Knowledge and approach towards Helicobacter pylori diagnosis and management among primary care physicians in Cameroon: a cross-sectional study.

BACKGROUND: Low- and middle-income countries have a high prevalence of Helicobacter pylori infection (HPI). In Cameroon, the majority of HPIs are diagnosed and treated by primary care physicians (PCPs). We sought to assess the knowledge and practices of PCPs in the diagnosis and management of HPI in Cameroon. METHODS: A hospital-based cross-sectional study was carried out in four randomly selected regions of Cameroon from November 2021 to June 2022. In each of the selected regions, PCPs were recruited by non-probability convenience sampling and interviewed using a pre-structured questionnaire. Chi-squared, Fisher's exact and Student's t-tests were performed for descriptive analyses. Multivariable logistic regression was used to examine associations between knowledge and practice, with the model adjusted by age of the PCP, geographic region, number of patients and years in practice. Analysis was performed in SAS version 9.4 (SAS Institute, Cary, NC, USA). RESULTS: A total of 382 PCPs were included in the analysis. The majority (60.0%) were males between the ages of 20-29 y (64.1%). Most PCPs (80.9%) reported that HPI is the cause of gastroesophageal reflux disease and 41.8% reported that HPI is the main cause of dyspeptic symptoms. The dominant diagnostic tests used for HPI were serology (52.8%) and stool antigen (30.9%). The most frequently used first-line therapies were amoxicillin (AMX), clarithromycin (CLA), metronidazole (MNZ) and proton pump inhibitor (PPI) concomitant therapy (32.2%), AMX-CLA-PPI triple therapy (18.6%) and AMX-MNZ-PPI triple therapy (13.1%). Half of the practitioners (48.6%) treat HPI empirically, without positive H. pylori testing. About half of the PCPs (48%) do not request laboratory confirmation of H. pylori eradication following treatment. CONCLUSIONS: There is inadequate knowledge and significant differences in the clinical approach towards HPI among PCPs in Cameroon. We recommend more teaching programs and continuous medical education on HPI.

Evolving Concepts in Helicobacter pylori Management.

Helicobacter pylori is the most common chronic bacterial infection worldwide and the most significant risk factor for gastric cancer, which remains a leading cause of cancer-related death globally. H pylori and gastric cancer continue to disproportionately impact racial and ethnic minority and immigrant groups in the United States. The approach to H pylori case-finding thus far has relied on opportunistic testing based on symptoms or high-risk indicators, such as racial or ethnic background and family history. However, this approach misses a substantial proportion of individuals infected with H pylori who remain at risk for gastric cancer because most infections remain clinically silent. Moreover, individuals with chronic H pylori infection are at risk for gastric preneoplastic lesions, which are also asymptomatic and only reliably diagnosed using endoscopy and biopsy. Thus, to make a significant impact in gastric cancer prevention, a systematic approach is needed to better identify individuals at highest risk of both H pylori infection and its complications, including gastric preneoplasia and cancer. The approach to H pylori eradication must also be optimized given sharply decreasing rates of successful eradication with commonly used therapies and increasing antimicrobial resistance. With growing acceptance that H pylori should be managed as an infectious disease and the increasing availability of susceptibility testing, we now have the momentum to abandon empirical therapies demonstrated to have inadequate eradication rates. Molecular-based susceptibility profiling facilitates selection of a personalized eradication regimen without necessitating an invasive procedure. An improved approach to H pylori eradication coupled with population-level programs for screening and treatment could be an effective and efficient strategy to prevent gastric cancer, especially in minority and potentially marginalized populations that bear the heaviest burden of H pylori infection and its complications.

Gastric Intestinal Metaplasia: Real Culprit or Innocent Bystander as a Precancerous Condition for Gastric Cancer?

Gastric intestinal metaplasia (GIM), which denotes conversion of gastric mucosa into an intestinal phenotype, can occur in all regions of the stomach, including cardiac, fundic, and pyloric mucosa. Since the earliest description of GIM, its association with gastric cancer of the differentiated (intestinal) type has been a well-recognized concern. Many epidemiologic studies have confirmed GIM to be significantly associated with subsequent gastric cancer development. Helicobacter pylori, the principal etiologic factor for gastric cancer, plays the most important role in predisposing to GIM. Although the role of GIM in the stepwise progression model of gastric carcinogenesis (the so-called "Correa cascade") has come into question recently, we review the scientific evidence that strongly supports this long-standing model and propose a new progression model that builds on the Correa cascade. Eradication of H pylori is the most important method for preventing gastric cancer globally, but the effect of eradication on established GIM, is limited, if any. Endoscopic surveillance for GIM may, therefore, be necessary, especially when there is extensive corpus GIM. Recent advances in image-enhanced endoscopy with integrated artificial intelligence have facilitated the identification of GIM and neoplastic lesions, which will impact preventive strategies in the near future.

