Randomized study of Helicobacter pylori eradication therapy and proton pump inhibitor monotherapy for idiopathic thrombocytopenic purpura

Helicobacter pylori (HP) eradication therapy is a useful treatment for idiopathic thrombocytopenic purpura (ITP). Some investigators have also reported the effects of proton pump inhibitor (PPI) monotherapy on ITP. We performed a randomized study of HP eradication therapy and PPI monotherapy on ITP. Four of nine patients achieved complete remission (CR), two of nine achieved partial remission (PR) in HP eradication therapy, three of eight achieved CR, and two of eight achieved PR in PPI monotherapy. No significant differences were observed in the CR + PR of these patients between HP eradication therapy and PPI monotherapy. As for cost comparisons, HP eradication therapy is cheaper than PPI monotherapy, but it is less effective.

The human gut microbiome plays an important role both in health and disease. Use of antibiotics can alter gut microbiota composition, which can lead to various deleterious events. Here we report a whole genome sequencing metagenomic/genomic study of the intestinal microbiota changes caused by Helicobacter pylori (HP) eradication therapy. Using approaches for metagenomic data analysis we revealed a statistically significant decrease in alpha-diversity and relative abundance of Bifidobacterium adolescentis due to HP eradication therapy, while the relative abundance of Enterococcus faecium increased. We have detected changes in general metagenome resistome profiles as well: after HP eradication therapy, the ermB, CFX group, and tetQ genes were overrepresented, while tetO and tetW genes were underrepresented. We have confirmed these results with genome-resolved metagenomic approaches. MAG (metagenome-assembled genomes) abundance profiles have changed dramatically after HP eradication therapy. Focusing on ermB gene conferring resistance to macrolides, which were included in the HP eradication therapy scheme, we have shown a connection between antibiotic resistance genes (ARGs) and some overrepresented MAGs. Moreover, some E. faecium strains isolated from stool samples obtained after HP eradication have manifested greater antibiotic resistance in vitro in comparison to other isolates, as well as the higher number of ARGs conferring resistance to macrolides and tetracyclines.

BackgroundAt present, eradication regimens for non-Helicobacter pylori Helicobacter (NHPH) have not been established yet. We investigated effectiveness of the standard triple-drug combination therapy for Helicobacter pylori eradication and of a proton pump inhibitor (PPI) monotherapy in eradication of NHPH.MethodsSubjects were the patients who were diagnosed with NHPH-infected gastritis based on microscopic findings, helical-shaped organisms obviously larger than Helicobacter pylori, in the gastric mucosal specimens using Giemsa staining at Kenwakai Hospital between November 2010 and September 2021, whose NHPH species were identified by polymerase chain reaction (PCR) analysis of urease genes in endoscopically-biopsied samples, and who consented to NHPH eradication with either the triple-drug combination therapy for one week or a PPI monotherapy for six months. Six months after the completion of eradication, its result was determined with esophagogastroduodenoscopy, microscopic examination, and PCR analysis. In cases of unsuccessful eradication, a second eradication with the other therapy was suggested to the patient.ResultsPCR analysis detected NHPH in 38 patients: 36 as Helicobacter suis and two as Helicobacter heilmannii/Helicobacter ailurogastricus. Fourteen Helicobacter suis-infected and one Helicobacter heilmannii/Helicobacter ailurogastricus-infected patients requested eradication therapy. The triple-drug combination therapy succeeded in four of five patients, while the PPI monotherapy succeeded in five of 10 patients. Three of five patients who had been unsuccessful with the latter therapy requested the triple-drug combination therapy as the second eradication and all three were successful. In total, the triple-drug combination therapy succeeded in seven out of eight (87.5%) attempted cases, while the PPI monotherapy in five out of 10 (50%) attempted cases.ConclusionsIn NHPH eradication, the triple-drug combination therapy was considered to be effective to some extent and to become the first-line therapy. While, although less successful, PPI monotherapy appeared to be a potentially promising option particularly for patients with allergy or resistance to antibiotics. Effectiveness of PPI monotherapy may be attributed to hyperacid environment preference of Helicobacter suis and PPI’s acid-suppressive effect. Additionally, male predominance in NHPH-infected gastritis patients may be explained by gender difference in gastric acid secretory capacity. However, further evidence needs to be accumulated.Study registrationThis study was approved by the Research Ethics Committee of Kenwakai Hospital (No. 2,017,024).

