The prevalence of peptic ulcer not related to Helicobacter pylori or non-steroidal anti-inflammatory drug use is negligible in southern Europe

BACKGROUND AND AIM: Helicobacter pylori is the major cause of peptic ulcer disease, but the proportion of H. pylori-negative peptic ulcers seems to be increasing in developed countries. We investigated the frequency of H. pylori-negative peptic ulcer without intake of nonsteroidal anti-inflammatory drugs (NSAIDs) in a Mediterranean European country. MATERIALS AND METHODS: We prospectively collected consecutive patients with an endoscopically verified active peptic ulcer over 6 months from different areas of Spain. Helicobacter pylori infection was assessed by rapid urease test and histologic examination (corpus and antral biopsies). A (13)C-urea breath test was performed if H. pylori was not detected with the invasive test. Patients were considered H. pylori-negative if all three tests were negative. NSAID use was determined by structured data collection. RESULTS: Of 754 consecutive peptic ulcer patients, 16 (2.1%) were H. pylori-negative and had not used NSAIDs before the diagnosis. Of the 472 patients who had duodenal ulcers, 95.7% (n = 452) were H. pylori-positive and only 1.69% (n = 8) were negative for both H. pylori infection and NSAID use; 193 patients had benign gastric ulcers and 87% (n = 168) of them were infected by H. pylori (p <.001 vs. duodenal ulcers). NSAID intake was more frequent in gastric ulcer patients (52.8%) than in duodenal ulcer patients (25.4%; p <.001). Consequently, the frequency of H. pylori-negative gastric ulcer in patients not using NSAID was 4.1% (n = 8). CONCLUSION: Peptic ulcer disease is still highly associated with H. pylori infection in southern Europe, and only 1.6% of all duodenal ulcers and 4.1% of all gastric ulcers were not associated with either H. pylori infection or NSAID use.     

Systematic review and meta-analysis: Helicobacter pylori eradication therapy after simple closure of perforated duodenal ulcer

Background: The most common complications of peptic ulcer are bleeding and perforation. In many regions, definitive acid reduction surgery has given way to simple closure and Helicobacter pylori eradication. Aim: To perform a systematic review and meta‐analysis to ask whether this change in practice is in fact justified. Materials and Methods: A search on the Cochrane Controlled Trials Register, Medline, and Embase was made for controlled trials of duodenal ulcer perforation patients using simple closure method plus postoperative H. pylori eradication therapy versus simple closure plus antisecretory non‐eradication therapy. The long‐term results for prevention of ulcer recurrence were compared. Results: The pooled incidence of 1‐year ulcer recurrence in H. pylori eradication group was 5.2% [95% confidence interval (CI) of 0.7 and 9.7], which is significantly lower than that of the control group (35.2%) with 95% CI of 0.25 and 0.45. The pooled relative risk was 0.15 with 95% CI of 0.06 and 0.37. Conclusions: Helicobacter pylori eradication after simple closure of duodenal ulcer perforation gives better result than the operation plus antisecretory non‐eradication therapy for prevention of ulcer recurrence. All duodenal ulcer perforation patients should be tested for H. pylori infection, and eradication therapy is required in all infected patients.     

13C-urea breath test during hospitalization for the diagnosis of Helicobacter pylori infection in peptic ulcer bleeding

Objective: To evaluate the accuracy of ¹³C‐urea breath test (UBT) to detect Helicobacter pylori infection in patients hospitalized with peptic ulcer bleeding and treated with proton pump inhibitors (PPIs). Methods: Patients hospitalized with peptic ulcer bleeding, and treated with omeprazole, had a first UBT performed the day after resuming oral feeding. Patients with a negative UBT during hospitalization underwent a repeated UBT 15 days after stopping PPIs. Results: The first UBT during hospitalization was positive in 86% of 131 patients. Time between admission and performance of the test was longer in patients with negative versus positive UBT (5.2 ± 0.7 versus 4.3 ± 0.5 days; p < .001). The repeated UBT became positive in 15 of 18 (83%) patients with a negative first UBT. In the multivariate analysis, the only variable associated with a negative first UBT was the time elapsed between admission and performance of the test (odds ratio = 6.6; 95%CI = 2.9–15.1). Conclusion: Most H. pylori‐positive patients with ulcer bleeding have a positive UBT (performed just after resuming oral feeding) despite previous treatment with high‐dose PPIs. Nevertheless, to preclude false‐negative results due to PPI therapy, the UBT should be performed as early as possible. If the infection cannot be demonstrated with this first UBT, H. pylori still needs to be definitively excluded with a second UBT performed after stopping PPIs.     

