Randomised controlled trial of effects of Helicobacter pylori infection and its eradication on heartburn and gastro-oesophageal reflux: Bris
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《英国医生杂志》
1 Frenchay Hospital, North Bristol NHS Trust, Bristol BS16 1LE, 2 Department of Social Medicine, University of Bristol, Bristol BS8 2PR, 3 Department of Epidemiology and Public Health, The Queen's University of Belfast, Belfast BT9 5EE, 4 School of Medicine, Health Policy and Practice, University of East Anglia, Norwich NR4 7TJ, 5 Peterborough General Hospital, Peterborough
Correspondence to: R F Harvey richard.harvey1@virgin.net
Abstract
Of the 10 537 participants who had a 13C-urea breath test, 1634 (15.5%) were positive for H pylori infection (figure). Of those with a positive test result, 1558 (95.3%) were randomised to receive either active treatment (787) or placebo (771). The characteristics of the two groups were similar (table 1).
Trial profile
Table 1 Baseline characteristics of two groups of participants with Helicobacter pylori infection who entered the prospective double blind study. Values are numbers (percentages)
Six months after treatment, the 13C-urea breath test was negative in 659/727 (90.7%) of participants after active treatment (60 non-attenders) and in 99/706 (14.0%) of those given placebo (65 non-attenders). Two year follow up was complete in 1433/1558 (92.0%) participants. The unexpectedly high apparent loss of H pylori infection in the placebo group was mainly due to our use of 3.5 rather than 5.0 as a cut-off point to define infection in the 13C-urea breath test. In 75 of the 99 instances of apparent eradication by placebo, the initial breath test reading was between 3.5 and 5.0. Such participants probably never had H pylori infection.
H pylori infection was associated with a small difference in the prevalence of heartburn ("any heartburn in the past month" 28.1% v 25.2%, 2 = 4.51, P = 0.034) (table 2), but not gastro-oesophageal reflux ("any reflux in the past month" 18.6% v 17.4%, 2 = 1.0, P = 0.32) (table 3).
Table 2 Effect of Helicobacter pylori infection on prevalence of heartburn. Values are numbers (percentages) unless stated otherwise
Table 3 Effect of Helicobacter pylori infection on prevalence of acid reflux. Values are numbers (percentages) unless stated otherwise
Heartburn was significantly associated with epigastric pain, acid reflux, obesity, regular consumption of non-steroidal anti-inflammatory drugs or proton pump inhibitors, smoking, and chest pain induced by exercise (table 4). Age, sex, alcohol intake, and socioeconomic status were not risk factors for heartburn.
Table 4 Factors associated with a significantly increased risk of heartburn. Values are numbers (percentages) unless stated otherwise
H pylori eradication treatment had no significant effect on the prevalence of either heartburn (odds ratio 0.99, 95% confidence interval 0.88 to 1.12) or gastro-oesophageal reflux (1.04, 0.91 to 1.19) two years after treatment (table 5). Treatment had no impact on the development of heartburn (0.90, 0.78 to 1.04) or reflux (1.05, 0.90 to 1.21) in previously asymptomatic participants. In participants who had these symptoms at baseline, no significant improvement occurred in either heartburn (0.90, 0.71 to 1.14) or reflux (0.89, 0.62 to 1.29).
Table 5 Effect of Helicobacter pylori eradication treatment on prevalence of heartburn and reflux at two years. Values are numbers (percentages) unless stated otherwise
In those participants who had gastro-oesophageal reflux without heartburn before treatment (n = 248), H pylori eradication treatment had a protective effect against the development of heartburn over the two year period (0.56, 0.35 to 0.90). The number of general practice consultations for heartburn or reflux over the two years after active treatment was not significantly greater than after placebo (1.63, 0.94 to 2.87).
