Newer Approaches to the Management of Pruritus in Cholestatic Liver Disease

Short Background:

Cholestasis is the reduction or complete stoppage of bile flow. Cholestasis within the liver is called intrahepatic cholestasis, cholestasis outside the liver is called extrahepatic cholestasis. Cholestasis does not only occur in PFIC but can also be part of other disorders.

– Pruritus means itch, and it is more common in intrahepatic cholestasis.

– Bile acids are made from cholesterol in the liver and help the digestion of fat. They are transported from the liver with bile into the small intestine, and later returned to the liver. This circuit is called enterohepatic circulation and is regulated by proteins. One of the proteins that is in charge of reabsorbing the bile acids from the intestine is called ileal bile acid transporter (IBAT).


This paper is a review of possible medical treatments of pruritus for patients with liver disease due to cholestasis (cholestatic liver disease). Itching (pruritus) can be severe and persistent, and it can result in a substantial reduction of quality of life. It is often not easy to treat successfully, and the authors of this paper present a list of medical treatments that can be tried before considering surgical options. They also look at available research to see how often patients suffer from itch, and what exactly might be the cause of it.

            Pruritus is common in patients with PFIC, and also in patients with other cholestatic disorders. It is less common in patients with obstructive types of cholestasis. The causes of itch are still largely unknown, and research is ongoing.

            Historically, bile salts have been thought to be the cause of itch, and there is some research showing this. There are some promising results concerning a method to remove bile salts by inhibiting the ileal bile acid transporter (IBAT). IBAT inhibition results in less absorption of bile acids, and therefore an increase of bile acid in the colon and less bile acid going back to the liver. This might help reduce the itch, but can also increase the risk of diarrhea. Also, if bile salts are the source of itch you would expect more itch if bile salt concentrations are high, but researchers have not found a no clear relation between severity of itch and bile salt concentrations in blood, urine, or skin.

            In addition to bile salts, opioids that exist within the body are being investigated as potential causes of itch, but again no connection between opioid concentrations in the body and severity of itch have been shown to exist so far.

            Another candidate that has been investigated as a cause for itch is an enzyme called ATX. The concentration of this enzyme was higher in patients with itch, and therapy that targeted this enzyme seemed to have some success.

            The authors of this paper suggest a stepwise approach to treating itch. If the general management of pruritus such as cooling the skin, avoiding irritations, etc. do not stop the itch, then medication can be tried. The only approved medicine for cholestatic itch is cholestyramine, all other medications are off-label, that means they were developed for other diseases, but studies have shown that they sometimes work to reduce itch. The authors of this paper recommend starting treatment with cholestyramine. If that does not work within a few weeks, Rifampicin can be tried. The next options are Bezafibrate, Naltrexone, and Sertraline. Unfortunately none of these medications necessarily stop pruritus. In addition to the listed medications, there are several experimental options such as gabapentin and phenobarbital, but these are recommended only in specialized settings.


Pruritis, itch treatment


Düll & Kremer. Newer Approaches to the Management of Pruritus in Cholestatic Liver Disease. Current Hepatology Reports, 2020

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