The thesis is dedicated to the study of pathology-based morphological features of the chronic gastritis (CG) types associated with H. pylori infection depending on genotype.
The following methods were used in the study: general histological, histochemical, molecular-genetic, lectin-based and immunohistochemical research of biopsic material taken from patients suffering from CG of different types, as well as laboratory and instrumental examination of these patients, and statistical processing of the study findings.
The study was conducted on biopsy material taken from 365 patients of the Pirogov Memorial Clinical Hospital, the Ukrainian Air Force Medical Center for the Central Region, and «Altamedika Plus» medical treatment facility in compliance with the international bioethical standards.
The study revealed that H. pylori-infected patients with an elevated relative risk of CG development (χ2 = 4.59, p = 0.032) dominated by 1.45 times (CI: 1.02–2.45) over uninfected ones among all CG patients; the patients over 45 also demonstrated a higher incidence of the disease. According to the first-ever molecular genetic assay conducted in Vinnytsia region, dysplastic changes of the gastric mucosa (GM) in patients with chronic nonatrophic gastritis (CNG) and chronic atrophic gastritis (CAG) infected with H. pylori strains carrying the cagA+ and vacA s1m1 alleles (p<0.001 and p<0.05) dominated over those observed in the cag- group, which made it possible to determine the H. pylori genotype with the greatest potential for preneoplastic and neoplastic GM transformations in patients with underlying chronic gastritis. The connection between the H. pylori invasiveness, the vacuolizing toxin gene (vacA) and the cytotoxin-associated gene (cagA) was proven. A close relationship between the cagA gene, invasiveness, activity and contamination of the chronic non-atrophic gastritis was established, the fact of which was substantiated by Fisher's exact test = 0.00235, p<0.05; 0.01204, p<0.05; and 0.01204, p<0.05 in case of low, moderate, and high contamination, accordingly.
As for chronic atrophic gastritis, the Fisher's exact test was equal to 0.01133, p<0.05; 0.00310, p<0.05; and 0.00135, p<0.05 in case of low, moderate and high contamination, accordingly. A close relationship between contamination degree and chronic gastritis activity was also reported, as patients with high contamination degree were diagnosed stages 2–3 of the disease activity. Inter- and intraepithelial microorganism localization prevailed at high contamination degree and stage 3 activity in 76% of H. pylori cagA+ patients compared with the low contamination degree and stage 1 activity in patients with chronic nonatrophic gastritis. At the same time, cagA negative (cagA-) CNG patients presented inter- and intraepithelial localization of microorganisms only in 10% of high-contamination stage 3 activity patients compared to those with low-contamination stage 1 of the disease (p<0.001). However, inter- and intraepithelial localization of microorganisms in cagA+ patients was observed only in 35% of cases with high contamination degree and stage 3 disease activity, and in 5% in cagA- subjects. H. pylori was determined predominantly in the mucosa adjacent to the superficial epithelium at low-contamination and stage 1 activity of the disease in both CG groups. In our study, the inflammatory response depended on the availability of H. pylori strains carrying the cagA+ and vacA s1m1 alleles, which we believe played a key role in triggering the cascade of GM inflammatory changes and the progression of the disease. Histochemical analysis revealed a statistically-significant decrease in the production of neutral mucins and the emergence of sialomucins in the areas of severe dysplasia (D) of CNG and cagA+ vacA s1m1 CAG patients.
We developed a screening system for early diagnosis of precancerous GM changes based on different H. pylori genotypes, which would facilitate optimizing disease management of patients with chronic gastritis of different types and improve the efficiency of detecting dysplastic and atrophic GM changes at early stages.
