Gut Check: H pylori Part 1—Prevalence and Diagnosis

In this first of a two-part podcast on Helicobacter pylori, Drs Brian Lacy and William Chey discuss the prevalence of H pylori infection and how to best diagnose the condition.

Brian Lacy, MD, is professor of medicine at the Mayo Clinic in Jacksonville, Florida. William Chey, MD, is section chief of the division of gastroenterology and hepatology and professor of medicine at the University of Michigan in Ann Arbor, Michigan.

TRANSCRIPT:

Any views and opinions expressed are those of the author and or participants, and do not necessarily reflect the views, policy, or position of Gastroenterology Learning Network or HMP Global, their employees and affiliates.

Welcome to Gut Check, a podcast from the Gastroenterology Learning Network. My name is Brian Lacy. I'm a professor of medicine at the Mayo Clinic in Jacksonville, Florida, and I am absolutely delighted to be speaking today with Dr. William Chey, section chief and professor of Medicine in the division of gastroenterology and hepatology at the University of Michigan in Ann Arbor, Michigan.

And Dr. Chey, as many of you who are listening in today know, that he's an international expert in disorders of gut-brain interaction, but more pertinent to our discussion today, Dr. Chey is also an expert in the diagnosis and treatment of H. pylori, Helicobacter pylori, and is the author of the key American College of Gastroenterology guideline on the treatment of H. pylori. Today we're going to focus on H. pylori with an emphasis on why this is still so important and how best to diagnose it. In a subsequent podcast, we'll discuss the ins and outs of treating H. pylori. So Bill, welcome.

Let's begin by trying to understand the scope of the problem. How common is H. pylori worldwide and how common is H. pylori in the United States?

Dr. William Chey:

Well, first of all, thanks, Brian, for having me on the podcast. And the prevalence of H. pylori is a good news, bad news story. So the good news is that the overall worldwide prevalence of H. pylori infection seems to be decreasing over time. So a recent meta-analysis that was just published in Lancet Gastroenterology and Hepatology reported that from 2011 to 2022, the worldwide prevalence of H. pylori infection decreased from around 58% down to around 43%. So that's the good news. The bad news is the worldwide prevalence of H. pylori infection is still 43%. That's remarkable. Almost half of the world's population is infected by H. pylori. It remains one of the most common worldwide human infections. And in the United States, good news, bad news again here, the prevalence is lower. Like in most developed countries, our prevalence is probably closer to 30%, but still, almost a third of US citizens are infected with H. pylori.

Dr Brian Lacy:

And Bill, I liked the way you said that, that some people really consider H. pylori the most common worldwide infection, and 43% is impressive. So what are the risk factors for developing H. pylori?

Dr. William Chey:

Yeah, I think it boils down to a relatively small number of things. So first thing is older age, and that probably reflects more so a cohort effect than it does actual getting new infection, for example. But what I mean by that is that H. pylori tends to, the infection tends to occur during childhood. So older individuals had a higher likelihood of becoming infected as children compared to children in today's day and age who have a much lower risk of getting infected. Now, having said that, it's important to recognize that there's tremendous variability in H. pylori prevalence based on geography.

So for example, urban areas. So large cities tend to have a much higher prevalence of H. pylori infection than rural areas. Why? It's thought that because of crowding and poor hygiene, which is more prevalent amongst very large urban centers, there's a higher likelihood of spreading the infection. But equally important and arguably more important is the prevalence of H. pylori infection and the new infections in the United States are largely being driven by folks that are born outside of the United States. So folks that are immigrating here from less developed countries have a much higher likelihood of being infected than individuals that are born in the United States.

Dr Brian Lacy:

Wonderful. And so Bill, thinking about setting the stage for our later discussion about treatment, why do we really care about H. pylori? Is it just the increased risk for ulcer disease, or should we be concerned about other things as well?

Dr. William Chey:

Well, H. pylori has or can lead to a wide range of downstream consequences, the most well-recognized of which is peptic ulcer disease. Brian, you and I are both old enough to remember a time when it was thought that peptic ulcer was a consequence of excess acid in the stomach, and it was a paradigm shift and a violent paradigm shift—if you recall how much hand-to-hand comment there was when this topic was first discussed—that H. pylori or peptic ulcer disease was actually an infectious disease as opposed to a disorder of increased acid production. But peptic ulcer disease, although that's where the story started, isn't where the story ends. So another really important part of the H. pylori story is the relationship between H. pylori infection, the development of chronic gastritis, which then progresses to intestinal metaplasia and serves as the precursor for gastric cancer.

