Efficacy of Helicobacter pylori eradication therapy for functional dyspepsia: updated systematic review and meta-analysis

ObjectiveFunctional dyspepsia (FD) is a chronic disorder that is difficult to treat. Helicobacter pylori may contribute to its pathophysiology. A Cochrane review from 2006 suggested that eradication therapy was beneficial, but there have been numerous randomised controlled trials (RCTs) published since. We evaluated impact of eradication therapy on both cure and improvement of FD, as well as whether any benefit was likely to arise from eradication of H. pylori.DesignWe searched the medical literature through October 2021 to identify RCTs examining efficacy of eradication therapy in H. pylori-positive adults with FD. The control arm received antisecretory therapy or prokinetics, with or without placebo antibiotics, or placebo alone. Follow-up was for ≥3 months. We pooled dichotomous data to obtain a relative risk (RR) of symptoms not being cured or symptoms not improving with a 95% CI. We estimated the number needed to treat (NNT).ResultsTwenty-nine RCTs recruited 6781 H. pylori-positive patients with FD. Eradication therapy was superior to control for symptom cure (RR of symptoms not being cured=0.91; 95% CI 0.88 to 0.94, NNT=14; 95% CI 11 to 21) and improvement (RR of symptoms not improving=0.84; 95% CI 0.78 to 0.91, NNT=9; 95% CI 7 to 17). There was no significant correlation between eradication rate and RR of FD improving or being cured (Pearson correlation coefficient=−0.23, p=0.907), but the effect was larger in patients with successful eradication of H. pylori than with unsuccessful eradication (RR=0.65; 95% CI 0.52 to 0.82, NNT=4.5, 95% CI 3 to 9). Adverse events (RR=2.19; 95% 1.10 to 4.37) and adverse events leading to withdrawal (RR=2.60; 95% CI 1.47 to 4.58) were more common with eradication therapy.ConclusionThere is high quality evidence to suggest that H. pylori eradication therapy leads to both cure and improvement in FD symptoms, although the benefit is modest.

Efficacy of Twice a Day Bismuth Quadruple Therapy for Second-Line Treatment of Helicobacter pylori Infection

Bismuth quadruple therapy (BQT) is an effective treatment for Helicobacter pylori infection. However, frequent dosing schedules of BQT regimen often compromise drug adherence and may affect treatment outcomes. This retrospective study aimed to investigate the efficacy of twice-daily BQT compared to that of four times a day therapy. From August 2018 to November 2020, adult patients who failed first-line standard triple therapy and underwent BQT were eligible. Patients were categorized into two groups according to dosing schedule: (i) the BQT group (n = 213) who received standard BQT administered four times a day; and (ii) the BQTb group (n = 141) who received proton pump inhibitor, bismuth 600 mg, metronidazole 500 mg, and tetracycline 1 g twice a day. The eradication rate did not differ between the BQT (92.5%) and the BQTb groups (90.1%) (p = 0.441). Adherence and adverse event rate were similar between the two groups. Multivariate analysis showed that current smoking was associated with eradication failure; however, dosing frequency was not associated with the efficacy of eradication therapy. This study suggested that twice a day BQT is as effective as four times a day therapy for second-line treatment of H. pylori infection.

Who Could Be Blamed in the Case of Discrepant Histology and Serology Results for Helicobacter pylori Detection?

Background. Discrepancies between histology and serology results for Helicobacter pylori detection could be caused by a variety of factors, including a biopsy sampling error, expertise of the pathologist, natural loss of infection due to advanced atrophy, or a false-positive serology in the case of a previous infection, since antibodies may be present in blood following recovery from the infection. Aims. To identify true H. pylori-positive individuals in discrepant cases by serology and histology using real time polymerase chain reaction (RT-PCR) as a gold standard. Methods. Study subjects with discrepant histology and serology results were selected from the GISTAR pilot study data base in Latvia. Subjects having received previous H. pylori eradication therapy or reporting use of proton pump inhibitors, antibacterial medications, or bismuth containing drugs one month prior to upper endoscopy were excluded. We compared the discrepant cases to the corresponding results of RT-PCR performed on gastric biopsies. Results. In total, 97 individuals with discrepant results were identified: 81 subjects were serology-positive/histology-negative, while 16 were serology-negative/histology-positive. Among the serology-positive/histology-negative cases, 64/81 (79.0%) were false-positives by serology and, for the majority, inflammation was absent in all biopsies, while, in the serology-negative/histology-positive group, only 6.2% were proven false-positives by histology. Conclusions. Among this high H. pylori prevalent, middle-aged population, the majority of discrepant cases between serology and histology were due to false positive-serology, rather than false-negative histology. This confirms the available evidence that the choice of treatment should not be based solely on the serological results, but also after excluding previous, self-reported eradication therapy.

