DOES THE ERADICATION OF HELICOBACTER PYLORI CURE DUODENAL ULCER DISEASE IN COMMUNITIES WITH A HIGH PREVALENCE RATE? COMPARISON WITH LONG-TERM ACID SUPPRESSION

The long-term effect of Helicobacter pylori eradication on the natural history of duodenal ulcer has been investigated and compared with long-term acid suppression treatment in an endemic community for infection. Seventy-three patients with endoscopically verified H. pylori positive active duodenal ulcer disease were included in this prospective study. Patients were divided into two groups. Group A patients (n = 39) were given an omeprazole-based triple eradication regimen, while group B patients (n = 34) were given omeprazole alone followed by long-term famotidine 20 mg daily as maintenance treatment. A control endoscopy was performed at the third month of treatment. The bacterium was eradicated in 32 (82%) of group A patients. All patients were followed up for two years and an endoscopy performed at the end of each year. H. pylori recurred in 13 patients and the reinfection rate was 44.8% over two years. Duodenal ulcer recurred in seven of these patients at two years (24.1%). There was a close association between H. pylori reinfection and ulcer relapse. Group B patients remained H. pylori positive during the study and the ulcer recurred in five of these patients (6.6%) despite continuous famotidine treatment. There was no statistically significant difference in ulcer relapse rate between the groups. These results suggested that H. pylori eradication is not an absolute solution for duodenal ulcer disease in high endemic regions and continuous maintenance treatment with H2-receptor antagonists is still an alternative approach in some chronic recurrent cases.     

Recurrence rate of H. pylori after successful eradication and second eradication therapy after initial failure of treatment

Three hundred thirty-three patient (116 gastric ulcer, 119 duodenal ulcer, 98 gastritis) who were successfully eradicated were enrolled in the study of H. pylori recurrence rate. H. pylori status was determined by histology, rapid urease test, 13C-urea breath test. The mean of the follow-up period was 13.3 months (2-56 months), and 15 patients showed negative to positive conversion of H. pylori. The recurrence rate was 4.4% for one year and 8.3% for two years using Kaplan-Meier analysis. Second eradication therapy after initial failure is another concern. Nineteen patients were assigned to receive an 1-week new triple therapy (clarithromycin, metronidazole and PPI), in whom a 2-week course of dual therapy (amoxicillin plus PPI) failed (group1). Another 15 patients in whom the 1-week new triple therapy failed were switched to the 2-week course of dual therapy plus ecabet sodium (group2). H. pylori was eradicated in 84.2% (16/19) of patients in group1 and 86.7% (13/15) in group2.     

十二指肠球部溃疡合并幽门螺杆菌感染时胃局部胃泌酸、生长抑素和前列腺素E_2含量的变化

该研究通过测定十二指肠球部溃疡合并幽门螺杆菌感染患者胃液、胃窦粘膜胃泌素、生长抑素、前列腺素E_2的含量,观察幽门螺杆菌根除后上述指标变化,并与浅表性胃炎患者对照,探讨幽门螺杆菌感染在十二指肠球部溃疡发病中的作用。     

Investigation about usefulness of serum antibody of Helicobacter pylori and serum pepsinogen I/II ratio as a marker of the judgment after eradication therapy

To clarify that serum antibody of Helicobacter pylori (H. pylori) and serum pepsinogen I/II ratio are useful or not as a marker of the judgment after eradication therapy, we followed up 84 cases who received eradication therapy comparing with culture and histology (Carnoy's fixation and immunostaining using anti-H. pylori antibody, MIA method). Successful eradication was recognized in 45 of 84 cases (successful group), and remaining 39 cases were unsuccessful (unsuccessful group). Titers of serum H. pylori antibody went down gradually in the successful group, on the other hand, they did not go down constantly and often re-went up in the unsuccessful group. The difference of the various rate of titers in the both groups became clear statistically since 6 months after eradication therapy (p < 0.05). Supposing that cut-off rate of titer was 60% of pre-eradicated titer, sensitivity, specificity, and accuracy were 86.2%, 77.7%, and 84.2%, respectively, at 6 months after eradication therapy. Serum pepsinogen I/II ratio increased regardless of successful or unsuccessful eradication, but the various rate of serum pepsinogen I/II ratio was different in both groups at 1 month and 3 months after eradication therapy (p < 0.05). Serum antibody of H. pylori and serum pepsinogen I/II ratio could be a marker of the judgment after eradication therapy, especially the various rate of serum antibody of H. pylori is useful for the monitor of H. pylori infection in the long term.     

