Caroli's Disease
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Caroli disease (communicating cavernous ectasia, or congenital cystic dilatation of the intrahepatic biliary tree) is a rare inherited disorder characterized by cystic dilatation (or
ectasia Ectasia (), also called ectasis (), is dilation or distention of a tubular structure, either normal or pathophysiologic but usually the latter (except in atelectasis, where absence of ectasis is the problem). Specific conditions * Bronchiectasis ...
) of the bile ducts within the liver. There are two patterns of Caroli disease: focal or simple Caroli disease consists of abnormally widened bile ducts affecting an isolated portion of liver. The second form is more diffuse, and when associated with
portal hypertension Portal hypertension is defined as increased portal venous pressure, with a hepatic venous pressure gradient greater than 5 mmHg. Normal portal pressure is 1–4 mmHg; clinically insignificant portal hypertension is present at portal pressures 5â ...
and
congenital hepatic fibrosis Congenital hepatic fibrosis is an inherited fibrocystic liver disease associated with proliferation of interlobular bile ducts within the portal areas and fibrosis that do not alter hepatic lobular architecture. The fibrosis would affect resist ...
, is often referred to as "Caroli syndrome". The underlying differences between the two types are not well understood. Caroli disease is also associated with
liver failure Liver failure is the inability of the liver to perform its normal synthetic and metabolic functions as part of normal physiology. Two forms are recognised, acute and chronic (cirrhosis). Recently, a third form of liver failure known as acute- ...
and
polycystic kidney disease Polycystic kidney disease (PKD or PCKD, also known as polycystic kidney syndrome) is a genetic disorder in which the renal tubules become structurally abnormal, resulting in the development and growth of multiple cysts within the kidney. These ...
. The disease affects about one in 1,000,000 people, with more reported cases of Caroli syndrome than of Caroli disease. Caroli disease is distinct from other diseases that cause ductal dilatation caused by obstruction, in that it is not one of the many choledochal cyst derivatives.


Signs and symptoms

The first symptoms typically include
fever Fever or pyrexia in humans is a symptom of an anti-infection defense mechanism that appears with Human body temperature, body temperature exceeding the normal range caused by an increase in the body's temperature Human body temperature#Fever, s ...
, intermittent
abdominal pain Abdominal pain, also known as a stomach ache, is a symptom associated with both non-serious and serious medical issues. Since the abdomen contains most of the body's vital organs, it can be an indicator of a wide variety of diseases. Given th ...
, and an
enlarged liver Hepatomegaly is enlargement of the liver. It is a non-specific medical sign, having many causes, which can broadly be broken down into infection, hepatic tumours, and metabolic disorder. Often, hepatomegaly presents as an abdominal mass. Dependi ...
. Occasionally, yellow discoloration of the skin occurs. Caroli disease usually occurs in the presence of other diseases, such as autosomal recessive
polycystic kidney disease Polycystic kidney disease (PKD or PCKD, also known as polycystic kidney syndrome) is a genetic disorder in which the renal tubules become structurally abnormal, resulting in the development and growth of multiple cysts within the kidney. These ...
, cholangitis,
gallstones A gallstone is a stone formed within the gallbladder from precipitated bile components. The term cholelithiasis may refer to the presence of gallstones or to any disease caused by gallstones, and choledocholithiasis refers to the presence of ...
, biliary abscess,
sepsis Sepsis is a potentially life-threatening condition that arises when the body's response to infection causes injury to its own tissues and organs. This initial stage of sepsis is followed by suppression of the immune system. Common signs and s ...
, liver
cirrhosis Cirrhosis, also known as liver cirrhosis or hepatic cirrhosis, chronic liver failure or chronic hepatic failure and end-stage liver disease, is a chronic condition of the liver in which the normal functioning tissue, or parenchyma, is replaced ...
,
kidney failure Kidney failure, also known as renal failure or end-stage renal disease (ESRD), is a medical condition in which the kidneys can no longer adequately filter waste products from the blood, functioning at less than 15% of normal levels. Kidney fa ...
, and
cholangiocarcinoma Cholangiocarcinoma, also known as bile duct cancer, is a type of cancer that forms in the bile ducts. Symptoms of cholangiocarcinoma may include abdominal pain, yellowish skin, weight loss, generalized itching, and fever. Light colored stoo ...
(7% affected). People with Caroli disease are 100 times more at risk for cholangiocarcinoma than the general population. After recognizing symptoms of related diseases, Caroli disease can be diagnosed. Morbidity is common and is caused by complications of cholangitis, sepsis,
choledocholithiasis Common bile duct stone, also known as choledocholithiasis, is the presence of gallstones in the common bile duct (CBD) (thus '' choledocho-'' + '' lithiasis''). This condition can cause jaundice and liver cell damage. Treatments include choledocho ...
, and cholangiocarcinoma. These morbid conditions often prompt the diagnosis. Portal hypertension may be present, resulting in other conditions including
enlarged spleen Splenomegaly is an enlargement of the spleen. The spleen usually lies in the left upper quadrant (LUQ) of the human abdomen. Splenomegaly is one of the four cardinal signs of ''hypersplenism'' which include: some reduction in number of circulatin ...
,
hematemesis Hematemesis is the vomiting of blood. It can be confused with hemoptysis (coughing up blood) or epistaxis (nosebleed), which are more common. The source is generally the upper gastrointestinal tract, typically above the suspensory muscle of du ...
, and
melena Melena is a form of blood in stool which refers to the dark black, tarry feces that are commonly associated with upper gastrointestinal bleeding. The black color and characteristic strong odor are caused by hemoglobin in the blood being alter ...
. These problems can severely affect the patient's quality of life. In a 10-year period between 1995 and 2005, only 10 patients were surgically treated for Caroli disease, with an average patient age of 45.8 years. After reviewing 46 cases of Caroli disease before 1990, 21.7% of the cases were the result of an intrahepatic cyst or nonobstructive
biliary tree The biliary tract (also biliary tree or biliary system) refers to the liver, gallbladder and bile ducts, and how they work together to make, store and secrete bile. Bile consists of water, electrolytes, bile acids, cholesterol, phospholipids a ...
dilation, 34.7% were linked with
congenital hepatic fibrosis Congenital hepatic fibrosis is an inherited fibrocystic liver disease associated with proliferation of interlobular bile ducts within the portal areas and fibrosis that do not alter hepatic lobular architecture. The fibrosis would affect resist ...
, 13% were isolated choledochal cystic dilation, and the remaining 24.6% had a combination of all three.


