Post Helicobacter pylori Gastric Diseases

  • Kazunari Tominaga
  • Kazuhide Higuchi


A variety of researches have been focused on Helicobacter pylori (H. pylori) in gastroenterological field, and H. pylori has been recognized as etiologically responsible for gastritis-associated peptic ulcers and the majority of gastric cancers. The incidence rate of H. pylori infection is higher in Asian countries including Japan than in Western countries. However, past natural circumstances in Japan suitable for an inhabiting of H. pylori have been improved in parallel with the sanitary developments. In addition, the eradication therapy has been permitted with national insurance to most patients with H. pylori infection in 2013. As a result, the present infection rate is gradually decreasing. Based on the above surrounding environment, an age-depending decrease in acid secretion due to mucosal atrophy caused by chronic H. pylori infection is recently lacking. Therefore, certain acid secretion is continuously maintained with no age relationship. Accordingly, most Japanese physicians must switch their focus to the acid-related diseases (H. pylori-non-associated diseases) from the H. pylori-associated diseases throughout the entire generations.

As post H. pylori gastric diseases, this part will give the information about (1) H. pylori-negative mucosal injury excluding gastric cancer because it is introduced in the next chapter, (2) functional dyspepsia whose pathophysiology is in part associated with mucosal sensitivity to acid exposure, and (3) association of non-alcoholic fatty liver disease with gastroesophageal diseases.


