H Pylori eradication and decreased gastric cancer

Another large study, this one from Korea, found that H pylori eradication was associated with reduced risk of gastric cancer (see hpylori eradication gastric cancer dec gastroendosc2019 in dropbox, or doi.org/10.1016/j.gie.2019.04.232.)

Details:

-- 10,328 healthy subjects underwent EGD endoscopy and H pylori testing from 2003-2011, and had follow-up endoscopy and H pylori testing until 2013

-- mean age 49, 58% men, BMI 24, current/past smoker 50%, current/past drinker 70%, fam history gastric cancer 14%, lipid lowering drugs 8%, atrophic gastritis 23%, total cholesterol 200/LDL 126/HDL 55

-- H pylori was detected using the rapid urease test or histologic test on EGD. Baseline H pylori detection rate was 54%

    -- of note, of the 5061 patients with negative rapid urease test at baseline, 291 (5.7%) had H pylori on simultaneous histologic samples [ie, there are false negatives for the rapid urease test]

-- 3 groups identified: successful H pylori eradication, persistent H pylori infection (either eradication failure, or eradication not attempted), and no H pylori identified

Results:

-- 31 gastric cancers were detected during a median follow-up of 5.5 years (21 of them had well-to-moderate differentiation, 29 in the non-cardia, 29 Stage 1)

    -- 21 cancers, in 3508 subjects in the non-eradication group (0.6%)

    -- 4, in 2050 persons with successful H pylori eradication (0.2%)

    -- 6 of 4770 participants in the group without H pylori (0.13%)

-- in adjusted analysis (sex, older age, BMI, use of lipid lowering drugs, presence of atrophic gastritis, family history gastric cancer, higher LDL, current/past smoker), H pylori eradication decreased de novo gastric cancer risk by 71%, HR 0.29 (0.10-0.86) 

    -- the overall group without H pylori (eradicated successfully or did not have in the first place) had a 76% decreased risk compared to those with persistent H pylori infection, HR 0.24 (0.09-0.60)

-- review of the Kaplan-Meier incidence: cumulative incidence gastric cancer in those with H pylori non-eradication increased sharply after 8 years. a very slight increase in those with H pylori eradication after 8 years

-- those with a low serum HDL had an increased risk of de novo gastric cancer, HR 2.67 (1.14-6.16)

Commentary:

--these are 2 pretty common conditions: H pylori is the most common bacterial infection in the world (>50% of the world’s population), and gastric cancer is quite common (2^nd more common cancer and third leading cause of death worldwide), especially in areas where H Pylori is prevalent

--and, H Pylori is also pretty prevalent in the US: the third National Health and Nutritional Examination Survey (1988-91) of 7465 adults found: overall 32.5% seropositivity, with increases by age (16.7% of 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 ]

--there have been many relevant prior blogs: 

    -- http://gmodestmedblogs.blogspot.com/2018/06/h-pylori-treatment-in-elderly-dec.html : Hong Kong study of >70K people who had H pylori treatment, finding 18% dec risk of gastric cancer

    -- http://gmodestmedblogs.blogspot.com/2018/04/h-pylori-eradication-decreases.html : South Korean study finding that patients with early gastric cancer had a 50% decrease in metachronous (subsequent) cancer

    -- http://gmodestmedblogs.blogspot.com/2019/04/h-pylori-eradication-and-reduced-risk.html : 24 studies in a meta-analysis, finding a 46% lower incidence of gastric cancer when H Pylori was eradicated

    -- http://gmodestmedblogs.blogspot.com/2018/11/h-pylori-colorectal-cancer-and-general.html : some genetic variants of H pylori (eg VacA) are associated with colon cancer

--the association between gastric cancer and low HDL levels is new to me, though there are articles in the literature finding an association (eg see gastric ca and low HDLJgastrohep2012 in dropbox, or doi:10.1111/j.1440-1746.2012.07189.x). Not sure what this means.  ?relationship between metabolic syndrome (with low HDL) and gastric cancer.  (?related to high insulin levels/inflammation in metabolic syndrome).  ??if there is any real or causal relationship

