A four-year follow-up of duodenal ulcer patients after Helicobacter pylori eradication.

BACKGROUND/AIMS: The aim of our study was to evaluate the clinical course of disease in 63 duodenal ulcer (DU) patients during a 4-year follow-up after Helicobacter pylori (H. pylori) eradication. METHODOLOGY: Upper gastrointestinal endoscopy and a clinical interview were performed before antimicrobial therapy, 2 months after, yearly and when symptoms recurred. Two antral and two corporal specimens were taken for histology, and one additional specimen from antrum was taken for rapid urease test at the first endoscopy and for culture at the following endoscopies. All patients received triple antimicrobial regimens based on colloidal bismuth subcitrate, amoxycillin and metronidazole for at least 2 weeks. Patients with a negative histology and culture 2 months after antimicrobial therapy were included in the study. RESULTS: After H. pylori eradication, ulcer recurrence dropped from 84.1% per year in the year before H. pylori eradication to a mean value of 5.2% per year during 2076 patient months (p<0.01). The increased incidence of gastroesophageal reflux disease (GERD) was found only in the first year of the follow-up period. The average percentage of anti-ulcer drug users per year was 30.8% because of GERD, reflux symptoms, ulcer recurrence or non-ulcer dyspepsia. Ulcers or acute erosions recurred in 9 H. pylori-negative patients; recurrences were attributable to non-steroidal anti-inflammatory drugs (NSAID) in 4 out of 9 cases (44.4%). CONCLUSIONS: H. pylori eradication changed the long-term course of DU disease.     

Helicobacter pylori eradication improves pre-existing reflux esophagitis in patients with duodenal ulcer disease.

BACKGROUND & AIMS: There has been significant controversy over the relationship between Helicobacter pylori infection and reflux esophagitis. We investigated the effects of eradicating H. pylori on the reflux esophagitis found in patients with peptic ulcers. METHODS: Prospective posteradication evaluations were conducted yearly in 162 H. pylori-positive patients who had reflux esophagitis together with peptic ulcer disease (4 women and 158 men, mean age = 49.1 yr). The Los Angeles classification of the patients' esophagitis was: grade A, 90; grade B, 63; and grade C, 9. The follow-up evaluations began 1 to 2 months after completion of the eradication treatment (mean time of follow-up = 22 mo), and consisted of endoscopy and an interview focusing on heartburn. RESULTS: Six patients were withdrawn from the study because of adverse drug reactions or a failure to regularly keep their appointments. After eradication therapy, we observed endoscopically that reflux esophagitis had improved in 87 (55.8%) of the 156 patients. The improvement rate was significantly higher in patients cured of infection (60.8%) than in those with persistent H. pylori infection (38.9%) (P = 0.04). Body mass index (odds ratio = 0.86, 95% confidence interval [CI] = 0.76-0.97), cure of infection (3.68, 95% CI = 1.56-8.69), the absence of a hiatal hernia (3.90, 95% CI = 1.83-8.28), and an ulcer located in the duodenum (2.75, 95% CI = 1.33-5.70) were identified as significant independent factors for the improvement of reflux esophagitis. CONCLUSIONS: In patients with reflux esophagitis associated with duodenal ulcer, a significant improvement in pre-existing reflux esophagitis was noted after H. pylori eradication.     

Effect of Helicobacter pylori eradication on the treatment of gastro-oesophageal reflux disease

The important issue of whether Heliobacter pylori eradication leads to increased reflux has been the subject of many apparently contradictory publications, but when we asked two leading authorities to give us their views, there turned out to be considerable consensus, as you can read below.     

Helicobacter pylori genotypes and expression of gastritis in erosive gastro-oesophageal reflux disease

