Helicobacter Pylori Eradication Therapy in both Erosive and Non-erosive Gastritis — A Prospective Study

Background: Infection with Helicobacter pylori (H. pylori) is a recognized cause of peptic ulcer and gastritis. Persistence of infection is a definite risk factor for gastric malignancy. Healing of gastritis after eradication of H. pylori reduces the risks of peptic ulcer disease and gastric malignancy. Objectives: To find out the relationship of H. pylori with erosive and nonerosive gastritis, the effect of anti-H. pylori therapy and to compare the effects of anti-H. pylori therapy between two types of gastritis. Materials and Methods: This prospective study was done in the Gastroenterology department of Bangabandhu Sheikh Mujib Medical University, Dhaka from June 2008 to May 2009. One hundred eighty dyspeptic patients were enrolled for the study. Patients with gastritis diagnosed by endoscopy underwent rapid urease test (RUT). RUT positive patients were considered to have H. pylori infection and were treated with triple therapy (omeprazole, amoxycillin and metronidiazole) for 14 days. Treatment responses were assessed by clinical history and also by endoscopic biopsy and RUT. Results of endoscopic findings and RUT after treatment were compared with pretreatment status. Results: Seventy patients completed the treatment and finally could be assessed. Endoscopic findings of 70 patients revealed that 56 (80%) patients had erosive gastritis and 14 (20%) patients had nonerosive gastritis. After treatment, 47 (67.1%) lesions became normal, 16 (22.9%) remained erosive and 7 (10%) non-erosive as before. Out of 14 non-erosive diseases, 7 became normal, while out of 56 erosive diseases 40 became normal. The erosive group responded significantly better than the non-erosive group (χ2=32.766, p<0.001). Fifty nine (84.3%) patients with gastritis showed negative urease test after treatment. Conclusion: Strong relation between H. pylori infection and gastritis was found. Majority were antral erosive gastritis. Erosive group responded better than non-erosive group.


Helicobacter Pylori Eradication Therapy in both Erosive and Non-erosive Gastritis -A Prospective Study
There are certain subtle changes in gastric mucosa which can be due to H. pylori and these changes are evaluated to predict the presence of H. pylori.
According to modified Sydney system of classification, the "abnormal" looking endoscopic features of gastric mucosa are erythema/exudation, erosion (raised or flat), mosaic pattern or cobble stoning, hypertrophic rugae, atrophic (thinning of the mucosa accompanied by visibility of ramifying vessels) and nodular appearance. 5ite-base lesions, raised or flat, surrounded by a margin of intense erythema are designated as erosive gastritis.Unequivocal eythema/exudation, mosaic pattern, hypertrophic rugae, atrophic and nodular appearance at endoscopy are features of non-erosive gastritis. 5The rapid urease test (RUT) can detect H. pylori within one hour with a satisfactory accuracy (>90%) and is acceptable to initiate eradication therapy. 6mbined antibiotic therapy is routinely used to treat H. pylori infection.The success of treatment in H. pylori i n fection depends mainly on antibiotic sensitivity.Triple therapy, including two antibiotics, amoxycillin and clarithromycin, and a proton pump inhibitor (PPI) given for 2 weeks has been recommended as the treatment of choice at several concensus conferences, but increasing antibiotic resistance is a problem. 6,7e aim of the study was to find out the relationship of H. pylori infecion with erosive and non-erosive gastritis, effect of anti-H.pylori therapy on both types of gastritis and also to compare the effects of anti-H.pylori therapy on erosive and non-erosive gastritis.

History and physical examination
After taking history and physical examination, patients were referred for upper GI endoscopy.Patients receiving PPI, H 2 -receptor blocker (H 2 RB) and antibiotic were advised to come for endoscopy after stopping these drugs for at least two weeks.

