Does Helicobacter pylori Status Affect Nonsteroidal Anti-inflammatory Drug–Associated Gastroduodenal Pathology?

doi:10.1016/S0002-9343(97)00209-X

The American Journal of Medicine

Volume 104, Issue 3, Supplement 1, 30 March 1998, Pages 35S-40S

https://doi.org/10.1016/S0002-9343(97)00209-X Get rights and content

Abstract

There are two lines of thought regarding the interrelationship between the damaging effects of Helicobacter pylori and those of nonsteroidal anti-inflammatory drugs (NSAIDs) on the gastroduodenal mucosa. First, both pathogenic factors exert a damaging effect on the mucosa, and therefore an additive, or even synergistic, effect occurs, leading to aggravation of mucosal damage. Second, mutual antagonism exists, leading to one of the pathogenic factors actually deriving some protection from the damaging potential of the other. Microscopically, H. pylori– and NSAID-associated gastritis are recognized as two separate entities. Furthermore, pathologically, the mechanisms of mucosal damage of the two factors have important differences; for example, H. pylori increases the synthesis of prostaglandins, whereas NSAIDs inhibit prostaglandin synthesis. The role of H. pylori infection in patients with NSAID-associated peptic ulcers has been addressed recently in two large, randomized, multicenter trials. From these studies, it appears that antisecretory drugs are more effective in H. pylori–positive peptic ulcer patients taking NSAIDs than in H. pylori–negative patients taking these drugs. The studies, however, do not provide any evidence that H. pylori infection reduces the pathogenic effects of NSAIDs. Other studies, however, have shown protection against NSAID-associated gastroduodenal damage in H. pylori–negative patients. Thus, there are no firm conclusions on the role of H. pylori infection in patients with NSAID-associated peptic ulcers. Based on the available data, however, practical considerations and guidelines are listed.

Section snippets

Epidemiologic Aspects

Epidemiologic data are lacking on a large scale; however, several reports are available on the prevalence of H. pylori infection in NSAID users.1, 2, 3, 4, 5, 6 In some early studies, the prevalence of H. pylori infection was found to be lower in NSAID users when compared with nonusers (e.g., 31% versus 59%, respectively[1]). Damage of the ecological niche by NSAIDs and a consequent reduction in both H. pylori colonization and persistence were suggested to be responsible for this finding.

Microscopic Features of Mucosal Damage

The Sydney System for the classification of gastritis, in addition to grading the severity of mucosal abnormalities, introduced the concept of morphologically derived information on the different etiologies of mucosal damage.[10]H. pylori–induced chronic gastritis and NSAID-associated chemical gastritis are recognized as two separate entities using this classification. Fig. 1 summarizes the major common characteristics as well as the essential features discriminating the two forms of chronic

Pathologic Mechanisms of Mucosal Damage

H. pylori and NSAIDs exert their damaging effects on the gastric mucosa via independent mechanisms. The major question is whether these effects are additive or synergistic, leading to an increased risk of peptic ulceration.

H. pylori infection results in mucosal inflammation immediately following colonization of the gastric mucosa. Bacterial antigens, such as the cytotoxin-associated gene A protein, the vacuolating cytotoxin, lipopolysaccharide (endotoxin), heat shock protein, and a battery of

Impact of NSAIDs on the Healing of Peptic Ulcers in H. pylori–Positive Patients Receiving Eradication Therapy

The majority of peptic ulcers are undoubtedly caused by H. pylori infection. It has been shown that antibiotics alone can heal duodenal ulcers[19]; however, the addition of inhibitors of gastric acid secretion to antibiotics accelerates ulcer healing.[20] Indeed, 1-week H. pylori–eradication therapy is sufficient to heal almost all duodenal and gastric ulcers associated with H. pylori infection.21, 22, 23 The majority of these studies, though, excluded patients with an ongoing need to take

