disease.
Caroli disease and Caroli syndrome are thought to be genetic conditions. Caroli disease usually occurs sporadically, but has been reported to follow autosomal dominant inheritance in some families.
Caroli syndrome, on the other hand, is associated with genetic changes (mutations) in the PKHD1 gene. This gene makes a protein that helps build the bile ducts as well as the kidneys. Mutations in this gene are also associated with a kidney condition called polycystic kidney disease. Since this disease has been linked to Caroli syndrome, it may be that PKHD1 is linked to Caroli disease, although it is not certain.
Recessive genetic disorders occur when an individual inherits a non-working gene from each parent. If an individual receives one working gene and one non-working gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the non-working gene and, therefore, have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier, like the parents, is 50% with each pregnancy. The chance for a child to receive working genes from both parents is 25%. The risk is the same for males and females. People who are related (consanguineous) have a greater chance of being carriers for the same condition and have an increased chance of having a child with a recessive condition.
Dominant genetic disorders occur when only a single copy of a non-working gene is necessary to cause a particular disease. The non-working gene can be inherited from either parent or can be the result of a mutated (changed) gene in the affected individual. The risk of passing the non-working gene from an affected parent to an offspring is 50% for each pregnancy. The risk is the same for males and females.
Caroli disease and Caroli syndrome can affect people of all ethnic and ancestral backgrounds. Symptoms typically start in adulthood, but can sometimes start in childhood. Caroli disease is rarer than Caroli syndrome, but it is estimated that 1 out of 1,000,000 individuals are affected by Caroli disease. Caroli syndrome has been estimated to affect 1 out of 100,000 individuals, but it is difficult to identify people with Caroli syndrome since features can overlap with other conditions.
Based on symptoms, imaging may be done to see if there are any problems with the liver or bile ducts.
Ultrasounds, CT scans, ERCPs, MRCPs, and MRIs are needed to make a diagnosis. ERCP (endoscopic retrograde cholangiopancreatography) is a procedure that is done using a small, bendable tube (endoscope) that is placed through the mouth and into the stomach. ERCP is able to see the bile ducts and the liver to see if there are any scars or masses. ERCP is an invasive procedure, but it can help rule out other conditions. It is accurate in diagnosing Caroli disease and Caroli syndrome.
MRCP (magnetic resonance cholangiopancreatography) is a special type of test that can measure how wide the bile ducts are. MRCP can also see if there are any bile duct stones. Other types of imaging, including CT scans, can see if there are scars on the liver. It is difficult to tell if liver scars are due to Caroli syndrome or another unrelated condition.
A complete blood count (CBC) is a blood test that may also be done to see if someone has Caroli disease or Caroli syndrome. People with Caroli syndrome may have lower white blood cells, lower red blood cells, or lower platelets than people with Caroli disease. Combining imaging and blood work can help determine what type of Caroli disease a person has, since the symptoms are similar.
Clinical Testing and Work-Up
Tests are ordered based on the type of symptoms a person has. If someone has symptoms of Caroli disease, they will have an ERCP, an MRCP, a CT scan, or another type of scan. It is important to measure the bile ducts in the liver to see if they are wider than usual, since that is the main sign of Caroli disease. Having these types of tests can rule out Caroli syndrome.
Treatment
Treatment for Caroli disease is based on where the wide bile ducts are located inside of the liver. If the wider bile ducts are on the left or right half of the liver, then that portion of the liver can be removed through surgery. People who have part of their liver removed (hemi-hepatectomy) in order to treat Caroli disease often do not experience future symptoms.
If the dilated bile ducts are located throughout the liver, using antibiotics may be able to prevent cholangitis. Surgeries can also be done to help get the bile out of the liver (internal biliary bypass). For some people, this is difficult to manage, so a liver transplant may be the best option.
People with Caroli disease are usually followed by a care team made up of doctors who specialize in diseases of the digestive tract (gastroenterologists), doctors who specialize in diseases of the liver (hepatologists), and doctors who perform surgeries. They may also be cared for by a surgeon that specializes in liver transplants (transplant hepatologist).
Information on current clinical trials is posted on the Internet at https://clinicaltrials.gov/ All studies receiving U.S. Government funding, and some supported by private industry, are posted on this government web site.