BACKGROUND: Epidemiological studies suggest a negative association between Helicobacter pylori and gastro-oesophageal reflux disease (GORD). Moreover, cagA-positive strains are reported to protect from complications of GORD. The aim of this study was to determine virulence factors (cagA, vacA and iceA) of H. pylori strains and the pattern of gastritis in patients with GORD in comparison with patients with duodenal ulcer (DU) or functional dyspepsia (FD). METHODS: H. pylori strains isolated from gastric biopsies of 105 consecutive patients with mild to moderate erosive GORD (n = 35, LA grade A-B), and from sex- and age-matched patients with DU (n = 35) or FD (n = 35 without reflux symptoms) were investigated. CagA, vacA, and iceA genotypes were determined by PCR analysis of the isolates. Gastritis was classified in accordance with the updated Sydney classification. RESULTS: The prevalence of all three H. pylori virulence factors was higher in patients with GORD (cagA+ 80%, vacA s1 77%, iceA1 71%) and DU (cagA+ 83%, vacA s1 80%, iceA1 74%) than in patients with FD (cagA+ 40%, vacA s1 49%, iceA1 46%). Gastritis activity in the antrum and corpus did not differ between the three groups. However, lymphocytic infiltration of the gastric antral mucosa was more pronounced in DU patients than in those with GORD or FD. CONCLUSIONS: H. pylori strains obtained from patients with mild to moderate erosive GORD show a virulence pattern similar to that found in DU patients. The presence of these virulence factors does not appear to protect against erosive lesions in the oesophagus.     

Helicobacter pylori and gastro-oesophageal reflux disease: a cross-sectional epidemiological study

BACKGROUND: H. pylori infection is accompanied by a lower prevalence of reflux disease. There is still an ongoing debate as to whether H. pylori actually protects against the development of reflux oesophagitis or is merely an epiphenomenon. A cross-sectional study was performed to study the relation of H. pylori with reflux oesophagitis, hiatus hernia and Barrett's oesophagus. MATERIAL AND METHODS: Consecutive patients undergoing upper gastrointestinal endoscopy in a period of ten years were studied. Included were patients with active reflux oesophagitis and/or hiatus hernia and/or Barrett's oesophagus. As a reference group, patients without macroscopic abnormalities were included. H. pylori was detected applying routine diagnostic modalities. RESULTS: In the ten years 11,691 consecutive patients were studied. Reflux oesophagitis was seen in 1535 patients, 307 patients had Barrett's oesophagus and a hiatus hernia was present in 2116 patients. The reference group consisted of 5341 patients. H. pylori was significantly less often detected in patients with reflux oesophagitis or Barrett's oesophagus compared with the reference group, 20 vs 29% (p<0.001). Also presence of H. pylori was significantly lower in patients with hiatus hernia 20 vs 29% (p<0.0001). CONCLUSION: The present study confirms, in a very large group of patients studied in one single centre, the findings of earlier papers. Patients without H. pylori gastritis suffer more often from reflux disease. There is a relation between H. pylori and reflux disease. However, the consequence of this relation will not be the same in every patient.     

Hypersecretory duodenal ulcer and Helicobacter pylori infection: a four-year follow-up study.

BACKGROUND: About 10% of duodenal ulcer patients are characterized by gastric acid hypersecretion with normal gastrin values. Relapsing duodenal ulcer after Helicobacter pylori cure has been related to high acid output and maintenance antisecretory therapy has been suggested in hypersecretory duodenal ulcer patients. The role of Helicobacter pylori infection and the effects of Helicobacter pylori cure in hypersecretory duodenal ulcer patients still remain to be fully studied. AIM: To study: a) whether gastric acid hypersecretion "per se" is a risk factor for duodenal ulcer recurrence; b) whether maintenance antisecretory therapy is necessary after eradication in hypersecretory duodenal ulcer patients. PATIENTS: The study population comprised 8 hypersecretory duodenal ulcer patients, selected from a population of 79 Helicobacter pylori-positive duodenal ulcer patients. METHODS: Hypersecretory duodenal ulcer patients were followed-up for at least 4 years after eradication. Gastric acid secretion was measured again 12 months after Helicobacter pylori eradication. Gastroscopy with histology was performed 3, 6, 12 and 36 months after treatment, 13C-urea breath test after 42 months; clinical questionnaires were completed every 6 months. RESULTS: After eradication, despite a not significantly reduced high acid output (median value of basal acid output and pentagastrin-stimulated acid output, respectively, 23.1 mEq/h and 64.1 mEq/h before treatment vs 16 mEq/h and 49.7 mEq/h 12 months after treatment), all patients were free from symptoms, none of them had duodenal ulcer relapse or complications (7/8 before treatment), or needed antisecretory maintenance therapy, except for one patient taking non-steroidal anti-inflammatory drugs. CONCLUSIONS: These findings, obtained in a selected population of hypersecretory duodenal ulcer patients with long-term follow-up, suggest that after successful Helicobacter pylori eradication gastric acid hypersecretion "per se" is not able to determine the recurrence of duodenal ulcer.     