Time course changes in morphological and functional characteristics of gastric mucosa after eradication of Helicobacter pylori in duodenal ulcers

AIM: To study trends in morphological changes of gastric mucosa (GM) and its functional characteristics (serum gastrin-17, pepsinogens I and II) in eradication of Helicobacter pylori (HP) in patients with duodenal ulcer (DU). MATERIAL AND METHODS: HP infection was detected with a rapid urease test, morphological study of gastrobiopsies and polymerase chain reaction in 59 patients with DU. The results of HP eradication were assessed two months after the treatment. Morphological study of gastrobiopsies, assays for gastrin-17, pepsinogens I and II in blood serum were made before the treatment and one year after HP eradication. RESULTS: By the results of eradication two groups were formed: with effective eradication and uneffective eradication of H. pylori. Examination of GM one year after successful H. pylori eradication in DU patients GM inflammation relieved: reduction in polymorphonuclear (by 42.6%), mononuclear (by 29.3%) infiltration and number of lymphocytic follicules (16.8-fold). GM atrophy decreased by 47.8%. In patients with uneffective eradication the above positive changes were not registered. After H. pylori eradication, serum gastrin-17 lowered by 46. 7%, pepsinogen I--by 30.5%, pepsinogen II--by 36.9%. In uneffective eradication this decrease did not occur. CONCLUSION: H. pylori eradication leads to positive changes in morphological and functional indices reflecting GM condition.     

Selection of antibiotics and planning of eradication for H. pylori infection

There is general agreement that H. pylori should be eradicated in patients with peptic ulcers. But the optimal therapeutical regimen to be used still remains a matter for many investigations. An increase in the prevalence of antibiotic-resistant H. pylori strains has been reported recently. The recommended drugs for the eradication in Japan are clarithromycin (CAM) and amoxicillin (AMPC) because metronidazole (MNZ) is anti-parasites drug in Japan. A total of 392 H. pylori strains in the last twelve years were tested for sensitivity to CAM, MNZ, and AMPC. The Primary resistance of H. pylori to CAM, MNZ, and AMPC were found in 10.2%, 26.5%, and 0.3% strains, respectively. The resistant strains to CAM were gradually increasing in the last few years. The eradication therapies which do not increase antibiotics resistant strains after eradication failure were reported. The recommendation for eradication in patients with peptic ulcer disease includes those with bleeding ulcers. The pretreatment with proton pump inhibitors (PPI) does not influence the success of PPI-based triple therapy in eradicating H. pylori.     

Peptic ulcer recurrence after successful eradication of Helicobacter pylori--clinical characteristics and management

Peptic ulcer recurrence after successful eradication of Helicobacter pylori(H. pylori) is not rare. We evaluated the effect of H. pylori eradication on prevention of gastric ulcer recurrence. Ulcer recurrence had occurred in 20 of 256 H. pylori-eradicated patients, and most of ulcer recurrence were found within 1 year after eradication. NSAIDs and psychological stress, but not sex, smoking habit, drinking habit, and past history of ulcer, seem to be associated with ulcer recurrence. Intractable ulcers after the eradication of H. pylori frequently recurred. Some recurrent ulcers were refractory to treatment with H2-receptor antagonists or proton pump inhibitors. The mechanism(s) by which healed ulcers recur after successful eradication of H. pylori remains unclear.     

