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.     

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.     

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.     

Effects of Helicobacter pylori and nonsteroidal anti-inflammatory drugs on peptic ulcer disease: a systematic review.

BACKGROUND & AIMS: The aim was to systematically review the interactions between Helicobacter pylori (HP) infection and NSAID use on the risk of uncomplicated or bleeding peptic ulcer. METHODS: All relevant full articles published in MEDLINE from January 1989-June 2004 were included. Sensitivity analyses for type of controls or use of aspirin or non-aspirin NSAIDs were performed. RESULTS: In 21 studies involving 10,146 patients, uncomplicated peptic ulcer was more common in HP-positive than HP-negative patients (pooled odds ratio [OR], 2.17) or in HP-positive than HP-negative NSAID users (OR, 1.81). In 6 age-matched controlled studies, ulcer was more common in HP-positive than HP-negative patients (OR, 4.03), irrespective of NSAID use, and in NSAID users than non-users (OR, 3.10), irrespective of HP status; the risk of ulcer was 17.54-fold higher in HP-positive NSAID users than HP-negative non-users. The use of aspirin or non-aspirin NSAIDs did not affect the results. Ulcer bleeding was evaluated in 17 studies involving 4084 patients. NSAID use was more frequent in bleeding patients than control subjects (OR, 5.13), irrespective of HP status and type of controls. In contrast, HP infection in bleeding patients compared with control subjects was less frequent in the 8 studies with ulcer cases as control subjects (OR, 0.40) and more frequent in the 9 studies with uninvestigated subjects as controls (OR, 2.56). In the latter studies, presence compared with the absence of both HP and NSAIDs increased the risk of bleeding 20.83-fold. CONCLUSION: HP infection and NSAID use represent independent and synergistic risk factors for uncomplicated and bleeding peptic ulcer.     

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.     

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.     

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。     

Effect of helicobacter pylori infection on the risk of upper gastrointestinal bleeding in users of nonsteroidal anti-inflammatory drugs

PURPOSE: We evaluated whether infection with Helicobacter pylori, including specific cytotoxic-associated antigen (CagA)-positive strains, increase the risk of upper gastrointestinal bleeding in users of nonsteroidal anti-inflammatory drugs (NSAIDs). METHODS: Cases with upper gastrointestinal bleeding and recent NSAID use, including aspirin, who were admitted during 2001, were compared with age- and sex-matched outpatient controls who had recent NSAID use. H. pylori infection was diagnosed by serum antibodies or the (13)C-urea breath test; and CagA seropositivity was diagnosed by enzyme-linked immunoassay. RESULTS: H. pylori was detected significantly more frequently in cases of bleeding than controls (79% [63/80] vs. 56% [45/80], P = 0.004). Cases of bleeding were more likely than controls to have a history of peptic ulcer (34% [n = 27] vs. 13% [n = 10], P = 0.003), previous upper gastrointestinal bleeding (19% [n = 15] vs. 6% [n = 5], P = 0.03), recent dyspepsia (29% [n = 23] vs. 15% [n = 12], P = 0.06), and <3 months of NSAID use (58% [n = 46] vs. 40% [n = 32], P = 0.04). CagA positivity was not associated with gastrointestinal bleeding. In a multivariate analysis, H. pylori infection was the only significant risk factor for upper gastrointestinal bleeding (odds ratio = 1.7; 95% confidence interval: 1.2 to 2.5; P = 0.004). CONCLUSION: H. pylori infection almost doubles the risk of upper gastrointestinal bleeding among users of NSAIDs.     

幽门螺杆菌阴性消化性溃疡与出血关系的多中心对照研究

目的明确中国大陆地区幽门螺杆菌（Hp）阴性消化性溃疡与出血的关系。方法拟定于2006年4月至2007年3月期间在国内14个研究中心中进行,每个中心预期调查30例经急诊内镜诊断为胃溃疡和（或）十二指肠溃疡合并出血的患者（PUB组）,同时调查30例不伴出血的胃溃疡和（或）十二指肠溃疡患者作为对照（PU组）。共拟人选840例患者,消化性溃疡合并及不合并出血组各420例。在内镜检查中采用快速尿素酶试验和病理检测却感染,并对初次检查却阴性者于1个月后进行尿素呼气试验复查。结果共617例患者纳入分析,其中PUB组263例、PU组354例,2组在性别比、平均年龄等一般状况方面差异无统计学意义（P均〉0．05）。PUB组却阳性率61．2％（161／263）显著低于PU组的87．9％（311／354）（P〈0．001）;PUB组跏阳性的溃疡出血发生复合溃疡的比例7．5％（12／161）显著高于Hp阴性溃疡出血者1．0％（1／102）（P=0．018）,但两者在平均发病年龄、性别比、呕血发生率、十二指肠球部溃疡发生率、胃溃疡发生率及溃疡平均直径方面差异无统计学意义（P均〉0．05）。对于初次tip阴性的溃疡出血患者,1个月后的呼气试验复查未发现阳性病例。结论目前中国大陆缉,阴性溃疡在消化性溃疡出血中的比例较高,坳阴性溃疡可能更容易并发消化道出血,需要引起消化专科医生的重视。     

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.     

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.     

Nonsteroidal anti-inflammatory drugs and gastrointestinal bleeding. A case-control study

This study looked at the association between nonsteroidal anti-inflammatory drug (NSAID) use and acute nonvariceal upper gastrointestinal tract bleeding (AUGIB). Fifty-seven consecutive patients presenting to hospital with AUGIB were compared with 123 sex- and age-matched controls. Twenty-four (42.1%) of the 57 AUGIB patients were taking NSAIDs compared with 23 (18.1%) of the 123 control subjects. Patients whose AUGIB was associated with NSAID use were significantly older than the group whose bleeding was not associated with drug use; no other differences between these two groups was found. Seventy percent of patients taking nonacetylsalicylic acid who developed bleeding in this study did so within three months of starting therapy. Abdominal pain was an infrequent presenting complaint.     

An ulcer negative for Helicobacter pylori and nonsteroidal anti-inflammatory drugs? Consider herbal treatment as the culprit!

The cause of peptic ulcers that are negative for Helicobacter pylori or nonsteroidal anti-inflammatory drug/aspirin use is an area of immense interest. We report here, for the first time, a case report of a young female who developed reflux-like symptoms and multiple ulcers as a result of herbal treatment with turmeric for osteoarthritis. With the current marked increase in usage of herbal products as part of a complementary medicine approach, gastroenterologists must be vigilant when evaluating patients with peptic ulcer disease of unknown cause.     

加强对非甾体类抗炎药相关性溃疡的研究

近年来由于幽门螺杆菌 (Hp)的有效根除 ,使Hp相关性消化性溃疡的发病率明显下降 ;而随着非甾体类抗炎药 (NSAIDs)抗炎、镇痛、抗血栓、抗肿瘤作用的开发和临床应用的越来越广泛 ,NSAIDs相关性溃疡和溃疡出血的发病率持续上升 ,在老年患者中尤为明显。据国外资料 ,长期应用NSAIDs者 ,胃溃疡的发病率为 10 %～ 2 0 % ,十二指肠溃疡的发病率为 2 %～ 5 % ,内镜下溃疡的发生率为 14 %～ 4 4% [1] 。约 1%～ 2 %的患者在 1年内发生严重胃肠道并发症 ,大多为上消化道出血、胃十二指肠梗阻或溃疡穿孔。出血、穿孔而致死亡的人数至少是不服用…