H. pylori eradication cuts stomach cancer risk, unless PPIs used long-term

Helicobacter pylori eradication reduced the risk for gastric cancer in patients aged older than 60 years, who showed a 22% lower risk vs. the general population, according to new research shared at UEG Week.

However, additional data published in Gut on the same population-based cohort of more than 60,000 H. pylori patients in Hong Kong showed gastric cancer risk increased with long-term use of proton pump inhibitors (PPIs) in a time- and dose-dependent manner, even after eradication therapy.

These data support the value of eradication therapy in older patients, and suggest that physicians should be cautious when prescribing PPIs to patients with H. pylori infection, even after successful eradication, according to Wai Keung Leung, MD, of the department of medicine at The University of Hong Kong, Queen Mary Hospital, China, and colleagues.

“We saw a significantly lower risk of gastric cancer in people over 60 who received antibiotic therapy for their H. pylori infection, in comparison to the general population,” he said during the opening plenary session at UEG Week, according to a press release. “The 22% reduction is remarkable, and suggests that there is real value in the treatment of this infection.”

To compare gastric cancer risk among H. pylori patients who underwent antibiotic eradication therapy vs. the general population, Leung and colleagues used a regional health database to identify 63,397 H. pylori patients who received clarithromycin-based triple therapy between 2003 and 2012 (median age 54.7 years; 46.5% men). They then compared their gastric cancer incidence with age-matched groups from the general population, which included individuals with and without H. pylori infection.

Throughout a median follow-up period of 7.5 years, 0.24% of the H. pylori patients who received eradication therapy developed gastric cancer, for an overall incidence of 3.2 cases per 10,000 person-years.

When stratifying by age, Leung and colleagues showed that at 12 years, 0.8% of the H. pylori eradication patients aged 60 years and older vs. 1.1% of the matched general population, developed gastric cancer — a significant difference.

In contrast, the cumulative incidence rates were the same for those aged younger than 40 years (0.1%) and for those aged 40 to 59.9 years (0.3%).

“Although it has been commonly thought that it may be too late to give H. pylori eradication therapy to older subjects, we can now confidently recommend that the H. pylori infection should be treated in the elderly to help reduce their risk of developing gastric cancer,” Leung said in the press release.

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For the study published in Gut, Leung and colleagues looked at the same cohort to evaluate for associations between PPI use and gastric cancer among H. pylori eradication patients. Prior studies have shown a 43% increased gastric cancer risk among PPI users, but were unable to determine a causal link to H. pylori itself. Therefore, they used histamine-2 receptor antagonists (H2RAs) as a negative control exposure.

They found that those who used long-term PPIs showed a 2.4-fold increase in the risk for gastric cancer vs. non-users (HR = 2.44; 95% CI, 1.42-4.2), while those who took H2RAs showed no increased risk. The median time between eradication therapy and gastric cancer diagnosis was 4.9 years.

Further, they showed the risk increased with duration of use, increasing fivefold after a year of use, to more than sixfold after 2 years and eightfold after 3 years. The risk also increased with frequency of use, to more than fourfold higher with daily vs. weekly use.

Leung and colleagues cautioned that causal conclusions cannot be drawn from these observational data, and that PPIs are generally considered safe. However, they concluded that the “clear dose-response and time-response trend of PPIs use and gastric cancer risk” warrants caution in prescribing PPIs to these patients.

H. pylori infection is believed to affect more than half of the global population, and is the most significant risk factor for gastric cancer, linked to 78% of all cases worldwide, according to the release from UEG Week. – by Adam Leitenberger

References:

Leung WK, et al. Abstract OP004. Presented at: UEG Week; Oct. 28 to Nov. 1, 2017; Barcelona.

Leung WK, et al. Gut. 2017; doi:10.1136/gutjnl-2017-314605.

Disclosures: Leung reports he has received honoraria for attending advisory board meetings for Takeda and Abbott Laboratories.