Caroli Disease from Pediatrics / Gastroenterology

eMedicine Journal > Pediatrics > Gastroenterology Caroli Disease Synonyms, Key Words, and Related Terms: Caroli disease, Caroli’s disease, congenital hepatic fibrosis, autosomal recessive polycystic kidney disease, ARPKD, simple form Caroli disease, choledochal cyst type V, Caroli syndrome, Caroli’s syndrome, ductal plate malformation, ductal-plate malformation, DPM
Author Information \| Introduction \| Clinical \| Differentials \| Workup \| Treatment \| Medication \| Follow-up \| Miscellaneous \| Test Questions \| Pictures \| Bibliography

AUTHOR INFORMATION Section 1 of 12

Authored by Joshua R Friedman, MD, PhD, Assistant Professor, Department of Pediatrics, Division of Gastroenterology and Nutrition, The Children's Hospital of Philadelphia

Coauthored by David Piccoli, MD, Chief, Division of Gastroenterology and Nutrition, The Children's Hospital of Philadelphia; Professor, Department of Pediatrics, University of Pennsylvania School of Medicine; Robert Baldassano, MD, Director, Center for Pediatric Inflammatory Bowel Disease, Associate Professor, Department of Pediatrics, Division of Gastroenterology and Nutrition, The Children's Hospital of Philadelphia, University of Pennsylvania

Joshua R Friedman, MD, PhD, is a member of the following medical societies: American Academy of Pediatrics, American Association for the Study of Liver Diseases, and North American Society for Pediatric Gastroenterology and Nutrition

Edited by Robert Baldassano, MD, Director, Center for Pediatric Inflammatory Bowel Disease, Associate Professor, Department of Pediatrics, Division of Gastroenterology and Nutrition, The Children's Hospital of Philadelphia, University of Pennsylvania; Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine.com, Inc; Carmen Cuffari, MD, Associate Professor, Department of Pediatrics, Division of Gastroenterology/Nutrition, The Johns Hopkins University School of Medicine; Steven M Schwarz, MD, FAAP, FACN, Chair, Department of Pediatrics, Long Island College Hospital; Professor of Pediatrics, State University of New York, Downstate Medical Center College of Medicine; and Carmen Cuffari, MD, Associate Professor, Department of Pediatrics, Division of Gastroenterology/Nutrition, The Johns Hopkins University School of Medicine

Author's Email: Joshua R Friedman, MD, PhD
Editor's Email: Robert Baldassano, MD

Author's Email:	Joshua R Friedman, MD, PhD
Editor's Email:	Robert Baldassano, MD

eMedicine Journal, April 11 2006, VOLUME 7, Number 4

INTRODUCTION Section 2 of 12

Background: Caroli disease and Caroli syndrome are rare congenital disorders of the intrahepatic bile ducts. They are both characterized by dilatation of the intrahepatic biliary tree. The term Caroli disease is applied if the disease is limited to ectasia or segmental dilatation of the larger intrahepatic ducts. This form is less common than Caroli syndrome, in which malformations of small bile ducts and congenital hepatic fibrosis are also present. Caroli disease is sporadic, whereas Caroli syndrome is generally inherited in an autosomal recessive manner. As with congenital hepatic fibrosis, Caroli syndrome is often associated with autosomal recessive polycystic kidney disease (ARPKD). A rare association with autosomal dominant polycystic kidney disease (ADPKD) has also been reported.

Pathophysiology: The precursor of the intrahepatic biliary tree is a double-layered sleeve of cells known as the ductal plate (DP). The DP first arises from hepatocyte precursors surrounding hilar portal vein vessels at 8 weeks’ gestation, and peripheral regions of the DP then develop sequentially. During the remainder of gestation, a process of DP remodeling occurs in which small areas of the double layer separate to form tubules, which join to form the intrahepatic biliary tree, while the remaining regions of the DP become involuted. Caroli syndrome belongs to a subcategory of diseases thought to originate from failures of this process collectively known as ductal-plate malformation.

In Caroli disease, abnormalities of the bile duct occur at the level of the large intrahepatic ducts (ie, left and right hepatic ducts, segmental ducts), resulting in dilatation and ectasia. Resulting biliary stasis may lead to cholelithiasis, cholangitis, and sepsis, as well as an increased risk of cholangiocarcinoma.

