Randomised controlled trial of Helicobacter pylori eradication in patients on non-steroidal anti-inflammatory drugs: HELP NSAIDs study

Hawkey, Christopher J.; Tulassay, Zsolt; Szczepański, L; Rensburg, C. J. Van; Filipowicz-Sosnowska, Anna; Lanas, Ángel; Wason, C. M.; Peacock, Robert; Gillon, K. R. W.

doi:10.1016/s0140-6736(98)04206-8

Cited by 338 publications

(194 citation statements)

References 26 publications

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“…This idea is supported by clinical results that eradication of H. pylori significantly decreases the risk of these gastric diseases (2,30,31). Infection with H. pylori damages gastric mucosa through production of ammonia and cytotoxic proteins such as vacuolating cytotoxin A (VacA) and cytotoxin-associated gene A (CagA) and induction of host inflammatory responses (32)(33)(34)(35)(36).…”

mentioning

confidence: 92%

Suppression of Expression of Endoplasmic Reticulum Chaperones by Helicobacter pylori and Its Role in Exacerbation of Non-steroidal Anti-inflammatory Drug-induced Gastric Lesions

Namba

Hoshino

Suemasu

et al. 2010

Journal of Biological Chemistry

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Both the use of non-steroidal anti-inflammatory drugs (NSAIDs), such as indomethacin, and infection with Helicobacter pylori are major causes of gastric ulcers. Although some clinical studies suggest that infection with H. pylori increases the risk of developing NSAID-induced gastric lesions, the molecular mechanism governing this effect is unknown. We recently found that in cultured gastric cells, expression of endoplasmic reticulum (ER) chaperones (such as 150-kDa oxygenregulated protein (ORP150) and glucose-regulated protein 78 (GRP78)) is induced by NSAIDs and confers protection against NSAID-induced apoptosis, which is important in the development of NSAID-induced gastric lesions. In this study we have found that co-culture of gastric cells with H. pylori suppresses the expression of ER chaperones. This suppression was regulated at the level of transcription and accompanied by a reduction in the level of activating transcription factor 6 (ATF6), one of the transcription factors for ER chaperone genes. In vivo, inoculation of mice with H. pylori suppressed the expression of ER chaperones at gastric mucosa both with and without administration of indomethacin. Inoculation with H. pylori also stimulated formation of indomethacin-induced gastric lesions and mucosal cell death. In addition, we found that heterozygous ORP150-deficient mice are sensitive to the development of indomethacin-induced gastric lesions and mucosal cell death. The results of this study suggest that H. pylori exacerbates NSAID-induced gastric lesions through suppression of expression of ER chaperones, which stimulates NSAID-induced mucosal cell death.The balance between aggressive and defensive factors determines whether gastric ulcers develop. The gastric mucosa is challenged by a variety of aggressive factors, and of these, both non-steroidal anti-inflammatory drugs (NSAIDs) 2 and Helicobacter pylori are major causes of gastric lesions. Therefore, an important question is whether infection with H. pylori increases the risk of developing NSAID-induced gastric lesions (in other words, if eradication of H. pylori would reduce the risk of developing NSAID-induced gastric lesions). Recent clinical studies suggest that infection with H. pylori increases the risk of developing NSAID-induced gastric lesions (1-4); however, some studies have shown the opposite effect (5, 6). Animal models could be useful to address this issue. For example, some reports have demonstrated that NSAID-induced gastric lesions in mongolian gerbils are exacerbated by infection with H. pylori (7-9), although the molecular mechanism governing this exacerbation is unclear.An inhibitory effect of NSAIDs on cyclooxygenase (COX) activity and the resulting decrease in the gastric level of prostaglandins (PGs), especially PGE 2 , was believed to be the only explanation for the gastric side effects of NSAIDs because PGE 2 is a strong protective factor for gastric mucosa (10). However, the increased incidence of gastrointestinal lesions and the decrease in PG levels induced by NSA...