Anti-ulcer therapy after eradication of Helicobacter pylori

Helicobacter pylori (H. pylori) infection is the cause of the frequent relapse of peptic ulcer disease. Successful eradication therapy of H. pylori is associated with a decline in the recurrence of peptic ulcer. In this paper, we discussed the significance of anti-ulcer therapy after H. pylori eradication therapy. In patients with duodenal ulcer, maintenance therapy for preventing ulcer recurrence is not necessary because the rate of ulcer recurrence after eradication therapy is very low. However, in patients with gastric ulcer, the rate of ulcer relapse and reflux esophagitis ranges between 5-10% in the Japanese population even after successful eradication therapy; therefore, maintenance therapy for 1 year may be permissible in patients with gastric ulcer even after successful eradication therapy.     

Serum IL-8 as a possible marker for determining the status of<Emphasis Type="Italic">Helicobacter pylori</Emphasis> infection in patients with untreated and treated peptic ulcer

Failure to eradicateHelicobacter pylori can lead to peptic ulcer recurrence and gastric malignancy. Therefore, the objective of this study was to develop a noninvasive method for determining whetherH pylori infection was eradicated with antibiotic-based triple therapy. A total of 17 patients with duodenal ulcer (DU) and 17 with gastric ulcer (GU) were evaluated both before and after treatment. Outcomes included serum levels of interleukin-8 (IL-8), pepsinogen I, and gastrin, and the Wilcoxon signed rank test was used to test significance. Changes in these parameters were also correlated with disease status. In those patients where both GU and DU healing occurred as a result of treatment, most showed an increase in serum IL-8 and a decrease in serum pepsinogen. Serum gastrin levels were not significantly changed in either group. Posttreatment increases in serum IL-8 were seen in 15 of 17 (88%) recovered DU patients and 14 of 17 (82%) recovered GU patients (P < .05 for each). Posttreatment decreases in pepsinogen I were found in 15 of 17 DU and 15 of 17 GU patients (P < .05 for each). These preliminary findings suggest that an increase in serum IL-8 and possibly a decrease in pepsinogen I may be useful in identifying the successful eradication ofH pylori infection in patients with peptic ulcer treated with antibiotics. A more systematic analysis of these putative diagnostic markers is now warranted.     

两种方案治疗十二指肠溃疡幽门螺杆菌感染的临床分析

目的分析小剂量奥关拉唑、左氧氟沙星及呋喃唑酮新三联与小剂量奥关拉唑、阿莫西林及甲硝唑标准三联疗法治疗十二指肠溃疡幽门螺杆菌(Helicobacter pylori,Hp)感染的临床疗效对比。方法98例符合条件的患者随机分成两组,其中47例为新三联疗法,即口服小剂量奥美拉唑20mg,1次／d,连服6周,左氧氟沙星200mg及呋喃唑酮200mg,均为2次／d,连服2周。另一组51例为标准三联疗法,即口服小剂量奥关拉唑20mg,1次／d,连服6周,阿莫西林1000mg及甲硝唑400mg,均为2次／d,连服2周,疗程结束后1个月复查胃镜。结果96例患者完成治疗及随访,小剂量奥美拉唑新三联组与小剂量奥关拉唑标准三联组疗法Hp根除率分别为84．8％、82．0％,差异无统计学意义(P=0．715);溃疡愈合率分别为95．7％、92．0％,差异无统计学意义(P=0．752)。两组患者不良反应发生率分别为12．8％、15．7％,差异无统计学意义(P=0．680)。HP根除组溃疡愈合率(100．0％)明显高于HP未根除组(62．5％),差异有统计学意义(P=0．001)。结论小剂量奥关拉唑新三联组与标准三联组疗法均有较理想的Hp根除率及溃疡愈合率,新三联组疗法不良反应发生率与标准三联组疗法相当;同时发现Hp根除有利于溃疡愈合。因此,在当今面临Hp对常规抗生素耐药率上升的情况下,推荐新三联疗法在阿莫西林及甲硝唑耐药地区可作为根除十二指肠溃疡HP感染的一线治疗或失败后的补救治疗方案。     

Efficacy of omeprazole plus two antimicrobials for the eradication of Helicobacter pylori in a Turkish population.

