Rogaška Medical Centre

BackgroundManagement of Helicobacter pylori (H. pylori) infection requires co‐treatment with proton pump inhibitors (PPIs) and the use of antibiotics to achieve successful eradication.AimTo evaluate the role of dosage of PPIs and the duration of therapy in the effectiveness of H. pylori eradication treatments based on the ‘European Registry on Helicobacter pylori management’ (Hp‐EuReg).MethodsHp‐EuReg is a multicentre, prospective, non‐interventionist, international registry on the routine clinical practice of H. pylori management by European gastroenterologists. All infected adult patients were systematically registered from 2013 to 2022.ResultsOverall, 36,579 patients from five countries with more than 1000 patients were analysed. Optimal (≥90%) first‐line‐modified intention‐to‐treat effectiveness was achieved with the following treatments: (1) 14‐day therapies with clarithromycin‐amoxicillin‐bismuth and metronidazole‐tetracycline‐bismuth, both independently of the PPI dose prescribed; (2) All 10‐day (except 10‐day standard triple therapy) and 14‐day therapies with high‐dose PPIs; and (3) 10‐day quadruple therapies with clarithromycin‐amoxicillin‐bismuth, metronidazole‐tetracycline‐bismuth, and clarithromycin‐amoxicillin‐metronidazole (sequential), all with standard‐dose PPIs. In first‐line treatment, optimal effectiveness was obtained with high‐dose PPIs in all 14‐day treatments, in 10‐ and 14‐day bismuth quadruple therapies and in 10‐day sequential with standard‐dose PPIs. Optimal second‐line effectiveness was achieved with (1) metronidazole‐tetracycline‐bismuth quadruple therapy for 14‐ and 10 days with standard and high‐dose PPIs, respectively; and (2) levofloxacin‐amoxicillin triple therapy for 14 days with high‐dose PPIs. None of the 7‐day therapies in both treatment lines achieved optimal effectiveness.ConclusionsWe recommend, in first‐line treatment, the use of high‐dose PPIs in 14‐day triple therapy and in 10‐or 14‐day quadruple concomitant therapy in first‐line treatment, while standard‐dose PPIs would be sufficient in 10‐day bismuth quadruple therapies. On the other hand, in second‐line treatment, high‐dose PPIs would be more beneficial in 14‐day triple therapy with levofloxacin and amoxicillin or in 10‐day bismuth quadruple therapy either as a three‐in‐one single capsule or in the traditional scheme.

AIMTo determine the sensitivity and specificity of the 13C-urea breath test (UBT) in patients taking proton pump inhibitors (PPIs), using a new test meal Refex.METHODSOne hundred and fourteen consecutive patients with dyspepsia, 53 Helicobacter pylori (H. pylori) positive, 49 H. pylori negative, were included in the study. The patients were then given esomeprazole 40 mg for 29 consecutive days, and the 13C-UBT with the new test meal was performed the next morning.RESULTSThe sensitivity of the 13C-UBT with a cut off 2.5‰ was 92.45% (95%CI: 81.79%-97.91%) by per-protocol (PP) analysis and 78.13% (95%CI: 66.03%-87.49%) by intention-to-treat (ITT) analysis. The specificity of the 13C-UBT test was 96.00% in the ITT population (95%CI: 86.29%-99.51%) and 97.96% in the PP population (95%CI: 89.15%-99.95%).CONCLUSIONThe new test meal based 13C-UBT is highly accurate in patients on PPIs and can be used in those unable to stop their PPI treatment.

BackgroundHelicobacter pylori infection is the main cause of gastric cancer. The disease progression is influenced by the host inflammatory responses, and cytokine single nucleotide polymorphisms (SNPs) may have a role in the course of the disease. The aim of our study was to investigate proinflammatory cytokine polymorphisms, previously associated with the development of gastric cancer, in a Slovenian population.Patients and methods.In total 318 patients and controls were selected for the study and divided into three groups: (i) patients with gastric cancer (n = 58), (ii) patients with chronic gastritis (n = 60) and (iii) healthy control group (n = 200). H. pylori infection in patient groups was determined by serology, histology and culture. Four proinflammatory gene polymorphisms were determined (IL-1β, IL-1ra, TNF-α, TLR-4) in all subjects.ResultsWe found a statistically significant difference between males and females for the groups (p = 0.025). Odds ratio (OR) for gastric cancer risk for females was 0.557 (95% confidence interval [CI]: 0.233–1.329) and for chronic gastritis 2.073 (95% CI: 1.005–4.277). IL-1B-511*T/T homozygous allele for cancer group had OR = 2.349 (95% CI: 0.583–9.462), heterozygous IL-1B-511*T had OR = 1.470 (95% CI: 0.583–3.709) and heterozygotes in TNF-A-308 genotype for chronic gastritis had OR = 1.402 (95% CI: 0.626–3.139). Other alleles had OR less than 1.ConclusionsWe could not prove association between gastric cancer and chronic gastritis due to H. pylori in any cytokine SNPs studied in Slovenian population. Other SNPs might be responsible besides infection with H. pylori for the progression from atrophy to neoplastic transformation.

Proton pump inhibitors (PPIs) are the drugs of choice in the therapy of acid-related disorders. PPIs are as a class remarkably safe. Serious adverse events such as acute interstitial nephritis are extremely rare. Some reports in recent years have placed some concern on the long-term use of PPIs. Long-term therapy with PPIs can cause hypochlorhydria, hypergastrinemia and has interactions on hepatic cytochrome P450 enzymes which might increase the risk of infectious complications, nutritional deficiencies and drug-drug interactions. The vast majority of data came from retrospective case-control or cohort studies which are prone to confounders. At the moment we cannot conclude that long-term PPI use causes anemia, osteoporosis and bone fractures, increases the risk for pulmonary or enteric infections, has an effect on GUT mucosa, polyp or tumor formation, or that PPI use increases the risk of cardiovascular events in patients on PPIs and clopidogrel. We need prospective randomized trials to be able to definitely answer the questions raised in epidemiologic studies. Maintenance therapy with PPIs should be started only if strict indications for that therapy are fulfilled.

The aim of our study was to evaluate the clinical course of disease in 63 duodenal ulcer (DU) patients during a 4-year follow-up after Helicobacter pylori (H. pylori) eradication. Upper gastrointestinal endoscopy and a clinical interview were performed before antimicrobial therapy, 2 months after, yearly and when symptoms recurred. Two antral and two corporal specimens were taken for histology, and one additional specimen from antrum was taken for rapid urease test at the first endoscopy and for culture at the following endoscopies. All patients received triple antimicrobial regimens based on colloidal bismuth subcitrate, amoxycillin and metronidazole for at least 2 weeks. Patients with a negative histology and culture 2 months after antimicrobial therapy were included in the study. After H. pylori eradication, ulcer recurrence dropped from 84.1% per year in the year before H. pylori eradication to a mean value of 5.2% per year during 2076 patient months (p<0.01). The increased incidence of gastroesophageal reflux disease (GERD) was found only in the first year of the follow-up period. The average percentage of anti-ulcer drug users per year was 30.8% because of GERD, reflux symptoms, ulcer recurrence or non-ulcer dyspepsia. Ulcers or acute erosions recurred in 9 H. pylori-negative patients; recurrences were attributable to non-steroidal anti-inflammatory drugs (NSAID) in 4 out of 9 cases (44.4%). H. pylori eradication changed the long-term course of DU disease.