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Caroli Disease

Caroli's Syndrome

Caroli disease is a rare congenital disorder characterized by segmental, nonobstructive dilatation of the intrahepatic bile ducts.


Presentation

Patients of Caroli disease present with different complaints depending upon the age of onset and the mutation of the underlying gene.

  • Up to 60% of the patients suffering from Caroli disease also have involvement of the kidneys in the form of autosomal recessive polycystic kidney disease (ARPKD). The reason for this association is that both of these diseases have the same underlying gene mutation.
  • Fever is the one of the most common presenting complaints of the patients suffering from Caroli disease. This is because bile contains many toxic wastes that need to be excreted from the body. However, owing to the blockage of bile drainage, these toxic metabolites are absorbed in the body which leads to ascending cholangitis that manifests as high grade fever and chills.
  • Pruritis in Caroli disease manifests in the body due to blockage of biliary drainage. Chenodeoxycholic acid is one of the constituents of bile. When blockage occurs, chenodeoxycholic acid starts accumulating under skin and causes severe itching.
  • Intermittent abdominal pain in the right hypochondrium is also common in Caroli disease. Pain and distention of the gall bladder is due to stasis of bile. When the gall bladder becomes inflamed (acute cholecystitis), pain becomes the major presenting complaint.
  • Hepatomegaly is present in some patients of Caroli disease because of the dilatation of the intra-hepatic bile ducts. It is associated with enlargement of the liver parenchyma and is the most common finding on general physical examination of the patient.
  • When blockage of bile is for long duration, then super-saturation of cholesterol in the bile takes place. Initially, crystals are formed. Later on with the passage of time, the formation of gall stones takes place.
  • Cirrhosis of the liver occurs when recurrent attacks of ascending cholangitis form the dominant picture of this disease. After cholangitis occurs, a large number of patients die within 5 to 10 years.
  • Incidence of cholangiocarcinoma is higher in the patients suffering from Caroli disease. It is reported in up to 7 to 14% of the cases [3].
Fever
  • A case of Carolis disease in a boy of 6 years with bilobal involvement presenting with intermittent abdominal pain, fever and hepatomegaly is reported here.[ncbi.nlm.nih.gov]
  • The clinical features of Caroli's disease include jaundice, right upper abdominal pain, and fever due to the associated complications of hepatolithiasis or bacterial cholangitis.[ncbi.nlm.nih.gov]
  • Presenting signs and symptoms were (hepato)splenomegaly, hematemesis and/or melena, cholangitis, jaundice, and recurrent fever.[ncbi.nlm.nih.gov]
  • However, owing to the blockage of bile drainage, these toxic metabolites are absorbed in the body which leads to ascending cholangitis that manifests as high grade fever and chills.[symptoma.com]
  • @article{4286212bf32744dbbe349d9d07fa8ab4, title "A 52-year-old man with Caroli's disease and recurrent obstructive jaundice, fever, and bacteremia", author "B.[asu.pure.elsevier.com]
Pediatric Disorder
  • Anatomy, anomalies, and pediatric disorders of the biliary tract. Sleisenger and Fordtran's Gastrointestinal and Liver Disease: Pathophysiology/Diagnosis/Management. WB Saunders Co; 1993. 917-927. Suchy FJ. The cholangiopathies.[emedicine.medscape.com]
Intermittent Fever
  • She was hospitalized at the pediatric unit of the Cocody Teaching Hospital for an intermittent fever. During the clinical examination, we found a likely cirrhotic hepatomegaly associated to an edematous-ascitic syndrome.[file.scirp.org]
Abdominal Pain
  • A case of Carolis disease in a boy of 6 years with bilobal involvement presenting with intermittent abdominal pain, fever and hepatomegaly is reported here.[ncbi.nlm.nih.gov]
  • The clinical features of Caroli's disease include jaundice, right upper abdominal pain, and fever due to the associated complications of hepatolithiasis or bacterial cholangitis.[ncbi.nlm.nih.gov]
  • After that he has had recurrent episodes of right upper quadrant abdominal pain and fever.[kjim.org]
  • This is a case study of a 32 years old female patient with non specific abdominal pain, without symptoms or signs of hepatopathy. Abdominal ultrasound showed sparse cystic anechoic formations in the liver parenchyma of about 1.1 cm.[imagejournals.org]
  • pain, fever; due to associated complications of hepatolithiasis or bacterial cholangitis Gross description 1 - 4 cm cysts separated by normal bile ducts Gross images Images hosted on other servers : Dilated bile ducts Microscopic (histologic) description[pathologyoutlines.com]
Nausea
  • Other symptoms are nonspecific, such s vomiting, nausea, and enlarged liver. Patients may not experience symptoms for long periods.[medigest.uk]
  • I always keep nausea pills on hand all the time and my dr. will always see me that day. I'm in the middle of being diagnosed. I was having an ERCP the other day when the doctor mentioned my cysts are Caroli's Disease.[inspire.com]
  • This video shows a case of Caroli s disease occured in a 58 years old male admitted at the gastroenterology department for sudden onset of abdominal pain associated with fever ( 38C ), nausea and shivering.[jove.com]
Colic
  • Manifestations are those of complications, mostly bacterial cholangitis, and include abdominal pain and biliary colic, fever with chills, and jaundice.[orpha.net]
Severe Abdominal Pain
  • After that he had been well, but during his military service, about 10 years before admission to our hospital, sudden severe abdominal pain developed so he received exploratory laparotomy.[kjim.org]
Recurrent Jaundice
  • Lauga: [Chronic recurrent jaundice in young persons: malignant hepatoma, blood clots and tumoral pustules obstructing the right biliary tract and the hepatic duct. Palliative choledoco-duodenal anastomosis. Secondary right hepatectomy.[whonamedit.com]
Pruritus
  • Her main complaint on referral was intense pruritus which failed to respond to most of the antihistamines, Ursodeoxycholic acid, Rifampicin, Naltrexone or Gabapentin. She did respond only to recurrent Molecular Adsorbents Recycling System (MARS).[jscimedcentral.com]
Yellow Discoloration of the Skin
  • Occasionally, yellow discoloration of the skin occurs. [4] 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[en.wikipedia.org]
Claustrophobia
  • MRI and MRCP can be hampered by artifact, as well as by such patient factors as claustrophobia or excessive weight.[emedicine.com]

