H pylori in US veterans
Geoff A. Modest, M.D.
Mon 12/16/2019 8:15 AM
A new large retrospective US study from the Veterans Health Administration confirmed a large presence of H pylori infections in the US, an increased incidence of gastric cancer, and a decreased risk with adequate H pylori therapy (see hpylori VA gast ca gastro2019 in dropbox, or doi.org/10.1053/j.gastro.2019.10.019).
Details:
-- 371,813 patients had a diagnosis of H pylori from 1994-2019
-- mean age 62, 92% male, 28% ever-smokers, most were identified as having H pylori by record review showing appropriate therapy (about 75%)
-- 2024 (0.54%) developed gastric cancer, with median follow-up of 7.4 years.
--Median age of cancer diagnosis: 69
-- cases by race:
-- white: 214,090 cases (58% of total), future gastric cancer 984 cases (49% of total)
-- black/African-American: 87,989 cases (24%), gastric cancer 641 cases (32%)
-- American Indian/Alaskan native: 3022 cases (0.9%), gastric cancer 17 cases (0.8%)
-- Asian: 2483 cases (0.7%), gastric cancer 21% (1%)
-- native Hawaiian/Pacific Islander: 3837 cases (1%), gastric cancer 13 cases (0.6%)
-- they linked detection of H pylori with the VA’s Central Cancer Registry, a comprehensive national database of cancers diagnosed and treated in the VA system since 1995
-- the primary outcome was the diagnosis of distal gastric adenocarcinoma 30 days or more after detection of H pylori infection
Results:
-- cumulative incidence of gastric cancer:
-- 5 years after detection of H pylori: 0.37%
-- 10 years after detection of H pylori: 0.5%
-- 20 years after detection of H pylori: 0.65%
-- 13% increase in gastric cancer diagnosis per each 5 year increase in age at H pylori diagnosis, HR 1.13 (1.11- 1.15), p<0.001
-- With white patients as the reference and with multivariable adjustment, gastric cancer cases were, by racve/ethnicity:
-- black/African-American cases: twice as frequent, HR 2.00 (1.80-2.22), p<0.001
-- Latinx: 59% increased, HR 1.59 (1.34-1.87), p<0.001
-- Asian: 2.5 times, HR 2.52 (1.64-3.89), p<0.001
-- other notable associations: history of smoking had 38% increased risk, HR 1.38 (1.25-1.52), p<0.001; female sex half as likely, HR 0.52 (0.40-0.68), p<0.001
-- no clear association with the poverty level as determined by ZIP Code of where the patients lived
-- those with confirmed H pylori eradication after treatment:
-- 76% decreased risk of gastric cancer, HR 0.24 (0.15-0.41), p<0.001
-- but there was no significant decrease in those treated but did not have confirmed H pylori eradication
-- in terms of race/ethnicity, those with documented H pylori eradication:
--for black/African-American, gastric cancer case frequency vs white decreased somewhat to a 62% increase, HR 1.62 (1.19-2.21). also by considering those with documented eradication, the only other groups reaching statistical significance included: by stratified by age (21% increase per 5-year increase in age), and smoking history (39% increase)
Commentary:
-- the reason I bring up yet another H pylori study is to demonstrate the high prevalence of H pylori in the US, and extend the argument that we should consider testing and treating this infection in the US
-- of note, the national cancer databases that include gastric adenocarcinomas in the US do not include data on H pylori infections, the most well-known and significant risk factor for gastric cancer
-- one issue with H pylori and gastric cancer is that though H pylori is the strongest of the known risk factors, there are discrepancies; for example, sub-Saharan Africa has a high H pylori incidence but relatively low incidence of gastric cancer, suggesting that there may be other factors involved, perhaps either environmental or related to the genetic variants of H pylori (e.g. those variants that are CagA-positive or VacA-positive seem to be more carcinogenic: see http://gmodestmedblogs.blogspot.com/2018/11/h-pylori-colorectal-cancer-and-general.html)
-- in this VA study, for example, there was a residual increased risk of gastric cancer overall (24% with eradication still had gastric cancer): though the risk was reduced, there was still some residual increased risk in black/African-American patients as well as smokers. And some studies suggest that the CagA-positive variant is more prevalent in African-Americans, for unclear reasons
-- though the VA study involved veterans who may well have had overseas exposures, there have been a few studies suggesting that H pylori infections are relatively common in US (though these studies were not stratified by veteran status), including the 3rd NHANES survey finding that of 7465 adults: overall there was a 32.5% seropositivity for H pylori, with increases by age (16.7% 20-29 yo, up to 56.9% of >70yo), and by ethnicity/race (52.7% of non-Hispanic blacks, 61.6% of Mexican Americans, 26.2% non-Hispanic whites), see https://academic.oup.com/jid/article/181/4/1359/856832 ]
