Gut 1999;45(Suppl I):I13–I17 I13 Gastro-oesophageal reflux disease and Helicobacter pylori: an intricate relation Gut: first published as 10.1136/gut.45.2008.i13 on 1 July 1999. Downloaded from D McNamara, C O’Morain Summary treatment, 24 hour oesophageal pH assess- Heartburn is a common symptom aVecting ment, and/or histological evidence of oesoph- 21–44% of the adult population on a monthly agitis. Long term sequelae include benign basis. Oesophagitis is less common, aVecting strictures, Barrett’s oesophagus, and adenocar- 2% of individuals. cinoma. Epidemiological studies have shown that Pathophysiological mechanisms described patients with gastro-oesophageal reflux disease include abnormal transient relaxation of the (GORD) have similar incidence rates of lower oesophageal sphincter (TLOSR),10–14 Helicobacter pylori infection as do controls. impaired oesophageal motility,15 delayed gas- Some groups have reported that there is a lower tric emptying,16 17 impaired mucosal incidence, deducing that infection does not defences,18 19 toxic nature of refluxed material cause, and in some way confers protection (acid, bile),20–24 and the presence of hiatus her- against GORD. Additional supportive evidence nia. Although it would appear that GORD is a is available from reports of GORD develop- multifactorial condition predominantly related ment following successful H pylori eradication. to abnormal upper gastrointestinal motility, The mechanisms involved are complicated. recent interest has focused on the relation Individuals with H pylori induced pangastritis between Helicobacter pylori infection and and subsequent hypochlorhydria may be pro- GORD. tected whereas those with an antral predomi- nant gastritis, as in duodenal ulcer disease, with an increased acid output may be prone to H pylori and the aetiology of GORD development of GORD. H pylori is a common infection, responsible for Recent evidence has linked H pylori infection a variety of gastroduodenal pathology, duode- with the development of inflammation of the nal and gastric ulcer, mucosa associated gastric cardia—carditis. Reports are available lymphoid tissue (MALT) lymphoma, and gas- which show that carditis is a frequent finding in tric carcinoma. The eVects of H pylori infection patients with GORD. The incidence of both on the pathophysiological mechanisms in- http://gut.bmj.com/ cardia and oesophageal carcinoma is increas- volved in the aetiology of GORD have been ing. The relation between GORD, carditis, examined. H pylori infection has been shown to intestinal metaplasia, and cardia carcinoma is produce an increase in basal and stimulated unclear. Intestinal metaplasia may result from gastric acid output through a number of multifocal atrophic gastritis, linked to H pylori mechanisms, including gastrin, somatostatin, infection or from GORD and the development and inflammatory mediators, and this phe- of Barrett’s oesophagus. Long term follow up nomenon of increased acid output has been on September 26, 2021 by guest. Protected copyright. studies will be required to assess the malignant shown to occur in asymptomatic cases as well potential of these histological entities and as those with peptic ulcer disease and non- whether or not H pylori infection has an aetio- ulcer dyspepsia.25–32 Increased acid secretion as logical role. a result of H pylori infection is a plausible aetiological mechanism of GORD in a subset Introduction of cases, supported by the observation that Gastro-oesophageal reflux disease refers to the patients with duodenal ulceration are more abnormal exposure of the oesophageal mucosa likely to suVer from reflux oesophagitis.33 to gastric contents, resulting in a spectrum of However, H pylori colonisation of the gastric conditions. Symptoms of heartburn or acid mucosa may result in hypochlorhydria as seen regurgitation aVect 21–44% of the adult popu- in individuals with a diVuse gastritis and gastric lation on a monthly basis.1–3 Oesophagitis is less atrophy.34 Patients with this pattern of disease prevalent, and is reported to occur in up to 2% seem to be at less risk of developing GORD of individuals.45 Symptoms have been shown than controls.35 36 There is evidence to associate to have a specificity of 85–95% and sensitivity H pylori infection with both the development of of 6–39%.6 Patients with GORD frequently hypochlorhydria and increased acid secretion, present with atypical symptoms; up to 50% of depending on the inflammatory response endoscopically diagnosed cases of oesophagitis induced. As a result, the eVect of H pylori Department of infection on the development of GORD is Gastroenterology, present with symptoms other than heartburn 7–9 Meath and Adelaide or acid regurgitation. In addition GORD is similarly contradictory. Hospitals, Dublin 