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.     

非幽门螺杆菌非NSAID药物相关性溃疡

幽门螺旋杆菌(H pylori)和非甾体类抗炎药(NSAIDs)已被公认为消化性溃疡的两个最主要的病因.近年来,越来越多的临床证据表明,非H pylori和非NSAID溃疡的发生比例正在逐渐增加.这可能与H pylori感染率的降低以及临床规范的根除H pylori治疗有关,同时也与使用NSAIDs时注意防范其对胃肠道的损害有关.非H pylori和非NSAIDs溃疡病与胃酸分泌变化、胃排空异常、胃黏膜防御机制下降、应激、吸烟、遗传以及其他慢性疾病有关.在治疗上抑制胃酸,保护胃黏膜仍然是主要的手段.对这类溃疡病治疗上应更积极.     

Helicobacter pylori and bleeding duodenal ulcer: prevalence of the infection and role of non-steroidal anti-inflammatory drugs.

BACKGROUND: Several authors have reported low prevalence of Helicobacter pylori infection in patients with upper gastrointestinal bleeding (UGIB). Our aim was to study the prevalence of H. pylori in bleeding duodenal ulcer (DU), with both invasive and non-invasive methods, and to assess the role of non-steroidal anti-inflammatory drugs (NSAIDs). METHODS: Ninety-two patients with bleeding DU were prospectively studied. The use of NSAIDs was evaluated by specific questionnaire. As a control group, 428 patients undergoing outpatient evaluation for the investigation of dyspepsia and found to have a DU at endoscopy were included. At endoscopy, two antral biopsies were obtained (H&E stain). A 13C-urea breath test was carried out in all patients. Breath test was repeated in patients treated with omeprazole during the hospitalization if H. pylori was not detected with the first test. RESULTS: Gastric biopsies could be obtained in 39 patients with UGIB. Three patients with UGIB treated with omeprazole and being H. pylori-negative with the first breath test were finally considered infected with the second test. Overall, 92.4% (95% CI, 85%-96%) of the patients with UGIB were infected (89.7% with histology and 92.4% with breath test (P = 0.15)). Concordance kappa value for both diagnostic tests was 0.64. NSAID intake was more frequent in patients with UGIB (34%) than in those without UGIB (5.6%) (P < 0.001), while H. pylori infection was less frequent in patients with UGIB (92.4% (85%-96%)) than in those without UGIB (99.1% (98%-100%); P < 0.001). Even in patients with UGIB, NSAID intake was the only risk factor in 5% of cases. The proportion of cases without H. pylori infection and without NSAID intake was very low in both bleeding and non-bleeding ulcers (2% and 0.5%, respectively; P = 0.146). H. pylori prevalence in bleeding ulcers was of 84% (67%-93%) in patients with NSAID intake, and 96.7% (89%-99%) when patients taking NSAIDs were excluded. In the multivariate analysis, NSAID intake (odds ratio, 9.8 (5.2-18.4)) correlated with UGIB; however, neither H. pylori status nor the interaction between H. pylori infection and NSAID intake correlated with UGIB. In the multivariate analysis in the subgroup of patients with UGIB, NSAID use was the only variable which correlated with H. pylori prevalence (odds ratio, 0.18 (0.03-0.97)). CONCLUSIONS: The most important factor associated with H. pylori-negative bleeding DU is NSAID use, and if this factor is excluded prevalence of infection is almost 100% (97%), similar to that found in patients with non-bleeding DU (and without NSAID intake). Bleeding DU patients with neither H. pylori infection nor NSAID use are extremely rare (only 2%), which suggests that the pathogenesis of bleeding DU is similar to that of non-complicated DU disease.     

消化性溃疡与ABO血型、Lewis表型分布及幽门螺杆菌感染的相关性研究

目的探讨消化性溃疡（PU）与ABO血型、Lewis表型的分布及幽门螺杆菌（H．pylori）感染的关系。方法70例消化性溃疡患者为研究组,96例健康志愿者为对照组,比较ABO血型、Lewis表型分布和H．pylori感染的差异。结果PU组O型血者占52．9％,明显高于O型血在正常人群中的分布（31．3％,P〈0．05）;在非O型血患者中Lewis表型为Le（a＋b＋）者占51．5％,明显高于Le（a＋b＋）表型在对照组非O型血中的频率（9．1％,P〈0．001）。PU组不同ABO血型者H．pylori感染率比较无统计学差异（P〉0．05）;PU组Le（a-b＋）表型者H．pylori感染率为67．6％,明显高于其他Lewis表型（P〈0．05）。结论ABO血型中O型血者易患消化性溃疡,且非O型血Lewis表型为Le（a＋b＋）者也是消化性溃疡的高危人群。ABO血型间H．pylofi感染比较无显著性差异,Le（a-b＋）表型可能是H．pylori感染的一个危险因素。     

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.     

