Introduction To improve the eradication success rate of Helicobacter pylori, treatment combined with antimicrobial susceptibility testing (AST) is recommended. However, AST procedures are not yet standardized in Japan. Understanding the implementation status of AST at individual facilities, identifying the associated issues, and addressing the challenges to standardization are crucial. Methods A questionnaire-based survey was used in this study to investigate the current status of eradication therapy and AST among physicians certified in H. pylori infection from the Japanese Society for Helicobacter Research and members of the Japanese Society for Clinical Microbiology. Results The vonoprazan/amoxicillin/clarithromycin regimen was selected as first-line therapy in 94% of the facilities. Approximately 24% of facilities reported a first-line eradication success rate of below 80%. Regarding AST, 18% of physicians certified in H. pylori infection from the Japanese Society for Helicobacter Research reported performing the test, compared to 70% of members from the Japanese Society for Clinical Microbiology. The most commonly used methods differed between the two groups: the agar dilution method was predominant in the former, whereas disk diffusion methods, including the E-test, and microdilution method were common in the latter. Conclusion The status of AST for H. pylori varies widely across Japan. To achieve nationwide standardization, it is essential to establish robust quality control measures and promote the use of standardized reference panel strains for AST.

In 2026, the fourth edition of the evidence-based clinical practice guidelines for peptic ulcer disease by the Japanese Society of Gastroenterology (JSGE) was revised. These revised guidelines cover epidemiology, hemorrhagic peptic ulcers, Helicobacter pylori eradication therapy, non-eradication therapy, drug-induced ulcers, non-H. pylori, and nonsteroidal anti-inflammatory drug (NSAID) ulcers, remnant gastric ulcers, surgical treatment, and conservative therapy for perforation and stenosis. Although H. pylori infection and NSAIDs use remain two major causes of peptic ulcers, the prevalence and mortality rates of peptic ulcer have been declining due to the widespread use of eradication therapy and development of potent acid-inhibitory drugs in recent years. However, an increasing trend in idiopathic ulcers and ulcers caused by non-H. pylori Helicobacter (NHPH) infection has attracted attention. In this revised edition, therapeutic algorithms for the treatment of peptic ulcers based on H. pylori infection, low-dose aspirin (LDA) or NSAID use, ulcer history, and ulcer complications (e.g., hemorrhage) remain largely unchanged. This edition shows options for H. pylori eradication in various situations compared with the previous edition, and recommends the most effective regimens, regardless of Japanese insurance coverage. In addition, a new flowchart outlining the eradication treatment process has been presented. Compared with the previous version, the main changes in pharmacological treatment have been made: due to its acid-inhibitory characteristics compared with proton pump inhibitors and increased evidence of its efficacy and safety, vonoprazan has now been selected as the first-line treatment for peptic ulcers and NSAID- and LDA-induced ulcers.

INTRODUCTION:This study aimed to conduct an epidemiological investigation of the relationship between gastric mucosal atrophy and exhaled hydrogen gas concentration, including gut microbiota, in residents who participated in health checkups. METHODS:Based on pepsinogen I <70 ng/mL and PG I/PG II <3 as cutoff values, the participants were divided into a control (n = 903) and atrophy (n = 63) groups. The exhaled hydrogen gas concentrations and gut microbiota were compared in 212 participants from the control group and 53 participants from the atrophy group, selected through propensity score matching. Furthermore, participants were categorized as non-infection, persistent infection, or post-eradication groups based on their Helicobacter pylori (H. pylori) infection status. RESULTS:In the atrophy group, 66.0% were persistent H. pylori carriers, whereas 39.6% of the control group had undergone H. pylori eradication. The atrophy group showed lower exhaled hydrogen concentration than those of the control group. In the gut microbiota of the atrophy group, an increase in Streptococcus, and a decrease in Blautia were observed. Among H. pylori infection statuses, persistent infection group showed reduced exhaled hydrogen gas concentration and increased gut Streptococcus compared to the non-infection group, but no association was observed with the post-eradication group. CONCLUSIONS:Most individuals infected with H. pylori showed evidence of gastric mucosal atrophy, accompanied by decreased breath hydrogen concentrations and alterations in the gut microbiota. Eradication of H. pylori may ameliorate gastric mucosal atrophy, which could subsequently normalize the gut microbial composition and lead to increased levels of exhaled hydrogen.

