Caroli disease

Template:Infobox medical condition (new) 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) 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 and congenital hepatic fibrosis, is often referred to as "Caroli syndrome".<ref name="Karim">Template:Cite journal</ref> The underlying differences between the two types are not well understood. Caroli disease is also associated with liver failure and polycystic kidney disease. The disease affects about one in 1,000,000 people, with more reported cases of Caroli syndrome than of Caroli disease.<ref name=EMedRad>Template:EMedicine</ref>

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.<ref name=Karim/>

Signs and symptoms

The first symptoms typically include fever, intermittent abdominal pain, and an enlarged liver. Occasionally, yellow discoloration of the skin occurs.<ref name="Medcyc">Template:Cite web</ref> Caroli disease usually occurs in the presence of other diseases, such as autosomal recessive polycystic kidney disease, cholangitis, gallstones, biliary abscess, sepsis, liver cirrhosis, kidney failure, and cholangiocarcinoma (7% affected).<ref name=Karim/> People with Caroli disease are 100 times more at risk for cholangiocarcinoma than the general population.<ref name="Medcyc"/> After recognizing symptoms of related diseases, Caroli disease can be diagnosed.Template:Citation needed

Morbidity is common and is caused by complications of cholangitis, sepsis, choledocholithiasis, and cholangiocarcinoma.<ref name="Lendoire">Template:Cite journal</ref> These morbid conditions often prompt the diagnosis. Portal hypertension may be present, resulting in other conditions including enlarged spleen, hematemesis, and melena.<ref name="EMedPed" /> 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.<ref name="Lendoire" />

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 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.<ref name="pmid2294544">Template:Cite journal</ref>

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 form is an autosomal recessive trait.<ref name="Karim" /> Females are more prone to Caroli disease than males.<ref name="Kahn">Kahn, Charles E, Jr. January 2003. Collaborative Hypertext of Radiology. Medical College of Wisconsin. Template:Webarchive</ref> Family history may include kidney and liver disease due to the link between Caroli disease and ARPKD.<ref name="EMedPed">Template:EMedicine</ref> 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.<ref name="Karim" /><ref name="EMedPed" /> The genetic basis for the difference between Caroli disease and Caroli syndrome has not been defined.Template:Cn

Diagnosis

Magnetic resonance cholangiopancreatography (MRCP) of Caroli disease, showing cystic dilatations of bile ducts.<ref name=Maurea/>Template:Predatory

Modern imaging techniques allow the diagnosis to be made more easily and without invasive imaging of the biliary tree.<ref name=p17418061>Template:Cite journal</ref> Commonly, the disease is limited to the left lobe of the liver. Images taken by CT scan, X-ray, or MRI 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.<ref name="Medcyc"/> 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.<ref name=Chiba/> Caroli disease is commonly diagnosed after this “central dot sign” is detected on a CT scan or ultrasound.<ref name=Chiba>Template:Cite journal</ref> However, cholangiography is the best, and final, approach to show the enlarged bile ducts as a result of Caroli disease.Template:Citation needed

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.<ref name=Taylor>Template:Cite journal</ref> Good evidence suggests that malignancy complicates Caroli disease in roughly 7% of cases.<ref name=Taylor/>

Antibiotics are used to treat the inflammation of the bile duct, and ursodeoxycholic acid is used for hepatolithiasis.<ref name=p17418061/> 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.<ref name=Taylor/> Surgical resection has been used successfully in patients with monolobar disease.<ref name=p17418061/> 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.<ref>Template:Cite journal</ref>

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

Prognosis

Mortality is indirect and caused by complications. After cholangitis occurs, patients typically die within 5–10 years.<ref name="EMedRad" />

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.Template:Cn

History

Jacques Caroli, a gastroenterologist, first described a rare congenital condition in 1958 in Paris, France.<ref name="Kahn" /><ref name="WhoNamedIt">Template:WhoNamedIt</ref> 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 disease. <ref>Template:Cite journal</ref> 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.<ref name="WhoNamedIt" />