Role of Helicobacter pylori eradication in aspirin or non-steroidal anti-inflammatory drug users

Helicobacter pylori(H pylori) infection and the use of non steroidal anti-inflammatory drugs (NSAIDs) including aspirin at any dosage and formulation represent well-established risk factors for the development of uncomplicated and complicated peptic ulcer disease accounting for the majority of such cases. Although the interaction between H pylori and NSAID/aspirin use in the same individuals was questioned in some epidemiological studies, it has now become widely accepted that they are at least independent risk factors for peptic ulcer disease. According to data from randomized intervention trials, naive NSAID users certainly benefit from testing for H pylori infection and, if positive, H pylori eradication therapy prior to the initiation of NSAID. A similar strategy is also suggested for naive aspirin users, although the efficacy of such an approach has not been evaluated yet. Strong data also support that chronic aspirin users with a recent ulcer complication should be tested for H pylori infection and, if positive, receive H pylori eradication therapy after ulcer healing, while they appear to benefit from additional long-term therapy with a proton pump inhibitor (PPI). A similar approach is often recommended to chronic aspirin users at a high risk of ulcer complication. H pylori eradication alone does not efficiently protect chronic NSAID users with a recent ulcer complication or those at a high-risk, who certainly should be treated with long-term PPI therapy, but H pylori eradication may be additionally offered even in this setting. In contrast, testing for H pylori or PPI therapy is not recommended for chronic NSAID/aspirin users with no ulcer complications or those at a low risk of complications.     

Relative contribution of mucosal injury and Helicobacter pylori in the development of gastroduodenal lesions in patients taking non-steroidal anti-inflammatory drugs

BACKGROUND AND AIMS: A past history of peptic ulceration increases the risk of an ulcer developing during non-steroidal anti-inflammatory drug (NSAID) use. Whether this is due to Helicobacter pylori infection or to reactivation of the original lesion is unclear. METHODS: We used multivariate regression analyses of three large similar trials to identify factors that placed patients at high risk of ulcer development or relapse. We compared the efficacy of omeprazole 20 mg daily, misoprostol 200 micro g twice daily, and ranitidine 150 mg twice daily in preventing ulcers and erosions at different sites and in patients who were H pylori positive and negative. RESULTS: Patients with endoscopic lesions (which healed) initially were significantly more likely than those without to develop further erosions or ulcers during treatment (rate ratio 2.12, 1.07-4.17). Risk mounted further with ulcers versus erosions, particularly those that had been slow to heal. There was a highly significant tendency for the relapse lesion to replicate the site and type of the original lesion (mean odds ratios ranging from 3 to 14). Treatment failure was significantly less likely with omeprazole than with placebo, misoprostol, or ranitidine. This advantage was especially evident in H pylori positive patients receiving acid suppression (5.7% v 16.6% for gastric ulcer with omeprazole). CONCLUSIONS: Relapse of lesions in patients taking NSAIDs was highly site and type specific and not adversely affected by H pylori status. This strongly implies that local mucosal factors predispose to ulcer development in patients taking NSAIDs. Identification of the responsible mucosal changes would aid understanding and could promote better treatment.     

Helicobacter pylori, non-steroidal anti-inflammatory drugs and smoking in risk pattern of gastroduodenal ulcers

BACKGROUND: Helicobacter pylori, NSAID and cigarette smoking are major risk factors for gastroduodenal ulcers. However, the results of studies on the interaction between these factors on ulcerogenesis are controversial. This study was designed to examine the association between gastroduodenal ulcers and H. pylori infection, NSAID use, smoking and age. METHODS: 5967 dyspeptic patients underwent 13C-urea breath test (UBT) and upper endoscopy, while age and dyspeptic symptoms were reported. RESULTS: Out of 5967 patients, 31.8% were ulcerated; 9.2% had gastric, 17.2% duodenal and 5.4% both gastric and duodenal ulcers. H. pylori was found in 72.5% of gastric ulcer patients, in 83.6% of duodenal ulcer patients, in 76.9% of gastroduodenal ulcer patients and in 64.8% of dyspeptic patients. The gastric, duodenal and gastroduodenal ulcers were related to H. pylori significantly and the respective ORs were: 1.44, 2.77 and 1.81. NSAID alone was used by 6.2%-12.7% of ulcer patients, tending to raise only the risk of gastric ulcer but reducing that of duodenal and gastroduodenal ulcers. The H. pylori prevalence was significantly higher in smokers (76%) than in non-smokers (67%) and the ulcer risk was also significantly higher in smokers than in non-smokers. About 20% of ulcers were 'idiopathic', i.e. without NSAID and H. pylori and the ratio of these ulcers to all ulcers significantly increased during the 5 years of the study. CONCLUSIONS: Based on multivariable logistic regression analysis we conclude that: 1) H. pylori infection, NSAID use, smoking and age play major roles in the pathogenesis of peptic ulcerations; 2) there is a negative interaction between H. pylori and NSAID on duodenal ulcers, suggesting that H. pylori reduces the development of these ulcers in NSAID users, and 3) about 20% of peptic ulcers in the Polish population are unrelated to H. pylori and NSAID use (idiopathic ulcers).     