Discussion
The most obvious mechanism by which H pylori infection might affect reflux oesophagitis is by affecting secretion of gastric acid. H pylori infection usually causes a predominantly antral gastritis, which results in a net increase in acid secretion.16 In people with an incompetent antireflux mechanism, this would increase exposure of the lower oesophagus to acid, increasing the prevalence of heartburn.4 5 Our findings that H pylori is associated with an increased prevalence of heartburn and that H pylori eradication treatment reduces the risk of patients with acid reflux developing heartburn support this hypothesis. Acid reflux depends more on the integrity of the lower oesophageal sphincter, hence the insignificant effect of H pylori infection on reflux. Patients with severe reflux oesophagitis are less likely to have H pylori infection,17-26 possibly because corpus gastritis caused by helicobacter infection limits maximum acid output in these patients,27-32 thus protecting them against the more severe forms of reflux oesophagitis. Such people might theoretically be at risk of increased exposure of the lower oesophagus to acid after eradication of H pylori infection.29 31 However, our study suggests that no significant worsening of heartburn or reflux occurs after eradication of H pylori in patients in the community.
Our study has weaknesses. As it was community based, we had no direct information (from endoscopy, for example) as to the actual pathology underlying the symptoms of our participants. The randomised double blind design, the large numbers of participants, the high rate of H pylori eradication, the avoidance of prolonged acid suppression as part of the treatment, and the length and completeness of the two year period of follow up are compensating strengths.
What is already known on this topic
Heartburn and gastro-oesophageal reflux are common symptoms in the population
Helicobacter pylori gastritis is also very common and might influence these symptoms by altering gastric acid secretion
Previous studies have reached differing conclusions about the effect of H pylori eradication on gastro-oesophageal reflux disease
What this study adds
In a general practice population, people with Helicobacter pylori infection had a slightly higher prevalence of heartburn (but not reflux) than other people
Helicobacter pylori eradication had no net effect on symptoms of gastro-oesophageal reflux disease
We thank the participants in the Bristol helicobacter project and the general practitioners and health centre staff; the nursing team of Lynne Bradshaw, Julie Watson, Tina Critchley, Jo Lee, Carol Everson-Coombe, Penny Nettlefield, and Joanne Smith; Judy Millward, Helen Davies, Amy Hawkins, and Sarah Pike for secretarial support; and Erwin Brown, Paul Thomas, Nick Pope, and Phil Hedges of the microbiology department and Peter Spurr, Martin Bullock, and Fiona Greenwood of the pharmacy department, Frenchay Hospital, for help with the breath tests.
Contributors: RFH initiated the study, helped to plan the project, analysed the results, wrote the initial draft of the paper, and is the guarantor. JAL ran the Bristol helicobacter project from day to day and helped with analysis of the data and the final version of the paper. PN helped to set up the project. LJM, IMH, and JLD helped to plan the project, analyse the results, and produce the final version of the paper.
Funding: This study was funded jointly by the NHS South and West Regional Research and Development Directorate and GlaxoSmithKline UK. The Department of Social Medicine is the lead centre for the MRC Health Services Research Collaboration.
Competing interests: RFH and JAL were reimbursed by GlaxoSmithKline for attending the AGA symposium in 2000.
Ethical approval: The local research ethics committee approved the study.
References
Tarpila S, Kekki M, Samloff IM, Sipponen P, Siurala M. Morphology and dynamics of the gastric mucosa in duodenal ulcer patients and their first-degree relatives. Hepatogastroenterology 1983;30: 198-201.
Calam J. Clinicians' guide to Helicobacter pylori. London: Chapman & Hall Medical, 1996: 39-77.
Labenz J, Blum AL, Bayerdorffer E, Meining A, Stolte M, Borsch G. Curing Helicobacter pylori infection in patients with duodenal ulcer may provoke reflux esophagitis. Gastroenterology 1997;112: 1442-7.
Hamada H, Haruma K, Mihara M, Kamada T, Yoshihara M, Sumii K, et al. High incidence of reflux oesophagitis after eradication therapy for Helicobacter pylori: impacts of hiatal hernia and corpus gastritis. Aliment Pharmacol Ther 2000;14: 729-35.
Manes G, Mosca S, De Nucci C, Lombardi G, Lioniello M, Balzano A. High prevalence of reflux symptoms in duodenal ulcer patients who develop gastro-oesophageal reflux disease after curing Helicobacter pylori infection. Dig Liver Dis 2001;33: 665-70.
Veldhuyzen van Zanten SJ. Treatment of Helicobacter pylori infection unmasks rather than induces symptoms of gastro-oesophageal reflux disease. Dig Liver Dis 2001;33: 647-8.