Helicobacter pylori stool antigen test in patients with bleeding peptic ulcers

BACKGROUND: Helicobacter pylori has been linked to chronic gastritis, peptic ulcers, gastric cancer and mucosa-associated lymphoid tissue lymphoma. Invasive tests are less sensitive than noninvasive tests in diagnosing H. pylori infection in patients with bleeding peptic ulcers. The H. pylori stool antigen test has been useful in diagnosing H. pylori in patients with peptic ulcers before and after eradication of H. pylori. The aim of this study was to evaluate the H. pylori stool antigen test in patients with bleeding peptic ulcers. METHODS: Patients with bleeding and nonbleeding peptic ulcers underwent a rapid urease test, histology, bacterial culture and H. pylori stool antigen test. Positive H. pylori infection was defined as a positive culture or both a positive histology and a positive rapid urease test. Helicobacter pylori stool antigen was assessed with a commercial kit (Diagnostec H. pylori antigen EIA Kit, Hong Kong). RESULTS: Between October 2000 and April 2002, 93 patients with bleeding peptic ulcers (men/women: 78/15, gastric ulcer/duodenal ulcer: 58/35) and 59 patients with nonbleeding peptic ulcers (men/women: 47/12, gastric ulcer/duodenal ulcer: 30/29) were enrolled in this study. Forty-seven (50.5%) patients with bleeding peptic ulcers and 30 (50.8%) patients with nonbleeding peptic ulcers, were found to be infected with H. pylori (p > .1). Helicobacter pylori stool antigen tests were positive in 54 (58.1%) and 30 (50.8%) patients with bleeding peptic ulcers and nonbleeding peptic ulcers, respectively (p > .1). The sensitivity (82% vs. 93%), specificity (68% vs. 93%), positive predictive value (74% vs. 93%), negative predictive value (77% vs. 93%) and diagnostic accuracy (75% vs. 93%) were all lower in patients with bleeding vs. nonbleeding peptic ulcers. The specificity, positive predictive value, and diagnostic accuracy of the H. pylori stool antigen test in patients with bleeding peptic ulcers were significantly lower than those in patients with nonbleeding peptic ulcers (p = .01, p = .02 and p = .003, respectively). CONCLUSION: The H. pylori stool antigen test is not reliable for diagnosing H. pylori infection in patients with bleeding peptic ulcers.     

Eradication of Helicobacter pylori for the prevention of peptic ulcer rebleeding

AIM: To evaluate the effect of Helicobacter pylori eradication on ulcer bleeding recurrence in a prospective, long-term study including more than 400 patients. METHODS: Patients with peptic ulcer bleeding were prospectively included. H. pylori infection was confirmed by rapid urease test, histology or (13)C-urea breath test. Several eradication regimens were used. Ranitidine 150 mg was administered daily until eradication was confirmed by breath test 8 weeks after completing eradication therapy. Patients with therapy failure received a second or third course of therapy. Patients with eradication success did not receive maintenance anti-ulcer therapy, and were controlled yearly with a repeated breath test. RESULTS: Four hundred and twenty-two patients were followed up for at least 12 months, with a total of 906 patient-years of follow up. Mean age was 59 years, and 35% were previous nonsteroidal anti-inflammatory drug (NSAID) users. Sixty-nine percent had duodenal, 24% gastric, and 7% pyloric ulcer. Recurrence of bleeding was demonstrated in two patients at 1 year (incidence: 0.22% per patient-year of follow up), which occurred after NSAID use in both cases. CONCLUSION: Peptic ulcer rebleeding does not occur in patients with complicated ulcers after H. pylori eradication. Maintenance anti-ulcer (antisecretory) therapy is not necessary if eradication is achieved.     

益生菌对幽门螺杆菌阳性消化性溃疡治疗有效性的Meta分析

目的 探讨益生菌+H.pylori标准疗法对消化性溃疡患者H.pylori感染的根除率与安全性。 方法 计算机检索2019年3月20日以前公开发表的中英文数据库文献(知网数据库、万方数据库、EMBASE数据库、MEDLINE数据库以及PubMed数据库等),借助RevMan 5.2软件分析与评价相关数据。 结果 检索符合条件研究文献共11篇。Meta分析证实,益生菌+H.pylori标准治疗方案可以有效提高H.pylori根除率(OR=2.94,P结论 益生菌+H.pylori标准疗法对消化性溃疡患者H.pylori感染的根除率以及溃疡愈合好转率均有提升,并显著降低不良反应发生率,具备临床推广价值。     

