Colloidal bismuth subcitrate in non-ulcer dyspepsia.MU Khanna, P Abraham, NG Nair, FP Mistry, IM Vora
Dept of Gastroenterology, KEM Hospital, Parel, Bombay, Maharashtra.
The effect of colloidal bismuth subcitrate (De-Nol) on symptoms, Helicobacter pylori status and histological features was studied in 35 patients with non-ulcer dyspepsia. Pain (34 cases) and gas bloat (18) were the predominant symptoms. H pylori was present in 26 (74.3%) patients. Gastritis and duodenitis were present in 29 of 32 and 22 of 31 cases respectively in whom biopsies were available. Relief in symptoms after treatment was seen in 29 (82.8%) cases. Improvement in gastritis and duodenitis was noted in 60.8% and 58.8% respectively; over 70% of H pylori positive patients cleared the organism. These changes did not correlate with the relief in symptoms. We conclude that colloidal bismuth subcitrate is effective in the short term treatment of non-ulcer dyspepsia. It also clears H pylori infection and results in improvement of histological features.
Keywords: Adult, Antacids, therapeutic use,Anti-Ulcer Agents, therapeutic use,Biopsy, Bismuth, therapeutic use,Duodenitis, drug therapy,pathology,Dyspepsia, drug therapy,pathology,Female, Gastritis, drug therapy,pathology,Helicobacter Infections, drug therapy,Helicobacter pylori, Human, Male, Middle Age, Organometallic Compounds, therapeutic use,Support, Non-U.S. Gov′t,
Non-ulcer dyspepsia (NUD) is a heterogenous disorder with upper gastrointestinal symptoms but without any consistent organic lesion detected. Though its association with gastritis, duodenitis and Helicobacter pylori has been reported, their causative relationship has not been conclusively proved. Treatment of NUD with various drugs has been reported, with variable results ,. We undertook this trial to study the relationship of H pylori infection, gastritis and duodenitis with NUD and the effect of colloidal bismuth subcitrate on these.
Patients with non-ulcer dyspepsia, i.e. those with meal-related upper gastrointestinal symptoms lasting for a minimum of four weeks, but without any focal lesion or systemic disease, were included in the trial. All patients underwent ultrasonography and upper gastrointestinal endoscopy. Patients with any abnormality on ultrasonography or on endoscopy except for gastritis and duodenitis were excluded from the study. Other exclusion criteria were: previous gastric surgery; ingestion of any drugs including non-steroidal anti-inflammatory drugs and drugs likely to modify upper gastrointestinal symptoms (e.g. anti-ulcer or prokinetic drugs) in the previous month; and pregnancy.
Thirty-five patients met these criteria and completed the study. Pre-treatment endoscopic biopsies were obtained from the antrum for the rapid urease test (CLO(R) test), culture and histopathology, and from the duodenum for histopathology. The biopsies were stained with haematoxylin and eosin for morphology and with Gimenez stain for H pylori. Warthin-Starry stain was used whenever the results with the Gimenez stain were doubtful. The biopsies were studied by a pathologist who had no prior knowledge of the clinical data and the results of the CLO(R) test. For culture the biopsies were transported in Brucella More Details broth and were incubated on blood agar medium under micro-aerophilic conditions.
Gastritis was graded according to a modified Whitehead classification as follows - grade 0: gastric histology within normal limits; grade 1: slight increase in mononuelear cells; grade 2: increase in mononuclear cells, and polymorphonuclear cells present; grade 3: increase in mononuclear and polymorphonuclear cells with polymorphonuclear cells invading the epithelium. Duodenitis was graded as follows - grade 1: mild increase in cellular infiltration, mainly mononuclear, in the lamina propria; grade 2: moderate mixed infiltration in the lamina propria with epithelial infiltration and regeneration; grade 3: marked mixed cellular infiltration with epithelial erosions and regeneration.
While the pre-treatment urease test was done in all patients, histopathology and culture were available in only 32 and 22 patients respectively. All patients had at least two of the three tests done. Patients were considered H pylori positive if any two of the three tests i.e. the CLO test, histopathology and culture were positive.
All patients received 240 mg of colloidal bismuth subcitrate (De-Nol (R)) twice a day for four weeks. 'Symptom re-evaluation was done at 2 and 4 weeks. At 4 weeks, endoscopy and the urease test were repeated in all patients. Culture could not be done at this stage. Endoscopic biopsies with histopathology were obtained in 26 patients; these patients were considered H pylon negative only if both urease and histopathology were negative.
