Helicobacter pylori, a stomach-dwelling bacterium, is a strong risk factor for gastric cancer, peptic ulcers and other debilitating gastrointestinal disorders. Yet efforts to eradicate it using a combination of antibiotics and proton pump inhibitors (PPIs), which suppress gastric acid production, often fail.

Now a team led by scientists at Vanderbilt University Medical Center and the Nashville Veterans Affairs Medical Center has linked eradication failure with polymorphisms or genetic variations that increase the activity of the CYP2C19 enzyme, which metabolizes or breaks down first-generation PPIs.

These so-called “fast metabolizers” may prevent adequate suppression by PPIs of gastric acid production, which is necessary for successful H. pylori eradication.

Reporting Aug. 3 in the journal Gastroenterology, the researchers analyzed 57 studies from 11 countries, and found that the failure rate of H. pylori eradication more than doubled in people who carried a version of the CYP2C19 gene that enhanced its metabolic activity.

There was no association between CYP2C19 variants and eradication failure, however, if the rapid metabolizers were treated with newer PPIs such as esomeprazole and rabeprazole, which are less metabolized by the enzyme or which bypass CYP2C19 metabolism entirely.

Further well-designed studies, especially in U.S. populations, are needed to determine whether giving higher or more frequent dosages of first-generation PPIs to people who have rapid-metabolizer variants of CYP2C19 might improve eradication rates, noted the paper’s corresponding author, Shailja Shah, MD, MPH.

Studies of U.S. populations are needed because the majority of the studies have been conducted in Asian-Pacific countries, she said. Shah, a gastroenterologist and former assistant professor of Medicine at VUMC, is now at the University of California San Diego and the VA San Diego Healthcare System.

“Even small improvements in H. pylori eradication rates would likely translate to substantial collateral health, economic and societal benefits,” the researchers concluded.

Co-authors from VUMC were Cecilia Chung, MD, MPH, Giiovanni Suarez, PhD, Richard Peek, MD, Adriana Hung, MD, MPH, and Christianne Roumie, MD, MPH.

The study was supported by the Agency for Healthcare Research and Quality and Patient-Centered Outcomes Research Institute, a 2019 American Gastroenterological Association Research Scholar Award, a Veterans Affairs Career Development Award and National Institutes of Health grants DK058587 and CA077955.

—Bill Snyder