Episode Transcript
[00:00:02] Speaker A: Welcome to ingest, the educational podcast series brought to you by the Primary Care Society for Gastroenterology and designed for primary care clinicians.
I'm your host, Charlie Andrews, a GP with an extended role in gastroenterology based near Bath.
I am absolutely delighted to be joined today by Jan Bornschein. He is a gastroenterologist and we're going to be talking about H. Pylori. So, Jan, do you want to introduce yourself to our audience?
[00:00:29] Speaker B: Yes, thank you, Charlie, and thanks for having me today.
Yeah, my name is Jan Bernschein. I'm originally from Germany, so I grew up there and also my main training there. But then I came to the UK now 12 years ago, first to Cambridge and now I work as a consultant gastroenterologist in Oxford.
I have a passion for the stomach, I would like to say, not only when it comes to food, but also when it comes to pathology.
I started working on my thesis in the area of Helicobacter now way over 20 years ago, and never lost the interest in that field. I have been involved in the German guidelines for H. Pylori management since 2007 in the last few iterations, and I'm now currently also leading a redo revision of the UK guidelines on that topic. So I hope I can have a good discussion with you in that, in that respect today.
[00:01:33] Speaker A: Well, Jan, I love this topic. I've been really looking forward to this episode for quite a long time.
Around two and a half years ago, we recorded an episode for Ingest with Barry Marshall.
So for any listeners out there, you could always have a listen to that in conjunction with this episode.
But H. Pylori is a fascinating topic, I find, and I know we're not allowed to have favorites, but I think H. Pylori is probably my favorite bug.
I think it's fascinating.
You know, there's so much about it that's really interesting, including kind of the genetics of it and how you can follow the spread of humans around the world by looking at H. Polary. I think there's so much that's really interesting about this bug. So I'm really looking forward to kind of getting into the weeds with you about this and I was hoping that during this episode we could really kind of look at some practical advice for GPs about diagnosis and management. Really, before we get into that, Jan, do you think you could give us a bit of an overview of what H. Pylori is and why primary care clinicians really need to know about this?
[00:02:47] Speaker B: Right, okay. That's a. A broad topic. Please interrupt me at any time if I start waffling too much. So you just mentioned already that there have been studies where the ancient migration patterns of populations could be followed based on H. Pylori genetics, and that already outlines how long this bug is around. So it's been with humans for ever, essentially.
And that entered a lot of the discussion over the last 20 years, how much harm the bug actually does, or if it's rather commensal, if there are any benefits with it. Because as up to today, still with the fight against H. Pylori infection, the current estimate is that still up to 50% of the world population are infected by it.
With all that we know, the current stance is that it is a pathogen. In 2014, there was a global consensus, the Kyoto consensus, that labeled it properly as an infectious disease. And as such, there is no doubt anymore about it. When you find it, you need to get rid of it. So especially in adults, there's no evidence for anything positive or no conclusive evidence for anything positive why you should leave the bug. It always causes gastritis. So infection usually happens, or is currently presumed to happen, in infants or toddlers when the immune system is not yet mature enough. So you get it among your family, usually from your parents down to the children.
So you get it at a very young age and then you carry it around with you forever if it's not found and treated. Because it has a lot of very good strategies to avoid the human immune response. One of the main initial ones is obviously because it's not an invasive bug, it sits happily in the mucus of the stomach and lives there around and causes its damage. It always causes an immune response. So everyone, symptoms or no symptoms, has chronic active gastritis with H. Pylori. So it always causes damage to the stomach. Some patients don't feel it, but it's there.
And it is obviously the main risk factor for both peptic ulcer disease and for stomach cancer. So the link between H. Pylori and stomach cancer has been established in the 90s, and that has also just been reiterated a few weeks back when our iarc, the cancer branch of the World Health Organization, published a new report spanning several hundred pages, reiterating that the fight against H. Pylori is the main key for the fight against gastric cancer globally.
[00:05:29] Speaker A: That's amazing. 50% of the global population. And do we know what proportion of the population of the UK has H. Pylori?
[00:05:38] Speaker B: No, that's one of the sore bits. So the UK is in a very good position in A way that across Europe, in comparison, the gastric cancer incidence in the UK is among the lowest and the prevalence of H. Pylori has also dropped because of the treatment, the awareness over the last 25 years, so it got a bit neglected. So there is no, there are no valid data on prevalence and the general infection rates in the adult population for the last 15, 20 years from the UK. So we don't quite know what's going on. And similarly we have not many studies, just a couple or so on. Also we get back to that later on efficacy of treatment and resistance rate. So we don't quite know what we do know in comparison from other countries, let's say, for example, Germany has a prevalence rate around 30%.
