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Itching in Liver Disease

Itching secondary to liver diseases, including primary biliary cirrhosis, primary sclerosing cholangitis, and
hepatitis C, is a very difficult symptom for patients to endure and for physicians to manage. The reason
why patients with liver disease itch is not known. It has been thought that some substances accumulate in
the blood as a result of liver disease, causing itch.

Although the nature of the substance(s) that cause itch in liver disease is not known, evidence has been
accumulating over the past several years to suggest that some substances that are found normally in plasma known as endogenous opioids (e.g. enkephalins), contribute, at least in part to the itch secondary to liver disease. It has been proposed that these neurotransmitters cause itch by acting on special areas of the brain. Other substances that also accumulate in the blood in liver disease, including bile acids, may also play a role in this type of itch. There is no strong evidence, however, to support that bile acids cause this type of itch.

Traditionally, the way itch has been studied has been by measuring the concentration of substances known to accumulate in the blood of patients with liver disease who itch. This method, however, has not advanced the understanding of what causes this type of itch.

In order to conduct scientific investigation, investigators have to apply reliable methods that allow for the
collection of information that can be analyzed and interpreted in an objective way. The need for the
availability of good methods has been recognized for many years by investigators in the field of itch. In this
spirit, an instrument was designed over ten years ago that allows for the measurement of the human
behavior that results from feeling the sensation of itch: scratching. Several clinical trials that use this
method to record scratching have been conducted. These studies have provided some insight into itching
and scratching, including the demonstration that some patients scratch with a 24-hour rhythm, known as
circadian rhythm. This finding has suggested further that the itch secondary to liver disease is mediated in
the brain.

At present there are several medications that are used for the treatment of itch in liver disease. These
medications include cholestyramine, the antibiotic rifampicin, the opiate antagonists naloxone and naltrexone, and the serotonin type-3 receptor antagonist. These medications appear to decrease itching in
many patients, but there is no medication that works well for all the patients. This reality underscores the
need to continue to look for other medications that may relief the itch secondary to liver disease.