--also, it is a bit disconcerting that 5.7% of those in this study with negative rapid urease test were positive on biopsy for H pylori; the stool antigen test has sensitivity and specificity in the mid-90 range, even if done right (ie, no antibiotics or PPIs in prior 4 weeks), so may not be sensitive enough in high risk people [which means that in those with high pre-test probability of H pylori infection, a negative noninvasive rapid urease test or stool antigen may well be a false negative: leaving 2 options, either an EGD or just treating presumptive infections)

As asides to the above:

-- I do test pretty much all of my patients for H pylori and find many people who are positive who have never left the US.  As a pretty remarkable example:  about 20+ years ago i saw a 50yo white, middle-class US patient without foreign travel who had severe refractory steroid-resistant ITP about to get splenectomy. i had read a report of an association between H pylori and ITP, tested him, found H pylori, treated it, and the ITP vanished within days, never to return. 

--I recently saw a person from Africa who was asymptomatic, but H Pylori positive on routine testing (which is the most common scenario). He also had chronic pruritus of unknown cause. I put him on a 14-day course of sequential therapy for H Pylori (see http://gmodestmedblogs.blogspot.com/2016/10/h-pylori-regimens-stratified-by.html, for treatments) and he came back in a month or so. During that time I happened to see an article on H Pylori causing pruritus. so, when he came back i asked him about the pruritus: his chronic pruritus had evaporated….

    --So, I did a little research and found that a slew of reports of H Pylori being associated with chronic urticaria, and a review article suggesting linkages between H pylori infection and several skin problems, including urticaria, Behcet’s dz, lichen planus, pruritus, prurigo nodularis and prurigo chronica.  (see hpylori and skin disease amjclinderm2002 in dropbox, or Wedi B. Am J Clin Dermatol. 2002; 3(4): 273).  So, I think it makes sense to check for H pylori in patients with these conditions and treat if positive. Maybe it will help the skin problem, as well as prevent ulcers/bleeding with NSAIDs/gastric cancer… 

-- also, see http://gmodestmedblogs.blogspot.com/2015/05/h-pylori-and-nsaids-increased-gi.html which looks at some of the studies finding increased risk of major GI bleeding with NSAIDs if there is an underlying H pylori infection (and 2/3 reduction if H pylori is treated before starting NSAIDs)

--and, one interesting finding is the apparently low rate of recurrence of H pylori after successful eradication. A 2017 systematic review of 132 articles (53,934 patient-yrs), found that the overall rate of H Pylori reinfection was low (3.1%), though did increase as patients were from lower SES (up to 10.9%) and if high prevalence in the country (also 10.9%), though "recurrence" in some studies is related to inadequate initial treatment or inadequate confirmation of eradication (see hpylori recurrence rates alimentpharmther2017 in dropbox, or DOI: 10.1111/apt.14319). not sure what is happening here, given that these numbers of recurrent infectiosn are so much lower than the untreated infection rate. is there some protection (immunologic?) from developing a reinfection when the patient lives in a country with >50% of people are infected? are there decreases in patients' H pylori exposure after treatment??

so, i am concerned about the multitude of potential bad outcomes with H pylori infection: chronic dyspepsia, gastric cancer, mucosa-associated lymphoid tissue lymphoma, atrophic gastritis, peptic ulcer disease with potential major bleeds, increased major GI bleeds in those concomitantly taking NSAIDs, maybe colon cancer, likely several skin conditions including urticaria (and some reported incidences of severe angioedema), and ITP.  

i personally am pretty aggressive in checking for H pylori infections in pretty much all of my patients and treating them with 14 days of sequential antibiotics (which have the advantage of working even if there is clarithromycin resistance)... though i do have a skewed population of patients: mostly immigrants from resource-poor countries, and the locals are of lower socioeconomic status, considered a risk factor for H pylori.  And i do find a remarkably large % of my patients who are actively infected with H pylori....

geoff

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