CLINICAL AND MORPHOLOGICAL CHARACTERISTICS OF H. PYLORI-ASSOCIATED GASTRODUODENAL ZONE DISEASES: AGE-RELATED ASPECTS

The aim of the paper is to study the clinical and morphological characteristics of H. pylori-associated gastroduodenal zone diseases, depending on patients’ age. Materials and Methods. Three groups of patients of various ages with H. pylori-associated gastroduodenal zone diseases were formed in the course of a prospective clinical study. We studied the clinical picture, and morphological characteristics of the gastroduodenal zone before and after eradication therapy. Average length of the observation period was 172 days. All patients underwent esophagogastroduodenoscopy with biopsy. Results. Severe dyspeptic disorders were diagnosed in all young patients belonging to group 1 (100 %). The dyspeptic index corresponded to a high degree of severity. Morphological changes in the gastric mucosa were more significant in patients with a less pronounced clinical picture (Groups 2 and 3). In group 3, atrophic transformations of the gastric corpus were found in 30.5 %, atrophic transformations of the pylorus – in 11 %, and intestinal metaplasia – in 2.8 % of patients. Unlike young and middle-aged patients with pronounced dyspeptic syndrome, elderly patients were characterized by a low-symptom clinical picture, which was accompanied by morphological gastroduodenal zone transformations with the possible progression. Conclusions. Effective eradication therapy contributes to clinical, endoscopic and morphological remission of the gastroduodenal zone and prevents the progression of the inflammatory cascade. Key words: Helicobacter pylori, gastroduodenal diseases, eradication therapy, age characteristics. Цель исследования – изучить клинико-морфологические особенности H. рylori-ассоциированных заболеваний гастродуоденальной зоны в зависимости от возраста пациентов. Материалы и методы. В процессе проспективного клинического исследования были сформированы три группы пациентов разного возраста, имеющих H. pylori-ассоциированные заболевания гастродуоденальной зоны. Изучали клиническую картину, морфологические особенности гастродуоденальной зоны до и после эрадикационной терапии. Период наблюдения больных составил в среднем 172 дня. Всем пациентам выполнялась ззофагогастродуоденоскопия с биопсией. Результаты. У 100 % пациентов молодого возраста (I группа) установлены выраженные диспепсические расстройства. Диспепсический индекс соответствовал высокой степени тяжести. Для пациентов II и Ш групп при менее выраженной клинической картине морфологические изменения слизистой оболочки желудка оказались более существенны. В старшей группе (Ш группа) атрофические преобразования тела желудка выявлены у 30,5 % пациентов, привратника желудка – у 11 %, кишечная метаплазия – у 2,8 %. В отличие от пациентов молодого и среднего возраста, имеющих выраженный диспепсический синдром, для пациентов пожилого возраста характерна малосимптомная клиническая картина, которая сопровождалась морфологическими преобразованиями гастродуоденальной зоны с возможностью прогрессирования. Выводы. Эффективная эрадикационная терапия способствует достижению клинико-эндоскопической и морфологической ремиссии состояния гастродуоденальной зоны и создает условия для предотвращения прогрессирования воспалительного каскада. Ключевые слова: Helicobacter pylori, заболевания гастродуоденальной зоны, эрадикационная терапия, возрастные особенности.

Clinical Recommendations of Russian Gastroenterological Association and RENDO Endoscopic Society on Diagnosis and Treatment of Gastritis and Duodenitis

Aim. The clinical guidelines are intended to supplement specialty decision-making for improved aid quality in patients with gastritis and duodenitis though acknowledging the latest clinical evidence and principles of evidencebased medicine.Key points. Gastritis is an inflammatory disease of stomach mucosa, with a separate definition of acute and chronic gastritis. Chronic gastritis is a cohort of chronic diseases uniting a typical morphology of persistent inflammatory infiltration, impaired cellular renewal with emergent intestinal metaplasia, atrophy and epithelial dysplasia of gastric mucosa. Oesophagogastroduodenoscopy (OGDS) or high-resolution OGDS with magnified or non-magnified virtual chromoendoscopy, including targeted biopsy for atrophy and intestinal metaplasia grading and neoplasia detection, are recommended to verify gastritis and duodenitis, precancer states and/or gastric mucosal changes. All chronic gastritis patients positive for H. рylori should undergo eradication therapy as aetiological and subsidiary for gastric cancer prevention. Chronic gastritis patients with symptoms of dyspepsia (epigastric pain, burning and congestion, early satiety), also combined with functional dyspepsia, are recommended proton pump inhibitors, prokinetics, rebamipide and bismuth tripotassium dicitrate in symptomatic treatment. With focal restricted intestinal metaplasia, follow-up is not required in most cases, mainly when advanced atrophic gastritis is ruled out in high-quality endoscopy with biopsy. However, a familial history of gastric cancer, incomplete intestinal metaplasia and persistent H. pylori infection render endoscopy monitoring with chromoendoscopy and targeted biopsy desirable once in three years. Patients with advanced atrophic gastritis should have high-quality endoscopy every 3 years, and once in 1–2 years if complicated with a familial history of gastric cancer.Conclusion. The recommendations condense current knowledge on the aetiology and pathogenesis of gastritis and duodenitis, as well as laboratory and instrumental diagnostic techniques, main approaches to aetiological H. pylori eradication and treatment of dyspeptic states.