In Caroli syndrome, ductal-plate malformation is present at the level of the smallest portal tracts and associated with varying degrees of portal fibrosis. These findings are typical of congenital hepatic fibrosis; therefore, Caroli syndrome is thought to exist in the same spectrum of disease as congenital hepatic fibrosis. As with congenital hepatic fibrosis, the pathology may also include features of ARPKD.

Frequency:

In the US: Because Caroli disease/syndrome rarely occurs in the United States, the exact frequency is unknown. Caroli syndrome (ectasia of the large and small bile ducts with congenital hepatic fibrosis) is more common than Caroli disease (ectasia of only the large bile ducts).

Mortality/Morbidity: Patients with Caroli disease or syndrome may have recurrent episodes of cholangitis, and they are also at risk for associated bacteremia and sepsis.

Patients with Caroli syndrome may have cholangitis, as do those with Caroli disease; however, they may also have the complications of portal hypertension observed in congenital hepatic fibrosis.

Caroli syndrome is associated with ARPKD, and patients may have various degrees of renal cysts, interstitial fibrosis, and renal failure.

Both Caroli disease and Caroli syndrome are associated with a risk of cholangiocarcinoma at a rate of 100 times that of the general population.

Sex: Symptoms of Caroli disease or syndrome are more common in female patients than in male patients.

Age: Symptoms appear first in adults, though childhood and neonatal cases have been reported. Cases of prenatal diagnosis based on ultrasonographic findings have been reported.
CLINICAL Section 3 of 12

History:

The patient may have a history of intermittent abdominal pain, which reflects episodes of bile stasis or the passage of bile stones.

Patients with cholangitis may report fever and pain in the right upper quadrant.

In Caroli syndrome, portal hypertension may result in hematemesis or melena.

Because Caroli syndrome is associated with ARPKD and because it appears to be inherited in an autosomal recessive manner, the patient may have a family history of kidney or liver disease.

Physical:

Hepatomegaly is present.

Splenomegaly occurs.

Tenderness of the right upper quadrant is occasionally present.

Abdominal mass or masses occur if large polycystic kidneys are present.

Jaundice is rarely present.

Causes:

A genetic cause is likely, given the association with ARPKD.

- Mutations in PKHD1, the gene linked to ARPKD have also been identified in patients with Caroli syndrome.
- The number of cases of Caroli syndrome caused by PKHD1 mutations is not known.
Caroli syndrome appears to be inherited in an autosomal recessive manner.

DIFFERENTIALS

Section 4 of 12

Cholelithiasis
Congenital Hepatic Fibrosis

Other Problems to be Considered:

Cholangitis
Choledochal cyst
Polycystic liver disease
Hepatic abscesses

WORKUP Section 5 of 12

Lab Studies:

Bilirubin levels are usually in the reference range.

Transaminase levels may be slightly elevated.

The CBC may reveal thrombocytopenia and leukopenia if portal hypertension and hypersplenism are present. An elevated WBC count or erythrocyte sedimentation rate (ESR) may indicate cholangitis.

Creatinine and BUN values should be obtained to detect associated renal disease.

Imaging Studies:

Ultrasonography is the best initial imaging study because it reveals the irregular dilatation of the large intrahepatic bile ducts typical of Caroli disease or syndrome.

- Extrahepatic biliary dilatation may also be present as a result of prior cholelithiasis.
- Doppler evaluation of the liver can be used to detect portal hypertension.
- The kidneys can also be assessed for evidence of polycystic kidney disease.
Magnetic resonance cholangiography is increasingly used to diagnose Caroli disease or syndrome.

- It provides excellent images of the intrahepatic and extrahepatic biliary trees, and it can also depict renal involvement.
- Its use is currently limited by the availability of the necessary equipment and expertise.
CT may be used, particularly if sonograms cannot be obtained because of bowel gas or body habitus.

Hepatobiliary scintigraphy can be useful to document communication between cysts and the biliary system, a feature present in Caroli disease or syndrome but absent in polycystic liver disease and hepatic abscesses.

Invasive modalities, such as percutaneous transhepatic cholangiography (PTC) and endoscopic retrograde cholangiopancreatography (ERCP), enable excellent visualization of the biliary tree. However, these studies are limited by the risks of complications.

Procedures:

Liver biopsy and culture should be performed in cases of suspected chronic cholangitis.

ERCP has been used to identify and treat biliary stones in patients with Caroli disease or syndrome, but it is associated with a postprocedural risk of cholangitis.

Portosystemic shunting may be indicated in patients who have portal hypertension.

