Diagnosis of Helicobacter pylori infection using urease rapid test in patients
with bleeding duodenal ulcer: influence of endoscopic signs and simultaneous
corporal and antral biopsies

M. Castro Fernández, D. Sánchez Muñoz, E. García Díaz, M. V. Galán Jurado and C. Rodríguez Alonso

Service of Digestive Diseases. Hospital Universitario de Valme. Sevilla. Spain

 

ABSTRACT

Introduction: the sensitivity of invasive diagnostic methods for Helicobacter pylori (H. pylori) infection, particularly of urease rapid test, is decreased in cases of gastroduodenal ulcer and upper gastrointestinal bleeding.
Objectives: to assess the influence of blood in the stomach or recent bleeding endoscopic signs in the diagnostic sensitivity of urease rapid test among patients with bleeding duodenal ulcer, as well as the influence of simultaneously collected corporal and antral biopsy samples.
Patients and methods: 120 patients, 85 male and 35 female, with an average age of 62 (18-88) years, who were admitted to our Hospital due to bleeding duodenal ulcer and who received an endoscopic diagnosis within 24 hours of admission were included. None of the patients had been under treatment with non-steroideal antiinflammatory drugs, proton-pump inhibitors or antimicrobial drugs in the two weeks prior to the bleeding event, and none had received eradicating therapy for H. pylori. In this group of selected patients an H. pylori infection rate nearing 100% was assumed. H. pylori infection was ruled out using antral biopsy (69 cases) or both antral and fundic biopsies (51 cases) for urease rapid testing (Jatrox^®-H.p.-Test). Patients were classified in three groups according to their endoscopic bleeding signs: a) presence of blood in the stomach or recent bleeding ulcer (21 cases); b) ulcer showing non-recent bleeding signs (38 cases); and c) ulcer without bleeding signs (61 cases). The sensitivity of the urease rapid test was compared between patient groups. Similarly, urease test results with an antral biopsy sample were compared in 100 patients with non-bleeding duodenal ulcer.
Results: urease test was positive in 93% of patients with non-bleeding duodenal ulcer, and in 83% of patients with upper gastrointestinal bleeding, which reached statistical significance (p = 0.019). This test was positive in 82.6% of patients with an antral biopsy, and in 82.3% of patients with combined antral and fundic biopsies. In group A, urease test was positive in 90.5% of patients; in group B, it was positive in 89.5% of patients, and in group C, the test turned positive in 75.4% of patients. Statistical differences were only reached when patients in group C were compared to patients in groups A and B together (p = 0.037).
Conclusions:
1. The presence of either blood in the stomach or recent bleeding endoscopic signs appeared not to be the conditioning factor for the decreased sensitivity of urease test among patients with bleeding duodenal ulcer.
2. The decreased sensitivity of this test in patients with upper gastrointestinal bleeding is more evident during the resolution stage, and it does not seem to occur because of H. pylori migration from the antrum to the corporal gastric region.

Key words: Helicobacter pylori. Urease test. H. pylori diagnosis. Bleeding duodenal ulcer.

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Castro Fernández M, Sánchez Muñoz D, García Díaz E, Galán Jurado MV, Rodríguez Alonso C. Diagnosis of Helicobacter pylori infection using urease rapid test in patients with bleeding duodenal ulcer: influence of endoscopic signs and simultaneous corporal and antral biopsies. Rev Esp Enferm Dig 2004; 96: 599-605.

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Recibido: 16-10-03
Aceptado: 27-01-04

Correspondencia: Manuel Castro Fernández. Servicio de Aparato Digestivo (9ª planta izda.). Hospital Universitario de Valme. Ctra. de Cádiz, s/n. 41014 Sevilla. e-mail: mcastrof@meditex.es

 

INTRODUCTION

Helicobacter pylori (H. pylori) infection represents the most frequent etiology of gastroduodenal ulcer. The prevalence of this infection in duodenal and gastric ulcer is about 85-95% and 75-85%, respectively (1,2). Patients with gastroduodenal ulcer may develop complications such as upper gastrointestinal bleeding or perforation, which calls for a precise diagnosis of H. pylori infection since eradication reduces significantly the risk of ulcer reactivation, and thus prevents new episodes of upper gastrointestinal bleeding (3-5). Several diagnostic methods for H. pylori infection are available, either invasive -which require endoscopy and gastric biopsies (urease rapid test, histology and cultures)- or non-invasive (urea C¹³ breath test, stool antigen detection and serology), all of them exhibiting both advantages and disadvantages regarding availability, rapidity of results, value, and diagnostic accuracy (6-9). Invasive methods, specially the urease rapid test, show decreased sensitivity in cases of bleeding gastroduodenal ulcers (6-7,10-14).