Acid secretion Chemical sensitivity Functional disorders Metabolic syndrome 


  1. 1.
    Warren JR, Marshall BJ. Unidentified curved bacilli on gastric epithelium in active chronic gastritis. Lancet. 1983;1:1273–5.PubMedGoogle Scholar
  2. 2.
    Marshall BJ, Warren JR. Unidentified curved bacilli in the stomach of patients with gastritis and peptic ulceration. Lancet. 1984;1:1311–5.CrossRefGoogle Scholar
  3. 3.
    Namekata T, Miki K, Kimmey M, Fritsche T, Hughes D, Moore D, et al. Chronic atrophic gastritis and Helicobacter pylori infection among Japanese Americans in Seattle. Am J Epidemiol. 2000;151:820–30.CrossRefGoogle Scholar
  4. 4.
    Correa P. Human gastric carcinogenesis: a multistep and multifactorial process--First American Cancer Society Award Lecture on Cancer Epidemiology and Prevention. Cancer Res. 1992;52:6735–40.PubMedGoogle Scholar
  5. 5.
    International Agency for Research on Cancer, World Health Organization. Schistosomes, liver flukes and Helicobacter pylori. IARC Monogr Eval Carcinog Risks Hum. 1994;61:177–241.Google Scholar
  6. 6.
    International Agency for Research on Cancer. Helicobacter pylori. Biologic agents: a review of human carcinogens, vol. 100B. Leon: International Agency for Research on Cancer; 2012. p. 385–435.Google Scholar
  7. 7.
    Higuchi K, Fujiwara Y, Tominaga K, Watanabe T, Shiba M, Nakamura S, et al. Is eradication sufficient to heal gastric ulcers in patients infected with Helicobacter pylori? A randomized, controlled, prospective study. Aliment Pharmacol Ther. 2003;17:111–7.CrossRefGoogle Scholar
  8. 8.
    Tsumoto C, Tominaga K, Okazaki H, Tanigawa T, Yamagami H, Watanabe K, et al. Long-term efficacy of Helicobacter pylori eradication in patients with idiopathic thrombocytopenic purpura: 7-year follow-up prospective study. Ann Hematol. 2009;88:789–93.CrossRefGoogle Scholar
  9. 9.
    Miwa H, Sakaki N, Sugano K, Sekine H, Higuchi K, Uemura N, et al. Recurrent peptic ulcers in patients following successful Helicobacter pylori eradication: a multicenter study of 4940 patients. Helicobacter. 2004;9:9–16.CrossRefGoogle Scholar
  10. 10.
    Fukase K, Kato M, Kikuchi S, Inoue K, Uemura N, Okamoto S, et al. Effect of eradication of Helicobacter pylori on incidence of metachronous gastric carcinoma after endoscopic resection of early gastric cancer: an open-label, randomised controlled trial. Lancet. 2008;372:392–7.CrossRefGoogle Scholar
  11. 11.
    Aoyama N, Shinoda Y, Matsushima Y, Shirasaka D, Kinoshita Y, Kasuga M, et al. Helicobacter pylori-negative peptic ulcer in Japan: which contributes most to peptic ulcer development, Helicobacter pylori, NSAIDS or stress? J Gastroenterol. 2000;35(Suppl 12):33–7.PubMedGoogle Scholar
  12. 12.
    Kanno T, Iijima K, Abe Y, Yagi M, Asonuma S, Ohyauchi M, et al. A multicenter prospective study on the prevalence of Helicobacter pylori-negative and nonsteroidal anti-inflammatory drugs-negative idiopathic peptic ulcers in Japan. J Gastroenterol Hepatol. 2015;30:842–8.CrossRefGoogle Scholar
  13. 13.
    Wong GL, Wong VW, Chan Y, Ching JY, Au K, Hui AJ, et al. High incidence of mortality and recurrent bleeding in patients with Helicobacter pylori-negative idiopathic bleeding ulcers. Gastroenterology. 2009;137:525–31.CrossRefGoogle Scholar
  14. 14.
    Hawkey CJ, Tulassay Z, Szczepanski L, van Rensburg CJ, Filipowicz-Sosnowska A, Lanas A, et al. Randomised controlled trial of Helicobacter pylori eradication in patients on non-steroidal anti-inflammatory drugs: HELP NSAIDs study. Helicobacter eradication for lesion prevention. Lancet. 1998;352:1016–21.CrossRefGoogle Scholar
  15. 15.
    de Leest HT, Steen KS, Lems WF, Bijlsma JW, van de Laar MA, Huisman AM, et al. Eradication of Helicobacter pylori does not reduce the incidence of gastroduodenal ulcers in patients on long-term NSAID treatment: double-blind, randomized, placebo-controlled trial. Helicobacter. 2007;12:477–85.CrossRefGoogle Scholar
  16. 16.
    Tang CL, Ye F, Liu W, Pan XL, Qian J, Zhang GX. Eradication of Helicobacter pylori infection reduces the incidence of peptic ulcer disease in patients using nonsteroidal anti-inflammatory drugs: a meta-analysis. Helicobacter. 2012;17:286–96.CrossRefGoogle Scholar
  17. 17.
    Chan FK, Ching JY, Suen BY, Tse YK, Wu JC, Sung JJ. Effects of Helicobacter pylori infection on long-term risk of peptic ulcer bleeding in low-dose aspirin users. Gastroenterology. 2013;144:528–35.CrossRefGoogle Scholar
  18. 18.
    Kamada T, Haruma K, Ito M, Inoue K, Manabe N, Matsumoto H, et al. Time trends in Helicobacter pylori infection and atrophic gastritis over 40 years in Japan. Helicobacter. 2015;20:192–8.CrossRefGoogle Scholar
  19. 19.
    Haruma K, Kamada T, Kawaguchi H, Okamoto S, Yoshihara M, Sumii K, et al. Effect of age and Helicobacter pylori infection on gastric acid secretion. J Gastroenterol Hepatol. 2000;15:277–83.CrossRefGoogle Scholar
  20. 20.
    Kinoshita Y, Kawanami C, Kishi K, Nakata H, Seino Y, Chiba T. Helicobacter pylori independent chronological change in gastric acid secretion in the Japanese. Gut. 1997;41:452–8.CrossRefGoogle Scholar
  21. 21.
    Ishimura N, Owada Y, Aimi M, Oshima T, Kamada T, Inoue K, et al. No increase in gastric acid secretion in healthy Japanese over the past two decades. J Gastroenterol. 2015;50:844–52.CrossRefGoogle Scholar
  22. 22.