Omeprazole combined with 2 antimicrobials has been suggested as a first-line option for Helicobacter pylori eradication in recent years. However, controversy exists regarding the efficacy of this protocol. This open-label, prospective clinical study investigated the efficacy of omeprazole-based triple therapy for H pylori eradication in 518 patients with H pylori-positive functional dyspepsia with or without duodenal ulcer. Amoxicillin, macrolides (clarithromycin or roxithromycin), and nitroimidazoles (metronidazole, ornidazole, or tinidazole) were the antibiotics used in the study. Nonulcer patients were randomly assigned to 1 of 8 different treatment protocols and duodenal ulcer patients were randomly assigned to 1 of 4 different treatment protocols consisting of omeprazole (20 mg once daily for nonulcer patients, 20 mg twice daily for ulcer patients for 14 days) with a combination of 2 of the above antimicrobials (for 10 days). H pylori infection was assessed by histologic findings and a rapid urease test before therapy and 4 weeks after therapy ended. Four hundred fifty-nine patients completed their regimens; 327 had functional dyspepsia (180 men, 147 women; median age, 39 years; range, 18 to 70 years) and 132 had ulcers (81 men, 51 women; median age, 40 years; range, 18 to 70 years). Eradication of H pylori was achieved in 58.8% (270 of 459) of all patients, 58.1% (190 of 327) of nonulcer dyspeptic patients, and 60.6% (80 of 132) of duodenal ulcer patients. The eradication rate varied from 47.2% to 69.4% in different treatment protocols. There were no statistically significant differences in eradication rates in any treatment group. All drugs were generally well tolerated in all groups, and no patient discontinued treatment because of side effects. Therapy with omeprazole and 2 antimicrobials for H pylori had limited efficacy in a Turkish population. The reason for these results, which conflict with those of other studies, is not clear. Further investigations of regimens for the eradication of H pylori in our population are necessary.     

阿奇霉素三联疗法根除幽门螺杆菌的疗效观察──附69例报告

目的:观察阿奇霉素三联疗法根除十二指肠球部溃疡病人的幽门螺杆菌(Hp)的临床疗效,对比阿奇霉素三联疗法一周与两周方案的疗效差别。方法:69例经胃镜检查证实为十二指肠球部溃疡并有Hp感染的病人,随机分为两组。A组(35例)口服奥美拉唑40mg每日1次,共2周;阿奇霉素500mg/d,仅疗程开始的头3日口服;阿莫西林500mg口服,每日4次,共2周。B组(34例)奥美拉唑与阿奇霉素的剂量和疗程同A组,阿莫西林500mg口服,每日3次,共1周。疗程结束后停用所有抗生素,4周后胃镜复查溃疡愈合情况,14C-尿素呼气试验复查Hp根除情况。结果:Hp根除率:A组和B组分别为89%(31/35)、85%(29/34),两组比较无显著性差异(P>0.05);溃疡愈合率:A组和B组分别为97%(28/29)、94%(29/31),两组比较无显著性差异(P>0.05);全部病人均完成治疗,仅2例出现恶心,1例轻度腹泻,总不良反应率为4%。结论:①阿奇霉素三联疗法具有Hp根除率高、安全性好、不良反应少及依从性好的优点;②阿奇霉素三联疗法一周方案与两周方案比较疗效相当;③阿奇霉素可作为根除Hp治疗方案中的一个新选择。     

Changes in endoscopic features and histological findings of H. pylori-related gastritis with a follow-up over a year after eradication of H. pylori

This study reviews the cases of patients examined repeatedly by endoscopy with biopsies for over one year after eradication of H. pylori, measured according to the Sydney system. For 81 patients in whom H. pylori was successfully eradicated, the endoscopic features of edema, erythema, friability, exudate, erosion and rugal hypertrophy disappeared or diminished at 1-3 months after the therapy and endoscopic features of nodularity disappeared or diminished 12-15 months after the therapy. In these H. pylori-eradicated patients, the histological findings of inflammation and activity regressed 1-3 months after therapy, and atrophy and intestinal metaplasia regressed in 22(27%) and 28(35%) of the 81 patients examined 12-15 months after therapy. Regression of the atrophic pattern was observed in 38(47%) of these H. pylori-eradicated patients. In some H. pylori-eradicated patients, the regressions of atrophy and intestinal metaplasia were observed over one year after H. pylori eradication therapy. Inflammation and activity in the histological findings were related to the endoscopic findings of edema, erythema, friability, exudate, erosion and rugal hypertrophy.     