The causes of this decreased sensitivity are not yet established, and various factors such as therapy with proton pump inhibitors (PPI) or the presence of blood in the stomach have been implicated.

The aims of this study were to establish the influence of the presence of blood in the stomach or bleeding endoscopic signs, as well as of simultaneous antral and fundic biopsy collection, in the diagnostic sensitivity of urease test in patients with bleeding duodenal ulcer.

PATIENTS AND METHODS

Patients

We included 120 patients (85 males and 35 females) with an mean age of 62 years (18-88 years) who were admitted to our hospital with bleeding duodenal ulcer and who underwent upper gastrointestinal endoscopy within 24 hours after admission. They had not been under treatment with non-steroideal anti-inflammatory drugs (NSAID), PPIs or antibiotics for the two weeks prior to the bleeding event, and they had not received eradicating therapy for H. pylori either; these data were revealed in a directed interview. In this selected group of patients, a H. pylori infection rate of almost 100% was assumed. Intravenous omeprazole was given to all patients before endoscopy for a period shorter than 24 hours, using a variable dosage between 40 and 160 mg.

We also studied a second group of 100 patients (87 males and 13 females), aged 55 years (20-77 years), with duodenal ulcer and dyspepsia, without gastrointestinal bleeding, diagnosed endoscopically, and with no prior intake of either NSAID or H. pylori eradicating therapy.

Informed consent in writing was obtained from each patient before gastroscopy.

Diagnostic methods

Patients with bleeding duodenal ulcer were investigated for H. pylori infection using either antral biopsies (69 cases) or both antral and fundic biopsies (51 cases) for urease rapid testing (Jatrox^®-H.p.-Test). The decision to take additional fundic biopsies was not conditioned by the endoscopic diagnosis. The test was considered positive when the color turned from yellow to red within 24 hours following the inclusion of biopsy specimen into a reagent-containing cuvette with 0.5 ml of distilled water. Patients were distributed in three groups according to the endoscopic findings: a) presence of blood in the stomach or signs of recent (direct) bleeding (active hemorrhage, visible vessel or adherent clot) (n = 21); b) presence of signs of non-recent (indirect) bleeding (black points or spot) (n = 38); and c) absence of bleeding signs (ulcer with fibrin base) (n = 61). In patients with non-bleeding duodenal ulcer only antral biopsies were taken for urease testing.

Statistical study

Statistical significance of differences between groups of patients was analyzed using the Chi-square, Fisher's exact, and McNemar tests. We considered the results to be statistically significant when p < 0.05. Confidence intervals at 95% were also calculated.

RESULTS

Urease test was positive in 99 out of 120 patients (83%) with bleeding duodenal ulcer, and in 93 out of 100 patients (93%) with non-bleeding duodenal ulcer. This difference was statistically significant (p = 0.019; OR: 0.35; CI 95% [0.13-0.93]).

Sex and age distribution was similar in both groups.

In the group of patients where only antral biopsies were taken (n = 69), the urease test was positive in 57 cases (82.6%), whereas, in the group of patients in which both antral and fundic biopsies were taken (n = 51), the test was positive in 42 cases (82.3%). This difference was not statistically significant (p = 0.97; OR: 1.01; CI 95% [0.35-2.89]).

Table I shows the sensitivity of the urease test according to the site where the gastric biopsies were taken or the presence of endoscopic signs of bleeding. These differences were not significant when comparing the three groups of patients with bleeding duodenal ulcer together. Nevertheless, a significant association was found when comparing group C (absence of bleeding signs) with groups A and B together (presence of bleeding signs); [p = 0.037: OR: 2.88; CI 95% (0.94-9.14)] (Table II).