Brief communication: global temporal trends in the efficacy of clarithromycin-based regimens for the treatment of Helicobacter pylori infection.

Background: Helicobacter pylori eradication rates achieved with clarithromycin-based triple therapies are declining due to antibiotic resistance, but data regarding temporal changes in efficacy with these eradication therapies are scarce. Objective: To evaluate the efficacy of clarithromycin-based triple eradication regimens over time. Design: A comprehensive literature review and time-trend analysis. Data sources and methods: Bibliographies of recently published systematic literature reviews were searched and supplemented with a targeted literature review conducted using Medline and Embase databases and ProQuest from conception to May 2021. Studies reporting H. pylori eradication rates of clarithromycin-based triple therapies were included and temporal trends were estimated using a random-effects model. Results: Eradication rates for triple therapies containing proton pump inhibitors (PPIs), clarithromycin, and amoxicillin showed a significant decline over the past 23 years (p = 0.0315). However, this decline was not significant when eradication rates achieved with vonoprazan-based triple therapy were included (p = 0.3910). Conclusion: Vonoprazan-based triple therapy partially mitigated the decline in eradication rates seen with PPI-based triple therapy, likely due to more powerful acid suppression of vonoprazan.

Diagnostic and Treatment Practices for Helicobacter Pylori Infection in an Academic Pediatric Hospital.

BACKGROUND: In 2016, ESPGHAN/NASPGHAN issued revised guidelines for the management of Helicobacter pylori (H. pylori) infection in children and adolescents. Recommendations include performing antibiotic susceptibility testing to tailor therapy. The aim of our study was to evaluate the H. pylori treatment landscape in pediatric patients at our institution. METHODS: We performed a retrospective study of patients diagnosed with H. pylori infection at a single academic children's hospital from 2015 to 2021. The frequency of each treatment regimen and their respective eradication rates were calculated. We compared trends in antibiotic prescriptions and eradication rates before and after 2016. RESULTS: One hundred and ninety-six patients were included. Triple therapy with amoxicillin, clarithromycin, and a proton pump inhibiter (PPI) was the most often prescribed regimen (46.5%), followed by amoxicillin, metronidazole, and PPI (33%). Eradication rates were 70% for amoxicillin, clarithromycin, and PPI and 64% for amoxicillin, metronidazole, and PPI. CONCLUSION: Our results show eradication rates for both regimens were comparable but suboptimal, highlighting the need to incorporate resistance testing into broader practice.

Clinical Implication of Drug Resistance for H. pylori Management.

Rates of antimicrobial-resistance among H. pylori strains are increasing worldwide, resulting in declining eradication rates with current therapies, especially those containing clarithromycin or levofloxacin. To improve H. pylori management, a paradigm shift is needed, from the empiric approaches formerly employed, to regimen selection based upon knowledge of local and patient-level antimicrobial susceptibility data. We review the mechanisms of H. pylori antimicrobial resistance and the available worldwide pattern of resistance to key antimicrobials used in H. pylori therapy. The practicalities and challenges of measuring susceptibility in clinical practice is discussed, including not only conventional culture-based techniques but also novel sequencing-based methods performed on gastric tissue and stool samples. Though clinical trials of "tailored" (susceptibility-based) treatments have yet to show the clear superiority of tailored over empiric regimen selection, the ability to measure and modify treatment based upon antimicrobial susceptibility testing is likely to become more frequent in clinical practice and should lead to improved H. pylori management in the near future.

Helicobacter pylori Treatment Regimens: A US Perspective.

Helicobacter pylori infects nearly one-third of the US population. H pylori is a significant cause of gastroduodenal disease, including peptic ulcers and cancers. However, rising antibiotic resistance has complicated management of H pylori. This article provides a practical review of management strategies, including first-line empiric therapies and how to treat patients when prior therapies fail. Bismuthbased quadruple therapy remains the standard initial empiric regimen, although a rifabutin-based triple regimen is another approach for empiric therapy in the United States. Clarithromycin and levofloxacin therapies should be avoided except when treating a strain of known susceptibility. When therapies fail, resistance should be tested with molecular or culture-based methods. Knowing local resistance patterns and/or using practice-based eradication rates is important for devising logic-based clinical choices. Ultimately, shared decision-making, patient counseling, and careful attention to drug type and dosage are essential for refractory cases.

