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A series of video presentations exploring information relevant to gastroenterologists, including summaries from key conferences.

Bile acid diarrhoea: who should I test 
Professor David S. Sanders

Professor Sanders discusses which clinical scenarios might warrant investigation for bile acid diarrhoea (BAD) and how this could improve treatment for these patients.

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Hello, my name is David Sanders and I am the Professor of Gastroenterology here at the Royal Hallamshire Hospital and with the University of Sheffield, United Kingdom. And the question I’d like to ask you regards to bile acid diarrhoea: Who do you feel we should be testing to look for this diagnosis? I hope I can answer that in the course of the following slides.

As we all know, to look for bile acid diarrhoea, you need to consider a SeHCAT test and I’ve put up in this slide the pathway and what is involved and please bear in mind that it’s about retention. So, if you have a low retention, which is less in some cases, than 15% and perhaps less than 5% is more severe, then you have evidence of bile acid diarrhoea.

So, who are the groups that we should be looking at and when do you think this should trigger in your mind to test in your clinical practice? In this slide I’ve made the suggestion of a number of conditions, chronic diarrhoea, patients who’ve had a cholecystectomy who then return with gastrointestinal symptoms, microscopic colitis, inflammatory bowel disease, irritable bowel syndrome and individuals who've had cancer but have new gastrointestinal symptoms, what’s often termed ‘late effects’. So I’d like to walk you through that.

Here you can see a systematic review of numerous studies looking at the diagnostic yield, when investigating individuals with chronic diarrhoea and in some cases what has been described as IBS-type symptoms but again with a diarrhoea focus. And what comes out is a signal, which is that something like 30% of these individuals will have evidence of bile acid diarrhoea when a SeHCAT is performed, and if you look at the numerous studies that are listed in this table, then we are talking about a dataset of greater than 1,000 patients.

What about individuals who have had a cholecystectomy and their gall bladder removed? Now remember that bile is retained and stored in the gall bladder, so once you have removed that organ, it will follow that there will be a reduction in bile salts. That’s what this slide shows you, as you can see, with the passage of time following cholecystectomy. Why is that relevant? Well, I think if you are seeing individuals in your clinic with diarrhoea or IBS-type symptoms, diarrhoea predominant and you should then be asking them about whether they have had a cholecystectomy and if they have, then I think it is very important that you consider testing in this group, because you will have a high diagnostic yield.

Moving on to microscopic colitis. I like this study very much by Fernandez-Bañares and his group, because what it’s really looked at is the different forms of microscopic colitis and very specifically at the association between microscopic colitis and bile acid diarrhoea. And the headline is this: If you see individuals with this diagnosis, which is increasingly more common and thought to affect perhaps 7% of individuals with IBS-type symptoms, then you can have an anticipation of a very high prevalence of associated bile acid diarrhoea. So SeHCAT testing I think is mandatory under these circumstances.

We all see individuals who come with gastrointestinal symptoms having had a previous cancer treatment and I’ve put this beautiful slide up, borrowed from my friend and colleague Jervoise Andreyev, who really tried to make me understand the effects of radiotherapy. What this picture shows you, is that radiotherapy, despite what everyone says, is not localised. It’s kind of like a shotgun effect and splatters right across as you can see, which means that these individuals are susceptible to developing bile acid diarrhoea because the reabsorption that is required occurs in the terminal ileum, which may be damaged as a result or a side effect of radiotherapy treatments. And what is important is that not only is it high prevalence, but these individuals respond to bile acid treatment replacement therapy, whether that be with sachets or with colesevelam. So, again from my perspective and my practice, if I see anybody and they have a history of previous radiotherapy and cancer treatments, then I think testing for bile acid diarrhoea is mandatory.

The final condition that I’d like to talk about is IBS. IBS affects probably 5-15% of the general population. In the United Kingdom, it accounts for something like 40% of our outpatient workload. So it’s an incredibly common condition. And of course, irritable bowel syndrome does have a lot of very well validated pathophysiological mechanisms as you can see from this slide. But the question that I’ve always asked is, IBS appears to be a unique diagnosis where we come to a diagnosis with minimal tests. There’s very little else in gastroenterology where we take that approach and you wonder that why is it that perhaps not all the treatments that we use in IBS work? Why is there such a high placebo response? And I think that the reason for that is that not all of these individuals actually have IBS. It’s really important to be clear about what I’m suggesting. I think there is a difference between patients who come to you with IBS-type symptoms and those who are then found to have IBS and I think by investigating for a number of conditions, you then remove individuals who are mimicking IBS-type symptoms and actually have another disease. You are then left with a true IBS cohort.