Idiopathic thrombocytopenic purpura (ITP) is the autoimmune-mediated destruction of platelets. ITP is a diagnosis of exclusion after other identifiable etiologies have been ruled out. After the first report by Gasbarrini et al. (1998) showing rising platelet counts in ITP patients following Helicobacter pylori (HP) eradication therapy, there is growing evidence that highlights the role of HP in triggering ITP. However, the exact pathophysiology of HP-associated ITP is still unclear, but many theories have been implicated in this regard. According to various reports, the postulated mechanisms for the role of HP in cITP include molecular mimicry, increased plasmacytoid dendritic cell numbers, phagocytic perturbation, and variable host immune response to HP virulence factors. One famous theory suggested molecular mimicry between platelet surface antigen and bacterial virulence factor, i.e. cytotoxin-associated gene A (CagA). It is thought that a chronic inflammatory response following an HP infection induces the host autoantibodies' response against CagA, which cross-reacts with platelet surface glycoproteins; therefore, it may accelerate platelet destruction in the host reticuloendothelial system. However, further studies are mandated to better understand the causal link between ITP and HP and study the role of biogeography. Nowadays, it is recommended that every patient with ITP should undergo HP diagnostic testing and triple therapy should be administered in all those candidates who test positive for HP infection. In our review, there were a few pregnant female ITP patients who took HP eradication therapy mainly after 20 weeks of gestation without maternal or fetal worst outcomes. However, large-scale studies are advisable to study the adverse fetal outcomes following triple therapy use.

Helicobacter pylori eradication therapy is effective in the treatment of early-stage H pylori–positive gastric diffuse large B-cell lymphomas

The number of patients who undergo Helicobacter pylori (HP) eradication therapy has been increasing since it became covered by insurance in Japan. As such, an increasing number of patients develop drug eruption as a result of HP eradication therapy. In the present study, we describe the clinical course of 28 patients who were treated at our hospital for drug eruption following HP eradication therapy between April 2008 and March 2016. The majority of the patients were women (21 women, 7 men). The average length of time from the start of treatment to the onset of eruption was 7.6 days. A drug-induced lymphocyte stimulation test (DLST) was performed in 10 patients. Amoxicillin was the most common cause of eruption, with 6 patients testing positive. Patients who were considered likely to have developed sensitivity prior to the treatment required the systemic administration of steroids. On the other hand, symptoms were relieved with topical steroids in some of the patients who were considered likely to have developed sensitivity during the course of treatment. Since penicillin antibiotics have long been used, some patients may have become sensitized without being aware of this. Our findings highlight the need for the careful management of patients developing sensitivity prior to treatment as they require the systemic administration of steroids.