Cytomegalovirus (CMV)-associated gastrointestinal disease can precipitate life-threatening hemorrhages; therefore, heightened vigilance is warranted in patients administered immunosuppressive agents. Moreover, acute liver failure compromises cellular immunity by disrupting immune regulatory mechanisms. Herein, we describe a case of duodenal ulcer caused by CMV reactivation during treatment for autoimmune hepatitis (AIH), complicated by acute liver failure. The patient was admitted with acute-onset AIH and steroid pulse therapy was initiated; however, progression to acute liver failure followed. Although acute liver failure improved after plasma exchange and continuous hemodiafiltration, multiple duodenal ulcers developed owing to CMV reactivation following the introduction of azathioprine. Subsequently, the patient developed a microperforation, which resolved with conservative management. However, gastrointestinal bleeding occurred at multiple sites, making endoscopic hemostasis difficult. As the patient's general condition was poor, and surgical intervention was deemed infeasible, interventional radiology (IVR) was conducted thrice within a single day, successfully achieving hemostasis and ultimately saving the patient's life. Although immunosuppressive therapy is indispensable for AIH management, caution regarding CMV reactivation is required during the development of acute liver failure. Furthermore, IVR is a minimally invasive modality that can be performed repeatedly, making it an effective therapeutic option for managing gastrointestinal bleeding.

BackgroundThe 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.MethodsThis 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.ResultsThere 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.ConclusionThe revised guidelines facilitate the appropriate management of H. pylori infection and gastric cancer prevention.

Background: Steatotic liver disease (SLD) and sarcopenia are lifestyle-related conditions for which prevention is critical. The phase angle, which is derived from impedance, reactance, and resistance values obtained via bioelectrical impedance analysis, has emerged as a potential marker of sarcopenia. Additionally, amino acids have been implicated in the pathogenesis of both SLD and sarcopenia. This epidemiological study investigated the association between SLD and sarcopenia in a general population cohort. Methods: This cross-sectional study included 281 participants with metabolic dysfunction-associated steatotic liver disease (MASLD), 72 with metabolic alcohol-associated liver disease (MetALD), and 54 with alcohol-associated liver disease (ALD). Associations between phase angle, Mac-2-binding protein glycosylation isomer (M2BPGi) as a marker of liver fibrosis, and serum amino acid levels were analyzed. Results: The phase angle was significantly higher in the MetALD group than in the MASLD and ALD groups. Multivariate analysis identified MASLD as an independent risk factor for a low phase angle compared with MetALD. M2BPGi levels were lower in MetALD than in MASLD, and M2BPGi showed a negative correlation with the phase angle. Furthermore, MetALD was characterized by lower serine and glutamine levels than MASLD, with serine demonstrating a negative correlation with the phase angle. Conclusions: Although the possibility of residual confounding factors cannot be excluded, the present study suggests that phase angle may serve as a sensitive marker for the early decline in muscle mass in patients with SLD, comparable to grip strength and skeletal muscle mass index.

Background/Objective: This study investigated the relationship between the composition of oral microbiota and metabolic dysfunction-associated steatotic liver disease (MASLD) in the general population. Methods: In total, 712 participants in a health check-up project were divided into four oral microbiota patterns by principal component analysis and cluster analysis; they were included in Neisseria, Streptococcus, Fusobacterium, and Veillonella groups. The Neisseria group had the largest number of patients and was used as a reference group to compare the incidence of MASLD and cardiometabolic criteria with the other groups. Results: In a multivariate analysis, the Veillonella group was a risk factor for MASLD independent of cardiometabolic criteria compared with the Neisseria group. The correlation between oral bacterial species and MASLD-related items showed that Neisseria was negatively correlated with controlled attenuation parameters, body mass index, waist circumference, hemoglobin A1c, alanine aminotransferase, and fatty liver index. Veillonella showed a positive correlation with controlled attenuation parameters, waist circumference, body mass index, blood pressure, triglycerides, alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transpeptidase, and fatty liver index, and a negative correlation with high-density lipoprotein cholesterol. In contrast, the Streptococcus and Fusobacterium groups were not clearly associated with MASLD. Conclusions: Maintaining oral hygiene and preventing periodontitis may contribute to preventing MASLD and extending a healthy lifespan.

