Primary Motility  Disorders of the  Esophagus
 The Esophageal
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Volume: Barrett's Esophagus
Chapter: Pathophysiology

Should the non-eradication of Helicobacter pylori and gastritis allow for the reduction of parietal cell mass to the point that reflux associated symptoms are no longer a problem?

R.H. Riddell (Hamilton)

This provocative question raises a series of interesting issues. These include:
1. Does non-eradication (persistence) of Helicobacter pylori inevitably lead to gastric atrophy?
2. If atrophy is achieved, should H. pylori then be eradicated to try to keep the risk of gastric cancer to a minimum?
3. What is the effect of H. pylori in both the short and long-term on:
- Barrett's esophagus,
- the stomach,
- do long-term proton pump inhibitors (PPIs) affect these?
4. Is the routine eradication of PPIs justified?

Does non-eradication (persistence) of Helicobacter pylori inevitably lead to gastric atrophy?

This is a highly complex issue. It is likely related to the parietal cell mass, which in turn seems to have a somewhat geographical distribution. In many Asian countries, parietal cell mass in relatively small, so that progression of atrophy may progress faster, and therefore be present at a more advanced state earlier in life. Dietary substances such as salt also appear to have some correlation with atrophy. Conversely, in Western countries, atrophy is relatively uncommonly seen in routine biopsies from Helicobacter positive individuals. However, it may be accelerated in patients with autoimmune gastritis and parietal cell antibodies.

If atrophy is achieved, should Helicobacter pylori then be eradicated to try to keep the risk of gastric cancer to a minimum?

There are numerous studies that have examined the potential reversibility of atrophy that has occurred. There are numerous design problems with these studies, for they assume that the extent of atrophy and metaplasia can be reasonably defined using multiple biopsies prior to eradication, and that this is sensitive enough when quantitations are applied to detect a decrease in the extent of atrophy or metaplasia. They also assume that the appropriate parts of the stomach most susceptible to these changes are the angulus and the mucosa extending from this region, which is not always the case The results show either little or modest reversal but complete reversal seems not to occur over the life of these studies[l ,8-l8]. Nevertheless, the fact that some reversal does occur even when methods as insensitive as these are used, suggests that, should eradication be carried out when atrophy has been achieved, there may well be sufficient regeneration of the parietal cell mass that PPIs may again need be used.

A side issue is that to determine whether when atrophy has occurred, there will need to be periodic endoscopy with multiple biopsies. However, as patients already require regular endoscopy for surveillance, this will only add a little in taking additional biopsies of oxyntic mucosa to assess atrophy in an endoscopy that was already scheduled.

What is the effect of Helicobacter pylori in both the short- and long-term on:

a) Barrett's esophagus

All forms of gastroesophageal reflux disease (GERD) affect Caucasians more often than African Americans or native Americans The prevalence of GERD is high among developed countries in North America and Europe and relatively low in developing countries in Africa and Asia. During the past three decades, hospital discharges and mortality rates of gastric cancer, gastric ulcer and duodenal ulcer have declined, while those of esophageal adenocarcinoma and GERD have markedly risen. These opposing time trends suggest that corpus gastritis secondary to H. pylori infection protects against GERD. This hypothesis is consistent with the geographic and ethnic distributions of GERD. Case-control studies also indicate that cases with erosive esophagitis are less likely to harbor active or chronic corpus gastritis than controls without esophagitis [3].

The evidence is increasing that Helicobacter appears to be correlated negatively with Barrett's esophagus [4, 6, 7]. In a European study, 137 GERD patients were followed up for a mean 56.6 months; 49 (36%) of them were infected with H. pylori. H. pylori-infected and -uninfected patients did not differ with respect to age (60 13 versus 61 14 years; p = 0.65) or duration of follow-up (54 30 versus 58 31 months, p = 0.12). H. pylori-negative patients tended to present with more severe esophagitis at baseline (median Savary-Miller score 3 versus 2, p = 0.06) and had a higher prevalence of Barrett's esophagus (39/88 versus 10/49, p = 0.006). However, no difference was found with respect to the dose of omeprazole needed for maintained relief of symptoms and endoscopic signs of esophagitis (median 40 mg in both groups, p = 0.35) [7]. In a study of 225 ethnic Chinese patients with frequent heartburn and/or endoscopic esophagitis,77 (34%) were infected with H. pylori. Esophagitis and Barrett's esophagus were found in 140 patients (62%) and six patients (3%), respectively. H. pylori infected patients had significantly less severe esophagitis compared to the uninfected group (p = 0.022). All patients with Barrett's esophagus were uninfected. Factors that predicted severe esophagitis included age over 60 years (p < 0.001) and hiatus hernia (p < 0.001). H. pylori infection was the only factor that showed a negative correlation with severe esophagitis (p = 0.011). The prevalence of the cagA positive strain in endoscopy-negative GERD, erosive esophagitis and control subjects was 70%, 76% and 78%, respectively (p = 0.75) [4].