Prognostic influence of Barrett's oesophagus and Helicobacter pylori infection on healing of erosive gastro-oesophageal reflux disease (GORD) and symptom resolution in non-erosive GORD: report from the ProGORD study

BACKGROUND: Adequacy of acid suppression is a critical factor influencing healing in gastro-oesophageal reflux disease (GORD). The European prospective study ProGORD was set up to determine the endoscopic and symptomatic progression of GORD over five years under routine care, after initial acid suppression with esomeprazole. We report on factors influencing endoscopic healing and symptom resolution during the acute treatment phase. METHODS: Patients with symptoms suggestive of GORD underwent endoscopy and biopsies were obtained from the oesophagus for diagnosis of abnormalities, including Barrett's oesophagus (BO). Data from 6215 patients were included in the "intention to treat" analysis, 3245 diagnosed as having erosive reflux disease (ERD) and 2970 non-erosive reflux disease (NERD). ERD patients were treated with esomeprazole 40 mg for 4-8 weeks for endoscopic healing while NERD patients received 20 mg for 2-4 weeks for resolution of heartburn symptoms. RESULTS: Endoscopic healing occurred overall in 87.7% of ERD patients although healing was significantly lower in those with more severe oesophagitis (76.9%) and in those with BO (72.4%), particularly in Helicobacter pylori negative BO patients (70.1%). Age, sex, and body mass index appeared to have no significant impact on healing. Complete heartburn resolution was reported by 70.4% of ERD patients and by 64.8% of NERD patients at the last visit. Only H pylori infection had a significant influence on complete heartburn resolution in the NERD group (68.1% and 63.7% for H pylori positive and H pylori negative, respectively; p = 0.03). CONCLUSION: The presence of Barrett's mucosa, as well as severe mucosal damage, exerts a negative impact on healing. H pylori infection had a positive influence on healing in ERD patients with coexistent BO but no influence on those without BO.     

High prevalence of reflux symptoms in duodenal ulcer patients who develop gastro-oesophageal reflux disease after curing Helicobacter pylori infection

BACKGROUND: Gastro-oesophageal reflux disease may develop following eradication of Helicobacter pylori. However gastro-oesophageal reflux disease could be preexistent and misdiagnosed since patients often misinterpret gastro-oesophageal reflux disease symptoms or focus their attention on abdominal symptoms. A questionnaire for analysis of gastro-oesophageal reflux disease symptoms has not been used until now. METHODS: A total of 70 patients with duodenal ulcer and Helicobacter pylori gastritis, without oesophagitis and/or typical gastro-oesophageal reflux disease symptoms were studied. All patients received a questionnaire with 5 items focused on abdominal symptoms and 5 on gastro-oesophageal reflux disease symptoms. The two symptom scores were calculated separately. After Helicobacter pylori treatment, follow-up consisted of clinical controls every 3 months for 1 year. Patients were asked to describe their complaints and to answer the questionnaire. If gastro-oesophageal reflux disease symptoms recurred endoscopy was performed. RESULTS: At interview, all patients reported a significant improvement in their abdominal symptoms after eradication; however 23 patients (32.8%: group A) reported the occurrence of gastro-oesophageal reflux disease symptoms, and 5 of them developed oesophagitis; gastrooesophageal reflux disease symptoms did not appear in the remaining 47 patients (group B). Basal gastro-oesophageal reflux disease score was significantly higher in group A than in group B (1.9+/-1.5 vs 0.9+/-0.9, p<0.005), while the abdominal symptoms score was not different. Following eradication, the score for abdominal symptoms decreased significantly (4.2+/-1.5 vs 1+/-0.8, p<0.0001) in the two groups; conversely, the total gastro-oesophageal reflux disease score remained unchanged, improving in 2 patients in group A and 11 in B, and worsening in 5 in group A and in 1 in B. Presence of hiatus hernia and male sex significantly correlated with the development of reflux symptoms. CONCLUSIONS: Patients who present with gastro-oesophageal reflux disease after Helicobacter pylori eradication are likely to already be affected by gastro-oesophageal reflux disease.     

