Renewed Interest in the Management of Helicobacter pylori Infection

Supplements and Featured Publications, The Effect of Antibiotic Resistance on the Management of Helicobacter pylori Infection,

A Q&A With William D. Chey, MD

The American Journal of Managed Care® (AJMC®): What has led to the recent increase in attention given to Helicobacter pylori treatments?

CHEY: It’s been an interesting time because there’s been a real renaissance in terms of interest in H pylori. There’s been a lot of movement in this space over the past year, year and a half, whereas for the previous 20 years there was absolutely no movement in this space whatsoever. I think the growing recognition and concern with the rising prevalence of clarithromycin-resistant H pylori strains have been responsible for this increase in interest. I’ve been the lead author on the last 2 iterations of the American College of Gastroenterology Clinical Practice Guideline in H pylori, and the one that we wrote, I think it was in 2007, we started to look for alternatives to clarithromycin triple therapy because rates of clarithromycin resistance appear to be rising and the eradication rates with that regimen appear to be 80% or less. By the 2017 guideline, we were waving a red flag that we should not be using this regimen except in very specific circumstances.

Our group, as well as other groups in the United States, [has] been tracking the eradication rates associated with clarithromycin triple therapy (PPI [proton pump inhibitor], clarithromycin, amoxicillin) and it is now very consistently under 80%; usually in the mid to high 70% range. Which means that roughly 1 in 4 patients with H pylori treated with that regimen isn’t going to be successfully cured of their infection. I think increasingly, people have been looking for alternatives and finally, I think we’ve found some. As far as what I refer to as the legacy regimens— the regimens we’ve been using for many years—we need to move away from clarithromycin triple therapy and favor bismuth quadruple therapy, which consists of a PPI, bismuth, tetracycline, and metronidazole. Aside from the legacy regimens, there are a number of exciting new combination therapies that I think will provide very viable alternatives and should be preferred over traditional clarithromycin triple therapy.

AJMC®: Do you feel that outcome monitoring would be a useful investment, and, if so, how big of a challenge would it be to implement?

CHEY: Outcome monitoring is already being done in Europe. What’s so interesting about what they’re doing in Europe is that it is across many different nations; they’ve made a conscious effort to collaborate and create a consortium of like-minded investigators across Europe who all submit their data and samples regarding H pylori to a central repository. They’ve been able to do some very interesting and valuable studies looking at resistance patterns as well as real-world eradication rates in association with commonly used H pylori treatment regimens. There’s nothing that would stop us from doing the same thing here, other than resources and resolve. I hope we can have the vision to make an investment because H pylori infection isn’t going anywhere anytime soon. The good news is that the United States is a medium- to low-prevalence country relative to many other parts of the world like Asia or Latin America, where H pylori infection affects well over 60% of the population. In the United States, we’re probably in a range of around 30% to 35%, so it’s substantially lower, but that’s still 1 in 3 people who [is] infected. It’s also important to remember that [those who] immigrate to the United States, particularly from Russia, Asia, and Latin America, [can be coming from countries that] have a much higher prevalence of H pylori infection. So, as I said, H pylori is going to be around and going to be an issue for the foreseeable future, I think for many years to come.

AJMC®: You’ve noted “resources” and “the resolve to participate” as being roadblocks to outcome monitoring here in the United States. Do you have any ideas on how to overcome that?

CHEY: In the 1990s, there was something called the Surveillance of H pylori Antimicrobial Resistance Partnership (SHARP) program, which was a national H pylori antimicrobial resistance monitoring program. So, for a short period of time, there was a surveillance program in the United States. You wonder whether or not there might be the interest or the will at the level of the National Institutes of Health, for example, to fund some type of a consortium that would follow resistance rates and track data around the effectiveness of H pylori treatment regimens in the United States. I think the other possibility is whether the companies that are making these novel regimens might be interested in creating a registry where participants could input data around the regimens that they use—just practical effectiveness data, even that would be potentially helpful.

AJMC®: What role does H pylori screening have in patients who are symptomatic compared with patients who are asymptomatic?

