Gastroenterology

Gastroenterology

Volume 148, Issue 4, April 2015, Pages 719-731.e3
Gastroenterology

Reviews and Perspectives
Reviews in Basic and Clinical Gastroenterology and Hepatology
Helicobacter pylori Update: Gastric Cancer, Reliable Therapy, and Possible Benefits

https://doi.org/10.1053/j.gastro.2015.01.040Get rights and content

Helicobacter pylori infection contributes to the development of diverse gastric and extragastric diseases. The infection is necessary but not sufficient for the development of gastric adenocarcinoma. Its eradication would eliminate a major worldwide cause of cancer death, therefore there is much interest in identifying how, if, and when this can be accomplished. There are several mechanisms by which H pylori contributes to the development of gastric cancer. Gastric adenocarcinoma is one of many cancers associated with inflammation, which is induced by H pylori infection, yet the bacteria also cause genetic and epigenetic changes that lead to genetic instability in gastric epithelial cells. H pylori eradication reduces both. However, many factors must be considered in determining whether treating this bacterial infection will prevent cancer or only reduce its risk—these must be considered in designing reliable and effective eradication therapies. Furthermore, H pylori infection has been proposed to provide some benefits, such as reducing the risks of obesity or childhood asthma. When tested, these hypotheses have not been confirmed and are therefore most likely false.

Section snippets

H pylori as the Primary Cause of Gastric Cancer

H pylori infection is necessary but not sufficient for the development of H pylori–associated gastric cancer,11 similar in concept to hepatitis B and C viruses and the human papilloma virus. The infection is required for gastric cancer to develop, but H pylori infection alone is not sufficient for gastric carcinogenesis—other events also are involved. However, H pylori is not the only cause of gastric cancer—other less common causes account for 3%–5% of gastric adenocarcinomas and include

H pylori–Associated Gastric Cancer

Atrophic gastritis, the precursor to gastric cancer, leads to little or no secretion of acid, which alters the gastric microbiome.6 The outcome of each individual infection is unpredictable, as is the rate of progression of the gastric mucosal damage. However, further progression is stopped by eradication. Eradicating H pylori before the development of atrophic changes essentially can eliminate cancer risk. Depending on the degree and extent of atrophic changes, eradication can stop and

Clinical Research Findings

H pylori eradication eliminates the noxious stimulus and promotes resolution of inflammation. However, resolution of inflammation is a highly coordinated process regulated by anti-inflammatory molecules, including lipid mediators such as lipoxins and resolvins. This brings up the issue of whether and/or when H pylori–induced inflammation has resolved.37 Gastric cancer development is associated with inflammation. Increasing our ability to identify whether inflammation has resolved (or not), and

Eradication Therapy

Reducing gastric cancer from a major clinical problem and cause of cancer death to a rare disease requires that we reliably eradicate or prevent H pylori infections. Theoretically, H pylori cause a relatively straightforward gastric infection—they are an organism that is susceptible to many antibiotics. Traditionally, studies of antimicrobial therapy for other infections have been performed and interpreted under conditions of well-defined drug susceptibility. In other infectious diseases the

Patient-Specific Therapy

H pylori eradication therapy is relatively simple; health care workers must consider only drug availability, acceptability (such as whether patients might have allergies or the drugs have side effects), cost, and known or suspected patterns of resistance, based on prior experience with the drug in the same population. Whenever possible, only regimens that reliably yield more than 90%, preferably more than 95%, treatment success should be used. Data on resistance or susceptibility of each

Identifying Treatment Failure

13C urea breath tests frequently are used to detect H pylori infection. However, false-positive results have been reported from Spain and Korea.55, 56 These occurred for results that were near the cut-off value, such as between a delta over baseline between the cut-off value (such as 3) and 10.55, 56, 57 The problem is most common for patients with atrophic gastritis, likely owing to the presence of non–H pylori urease–containing organisms.55, 56, 57 It was proposed that the addition of citric

Is the Only Good H pylori a Dead H pylori?

Any claim that a major human pathogen also might provide a meaningful health benefit, and that plans to eradicate it should be reconsidered, is guaranteed to elicit interest from the press. H pylori was no exception and the press has continued to carry stories regarding a possible relationship between reductions in H pylori infections and the increased prevalence of esophageal adenocarcinoma, childhood asthma, and obesity. H pylori infection has been proposed to protect against these disorders.

Nonesophageal Diseases

Ptolemy proposed that the earth was the center of the universe. He had observed that when he looked at the northern sky he (and everyone after him) saw that the stars circled around the earth. Thomas Henry Huxley said in 1870 “The great tragedy of science is the slaying of a beautiful hypothesis by an ugly fact.” Although thousands of experiments can support a hypothesis, it only takes 1 finding to disprove it. For example, despite countless observations over more than a thousand years that

Obesity

Obesity is an extremely complicated problem. Fundamentally, obesity develops via an imbalance between energy intake and expenditure. In the 20th century, there were enormous changes in the production and availability of food, related to the green revolution, to increases in standards of living, and to improvements to the transportation infrastructure. Giant companies began producing calorie-dense processed foods, sugary soft drinks, and fast foods, while the proportion of the population that

Acknowledgments

The author thanks Mohammad H. Shakatreh for his help and expertise in preparing Figure 5, and Aaron P. Thrift for his assistance in providing data for Figure 6.

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    Conflicts of interest The author discloses the following: The author is an unpaid consultant for Novartis in relation to vaccine development for the treatment or prevention of H pylori infection, is a paid consultant for RedHill Biopharma regarding novel H pylori therapies and for Otsuka Pharmaceuticals regarding diagnostic testing, and has received royalties from Baylor College of Medicine patents covering materials related to the 13C-urea breath test.

    Funding Supported in part by the Office of Research and Development, Medical Research Service, Department of Veterans Affairs, Public Health Service grant DK56338, which funds the Texas Medical Center Digestive Diseases Center, and grant DK067366. The contents are solely the responsibility of the author and do not necessarily represent the official views of the VA or the National Institutes of Health.

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