H pylori infection and reflux oesophagitis

We read with considerable interest the paper by Kuipers et al (Gut 2004;53:12–20) which found no significant adverse impact on the severity of reflux disease or its control after two years of omeprazole therapy following H pylori eradication, during which time gastritis largely healed. In the commentary by McColl (Gut 2004;53:5–7), it is stated that although published data are conflicting, Schwizer et al reported improvement in reflux symptoms following H pylori treatment.¹ Our preliminary published data,² which are in accordance with those of Schwizer and colleagues,¹ consisted of a small cohort of 69 patients with gastro-oesophageal reflux disease (GORD) and irritable bowel syndrome (IBS). Forty patients were treated with omeprazole (20 mg/day) plus trimebutine (600 mg/day) for three months (group A) and 29 were treated with omeprazole (20 mg/day) as monotherapy for an equal period of time (group B). Inclusion and exclusion criteria matched those of Kuipers et al. Upper and lower gastrointestinal endoscopic, histological, and clinical evaluations were made at baseline. Furthermore, upper gastrointestinal evaluation was repeated three months post-treatment. At baseline, oesophagitis, confirmed by histology, and the histological presence of H pylori were observed in 67.5% and 62.1% and in 80% and 82.8% of groups A and B of patients, respectively. All H pylori positive patients received eradication treatment, as analysed in Kuipers et al’s paper. The eradication rate was observed in 84% of H pylori/positive patients in group A and in 83% of H pylori/positive patients in group B. Three months post-treatment, there was a significant improvement in GORD (p = 0.003), IBS symptoms (p<0.0001), and oesophagitis (p = 0.029) in group A compared with group B. At baseline, all 24 H pylori/positive patients who received omeprazole and the eradication regimen had GORD symptoms and 15 (62.5%) had histologically proven oesophagitis. Three months post-treatment, GORD was present in 12 (50%) patients (p<0.0001) and oesophagitis in nine (37.5%) (p>0.05). As improvement in oesophagitis did not reach a statistically significant level, our study was continued and results are shown in table 1 ▶ (unpublished data). All 45 H pylori/positive patients who received omeprazole and the eradication regimen had GORD and 29 (64.4%) had oesophagitis at baseline. Three months post-treatment, 22 (48.9%) had GORD symptoms (p<0.00001) and 18 (40%) had oesophagitis (p = 0.03) (Wilcoxon’s rank sum test, two tailed p values; data not shown in table 1 ▶). There was a statistically better response in patients who also received trimebutine.

Table 1.

Patient profile prior to and after the therapeutic regimens and comparisons between the two groups

	Group A (n = 92) (omeprazole plus trimebutine)					Group B (n = 56) (omeprazole)					Significance (p)
	Prior		After 3 months			Prior		After 3 months			A v B		A1b v B1b	A2 v B2
	A1 (n = 73)	A2 (n = 19)	A1a (n = 12)	A1b (n = 61)	A2 (n = 19)	B1 (n = 45)	B2 (n = 11)	B1a (n = 8)	B1b (n = 37)	B2 (n = 11)	Prior	After	After	After
GORD symptoms	73	19	5	10	3	45	11	4	18	7	NS	<0.001	<0.005	<0.025
Oesophagitis	51	12	5	10	3	29	7	2	16	5	NS	<0.01	<0.01	NS
IBS symptoms	73	19	2	7	3	45	11	4	23	7	NS	<0.001	<0.001	<0.025

p values between the two groups were calculated using the χ² test with Yates’ correction (two tailed p values).

Group A, patients were assigned to three months of omeprazole plus trimebutine treatment; group B, patients were assigned to three months of omeprazole monotherapy; groups A1, B1, H pylori positive patients prior to treatment assigned to omeprazole plus trimebutine or omeprazole alone, respectively; groups A1a, B1a, patients from groups A1 and B1, respectively, who remained H pylori positive after the eradication regimen; groups A1b, B1b, patients from groups A1 and B1, respectively, in whom H pylori infection was eradicated; groups A2, B2, H pylori negative patients prior to and after treatment with omeprazole plus trimebutine or omeprazole alone, respectively

In our preliminary study, Barrett’s oesophagus was observed in eight (20%) of 40 and in five (17.2%) of 29 patients in groups A and B, respectively, similar to that (24.3%) observed by Kuipers et al. As there is an increased prevalence of IBS in patients with GORD,³ it would be interesting to know how many of the patients in Kuipers et al’s study had symptoms suggestive of IBS, and if their regimen had results similar to ours.

Our data show that H pylori is frequent in GORD and may contribute to the pathogenesis of GORD by several mechanisms.² Also, we propose that the increasing prevalence of GORD may be partially explained not just by the decrease in prevalence of H pylori infection, as suggested by McColl (Gut 2004;53:5–7), but rather by healing of H pylori associated peptic ulcer disease, which coexists with GORD.^4,5 Thus eliminating peptic ulcer disease unmasks GORD.⁵

In our latest unpublished data, 18 (48.6%) of 37 patients, in whom H pylori was eradicated, had reflux symptoms on omeprazole compared with four (50%) of eight patients in whom H pylori was not eradicated. Although the latter group was too small to draw definite conclusions, it seems that eradicating H pylori did not make GORD more difficult to control. While the editorial advocates that H pylori eradication makes it more difficult to achieve long term control of GORD with omeprazole therapy, we suggest that H pylori eradication leads to better control of GORD symptoms and improves oesophagitis.