Takeshi Matsuhisa

Genetic differences in CYP2C19 single nucleotide polymorphisms among four Asian populations

Background. This study was designed to compare genetic differences in single-nucleotide polymorphisms of the S-mephenytoin 4′-hydroxylation (CYP2C19) gene among four Asian populations. Methods. Polymerase chain reaction with restriction fragment length polymorphism (PCR-RFLP) analysis of CYP2C19 was conducted in Japanese, Chinese, Thai, and Vietnamese populations. All genotype frequencies were analyzed. Wild-type homozygote and wild-type heterozygote genotypes were extensive proton pump inhibitor (PPI) metabolizers. Mutant-type heterozygote and mutant-type homozygote genotypes were poor PPI metabolizers. Results. No significant differences in CYP2C19 phenotype, calculated based on genotype frequencies, (P > 0.05) were found among the four populations. Conclusions. Many factors, including CYP2C19 polymorphisms, affect the success rate of Helicobacter pylori eradication with PPI-based therapy. We suspect that CYP2C19 polymorphisms may not be the main factor associated with differences among these four Asian populations in the success rates of H. pylori eradication with PPI-based therapy.

Helicobacter pylori Infection, Mucosal Atrophy and Intestinal Metaplasia in Asian Populations: A Comparative Study in Age-, Gender- and Endoscopic Diagnosis-Matched Subjects

Background. It is known that the incidence and mortality rate of gastric cancer is high among Japanese and Chinese populations, but extremely low in Thai and Vietnamese populations. The aim of this study was to investigate the prevalence of Helicobacter pylori infection and the differences in the glandular atrophy and intestinal metaplasia scores in stomach specimens of Asian adult subjects of different races.

Helicobacter pylori infection and gastroduodenal diseases in Vietnam: a cross-sectional, hospital-based study

BackgroundThe rate of H. pylori infection in Vietnam is reportedly high, but the spectrum of H. pylori-associated gastroduodenal diseases has not been systematically investigated. Moreover, despite the similarities of ethnicity and diet, the age-standardized incidence rate of gastric cancer in the northern city of Hanoi is higher than that in the southern city of Ho Chi Minh, but the reason for this phenomenon is unknown. The virulence of Vietnamese H. pylori has also not been investigated in detail.MethodsIndividuals undergoing esophagogastroduodenoscopy were randomly recruited. H. pylori infection status was determined based on the combined results of culture, histology, immunohistochemistry, rapid urine test and serum ELISA. Peptic ulcer (PU) and gastroesophageal reflux disease was diagnosed by endoscopy, and chronic gastritis was determined histologically. H. pylori virulence factors were investigated by PCR and sequencing.ResultsAmong the examined patients, 65.6% were infected with H. pylori. The prevalence of infection was significantly higher in those over 40 years of age than in those aged ≤40. Chronic gastritis was present in all H. pylori-infected individuals, 83.1% of whom had active gastritis, and 85.3% and 14.7% had atrophy and intestinal metaplasia, respectively. PU was present in 21% of infected patients, whereas its incidence was very low in non-infected individuals. The prevalence of PU was significantly higher in Hanoi than in Ho Chi Minh. The prevalence of vacA m1, which has been identified as an independent risk factor for PU in Vietnam, was significantly higher among H. pylori isolates from Hanoi than among those from Ho Chi Minh.ConclusionsH. pylori infection is common in Vietnam and is strongly associated with PU, active gastritis, atrophy and intestinal metaplasia. vacA m1 is associated with an increased risk for PU and might contribute to the difference in the prevalence of PU and gastric cancer between Hanoi and Ho Chi Minh.

Analysis of virulence factors of Helicobacter pylori isolated from a Vietnamese population

BackgroundThe incidence of gastric cancer differs among countries in Asia, and it has been suggested that virulence factors associated with Helicobacter pylori are partly responsible. The aim of this study was to investigate several genetic factors regarded as virulence or molecular epidemiologic markers in H. pylori isolates from Vietnamese subjects.ResultsThe cagA, vacA and cag right-end junction genotypes of 103 H. pylori strains from Vietnam (54 from Hanoi and 49 from Ho Chi Minh) were determined by PCR and sequencing. Three types of deletion in the region located upstream of the cagA Glu-Pro-Ile-Tyr-Ala (EPIYA) repeat region were identified: the 39-bp deletion type, the 18-bp deletion type, and the no-deletion type. The majority of strains studied (77%; 80/103) had the 18-bp deletion irrespective of geographical location in the country or clinical outcome. All of the 39-bp and 18-bp deletion-type strains possessed the East Asian type cagA repeat region. The type II cag right-end junction genotype was predominant (84%). The vacA m1 genotype was significantly more common in strains isolated in Hanoi, where the incidence of gastric cancer is higher, than in strains from Ho Chi Minh.ConclusionPre-EPIYA-region typing of the cagA gene could provide a new genetic marker of H. pylori genomic diversity. Our data support the hypothesis that vacA m1 is closely associated with gastric carcinogenesis.

