Epithelium-protective therapy for patients with autoimmune gastritis with different status of Helicobacter pylori

Introduction. Helicobacter pylori (H. pylori) and autoimmune inflammation are leading etiologic factors of chronic gastritis. Given the lack of etiological treatment for autoimmune gastritis (AIG), there is a need to consider the use of epithelial-protective therapy for this group of patients and analyze of its effectiveness.

Aim. To assess the effectiveness of therapy with the cytoprotector rebamipide in patients with AIG with different status of infection with H. pylori.

Materials and methods. An open, cohort randomized study was conducted involving 60 patients with chronic atrophic gastritis (CAG). Three groups were formed considering the etiologic factor of CAG: the main group of patients with AIG, comparison group 1 – with AIG in combination with H. pylori, comparison group 2 – with H. pylori-associated gastritis. Patients with AIG, some with AIG in combination with H. pylori and those with H. pylori-associated gastritis received rebamipide for 12 weeks. A statistical analysis of the control results of the dynamics of dyspepsia symptoms and a morphological study of gastrobiopsy samples, was performed.

Results. In groups of patients receiving rebamipide therapy, a statistically significant decrease in the severity and incidence of dyspepsia symptoms was observed by the 4th and 12th weeks of observation. When assessing the results of a control morphological study in the groups of patients with AIG and AIG in combination with H. pylori, a statistically significant trend towards a decrease in the degree of inflammation was observed. In the group of patients with H. pylori-associated gastritis, a statistically significant decrease in the degree of inflammation was also noted.

Conclusion. The use of epithelium-protective therapy in patients with AIG has a beneficial effect on the manifestations of dyspepsia syndrome. A statistically significant trend towards a decrease in the severity of inflammatory changes in the gastric mucosa in patients with AIG was observed while taking rebamipide. Further studies are required regarding the effectiveness of rebamipide in patients with AIG with a long follow-up period.

1. Rugge M, Genta RM, Malfertheiner P, Dinis-Ribeiro M, El-Serag H, Graham DY et al. RE.GA.IN.: the Real-world Gastritis Initiative-updating the updates. Gut. 2024;73(3):407–441. https://doi.org/10.1136/gutjnl-2023-331164.

2. Bordin DS, Mozgovoy SI, Livzan MA, Gaus OV, Maev IV. Interdisciplinary Consensus RE.GA.IN.: What is New? Part I: Definitions, Helicobacter pyloriAssociated and Autoimmune Gastritis. Effective Pharmacotherapy. 2024;20(2): 54–70. (In Russ.) https://doi.org/10.33978/2307-3586-2024-20-2-54-70.

3. Rawla P, Barsouk A. Epidemiology of gastric cancer: global trends, risk factors and prevention. Prz Gastroenterol. 2019;14(1):26–38. https://doi.org/10.5114/pg.2018.80001.

4. Watari J, Chen N, Amenta PS, Fukui H, Oshima T, Tomita T et al. Helicobacter pylori associated chronic gastritis, clinical syndromes, precancerous lesions, and pathogenesis of gastric cancer development. World J Gastroenterol. 2014;20(18):5461–5473. https://doi.org/10.3748/wjg.v20.i18.5461.

5. Salvatori S, Marafini I, Laudisi F, Monteleone G, Stolfi C. Helicobacter pylori and Gastric Cancer: Pathogenetic Mechanisms. Int J Mol Sci. 2023;24(3):2895. https://doi.org/10.3390/ijms24032895.

6. Goldenring J. No H. pylori, no adenocarcinoma for patients with autoimmune gastritis. Gut. 2023;72(1):1–2. https://doi.org/10.1136/gutjnl-2022-328068.

7. Nehme F, Rowe K, Palko W, Tofteland N, Salyers W. Autoimmune metaplastic atrophic gastritis and association with neuroendocrine tumors of the stomach. Clin J Gastroenterol. 2020;13(3):299–307. https://doi.org/10.1007/s12328-019-01074-7.

