The response of patients with bile acid diarrhoea to the farnesoid X receptor agonist obeticholic acid

  title={The response of patients with bile acid diarrhoea to the farnesoid X receptor agonist obeticholic acid},
  author={Julian R. F. Walters and Ian M. Johnston and Jonathan D. Nolan and Claire Vassie and Mark Pruzanski and David Shapiro},
  journal={Alimentary Pharmacology \& Therapeutics},
Bile acid diarrhoea is a common cause of chronic diarrhoea, occurring as a primary condition or secondary to ileal disease or resection. Many patients have reduced levels of the ileal hormone fibroblast growth factor 19 (FGF19), an inhibitory regulator of hepatic bile acid synthesis, secreted in response to farnesoid X receptor (FXR) activation. 

Review article: bile acid diarrhoea – pathogenesis, diagnosis and management

Bile acid diarrhoea results from imbalances in the homoeostasis of bile acids in the enterohepatic circulation. It can be a consequence of ileal disease/dysfunction, associated with other GI

Long‐term effect of medical treatment of diarrhoea in 377 patients with SeHCAT scan diagnosed bile acid malabsorption from 2003 to 2016; a retrospective study

Diagnosis is possible by measuring the retention fraction of orally ingested 75Selenium homotaurocholic acid (SeHCAT), which indicates excessive amounts of bile acids entering the colon due to bile Acid malabsorption cause chronic bile acid diarrhoea.

Does your patient have bile acid malabsorption

The synthesis, enterohepatic circulation, and function of bile acids are briefly reviewed followed by a discussion of biles acid malabsorption.

Bile acid diarrhoea: pathophysiology, diagnosis and management

Patients with suspected BAD are investigated in various ways including radionucleotide imaging such as SeHCAT scans and blood tests, however, other methods such as bile acid measurement in stool and urine tests have been explored.

Obeticholic Acid: First Global Approval

The milestones in the development of obeticholic acid leading to this first approval for primary biliary cholangitis are summarized.

Bile Acid Diarrhea in Adults and Adolescents

  • M. CamilleriS. Nurko
  • Medicine, Biology
    Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society
  • 2021
Advances in diagnosis of BAD provide opportunities for generalists and pediatric and adult gastroenterologists to provide targeted treatment for BAD presenting as chronic non‐bloody diarrhea.

Randomised clinical trial: Significant biochemical and colonic transit effects of the farnesoid X receptor agonist tropifexor in patients with primary bile acid diarrhoea.

Slowing of ascending colon emptying suggests therapeutic potential of tropifexor in patients with primary bile acid diarrhoea and changes in FGF19 and C4 showed effective target engagement; however, higher doses may be required to observe stool frequency changes.

Obeticholic acid for severe bile acid diarrhea with intestinal failure: A case report and review of the literature

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, and third-line treatment with obeticholic acid reduced the number of stools and improved the patient's quality of life.

Ileal Bile Acid Transporter Inhibition for the Treatment of Chronic Constipation, Cholestatic Pruritus, and NASH

In patients with idiopathic chronic constipation, an increased number of bowel movements was observed and various IBAT inhibitors showed potential to improve itching, and difficulties that should be addressed in future studies are discussed.

Bile Acid Diarrhea




Fibroblast growth factor 19 in patients with bile acid diarrhoea: a prospective comparison of FGF19 serum assay and SeHCAT retention

It is shown patients with bile acid diarrhoea have lower median levels compared with healthy controls, of the ileal hormone fibroblast growth factor 19 (FGF19), which regulates bile Acid synthesis.

Chronic diarrhea due to excessive bile acid synthesis and not defective ileal transport: a new syndrome of defective fibroblast growth factor 19 release.

  • A. HofmannD. MangelsdorfS. Kliewer
  • Medicine
    Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association
  • 2009

Idiopathic bile acid catharsis.

It is suggested that idiopathic bile acid catharsis should be suspected in patients with unexplained chronic diarrhoea and especially in those with a diagnosis of irritable colon with diarrhoeA.

Bile Acid Malabsorption in Persistent Diarrhoea

  • Michael J SmithPradip CherianG. RajuBarbara F DawsonSuzanne MahonKarna Dev Bardhan
  • Medicine
    Journal of the Royal College of Physicians of London
  • 2000
It is indicated that BAM is common in patients with chronic diarrhoea, and is frequently found in IBS, and the results of open treatment suggest that, where antidiarrhoeal drugs fail in such patients, BAS are often effective.

Systematic review: the prevalence of idiopathic bile acid malabsorption as diagnosed by SeHCAT scanning in patients with diarrhoea‐predominant irritable bowel syndrome

Recurrent, watery diarrhoea affects one‐third of patients diagnosed with irritable bowel syndrome and Idiopathic bile acid malabsorption (‘I‐BAM’) may be the cause.

Increased colonic bile acid exposure: a relevant factor for symptoms and treatment in IBS

A high response rate to open label treatment with colestipol supports this, but placebo-controlled studies are warranted.

Fibroblast Growth Factor 19 and 7α-Hydroxy-4-Cholesten-3-one in the Diagnosis of Patients With Possible Bile Acid Diarrhea

Serum FGF19 could be developed as a simple blood test to increase the diagnostic rates of BAD, and was found to be more marked when secondary to ileal disease, in particular ILEal resection, than in primary BAD.

Altered enterohepatic circulation of bile acids in Crohn’s disease and their clinical significance: a new perspective

The consequences of altered FXR activation in the context of BA malabsorption in Crohn’s disease and the potential benefits of FXR agonists inCrohn's disease are examined.

A new mechanism for bile acid diarrhea: defective feedback inhibition of bile acid biosynthesis.

Pronounced variation in bile acid synthesis in humans is related to gender, hypertriglyceridaemia and circulating levels of fibroblast growth factor 19

Pronounced variation in bile acid synthesis in humans is related to gender, hypertriglyceridaemia and circulating levels of fibroblast growth factor 19 (Rapid Communication).