Long Term Effects of H.Pylori Eradication on Microbiome and Adverse Events

The current international guidelines and expert working groups are encouraging "search-and-treat" strategy for H.pylori to prevent gastric cancer1, 2. The highest yield of this approach is expected in countries with high incidence of gastric cancer and high prevalence of H.pylori infection. This approach will be further supported by the Maastricht V European guidelines (manuscript in preparation). The rationale for this approach is that 1-2% of the infected individuals are developing gastric cancer; the International Agency for Research on Cancer has classified H.pylori infection as Class I carcinogen3, 4. A study in Matsu island with high gastric cancer risk has suggested that gastric cancer incidence can be decreased by 25% by such strategy5; the limitations, however, include lack of the control group.

Three recent meta-analysis have confirmed the cost-effectiveness of such approach6-8; of course, those are based on the limited currently available data on potential risks caused by population-based strategy application.

In the countries which are expected to benefit from the strategy most this would mean offering eradication treatment to the majority of population, e.g. in Latvia this would require antibiotic treatment to 79% of population9, and would change the current status of low antibiotic consumption country to an average consumption country. This could potentially result in adverse consequences unrelated to H.pylori.

In a country with low H.pylori resistance to clarithromycin (such as Latvia), the recommended H.pylori 1st-line standard eradication regimen would consist of clarithromycin in combination to either amoxicillin or metronidazole, and a proton-pump inhibitor; the duration would be at least 10 days10. Areas with higher H.pylori resistance to clarithromycin would require more aggressive treatment modalities, e.g. by including levofloxacin to the regimen. The potential adverse events caused by such therapies to microbiome are insufficiently studied; the expert opinion that are developing guidelines is generally limited to the consideration that 1-2 week single-time antibiotic treatment would be a minor and fully reversible intervention upon microbiome since according to the available statistic in many countries the average antibiotic intake rates one or several treatments per year in a subject.

However, from the limited data available, there is a clear message that even one-week treatment with macrolides (clarithromycin, azithromycin) is increasing the resistance of macrolide-resistant S.pneumoniae in pharynx in healthy volunteers; this difference was statistically significant within a period of 180 days11.