Risk of ulcer bleeding in patients infected with Helicobacter pylori taking non-steroidal anti-inflammatory drugs

OBJECTIVE: To determine whether Helicobacter pylori is an independent risk factor for bleeding peptic ulcer in users of non-steroidal anti-inflammatory drugs (NSAIDs), including aspirin. DESIGN: A prospective matched case-control study. SETTING: Odense University Hospital, Denmark. SUBJECTS: 132 patients with a bleeding peptic ulcer (n=124) or haemorrhagic gastritis (n=8) at endoscopy who had taken an NSAID in the previous week and 136 controls who had taken NSAIDs without gastrointestinal complications. The controls were recruited from rheumatology and geriatric outpatient clinics. MEASUREMENTS: H pylori status assessed by serology and 13C-urea breath test and regarded as positive if either test was positive. Data on potential confounding factors including smoking and alcohol were collected by interview. MAIN RESULT: H pylori was present in 57% of cases and 43% of controls. The adjusted odds ratio of bleeding from a peptic ulcer owing to H pylori infection in NSAID users was 1.81 (95% CI 1.02 to 3.21) and was similar in aspirin and non-aspirin NSAID users. Peptic ulcer bleeding was also statistically significantly associated with a history of previous ulcer bleeding, dyspepsia within the previous 3 months, drinking alcohol but not with smoking. About 16% of bleeding peptic ulcers in NSAID users could be attributed to H pylori infection. CONCLUSION: NSAID users infected with H pylori have an almost doubled risk of bleeding peptic ulcer compared with uninfected NSAID users.     

Peptic ulcer bleeding: accessory risk factors and interactions with non-steroidal anti-inflammatory drugs

AIMS: To determine risk factors for peptic ulcer bleeding other than non-steroidal anti-inflammatory drugs (NSAIDs). Methods-Data on possible antecedent risk factors obtained in a large case control study of 1121 patients admitted to hospitals in Glasgow, Newcastle, Nottingham, Oxford, and Portsmouth with bleeding peptic ulcers were compared with the same information obtained in 989 population controls. Data were analysed by logistic regression with the calculation of odds ratios (OR) and 95% confidence intervals (CI). RESULTS: From a logistic regression model, oral anticoagulants (OR 7. 8; 95% CI 2.8-21.5), previous peptic ulcer (3.8; 2.6-4.9), treatment for heart failure (5.9; 2.3-13.1), oral corticosteroid use (2.7; 1. 3-4.5), treatment for diabetes (3.1; 1.2-4.3), and current smoking (1.6; 1.2-2.0) were all independent risk factors. No association was found with use of calcium channel antagonists. Odds ratios for concomitant NSAID usage were multiplicative with the exception of current smoking. CONCLUSIONS: Some 45% of admissions for peptic ulcer bleeding in England and Wales in those aged 60 or more are calculated to be attributable to, or associated with, these accessory risk factors, which, together with those associated with aspirin or other NSAID use will account for over 80% of predisposing factors to ulcer bleeding.     

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.     

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.     

Helicobacter pylori infection in bleeding peptic ulcer patients after non-steroidal antiinflammatory drug consumption

AIM:To establish the prevalence of Helicobacter pylori (H. pylori ) infection in patients with a bleeding peptic ulcer after consumption of non-steroidal antiinflamma- tory drugs (NSAIDs). METHODS:A very early upper endoscopy was performed to find the source of upper gastrointestinal bleeding and to take biopsy specimens for analysis of H. pylori infection by the rapid urease (CLO) test, histological examination, and bacterial culture. IgG anti-CagA were also sought. The gold standard for identifying H. pyl...     

