clinical aspects of Helicobacter pylori eradication therapy in peptic ulcer disease

Background and aims : Although the role of H. pylori in peptic ulcer disease is no longer in dispute, certain aspects of eradication therapy in this condition have yet to be settled. Uncertainties still surround the relationship between Helicobacter pylori status and ulcer healing, the efficacy of eradication therapy in alleviating acute symptoms and healing ulcers, and the prognosis after eradication with respect to recurrence of symptoms, ulcers and complications. The present literature review, encompassing studies published up to October 1995, specifically addresses these issues.
Results : Pooled data show that eradication therapy heals 90% of duodenal ulcers and 85% of gastric ulcers, while individual studies repeatedly confirm that it is more effective at healing ulcers than conventional treatment with anti-secretory drugs. Recent reports indicate that triple therapy regimens for 1 week, provided they include an anti-secretory drug, are sufficient to achieve high rates of healing and rapid symptom relief. A detailed analysis of the data, particularly those from studies reporting healing rates in relation to H. pylori status after eradication therapy, provides strong evidence that eradication of H. pylori produces ulcer healing. Follow-up studies show that ulcer recurrence and complications are rare after eradication treatment in patients with either gastric or duodenal ulcer disease. However, while ulcer symptoms are infrequent during follow-up, a proportion of patients appear to develop gastrooesophageal reflux after eradication.
Conclusions : H. pylori eradication is highly effective in promoting ulcer healing and preventing subsequent ulcer recurrence. These beneficial effects of eradication therapy are observed in patients with either gastric or duodenal ulcers which are associated with H. pylori infection.     

三九胃泰四联疗法治疗消化性溃疡及根除幽门螺杆菌的多中心临床研究

目的：观察含三九胃泰的四联疗法对消化性溃疡的治疗作用及根除幽门螺杆菌（Hp)的效果。方法：经胃镜确诊的102例消化性溃疡患者随机分成3组，试验组（A组，48例）给予三九胃2.5 雷尼替丁150mg 阿莫西林500mg 甲硝唑400mg,bid；对照组1（B1组，31例）给予铋剂220mg 雷尼替丁150mg 阿莫西林500mg 甲硝唑400mg,bid；对照组2（B2组，23例）给予雷尼替丁150mg 阿莫西林500mg 甲硝唑400mg,bid；以上药物除抗菌药只服用2周外，其余药物服至6周末疗程结束，第7周复查胃镜和／或^13C呼气试验。结果：溃疡总愈合率A组、B1组、B2组分别为90．9％，100％和86．4％，S2获得率分别为68．2％，73．1％和45．5％，Hp根除率分别为76．1％，73．3％，52．6％，症状缓解率大致相似，3组均无明显不良反应发生。结论：雷尼替丁三联疗法加用三九胃泰治疗消化性溃疡，可使S2获得率增加，同时Hp根除率上升，其效果与加用铋剂效果相近，临床观察无明显不良反应。     

Effect of CYP2C19*17 gene variant on Helicobacter pylori eradication in peptic ulcer patients

Objective Eradication of Helicobacter pylori is an important treatment strategy in peptic ulcer patients. Current regimens of eradication consist of proton pump inhibitor (PPI) and two antibiotics. The principal enzyme involved in PPIs metabolism is CYP2C19, which exhibits an interindividual variability of activity, mainly due to genetic polymorphism. Two alleles (CYP2C19*2 and CYP2C19*3), responsible for slow PPIs metabolism, were previously associated with higher efficacy of eradication. Recently, a novel CYP2C19 gene variant (CYP2C19*17), associated with faster metabolism of CYP2C19 substrates, was described. In the present study, a potential association between CYP2C19*17 allele and lower H. pylori eradication efficacy was tested in a group of peptic ulcer patients.Methods A total of 125 peptic ulcer patients, positive for H. pylori infection, were treated with triple therapy (pantoprazole+amoxicillin+metronidazole). Subsequently, the patients were divided into two groups (group 1 – success, and group 2 – failure of eradication after therapy) and genotyped for the presence of CYP2C19 variant alleles (*2, *3, and *17).Results Frequency of CYP2C19 alleles in two groups of patients were: 56.4 versus 65 (p=0.060) for *1, 15.4 versus 5.3 (p=0.015) for *2, and 28.2 versus 25.5 (p=0.663) for *17 allele, respectively. CYP2C19*3 was not detected in the evaluated population. No significant differences in frequency nor distribution of *17 allele were found between two groups of patients. CYP2C19*2 allele was associated with successful H. pylori eradication (p<0.02), *2 allele carriers were found to be over 4-times more prone to the treatment compared to *1/*1 homozygotes (OR=4.2, p=0.015).Conclusion Our results suggest that, contrary to CYP2C19*2, CYP2C19*17 allele has no impact on efficacy of H. pylori eradication in peptic ulcer patients treated with pantoprazole.     

