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Use of a proton-pump inhibitor (PPI) after Helicobacter pylori eradication to a greater extent than than doubles the risk for gastric cancer, according to a population-based report from Hong Kong.
The "clear dose-response too time-response" tendency inwards PPI exercise too gastric cancer risk observed suggests the demand for "caution when prescribing long-term PPIs to these patients fifty-fifty later successful eradication of H. pylori," write Wai Keung Leung, MBChB, MD, from Queen Mary Hospital, Hong Kong, too colleagues.
The report was published online October 31 in Gut.
The researchers indicate out, however, that this was an observational study, which can't evidence displace too effect.
The novel results besides conflict amongst a lately published, the US Food too Drug Administration–mandated follow-up report conducted amongst pantoprazole, said David A. Johnson, MD, primary of gastroenterology at Eastern Virginia Medical School in Norfolk (Aliment Pharmacol Ther. 2016;43:73-82).
"No increased risk [for gastric cancer] was observed amongst prolonged PPI exposure," he said.
Dr Johnson, who was asked for comment, besides stated that the report has a "geographic bias" because it is from Hong Kong too "specific risks for gastric cancer are good recognized inwards Asian patients."
In the novel study, Dr Leung too colleagues partly focused on H pylori infection and its human relationship amongst gastric cancer.
H pylori eradication has been shown to bring down the risk for gastric cancer past times 33% to 47%, but many patients educate gastric cancer fifty-fifty later eradication of H pylori. PPI therapy, "although by too large considered safe," is associated amongst worsening gastric atrophy, especially inwards H pylori–infected patients, the researchers indicate out. Influenza A virus subtype H5N1 recent meta-analysis found a 43% increased risk for gastric cancer amidst long-term PPI users, but it is was unable to conform for H pylori, the major confounding factor.
Using a territory-wide wellness database inwards Hong Kong, Dr Leung too colleagues compared the risk for gastric cancer inwards PPI users too histamine-2 receptor antagonist (H2RA) users amidst 63,397 adults successfully treated amongst a 7-day class of triple therapy to eradicate H pylori between 2003 too 2012.
"PPIs are much to a greater extent than strong than H2RA inwards damage of gastric acid suppression, too previous studies did non expose whatsoever association betwixt gastric cancer evolution too H2RA. Hence, H2RA was selected equally a negative command exposure inwards our study," the researchers explain.
During a median follow-up of 7.6 years, 153 (0.24%) people developed gastric cancer after H pylori eradication therapy, mostly inwards noncardia regions (62%). None of the patients amongst gastric cancer tested positive for H pylori at diagnosis, but all had long-standing gastritis. The median historic current at cancer diagnosis was 71.4 years, too the median fourth dimension from H pylori eradication to gastric cancer was 4.9 years.
After propensity grade adjustment, people taking PPIs at to the lowest degree weekly had a greater than twofold increased risk for gastric cancer evolution (hazard ratio [HR], 2.44; 95% confidence interval [CI], 1.42 - 4.20). The propensity score–adjusted absolute risk departure betwixt PPI exercise too non-PPI exercise was 4.29 excess gastric cancer cases per 10,000 person-years.
H2RA users had no increased risk (HR, 0.72; 95% CI, 0.48 - 1.07), which "further supports the specific purpose of PPIs on gastric cancer development," the researchers say.
After stratification past times tumor site, PPI exercise was exclusively significantly associated amongst an increased risk for noncardia gastric cancer (HR, 2.59; 95% CI, 1.42 - 4.72) but non cardia cancer (HR, 1.97; 95% CI, 0.57 - 6.82); "although this outcome should last interpreted amongst caution equally this subgroup analysis has a relatively pocket-size issue of cardia cancers," the researchers say.
Gastric cancer risk increased amongst longer duration of PPI use. The HR was 5.04 (95% CI, 1.23 - 20.61) for 1 twelvemonth of exercise or longer, 6.65 (95% CI, 1.62 - 27.26) for 2 years of exercise or longer, too 8.34 (95% CI, 2.02 - 34.41) for three years exercise or longer.
More frequent exercise was besides associated amongst greater risk. When compared amongst the reference grouping (less than weekly use), gastric cancer risk progressively increased amongst to a greater extent than frequent PPI use. The HR was 2.43 (95% CI, 1.37 - 4.31) for weekly to less than daily use, increasing to 4.55 (95% CI, 1.12 - 18.52) for daily PPI use.
The results remained important past times diverse sensitivity analyses.
Influenza A virus subtype H5N1 forcefulness of the report is its exercise of information from a large population-based database amongst consummate information on subsequent diagnoses too drug prescriptions, which minimizes selection, information, too think biases, the researchers say. Use of strict exclusion criteria equally good equally propensity grade adjustment to command for potential confounders too restricting the sample to patients amongst successful H pylorieradication are other strengths.
In damage of report weaknesses, the researchers lacked information on roughly risk factors, such equally diet, identify unit of measurement history, too socioeconomic status. And despite the large sample of to a greater extent than than 63,000 H pylori–infected patients, the pocket-size issue of gastric cancer cases did non permit for whatsoever "meaningful evaluation of the dosage outcome too purpose of dissimilar PPIs," the researchers say.
The squad besides notes that PPIs users may convey a higher run a risk of undergoing endoscopy than non-PPI users, leading to regain of to a greater extent than gastric cancers due to surveillance bias.
Dr Johnson said at that spot was roughly other report weakness: "Important" demographic variables that are risk factors for gastric cancer — such equally smoking, alcohol use, obesity, diet, too identify unit of measurement history — are non accounted for.
He besides made a full general observation most PPI-related research: "Most studies showed that whatsoever potential effects of PPIs tend to disappear amongst fourth dimension too that the most probable explanation for the effects is confounding past times indication rather than causality."
Despite these limitations, Dr Leung too colleagues write that, to their knowledge, "this is the outset report to demonstrate that long-term PPIs use, fifty-fifty after H. pylori eradication therapy, is soundless associated amongst an increased risk of gastric cancer. This is probable related to the profound acid suppression of PPIs that worsens atrophic gastritis, especially inwards those patients amongst established gastric atrophy equally a outcome of chronic H. pylori-induced inflammation."
EDITOR'S NOTE: The even out has been updated to included comments from an proficient non involved amongst the study.
The report had no specific funding. Dr Leung has received honorarium for help advisory board meetings of Takeda too Abbott Laboratories. Dr Johnson has or has had fiscal ties to Pfizer Inc, which makes a PPI; Epigenomics; WebMD; CRH Medical; too Medtronic.
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