Peptic ulcer and Helicobacter pylori

Although there has been an explosion of data not only since the discovery of H. pylori in 1982, but also since the first comprehensive review of H. pylori in the Gastroenterology Clinics in 1993, much remains to be learned. In 1993, there were many skeptics doubting the importance of H. pylori in ulcer disease. Although this skepticism has dissipated, many ulcer patients infected with H. pylori still do not receive appropriate therapy. This situation possibly relates to the safety, efficacy, and simplicity of prescribing acid-suppressive therapy in contrast to the confusion regarding anti-H. pylori treatment regimens. Among the many continuing unanswered questions regarding the role of H. pylori and PUD are the still enigmatic nature of host, environmental, and H. pylori-related factors that determine outcome. Why do only some infected individuals (and why do more men than women) develop PUD, and what determines whether gastric ulcers or duodenal ulcers develop? What is the explanation for the seasonal variation in ulcer disease? Although PUD is an infectious disease, are other environmental factors critical for the manifestation of ulcers in association with infection? What factors govern the outcome of the combination of H. pylori infection and NSAID use? Has attention been too focused first on the pathophysiology of acid secretion and now on H. pylori? In curing H. pylori in association with PUD, are clinicians going to displace disease northward, substituting erosions, inflammation, and neoplasia (and associated symptoms) in the esophagus and gastroesophageal junction for an ulcer crater (and its associated symptoms) in the duodenum or stomach? The epidemiology of PUD is changing--in more recent reports of ulcer patients, H. pylori and NSAID use are less prevalent than in earlier reports. These questions and comments should not be misinterpreted as advocating a lack of aggressiveness in diagnosis and treatment of H. pylori in the setting of PUD, however. Nevertheless, the pendulum is swinging.     

Peptic ulcer and non-steroidal anti-inflammatory agents.

Aspirin is generally regarded as a cause of gastric ulcer but the role of non-steroidal anti-inflammatory agents and paracetamol in the aetiology of peptic ulcer is unclear. To investigate this we conducted a case control study of 180 matched pairs of peptic ulcer patients and controls obtained from surgical and dermatology outpatient clinics. There were 95 gastric ulcer and 85 duodenal ulcer patients. A statistically and clinically association (relative risk = 5) was found between the regular use of non-steroidal anti-inflammatory agents and gastric ulcer. There was also evidence of positive associations between gastric ulcer and aspirin containing preparations with or without non-steroidal anti-inflammatory agents. By contrast, duodenal ulcer was unrelated to these drugs. Too few patients used paracetamol for any conclusion to be drawn on its role.     

Outcome of peptic ulcer bleeding, nonsteroidal anti-inflammatory drug use, and Helicobacter pylori infection.

BACKGROUND & AIMS: NSAIDs and Helicobacter pylori are risk factors for the development of peptic ulcers. A prospective study was conducted to determine prevalence of NSAID use, H pylori infection, and outcome of peptic ulcer bleeding. METHODS: In 2000, data of all 361 patients presenting with peptic ulcer bleeding were prospectively collected in a defined geographical area, including 14 hospitals, and serving a catch area of 1.68 million persons. Follow-up data after a mean of 31 months were obtained from 211 patients. RESULTS: The overall incidence was 21.5 cases per 100,000 persons. Mean age of the group was 70.9 years, 55% were male, and 41% had severe or life-threatening comorbidity. NSAIDs were used by 52%, and in only 17% concomitant acid suppressive therapy was given. H pylori infection was tested in 64%. Of the patients tested for H pylori, 43% were positive. Twenty-three percent were H pylori negative and not using NSAIDs. Rebleeding during initial admission occurred in 19%. Mortality during initial admission was 14%. During follow-up mortality was high, 29%. CONCLUSIONS: Half of all ulcer bleeding was associated with NSAID use. Only a minority of NSAID users used concomitant acid suppressive therapy. H pylori is not assessed systematically in all patients with ulcer bleeding. Almost a quarter of the ulcers were associated with neither H pylori infection nor NSAID use. Mortality, both during hospitalization and follow-up, was substantial.     

