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Primary Sclerosing Cholangitis Workup

  • Author: Vikas Khurana, MD, FACP, FACG; Chief Editor: Julian Katz, MD  more...
 
Updated: Jan 03, 2016
 

Approach Considerations

Liver function tests and histology are used in the evaluation of patients with suspected primary sclerosing cholangitis (PSC).[2]

Liver function tests are the most valuable in the laboratory workup, including serum alkaline phosphatase, serum aminotransferase, and hypergammaglobulinemia. The most important imaging study is endoscopic retrograde cholangiopancreatography (ERCP). Transhepatic cholangiography and magnetic resonance cholangiopancreatography may also be utilized. The most common characteristic histologic feature is onion skin fibrosis (concentric periductal fibrosis) (see the image below). Liver biopsy is rarely diagnostic of PSC, although it does help determine both the stage and the prognosis of the disease.

Periductal onion skin fibrosis seen in primary scl Periductal onion skin fibrosis seen in primary sclerosing cholangitis.
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Laboratory Studies

Liver function tests

The most valuable lab studies in PSC are liver function tests. Serum alkaline phosphatase dominates the profile, which is cholestatic in nature. levels are usually 3-5 times reference-range values. Alkaline phosphatase can be divided into its various fractions to ascertain its origin from liver disease, as opposed to bone disease. Serum gamma-glutamyl transpeptidase levels mirror this rise and can help differentiate cholestasis from bone disease. Some patients with hypothyroidism, hypophosphatemia, or zinc or magnesium deficiency may have normal alkaline phosphatase levels.

Serum aminotransferase levels are increased but not markedly so. Serum bilirubin levels, with the conjugated component, are usually increased, but fluctuations in the level can occur. Serum albumin levels decrease later in the course of the disease, and the presence of hypoalbuminemia earlier in the disease may indicate active inflammatory bowel disease (IBD).

Hypergammaglobulinemia is present in 30% of patients, and 50% have increased immunoglobulin (IgM) levels. Perinuclear antineutrophil cytoplasmic antibodies (p-ANCA) are present in 84% of patients; anticardiolipin (aCL) antibodies, in 66%; and antinuclear antibodies (ANA), in 53%.

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Imaging Studies

Endoscopic retrograde cholangiopancreatography (ERCP) is considered the criterion standard for confirming a diagnosis of primary sclerosing cholangitis. ERCP findings include multiple strictures and dilations of the intrahepatic and extrahepatic biliary ducts. Transhepatic cholangiography is performed when ERCP is unsuccessful. Because it is noninvasive, magnetic resonance cholangiopancreatography (MRCP) is rapidly developing as the preferred study to evaluate the bile ducts. As image quality continues to improve, MRCP may become the preferred study.

See the related images below.

Endoscopic retrograde cholangiopancreatography per 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 t 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 dila 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 com 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 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 reten 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.

Magnetic resonance elastography (MRE) measurement of liver stiff appears to show promise as a potential biomarker in chronic liver disease.[21] In a retrospective review of 266 patients with primary sclerosing cholangitis, MRE not only showed a 100% sensitivity and 94% specificity for detecting cirrhosis, but it was also predictive of the development of decompensated liver disease. The investigators noted that advanced liver stiffness was unlikely in the presence of a serum alkaline phosphatase level less than 1.5 times the upper limit of normal.[21]

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Histologic Findings

A variety of histopathologic liver changes are noted in patients with PSC. The most common characteristic feature is onion skin fibrosis (see the image below), which describes the appearance of periductal concentric fibrosis around the interlobular and septal bile ducts. This is present in only half of all biopsy specimens from patients with otherwise typical primary sclerosing cholangitis, whereas concentric fibrosis with obliteration of the small ducts (obliterative fibrous cholangitis)—a virtually diagnostic histopathologic lesion—is found in less than 10% of biopsy specimens. Periductal fibrosis may be accompanied by infiltrates of inflammatory cells. Piecemeal necrosis, as occurs in patients with chronic hepatitis, may be observed as well.

Periductal onion skin fibrosis seen in primary scl Periductal onion skin fibrosis seen in primary sclerosing cholangitis.
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Contributor Information and Disclosures
Author

Vikas Khurana, MD, FACP, FACG Assistant Professor, Department of Medicine, Division of Gastroenterology and Hepatology, Graduate Hospital, Gastroenterology Associates, PC

Disclosure: Nothing to disclose.

Coauthor(s)

Hisham Nazer, MB, BCh, FRCP, , DTM&H Professor of Pediatrics, Consultant in Pediatric Gastroenterology, Hepatology and Clinical Nutrition, University of Jordan Faculty of Medicine, Jordan

Hisham Nazer, MB, BCh, FRCP, , DTM&H is a member of the following medical societies: American Association for Physician Leadership, Royal College of Paediatrics and Child Health, Royal College of Surgeons in Ireland, Royal Society of Tropical Medicine and Hygiene, Royal College of Physicians and Surgeons of the United Kingdom

Disclosure: Nothing to disclose.

Praveen K Roy, MD, AGAF Chief of Gastroenterology, Presbyterian Hospital; Medical Director of Endoscopy, Presbyterian Medical Group; Adjunct Associate Research Scientist, Lovelace Respiratory Research Institute

Praveen K Roy, MD, AGAF is a member of the following medical societies: American Gastroenterological Association, American Society for Gastrointestinal Endoscopy

Disclosure: Nothing to disclose.

Tejinder Singh, MD Lead Physician, Section of Emergency Services, Overton Brooks Veterans Affairs Medical Center

Disclosure: Nothing to disclose.

Chief Editor

Julian Katz, MD Clinical Professor of Medicine, Drexel University College of Medicine

Julian Katz, MD is a member of the following medical societies: American College of Gastroenterology, American College of Physicians, American Gastroenterological Association, American Geriatrics Society, American Medical Association, American Society for Gastrointestinal Endoscopy, American Society of Law, Medicine & Ethics, American Trauma Society, Association of American Medical Colleges, Physicians for Social Responsibility

Disclosure: Nothing to disclose.

Acknowledgements

Simmy Bank, MD Chair, Professor, Department of Internal Medicine, Division of Gastroenterology, Long Island Jewish Hospital, Albert Einstein College of Medicine

Disclosure: Nothing to disclose.

David Greenwald, MD Associate Professor of Clinical Medicine, Fellowship Program Director, Department of Medicine, Division of Gastroenterology, Montefiore Medical Center, Albert Einstein College of Medicine

David Greenwald, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Gastroenterology, American College of Physicians, American Gastroenterological Association, American Society for Gastrointestinal Endoscopy, and New York Society for Gastrointestinal Endoscopy

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

References
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Periductal onion skin fibrosis seen in primary sclerosing cholangitis.
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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