Upper GI endoscopy
Selected patients underwent upper GI video endoscopy by experienced gastroenterologists.Endoscopic inflammation was defined as the presence of visible alterations of the mucosal appearance, presumably caused by vascular or infiltrative changes.Endoscopic or macroscopic inflammation was diagnosed when at least one of the abnormalities described below was unequivocally visible, either focally or diffusely, but most often a combination of abnormalities was found.White-base lesion (raised or flat) surrounded by a margin of intense erythema was designated as erosive gastritis.
The intervening mucosa was usually normal or simply erythematous.Unequivocal eythema/exudation, mosaic pattern, hypertrophic rugae, atrophic and nodular appearance at endoscopy were designated as features of non-erosive gastritis.Endoscopic findings suggestive of erosive and non-erosive gastritis were documented with the clinical history.Biopsy specimens were collected from the predominant site of gastritis and rapid urease tests (RUT) for H. pylori were done instantly.Following findings were noted on the data sheet.

Rapid urease test (RUT)
RUT was done with one of the specimens of the predominant site of gastritis using CLO test (Campylobacter-like organism test) kit for diagnosis of gastritis and was repeated four weeks after the completion of anti-H.pylori therapy.H. pylori status was defined by RUT.

H. pylori eradication therapy
All the patients with erosive and non-erosive gastritis with positive RUT were treated with anti-H.pylori therapy consisting of omeprazole (20 mg bd), metronidazole (500 mg bd) and amoxycillin (1 gm bd) for 14 days.

Follow-up
Follow-up visits were made for compliance and sideeffects.After completion of therapy, clinical history was again taken and compared against the pretreatment symptoms.Follow-up endoscopy was performed at least four weeks after completion of therapy.At least two weeks period, free of any PPI, H 2 RB or antibiotics prior to follow-up endoscopy were ensured.Improvement in the endoscopy findings was noted and compared with pre-treatment findings.Biopsy specimens were collected from antrum of the stomach for RUT.

Statistical analysis
Frequency of H. pylori infection was calculated among endoscopically proven gastritis patients.Clinical features, endoscopic findings, pre-and posttreatment disease status were compared.SPSS (Statistical Package for Social Services) 10.0 was used for statistical calculations.