Practical Considerations and Guidelines

H. pylori does not necessarily require the presence of NSAIDs for the induction of peptic ulcers, and vice versa. Currently, it remains controversial whether H. pylori is a relevant factor in the pathogenesis of NSAID-associated peptic ulcers, whether H. pylori and NSAIDs interact with respect to microscopic and macroscopic damage of the gastroduodenal mucosa, or, although less likely, whether H. pylori protects, to a certain degree, against NSAID-associated toxicity of the gastrointestinal

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Cited by (21)

Nonsteroidal Anti-Inflammatory Drugs: Adverse Effects and Their Prevention
2010, Seminars in Arthritis and Rheumatism
Citation Excerpt :
Furthermore, the risk of uncomplicated ulcers was almost twice as high among H. pylori-positive compared with H. pylori-negative NSAID users (odds ratio, 1.81), and 17.5 times higher among H. pylori-positive NSAID users compared with H. pylori-negative nonusers. Possible explanations for the increased risk of ulcers in H. pylori-positive NSAID users are deterioration of the mucosal barrier caused by inflammation, increased acid secretion, a higher level of apoptosis in the infected mucosa, and decreased gastric adaptation to NSAIDs (45). Whether eradication of H. pylori before, or during, NSAID treatment can reduce the risk of gastroduodenal ulcers has yet to be determined.
To discuss nonsteroidal anti-inflammatory drugs (NSAIDs), their history, development, mode of action, toxicities, strategies for the prevention of toxicity, and future developments.
Medline search for articles published up to 2007, using the keywords acetylsalicylic acid, aspirin, NSAIDs, cyclooxygenase 2, adverse effects, ulcer, and cardiovascular.
NSAIDs are 1 of the oldest, most successful drugs known to modern medicine. They are effective for alleviating pain, fever, and inflammation by inhibiting prostaglandin synthesis. Aspirin, by its irreversible inhibition of blood platelet function, is also effective in the prevention of cardiovascular disease. NSAIDs may cause gastrointestinal ulcers, serious cardiovascular events, hypertension, acute renal failure, and worsening of preexisting heart failure. These adverse effects may be prevented by limiting NSAID dosage and duration and by performing individual risk assessments and treating patients accordingly. Those at risk for gastroduodenal ulcers may be treated with concomitant proton-pump inhibitors, misoprostol and/or COX-2 selective NSAIDs. Those at risk for cardiovascular events may be treated with naproxen and a proton-pump inhibitor or misoprostol, but should best avoid NSAID use altogether.
Physicians should always prescribe the lowest effective dose for the shortest possible time and must take into account both the gastrointestinal and the cardiovascular risks of individual patients when prescribing NSAIDs.
Helicobacter pylori infection and the use of NSAIDs
2001, Best Practice and Research: Clinical Gastroenterology
Helicobacter pylori infection and the use of non-steroidal anti-inflammatory drugs (NSAIDs) can each result in gastroduodenal ulcers and ulcer complications. Recent studies have suggested that there is an interaction between the two causes such that elimination of H. pylori before NSAID treatment decreases the occurrence of ulcers. This led to the conclusion of the Maastricht 2000 meeting that H. pylori eradication should be considered before embarking on long-term NSAID therapy. One of the main sources of confusion is related to the fact that prospective endoscopic studies testing various drugs for prevention of NSAID ulcers among chronic NSAID users are probably not directly applicable to problems of clinical ulcers and of ulcer complications. It has become clear that, to be interpretable clinically, such studies must provide separate analyses based on H. pylori status, history of ulcer, or an ulcer complication. Overall, the data strongly support the notion that eradication therapy is beneficial for primary prophylaxis. In contrast, one would expect little benefit when NSAIDs caused the clinical ulcer (secondary prevention) and, at best, H. pylori eradication has a modest effect on the prevention of recurrent ulcer bleeding in NSAID users who have suffered ulcer complications. The data support the notion that H. pylori eradication therapy should be given to all H. pylori -infected patients with peptic ulcers irrespective of whether or not they have used NSAIDs. Proton pump inhibitors are superior to placebo for the prevention of ulcer recurrence but are inferior to full-dose misoprostol for the prevention of ulcers among those with NSAID ulcers and no H. pylori infection. Selective COX-2 inhibitors appear to reduce markedly, but not eliminate, ulcer complications among chronic NSAID users.