8. Gubanova AV, Livzan MA, Krolevets TS, Mozgovoi SI, Rubtsov AV, Stepanchenko MA. Autoimmune gastritis and stomach cancer: assessing the risks. Experimental and Clinical Gastroenterology. 2023;211(3):112–119. (In Russ.) Available at: https://elibrary.ru/ilvnvd.

9. Castellana C, Eusebi LH, Dajti E, Iascone V, Vestito A, Fusaroli P et al. Autoimmune Atrophic Gastritis: A Clinical Review. Cancers. 2024;16(7):1310. https://doi.org/10.3390/cancers16071310.

10. Ivashkin VT, Maev IV, Lapina TL, Fedorov ED, Sheptulin AA, Trukhmanov AS et al. Clinical Recommendations of Russian Gastroenterological Association and RENDO Endoscopic Society on Diagnosis and Treatment of Gastritis and Duodenitis. Russian Journal of Gastroenterology, Hepatology, Coloproctology. 2021;31(4): 70–99. (In Russ.) https://doi.org/10.22416/1382-4376-2021-31-4-70-99.

11. Bordin DS, Livzan MA, Osipenko MF, Mozgovoy SI, Andreyev DN, Maev IV. The key statements of the Maastricht VI consensus. Experimental and Clinical Gastroenterology. 2022;205(9):5–21. (In Russ.) Available at: https://elibrary.ru/kqdihj.

12. Orgler E, Dabsch S, Malfertheiner P, Schulz C. Autoimmune Gastritis: Update and New Perspectives in Therapeutic Management. Curr Treat Options Gastroenterol. 2023;21:64–77. https://doi.org/10.1007/s11938-023-00406-4.

13. Kaibysheva VO, Tykhonov SV, Kashin SV, Kuvaev RO, Kraynova EA, Baculina NV et al. Algorithm of autoimmune gastritis diagnosis and treatment. Profilakticheskaya Meditsina. 2024;27(9):101–110. (In Russ.) https://doi.org/10.17116/profmed202427091101.

14. Shah SC, Piazuelo MB, Kuipers EJ, Li D. AGA Clinical Practice Update on the Diagnosis and Management of Atrophic Gastritis: Expert Review. Gastroenterology. 2021;161(4):1325–1332.e7. https://doi.org/10.1053/j.gastro.2021.06.078.

15. Абдулхаков РА, Абдулхаков СР, Алексеева ОП, Алексеенко СА, Андреев ДН, Барановский АЮ и др. Гастрит и дуоденит: клинические рекомендации. М.; 2024. 70 с. Режим доступа: https://cr.minzdrav.gov.ru/view-cr/708_2.

16. Lenti MV, Rugge M, Lahner E, Miceli E, Toh BH, Genta RM et al. Autoimmune gastritis. Nat Rev Dis Primers. 2020;6(1):56. https://doi.org/10.1038/s41572-020-0187-8.

17. Miceli E, Vanoli A, Lenti MV, Klersy C, Di Stefano M, Luinetti O et al. Natural history of autoimmune atrophic gastritis: a prospective, single centre, longterm experience. Aliment Pharmacol Ther. 2019;50(11-12):1172–1180. https://doi.org/10.1111/apt.15540.

18. Han X, Jiang K, Wang B, Zhou L, Chen X, Li S. Effect of Rebamipide on the Premalignant Progression of Chronic Gastritis: A Randomized Controlled Study. Clin Drug Investig. 2015;35(10):665–673. https://doi.org/10.1007/s40261-015-0329-z.

19. Andreev DN, Maev IV. Rebamipide: evidence base for use in gastroenterology. Terapevticheskii Arkhiv. 2020;92(12):97–104. (In Russ.) https://doi.org/10.26442/00403660.2020.12.200455.

20. Lapina TL, Ivashkin VT. Rebamipide During chronic gastritis: H. pylori eradication therapy and restoration of gastric mucosa barrier function. Russian Journal of Gastroenterology, Hepatology, Coloproctology. 2023;33(6):81–87. (In Russ.) https://doi.org/10.22416/1382-4376-2023-33-6-81-87.

