Rina Mohanty1, Manorama Swain2, Sanjib Kumar Kar3,
Shivaram Prasad Singh3 and Niranjan Rout4
1Department of Medicine, 2Department of Biochemistry, 3Department of Gastroenterology,
S. C. B. Medical College, Cuttack 753007, Odisha, India.
4A.H. Regional Cancer Centre, Cuttack 753007, Odisha, India.
Helicobacter Pylori infection is ubiquitous. Endoscopic Rapid urease test [RUT] is sensitive and specific for diagnosing H. Pylori organism during endoscopy. Retrospective analysis of the pattern of RUT performance by endoscopists in Southeast Bengal region in patients evaluated for upper gastrointestinal disorders. The gastroscopy reports of consecutive patients from South-eastern Bengal attending a gastroenterology clinic were studied. The data along with relevant treatment history were entered into a questionnaire and the data was analyzed. Data of 151 patients were analyzed. 16 patients with reflux oesophagitis and growth in duodenum were excluded. Out of 135 patients 47.4 % and 52.6% had peptic ulcers and non ulcer dyspepsia [NUD] respectively. Often males present with peptic ulcers and females with NUD (p=0.002). Rapid urease test (RUT) was positive in 40.62% and 33.80% of peptic ulcer and NUD patients respectively (p = 0.477). However 32.45% patients on “premedication” and 62% without “premedication’’were RUT positive, which was statistically significant (p= 0.014). There is also no difference (P >0.05) in endoscopic diagnosis or result of RUT performed by gastroenterologists or nongastroenterologists. 81.25% of RUT positive NUD patients who received Triple therapy for H. Pylori did not respond; but all [100%] responded to antidepressants. RUT was performed routinely in all patients undergoing gastroscopy irrespective of diagnosis. The RUT was performed without cognizance of pre-endoscopy treatment. “Pre-treatment” results in erroneous underestimation of H. Pylori infection. Antidepressants were superior to triple therapy for NUD even in H. pylori infected patients.
Keywords: Helicobacter pylori, Rapid urease test, Non-ulcer dyspepsia.
Helicobacter Pylori infection is ubiquitous in both developing as well as developed countries. It is a gram negative, curved, microaerophilic and motile organism with multiple polar flagella having extraordinary ability to establish infections in human stomachs for years or decades. More than 50% of the world population is colonized with H.pylori. [1, 2] Exposure occurs in childhood and approximately 80% of adults have been infected at some time. Sero-surveys indicate a seroprevalence of 22%-57% in children under the age of five, increasing to 80%-90% by the age of 20, and remaining constant thereafter.[3-6] H. Pylori commonly causes peptic ulcer, presenting as recurrent abdominal pain and is associated with 90% of duodenal ulcers and 80% of gastric ulcers. H.Pylori is also associated with gastric mucosa associated lymphoid tissue (MALT) lymphomas and gastric adenocarcinoma.There is an imperfect relation between non-ulcer dyspepsia and infection with H pylori. The pathophysiology of dyspepsia with H. Pylori infection is unclear, but may include changes in acid secretion, abnormal motility, or altered visceral perception.  The prevalence of H pylori is higher in patients with non-ulcer dyspepsia than in healthy controls. 
Various methods to diagnose H.Pylori infection are grouped as (a) Invasive methods and (b) Non invasive methods. The invasive methods are based on collection of endoscopic gastric biopsy specimens that are subjected to urease test, staining, culture, histology and molecular diagnostic techniques. The non invasive methods comprise urea breath test, serology and stool antigen test. Among invasive tests, Rapid urease test is a rapid, non expensive, sensitive and specific diagnostic modality, which can identify H. pylori organism and can be also used for monitoring therapy. In the presence of H Pylori infection, urea is hydrolyzed to ammonia and carbon dioxide (CO2) due to release of urease enzyme. The change in colour of the broth from pale yellow to deep pink was taken as a positive result. Bacteria other than H Pylori that produce urease in a small amount cannot survive in the gastric mucosa.