Genotypes of Helicobacter pylori obtained from gastric ulcer patients taking or not taking NSAIDs
1999, American Journal of Gastroenterology
OBJECTIVE:
Whether Helicobacter pylori infection and use of nonsteroidal antiinflammatory drugs (NSAIDs) are independent risk factors for ulcerogenesis remains unclear. We undertook this study to evaluate H. pylori isolates from gastric ulcer patients to determine whether the genotype of the infecting isolate could be correlated with the use or nonuse of NSAIDs.
METHODS:
Fifty-two patients presenting with gastric ulcer and infected with H. pylori were included; 26 patients were taking NSAIDs or aspirin (ASA) regularly at the time of ulcer diagnosis. Polymerase chain reaction (PCR) was employed to assess the presence and mosaicism of the following H. pylori genes: cagA, vacA, iceA, and picB.
RESULTS:
We found no statistical differences in the presence of these genes in H. pylori isolates from gastric ulcer patients taking or not taking prescription NSAIDs or ASA. A 297-bp fragment of the cagA gene was detected in 96% of the isolates from the NSAID and ASA users and 100% from the non-NSAID users (p = 1.0). A larger and more variable region of the cagA gene was detected more frequently among the isolates from non-NSAID users than those from NSAID users (p = 0.05). Ninety-two percent of the isolates were identified as vacA genotype s1. The dominant vacA subtype was s1b, 76.9% and 65.4% in isolates from non-NSAID–taking or NSAID–taking patients, respectively (p = 0.4). iceA1 genotype was not correlated with gastric ulcer as this allele was only detected in 17.3% of all isolates.
CONCLUSIONS:
No significant differences in the presence of the candidate virulence genes vacA, cagA, picB, or iceA were detected in isolates from gastric ulcer patients taking prescription NSAIDs or ASA, compared with those not taking these drugs, indicating that single gene presence does not allow discrimination of isolates that may be important in NSAID-induced ulcerogenesis. A variable region of the cagA gene was more frequently detected in isolates from patients not taking NSAIDs or ASA, suggesting that this gene may be modified by NSAID- or ASA-related factors or that certain strains may be selected for in patients taking these medications.
Comparison of the upper gastrointestinal safety of Arthrotec® 75 and nabumetone in osteoarthritis patients at high risk for developing nonsteroidal anti-inflammatory drug-induced gastrointestinal ulcers
1999, Clinical Therapeutics
A 6-week, multicenter, double-masked, placebo-controlled, paralle1-group study compared the upper gastrointestinal (UGI) safety of Arthrotec^® 75 (diclofenac sodium 75 mg-misoprostol 200 μg; G.D. Searle & Co., Skokie, Illinois) administered twice daily with that of nabumetone 1500 mg administered once daily in 1203 patients with symptomatic osteoarthritis (OA) of the hip or knee. All patients had a documented clinical history of endoscopically confirmed gastric, pyloric-channel, or duodenal ulcer or ≥10 erosions in the stomach or duodenum. UGI endoscopy was performed at baseline and again at week 6 or early withdrawal. Treatment with Arthrotec 75 resulted in a significantly lower combined incidence of endoscopically confirmed gastric and duodenal ulcers compared with nabumetone (4% vs 11 %), and its rate of endoscopically confirmed ulceration was equivalent to that of placebo. The incidence of gastric ulcers alone was also significantly lower with Arthrotec 75 than with nabumetone (1% vs 9%). The incidence of duodenal ulcer with Arthrotec 75 was not significantly different from that with nabumetone (4% vs 3%). Types of adverse events were similar for all treatment groups, with GI adverse events predominating. Arthrotec 75 was well tolerated by the majority of patients. The results of this study demonstrate that Arthrotec 75 has a superior UGI safety profile, causing significantly fewer UGI ulcers, in comparison with nabumetone in patients with symptomatic OA and a documented history of ulcers or ≥10 erosions.
Healing of nonsteroidal anti-inflammatory drug-associated ulcers and erosions, and relief of dyspeptic symptoms: A commentary on the new data
1998, American Journal of Medicine
Protective effect of H pylori infection in non-steroidal anti-inflammatory drug users
2005, Iranian Journal of Medical Sciences

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ArticlesDoes Helicobacter pylori Status Affect Nonsteroidal Anti-inflammatory Drug–Associated Gastroduodenal Pathology?

