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Eradication of Hp

The effect of eradicating Hp on the subsequent risk of gastric cancer is not entirely clear, although the majority of studies suggest a reduction in cancer risk. There is little question that chronic inflammation in a variety of organ systems can lead to malignancy and that Hp eradication can reduce or alleviate gastric inflammation. Hp eradication can lead to decreased oxidative stress and cell proliferation.248 In addition, limited studies involving eradication of gastric Helicobacter organisms in Mongolian gerbils suggest that eradication of infection can partially reverse atrophy and metaplasia and inhibit progression to gastric cancer.249 Studies in mice confirm the reversibility of metaplasia and prevention of gastric cancer with early eradication. With later eradication, cancer progression was slowed and cancer mortality dramatically decreased.15

Nevertheless, with regard to published trials in humans, the evidence that treatment of Hp infection prevents gastric cancer is less conclusive, in part because of the rare endpoint— gastric cancer—needed for these studies. One approach has been to examine intermediate biomarkers such as gastric atrophy and intestinal metaplasia, which are generally considered premalignant lesions. Thus, a number of studies have looked at the effect of Hp eradication on these intermediate biomarkers, and a majority has shown a beneficial effect in preventing progression of gastric disease.250-255 In 1 randomized placebo-controlled trial from China of 587 patients with Hp infection, assignment to eradication was associated with a significantly reduced risk of progression of intestinal metaplasia (odds ratio, 0.63).255 In contrast, a separate randomized placebo-controlled trial of Mexican adults did not demonstrate a benefit of Hp eradication for the prevention of histologic progression.254

A prospective randomized placebo-controlled trial sought to determine whether Hp eradication in a high-risk population in China would reduce the incidence of gastric cancer.253 Although no overall benefit was seen in the group receiving Hp eradication, there was a clear reduction in gastric cancer incidence in the subgroup of Hp carriers who did not already have precancerous lesions (gastric atrophy, intestinal metaplasia, or dysplasia) at study initiation. It is possible that some of the patients in the eradication arm had passed a “point of no return,” when cellular alterations had sufficiently accumulated to promote cancer.256 A more recent meta-analysis of randomized trials found that Hp eradication was associated with a significant 35% reduction in the risk of gastric cancer.257

There may also be benefit to Hp eradication after treatment of early gastric cancer in light of the high rate of multifocal dysplasia and subsequent progression to cancer. In a an open-label randomized controlled trial of patients with resected early gastric cancer, Hp eradication was associated with a reduction in the risk of development of metachronous gastric cancer (odds ratio, 0.35).258

In Western countries, gastric cancer prevention has not been extensively pursued due to the lower prevalence of Hp infection and decreasing incidence of gastric cancer. However, a cost-effectiveness model by Parsonnet and colleagues259 suggested that screening and treatment of Hp infection would be potentially cost-effective in the prevention of gastric cancer, particularly in high-risk populations, if it was assumed that treatment of Hp infection prevented 30% of attributable gastric cancers. Using a more conservative 10% reduction in gastric cancer risk, an analysis from the United Kingdom also concluded that Hp eradication was cost-effective.260