21. Simanenkov VI, Maev IV, Tkacheva ON, Alekseenko SA, Andreev DN, Bakulina NV et al. Epithelial protective therapy in comorbid diseases. Practical Guidelines for Physicians. Terapevticheskii Arkhiv. 2022;94(8):940–956. (In Russ.) https://doi.org/10.26442/00403660.2022.08.201523.

22. Suzuki T, Yoshida N, Nakabe N, Isozaki Y, Kajikawa H, Takagi T et al. Prophylactic effect of rebamipide on aspirin-induced gastric lesions and disruption of tight junctional protein zonula occludens-1 distribution. J Pharmacol Sci. 2008;106(3):469–477. https://doi.org/10.1254/jphs.fp0071422.

23. Zvyaglova MYu, Knyazev OV, Parfenov AI. Pharmacological and clinical feature of rebamipide: new therapeutic targets. Terapevticheskii Arkhiv. 2020;92(2): 104–111. (In Russ.) https://doi.org/10.26442/00403660.2020.02.000569.

24. Maev IG, Kazyulin AN. New opportunities for the prevention of gastric cancer. Terapevticheskii Arkhiv. 2017;89(4):101–109. (In Russ.) https://doi.org/10.17116/terarkh2017894101-109.

25. Nishizawa T, Suzuki H, Nakagawa I, Minegishi Y, Masaoka T, Iwasaki E, Hibi T. Rebamipide-promoted restoration of gastric mucosal sonic hedgehog expression after early Helicobacter pylori eradication. Digestion. 2009;79(4):259–262. https://doi.org/10.1159/000213241.

26. Naito Y, Yoshikawa T. Rebamipide: a gastrointestinal protective drug with pleiotropic activities. Expert Rev Gastroenterol Hepatol. 2010;4(3):261–270. https://doi.org/10.1586/egh.10.25.

27. Rugge M, Meggio A, Pennelli G, Piscioli F, Giacomelli L, De Pretis G, Graham DY. Gastritis staging in clinical practice: the OLGA staging system. Gut. 2007;56(5):631–636. https://doi.org/10.1136/gut.2006.106666.

28. Aruin LI, Kononov AV, Mozgovoi SI. International classification of chronic gastritis: what should be taken and what is in doubt. Arkhiv Patologii. 2009;71(4):11–18 (In Russ.) Available at: https://elibrary.ru/kwqqol.

29. Новик АА, Ионова ТИ, Шевченко ЮЛ (ред.). Руководство по исследованию качества жизни в медицине. 2-е изд. М.: ОЛМА Медиа групп; 2007. 320 с. Режим доступа: https://rehab-base.ru/wp-content/uploads/2023/03/novik.pdf.

30. Rossi RE, Elvevi A, Sciola V, Mandarino FV, Danese S, Invernizzi P, Massironi S. Paradoxical association between dyspepsia and autoimmune chronic atrophic gastritis: Insights into mechanisms, pathophysiology, and treatment options. World J Gastroenterol. 2023;29(23):3733–3747. https://doi.org/10.3748/wjg.v29.i23.3733.

31. Lee JS, Jeon SW, Lee HS, Kwon YH, Nam SY, Bae HI, Seo AN. Rebamipide for the Improvement of Gastric Atrophy and Intestinal Metaplasia: A Prospective, Randomized, Pilot Study. Dig Dis Sci. 2022;67(6):2395–2402. https://doi.org/10.1007/s10620-021-07038-7.

32. Kamada T, Sato M, Tokutomi T, Watanabe T, Murao T, Matsumoto H et al. Rebamipide improves chronic inflammation in the lesser curvature of the corpus after Helicobacter pylori eradication: a multicenter study. Biomed Res Int. 2015;2015:865146. https://doi.org/10.1155/2015/865146.

33. Bakulin IG, Sushilova AG, Zharkov AV, Malkov VA. Effectiveness of 6-Month Rebamipide Therapy in Chronic Atrophic Gastritis: Results of the OPLOT Study. Effektivnaya farmakoterapiya. 2024; 20(46):28–34. (In Russ.) Available at: https://elibrary.ru/lhqcds.