BackgroundHelicobacter pylori (HP) has been considered to be one of the primary causes of gastric mucosa-associated lymphoid tissue (MALT) lymphoma since 1993. Low-grade gastric MALT lymphoma with HP is widely treated with HP eradication therapy, according to each specific clinical situation. However, several studies and guidelines indicate that the modified HP eradication therapy is also valid for HP-negative gastric MALT lymphoma. The aim of this study was to perform a meta-analysis of the clinical efficacy of the modified HP eradication therapy for gastric MALT lymphoma without HP.MethodsWe searched studies that reported the response rate of the modified HP eradication therapy regimen for gastric MALT lymphoma without HP by using PubMed, Medline, and Ebsco from January 1971 until February 2019. All statistical analyses were carried out using R 3.5.3 (Mathsoft Company, Cambridge, MA, USA). The pooled response rate was expressed as a decimal. The heterogeneity test was performed using the I-squared (I2) statistic.ResultsA total of 14 studies were selected with a total of 148 patients with HP-negative gastric MALT lymphoma. The overall pooled response rate was 0.38 (95% confidence interval [CI]: 0.29–0.47). The combined estimate is I2 = 57% (P < 0.01). The study subjects were categorized by factors (area of patients). The pooled response rate of the sub-groups (Korea, Japan, China, and Western countries) was 0.63 (95% CI: 0.50–0.76), 0.16 (95% CI: 0.05–0.30), 0.38 (95% CI: 0.20–0.55), and 0.57 (95% CI: 0.08–1.00). The response rate showed that the modified HP eradication therapy was effective for patients with HP-negative gastric MALT lymphoma, especially in Korea and Western countries.ConclusionTherefore, the modified HP eradication therapy can be considered an optional therapy for patients with low-grade HP-negative gastric MALT lymphoma. However, several limitations were revealed in the meta-analysis. Further systematic reviews and research are required.

To investigate the effect of Helicobacter pylori (HP) eradication therapy on salivary pepsin concentration in laryngopharyngeal reflux (LPR) patients with HP infection. A total of 477 patients with suspected LPR were enrolled from June 2020 to September 2021. Reflux symptom index, reflux finding score, the positive rates and disintegrations per minute values of HP infection detected by 14C urea breath test and salivary pepsin concentrations analyzed using enzyme-linked immunosorbent assay were compared in LPR patients and non-LPR patients with or without HP infection. HP-positive patients were treated with HP eradication therapy while HP-negative patients with PPI therapy. The scores of nagging cough (0.88 vs. 0.50, P = 0.035), erythema or hyperemia (1.93 vs. 1.78, P = 0.035) and vocal fold edema (1.04 vs. 0.85, P = 0.025) were higher in the LPR (+) Hp (+) subgroup than in LPR (+) Hp (-) subgroup. The concentrations of salivary pepsin in the Hp (+) subgroup were higher than in the Hp (-) subgroup either in LPR patients (75.24ng/ml vs. 61.39ng/ml, P = 0.005) or the non-LPR patients (78.42ng/ml vs. 48.96ng/ml, P = 0.024). Compared to baseline (before treatment), scores of nagging cough (0.35 vs. 0.84, P = 0.019) and erythema or hyperemia (1.50 vs. 1.83, P = 0.039) and the concentrations of salivary pepsin (44.35ng/ml vs. 74.15ng/ml, P = 0.017) in LPR patients with HP infection decreased after HP treatment; yet, this was not observed for the LPR patients without HP infection treated with PPI only (P > 0.05). HP infection may aggravate the symptoms and signs of LPR patients, partly by increasing their salivary pepsin concentration.

Helicobacter pylori (HP) infection is considered to play a role in the pathogenesis of chronic spontaneous urticaria (CSU). However, the efficacy of HP eradication therapy on CSU symptom improvement has not been well established. This meta-analysis was conducted to estimate the association between HP infection and CSU and to evaluate whether HP eradication therapy benefits patients with CSU. In October 2018, we searched databases for studies investigating the efficacy of HP eradication therapy for patients with CSU. Risk ratios (RRs) and 95% confidence intervals (CIs) were pooled using random effects models. The meta-analysis included 22 studies with a total of 1385 patients with CSU. When comparing the spontaneous remission of urticarial symptom in patients with HP-positive to HP-negative patients, HP-negative patients showed significantly higher spontaneous remission of urticarial symptoms. (risk ratio 0.39; 95% confidence interval: 0.19-0.81). Among HP-positive CSU patients, remission of CSU was more likely shown in HP eradication therapy group compared to untreated group, aside from achieving HP elimination (risk ratio 2.10; 95% confidence interval: 1.20-3.68). However, there was no significant difference in the remission of CSU whether antibiotic therapy was successful in eradication of HP or not (risk ratio 1.00; 95% confidence interval: 0.65-1.54). The results of this meta-analysis show that HP might be associated with the occurrence and persistence of CSU. The effectiveness of HP eradication therapy in suppressing CSU symptoms was significant. Interestingly, we found that resolution of CSU was not associated with successful eradication of HP infection. CSU Patients who were undergone antibiotic therapy for HP eradication showed significant higher CSU remission with or without HP eradication. Further studies are recommended to evaluate the mechanisms associated with relation of HP with CSU.