-- one issue is that the absolute incidence of gastric cancer in this study was actually pretty low (under 1%). Is that because the incidence of more virulent H pylori is low in the US (which might negate the utility of mass screening and treatment, with their attendant potential adverse effects)?? Or perhaps because there was only a median followup of 7.4 years?? In support of the latter, there was an increasing gastric cancer incidence with increasing age, likely a proxy for longer H pylori exposure. And a review of their graph found that those with eradicated H pylori infections found a continuous and dramatic relative decrease in gastric cancer over 20 years after H pylori diagnosis, as compared to those who did not have a documented eradication (see their graph 3D)
--and the mean age in this study was 62. What if people were systematically identified in their 20’s or 30’s and received eradication therapy?? A recent meta-analysis documented improved outcomes in those <40yo who were treated, vs older age groups (see hpylori eradication gastric cancer gastro2018 in dropbox, or doi.org/10.1053/j.gastro.2018.03.028)
--a Swedish study of similar length to the VA study also found similar benefits of eradicating H pylori infection: they had 95,176 individuals who had eradication therapy, and after a max followup of 7.5 years, had a 57% decrease in non-cardia adenocarcinomas, the ones associated with H pylori infection (though a 69% decrease in all gastric adenocarcinomas for unclear reasons). See hpylori eradication sweden gut2018 in dropbox, or doi:10.1136/gutjnl-2017-315363
--also, see http://gmodestmedblogs.blogspot.com/2019/06/h-pylori-eradication-and-decreased.html , a recent blog finding marked decreased gastric cancer in Hong Kong with H pylori elimination; this blog references many other relevant blogs on genetic variants, some unusual H pylori presentations (pruritus, urticaria, ITP), and studies suggesting a low recurrence rate of H pylori after eradication.
--but, in making decisions about testing and treating H pylori in the US, there is the background that though gastric cancer used to be a major killer in the US many decades ago, the incidence rates over the past 40 years have been decreasing (which is not to say that further decreases are unnecessary...). And, we know only too well that antibiotics have their downsides (short-term adverse effects, long-term microbiome changes and resistance. see the many many blogs on these in the blog website as below)
-- the limitations of the VA study include its retrospective observational nature, making it difficult to draw causal conclusions. However, the sheer magnitude of the study was impressive. The study also was of veterans, so may not be as generalizable to the general population or to women in particular. Also veterans who sought care outside of the VA system would not be included in the analysis. And were there selection biases in who were tested, or treated, or had tests-of-cure?? Also, this study likely included more of those with symptomatic H pylori infections. other studies have found important gastric cancer reductions in asymptomatic individuals. does that apply to the US?? It would also have been good to have baseline gastric cancer rates in those without H pylori as a comparison.
So, the study shows a few things:
-- it appears that H pylori infections are pretty common in the US, at least in veterans who might have had exposures overseas. And this supplements other survey data in the US. And, of course, the infection rate is quite high in many who immigrate to the US, including Central and South Americans, where the incidence of gastric cancer is much higher than in the US (eg see http://gmodestmedblogs.blogspot.com/2019/10/h-pylori-rx-vitamins-and-dec-gastric.html )
-- though there were many cases of both H pylori infection and gastric cancer independent of race or ethnicity, it seems clear that there are higher risks of cancer in African-Americans, Latinx, and Asians
-- and, it seems that the risk of gastric cancer is reduced by confirmed treatment of H pylori, which also reinforces the utility of repeat testing for cure (most easily done with H pylori stool antigen testing, though the patient should be off PPIs for 2-4 weeks and antibiotics for 4 weeks for an accurate result)
-- and, it does appear to be quite likely that treating those with H pylori infections in the US might well be beneficial in decreasing their likelihood of gastric cancer, though a randomized controlled trial would be quite useful
-- for one thing, we might be able to avert more gastric cancers with earlier detection and treatment of H pylori: even with the low absolute risk reduction of gastric cancers in the US as this study found, this still may be an important intervention given how awful gastric cancer can be
--another point: this is yet another reason to engage patients in smoking cessation, since that is the other potentially reversible risk factor found in this study
geoff
If you would like to be on the regular email list for upcoming blogs, please contact me at gmodest@uphams.org
to get access to all of the blogs:
2. click on 3 parallel lines top left, if you want to see blogs by category, then click on "labels" and choose a category
3. or you can just click on the magnifying glass on top right, then type in a name in the search box and get all the blogs with that name in them
please feel free to circulate this to others. also, if you send me their emails, i can add them to the list
Comments
Post a Comment
if you would like to receive the near-daily emails regularly, please email me at gmodest@uphams.org