Efficacy of Metronidazole as Second-Line Drug for the Treatment of Helicobacter pylori Infection in the Japanese Population: A Multicenter Study in the Tokyo Metropolitan Area

Background:  With the increase in the frequency of clarithromycin‐resistant Helicobacter pylori (H. pylori), there is rising concern about the decline of the eradication rate of this infection following treatment. The Tokyo Hp Study Group examined the eradication rate in response to a second‐line regimen consisting of proton pump inhibitor (PPI), amoxicillin, and metronidazole by conducting a multicenter study in the Tokyo Metropolitan Area.

Helicobacter pylori Infection in the Remnant Stomach After Gastrectomy: With Special Reference to the Difference Between Billroth I and II Anastomoses

Helicobacter pylori infection is associated with many gastric diseases, such as peptic ulcer and gastric cancer. We examined the remnant stomach for H. pylori infection after gastrectomy for gastric cancer or peptic ulcer between October 1992 and July 1997. H. pylori DNA in the gastric juice of 109 patients [mean age 62.4 years, male/female 78/31, gastrectomy for gastric cancer 83/peptic ulcer 26, Billroth I (BI) anastomosis 72/Billroth II (BII) 37, mean postoperative interval 6.0 years] was amplified by PCR and detected by Southern blot hybridization. The serum of 135 patients was assayed by ELISA for IgG antibody against H. pylori (mean age 61.8 years, male/female 99/36, gastrectomy for gastric cancer 111/peptic ulcer 24, BI anastomosis 93/BII 42, mean postoperative interval 5.4 years). H. pylori was positive in 68/109 (62.4%) by PCR and 113/ 135 (83.7%) by ELISA. H. pylori cytotoxin gene cagA, a H. pylori virulence factor gene, was found in 15/16 (93.8%) cases by PCR. A significant difference in H. pylori positivity by PCR was found according to the type of anastomosis (BI vs. BII) but not according to age group, sex, disease (cancer or ulcer), or postoperative interval by PCR and ELISA. BII anastomosis was followed by a significantly lower rate of H. pylori infection (17/37; 45.9%) than BI anastomosis (51/72; 70.8%; p=0.01) according to the results of PCR. Moreover, some patients with BII anastomosis (3/8; 37.5%) showed positive to negative seroconversion for H. pylori infection after the operation (mean 2.47 years) according to the results of ELISA, but this phenomenon was not observed in patients with BI (0/12) anastomosis. This may reflect the role of bile reflux, which is more common in BII than BI, because bile reflux interferes with colonization by H. pylori.

Comparison between the 13C-urea breath test and stool antigen test for the diagnosis of childhood Helicobacter pylori infection.

BackgroundAs noninvasive tests for Helicobacter pylori infection, the 13C-urea breath test (UBT) and stool antigen test have been widely used. In children, however, there are few studies reporting which test shows superior performance. The purpose of this study was to compare the 13C-UBT and stool antigen test for their accuracy in diagnosing H. pylori infection in children.MethodsA total of 123 Japanese children, ages 2 to 17 years (mean, 12 years) who underwent gastric biopsies for H. pylori infection were studied. The diagnoses included gastritis (n = 55), gastric ulcer (n = 5), duodenal ulcer (n = 20), iron-deficiency anemia (n = 7), and other conditions (n = 36). The cutoff value of the 13C-UBT was defined to be 3.5‰. The stool antigen test was performed using the HpSA enzyme-linked immunosorbent assay (ELISA) (Premier Platinum HpSA). In 16 patients who received eradication therapy, the 13C-UBT and HpSA were repeated 2 months after treatment.ResultsBased on biopsy tests, 60 children were infected with H. pylori and 63 children were not. For the 13C-UBT, the sensitivity, specificity, and accuracy were 95.0% (95% confidence interval [CI], 86.1%–99.0%), 98.4% (95% CI, 91.5%–100%), and 96.4% (95% CI, 93.6%–99.9%), respectively. For the HpSA, the sensitivity, specificity, and accuracy were 98.3% (95% CI, 90.8%–100%), 98.4% (95% CI, 91.2%–100%), and 98.3% (95% CI, 96.0%–100%), respectively. There were no significant differences between the performance of these two tests. In the assessment of H. pylori eradication, the results of 13C-UBT and HpSA agreed with those of biopsy tests.ConclusionsThe 13C-UBT and the HpSA are equally accurate for the diagnosis of active H. pylori infection in Japanese children.

