Journal of Gastroenterology

, Volume 53, Issue 8, pp 924–931 | Cite as

Serum pepsinogen levels indicate the requirement of upper gastrointestinal endoscopy among Group A subjects of ABC classification: a multicenter study

  • Daisuke Chinda
  • Tadashi ShimoyamaEmail author
  • Tatsuya Mikami
  • Tetsu Arai
  • Daisuke Chiba
  • Yoshio Sasaki
  • Kazuo Komai
  • Yoshihiko Sawada
  • Yoshiharu Saito
  • Hironobu Chiba
  • Shinsaku Fukuda
  • RINGO Study Group
Original Article—Alimentary Tract



ABC classification has been used to assess the risk for gastric cancer. The current problem of ABC classification is that Group A contains individuals with current and past H. pylori infection. The aims of this study were to assesse the proportion of current and past infection in Group A and to establish a criteria for the identification of subjects with past infection from Group A subjects with negative results of urea breath test (UBT) and/or stool antigen test.


201 subjects classified into Group A received UBT and/or stool antigen test, and also subsequent upper gastrointestinal endoscopy. The subjects were classified by the status of H. pylori infection defined by endoscopic findings. Levels of pepsinogen (PG) I, PG II and PG I/II ratio were compared between the groups, and receiver operating characteristic curves were constructed to extract the corresponding cutoff values.


22 subjects were tested positive by UBT and/or stool antigen test. Endoscopic images of 157 out of 179 subjects were studied. 15 of the subjects were regarded to have past H. pylori infection. The optimal cut-off value of PG I and PG I/II ratio for the determination of past H. pylori infection were ≤ 31.2 ng/mL and ≤ 4.6, respectively.


Approximately 20% of Group A subjects have current or past H. pylori infection. Addition of UBT and/or stool antigen test can identify current but not past infection. Serum PG levels would be useful to identify subjects with past H. pylori infection.


Helicobacter pylori infection Group A of ABC classification Pepsinogen levels Upper gastrointestinal endoscopy 



We gratefully acknowledge the members of The RINGO Study Group. The names of the RINGO study group are as follows: Chinda D, M.D, Ph.D. (author); Shimoyama T, M.D, Ph.D. (author); Sasaki Y, M.D., Ph.D. (author); Komai K, M.D., Ph.D. (author); Sawada Y, M.D., Ph.D. (author); Saito Y, M.D., Ph.D. (author); Chiba H, M.D., Ph.D. (author); Fukuda S, M.D., Ph.D. (author); Akiyama M, M.D., Ph.D.; Ebina T, M.D., Ph.D.; Fukushi G, M.D., Ph.D.; Fukushi M, M.D., Ph.D.; Ichinohe H, M.D., Ph.D.; Ishizawa M, M.D., Ph.D.; Ito J, M.D., Ph.D.; Iwamura H, M.D., Ph.D.; Iwane S, M.D., Ph.D.; Kawaguchi H, M.D., Ph.D.; Kawaguchi S, M.D., Ph.D.; Konuma Y, M.D., Ph.D.; Moriyama Y, M.D., Ph.D.; Nakajima M, M.D., Ph.D.; Nakasato F, M.D., Ph.D.; Nishiya D, M.D., Ph.D.; Okamoto K, M.D., Ph.D.; Soma Y, M.D., Ph.D.; Suzuki H, M.D., Ph.D.; Tomita T, M.D., Ph.D.; Tsushima K, M.D., Ph.D.; Wada T, M.D., Ph.D.

Compliance with ethical standards

Conflict of interest

The authors declare that there is no conflict of interests regarding the publication of this paper.