Dear Sir, Steroid therapy is the first-line treatment for autoimmune thrombocytopenias requiring immunosuppressive therapy. Splenectomy, thrombopoietin receptor agonists and rituximab are considered treatments for relapsed thrombocytopenias. However, for some years it has been proposed that Helicobacter pylori (H. pylori) eradication therapy could be used to treat infected patients with chronic idiopathic thrombocytopenia (ITP). Indeed, in 1998 some Japanese authors reported the case of an elderly patient with chronic ITP who was treated with a proton pump inhibitor because of a concomitant peptic ulcer and who had a significant increase in platelet count1. Subsequently, Gasbarrini et al.2 reported significant increases in platelet counts in eight of eleven patients with ITP in whom H. pylori infection was successfully eradicated: this increase was accompanied, in six of the eight patients, by the disappearance of antiplatelet antibodies. Since then, H. pylori eradication has been variably associated with substantial and persistent improvements of platelet count in patients with ITP. The percentages of partial and complete responses reported in various studies and meta-analyses are around 50% in Japanese and Italian populations and lower in trials in France, Spain and North America3. Following these results, ITP is currently one of the two extra-intestinal pathologies for which H. pylori eradication is indicated according to the Third Consensus Conference in Maastricht and a search for H. pylori is listed among the first-line tests for the diagnosis of ITP in the new guidelines for the diagnosis and treatment of ITP in the recent International Consensus Report4. As yet no distinctive clinical characteristics or specific factors predicting the platelet response to infection eradication therapy have been identified; it does, however, seem that ITP of long duration and profound thrombocytopenia (platelet count below 30,000/μL) respond less well to eradication therapy, although this aspect was not systematically investigated in most of the studies so far, in which patients treated usually had moderate thrombocytopenia. In this study we, therefore, evaluated whether the duration of thrombocytopenia prior to treatment could influence the effect of H. pylori eradication therapy in patients with ITP. We analysed 46 consecutive patients with ITP (platelet counts below 30,000/μL) who were seen at our Haematology Department between 2001 and the end of 2008 and for whom follow-up data for at least 1 year were available. The diagnosis of ITP was made by excluding other possible causes of thrombocytopenia such as EDTA-related pseudothrombocytopenia, infections by hepatitis C virus and human immunodeficiency virus, drugs, autoimmune diseases and lymphoproliferative disorders. Bone marrow studies and chromosome mapping was carried out in patients over 60 years old in order to exclude possible myelodysplastic syndromes. Results from 40 of the 46 patients initially enrolled could be evaluated; two cases of pregnancy-related ITP with a follow-up shorter than 1 year were excluded and four cases were lost from follow-up. The patients’ median age was 52.2 years (range, 15–87 years). There were 20 males and 20 females, 38 Caucasians and two patients from South America. The median platelet count at the time of the first observation was 9,000/μL (range, 1,000–24,000/μL). For the 40 patients analysed it was determined whether tests for H. pylori infection had been conducted and the mean duration of the thrombocytopenia prior to the first observation in our Division. Furthermore, the behaviour of the platelet counts was compared between H. pylori-positive patients who received eradication therapy and patients who were H. pylori-negative. Thirty-four of the patients had new-onset ITP, while six patients had a recurrence of thrombocytopenia that had been diagnosed and followed in other centres. Of these six patients, four had recurrences after treatment with steroids and immunoglobulins and two had relapsed after splenectomy. Investigations for H. pylori had been carried out in 22/40 of the patients (55%); 12/22 (54.5%) patients were positive and 10/22 (45.5% ) negative. The mean platelet count at the time of the first observation was similar between the H. pylori-positive and -negative patients (9,583.3±3,987.6/μL versus 12,000±9,568.4/μL; p=0.74). The 22 patients in whom H. pylori was looked for included three with recurrent ITP at the time of first observation; it is interesting to note that all three of these patients were positive for the infection. All the patients had received immunosuppressive therapy (steroids or steroids combined with immunoglobulins), given their marked thrombocytopenia. Eradication therapy in H. pylori-positive patients was carried out within 4 months of the first observation and consisted of amoxicillin 1 g twice daily and clarithromycin 500 mg twice daily, both for 7 days, together with omeprazole 20 mg twice a day for 14 days. The efficacy of the eradication therapy was evaluated at least 12 weeks after its completion. A response was defined as a platelet count of 100,000/μL or more, 1 year after the first observation without the need for further treatment. First-line immunosuppressive therapy led to a complete remission in 11 patients (57.14%); 6/12 (50%) patients were H. pylori-positive and 5/10 (50%) were H. pylori-negative. The complete remission was maintained for 1 year in 3/6 H. pylori-positive patients in whom the infection was eradicated and in 4/5 of those who were H. pylori negative. One H. pylori-positive patient who was unresponsive to immunosuppressive therapy was resistant to the eradication treatment. There were no statistically significant differences at 1 year between H. pylori-positive and -negative patients, with regards to the type of response and age, sex or median platelet count at the time of diagnosis. However, in H. pylori-positive patients there was a statistically significant (p=0.01) inverse correlation between the duration of the thrombocytopenia before eradication and the response at 1 year: this was also confirmed in multivariable analysis. The mean duration of the thrombocytopenia in H. pylori-positive patients was longer than that of uninfected patients (52.7±116.1 months versus 2.8±1.9 months), given that all the patients with relapsed thrombocytopenia at the time of the first observation belonged to the infected group. However, even when the cases with recurrent ITP at first observation were excluded, the mean duration of thrombocytopenia was longer in the H. pylori-positive patients than in the H. pylori-negative ones (4.3±2.1 months versus 2.8±1.9; p=0.04). The results of our study do not show a benefit of eradicating H. pylori infection in patients with marked thrombocytopenia, since the percentage of complete remissions was about 27% at 1 year, in line with published data. However, our study did confirm that early eradication therapy, started promptly when the thrombocytopenia was still moderate, was more effective: reducing the bacterial load and blocking the initial platelet destruction independent of the production of auto-antibodies could decrease the formation of cross-reacting antibodies, thus switching off the autoimmune mechanism that perpetuates the thrombocytopenia. Alternatively, increased clearance by the reticulo-endothelial system means that the bacterial antigens are presented to T-lymphocytes which, stimulated, amplify the humoral response against H. pylori. Somatic mutations of the antibody repertoire could lead to the formation of a second generation of immunoglobulins able to recognise bacterial antigens bound to the platelets or which cross-react with platelet antigens, increasing platelet destruction. In cases of long-lasting ITP it is possible that, following further somatic mutations, a third class of antibodies develops which lose antigenic specificity against bacterial antigens but maintain reactivity against platelets: in this phase, eradication therapy would be totally ineffective5. In conclusion, on the basis of our results, the promptness of investigations for the presence of H. pylori infection and eradication treatment in positive cases could explain, alongside the severity of the thrombocytopenia, possible virulence factors of the different strains of H. pylori and particular genetic features of the infected individuals, some of the differences in the published results concerning the efficacy of such eradication treatment.

