Pediatric Primary Sclerosing Cholangitis Workup

  • Author: David A Piccoli, MD; Chief Editor: Carmen Cuffari, MD   more...
 
Updated: Apr 5, 2012
 

Approach Considerations

In patients with primary sclerosing cholangitis (PSC), the most valuable lab studies are liver function tests, including serum alkaline phosphatase, serum aminotransferase, and hypergammaglobulinemia. Endoscopic retrograde cholangiopancreatography (ERCP) is the most important imaging study. Magnetic resonance cholangiography and ultrasonography are also utilized. The most characteristic histologic findings of primary sclerosing cholangitis are periductal fibrosis with inflammation, bile duct proliferation, and ductopenia.

Liver biopsy findings are nonspecific and are infrequently diagnostic. However, liver histology remains important to exclude other causes of chronic cholestasis and to stage the disease.

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Laboratory Studies

The most common abnormality in patients with primary sclerosing cholangitis (PSC) is an elevated alkaline phosphatase or gamma-glutamyl transferase (GGT) level. Serum transaminase levels may be normal or elevated to several times normal. The serum bilirubin level is elevated in advanced stages of primary sclerosing cholangitis.

Results from hepatic synthetic function tests (eg, serum albumin, prothrombin time [PT]) become abnormal with advanced disease activity. Serum cholylglycine is often markedly elevated, out of proportion to the elevation of serum bilirubin.

Immunoglobulin G (IgG) and immunoglobulin M (IgM) levels are elevated in 48% and 80% of cases of PSC, respectively. The serum globulin fraction may also be elevated in some patients with primary sclerosing cholangitis. Perinuclear antineutrophil cytoplasmic antibodies (p-ANCAs) have been found to be present in 60-82% of patients with primary sclerosing cholangitis but lack diagnostic specificity for PSC; frequency in ulcerative colitis is similar.

Assessment of the target antigens for ANCA (eg, catalase, alpha-enolase, lactoferrin) does not significantly contribute to their clinical importance. The presence of ANCA is associated with a more severe course of autoimmune liver disease. The anti– Saccharomyces cerevisiae antibody is also found in some patients with PSC, independent of inflammatory bowel disease status.

A serum carbohydrate antigen 19-9 (CA 19-9) level greater than 100 U/mL has 75% sensitivity and 80% specificity in identifying patients with primary sclerosing cholangitis who have cholangiocarcinoma.

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Magnetic Resonance Cholangiography

Peripheral wedge-shaped areas of high T2 signal intensity and dilatation of bile ducts are characteristic magnetic resonance findings in primary sclerosing cholangitis (PSC). Pathologic correlation of MR cholangiography (MRC) findings suggests that these features may be related to underlying perfusion changes and bile duct inflammation.

The overall diagnostic accuracy of MRC in patients with PSC is 90%, compared to 97% for endoscopic retrograde cholangiopancreatography (ERCP) or percutaneous transhepatic cholangiography (PTC).[10] The advantages of MRC include less risk of complications, as compared with ERCP. In addition, MRC has the advantage of visualizing bile ducts proximal to obstructed areas.[11, 12]

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Ultrasonography

Ultrasonography may reveal intrahepatic and extrahepatic ductal dilatation; increased echogenicity and heterogeneity observed with cirrhosis; and splenomegaly and ascites observed with portal hypertension.[13] Ultrasonographic findings may be normal in as many as 50% of patients.

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Endoscopic Retrograde Cholangiopancreatography

Endoscopic retrograde cholangiopancreatography (ERCP) remains the criterion standard for establishing the diagnosis of primary sclerosing cholangitis (PSC). ERCP demonstrates irregularly distributed areas of segmental bile duct fibrosis interposed by areas of saccular dilation that result in the characteristic appearance of beading.