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

The importance of erosions in longterm non-steroidal anti-inflammatory drug (NSAID) users, their relevance to ulceration and their relation to Helicobacter pylori are unclear. This study assessed the incidence of peptic ulcers in the presence or absence of erosions or H pylori in a group of longterm NSAID users (n = 50), undergoing endoscopy at 0, 4, 12, and 24 weeks while continuing with NSAIDs. Ulcers diagnosed at baseline endoscopy were excluded. Ulcers developed in nine of 23 patients (39%) with pre-existing erosions compared with six of 27 (22%) without erosions (p < 0.05). The group infected with H pylori (n = 30) had a total of 18 patients (60%) with erosions, a total of 12 ulcers (40%), and eight ulcers (27%) complicating previous erosions, compared with five (25%, p < 0.01), three (15%, p < 0.05), and one (5%, p < 0.01) respectively in patients not infected with H pylori (n = 20). Ulcer development was not influenced by the initial number of erosions but strongly associated with H pylori positive duodenal erosions. It is concluded that ulcers are more likely to develop in longterm NSAID users who have mucosal erosions or H pylori, or both.     

Helicobacter pylori management in non-steroidal anti-inflammatory drug therapy patients in primary care

Non-steroidal anti-inflammatory drugs (NSAIDs) may cause gastroduodenal ulcers and its complications. Helicobacter pylori infection is recognized as an additional risk factor for ulcer development, its eradication in NSAIDs users being recommended. In this cross-sectional study, during a 1-week period, consecutive patients who were routinely visiting in 58 primary care clinics were enrolled. A questionnaire was used to collect clinical data on the patients who were chronically taking NSAIDs. Patients with age >65?years, a personal history of peptic ulcer, concomitant therapy with steroids, anti-coagulants, multiple NSAIDs, or relevant co-morbidities were considered at high risk for NSAIDs gastroduodenal complications. Data on H. pylori infection management were collected. Overall, H. pylori was searched for in 140 (16.1%) out of 869 patients receiving chronic NSAID therapy, and it was eventually cured in 43 (72.9%) of the infected cases. In detail, H. pylori status was not investigated in 670 (77.1%) of those patients at high risk of NSAID-related gastroduodenal lesions, including 516 patients ??65?years old, and 154 younger, but with at least 1 adjunctive risk factor. In addition, 234 (35%) of these high-risk patients were not receiving any gastric mucosa protection. Our data find that H. pylori infection is investigated in fewer than one of every five NSAID-user patients in primary care. The low alertness towards such an infection in these patients suggests a need for prompt implementation of current guidelines.     

Epidemiology and treatment of gastroduodenal lesions caused by non-steroidal anti-inflammatory agents

The most common serious adverse reactions to nonsteroidal anti-inflammatory drugs (NSAIDs) are those affecting the gastro-intestinal tract. There is epidemiologic evidence that NSAIDs use is associated with the development of gastric ulcer and with upper gastrointestinal bleeding and perforation of both duodenal and gastric ulcers. The individual risk is low but given the widespread use of NSAIDs, the number of cases is large with appreciable morbidity and mortality. The main risk factors are age above 65, previous ulcer history and treatment with several NSAIDs. Prophylactic therapy is justified in high risk patients. Synthetic prostaglandin misoprostol has been shown to reduce significantly the frequency of gastric ulcer in patients on NSAIDs. By contrast, H2 receptor blockade with ranitidine has been demonstrated to prevent duodenal but not gastric ulcers. Gastric and duodenal ulcers associated with NSAIDs appear to heal on H2 receptors antagonists and prostaglandins even if NSAIDs are continued. However, large gastric ulcer may heal slowly over 8 to 12 weeks. The place of omeprazole remains to be determined.     

Long-term nonsteroidal anti-inflammatory drug use and gastroduodenal injury: the role of Helicobacter pylori.