Causes

The cause appears to be genetic; the simple form is an
autosomal dominant In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the Phenotype, effect of a different variant of the same gene on Homologous chromosome, the other copy of the chromosome. The firs ...
trait, while the complex form is an
autosomal recessive In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the Phenotype, effect of a different variant of the same gene on Homologous chromosome, the other copy of the chromosome. The firs ...
trait. Females are more prone to Caroli disease than males.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. '' 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 The liver is a major metabolic organ (anatomy), organ exclusively found in vertebrates, which performs many essential biological Function (biology), functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of var ...
,
pancreas The pancreas (plural pancreases, or pancreata) is an Organ (anatomy), organ of the Digestion, digestive system and endocrine system of vertebrates. In humans, it is located in the abdominal cavity, abdomen behind the stomach and functions as a ...
, and
lungs The lungs are the primary organs of the respiratory system in many animals, including humans. In mammals and most other tetrapods, two lungs are located near the backbone on either side of the heart. Their function in the respiratory syste ...
, a pattern consistent with phenotype of the disease, which primarily affects the liver and
kidneys In humans, the kidneys are two reddish-brown bean-shaped blood-filtering organs that are a multilobar, multipapillary form of mammalian kidneys, usually without signs of external lobulation. They are located on the left and right in the retro ...
. The genetic basis for the difference between Caroli disease and Caroli syndrome has not been defined.


Diagnosis

Modern imaging techniques allow the diagnosis to be made more easily and without invasive imaging of the biliary tree. Commonly, the disease is limited to the left lobe of the liver. Images taken by
CT scan A computed tomography scan (CT scan), formerly called computed axial tomography scan (CAT scan), is a medical imaging technique used to obtain detailed internal images of the body. The personnel that perform CT scans are called radiographers or ...
,
X-ray An X-ray (also known in many languages as Röntgen radiation) is a form of high-energy electromagnetic radiation with a wavelength shorter than those of ultraviolet rays and longer than those of gamma rays. Roughly, X-rays have a wavelength ran ...
, or
MRI Magnetic resonance imaging (MRI) is a medical imaging technique used in radiology to generate pictures of the anatomy and the physiological processes inside the body. MRI scanners use strong magnetic fields, magnetic field gradients, and rad ...
show enlarged intrahepatic (in the liver) bile ducts due to ectasia. Using an
ultrasound Ultrasound is sound with frequency, frequencies greater than 20 Hertz, kilohertz. This frequency is the approximate upper audible hearing range, limit of human hearing in healthy young adults. The physical principles of acoustic waves apply ...
, 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. 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, so 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. Caroli disease is commonly diagnosed after this “central dot sign” is detected on a CT scan or ultrasound. However,
cholangiography Cholangiography is the imaging of the bile duct (also known as the biliary tree) by x-rays and an injection of contrast medium. __TOC__ Types There are at least four types of cholangiography: # Percutaneous transhepatic cholangiography (PTC): Ex ...
is the best, and final, approach to show the enlarged bile ducts as a result of Caroli disease.


