Impact of clarithromycin resistance and CYP2C19 genetic polymorphism on treatment efficacy of Helicobacter pylori infection with lansoprazole- or rabeprazole-based triple therapy in Japan.

OBJECTIVE: Helicobacter pylori treatment failure is thought to be due mainly to polymorphic cytochrome P450 2C19 (CPY2C19) genetic polymorphism, associated with proton pump inhibitor metabolism, and antimicrobial susceptibility. This report has ascertained which was more important, CPY2C19 polymorphism or antimicrobial susceptibility, when using 1-week lansoprazole-based or rabeprazole-based triple therapy in Japan. DESIGN: An open, randomized, parallel group study. SETTING: One hundred and forty-five subjects with H. pylori-positive gastritis or peptic ulcers were randomly assigned to receive 30 mg lansoprazole twice daily (LAC group), 10 mg rabeprazole twice daily (RAC20 group), or 20 mg rabeprazole twice daily (RAC40 group), with 1000 mg amoxicillin twice daily and 400 mg clarithromycin twice daily for 1 week. Antimicrobial resistance testing was performed by E-test. More than 4 weeks after completion of treatment, H. pylori status was assessed by 13C-urea breath test, histology, and culture. RESULTS: Cure rates expressed as intention-to-treat and per-protocol analyses, respectively, were 79.6 and 83.0% with LAC, 85.4 and 89.1% with RAC20, and 83.3 and 88.9% with RAC40. In the case of clarithromycin-sensitive strains, the cure rates were more than 97%, regardless of CPY2C19 polymorphism. However, treatment succeeded in only one out of 16 clarithromycin-resistant strains. CONCLUSIONS: The key to successful eradication of H. pylori, using lansoprazole or rabeprazole with clarithromycin and amoxicillin, is clarithromycin susceptibility, not CPY2C19 polymorphism.

Relationship between gastric ulcer and Helicobacter pylori VacA detected in gastric juice using bead-ELISA method.

BACKGROUND: VacA is an important pathogenetic factor produced by Helicobacter pylori. VacA has often been detected in supernatants of liquid cultures or lysates of whole bacterial cells. However, no studies have ever tried to assay VacA produced in the human stomach. We applied a very sensitive and simple method, bead-ELISA, to detect VacA in gastric juice. MATERIALS AND METHODS: Forty-eight H. pylori-positive patients (16 nonulcer dyspepsia, 16 gastric ulcer, and 16 duodenal ulcer) and four H. pylori-negative nonulcer dyspepsia patients had endoscopy performed and gastric juice were aspirated. Polystyrene beads coated with the antibody to VacA, were used in this bead-ELISA method. The nucleotide sequences of vacA in the signal and middle regions were investigated. RESULTS: Of the 48 samples that were positive for H. pylori, 21 [43.8%] were found to be VacA positive in gastric juice. The average and maximum concentrations of detected VacA in gastric juice were 143.2 +/- 216.5 and 840 pg/ml, respectively. The average density of VacA from gastric ulcer patients (227.5 +/- 276.7 pg/ml) was higher than that found in nonulcer dyspepsia (51.8 +/- 39.8 pg/ml) and duodenal ulcer (49.2 +/- 21.5 pg/ml) patients. There was no relationship between VacA in gastric juice and vacA genotype. CONCLUSIONS: VacA in gastric juice could be directly detected by bead-ELISA. In this study, the diversity of disease outcome was associated with not the quality but the quantity of VacA. Therefore, not only the quality but also the quantity of VacA is important etiological factors in the pathogenesis of mucosal damage.