<i>Helicobacter pylori</i> Management in Older Adults: Current Perspectives From Japan

Hideki Mori; Hidekazu Suzuki

doi:10.7704/kjhugr.2025.0091

Korean J Helicobacter Up Gastrointest Res > Volume 26(1); 2026 > Article

Mori and Suzuki: Helicobacter pylori Management in Older Adults: Current Perspectives From Japan

Review

The Korean Journal of Helicobacter and Upper Gastrointestinal Research 2026;26(1):42-49.

Published online: March 5, 2026

DOI: https://doi.org/10.7704/kjhugr.2025.0091

Helicobacter pylori Management in Older Adults: Current Perspectives From Japan

Hideki Mori¹

, Hidekazu Suzuki²

¹Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan

²Division of Gastroenterology and Hepatology, Department of Internal Medicine, Tokai University School of Medicine, Isehara, Kanagawa, Japan

Corresponding author Hidekazu Suzuki, MD, PhD Division of Gastroenterology and Hepatology, Department of Internal Medicine, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa 259-1193, Japan E-mail: hsuzuki@tokai.ac.jp

Received December 19, 2025; Revised December 31, 2025; Accepted January 1, 2026;

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Helicobacter pylori infection—although its overall prevalence has declined over time—remains a major cause of peptic ulcer disease and gastric cancer, particularly among older adults in aging societies such as Japan. While eradication therapy is known to reduce the gastric cancer risk, its use in older adults is often complicated by comorbidities, polypharmacy, altered drug metabolism, and limited life expectancy. This review summarizes current perspectives on the management of H. pylori infection in older patients, based on Japanese clinical practice and recent evidence. Older individuals frequently have long-standing infections accompanied by advanced gastric atrophy and intestinal metaplasia, which may adversely affect diagnostic accuracy and therapeutic outcomes. Diagnostic evaluation is further complicated by severe mucosal atrophy and the frequent use of acid-suppressive medications, requiring careful interpretation of test results and, in some cases, correlation with endoscopic findings. In Japan, vonoprazan-based eradication regimens have become the standard of care because of their high efficacy and pharmacological stability regardless of CYP2C19 genotype. Available data indicate that eradication therapy is generally safe and well tolerated in older patients, with adverse event rates comparable to those observed in younger populations. Eradication therapy is highly recommended for disease-specific indications (e.g., peptic ulcer) and for primary prevention of gastric cancer. Overall, older age alone should not be considered a contraindication to eradication therapy; rather, treatment decisions should be based on a comprehensive assessment of comorbidities, concomitant medications, the patient’s functional status, and the patient’s preferences.

Key words: Elderly population; Gastric atrophy; Polypharmacy; Vonoprazan; Individualized therapeutic strategies

INTRODUCTION

Helicobacter pylori infection remains a major cause of peptic ulcer disease, gastric cancer, and mucosa-associated lymphoid tissue (MALT) lymphoma [1]. In Japan, a rapidly aging society, a substantial proportion of individuals with H. pylori infection are older adults [2]. Although eradication therapy has been shown to reduce the incidence of gastric cancer [3], the management of H. pylori infection in older adults presents unique challenges, including comorbidities, polypharmacy, age-related alterations in drug metabolism, and limited life expectancy [4-6]. This review summarizes key aspects of H. pylori management in older patients in light of the latest available evidence.

EPIDEMIOLOGY AND CHARACTERISTICS IN OLDER ADULTS

From an epidemiological perspective, the prevalence of H. pylori infection in Japan exhibits a marked age-dependent gradient. National surveys conducted between 2010 and 2013 reported infection rates exceeding 50% among individuals older than 70 years, whereas the prevalence was below 20% among those younger than 40 years [2]. Historically, the burden was even higher; surveys conducted in 1975 and 1978 demonstrated infection rates exceeding 80% among adults aged 30 years and older [2]. In contrast, recent school-based studies have shown that the prevalence of H. pylori infection among Japanese adolescents has declined to approximately 1%–3%, suggesting that the downward trend is likely to continue in the coming decades [7,8].

