Bismuth Tripotassium Dicitrate Research Articles

The ways of antihelicobacter therapy in Ukraine (based on the data of analysis of the Ukrainian Registry Hp-EuReg — UKRAINE)

Objective — to assess the state of affairs in the diagnosis and treatment of Helicobacter pylori infection in Ukraine and their conformity with the modern international recommendations. Materials and methods. The performed analysis included data of 500 patients with H. pylori-associated gastrointestinal diseases, registered in the period of the year 2013 to 26.10.2018 in the Ukrainian Registry «gfadeenko» within the frameworks of the multicentre prospective trial Hp-EuReg — UKRAINE, initiated by the European Group on the investigation H. pylori infection and microbiota (EHMSG). All patients were administered antihelicobacter therapy (AHBT). Results. The predominated nosological units, for which AHBT was prescribed, were chronic gastritis (73.7 %) and duodenal ulcer 23.3 %. The mostly prevailed methods of primary H. pylori diagnosis were histological (50.8 %), serologic (26.7 %) and fast urease test (19.5 %). The AHBT duration was 7 days in 15.4 % of cases, 10 days in 37.6 %, and 14 days in 47.0 % of cases. The proton pump inhibitor pantoprazole was administered in the AHBT schemes most frequently (80.5 %). For the eradication control, stool test with H. pylori antigen identification in feces was actively used (90.5 %), and not actively the histological method (5.7 %) and urease breast test (1.9 %). Serological test was used in 2.9 % cases, and this was a significant diagnostic error. The eradication efficacy at the administration of the standard triple therapy was 53.5 % at 7-days course, 68.2 %, at 10-days course and 75.0 % at 14-days treatment. The use of triple therapy with addition of bismuth tripotassium dicitrate (VTD), the eradication level at 7-days course reached 71.4 %, at 10-days 92.6 %, and at 14-days 94.1 %. Conclusions. The non-compliance of the Maastricht-V recommendations regarding the duration of AHBT and eradication control has been revealed. Pantoprazole was administered in the AHBT schemes most frequently, that was stipulated by the comorbidity presence in the most of patients and risk of the inter-medication interactions. The insufficient efficacy of 7-days triple therapy has been established, as well as sub-optimal efficacy of 10- and 14-days schemes of triple AHBT and 7-days of triple AHBT with VTD addition. The VTD addition in 10- and 14-days schemes of triple therapy promoted the increase of eradication efficacy (more than 90 %), thus making this method of AHBT optimization actual for Ukraine.

The Role of the Pathoanatomical Diagnosis «Chronic Gastritis» in the System of Personified Cancer Prevention

Aim.The aim of the review is to systematize the principles of interpretation of morphological and molecular-cellular signs underlying the biopsy diagnosis of chronic gastritis from the standpoint of personified prevention of gastric cancer.Background. The chronicle of cancer prevention is presented as an evolution of views on the possibility of clinical interpretation of structural changes in the gastric mucosa such as early (inflammation, metaplasia, atrophy) and pronounced (intraepithelial neoplasia/dysplasia) precancerous changes. The protocols of taking gastric bioptates and their violations, the principles of formulating the pathoanatomical conclusion (Updated Sydney system, OLGA system) and a personalized forecast of the risk of gastric cancer are discussed. Molecular classification of gastric cancer is considered from the standpoint of carcinogenesis cascade and WHO 2010 histological classification. New molecular and cellular targets for the preparation of bismuth tripotassium dicitrate and practical steps of its use in the prevention of gastric cancer in chronic inflammation of the mucosa of various etiologies are conceptually described.Conclusion. Biopsy diagnosis of chronic gastritis combined with the evaluation of gene structure (genetic polymorphism) and epigenomic mechanisms (microRNA) allows the risk of gastric cancer to be ranked in a particular patient even with early precancerous changes in the gastric mucosa. The activity of gastritis (infiltration of the mucosa with neutrophilic leukocytes) of any etiology is the theoretical justification for the use of bismuth tripotassium dicitrate pharmacological preparation to protect the genome of stem cells of the gastric epithelium as a secondary prevention of gastric cancer.

Роль препаратов висмута в повышении эффективности эрадикации инфекции Helicobacter pylori

Aim of review. To demonstrate modern potential of bismuth agents administration for increasing of Helicobacter pylori (H. pylori) eradication efficacy. Summary. Prevention of peptic ulcer and stomach cancer makes eradication of H. pylori infection more and more important. At the same time efficacy of some eradication modes, first of all - that of standard triple therapy, steadily decreases because of growing antibiotic resistance of H. pylori strains, first of all - clarithromycin resistance. The concept that empirical prescription of standard triple therapy should be abandoned in favor of initial H. pylori clarithromycin-resistance testing by culture or real-time polymerase chain reaction became widely accepted. Bismuth-based quadrotherapy mainly - with bismuth tripotassium dicitrate (BTD) is alternative to standard triple mode therapy nowadays. Potential of BTD combination not only to tetracycline but to other antibiotics as well was demonstrated. Addition of BTD to triple therapy containing clarithromycin, levofloxacin, metronidazole allows to increase eradication efficacy for 30-40% at H. pylori-resistant strains. Absence of H. pylori resistance development to BTD, combined antibacterial and cytoprotective effects as well as good tolerance are important advantages of the drug. Conclusion. Addition of BTD to triple H. pylori eradication modes, that include different antibiotics (clarithromycin, levofloxacin and metronidazole) provide significant increase in efficacy of eradication at antibioticresistant Helicobacter pylori strains.

