Dynamics of <i>Helicobacter pylori</i> infection as a determinant of progression of gastric precancerous lesions: 16-year follow-up of an eradication trial.

Abstract

To evaluate the long-term effect of cumulative time exposed to <i>Helicobacter pylori</i> infection on the progression of gastric lesions. 795 adults with precancerous gastric lesions were randomised to receive anti-<i>H. pylori</i> treatment at baseline. Gastric biopsies were obtained at baseline and at 3, 6, 12 and 16 years. A total of 456 individuals attended the 16-year visit. Cumulative time of <i>H. pylori</i> exposure was calculated as the number of years infected during follow-up. Multivariable logistic regression models were used to estimate the risk of progression to a more advanced diagnosis (versus no change/regression) as well as gastric cancer risk by intestinal metaplasia (IM) subtype. For a more detailed analysis of progression, we also used a histopathology score assessing both severity and extension of the gastric lesions (range 1-6). The score difference between baseline and 16 years was modelled by generalised linear models. Individuals who were continuously infected with <i>H. pylori</i> for 16 years had a higher probability of progression to a more advanced diagnosis than those who cleared the infection and remained negative after baseline (p=0.001). Incomplete-type IM was associated with higher risk of progression to cancer than complete-type (OR, 11.3; 95% CI 1.4 to 91.4). The average histopathology score increased by 0.20 units/year (95% CI 0.12 to 0.28) among individuals continuously infected with <i>H. pylori</i>. The effect of cumulative time of infection on progression in the histopathology score was significantly higher for individuals with atrophy (without IM) than for individuals with IM (p<0.001). Long-term exposure to <i>H. pylori</i> infection was associated with progression of precancerous lesions. Individuals infected with <i>H. pylori</i> with these lesions may benefit from eradication, particularly those with atrophic gastritis without IM. Incomplete-type IM may be a useful marker for the identification of individuals at higher risk for cancer.