There are eastern countries where it's much higher, but if we compare to Western European countries similar, with a similar structure buildup, then we should assume it's somewhere in the range of 30% prevalence.
What we do know is that migration plays a huge role. So there's obviously the background UK population, but with migration from areas that have a higher prevalence, let's say Eastern European countries or Asian countries, by that you also get an increase in your national prevalence because they bring the bug with them and then it's essentially there. So that's also something to be aware of because we obviously have a lot of migrants in the country, such as myself.
[00:07:33] Speaker A: Yeah, I've got so many questions that I could ask about this, but I think we want to try to stay to the mission, which is to try and deliver really practical points. So I'm going to move on to diagnosis and start thinking about that, if that's all right, Jan. So diagnosis, how do we do that?
[00:07:54] Speaker B: So in the first instance, well, there are different modalities that you can use.
There are invasive tests which are all based on gastroscopy, endoscopy and tissue based sampling which should be applied for those with certain alarm symptoms. So certain age groups, usually we come back to the dyspepsia guideline, those over the age of 55, those with new symptoms, unexplained weight loss, unexplained anemia, for example.
There you could consider invasive testing via gastroscopy. When you have the modalities, there is either immunohistochemistry, standard pathology and the quick and cheapest one is a so called CLO test, which is a chemical test. So you take a tiny, tiny biopsy, put it on a cartridge, that shows then a reaction to the urease potential that the bug has. So basically the bug causes A ph change in the cartridge and the cartridge turns from yellow to pink. That gives you a very good indicator if the bug is there or not. Because there are not any other bugs in the stomach that could do that.
That test costs just one pound. So when you want a cheap, quick test while you do your gastroscopy, that's always something good to do. If you have someone who had several rounds of treatment, then there is also the option of, of culture.
We get back to that later, I think.
But in the first instance, for the vast majority of patients, you should always consider non invasive tests because they are cheaper, they are safer and they are obviously much more convenient for the patient.
There are still three main modalities. The gold standard used to be and still is a urea breath test. Again, it uses the capacity of the buck to metabolize urine urea in the stomach. It's a carbon isotope, it's a 13C carbon isotope that's used. So how that works essentially is that the patient comes in fasting, he gets a test meal, essentially some urea, some acid and the carbon isotope. And then before that's ingested, and then 30 minutes after needs to breathe into either, depending on the assay that's used, a little tube or a bag that's then analyzed and depending on the peak of the metabolized carbon as it is breathed out, you can then make a judgment. If there is a bug that's metabolizing that carbonated urea that costs around 20 to 25 pounds, the instructions are sometimes a bit clumsy, patients are sometimes a little bit overwhelmed. So it's always good to explain that separately or ideally do that under supervision.
But it has a very high specificity and sensitivity and it's obviously non invasive. The alternative that got better and better and is nearly in the same range with regards to the diagnostic accuracy is a stool antigen test. There are a lot of different panels, so there are some kind of more quick tests around and they are the classic stool based elisas as well.
So you need to, if you consider a stool test, you need to check what assay is actually used because some are better in their diagnostic accuracy than others. The cost for these are somewhere between five and eight pounds I think.
And again they're non invasive, they can be done from home and then send off. Some patients obviously don't like handling poo, but I think it's actually more convenient than going through the ordeal with the breath test. So the stool test is obviously a very good hands on alternative.
The third option is a blood Test. The problem with the blood test is that it doesn't indicate to you if it's an active infection or not. So if someone has been treated successfully, the blood test will remain positive for several years.
So if someone comes with a positive, so you cannot use that, for example, as a test after treatment, or if someone had antibiotics for hip replacement ear infection, what do I know?
Then there might have been what we call accidental or incidental eradication. So we don't know. The blood test is a good screening test in lot of situations. The European guidelines say, for example, you should use the blood test if there is acute bleeding, for example, and you cannot apply any of the other tests safely.
But you need to be aware of the caveats.
