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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 written report from Hong Kong.
The "clear dose-response in addition to time-response" tendency inwards PPI utilization in addition to gastric cancer risk observed suggests the demand for "caution when prescribing long-term PPIs to these patients fifty-fifty subsequently successful eradication of H. pylori," write Wai Keung Leung, MBChB, MD, from Queen Mary Hospital, Hong Kong, in addition to colleagues.
The written report was published online October 31 in Gut.
The researchers signal out, however, that this was an observational study, which can't testify campaign in addition to effect.
The novel results likewise conflict with a latterly published, U.S.A. Food in addition to Drug Administration–mandated follow-up written report conducted with pantoprazole, said David A. Johnson, MD, main of gastroenterology at Eastern Virginia Medical School in Norfolk (Aliment Pharmacol Ther. 2016;43:73-82).
"No increased risk [for gastric cancer] was observed with prolonged PPI exposure," he said.
Dr Johnson, who was asked for comment, likewise stated that the written report has a "geographic bias" because it is from Hong Kong in addition to "specific risks for gastric cancer are good recognized inwards Asian patients."
In the novel study, Dr Leung in addition to colleagues partly focused on H pylori infection and its human relationship with gastric cancer.
H pylori eradication has been shown to trim down the risk for gastric cancer past times 33% to 47%, but many patients educate gastric cancer fifty-fifty subsequently eradication of H pylori. PPI therapy, "although to a greater extent than oft than non considered safe," is associated with worsening gastric atrophy, peculiarly inwards H pylori–infected patients, the researchers signal out. Influenza A virus subtype H5N1 recent meta-analysis found a 43% increased risk for gastric cancer alongside long-term PPI users, but it is was unable to adapt for H pylori, the major confounding factor.
Using a territory-wide wellness database inwards Hong Kong, Dr Leung in addition to colleagues compared the risk for gastric cancer inwards PPI users in addition to histamine-2 receptor antagonist (H2RA) users alongside 63,397 adults successfully treated with a 7-day course of written report of triple therapy to eradicate H pylori between 2003 in addition to 2012.
"PPIs are much to a greater extent than strong than H2RA inwards price of gastric acid suppression, in addition to previous studies did non let on whatsoever association betwixt gastric cancer evolution in addition to H2RA. Hence, H2RA was selected every bit 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 with gastric cancer tested positive for H pylori at diagnosis, but all had long-standing gastritis. The median historic catamenia at cancer diagnosis was 71.4 years, in addition to 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 utilization in addition to non-PPI utilization 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 run of PPIs on gastric cancer development," the researchers say.
After stratification past times tumor site, PPI utilization was alone significantly associated with 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 resultant should last interpreted with caution every bit this subgroup analysis has a relatively pocket-size issue of cardia cancers," the researchers say.
Gastric cancer risk increased with longer duration of PPI use. The HR was 5.04 (95% CI, 1.23 - 20.61) for 1 twelvemonth of utilization or longer, 6.65 (95% CI, 1.62 - 27.26) for 2 years of utilization or longer, in addition to 8.34 (95% CI, 2.02 - 34.41) for iii years utilization or longer.
More frequent utilization was likewise associated with greater risk. When compared with the reference grouping (less than weekly use), gastric cancer risk progressively increased with 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 written report is its utilization of information from a large population-based database with consummate information on subsequent diagnoses in addition to drug prescriptions, which minimizes selection, information, in addition to recollect biases, the researchers say. Use of strict exclusion criteria every bit good every bit propensity grade adjustment to command for potential confounders in addition to restricting the sample to patients with successful H pylorieradication are other strengths.
In price of written report weaknesses, the researchers lacked information on to a greater extent than or less risk factors, such every bit diet, household unit of measurement history, in addition to 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 resultant in addition to run of dissimilar PPIs," the researchers say.
The squad likewise notes that PPIs users may bring a higher withdraw a opportunity 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 to a greater extent than or less other written report weakness: "Important" demographic variables that are risk factors for gastric cancer — such every bit smoking, alcohol use, obesity, diet, in addition to household unit of measurement history — are non accounted for.
He likewise made a full general observation virtually PPI-related research: "Most studies showed that whatsoever potential effects of PPIs tend to disappear with fourth dimension in addition to that the most probable explanation for the effects is confounding past times indication rather than causality."
Despite these limitations, Dr Leung in addition to colleagues write that, to their knowledge, "this is the offset written report to demonstrate that long-term PPIs use, fifty-fifty after H. pylori eradication therapy, is silent associated with an increased risk of gastric cancer. This is probable related to the profound acid suppression of PPIs that worsens atrophic gastritis, peculiarly inwards those patients with established gastric atrophy every bit a resultant of chronic H. pylori-induced inflammation."
EDITOR'S NOTE: The storey has been updated to included comments from an proficient non involved with the study.
The written report had no specific funding. Dr Leung has received honorarium for assist advisory board meetings of Takeda in addition to Abbott Laboratories. Dr Johnson has or has had fiscal ties to Pfizer Inc, which makes a PPI; Epigenomics; WebMD; CRH Medical; in addition to Medtronic.
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