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Non-malignant Helicobacter pylori-Associated Diseases

  • Christina Falkeis-Veits
  • Michael ViethEmail author
Part of the Advances in Experimental Medicine and Biology book series


Helicobacter pylori infection of the human stomach is associated with chronic gastritis, peptic ulcer disease or gastric carcinoma, and thus a high burden for the public health systems worldwide. Fortunately, only a small subfraction of up to 15–20% of infected individuals will develop serious complications. Unfortunately, it is not always known upfront, who will be affected by serious diesease outcome. For risk stratifications, it is therefore necessary to establish a common terminology and grading system, that can be applied worldwide to compare population data. The updated Sydney System for classification of gastritis with its semi-quantitative analogue scale is the system, that is currently used worldwide. Additionally, pathologists should always try to classify the etiology of the inflammatory infiltrates in the stomach to instruct the clinicians for choosing a proper treatment regime. Risk factors such as intestinal metaplasia, atrophy and scoring systems to classify these risk factors into a clinical context such as OLGA and OLGIM are discussed. Also, special forms of gastritis like lymphocytic gastritis, autoimmune gastritis and peptic ulcer disease are explained and discussed e.g. how to diagnose and how to treat. Extra-gastric sequelae of H. pylori infections inside and outside the stomach are shown in this chapter as well. Important host and bacterial risk factors such as pathogenicity islands are dicussed to draw a complete landscape around a H. pylori infection, that still can be diagnosed in patients. However, it needs to be noted that some countries have almost no H. pylori infection anymore, while others have still a very high frequency of infections with or without serious complications. The understanding and application of risk assessements may help to save money and quality of life. Extra-gastric H. pylori infections are rarely reported in the literature until today. The pathogenitiy is still under debate, but especially in the bile ducts and gallbladder, several pathological conditions may be also based on H. pylori infection, and will be also discussed.


