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Dynamics of Helicobacter pylori infection as a determinant of progression of gastric precancerous lesions: 16-year follow-up of an eradication trial
  1. Robertino M Mera1,
  2. Luis E Bravo2,
  3. M Constanza Camargo3,
  4. Juan C Bravo2,
  5. Alberto G Delgado1,
  6. Judith Romero-Gallo1,
  7. Maria C Yepez4,
  8. José L Realpe4,
  9. Barbara G Schneider1,
  10. Douglas R Morgan1,
  11. Richard M Peek Jr1,5,6,
  12. Pelayo Correa1,
  13. Keith T Wilson1,5,6,7,8,
  14. M Blanca Piazuelo1,7
  1. 1 Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, Vanderbilt University Medical Center, Nashville, Tennessee, USA
  2. 2 Department of Pathology, Universidad del Valle School of Medicine, Cali, Colombia
  3. 3 Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland, USA
  4. 4 Centro de Estudios en Salud, Universidad de Nariño, Pasto, Colombia
  5. 5 Department of Cancer Biology, Vanderbilt University Medical Center, Nashville, Tennessee, USA
  6. 6 Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee, USA
  7. 7 Center for Mucosal Inflammation and Cancer, Vanderbilt University Medical Center, Nashville, Tennessee, USA
  8. 8 Veterans Affairs Tennessee Valley Healthcare System, Nashville, Tennessee, USA
  1. Correspondence to Dr M Blanca Piazuelo, Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, Vanderbilt University Medical Center, Nashville, TN 37232, USA; maria.b.piazuelo{at}Vanderbilt.Edu


Objective To evaluate the long-term effect of cumulative time exposed to Helicobacter pylori infection on the progression of gastric lesions.

Design 795 adults with precancerous gastric lesions were randomised to receive anti-H. pylori treatment at baseline. Gastric biopsies were obtained at baseline and at 3, 6, 12 and 16 years. A total of 456 individuals attended the 16-year visit. Cumulative time of H. pylori exposure was calculated as the number of years infected during follow-up. Multivariable logistic regression models were used to estimate the risk of progression to a more advanced diagnosis (versus no change/regression) as well as gastric cancer risk by intestinal metaplasia (IM) subtype. For a more detailed analysis of progression, we also used a histopathology score assessing both severity and extension of the gastric lesions (range 1–6). The score difference between baseline and 16 years was modelled by generalised linear models.

Results Individuals who were continuously infected with H. pylori for 16 years had a higher probability of progression to a more advanced diagnosis than those who cleared the infection and remained negative after baseline (p=0.001). Incomplete-type IM was associated with higher risk of progression to cancer than complete-type (OR, 11.3; 95% CI 1.4 to 91.4). The average histopathology score increased by 0.20 units/year (95% CI 0.12 to 0.28) among individuals continuously infected with H. pylori. The effect of cumulative time of infection on progression in the histopathology score was significantly higher for individuals with atrophy (without IM) than for individuals with IM (p<0.001).

Conclusions Long-term exposure to H. pylori infection was associated with progression of precancerous lesions. Individuals infected with H. pylori with these lesions may benefit from eradication, particularly those with atrophic gastritis without IM. Incomplete-type IM may be a useful marker for the identification of individuals at higher risk for cancer.

  • H. pylori
  • eradication
  • Latin America
  • atrophy
  • intestinal metaplasia
  • dysplasia
  • gastric cancer
  • OLGA

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  • Contributors RMM had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: PC, RMM and LEB. Acquisition of data: PC, LEB, MBP, JCB, MCY and JLR. Analysis and interpretation of data: PC, RMM, MCC, MBP and KTW. Statistical analysis: RMM. Drafting of the manuscript: RMM, MCC, MBP, KTW and BGS. Critical revision of the manuscript for intellectual content: all authors. Obtained funding: KTW, PC, LEB, MCY and RMP. Administrative, technical or material support: KTW, PC, LEB, DRM, AGD, MCY, JRG and JLR. Study supervision: PC, LEB and MCY.

  • Funding This work was supported by US National Institutes of Health grants P01CA028842 (KTW, PC and DRM), R01DK053620 and R01AT004821 (KTW), R01CA190612 (KTW and DRM), P01CA116087 (RMP and KTW), R01CA077955 and R01DK058587 (RMP), UL1RR024975 (Vanderbilt CTSA, Pilot Project to KTW) and 5P30 DK058404 (Vanderbilt Digestive Disease Research Center; RMP and KTW); Merit Review Grant I01BX001453 from the Office of Medical Research, Department of Veterans Affairs (KTW); and the Pasto Cancer Registry of the Centro de Estudios en Salud, Universidad de Nariño, Colombia. MCC is supported by funds from the intramural research program of the US National Institutes of Health, National Cancer Institute.

  • Competing interests None declared.

  • Patient consent Detail has been removed from this case description/these case descriptions to ensure anonymity. The editors and reviewers have seen the detailed information available and are satisfied that the information backs up the case the authors are making.

  • Ethics approval Committees on Ethics of Universidad del Valle and Hospital Departamental de Nariño in Colombia; Institutional Review Boards of Louisiana State University Health Sciences Center and of Vanderbilt University.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement Coded data from all subjects in our study are available for sharing as required by other investigators.

  • Correction notice This paper has been amended since it was published Online First. Owing to a scripting error, some of the publisher names in the references were replaced with ’BMJ Publishing Group'. This only affected the full text version, not the PDF. We have since corrected these errors and the correct publishers have been inserted into the references.