Korean J Gastroenterol.  2018 Sep;72(3):104-115. 10.4166/kjg.2018.72.3.104.

Reversibility of Atrophic Gastritis and Intestinal Metaplasia by Eradication of Helicobacter pylori

• Yoon K
• Kim N

• KMID: 2420747
• DOI: http://doi.org/10.4166/kjg.2018.72.3.104

Abstract

Although there are many guidelines recommending Helicobacter pylori (H. pylori) eradication therapy for atrophic gastritis (AG) and intestinal metaplasia (IM), there have been contradictory reports regarding the reversibility of precancerous lesions such as AG and IM after eradication of H. pylori. There have been many reports that have shown AG seems to improve upon eradication of H. pylori to some extent. In contrast, IM has been regarded as "˜the point of no return' according to previous reports. However, as recent studies have suggested the improvement of intestinal metaplasia as well, early eradication therapy for reversible histological status is important and necessary for the prevention of gastric cancer. In this review, we focused on the progress of gastritis resulting in AG and IM mainly by H. pylori, the relationship of AG and IM with gastric cancer, the subtype of IM, and the reversibility of AG and IM by eradication of H. pylori. Finally, we introduced the recent extension of indications for H. pylori eradication with coverage by medical insurance, which was published by the Korean Ministry of Health and Welfare in January 2018.

Keyword

Atrophic gastritis; Intestinal metaplasia; Helicobacter pylori

MeSH Terms

Gastritis
Gastritis, Atrophic*
Helicobacter pylori*
Helicobacter*
Insurance
Metaplasia*
Stomach Neoplasms

Figure

• 

  Fig. 1 Classification of gastritis (H&E,×400). (A) Normal, (B) superficial gastritis, (C) atrophic gastritis, and (D) intestinal metaplasia. Upper panel is endoscopic, and lower panel is histologic finding. Adapted from Park and Kim56, with permission from J Cancer Prev.

• 

  Fig. 2 The optimal gastric biopsy sites recommended by the updated Sydney system. Biopsy specimens are taken at five different sites. (A) Lesser curvature of the antrum. (B) Greater curvature of the antrum. (C) Lesser curvature of the corpus. (D) Greater curvature of the corpus. (E) Incisura angularis.

Reference

1. Dixon MF, Genta RM, Yardley JH, Correa P. Classification and grading of gastritis. The updated Sydney system. International Workshop on the Histopathology of Gastritis, Houston 1994. Am J Surg Pathol. 1996; 20:1161–1181.

2. Rugge M, Correa P, Dixon M, et al. Gastric mucosal atrophy: interobserver consistency using new criteria for classification and grading. Aliment Pharmacol Ther. 2002; 16:1249–1259.

3. Stemmermann GN. Intestinal metaplasia of the stomach. A status report. Cancer. 1994; 74:556–564.

4. Lee JY, Kim N, Lee HS, et al. Correlations among endoscopic, histologic and serologic diagnoses for the assessment of atrophic gastritis. J Cancer Prev. 2014; 19:47–55.

5. Eshmuratov A, Nah JC, Kim N, et al. The correlation of endoscopic and histological diagnosis of gastric atrophy. Dig Dis Sci. 2010; 55:1364–1375.

6. Dinis-Ribeiro M, da Costa-Pereira A, Lopes C, et al. Magnification chromoendoscopy for the diagnosis of gastric intestinal metaplasia and dysplasia. Gastrointest Endosc. 2003; 57:498–504.

7. Anagnostopoulos GK, Yao K, Kaye P, et al. High-resolution magnification endoscopy can reliably identify normal gastric mucosa, Helicobacter pylori-associated gastritis, and gastric atrophy. Endoscopy. 2007; 39:202–207.

8. Joo YE, Park HK, Myung DS, et al. Prevalence and risk factors of atrophic gastritis and intestinal metaplasia: a nationwide multicenter prospective study in Korea. Gut liver. 2013; 7:303–310.

9. Kim N, Park YS, Cho SI, et al. Prevalence and risk factors of atrophic gastritis and intestinal metaplasia in a Korean population without significant gastroduodenal disease. Helicobacter. 2008; 13:245–255.