Our study is aimed at to analyze the pattern of RUT performance by endoscopists and audit of the response to treatment, in Southeast Bengal region in patients evaluated for upper gastrointestinal disorders.
Materials and Methods
Retrospective analysis of records of consecutive patients attending a gastroenterology clinic for upper G.I. disorder with a past upper UGI endoscopy report were done over a period of 7 Years from 05.11.03 to 24.06.10 . During this period a total of 151 patients with dyspeptic symptoms were studied with their previous report. The records of these patients including endoscopic findings, RUT report and details of pre-procedure PPI/H2RA therapy within 2 weeks, and post UGIE treatment were analyzed. As Rapid ureaseTest (RUT) has high sensitivity, specificity, positive predictive value in the order of > 98%, >99 %,> 99% respectively , positive RUT was considered as presence of H.Pylori in the gastric mucosa in the above patients. The patients having “peptic ulcer disease’’ (gastric ulcer and duodenal ulcer) and normal or near-normal endoscopies (including findings of questionable clinical significance such as gastritis or duodenitis) categorized as “nonulcer dyspepsia’’ on endoscopy were included in the study. Presence of reflux oesophagitis, any growth in stomach or duodenum, and any disease outside the stomach were excluded from this study. Peptic ulcer disease (PUD) group and nonulcer dyspepsia (NUD) group again each subdivided into two categories based on with premedication or without premedication with PPI/H2RA before endoscopy.
Results of rapid urease test in all categories were analyzed. An audit of treatments used for H.Pylori positive NUD patients and also the subjective [symptomatic] response to anti H.Pylori treatment / anti- depressants was also analyzed during the current visit.
Non ulcer dyspepsia (NUD) is defined as patients with central upper abdominal pain or discomfort for at least 12 weeks but a normal endoscopic appearance. Premedication means intake of proton pump inhibitors (PPIs) or histamine 2-receptor antagonists (H2RAs) [within 2 weeks] prior to rapid urease testing.
Fig 1. Endoscopic findings
Fig -2 : Flow chart of study population
Data was entered and analyzed in Statistical Package for Social Sciences (SPSS) ver17.0. Chi square test/ Fisher’s Exact Test was used for nominal values.
Out of 151 patients, 128 were males and 23 were females with M: F ratio 5.6: 1. Diagnosis by endoscopic findings was shown in Fig 1. Majority of patients had nonulcer dyspepsia (47%) followed by duodenal ulcer (31%) and gastric ulcer (11%). To prevent confounding in this study, sixteen were excluded due to presence of reflux oesophagitis in 15 patients and duodenal growth in one patient. Rest 135 patient i.e. 64 patients with peptic ulcer disease (47 duodenal ulcer, 17 gastric ulcer) and 71 patients of nonulcer dyspepsia (NUD) were taken into study (Fig 2).
Peptic ulcers were found in more number of males (53.04%) than females (15%). In contrary females suffer from more nonulcer dyspepsia than males (p= 0.002) as in Fig 3. Rapid urease test was negative in 62.6% of males and 65% of females respectively (p=1.000) as in Table 2. So there was no difference in positive rapid urease test according to gender. Rapid urease test was positive in 40.62% and 33.80% of peptic ulcer and NUD patients respectively (p =0.477). Further subgroup analysis was done with premedication and without premedication to find out any significance. In peptic ulcer group 36.5% with premedication and 58.3% without premedication were RUT positive (p=0.165). In NUD patients 29% with premedication and 66.6% without premedication were RUT positive (p=0.053). As premedication [PPIs or antibiotics prior to endoscopy] can influence the rapid urease test, further analysis was done in patients of both groups without premedication. So in patients without premedication (Fig 2), positive rapid urease test was found only 58.3 % in peptic ulcer and 66.6% of NUD patients respectively (p=1.000). Overall in 135 patients (Table-1), RUT positive was found in 32.45% and 61.9% on premedication and without premedication respectively (p = 0.014).
