Helicobacter pylori Persistence in Patients with Peptic Ulcer Disease and Chronic Gastritis in the Treatment with Antibiotics and Acid-Suppressive Agents

Background. Chronic gastritides still have no division into forms according to the data of the genotyping of Helicobacter pylori isolates. Monitoring the results of anti-Helicobacter pylori therapy cannot be limited to eradication, by taking into account the data on Helicobacter pylori detection in healthy individuals. Is increased acid production associated with the presence of virulent or nonvirulent strains?

Objective. To search for the predominance of cagA or any allelic combination of vacA in the isolates from patients with mild and severe chronic gastritis and from those with peptic ulcer disease. To track the time course of changes in the disappearance and repeated gastric colonization with different Helicobacter pylori strains in patients with peptic ulcer disease immediately after anti-Helicobacter pylori therapy and 1.5–2 months later. To confirm or refute the fact that the increased acid production is associated with the presence of virulent Helicobacter pylori strains rather than with the persistence of nonvirulent strains.

Methods. The Helicobacter pylori isolates from the gastric biopsy specimens taken from patients with chronic gastritis and peptic ulcer disease were genotyped for cagA and allelic combinations of vacA. The strains from patients who had received anti-Helicobacter pylori therapy were genotyped using the variable number tandem repeat (VNTR) method. Patients with an exacerbation of peptic ulcer disease and those wth an exacerbation of chronic pancreatitis with concomitant gastritis were compared from the level of acid production and from the belonging of Helicobacter pylori to virulent strains.

Results. Patients with mild chronic gastritis were observed to have an abundance of nonvirulent allelic combination of vacAs2m2, which differed significantly from its frequency in both the patients with severe chronic gastritis and those with peptic ulcer disease. In the latter patients, the differences between the background bacteriological pattern and the pattern observed after 1.5–2 months had a high degree of significance; in these follow-up periods, in contrast to the control immediately after therapy, the number of eradications increased and the number of cagA-containing strains decreased due to the change of strains. Acid production was significantly higher in the patients with peptic ulcer disease than in those with chronic pancreatits and concomitant gastritis; the former patients show a statistically significant predominance of virulent strains; the latter patients had nonvirulent strains (at the same rate of Helicobacter pylori detection).

Conclusion. Filling the blank spots in the study of helicobacteriosis remains relevant due to the progress of genetic methods in bacteriology and to the introduction of novel approaches to assessing the results of anti-Helicobacter pylori therapy.

1. Cimmerman Ja.S. Kriticheskij analiz koncepcii o vedushhej roli H.pylori infekcii v razvitii gastroduodenal'nyh zabolevanij. Klinicheskaja Farmakologija i Terapija, 2019; 28 (2): 19–27. doi https://doi.org/10.32756/0869-5490-2019-2-19-27 (in Russian)

2. Khelikobakterioz. V. A. Isakova, I. V. Domaradskogo (ed.). Moscow: Medpraktika-M, 2003. (in Russian)

3. Sorokin V.M., Pisanov R.V., Vodop'yanov A.S., Golubkina E.V., Bereznyak E.A. Sravnitel'nyi analiz genotipov shtammov Helicobacter pylori v Rostovskoi i Astrakhanskoi oblastyakh. Meditsinskii Vestnik Yuga Rossii. 2018; 9 (4): 81–86. doi: https://doi.org/10.21886/2219-8075-2018-9-4-81-86. (in Russian)

4. Golubkina E. V., Sorokin V. M., Levitan B. N., Umerova A. R., Kamneva N. V. Geneticheskie razlichija shtammov Helicobacter pylori, vydelennyh u bol'nyh hronicheskim gastritom ljogkogo i tjazhjologo techenija. Antibiotiki i Khimioter. 2021; 66 (9–10): 24–29. doi: 10.24411/0235-2990-2021-66-9-10-24-29 (in Russian)

5. Chattopadhyay R. P., Ramamurthy T., Chowdhury A., Santra A., Dhali G. K. Multiplex PCR assay for rapid detection and genotyping of Helicobacter pylori directly from biopsy specimen. J Clin Microbiol. 2004; 42 (6): 2921–2824. doi: 10.1128/JCM.42.6.2821-2824.2004.