Topography of chronic active gastritis in Helicobacter pylori-positive Asian populations : age-, gender-, and endoscopic diagnosis-matched study

BackgroundThe incidence and mortality of gastric cancer is high among Japanese and Chinese populations but extremely low in Thailand and low in Vietnam. The aim of this study was to compare the degree of corpus-predominant gastritis, which is considered to be one of risk factors of gastric cancer, in Helicobacter pylori-positive Asian adult populations.MethodsH. pylori-positive Chinese (Beijing and Fuzhou), Thai, and Vietnamese patients were paired with Japanese patients by age, gender, and endoscopic diagnosis to compare the ratio of corpus gastritis to antrum gastritis (C/A ratio) (105, 85, 195, and 154 pairs, respectively).ResultsThe Japanese C/A ratio was significantly higher than that in other groups. Corpus-predominant gastritis (C/A ratio > 1.00) was characteristic in aged Japanese and Chinese (Fuzhou), but Chinese (Beijing), Thai, and Vietnamese were antrum predominant (C/A ratio < 1.00) in every age group except for the Vietnamese over-70 group. There was a similarity between degree of H. pylori colonization and neutrophil activity score.ConclusionsCorpus-predominant gastritis was found in aged Japanese and Chinese (Fuzhou) and antrum-predominant gastritis was found in Chinese (Beijing), Thai, and Vietnamese patients. These results correlate with the low incidence of gastric cancer in Thai and Vietnamese populations.

Gastrospirillum hominis and Helicobacter pylori infection in Thai individuals: Comparison of histopathological changes of gastric mucosa

The presence of Helicobacter pylori (H. pylori) in the stomach is closely associated with histological signs of chronic active gastritis and peptic ulcer. Another spiral organism named Gastrospirillum hominis (G. hominis) has led to further interest in the bacterial pathogenesis of gastritis. Due to the low prevalence of G. hominis, it is difficult to evaluate its biological behavior. Recently 16 cases of G. hominis‐associated gastritis were found in 257 Thai individuals, which made it possible to study the biological characteristics of G. hominis and its relationship with gastric mucosal inflammation. The results showed that H. pylori and G. hominis could be easily observed in the lower third of the mucous layer and in the mucosa of the gastric pits by means of toluidlne blue staining. Both bacteria immunostained positive. Helicobacter pylori were usually in the shape of curved bacillary while G. hominis often appeared in spiral configuration. In 257 cases of Thai subjects, 169 cases were found to be H. pylori positive, the detection rate was 65.7%, and 16 cases were G. hominis positive, with a 6.2% detection rate. In G. hominis infection, 43.6% of cases had normal gastric mucosa. Superficial, erosive and atrophlc gastritis cases were 13.2, 10.9 and 12.5%, respectively. Mucosal inflammation was usually severe in H. pylori, but neutrophil polymorph infiltration was often mild and focal in G. hominis Infection. Although no G. hominis infection with carcinoma was shown in our cases, the occurrence of mucosal atrophy, metaplasia and dysplasia was higher in both bacterial infections compared with H. pylori‐ and G. hominis‐negative cases. It is suggested that G. hominis may be partly responsible for the mucosal inflammation and some malignant‐associated lesions.

Clinical relevance of cagPAI intactness in Helicobacter pylori isolates from Vietnam

The purpose of this paper is to investigate the relationship between clinical outcome and the intactness of cagPAI in Helicobacter pylori strains from Vietnam. The presence or absence of 30 cagPAI genes was investigated by polymerase chain reaction (PCR) and dot-blotting. H. pylori-induced interleukin-8 secretion and hummingbird phenotype, and H. pylori adhesion to gastric epithelial cells were examined. The serum concentration of pepsinogen 1, pepsinogen 2, and gastrin was also measured in all patients. cagPAI was present in all 103 Vietnamese H. pylori isolates, of which 91 had intact cagPAI and 12 contained only a part of cagPAI. Infection with the partial cagPAI strains was less likely to be associated with peptic ulcer and chronic gastric mucosal inflammation than infection with strains possessing intact cagPAI. The partial cagPAI strains lacked almost all ability to induce interleukin-8 secretion and the hummingbird phenotype in gastric cells. Their adhesion to epithelial cells was significantly decreased in comparison with intact cagPAI strains. Moreover, for the first time, we found an association between cagPAI status and the serum concentration of pepsinogens 1 and 2 in infected patients. H. pylori strains with internal deletion within cagPAI are less virulent and, thus, less likely to be associated with severe clinical outcomes.