Клинические рекомендации Российской гастроэнтерологической ассоциации по диагностике и лечению инфекции Helicobacter pylori

Aim of publication. To present indications for antihelicobacter therapy, methods and sequence of diagnostics and eradication treatment of Helicobacter pylori (H. pylori) infection to general practitioners. Key points. Chronic gastritis caused by H. pylori infection, including that in «asymptomatic» patients can be considered to be an indication for H. pylori eradication therapy both as etiological treatment and opportunistic screening diagnostics for gastric cancer prevention. Indications for obligatory antihelicobacter therapy include stomach and a duodenum peptic ulcer (PU), stomach MALT-lymphoma, early gastric cancer with endoscopic resection. Breath test with 13С-labeled urea, laboratory test for assessment of anti-H. pylori antibodies in feces, rapid urease test and serological method can be recommended for primary diagnostics of infection. Serological test is not applicable after antihelicobacter therapy. According to the bulk of regional studies clarithromycin resistance level of H. pylori strains in Russia does not exceed 15%. Obtained data indicate the absence of high metronidazole-resistance of H. pylori as well as double resistance to clarithromycin and metronidazole. Standard triple therapy including proton pump inhibitor (PPI), clarithromycin and amoxicillin is recommended as first-line treatment for H. pylori eradication. Standard triple therapy should be carried out, applying various means that increase its efficacy. Alternatively to standard triple therapy, first-line eradication treatment may include four-component bismuth tripotassium dicitratebased therapy or non-bismuth quadrotherapy which includes PPI, amoxicillin, clarithromycin and metronidazole. Quadrotherapy with bismuth tripotassium dicitrate can also be applied as a basic mode of the second line treatment at inefficiency of standard triple therapy. Alternative mode of second line eradication treatment includes PPI, levofloxacin and amoxicillin. Levofloxacinbased triple therapy prescription in the presence of strict indications should be limited to gastroenterologists. The third-line eradication treatment is adjusted individually according to the history of previous treatment modes. Eradication efficacy may be increased by prolongation of treatment up to 14 days, applicaiton of modern PPIs or increase of PPI doze, addition of bismuth tripotassium dicitrate or probiotic. Conclusion. In each case of H. pylori detection it is reasonable to consider eradication therapy that is especially actual as H. pylori infection eradication is recognized as effective method of stomach cancer prevention. H. pylori eradication optimization methods can be applied both to standard and alternative modes while combination of these approaches allows to achieve the best result in a given patient.

Новое в изучении инфекции Helicobacter pylori и основные положения Согласительного совещания «Маастрихт-V» (2016)

Aim of review. To review in brief the reports of the XXIX international working meeting of the European Helicobacter pylori (H. pylori) and Microbiota Study Group (Magdeburg, 2016) and to discuss the key points of «Maastricht V» consensus meeting, devoted to diagnosis and treatment of infection. Key points. Association of H. pylori to both gastroenterological and non-gastrointestinal diseases and optimization of eradication therapy modes were discussed at the consensus conference. The special attention was paid for decreasing of infection burden and the stomach cancer prevention. New eradication therapy modes were presented for the regions with high and low H. pylori resistance to clarithromycin and metronidazole. It was demonstrated that clarithromycin resistance in Russia significantly varies in different regions and highest efficacy was observed for bismuth-based (in particular - bismuth tripotassium dicitrate) eradication modes. Conclusion. The guidelines of «Maastricht V» consensus meeting provide significant improvement of treatment results in H.pylori-infected patients as well as decrease of the risk of associated diseases (first of all - the stomach cancer).

EXPERIENCE IN TREATMENT OF PATIENTS WITH H. PYLORI-ASSOCIATED DISEASES

Efforts are under way to find optimal therapy for Helicobacter pylori (H. Pylori)-associated gastrointestinal diseases. Among such diseases are gastric and duodenal ulcers, gastritis (atrophic gastritis), functional dyspepsia, gastropathies induced by non-steroidal antiulcer drugs (NSAIDs). Various regimens for eradication of Helicobacter pylori infection are typically chosen on the basis of administration of proton pump inhibitors (PPI), antibiotics, metronidazole in different doses and combinations, as well as bismuth salts products, mainly bismuth tripotassium dicitrate (BTD). The article explores the possibility for participation in the eradication therapy regimens with a domestic BTD-based drug – Novobismol®. The studies showed that Novobismol® was successfully used in anti-Helicobacter therapy in patients with peptic ulcer, chronic gastritis, and in patients with functional dyspepsia. It can be concluded that the BTD-based drug Novobismol® is effective and safe, and its use extends the possibilities of treating H. Pylori-associated diseases.