非甾体抗炎药相关性溃疡并出血的临床特点

目的 研究非甾体抗炎药(NSAIDs)相关性胃十二指肠溃疡并出血的临床特点。方法 调查我院1997年1月-2001年12月间因胃十二指肠溃疡并出血收住院治疗患者的临床资料,根据人院前1周内有无服用NSAIDs史将患者分为2组,对2组病人的临床资料进行分析比较。结果 本研究共纳入446例患者,其中服药组86例,未服药组360例。2组病人在性别、出血方式、既往消化性溃疡史、胃及十二指肠溃疡的具体部位、糜烂,以及是否需要内镜治疗等方面的差异无显著性。但是服药组患者的年龄较未服药组更高,血红蛋白在服药组下降更明显(P＝0.004);胃溃疡和复合溃疡、多发溃疡在服药组更多见(P＜0．001),而未服药组幽门螺杆菌(Hp)的感染率较服药组更高,分别为72．5％和53.4％(P＝0.001)。进一步的研究发现,患者年龄和Hp感染状态对NSAIDs相关溃疡并出血的临床特点无明显影响。结论 应加强对NSAIDs相关性胃十二指肠溃疡并出血临床特点的认识,尽量减少NSAIDs的不良反应。     

Relationship between non-steroidal anti-inflammatory drug use and Helicobacter pylori infection in bleeding or uncomplicated peptic ulcers: A case-control study

BACKGROUND AND AIMS: Non-steroidal anti-inflammatory drug (NSAID) use has been closely associated with an increased risk of bleeding peptic ulcers, while the prevalence of Helicobacter pylori infection has been reported to be lower in bleeding ulcers than in non-bleeding ones. However, whether an interaction exists between NSAID use and H. pylori infection has not clearly been elucidated yet. The aims of this study were to determine the frequency of NSAID use and H. pylori infection, to predict risk factors in bleeding peptic ulcers and to determine whether NSAID use and H. pylori infection interact with each other. METHODS: Ninety-six patients with bleeding ulcer were included in the study. The control group consisted of 106 patients with non-bleeding ulcer. Data were analyzed by using the chi-squared test, Fisher's exact test and logistic regression analysis with or without interaction term (H. pylori by NSAID). RESULTS: Non-steroidal anti-inflammatory drug use was significantly more common in patients with bleeding ulcers than in controls (79.2 vs 38.7%, unadjusted odds ratio (OR): 6.02, 95% confidence interval (CI): 3.21-11.29). The frequency of the H. pylori infection was significantly lower in patients with bleeding ulcers than in controls (66.7 vs 89.6%, unadjusted OR: 0.23, 95% CI: 0.10-0.49). In the logistic regression analysis with the interaction term, male sex (adjusted OR: 3.70, 95% CI: 1.65-8.29), multiplicity of ulcers (adjusted OR: 4.10, 95% CI: 1.02-16.45) and NSAID use (adjusted OR: 33.87, 95% CI: 4.36-262.97) were independent risk factors for bleeding ulcers. There was a negative interaction between H. pylori and NSAID use (adjusted OR: 0.09, 95% CI: 0.01-0.83). CONCLUSIONS: The negative interaction between the two variables suggests that the presence of H. pylori is associated with a lower risk of bleeding in ulcer patients taking NSAIDs.     

Interaction or relationship between Helicobacter pylori and non-steroidal anti-inflammatory drugs in upper gastrointestinal diseases

According to a meta-analysis, H pylori and non-steroidal anti-inflammatory drugs (NSAID) independently and significantly increase the risk of gastroduodenal ulcer and ulcer bleeding. Their coincidence is frequent, demonstration of a possible relationship and consequent attitude is of important implications. But unfortunately, no consensus has been approved in the past years and their interactions are still controversial. H pylori and NSAID are known to share a number of pathogenic mechanisms, but there is no evidence for the significant synergic action between these two risk factors. Their relationship is independent, additive, synergistic or antagonistic without considering the influence of other factors because studies on this subject are different in almost all aspects of their methodology, including the definition of a NSAID user as well as the types, doses, duration and their indications for NSAID use, as well as their end-points, definition of dyspepsia and regimes used for eradication of H pylori. These might contribute to the conflicting results and opinions. H pylori infection in humans does not act synergistically with NSAID on ulcer healing, and there is no need to eradicate it. This notion is supported by the finding that the eradication of H pylori does not affect NSAID-induced gastropathy treated with omeprazole and that H pylori infection induces a strong cyclooxygenase-2 (COX-2) expression resulting in excessive biosynthesis of gastroprotective prostaglandin which in turn counteracts NSAID-induced gastropathy and heals the existing ulcer. Other investigators claimed that H pylori infection acts synergistically with NSAID on ulcer development, and H pylori should be eradicated, particularly at the start of long-term NSAID therapy. Eradication of H pylori prior to NSAID treatment does not appear to accelerate ulcer healing or to prevent recurrent ulcers in NSAID users. However, some recommendations can be drawn from the results of clinical trails.