Melvin Lau, MD Series Editor: Richard W. Goodgame, MD


April 09, 2008

Differential Diagnosis of Cholestatic Liver Disease

Cholestasis due to extrahepatic biliary obstruction (ie, bile duct tumor, stone, or stricture) is unlikely in this patient because the bilirubin is normal. In extrahepatic biliary obstruction, an alkaline phosphatase >1000 U/L would usually be associated with jaundice. Of course, an ultrasound or computed tomography (CT) scan should be ordered to definitively rule out the possibility of extrahepatic biliary obstruction.

The 2 most common causes of intrahepatic cholestasis -- primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) -- fit the pattern of the liver chemistries in this case.[2] However, they are not consistent with all of the other features of the clinical presentation. This patient not only has liver disease, but also has severe proteinuria, in the range (greater than 4 g per day) that is seen in severe nephrotic syndrome. Although PBC can be associated with tubular and interstitial renal disease,[3] neither PBC nor PSC are associated with nephrotic syndrome.

The most likely reason for the very high level of alkaline phosphatase is an infiltrative disorder of the liver, causing intrahepatic cholestasis. A variety of systemic diseases with hepatic involvement cause very high alkaline phosphatase and gamma-glutamyltransferase levels:[4] sarcoidosis and other causes of granulomatous hepatitis;[5,6] tumors, including primary and metastatic tumors and lymphoma; and amyloidosis.[7,8,9] Of these disorders, the one most likely to be associated with massive proteinuria is amyloidosis.[10]

The patient underwent abdominal CT scan (Figure 2).

Diagnostic Question

Which of the following diagnostic tests should you perform next?

  • Endoscopic retrograde cholangiopancreatography (ERCP)

  • Magnetic resonance cholangiopancreatography (MRCP)

  • Liver biopsy

  • Renal biopsy

  • Rectal biopsy

View the correct answer.


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