Pantoprazole, amoxycillin and either azithromycin or clarithromycin for eradication of Helicobacter pylori in duodenal ulcer

BACKGROUND: Studies have shown that 1-week triple therapy consisting of a proton pump inhibitor, amoxycillin and clarithromycin may cure Helicobacter pylori infection in the majority of patients. AIM: To establish whether pantoprazole plus amoxycillin in association with either azithromycin or clarithromycin is useful in curing H. pylori infection in patients with a duodenal ulcer. METHODS: One hundred and ten patients with active duodenal ulcers and H. pylori infection were treated with pantoprazole (days 1-7, 40 mg b.d.; days 8-28 40 mg o.d.) plus amoxycillin 1 g b.d. for the first 7 days. Patients were randomly assigned to receive either azithromycin 500 mg o.d. for the first 6 days (PAAz group; n=55) or clarithromycin 500 mg b.d. for the first 7 days of treatment (PAC group; n=55). H. pylori status was determined by urease test and histology before the treatment, and again 4 weeks after cessation of any medication. RESULTS: One hundred and three patients completed the study. H. pylori infection was eradicated in 78% (39/50) of patients in the PAAz group (ITT analysis: 71%, 95% CI: 61-83%) vs. 81% (43/53) of patients in the PAC group (ITT analysis: 78%, 95% CI: 69-90%) (N.S.). All ulcers had healed. CONCLUSION: Our study shows that 1-week triple therapy with pantoprazole, amoxycillin and either azithromycin or clarithromycin is not satisfactory (<80% ITT H. pylori eradication rate).     

Omeprazole, clarithromycin and furazolidone for the eradication of Helicobacter pylori in patients with duodenal ulcer

AIM: To evaluate the efficacy of omeprazole plus clarithromycin and furazolidone in Helicobacter pylori eradication and duodenal ulcer healing in Brazilian patients. METHODS: Forty H. pylori-positive patients with duodenal ulcer were randomized to receive 20 mg omeprazole o.m. or b.d. for 1 month plus 500 mg clarithromycin (b.d. ) and 200 mg furazolidone (b.d.) for 1 week. RESULTS: Three months after the end of the treatment the eradication rates were 90% by intention-to-treat analysis, and 97% by per protocol analysis. Mild side-effects were observed in 25 patients, none of whom abandoned the protocol. No difference was observed between the 20 mg and 40 mg omeprazole daily doses. Cure or significant improvement of the symptoms and of the histological alterations were observed after H. pylori eradication. CONCLUSION: Our results demonstrate that clarithromycin and furazolidone in combination with omeprazole are a good alternative for H. pylori eradication in Brazilian patients with duodenal ulcer.     

Helicobacter pylori infection in peptic ulcer haemorrhage

In this overview, medical advice for routine clinical practice regarding peptic ulcer haemorrhage (PUH) is given, based on the extensive literature about Helicobacter pylori and the controversial results about the interaction of H. pylori infection and nonsteriodal anti-inflammatory drug (NSAID) use. PUH remains an important emergency situation with an incidence between 32 and 51/100 000 persons per year. There is a high association between H. pylori infection and peptic ulcer disease. The association between H. pylori infection and PUH is less clear, but a strong argument for the aetiological role is the fact that eradication of H. pylori decreases recurrence of bleeding. NSAID use is another important risk factor for PUH. H. pylori infection and NSAID use seem to act independently, although some studies show a synergistic interaction while other studies report that H. pylori is protective against the development of PUH in NSAID users. All patients with PUH should be tested for H. pylori infection, regardless of the use of NSAIDs. Because invasive tests are less sensitive in PUH patients, negative tests in patients with no other risk factors should be confirmed by serology or urea breath test (UBT). Eradication therapy with a proton pump inhibitor or ranitidine bismuth citrate-based triple therapy should be given to all H. pylori- positive patients. Only for nonaspirin–NSAID users does the effect of eradication therapy on the healing of gastric ulcers remain controversial, but currently we also advise eradication of H. pylori in this subgroup. After eradication therapy, acid-suppressant therapy is advised to heal the ulcer. The success of eradication should always be confirmed because of the risk of recurrence of peptic ulcer disease and bleeding in H. pylori- infected patients.     