Befrits R, Sjostedt S, Odman B, Sorngard H, Lindberg G. Curing Helicobacter pylori infection in patients with duodenal ulcer does not provoke gastroesophageal reflux disease. Helicobacter 2000;5: 202-5.
Moayyedi P, Bardhan C, Young L, Dixon MF, Brown L, Axon AT. Helicobacter pylori eradication does not exacerbate reflux symptoms in gastroesophageal reflux disease. Gastroenterology 2001;121: 1120-6.
Laine L, Sugg J. Effect of Helicobacter pylori eradication on development of erosive esophagitis and gastroesophageal reflux disease symptoms: a post hoc analysis of eight double blind prospective studies. Am J Gastroenterol 2002;97: 2992-7.
Schwizer W, Thumshirn M, Dent J, Guldenschuh I, Menne D, Cathomas G, et al. Helicobacter pylori and symptomatic relapse of gastro-oesophageal reflux disease: a randomised controlled trial. Lancet 2001;357: 1738-42.
Stuart RC, Craig CF, Morran C, Burns H, Harden K, Power A, et al. A beneficial effect of H. pylori eradication in reflux patients in the community. Gastroenterology 2001;120(suppl 1): A48.
Moayyedi P, Feltbower R, Brown J, Mason S, Mason J, Nathan J, et al. Effect of population screening and treatment for Helicobacter pylori on dyspepsia and quality of life in the community: a randomized controlled trial. Lancet 2000;355: 1665-9.
Wildner-Christensen M, Moller Hansen J, Schaffalitzky de Muckadell OB. Rates of dyspepsia one year after Helicobacter pylori screening and eradication in a Danish population. Gastroenterology 2003;125: 372-9.
Lane JA, Harvey RF, Murray L, Harvey IM, Nair P, Egger M, et al. A placebo-controlled randomized trial of eradication of Helicobacter pylori in the general population: study design and response rates of the Bristol helicobacter project. Control Clin Trials 2002;23: 321-32.
Dominguez-Munoz JE, Leodolter A, Sauerbruch T, Malfertheiner P. A citric acid solution is an optimal test drink in the 13C-urea breath test for Helicobacter pylori infection. Gut 1997;40: 459-62.
El Omar EM, Penman ID, Ardill JE, Chittajallu RS, Howie C, McColl KE. Helicobacter pylori infection and abnormalities of acid secretion in patients with duodenal ulcer disease. Gastroenterology 1995;109: 681-91.
Koike T, Ohara S, Sekine H, Iijima K, Kato K, Shimosegawa T, et al. Helicobacter pylori infection inhibits reflux esophagitis by inducing atrophic gastritis. Am J Gastroenterol 1999;94: 3468-72.
Haruma K, Hamada H, Mihara M, Kamada T, Yoshihara M, Sumii K, et al. Negative association between Helicobacter pylori infection and reflux esophagitis in older patients: case-control study in Japan. Helicobacter 2000;5: 24-9.
Labenz J, Jaspersen D, Kulig M, Leodolter A, Lind T, Lindner D, et al. Risk factors for the development of erosive reflux disease: a multivariate analysis based on the proGERD initiative. Gastroenterology 2002; W1163.
Shirota T, Kusano M, Kawamura O, Horikoshi T, Mori M, Sekiguchi T. Helicobacter pylori infection correlates with severity of reflux esophagitis: with manometry findings. J Gastroenterol 1999;34: 553-9.
Varanasi RV, Fantry GT, Wilson KT. Decreased prevalence of Helicobacter pylori infection in gastroesophageal reflux disease. Helicobacter 1998;3: 188-94.
Werdmuller BF, Loffeld RJ. Helicobacter pylori infection has no role in the pathogenesis of reflux esophagitis. Dig Dis Sci 1997;42: 103-5.
Weston AP, Badr AS, Topalovski M, Cherian R, Dixon A, Hassanein RS. Prospective evaluation of the prevalence of gastric Helicobacter pylori infection in patients with GERD, Barrett's esophagus, Barrett's dysplasia, and Barrett's adenocarcinoma. Am J Gastroenterol 2000;95: 387-94.