Helicobacter pylori Gastritis Sydney system Atrophic gastritis 


  1. Backert S, Tegtmeyer N, Fischer W (2015) Composition, structure and function of the Helicobacter pylori cag pathogenicity island encoded type IV secretion system. Future Microbiol 10(6):955–965. Scholar
  2. Backert S, Tegtmeyer N, Oyarzabal OA, Osman D, Rohde M, Grützmann R, Vieth M. (2018)Unusual manifestation of live Staphylococcus saprophyticus, Corynebacterium urinapleomorphum and Helicobacter pylori in the gallbladder with cholecystitis. Int J Mol Sci 19(7) pii:E1826. Scholar
  3. Bansal VK, Misra MC, Chaubal G, Datta Gupta S, Da B, Ahuja V, Sagar S (2012) Helicobacter pylori in gallbladder mucosa in patients with gallbladder disease. Indian J Gastroenterol 31:57–60. Scholar
  4. Bauwens E, Joosten M, Taganna J, Rossi M, Debraekeleer A, Tay A, Peters F, Backert S, Fox J, Ducatelle R, Remaut H, Haesebrouck F, Smet A (2018) In silico proteomic and phylogenetic analysis of the outer membrane protein repertoire of gastric Helicobacter species. Sci Rep 8(1):15453. Scholar
  5. Capelle LG, de Vries AC, Haringsma J, Ter Borg F, de Vries RA, Bruno MJ, van Dekken H, Meijer J, van Grieken NC, Kuipers EJ (2010) The staging of gastritis with the OLGA system by using intestinal metaplasia as an accurate alternative for atrophic gastritis. Gastrointest Endosc 71(7):1150–1158. https// Scholar
  6. Chen DF, Hu L Yi P, Liu WW, Fang DC, Cao H (2007) H pylori exist in the gallbladder mucosa of patients with chronic cholecystitis. World J Gastroenterol 13(10):1608–1611. Scholar
  7. da Costa DM, Pereira Edos S, Rabenhorst SH (2015) What exists beyond cagA and vacA? Helicobacter genes in gastric diseases. World J Gastroenterol 21(37):10563–10572. Scholar
  8. da Silva-Etto JMK, Mattar R, Villares-Lopes CA, Marques SB, Carrilho FJ (2017) Evaluation of diagnostic accuracy of two rapid stool antigen tests using an immunochromatographic assay to detect Helicobacter pylori. Clin Biochem 50(16–17):959–962. Scholar
  9. De Groote D, van Doorn LJ, van den Bulck K, Vandamme P, Vieth M, Stolte M, Debongnie JC, Burette A, Haesebrouck F, Ducatelle R (2005) Detection of non-pylori species in “Helicobacter heimannii” infected humans. Helicobacter 10(5):398–402. Scholar
  10. Dixon MF, Genta RM, Yardley JH, Correa P (1996) Classification and grading of gastritis. The updated Sydney System. International workshop on the histopathology of gastritis, Houston 1994. Am J Surg Pathol 20(10):1161–1181Google Scholar
  11. Dye KR, Marshall BJ, Frierson HF Jr, Pambianco DJ, McCallum RW (1990) Camplyobacter pylori colonizing heterotopic gastric tissue in the rectum. Am J Clin Pathol 93(1):144–147Google Scholar
  12. Giroux V, Rustqi AK (2017) Metaplasia: tissue injury adaption and a precursor to the dysplasia-cancer sequence. Nat Rev Cancer 17(10):594–604. Scholar
  13. Goji S, Tamujra Y, Sasaki M, Nakamura M, Matsui H, Murayama SY, Ebi M, Ogasawara N, Funaki Y, Kasugai K (2015) Helicobacter suis-infected nodular gastritis and a review of diagnostic sensitivity for Helicobacter heilmanii-like organisms. Case Rep Gastroenterol 9(2):179–197. Scholar
  14. Graham DY, Zou WY (2018) Guilt by association: intestinal metaplasia does not progress to gastric cancer. Curr Opin Gastroenterol 34(6):458–464. Scholar
  15. Iannone A, Giorgio F, Russo F, Riezzo G, Girardi B, Pricci M, Palmer SC, Barone M, Principi M, Strippoli GF, Di Leo A, Ierardi E (2018) New fecal test for non-invasive Helicobacter pylori detection: a diagnostic accuracy study. World J Gastroenterol 24(27):3021–3029. Scholar
  16. Kast RE (2007) Some fibrocystic breast change may be caused by sexually transmitted H. pylori during oral nipple contact: supporting literature and case report of resolution after gut H. pylori eradication treatment. Med Hypotheses 68(5):1041–1046. Scholar
  17. Kawaguchi M, Saito T, Ohno H, Midorikawa S, Sanji T, Handa Y, Morita S, Yoshida H, Tsurui M, Misaka R, Hirota T, Saito M, Minami K (1996) Bacteria closely resembling Helicobacter pylori detected immunohistologically and genetically in resected gallbladder mucosa. J Gastroenterol 31:294–298. Scholar
  18. Kubota-Aizawa S, Ohno K, Fukushima K, Kenemoto H, Nakashima K, Uchida K, Chambers JK, Goto-Koshino Y, Watanabe T, Sekizaki T, Mimuro H, Tsujimoto H (2017) Epidemiological study of gastric Helicobacter spp. in dogs with gastrointestinal disease in Japan and diversity of Helicobacter heilmanii sensu stricto. Vet J 225:56–62. Scholar
  19. Kulnigg-Dabsch S (2016) Autoimmune gastritis. Wien Med Wochenschr 166:424–430. Scholar
  20. Kusters JG, van Vliet AH, Kuipers EJ (2006) Pathogenesis of Helicobacter pylori infection. Clin Microbiol Rev 19(3):449–490. Scholar
  21. Labenz J, Blum AL, Bayerdörffer E, Meining A, Stolte M, Börsch G (1997) Curing Helicobacter pylori infection in patients with duodenal ulcer may provoke reflux esophagitis. Gastroenterology 112(5):1442–1447. Scholar
  22. Lind J, Backert S, Pfleiderer K, Berg DE, Yamaoka Y, Sticht H, Tegtmeyer N (2014) Systematic analysis of phosphotyrosine antibodies recognizing single phosphorylated EPIYA-motifs in CagA of Western-type Helicobacter pylori strains. PLoS One 9(5):e96488. Scholar
  23. Lind J, Backert S, Hoffmann R, Eichler J, Yamaoka Y, Perez-Perez GI, Torres J, Sticht H, Tegtmeyer N (2016) Systematic analysis of phosphotyrosine antibodies recognizing single phosphorylated EPIYA-motifs in CagA of East Asian-type Helicobacter pylori strains. BMC Microbiol 16(1):201. Scholar