Because H. pylori infection is typically acquired during early childhood, most older adults have harbored the bacterium for several decades [9]. Consequently, they often exhibit advanced gastric mucosal damage, including severe atrophy, intestinal metaplasia, and an increased risk of gastric cancer [10,11]. Kamada et al. [2] reported that, even among individuals with H. pylori infection, the severity of gastric atrophy and intestinal metaplasia is lower in more recent birth cohorts. Although the underlying mechanisms remain unclear, this phenomenon may reflect changes in the gastric microenvironment influenced by factors such as shifts in coexisting microbiota, dietary patterns, alcohol consumption, or smoking behavior [12-14].

Additionally, older patients frequently have multiple comorbidities, including chronic kidney disease, cardiovascular disease, diabetes, and malignancies, which may modify both the natural history of H. pylori-associated diseases and the risk–benefit balance of eradication therapy [15]. Polypharmacy is common in this population, and the use of antithrombotic agents, antihypertensive agents, antihyperglycemic agents, or antipsychotic drugs can complicate treatment selection by increasing the risk of drug–drug interactions and adverse effects. These factors influence not only the choice and dosing of eradication regimens but also treatment adherence, tolerability, and ultimately, the likelihood of successful eradication. Therefore, the management of H. pylori infection in older adults requires a comprehensive assessment of comorbid conditions, concomitant medications, and individualized therapeutic strategies to optimize both efficacy and safety.

DIAGNOSIS IN OLDER ADULTS

Accurate diagnosis is essential before initiating H. pylori eradication therapy. In Japan, noninvasive tests such as the urea breath test (UBT) and the stool antigen test are widely used for both initial diagnosis and confirmation of eradication. However, several diagnostic challenges are particularly relevant in older patients.

The UBT can be used before and after eradication therapy, but the cutoff value for post-eradication assessment is typically higher than that used before treatment [16]. Moreover, the UBT is prone to false-positive results in patients with advanced gastric atrophy [5,17]. Since older adults often have long-standing H. pylori infection, they are more likely to exhibit severe atrophic gastritis, thereby increasing the risk of false-positive UBT results [17,18]. Consequently, post-eradication assessment of H. pylori infection in older patients is performed in a clinical context that is particularly susceptible to false positivity.

Older patients frequently receive proton pump inhibitors (PPIs) for the treatment of gastroesophageal reflux disease or for prophylaxis against antiplatelet therapy-associated ulcers [19]. In such cases, false-negative UBT results may occur, necessitating temporary discontinuation of PPIs before testing. Although the stool antigen test is considered less affected by PPIs because it directly detects bacterial antigens directly [20], several studies have reported reduced detection rates during PPI therapy [21,22], indicating that its diagnostic accuracy may also be compromised in this setting.

In routine clinical practice in Japan, endoscopy plays a central role in the management of older patients, serving not only diagnostic purposes but also functioning as a key component of gastric cancer screening programs [23,24]. Accordingly, the diagnosis of H. pylori infection is frequently integrated with endoscopic evaluation, particularly in individuals undergoing gastric cancer screening. In older patients, follow-up endoscopy after eradication therapy is especially recommended. Resolution of inflammation-associated erythema following eradication improves mucosal contrast, which may facilitate the detection of gastric cancer lesions that were previously obscured by active gastritis [25]. Furthermore, if post-eradication endoscopic findings differ from the characteristic features of post-eradication gastritis defined by the Kyoto classification, further diagnostic assessment using alternative testing modalities should be considered [26-30].

Since 2022, polymerase chain reaction (PCR)-based testing using gastric juice has been covered by the national health insurance system in Japan as a diagnostic modality for H. pylori infection [31]. Until recently, endoscopy-based diagnostic methods reimbursed in Japan included the rapid urease test, histological examination, and culture; however, all require gastric biopsy sampling [32]. Because biopsy-based procedures are inherently invasive, their use may be discouraged, particularly in elderly patients or in those receiving antiplatelet or anticoagulant therapy [33,34]. As a result, such tests have often been avoided in cases in which the diagnosis of infection is uncertain.