10. Kuipers EJ, Pérez-Pérez GI, Meuwissen SG, Blaser MJ. Helicobacter pylori and atrophic gastritis: importance of the cagA status. J Natl Cancer Inst. 1995; 87:1777–1780.

11. Atherton JC. The clinical relevance of strain types of Helicobacter pylori. Gut. 1997; 40:701–703.

12. Correa P. Human gastric carcinogenesis: a multistep and multifactorial process-first American cancer society award lecture on cancer epidemiology and prevention. Cancer Res. 1992; 52:6735–6740.

13. Annibale B, Aprile MR, D'ambra G, Caruana P, Bordi C, Delle Fave G. Cure of Helicobacter pylori infection in atrophic body gastritis patients does not improve mucosal atrophy but reduces hypergastrinemia and its related effects on body ECL-cell hyperplasia. Aliment Pharmacol Ther. 2000; 14:625–634.

14. Yamada T, Miwa H, Fujino T, Hirai S, Yokoyama T, Sato N. Improvement of gastric atrophy after Helicobacter pylori eradication therapy. J Clin Gastroenterol. 2003; 36:405–410.

15. Lahner E, Bordi C, Cattaruzza MS, et al. Long-term follow-up in atrophic body gastritis patients: atrophy and intestinal metaplasia are persistent lesions irrespective of Helicobacter pylori infection. Aliment Pharmacol Ther. 2005; 22:471–481.

16. Rokkas T, Pistiolas D, Sechopoulos P, Robotis I, Margantinis G. The long-term impact of Helicobacter pylori eradication on gastric histology: a systematic review and meta-analysis. Helicobacter. 2007; 12:32–38.

17. Toyokawa T, Suwaki K, Miyake Y, Nakatsu M, Ando M. Eradication of Helicobacter pylori infection improved gastric mucosal atrophy and prevented progression of intestinal metaplasia, especially in the elderly population: a long-term prospective cohort study. J Gastroenterol Hepatol. 2010; 25:544–547.

18. Wang J, Xu L, Shi R, et al. Gastric atrophy and intestinal metaplasia before and after Helicobacter pylori eradication: a meta-analysis. Digestion. 2011; 83:253–260.

19. Lee YC, Chen TH, Chiu HM, et al. The benefit of mass eradication of Helicobacter pylori infection: a community-based study of gastric cancer prevention. Gut. 2013; 62:676–682.

20. Hwang YJ, Kim N, Lee HS, et al. Reversibility of atrophic gastritis and intestinal metaplasia after Helicobacter pylori eradication - a prospective study for up to 10 years. Aliment Pharmacol Ther. 2018; 47:380–390.

21. Hwang YJ, Kim N, Yun CY, et al. Prediction factors for improvement of atrophic gastritis and intestinal metaplasia: a long-term prospective clinical study. Korean J Helicobacter Up Gastrointest Res. In press 2018.

22. Korean Cancer Statistics 2015. [Internet]. Goyang: National Cancer Information Center;2017. updated 2017 Dec 26. cited 2018 Jul 29. Available from: https://www.cancer.go.kr/lay1/S1T639C641/contents.do.

23. Leung WK, Wu MS, Kakugawa Y, et al. Screening for gastric cancer in Asia: current evidence and practice. Lancet Oncol. 2008; 9:279–287.

24. Lauren P. The two histological main types of gastric carcinoma: diffuse and so-called intestinal-type carcinoma: an attempt at a histo-clinical classification. Acta Pathol Microbiol Scand. 1965; 64:31–49.

25. Balkwill F, Mantovani A. Inflammation and cancer: back to Virchow? Lancet. 2001; 357:539–545.

26. Coussens LM, Werb Z. Inflammation and cancer. Nature. 2002; 420:860–867.

27. Ohshima H, Tazawa H, Sylla BS, Sawa T. Prevention of human cancer by modulation of chronic inflammatory processes. Mutat Res. 2005; 591:110–122.

28. Tsuji S, Kawai N, Tsujii M, Kawano S, Hori M. Review article: inflammation-related promotion of gastrointestinal carcinogenesis– a perigenetic pathway. Aliment Pharmacol Ther. 2003; 18:Suppl 1. 82–89.

29. Suganuma M, Yamaguchi K, Ono Y, et al. TNF-alpha-inducing protein, a carcinogenic factor secreted from H. pylori, enters gastric cancer cells. Int J Cancer. 2008; 123:117–122.