Table 1. Factors associated with rapid urease test result.
|RUT +VE(50)||RUT –VE(85)||p value|
Fig 3. : Diagnosis according to gender
Analysis of endoscopic pattern was done according to type of physicians (Table 2). Untrained (nongastroenterologists) physicians had diagnosed 68.42% of Peptic ulcers, whereas 26.76% of NUD cases were diagnosed by trained (gastroenterologists) physicians (p=0.575).Similarly there was no difference in RUT result (p=0.570) performed by different type of physicians (Table 2).
As we have considered positive RUT as evidence of H. Pylori infection, so percentage of positive RUT without prior therapy can be extrapolated as prevalence of H. Pylori infection in peptic ulcers (58.3%), NUD(66.6%) and total patients (61.9%).
Table 2. Diagnosis according to type of physicians.
Fig-4: Study flow chart of treatment.
Fig-5: Treatment response in positive rapid urease test NUD patients
Here analysis of response to triple therapy in RUT positive NUD patients was done (Fig-4: study flow chart). Out of 71 NUD patients, 24 patients had positive RUT. Among these positive RUT patients 18 patients were given triple therapy and 6 patients were given PPI or other medications. Two patients, who had taken triple therapy, did not come for follow up. Out of 16 patients of NUD, taking triple therapy, were assessed for symtomatical improvement after one month. Thirteen (81%) patients of RUT positive NUD patients who received triple therapy for H. Pylori did not respond, but all thirteen [100%] patients not responding to triple therapy responded to antidepressants (Fig-5). Using Fisher’s exact test, antidepressants are extremely effective than triple therapy regimen for non ulcer dyspepsia (p value=<0.0001), even if in Helicobacter pylori infected patients. However response to anti-H.Pylori triple regimen was also significant (p=0.0011) in RUT positive peptic ulcer (80%) patients than NUD (18.75%) patients.
Endoscopic findings of patients with upper gastrointestinal disorders from Southeast Bengal region revealed varied diagnosis. Non ulcer dyspepsia (47%) accounted major diagnosis followed by peptic ulcers (42%) and reflux oesophagitis (10%). However an endoscopic review of four series of dyspeptic patients in U.K. revealed NUD 34% followed by GERD 24% and peptic ulcers 20%.[ 11,12] High prevalence of peptic ulcers in our study may be due to increased prevalence of causative factor like H.Pylori infection in low hygienic environment, overcrowding, which also supports less prevalence of GERD in this region.
In our study, males suffer more from peptic ulcers than females, which may be due to more proneness for stress and strain as well as addiction for alcohol, smoking in males. Females seek medical attention for functional dyspepsia (85%) rather than ulcers (47%). Endoscopy is done by both trained and untrained physicians throughout the country due to lack of sufficient number of trained doctors as well as proximity of patients to untrained physicians. However there is no difference in diagnosing peptic ulcers and performance of rapid urease test.
There are very limited studies in literature comparing response of rapid urease test with premedication in peptic ulcers or non ulcer dyspepsia. In our study, there is no significant difference in result of rapid urease test in peptic ulcer and non ulcer dyspepsia patients with regards to premedication, which may be due to few study samples and noneradication of H. pylori with respect to premedication. Overall in 135 patients, prior PPI/H2 RA therapy has shown to decrease the degree of positivity of rapid urease Test (RUT) significantly, compared to the group who had not received prior PPI, similar to other studies.[13, 14].
