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Background: Helicobacter pylori infection is a well-established risk factor for gastric cancer and has been linked to other gastrointestinal diseases, including pancreatic and biliary tract cancers; however, the relevance of enterohepatic non-H. pylori helicobacters to the pathophysiology of these diseases remains unclear., Materials and Methods: We estimated the prevalence of two enterohepatic non-H. pylori helicobacters (Helicobacter hepaticus and Helicobacter bilis) in the framework of a hospital-based case-control study involving 121 patients with biliary tract cancer, pancreatic cancer, or other gastrointestinal diseases. Bile and blood samples were collected from the patients undergoing endoscopic retrograde cholangiopancreatography. The presence of H. bilis, H. hepaticus, and other Helicobacter spp. was examined using bacterial culture, PCR-based detection, and serological tests., Results: Culture of Helicobacter spp. from biliary brush samples was unsuccessful. Approximately 13.0% (15/115) of the bile samples collected from patients with a variety of gastrointestinal cancers, including pancreatic and biliary tract cancers, tested positive for one of the enterohepatic non-H. pylori helicobacter species as determined by PCR. Specifically, H. bilis and H. hepaticus DNA were detected in 11 and 4 bile samples, respectively. Approximately 20%-40% of the patients tested positive for serum non-H. pylori helicobacter IgG antibodies. The seroprevalence of H. bilis and H. hepaticus in the patients without evidence of H. pylori infection appeared to be higher in the pancreatic cancer group than in the control group., Conclusion: Our findings suggest a role for Helicobacter spp., especially H. bilis and H. hepaticus, in the etiology of pancreatic and biliary tract cancers., (© 2022 The Authors. Helicobacter published by John Wiley & Sons Ltd.)

Background: Since "Helicobacter pylori (H. pylori) infection" was set as the indication in the Japanese Society for Helicobacter Research (JSHR) Guidelines 2009, eradication treatment for H. pylori gastritis is covered under insurance since 2013 in Japan, and the number of H. pylori eradication has rapidly increased. Under such circumstances, JSHR has made the third revision to the "Guidelines for diagnosis and treatment of H. pylori infection" for the first time in 7 years., Methods: The Guideline Committee held 10 meetings. Articles published between the establishment of the 2009 Guidelines and March 2016 were reviewed and classified according to the evidence level; the statements were revised on the basis of this review. After inviting public comments, the revised statements were finalized using the Delphi method., Results: There was no change in the basic policy that H. pylori infectious disease is an indication for eradication. Other diseases presumed to be associated with H. pylori infection were added as indications. Serum pepsinogen level, endoscopic examination, and X-ray examination were added to the diagnostic methods. The effects of 1-week triple therapy consisting of potassium-competitive acid blocker (P-CAB), amoxicillin, and clarithromycin have improved, and high eradication rates can also be expected with proton pump inhibitors (PPI) or P-CAB combined with amoxicillin and metronidazole. If the susceptibility test is not performed, the triple PPI or P-CAB/amoxicillin/metronidazole therapy should be chosen, because the PPI/amoxicillin/metronidazole combination demonstrated a significantly higher eradication rate than PPI/amoxicillin/clarithromycin. In the proposal for gastric cancer prevention, we divided gastric cancer prevention measures by age from adolescent to elderly, who are at an increased gastric cancer risk, and presented measures for gastric cancer prevention primarily based on H. pylori eradication., Conclusion: We expect the revised guidelines to facilitate appropriate interventions for patients with H. pylori infection and accomplish its eradication and prevention of gastric cancer., (© 2019 John Wiley & Sons Ltd.)

Background: Metronidazole is an antiprotozoal drug used to treat a broad spectrum of infectious diseases, including Helicobacter pylori (H pylori) infections. In Japan, metronidazole is approved for the eradication therapy of H pylori as a second-line regimen among adults, but it has not yet been approved for use among children and adolescents., Materials and Methods: To perform this narrative review, we searched the relevant literature on important events in the history of the use of metronidazole, its mechanisms of action, its efficacy, and the adverse effects reported in clinical trials or cohort studies in Japan., Results: At present, metronidazole resistance has not been a serious issue in Japan in large part due to its restricted use. Emerging evidence from randomized controlled trials demonstrates higher eradication rates for metronidazole than for clarithromycin, supporting its use in both first-line and second-line eradication therapies. Among the reported adverse effects, there has been lingering concern over the potential carcinogenicity of metronidazole in humans. However, the possibility of an increased cancer risk is not limited to metronidazole; the long-term use of antibiotics has been linked to increased risk for some site-specific cancers. However, recent prospective studies have suggested that short-term exposure to antibiotics is not associated with an increased cancer risk., Conclusion: Sensible use of metronidazole backed by research evidence could maximize the benefits associated with H pylori eradication in Japan., (© 2019 John Wiley & Sons Ltd.)