Abstract

Section snippets

Epidemiologic Aspects

Microscopic Features of Mucosal Damage

Pathologic Mechanisms of Mucosal Damage

Impact of NSAIDs on the Healing of Peptic Ulcers in H. pylori–Positive Patients Receiving Eradication Therapy

Practical Considerations and Guidelines

Am J Med

Lancet

Gastroenterology

Gastroenterology

Gastroenterology

Campylobacter-like organisms, non-steroidal anti-inflammatory drugs and gastric lesions in patients with rheumatoid arthritis

Digestion

The presence of Campylobacter pylori in non-steroidal anti-inflammatory drug associated gastritis

J Rheumatol

Serological evidence of infection with Helicobacter pylori may predict gastrointestinal intolerance to non-steroidal antiinflammatory drug (NSAID) treatment in rheumatoid arthritis

Br J Rheumatol

Do non-steroidal anti-inflammatory drugs or smoking predispose to Helicobacter pylori infection?

Postgrad Med J

NSAID-associated gastritis and Helicobacter pylori

J Rheumatol

Duodenal histology, ulceration, and Helicobacter pylori in the presence or absence of non-steroidal anti-inflammatory drugs

Gut

Helicobacter pyloria risk factor of non-steroidal anti-inflammatory drug induced gastropathy

Gut

Nonsteroidal antiinflammatory drugs and dyspepsia in the elderly

Dig Dis Sci

The Sydney Systemhistological division

J Gastroenterol Hepatol

Classification and grading of gastritis. The updated Sydney System

J Am Surg Pathol

Histological findings in gastric mucosa in patients treated with non-steroidal anti-inflammatory drugs

J Clin Pathol

Mechanisms of gastrointestinal toxicity of non-steroidal anti-inflammatory drugs

Scand J Gastroenterol

Gastric ulceration induced by non-steroidal anti-inflammatory drugs in a neutrophil dependent process

Am J Physiol

Interaction of NSAIDs and Helicobacter pylori on gastrointestinal injury and prostaglandins productiona controlled double-blind trial

Aliment Pharmacol Ther

Severe gastric mucosal damage induced by NSAIDs in healthy subjects is associated with Helicobacter pylori infection and high levels of serum pepsinogens

Dig Dis Sci

Interrelationships between Helicobacter pylori infection nonsteroidal antiinflammatory drugs and gastroduodenal diseasea prospective study in healthy volunteers

Dig Dis Sci

Mucosal erosions in longterm non-steroidal anti-inflammatory drug users; predisposition and relation to Helicobacter pylori

Gut

Does treatment of Helicobacter pylori (Hp) with antibiotics alone heal duodenal ulcer (DU)?

Gastroenterology

Antibiotics accelerate healing of duodenal ulcer (DU) when combined with proton pump inhibitors (PPI) or H2-receptor antagonists (H2-RA)

Gastroenterology

One-week low-dose triple therapy for Helicobacter pylori is sufficient for relief from symptoms and healing of duodenal ulcers

Aliment Pharmacol Ther

Antibacterial treatment of gastric ulcers associated with Helicobacter pylori

N Engl J Med

Articles
Does Helicobacter pylori Status Affect Nonsteroidal Anti-inflammatory Drug–Associated Gastroduodenal Pathology?

Antibiotics accelerate healing of duodenal ulcer (DU) when combined with proton pump inhibitors (PPI) or H₂-receptor antagonists (H₂-RA)