The beneficial effects of water-soluble dietary fiber on liver fat and fibrosis involve the gut microbiota; however, few epidemiological studies have investigated this association. This large-scale epidemiological study aimed to determine the effect of water-soluble dietary fiber intake on liver fat and fibrosis via gut microbiota for the general population. We divided low- and high-intake groups by median daily water-soluble dietary fiber intake and matched background factors by propensity score matching for sex and age. The high-intake group had lower controlled attenuation parameters, a lower fatty liver index, and a lower mac-2-binding protein glycosylated isomer level than the low-intake group. Furthermore, in the high-intake group, the prevalences of metabolic dysfunction-associated steatotic liver disease and cardiometabolic criteria were significantly lower than in the low-intake group. In the high-intake group, there were increases and decreases in 16 bacterial species. Of them, those belonging to Faecalibacterium and Gemmiger had higher relative abundances than the other species and had a negative correlation with the fatty liver index and its components triglyceride and glutamyl transpeptidase in a multivariate analysis adjusted for confounding factors. On the other hand, Dorea showed a significant negative correlation with liver stiffness measure, even though Dorea was decreased in the high-intake group. Faecalibacterium and Gemmiger are butyrate-producing bacteria, suggesting that water-soluble dietary fiber may inhibit fatty liver via gut butyric acid production.

Helicobacter pylori is considered to contribute to gastric cancer and is also used as a marker to trace human migration due to its co-evolution with humans. To understand the recently proposed tripartite model suggesting three ancestral origins for the Japanese population and address the enigma of the high incidence of gastric cancer in Northeast Hondo (Hondo is mainland Japan), we conducted a fine-scale population structure analysis using a large Japanese H. pylori dataset, including 438 strains from 9 regions based on whole-genome sequences. As a result of fineSTRUCTURE analysis, it was found that H. pylori in Northeast Hondo is genetically distinct from hspEAsia subgroup 7 (sg7), which is widely distributed elsewhere in Hondo. We named this new subgroup hspEAsia-sg8 (Northeast Hondo). Ancestry analysis using ChromoPainter revealed that, while a large proportion of the genomes of hspEAsia-sg8 strains were painted by donors from their own population, the ancestry components of hspEAsia-sg7 showed a high proportion of Chinese and Korean components, suggesting that they were formed through admixture with continental hspEAsia subgroups. These results align with human genome studies, which indicate an original ancestry component in Northeast Hondo and a higher proportion of East Asian components in West Hondo, supporting the tripartite model. This also suggests novel potential for biogeographic ancestry inference in forensic science, as the H. pylori genome can distinguish Hondo populations. Furthermore, fixation index analysis comparing the genome of hspEAsia-sg8 with other Japanese hspEAsia subgroups revealed a high number of nonsynonymous mutations in hp0378 ( ccsBA ) and hp0377 ( dsbC / ccmG ). Because these genes are involved in cytochrome c maturation and disulphide bond formation, the detected mutations may affect bacterial survival, growth or pathogenicity. This study supports the tripartite model for the formation of modern Japanese people and suggests that the strain of H. pylori prevalent in the Northeast Hondo region may contribute to the high incidence of gastric cancer there.

Breath hydrogen concentration measurement is a valuable tool for assessing the intestinal environment; however, few epidemiological studies have investigated the relationship between exhaled hydrogen and gut microbiota in healthy subjects. This study aimed to epidemiologically elucidate the relationships between exhaled hydrogen, gut microbiota, and nutrient intake in healthy residents of the Iwaki area of Hirosaki City, Aomori Prefecture, including those who exhaled methane. We categorized participants into low- and high-exhaled hydrogen groups based on the median exhaled hydrogen concentration of 6.13 ppm and matched background factors by propensity score matching for age, body mass index, and defecation habits. In the high exhaled hydrogen group, intestinal butyrate-producing bacteria such as Faecalibacterium, Anaerostipes, and Roseburia increased, and Bacteroides strains decreased. In addition, the group with high exhaled hydrogen concentrations had a high dietary fiber intake, and positive correlation was observed between dietary fiber intake and butyrate-producing bacteria. This trend was particularly pronounced for soluble dietary fiber. The exhaled methane concentration decreased in the higher exhaled hydrogen concentration group, and intestinal Methanobrevibacter was positively correlated with the exhaled methane concentration, although in extremely small amounts. No significant relationship was found between each nutrient intake and Methanobrevibacter strain. Measurement of the exhaled hydrogen concentration is useful for assessing the intestinal environment associated with nutritional intake. However, methane gas production was not changed by dietary intake, suggesting that intervention with prebiotics may be necessary.

