Diagnostics of pathogenic <i>Helicobacter pylori</i> strains: is this a potential solution for ungrounded eradication therapy?

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.

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.

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.

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.

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.

Family History As a Positive Prognostic Factor in Gastric Cancer

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.

BackgroundHelicobacter pylori infection and a family history of gastric cancer are the main risk factors for gastric cancer. Whether treatment to eradicate H. pylori can reduce the risk of gastric cancer in persons with a family history of gastric cancer in first-degree relatives is unknown.MethodsIn this single-center, double-blind, placebo-controlled trial, we screened 3100 first-degree relatives of patients with gastric cancer. We randomly assigned 1838 participants with H. pylori infection to receive either eradication therapy (lansoprazole [30 mg], amoxicillin [1000 mg], and clarithromycin [500 mg], each taken twice daily for 7 days) or placebo. The primary outcome was development of gastric cancer. A prespecified secondary outcome was development of gastric cancer according to H. pylori eradication status, assessed during the follow-up period.ResultsA total of 1676 participants were included in the modified intention-to-treat population for the analysis of the primary outcome (832 in the treatment group and 844 in the placebo group). During a median follow-up of 9.2 years, gastric cancer developed in 10 participants (1.2%) in the treatment group and in 23 (2.7%) in the placebo group (hazard ratio, 0.45; 95% confidence interval [CI], 0.21 to 0.94; P=0.03 by log-rank test). Among the 10 participants in the treatment group in whom gastric cancer developed, 5 (50.0%) had persistent H. pylori infection. Gastric cancer developed in 0.8% of participants (5 of 608) in whom H. pylori infection was eradicated and in 2.9% of participants (28 of 979) who had persistent infection (hazard ratio, 0.27; 95% CI, 0.10 to 0.70). Adverse events were mild and were more common in the treatment group than in the placebo group (53.0% vs. 19.1%; P<0.001).ConclusionsAmong persons with H. pylori infection who had a family history of gastric cancer in first-degree relatives, H. pylori eradication treatment reduced the risk of gastric cancer. (Funded by the National Cancer Center, South Korea; ClinicalTrials.gov number, NCT01678027.)

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.

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 infection in children: recommendations for diagnosis and treatment.

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.

BackgroundHelicobacter pylori (H. pylori) eradication therapy has been shown to reduce the risk of gastric cancer in patients who have a family history of gastric cancer in first-degree relatives. The aim of this study was to assess the cost-effectiveness of H. pylori eradication therapy in a select population in the People's Republic of China.MethodsA Markov model was applied to evaluate the cost-effectiveness of H. pylori eradication therapy. The long-term costs of H. pylori eradication therapy were calculated from the Chinese perspective. Health outcomes were measured by quality-adjusted life years (QALYs). Epidemiological information and health utilities used in the model were collected from published literatures or statistical bureaus. A sensitivity analysis was conducted to explore the influence of parameters on the uncertainty of the model.ResultsCompared with the no eradication therapy group, H. pylori eradication therapy prolonged an average of 4.52 QALYs (32.64 QALYs vs 28.12 QALYs) and saved $3227.07 ($2472.83 vs $5699.90). The cost-effectiveness analysis demonstrated that no H. pylori eradication therapy cost more and produced less QALYs. It was dominated by H. pylori eradication therapy. The one-way sensitive analyses proved that the results were robust to the fluctuations of the input parameters.ConclusionH. pylori eradication therapy not only reduced the risk of gastric cancer in first-degree relatives of patients with gastric cancer but also was an economical strategy with lower costs and greater efficacy.

Effective eradication of Helicobacter pylori infection is an important means to reduce the risk of precancerous changes in the gastric mucosa and prevention of gastric cancer. A search for non-invasive diagnostic tools for Helicobacter pylori infection, evaluation of the effectiveness of eradication remains of high importance.The aim of the study was to assess an informative value of detecting pepsinogen I and II as well as serum antibodies to Helicobacter pylori while assessing an efficacy of treated chronic Helicobacter gastritis and identifying preneoplastic changes in the stomach mucosa. There enrolled 113 male patients with chronic gastritis aged 41 to 76, average age- (56.7±0.7) years. Examination of patients was carried out at admission to the clinic, as well as at 2 and 12 months after administering a standard eradication therapy. It was found that Helicobacter pylori infection was detected in 101 (89.4%) patients. Groups of patients with effective eradication therapy were noted. A time-dependent level of antibodies to Helicobacter pylori, as well as measured concentration of pepsinogen I and II after the onset of eradication treatment were determined. Which were analyzed in connection with the results of histology examination of gastric mucosa biopsy specimens and expression of oncoproteins Ki-67, Bcl-2, c-erbB-2, p16 in the gastric mucosa depending on efficacy of eradication therapy. It is shown that effective eradication therapy was characterized by significantly decreased serum level of IgG antibodies to Helicobacter pylori 2 months after the onset of treatment. Moreover, a significantly decreased pepsinogen II and serum IgG antibodies to Helicobacter pylori during eradication therapy were accompanied by a significant decrease in Ki-67 expression in the gastric epithelium. Decreased concentration of pepsinogen II within the first year after Helicobacter pylori eradication therapy was due to a greater decrease in activity of inflammatory changes in the gastric mucosa than to dynamic changes in gastric atrophy and metaplasia. An inverse relation between the serum level of pepsinogen I and atrophy as well as intestinal metaplasia within the gastric mucosa were found.

Lynch syndrome (LS) is an inherited disorder associated with an increased risk of colorectal and extracolonic malignancies, including gastric cancer (GC). This study quantifies the association between specific risk factors and GC development in patients with LS. We searched the PubMed and Scopus databases for prospective and retrospective cohort studies that evaluated patients with genetically confirmed LS and reported associations between demographic, clinical, or genetic characteristics and GC. We conducted a meta-analysis to pool risk ratios (RR) for key risk factors, including sex, genetic mutations, family history of GC, and Helicobacter pylori (HP) infection. We assessed heterogeneity using Cochran's Q test and the I2 statistic. A total of 14 studies comprising 29,170 patients with LS met the inclusion criteria, of which 13 were included in the meta-analysis. Male sex (RR 2.8; 95% CI 2.2, 3.6; p < 0.001; I2 = 0%), MLH1 (RR 1.8; 95% CI 1.4, 2.3; p < 0.001; I2 = 0%) and MSH2 variants (RR 2.5; 95% CI 2.0, 3.2; p < 0.001; I2 = 0%), family history of GC (RR 3.5; 95% CI 2.0, 5.8; p < 0.001; I2 = 0%), and HP infection (RR 2.8; 95% CI 1.2, 6.8; p = 0.023; I2 = 12.8%) were associated with increased GC risk. In contrast, the MSH6 variant was associated with lower GC risk (RR 0.6; 95% CI 0.4, 0.8; p = 0.006; I2 = 0%). Our findings confirm that male sex, MLH1 and MSH2 variants, family history of GC, and HP infection are significant risk factors for GC in individuals with LS. These findings support the need for individualized surveillance strategies and targeted risk-reduction measures to improve early detection and patient outcomes.