Gastric juice–based PCR testing offers several advantages, as it requires submission of gastric lavage fluid without the need for additional biopsy procedures. Moreover, its diagnostic accuracy, in terms of sensitivity and specificity, is comparable to that of culture-based methods. Importantly, PCR-based testing can be performed even during ongoing PPI or potassium-competitive acid blocker (P‑CAB) therapy and allows simultaneous assessment of antimicrobial susceptibility; in Japan, reimbursement is currently limited to the detection of clarithromycin resistance [31]. Given these advantages, gastric juice PCR testing is expected to be increasingly utilized in clinical practice, particularly in populations for whom invasive diagnostic procedures are less desirable.

TREATMENT CONSIDERATIONS

Indications and rationale

The benefits of H. pylori eradication therapy in older patients must be carefully balanced against potential risks, including drug-related adverse events and the presence of multiple comorbidities. In this context, the indications for eradication therapy can be conceptually categorized into three priorities: 1) conditions in which eradication itself constitutes disease-directed treatment; 2) secondary prevention of disease recurrence or metachronous disease; and 3) primary prevention of future disease (Fig. 1).

Representative conditions in which eradication therapy directly serves as disease-directed treatment include immune thrombocytopenic purpura (ITP) and gastric MALT lymphoma. For H. pylori-positive ITP, eradication therapy is recommended as first-line treatment in Japanese guidelines [35]. Given its relatively low invasiveness compared with alternative therapeutic options, eradication therapy should be prioritized whenever feasible [35,36]. Similarly, in patients with H. pylori-positive gastric MALT lymphoma confined to the stomach, eradication therapy induces lymphoma regression in approximately 70%– 80% of cases, representing a highly effective and minimally invasive therapeutic strategy [37,38].

Conditions targeted by secondary prevention through eradication therapy include gastric and gastroduodenal ulcers, as well as gastric cancer. In patients with gastroduodenal ulcers, eradication of H. pylori markedly reduces the risk of ulcer recurrence and is therefore strongly recommended to prevent relapse [19,39]. With respect to gastric cancer, multiple randomized controlled trials have demonstrated the benefit of eradication therapy for secondary prevention, particularly in patients who have undergone endoscopic treatment, such as endoscopic submucosal dissection (ESD) [3,40]. However, evidence supporting a prophylactic effect of eradication therapy against metachronous gastric cancer after surgical resection remains limited [41].

In contrast to secondary prevention, the role of eradication therapy as primary prevention in older adults requires more careful consideration. Given the relatively low annual incidence of gastric cancer among individuals with H. pylori infection (approximately 0.2%–0.3% per year) [42], routine implementation of eradication therapy in this population remains controversial, and careful individualized decision-making is warranted. From a primary prevention perspective, populationbased data from Hong Kong indicate that H. pylori eradication is associated with a reduced incidence of gastric cancer in older adults (≥60 years) compared with expected age- and sexmatched population rates, supporting a potential preventive benefit even in older individuals [43]. However, this evidence is derived from observational cohort studies, and robust prospective or randomized data specifically addressing primary prevention in older populations remain limited. Consequently, the overall strength of evidence is currently insufficient to support uniform recommendations for eradication solely for primary prevention in this age group. Accordingly, the indi-cation for eradication therapy in older patients should be individualized, considering chronological age, activities of daily living, comorbidities and past medical history, concomitant medications, patient preferences, and the potential risk of eradication-related adverse events.