Hypercontractile esophagus is a motility disorder characterized by excessive contractions in the esophageal body. Certain cases of hypercontractile esophagus exhibit eosinophilic infiltration in the muscle layer; however, its clinical significance is unclear. Here, we report a case of hypercontractile esophagus with possible eosinophilic inflammation despite the absence of eosinophilic infiltration on hematoxylin and eosin staining. A 75-year-old man presented with dysphagia, primarily triggered by the ingestion of meat. Esophagogastroduodenoscopy showed abnormal peristalsis of the esophageal body, while the lower esophageal sphincter function remained normal. High-resolution manometry confirmed hypercontractile esophagus, according to the Chicago Classification version 4.0. As symptoms persisted despite medical treatment, the patient underwent peroral endoscopic myotomy. Biopsies obtained from the inner circular muscle layer revealed no notable eosinophilic infiltration on hematoxylin and eosin staining. However, immunofluorescence staining for major basic protein (MBP), a cytotoxic eosinophil granule protein that persists in tissues, showed patchy depositions. Corresponding counterstaining revealed collapsed nuclei surrounded by eosinophilic material, suggesting MBP release via eosinophil cytolysis. This case demonstrated that immunostaining for eosinophil granule proteins may uncover eosinophilic activity in the esophageal muscle layer, even in the absence of eosinophils. While the precise pathogenic role of eosinophilic inflammation in hypercontractile esophagus remains unclear, MBP deposition could reflect a localized immune-mediated process contributing to motility disturbance. Further investigation is needed to determine the prevalence, mechanisms, and clinical implications of these findings in esophageal motor disorders.

Objectives:Peroral endoscopic myotomy (POEM) is an established treatment for esophageal achalasia. Despite favorable outcomes, the risk of reflux aspiration during general anesthesia induction in POEM remains a concern. This study aimed to identify the risk factors for food residue in the esophagus before POEM and evaluate the necessity of esophagogastroduodenoscopy (EGD) and cleansing the day before POEM. Methods:A retrospective analysis of 61 patients with esophageal achalasia and esophagogastric junction outflow obstruction undergoing POEM between July 2017 and March 2024 was performed. Patients were divided into two groups based on the presence of food residue observed during preoperative EGD: residual (n = 16) and no-residual (n = 45) food groups. The factors compared included age, sex, Chicago criteria, duration of symptoms, Eckardt score, integrated relaxation pressure, esophageal dilation grade and type on esophagography, and presence of residual food during the initial EGD. Results:In univariate analysis, residual food was more common in patients aged <60 years (p < 0.05) and those with higher esophageal dilation grades (p < 0.05). Additionally, residual food during the initial EGD was identified as a significant predictor (p < 0.05). Conclusions:Preoperative EGD and esophageal cleansing the day before POEM may be warranted in patients with initial EGD-detected residue, younger age, and marked dilation, to reduce reflux aspiration risk and improve procedural safety.

This study aimed to evaluate the physical stress associated with transarterial chemoembolization (TACE), a catheter-based treatment for hepatocellular carcinoma, by examining changes in serum opsonic activity (SOA). SOA was examined by measuring reactive oxygen species (ROS) produced by neutrophils using lucigenin-dependent chemiluminescence (LgCL) and luminol-dependent chemiluminescence (LmCL). Sixty-four patients were enrolled, and SOA was measured at admission, the following day, and 3 days after TACE. The area under the curve (AUC) for LgCL did not change significantly from baseline to the day after TACE but increased significantly from the following day to 3 days post-TACE. In contrast, no changes were observed in the AUC of LmCL. Subgroup analyses revealed a significant increase in LgCL from day 1 to day 3 post-TACE among patients aged >75 years, males, body mass index (BMI) <25 ‍kg/m2, those with a FIB-4 index of ≥2.67, cisplatin use, Hepatitis B virus/Hepatitis C virus-related liver disease, or a procedure time ≥120 ‍min. Multivariate analyses identified BMI <25 ‍kg/m2 and cisplatin use as significant risk factors for increased LgCL. Although TACE is considered a minimally invasive procedure, low BMI and cisplatin use have been identified as notable sources of significant physical stresses.

