The association of Helicobacter pylori infection and nonsteroidal anti-inflammatory drugs in peptic ulcer disease.

BACKGROUND AND AIM: Peptic ulcer disease (PUD) affects 10% of the world population. Helicobacter pylori infection and the use of a nonsteroidal anti-inflammatory drug (NSAID) are the principal factors associated with PUD. The aim of the present study was to evaluate a cohort of patients with PUD and determine the association between H pylori infection and NSAID use. PATIENTS AND METHODS: The medical charts of patients with endoscopic diagnosis of PUD were retrospectively reviewed from September 2002 to August 2003. Patients were divided into three groups according to ulcer etiology: H pylori infection (group 1); NSAID use (group 2); and combined H pylori infection and NSAID use (group 3). RESULTS: One hundred two patients were evaluated: 36 men (35.3%) and 66 women (64.7%). Forty patients had H pylori infection, 43 had used NSAIDs and 15 had combined H pylori infection and NSAID use; four patients with ulcers secondary to malignancy were excluded. The frequency of women was significantly higher in group 2 (P=0.01). The mean age of patients in group 1 was significantly lower than in the other two groups (P=0.003). PUD developed earlier in group 3 than in group 2 (5.0+/-4.7 months versus 1.4+/-2.1 months, respectively, P=0.018). Thirty-two patients (32.7%) had bleeding peptic ulcer. Group 2 had a higher risk of bleeding peptic ulcer than the other two groups (P=0.001). CONCLUSIONS: The development of PUD was observed earlier in the combined H pylori and NSAID group than in patients with only NSAID use. This suggests a synergic effect between the two risks factors in the development of PUD.     

Helicobacter pylori and nonsteroidal anti-inflammatory drugs.

The complex interaction between H. pylori and NSAIDs implies that it is over simplistic to conclude that their relationship is independent, synergistic, or antagonistic without considering the influence of other factors. Factors such as previous exposure to NSAIDs, a history of ulcer complication, concurrent use of acid-suppressant therapy, and the difference between NSAIDs and low-dose aspirin all affect the outcome. Several recommendations can be made with regard to the indications of H. pylori eradication for patients requiring NSAIDs. First, patients taking NSAIDs who have ulcers or previous ulcer disease should be tested for the bacterium, and it should be eradicated if present because it is impossible to determine whether the ulcers are caused by H. pylori or NSAIDs or both. Antiulcer drugs should be prescribed to prevent ulcer recurrence for patients who continue to require NSAIDs. Although the efficacy of omeprazole is enhanced by H. pylori infection, it is not justified to leave a pathogen in the stomach in exchange for a modest therapeutic gain. Second, for patients who take low-dose aspirin, eradication of H. pylori substantially reduces the risk of ulcer bleeding. It is advisable that patients taking low-dose aspirin who are at risk of ulcer bleeding should be tested for H. pylori and treated for it if the infection is found. Third, for patients who are about to start NSAIDs, screen-and-treat H. pylori has the potential of reducing the ulcer risk at an affordable incremental cost. It might be argued that any interaction between H. pylori and NSAIDs would become irrelevant in the era of COX-2-selective NSAIDs. Even among patients who are receiving a COX-2-selective NSAID, however, a large-scale study showed that the ulcer risk is significantly higher in H. pylori-positive patients than in uninfected patients. This finding suggests that the relative importance of H. pylori in ulcer development might increase with a reduced toxicity of COX-2-selective NSAIDs. With an increasing use of low-dose aspirin for cardiovascular prophylaxis, the problem of aspirin-related ulcer disease is expected to rise. Given the significant role of H. pylori in the latter condition, screen-and-treat H. pylori might be a useful strategy for the prevention of ulcer complications in high-risk patients receiving low-dose aspirin in the future.     

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.     

Corticosteroid use and peptic ulcer disease: role of nonsteroidal anti-inflammatory drugs

OBJECTIVE: To estimate the relative risk for peptic ulcer disease that is associated with the use of oral corticosteroids. DESIGN: A nested case-control study. SETTING: Tennessee Medicaid program. PARTICIPANTS: The case patients (n = 1415) were hospitalized between 1984 and 1986 for gastric or duodenal ulcer or for upper gastrointestinal hemorrhage of unknown cause. The controls (n = 7063) were randomly selected from Medicaid enrollees not meeting the study criteria for inclusion as case patients. MEASUREMENTS AND MAIN RESULTS: The estimated relative risk for the development of peptic ulcer disease among current users of oral corticosteroids was 2.0 (95% CI, 1.3 to 3.0). However, the risk was increased only in those who concurrently received nonsteroidal anti-inflammatory drugs (NSAIDs); these persons had an estimated relative risk associated with current corticosteroid use of 4.4 (CI, 2.0 to 9.7). In contrast, the estimated relative risk for those corticosteroid users not receiving NSAIDs was 1.1 (CI, 0.5 to 2.1). Persons concurrently receiving corticosteroids and NSAIDs had a risk for peptic ulcer disease that was 15 times greater than that of nonusers of either drug. CONCLUSION: Discrepant findings among earlier studies regarding steroids and the risk for peptic ulcer disease could in part be due to differences in the use of NSAIDs among study participants. The high risk for peptic ulcer disease associated with combined use of NSAIDs and corticosteroids indicates the need to prescribe this drug combination cautiously.     