Acid suppression, whether the result of atrophy or iatrogenic, results in decreased acid and increased alkali [4]. The effect of PPIs on the esophagus is unclear, but can be postulated. The association with alkaline reflux and Barrett's esophagus, as defined by the presence of goblet cells, is well documented [2]. Further, esophageal adenocarcinoma is very dependent on the presence of goblet cells, to the extent that in the absence of goblet cells there is virtually no increased risk of carcinoma. If PPIs increase the amount of alkaline reflux, which seems likely in the absence of acid, one could postulate that this will result in more intestinal metaplasia (IM) and an increased risk of carcinoma. However, because gastric acid secretion is virtually abolished, the volume of gastric acid is markedly diminished. This would result in less GERD. It is unclear whether these two factors offset each other, that is, there is less reflux but of almost entirely alkaline refluxate.

b) The stomach and the effect of proton pump inhibitors

There are copious data showing that patients with H. pylori have more gastritis, atrophy, and IM than their non-infected counterparts, and modest data suggesting that these changes may be partially reversible following eradication of H. pylori. The influence of PPIs on this process is a little more contentious. The lack of acid promotes proximal migration of H. pylori from the antrum to body, and rarely the inflammation may be limited entirely to the oxyntic mucosa. In 230 patients (mean age, 63 years at entry) on long-term omeprazole for GERD, the annual incidence of gastric corpus mucosal atrophy was 4.7% and 0.7% in H. pylori-positive and -negative patients, respectively, which was mainly observed in elderly patients who had moderate/severe gastritis at entry. In patients with baseline moderate/severe gastritis, the incidences were similar: 7.9% and 8.4%, respectively. Corpus IM was rare, and no dysplasia or neoplasms were observed [5]. The relationship between PPIs and hypertrophy and hyperplasia of parietal cells, and also with fundic gland polyps, is well documented but irrelevant to the issue under discussion.

These can be summarized in Table I.

Table I.

Summary: there is an increased theoretical risk of gastric adenocarcinoma associated with persistent H. pylori that may be enhanced in the presence of PPIs. There is a possible change in the risk of esophageal adenocarcinoma but this remains speculative.

Is the routine eradication of proton pump inhibitors justified?

Routine eradication of H. pylori found incidentally is not recommended in any of he numerous European, North American or Asian groups of patients. Eradication is however recommended if H. pylori is sought as a cause of a specific disease (e.g. duodenal ulcer, MALT lymphoma). Because there are no data suggesting that H. pylori is causally related to Barrett's esophagus, there can be no justification in either seeking its presence or eradicating it if present.


1. Does non-eradication (persistence) of Helicobacter pylori inevitably lead to gastric atrophy? No, it takes a long time, and is unpredictable.
2. If atrophy is achieved, should H. pylori then be eradicated to try to keep the risk of gastric cancer to a minimum? There are numerous papers suggesting some degree of reversibility of atrophy following eradication, including increase in parietal cells. This would result in acid secretion and likely the need to reinstitute PPIs.
3. What is the effect of H. pylori in both the short- and long-term on:
- Barrett's esophagus: H. pylori is likely protective against Barrett's esophagus. It is associated with carditis but there seems to be no increased risk of esophageal adenocarcinoma irrespective of the cagA status of the organism;
- the stomach: some atrophy, but is unpredictable. Long-term risk of carcinoma and theoretically endocrine cell hyperplasia or neoplasia, if achieved;
- do long-term PPIs affect these? May enhance atrophy of oxyntic mucosa. Long-term follow-up studies are still very short in comparison to the time needed for carcinomas to develop. Inflammation with and without atrophic changes is associated with increased risk of diffuse and intestinal carcinoma. If atrophy is achieved, the associated hypergastrinemia may result in ECL-cell hyperplasia or neoplasia.
4. Is the routine eradication of H. pylori justified? No.