Loffeld RJ, Werdmuller BF, Kuster JG, Perez-Perez GI, Blaser MJ, Kuipers EJ. Colonization with cagA-positive Helicobacter pylori strains inversely associated with reflux esophagitis and Barrett's esophagus. Digestion 2000;62: 95-9.
Warburton-Timms VJ, Charlett A, Valori RM, Uff JS, Shepherd NA, Barr H, et al. The significance of cagA+ Helicobacter pylori in reflux oesophagitis. Gut 2001;49: 341-6.
Fallone CA, Barkun AN, Gottke MU, Best LM, Loo VG, Veldhuyzen van Zanten S, et al. Association of Helicobacter pylori genotype with gastroesophageal reflux disease and other upper gastrointestinal diseases. Am J Gastroenterol 2000;95: 659-69.
El Omar EM, Oien K, El Nujumi A, Gillen D, Wirz A, Dahill S, et al. Helicobacter pylori infection and chronic gastric acid hyposecretion. Gastroenterology 1997;113: 15-24.
El Serag HB, Sonnenberg A, Jamal MM, Inadomi JM, Crooks LA, Feddersen RM. Corpus gastritis is protective against reflux oesophagitis. Gut 1999;45: 181-5.
Wu JC, Chan FK, Wong SK, Lee YT, Leung WK, Sung JJ. Effect of Helicobacter pylori eradication on oesophageal acid exposure in patients with reflux oesophagitis. Aliment Pharmacol Ther 2002;16: 545-52.
Iijima K, Ohara S, Sekine H, Koike T, Kato K, Asaki S, et al. Changes in gastric acid secretion assayed by endoscopic gastrin test before and after Helicobacter pylori eradication. Gut 2000;46: 20-6.
Koike T, Ohara S, Sekine H, Iijima K, Kato K, Toyota T, et al. Increased gastric acid secretion after Helicobacter pylori eradication may be a factor for developing reflux oesophagitis. Aliment Pharmacol Ther 2001;15: 813-20.
Yamaji Y, Mitsushima T, Ikuma H, Okamoto M, Yoshida H, Kawabe T, et al. Inverse background of Helicobacter pylori antibody and pepsinogen in reflux oesophagitis compared with gastric cancer: analysis of 5732 Japanese subjects. Gut 2001;49: 335-40.(Richard F Harvey, consult)
Correspondence to: R F Harvey richard.harvey1@virgin.net
Abstract
Of the 10 537 participants who had a 13C-urea breath test, 1634 (15.5%) were positive for H pylori infection (figure). Of those with a positive test result, 1558 (95.3%) were randomised to receive either active treatment (787) or placebo (771). The characteristics of the two groups were similar (table 1).
Trial profile
Table 1 Baseline characteristics of two groups of participants with Helicobacter pylori infection who entered the prospective double blind study. Values are numbers (percentages)
Six months after treatment, the 13C-urea breath test was negative in 659/727 (90.7%) of participants after active treatment (60 non-attenders) and in 99/706 (14.0%) of those given placebo (65 non-attenders). Two year follow up was complete in 1433/1558 (92.0%) participants. The unexpectedly high apparent loss of H pylori infection in the placebo group was mainly due to our use of 3.5 rather than 5.0 as a cut-off point to define infection in the 13C-urea breath test. In 75 of the 99 instances of apparent eradication by placebo, the initial breath test reading was between 3.5 and 5.0. Such participants probably never had H pylori infection.
H pylori infection was associated with a small difference in the prevalence of heartburn ("any heartburn in the past month" 28.1% v 25.2%, 2 = 4.51, P = 0.034) (table 2), but not gastro-oesophageal reflux ("any reflux in the past month" 18.6% v 17.4%, 2 = 1.0, P = 0.32) (table 3).
Table 2 Effect of Helicobacter pylori infection on prevalence of heartburn. Values are numbers (percentages) unless stated otherwise
Table 3 Effect of Helicobacter pylori infection on prevalence of acid reflux. Values are numbers (percentages) unless stated otherwise
Heartburn was significantly associated with epigastric pain, acid reflux, obesity, regular consumption of non-steroidal anti-inflammatory drugs or proton pump inhibitors, smoking, and chest pain induced by exercise (table 4). Age, sex, alcohol intake, and socioeconomic status were not risk factors for heartburn.