Helicobacter pylori Antibiotic Resistance in the United States Between 2011 and 2021: A Systematic Review and Meta-Analysis.

INTRODUCTION: Antimicrobial resistance among Helicobacter pylori strains has been rising globally, leading to declining eradication rates. We performed a systematic review and meta-analysis of the resistance patterns of H. pylori strains in the United States between 2011 and 2021. METHODS: Ovid MEDLINE, Embase, CINAHL, and Cochrane CENTRAL databases were searched for manuscripts and conference abstracts published between 2011 and 2021 reporting H. pylori antibiotic resistance. A mixed-effects model estimated pooled rates of resistance to clarithromycin, amoxicillin, metronidazole, tetracycline, rifabutin, levofloxacin, or a combination of these, with 95% confidence intervals (CIs). RESULTS: A total of 19 studies including 2,660 samples, met inclusion criteria. The pooled rate of resistance to metronidazole was 42.1% (95% CI 27.3%-58.6%), levofloxacin 37.6% (95% CI 26.3%-50.4%), clarithromycin 31.5% (95% CI 23.6%-40.6%), amoxicillin 2.6% (95% CI 1.4%-5.0%), tetracycline 0.87% (95% CI 0.2%-3.8%), rifabutin 0.17% (95% CI 0.00%-10.9%), and dual clarithromycin and metronidazole 11.7% (95% CI 0.1%-94.0%). Considerable data heterogeneity was evident for pooled resistance prevalence rates (I 2 > 50%), with the exception of rifabutin resistance. DISCUSSION: Metronidazole, levofloxacin, and clarithromycin resistance rates each exceed 30%; thus, choosing an empiric antibiotic regimen without knowledge of the likely pattern of antibiotic resistance is not appropriate. Resistance to tetracycline, rifabutin, and amoxicillin remains low. Given the scarcity of available data with considerable heterogeneity among studies, continued surveillance, ideally with a more systematic approach to data collection, is an increasingly important goal in H. pylori management.

Potassium-Competitive Acid Blocker and Proton Pump Inhibitor-Based Regimens for First-Line Helicobacter pylori Eradication: A Network Meta-Analysis.

Background and Aims: Effective acid suppression is a crucial component of Helicobacter pylori (H. pylori) eradication regimens. Approved treatments include dual, triple, and quadruple therapies composed of certain antibiotics in combination with proton pump inhibitors (PPIs). Vonoprazan, a potassium-competitive acid blocker, provides more potent and durable acid suppression than PPIs. We compared the efficacy of vonoprazan-based therapies vs approved standard regimens using new evidence from the phase 3 pHalconHP trial in North America and Europe. Methods: Studies reporting first-line H. pylori eradication rates from empiric treatment with Food and Drug Administration-approved therapies and vonoprazan-containing therapies were identified via bibliographic searches of systematic literature reviews and a subsequent MEDLINE/Embase search using index terms for H. pylori and eradication. Randomized controlled trials comparing 2 or more relevant comparators were included in Bayesian network meta-analyses for grouped and distinct therapies. Results: Twenty-three distinct regimens from 42 trials including 12,773 patients were identified. Vonoprazan-based triple therapy showed the highest relative efficacy (odds ratio: 2.73, 95% credible interval 2.11, 3.54) and 72.1% probability of being the best. North American, Western, and global scenarios were largely consistent. Vonoprazan-based therapies demonstrated higher odds of H. pylori eradication than each PPI-based triple therapy. Furthermore, vonoprazan-based triple therapy was superior to bismuth subcitrate quadruple therapy (odds ratio: 1.60, 95% credible interval: 1.07, 2.38). Conclusion: Vonoprazan-based eradication regimens represent novel treatments for H. pylori infection on a global scale, offering efficacy that, in this analysis, is superior to PPI-based triple therapy and comparable or better than bismuth quadruple therapy.

The prevention of gastric cancer by Helicobacter pylori eradication.

PURPOSE OF REVIEW: Gastric cancer remains one of the most common causes of death globally. Increasing evidence suggests that many gastric cancer cases can be prevented by eradicating its most important etiological agent, Helicobacter pylori. Using the search terms 'H. pylori' and 'gastric cancer' we reviewed the scientific literature regarding the association between H. pylori and gastric cancer published from 1 January 2020 to 30 May 2021. We review the most important articles relevant to the clinical issues regarding H. pylori eradication for gastric cancer prevention. RECENT FINDINGS: In randomized trials, eradication of H. pylori is associated with an approximately 50% reduction in sporadic gastric cancer. A similar benefit was observed when screening first-degree relatives of gastric cancer cases, after resection of early gastric cancer to prevent metachronous neoplasia, and in population-based screen and treatment programs in areas of high H. pylori and gastric cancer prevalence. Even in relatively low gastric cancer countries such as the United States, gastric cancer may potentially be avoided by screening for H. pylori, especially among minority groups who are at greatest risk. SUMMARY: Gastric cancer is preventable, at least in part, by H. pylori eradication. Ongoing screening trials will help determine whether population-based H. pylori screening programs are feasible and cost-effective. Their results are likely to differ according to H. pylori and gastric cancer prevalence rates.