30. 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; 98:790–794.

31. Uemura N, Okamoto S, Yamamoto S, et al. Helicobacter pylori infection and the development of gastric cancer. N Engl J Med. 2001; 345:784–789.

32. 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; 109:138–143.

33. Kim N, Park RY, Cho SI, et al. Helicobacter pylori infection and development of gastric cancer in Korea: long-term follow-up. J Clin Gastroenterol. 2008; 42:448–454.

34. Oh S, Kim N, Yoon H, et al. Risk factors of atrophic gastritis and intestinal metaplasia in first-degree relatives of gastric cancer patients compared with age-sex matched controls. J Cancer Prev. 2013; 18:149–160.

35. Craanen ME, Blok P, Dekker W, Ferwerda J, Tytgat GN. Prevalence of subtypes of intestinal metaplasia in gastric antral mucosa. Dig Dis Sci. 1991; 36:1529–1536.

36. Rokkas T, Filipe MI, Sladen GE. Detection of an increased incidence of early gastric cancer in patients with intestinal metaplasia type III who are closely followed up. Gut. 1991; 32:1110–1113.

37. Kang KP, Lee HS, Kim N, et al. Role of intestinal metaplasia subtyping in the risk of gastric cancer in Korea. J Gastroenterol Hepatol. 2009; 24:140–148.

38. Almeida R, Silva E, Santos-Silva F, et al. Expression of intestinespecific transcription factors, CDX1 and CDX2, in intestinal metaplasia and gastric carcinomas. J Pathol. 2003; 199:36–40.

39. Kang JM, Lee BH, Kim N, et al. CDX1 and CDX2 expression in intestinal metaplasia, dysplasia and gastric cancer. J Korean Med Sci. 2011; 26:647–653.

40. Shin CM, Kim N, Chang H, Kim JS, Lee DH, Jung HC. Follow-up study on CDX1 and CDX2 mRNA expression in noncancerous gastric mucosae after Helicobacter pylori eradication. Dig Dis Sci. 2016; 61:1051–1059.

41. Capelle LG, de Vries AC, Haringsma J, et al. The staging of gastritis with the OLGA system by using intestinal metaplasia as an accurate alternative for atrophic gastritis. Gastrointest Endosc. 2010; 71:1150–1158.

42. Rugge M, Genta RM, Graham DY, et al. Chronicles of a cancer foretold: 35 years of gastric cancer risk assessment. Gut. 2016; 65:721–725.

43. Isajevs S, Liepniece-Karele I, Janciauskas D, et al. Gastritis staging: interobserver agreement by applying OLGA and OLGIM systems. Virchows Archiv. 2014; 464:403–407.

44. Sugano K, Tack J, Kuipers EJ, et al. Kyoto global consensus report on Helicobacter pylori gastritis. Gut. 2015; 64:1353–1367.

45. Yoon H, Kim N, Shin CM, et al. Risk factors for metachronous gastric neoplasms in patients who underwent endoscopic resection of a gastric neoplasm. Gut Liver. 2016; 10:228–236.

46. Cho SJ, Choi IJ, Kook MC, et al. Staging of intestinal- and diffuse-type gastric cancers with the OLGA and OLGIM staging systems. Aliment Pharmacol Ther. 2013; 38:1292–1302.

47. Solcia E, Fiocca R, Villani L, et al. The role of Helicobacter pylori gastritis in ulcerogenesis and carcinogenesis. In : Gasbarrini G, Pretolani S, editors. Basic and clinical aspects of Helicobacter pylori infection. Berlin: Springer;1994. p. 101–112.

48. Solcia E, Fiocca R, Luinetti O, et al. Intestinal and diffuse gastric cancers arise in a different background of Helicobacter pylori gastritis through different gene involvement. Am J Surg Pathol. 1996; 20:Suppl 1. S8–S22.

49. de Vries AC, van Grieken NC, Looman CW, et al. Gastric cancer risk in patients with premalignant gastric lesions: a nationwide cohort study in the Netherlands. Gastroenterology. 2008; 134:945–952.

50. Leung WK, Sung JJ. Review article: intestinal metaplasia and gastric carcinogenesis. Aliment Pharmacol Ther. 2002; 16:1209–1216.