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mentioning

confidence: 92%

Suppression of Expression of Endoplasmic Reticulum Chaperones by Helicobacter pylori and Its Role in Exacerbation of Non-steroidal Anti-inflammatory Drug-induced Gastric Lesions

Namba

Hoshino

Suemasu

et al. 2010

Journal of Biological Chemistry

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“…3 However, in chronic NSAID users with a history of peptic ulcers, the eradication of H. pylori has not been shown to reduce the occurrence of ulcer relapse. 4 Several studies have reported that the site and nature of subsequent ulcer relapse in NSAID users are determined mainly by the site and nature of the initial endoscopic lesion. This relationship is independent of H. pylori status.…”

Section: Discussionmentioning

confidence: 99%

“…With the exception of those who are about to commence NSAID therapy anew, H. pylori eradication is of no benefit to long-term NSAID users with or without a history of ulcers. 4 …”

Section: Discussionmentioning

confidence: 99%

“…In the intention-to-treat analysis, five patients (7.1%; 95% CI, 2-16) in the treatment group developed peptic ulcers (all gastric ulcers) at the end of 12 weeks, compared with six patients (8.6%; 95% CI, [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18] in the placebo group (four gastric ulcers and two duodenal ulcers) (P ¼ 1.00). The ulcer size ranged from 5 to 12 mm.…”

Section: Development Of Gastroduodenal Ulcers and Erosionsmentioning

confidence: 99%

“…3 The same benefit is not seen after 6 months in patients with a past history of peptic ulcer disease taking longterm NSAID therapy. 4 The long-term use of NSAIDs is associated with a continuous risk of the development of ulcers, with their attendant complications. It is unknown whether H. pylori or NSAIDs play a more important role in determining the development of ulcers in long-term NSAID users with no history of gastric or duodenal ulcer.…”

Section: Introductionmentioning

confidence: 99%

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Effect of treatment of Helicobacter pylori on the prevention of gastroduodenal ulcers in patients receiving long‐term NSAIDs: a double‐blind, placebo‐controlled trial

Lai¹,

Lau²,

et al. 2003

Aliment Pharmacol Ther

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SUMMARYBackground: There is controversy as to whether Helicobacter pylori and non-steroidal anti-inflammatory drugs interact to cause peptic ulcers. Aim: To study whether the eradication of H. pylori in patients on long-term non-steroidal anti-inflammatory drug therapy prevents the development of ulcers. Methods: Patients infected with H. pylori whilst receiving long-term non-steroidal anti-inflammatory drug therapy, but with no ulcers at baseline endoscopy, were randomized to receive either triple antibiotic therapy (metronidazole 300 mg, clarithromycin 250 mg and amoxicillin 500 mg, given four times daily; n ¼ 70) or placebo (n ¼ 70) for 2 weeks. Non-steroidal antiinflammatory drugs were continued throughout the study period. Endoscopy was repeated 12 weeks after

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Specific Cyclooxygenase 2 Inhibitors: A New Choice of Nonsteroidal Anti-Inflammatory Drug Therapy

Osiri

Moreland

1999

Arthritis & Rheumatism

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Randomised controlled trial of Helicobacter pylori eradication in patients on non-steroidal anti-inflammatory drugs: HELP NSAIDs study

Cited by 338 publications

References 26 publications

Suppression of Expression of Endoplasmic Reticulum Chaperones by Helicobacter pylori and Its Role in Exacerbation of Non-steroidal Anti-inflammatory Drug-induced Gastric Lesions

Suppression of Expression of Endoplasmic Reticulum Chaperones by Helicobacter pylori and Its Role in Exacerbation of Non-steroidal Anti-inflammatory Drug-induced Gastric Lesions

Effect of treatment of Helicobacter pylori on the prevention of gastroduodenal ulcers in patients receiving long‐term NSAIDs: a double‐blind, placebo‐controlled trial

Specific Cyclooxygenase 2 Inhibitors: A New Choice of Nonsteroidal Anti-Inflammatory Drug Therapy

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