Remember that gastric adenocarcinoma remains the fourth leading cause of cancer-related mortality worldwide. So this is a huge deal. Now in the United States, it's a bit less of a deal because gastric cancer is probably the 10th leading cause of cancer-related mortality. But remember that the World Health Organization actually has designated H. pylori as a class 1 carcinogen for gastric cancer. So this relationship between H. pylori infection and gastric cancer is well codified. The good news is the vast majority of people with H. pylori will never go on to develop gastric cancer, but people with gastric cancer are much more likely to have been infected with H. pylori infection than people without gastric cancer. There are other indications as well, and I know in subsequent questions we'll go over this, but things like iron deficiency anemia, idiopathic thrombocytopenic purpura, patients with dyspeptic symptoms, as well as those that are starting therapy chronic therapy with NSAIDs or aspirin, are all at higher risk of complications related to H. pylori.

Dr Brian Lacy:

Wonderful summary. Thank you. And certainly for some of our younger providers doing endoscopy, when you refer that patient with IDA, iron deficiency anemia, or consideration for ITP, taking those gastric biopsies, and we'll talk about that a little bit later, is important. So Bill, let's consider the US population. If somebody has H. pylori and is not treated, what's the likelihood of developing an ulcer? What do we tell them in clinic?

Dr. William Chey:

The dogma has always been that around 10 to 15% of patients with H. pylori infection will go on to develop peptic ulcer disease, and I think that's still the number that most people would adhere to.

Dr Brian Lacy:

So not that high, but certainly a reasonable risk and thus a reason to treat. So let's shift gears a little bit and think about the diagnosis because I think there are a lot of myths and misconceptions about diagnosis. So first of all, who should be tested to see if they have H. pylori?

Dr. William Chey:

Yeah, it really revolves around those indications that we already reviewed. So patients with peptic ulcer, patients that are starting chronic therapy with NSAIDs or aspirin, you should think about screening them for H. pylori infection. Individuals with uninvestigated or functional dyspepsia in which H. pylori testing has not been done, it's reasonable to screen for H.pylori infection. That's been the test and treat strategy. Most primary care doctors will definitely know this. It has been shown to be a cost-effective way by which to manage uninvestigated dyspepsia. And there is data to suggest that there's a small but statistically significant benefit to eradicating H. pylori in individuals with functional dyspepsia.

So we oftentimes joke, Colin Howden used to always say to me that patients go into the endoscopy suite with uninvestigated dyspepsia and they come out of the endoscopy suite with functional dyspepsia. Although the therapeutic gain, that is the likelihood of dyspeptic symptoms getting better in functional dyspepsia after H. pylori eradication, is less than 10%. So it's a pretty marginal therapeutic gain. H. pylori eradication is the only long-lasting, potentially reversible cause of functional dyspepsia. So although it benefits a small proportion of patients, it potentially cures those patients of their disease. So it's, in my opinion, worth pursuing.

Dr Brian Lacy:

A small but very important number. Bill, thinking about testing, some clinicians still use a serum test to check for H. pylori. Is that of any value?

Dr. William Chey:

It can be. I think that early on in our whole H. pylori journey, screening was almost exclusively done with serology. And what we came to learn pretty quickly was that is fraught with problems. So let me give you an example, is that the positive predictive value of an antibody test is highly influenced by the pretest probability of infection. So if you're in a high pretest probability place, let's say you're in Houston, Texas or you're in San Diego, where the background prevalence of H. pylori infection is relatively high, the positive predictive value of an antibody test is going to be pretty good, probably in the range of 75 to 80%. Certainly not perfect, but not bad. On the other hand let's go to Ann Arbor, Michigan, where I live, the pretest probability of H. pylori infections probably around 20%. The positive predictive value of an antibody test in my population is less than 50%.

So if I get a positive antibody test back, I might as well flip a coin. I'd probably get a more accurate result from flipping a coin than relying upon that H. pylori serology test. So based upon your pretest probability, an antibody test can be reasonably appropriate or entirely inappropriate. If you're going to use an antibody test in a low pretest probability population, you would just want to make sure that you confirm a positive result before exposing a patient to multiple antibiotics. So do, for example, a urea breath test or a fecal antigen test in a patient with a positive antibody test to confirm that it's indeed a true positive.

Dr Brian Lacy:

That's wonderful. Thank you for clarifying that, Bill. And since you mentioned that, what about stool tests for H. pylori? And are these better than a breath test? Do you prefer one over the other?