51. You WC, Li JY, Blot WJ, et al. Evolution of precancerous lesions in a rural Chinese population at high risk of gastric cancer. Int J Cancer. 1999; 83:615–619.

52. Yoon H, Kim N. Diagnosis and management of high risk group for gastric cancer. Gut Liver. 2015; 9:5–17.

53. Ford AC, Forman D, Hunt RH, Yuan Y, Moayyedi P. Helicobacter pylori eradication therapy to prevent gastric cancer in healthy asymptomatic infected individuals: systematic review and meta-analysis of randomised controlled trials. BMJ. 2014; 348:g3174.

54. Lee YC, Chiang TH, Chou CK, et al. Association between Helicobacter pylori eradication and gastric cancer incidence: a systematic review and meta-analysis. Gastroenterology. 2016; 150:1113–1124.e5.

55. Fock KM. Review article: the epidemiology and prevention of gastric cancer. Aliment Pharmacol Ther. 2014; 40:250–260.

56. Park YH, Kim N. Review of atrophic gastritis and intestinal metaplasia as a premalignant lesion of gastric cancer. J Cancer Prev. 2015; 20:25–40.

57. González CA, Agudo A. Carcinogenesis, prevention and early detection of gastric cancer: where we are and where we should go. Int J Cancer. 2012; 130:745–753.

58. Mera R, Fontham ET, Bravo LE, et al. Long term follow up of patients treated for Helicobacter pylori infection. Gut. 2005; 54:1536–1540.

59. You WC, Brown LM, Zhang L, et al. Randomized double-blind factorial trial of three treatments to reduce the prevalence of precancerous gastric lesions. J Natl Cancer Inst. 2006; 98:974–983.

60. Leung WK, Lin SR, Ching JY, et al. Factors predicting progression of gastric intestinal metaplasia: results of a randomised trial on Helicobacter pylori eradication. Gut. 2004; 53:1244–1249.

61. Kim N, Lim SH, Lee KH, et al. Long-term effects of Helicobacter pylori eradication on intestinal metaplasia in patients with duodenal and benign gastric ulcers. Dig Dis Sci. 2000; 45:1754–1762.

62. Kong YJ, Yi HG, Dai JC, Wei MX. Histological changes of gastric mucosa after Helicobacter pylori eradication: a systematic review and meta-analysis. World J Gastroenterol. 2014; 20:5903–5911.

63. Li Z, Wu C, Li L, et al. Effect of long-term proton pump inhibitor administration on gastric mucosal atrophy: a meta-analysis. Saudi J Gastroenterol. 2017; 23:222–228.

64. Crabtree JE, Covacci A, Farmery SM, et al. Helicobacter pylori induced interleukin-8 expression in gastric epithelial cells is associated with CagA positive phenotype. J Clin Pathol. 1995; 48:41–45.

65. Wong BC, Lam SK, Wong WM, et al. Helicobacter pylori eradication to prevent gastric cancer in a high-risk region of China: a randomized controlled trial. JAMA. 2004; 291:187–194.

66. Fukase K, Kato M, Kikuchi 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; 372:392–397.

67. Maehata Y, Nakamura S, Fujisawa K, et al. Long-term effect of Helicobacter pylori eradication on the development of metachronous gastric cancer after endoscopic resection of early gastric cancer. Gastrointest Endosc. 2012; 75:39–46.

68. Take S, Mizuno M, Ishiki K, et al. The long-term risk of gastric cancer after the successful eradication of Helicobacter pylori. J Gastroenterol. 2011; 46:318–324.

69. Choi IJ, Kook MC, Kim YI, et al. Helicobacter pylori therapy for the prevention of metachronous gastric cancer. N Engl J Med. 2018; 378:1085–1095.

70. Wu CY, Kuo KN, Wu MS, Chen YJ, Wang CB, Lin JT. Early Helicobacter pylori eradication decreases risk of gastric cancer in patients with peptic ulcer disease. Gastroenterology. 2009; 137:1641–1648. 1648.e1–1648.e2.

71. Chey WD, Leontiadis GI, Howden CW, Moss SF. ACG clinical guideline: treatment of Helicobacter pylori infection. Am J Gastroenterol. 2017; 112:212–239.