"Reappearance" of Helicobacter pylori after eradication: implications on duodenal ulcer recurrence: a prospective 6 year study.

We estimated the rate of Helicobacter pylori "reappearance" and of duodenal ulcer relapse up to 6 years after eradication of H. pylori. Of 220 patients in whom H. pylori was eradicated, 165 were eligible at 12 months to follow-up. Endoscopy was scheduled every 12 months or whenever symptoms appeared. Baseline H. pylori eradication was confirmed by CLO test, histology (hematoxylin-eosin and Giemsa stain), and culture. H. pylori was tested for by the three methods at 12 months and subsequently by 2 methods (CLO, histology) on biopsies obtained from the gastric antrum and body. We reviewed 90 patients after 1 year, 32 after 2 years, 13 after 3 years, 12 after 4 years, 2 after 5 years, and 16 after 6 years (range, 12 to 72 months; average, 25.23 months; patient-years, 347). At 12 months after eradication, 16 of 165 patients (9.7%) were H. pylori positive and 5 had ulcer relapse. Of 75 patients evaluated at 24 months, 7 (9.3%) were H. pylori positive and 1 (1.3%) had ulcer relapse. At 36 months, 43 patients were seen and 1 (2.3%) was H. pylori positive and had ulcer relapse (2.3%). Thirty, 18, and 16 patients were seen at 48, 60, and 72 months, respectively. None was H. pylori positive and none had ulcer relapse. Overall, 24 H. pylori-positive patients were found, two thirds of them in the first year after eradication. In 7 of 24 (29%, 6 smokers), ulcer recurred. None of the H. pylori-negative patients had ulcer relapse. The H. pylori reappearance rate was 7% and the ulcer relapse rate was 2% per patient-year. If the 16 H. pylori-positive patients who were found the first year are considered as recrudescence, then the reinfection rate will be 2.3% per patient-year.     

Response of blood endothelin-1 and nitric oxide activity in duodenal ulcer patients undergoing Helicobacter pylori eradication

AIM: To investigate the effect of Helicobacter pylori eradication on endothelin-1 (ET-1) and nitric oxide (NO) in duodenal ulcer (DU) patients. METHODS: Sixty-six Hpylori-infected active DU patients were consecutively enrolled to receive one-week triple therapy (rabeprazole, amoxicillin and metronidazole) and then one-month rabeprazole therapy. They were asked back to determine ulcer and Hpylori status using endoscopy one month later. Thirty-seven healthy controls (H pylori +/-:17/20) were enrolled for comparison. Blood samples were collected in each visit to measure plasma ET-1 and nitrate/nitrite levels using an enzyme immunoassay kit. RESULTS: Sixty DU patients finished trial per protocol. The ulcer healing and Hpylori-eradication rates were 86.7% and 83.3%, respectively. Plasma ET-1 level in DU patients was higher than that of Hpylori-negative and positive controls (3.59±0.96 vs0.89±0.54 vs0.3±0.2 pg/mL,P<0.01), while nitrate/nitrite levels among them were also significantly different (8.55±0.71 vs5.27±0.68 vs 6.39±0.92 μmol/L, P<0.05). H pylori eradication diminished ET-1 levels (3.64±0.55 vs2.64±0.55 pg/mL, P<0.01) but elevated nitrate/ nitrite level (8.16±0.84 vs11.41±1.42 umol/L,P<0.05). CONCLUSION: Both plasma ET-1 and nitrate/nitrite levels increase in active DU patients. After an effective H pylori eradication, DU healing is associated with diminished blood ET-1 level and elevated nitrate/nitrite level.     

Medical treatment of duodenal ulcer: Acid inhibition or Helicobacter pylori eradication?

