Case Report
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jun 7, 2018; 24(21): 2320-2326
Published online Jun 7, 2018. doi: 10.3748/wjg.v24.i21.2320
Obeticholic acid for severe bile acid diarrhea with intestinal failure: A case report and review of the literature
Christian Lodberg Hvas, Peter Ott, Peter Paine, Simon Lal, Søren Peter Jørgensen, Jens Frederik Dahlerup
Christian Lodberg Hvas, Peter Ott, Søren Peter Jørgensen, Jens Frederik Dahlerup, Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus C 8000, Denmark
Peter Paine, Simon Lal, Department of Gastroenterology, Salford Royal NHS Foundation Trust, Salford, Manchester M6 8HD, United Kingdom
Author contributions: Hvas CL treated the intestinal failure in the patient and wrote the first draft of the manuscript; Ott P managed the communications with Intercept Pharmaceuticals, discussed the treatment and drafted the manuscript; Paine P and Lal S discussed the differential diagnoses during the treatment of the patient and revised the manuscript; Jørgensen SP provided expertise on BAD and FXR biology and revised the manuscript; Dahlerup JF was responsible for treating the patient, handled the communication with National Health Authorities, and revised the manuscript; all authors approved the final version of the manuscript.
Informed consent statement: The patient gave oral and written consent for the publication of this case report. A signed informed consent statement has been uploaded with the submission of the manuscript.
Conflict-of-interest statement: Hvas CL reports lecture fees from Takeda, Ferring, Novartis, MSD, and Tillotts. Ott P reports a lecture fee from Intercept Pharmaceuticals. Lal S reports grants from Fresenius Kabi and Shire. Dahlerup JF reports lecture fees from Pharmacosmos, MSD, and Takeda. All other authors declare that they have no conflicts of interest.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Correspondence to: Christian Lodberg Hvas, MD, PhD, Associate Professor, Department of Hepatology and Gastroenterology, Aarhus University Hospital, Nørrebrogade 44, Aarhus C 8000, Denmark.
Telephone: +45-78463895 Fax: +45-78462820
Received: January 20, 2018
Peer-review started: January 22, 2018
First decision: February 26, 2018
Revised: March 8, 2018
Accepted: March 31, 2018
Article in press: March 31, 2018
Published online: June 7, 2018

Bile acid diarrhea results from excessive amounts of bile acids entering the colon due to hepatic overexcretion of bile acids or bile acid malabsorption in the terminal ileum. The main therapies include bile acid sequestrants, such as colestyramine and colesevelam, which may be given in combination with the opioid receptor agonist loperamide. Some patients are refractory to conventional treatments. We report the use of the farnesoid X receptor agonist obeticholic acid in a patient with refractory bile acid diarrhea and subsequent intestinal failure. A 32-year-old woman with quiescent colonic Crohn’s disease and a normal terminal ileum had been diagnosed with severe bile acid malabsorption and complained of watery diarrhea and fatigue. The diarrhea resulted in hypokalemia and sodium depletion that made her dependent on twice weekly intravenous fluid and electrolyte infusions. Conventional therapies with colestyramine, colesevelam, and loperamide had no effect. Second-line antisecretory therapies with pantoprazole, liraglutide, and octreotide also failed. Third-line treatment with obeticholic acid reduced the number of stools from an average of 13 to an average of 7 per 24 h and improved the patient’s quality of life. The fluid and electrolyte balances normalized. The effect was sustained during follow-up for 6 mo with treatment at a daily dosage of 25 mg. The diarrhea worsened shortly after cessation of obeticholic acid. This case report supports the initial report that obeticholic acid may reduce bile acid production and improve symptoms in patients with bile acid diarrhea.

Keywords: Bile acid malabsorption, Diarrhea, Farnesoid X-activated receptor, Crohn’s disease

Core tip: Bile acid diarrhea develops when excessive amounts of bile acids enter the terminal ileum and exceed the intestinal absorptive capacity. The excess bile acids enter the colon and cause secretory diarrhea. We report a patient with multiple potential causes of chronic diarrhea and suggest a systematic strategy for the diagnosis and treatment of this condition. Furthermore, we describe the use of a new treatment for severe bile acid diarrhea, obeticholic acid, which stimulates the farnesoid X receptor of the terminal ileum and increases fibroblast growth factor 19, thereby decreasing hepatic bile acid production via negative feedback.