The significance of H. pylori eradication in NSAIDs ulcer

The significance of H. pylori eradication for NSAIDs induced gastroduodenal ulcer has not been clarified. NSAIDs and H. pylori infection are independent causal factors for gastroduodenal mucosal injuries. However, the interaction between these two factors is complicated. H. pylori eradication can reduce the risk of NSAIDs induced ulcer in NSAIDs naive patients. However, H. pylori eradication is not recommended in NSAIDs user because of no ulcer suppression and ulcer healing delay. In prevention of NSAIDs induced ulcer recurrence, H. pylori eradication plus PPI treatment is necessary.     

The appropriate time for the assessment of Helicobacter pylori eradication

As all of the guidelines on the management of H. pylori infection suggest, the assessment of the eradication is generally performed at least 4 weeks after the completion of eradication treatment. However, H. pylori occasionally re-appears after one month, even the successful eradication was confirmed by the guideline. In this study, we investigated the appropriate time for the assessment of H. pylori eradication, mainly by using 13C urea breath tests (UBT) as a positive standard. From July 1992 to December 1997, 386 patients with H. pylori infection received eradication treatments. The presence of H. pylori was assessed by rapid urease test, UBT, culture and histologic examination. Eradication of the bacteria was determined by the negative results in all of these four tests. At 4 weeks after completion of therapy, 312 cases (80.8%) were judged as being free of H. pylori. Mean observation period was up to 12 months, and 113 cases were followed up to more than 1 year, and 50 cases were followed up to more than 2 years. H. pylori had re-appeared in 3 cases after 3 months, 1 case after 6 months, 2 cases after 12 months, and 1 case 24 months after the treatment, respectively. For the purpose of more accurate diagnosis, the assessment of eradication of H. pylori should be performed at 1 year after the completion of therapy. Since all the recrudescence could be diagnosed with UBT earlier and be confirmed by the other tests later, UBT is recommended as a useful methods in the assessment of Helicobacter pylori eradication.     

高原地区幽门螺杆菌相关溃疡血清白细胞介素-2和白细胞介素-4水平变化及意义

目的测定青海地区幽门螺杆菌(Hp)相关溃疡患者血清白细胞介素-2(IL-2)和白细胞介素-4(IL-4)的水平,观察根除Hp治疗对其的影响,以探讨Hp在溃疡发病中的可能免疫致病机制,为临床治疗提供理论依据。方法应用放射免疫法测定55例(Hp感染30例,非Hp感染25例)溃疡患者血清IL-2和IL-4的含量,比较Hp感染与非感染患者其含量的差异,对Hp阳性者进行以洛赛克为中心的三联根除治疗,比较Hp根除前、后及Hp根除者和未根除者其含量的差异,同时比较Hp根除组和未根除组溃疡的愈合率。结果Hp感染者血清IL-4含量明显低于非感染者(P<0.01),Hp根除后明显高于根除前(P<0.001),Hp未根除者前后无变化(P>0.05),Hp根除者明显高于未根除者(P<0.05),Hp根除组溃疡愈合率明显高于Hp未根除组(P<0.05)。而IL-2在Hp感染者与非感染者中差异无显著性(P>0.05),根除Hp治疗对其亦无明显影响(P>0.05)。结论Hp感染后IL-4分泌减少引起的TH2弱势应答为本地区Hp相关性溃疡发生的主要免疫致病机制,对Hp阳性的溃疡患者进行根除Hp治疗可调节优势免疫应答类型和TH1/TH2平衡,从而达到治疗疾病的目的。     

The trend of the research on H. pylori eradication and gastric cancer prevention

The strongest evidence for the association between H. pylori infection and gastric cancer(GC) development in the current is provided by the prospective study that a large number of patients with H. pylori infection were followed with serial endoscopic examinations. Over time, GC was not diagnosed in negative patients. In contrast, the risk for GC was highly increased in positive patients. It was also revealed that in patients with early GC subjected to endoscopic mucosal resection but without eradication therapy, new GC was found in 13% as opposed to only 1% on GC relapse during 8 years in patients with eradication. These studies indicate that some positive patients should be eradicated to reduce the progression of ongoing gastric carcinogenesis.     

