Shu Sahara

Potent acid inhibition by vonoprazan in comparison with esomeprazole, with reference to CYP2C19 genotype.

Acid inhibitory effects of proton pump inhibitors (PPIs) are influenced by CYP2C19 genotype. In contrast, the potent acid inhibition of vonoprazan is not influenced by CYP2C19 genotype.

Role of Helicobacter pylori cagA EPIYA motif and vacA genotypes for the development of gastrointestinal diseases in Southeast Asian countries: a meta-analysis.

BackgroundInfection with cagA-positive, cagA EPIYA motif ABD type, and vacA s1, m1, and i1 genotype strains of Helicobacter pylori is associated with an exacerbated inflammatory response and increased risk of gastroduodenal diseases. However, it is unclear whether the prevalence and virulence factor genotypes found in Southeast Asia are similar to those in Western countries. Here, we examined the cagA status and prevalence of cagA EPIYA motifs and vacA genotypes among H. pylori strains found in Southeast Asia and examined their association with gastroduodenal disease.MethodsTo determine the cagA status, cagA EPIYA motifs, and vacA genotypes of H. pylori, we conducted meta-analyses of 13 previous reports for 1,281 H. pylori strains detected from several Southeast Asian countries.ResultsThe respective frequencies of cagA-positive and vacA s1, m1, and i1 genotypes among examined subjects were 93% (1,056/1,133), 98% (1,010/1,033), 58% (581/1,009), and 96% (248/259), respectively. Stratification showed significant variation in the frequencies of cagA status and vacA genotypes among countries and the individual races residing within each respective country. The frequency of the vacA m-region genotype in patients infected with East Asian-type strains differed significantly between the northern and southern areas of Vietnam (p < 0.001). Infection with vacA m1 type or cagA-positive strains was associated with an increased risk of peptic ulcer disease (odds ratio: 1.46, 95%CI: 1.01-2.12, p = 0.046 and 2.83, 1.50-5.34, p = 0.001, respectively) in the examined Southeast Asian populations.ConclusionsBoth Western- and East Asian-type strains of H. pylori are found in Southeast Asia and are predominantly cagA-positive and vacA s1 type. In Southeast Asia, patients infected with vacA m1 type or cagA-positive strains have an increased risk of peptic ulcer disease. Thus, testing for this genotype and the presence of cagA may have clinical usefulness.

Twice‐daily dosing of esomeprazole effectively inhibits acid secretion in CYP2C19 rapid metabolisers compared with twice‐daily omeprazole, rabeprazole or lansoprazole

Twice‐daily dosing of proton pump inhibitors (PPIs) is used to treat Helicobacter pylori or acid‐related diseases, such as gastro‐oesophageal reflux disease (GERD) refractory to standard dose of a PPI. Genetic polymorphisms of CYP2C19 are involved to different extents in the metabolism of four kinds of PPIs (omeprazole, lansoprazole, rabeprazole and esomeprazole) available in Japan.

Efficacy of Tailored Helicobacter pylori Eradication Treatment Based on Clarithromycin Susceptibility and Maintenance of Acid Secretion

Insufficient acid inhibition during Helicobacter pylori eradication treatment and bacterial resistance to antibiotics often causes eradication failure. Four times daily dosing (q.i.d.) of a proton‐pump inhibitor (PPI) achieves potent acid inhibition, suggesting its potential usefulness as a regimen for eradicating H. pylori infection. Therefore, a tailored eradication regimen based on antibiotic susceptibility and maintenance of acid inhibition should have a high success rate. We investigated the efficacy of such treatment based on clarithromycin (CAM) susceptibility.

Sitafloxacin-based third-line rescue regimens for Helicobacter pylori infection in Japan.

Quinolone‐based regimens have been used as the rescue for eradication of Helicobacter pylori. Sitafloxacin is known to have low minimum inhibitory concentration for H. pylori. Here, we compared two sitafloxacin‐based eradication regimens as rescue for the eradication of H. pylori.

Rabeprazole 10 mg q.d.s. decreases 24‐h intragastric acidity significantly more than rabeprazole 20 mg b.d. or 40 mg o.m., overcoming CYP2C19 genotype

Standard dosing (i.e. once daily) of proton pump inhibitors (PPIs) cannot inhibit acid secretion for a full 24 h. Better therapeutic regimens using PPIs are required to sustain potent acid inhibition for the full 24 h in all patients with acid‐related diseases.

Ability of rabeprazole to prevent gastric mucosal damage from clopidogrel and low doses of aspirin depends on CYP2C19 genotype

BACKGROUND & AIMS Low doses of aspirin can injure the gastric mucosa. It is not clear whether other drugs such as the antiplatelet agent clopidogrel also cause gastric mucosal injury or exacerbate aspirin-induced injury, or whether proton pump inhibitors prevent damage. METHODS Twenty Japanese subjects with different CYP2C19 genotypes were randomly assigned to groups that were given a low dose of aspirin (100 mg; A), clopidogrel (75 mg; C), low dose of aspirin and clopidogrel (AC), or low dose of aspirin in combination with clopidogrel and rabeprazole (10 mg; ACR) once daily for 7 days. Subjects underwent gastroduodenoscopy and platelet tests on days 3 and 7; gastric mucosal damage was assessed by using the modified Lanza score (MLS). We performed 24-hour intragastric pH monitoring on day 7 of each regimen. We also analyzed the effects of the AC regimen on 30 patients with different CYP2C19 genotypes. RESULTS Subjects in groups A, C, and AC had significantly higher levels of gastric mucosal damage on days 3 and 7, compared with baseline. The median MLS for the AC group was similar to that of the A group. Helicobacter pylori-negative subjects in the ACR group with different CYP2C19 genotypes had significant differences in MLS, intragastric pH, and platelet function. Gastric mucosal injury was inhibited equally among H pylori-positive subjects in the ACR group. Rabeprazole did not appear to affect platelet function or intragastric pH in subjects given clopidogrel. CONCLUSIONS Clopidogrel and low doses of aspirin cause a similar degree of gastric mucosal damage. Rabeprazole prevented this damage without reducing the antiplatelet function of clopidogrel. However, its prophylactic effect varies with CYP2C19 genotype in H pylori-negative subjects.

High Helicobacter pylori cure rate with sitafloxacin-based triple therapy.

Bacterial resistance of Helicobacter pylori to antibiotics is increasing and it often leads to failure of antibiotic treatment. A new sitafloxacin‐based triple therapy was developed to counter this situation; the fluoroquinolone sitafloxacin has a low minimum inhibitory concentration for H. pylori.

Effect of dosing schemes of amoxicillin on eradication rates of Helicobacter pylori with amoxicillin-based triple therapy

In standard regimens for Helicobacter pylori infection, amoxicillin is dosed twice daily, although the bactericidal effect of amoxicillin depends on the %time‐above‐MIC. We aimed to examine whether dosing schemes of amoxicillin influenced eradication rates of amoxicillin‐based regimens.

Influence of prostate stem cell antigen gene polymorphisms on susceptibility to Helicobacter pylori-associated diseases: a case-control study.

Patients with duodenal ulcer have a reduced risk of developing gastric cancer compared to those without. Recently, the prostate stem cell antigen (PSCA) rs2294008 C>T polymorphism was found to be associated with different pathogenesis of duodenal ulcer and gastric cancer developments. However, whether PSCA rs2294008 C>T polymorphism is associated with severity of gastric mucosal atrophy is unclear. We examined the influence of the PSCA rs2294008 C>T polymorphism on susceptibility to H. pylori‐related diseases and the relationships between PSCA polymorphism and gastric mucosal atrophy.