Background: In Japan, there have been approximately 50 000 deaths from gastric cancer annually for over 40 years with little variation. It has been reported that most gastric cancers in Japan are caused by Helicobacter pylori infection. H. pylori eradication therapy was approved for patients with chronic gastritis by the Japanese national health insurance scheme in February 2013 for patients with an endoscopic diagnosis of chronic gastritis is positive for H. pylori. We examined the effect on gastric cancer death rate 4 years after expansion of health insurance coverage., Aim: We conducted an epidemiological study and analyzed trends in prescription for H. pylori eradication therapy. We used the electronic medical claims database from Hokkaido, Japan to evaluate the impact of expansion of national health insurance coverage for H. pylori eradication therapy on deaths from gastric cancer., Methods: Data on deaths from gastric cancer were obtained from the Japanese Ministry of Health, Labour and Welfare and the Cancer Statistics in Japan (2015). Analysis of electronic claims records was performed using the National Database, mainly focusing on Hokkaido. Prescriptions for H. pylori eradication therapy and the number of patients treated for gastric cancer were also extracted from the Hokkaido database., Results: Approximately 1.5 million prescriptions for H. pylori eradication therapy were written annually. Gastric cancer deaths fell each year: 48 427 in 2013, 47 903 in 2014, 46 659 in 2015, and 45 509 in 2016, showing a significant decrease after expansion of insurance coverage for H. pylori eradication therapy (P<.0001)., Conclusions: Prescriptions for H. pylori eradication therapy increased markedly after approval of the gastritis indication by the national health insurance scheme and was associated with a significant decrease in gastric cancer deaths., (© 2017 The Authors. Helicobacter Published by John Wiley & Sons Ltd.)

Background: There have been few reports on Helicobacter pylori (H. pylori) infection in asymptomatic Japanese children and adolescents. We hypothesized that the prevalence of H. pylori infection is very low among Japanese children and that clinical variables such as serum pepsinogen and iron levels are associated with H. pylori infection., Materials and Methods: We conducted a cross-sectional analysis of a sample of 454 junior high school students aged 12-15 years in four areas in Nagano Prefecture. A commercial ELISA kit (E-plate Eiken H. pylori antibody) was used to measure IgG antibody against H. pylori. Serum pepsinogen and iron levels were also measured using standard methods. A urea breath test was performed for seropositive students., Results: The overall prevalence of H. pylori was 3.1% (14/454). There were no significant differences in H. pylori prevalence among mountain, rural, and urban areas. The mean level of both serum pepsinogen (PG I) and PG II was significantly increased in the seropositive subjects compared with the seronegative subjects. When the cutoff values for adults (PG I: 70 ng/mL and PG I/II ratio: 3) were used, 4 of 14 subjects had PG I ≤70 ng/mL and PG I/II ratio ≤3. The results of a logistic regression analysis showed that low serum iron levels were significantly associated with H. pylori infection (P=.02)., Conclusions: The prevalence of H. pylori infection is as low as 3% among junior high school students aged 12-15 years in Japan. The disappearance of H. pylori is accelerating in Japanese children., (© 2016 John Wiley & Sons Ltd.)