One of the issues with the any tests apart from the blood test is that they are not valid when a patient is on a ppi, and that is often, there is often misjudgment, even among the gastroenterologists. So for all of you in primary care, when you get an endoscopy report back, and the colleague wrote, Diana took biopsies to rule out H. Pylori if the patient on the day and the two weeks prior to the procedure was on a ppi, frankly, that's rubbish. You cannot make a judgment. What happens with the PPI is that you reduce the colonization density, so you have far less bugs in the stomach.
They are still there, the infection is there, but it's much, much more difficult to pick it up. And for all tests for histology, even immunohistochemistry, for the CLO breath test and stool test, you have a high risk for false negative results.
So if the test is positive, then you can still go ahead. You know the bug is there. But if the test is negative and the patient was on a ppi, then you.
No, nothing. So it's important that before any of these tests, the patient is instructed to stop their ppi, and a lot of them struggle with that for two weeks prior to testing.
For reasons that I haven't fully understood. I have to admit H2 receptor antagonists are not so much of a problem. So they can be taken until a few days prior.
But the PPI is an issue, and that's something many, many people are not aware of.
[00:14:28] Speaker A: I think there's also an issue with antibiotic exposure prior to the test as well. Is that right?
[00:14:32] Speaker B: Yes, because again, you cause a shift. So a lot of antibiotics, even if they don't really treat H. Pylori, they have an impact on its presence, again, colonization density. So antibiotics is the second issue. So you should ideally not have any antibiotics for four weeks prior to testing. So no PPI for two weeks, no antibiotics for four weeks.
That's also why you should wait at least that month after treatment. If you want to check if the treatment has worked, it's an issue. For example, those coming in with the peptic ulcer bleed, they often get high dose PPI for four, eight weeks. So you need to wait till they're finished with that, after antibiotics, after ppi, and then you can test if it all worked or not.
[00:15:22] Speaker A: That's really helpful. It was really good to go through the different options there. In my clinical practice, we're often using the stool antigen test and it's really helpful just to run through some of those things that can cause a false negative. So I think that was a really helpful overview. Thanks.
Just thinking a bit about who to test.
I think it'd be useful just to. Just to run through that a little bit and think about who. Within a primary care setting we would be testing.
In my sort of, my clinical setting, I would generally be thinking about people with dyspepsia.
So someone presenting with new dyspepsia I would be certainly wanting to do an H. Pylori test on.
Could you talk about when you might time that test within that diagnostic process and maybe any other groups that you might want to test for H. Pylorian?
[00:16:15] Speaker B: So, yeah, dyspepsia, you taunt that very first in the beginning because you can do your empiric treatment with PPI or dietary adjustments or whatnot, but if he has the H. Pylori, it won't sort it out. Whereas if the patient is H. Pylori, you find the H. Pylori, you treat it, there is a fair chance to improve the symptoms. The number needed to treat for dyspepsia, h. Pylori is 14. So you still have a fair amount of people that might have other reasons for their dyspeptic symptoms, but H. Pylori is still among the top range that can cause these symptoms. And as said before, there are non invasive, reasonably cheap tests that you can rule out and instead of throwing lots of other medication and drastic dietary changes to them, a week of antibiotics might solve the problem. So the UK dyspepsia guidelines also say that on the first instance you should rule out H. Pylori in these patients.
One thing that I just want to mention here, before we come to the other indications or the other groups to check the current guideline in the UK, and that was reiterated three years ago in 2022 by the Dyspepsia guideline does not recommend that you should follow up your treatment.
The way it's phrased there says you should judge on treatment success based on the patient's symptoms. And that's just simply wrong.
And we will bring that in the new guideline revision. Now, as a very clear statement, you should always check with a proper test if the etorication has worked.
There are two reasons for that.
Both scenarios, let's say a patient doesn't get better. Let's take functional dyspepsia. It might have been completely different reasons for the symptoms. But you say, oh, I've treated, it's not getting better. So I treat again. And then I treat again, I treat again. So that's one scenario where it's wrong because you throw more and more antibiotics at them and actually you need to get into a different treatment path. And the second option is a lot of them get better even if the eradication doesn't work. Again. We talked a few times about colonization density with the ppi. With the antibiotics, you improve, improve the gastritis that's there. So they often have symptom relief, sometimes even for several months. And then you say, oh, that's great, that worked. So we don't need to do anything, but they actually still have the infection. So you need a valid test to confirm that.