Novel Cyclophilin Inhibitor Decreases Cell Proliferation and Tumor Growth in Models of Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC), the most common primary liver cancer, is usually diagnosed in its late state. Tyrosine kinase inhibitors such as sorafenib and regorafenib are one of the few treatment options approved for advanced HCC and only prolong the patient's life expectancy by a few months. Therefore, there is a need for novel effective treatments. Cyclophilins are intracellular proteins that catalyze the cis/trans isomerization of peptide bonds at proline residues. Cyclophilins are known to be overexpressed in HCC, affecting therapy resistance and cell proliferation. In the present study, we explored the potential of cyclophilin inhibitors as new therapeutic options for HCC in vitro and in vivo. Our results showed that the novel cyclophilin inhibitor, NV651, was able to significantly decrease proliferation in a diverse set of HCC cell lines. The exposure of HCC cells to NV651 caused an accumulation of cells during mitosis and consequent accumulation in the G2/M phase of the cell cycle. NV651 reduced tumor growth in vivo using an HCC xenograft model without affecting the body weights of the animals. The safety aspects of NV651 were also confirmed in primary human hepatocytes without any cytotoxic effects. Based on the results obtained in this study, we propose NV651 as a potential treatment strategy for HCC.

Helicobacter pylori Infection.

Helicobacter pylori infection remains one of the most prevalent infections worldwide, causing significant morbidity and mortality from gastric malignancies and peptic ulcers. This article provides a summary of the microbiology and pathogenesis of this bacterium, emphasizing the complex and protean effects of H pylori on gastric epithelial cells, including stem and progenitor populations, and evasion of host immune defenses. Increasing antibiotic resistance has made management more challenging. This article discusses the appropriate diagnostic modality for different clinical scenarios, and the evolving treatment of H pylori infections, including the use of antibiotic susceptibility testing to aid regimen selection.

AGA Clinical Practice Update on the Management of Refractory Helicobacter pylori Infection: Expert Review.

The purpose of this CPU Expert Review is to provide clinicians with guidance on the management of Helicobacter pylori after an initial attempt at eradication therapy fails, including best practice advice on specific regimen selection, and consideration of patient and systems factors that contribute to treatment efficacy. This Expert Review is not a formal systematic review, but is based upon a review of the literature to provide practical advice. No formal rating of the strength or quality of the evidence was carried out. Accordingly, a combination of available evidence and consensus-based expert opinion were used to develop these best practice advice statements.

Association Between Obstructive Sleep Apnea and Barrett's Esophagus: A Systematic Review and Meta-Analysis.

BACKGROUND: Obstructive sleep apnea (OSA) has gastrointestinal implications as it is associated with gastroesophageal reflux disease. Less certain is an independent association between OSA and Barrett's esophagus. We performed a systematic review and meta-analysis to evaluate the association between OSA and Barrett's esophagus. METHODS: A systematic search of Ovid MEDLINE, Embase, Web of Science, CINAHL, and the Cochrane Central Register of Controlled Trials was performed. Inclusion criteria were observational studies (retrospective and case-control) assessing the association between OSA and Barrett's esophagus in adult subjects. Data from the included studies were extracted and used to calculate the pooled odds ratio of OSA with 95% confidence interval (CI) between patients with Barrett's esophagus and those without, using a random-effects model. RESULTS: Altogether six studies involving 2333 subjects met the inclusion criteria and were included in this meta-analysis. The pooled analysis found a significantly increased risk of OSA, high risk of OSA, and patient-reported OSA symptoms among patients with Barrett's esophagus versus those without Barrett's esophagus, with a pooled odds ratio (OR) of 2.19 (95% CI 1.53-3.15). A subgroup analysis for cases of definite OSA (formally diagnosed via polysomnography) and Barrett's esophagus (n = 2 studies) also demonstrated significant association (OR 2.59, 95% CI 1.39-4.84). CONCLUSION: A significantly increased risk of OSA among patients with Barrett's esophagus was demonstrated in this meta-analysis. Further investigation is warranted to determine the pathophysiology and clinical implications of this association.