Salivary Multi Test (SMT) is a device that can quickly and noninvasively measure seven parameters related to the oral environment using saliva as a sample: (1) bacteria that cause tooth decay, (2) acidity, (3) buffering capacity, (4) occult blood, (5) white blood cells, (6) protein, and (7) ammonia. This longitudinal study aimed to investigate the relationship between SMT and oral and gut microbiota in healthy general residents. After propensity score matching, 198 participants were included (low SMT group: 99 participants; high SMT group: 99 participants). We reclassified participants four years after the follow-up survey and compared the low- and high-SMT groups. The high SMT score group indicating a poor oral environment showed increased Olsenella in both the oral cavity and gut at the start of the survey and four years later. Oral Olsenella was strongly correlated with occult blood and protein levels. In contrast, a 4-year follow-up study demonstrated that changes in oral Olsenella were associated with occult blood changes. Conversely, changes in gut Olsenella were associated with changes in occult blood and protein. A poor SMT score has been shown to be linked to increased oral and gut Olsenella and improving the oral environment can improve the oral–gut microbial environment.

Severe esophageal strictures resulting from chemoradiotherapy pose persistent therapeutic challenges despite the availability of treatments such as endoscopic balloon dilation and medications. Hyperbaric oxygen therapy (HBOT) has emerged as a promising treatment option for refractory radiation-induced injury to several organs. Herein, we present the case of a 79-year-old male patient with refractory radiation-induced ulcerative esophageal strictures after chemoradiotherapy. Despite multiple interventions, including endoscopic balloon dilation, steroids, and proton-pump inhibitors, the patient remained unable to tolerate oral intake. HBOT was initiated, leading to significant improvement in the esophageal ulcers and strictures within 1 month. HBOT was well tolerated; the patient experienced a sustained improvement in his quality of life. Two years after HBOT, esophagogastroduodenoscopy confirmed persistent improvement in esophageal ulcers and strictures. This case highlights the potential of HBOT as a therapeutic option for ulcerative esophageal strictures unresponsive to conventional treatments.

Lactococcus lactis subsp. lactis (L. lactis) is a common species of lactic acid bacteria (LAB). There is increasing evidence that probiotic L. lactis ameliorates experimental colitis in mice, whereas few studies have revealed the effects of the paraprobiotics, i.e., inactivated forms of bacteria. L. lactis L8 strain is a newly identified plant-derived LAB. The present study aimed to investigate the effects of heat-killed L. lactis L8 on dextran sulfate sodium (DSS)-induced colitis in mice. C57BL/6J mice were orally administered L. lactis L8 for 12 days. Colitis was induced by adding 3.5% DSS to the drinking water for 7 days. Mice were euthanized on day 12, and colon tissues and fecal samples were collected. Results demonstrated that administration of L. lactis L8 alleviated the clinical score of the colitis and the histological abnormalities. Additionally, L. lactis L8 led to a significant reduction in the level of colon tumor necrosis factor (TNF)-α. Administration of L. lactis L8 did not affect the gut microbial structure, whereas it altered the relative abundance of Clostridiaceae and Rikenellaceae in colitis mice. Our findings suggest that paraprobiotic L. lactis L8 has an immunomodulatory effect on intestinal inflammation in mice, providing important insight into the biological function of L. lactis L8.

Objectives: Delayed bleeding is the most frequent adverse event associated with endoscopic mucosal resection (EMR) and hot snare polypectomy (HSP) of colorectal polyps. However, whether the incidence of delayed bleeding differs between outpatient and inpatient treatment is unknown. Therefore, in this study, we aimed to evaluate delayed bleeding rates between outpatient and inpatient endoscopic treatments and clarify the safety of outpatient treatment. Methods: We enrolled 469 patients (1077 polyps) and 420 patients (1080 polyps) in the outpatient and inpatient groups, respectively, who underwent EMR or HSP for colorectal polyps at our institution between April 2020 and May 2023. Using propensity score matching, we evaluated the delayed bleeding rates between the two groups. Delayed bleeding was defined as a hemorrhage requiring endoscopic hemostasis occurring within 14 days of the procedure. Results: Propensity score matching created 376 (954 polyps) matched patient pairs. The median maximum diameter of polyps removed was 10 mm in both groups. Delayed bleeding rates per patients were 1.3% (5/376) in the outpatient group and 2.9% (11/376) in the inpatient group (P=0.21). In term of per polyp, early delayed bleeding (occurring within 24 hours) rates were higher in the inpatient group than outpatient group (0.2% [2/954] vs. 1.1% [10/954], respectively; P=0.04). No severe bleeding requiring a transfusion occurred in either group. Conclusions: Outpatient endoscopic treatment did not increase delayed bleeding compared with inpatient treatment. Outpatient treatment would be safe and common for the removal of colorectal polyps.