Other indications. We talked about peptic ulcer disease. There is no reason for empiric treatment. I also want to say that here, some colleagues still recommend, say, oh, there's a duodenal ulcer bleed, please treat H. Pylori. But they've never checked if the infection is actually there. There are other reasons for ulcers. I know the probability is very high, particularly for duodenal ulcers, but there are other reasons there as well. So you should always check if a patient has H. Pylori before you treat them. You need to confirm that diagnosis. The only indication where even in case of a negative test treatment is given is mild lymphoma, but gastric mult lymphoma. But that should probably not then happen in primary care.
So we have dyspepsia peptic ulcer disease. Now we get more to the a bit more unusual cases.
One issue is unexplained iron deficiency anaemia and idiopathic thrombocytopenic purpura. So the two hematological conditions, the helicobacter, messes a lot with the iron metabolism in various ways. There have been Some very good studies from Tennessee, from Wonderbilt recently.
So even without any polyps or ulcers or anything clearly visible, simply the presence of the H. Pylori can cause significant iron deficiency anaemia. So in those patients where you don't find any other reasons, the helicobacter should always be ruled out. And as an autoimmune condition, again, the pathways are not entirely understood. There's some antigen mimicking. Idiopathic Thrombocytopenic purpura is another condition where helicobacter should be checked. There are a few rarer types of gastritis, but we won't go into that now because I think that's then something when someone had already the gastroscopy. It's more than secondary care to sort that out.
Recommendations are now that you should check first degree relatives of gastric cancer patients because we talked about earlier that the infection gets handed down among the family. So if you have someone with gastric cancer, there's a very high chance. The current estimate is that 90 plus percent of all gastric cancer cases worldwide are somewhat linked to H. Pylori.
So you should always then check the immediate family members as well for the infection. And we changed that in the German guideline from the topic section from indication for treatment to indication for testing. So when you find an helicobacter, even if it's an incidental finding on a biopsy and a patient was sent for different reasons like confirmation of celiac or whatnot, you should always treat it. So that's the basic thing. But the key groups are functional dyspepsia, peptic ulcer disease, gastric cancer linked to that. Also with regards to family history and the two hematological conditions, especially iron deficiency anaemia, always think of the helicobacter.
[00:21:58] Speaker A: I've got two further questions, Jan, about this, if that's okay. So we talk about dyspepsia and you know, gastroesophageal reflux disease sort of often overlaps with that. And you know, would you be testing if someone's got predominantly reflux symptoms? Is it worth us checking for H.
[00:22:19] Speaker B: Pylori now you open a can of worms.
No, reflux is reflux, dyspepsia is dyspepsia. I was just going through some of the some health leaflets from a charity where this is also a bit muddled up in the text blocks.
H. Pylori does not cause heartburn or reflux, so it doesn't cause any problems in the chest and equally when someone. Yeah, when someone has heartburn, the helicobacter is not the reason. It's these dyspeptic symptoms. It's the epigastric pain, it's a bit of bloating, the slight nausea, lower appetite response to food, depending on where the main part of the inflammation sits.
The can of worms that I just mentioned is the discussion if helicobacter has a positive effect on reflux disease. So there are historic battles over the last 20, 30 years around some studies and meta analysis that look into reflux as such, Barrett's esophagus and esophageal cancer.
And some of these suggest a lower risk for particularly Barrett's and esophageal cancer among those with helicobacter.
The broad understanding at the moment is that there is no clear link historically, that was from a time when 1. One of the links that was understood was when helicobacter persists and the chronic inflammation persists. At some point you get a destruction of the glandular structure of the stomach, so you can develop atrophic gastritis, which then also leads to lower acid output, which also then obviously with low acid output you have less reflux, less acid damage. So in the kind of older population with atrophic gastritis, you get less chronic acid damage. So that was one of the links that was there for explanation. There is a few more molecular pathways that came up now, but essentially the current position is that there is no need to not eradicate, even in patients with Barrett's esophagus or reflux symptoms, because the evidence is not clear and not strong enough to say there is any kind of, to phrase it in the extreme protective effect. So to answer your first question, no, reflux and dyspepsia are two different conditions. So reflux, nothing to do with the helicobacter. The concerns, oh, there's someone with a complex reflux condition. Should we not leave. The helicobacter is a clear no. When you have it, you should treat it.
[00:25:07] Speaker A: Brilliant. Thanks, Jan, for clearing that one up.
My second and final question about diagnosis is one that's actually based on a question I've had in primary care.