Table 4 Factors associated with a significantly increased risk of heartburn. Values are numbers (percentages) unless stated otherwise
H pylori eradication treatment had no significant effect on the prevalence of either heartburn (odds ratio 0.99, 95% confidence interval 0.88 to 1.12) or gastro-oesophageal reflux (1.04, 0.91 to 1.19) two years after treatment (table 5). Treatment had no impact on the development of heartburn (0.90, 0.78 to 1.04) or reflux (1.05, 0.90 to 1.21) in previously asymptomatic participants. In participants who had these symptoms at baseline, no significant improvement occurred in either heartburn (0.90, 0.71 to 1.14) or reflux (0.89, 0.62 to 1.29).
Table 5 Effect of Helicobacter pylori eradication treatment on prevalence of heartburn and reflux at two years. Values are numbers (percentages) unless stated otherwise
In those participants who had gastro-oesophageal reflux without heartburn before treatment (n = 248), H pylori eradication treatment had a protective effect against the development of heartburn over the two year period (0.56, 0.35 to 0.90). The number of general practice consultations for heartburn or reflux over the two years after active treatment was not significantly greater than after placebo (1.63, 0.94 to 2.87).
Discussion
The most obvious mechanism by which H pylori infection might affect reflux oesophagitis is by affecting secretion of gastric acid. H pylori infection usually causes a predominantly antral gastritis, which results in a net increase in acid secretion.16 In people with an incompetent antireflux mechanism, this would increase exposure of the lower oesophagus to acid, increasing the prevalence of heartburn.4 5 Our findings that H pylori is associated with an increased prevalence of heartburn and that H pylori eradication treatment reduces the risk of patients with acid reflux developing heartburn support this hypothesis. Acid reflux depends more on the integrity of the lower oesophageal sphincter, hence the insignificant effect of H pylori infection on reflux. Patients with severe reflux oesophagitis are less likely to have H pylori infection,17-26 possibly because corpus gastritis caused by helicobacter infection limits maximum acid output in these patients,27-32 thus protecting them against the more severe forms of reflux oesophagitis. Such people might theoretically be at risk of increased exposure of the lower oesophagus to acid after eradication of H pylori infection.29 31 However, our study suggests that no significant worsening of heartburn or reflux occurs after eradication of H pylori in patients in the community.
Our study has weaknesses. As it was community based, we had no direct information (from endoscopy, for example) as to the actual pathology underlying the symptoms of our participants. The randomised double blind design, the large numbers of participants, the high rate of H pylori eradication, the avoidance of prolonged acid suppression as part of the treatment, and the length and completeness of the two year period of follow up are compensating strengths.
What is already known on this topic
Heartburn and gastro-oesophageal reflux are common symptoms in the population
Helicobacter pylori gastritis is also very common and might influence these symptoms by altering gastric acid secretion
Previous studies have reached differing conclusions about the effect of H pylori eradication on gastro-oesophageal reflux disease
What this study adds
In a general practice population, people with Helicobacter pylori infection had a slightly higher prevalence of heartburn (but not reflux) than other people
Helicobacter pylori eradication had no net effect on symptoms of gastro-oesophageal reflux disease
We thank the participants in the Bristol helicobacter project and the general practitioners and health centre staff; the nursing team of Lynne Bradshaw, Julie Watson, Tina Critchley, Jo Lee, Carol Everson-Coombe, Penny Nettlefield, and Joanne Smith; Judy Millward, Helen Davies, Amy Hawkins, and Sarah Pike for secretarial support; and Erwin Brown, Paul Thomas, Nick Pope, and Phil Hedges of the microbiology department and Peter Spurr, Martin Bullock, and Fiona Greenwood of the pharmacy department, Frenchay Hospital, for help with the breath tests.
Contributors: RFH initiated the study, helped to plan the project, analysed the results, wrote the initial draft of the paper, and is the guarantor. JAL ran the Bristol helicobacter project from day to day and helped with analysis of the data and the final version of the paper. PN helped to set up the project. LJM, IMH, and JLD helped to plan the project, analyse the results, and produce the final version of the paper.