  1. 1.
    Miki K. Gastric cancer screening by combined assay for serum anti-Helicobacter pylori IgG antibody and serum pepsinogen levels—“ABC method”. Proc Jpn Acad Ser B Phys Biol Sci. 2011;87:405–14.CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Matsuo T, Ito M, Takata S, et al. Low prevalence of Helicobacter pylori-negative gastric cancer among Japanese. Helicobacter. 2011;16:415–9.CrossRefPubMedGoogle Scholar
  3. 3.
    Kudo T, Kakizaki S, Sohara N, et al. Analysis of ABC (D) stratification for screening patients with gastric cancer. World J Gastroenterol. 2011;17:4793–8.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Ohata H, Kitauchi S, Yoshimura N, et al. Progression of chronic atrophic gastritis associated with Helicobacter pylori infection increases risk of gastric cancer. Int J Cancer. 2004;109:138–43.CrossRefPubMedGoogle Scholar
  5. 5.
    Uemura N, Okamoto S, Yamamoto S, et al. Helicobacter pylori infection and the development of gastric cancer. N Engl J Med. 2001;345:784–9.CrossRefPubMedGoogle Scholar
  6. 6.
    Miki K, Fujishiro M, Kodashima S, et al. Long-term results of gastric cancer screening using the serum pepsinogen test method among an asymptomatic middle-aged Japanese population. Dig Endosc. 2009;21:78–81.CrossRefPubMedGoogle Scholar
  7. 7.
    Yoshihara M, Hiyama T, Yoshida S, et al. Reduction in gastric cancer mortality by screening based on serum pepsinogen concentration: a case–control study. Scand J Gastroenterol. 2007;42:760–4.CrossRefPubMedGoogle Scholar
  8. 8.
    Miki K, Urita Y. Using serum pepsinogens wisely in a clinical practice. J Dig Dis. 2007;8:8–14.CrossRefPubMedGoogle Scholar
  9. 9.
    Miki K. Gastric cancer screening using the serum pepsinogen test method. Gastric Cancer. 2006;9:245–53.CrossRefPubMedGoogle Scholar
  10. 10.
    Oishi Y, Kiyohara Y, Kubo M, et al. The serum pepsinogen test as a predictor of gastric cancer: the Hisayama study. Am J Epidemiol. 2006;163:629–37.CrossRefPubMedGoogle Scholar
  11. 11.
    Dinis-Ribeiro M, Yamaki G, Miki K, et al. Meta-analysis on the validity of pepsinogen test for gastric carcinoma, dysplasia or chronic atrophic gastritis screening. J Med Screen. 2004;11:141–7.CrossRefPubMedGoogle Scholar
  12. 12.
    Urita Y, Hike K, Torii N, et al. Serum pepsinogens as a predicator of the topography of intestinal metaplasia in patients with atrophic gastritis. Dig Dis Sci. 2004;49:795–801.CrossRefPubMedGoogle Scholar
  13. 13.
    Kiso M, Yoshihara M, Ito M, et al. Characteristics of gastric cancer in negative test of serum anti-Helicobacter pylori antibody and pepsinogen test: a multicenter study. Gastric Cancer. 2017;20:764–71.CrossRefPubMedGoogle Scholar
  14. 14.
    Kishikawa H, Kimura K, Takarabe S, Kaida S, Nishida J. Helicobacter pylori antibody titer and gastric cancer screening. Dis Markers. 2015. Scholar
  15. 15.
    Kishikawa H, Nishida J, Ichikawa H, et al. Fasting gastric pH of Japanese subjects stratified by IgG concentration against Helicobacter pylori and pepsinogen status. Helicobacter. 2011;16:427–33.CrossRefPubMedGoogle Scholar
  16. 16.
    Kawai T, Miki K, Ichinose M, et al. Changes in evaluation of the pepsinogen test result following Helicobacter pylori eradication therapy in Japan. Inflammopharmacology. 2007;15:31–5.CrossRefPubMedGoogle Scholar
  17. 17.
    Kawai T, Kawakami K, Kudo T, et al. A new serum antibody test kit (E plate) for evaluation of Helicobacter pylori eradication. Intern Med. 2002;41:780–3.CrossRefPubMedGoogle Scholar
  18. 18.
    Ohara S, Kato M, Asaka M, et al. Studies of 13C-urea breath test for diagnosis of Helicobacter pylori infection in Japan. J Gastroenterol. 1998;33:6–13.CrossRefPubMedGoogle Scholar
  19. 19.
    Sato M, Shimoyama T, Takahashi R, et al. Characterization and usefulness of stool antigen tests using a monoclonal antibody to Helicobacter pylori catalase. J Gastroenterol Hepatol. 2012;27(Suppl 3):23–8.CrossRefPubMedGoogle Scholar
  20. 20.
    Kimura K, Takemoto T. An endoscopic recognition of the atrophic border and its significance in chronic gastritis. Endoscopy. 1969;3:87–97.CrossRefGoogle Scholar
  21. 21.
    Haruma K, Kato M, Inoue K, et al. Kyoto classification of gastritis. 1st ed. Tokyo: Nihon Medical Center; 2017.Google Scholar
  22. 22.
    Kato T, Yagi N, Kamada T, et al. Study group for establishing endoscopic diagnosis of chronic gastritis diagnosis of Helicobacter pylori infection in gastric mucosa by endoscopic features: a multicenter prospective study. Dig Endosc. 2013;25:508–18.CrossRefPubMedGoogle Scholar
  23. 23.
    Iino C, Shimoyama T, Oyama T, et al. Evaluation of the appropriate cut-off value for serological diagnosis of Helicobacter pylori infection by comparison with a stool antigen test. Hirosaki Med J. 2012;63:48–54.Google Scholar
  24. 24.
    Koizumi W, Tanabe S, Imaizumi H, et al. Effect of anti-Helicobacter pylori IgG antibody titer following eradication of Helicobacter pylori infection. Hepatogastroenterology. 2003;50:293–6.PubMedGoogle Scholar
  25. 25.
    Marchildon P, Balaban DH, Sue M, et al. Usefulness of serological IgG antibody determinations for confirming eradication of Helicobacter pylori infection. Am J Gastroenterol. 1999;94:2105–8.CrossRefPubMedGoogle Scholar
  26. 26.
    Yamaguchi Y, Nagata Y, Hiratsuka R, et al. Gastric cancer screening by combined assay for serum anti-Helicobacter pylori IgG antibody and serum pepsinogen levels—the ABC method. Digestion. 2016;93:13–8.CrossRefPubMedGoogle Scholar
  27. 27.
    Terasawa T, Nishida H, Kato K, et al. Prediction of gastric cancer development by serum pepsinogen test and Helicobacter pylori seropositivity in Eastern Asians: a systematic review and meta-analysis. PLoS One. 2014. Scholar
  28. 28.
    Boda T, Ito M, Yoshihara M, et al. Advanced method for evaluation of gastric cancer risk by serum markers: determination of true low-risk subjects for gastric neoplasm. Helicobacter. 2014;19:1–8.CrossRefPubMedGoogle Scholar
  29. 29.
    Ono S, Kato M, Suzuki M, et al. Frequency of Helicobacter pylori -negative gastric cancer and gastric mucosal atrophy in a Japanese endoscopic submucosal dissection series including histological, endoscopic and serological atrophy. Digestion. 2012;86:59–65.CrossRefPubMedGoogle Scholar
  30. 30.
    Kakinoki R, Kushima R, Matsubara A, et al. Re-evaluation of histogenesis of gastric carcinomas: a comparative histopathological study between Helicobacter pylori-negative and H. pylori-positive cases. Dig Dis Sci. 2009;54:614–20.CrossRefPubMedGoogle Scholar
  31. 31.
    Kato S, Matsukura N, Tsukada K, et al. Helicobacter pylori infection-negative gastric cancer in Japanese hospital patients: incidence and pathological characteristics. Cancer Sci. 2007;98:790–4.CrossRefPubMedGoogle Scholar
  32. 32.
    Watabe H, Mitsushima T, Yamaji Y, et al. Predicting the development of gastric cancer from combining Helicobacter pylori antibodies and serum pepsinogen status: a prospective endoscopic cohort study. Gut. 2005;54:764–8.CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Shimoyama T. Stool antigen tests for the management of Helicobacter pylori infection. World J Gastroenterol. 2013;19:8188–91.CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Kishikawa H, Kimura K, Ito A, et al. Cutoff pepsinogen level for predicting unintendedly eradicated cases of Helicobacter pylori infection in subjects with seemingly normal pepsinogen levels. Digestion. 2017;95:229–36.CrossRefPubMedGoogle Scholar
  35. 35.
    Yanaoka K, Oka M, Yoshimura N, et al. Risk of gastric cancer in asymptomatic, middle-aged Japanese subjects based on serum pepsinogen and Helicobacter pylori antibody levels. Int J Cancer. 2008;123:917–26.CrossRefPubMedGoogle Scholar

