1. Bile Acids: The Good, the BAD and the Ugly Dr Matthew Kurien Academic Clinical Lecturer in Gastroenterology, University of Sheffield

2. Conflict of Interest: Good or BAD? Ben, Age - 4 Sam, Age - 2

3. Chenodeoxycholic acidDeoxycholic acid Cholic acid Bile Acids Lithocholic acid What are Bile Acids? “Digestive Detergents” Important role in absorbing Fats

4. Bile Acids: What do they do? TI absorption reduced Excess BA spills into colon Reduces calcium- mediated water & electrolyte absorption: Net fluid loss Watery diarrhoea Courtesy of KD Bardhan, Emeritus Professor, Rotherham Released into the small intestine After function performed – recycled back to the liver 97% Gallbladder Liver Ileum 3% Released into the small intestine After function performed – recycled back to the liver

5. TI absorption reduced Excess BA spills into colon Reduces calcium- mediated water & electrolyte absorption: Net fluid loss Watery diarrhoea Role in Fat Digestion Secreted into the small intestine After function performed – recycled back to the liver Reabsorption reduced Excess BA spills into colon Watery diarrhoea Salt and Water Secretion <<97% Gallbladder Liver Courtesy of KD Bardhan, Emeritus Professor, Rotherham Diarrhoea Bile Acid Malabsorption (BAM) 1.Active inflammation of the Terminal Ileum (Crohn’s) 2.Surgically removed Ileum >>3% Problems with Bile Acids

6. More than BAM Seen : – After gallbladder surgery (cholecystectomy) – After radiation treatment (Radiation enteritis) – With Microscopic Colitis/ Coeliac Disease – 40% is idiopathic BILE ACID DIARRHOEA (BAD) – Excessive Bile Acids – Increased Gut Movements

7. Diarrhoea – Bread & Butter One of the commonest reasons for referral to a Gastroenterologist Estimated that 4-5% of the general population have chronic diarrhoea Associated with reduced quality of life.

8. Causes of Diarrhoea Inflammatory bowel disease Coeliac disease Colorectal cancer Microscopic colitis Pancreatic insufficiency GI infections and infestations Bacterial overgrowth Lactose intolerance Functional diarrhoea Diarrhoea-predominant irritable bowel syndrome (IBS-D) Drugs (including laxative abuse) Bile Acid Diarrhoea (BAD)

10. How common is Bile Acid Diarrhoea in the UK? 1:100,000 1:10,0001:1,000 1:100

11. Wheat Field with Sheaves, 1888 Vincent Van Gogh Coeliac Disease – 1%

12. Guidelines on Diarrhoea British Society of Gastroenterology Guidelines, 2003

13. Diagnosis of BAD In the UK, Europe and Canada 23-Seleno-25-homo-tauro-cholic acid (SeHCAT) scanning. Uses 370KBq capsule of 75 Se homocholyltaurine Normal - ≥15% retention at day 7 15 CXRs However, limited access in some centres, and in the USA, SeHCAT scanning is not available Other potential methods include: Serum 7 α -hydroxy-4cholesten-3-one (also known as C4) Faecal bile acid measurement Trial of a bile acid sequestrant, with response used as a positive test for BAM

14. Not just chronic diarrhoea

15. When Judith’s three daughters were young she often had to leave them unattended in the pram outside a public toilet because she was caught short. ‘This is one of my nightmare images of my illness,’ says Judith. ‘I hated leaving them on their own but I had no alternative — such was the urgency that I needed the toilet.’

16. Under-recognised and Under- utilised Survey of 436 UK Gastroenterologists: – 34% of all new patients seen had chronic diarrhoea – BAM was considered as a possible cause in only 22% – 72% of Gastroenterologists only considered after other investigations negative – Estimated 184 new diagnoses of BAM per month – Equates to 5 cases per Gastroenterologist per year – 50% of all SeHCAT scans in the UK come from 10 hospitals – <80 of the 250 departments in the UK equipped to perform SeHCAT do so Khalid et al. Clin Medicine 2010;10:124-126

17. Testing may be improving Proportion of patients with a positive test in each year did not vary significantly (χ 2 for trend = 1.46, P = 0.96) Gracie et al. Neurogastroenterol Motil 2012;24:983-e538

18. Coeliac Disease 1988: 273 publications 1993: 332 publications 1998: 470 publications 2003: 658 publications 2008: 908 publications 2013: 972 publications Bile Acid Malabsorption 1988: 27 publications 1993: 18 publications 1998: 31 publications 2003: 26 publications 2008: 11 publications 2013: 23 publications SeHCAT = 87 in total Why the difference between coeliac disease and bile acid malabsorption??!!

19. Take Home Messages BAD is common and under-recognised Diagnosing BAD can reduce misdiagnosis, inappropriate treatments and potentially improve quality of life Growing research area in the UK Professor Julian Walters Professor KD Bardhan Professor Jervoise Andreyev