As many as 40% of children with PSC lack extrahepatic duct involvement at the time of diagnosis. Serial cholangiograms have shown that in most patients with disease limited to the intrahepatic ducts, the disease progresses to involvement of the extrahepatic ducts.

Therapeutic interventions, such as dilation of strictures or placement of an endoprosthesis, can be performed during ERCP, but they carry an increased complication rate. Short-term stenting for symptomatic dominant strictures may have a role in PSC,[14] with a decrease in cholestatic complaints and improvement of the cholestatic biochemical profile (alkaline phosphatase, gamma-glutamyl transferase, conjugated bilirubin) for several years.

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Liver Biopsy

Certain liver histologic findings are highly suggestive of primary sclerosing cholangitis. More often, liver biopsy findings are nonspecific and infrequently diagnostic. Nevertheless, liver histology remains important to exclude other causes of chronic cholestasis and to stage the disease.

Sampling variability is observed in needle or core liver biopsies secondary to the heterogeneous distribution of biliary lesions.

Histologic Findings

A wide range of histologic findings is observed in primary sclerosing cholangitis (PSC). Nonspecific features include a periductal concentration of mononuclear cells and ductular proliferation. Less specific liver histology can present with a picture resembling chronic active hepatitis. One series of childhood cases described consistent periportal copper-associated protein (orcein stain) positivity.

The most characteristic findings of primary sclerosing cholangitis are periductal fibrosis with inflammation, bile duct proliferation, and ductopenia. This pathognomonic fibro-obliterative cholangiopathy (see the image below) has been occasionally observed in children with PSI.

Fibro-obliterative cholangiopathy. Image courtesy Fibro-obliterative cholangiopathy. Image courtesy of Dr. Kay Washington.
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Contributor Information and Disclosures
Author

David A Piccoli, MD  Chief of Pediatric Gastroenterology, Hepatology and Nutrition, The Children's Hospital of Philadelphia; Professor, University of Pennsylvania School of Medicine

David A Piccoli, MD is a member of the following medical societies: American Association for the Study of Liver Diseases, American Gastroenterological Association, and North American Society for Pediatric Gastroenterology and Nutrition

Disclosure: Nothing to disclose.

Chief Editor

Carmen Cuffari, MD  Associate Professor, Department of Pediatrics, Division of Gastroenterology/Nutrition, Johns Hopkins University School of Medicine

Carmen Cuffari, MD is a member of the following medical societies: American College of Gastroenterology, American Gastroenterological Association, North American Society for Pediatric Gastroenterology, Hepatology and Nutrition, and Royal College of Physicians and Surgeons of Canada

Disclosure: Nothing to disclose.

Additional Contributors

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

Robert Baldassano, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Pediatrics, American Gastroenterological Association, and North American Society for Pediatric Gastroenterology and Nutrition

Disclosure: Nothing to disclose.

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

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Fibro-obliterative cholangiopathy. Image courtesy of Dr. Kay Washington.
Endoscopic retrograde cholangiopancreatography performed in a patient with abnormal liver function test results shows multiple intrahepatic bile duct strictures and beading.
Double-contrast barium enema (same patient as in the previous image) shows filiform polyps and an ahaustral colon resulting from ulcerative colitis.
Percutaneous transhepatic cholangiogram shows dilatation, stricturing, and beading of the intrahepatic bile ducts. Note the surgical clips from a previous cholecystectomy.
T-tube cholangiogram shows irregularity of the common bile duct, stricturing, beading, and dilatation of the intrahepatic bile ducts. Note a calculus in the termination of the left hepatic duct (arrow).
Magnetic resonance cholangiopancreatography shows a normal-sized common bile duct, but strictures of both the left and right ducts are noted as well as a dilated proximal left hepatic duct.
Technetium-99m iminodiacetic acid scan shows retention of the radionuclide proximal to strictures in the distribution of the left hepatic duct. Note the lack of filling of the gallbladder because of a previous cholecystectomy. Isotope has entered the small bowel.
 
 
 
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