    Schuligoi R, Joci M, Heinemann A, Scho¨ninkle E, Pabst MA, Holzer P. Gastric acid–evoked c-fos messenger RNA expression in rat brainstem is signaled by capsaicin-resistant vagal afferents. Gastroenterology. 1998;115:649–60.CrossRefGoogle Scholar
  23. 23.
    Lamb K, Kang YM, Gebhart GF, Bielefeldt K. Gastric inflammation triggers hypersensitivity to acid in awake rats. Gastroenterology. 2003;125:1410–8.CrossRefGoogle Scholar
  24. 24.
    Miwa H, Nakajima K, Yamaguchi K, Fujimoto K, Veldhuyzen VAN Zanten SJ, et al. Generation of dyspeptic symptoms by direct acid infusion into the stomach of healthy Japanese subjects. Aliment Pharmacol Ther. 2007;26:257–64.CrossRefGoogle Scholar
  25. 25.
    Oshima T, Okugawa T, Tomita T, Sakurai J, Toyoshima F, Watari J, et al. Generation of dyspeptic symptoms by direct acid and water infusion into the stomachs of functional dyspepsia patients and healthy subjects. Aliment Pharmacol Ther. 2012:175:175–82.CrossRefGoogle Scholar
  26. 26.
    Moayyedi P, Soo S, Deeks J, Delaney B, Innes M, Forman D. Pharmacological interventions for non-ulcer dyspepsia. Cochrane Database Syst Rev. 2006;(5):178–85.Google Scholar
  27. 27.
    Peura DA, Kovacs TO, Metz DC, Siepman N, Pilmer BL, Talley NJ. Lansoprazole in the treatment of functional dyspepsia: two double-blind, randomized, placebo-controlled trials. Am J Med. 2004;116:740–8.CrossRefGoogle Scholar
  28. 28.
    van Zanten SV, Armstrong D, Chiba N, Flook N, White RJ, Chakraborty B, et al. Esomeprazole 40 mg once a day in patients with functional dyspepsia: the randomized, placebo-controlled "ENTER" trial. Am J Gastroenterol. 2006;101:2096–106.CrossRefGoogle Scholar
  29. 29.
    Iwakiri R, Tominaga K, Furuta K, Inamori M, Furuta T, Masuyama H, et al. Randomised clinical trial: rabeprazole improves symptoms in patients with functional dyspepsia in Japan. Aliment Pharmacol Ther. 2013;38:729–40.CrossRefGoogle Scholar
  30. 30.
    Sakurai K, Nagahara A, Inoue K, Akiyama J, Mabe K, Suzuki J, et al. Efficacy of omeprazole, famotidine, mosapride and teprenone in patients with upper gastrointestinal symptoms: an omeprazole-controlled randomized study (J-FOCUS). BMC Gastroenterol. 2012;12:42. Scholar
  31. 31.
    Sugano K, Tack J, Kuipers EJ, Graham DY, El-Omar EM, Miura S, et al. Kyoto global consensus report on Helicobacter pylori gastritis. Gut. 2015;64:1353–67.CrossRefGoogle Scholar
  32. 32.
    Stanghellini V, Chan FK, Hasler WL, Malagelada JR, Suzuki H, Tack J, et al. Gastroduodenal Disorders. Gastroenterology. 2016;150:1380–92.CrossRefGoogle Scholar
  33. 33.
    Miwa H, Kusano M, Arisawa T, Oshima T, Kato M, Joh T, et al. Evidence-based clinical practice guidelines for functional dyspepsia. J Gastroenterol. 2015;50:125–39.CrossRefGoogle Scholar
  34. 34.
    Xu H, Barnes GT, Yang Q, Tan G, Yang D, Chou CJ, et al. Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J Clin Invest. 2003;112:1821–30.CrossRefGoogle Scholar
  35. 35.
    Marchesini G, Bugianesi E, Forlani G, Cerrelli F, Lenzi M, Manini R, et al. Nonalcoholic fatty liver, steatohepatitis, and the metabolic syndrome. Hepatology. 2003;37:917–23.CrossRefGoogle Scholar
  36. 36.
    Fujikawa Y, Tominaga K, Fujii H, Machida H, Okazaki H, Yamagami H, et al. High prevalence of gastroesophageal reflux symptoms in patients with non-alcoholic fatty liver disease associated with serum levels of triglyceride and cholesterol but not simple visceral obesity. Digestion. 2012;86:228–37.CrossRefGoogle Scholar
  37. 37.
    Ledeboer M, Mascle AAM, Biemond I, Lamers CBHW. Effect of medium- and long-chain triglycerides onlower esophageal sphincter pressure: role of CCK. Am J Phys. 1998;274:1160–5.Google Scholar
  38. 38.
    Trudgill NJ, Riley SA. Tansient lower esophageal sphincter relaxations are no more frequent in patients with gastroesophageal reflux disease than in asymptomatic volunteers. Am J Gastroenterol. 2001;96:2569–74.CrossRefGoogle Scholar
  39. 39.
    Shapiro M, Green C, Bautista M, Dekel R, Risner-Adler S, Whitacre R, et al. Assessment of dietary nutrients that influence perception of intra-oesophageal acid reflux events in patients with gastro-oesophageal reflux disease. Aliment Pharmacol Ther. 2007;25:93–101.CrossRefGoogle Scholar
  40. 40.
    Matsuzaki J, Suzuki H, Iwasaki E, Yokoyama H, Sugino Y, Hibi T. Serum lipid levels are positively associated with non-erosive reflux disease, but not with functional heartburn. Neurogastroenterol Motil. 2010;22:965–70.CrossRefGoogle Scholar
  41. 41.
    Wu P, Ma L, Dai GX, Chen Y, Tong YL, Wang C, et al. The association of metabolic syndrome with reflux esophagitis: a case-control study. Neurogastroenterol Motil. 2011;23:989–94.CrossRefGoogle Scholar
  42. 42.
    Schulz MD, Atay C, Heringer J, Romrig FK, Schwitalla S, Aydin B, et al. High-fat-diet-mediated dysbiosis promotes intestinal carcinogenesis independently of obesity. Nature. 2014;514:508–12.CrossRefGoogle Scholar
  43. 43.
    Hirata Y, Sezaki T, Tamura-Nakano M, Oyama C, Hagiwara T, Ishikawa T, et al. Fatty acids in a high-fat diet potentially induce gastric parietal-cell damage and metaplasia in mice. J Gastroenterol. 2017;52:889–903.CrossRefGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  • Kazunari Tominaga
    • 1
    • 2
  • Kazuhide Higuchi
    • 2
  1. 1.Premier Developmental Research of MedicineOsaka Medical CollegeOsakaJapan
  2. 2.Second Department of Internal MedicineOsaka Medical CollegeOsakaJapan

Personalised recommendations