6. Koterov A.N., Ushenkova L.N., Zubenkova E.S., Kalinina M.V., Biryukov A.P., Lastochkina E.M. i dr. Sila svyazi. Soobshchenie 2. Gradatsii velichiny korrelyatsii. Meditsinskaya Radiologiya i Radiatsionnaya Bezopasnost. 2019; 64 (6): 12–24. doi: https://doi.org/1010.12737/1024-6177-2019-64-6-12-24. (in Russian)

7. Sidorenko E.V. Metody matematicheskoj obrabotki v psihologii. SPb: OOO «Rech'», 2000; 350. ISBN 5-9268-0010-2 (in Russian).

8. Bereznyak E.A., Sorokin V.M., Karpova I.O., Stupina N.A., Terent'ev A.N. Osobennosti genotipov shtammov Helicobacter pylori, tsirkuliruyushchikh v Rostovskoi oblasti. Epidemiologiya i Vaktsinoprofilaktika. 2013; 4 (71): 30–33. (in Russian)

9. Orlov S.V., Kalashnikova V.A., Baryshnikova N.V., Uspenskij Ju.P. Geneticheskie osobennosti infekcii Helicobacter pylori u nizshih primatov i cheloveka. Dnevnik Kazanskoj Medicinskoj Shkoly. 2015; 1: 15–21. (in Russian)

10. Nizhevich A.A, Je. N. Ahmadeeva, E. S. Kuchina, M. M. Tujgunov, V. U. Sataev Regional'nye genotipy Helicobacter pylori sredi detej s gastroduodenal'nymi zabolevanijami v respublike Bashkortostan. Medicinskij Vestnik Juga Rossii. 2013; 2: 94–97 (in Russian).

11. Chernin V. V., Bondarenko V. M., Chervinec V. M., Bazlov S. N. Helicobacter pylori kak sostavnaja chast' mikrobiocenoza mukoznoj mikroflory jezofagogastroduodenal'noj zony v norme i patologii. Jeksperimental'naja i Klinicheskaja Gastrojenterologija. 2011; 8: 66–72 (in Russian)

12. Gasanova E. V. Helikobakter: mify i real'nost'. [Jelektronnyj resurs]. — Rezhim dostupa: https://www.eurolab-portal.ru/encyclopedia/Gastroenterology.patient/49687/ (in Russian).

13. Malfertheiner P., Megraud F., O’Morain C.A. et al. Management of Helicobacter pylori infection — the Maastricht V/Florence Consensus Report. Gut. 2017; 66: 6–30. doi: 10.1136/gutjnl-2016-312288. Epub 2016 Oct 5.

14. Ivashkin V.T., Maev I.V., Lapina T.L., A.A. Sheptulin, A.S. Trukhmanov, E.K. Baranskaya, R.A. Abdulkhakov, O.P. Alekseeva, S.A. Alekseenko, N.N. Dekhnich, R.S. Kozlov, I.L. Klyaritskaya, N.V. Korochanskaya, S.A. Kurilovich, M.F. Osipenko, V.I. Simanenkov, A.V. Tkachev, I.B. Khlynov, V.V. Tsukanov. Klinicheskie rekomendatsii Rossiiskoi gastroenterologicheskoi assotsiatsii po diagnostike i lecheniyu infektsii Helicobacter pylori u vzroslykh. Rossiiskii Zhurnal Gastroenterologii, Gepetologii, Koloproktologii. 2018; 28(1): 55–77 (in Russian)

15. Sorokin V.M., Pisanov R.V., Vodop'janov A.S., Golubkina E.V. New tool for phylogenetic analysis of Helicobacter pylori. World Journal of Advanced Research and Reviews. 2020; 6 (2): 60–67. doi: https://doi.org/10.30574/wjarr.2020.6.2.0128.