Background: To prevent gastric cancer, a Helicobacter pylori test-and-treat strategy has been proposed. In Japan, routine urine examinations are performed to screen for kidney diseases; it is therefore convenient to screen for H. pylori infection via urine antibody (u-Ab) testing., Aim: To evaluate the diagnostic accuracy of u-Ab testing in students using 13 C-urea breath testing (UBT) as a standard., Methods: The study population included 806 junior or senior high school students in Japan who provided urine samples and/or underwent UBT. Students with a positive u-Ab test or discrepant results between the u-Ab test and UBT were asked to provide additional stool and/or blood samples or to repeat the UBT. Urinary protein was detected using a urine test strip., Results: The positive rates for the u-Ab test and UBT were 8.9% (71/795) and 5.5% (44/801), respectively. The u-Ab test showed 88.4% sensitivity and 95.7% specificity using UBT as a standard. In the final diagnoses, the u-Ab test showed 97.6% sensitivity, 96.5% specificity, 61.2% positive predictive value (PPV), and 99.9% negative predictive value (NPV). Of the 508 samples tested using a urine test strip, negative results were obtained for 450 subjects with a sensitivity of 90%, specificity of 97.9%, PPV of 66.7%, and NPV of 99.5%. Proteinuria was detected in 58 samples, with a sensitivity of 100%, specificity of 88.9%, PPV of 40%, and NPV of 100%., Conclusions: The u-Ab test is highly accurate and suitable for detecting H. pylori infection. However, the occurrence of proteinuria may yield false-positive results., (© 2016 John Wiley & Sons Ltd.)

Background: Infection of Helicobacter pylori mainly occurs in childhood. In Japan, incidence of gastric cancer is still high in the senior citizen population, but little is known about the current H. pylori infection status among children or their family members., Methods: As a population-based study, the prevalence of H. pylori infection and change in infection status over a 1-year interval in children were determined. Family members of some participants were also invited to participate in the study to determine their infection status. All children of specific ages attending 16 schools in Sasayama, Hyogo Prefecture, were invited to participate. H. pylori infection was determined by the stool antigen test and diagnosis confirmed by polymerase chain reaction and the urea breath test., Results: Helicobacter pylori prevalence was 1.9% among 689 children aged 0-8 years in 2010 and 1.8% among 835 children aged 0-11 in 2011. No feco-conversion was observed in 430 children aged 0-8 years (170 were aged 0-4 years) who provided follow-up stool samples after 1 year. The prevalence of infection was 6% (2 of 33) and 38% (6 of 16) in mothers of negative and positive probands (p = .04), respectively, and 12% (3 of 25) and 50% (8 of 16) (p = .01), respectively, in fathers., Conclusion: Helicobacter pylori prevalence in Japanese children is approximately 1.8%, which is much lower than that reported in Japanese adults. New infection may be rare. Parent-to-child infection is thought to be the main infection route of the infrequent infection for children in Japan., (© 2014 John Wiley & Sons Ltd.)

Background: Helicobacter pylori (H. pylori)-related diseases are responsible for a tremendous amount of morbidity and mortality in Japan. We estimated the prevalence of H. pylori infection by sex, birth year, and geographic area among Japanese adults., Materials and Methods: This cross-sectional study included 14,716 subjects aged 20 years or more who underwent a health checkup between May 1997 and March 2013 in seven geographic areas throughout Japan. Relevant information on the demographics and status of H. pylori infection was retrieved from the electronic database. The univariate log-binominal regression model was used to estimate the prevalence of H. pylori infection, taking birth year into consideration. The multivariate log-binominal regression model was used to compare the prevalence of H. pylori infection between seven geographic areas., Results: The overall prevalence of H. pylori infection was 37.6% in women and 43.2% in men. Among seven geographic areas, Hokkaido showed the lowest prevalence (29.4%), while Yamagata Prefecture represented the highest (54.5%). The prevalence of H. pylori infection was highest in the 1940-1949 birth cohort and then decreased in the ensuing birth cohorts; the risk ratio (RR) was 0.85 (95% confidence interval (CI) 0.84-0.87) for changes in the 10-year birth cohort. Individuals in Yamagata Prefecture had the highest RR of acquiring H. pylori infection in all three birth cohorts (RR = 1.53 for 1940, RR = 1.69 for 1950, and RR = 1.85 for 1960) when compared with those in Hokkaido., Conclusions: The prevalence of H. pylori infection increases with age and exhibits geographic variation in Japan. There has been a striking decrease in the prevalence of H. pylori infection, especially in younger Japanese populations., (© 2014 John Wiley & Sons Ltd.)

