INTRODUCTION:

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 ductal dilatation caused by obstruction, in that it is not one of the many choledochal cyst derivatives.¹

Definition:

Caroli disease is a rare inherited disorder characterized by dilation of the intrahepatic bile ducts.

Incidence:

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

The simple form, Caroli disease, is apparently much less common than is the more complex form. Both forms are more common in females than among males. Most often the disorder presents in adults, although cases of neonatal and childhood presentation of symptoms are recorded.

Types:

According to the medical literature, there are two forms of Caroli disease. In most cases, the isolated or simple form is characterized by widening of the bile ducts (dilatation or ectasia). A second, more complex form is often called Caroli syndrome. The complex form or syndrome is associated with the presence of bands of fibrous tissue in the liver (congenital hepatic fibrosis) and high blood pressure in the portal artery (portal hypertension). This form of Caroli disease is also often associated, in ways that are not well understood, with polycystic kidney disease, and, in severe cases, liver failure.²

Causes:

The cause appears to be genetic; the simple form is an autosomal dominant trait while the complex form is an autosomal recessive trait.^[1] Females are more prone to Caroli disease than males.³ Family history may include kidney and liver disease due to the link between Caroli Disease and ARPKD.⁴ 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. The genetic basis for the difference between Caroli disease and Caroli syndrome has not been defined.

Caroli disease is a birth defect distinguished by abnormal prenatal development of the bile duct in the liver. The exact cause is unknown. In most cases, the simple or isolated form of Caroli disease is believed to result from a spontaneous genetic change (mutation) that occurs for unknown reasons (sporadic). Researchers believe that this form is inherited as an autosomal dominant genetic trait. In contrast, the more complex form of Caroli disease appears to be inherited as an autosomal recessive genetic trait. The gene responsible for the more complex form of the disorder has been tracked to chromosome 6.

Chromosomes, which are present in the nucleus of human cells, carry the genetic information for each individual. Human body cells normally have 46 chromosomes. Pairs of human chromosomes are numbered from 1 through 22 and the sex chromosomes are designated X and Y. Males have one X and one Y chromosome and females have two X chromosomes. Each chromosome has a short arm designated “p” and a long arm designated “q”. Chromosomes are further sub-divided into many bands that are numbered. The numbered bands specify the location of the thousands of genes that are present on each chromosome. Genetic diseases are determined by the combination of genes for a particular trait that are on the chromosomes received from the father and the mother.

Recessive genetic disorders occur when an individual inherits the same abnormal gene for the same trait from each parent. If an individual receives one normal gene and one 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 defective 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 normal genes from both parents and be genetically normal for that particular trait is 25%.

The risk is the same for males and females. All individuals carry 4-5 abnormal genes. Parents who are close relatives (consanguineous) have a higher chance than unrelated parents to both carry the same abnormal gene, which increases the risk to have children with a recessive genetic disorder. Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary for the appearance of the disease. The abnormal gene can be inherited from either parent, or can be the result of a new mutation (gene change) in the affected individual. The risk of passing the abnormal gene from affected parent to offspring is 50% for each pregnancy regardless of the sex of the resulting child.

Signs and Symptoms:

The first symptoms typically include fever, intermittent abdominal pain, and hepatomegaly. Occasionally jaundice occurs.⁵ Caroli disease usually occurs in the presence of other diseases, such as autosomal recessive polycystic kidney disease, cholangitis, gallstones, biliary bscess, septicemia, liver cirrhosis, renal failure, and cholangiocarcinoma (7% affected). People with Caroli disease are 100 times more at risk for cholangiocarcinoma than the general population.⁵ After recognizing symptoms of related diseases, Caroli disease can be diagnosed.

Morbidity is common and is caused by complications of cholangitis, sepsis, choledocholithiasis, and cholangio-carcinoma.⁶ These morbid conditions often prompt the diagnosis. Portal hypertension may be present, resulting in other conditions including splenomegaly, hematemesis and melena.⁴ These problems can severely affect 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.⁶

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.⁷

Caroli disease is a rare disorder that may occur as an isolated finding or associated with congenital hepatic fibrosis. Both forms of Caroli disease are characterized by abnormal widening of the ducts that carry bile from the liver (intrahepatic bile ducts). This widening may occur as a result of the formation of fluid-filled sacs or lumps (choledochal cysts) in the bile ducts. The isolated or simple form of Caroli disease is characterized by frequent recurring inflammation of the bile ducts inside the liver. There may also be localized accumulation of pus (abscess), stones that develop inside the bile ducts (intraductal lithiasis), abdominal pain, and/or fever. In rare cases, individuals may exhibit yellowing of the skin, mucous membranes, and whites of the eyes (jaundice) and/or abnormal enlargement of the liver (hepatomegaly).