No correlation of babA2 with vacA and cagA genotypes of Helicobacter pylori and grading of gastritis from peptic ulcer disease patients in Brazil

BACKGROUND: The babA2 gene, which encodes a blood-group antigen-binding adhesin that mediates attachment of Helicobacter pylori to human Lewis(b) antigens on gastric epithelial cells, has been associated with a higher risk of peptic ulcer and gastric cancer. The purpose of this study was to ascertain the frequency of babA2 genotype in H. pylori strains of patients with peptic ulcer and to correlate with other virulence factors. MATERIALS AND METHODS: vacA, cagA, and babA2 genotypes of H. pylori were determined by using polymerase chain reaction (PCR). DNA was extracted from positive urease test gastric samples of 150 patients with peptic ulcer. Antrum and corpus biopsies were taken for histologic examination according to the updated Sydney system classification. RESULTS: babA2 genotype was present in 104 (69.3%) and cagA in 113 (75.3%) gastric samples. No significant correlation was observed between babA2 and vacAs1 genotype or between babA2 and cagA status. The correlation of vacAs1 genotype with positive cagA was statistically significant ( p < .001). The babA2-positive strain was more frequently found from the gastric samples of men, than of women (p = .01). Strains harboring cagA, vacAs1, and babA2 genotypes had no association to the grading of gastritis, presence of glandular atrophy, or intestinal metaplasia. The simultaneous presence of cagA, vacAs1, and babA2 was found in 32.6% of the H. pylori strains. CONCLUSIONS: babA2 genotype is frequently found in H. pylori strains from peptic ulcer disease in Brazil, although it has no significant correlation to the worsening of the gastritis and to other virulence markers such as vacAs1 and cagA.     

Helicobacter pylori and Non-malignant Diseases

In 2007 Helicobacter pylori research continued to deal with some controversies raised in the last decade. The main problems remain unsolved: peptic ulcer disease negative for H. pylori , synergism of H. pylori infection and aspirin and other nonsteroidal anti-inflammatory drugs or cyclooxygenase 2 specific inhibitors, the role of H. pylori eradication in uninvestigated and nonulcer dyspepsia, and the possible protective effect of H. pylori infection against gastroesophageal reflux disease and its complications such as Barrett's esophagus and adenocarcinoma. The incidence and prevalence of peptic ulcer disease as well as ulcer-related mortality are continuing to decline all over the world. The increasing consumption of anti-inflammatory and antisecretory drugs was not found to change the trend over the last period and therefore H. pylori was considered the key factor in causing ulcer-related mortality. Some progress has been achieved in understanding H. pylori -induced immunological processes, and attack mechanisms, as well as specific pathogenesis in uremic and cirrhotic patients. There is still a lot to learn about the bacterium and host factors related to H. pylori infection and its complications.     

Accuracy of diagnostic tests for Helicobacter pylori in patients with peptic ulcer bleeding

Background and Aims: To assess the validity of biopsy‐based tests (histology, culture, and urease test) and serology in detecting current H. pylori infection for the peptic ulcer patients who had gastric bleeding. Methods: A total of 398 peptic ulcer patients were enrolled and divided into two groups, according to the presence or absence of bleeding. The diagnosis for current H. pylori infection was verified using the gold standard combining individual H. pylori tests. Sensitivity, specificity, and positive and negative predictive values of the culture, Campylobacter‐like organism (CLO) test (urease test), histology, and serology were compared. Results: Of the total study population (N = 398), 157 (39.4%) patients were categorized into the bleeding group. The sensitivities of the culture (40.0%) and CLO (85.0%) in the bleeding group were significantly lower than culture (58.1%) and CLO (96.4%) in the nonbleeding group (p = .012 and p < .001, respectively). In the bleeding group, the sensitivity of CLO (85.0%) was significantly lower than histology (92.5%) and serology (97.4%) (p = .013 and p = .002, respectively), which was not found in the nonbleeding group. The specificity of serology in the bleeding group (56.3%) was significantly lower than that of nonbleeding group (74.2%) (p = .038). Similarly, the specificity of serology was significantly lower than the other H. pylori tests in the bleeders. Conclusions: Bleeding decreased the sensitivity of H. pylori tests in patients with peptic ulcer, especially in urease test or culture. In contrast, histology was found to be a quite reliable test, regardless of the presence of bleeding.     