CHEY: If you first consider symptomatic patients, every clinical guideline recommends that you test and treat patients with dyspepsia. Our guideline also mentions that even for functional dyspepsia where you do an endoscopy and you don’t find an ulcer, but you do find H pylori infection, you should treat to eradication. The reason [is that] H pylori infection is one of the few curable and potentially reversible causes of dyspeptic symptoms. If you think about dyspepsia from a pragmatic standpoint, you could make an argument that the inflammation perhaps activates sensory nerves that lead to the symptom experience that we refer to as dyspepsia. There are also patients who probably have ulcers that come and go, so at the time you do the endoscopy maybe it just looks a little bit red but maybe if you did an endoscopy a month or 2 later, you might find erosions or an ulcer. That process of inflammation and mucosal injury is dynamic, and what you find, to some extent, depends on when you look. So, really, I think every organization that I’m aware of recommends that if you have a patient with uninvestigated dyspepsia or even functional dyspepsia, you should look for H pylori because it offers one of the only reversible or curable causes of these symptoms. That’s the good news. The bad news is that in patients with dyspepsia, only around one-third of the patients get better with eradication of H pylori infection. There is also the issue of antibiotic stewardship given the need for multidrug regimens. Still, I side with the guidelines and believe that the upside is enough to justify the downside of treating patients with dyspepsia.

It’s a completely different discussion in infected people who are asymptomatic. In asymptomatics, you’re presumably going after H pylori as a chemopreventive strategy for gastric cancer because H pylori, according to the World Health Organization, is a class 1 carcinogen. There’s a very nice meta-analysis that was published in Gastroenterology in 2016 by Lee and colleagues1 that summarized all the data to that point in terms of eradicating H pylori as a chemopreventive strategy for gastric cancer. The investigators came to the conclusion that, yes, there was potential benefit to screening asymptomatic individuals for H pylori and eradicating H pylori in the hopes of reducing the likelihood of developing gastric cancer. But it is important to note that the benefits seem to be confined to countries where the pretest probability of gastric cancer is high, but less robust or even nonexistent in countries like the United States, where the pretest probability of gastric cancer is quite low.

AJMC®: Should retesting after therapy be implemented routinely?

CHEY: Yes. In our 2017 guideline, we recommended that whenever practically possible, universal posttreatment testing to prove eradication be performed. It should be done with a urea breath test, [with a] stool antigen test, or, if an esophagogastroduodenoscopy is done, by histology or rapid urease testing at least 4 weeks after the completion of antibiotic therapy.

Unfortunately, retesting is not done consistently. There are many practitioners who have adopted our recommendations, and so if you were to poll gastroenterologists, they largely fall into 3 camps: the providers who routinely retest almost everybody, the ones who do it for certain indications, and the ones who don’t think it is important or that the treatments always work, and for those reasons, do not retest to prove eradication. I would offer this question: If you’re interested enough to find H pylori and treat it, shouldn’t you be interested enough to know that it’s gone?

AJMC®: How do you recommend managing a patient who has been treated for H pylori and is still infected?

CHEY: Let’s say a patient has dyspepsia. You test them for H pylori, you find it, you treat them, they come back for follow-up, and they still have symptoms. Don’t assume that the symptoms mean that the infection is still present. It’s really important to retest because only one-third of the patients with dyspepsia will get better even after you successfully eradicate H pylori infection. Persistent symptoms do not equal persistent infection. You have to do the test because you don’t want to give somebody 1, 2, or 3 antibiotics again if they don’t actually have the infection. If testing confirms persistent infection, it is important for the treating physician to avoid re-treating with the same antibiotics, to stress the importance of adherence, and to make sure to treat for 14 days. Adherence is key no matter where a patient is in the treatment journey. Remember that with each round of H pylori treatment, it becomes progressively more difficult to successfully eradicate the infection, regardless of what you use to treat it. Your first chance is your best chance to cure the infection. After that, things start going downhill really quickly. Other recommendations can be found in our ACG guideline. Also, the American Gastroenterological Association just published a clinical practice update with recommendations for patients with persistent H pylori infection.

REFERENCE

1. Lee YC, Chiang TH, Chou CK, et al. Association between Helicobacter pylori eradication and gastric cancer incidence: a systematic review and meta-analysis. Gastroenterology. 2016;150(5):1113-1124.e5 . doi:10.1053/j.gastro.2016.01.028