雷尼替丁枸橼酸铋联合克拉霉素根除幽门螺杆菌疗效观察

目的 比较雷尼替丁枸橼酸铋联合克拉霉素与奥美拉唑、甲硝唑、克拉霉素两种疗法对幽门螺杆菌（Hp）的根除效果。方法 123例Hp阳性的消化性溃疡患者分为2组：A组62例，以雷尼替丁枸橼酸铋1片（含：雷尼替丁100mg，枸橼酸铋钾110mg）、克拉霉素250mg口服，2次／d，疗程7d；B组61例，以奥美拉唑20mg、克拉霉素250mg加甲硝唑400mg口服，2次／d，疗程7d。结果 A、B两组的Hp根除率分别为86．9％和85．2％，活动期溃疡愈合率分别为97．6％和100％，副反应发生率分别为6．6％和8．2％，两组间Hp根除率、活动期溃疡愈合率和副反应发生率差异均无显著性（均P〉0．05）。结论 雷尼替丁枸橼酸铋联合克拉霉素与奥美拉唑、甲硝唑、克拉霉素两种疗法疗效相当，而雷尼替丁枸橼酸铋联合克拉霉素因价廉、安全在临床上更为实用。     

Drug combinations with amoxycillin reduce selection of clarithromycin resistance during Helicobacter pylori eradication therapy

This study investigated the relationship between the drug combinations of the eradication regimens and the prevalence of acquired resistance to clarithromycin. Of 540 patients treated with anti-Helicobacter pylori regimens containing clarithromycin, 55 patients (31 males, mean age, 45.6 years) with failed eradication of H. pylori that was susceptible to clarithromycin before treatment were included. The E test was used to test for susceptibility to clarithromycin (minimum inhibitory concentration (MIC) <1 mg/l). Of the 55 patients, 33 (60.0%) developed clarithromycin resistance after failed eradication. Of the dual therapies, the combination of a proton pump inhibitor (PPI) and clarithromycin resulted in 88.9% (8/9) of the patients acquiring clarithromycic-resistance. With the triple therapies, the percentages of patients acquiring clarithromycin resistant strains after using a PPI+clarithromycin+amoxycillin or a PPI+clarithromycin+metronidazole were 38.7% (12/31) and 90.0% (9/10), respectively (P<0.01). These data suggest that regimens containing amoxycillin may prevent the selection of secondary clarithromycin resistance.     

Meta-analysis: role of Helicobacter pylori eradication in the prevention of peptic ulcer in NSAID users

Aim : To evaluate whether eradication of Helicobacter pylori prevents peptic ulcer in non‐steroidal anti‐inflammatory drug users by means of a meta‐analysis. Material and methods : A systematic search was performed in MEDLINE, EMBASE, the Cochrane Controlled Trials Register and the AGA congress. Randomized trials comparing H. pylori eradication vs. non‐eradication or eradication vs. a proton pump inhibitor in patients receiving a non‐steroidal anti‐inflammatory drug were selected. Results : Five studies and 939 patients were included in the analysis; 34 of 459 (7.4%) patients developed a peptic ulcer in the eradicated group vs. 64 of 480 (13.3%) in the control group. The odds ratio was 0.43 (95% confidence interval: 0.20–0.93). Sub‐analyses showed a significant reduction of risk for non‐steroidal anti‐inflammatory drug‐naive (odds ratio = 0.26; 95% confidence interval: 0.14–0.49) but not for previously treated patients (odds ratio = 0.95, 95% confidence interval: 0.53–1.72). Two studies with a total of 385 patients compared eradication vs. a proton pump inhibitor; five of 196 (2.6%) developed a peptic ulcer in the eradicated group vs. zero of 189 (0%) in the proton pump inhibitor group (odds ratio = 7.43; 95% confidence interval: 1.27–43.6). Conclusion : Helicobacter pylori eradication reduces the incidence of peptic ulcer in the overall population receiving non‐steroidal anti‐inflammatory drugs. It appears to be especially effective when performed in non‐steroidal anti‐inflammatory drug‐naïve patients. Nonetheless, eradication seems less effective than treatment with a maintenance proton pump inhibitor for preventing non‐steroidal anti‐inflammatory drug‐associated ulcers.     