Background: Long-term Helicobacter pylori infection causes inflammatory sequelae such as atrophy and intestinal metaplasia in the stomach, which is thought to increase the risk of developing gastric malignancy. We previously reported that gastric atrophy can develop in Japanese children with H. pylori infection, predominantly in the antrum. However, detailed data about the age of children with atrophy are largely lacking., Methods and Results: In the present study, 131 children (79 boys) with H. pylori infection were re-analyzed for an association between age and the grade of gastric atrophy. The gastric antrum was histologically evaluated in all 131 patients and the corpus in 46 patients. Grade 2 and 3 antral atrophy was observed in 13 and one patients, respectively: the mean age was 12.1 years. Two patients (11 and 14 years old) had grade 2 corpus atrophy but no patients had grade 3. No significant difference was found in age among patients with grade 0, 1 and 2 or 3 atrophy in the antrum (p = .97) and in the corpus (p = .59). None of the patients with grade 2 or 3 atrophy had intestinal metaplasia either in the antrum or in the corpus., Conclusions: The results of the present study require a careful interpretation because of the retrospective analysis. In high-risk countries of gastric cancer, however, eradicating H. pylori in childhood could prove more effective in preventing gastric atrophy, ultimately, the development of cancer.

Background: A causal relationship between Helicobacter pylori infection and gastric cancer has been established. A nonrandomized study has shown eradication of H. pylori after endoscopic resection (ER) of early gastric cancer inhibits development of new carcinomas., Subjects and Methods: Eligible subjects are patients with H. pylori infection who are newly diagnosed with early gastric cancer and plan to have ER or who are in the post-resection follow-up phase after ER time of enrollment. Patients are randomly allocated to the eradication or the control arms (no eradication and standard of care). Patients will be evaluated by endoscopy at 0.5, 1, 2, and 3 years after randomization. Diagnosis of a new carcinoma at another site of the stomach is defined as primary endpoint, and recurrence of tumors at the resection site as a secondary endpoint. In addition to intention-to-treat and per-protocol analyses using proportional hazards models, time to recurrence will be compared between treatment and control using multiple logistic regression analyses. In the latter two situations, the models will be adjusted for the factors exerting significant influences on the results., Results: Five hundred and forty-two subjects have been enrolled into the study and are being followed-up., Conclusions: This study will have the statistical power to demonstrate whether H. pylori eradication therapy exerts any clinically relevant inhibitory effects on occurrence or recurrence of gastric cancer. In addition, it will be able to test the hypothesis that H. pylori infection is a promoter in gastric carcinogenesis.

This review summarizes epidemiologic studies published between April 2004 and March 2005. DNA of Helicobacter pylori was detected in river water, but the culture was unsuccessful. H. pylori infection was associated with Shigella infection. Despite many studies, predominant infection routes of H. pylori have not yet been clearly identified. In some limited populations in developing countries, H. pylori infection was rare or with strange distributions. Trials to reduce the H. pylori infection rate were performed including H. pylori eradication in total family units and fly control. The hypothesis of a causal role of Helicobacter species and H. pylori infection in cancer of the hepatobiliary tract was indeed confirmed.

Background: There are still insufficient data on the frequency of seroconversion and seroreversion of Helicobacter pylori antibodies. The frequency of serochange and related factors were investigated in this study over 9 years., Subjects and Methods: Using sera from 3104 workers who underwent health checks in 1989 and again in 1998, H. pylori antibodies were measured. Those with intermediate serology were excluded from the study. Information on past history was collected using a questionnaire., Results: Of the 912 seronegative and 1286 seropositive subjects in 1989, seroconversion was observed in 57 and seroreversion in 91 subjects. Seroconversion and seroreversion rates over the 9-year period were 6.3% and 7.1%, respectively, giving rates per 1000 person-years (with 95% confidence interval) of 7.0 (5.2-8.7) and 7.9 (6.3-9.4), respectively. Subjects that reported abdominal symptoms or gastric fiberscope use showed significantly higher seroconversion rates than controls (8.7 vs. 4.5 and 9.2 vs. 1.6, respectively), which remained significant after adjustment for age and gender. Those with a history of duodenal ulcers, a smoking habit or a drinking habit showed significantly lower seroreversion rates than controls (3.5 vs. 8.9, 5.4 vs. 9.2 and 5.9 vs. 13.3, respectively). After adjustment, the association between seroreversion and smoking habit disappeared, while the associations with history of duodenal ulcers and drinking habit remained., Conclusions: Those with a history of nonspecific abdominal symptoms and those with a history of gastric fiberscope use showed higher seroconversion rates. Alcohol consumption and duodenal ulcers may inhibit the autoeradication of H. pylori, possibly through increased acid secretion.