Concomitant, bismuth quadruple, and 14-day triple therapy in the first-line treatment of Helicobacter pylori: a multicentre, open-label, randomised trial

Whether concomitant therapy is superior to bismuth quadruple therapy or 14-day triple therapy for the first-line treatment of Helicobacter pylori infection remains poorly understood. We aimed to compare the efficacy and safety of 10-day concomitant therapy, 10-day bismuth quadruple therapy, and 14-day triple therapy in the first-line treatment of H pylori. In this multicentre, open-label, randomised trial, we recruited adult patients (aged >20 years) with H pylori infection from nine medical centres in Taiwan. Patients who had at least two positive tests from the rapid urease test, histology, culture, or serology or who had a single positive 13C-urea breath test for gastric cancer screening were eligible for enrolment. Patients were randomly assigned (1:1:1) to either concomitant therapy (lansoprazole 30 mg, amoxicillin 1 g, clarithromycin 500 mg, and metronidazole 500 mg, all given twice daily) for 10 days; bismuth quadruple therapy (bismuth tripotassium dicitrate 300 mg four times a day, lansoprazole 30 mg twice daily, tetracycline 500 mg four times a day, and metronidazole 500 mg three times a day) for 10 days; or triple therapy (lansoprazole 30 mg, amoxicillin 1 g, and clarithromycin 500 mg, all given twice daily) for 14 days. A computer-generated permuted block randomisation sequence with a block size of 6 was used for randomisation, and the sequence was concealed in an opaque envelope until the intervention was assigned. Investigators were masked to treatment allocation. The primary outcome was the eradication frequency of H pylori with first-line therapy assessed in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT01906879. Between July 17, 2013, and April 20, 2016, 5454 patients were screened for eligibility. Of these, 1620 patients were randomly assigned in this study. The eradication frequencies were 90·4% (488/540 [95% CI 87·6-92·6]) for 10-day bismuth quadruple therapy, 85·9% (464/540 [82·7-88·6]) for 10-day concomitant therapy, and 83·7% (452/540 [80·4-86·6]) for 14-day triple therapy in the intention-to-treat analysis. 10-day bismuth quadruple therapy was superior to 14-day triple therapy (difference 6·7% [95% CI 2·7-10·7, p=0·001), but not 10-day concomitant therapy. 10-day concomitant therapy was not superior to 14-day triple therapy. The frequency of adverse events was 67% (358/533) in patients treated with 10-day bismuth quadruple therapy, 58% (309/535) in patients treated with 10-day concomitant therapy, and 47% (252/535) in patients treated with 14-day triple therapy. Bismuth quadruple therapy is preferable to 14-day triple therapy in the first-line treatment in the face of rising prevalence of clarithromycin resistance. Concomitant therapy given for 10 days might not be optimum and a longer treatment length should be considered. National Taiwan University Hospital and Ministry of Science and Technology of Taiwan.

Improvement of Helicobacter pylori eradication efficacy at stomach and duodenum peptic ulcers

Aim of investigation. To estimate efficacy of the modified sequential therapy regimen of Helicobacter pylori (H. pylori) eradication (with addition of bismuth tripotassium dicitrate) at treatment of peptic ulcer of the stomach (PUS) and duodenum (PUD) of severe and complicated course in the Russian population. Material and methods. Original study included overall 105 patients with PUS and PUD with severe and complicated course of disease. The main group received modified sequential therapy regimen, the comparison group - standard triple mode. All patients underwent quantitative serological test for H. pylori-specific IgG antibodies, stool test for H. pylori antigen, fibrogastroscopy with stomach mucosa (SM) biopsy and rapid urease test, microscopic examination of SM biopsy specimens, polymerase chain reaction for H. pylori DNA in SM biopsy specimens. Results. Efficacy of H. pylori eradication at modified sequential therapy was 95,8%, at standard, also combined with bismuthate tripotassium dicitrate, - 86,4%. After successful H. pylori eradication decrease of inflammatory activity of the stomach mucosa at less prominent decrease of mononuclear infiltration was noted, however the tendency for reduction of these features was more significant in patients at modified sequential regimen. Conclusions. Growth of H. pylori antibiotic resistance requires accumulation of the Russian data on efficacy of sequential therapy to increase eradication rate and prevent growth of macrolide resistance. Sequential therapy was proposed as a way to overcome resistance to clarithromycin. Sequential eradication therapy with inclusion of bismuth tripotassium dicitrate has shown advantage over standard triple therapy at severe and complicated forms of gastroduodenal peptic ulcers. Results of original study allow to recommend sequential eradication therapy in Russia. Key words: peptic ulcer, Helicobacter pylori, eradication, modified sequential therapy, bismuth tripotassium dicitrate.