Therapeutic regimens in Japan

In Japan, the selection of medications and dosing regimens for H. pylori eradication therapy has not been adjusted according to patient age. Standard first-line eradication therapy typically comprises a P‑CAB- or PPI-based triple regimen combined with amoxicillin and either clarithromycin or metronidazole for 7 days [4,5,32]. The most commonly used first-line regimen includes amoxicillin 750 mg twice daily, clarithromycin 200 mg or 400 mg twice daily, and vonoprazan 20 mg or a standard-dose PPI twice daily for 7 days; this regimen is also available as a fixed-dose combination package. In cases of treatment failure with the first-line regimen or documented clarithromycin resistance, second-line therapy generally comprises amoxicillin (750 mg twice daily), metronidazole (250 mg twice daily), and vonoprazan 20 mg or a standard-dose PPI twice daily for 7 days [5,32,44], and is likewise available as a combination package. For third-line eradication, triple regimens including sitafloxacin are frequently employed [6,45-49], whereas rifabutinbased triple regimens are often used as fourth-line therapy [50,51]. However, no consensus currently exists regarding the optimal dosing or duration of these later-line regimens [52].

Vonoprazan, a P‑CAB, provides more potent and sustained acid suppression than conventional PPIs and has been shown to achieve consistently high eradication rates irrespective of CYP2C19 genotype [53-55]. Accumulating evidence indicates that vonoprazan-based regimens demonstrate superior efficacy compared with PPI-based regimens across all phases of eradication therapy, with vonoprazan currently preferred over PPIs in most clinical settings in Japan [5,49,56-58].

To avoid unnecessary eradication therapy and improve treatment efficiency, susceptibility-guided eradication strategies are recommended whenever feasible [59,60]. Although data specifically evaluating susceptibility-guided treatment in older populations remain limited, this approach not only increases the likelihood of successful eradication but may also reduce the overall risk of eradication-related adverse events by minimizing repeated treatment courses.

SPECIAL ISSUES IN OLDER PATIENTS

Comorbid conditions

Renal and hepatic function should be carefully assessed before initiating H. pylori eradication therapy in older patients (Fig. 2). Renal impairment is common in older adults and can substantially influence eradication therapy, particularly with respect to drug selection, dosing, and the risk of adverse events [61-64]. Reduced renal clearance may increase systemic exposure to antibiotics, thereby necessitating close monitoring during treatment. Additionally, amoxicillin-associated deterioration of renal function has been reported in patients with pre-existing kidney disease, suggesting that cautious use, appropriate dose adjustment, and regular monitoring of renal function are advisable when prescribing amoxicillin-containing regimens to older patients with renal impairment [61].

In contrast, the impact of hepatic dysfunction on eradication therapy appears to be relatively limited [65]. Although the overall level of evidence remains weak, available studies suggest that eradication efficacy and the incidence of adverse events in patients with chronic hepatitis or compensated liver cirrhosis are broadly comparable to those observed in individuals without liver disease [65]. Nevertheless, in patients with advanced cirrhosis or hepatic failure, the indication for eradication therapy should be determined only after careful consideration of the patient’s overall prognosis and a comprehensive assessment of the potential benefits and risks of treatment.

Concomitant medications and drug interactions

Older patients frequently have multiple comorbidities and are often prescribed several concomitant medications; therefore, caution is required regarding potential drug–drug interactions during eradication therapy (Fig. 2).

Clarithromycin is metabolized via cytochrome P450 3A4 (CYP3A4), and co-administration with other drugs sharing this metabolic pathway warrants close attention [66]. Concomitant use with tolvaptan should generally be avoided [67]. Additionally, the risk of rhabdomyolysis may be increased when clarithromycin is combined with certain statins, particularly in patients with underlying renal impairment [68]. Calcium channel blockers, such as nifedipine and verapamil, may also exhibit enhanced hypotensive effects when administered concurrently [69].

When metronidazole is included in the eradication regimen, special caution is required in patients receiving warfarin [70,71]. Concomitant use of metronidazole and warfarin has been associated with excessive prolongation of prothrombin time. In such cases, switching to an alternative anticoagulant should be considered. When coadministration is unavoidable, dose reduction of warfarin and close monitoring of coagulation parameters are mandatory.

Adherence

Adherence support is essential in older patients, as cognitive decline, physical frailty, and polypharmacy may compromise adherence to eradication regimens [72]. Because the duration of eradication therapy is typically 1–2 weeks, appropriate support measures can substantially improve treatment completion rates [73,74]. When concerns regarding adherence arise, involvement of family members or caregivers to assist with medication administration is strongly recommended. In Japan, fixeddose combination packages available for eradication therapy have been shown to improve medication adherence and are particularly useful in older populations [75]. Although infrequently used in Japan, fixed-dose combination regimens such as bismuth-containing quadruple therapy (e.g., Pylera®) may confer adherence-related benefits in clinical settings where they are employed [76].