16. Golubkina E.V., Sorokin V.M., Kamneva N.V., Umerova A.R. Otdaljonnye rezul'taty antihelikobakternoj terapii — genotipirovanie metodom VNTR. Ural'skij Medicinskij Zhurnal. 2016; 11 (144): 81–86. (in Russian)

17. Golubkina E.V., Sorokin V.M., Levitan B.N., Umerova A.R., Kamneva N.V. Jeradikacija, sohranenie shtamma, smena shtamma — ishody antihelikobakternoj terapii. Antibiotiki i khimioter. 2021; 66: 3–4. doi: https://doi.org/10.37489/0235-2990-2021-66-3-4-18-26 (in Russian)

18. Bordin D. S., Livzan M. A., Osipenko M. F., Mozgovoj S. I., Andreev D. N., Maev I. V. Kljuchevye polozhenija konsensusa Maastriht VI. Jeksperimental'naja i Klinicheskaja Gastrojenterologija. 2022; 205 (9): 5–21. [Jelektronnyj resurs]. Rezhim dostupa: https://doi.org/10.31146/1682-8658-ecg-205-9-5-21 (in Russian)

19. Sorokin V.M., Pisanov R.V., Golubkina E.V., Bereznyak E.A., Prozorova L.A. Comparative Multiple-Locus Variable-Number Tandem Repeat Analysis of Helicobacter Pylori Isolates from South of Russia. International Journal of Microbiology and Biotechnology. 2017; 2 (3): 135–138. https://doi.org/10.11648/j.ijmb.20170203.15.

20. Glants S. ediko-biologicheskaya statistika. «Praktika», Moscow: 1999; 459. (in Russian)

21. Wu W., Yang Y., Sun G. Recent insights into antibiotic resistance in Helicobacter pylori eradication. Gastroenterology Research and Practice. 2012; 723183 Published online 2012 Jul 5. doi: 10.1155/2012/723183.

22. Starostin, B.D., Starostina G.A. Gibridnaja antihelikobakternaja terapija. Rossijskij Zhurnal Gastrojenterologii, Gepatologii, Koloproktologii. Prilozhenie № 46. Materialy 21 Rossijskoj gastrojenterologicheskoj nedeli. 2015; XXV (5): 31 (in Russian)

23. Hamrabaeva F.I. K voprosu optimizacii jeradikacionnoj terapii pri jazvennoj bolezni dvenadcatiperstnoj kishki. Rossijskij Zhurnal Gastrojenterologii, Gepatologii, Koloproktologii. Prilozhenie № 44. Materialy Jubilejnoj 20 Rossijskoj gastrojenterologicheskoj nedeli. 2014; XXIV (5): 30 (in Russian)

24. Belova O.L., Belova I.M. Jeffektivnost' protivojazvennoj i jeradikacionnoj terapii jazvennoj bolezni dvenadcatiperstnoj kishki. Rossijskij Zhurnal Gastrojenterologii, Gepatologii, Koloproktologii. Prilozhenie № 46. Materialy 21 Rossijskoj gastrojenterologicheskoj nedeli. 2015; XXV (5): 17 (in Russian)

25. Ivaylo I. Ivanov & Kenya Honda. Intestinal. Commensal Microbes as Immune Modulators. Cell Host & Microbe. 2012; 12 (18): 496–508.