Funding: This study was funded jointly by the NHS South and West Regional Research and Development Directorate and GlaxoSmithKline UK. The Department of Social Medicine is the lead centre for the MRC Health Services Research Collaboration.
Competing interests: RFH and JAL were reimbursed by GlaxoSmithKline for attending the AGA symposium in 2000.
Ethical approval: The local research ethics committee approved the study.
References
Tarpila S, Kekki M, Samloff IM, Sipponen P, Siurala M. Morphology and dynamics of the gastric mucosa in duodenal ulcer patients and their first-degree relatives. Hepatogastroenterology 1983;30: 198-201.
Calam J. Clinicians' guide to Helicobacter pylori. London: Chapman & Hall Medical, 1996: 39-77.
Labenz J, Blum AL, Bayerdorffer E, Meining A, Stolte M, Borsch G. Curing Helicobacter pylori infection in patients with duodenal ulcer may provoke reflux esophagitis. Gastroenterology 1997;112: 1442-7.
Hamada H, Haruma K, Mihara M, Kamada T, Yoshihara M, Sumii K, et al. High incidence of reflux oesophagitis after eradication therapy for Helicobacter pylori: impacts of hiatal hernia and corpus gastritis. Aliment Pharmacol Ther 2000;14: 729-35.
Manes G, Mosca S, De Nucci C, Lombardi G, Lioniello M, Balzano A. High prevalence of reflux symptoms in duodenal ulcer patients who develop gastro-oesophageal reflux disease after curing Helicobacter pylori infection. Dig Liver Dis 2001;33: 665-70.
Veldhuyzen van Zanten SJ. Treatment of Helicobacter pylori infection unmasks rather than induces symptoms of gastro-oesophageal reflux disease. Dig Liver Dis 2001;33: 647-8.
Befrits R, Sjostedt S, Odman B, Sorngard H, Lindberg G. Curing Helicobacter pylori infection in patients with duodenal ulcer does not provoke gastroesophageal reflux disease. Helicobacter 2000;5: 202-5.
Moayyedi P, Bardhan C, Young L, Dixon MF, Brown L, Axon AT. Helicobacter pylori eradication does not exacerbate reflux symptoms in gastroesophageal reflux disease. Gastroenterology 2001;121: 1120-6.
Laine L, Sugg J. Effect of Helicobacter pylori eradication on development of erosive esophagitis and gastroesophageal reflux disease symptoms: a post hoc analysis of eight double blind prospective studies. Am J Gastroenterol 2002;97: 2992-7.
Schwizer W, Thumshirn M, Dent J, Guldenschuh I, Menne D, Cathomas G, et al. Helicobacter pylori and symptomatic relapse of gastro-oesophageal reflux disease: a randomised controlled trial. Lancet 2001;357: 1738-42.
Stuart RC, Craig CF, Morran C, Burns H, Harden K, Power A, et al. A beneficial effect of H. pylori eradication in reflux patients in the community. Gastroenterology 2001;120(suppl 1): A48.
Moayyedi P, Feltbower R, Brown J, Mason S, Mason J, Nathan J, et al. Effect of population screening and treatment for Helicobacter pylori on dyspepsia and quality of life in the community: a randomized controlled trial. Lancet 2000;355: 1665-9.
Wildner-Christensen M, Moller Hansen J, Schaffalitzky de Muckadell OB. Rates of dyspepsia one year after Helicobacter pylori screening and eradication in a Danish population. Gastroenterology 2003;125: 372-9.
Lane JA, Harvey RF, Murray L, Harvey IM, Nair P, Egger M, et al. A placebo-controlled randomized trial of eradication of Helicobacter pylori in the general population: study design and response rates of the Bristol helicobacter project. Control Clin Trials 2002;23: 321-32.
Dominguez-Munoz JE, Leodolter A, Sauerbruch T, Malfertheiner P. A citric acid solution is an optimal test drink in the 13C-urea breath test for Helicobacter pylori infection. Gut 1997;40: 459-62.