Histologic Findings: Liver biopsy reveals the typical pattern of ductal-plate malformation, with bile-duct ectasia, portal-vein malformations, and fibrosis. In Caroli syndrome, ductal-plate malformation is evident throughout the liver, whereas only large intrahepatic ducts are affected in relatively rare Caroli disease.

TREATMENT Section 6 of 12

Medical Care: Ursodeoxycholic acid can decrease the frequency of complications due to cholelithiasis. Broad-spectrum antibiotic coverage, including anaerobic coverage, is indicated in cases of cholangitis.

Surgical Care: Surgical treatment may be necessary for recurrent or refractory cholangitis. Obstructing stones can be removed and bile flow can be maintained by means of a hepaticojejunostomy or external drainage.

In cases of localized stasis, lobectomy can be curative and can also reduce the risk of cholangiocarcinoma.

In severe cases of refractory or chronic cholangitis or in cases of liver failure, transplantation may be considered.

MEDICATION

Section 7 of 12

Ursodiol can promote the dissolution of intrahepatic stones and promote bile flow in Caroli disease or syndrome.

Broad-spectrum antibiotics are used in the treatment of cholangitis associated with Caroli disease or syndrome.

Drug Category: Gallstone dissolution agents -- These agents are used to prevent and possibly to dissolve gallbladder stones. They enhance bile salt–dependent biliary flow. They also act as choleretic agents and may prove to be a valuable addition to therapy in repeated and refractory cholangitis.
Drug Name
Ursodiol (Urso, Actigall) -- Also called ursodeoxycholic acid. Naturally occurring bile used to dissolve radiolucent gallstones. Suppresses hepatic cholesterol synthesis, cholesterol secretion, and inhibits cholesterol intestinal absorption. Little inhibitory effect on synthesis and secretion into bile of endogenous bile acids and does not appear to affect phospholipid secretion into bile. Alters bile composition from supersaturated to unsaturated. Ursodiol-rich bile solubilizes cholesterol by increasing the concentration level at which cholesterol saturation occurs. Promotes bile flow in cholestatic conditions associated with patent extrahepatic biliary system.
Adult Dose 300 mg PO bid
Pediatric Dose 8-10 mg/kg/d PO divided q8-12h
Contraindications Documented hypersensitivity; bile pigment or radiopaque stones; stones >20 mm diameter; obstruction of extrahepatic biliary tree
Interactions Aluminum-containing antacids, cholestyramine, and colestipol may decrease absorption
Pregnancy B - Usually safe but benefits must outweigh the risks.

Precautions Stone dissolution may take months, and stones may recur; caution in nonvisualized gall bladder and chronic liver disease; GI effects include nausea, vomiting, diarrhea, or constipation; dermatologic effects include rash; monitor hepatic enzymes
Drug Category: Antibiotic agents -- Broad-spectrum antibiotics are used to treat cholangitis. Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting.
Drug Name
Ampicillin and sulbactam (Unasyn) -- Drug combination of beta-lactamase inhibitor with ampicillin. Used to treat infections involving skin, enteric flora, and anaerobes. Provides broad gram-positive and anaerobic coverage. Should be combined with an agent with gram-negative coverage, such as aminoglycoside.
Adult Dose 1.5 (1 g ampicillin + 0.5 g sulbactam) to 3 g (2 g ampicillin + 1 g sulbactam) IV/IM q6-8h; not to exceed 4 g/d sulbactam or 8 g/d ampicillin
Pediatric Dose 3 months to 12 years: 100-200 mg ampicillin/kg/d (150-300 mg Unasyn) IV divided q6h
>12 years: Administer as in adults; not to exceed 4 g/d sulbactam or 8 g/d ampicillin
Contraindications Documented hypersensitivity
Interactions Probenecid and disulfiram elevate ampicillin levels; allopurinol decreases ampicillin effects and has additive effects on ampicillin rash; may decrease effects of PO contraceptives
Pregnancy B - Usually safe but benefits must outweigh the risks.

