Applied Evidence

How best to manage chronic cholestasis

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Here's how to maximize your use of lab work and imaging techniques to identify the source of your patient's cholestasis and provide prompt treatment.


› Suspect intrahepatic cholestasis in a patient with pruritus, normal transaminases, and mildly elevated gamma glutamyl-transpeptidase and alkaline phosphatase levels. A

› Use ultrasonography as a first-line diagnostic tool for cholestasis. A

Strength of recommendation (SOR)

A Good-quality patient-oriented evidence
B Inconsistent or limited-quality patient-oriented evidence
C Consensus, usual practice, opinion, disease-oriented evidence, case series


From The Journal of Family Practice | 2018;67(7):E9-E15.



A 44-year-old nurse describes persistent fatigue and itching over the last 2 months. She is taking ramipril 5 mg/d for hypertension and has a family history of rheumatic disease. Lab tests reveal a recurrent moderate elevation of gamma glutamyl-transpeptidase (gGT; 75 U/L) associated with, on some occasions, mild elevation of alanine aminotransferase (ALT) levels (100 U/L) of unknown origin. She has no history of hepatitis virus infection, hepatotoxic medications, or alcohol intake. She is overweight with a body mass index of 28.5 kg/m2 and a waist circumference of 99 cm (39 inches). Liver ultrasonography detects an enlarged liver with diffuse echostructure dishomogeneity, but no signs of cirrhosis or portal hypertension. The patient’s biliary tree is not dilated.

How would you proceed with the care of this patient?

Cholestasis is characterized by the alteration of bile flow through any part of the biliary system, from the hepatocyte basocellular membrane to the duodenum. The condition is classified as intrahepatic when the cause is a defect of hepatocellular function or obstruction of the biliary tree within the liver. The extrahepatic form includes all conditions obstructing bile flow in the main biliary tract (choledochus, common bile duct).

Suspect intrahepatic cholestasis in a patient with chronic itching, normal transaminases, and mildly elevated gamma glutamyl-transpeptidase.

The key to successfully managing cholestasis lies in the early identification of subtle signs and symptoms before serious complications can arise. In the review that follows, we provide guidance for evaluating laboratory and imaging results that are vital to the accurate diagnosis of intrahepatic and extrahepatic cholestasis. We also detail treatment recommendations.

Clues—subtle and otherwise—of cholestasis

Clinical features of cholestasis include fatigue and itching all over the skin. The latter likely is caused by induction of the enzyme autotaxin, which produces the neuronal activator lysophosphatidic acid. Retention of pruritogenic substances that normally are excreted into bile might contribute to pruritus as well.1 Jaundice, dark urine, and pale and fatty stools occur with advanced disease. However, a cholestatic condition can be detected in asymptomatic patients with elevated biochemical markers.

Continue to: Mildly elevated gGT and/or alkaline phosphatase (ALP)


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