El Omar EM, Penman ID, Ardill JE, Chittajallu RS, Howie C, McColl KE. Helicobacter pylori infection and abnormalities of acid secretion in patients with duodenal ulcer disease. Gastroenterology 1995;109: 681-91.
Koike T, Ohara S, Sekine H, Iijima K, Kato K, Shimosegawa T, et al. Helicobacter pylori infection inhibits reflux esophagitis by inducing atrophic gastritis. Am J Gastroenterol 1999;94: 3468-72.
Haruma K, Hamada H, Mihara M, Kamada T, Yoshihara M, Sumii K, et al. Negative association between Helicobacter pylori infection and reflux esophagitis in older patients: case-control study in Japan. Helicobacter 2000;5: 24-9.
Labenz J, Jaspersen D, Kulig M, Leodolter A, Lind T, Lindner D, et al. Risk factors for the development of erosive reflux disease: a multivariate analysis based on the proGERD initiative. Gastroenterology 2002; W1163.
Shirota T, Kusano M, Kawamura O, Horikoshi T, Mori M, Sekiguchi T. Helicobacter pylori infection correlates with severity of reflux esophagitis: with manometry findings. J Gastroenterol 1999;34: 553-9.
Varanasi RV, Fantry GT, Wilson KT. Decreased prevalence of Helicobacter pylori infection in gastroesophageal reflux disease. Helicobacter 1998;3: 188-94.
Werdmuller BF, Loffeld RJ. Helicobacter pylori infection has no role in the pathogenesis of reflux esophagitis. Dig Dis Sci 1997;42: 103-5.
Weston AP, Badr AS, Topalovski M, Cherian R, Dixon A, Hassanein RS. Prospective evaluation of the prevalence of gastric Helicobacter pylori infection in patients with GERD, Barrett's esophagus, Barrett's dysplasia, and Barrett's adenocarcinoma. Am J Gastroenterol 2000;95: 387-94.
Loffeld RJ, Werdmuller BF, Kuster JG, Perez-Perez GI, Blaser MJ, Kuipers EJ. Colonization with cagA-positive Helicobacter pylori strains inversely associated with reflux esophagitis and Barrett's esophagus. Digestion 2000;62: 95-9.
Warburton-Timms VJ, Charlett A, Valori RM, Uff JS, Shepherd NA, Barr H, et al. The significance of cagA+ Helicobacter pylori in reflux oesophagitis. Gut 2001;49: 341-6.
Fallone CA, Barkun AN, Gottke MU, Best LM, Loo VG, Veldhuyzen van Zanten S, et al. Association of Helicobacter pylori genotype with gastroesophageal reflux disease and other upper gastrointestinal diseases. Am J Gastroenterol 2000;95: 659-69.
El Omar EM, Oien K, El Nujumi A, Gillen D, Wirz A, Dahill S, et al. Helicobacter pylori infection and chronic gastric acid hyposecretion. Gastroenterology 1997;113: 15-24.
El Serag HB, Sonnenberg A, Jamal MM, Inadomi JM, Crooks LA, Feddersen RM. Corpus gastritis is protective against reflux oesophagitis. Gut 1999;45: 181-5.
Wu JC, Chan FK, Wong SK, Lee YT, Leung WK, Sung JJ. Effect of Helicobacter pylori eradication on oesophageal acid exposure in patients with reflux oesophagitis. Aliment Pharmacol Ther 2002;16: 545-52.
Iijima K, Ohara S, Sekine H, Koike T, Kato K, Asaki S, et al. Changes in gastric acid secretion assayed by endoscopic gastrin test before and after Helicobacter pylori eradication. Gut 2000;46: 20-6.
Koike T, Ohara S, Sekine H, Iijima K, Kato K, Toyota T, et al. Increased gastric acid secretion after Helicobacter pylori eradication may be a factor for developing reflux oesophagitis. Aliment Pharmacol Ther 2001;15: 813-20.
Yamaji Y, Mitsushima T, Ikuma H, Okamoto M, Yoshida H, Kawabe T, et al. Inverse background of Helicobacter pylori antibody and pepsinogen in reflux oesophagitis compared with gastric cancer: analysis of 5732 Japanese subjects. Gut 2001;49: 335-40.(Richard F Harvey, consult)