24, the underlying diagnosis in 2–15% of subjects Ireland undergoing investigation for dyspepsia. Accu- D McNamara rate diagnosis of GORD can be diYcult with Abbreviations used in this paper: GORD, C O’Morain gastro-oesophageal reflux disease; TLOSR, transient currently accepted criteria including symptoms relaxation of the lower oesophageal sphincter; MALT, Correspondence to: of heartburn and/or acid regurgitation, im- mucosa associated lymphoid tissue; PPI, proton pump Dr McNamara. provement with proton pump inhibitor (PPI) inhibitor. I14 McNamara, O’Morain Table 1 Epidemiological studies investigating the role of inflammation in the corpus and antrum, Helicobacter pylori infection in gastro-oesophageal reflux potentiating the risk of developing gastric atro- disease (GORD) phy and achlorhydria.60–62 Gut: first published as 10.1136/gut.45.2008.i13 on 1 July 1999. Downloaded from Prevalence of H pylori in GORD Such mechanisms have been suggested to Similar to controls explain the negative association between cagA O’Connor and Cunnane45 positive strains and GORD. In addition an Borkent and Beker46 Walker and colleagues47 increased density of infection, associated with Cheng and colleagues48 virulent infecting strains, may result in an Newton and colleagues49 Befrits and colleagues50 increased production of ammonia, thus poten- 63 Liston and colleagues51 tiating the eVects of PPIs. The fact that viru- Decreased lent strains are responsible for 80–100% of Werdmuller and LoVeld52 Vicari and colleagues53 duodenal ulcers and are associated with an Ohara and colleagues35 increase in acid production seems Haruma and colleagues54 contradictory.64 Yet it is known that a history of Severity of GORD and H pylori Similar to controls peptic ulcer is associated with a reduced risk of O’Connor and Cunnane45 proximal and distal gastric cancers.65 With Newton and colleagues49 regard to Barrett’s oesophagus the majority of Werdmuller and LoVeld52 Increased studies have again found no association with H Cargill and colleagues57 pylori.66 67 Henihan et al have shown a positive Decreased correlation between the severity of chronic Grebenev56 Sehiguchi and colleagues55 inflammation in Barrett’s oesophagus and H pylori. The possible mechanisms underlying this observation are unknown.68 Delayed gastric emptying has been reported in association with GORD development. Re- Carditis, H pylori, and GORD sults of studies exploring the eVect of H pylori The gastric cardia is the most proximal portion on gastric emptying are variable. Several of the stomach, occupying a small zone just groups have reported no diVerence between H 37–39 distal to the oesophagogastric junction. Under pylori positive and negative subjects. Other normal circumstances, it comprises tightly groups have shown abnormal antroduodenal packed mucus secreting cells and is devoid of motility in patients with GORD and H pylori inflammatory cells. Recent interest has focused and delayed gastric emptying in patients with on carditis, as a possible marker or conse- antral predominant gastritis, with or without H 40–42 quence of GORD or as a possible extension of pylori infection. There is no clear evidence H pylori induced pangastritis. to associate H pylori infection with a definite Carditis has been reported to be a sensitive dysfunction of gastric emptying and it is marker of GORD. Oberg et al have revealed a unlikely to be a major aetiological factor linking positive association between carditis and http://gut.bmj.com/ H pylori and GORD. GORD, as determined by a 24 hour ambula- It has been postulated that H pylori colonisa- tory pH oesophageal probe assessment.69 This tion of the gastric cardia may result, through study did not examine the role of H pylori inflammatory mediators and vagal stimulation, infection. Others disagree, and have reported in increased TLOSR episodes, hence increas- 42–44 that carditis is a manifestation of extensive H ing the likelihood of GORD development. pylori colonisation and is independent of Several groups are investigating the role of car- 70–72 oesophagitis. on September 26, 2021 by guest. Protected copyright. ditis with respect to GORD but as yet there is The incidence of proximal gastric cancers no clear evidence to support this hypothesis. like that of oesophageal adenocarcinoma is increasing,73 whereas that of H pylori infection Epidemiology and distal gastric cancer is falling. Barrett’s Epidemiological studies have in general found oesophagus, a consequence of GORD, is a risk little or no association between H pylori factor for the development of oesophageal infection and GORD (table 1), similar infec- adenocarcinoma with known premalignant tion rates being reported in patients with histological markers including intestinal meta- GORD