There are various studies [15-18] about the effectiveness of triple therapy in peptic ulcer Patients, similar to our study. Whereas there are controversies regarding treatment of NUD patients. In our study, nearly 82% of NUD patients did not respond to anti H Pylori therapy, where as all NUD patients responded to anti-depressants, contrary to other studies. [16-18] Meta-analysis of twelve trials by Moayyedi  showed H pylori eradication treatment was significantly superior to placebo in treating non-ulcer dyspepsia (relative risk reduction 9% (95% confidence interval 4% to 14%)), one case of dyspepsia being cured for every 15 people treated. H pylori eradication cost £56 per dyspepsia-free month during first year after treatment.Canadian Helicobacter pylori consensus conference also favour the H pylori eradication to prevent development of ulcer or cancer as the lifetime risk of developing ulcers for people who are infected with H pylori is 5-15%. A recent randomized clinical trial of 294 patients with uninvestigated dyspepsia in Canada found that treatment resulted in a sustained improvement in symptoms at 12 months in 50% of the patients treated to eradicate H pylori compared with 36% in the placebo group. This result was significant, and seven patients needed to be treated to cure one patient. The trial also showed that treatment was cost effective. However another meta-analysis by Laine L and CO provided little support for the use of H. pylori eradication therapy in patients with nonulcer dyspepsia.[22 ] A study by Singh S P et el from Odisha showed the antipsychotics rather than anti H.pylori treatment has definite role in symptomatic amelioration of NUD patients. Another small randomized controlled trial by Mertz H et el demonstrated benefit for symptoms of non-ulcer dyspepsia treated with amitryptiline 50 mg once daily at night. A prospective study from sixty patients (seropositive) found no benefit in-patients with dysmotility like NUD with anti H.pylori treatment with comparison to ulcer variety. Possible suggestions can be made for the effectiveness of antidepressants over H. Pylori treatment. First, rampant use of antibiotics like amoxicillin, clarithromycin and metronidazole for other causes and sometimes with inadequate doses, may be responsible for resistance to these drugs used in H .Pylori treatment.Second, our study population may have pre-dominant psychosomatic features, contributing pathophysiology of NUD. Third, time to response measured after H. pylori treatment might be too short to get effective response from H .Pylori treatment, compared to other study.
Our study in peptic ulcer showed 58% prevalence of H.Pylori, contrast to an older study showing prevalence of H.pylori infection between 95% and 100%,  which might be because of few study samples. But in a recent study from Kolkata, 70.04% patients were H. Pylori –positive, which nearly supports our study. In our study Prevalence of H. pylori in NUD was found to be 67%, similar to other studies from different parts of India (South India 74%,  and New Delhi 54% ).
Various studies have demonstrated the role of H .Pylori in the pathophysiology of peptic ulcer, MALT, and gastric carcinoma. The question arises whether eradication of H .Pylori is a practically feasible or becomes compulsory in developing countries like India? According to Ramakrishna B.S., eradication of H.pylori in NUD is not justifiable in India. Prevalence of H. pylori in normal population varies from 60 -80% in different studies in different regions of
India. [3, 27, 30 – 33] To eradicate innocuous bacteria from our gastric flora, which is present since time immemorial, we have to treat nearly 70-80 crores of people, which is not possible as recurrence of infection occurs in around 60% of patients published in various Indian literature. In one Indian study of 45 patients followed up following eradication of H. pylori, recurrence of infection was detected in only one patient (2.4%) after one year.There are also some arguments against the eradication of H. Pylori infection. All strains inhabitating in gastric mucosa are not virulent. Production of increased acidic environment in stomach and other immune factors may be a barrier to other ingested pathogens.[37, 38] Possibility of protection from allergic and autoimmune diseases including asthma and Crohn’s disease due to H. Pylori infection compared developed countries may favour against eradication of this organism in developing countries like India. Various consensus statements regarding eradication of H.pylori in India have ruled out anti H.pylori therapy in NUD patients, which may aggravate the symptoms rather than amelioration.[40-43]
RUT was performed routinely in all patients undergoing gastroscopy irrespective of diagnosis and without cognizance of pre-endoscopy treatment. Functional dyspepsia patients seek advice of non DM physicians more than DM physicians. “Prior treatment” results in erroneous underestimation of H. Pylori infection. RUT performed in general practice (irrespective of recent drug therapy) can be fallacious for detecting H.pylori infection and therefore deciding about institution of eradication therapy. Antidepressants were superior to triple therapy for NUD even in H. pylori infected patients. There is no rationale for doing RUT in NUD Patients or treating these patients with anti H.pylori therapy. There is a need for developing rational guidelines for performing RUT
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