Workup

In the modern world, many non-invasive techniques are available for the diagnosis of biliary system diseases. Caroli disease is limited to the left lobe of the liver in most of the cases.

On ultrasonography, tubular dilatation of both the intra-hepatic and the extra-hepatic biliary ducts are seen. CT-scan usually shows many fluid filled structures extending to the liver.

Protrusions in the intrahepatic bile duct wall can also be seen in the form of central dots or elongated streaks [4]. Caroli disease is commonly diagnosed after this “central dot” sign is detected on a CT scan or ultrasound [5] [6].

Magnetic resonance cholangiopancreatography (MRCP) is a non-invasive technique and also provides the best diagnosis [7].

Nowadays, a specific endoscopic approach is also gaining a lot of popularity. It is called endoscopic retrograde cholangiopancreatography (ERCP) and provides both diagnostic as well as therapeutic facilities.

Enlargement of the Liver
  • It is associated with enlargement of the liver parenchyma and is the most common finding on general physical examination of the patient. When blockage of bile is for long duration, then super-saturation of cholesterol in the bile takes place.[symptoma.com]
  • We suspect these patients showed increased peripheral spherocytes due to hypersplenism from portal hypertension and were misdiagnosed as liver cirrhosis due to an apparent nodular enlarged liver.[kjim.org]

Treatment

Management and treatment of Caroli disease depends upon the age of patient and the location of biliary blockage. Minimally invasive surgery is the preferred method to treat this condition. If surgery cannot be performed or has to be delayed, Caroli disease can be managed symptomatically.

  • Strong, broad-spectrum antibiotics are given to provide relief from infections of the bile ducts and to combat the fever due to infection.
  • Pruritis is most distressing symptom as it is very severe and causes a lot of nuisance. It can be managed with cholestyramine or other similar bile sequestering agents.
  • When the pain starts in the right hypochondrium, it means that the gall bladder is inflamed. Pain of this type can be managed conservatively or by doing cholecystectomy (i.e. the surgical removal of gall bladder).
  • When a single lobe is involved, then the symptoms can be relieved by partial hepatectomy [8]. This intervention also reduces the risk of malignancy [9].
  • Bile solubilizing agents such as ursodiol are used to manage cholelithiasis.
  • Biliary stenting is also used to provide a route for bile flow and to relieve the symptoms of biliary stasis.
  • Roux-en-Y hepatico-jejunostomy or choledocho-jejunostomy can also be done to provide bypass routes to the bile flow when possible.
  • Liver transplant is the last resort in the treatment of advanced cases of Caroli disease. Liver transplant also reduces the long term probability of developing cholangiocarcinoma in such patients [10]. The survival rate of these patients after liver transplant is also very high [11].

Prognosis

The prognosis in cases suffering from Caroli disease is not very good. Patients usually die in 5 to 10 years once recurrent attacks of cholangitis start.

The prognosis primarily depends upon the variant of this disease. The autosomal dominant variety has a reasonable better prognosis as compared to the autosomal recessive type.

When surgical interventions or endoscopic stent placement for bile drainage are not possible, the patient usually dies of recurrent biliary infections and/or attacks of cholangitis.

Etiology

The causes of Caroli disease are not very obvious. The pattern of inheritance in case of simple disease is autosomal dominant.

However, in case of complex disease, the pattern of inheritance is autosomal recessive. The mutations responsible for this disease are found on PKHD1 gene. This gene is also associated with autosomal recessive polycystic kidney disease.