The second form of Caroli disease is associated with abnormal formation bands of fibrous tissue in the portal area of the liver (congenital hepatic fibrosis). The portal area of the liver is where the portal vein and the hepatic artery enter the liver. The portal vein is the blood vessel that carries blood from the stomach, intestine, and spleen to the liver, and the hepatic artery is the blood vessel that carries blood away from the aorta. This form of Caroli disease is also often associated with high blood pressure of the portal vein (portal hypertension) and liver abcess. In addition, this form of Caroli disease may also be associated with polycystic kidney disease and, in severe cases, liver failure. (For more information on this disorder, choose “polycystic kidney disease” as your search term in the Rare Disease Database.)

In some cases, individuals with Caroli disease may appear to be more prone to developing certain benign tumors or malignancies (e.g., cholangiocarcinoma) than the general population.

Diagnostic Evaluation:

Modern imaging techniques allow the diagnosis to be made more easily and without invasive imaging of the biliary tree.⁸ 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.⁸ 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.⁹ Caroli disease is commonly diagnosed after this “central dot sign” is detected on a CT scan or ultrasound.⁹ However, cholangiography is the best, and final, approach to show the enlarged bile ducts as a result of Caroli disease.

Management:

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. There is good evidence that malignancy complicates Caroli disease in approximately 7% of cases.¹⁰

Antibiotics are used to treat the inflammation of the bile duct, and ursodeoxycholic acid 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.¹⁰ Surgical resection has been used successfully in patients with monolobar disease. 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.¹¹

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

Complications:

· Simple type

· Intrahepatic stone formation

· Recurrent cholangitis

· Hepatic abscesses

· Periportal fibrosis type

· Cirrhosis and portal hypertension

· Varices

· There is an increased risk of cholangiocarcinoma, which develops in 7% of patients. ¹²

PROGNOSIS:

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

REFERENCE:

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2. Kahn, Charles E, Jr. January 2003. Collaborative Hypertext of Radiology. Medical College of Wisconsin. Archived September 29, 2008, at the Wayback Machine.

3. Lendoire J, Schelotto PB, Rodríguez JA, et al. (2007). "Bile duct cyst type V (Caroli's disease): surgical strategy and results".

4. Choi BI, Yeon KM, Kim SH, Han MC (1 January 1990). "Caroli disease: central dot sign in CT". Radiology. 174 (1): 161–3.

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6. Chiba T, Shinozaki M, Kato S, Goto N, Fujimoto H, Kondo F (March 2002). "Caroli's disease: central dot sign re-examined by CT arteriography and CT during arterial portography" (PDF).

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8. Ulrich F, Steinmüller T, Settmacher U, et al. (September 2002). "Therapy of Caroli's disease by orthotopic liver transplantation". Transplant. Proc. 34 (6): 2279–80.

9. Miller WJ, Sechtin AG, Campbell WL, Pieters PC (1 August 1995). "Imaging findings in Caroli's disease". AJR Am J Roentgenol. 165 (2): 333–7.

10. MLN Moorthy. I Venkata Ratnam, P Chandra Mohan, MD Riyaz Khan R Prabhakar Rao. Images: “Central dot sign” on ultrasound-Diagnostic of caroli disease. Ind J Radiol Imag 2000; 10.

11. Ros E, Navarros, Bru C, Crilbert R, Bianchi L, Bruguera M. Ursodeoxycholic acid treatment of primary hepatolothiasis in caroli syndrome. Lancet 1993; 342: 404-406.

12. Reymond MJ, Herguet C, Danan C, et al. Partial hepatectomy in the treatment of caroli disease. Diag Dis Sci 1984; 29: 367 – 310.

Received on 01.08.2017 Modified on 18.09.2017

Int. J. Adv. Nur. Management. 2017; 5(4): 354-356.

DOI: 10.5958/2454-2652.2017.00075.0