Precautions Adjust dose in patients with renal impairment; potential cross-sensitivity to other beta-lactams
Drug Name
Gentamicin (Garamycin) -- Used to treat cholangitis. Aminoglycoside antibiotic for gram-negative coverage. Used in combination with an agent against gram-positive organisms and one that covers anaerobes.
Adult Dose 5-6 mg/kg/d IV divided q8h; must adjust dose and frequency to serum drug levels
Pediatric Dose Postnatal age <7 days:
<28 weeks’ gestational age: 2.5 mg/kg IV q24h
28-34 week s’ gestational age: 2.5 mg/kg IV q18h
>34 week s’ gestational age: 2.5 mg/kg IV q12h
Postnatal age > 7 days:
1200-2000 grams: 2.5 mg/kg IV q12h
>2000 grams: 2.5 mg/kg IV q8h
Infants and children
<10 years: 2.5 mg/kg IV q8h
>10 years: Administer as in adults
Must adjust dose and frequency to serum drug levels
Contraindications Documented hypersensitivity
Interactions Coadministration with other aminoglycosides, cephalosporins, penicillins, and amphotericin B may increase nephrotoxicity; aminoglycosides enhance effects of neuromuscular blocking agents (prolonged respiratory depression may occur); coadministration with loop diuretics may increase auditory toxicity of aminoglycosides; possible irreversible hearing loss of varying degrees may occur (monitor regularly)
Pregnancy D - Unsafe in pregnancy

Precautions Narrow therapeutic index (not intended for long-term therapy); caution in renal failure (patient not receiving dialysis), myasthenia gravis, hypocalcemia, and conditions that depress neuromuscular transmission; adjust dose and frequency in renal insufficiency and renal impairment
FOLLOW-UP Section 8 of 12

Drug Name	Ursodiol (Urso, Actigall) -- Also called ursodeoxycholic acid. Naturally occurring bile used to dissolve radiolucent gallstones. Suppresses hepatic cholesterol synthesis, cholesterol secretion, and inhibits cholesterol intestinal absorption. Little inhibitory effect on synthesis and secretion into bile of endogenous bile acids and does not appear to affect phospholipid secretion into bile. Alters bile composition from supersaturated to unsaturated. Ursodiol-rich bile solubilizes cholesterol by increasing the concentration level at which cholesterol saturation occurs. Promotes bile flow in cholestatic conditions associated with patent extrahepatic biliary system.
Adult Dose	300 mg PO bid
Pediatric Dose	8-10 mg/kg/d PO divided q8-12h
Contraindications	Documented hypersensitivity; bile pigment or radiopaque stones; stones >20 mm diameter; obstruction of extrahepatic biliary tree
Interactions	Aluminum-containing antacids, cholestyramine, and colestipol may decrease absorption
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Stone dissolution may take months, and stones may recur; caution in nonvisualized gall bladder and chronic liver disease; GI effects include nausea, vomiting, diarrhea, or constipation; dermatologic effects include rash; monitor hepatic enzymes

Drug Name	Ampicillin and sulbactam (Unasyn) -- Drug combination of beta-lactamase inhibitor with ampicillin. Used to treat infections involving skin, enteric flora, and anaerobes. Provides broad gram-positive and anaerobic coverage. Should be combined with an agent with gram-negative coverage, such as aminoglycoside.
Adult Dose	1.5 (1 g ampicillin + 0.5 g sulbactam) to 3 g (2 g ampicillin + 1 g sulbactam) IV/IM q6-8h; not to exceed 4 g/d sulbactam or 8 g/d ampicillin
Pediatric Dose	3 months to 12 years: 100-200 mg ampicillin/kg/d (150-300 mg Unasyn) IV divided q6h >12 years: Administer as in adults; not to exceed 4 g/d sulbactam or 8 g/d ampicillin
Contraindications	Documented hypersensitivity
Interactions	Probenecid and disulfiram elevate ampicillin levels; allopurinol decreases ampicillin effects and has additive effects on ampicillin rash; may decrease effects of PO contraceptives
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Adjust dose in patients with renal impairment; potential cross-sensitivity to other beta-lactams

Drug Name	Gentamicin (Garamycin) -- Used to treat cholangitis. Aminoglycoside antibiotic for gram-negative coverage. Used in combination with an agent against gram-positive organisms and one that covers anaerobes.
Adult Dose	5-6 mg/kg/d IV divided q8h; must adjust dose and frequency to serum drug levels
Pediatric Dose	Postnatal age <7 days: <28 weeks’ gestational age: 2.5 mg/kg IV q24h 28-34 week s’ gestational age: 2.5 mg/kg IV q18h >34 week s’ gestational age: 2.5 mg/kg IV q12h Postnatal age > 7 days: 1200-2000 grams: 2.5 mg/kg IV q12h >2000 grams: 2.5 mg/kg IV q8h Infants and children <10 years: 2.5 mg/kg IV q8h >10 years: Administer as in adults Must adjust dose and frequency to serum drug levels
Contraindications	Documented hypersensitivity
Interactions	Coadministration with other aminoglycosides, cephalosporins, penicillins, and amphotericin B may increase nephrotoxicity; aminoglycosides enhance effects of neuromuscular blocking agents (prolonged respiratory depression may occur); coadministration with loop diuretics may increase auditory toxicity of aminoglycosides; possible irreversible hearing loss of varying degrees may occur (monitor regularly)
Pregnancy	D - Unsafe in pregnancy
Precautions	Narrow therapeutic index (not intended for long-term therapy); caution in renal failure (patient not receiving dialysis), myasthenia gravis, hypocalcemia, and conditions that depress neuromuscular transmission; adjust dose and frequency in renal insufficiency and renal impairment