幽门螺杆菌根除治疗对消化性溃疡患者血清胃泌素水平的影响

目的 观察幽门螺杆菌(H.pylori)根除治疗对消化性溃疡患者血清胃泌素水平的影响,为该病治疗提供参考。 方法 选择我院2017年8月至2019年8月收治的120例H.pylori感染的消化性溃疡患者作为观察组,根据H.pylori分型结果进一步分为HPⅠ型组和HPⅡ型组,观察组患者接受根除幽门螺杆菌治疗。选择同期入院的40例非幽门螺杆菌感染消化性溃疡患者作为对照组,对照组患者接受常规治疗。比较两组患者治疗效果、胃镜检查结果、H.pylori清除情况及血清胃泌素、IL10、IL17水平。 结果 HPⅠ型组、HPⅡ型组和对照组患者临床总有效率差异无统计学意义(92.75%、96.08%、97.50%,χ2=1.384,P=0.051)。HPⅠ型组、HPⅡ型组、对照组患者胃镜检查总有效率差异无统计学意义(91.30%,96.08%,97.50%,χ2=1.384,P=0.051)。HPⅡ型组患者幽门螺杆菌根除率高于HPⅠ型组(98.04% vs 85.51%,χ2=4.129,P=0.042)。HPⅠ型组患者治疗后血清胃泌素、IL10、IL17水平均高于对照组(均P结论 不同类型H.pylori感染消化性溃疡患者行幽门螺杆菌根除治疗后临床效果无显著差异。幽门螺杆菌根除治疗可降低消化性溃疡患者血清胃泌素、IL10、IL17水平。     

Eradication of Helicobacter pylori infection reduces the incidence of peptic ulcer disease in patients using nonsteroidal anti-inflammatory drugs: a meta-analysis

Aim: To investigate the association between use of nonsteroidal anti‐inflammatory drugs (NSAID) and Helicobacter pylori infection, interactive effect of H. pylori infection and NSAID use on the development of peptic ulcer disease (PUD), and the effect of H. pylori eradication therapy on PUD development. Material and Methods: We performed a systematic literature search in EMBASE and PubMed for relevant articles published in English between January 1989 and August 2010, with the following MeSH and/or key words: non‐steroidal anti‐inflammatory drugs, or NSAIDs, Helicobacter pylori, or H. pylori, peptic ulcer disease or PUD, and randomized‐control study or clinical trial. The meta‐analysis was conducted using the Review Manager 4.2.2. Results: In the analysis of five studies, the pooled prevalence of H. pylori infection was 74.5% and 71.1% in NSAID users and non‐NSAID users, respectively, (OR = 0.65; 95% CI: 0.35–1.20, p = .170). In the analysis of nine studies, the pooled prevalence of PUD in NSAID users was 31.2% and 17.9% in the presence and absence of H. pylori infection, respectively, (OR = 3.08; 95% CI: 1.26–7.55, p = .010). Moreover, in the analysis of seven studies, PUD developed in 6.4% and 11.8% of NSAID users with and without eradication therapy, respectively (OR = 0.50; 95% CI: 0.36–0.74, p < .001). The preventive effect of the eradication therapy was further revealed in NSAID‐naive users (OR = 0.26; 95% CI: 0.14–0.49, p < .0001) and in the Asian population (OR = 0.30; 95% CI: 0.16–0.56, p < .001). Conclusion: NSAID use is not associated with H. pylori infection in patients with PUD. PUD is more common in H. pylori positive than in negative NSAID users. Moreover, H. pylori eradication therapy reduces PUD incidence in NSAID users, especially in naive users and in the Asian population.     

Eradicating Helicobacter pylori in Peptic Ulcer Disease Reduces Medical Costs in the Community

Background: Eradicating Helicobacter pylori markedly reduces ulcer recurrence in patients with peptic ulcer disease (PUD). Many decision analysis studies have concluded that eradicating H. pylori in PUD patients is more cost‐effective than maintaining antisecretory therapy. In 1995, we introduced an H. pylori eradication program into a large transportation company that experienced increased incidences of PUD among its employees along with increased medical costs, and we performed trend analysis of the actual medical costs of PUD in this cohort. Methods: In this cohort, there were approximately 8500 employees. H. pylori‐positive PUD patients were identified at the annual health check up. The patients received eradication therapy with lansoprazole, amoxicillin, and clarithromycin. After eradication, the patients were followed up by a yearly health check up. The annual number of patients who received eradication was recorded, and the annual direct medical costs of PUD therapy were analyzed. Results: A total of 440 H. pylori‐positive PUD patients received eradication therapy in a 7‐year period. Based on an intention‐to‐treat analysis, the eradication rate was 84.5% (372 of 440). The largest number of patients who received eradication therapy was found in 1995 (n = 115), and from 1995 to 2001 this number decreased yearly by 12.5 (95% confidence interval (CI): 5 to 20). Between 1989 and 1995, the annual medical costs arising of PUD therapy increased by ¥2.25 million (95% CI: 1.19 to 3.31) per year, being highest (¥22.75 million) in 1995. Between 1995 and 2001, the costs decreased by ¥3.88 million (95% CI: 3.16 to 4.59) per year. The cost in 2001 was 5.7% of the cost in 1995. The eradication program was terminated in 2001 because the prevalence of PUD diminished markedly, and the associated medical costs decreased as well. Conclusions: H. pylori eradication could reduce the number of PUD patients and associated medical costs in the workplace setting.     