Copyright information

© Japanese Society of Gastroenterology 2018

Authors and Affiliations

  • Daisuke Chinda
    • 1
  • Tadashi Shimoyama
    • 1
    Email author
  • Tatsuya Mikami
    • 2
  • Tetsu Arai
    • 1
  • Daisuke Chiba
    • 1
  • Yoshio Sasaki
    • 3
  • Kazuo Komai
    • 4
  • Yoshihiko Sawada
    • 5
  • Yoshiharu Saito
    • 6
  • Hironobu Chiba
    • 7
  • Shinsaku Fukuda
    • 1
  • RINGO Study Group
    • 1
    • 2
    • 3
    • 4
    • 5
    • 6
    • 7
    • 8
  1. 1.Department of Gastroenterology and HematologyHirosaki University Graduate School of MedicineHirosakiJapan
  2. 2.Division of EndoscopyHirosaki University HospitalHirosakiJapan
  3. 3.Sasaki Clinic of Gastroenterology and Internal MedicineAomoriJapan
  4. 4.Komai Clinic of Gastroenterology and Internal MedicineAomoriJapan
  5. 5.Sawada Clinic of Internal MedicineHirosakiJapan
  6. 6.Shinjo Clinic of Gastroenterology and Internal MedicineAomoriJapan
  7. 7.Chiba Clinic of Gastroenterology and Internal MedicineHirosakiJapan
  8. 8.Risk Investigation of Gastric Cancer and Observation After Eradication Study GroupHirosakiJapan

Personalised recommendations