AIM: To determine the general risk factors affecting the failure rate of first-line eradication therapy in Japanese patients with Helicobacter pylori (H. pylori) infection.

METHODS: The present study enrolled 253 patients who had an H. pylori infection, underwent gastro-endoscopy, and were treated with H. pylori eradication therapy. Eradication therapy consisted of 30 mg lansoprazole plus 750 mg amoxicillin and 400 mg clarithromycin twice daily for 7 d. All of the patients underwent a ¹³C urea breath test at least 1 mo after the completion of eradication therapy. The current study investigated the independent factors associated with successful H. pylori eradication using a multiple logistic regression analysis.

RESULTS: The overall success rate in the patients was 85.8%. Among the general factors examined in the multivariate analyses, only having an age less than 50 years was found to be significantly associated with a poor response to H. pylori eradication. Moreover, side effects were the only clinical factors in the patients who were under 50 years of age that significantly influenced the poor response to H. pylori eradication.

CONCLUSION: H. pylori-positive elderly patients should undergo eradication therapy. In addition, it is necessary to improve H. pylori eradication therapy in younger patients.

Helicobacter pylori (H. pylori) infections cause chronic gastritis and are associated with an increased risk of major upper gastrointestinal diseases, such as peptic ulcer disease, gastric adenocarcinoma, and mucosa-associated lymphoid tissue lymphoma[1]. Proton-pump inhibitor (PPI)-based triple therapy, with a PPI, clarithromycin (CAM), and either amoxicillin (AMPC) or metronidazole, is a widely recommended eradication therapy[2]. In addition, this triple therapy has been approved by the medical insurance system in Japan, and the eradication therapy is administered by physicians in general practice. Consensus conferences have recommended therapeutic regimens that achieve H. pylori cure rates of over 80% on an intent-to-treat basis[3-5]. However, several large-scale clinical trials and meta-analyses have demonstrated that the most common first-line therapies fail in up to 20% of patients[6,7], and in the clinical setting, the actual treatment failure rate may be even higher[8]. Few studies have examined the causes of patient failure in these therapies among the general clinical factors in Japan. The aims of the current study were to determine the general risk factors that affect the failure rate of first-line eradication therapy in Japanese patients with H. pylori infection using a multivariate analysis.

The current series included 253 patients who underwent a gastro-endoscopy between January 2006 and September 2007 in the Shinko hospital in Kobe, Japan, and who were diagnosed with an H. pylori infection by the presence of the bacterium at endoscopy, detection of the bacteria or an antibody in patient urine, or a positive ¹³C urea breath test (UBT; with a cut-off value of 2.5‰; Ubit, Otsuka Pharmaceuticals, Tokyo, Japan). All patients were treated with H. pylori eradication therapy, consisting of 30 mg lansoprazole, 750 mg amoxicillin, and 400 mg clarithromycin twice daily for 7 d. Patient compliance and treatment-related side effects were assessed at the end of the treatment period. The patients underwent a UBT at least 1 mo after the completion of eradication therapy. Successful H. pylori eradication was defined as a negative result on the UBT. Independent factors that may have been associated with successful H. pylori eradication were studied using multiple logistic regression analysis. The following variables were evaluated as independent factors: sex, age (generation), diagnosis, and side effects. The StatView system software package (version 5.0) was used for the statistical analysis. A P-value of less than 0.05 was considered to be statistically significant.

The current study showed that first-line eradication treatment failures occurred significantly more frequently in patients aged less than 50 years of age. Elderly patients are frequently infected with H. pylori for a longer period of time, present with enlarged atrophic gastritis, and progress to intestinal metaplasia. These patients may experience easier H. pylori eradication with first-line eradication treatment. In addition, the gastric mucosa becomes more atrophic in elderly patients in comparison to younger patients, and elderly patients also display gastric acid hyposecretion. This can compromise their ability to inactivate the AMPC and CAM. These conditions may contribute to the current results.

Pretreatment antibiotic resistance is the primary reason some patients do not respond to initial treatment[9-13]. In particular, antibiotic CAM resistance has been identified as a major factor affecting the ability to cure H. pylori infection, and the rate of resistance to this antibiotic is increasing in many geographical areas[14,15]. A similar tendency is believed to be occurring in Japan. The efficacy of PPI-based regimens is decreasing, and several studies have reported intention-to-treat eradication rates lower than 75%[16-24]. The overall success rate in patients was greater than 85% in the current series. This high success rate may be due to patients having been diagnosed with an H. pylori infection during the medical examination, and the fact that few patients were receiving any medication. Future studies will examine whether patients with H. pylori infections display antibiotic resistance.

The only factors that significantly influenced the response to eradication therapy in patients were being under 50 years of age and diarrhea, which was the most common side effect for half of the patients. It is necessary to determine how to increase the treatment success rate among younger patients. A previous study from Japan reported that the use of the probiotic bacterium Clostridium butyricum MIYAIRI 588 strain reduced fluctuations in the intestinal flora and decreased the incidence of gastrointestinal side effects[25]. Supplementation with probiotics may have several beneficial effects on H. pylori eradication, especially in younger patients.

Elderly patients also exhibited a good success rate in the current series. A previous report showed that approximately 53%-73% of elderly peptic ulcer patients are H. pylori-positive; however, the percentage of H. pylori-positive elderly patients who are treated for an H. pylori infection remains low. One-week PPI-based triple therapy regimens are highly effective and well tolerated in elderly patients[26]. Therefore, it is recommended that H. pylori-positive elderly patients be treated with eradication therapy.

In conclusion, the current study was conducted to determine the general risk factors that affect the failure rate of first-line eradication therapy in Japanese patients with an H. pylori infection. The overall success rate in patients was 85.8%. Among the general factors examined in the multivariate analyses, a patient age of less than 50 years significantly influenced the response to H. pylori eradication. Moreover, among the other clinical factors in patients under 50 years of age, only the presence of side effects was found to be significantly associated with the response to H. pylori eradication. It is necessary to determine how to increase the eradication success rate among younger patients.