MEILIODOSIS - AN ENIGMA WITH VARYING ANTIBIOTIC RESPONSE

Melioidosis or Whitmore's disease is an infection of humans and animals caused by aerobic gram negative bacillus Burkholderia pseudomallei. This infection with a wide clinical spectrum is predominantly present in tropical climates, mainly Southeast Asia and Northern Australia. The clinical manifestations include pneumonia, skin ulcers or abscesses, osteomyelitis, prostatitis, encephalomyelitis and fulminant septic shock. The denitive diagnosis is made by a positive culture of Burkholderia pseudomallei. The bacteria is innately resistant to 6 classes of commonly used antibiotics. CDC recommends an intensive phase of intravenous antibiotics for 10 to 14 days followed by eradication therapy with oral antibiotics for 3 – 6 months. The intravenous agents effective against the bacteria are meropenem and ceftazidime. Trimethoprim sulfamethoxazole and amoxicillin/clavulanic acid are the oral antimicrobial agents used. Here we present two cases of Melioidosis, at opposite ends of the spectrum with varying antibiotic response. One patient is a young non immunocompromised female and the second an elderly immunocompromised (T2DM) male, both presented with skeletal melioidosis.

Human microbiota. Friend? Enemy? Neighbors?

The review is dedicated to the modern ideas about the composition of the human intestinal microbiome, factors that determine the bacterial «landscape» and affect its activity. The main functions of normal microflora have been described, including intestinal motility, protection of intestinal barrier against pathogenic bacteria, parasites, intestinal epithelial regeneration, metabolic and immunological functions, participation in digestive processes, synthesis of amino acids and proteins, antibiotics, vitamins, hormonally active substances, promoting the absorption of minerals and nutrients, preventing the development of pathological conditions. Determination of intestinal microbiota expression of the innate immune system explains the role of microflora in chronic inflammation and diseases such as liver fibrosis, metabolic syndrome, type 2 diabetes mellitus, atherosclerosis, cardiovascular, neurodegeneration and cancer. A promising way is the use of microorganisms with beneficial properties (probiotics), the necessary substrate for them (prebiotics), their metabolites (metabiotics) and complexes of pro‑ and prebiotics (synbiotics) not only to restore and regulate the intestinal microflora, but also as therapeutic agents in some diseases, in particular during eradication therapy of the bacterium Helicobacter pylori. The functions of some species and strains of beneficial bacteria have being discussed, in particular the strain Bacillus causii UBBC‑07, as well as the results of preclinical and clinical trials of its use at antibiotic‑associated diarrhea in the inhibition of Clostridium difficile. The issues of safety and facts of positive impact on human health of probiotic products of Probeez line (Organosyn Ltd.) are considered, which differ in the personification of appointments to certain segments of the population: Probeez®, Probeez® Femina, Probeez® Kids, Probeez® DUO and Probeez® Immuno contain successfully selected live probiotic bacteria. The available range of monocomponent (Probeez® with Kids, Probeez® DUO), multicomponent (Probeez®, Probeez® Femina) and synbiotic (Probeez® Immuno) products allows to choose the best option in specific conditions for their application not only in inflammatory diseases of the gastrointestinal tract, but also in chronic disorders of other systems and organs.

Damage to the musculoskeletal system during eradication therapy of Helicobacter pylori with levofloxacin

Eradication therapy is the mainstay of treatment for H. pylori-associated diseases. A case of the development of tendinitis of the left patellar ligament proper during eradication therapy using a triple regimen with levofoloxacin for 14 days for exacerbation of duodenal ulcer is presented.

Eradication therapy of helicobacteriosis with probiotics, problems, and prospects

Currently, there is an urgent question of optimizing the treatment of stomach diseases associated with Helicobacter pylori, due to the increasing resistance of the pathogen to antibiotics and the presence of side effects of standard therapy. To optimize it, it is proposed to use probiotics as an additional or monotherapy. The review presents the results of studies of anti-helicobacter activity by in vitro and in vivo systems, as well as an assessment of the clinical effectiveness of various probiotic strains of microorganisms in eradication therapy. Several mechanisms of action of probiotics in the treatment of HP-related diseases are discussed. The problems and prospects of using personalized therapy of helicobacteriosis with probiotics and autoprobiotics, based on strains obtained from the gastrointestinal tract, are indicated.