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.     

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 and risk of ulcer bleeding among users of nonsteroidal anti-inflammatory drugs: a case-control study.

BACKGROUND & AIMS: Peptic ulcer complications related to use of nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most common serious adverse drug reactions. Whether Helicobacter pylori infection potentiates this gastrointestinal toxicity of NSAIDs is still unresolved. In this study, we investigated the role of H. pylori as a cause of bleeding peptic ulcer among NSAID users. METHODS: A case-control study of current users (n = 132) of NSAIDs (including acetylsalicylic acid), admitted because of bleeding peptic ulcer, was performed. Controls were 136 NSAID users without gastrointestinal complications. H. pylori was diagnosed by either increased levels of serum immunoglobulin G or by 13C-urea breath test. RESULTS: Fifty-eight (44%) case subjects had a bleeding gastric ulcer, 54 (41%) had a bleeding duodenal ulcer, 12 (9%) had both gastric and duodenal ulcers, and 8 (6%) had hemorrhagic gastritis. H. pylori was present in 75 (57%) cases compared with 59 (43%) controls. The adjusted odds ratio of bleeding peptic ulcer among NSAID users associated with H. pylori infection was 1.81 (95% confidence interval, 1.02-3.21). H. pylori accounted for approximately 24% of bleeding peptic ulcers among elderly NSAID users. CONCLUSIONS: NSAID users infected with H. pylori have an almost twofold increased risk of bleeding peptic ulcer compared with NSAID users without H. pylori.     

非甾体类抗炎药物与消化性溃疡出血的关系

目的探讨非甾体类抗炎药物(NSAIDs)诱发消化性溃疡出血的临床流行病学特点。方法回顾分析1991~2004年我院诊治的消化性溃疡出血的临床资料,并用电脑数据库处理分析。结果在694例消化性溃疡并出血患者中,26.80%近期内有服用NSAIDs史。服用NSAIDs组与未服用NSAIDs组比较,服用NSAIDs组前驱症状(腹痛、消化不良等)发生率较低(30.65%比61.42%P<0.01);平均年龄较大[(44.16±13.25)岁比(35.23±11.49)岁,P<0.05];女性比例相对较多(26.34%比15.55%,P<0.01);胃溃疡比例较高(28.50%比20.67%,P<0.01);外科手术率无明显差别(P>0.05);结论NSAIDs是诱发消化性溃疡出血的一常见原因,应加强对NSAIDs胃肠毒副作用的防治。     

Eradication therapy in Helicobacter pylori positive peptic ulcer disease: systematic review and economic analysis

BACKGROUND AND AIM: We conducted a systematic review and economic analysis to ascertain the efficacy of eradication therapy in the treatment of H. pylori positive peptic ulcer disease. METHODS: Comprehensive search of electronic databases, bibliographies of retrieved articles, contact with pharmaceutical companies, and experts in the field to identify published and unpublished literature from 1966 to the present. The data were incorporated into a Monte Carlo simulation Markov model that incorporated all the uncertainty in the estimates to evaluate cost-effectiveness. RESULTS: Fifty-two trials were included in the final metaanalysis. In duodenal ulcer healing, H. pylori eradication therapy was superior to ulcer healing drug (relative risk (RR) of ulcer persisting = 0.66; 95% confidence interval (CI) = 0.58 to 0.76) and no treatment (RR = 0.37; 95% CI 0.26 to 0.53). In gastric ulcer healing, H. pylori eradication therapy was not statistically superior to ulcer healing drug (RR = 1.32; 95% CI = 0.92 to 1.90). In preventing duodenal ulcer recurrence, H. pylori eradication therapy was not statistically superior to maintenance therapy with ulcer healing drug (RR of ulcer recurring = 0.73; 95% CI = 0.42 to 1.25), but was superior to no treatment (RR = 0.19; 95% CI = 0.15 to 0.26). In preventing gastric ulcer recurrence, H. pylori eradication was superior to no treatment (RR = 0.31; 95% CI 0.19 to 0.48). The Markov model suggested H. pylori eradication is cost-effective for duodenal ulcer over 1 year and gastric ulcer over 2 years with over 95% confidence despite the uncertainty in the data. CONCLUSIONS: H. pylori eradication therapy reduces the recurrence of peptic ulcer disease and is cost-effective.     