  24. Livzan MA, Kononov AV, Mozgovoĭ SI (2004) Ex-Helicobacter gastritis: is it a neologism or clinical reality? Eksp Klin Gastroenterol 148(5):55–59Google Scholar
  25. Madisch A, Miehlke S, Neuber F, Morgner A, Kuhlisch E, Rappel S, Lehn N, Bayerdörffer E, Seitz G, Stolte M (2006 Feb 15) Healing of lymphocytic gastritis after helicobacter pylori eradication therapy–a randomized, double-blind, placebo-controlled multicentre trial. Aliment Pharmacol Ther 23(4):473–479Google Scholar
  26. Mäkinen JM, Niemelä S, Kerola T, Lehtola J, Karttunen TJ (2003 Dec) Epithelial cell proliferation and glandular atrophy in lymphocytic gastritis: effect of H. pylori treatment. World J Gastroenterol 9(12):2706–2710Google Scholar
  27. Malfertheiner P, Selgrad M (2010) Helicobacter pylori infection and current clinical areas of contention. Curr Opin Gastroenterol 26(6):618–623. Scholar
  28. Marshall BJ, Warren JR (1984) Unidentified curved bacilli in the stomach of patients with gastritis and peptic ulceration. Lancet 1(8390):1311–1315Google Scholar
  29. Mueller D, Tegtmeyer N, Brandt S, Yamaoka Y, De Poire E, Sgouras D, Wessler S, Torres J, Smolka A, Backert S (2012) c-Src and c-Abl kinases control hierarchic phosphorylation and function of the CagA effector protein in Western and East Asian Helicobacter pylori strains. J Clin Invest 122(4):1553–1566. Scholar
  30. Naumann M, Sokolova O, Tegtmeyer N, Backert S (2017) Helicobacter pylori: a paradigm pathogen for subverting host cell signal transmission. Trends Microbiol 25(4):316–328. Scholar
  31. Oberhuber G, Haidenthaler A (2000) Histopathology of Helicobacter pylori infections. Acta Med Austriaca 27(4):100–103Google Scholar
  32. Pachathundikandi SK, Muller A, Backert S (2016) Inflammasome activation by Helicobacter pylori and its implications for persistence and immunity. Curr Top Microbiol Immunol 397:117–131. Scholar
  33. Parsons BN, Ijaz UZ, D’Amore R, Burkitt MD, Eccles R, Lenzi L, Duckworth CA, Moore AR, Tiszlavicz L, Varro A, Hall N, Pritchard DM (2017) Comparison of the human gastric microbiota in hypochlorhydric states arising as a result of Helicobacter pylori- induced atrophic gastritis, autoimmune gastritis and proton pump inhibitor use. PLoS Pathog 13(11):e1006653. Scholar
  34. Pech O, May A, Gossner L, Vieth M, Trump F, Stolte S, Ell C (2001) Early stage adenocarcinoma of the esophagus arising in circular heterotopic gastric mucosa treated by endoscopic mucosal resection. Gastrointest Endosc 54(5):658–658Google Scholar
  35. Posselt G, Backert S, Wessler S (2013) The functional interplay of Helicobacter pylori factors with gastric epithelial cells induces a multi-step process in pathogenesis. Cell Commun Signal 11:77. Scholar
  36. Rebora A, Drago F, Parodi A (1995) May Helicobacter pylori be important for dermatologists. Dermatology 191(1):6–8. Scholar
  37. Reddy KM, Chang JI, Shi JM, Wu BU (2016) Risk of gastric cancer among patients with intestinal metaplasia of the stomach in a US integrated health care system. Clin Gastroenterol Hepatol 14(10):1420–1425. Scholar
  38. Rugge M, Genta RM, OLGA Group (2005) Staging gastritis: an international proposal. Gastroenterology 129(5):1807–1808. Scholar
  39. Sipponen P, Stolte M (1997 Sep) Endoscopy 29(7):671–678. PMID: 9360882Google Scholar
  40. Smet A, Yahara K, Rossi M, Tay A, Backert S, Armin E, Fox JG, Flahou B, Ducatelle R, Haesebrouck F, Corander J (2018) Macroevolution of gastric Helicobacter species unveils interspecies admixture and time of divergence. ISME J 12(10):2518–2531. Scholar
  41. Sonnenberg A (1987) Causative factors in the etiology of peptic ulcer disease become effective before the age of 15 years. J Clin Epidemiol 40:193–202. Scholar
  42. Susser M, Stein Z (1962) Civilisation and peptic ulcer. Lancet 1(7221):115–119Google Scholar
  43. Vaira D, Malfertheiner P, Mégraud F, Axon AT, Deltenre M, Hirschl AM, Gasbarrini G, O’Morain C, Garcia JM, Quina M, Tytgat GN (1999) Diagnosis of Helicobacter pylori infection with a new non-invasive antigen-based assay. HpSA European study group. Lancet 354(9172):30–33. Scholar
  44. Vieth M, Stolte M, De Groote D, Deeg KH, Seitz G (2001) Death kisses for newborns? Arch Dis Child 84(6):525. PMID:11372081Google Scholar
  45. Wang J, Xu L, Shi R, Huang X, Li SW, Huang Z, Zhang G (2011) Gastric atrophy and intestinal metaplasia before and after helicobacter pylori eradication: a meta-analysis. Digestion 83(4):253–260. Epub 2011 Feb 1. PMID: 21282951
  46. Warren JR, Marshall B (1984) Unidentified curved bacilli on gastric epithelium in active chronic gastritis. Lancet 1(8336):1273–1275. Scholar
  47. Ye W, Nyren O (2003) Risk of cancers of the oesophagus and stomach by histology or subsite in patients hospitalised for pernicious anaemia. Gut 52(7):938–941Google Scholar
  48. Zhou D, Guan WB, Wang JD, Zhang Y, Gong W, Quan ZW (2013) A comparative study of clinicopathological features between chronic cholecystitis patients with and without Helicobacter pylori infection in gallbladder mucosa. PLoS One 8(7):e70265. Scholar

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© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Institute of PathologyKlinikum BayreuthBayreuthGermany

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