After diagnosing someone with H. Pylori, the question they said to me was, well, I've read that it could be really contagious. Should I get the rest of my family checked? What's your answer to that?
[00:25:30] Speaker B: So it's not very contagious.
As I said earlier, you have this link from parents to children so but that's at the stage when the immune system is not mature enough. So just as a little anecdote. Good. Fifteen years ago I was involved in a vaccine trial where we tried to infect the healthy volunteers between 20 and 40 years old who had, some had placebo, some had the vaccine and we really, really struggled to get them infected and we had to give them jugs full, full to the rim with high colony forming units of Helicobacter in a certain beef broth with high dose PPI before to get the atmosphere right. And even then we only got a fraction of them infected. So the adult immune system is normally capable enough to repel the infection, particularly when exposed to just minor.
Yeah, when there's just minor exposure. There are a few studies that seem to be a bit contradicting that issue where there is an accumulation of H. Pylori positive cases among endoscopy staff where they say, oh, but you're more exposed, there's aerosol generating procedures. Is there a link?
I would need to dig into these. I don't think that's quite right. So to answer your question, it's not very contagious. There is a risk that you give it to your children, but you should not test the children. So if they don't have any symptoms in that direction, then you should at least wait to their early mid-20s before you check them and leave them be kids at the time.
[00:27:12] Speaker A: And why do we not check children generally?
[00:27:16] Speaker B: So there are two aspects. One is that you don't want to expose children to unnecessary treatment. So if they don't have any symptoms, then there is at that age, no need to treat, they will have bit of inflammation, but the more harmful consequences or complications, let's say ulcers or then later even the cancer that happens decades later. So at that time you will be still in a position in their 20s to treat them effectively without any negative long term consequences.
There are again old studies that suggest there might be a positive influence on certain immune conditions by the inflammatory environment the Helicobacter generates in particularly atopic conditions, atopic eczema, asthma and these things. Again, this is something that has never been fully resolved, but the data suggests that this might play a role somewhat during again maturation of the immune system.
So if not needed, then the suggestion is there. Or leave the bug during puberty and then treat it later when they're adults.
[00:28:27] Speaker A: I love that. Jan, we're starting to veer into the microbiome.
We're not going to open that can of worms today, but I really like that discussion there. But I think we should move on to treatment now, Jan, and think about how we treat patients with H. Pylori.
So could you talk to us a bit about kind of the first line treatments? Someone's been diagnosed with H. Pylori in primary care.
Which antibiotics, which treatments are we going to be reaching for as a gp?
[00:28:56] Speaker B: Right.
[00:28:58] Speaker A: And I know this is going to be a bit controversial. I know there is some aspects here and I'm looking forward to discussing it because I want to hear a bit about the Maastricht consensus.
But what would we be treating patients with who've been diagnosed?
[00:29:12] Speaker B: So I'm just thinking how best to start that answer, because there are multiple levels and I think that will be a bit. There's no straightforward answer. There is a straightforward answer, but I don't like it very much. So we will need to discuss that a little bit. So the current recommended treatment is the good old fashioned from the time called either French or Italian triple therapy. So that's a combination of two antibiotics. For those who can tolerate penicillins, it's amoxicillin, claritomycin with the ppi. For those who don't tolerate penicillins, it's claritomycin, metronidazole and ppi. And that remains in the UK for now, the standard. I say for now because there comes in again, what I mentioned at the very beginning, that we, we don't have data here on primary resistance rates. So studies from the rest of the world, and there have been some very good papers just came out just, just this year, again show that there is, has been over the last 25, 30 years, increasing resistance to 3, at least of the key antibiotics used with Helicobacter, that's claritomycin massively, but metronidazole not far behind that. And now also levofloxacin is spiking up. There are some studies that show with the awareness of that, with some adjustments of the treatments used, and also with the introduction of antibiotic stewardship protocols, that this now plateaued a little bit and it's not as steep an incline as it used to be anymore, but it's still present. And it's a huge problem that we don't know what the actual resistance figures. Here are the Maastricht guideline suggested, I think in our third iteration, or even the second might been already we have Maastricht 6 at the moment and that has been published three, four years ago.
Yeah.
[00:31:09] Speaker A: And it Might be worth just mentioning what that is actually. What is the mastery guideline? Because I think most of the audience probably won't know and I think it's really important that we do so.
[00:31:17] Speaker B: Maastricht has been the front runner of essentially all European guidance on H. Pylori management. It started in the 90s, it was an expert panel based on the European Helicobacter and now European Helicobacter Microbiota Study Group.
