Primary Sclerosing Cholangitis Workup

Updated: Nov 21, 2019
  • Author: Vikas Khurana, MD, FACP, FACG; Chief Editor: Vinay Kumar Kapoor, MBBS, MS, FRCS, FAMS  more...
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Workup

Approach Considerations

Liver function tests (LFTs) and histology (liver biopsy) are used in the evaluation of patients with suspected primary sclerosing cholangitis (PSC). [6]

LFTs, including levels of serum alkaline phosphatase (ALP), serum aminotransferase (ALT and AST), and gamma glutamyl transpeptidase (GGTP), and the presence of hypergammaglobulinemia, are the most valuable in the laboratory workup.

The most important imaging study is magnetic resonance cholangiopancreatography (MRCP). Percutaneous transhepatic cholangiography (PTC) and endoscopic retrograde cholangiopancreatography (ERCP) may also be utilized, more for therapeutic intent than for diagnosis. The most common characteristic histologic feature is onion skin fibrosis (concentric periductal fibrosis) (see the image below). Liver biopsy is rarely used for diagnosis 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 laboratory studies in primary sclerosing cholangitis (PSC) are liver function tests. Serum alkaline phosphatase dominates the profile, which is cholestatic in nature. Levels are usually 3-5 times the 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 in PSC 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%. Multispecific ANCA with ANA and anti-smooth muscle antibody (ASMA) may be potential markers for PSC. [29]

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Imaging Studies

Because it is noninvasive, magnetic resonance cholangiopancreatography (MRCP) is the preferred study to evaluate the bile ducts. [5] MRCP findings include multiple annular strictures and dilatations of the intrahepatic and extrahepatic biliary ducts giving a beaded appearance and a pruned tree appearance. MRCP combined with magnetic resonance imaging (MRI) is able to demonstrate focal biliary anomalies and subtle liver lesions. [8]

Although endoscopic retrograde cholangiopancreatography (ERCP) is the gold standard for diagnosis of cholangitis, it is used more for therapeutic intervention than for confirming the diagnosis of primary sclerosing cholangitis (PSC). [5] Percutaneous transhepatic cholangiography (PTC) is performed when ERCP is unsuccessful. If ERCP or PTC are performed, brush cytology may be obtained to rule out cholangiocarcinoma. Serum CA 19-9 levels may also be obtained.

Although ultrasonography is commonly used for the initial evaluation of patients with PSC, it is not good at detecting small tumors in the heterogeneous liver. [8] However, contrast-enhanced ultrasonography can be useful for revealing cholangiocarcinoma by demonstrating rapid and marked washout. [8]

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.
This T-tube cholangiogram shows an irregularity of This T-tube cholangiogram shows an 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.
This technetium-99m iminodiacetic acid scan shows This 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 stiffness appears to show promise as a potential biomarker in chronic liver disease. [30] In a retrospective review of 266 patients with PSC, 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. [30]

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Histologic Findings

Liver biopsy is not required for the diagnosis of primary sclerosing cholangitis (PSC) if magnetic resonance cholangiopancreatography (MRCP) findings are suggestive.

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 PSC, 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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Staging

Ludwig and associates described 4 stages of PSC, [31] as follows:

  • Stage 1: Portal hepatitis, degeneration of bile ducts with inflammatory cell infiltrate

  • Stage 2: Extension of disease to periportal area with prominent bile ductopenia

  • Stage 3: Septal fibrosis and necrosis

  • Stage 4: Frank cirrhosis

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