The stomach is the most common extranodal site of non-Hodgkin lymphoma (NHL) accounting for 7.1 to 10% of adult NHL (Danzon et al., 2009). The most frequent histotypes of gastric lymphomas are MALT lymphomas that arise from the stomach-associated lymphatic tissue and the Diffuse Large B-Cell Lymphoma (DLBCL) (Koch et al., 2001). Several studies have observed that in recent years both gastric-NHL incidence and survival are increasing (Danzon et al., 2009). Furthermore, the management of gastric lymphomas has changed during the last two decades with a strong reduction of surgery in flavor to conservative treatments (Yoon S.S. et al., 2004). Indeed, the progress in biologic understanding of the pathogenesis, the introduction of Helicobacter pylori (HP) eradication therapy and the introduction of conservative treatment have definitely changed the approach to the disease and gastrectomy is no longer the first choice (Fischbach, 2010). The role of HP is a consolidated finding and several studies have confirmed that a simple antibiotic therapy (AT) for HP eradication is an effective treatment for MALT lymphomas with limited extension (Fischback et al., 2004), whereas, for advanced gastric lymphomas, the golden standard of treatment is the antineoplastic chemotherapy with alkylating agents in monochemotherapy such as Clorambucil for MALT lymphomas and polichemotherapy together with immunotherapy such as R-CHOP for DLBCL (Zucca & Dreyling, 2010). The loco-regional staging of gastric lymphomas with limited disease is important in order to better understand how to treat patients and endoscopic ultrasound (EUS) technique plays in this context a pivotal role by giving information for the prevision of response to HP eradication therapy since this therapy has shown to induce a high percentage of histological remission (up to 88%) when the disease is confined to mucosa and submucosa (Caletti et al., 2002). However, the importance of EUS in assessing the response to treatment and the follow-up is controversial. During the last decade, some reports indicated the importance of EUS in evaluating the response to treatment and also in long-term follow-up of gastric lymphomas with limited disease (Yeh et al., 2003), whereas other recent reports indicated the importance of EUS also in the follow-up of local-advanced MALT lymphoma (Pavlovic et al., 2005). That notwithstanding, the latest ESMO clinical guidelines for diagnosis, treatment and follow-up