One-week clarithromycin triple therapy regimens for eradication of Helicobacter pylori

Background:

One-week triple therapies have been endorsed as the treatment regimens of choice for eradication of Helicobacter pylori infection. Those that include clarithromycin appear to be the most effective.

Aim:

To review reports of triple therapies that include clarithromycin.

Methods:

Reports were identified from the literature to May 1998. The variation between study designs prevents a formal meta-analysis. A measure of the relative efficacies of regimens has, however, been gained by comparison and by pooling of intention-to-treat eradication rates.

Results:

One hundred and ninety-two studies were identified which included 264 treatment arms of a 1-week triple therapy composed of clarithromycin with amoxycillin or a nitroimidazole (metronidazole or tinidazole), and either ranitidine bismuth citrate or a proton pump inhibitor (omeprazole, lansoprazole or pantoprazole). From reports of these studies, an intention-to-treat H. pylori eradication rate could be determined from 210 treatment arms of 151 studies.

Conclusions:

There is little to choose between the efficacies of 1-week clarithromycin-based triple therapy eradication regimens. However, those comprising clarithromycin, a nitroimidazole and either ranitidine bismuth citrate or a high dose of omeprazole are, in general, the most effective. Against antibiotic-resistant strains of H. pylori, regimens including ranitidine bismuth citrate may be more effective than those including a proton pump inhibitor.

     

Impact of intravenous omeprazole on Helicobacter pylori eradication by triple therapy in patients with peptic ulcer bleeding

AIM: To test the impact of intravenous omeprazole on Helicobacter pylori eradication for bleeding peptic ulcers. METHODS: A total of 175 H. pylori-infected patients with bleeding peptic ulcers were randomized into either an omeprazole group or a ranitidine group, receiving intravenous omeprazole or ranitidine for 3 days after endoscopy. Afterwards, 1-week triple therapy was used to eradicate H. pylori for both groups. Six weeks later, either a 13C-urea breath test or follow-up endoscopy was performed to assess the success of H. pylori eradication. RESULTS: The rebleeding rate was lower in the omeprazole group vs. the ranitidine group (6% vs. 17%, P < 0.05). The H. pylori eradication rate was higher in the omeprazole group (intention-to-treat analysis: 83% vs. 66%, P < 0.05; per protocol analysis: 93% vs. 80%, P < 0.05). For patients with duodenal ulcers, the per protocol H. pylori eradication rate of the omeprazole group was higher than that of the ranitidine group (93% vs. 73%, P < 0.05). CONCLUSIONS: Intravenous omeprazole can decrease the risk of rebleeding of peptic ulcers. For duodenal ulcers, in particular, intravenous omeprazole may even improve the H. pylori eradication rate of the subsequent triple therapy.     

四联疗法治疗幽门螺杆菌阳性消化性溃疡疗效观察

目的观察四联疗法治疗HP阳性的十二指肠溃疡、胃溃疡HP根除率及疗效。方法经胃镜和快速尿素酶方法确诊的HP阳性十二指肠溃疡和胃溃疡共247例。予雷贝拉唑20 mg,2次/日+胶体果胶铋0.2,2次/日+克拉霉素0.5,2次/日+甲硝唑0.4,2次/日,口服一周,继而连服雷贝拉唑20 mg,一次/日共5周。疗程结束四周后胃镜及快速尿素酶试验复查。结果随访成功196例,HP总根除率81.6%,其中十二指肠溃疡根除率86%,胃溃疡根除率67.4%,溃疡病总有效率88.3%,其中十二指肠溃疡有效率89.3%,胃溃疡有效率84.8%,两组比较差异显著(P0.01)。结论含雷贝拉唑的四联疗法,对HP阳性的十二指肠溃疡HP根除及疗效优于HP阳性的胃溃疡。     

Duodenal ulcer relapse after eradication of Helicobacter pylori

Thirty-six patients with healed duodenal ulcers, 27 infected with Helicobacter pylori and nine uninfected, were followed for up to 12 months to determine the rate of ulcer relapse. Eight patients withdrew over the follow up period. At one year, 15 of 20 (75%) infected patients and one of eight (13%) uninfected patients had relapsed, p less than 0.05. Eradication of H pylori favourably influences the natural history of duodenal ulcer recurrence. Significant patient morbidity may be prevented by using measures to eradicate H pylori during or after duodenal ulcer healing.     

