This study has provided further insight into the factors that may or may not interfere with the healing of oesophageal lesions in ERD or with symptom resolution in both ERD and NERD. Whereas the severity of mucosal lesions was confirmed as a major factor influencing healing in ERD, the negative impact of Barrett’s mucosa on healing of erosive lesions in a large prospective study is a novel finding. Furthermore, the variable impact of H pylori infection on healing in relation to the coexistence of Barrett’s mucosa in the oesophagus was unexpected and, to our knowledge, has not been described previously.
The pattern of ERD healing with 40 mg esomeprazole at eight weeks, according to the endoscopic grades of the LA classification, is in line with that observed in large trials conducted in the USA.18–20
However, the crude healing rates in the US studies were higher than those observed in this study, largely due to the higher proportion of missing healing data in our large study (12% v
5% in the US studies). Healing of LA grades A and B were similar across the studies although healing in patients with LA grades C and D was found to be lower in this study. In searching for a possible explanation, the coexistence of BO with erosions emerged as the critical factor accounting for significantly impaired healing of severe oesophageal lesions. Interestingly, the presence of BO reduced healing in ERD patients to a similar extent, regardless of the method of diagnosis, whether by endoscopy with confirmatory histology or by endoscopy alone. We have to accept that there are certain limitations in a study of this size regarding interobserver variability and correct diagnosis of BO if based on endoscopy without histological confirmation. Indeed, in another large trial, the positive predictive value of endoscopy for BO diagnosis was only 34% (with a negative predictive value of more than 90%).21
In our series, 60% of the BO suspected by endoscopy was confirmed histologically and this indicates that we complied with the standardised protocol for biopsies. Moreover, the absence of intestinalised metaplasia in the histologically confirmed columnar lined epithelium is not an infrequent finding in patients with endoscopically suspected BO. We may have missed some BO in the more advanced stages of LA grades C and D or we may have overlooked some patients with BO in the NERD group. However, both groups included in the BO population behaved similarly in terms of healing of erosive lesions. The presence of BO did not have an impact on symptom resolution in either ERD or NERD patients.
The greater therapeutic effect in the absence of BO and the higher prevalence of BO in patients with ERD is in accordance with the fact that the amount of acid exposure is correlated with the severity of erosive lesions and the presence of BO mucosa.16
In addition, patients with more severe lesions and those with BO had a longer history of GORD (table 1). The traditional concept proposes a shifting from non-erosive to erosive and eventually to the metaplastic condition in GORD over time.22,23
The observation that BO is more prevalent in ERD would support the hypothesis that the development of BO mucosa, at least in a subset of patients, follows the route of inflammation via mucosal breaks rather than an inflammatory non-erosive pathway. This to some extent challenges the new hypothetical concept of Fass and Offman14
that NERD, ERD, and BO are distinct entities of GORD, rather than a potentially evolving continuum.
The role of H pylori
in relation to GORD is complex.24
We found the prevalence of H pylori
to be lower in ERD versus NERD and this, at first glance, would fuel the opinion that there is some beneficial effect of H pylori
against more severe forms of GORD. The higher prevalence of peptic ulcer history and lower H pylori
prevalence observed in our patients with ERD (table 1) may have several explanations however. It may be that patients with ERD have been treated more frequently for H pylori
or that ERD is a consequence of H pylori
eradication. However, recent data25–27
do not support the claim that ERD may develop as a consequence of H pylori
Finally, regarding the inverse relationship between H pylori
infection and GORD, there is also the possibility that environmental conditions giving rise to the development of GORD may reduce the risk of H pylori
Healing of erosive lesions with proton pump inhibitor treatment is reportedly enhanced in the presence of H pylori
The suggested mechanisms are either that there is stronger expression of inflammation at the corpus site in the presence of H pylori
, which augments acid suppression via higher release of IL-1β,30
or that H pylori
causes release of substantial amounts of ammonia, which has an acid buffering effect.31
In this study, the positive effect of H pylori
on healing was indeed observed but only in ERD patients with concurrent BO. This finding may explain conflicting earlier reports on the role of H pylori
in ERD healing where BO was not investigated.19,20,29
A possible explanation for this selective effect of H pylori
may be that BO patients represent the most severe stage of GORD and therefore obtain the greatest benefit from profound acid suppression during a short term treatment course. The clinical benefit of retaining H pylori
is to date only related to short term treatment in this study and should not be the rationale for avoiding H pylori
eradication in the long term management of these patients.32
The long term follow up of patients included in this trial should further contribute to our understanding of whether there are distinct entities of GORD or whether they exist as a continuum of the disease. In the clinical setting, when patients present with both severe erosive oesophagitis and BO, we would suggest a higher dose of acid suppressant for optimal healing, especially if these patients are also H pylori
negative. However, further controlled prospective studies are warranted to confirm these findings, which may influence management of GORD in the future.
In conclusion, the degree of erosive mucosal damage and, to a major extent, the presence of Barrett’s mucosa, exerts a negative impact on healing. The presence of H pylori only influenced healing of ERD patients who had coexistent Barrett’s oesophagus.