DISCUSSION

The prevalence of H. pylori infection in gastroduodenal ulcer is high (75-85% in gastric ulcers; 85-95% in duodenal ulcers) (1,2). This prevalence is similar, or just slightly lower, in bleeding gastroduodenal ulcers because of the influence of NSAID intake (15). The urease rapid test can be considered the diagnostic method of choice in these patients requering endoscopy, because of its simplicity, diagnostic accuracy and rapidity of results (18,19), although decreased sensitivity has been reported in cases of bleeding duodenal ulcer (6,11,13,20-22). In such cases, histology, simultaneous urease test and histology, or C¹³ breath test after a hemorrhagic event (with no invasive test being performed) have been proposed by some authors (7,10).

The cause for this decreased diagnostic sensitivity of the urease test in cases of bleeding duodenal ulcer remains controversial. Several circumstances have been considered to explain this fact, such as the presence of blood in the stomach, which might induce a transient mucosal bacterial clearance because of a bactericide effect of the serum (7,25). Another possibility is that serum albumin may induce a buffering effect on the pH indicator used for urease testing, which might prevent color change (26). The common use of PPI by these patients may also reduce the mucosal bacterial load, resulting in bacterial migration to the upper regions of the stomach (6).

However, “in vitro” studies, such as those performed by Perry et al. (27), failed to demonstrate that the presence of blood in the stomach reduces the sensitivity of the rapid urease test, while some other “in vitro” studies find this decreasing as a late effect of the bleeding (28). These results are consistent with those obtained in the present study. However, some other authors do not find differences between bleeding and non-bleeding ulcers, neither in sensitivity nor in specificity of the rapid urease test. However, a decreased sensitivity of this test when it is performed under the influence of blood in the stomach has been reported (29).

Patients with bleeding duodenal ulcer without the influence of NSAIDs, antibiotics or eradicating drugs for H. pylori infection were included in the present study. In this group of patients, a H. pylori infection rate of near 100%, as it is well defined in some studies (15-17) (and personally observed in our hospital), can be assumed. This fact allows the rate of rapid urease test false negative results to be assessed without the exclusion of patients with non-confirmed negative results (using other diagnostic methods) for the absence or presence of H. pylori infection. Nevertheless, it is not advisable to routinely assume, without additional investigation, that all patients with gastroduodenal ulcer and no previous history of NSAID ingestion are infected with H. pylori.

In patients with blood in the stomach or endoscopic signs of bleeding ulcer (either recent or not), the sensitivity of the urease test is almost 90%, and this rate is higher than that found in patients without endoscopic signs of bleeding (75.4%). This situation could be explained by the possibility of a late effect of blood on the decreased sensitivity of the urease test, which concur with the results obtained by other studies (26). It is not possible to assess the influence of intravenous omeprazole in each group of patients. However, none of the patients included in our study received this therapy for more than 24 hours. Urease test was positive in 93% of patients with non-bleeding duodenal ulcer. This rate of positivity is higher than that observed in patients with bleeding duodenal ulcer, in whom we found a 75.4% of positive results.

In our opinion, according to the results of the present study, the presence of blood in the stomach or of endoscopic signs of bleeding at the time of biopsy does not represent a conditioning factor for decreased sensitivity of the urease test. Likewise, this decreased sensitivity does not seem to be due to the migration of the H. pylori to the fundic region of the stomach. The reduced sensitivity of this test may be a late, neither immediate nor early, phenomenon in upper gastrointestinal bleeding.

The presence or absence of blood or endoscopic signs of bleeding at the time of biopsy should not be the factor determining an investigation of H. pylori infection by using the urease test. The lower sensitivity of the urease test in patients with upper gastrointestinal bleeding may not be a factor for turning urease testing down, since a precise and early diagnosis of H. pylori infection is established in a high proportion of such patients (83%). Nevertheless, controlled studies are necessary to define which diagnostic method (or combination thereof) is better for the diagnosis of H. pylori infection in patients with bleeding gastroduodenal ulcer.

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