Answer to the question "Should the non-eradication of Helicobacter pylori and gastritis allow for the reduction of parietal cell mass to the point that reflux associated symptoms are no longer a problem?" is therefore NO, although there are currently few hard prospective data that it is harmful and most of the risks are theoretical.


1. Tytgat GNJ. Long-term therapy for reflux esophagitis. N Engl J Med 1995;333:l148-1150.

2. Oberg S, Peters JH, DeMeester TR, et al. Determinants of intestinal metaplasia within the columnar-lined esophagus. Arch Surg 2000;135:651-665.

3. Sonnenberg A, El-Serag HB. Clinical epidemiology and natural history of gastroesophageal reflux disease. Yale J Biol Med 1999;72:81-92.

4. Wu JC, Sung JJ, Chan FK, et al. Helicobacter pylori infection is associated with milder gastro-oesophageal reflux disease. Aliment Pharmacol Ther 2000;14:427-432.

5. Klinkenberg-Knol EC, Nelis F, Dent J, et al. Long-term omeprazole treatment in resistant gastroesophageal reflux disease: efficacy, safety, and influence on gastric mucosa. Gastroenterology 2000;l18:661-669.

6. Lord RV, Frommer DJ, Inder S, Tran D, Ward RL. Prevalence of Helicobacter pylori infection in 160 patients with Barrett's oesophagus or Barrett's adenocarcinoma. Aust NZJ Surg 2000;70:26-33.

7. Schenk BE, Kuipers EJ, Klinkenberg-Knol EC, Eskes SA, Meuwissen SG. Helicobacter pylori and the efficacy of omeprazole therapy for gastroesophageal reflux disease. Am J Gastroenterol. 1999;94:884-887.

8. Uemura N, Mukai T, Okamoto S, et al. Effect of Helicobacter pylori eradication on subsequent development of cancer after endoscopic resection of early gastric cancer. Cancer Epidemiol Biomark Prev 1997;6:639-642.

9. Haruma K, Komoto K, Kamada T, et al. Helicobacter pylori infection is a major risk factor for gastric carcinoma in young patients. Scand J Gastroenterol 2000;35:255-259.

10. Kyzekova J, Mour J. The effect of eradication therapy on histological changes in the gastric mucosa in patients with nonulcer dyspepsia and Helicobacter pylori infection. Prospective randomized intervention study. Hepatogastroenterology 1999;46:2048-2056.

11. Satoh K, Kihira K, Kimura K, Sugano K. Changes in the severity of atrophic gastritis after Helicobacter pylori eradication. Nippon Rinsho 1 999;57:185-190.

12. Ohkusa T, Kumagai J, Tanizawa T. Changes in endoscopic features and histological findings of H. pylori-related gastritis with a follow-up over a year after eradication of H. pylori. Nippon Rinsho 1999;57:173-178.

13. Wang CC, Wu MS, Wang HH, et al. Helicobacter pylori infection and age on the development of intestinal metaplasia; a multiple logistic regression analysis. Hepatogastroenterology 1998;45:2234-2237.

14. Satoh K, Kimura K, Takimoto T, Kihira K. A follow-up study of atrophic gastritis and intestinal metaplasia after eradication of Helicobacter pylori. Helicobacter 1998;3:236-240.

15. Len O, Fiocca F, Mastropasqua M, et al. Improvement of intestinal metaplasia six month after misoprostol treatment. Eur Rev Med Pharmacol Sci 1998;2:37-40.

16. Ciok J, Dzieniszewski J, Lucer C. Helicobacter pylori eradication and antral intestinal metaplasia; two years follow-up study. J Physiol Pharmacol 1997;48:115-122.

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

18. Farinati F, Cardin R, Libera GD, et al. Determinants for the development of chronic atrophic gastritis and intestinal metaplasia in the stomach. Eur J Cancer Prev 1995;4:181-186.

Publication date: August 2003 OESO©2015