It was founded in the late 80s by enthusiasts around that topic and they came together with experts from Europe, but also a few from further afar in the 90s to generate a first European guidance on how to deal with the infection and aspects around it. They meet every few years to revise that and slightly also introduce topics that are relevant. So more recently they introduced impact on microbiota, for example, as well. In a previous iteration they focused more than on impact on gastric cancer prevention and other issues.
So they meet every few years and they're kind of the main framework for any guidance around helicobacter.
It's a European guidance, so you cannot take one to one everything that's mentioned or listed there and it might not apply for your setting in your country and some things might be a bit too detailed and too over the top, but it's a very good starting point to get a reference and then compare it to other sections.
So what they established was that you should aim for, you can use claritomycin based triple therapy when you have resistance rates, not high, local resistance rates, not higher than 15%.
But obviously to make that decision you need to know what your local resistance rate is. Now we have. That's not been published. Where we just presented that at the ugw, the European Gastro Conference three weeks ago. We have now for the first time a bit of data from the European Helicobacter Pylori registry from the uk. So we have roughly a thousand cases.
Yes. Registry data is always a bit dodgy to say because it's not a controlled trial as such. But the bottom line is that we show first line failure of a good 30%. So these basic standard claritomycin based triple, which was used in 75% of the patients in that cohort in the registry, 30% of them failed their first line treatment, which is not good because that gives them more follow up tests, more treatment again and more problems. So in the first instance, when you want to stick to the traditional regimens, there are two simple steps, how you can optimize treatment One is longer treatment and there loads of studies that have shown it massively increases your success rates. So longer, I mean, ideally 14 days. So instead of seven days, course you go to 14 days. And the other one is better acid suppression. So omeprazole 20 milligrams just won't cut it locally. We in Oxford have a standard now, 40 BD. And for rescue treatments I also switch to azo meprazole because it's just a bit better. There are studies coming from Asia that show that the potassium channel blockers, the PCAPs, have much better and consistent acid suppression potential. And they showed that with those, a combination of those with amoxicillin alone is often sufficient. So we don't have this here and it will take years for them to be here. But just to again underscore the need for adequate acid suppression, so give a higher dose of omeprazole and give 14 days treatment instead of seven days. That's the first thing to consider.
[00:35:13] Speaker A: And.
[00:35:18] Speaker B: The second step is compliance. So you always need to reiterate with your patients because they don't really understand it.
Sometimes there's a lot of tablets and they don't like it. And let's say metronisazole often causes a lot of side effects that they need to complete the course properly because Helicobacter really needs this compliance. We also see a massive significant drop if compliance is less than 90%.
And one thing also that I wanted to point out here, which is very, very dear to me, never ever give the same treatment twice.
It's very rare that a bug doesn't get resistant. So when you given claritomycin once, it's not likely to work.
Well, if it hadn't worked the first time, it's the old Einstein thing, why would it work the second time?
So if you have used one regimen, you need to alter at least one antibiotic if you go in for the second round. So if you used amoxiclur in the first round, then you should use amoxymetronazosole in the second round. Repeating the same treatment over and over again doesn't work. So you need to change.
[00:36:27] Speaker A: And Jan, can I just ask if they've had exposure to antibiotics in the past? So just looking through their medical record and you can see that they've had a couple of courses of clarithromycin five or six years ago and then they had some metronidazole two years ago. How is that an. Does that feed into our decision making around what we Give it should.
[00:36:46] Speaker B: It's not highlighted as such, but, well, at the moment here, but in some guidelines it is. So that's a very, very good point.
If you have the possibility, and obviously you, as primary care will have all these data available to see if there have been one of the key antibiotics given for other reasons, then you should ideally avoid that and choose an alternative. Because as I just said, once it's been given before, if the bug has been exposed to it, particularly to these three, clarimetro and levofloxacin, they're very adaptable and they are likely to be resistant. So you should then adapt the regimen that's chosen.
There is a new. Well, there is the option. It's not new, it's historic as well, but it came back into. The option now is bismuth based quadruple therapy.
We have the European guidelines. Maastricht recommend that generally as a first line treatment.