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.     

非甾体类抗炎药与消化性溃疡

非甾体类抗炎药(non-steroidal antiinflamma-tory drugs,NSAID)是世界上应用最广泛的一类药物,被用于抗炎镇痛、风湿性疾病、骨关节炎、心血管疾病等,然而它具有多种不良反应,其中常见的是消化性溃疡.因使用NSAID引起的胃肠道溃疡称NSAID相关性溃疡或NSAID溃疡.     

Nonsteroidal anti-inflammatory drugs and peptic ulcer disease

Evidence has accumulated that nonsteroidal anti-inflammatory drugs (NSAIDs) cause clinically important gastroduodenal ulcers. The pathogenesis, which involves the impairment of mucosal resistance to injury in an acid-peptic environment, is multifactorial and controversial. Ulcers caused by NSAIDs can occur either in mucosa inflamed because of infection with Helicobacter pylori or in histologically normal mucosa. The use of these drugs has been linked to an unexpectedly high incidence of ulcer complications, and a history of peptic ulcer disease is common in such cases. Nonsteroidal anti-inflammatory drugs thus appear both to exacerbate an underlying peptic diathesis and to cause de novo ulcers. The association between the use of these drugs and ulcer complications is supported by ulcer prevalence data from cross-sectional studies, and by data from case-controlled and cohort studies, and from randomized, experimental trials. Drug-induced gastric ulcers have been prevented by misoprostol, but not by H2 blocker therapy. Several therapies have been reported to promote ulcer healing despite continued use of NSAIDs, but adequate controlled trials have not been done. Small gastric and duodenal ulcers readily heal, whereas larger gastric ulcers require vigorous and prolonged therapy. The relative efficacies of various therapies in preventing ulcers, healing ulcers, or preventing complications remain to be established.     

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.     

The relationship between nonsteroidal anti-inflammatory drug use and peptic ulcer disease

It has become increasingly recognized that nonsteroidal anti-inflammatory drug (NSAID) use is associated with serious gastroduodenal mucosal injury that can eventuate in upper gastrointestinal bleeding or perforation. This article discusses the lack of predictive value of studies administering NSAIDs to normal volunteers. The new data concerning prevention and treatment of chronic NSAID ulcers is also discussed.     

Accuracy of Helicobacter pylori diagnostic tests in patients with bleeding peptic ulcer: a systematic review and meta-analysis

OBJECTIVE: To perform a systematic review and a meta-analysis of diagnostic accuracy of the different tests aimed to detect Helicobacter pylori infection in patients with upper gastrointestinal bleeding (UGIB). METHODS: Selection of studies: assessing the accuracy of H. pylori diagnostic methods in patients with UGIB. Search strategy: electronic bibliographical searches. Data extraction: independently done by two reviewers. Data synthesis: meta-analyses of the different tests were performed combining the sensitivities, specificities, and likelihood ratios (LRs) of the individual studies. RESULTS: Studies showed a high degree of heterogeneity. Pooled sensitivity, specificity, LR+ and LR- (95% confidence interval (CI)) for the different methods were: Rapid urease test (16 studies/1,417 patients): 0.67 (0.64-0.70), 0.93 (0.90-0.96), 9.6 (5.1-18.1), and 0.31 (0.22-0.44). Histology (10 studies/827 patients): 0.70 (0.66-0.74), 0.90 (0.85-0.94), 6.7 (2.5-18.4), and 0.23 (0.12-0.46). Culture (3 studies/314 patients): 0.45 (0.39-0.51), 0.98 (0.92-1.00), 19.6 (4-96), and 0.31 (0.05-1.9). Urea breath test (8 studies/520 patients): 0.93 (0.90-0.95), 0.92 (0.87-0.96), 9.5 (3.9-23.3), and 0.11 (0.07-0.16). Stool antigen test (6 studies/377 patients): 0.87 (0.82-0.91), 0.70 (0.62-0.78), 2.3 (1.4-4), and 0.2 (0.13-0.3). Serology (9 studies/803 patients): 0.88 (0.85-0.90), 0.69 (0.62-0.75), 2.5 (1.6-4.1), and 0.25 (0.19-0.33). CONCLUSION: Biopsy-based methods, such as rapid urease test, histology, and culture, have a low sensitivity, but a high specificity, in patients with UGIB. The accuracy of 13C-urea breath test remains very high in these patients. Stool antigen test is less accurate in UGIB. Although serology seems not to be influenced by UGIB, it cannot be recommended as the first diagnostic test for H. pylori infection in this setting.