Let’s use bile acid diarrhoea as an example. I showed you in an earlier slide the overlap between chronic diarrhoea and IBS-type symptoms and there has been a number of investigations showing that when they look at their investigational pathway of individuals with IBS-type symptoms, that they have a high prevalence of bile acid diarrhoea. Now these studies were all retrospective but we, here in Sheffield, in collaboration with another city in the United Kingdom, Leeds, ran a prospective study sequentially investigating more than 100 individuals as part of their IBS workup with a SeHCAT scan. And what we found was that 25% of these individuals had evidence of bile acid diarrhoea based on the SeHCAT scans findings and they improved symptomatically when treated.

Now, how does this change practice? Well in the UK, this is a condition which is wolfly under investigated. I’ve put up a paper here that’s looking at the practice of more than 700 gastrointestinal consultants. We’ve kind of worked out how many patients would they see per year and we then, having done that, looked at what percentage would they actually consider the diagnosis of bile acid diarrhoea. And you can see that it’s a very low figure. This condition is very low set in terms of the investigational path. It’s not something that’s done early it's something that is done very far down along the pathway and I think what that suggests is that it’s frequently missed or simply not tested for. 

Can I show you further proof of that? Well, here in Sheffield, Matthew Kurien published this work, who was my previous fellow, and he looked at our diagnostic yield for bile acid diarrhoea in individuals who have IBS-type symptoms and once again in this retrospective study showed that the diagnostic yield was greater than 30%. At the same time as he was conducting this retrospective audit data, he also looked at the practice of the consultants and he showed that in a cohort of 300 patients, who we did not know we were being assessed, if you wish, that we actually only tested in 6 occasions. So quite the opposite of the findings of the previous study. And of course if you don’t test, you will not find.

So, I’d like to use this slide to give you a construct for bile acid diarrhoea. Of course, if you have structural defects such as a right hemicolectomy with Chron’s disease, then it is very likely that you are going to have bile acid diarrhoea. There may be conditions which interfere with the normal bile acid reabsorption, such as cholecystectomy, perhaps microscopic colitis that I mentioned earlier. But here what’s termed type 2 historically, but I think accounts for the largest number, is the IBS-diarrhoea predominant population. And if you work this out, if we say that about 5% of the population have got IBS-type symptoms and about a quarter of them actually have bile acid diarrhoea, then may I suggest to you that bile acid diarrhoea affects more than 1% of the general population even if they don’t know and that often they are simply told they have IBS.

So, if we look at this slide, this gives us a very clear indicator of what I’m saying. These are investigational guidelines for chronic diarrhoea and I appreciate that is not IBS but it uses a very useful algorithm. Very high up in this algorithm is testing for Coeliac disease and we know that Coeliac disease affects about 1% of the population. You have to go many steps down before you get to having a SeHCAT test based on current guidelines. So, I think this explains why we are not diagnosing this, why these individuals are not being picked up. They have a very long journey to get there. And what I have suggested with this red arrow, is that it should be moved to the top of the investigational pathway. It should be something that is considered at the outset. And I hope that I have convinced you that in fact it's very common.

So, my message is this: I think there is not enough evidence to say that bile acid diarrhoea is common and affects 1% of the general population. I strongly suspect that we are seeing these individuals in clinic and I think there is now a strong evidence base to suggest that a quarter of individuals who have IBS-type symptoms, diarrhoea-predominant, actually may have bile acid diarrhoea. And the question I would like to pose is, Are you the generation of clinicians who will consider doing this test and diagnosing your patients? 

Job number: JB57410GBc Date of Preparation: June 2019

Let's talk about irritable bowel syndrome (IBS)
Professor David S. Sanders 

Professor Sanders highlights that many patients presenting with irritable bowel syndrome (IBS) have underlying diseases. He explores why  patients do not always benefit from having treatments that are well recognised for IBS and notes that some patients may in fact have another diagnosis, disease or disorder.

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Mechanism of bile acid diarrhoea
Professor Julian R.F. Walters

Professor Walters explores the classification of different causes of bile acid diarrhoea (BAD). Professor Walters describes the normal entrohepatic circulation of bile salts and what occurs when the system does not function correctly. 

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How common is bile acid diarrhoea (BAD)?
Professor David S. Sanders 

Professor Sanders argues that many patients presenting with irritable bowel syndrome (IBS) have underlying diseases. He explores a series of studies that suggest approximately 25% of patients presenting with IBS symptoms have BAD as the underlying cause. 

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Pathophysiology of bile acid diarrhoea
Professor Julian R.F. Walters

Professor Julian Walters discusses the pathophysiology of bile acid diarrhoea with regards to ileal disease and ileal resection; he also discusses primary idiopathic bile acid malabsorption diarrhoea.

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Irritable bowel syndrome (IBS) is a disorder of exclusion: An extensive diagnostic work-up is necessary
Professor David S. Sanders 

Professor Sanders highlights that many patients presenting with irritable bowel syndrome (IBS) have underlying diseases. He explores why patients do not always benefit from having treatments that are well recognised for IBS and notes that some patients may in fact have another diagnosis, disease or disorder.

Read More


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