To ascertain whether acid inhibition or Helicobacter pylori (HP) colonization is the decisive factor in the healing of duodenal ulcer, we treated 54 patients with famotidine and carried out long-term follow-up. Helicobacter pylori colonization was found in 70.4% of patients before treatment. There were no differences in the pre-treatment characteristics between patients with HP positive or HP negative ulcers. The 4-week and 8-week healing rates after famotidine treatment were 72.5% and 82.4% respectively. No difference in HP colonization was found between patients with ulcer healed and those with ulcer not healed (78.4% vs 64.3% at 4th week and 77.3% vs 71.4% at 8th week, P greater than 0.05). In patients with ulcer healed at 4th week, the intragastric pH was raised significantly and the antral acute inflammation was less severe than those with ulcer not healed. Ulcer recurrence was found in 76.9% of patients within 1 year, but there was no difference in ulcer recurrence between the patients with positive or negative HP colonization at the time of ulcer healing. Our results suggest that duodenal ulcer healing and recurrence are closely related to acid inhibition rather than to HP colonization.     

Acid secretory response in the late follow-up of proximal gastric vagotomy for duodenal ulcer without Helicobacter pylori eradication

BACKGROUND/AIMS: The profile of acid secretory responses was studied in 20 patients who had had proximal gastric vagotomy (PGV) surgery performed 11-22 years previously in order to treat duodenal ulcers (DU). The presence of Helicobacter pylori was detected in all of the patients. METHODOLOGY: The recurrence of DU was diagnosed in 10 patients and the other 10 remained without recurrence during the follow-up period. The control groups included 10 DU patients with refractory responses to H2 receptor antagonists and 10 "normal" subjects. Both control groups had untreated Helicobacter pylori infection. Measures of 1) basal acid output, 2) acid output for 30 min under continuous i.v. infusion of 0.2 ug/kg/h of pentagastrin acid, and 3) the response for 30 and 60 min after starting a sham feeding, modified by the "chew and spit" technique under simultaneous i.v. infusion of 0.2 ug/kg/h of pentagastrin were performed. Serum gastrin was measured during fasting and at sham feeding. The densities of the gastrin cells of antrum and duodenum were estimated by morphometric counting. RESULTS: Both basal output and acid response to sham feeding plus pentagastrin infusion were higher in the DU controls and DU recurrence patients. The response to pentagastrin infusion did not show any discriminant value. Fasting serum gastrin values increased after PGV, either with or without DU recurrence. Gastrin cell hyperplasia was not demonstrated in any of these groups. CONCLUSIONS: The secretory profile of patients with both late DU recurrence after PGV and Helicobacter pylori infection lies between DU patients refractory to the H2 receptor antagonist approach and those free of DU recurrence after PGV--both of them with current Helicobacter pylori infection. The characteristic pattern of late DU recurrence after PGV and untreated Helicobacter infection is that of increased basal acid output and higher acid secretion responsiveness to sham feeding plus pentagastrin in the presence of higher serum levels of gastrin.     

High prevalence of sustained remission of idiopathic thrombocytopenic purpura after Helicobacter pylori eradication: A long-term follow-up study

We studied the effect of Helicobacter pylori (H. pylori) eradication in 43 consecutive H. pylori-infected patients with idiopathic thrombocytopenic purpura. H. pylori was eradicated with antibiotics in 41 of them (95.3%). The difference between the mean platelet count before and after therapy was statistically significant (54.3?×?10⁹/l vs. 119.1?×?10⁹/l; P?<?0.001). A sustained remission was observed in 20 patients (48.8%), after a median follow-up of 31.2 months. None of the patients still infected by H. pylori after therapy reached normal platelet values. The long-term follow-up confirms the efficacy of H. pylori eradication in H. pylori-infected ITP patients.     

幽门螺杆菌根除后再感染与溃疡复发

为明确本地区患者幽门螺杆菌(Hp)根除后再感染和溃疡复发情况,本研究以~(14)C-尿素呼气试验和胃镜检查(尿素酶、组织学及细菌培养),对十二指肠溃疡患者 Hp 根除后共184例进行2年定期随访,并配合随机引物扩增的 DNA 多态指模技术鉴定 Hp 复发与再感染。结果发现:Hp 根除后第1、2年再感染率为0.55%和0.56%;Hp 持续阴性者仅有1.1%溃疡复发;全部病例未发生溃疡出血,而同期 Hp 无根除的对照组2年溃疡累积再出血率为26.6%(P<0.005)。结果证明,成人患者 Hp 根除后对 Hp 再感染不易感,发展中国家 Hp 根除后再感染率也相当低,以预防溃疡复发为目的的 Hp 根除疗法同样适用于高 Hp 感染率地区。