To evaluate the association of Helicobacter pylori infection with gastroduodenal ulceration and symptoms in rheumatoid arthritis patients chronically ingesting nonsteroidal anti-inflammatory drugs (NSAIDs), a population-based study was performed. Residents of Olmsted County, Minnesota, and surrounding counties, 40 years of age and over with active rheumatoid arthritis taking therapeutic dose of NSAIDs daily for 6 months or more were evaluated (n = 50). An endoscopic score from 0 to 5 was assigned and independently confirmed. Biopsies were obtained from the antrum and gastric body for the presence of H. pylori. A symptom score based on the frequency and severity of dyspeptic symptoms was calculated. Substantial mucosal injury (greater than or equal to grade 2) was observed at endoscopy in 33 patients (66%); 14 (28%) had chronic ulcers. Eleven of the community patients with rheumatoid arthritis (22%) were H. pylori positive; adjusting for age, the prevalence of H. pylori was not significantly different to that in 67 health controls (25%). One or more upper gastrointestinal symptoms were reported by 19 of the community patients (38%). Adjusting for age, community rheumatoid arthritis patients with H. pylori were not more likely to have visible mucosal damage or dyspepsia, but were significantly more likely to have histological gastritis (P less than 0.01). The results suggest that, in primarily asymptomatic persons from the community with rheumatoid arthritis taking daily NSAIDs for 6 months or more, H. pylori infection is not related to the severity of visible mucosal injury.     

Helicobacter pylori: a risk and severity factor of non-steroidal anti-inflammatory drug induced gastropathy.

This prospective study aimed to determine the prevalence of Helicobacter pylori infection in relation to the occurrence and severity of NSAIDs induced gastropathy. A total of 111 patients were studied-66 were taking NSAIDs and 45 were control patients. All patients underwent endoscopy during which antral biopsy specimens were taken to determine H pylori status (Gram and Giemsa staining, urease test, and cultures). The NSAID group comprised: group I, patients without mucosal damage (n = 28); group II, patients with gastropathy (n = 26); and group III, patients with bleeding associated with NSAID induced gastropathy (n = 12). Control patients had neither dyspeptic symptoms nor endoscopic lesions. There were no differences in age, sex ratio, or presence of H pylori (26% v 24%) between the NSAID and the control groups. Among patients taking NSAIDs, H pylori infection was more frequently (p < 0.02) diagnosed in those who presented with gastropathy (groups II and III: 37%) than in those without lesions (group I: 11%). The frequency of H pylori infection increased significantly with the severity of gastropathy (group I = 11%; group II = 31%; group III = 50%; p < 0.03). H pylori infection was associated with chronic active gastritis (group I = 21%; group II = 35%; group III = 67%; p < 0.05). These data suggest that H pylori may be a risk factor of NSAID induced gastropathy.     

非甾体抗炎药应用及幽门螺杆菌感染对消化性溃疡出血的影响

消化性溃疡(peptic ulcer)是消化系统常见的疾病之一,其病因多种多样.消化性溃疡的主要并发症是合并出血.近年来,幽门螺杆菌(Helicobacter pylori, H.pylori)感染和非甾体抗炎药(non-steroidal anti-inflammatory drugs, NSAIDs)应用对溃疡出血的影响日益受到重视.本文总结了这两方面因素与溃疡出血的关系,提出了相应的治疗策略.     

Interaction between Helicobacter pylori and non-steroidal anti-inflammatory drugs in peptic ulcer bleeding

BACKGROUND: Helicobacter pylori and non-steroidal anti-inflammatory drugs (NSAIDs) are the two primary causes of peptic ulcer disease. How H. pylori and NSAIDs interact and influence the development of ulcer bleeding is still not clear. METHODS: A hospital-based, age- and sex-matched case-control study was conducted. Multivariate and stratified analyses were performed for further evaluation of the interaction between H. pylori and NSAIDs. RESULTS: Ninety-seven patients (52 gastric ulcers, 45 duodenal ulcers) and 97 non-ulcer controls were enrolled in the study. H. pylori and NSAIDs were both found to be independent risk factors for ulcer bleeding (H. pylori odds ratio, 2.22; 95% confidence interval (CI), 1.23-4.01; NSAIDs odds ratio, 4.57; 95% CI, 2.50-8.35). There was no synergistic effect. In contrast, a negative interaction was observed in the logistic regression and stratified analysis, although the difference was not significant (H. pylori adjusted odds ratio, 3.47; 95% CI, 1.73-6.95; NSAID adjusted odds ratio, 6.16; 95% CI, 3.14-12.09). CONCLUSION: H. pylori increases the risk of peptic ulcer bleeding but may play a protective role in NSAID users.     