Safety and tolerability

Common short-term adverse events associated with eradication therapy for H. pylori infection include diarrhea, loose stools, dysgeusia, skin rash, stomatitis, glossitis, and hemorrhagic colitis [77]. Other reported adverse events include abdominal pain, headache, nausea, vomiting, dizziness, and abnormalities in liver function tests. Additionally, clinically relevant adverse reactions may result from drug–drug interactions, which can lead to increased plasma concentrations of concomitant medications; therefore, careful attention to potential interactions is required. With respect to long-term outcomes, eradication therapy has been associated with the development or exacerbation of gastroesophageal reflux disease, as well as metabolic changes such as weight gain and dyslipidemia [78-80]. Severe adverse events are uncommon but may include antibiotic-associated colitis [80].

Evidence regarding adverse events associated with eradication therapy for H. pylori infection in older patients is limited but suggests good tolerability. Two observational studies reported no significant differences in the incidence of adverse events between older (≥65 years) and younger patients receiving either first- or second-line eradication therapy [81,82]. Overall, these findings suggest that the incidence of eradication therapy-related adverse events is comparable across age groups, supporting its tolerability in older adults.

CONCLUSION

In routine clinical practice, clinicians may hesitate when deciding whether to offer H. pylori eradication therapy to older patients. However, this review indicates that eradication therapy is generally safe in older adults and may confer benefits in terms of gastric cancer or peptic ulcer prevention. Therefore, advanced age alone should not be considered a contraindication to treatment. Nevertheless, the indication for eradication therapy should be individualized, considering comorbid conditions, potential drug–drug interactions with concomitant medications, overall life expectancy, and the specific diseases targeted for eradication.

Notes

Availability of Data and Material

Data sharing is not applicable to this article, as no datasets were generated or analyzed during the study.

Conflicts of Interest

Hidekazu Suzuki, a contributing editor of the Korean Journal of Helicobacter and Upper Gastrointestinal Research, was not involved in the editorial evaluation or decision to publish this article. Hidekazu Suzuki has received research funding from Tohso Co., Ltd., and honoraria from Astellas Pharmaceutical Company, Otsuka Pharmaceutical Co., Ltd., and Takeda Pharmaceutical Co., Ltd. Hideki Mori declares no conflicts of interest.

Funding Statement

None

Acknowledgements

None

Authors’ Contribution

Conceptualization: Hideki Mori, Hidekazu Suzuki. Literature search: Hideki Mori. Supervision: Hidekazu Suzuki. Writing—original draft: Hideki Mori. Writing—review & editing: Hidekazu Suzuki. Approval of final manuscript: Hideki Mori, Hidekazu Suzuki.

Fig. 1.

Conceptual framework for H. pylori eradication in the older adults. The indications for eradication therapy are categorized as eradication as disease-directed therapy, secondary prevention, and primary prevention, and treatment decisions in older adults should be individualized based on clinical factors, including age, activities of daily living, frailty, comorbidities, concomitant medications, life expectancy, and patient preference. MALT, mucosa-associated lymphoid tissue; ESD, endoscopic submucosal dissection.

Fig. 2.

Diagnostic and therapeutic considerations in older adults. Diagnostic accuracy may be influenced by gastric atrophy and PPI use, affecting the UBT and stool antigen test, whereas endoscopy plays a central role in estimating infection status. Vonoprazan-based regimens are preferred without age-based dose adjustment, with careful attention to drug–drug interactions and renal function. Adherence support, including fixed-dose combination packages and caregiver involvement, is essential for successful eradication. UBT, urea breath test; PPI, proton pump inhibitor; PCR, polymerase chain reaction; MTZ, metronidazole; CAM, clarithromycin; CCBs, calcium channel blockers.

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