Relationship between the birth cohort pattern of Helicobacter pylori infection and the epidemiology of duodenal ulcer

BACKGROUND: Helicobacter-pylori-related duodenal ulcer (DU) is an important cause of dyspepsia. AIM: To determine the relationship between the pattern of H. pylori infection and the epidemiology of duodenal ulcer in a single population. DESIGN: Prospective two-part study of (i) patients with DU referred for endoscopy because of dyspepsia, and (ii) the incidence of H. pylori infection in the general population of the same area. METHODS: Details of 533 DU patients were recorded, and related to the pattern of H. pylori infection among 10 537 adults in the same community, determined by the (13)C-urea breath test. RESULTS: In patients with DU, birth year was more important than age in determining the rate of presentation for endoscopy (the 'birth cohort' effect). H. pylori infection showed a similar birth cohort effect, and the prevalence decreased steadily in those born in successive years, from 28.8% in the 1930s to 3.5% in the 1970s. The proportion of dyspeptic patients who had duodenal ulcers also fell progressively, from 22.2% in 1979 to 5.7% in 1998. H. pylori prevalence and duodenal ulcer incidence were closely correlated at all ages. DISCUSSION: Duodenal ulcer prevalence (as judged by the rate of referral of duodenal ulcer patients for endoscopy) is determined principally by the distribution of H. pylori infection in the local population. The birth cohort effect seen in adult duodenal ulcer patients reflects the acquisition of H. pylori in childhood. In Bristol, H. pylori prevalence and duodenal ulcer incidence are both declining to very low levels.     

Course of duodenal ulcer disease depending on personality type and effectiveness of differential psychotropic therapy

AIM: To determine features of duodenal ulcer (DU) course as regards personality traits and to validate a differentiated approach to psychopharmacological correction of such patients. MATERIAL AND METHODS: The personality type was determined in 102 DU patients using an experimental psychological examination. RESULTS: Among the examinees, submissive and excitable personalities predominated (56.9 vs 43.1%, respectively). Submissive personalities were anxiously accentuated, moderately psychically rigid and moderately neurotic. Morphologically, they had diffuse fundal and antral gastritis with moderate H. pylori dissemination, intact acid production, ulcer size > 1 cm. Excitable personalities had antral gastritis with moderate H. pylori dissemination, high acid production, ulcer defect 0.6-0.9 cm. CONCLUSION: Anti-acid and eradication therapy in combination with individual psychotropic therapy (amitriptilin in submissive and nozepam in excitable personalities) reduced the time of DU healing and prevent recurrence for one year.     

H2-receptor antagonist-refractory ulcer--its pathophysiology and role of proton-pump inhibitors]

Among H2-receptor antagonist (H2RA)-refractory ulcers, non-responders that did not heal after 5 months therapy had high intraluminal pH in the basal condition and high sensitivity to inhibition of acid secretion by H2RA but possessed gastric mucosa to generate less prostaglandins. Combination therapy of PGE1-analogue with H2RA healed these ulcers by 60%. Proton-pump inhibitor (PPI) exerted a complete inhibition of acid secretion in these patients and the rate of healing was 88%. Helicobacter pylori was present in the mucosa of all 4 ulcer patients refractory to treatment with PPI. The ulcers healed in 3 out of 4 patients after eradication of H. pylori. It is suggested that PG supplement or complete inhibition of acid secretion is effective for ulcers in H2RA-non-responders. PPI-refractory ulcers may relate to H. pylori infection.