Results
Total 180 dyspeptic patients underwent upper GI endoscopy.One hundred and ten patients had gastritis of which 79 had erosive and 31 had nonerosive gastritis (Table I).Among 110 gastritis patients, 78 (71%) were RUT positive and 32 (29%) were RUT negative (Table I).Out of 78 H. pylori positive patients 59 (76%) with erosive and 19 (24%) with non-erosive gastritis were treated and followedup subsequently.During the course of treatment eight patients were dropped-out.Finally, 70 patients returned for follow-up after completion of therapy and biopsy was taken from antrum for RUT.In most persons, H. pylori i n fection is largely restricted to the gastric antrum.Studies showed that H. pylori occurs in the antrum in at least 85% of patients with the disease, and in up to 15% of patients the organism is found only in the corpus. 11,12e found that 81.5% of RUT positive gastritis were located at antrum, 11.4% on the body of stomach, and 7.1% were diffusely distributed.
There is a great deal of ignorance about the normal macroscopic appearance of the gastric mucosal lining.Many of the appearances which endoscopists interprete as "Normal" are presumably not normal. 12,13Endoscopic findings such as erythema are frequently labeled as gastritis despite a long recognized lack of evidence supporting a correlation between endoscopic features and histologic gastritis. 14Some authors believe that there are certain subtle changes in gastric mucosa which can be due to H. pylori. 15 this study, we found that 80% had erosive gastritis and 20% non-erosive gastirits; all were RUT positive H. pylori gastritis.White-base lesion (raised or flat) Perhaps up to 40% or more of patients with endoscopically normal mucosa have histological gastritis visible on biopsy. 5When erythema is the most conspicuous endoscopic abnormality, histologic chronic gastritis has been found in 75% or more of patients. 13en the endoscopic changes are more pronounced and erosions or frank atrophic gastritis are present, there are almost always corresponding histologic inflammatory changes.In general, the more severe the endoscopic gastric abnormality, the better the correlation with histology. 14,16In this study we followed Sydney system --endoscopic appearance of gastritis for diagnosis of gastritis without histology. 5an et al 16 observed that the erythematous gastritis was the commonest single endoscopic finding and H. pylori was present in 74% of cases.Stolte and Edit 17 concluded that chronic erosion of the antral mucosa represents sequelae of H. pylori gastritis, and these H. pylori induced chronic erosion which in future would be differentiated from other erosions.The antral erosion showed the specificity of 92% and sensitivity of 22% with positive predictive value of 86% to H. pylori infection.The raised erosions were more precisely associated with H. pylori infection than flat erosions.H. pylori was strongly associated with gastritis 2 , 75% patients with gastritis were positive compared with 10% without gastritis (p<0.001).In this study, H. pylori infection rate in gastritis was 71%.
In eradication studies 18 there is continuing debate whether dyspeptic symptoms diminish with anti-H.pylori treatment.This is partly because of the high placebo-response rate and partly because many treatment regimens have not cured the infection.Suppression of bacterial growth may not affect symptoms significantly, if these are due to mucosal inflammation, and symptom resolution may take many weeks or months following cure of H. pylori and the associated gastritis.
In Due to patchy distribution of H. pylori infection after antibiotics or PPIs, biopsy for the RUT should be taken from two sites, the body at the gastric angularis and greater curvature of the antrum. 20Due to lack of facilities, we took biopsy from only predominant site of gastritis before treatment and only from antrum after treatment for RUT for diagnosis and assessment of eradication respectively.
In the current study, H. pylori status was considered to be positive by positive RUT.According to this criterion, out of 110 endoscopically proven gastritis patients, 71% had H. pylori gastritis.The remaining 29% patients were negative for RUT.This discordant result might be due to noncompliance of patients regarding prior use of PPI, H 2 RB, antibiotics or gastritis due to some other causes.
Non-invasive tests like urea breath test and stool antigen test should be employed for confirmation of eradication except in cases where repeat endoscopy is indicated, for example in patients with gastric ulcer. 19As repeat endoscopy was done to see the changes of gastritis after triple therapy, RUT tests were done for confirmation of eradication.
The treatment of H. pylori is a challenging clinical problem due to antimicrobial resistance and falling eradication rates.The third Maastricht Consensus Report agreed that effective treatment for H. pylori should achieve an intention-to-treat (ITT) eradication rate of over 80%. 6However, in clinical practice eradication rates are lower than 80% for many of the standard treatment regimes.A number of factors such as duration of treatment, choice of antibiotics, new drug combination, improved patient compliance and novel agents may help to improve eradication rates. 6,7 used PPI-amoxycillin-metronidazole for 14 days as anti-H.pylori regimen in this study.This regimen was chosen as majority of our patients were poor.In this regimen the eradication rate was 89% and 64% for metronidazole susceptible and resistant strains, respectively.In a clinical trial using anti-H.pylori treatment, the global eradication rate was 64%. 21his study showed that 84.3% of H. pylori gastritis exhibited negative RUT tests 4 weeks after treatment with triple therapy.We assumed that eradication rate after treatment was 84%.In the present study, strong relationship between H. pylori infection and gastritis was found.Majority cases had antral erosive gastritis.After treatment with H. pylori eradication therapy, significant improvement of endoscopic feature of gastritis occurred and erosive group responded better than non-erosive group.

Table IV :
Rapid urease test after treatment (n=70) 9,10So H. pylori infection and H. pylori gastritis should be identified and treated.

Table II :
Distribution of patients by clinical presentation (n=70*) Total figure will not correspond to frequency and percentage shown as many patients had multiple presentations surrounded by a margin of intense erythema was designated as erosive gastritis.Unequivocal eythema/exudation, mosaic pattern, hypertrophic rugae, atrophic and nodular appearance at endoscopy were designated as features of non-erosive gastritis. * The simplicity, low cost, and relatively rapid results make the RUT a practical and cost-effective means of testing for H. pylori in patients not taking antibiotics, bismuth, or PPIs who require upper GIT endoscopy.For these reasons, RUT was used as single test for diagnosis of H. pylori gastritis in this study.