The first study suggesting a possible association between H. pylori and GORD was published by Labenz et al[13] on 1997. In this study, 25.8% of patients with duodenal ulcer (DU) cured for H. pylori infection developed erosive oesophagitis (Savary-Miller classification) at 3-year follow-up as compared to 12.9% of DU patients with ongoing infection (P < 0.001). Identified risk factors were male sex, severity of corpus gastritis, and weight gain. These results deserve some considerations. As shown in Figure 1, the incidence of erosive oesophagitis in H. pylori eradicated patients constantly increased at follow-up, so that at 3-year follow-up the curve did not still reach the plateau. This would probably suggest that an even higher oesophagitis incidence is expected at longer follow-up in these patients. However, this contrasts with data of a recent 7-year follow-up study which showed that reflux oesophagitis occurred in only 1.9% of DU patients following H. pylori eradication[14]. In addition, it should be noted that the curve of oesophagitis incidence in not eradicated DU patients showed a very similar slope as compared to that of eradicated patients (Figure 1). In detail, following a questionable delay of 1 year, reflux oesophagitis started to increase also in H. pylori infected patients, and the increase of incidence parallels with that of eradicated patients. A plausible explanation of such phenomenon could be that several not eradicated DU patients were taking anti-acid therapy, at least for the first year follow-up in this study. Indeed, this patient group included either control cases of H. pylori eradication trials (75 cases) or H. pylori eradication failure patients (141 cases) in whom DU symptoms most likely persisted[13]. Therefore, the observation of a distorted phenomenon could not be ruled out. On the other hand, it was observed that oesophagitis occurred more frequently in those H. pylori cured patients with weight gain > 2 kg [odds ratio (OR): 3.2; 95%CI: 1.2-9.4; P < 0.05] within 3-year follow-up. Unfortunately, both mean and range of weigh gain was not provided in this study. However, it is plausible that several patients changed their dietary and voluptuary habits following complete DU healing, with consequent body mass index (BMI) increase. The direct relationship between BMI and GORD is widely documented in literature, so that the “guilty” of erosive oesophagitis onset - at least in some patients - probably was the BMI increase rather than the H. pylori cure. Unfortunately, the lack of multivariate regression including H. pylori eradication as an independent risk factor for GORD does not allow to confirm the significant role observed solely at univariate analysis. Finally, the reason for which the risk of erosive oesophagitis incidence following H. pylori eradication was 3.6 (95%CI: 1.1-10.6) higher in males as compared to females remains unclear. This would contrast with the prevalence of GORD in the general population which equally occurs in both sexes[15].

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Figure 1 Incidence of erosive oesophagitis in Helicobacter pylori eradicated and not eradicated duodenal ulcer patients (Modified from reference 13). The comparable curve slopes would indicate a similar phenomenon. The final difference between patient groups depends on the 1-year delay between curve which remains unexplained. H. pylori: Helicobacter pylori.

At least in theory, H. pylori eradication could cause GORD by: (1) recovering gastric acid secretion; (2) increasing the amount of reflux in the oesophagus; and (3) reducing the clearance of oesophageal acid exposure.

Regarding the first point, it has been observed that H. pylori-associated corpus-predominant gastritis is an independent risk factor (OR: 5.5; 95%CI: 2.8-13.6) for erosive oesophagitis development following H. pylori eradication in DU patients[13]. In this study, the body gastritis sum score before H. pylori eradication was 4.1 in those who developed oesophagitis as compared to 3.1 of those without oesophagitis onset. Therefore, it has been suggested that the higher degree of recovery leads into a higher acid secretion which, in turn, causes erosive oesophagitis[13]. However, by considering that the sum score (activity plus grade) of gastritis was ranging from 0 (absent) and 8 (severe), it is questionable that acid hypersecretion developed only in those patients in whom corpus gastritis score dropped from 4.1, but not from 3.1, to zero following bacterial cure. At this point, the crucial issue is to understand whether H. pylori eradication really causes gastric acid hypersecretion in DU patients. To our knowledge, neither pathophysiology nor clinical studies support such an event. It has been found that infected DU patients have a 3-fold increase of basal acid output (BAO) and a 6-fold increase of stimulated maximal acid output (MAO) as compared to uninfected controls[16]. Of note, both these alterations normalize 1-year following H. pylori eradication, suggesting that DU patients cured for the infection completely restore normal acid secretion[16]. The absence of an acid hypersecretive status in these patients is further documented by the clinical observation that DU recurrence is virtually abolished following H. pylori eradication[17]. Therefore, it is unclear the reason for which the hypothesized hypersecretion in DU patients after bacterial cure should cause erosive oesophagitis onset, but not DU recurrence. To search for a plausible explication, one could hypothesize the “tale of a crazy acid”. According to this theory, following the healing of corpus-predominant gastritis - a typical gastritis pattern of both gastric ulcer and cancer, but infrequent in DU[18] - acid hypersecretion occurs in some DU patients. In these patients the acid should invert its normal route - so failing to cause DU recurrence - and should turn into the oesophagus causing erosions (Figure 2). However, studies on 24-h intra-oesophageal pH recording before and after H. pylori eradication showed that the percentage time of pH < 4.0 did not significantly change following eradication[19,20]. Other putative mechanisms by which H. pylori eradication could favor GORD are alterations of both LES pressure and oesophageal peristalsis. However, two studies found no difference in basal LES pressure between H. pylori infected and matched controls[21,22], whilst another study showed an even lower basal LES pressure and higher rate of ineffective oesophageal motility in infected patients[23]. Based on these manometric observations, it could be expected that H. pylori eradication would reduce - rather than favor - acid reflux into the oesophagus.

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Figure 2 The “tale of a crazy acid”. Following Helicobacter pylori gastric in duodenal ulcer patients the hypothesized acid hypersecretion would U-turn into the oesophagus instead of in the duodenal bulb.

Several clinical trials assessing the onset of both reflux symptoms and erosive oesophagitis have been performed. A recent meta-analysis evaluated data of 10 trials where data of patients treated for H. pylori infection were compared to those receiving placebo[24]. At 8-30 mo follow-up the incidence of reflux symptoms did not significantly differ between the two patient groups (17% vs 22.6%), with a trend even favoring bacterial eradication (OR: 0.81; 95%CI: 0.56-1.71). Likewise, erosive oesophagitis equally occurred in both groups (5% vs 5.1%; OR: 1.13; 95%CI: 0.72-1.78). Noteworthy, a study on 156 patients with both peptic ulcer and reflux oesophagitis found that the oesophageal lesions improved more frequently in H. pylori eradicated patients as compared to those with persistent infection[25]. Overall, these data would suggest that H. pylori eradication is not significantly associated with either reflux symptoms or erosive oesophagitis onset, some data suggesting also an advantage in curing the infection when oesophagitis is already present.