The advantage is that the bismuth based quadruple therapy in a classic form contains bismuth, tetracycline, metronidazole and the ppi. There is rarely ever any resistance to tetracycline, so the bug can't cope with it, so it just can't adapt to that. And weirdly enough, in all the studies, resistance to metronidazole in that combination does not seem to have any significant effect. So the efficacy remains usually above 90%. So with Bismuth based quadruple therapy, you have a kind of one shot hits all option. The problem in the country was that for a few years we didn't have any bismuth. Now I hear that Pepto Bismol is available again, but mainly in its liquid form. You can't prescribe it. The patients need to buy it themselves, which is a bit tricky. And then there is obviously a new product which is this single capsule, which is very effective. The studies are very, very positive.
But we obviously need to be aware that there is no competitor on the market offering that.
So recommendations should always consider that as well.
[00:39:05] Speaker A: Is that a combination tablet?
[00:39:08] Speaker B: So the tablet is. It's a bit.
So their initial big slogan was that it's all in one capsule, which is partially correct. So you have the bismuth, the tetracycline and the metronidazole in the same tablet. The PPI still needs to be prescribed separately for pharmacological reasons.
The problem is that to get the right dose you would need a monster tablet. So the regimen with that particular single combination capsule or tablet is that you need to take three tablets four times a day, so you have 12 tablets of that and then two PPI on top for 10 days. So the patient needs to take 140 tablets in the 10 days.
But consistently, across all studies and registered data, you get eradication rates way above 90%. So it does work, but it's a bit more expensive and it's a lot of tablets.
So we need to see, with the guideline revision, where we then will be able, taking this all into consideration, where we'll be able to place it in the new algorithms.
[00:40:23] Speaker A: So, from what you're saying there, I'm just thinking about, as a gp, how I'm going to approach this. And so I've got my patient, we've diagnosed H Pylori.
We already know that we're going to be retesting after we finish treatment, which we've covered already in the testing, I'm going to give them the triple therapy, which is what our current guidance says. But as you said, that rate is not high. So 30% failure rate with that initial treatment, really. But I'll look back and see what they've had before and just make sure we're not kind of covering the same ground in terms of clarithromycin. So I might make my decision based on that.
And if we then repeat the test and, you know, following treatment, they are still positive.
Do we simply switch from the metronidazole to the clarithromycin or are there better ways that we can try and improve our clearance rate when we're approaching second line treatment and maybe moving even on to third line? Because I know that some patients sort of end up failing on several treatments.
[00:41:28] Speaker B: So there are different ways how to approach that. So the first thing is what you've highlighted already, like this. Get it right the first time. So you check your records, what they had before. Ideally you give them 14 days, ideally you give them a higher dose PPI. So that already puts you in a much neater position if that fails, although the guidelines do not recommended as such at the moment. So the traditional way is then, yes, exchange at least one antibiotic and go second round. I would probably then go with that single capsule approach because it is very reliable. It is, yes, it's a bit more expensive than the traditional ones, but it's.
If you get a good response rate and it prevents you from further treatments and the other option, which I mentioned next, then you will still have the costs much, much lower. Instead of going treatment after treatment, after treatment, because we know Also from study data that with second, third, fourth line treatment, the eradication rates drop massively further. So for example, in our registry data set we had 70% eradication rate of first line treatment. We had less than 50% with second line treatment.
So you have a lower proportion than even of those responding there.
The other option, and this is something that gets handled differently from country to country depending on the setting, is to send the patient at some point for endoscopy to get biopsies and culture the bug to get a kind of tailored result to see which antibiotics are actually responsive and which aren't, and then you can treat in a tailored way and then the over boringly over.
In the majority of cases this then works. But obviously it's an invasive test and it is also much more involved. Costs money and it takes also time. So you need to get them in for endoscopy, you need to wait for the culture results and it's all a big effort. So in the German guideline we Recommend Culture after first line failure. At the moment, Maastricht 6, the last edition of the Maastricht consensus says, oh, you should consider kind of resistance testing, maybe even already before first line. There are also some stool tests that are in consideration that might check for claritomycin resistance. That's something that's been discussed here in the uk.
It's mentioned in the current guideline as an option after second or third line failure, but it's not ingrained as such in the algorithm. We had a problem with capacity for these cultures because in the UK these are centralized, so they are not done by the individual trust. There is a central laboratory in London processing these and there have been problems with capacity, so they had to shut down their service for a few months and then we were without any culture nationwide for the first half of this year, which then also causes problems. And then we also need to rely more on empiric treatment.