Eradication therapy occupies a key place in the treatment of Helicobacter pylori (HP) infections. The presence of HP in the human body can affect the composition of gut microbiota in several ways, including the direct effect of infection or as a consequence of HP eradication regimes. Nowadays, one of the measures to increase the eradication therapy efficacy and reduce the probability of antibiotic-associated disorders is the strategy of gut microbiome modulation. The article discusses the HP effects on the gut microbiota, methods for probiotic correction in conditions of HP infection and eradication therapy. Probiotics have a destructive effect on the biofilm formed by HP, and its destruction can increase the efficacy of antibacterial therapy. The most rational regimen is the administration of probiotics before and during eradication, or at least for two weeks. At the same time, probiotics should include a variety of bacterial strains with proven efficacy and a high safety profile. KEYWORDS: Helicobacter pylori, microbiota, eradication therapy, probiotics, probiotic correction, antibiotic-associated disorders, inulin. FOR CITATION: Osipenko M.F., Zhuk E.A., Drobysheva V.P., Litvinova N.V., Livzan M.A., Gaus O.V. Probiotics in the Helicobacter pylori eradication therapy. Russian Medical Inquiry. 2023;7(5):274–282 (in Russ.). DOI: 10.32364/2587-6821-2023-7-5-5.

Amoxicillin sensitization rate in patients with eruptions after Helicobacter pylori eradication therapy