Functional dyspepsia is distinguishable from Helicobacter pylori-associated dyspepsia. However, distinguishing H. pylori-associated dyspepsia from functional dyspepsia before H. pylori eradication is difficult. Therefore, in the present study, we aimed to investigate whether serum pepsinogen levels before H. pylori eradication are associated with the amelioration of dyspepsia after successful H. pylori eradication. Additionally, we examined the usefulness of serum pepsinogen levels and other factors in predicting dyspepsia outcomes. H. pylori eradication was effective in 14 patients (Responders) and ineffective in 19 patients (Non-responders). The pepsinogen I/II ratio in Responders (3.4 ± 1.2) and Non-responders (2.3 ± 1.0) differed significantly (p = 0.006). The optimal cut-off pepsinogen I/II value was 2.3. Multivariate logistic regression analysis showed that the adjusted odds ratio for Non-responders was 26.1 (95% confidence interval: 2.0–338.0, p = 0.012) for a pepsinogen I/II ratio ≤ 2.3 and 8.10 (95% confidence interval: 1.1–57.6, p = 0.037) for smoking habits. The pepsinogen I/II ratio and smoking habits were associated with the effects of H. pylori eradication on dyspeptic symptoms. Thus, the pepsinogen I/II ratio cut-off value can be used to identify patients likely to respond to H. pylori eradication after the resolution of dyspeptic symptoms.

The Japanese diet is a healthy dietary pattern, and the oral or gut microbiota have been identified as the main factors underlying the beneficial effects of the Japanese diet. However, epidemiological studies on Japanese dietary patterns calculated from daily eating habits in the general population yielded inconsistent findings. This study aimed to determine the association between the 12-component modified Japanese Diet Index (mJDI12) and the oral and gut microbiota in the general population of a rural area in Japan. After propensity-score matching, 396 participants (198 each in the low and high mJDI12 groups) were picked out. One year after the follow up survey, we reclassified the subjects and compared the low and high mJDI12 groups again. Participants with a high mJDI12 had a higher relative abundance of butyric acid-producing bacteria in their gut microbiota. Moreover, the significantly higher dietary fiber intake in the high mJDI12 group suggested that the high intake of dietary fiber contributed to an increase in butyric acid-producing bacteria in the gut. In contrast, in individuals with a high mJDI12, only Allpprevotella was decreased in the oral microbiota. Thus, the Japanese dietary pattern can have beneficial effects by improving the oral and gut microbiota.

Background. Antimicrobial therapy is necessary to eradicate Helicobacter pylori infection. The emergence of antimicrobial-resistant bacteria poses a threat to continued treatment with antimicrobial agents. For those who prescribe antimicrobial therapy, it is necessary to constantly monitor the emergence of antimicrobial-resistant bacteria.Method. H. pylori clinical isolates were collected in Japan from August 2018 to December 2020 for antimicrobial susceptibility testing. The agar dilution method was used for the determination of the minimum inhibitory concentration (MIC) of clarithromycin (CLR), amoxicillin (AMX), metronidazole (MNZ), and sitafloxacin (STX).Results. MICs for 938 H. pylori isolates were examined. The primary resistance rates of H. pylori clinical isolates for CLR, AMX, MNZ, and STX in Japan were 35.5%, 2.7%, 4.2%, and 27.6%, respectively. The primary resistance rates for CLR, AMX, and MNZ were significantly higher than those of the 2002-2005 isolates. The resistance rate for CLR was significantly higher in females (males: 30.7%, females: 41.5%, p < 0.001) and higher in the <= 29 years age group (54.8%) than in the other age groups, although there were no significant differences (p = 0.104). The MNZ resistance rate was significantly higher in the <= 29 years age group than in the other age groups (p = 0.004). The resistance rate for STX increased with age, but a significant difference was only seen between the 30-49 years age group and the >= 70 years age group (p < 0.001), and the resistance rate was significantly higher in strains isolated in the Kyushu region than in the other regions (p < 0.001).Conclusions. The primary resistance rates for CLR, AMX, and MNZ of H. pylori clinical isolates in Japan were higher than those of the 2002-2005 isolates. Continuous surveillance is needed to monitor the trends in antimicrobial-resistant H. pylori.