So bottom line is get it right the first time. Latest second line, I would consider the single capsule approach because it gets very good results. If that doesn't work, then I would. Anyway, after second line I would get in touch with your local gastro team with secondary care and then leave it for them to give you advice or rule it out because the more you treat and the more you fail, the more difficult it gets to finally get them eradicated.
[00:45:08] Speaker A: That's great, Thanks a lot, Jan.
Really important there to highlight, kind of asking for help if it's not working really, isn't it? And with the rise of advice and guidance. It's probably quite a good thing to be using to try to get advice around where to go next once you've failed on a couple of treatments.
[00:45:26] Speaker B: I personally like it rather here in the region if the GPs send me an email a bit earlier rather than treating three times with the same regimen and then send them to me. So for these ones, this is no visitory, as you said, advice and guidance. That should not take much time to give you some feedback there and then give you advice. And if you say, okay, that's a regimen I'm comfortable with, I can do that fine. And I let you know if it worked or if you say, nah, this is a bit too complex and that's a weird rescue regimen you give me here. Can you handle that? And that's also fine. One thing that's important for that, however, is if you get in touch with your secondary care team for advice and guidance. They need to know what has been given before. So you cannot just say, oh, I treated three times, what do you think I should give now? You need to give them actually the details of what regimens have been given and probably even the timeframe like, okay, I gave that in 2023 and then this in October 2024 and to give the picture a bit better because then they can make sure they give you the proper advice.
[00:46:32] Speaker A: We've touched on retesting before.
Do we apply the same rules around the four weeks for antibiotics, minimum two weeks off a PPI before we do the retesting? How soon after treatment should we be checking?
[00:46:47] Speaker B: It's the same rule. So it's four weeks antibiotics break and two weeks ppi. So the antibiotics for retesting after treatment are, they're the rate limiting factor if there's nothing like an ulcer bleed, as I said before, where you might have a prolonged PPI treatment time, but yes, it's the same framework.
[00:47:08] Speaker A: So at least four weeks. Really?
Yeah. Okay, and then your feeling is that we should be retesting everyone?
[00:47:15] Speaker B: Yes, definitely. Yes. A test doesn't cost very much, so we talked about stool testing. It's 6, 8 pounds and you just get the certainty and you know when it's gone. It's also we talked earlier about how contagious the bug is. I, we, we see that often in referral letters and I said, okay, I treated this patient in 2018, it was all good, but now he recontracted the infection or the infection came back, it didn't come back, it wasn't treated properly. The first time. So they might still be fine for a few months or for a few years, but the bug is still there, causes the inflammation, causes the harm. So reinfection rates again, historically studies say are less than 1%. I would believe it's even lower.
These old data on reinfection is basically from a time when the treatment hasn't been checked properly. So usually when the bug is gone, it's gone. So once you treated it properly and you confirmed that it's been eradicated with a proper test, then you don't need to worry about it anymore.
[00:48:23] Speaker A: Brilliant. Jan. I could talk about this for hours, but I suspect that our audience might not want that. But I could keep on going. I think it's. I know, I think it's fascinating. I love it and it's been really, really practical. Loads of really useful advice in there.
Yeah. And to finish off, I think you're looking at updating the guidance at the moment, Is that right?
[00:48:47] Speaker B: Yes, yeah.
We kicked this off this summer with a panel of like minded people from across the uk, including gastroenterologists, primary care physicians, infectious disease specialists, microbiologists, pathologists, epidemiologists. So we try to get everyone represented in the field and hopefully by this time next year it's all out and done and we have a bit more of a guideline that's matching the rest of Europe because currently we are a bit behind what other countries do.
[00:49:20] Speaker A: Well, that'd be really interesting to see and to find out what that updated guidance says. But this episode has been great to give us a bit of a feel for how we can really optimize our diagnosis and treatment.
So I just want to say, Anne, thank you so much for, for sharing your time and your knowledge with me and with the audience today.
[00:49:39] Speaker B: No worries, it was a pleasure. Anytime.
We can also then dive into the whole aspect of gastric cancer prevention and things. So there will be more coming in the next few years with regards to that. So there's lots of topics around this topic I'm happy to discuss.
[00:49:57] Speaker A: That'll be great. And you know, once the guidance comes out, be great to invite you back again, if you're happy to do that and we'll, we can then talk through that.
But yeah, thank you so much for, for joining me.
[00:50:07] Speaker B: Thank you for having me.