For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
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Some current clinical trials also are posted on the following page on the NORD website:
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For information about clinical trials sponsored by private sources, contact:
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For information about clinical trials conducted in Europe, contact:
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TEXTBOOKS
Poreddy V, Kaplowitz N. Caroli Disease. In: NORD Guide to Rare Disorders. Lippincott Williams & Wilkins. Philadelphia, PA. 2003:336.
JOURNAL ARTICLES
Wambura C, Sharma M, Surani S. Revisiting Caroli syndrome in a Tanzanian patient. Cureus. 2020;12(1):e6661.
Rivas A, Epelman M, Danzer E, Adzick NS and Victoria T. Prenatal MR imaging features of Caroli syndrome in association with autosomal recessive polycystic kidney disease. Radiol Case Rep. 2019 Feb; 14(2): 265โ268.
Lv Y, et al. Etiological causes of intrahepatic and extrahepatic bile duct dilation. International Journal of New Technology and Research. 2015;1(8):53-57.
Wang, Z, et al. Clinical classification of Caroliโs disease: an analysis of 30 patients. International Hepato-Pancreato-Biliary Association. 2015;17:278-283.
Hao X, Liu S, et al. Whole exome sequencing identifies recessive PKHD1 mutations in a Chinese twin family with Caroli disease. PLoS One. 2014;9(4):e92661
Bayraktar, Y. Clinical characteristics of Caroliโs disease. World Journal of Gastroenterology. 2007;13(13):1930-1933.
Senyuz OF, Yesildag E, Kuruoglu S, et al. Caroliโs disease in children: is it commonly misdiagnosed? Acta Paediatr. 2005:94;117-20.
Madjov R, Chervenkov P, Madjova V, et al. Caroliโs disease. Report of 5 cases and review of literature. Hepatogastroenterology. 2005;52:606-09.
Sgro M, Rossetti S, Barozzino T, et al. Caroliโs disease: prenatal diagnosis, postnatal outcome and genetic analysis. Ultrasound Obstet Gynecol. 2004;23: 73-76.
Hernandez-Ortiz J, Corona R, Mendez-Sanchez N. Caroliโs disease and choledochal cyst. Ann Hepatol. 2002;1:196.
Levy AD, Rohrmann CA Jr, Murakata LA, et al. Caroliโs disease: radiologic spectum with pathologic correlation. AJR Am J Roentgenol. 2002;179:1053-57.
Carrera C, Castiella A, Fernandez J, et al. Caroliโs disease diagnosed by magnetic resonance cholangiopancreatography. Eur J Gastroenterol Hepatol. 2002;14:577.
Yuksel A, Has R, Isikoglu M, et al. Prenatal diagnosis of Caroliโs disease. Ultrasound Obstet Gynecol. 2002;19:525-26.
Harjai MM, et. al. Caroli Disease and Caroli Syndrome. Med J Armed Forces India. 1999;55(2):155โ156. doi:10.1016/S0377-1237(17)30276-9
INTERNET
McKusick VA, ed. Online Mendelian Inheritance In Man (OMIM). The Johns Hopkins University. Caroli Disease, Isolated. Entry Number; 600643: Last Edit Date; 06/27/2019. https://www.omim.org/entry/600643 Accessed July 20, 2020.
Sultan MI. Pediatric Caroli Disease. Medscape. Last Updated: October 20, 2017. www.emedicine.com/ped/topic325.htm Accessed July 20, 2020.
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The Genetic and Rare Diseases Information Center (GARD) has information and resources for patients, caregivers, and families that may be helpful before and after diagnosis of this condition. GARD is a program of the National Center for Advancing Translational Sciences (NCATS), part of the National Institutes of Health (NIH).
View reportOrphanet has a summary about this condition that may include information on the diagnosis, care, and treatment as well as other resources. Some of the information and resources are available in languages other than English. The summary may include medical terms, so we encourage you to share and discuss this information with your doctor. Orphanet is the French National Institute for Health and Medical Research and the Health Programme of the European Union.
View reportOnline Mendelian Inheritance In Man (OMIM) has a summary of published research about this condition and includes references from the medical literature. The summary contains medical and scientific terms, so we encourage you to share and discuss this information with your doctor. OMIM is authored and edited at the McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine.
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