Treatment

The treatment depends on clinical features and the location of the biliary abnormality. When the disease is localized to one hepatic lobe,
hepatectomy Hepatectomy is the surgical resection (removal of all or part) of the liver. While the term is often employed for the removal of the liver from a liver transplant donor, this article will focus on Segmental resection, partial resections of hepatic ...
relieves symptoms and appears to remove the risk of
malignancy Malignancy () is the tendency of a medical condition to become progressively worse; the term is most familiar as a characterization of cancer. A ''malignant'' tumor contrasts with a non-cancerous ''benign'' tumor in that a malignancy is not ...
. Good evidence suggests that malignancy complicates Caroli disease in roughly 7% of cases. Antibiotics are used to treat the inflammation of the bile duct, and ursodeoxycholic acid is used for hepatolithiasis. 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. Surgical resection has been used successfully in patients with monolobar disease. An
orthotopic liver transplant Liver transplantation or hepatic transplantation is the replacement of a diseased liver with the healthy liver from another person (allograft). Liver transplantation is a treatment option for end-stage liver disease and acute liver failure, alt ...
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. Family studies are necessary to determine if Caroli disease is due to inheritable causes. Regular follow-ups, including ultrasounds and liver biopsies, are performed.


Prognosis

Mortality is indirect and caused by complications. After cholangitis occurs, patients typically die within 5–10 years.


Epidemiology

Caroli disease is typically found in Asia, and diagnosed in persons under the age of 22. Cases have also been found in infants and adults. As medical imaging technology improves, diagnostic age decreases.


History

Jacques Caroli, a
gastroenterologist Gastroenterology (from the Greek gastḗr- "belly", -énteron "intestine", and -logía "study of") is the branch of medicine focused on the digestive system and its disorders. The digestive system consists of the gastrointestinal tract, sometime ...
, first described a rare congenital condition in 1958 in
Paris Paris () is the Capital city, capital and List of communes in France with over 20,000 inhabitants, largest city of France. With an estimated population of 2,048,472 residents in January 2025 in an area of more than , Paris is the List of ci ...
,
France France, officially the French Republic, is a country located primarily in Western Europe. Overseas France, Its overseas regions and territories include French Guiana in South America, Saint Pierre and Miquelon in the Atlantic Ocean#North Atlan ...
. He described it as "nonobstructive saccular or fusiform multifocal segmental dilatation of the intrahepatic bile ducts"; basically, he observed cavernous ectasia in the biliary tree causing a chronic, often life-threatening
hepatobiliary The biliary tract (also biliary tree or biliary system) refers to the liver, gallbladder and bile ducts, and how they work together to make, store and secrete bile. Bile consists of water, electrolytes, bile acids, cholesterol, phospholipids and ...
disease. Caroli, born in France in 1902, learned and practiced medicine in
Angers Angers (, , ;) is a city in western France, about southwest of Paris. It is the Prefectures of France, prefecture of the Maine-et-Loire department and was the capital of the province of Duchy of Anjou, Anjou until the French Revolution. The i ...
. After
World War II World War II or the Second World War (1 September 1939 – 2 September 1945) was a World war, global conflict between two coalitions: the Allies of World War II, Allies and the Axis powers. World War II by country, Nearly all of the wo ...
, 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 The National Order of the Legion of Honour ( ), formerly the Imperial Order of the Legion of Honour (), is the highest and most prestigious French national order of merit, both military and Civil society, civil. Currently consisting of five cl ...
in 1976.


References


External links

{{DEFAULTSORT:Caroli Disease Ciliopathy Hepatology Rare diseases Syndromes affecting the hepatobiliary system Syndromes with tumors