Helicobacter pylori negative gastroduodenal lesions in subjects treated with NSAID

The authors examined retrospectively the frequency of NSAID use by patients with gastroduodenal ulcer without HP. The objective was to evaluate whether the use of NSAID is the predominating factor in the development of ulceration in subjects with HP negative ulceration. The group comprised 525 patients with confirmed presence of H, incl. 52 who used NSAID. From the results ensues that the incidence of ulcerous lesions with HP negativity and NSAID medication is significantly higher than in subjects who use NSAID and suffer from a confirmed HP infection.     

Interobserver variation in assessment of gastroduodenal lesions associated with non-steroidal anti-inflammatory drugs.

Video endoscopic images were used to investigate whether gastroenterologists could agree on the definition of lesions within the stomach seen at endoscopy, with particular reference to those seen in patients taking non-steroidal anti-inflammatory drugs. Seven experienced endoscopists, unaware of the patients'' clinical history or drug consumption, recorded their classification for 93 randomised video images of gastric lesions. There was complete agreement in the diagnosis of ulceration for nine images from patients who were not taking non-steroidal anti-inflammatory drugs; eight of nine were classified as deep ulcers, with 86% agreement for this subclassification. By contrast, the overall agreement for lesions in patients taking non-steroidal anti-inflammatory drugs was only 55%. Only nine of 44 ulcers were subclassified as deep, and there was considerable cross classification of non-haemorrhagic erosions and ulcers. In conclusion, ulcers that occur in patients taking non-steroidal anti-inflammatory drugs differ from those in patients who are not taking these drugs in that they are often more superficial and difficult to distinguish from erosions. The prognostic importance of these lesions is, therefore, uncertain.     

Clinical significance of cytotoxin-associated gene A status of Helicobacter pylori among non-steroidal anti-inflammatory drug users with peptic ulcer bleeding: a multicenter case-control study

Background: The role of Helicobacter pylori infection and especially of the cytotoxin-associated gene A (CagA) product strain in peptic ulcer bleeding among non-steroidal anti-inflammatory drugs (NSAIDs) users remains controversial. Methods: A case-control study was carried out including 191 consecutive chronic NSAIDs users admitted to hospital because of peptic ulcer bleeding. Peptic ulcer was verified by endoscopy. Controls comprised 196 chronic NSAIDs users without signs of bleeding of similar age and gender to cases. Multivariate regression analysis was performed for further evaluation of the relationship between H. pylori, CagA status and other risk factors. Results:H. pylori infection was present in 121 (63.4%) cases compared with 119 (60.7%) controls (odds ratio (OR)?=?1.14, 95% CI, 0.76-1.72). CagA-positive strains were found to be significantly more frequent in cases than in controls (65/106 versus 41/99 P?=?0.008). Current smoking (OR?=?2.65; 95% CI, 1.14-6.15; P?=?0.02), CagA status (OR?=?2.28; 95% CI, 1.24-4.19; P?=?0.008), dyspepsia (OR?=?6.89; 95% CI, 1.84-25.76; P?=?0.004) and past history of peptic ulcer disease (OR?=?3.15; 95% CI, 1.43-6.92; P?=?0.004) were associated significantly with increased risk of bleeding peptic ulcer. Conclusions: The results suggest that CagA-positive H. pylori infection is associated with a more than 2-fold increased risk of bleeding peptic ulcer among chronic NSAIDs users.     

幽门螺杆菌和非甾体抗炎药对胃上皮细胞增殖的影响

目的　从体外研究的角度探讨幽门螺杆菌 (Hp)和非甾体抗炎药 (NSAID)对胃上皮细胞增殖的影响及其相互作用。方法　胃癌细胞株AGS与Hp和 (或 )吲哚美辛、阿司匹林体外共培养 ,通过MTT比色法和WesternBlot法检测增殖细胞核抗原 (PCNA) ,观察Hp和NSAID对胃上皮细胞增殖的影响。结果　MTT比色法显示CagA阳性的标准Hp菌株NCTC116 37能明显促进胃上皮细胞增殖 ,吸光度 (A)值明显升高 (P <0 .0 5 ) ,而CagA阴性的标准Hp菌株NCTC12 90 8则未发现有促增殖作用 ,且Hp对上皮细胞生长的效应取决于Hp作用的密度 ,在低密度 (3.2× 10 4～ 4 .0× 10 6CFU/ml)时NCTC116 37促进胃上皮细胞生长 ,在高密度 (>2× 10 7CFU/ml)时则抑制其生长 (P <0 .0 5 )。吲哚美辛和阿司匹林均能抑制胃上皮细胞生长 (P <0 .0 5 ) ,并呈浓度依赖性。当Hp和NSAID共同作用于AGS细胞时 ,Hp的促生长作用被逆转 ,呈现出抑制细胞生长的效应 ,A值明显降低 (P <0 .0 5 )。PCNA的WesternBlot检测结果发现 ,Hp菌株NCTC116 37可明显促进细胞PCNA的表达 ,而吲哚美辛和阿司匹林则抑制其表达 ,当两者共同作用于AGS细胞时 ,PCNA的表达明显减弱。结论　Hp对胃上皮细胞的增殖效应与Hp的密度及菌株差异有关 ,CagA阳性的Hp易促进胃上皮细胞生长 ,NSAID可抑制其     