Dr. William Chey:

Yeah, so I should have reviewed that in the last discussion, but antibody testing, as the name implies, identifies an antibody response to the infection. So it's an indirect test. It identifies the response to the infection. There are tests that identify only patients with active disease, and these include the urea breath test as well as a fecal antigen test. The urea breath test relies upon the identification of labeled carbon dioxide expelled in the breath that's produced as a consequence of H. pylori's urease activity. So it identifies active enzyme activity, urease activity, which leads to the production of either C 13 or C 14, labeled CO2 that can be measured in the breath. So only active infection. The fecal antigen test on the other hand, as the name implies, identifies antigens associated with H. pylori infection in stool samples. They're both highly accurate. When done properly, the sensitivity and specificity is over 90%.

By the way, that's true before you treat or after you treat. But the caveat is what I said a second ago, if done properly, okay. So for example, you want to make sure that a patient has withheld PPI therapy for ideally 2 weeks. You can probably get away with 1 week, 1 week's probably okay, but 2 weeks is the ideal. It's the standard, it's the recommendation for withholding a PPI before a UBT or a fecal antigen test. Antibiotics, 4 weeks. You really want to withhold an antibiotic or bismuth for 4 weeks before you do a fecal antigen test or a urea breath test to ensure that the results are accurate.

Now, it's worth saying here that a moment ago I talked about pretest probability and how the positive predictive value is influenced by pretest probability for antibody testing. Realize that in individuals that have used, recently used antibiotics or a PPI that are undergoing a urea breath test or a fecal antigen test, it affects sensitivity. Okay, not specificity. So a positive test is still evidence of infection. The problem is a negative test may be falsely negative as a consequence of the recent use of the PPI or antibiotics. So don't discount a positive test just because somebody's been taking a PPI or antibiotic. That's actual infection. It's only the negative test that you're concerned about.

Dr Brian Lacy:

Well, I love that last great teaching point. Thank you for really highlighting that. So we kind of discussed patients who might come in and you might consider taking biopsies to look for H. pylori, but there too are some confusing issues. So you've done this for a long time. How do you like to perform biopsies when you do endoscopy for H. pylori? Is it just the antrum? Is it just the fundus? Is it throughout the stomach? How many biopsies, specimens do we really need?

Dr. William Chey:

Yeah, this is still controversial. People still argue about this, but this is what I would say. The vast majority of the patients that are going to come to see you with upper GI symptoms are going to be on a PPI when they're undergoing endoscopy. That's just the reality of it. I mean, in an ideal world, you would have the patient stop a PPI for a week or ideally 2 weeks before the procedure to allow you to achieve the greatest sensitivity and specificity of testing for H. pylori infection. But that's not real world. Real world is that the patients usually don't get instructions to stop the PPI. And even if they do, they oftentimes don't want to stop their PPI.

So that being the case, I make it really easy on myself. I don't worry about whether they're taking a PPI or not. I do the biopsies the same in everybody, which is 2 from the antrum, 2 from the body. Now, that's probably adequate for H. pylori infection. But remember that when there are other standardized biopsy protocols, if you're really looking for or surveilling patients with intestinal metaplasia, that's an entirely different discussion. I don't want to go into that, but it bears mentioning that what's sufficient for diagnosing H. pylori may not be sufficient for surveilling or trying to identify intestinal metaplasia.

Dr Brian Lacy:

So Bill, this is wonderful too because it sounds as if in the ideal world, an endoscopy for a patient not on PPI might be best, maybe marginally better, but we don't operate in the ideal world. Most of these patients come in on PPIs. And so just doing those appropriate biopsies, antrum and body will likely be sufficient for most patients. Is that how you would view it?

Dr. William Chey:

Yes, absolutely correct. Doing antrum and body is better than doing just antrum alone.

Dr Brian Lacy:

Wonderful. Thank you. So Bill, for this podcast today we've kind of focused on the prevalence and the importance and the impact of H. pylori and the diagnosis. This has been just a wonderful conversation. Thank you so much. Any last thoughts for our listeners?

Dr. William Chey:

No, just it's easy to forget about, not think about H. pylori infection, but remember, a third of the US population remains infected. And particularly for those individuals that you're caring for that have been born outside of the US, let's say Latin countries, Asia, Africa, certain parts of Eastern Europe and Russia, H. pylori infection is an incredibly common problem. And remember that you have a number of diagnostic tests at your disposal, and when you biopsy, get the antrum and the body.

Dr Brian Lacy:

Wonderful. So again, this is Gut Check, a podcast from the Gastroenterology Learning Network. My name is Dr Brian Lacy. I'm a professor of medicine at Mayo Clinic in Jacksonville, and you've just heard really from world's expert on H. pylori, Dr. William Chey, a professor of medicine at the University of Michigan in Ann Arbor, Michigan. Thank you so much for listening in today. Whether you're listening in on Apple or Spotify or any other devices, look forward to another podcast in the near future where we discuss the treatment of H. pylori with Dr. Chey. Thank you so much for tuning in.