Statistical analysis was done by the chi square test with Yates' correction.
The 35 patients who completed the study included 18 males and 17 females, aged 19-60 years. Tests for H pylon were positive in 26/35 (74.3%) patients at entry. The mean age of H pylori positive patients (31 years) was similar to that of the H pylon negative patients (32 years).
Pain was present in 34/35 patients while gas bloat was present in 18/35 patients. There was no difference in symptoms between the H pylon positive and negative groups [Table - 1].
Gastritis was seen in 29 of the 32 patients in whom histopathology was available. Its prevalence was similar in the H pylori positive and negative groups. Duodenitis was present in 22/31 (70.9%) patients, and was equally common in the H pylori positive and negative patients.
Symptomatic improvement by more than 50% after treatment was seen in 29/35 (82.8%) patients. Gas bloat responded less frequently (14/18) as compared to pain (29/34), though the difference was not statistically significant. Of the 26 pre-treatment H pylon positive patients, 19 had post-treatment urease and histopathology results available; 14 of these 19 (73.7%) had cleared the organism, i.e. both tests wer6 negative. Of the remaining 7 pre-treatment positive patients, 6 converted to u rease- negative. Symptomatic improvement was not related to initial H pylori status or to later clearance.
Improvement in gastritis was seen in 14 of 23 (60.8%) patients; eight of these showed a complete reversal to normal. Improvement was not related to initial H pylori positivity or subsequent clearance of the organism [Table - 2]. Improvement in duodenitis was seen in 10 of 17 patients, and was also not related to H pylori status or clearance. Symptomatic response was not related to the presence of gastritis or duodenitis on the initial biopsy or to the improvement in these on subsequent biopsy.
There were no clinical adverse effects noted on treatment.
We have found that the symptoms and occurrence of gastritis and duodenitis in non-ulcer dyspepsia are not related to the presence or absence of H pylori. Colloidal bismuth subcitrate improved symptoms in the majority (83%) of patients irrespective of H pylori status; at the same time it cleared H pylon in over 70% and led to improvement in histopathological features. However, there was no correlation between these beneficial effects.
The causative role of H pylon in antral gastritis has been reasonably well established. Convincing evidence for a true causal relationship was provided by the occurrence of gastritis after experimental ingestion of H pylon.
The role of gastritis and duodenitis in NUD is controversial. Some studies show a correlation between symptoms and gastritis, duodenitis or both. Others did not find any such relationship. The prevalence of H pylon positive astritis in NUD has been reported to be 37% to 61 %;,, this has been reported to be significantly higher than in age matched controls.10 We found an H pylon prevalence rate of 74% in NUD, We also found a high incidence of gastritis (29132) and duodenitis (22131) in our study; their presence was not related to the presence of H pylori.
The beneficial effect of colloidal bismuth subcitrate in NUD that we found concurs with other reports,. NUD is a symptomatically heterogenous condition, with symptoms suggestive of acid-peptic disease, gastro-cluodenal dysmotility and gastro-oesophageal reflux occurring alone or in combination. All these symptoms may not respond to the same extent with any given drug. This may at least partly account for the varying results obtained with similar treatment modalities in NUD.
Absence of H pylori on one test after treatment with colloidal bismuth may not necessarily mean clearance of the organism. However, we considered H pylori as negative post-treatment only if both urease and histopathology were negative; we got a conversion rate of over 70%. The response in symptoms that we noted was not related to the initial H pylori and histological status, and to subsequent changes in these; this differs from the conclusions of another recent study. Our study had its limitations: this was an open uncontrolled study, evaluating only the short-term response to the drug. On the other hand, the response rates that we found in symptoms and investigative features compare well with those reported in controlled trials in NUD where the drug has been found superior to placebo,.
We conclude that colloidal bismuth subcitrate effectively relieves symptoms in the short-term treatment of non-ulcer dyspepsia. It also clears H pylori infection and leads to improvement in the histological features.
We thank M/s Elder Pharmaceuticals, Bombay for the support they extended through the study and free supply of De-Nol (R) and CLO (R) strips. We also thank Dr Shobna J Bhatia for her help in preparing the manuscript.
[Table - 1], [Table - 2]