Clinical significance of cytotoxin-associated gene A status of Helicobacter pylori among non-steroidal anti-inflammatory drug users with peptic ulcer bleeding: a multicenter case-control study

BACKGROUND: The role of Helicobacter pylori infection and especially of the cytotoxin-associated gene A (CagA) product strain in peptic ulcer bleeding among non-steroidal anti-inflammatory drugs (NSAIDs) users remains controversial. METHODS: A case-control study was carried out including 191 consecutive chronic NSAIDs users admitted to hospital because of peptic ulcer bleeding. Peptic ulcer was verified by endoscopy. Controls comprised 196 chronic NSAIDs users without signs of bleeding of similar age and gender to cases. Multivariate regression analysis was performed for further evaluation of the relationship between H. pylori, CagA status and other risk factors. RESULTS: H. pylori infection was present in 121 (63.4%) cases compared with 119 (60.7%) controls (odds ratio (OR) = 1.14, 95% CI, 0.76-1.72). CagA-positive strains were found to be significantly more frequent in cases than in controls (65/106 versus 41/99 P = 0.008). Current smoking (OR = 2.65; 95% CI, 1.14-6.15; P= 0.02), CagA status (OR = 2.28; 95% CI, 1.24-4.19; P = 0.008), dyspepsia (OR = 6.89; 95% CI, 1.84-25.76; P = 0.004) and past history of peptic ulcer disease (OR=3.15; 95% CI, 1.43-6.92; P=0.004) were associated significantly with increased risk of bleeding peptic ulcer. CONCLUSIONS: The results suggest that CagA-positive H. pylori infection is associated with a more than 2-fold increased risk of bleeding peptic ulcer among chronic NSAIDs users.     

How does Helicobacter pylori infection interact with non-steroidal anti-inflammatory drugs?

There have been conflicting clinical data on whether Helicobacter pylori (H. pylori) contributes to the pathogenesis of ulcers induced by non-steroidal anti-inflammatory drugs (NSAIDs). The discrepant findings reflect the complex interaction between H. pylori and NSAIDs, which has generated divergent results under different clinical conditions. This chapter reviews the pathogenetic mechanisms in ulcer formation that are common to H. pylori and NSAIDs, and explains how a better understanding of these factors might resolve some of the controversies. Existing evidence indicates that the interaction between H. pylori and NSAIDs is not an 'all-or-none' relationship. Factors such as previous exposure to NSAIDs, a past history of ulcer complication, gastric acid output, neutrophil infiltration, concurrent acid suppressive therapy and the type of NSAID used (aspirin versus non-aspirin NSAIDs) would influence the role of H. pylori as a risk factor in NSAID users. Recommendations on H. pylori eradication for different subgroups of NSAID users are proposed.     

幽门螺杆菌感染、服用非甾体抗炎药与消化性溃疡的关系

目的 研究消化性溃疡患者由于幽门螺杆菌（H.pylori）感染或服用非甾体抗炎药（NSAIDs）的发生率.方法 选取湖北省武汉市武昌医院2010年3月-2012年7月诊治的152例消化性溃疡患者,将其作为治疗组,同时选取同一时间段到消化科就诊的234例非消化性溃疡患者,将其作为对照组.结果 胃溃疡组感染H.pylori的几率是对照组的2.308倍,十二指肠溃疡组是对照组的8.186倍;胃溃疡组服用NSAIDs的几率是对照组的6.072倍,十二指肠溃疡组是对照组的2.823倍;胃溃疡组同时感染H.pylori和服用NSAIDs的几率是对照组的14.972倍,十二指肠溃疡组是对照组的28.873倍.结论 H.pylori感染同时服用了NSAIDs患者增加消化性溃疡的发生危险性,两种因素同时存在可以起协同作用,增加消化性溃疡的发生几率.     

Helicobacter pylori infection and gastroduodenal lesions in patients with systemic lupus erythematosus

Clinical Rheumatology - The aim of this study was to determine the frequency of Helicobacter pylori in SLE patients and to compare clinical characteristics and gastroduodenal lesions in patients...