72. Dinis-Ribeiro M, Areia M, De Vries AC, et al. Management of precancerous conditions and lesions in the stomach (MAPS): guideline from the European Society of Gastrointestinal Endoscopy (ESGE), European Helicobacter Study Group (EHSG), European Society of Pathology (ESP), and the Sociedade Portuguesa de Endoscopia Digestiva (SPED). Virchows Arch. 2012; 460:19–46.

73. Zagari RM, Romano M, Ojetti V, et al. Guidelines for the management of Helicobacter pylori infection in Italy: the III working group consensus report 2015. Dig Liver Dis. 2015; 47:903–912.

74. Malfertheiner P, Megraud F, O'morain CA, et al. Management of Helicobacter pylori infection-the Maastricht IV/Florence consensus report. Gut. 2012; 61:646–664.

75. Kim SG, Jung HK, Lee HL, et al. Guidelines for the diagnosis and treatment of Helicobacter pylori infection in Korea, 2013 revised edition. J Gastroenterol Hepatol. 2014; 29:1371–1386.

76. Asaka M, Kato M, Takahashi S, et al. Guidelines for the management of Helicobacter pylori infection in Japan: 2009 revised edition. Helicobacter. 2010; 15:1–20.

77. Lee SY. Current progress toward eradicating Helicobacter pylori in East Asian countries: differences in the 2013 revised guidelines between China, Japan, and South Korea. World J Gastroenterol. 2014; 20:1493–1502.

78. Jones NL, Koletzko S, Goodman K, et al. Joint ESPGHAN/NASPGHAN guidelines for the management of Helicobacter pylori in children and adolescents (update 2016). J Pediatr Gastroenterol Nutr. 2017; 64:991–1003.

79. Hiroi S, Sugano K, Tanaka S, Kawakami K. Impact of health insurance coverage for Helicobacter pylori gastritis on the trends in eradication therapy in Japan: retrospective observational study and simulation study based on real-world data. BMJ Open. 2017; 7:e015855.

80. Lim SH, Kim N, Kwon JW, et al. Trends in the seroprevalence of Helicobacter pylori infection and its putative eradication rate over 18 years in Korea: a cross-sectional nationwide multicenter study. PLoS One. In press 2018.

81. Sung JJ, Lin SR, Ching JY, et al. Atrophy and intestinal metaplasia one year after cure of H. pylori infection: a prospective, randomized study. Gastroenterology. 2000; 119:7–14.

82. Ohkusa T, Fujiki K, Takashimizu I, et al. Improvement in atrophic gastritis and intestinal metaplasia in patients in whom Helicobacter pylori was eradicated. Ann Intern Med. 2001; 134:380–386.

83. Ruiz B, Garay J, Correa P, et al. Morphometric evaluation of gastric antral atrophy: improvement after cure of Helicobacter pylori infection. Am J Gastroenterol. 2001; 96:3281–3287.

84. Ito M, Haruma K, Kamada T, et al. Helicobacter pylori eradication therapy improves atrophic gastritis and intestinal metaplasia: a 5-year prospective study of patients with atrophic gastritis. Aliment Pharmacol Ther. 2002; 16:1449–1456.

85. Kamada T, Haruma K, Hata J, et al. The long-term effect of Helicobacter pylori eradication therapy on symptoms in dyspeptic patients with fundic atrophic gastritis. Aliment Pharmacol Ther. 2003; 18:245–252.

86. Wambura C, Aoyama N, Shirasaka D, et al. Influence of gastritis on cyclooxygenase-2 expression before and after eradication of Helicobacter pylori infection. Eur J Gastroenterol Hepatol. 2004; 16:969–979.

87. Lu B, Chen MT, Fan YH, Liu Y, Meng LN. Effects of Helicobacter pylori eradication on atrophic gastritis and intestinal metaplasia: a 3-year follow-up study. World J Gastroenterol. 2005; 11:6518–6520.

88. Kamada T, Hata J, Sugiu K, et al. Clinical features of gastric cancer discovered after successful eradication of Helicobacter pylori: results from a 9-year prospective follow-up study in Japan. Aliment Pharmacol Ther. 2005; 21:1121–1126.

89. Yoon H. Atrophic gastritis and intestinal metaplasia. In : Kim N, editor. Helicobacter pylori. Singapore: Springer;2016. p. 515–520.