Epidemiology

Caroli disease is a rare inherited disorder. It affects 1 in every 2000 persons. It is most commonly diagnosed in the people under the age of 22.

Caroli disease is more common in the female gender as compared to the male gender [2].

Sex distribution
Age distribution

Pathophysiology

Normally, there is a proper balance in the expression of vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptors type 1 and 2 (VEGFR 1, 2). However, in Caroli disease mutated PKHD1 gene causes several malfunctions in molecular pathways that lead to Caroli disease. Some of them are explained below:

  • Cholangiocytes over expresses vascular endothelial growth factor (VEGF), its receptors (vascular endothelial growth factor receptors type 1 & 2) and angiopoietin 2. Overexpression of vascular endothelial growth factor causes cholangiocytes to become dense. VEGF also has a proliferative effect on cholangiocytes and produces hindrance in the bile flow.
  • Vascular endothelial growth factor also causes the dilatation of bile ducts through the proliferation of cholangiocytes via an autocrine effect.
  • Cholangiocytes are also activated through a separate rapamycin (mTOR) dependent mechanism.
  • Support around the intra-hepatic biliary ducts is provided by laminin and collagen type 4. In Caroli disease, however, these constituents are degraded and the resultant loss of supportive effects causes dilatation of the intra-hepatic biliary ducts.

Prevention

There are no guidelines for prevention of Caroli disease.

Summary

Caroli disease is related primarily to intra-hepatic biliary system. It affects the bile ducts inside the liver parenchyma. It is an inherited disorder characterized by dilatation of the intra-hepatic biliary ductal system. Dilatation occurs due to duct ectasia and increase in back pressure.

Depending upon the location of ducts involved, it is divided into following variants:

  • Caroli disease: It is less common and involves only the larger intra-hepatic ducts.
  • Caroli syndrome: It is more common as compared to Caroli disease. There is involvement of the smaller intra-hepatic ducts and congenital hepatic fibrosis [1].

The symptoms and signs of Caroli disease mainly result from the defective drainage of conjugated bile salts. Bile salts continue to accumulate within the liver.

As a result, there is an increase in the back pressure in the bile canaliculi. Later, there is an accumulation of bile salts under the skin (causing pruritis) and also in the sclera, which causes yellowing of eyes.

Caroli disease is a genetic disease and pattern of inheritance is usually autosomal recessive, although autosomal dominant pattern is also seen in a small number of cases.

Patient Information

Caroli disease results from the widening of the bile carrying ducts inside the liver. This results when a high back-pressure develops in these ducts.

When a person has yellowness of eyes or itching all over the body which do not respond to steroids or anti-allergy medications, then Caroli disease should be suspected.

Prognosis of this disease with proper treatment is reasonably fair.

References

Article

  1. Fabian W. Caroli syndrome: Isolated congenital dilatation of intrahepatic bile ducts. Fortschritte der Medizin. Jan 20 1991;109(2):46, 49-50.
  2. Kahn, Charles, F. Collaborative Hypertext of Radiology. Medical College of Wisconsin; 2003.
  3. Faria G, de Aretxabala X, Sierralta A, Flores P, Burgos L. [Primary cholangiocarcinoma associated with Caroli disease]. Revista medica de Chile. Dec 2001;129(12):1433-1438.
  4. Chiba T, Shinozaki, M, Kato, S, Goto, N, Fujimoto, H, Kondo, F. Caroli's disease: central dot sign re-examined by CT arteriography and CT during arterial portography. Eur Radiol. 2002;12(3):701-702.
  5. Choi BI, Yeon KM, Kim SH, Han MC. Caroli disease: central dot sign in CT. Radiology. Jan 1990;174(1):161-163.
  6. Lall NU, Hogan MJ. Caroli disease and the central dot sign. Pediatric radiology. Jul 2009;39(7):754.
  7. Folsing C, Helmberger T, Sittek H, Reiser M. [Caroli syndrome: diagnostic possibilities of magnetic resonance tomography and MR cholangiopancreaticography]. Rontgenpraxis; Zeitschrift fur radiologische Technik. Sep 1996;49(9):226-228.
  8. Badura J, Krol R, Kurek A, Hartleb M, Cierpka L. Left-hemihepatectomy as a method of treatment of locally limited Caroli disease. Polski przeglad chirurgiczny. Nov 1 2013;85(11):663-665.
  9. Taylor A, Palmer, KR. Caroli's disease. European journal of gastroenterology & hepatology. 1998;10(2):105-108.
  10. Ulrich F, Pratschke J, Pascher A, et al. Long-term outcome of liver resection and transplantation for Caroli disease and syndrome. Annals of surgery. Feb 2008;247(2):357-364.
  11. Harring TR, Nguyen NT, Liu H, Goss JA, O'Mahony CA. Caroli disease patients have excellent survival after liver transplant. The Journal of surgical research. Oct 2012;177(2):365-372.

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Last updated: 2019-07-11 21:59