Several recent studies have suggested that an association exists between Helicobacter pylori (HP) eradication and improvement in platelet count in a significant proportion of patients with idiopathic thrombocytopenic purpura (ITP). In this controlled study, we prospectively examined adult patients with chronic ITP for HP infection, and assessed the effect of HP eradication on platelet count. One hundred forty-two consecutive Iranian patients with chronic ITP were assessed. Those who met the criteria and had platelet counts >30 x 10(9)/L within the medication-free screening month were enrolled (n = 129; 66 females; mean age, 29.2 +/- 7.0 years). HP-positive patients received a 2-week course of triple HP eradication therapy (i.e., amoxicillin, clarithromycin, and omeprazole) and were followed for 48 weeks. An ITP response was defined as a platelet count of >100 x 10(9)/L 24 weeks after treatment, together with an increase in the platelet count >30 x 10(9)/L over the baseline value. HP infection was detected in 79 (61%) patients. HP-positive patients were significantly older than HP-negative subjects (P = 0.018). HP eradication was successful in 87% (62/71) of those who completed the eradication therapy. Whereas 48% (30/62) of HP-eradicated patients showed an ITP response, no HP-negative patient had an ITP response. The ITP response persisted for 48 weeks in 93% (28/30) of the responders. The ITP responders had a shorter disease duration than the nonresponders (P = 0.002). The management of mild-to-moderate chronic ITP in Iranian patients, especially those with a recent onset of disease, should include an investigation for and eradication of infection with HP.

Potassium-Competitive Acid Blockers (P-CABs) have been used in Helicobacter pylori (H. pylori) eradication therapies in recent years. However, the efficacy and safety of P-CABs compared to Proton-Pump Inhibitors (PPIs) in this setting remain controversial. The efficacy and safety of P-CABs and PPIs for H. pylori eradication were compared in a meta-analysis based on a systematic literature search of major electronic databases for relevant Randomized Controlled Trials (RCTs). Seven studies and 1,168patients were included. The pooled eradication rate determined by Intention-To-Treat (ITT) analysis was90.2% for P-CAB-based and 75.5% for PPI-based triple therapy (pooled RR [95%CI]=1.17[1.08-1.28], p < 0.001). The Per-Protocol (PP) analysis also demonstrated significant superiority of P-CABs (pooled eradication rate=92.4%vs.77.8%; pooled RR [95%CI]=1.14[1.03-1.26], p < 0.01). In a subgroup evaluation, P-CABs were significantly better than PPIs as a first-line eradication therapy, in both the ITT analysis (pooled eradication rate=91.8%vs.76.4%; pooled RR [95%CI]=1.18 [1.10-1.28], p < 0.0001) and the PP analysis (pooled eradication rate=93.0%vs.78.6%; pooled RR [95%CI]=1.13[1.02-1.26], p < 0.05). However, P-CABs were not superior to PPIs when administered as salvage therapy, as determined in the ITT (75.0%vs.66.0%, pooled RR [95%CI]=1.11[0.69-1.78], p=0.66) and PP (85.7%vs.70.0%, pooled RR [95%CI]=1.20[0.82-1.75], p=0.34) analyses. In a subgroup analysis limited to Japanese patients, both the ITT analysis (pooled eradication rate=89.6%vs.73.9%; RR [95%CI]=1.21[1.14-1.29], p < 0.01) and the PP analysis (pooled eradication rate=92.0%vs.75.7%; RR[95%CI]=1.18[1.06-1.32], p < 0.01) showed that P-CABs were significantly superior compared to PPIs as triple eradication therapy. However, in the subgroup analysis of patients from other countries, there was no significant difference in either the ITT analysis (pooled eradication rate=93.8%vs.85.2%; RR[95%CI]=1.10[0.99-1.22], p=0.07) or PP analysis (pooled eradication rate=95.0%vs.90.8%; RR[95%CI]=1.05[0.98-1.14], p=0.17). The incidence of adverse events associated with the two regimens did not significantly differ (P-CABsvs.PPIs: 33.6%vs.40.0%; RR [95%CI]=0.84 [0.71‒1.00], p=0.05). The incidence of serious adverse events and dropout rate due to adverse events also did not differ (p=0.44 and p=0.67, respectively). The efficacy of P-CAB-based triple therapy is superior to that of PPI-based triple therapy as a first-line approach to H. pylori eradication, particularly in Japanese patients. As salvage therapy, the efficacy of the two treatments did not significantly differ. The tolerability of P-CAB-based and PPI-based triple therapy was comparable, as was the incidence of adverse events.