New Hope for Patients with Chronic Diarrhea

A pilot study suggests that obeticholic acid (OCA) may reduce symptoms of chronic diarrhea in patients suffering from bile acid diarrhea (BAD).

Researchers at Imperial College London (United Kingdom) conducted a study to test OCA in three groups: 10 patients with primary BAD, where the intestine is otherwise healthy; 10 with secondary BAD, where malabsorption can occur as a result of another disease, such as Crohn's; and 8 others with chronic diarrhea who served as controls. The patients recorded their symptoms for two weeks before starting OCA treatment, for two weeks while taking the drug daily, and for two weeks afterwards. Blood tests were taken before and after the OCA treatment period.

The results showed that in primary BAD, OCA use resulted in a 24% reduction in median stool frequency and a 34% reduction in diarrhea index after two weeks of treatment. In the secondary BAD group, significant clinical improvements were found predominantly in patients with shorter ileal resections; symptoms of abdominal pain and urgency also improved. In the control group there was no significant clinical improvement. The treatment was generally well tolerated. The study was published on October 20, 2014, in Alimentary Pharmacology and Therapeutics.

“Many doctors are totally unaware of bile acid diarrhea, but it's more common than Crohn's disease and ulcerative colitis,” said lead author Prof. Julian Walters, MD, of the Imperial College London department of medicine. “This drug represents a new potential approach to treating BAD by restoring the levels of the FGF19 hormone and so controlling bile acid production in the liver.”

BAD is caused by excessive secretion of bile acids—normally absorbed in the ileum—into the intestine, which passes into the colon and causes watery diarrhea. It is estimated to affect 1 in 100 adults in western countries, but is often mistaken for irritable bowel syndrome (IBS). BAD often has a serious impact on patients' work and social lives, causing them to have up to 10 watery bowel movements a day, often for many months, with an urgent need to go to avoid accidental incontinence.

An inhibitory regulator hormone produced in the ileum, ileal hormone fibroblast growth factor 19 (FGF19), regulates hepatic bile acid synthesis, and is secreted in response to farnesoid X receptor (FXR) activation. Patients with BAD have low levels of FGF19, and thus OCA, the first in the new class of FXR agonists, can target the production of bile acid.

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Imperial College London