益生菌联合抗幽门螺杆菌治疗对消化性溃疡患者的疗效

目的 探讨益生菌联合抗幽门螺杆菌（H. pylori）治疗对消化性溃疡患者的疗效及其对患者肠道菌群的影响。方法 将120例经14C呼气试验（14C-UBT）检测确定为H. pylori感染阳性的消化性溃疡患者随机分为观察组和对照组,每组60例。其中,对照组采用四联疗法（奥美拉唑+阿莫西林+克拉霉素+铋剂）治疗,观察组采用四联疗法联合益生菌治疗;比较两组患者H. pylori根除情况、溃疡愈合质量及不良反应情况。治疗前后留取全部患者的新鲜粪便标本进行细菌培养,比较两组患者肠道菌群数量和肠道微生物定植抗力（B/E值）。结果 观察组患者H. pylori根除率和溃疡愈合率分别为88.3%、95.0%,显著高于对照组的70.0%和76.7%（P＜0.05）,不良反应率为3.3%,显著低于对照组的20.0%（P＜0.05）。与治疗前比,对照组患者治疗后肠道内产气荚膜梭菌、双歧杆菌及乳杆菌数量显著减少（P＜0.05）,肠杆菌、肠球菌及酵母菌数量显著增加（P＜0.05）,B/E值显著降低（P＜0.05）;观察组患者治疗后双歧杆菌和乳杆菌均显著增加（P＜0.05）,产气荚膜梭菌显著减少（P＜0.05）,肠杆菌、肠球菌及酵母菌无明显变化（P＞0.05）,B/E值显著升高（P＜0.05）。结论 常规抗H. pylori治疗易引起消化性溃疡患者肠道菌群紊乱,降低肠道定植抗力。益生菌联合治疗可有效改善患者肠道微生态,提高H. pylori根除率和溃疡愈合质量,减少不良反应。     

Interaction of Helicobacter pylori Infection and Nonsteroidal Anti‐Inflammatory Drugs in Gastric and Duodenal Ulcers

Background: Gastric (GU) and duodenal ulcers (DU) are in most instances either induced by Helicobacter pylori infection or by nonsteroidal anti‐inflammatory drugs (NSAIDs). Whether eradication of H. pylori is beneficial in NSAID users for preventing NSAID induced GU and DU has been the focus of different studies. Materials and Methods: Mechanisms shared by both H. pylori and NSAIDs for the induction of GU and DU were reviewed and randomized controlled trials on H. pylori eradication for prevention and healing of GU and DU in patients requiring NSAID therapy were identified by a PubMed search. Results: Key factors in the induction of GU and DU for both H. pylori and NSAIDs are a decrease in pH, imbalance between apoptosis and proliferation, reduction in mucosal blood flow, and recruitment of polymorphonucleates in distinct compartments. For primary ulcer prevention, H. pylori eradication before starting an NSAID therapy reduces the risk of NSAID induced GU and virtually abolishes the risk of DU. H. pylori eradication alone is not sufficient for secondary prevention of NSAID induced GU and DU. H. pylori infection appears to further increase the protective effects of proton‐pump inhibitors (PPI) to reduce the risk of ulcer relapse. H. pylori eradication does not influence the healing of both GU and DU if NSAID intake is discontinued. Conclusions: Duodenal ulcer is more closely related to H. pylori infection than GU in NSAID users. H. pylori eradication is recommended for primary prevention of GU and DU in patients requiring NSAID therapy. PPI therapy is mandatory for secondary prevention of gastroduodenal ulcers, and appears to further reduce the risk of ulcer relapse in the presence of H. pylori.     

幽门螺杆菌与 2005 年诺贝尔医学奖

今年的诺贝尔医学或生理学奖授予 Robin Warren 和 Barry Marshall 两位坚韧不拔且敢于挑战传统观念的科学家 . 奖励他们所做出的非凡的和出人意料的发现：慢性胃炎、胃溃疡以及十二指肠溃疡主要是由幽门螺杆菌感染所导致的 .