26. Otklonenie jempiricheskogo raspredelenija ot normal'nogo (vidy otklonenij i prichiny). [Jelektronnyj resurs]. Rezhim dostupa: https://cyberpedia.su/6xb6e9.html. (in Russian)

27. Pristenochnaja jendoskopija rN-metrija ZhKT. [Jelektronnyj resurs]. Rezhim dostupa: https://www.gastroscan.ru/physician/endoscopy/ (in Russian)

28. Statistics Kingdom. Shapiro-Wilk Test Calculator. https://www.statskingdom.com/shapiro-wilk-test-calculator.html.

29. Obrabotka jeksperimental'nyh dannyh: Konspekt lekcij. [Jelektronnyj resurs]. Rezhim dostupa: https://pandia.ru/text/80/281/37837-16.php. (in Russian)

30. Sravnitel'nyj analiz kriteriev proverki normal'nosti odnomernyh velichin (Chast' 1). [Jelektronnyj resurs]. Rezhim dostupa: https://ami.nstu.ru/~headrd/seminar/Kontrol_Q/new_normal_red.htm# (in Russian)

31. Shhelykalina S.P. Proverka normal'nosti vyborochnyh dannyh izmerenija peremennyh v nepreryvnoj shkale. [Jelektronnyj resurs]. Rezhim dostupa: http://do.rsmu.ru/fileadmin/user_upload/mbf/c_kibernetiki/23.10.2020_Lek_Proverka_normalnosti_vyborochnykh_dannykh_izmerenija_peremennykh_v_nepreryvnoi_.pdf (in Russian)

32. Golubkina E.V., A.R.Umerova, N.V.Kamneva, I.A.Metjolkin, A.A.Tjurin. Kislotosupressivnyj jeffekt pri provedenii podderzhivajushhej terapii u bol'nyh jazvennoj bolezn'ju. Astrahanskij Medicinskij Zhurnal. 2013; 2: 132–134 (in Russian)

33. Fandriks L., Lonroth H., Pettersson A., Vakil N. Can famotidine and omeprazole be combined on a once-daily basis? Scandinavian Journal of Gastroenterology. 2007; 42 (6): 869–894.

34. Shimatani T., Inoue M., Kuroiwa T., Moriwaki M. Which has superior acid-suppressive effect, 10 mg omeprazole once daily or 20 mg twice daily? Effects of single or repeated administration in Japanese Helicobacter pylori-negative CYP2C19 extensive metabolizers. Digestive Diseases and Sciences 2007; 52 (2): 390–395. doi: 10.1007/s10620-006-9490-9. Epub 2007 Jan 9.

35. Sotnikov V.N., Dubinskaja T.K., Volova A.V., Jakovlev G.A. Znachenie jendoskopicheskoj rN-metrii v opredelenii kislotoproducirushhej funkcii zheludka: posobie dlja vrachej. Rossijskaja medicinskaja akademija poslediplomnogo obrazovanija. Moscow: 2005: 35. (in Russian)

36. Domracheva E.V., Sarsenbaeva A.S., Ufimcev K.A. Neodnorodnost' geneticheskih variantov Helicobacter pylori u pacientov s razlichnymi kislotozavisimymi zabolevanijami. Jeksperimental'naja i Klinicheskaja Gastrojenterologija. 2014; 111 (11): 72. (in Russian)

37. Domracheva E.V., Sarsenbaeva A.S. Kliniko-funkcional'nye osobennosti bol'nyh hronicheskim pankreatitom i soputstvujushhim Helicobacter pylori-associirovannym gastritom. Jeksperimental'naja i Klinicheskaja Gastrojenterologija. 2019; 163(3): 31–37. doi: 10.31146/1602-8658-ecg-163-3-31-37. (in Russian)

38. Golubkina E. V., Sorokin V. M., Umerova A. R., Kamneva N. V. Kislotoobrazovanie u gastrojenterologicheskih bol'nyh pri kolonizacii zheludka virulentnymi i nevirulentnymi shtammami helikobaktera. Jeksperimental'naja i klinicheskaja gastrojenterologija. 2019; 169 (9): 32–37. doi: 10.31146/1682-8658-ecg-169-9-32-37. (in Russian)