Soichiro Sue and Shin Maeda. Gut and Liver -0001;0:. https://doi.org/10.5009/gnl20242

Background: The Japanese Society for Helicobacter Research (JSHR) published the fifth edition of the guidelines for the management of Helicobacter pylori ( H. pylori ) infection in 2024 in Japanese language. Methods: This edition of JSHR guidelines was first developed in accordance with the Minds Clinical Practice Guideline and Grading of Recommendations Assessment, Development, and Evaluation system. This was published after inviting public comments and external evaluations. Consensus on clinical questions (CQs) was achieved using the modified Delphi method. Results: There was no change in the basic policy that all H. pylori infectious diseases are indications for eradication. Nucleic acid amplification was added to the diagnostic methods. Effects of proton-pump inhibitors (PPIs) on diagnostic tests were updated. The superiority of potassium-competitive acid blockers to PPIs in 1-week triple therapy with amoxicillin and clarithromycin has been shown. A flowchart for eradication therapy was provided for use in real-world settings. For gastric cancer prevention, eradication in earlier age is recommended. The most appropriate test and treatment strategies for adolescents are also described. Some CQs concerning gastric cancer prevention were identified, although evidence level was insufficient to make recommendations based on clinical importance. Conclusion: The revised guidelines facilitate the appropriate management of H. pylori infection and gastric cancer prevention.

Aim: This was a prospective, multicenter, single-arm intervention, against historical controls, study of the efficacy of a vonoprazan-based 7-day triple regimen with metronidazole (VPZ-AMPC-MNZ) as a first-line therapy for eradicating clarithromycin-resistant Helicobacter pylori (H. pylori). Methods: We enrolled 35 patients positive for clarithromycin-resistant H. pylori, as assessed by culture, without a history of eradication. These 35 patients were prospectively eradicated with VPZ-AMPC-MNZ. As historical controls, we also assessed 98 patients with clarithromycin-resistant H. pylori from our prior prospective studies, who achieved H. pylori eradication with a 7-day triple regimen including clarithromycin (VPZ-AMPC-CAM). A preplanned analysis was performed as a superiority study against the historical controls (VPZ-AMPC-MNZ compared to VPZ-AMPC-CAM). In each regimen, vonoprazan was used at 20 mg bid, amoxicillin at 750 mg bid, metronidazole at 250 mg bid, and clarithromycin at 200 mg or 400 mg bid for 7 days. We assessed the outcome of eradication therapy using a ¹³C-urea breath test or H. pylori stool antigen test. We evaluated safety using patient questionnaires. Results: The intention-to-treat (ITT) and per-protocol (PP) eradication rates of VPZ-AMPC-MNZ were both 100% (95% confidence interval (95% CI) 90.0–100%, n = 35). The eradication rates of VPZ-AMPC-CAM were 76.5% (95% CI 66.9–84.5%, n = 98) in the ITT analysis and 77.3% (95% CI 67.7–85.2%, n = 97) in the PP analysis. The eradication rate of VPZ-AMPC-MNZ was significantly higher than that of VPZ-AMPC-CAM in both the ITT (p = 0.00052) and PP (p = 0.00095) analyses. Conclusions: The findings suggest that 7-day VPZ-AMPC-MNZ was superior to 7-day VPZ-AMPC-CAM as a first-line regimen for eradicating clarithromycin-resistant H. pylori. We suggest VPZ-AMPC-MNZ as the standard first-line regimen for eradication of clarithromycin-resistant H. pylori in Japan.

Background: In the absence of Helicobacter pylori (HP) infection, a characteristic gastric mucus adhesion may appear during the use of vonoprazan. We named this novel characteristic mucus “web-like mucus” (WLM). This study aimed to determine the incidence and risk factors for WLM. Methods: Between January 2017 and January 2022, 5665 patients were enrolled in this study. The patients were divided into a proton-pump inhibitor (PPI)-prescribed group (n = 2000), a vonoprazan-prescribed group (n = 268), and a no-PPI/vonoprazan-prescribed (n = 3397) group, and the presence of WLM was examined. After excluding four patients with autoimmune gastritis, the remaining 264 patients in the vonoprazan group were divided into WLM and non-WLM groups, and their clinical features were analyzed. Results: A total of 55 (21%) patients had WLM, all in the vonoprazan-prescribed group. There were no significant differences in factors such as, sex, age, chronic kidney disease, diabetes mellitus, HP eradication history, smoking, or alcohol consumption between the WLM and non-WLM groups. The median duration from the start of vonoprazan administration to the endoscopic detection of WLM was 2 (1–24) months. Conclusions: WLM appears to be a characteristic feature in patients treated with vonoprazan.

This is the first registered intervention study for vonoprazan, high-dose amoxicillin, clarithromycin, and metronidazole 14-day concomitant therapy based on a susceptibility test of Helicobacter pylori. We conducted this study as a fourth-line rescue regimen in Japan. Methods: Twenty patients who underwent three rounds of eradication therapies (first- or second-line 7-day triple therapy consisting of amoxicillin and clarithromycin, or metronidazole- and sitafloxacin-based third-line therapy) and had failed eradication based on a urea breath test or fecal antigen test were recruited. All patients underwent endoscopic examination and culture tests before starting eradication therapy. The intervention was concomitant therapy consisting of vonoprazan 20 mg bid, amoxicillin 500 mg qid, clarithromycin 400 mg bid, and metronidazole 250 mg bid for 14 days, which were modified based on the susceptibility test, and the resistant drugs were removed from the regimen. Patients with negative culture results were treated with quadruple therapy. The primary outcome was the eradication rate (UMIN000025765, jRCTs 031180208). Results: The eradication rate of susceptibility-testing-based fourth-line eradication therapy was 63.2% (95%CI: 38.4–83.7%) in intent-to-treat analysis and 70.6% (95%CI: 44.0–89.7%) in per-protocol analysis. Thirteen patients received quadruple therapy, with eradication rates of 61.5% and 75.0%, respectively. No serious adverse events were reported. Conclusions: This vonoprazan-based concomitant therapy modified by the susceptibility test is a potential option as fourth-line eradication after first-line clarithromycin-based 7-day triple, second-line metronidazole-based 7-day triple, and third-line sitafloxacin-based 7-day triple therapy failure.