Further Inpatient Care:

Indications for hospitalization

- Suspected cholangitis or sepsis
- Obstructing cholelithiasis requiring invasive intervention
- Complications of end-stage liver disease

Further Outpatient Care:

Liver function and transaminase levels can be monitored on an outpatient basis.

Ultrasonography can be used to monitor stones.

Prognosis:

Hepatic manifestations

- In the few patients who have intrahepatic ductal ectasia without associated congenital hepatic fibrosis (ie, Caroli disease), the frequency and severity of episodes of cholangitis, which may result in sepsis or death, largely determines the prognosis. Progressive liver failure may also develop, and liver transplantation may be required.
- Patients with both ductal ectasia and congenital hepatic fibrosis (ie, Caroli syndrome) are subject to the risks and consequences of recurrent cholangitis, as described above. They are also at risk for the complications of portal hypertension, namely, variceal bleeding, hypersplenism, and thrombocytopenia.
Renal manifestations

- The degree of polycystic kidney disease associated with Caroli disease or syndrome is variable.
- Patients who present with renal disease as neonates or infants are more likely to have severe disease with enlarged cystic kidneys and progressive renal failure than others.
- Other patients may have normal-appearing kidneys or minimal cystic changes with only mild deficits in renal function.

MISCELLANEOUS

Section 9 of 12

Medical/Legal Pitfalls:

Patients with Caroli disease or syndrome should be screened for associated renal anomalies and impaired renal function.

TEST QUESTIONS

Section 10 of 12

CME Question 1: When does the ductal plate (DP) first appear?

A: At 8 weeks’ gestation
B: At 12 weeks’ gestation
C: In the third trimester
D: In the neonatal period
E: None of the above

The correct answer is A: The DP first arises from hepatocyte precursors surrounding hilar portal-vein vessels at 8 weeks’ gestation, and peripheral regions of the DP then develop sequentially.

CME Question 2: Which statement about the difference between Caroli disease and Caroli syndrome is true?

A: In Caroli syndrome, renal disease is also present.
B: In Caroli syndrome, the small intrahepatic ducts are affected, and hepatic fibrosis is present.
C: Caroli disease occurs only in adults.
D: Caroli disease resolves without therapy.
E: None of the above is accurate.

The correct answer is B: In Caroli disease, the ductal-plate malformation occurs at the level of the larger intrahepatic ducts. In Caroli syndrome, the ductal-plate malformation occurs at all levels of bile-duct formation, with portal-vein malformations and fibrosis of the portal tracts and/or fibrous bands extending across adjacent portal tracts. These findings are typical of congenital hepatic fibrosis; therefore, Caroli syndrome is thought to exist in the same spectrum of disease as congenital hepatic fibrosis.

Pearl Question 1 (T/F): Hepatic ultrasonography is the first imaging study in diagnosing Caroli disease to syndrome.

The correct answer is True: Ultrasonography is the best initial imaging study because it reveals the irregular dilatation of the large intrahepatic bile ducts typical of Caroli disease or syndrome, as well as the associated renal abnormalities.

Pearl Question 2 (T/F): Caroli syndrome is limited to the hepatobiliary system.

The correct answer is False: Autosomal recessive polycystic kidney disease (ARPKD) has been associated with Caroli syndrome. The hepatic and renal malformations are suspected to reflect errors in related development processes, with resulting ductal-plate malformation in the liver and cyst formation in the kidneys.

Pearl Question 3 (T/F): Patients with Caroli disease or syndrome rarely develop jaundice.

The correct answer is True: The abnormality in bile drainage is rarely severe enough to result in clinically evident hyperbilirubinemia.

Pearl Question 4 (T/F): Caroli disease or syndrome may involve only part of the liver.