Impact of clarithromycin resistance on the effectiveness of a regimen for Helicobacter pylori: a prospective study of 1-week lansoprazole, amoxycillin and clarithromycin in active peptic ulcer

BACKGROUND: Clarithromycin is a key antimicrobial in the combinations used to cure Helicobacter pylori infections, so there is a need to define the impact of in vitro resistance on in vivo results. METHODS: A prospective trial was designed to study the effectiveness of the 1-week combination of lansoprazole, clarithromycin and amoxycillin in 102 consecutive patients with active peptic ulcer. The pre-treatment and post-treatment sensitivity to amoxycillin, metronidazole and clarithromycin were studied by E-test, and H. pylori status was defined by histology, culture and urease test at diagnosis and one month after treatment, and by urea-breath test 2 months after treatment. RESULTS: The eradication rate (intention-to-treat analysis) was 77% (95% CI: 69-86). No clinical factor was found to be different between eradicated and non-eradicated patients. Clarithromycin-resistant strains were found in 10 (10%; CI: 5-17) patients. The eradication rate was 20% (CI: 3-56) in these patients vs. 83% (CI: 75-91) in patients harbouring clarithromycin-sensitive strains (P < 0.001). A logistic-regression analysis confirmed clarithromycin resistance as the only factor associated with treatment failure. CONCLUSIONS: Clarithromycin resistance significatively impairs the effectiveness of the combination of lansoprazole, amoxycillin, and clarithromycin. The 80% efficacy goal will be difficult to reach in areas with high (>10%) primary clarithromyicin resistance, if currently recommended proton pump inhibitor-triple therapies are used.     

Review article: management of peptic ulcer bleeding-the roles of proton pump inhibitors and Helicobacter pylori eradication

Peptic ulcer bleeding is associated with substantial morbidity and mortality. The goals of management are to control any active bleeding and prevent re-bleeding and then to heal the ulcer and prevent its recurrence. Initial management strategies are guided by the patient's clinical condition and endoscopic findings. Thus, treatment may consist of endoscopic and medical therapy and, sometimes, surgery. Control of acid secretion, preferably with proton pump inhibitor therapy in the initial management continues to evolve; it has also been used as both an adjunct to endoscopic therapy and as primary treatment. These agents have been found to be effective in some trials in the reduction of re-bleeding and the need for surgery, although there is no clear benefit demonstrated for overall mortality. Proton pump inhibitors have been administered either intravenously or orally in different trials. The long-term management of patients with peptic ulcer, after the initial bleeding episode, should include patient stratification based upon risk factors for ulcer recurrence (i.e. Helicobacter pylori infection, use of aspirin or nonsteroidal anti-inflammatory drugs). Elimination or modification of these risk factors reduces the risk of ulcer recurrence and, hence, of recurrent ulcer bleeding.     

Helicobacter pylori, chronic gastritis and peptic ulcer.

H. pylori infection is strongly associated with chronic gastritis and is probably the main course of chronic inflammation in the gastric mucosa. Acquisition of the infection will lead to gastritis and the eradication of the bacterium results in healing and final cure of the gastritis. Chronic gastritis and H. pylori infection may occur in antrum and/or corpus, and will gradually result in atrophy of the underlying mucosa in a great number of affected persons. Correspondingly, impairments in several important functions of the gastric mucosa are consequences of the atrophy and inflammation. Hp infection and gastritis associate with important gastroduodenal diseases, such as peptic ulcer diseases and gastric cancer. There are reasons to suggest that the infection and subsequent gastritis precede these diseases, and that they are important risk factors for both disorders. In fact, peptic ulcer can be seen a late frequent complication of an H. pylori infection. In addition, the type and grade of gastritis can be used in prediction of the ulcer risk if adequate biopsy specimens are available for microscopy from both antrum and corpus mucosa (Table II). An association between chronic gastritis and Helicobacter pylori (Hp) infection is strong. Clearly more than 80% of cases with chronic gastritis are related to coexistent Hp infection. Furthermore, both Hp and gastritis are extremely common in patients with peptic ulcer supporting the view that they are causally related to the ulcer disease. Correspondingly, similar suggestions may also be presented about the links between Hp and gastritis in the pathogenesis of gastric cancer.(ABSTRACT TRUNCATED AT 250 WORDS)