The correct answer is True: Patients with localized disease may be candidates for lobectomy.
PICTURES Section 11 of 12

Caption: Picture 1. Hepatic ultrasonogram of a neonate with Caroli disease. Multiple dilated intrahepatic bile ducts are present. Courtesy of Richard Bellah, MD, The Children's Hospital of Philadelphia.
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BIBLIOGRAPHY Section 12 of 12

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D'Agata ID, Jonas MM, Perez-Atayde AR, et al: Combined cystic disease of the liver and kidney. Semin Liver Dis 1994 Aug; 14(3): 215-28[Medline].
Guy F, Cognet F, Dranssart M, et al: Caroli's disease: magnetic resonance imaging features. Eur Radiol 2002 Nov; 12(11): 2730-6[Medline].
Hunter FM, Akdamar K, Sparks RD, et al: Congenital dilation of the intrahepatic bile ducts. Am J Med 1966 Feb; 40(2): 188-94[Medline].
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Madjov R, Chervenkov P, Madjova V, Balev B: Caroli's disease. Report of 5 cases and review of literature. Hepatogastroenterology 2005 Mar-Apr; 52(62): 606-9[Medline].
Mall JC, Ghahremani GG, Boyer JL: Caroli's disease associated with congenital hepatic fibrosis and renal tubular ectasia. A case report. Gastroenterology 1974 May; 66(5): 1029-35[Medline].
Miller WJ, Sechtin AG, Campbell WL, et al: Imaging findings in Caroli's disease. AJR Am J Roentgenol 1995 Aug; 165(2): 333-7[Medline].
Nakanuma Y, Terada T, Ohta G, et al: Caroli's disease in congenital hepatic fibrosis and infantile polycystic disease. Liver 1982 Dec; 2(4): 346-54[Medline].
Piccoli DA, Witzleben CL: Disorders of the intrahepatic bile ducts. In: Pediatric Gastrointestinal Disease. Philadelphia, Pa: WB Saunders Co; 2000: 1124-1140.
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Sanzen T, Harada K, Yasoshima M, et al: Polycystic kidney rat is a novel animal model of Caroli's disease associated with congenital hepatic fibrosis. Am J Pathol 2001 May; 158(5): 1605-12[Medline][Full Text].
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Sleisenger MH, Fordtran JS, Feldman M, et al: Anatomy, anomalies, and pediatric disorders of the biliary tract. In: Sleisenger and Fordtran's Gastrointestinal and Liver Disease: Pathophysiology/Diagnosis/Management. WB Saunders Co; 1993:917-927.
Suchy FJ: The cholangiopathies. In: Sokol RJ, Balistreri WF, eds. Liver Disease in Children. Philadelphia, Pa: Lippincott Williams & Wilkins; 1994: 153-165.
Summerfield JA, Nagafuchi Y, Sherlock S, et al: Hepatobiliary fibropolycystic diseases. A clinical and histological review of 51 patients. J Hepatol 1986; 2(2): 141-56[Medline].

NOTE:
Medicine is a constantly changing science and not all therapies are clearly established. New research changes drug and treatment therapies daily. The authors, editors, and publisher of this journal have used their best efforts to provide information that is up-to-date and accurate and is generally accepted within medical standards at the time of publication. However, as medical science is constantly changing and human error is always possible, the authors, editors, and publisher or any other party involved with the publication of this article do not warrant the information in this article is accurate or complete, nor are they responsible for omissions or errors in the article or for the results of using this information. The reader should confirm the information in this article from other sources prior to use. In particular, all drug doses, indications, and contraindications should be confirmed in the package insert. FULL DISCLAIMER

NOTE:

Medicine is a constantly changing science and not all therapies are clearly established. New research changes drug and treatment therapies daily. The authors, editors, and publisher of this journal have used their best efforts to provide information that is up-to-date and accurate and is generally accepted within medical standards at the time of publication. However, as medical science is constantly changing and human error is always possible, the authors, editors, and publisher or any other party involved with the publication of this article do not warrant the information in this article is accurate or complete, nor are they responsible for omissions or errors in the article or for the results of using this information. The reader should confirm the information in this article from other sources prior to use. In particular, all drug doses, indications, and contraindications should be confirmed in the package insert. FULL DISCLAIMER

Caption: Picture 1. Hepatic ultrasonogram of a neonate with Caroli disease. Multiple dilated intrahepatic bile ducts are present. Courtesy of Richard Bellah, MD, The Children's Hospital of Philadelphia.
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