Negative Urea Breath Test Research Articles

13C-urea breath test in the management of Helicobacterpylori infection

The urea breath test is a noninvasive and very accurate test for the diagnosis of Helicobacter pylori infection. However, false negative urea breath test results have been reported to occur in a considerable percentage of the individuals taking proton pump inhibitors; the interval needed to be completely confident that false negative tests had been excluded has varied among the different studies between 6 and 14 days. The impact of H 2-receptor antagonists on the accuracy of urea breath test remains controversial, although, in contrast with proton pump inhibitors, the data suggest that H 2-receptor antagonists, for the most part, have little effect on the result of the urea breath test. The urea breath test does not represent a suitable tool for estimating the density of H. pylori colonization. The only quantitative information to be obtained from the urea breath test is that the higher the δ value, the lower the probability of a false-positive urea breath test result. Although some authors have demonstrated a correlation between urea breath test values and histological lesions of the gastric mucosa, the practical utility of this relationship remains unclear. It has been suggested that the pretreatment urea breath test has the potential to identify patients who require modification of the standard therapeutic regimen (for example, prolonging the duration of treatment or increasing the pharmacological dose when bacterial density is high), but other studies could not confirm this relationship. Some studies have shown that the urea breath test is less accurate in patients who have undergone partial gastrectomy. Finally, in contrast with biopsy-based methods, which are responsible for a high number of false-negative results when used to diagnose H. pylori infection in patients with upper gastrointestinal bleeding, urea breath test seems not to be negatively influenced by the presence of this complication.

Is the Remarkable Contradiction between Histology and 14C Urea Breath Test in the Detection of Helicobacter pylori due to False-negative Histology or False-positive 14C Urea Breath Test?

We assessed the diagnostic value of the 14C urea breath test (UBT) in the detection of Helicobacter pylori compared with histology and the rapid urease test (RUT). The study included 68 patients (22 men and 46 women) with dyspeptic symptoms. H. pylori status was evaluated by 14C UBT, RUT and histology. Sensitivity, specificity, positive and negative predictive values, and diagnostic accuracy were determined for 14C UBT and for RUT. Histology revealed dense yeast-like micro-organisms in the biopsy specimens in all patients with false-positive results by 14C UBT (n = 8), a significantly higher proportion than in patients with negative 14C UBT (five of 31). The low specificity of the H. pylori 14C UBT should not be neglected by accepting histology results as false-negative. Gastric mucosal colonization by yeast-like micro-organisms with urease activity can account for the high frequency of false-positive results for 14C UBT.

Evaluation of Stool Antigen Test for Helicobacter pylori Infection in Asymptomatic Children from a Developing Country Using 13C‐urea Breath Test as a Standard

Prevalence of asymptomatic Helicobacter pylori infection is very high in infants and children in developing countries. C urea breath test (UBT) is a reliable non-invasive diagnostic test for H. pylori infection in children that avoids invasive endoscopy. We compared a newly introduced H. pylori stool antigen test (with a high sensitivity and specificity in symptomatic children) with UBT in asymptomatic children mostly 1-5 years old, from a population with a high prevalence of infection. Eighty six asymptomatic children (42 boys and 44 girls) were tested for H. pylori infection using the UBT and a stool antigen test (HpSA) based on a sandwich enzyme immunoassay for antigen detection. Forty five of the eighty-six (52.3%) children tested positive for H. pylori using the breath test. In 34 of these forty-five children, H. pylori antigen was detected in stool (sensitivity = 75.6%, 95% CI = 63 to 88%). Of the 50 of 86 (58%) children positive by HpSA test, 34 were positive for breath test. Of the 41 children with negative UBT test 25 were negative for stool antigen test (specificity = 61%, 95% CI = 46 to 76%). The sensitivity and specificity of the new stool antigen test are lower in asymptomatic children with high H. pylori prevalence rate compared to those reported for children with gastrointestinal symptoms. Its usefulness is limited for diagnosis in an asymptomatic child with H. pylori infection.

One-week once-daily triple therapy with esomeprazole, levofloxacin and azithromycin compared to a standard therapy for Helicobacter pylori eradication

Background. Primary antibiotic-resistance and poor compliance are the main causes of Helicobacter pylori eradication failure of standard regimens. Aim. To investigate eradication rate, patient compliance and tolerability of a 1-week once-daily levofloxacin plus azithromycin triple therapy versus the standard twice-daily triple therapy. Patients and methods. A total of 164 H. pylori-positive patients were randomised to either esomeprazole 20 mg, levofloxacin 500 mg and azithromycin 500 mg once-daily (ELAz) or esomeprazole 20 mg, clarithromycin 500 mg and amoxycillin 1 g twice-daily (ECA) for 1 week. H. pylori infection was defined at entry by histology and urea breath test; cure of infection was determined both by negative urea breath test and H. pylori stool antigens. Results. H. pylori eradication rates of ELAz and ECA were similar at intention-to-treat (both 65%) and per-protocol analyses (70% versus 76%, respectively). Incidence of poor compliance was lower, although not significantly, in patients randomised to ELAz than to ECA (4% versus 10%); tolerability was significantly higher for ELAz than for ECA (88% versus 70%; P = 0.01). Conclusions. Once-daily levofloxacin plus azithromycin-based triple therapy achieves an H. pylori eradication rate comparable to that of standard twice-daily triple therapy, but is associated with higher patient compliance and might even be better tolerated.

Comparison of a monoclonal antigen stool test (Hp StAR) with the 13C-urea breath test (UBT) in monitoringHelicobacter pylorieradication therapy

To evaluate the agreement between a mAb-based stool test (HP StAR) and the urea breath test (UBT) in monitoring (H pylori) infection after eradication therapy. Patients with discordant results on UBT and Hp StAR underwent endoscopy with biopsies for rapid urease test, culture, and histology to confirm H pylori status. Among 250 patients (50+/-14 years), 240 (96.0%) had concordant UBT and Hp StAR tests with a significant correlation between DOB and A values (R = 0.87; P<0.0001). The remaining 10 (4.0%) patients had discordant tests (positive Hp StAR and negative UBT) with the Hp StAR inaccurate in five cases (false positive) and UBT inaccurate in the other five cases (false negative). The "maximal expected" sensitivity, specificity, +PV, -PV, +LR, and -LR were 91%, 100%, 100%, 97.4%, infinity, and 8.2 respectively, for the UBT, and 100%, 97.4%, 91%, 100%, 38.8, and 0, respectively, for the Hp StAR. Overall accuracy for both tests was 98%. Both the UBT and the Hp StAR are equally accurate in monitoring H pylori infection. Nowadays, the choice of the "best" non-invasive H pylori test in the post-treatment setting should be done not only in terms of diagnostic accuracy but also in view of cost and local facilities.

Helicobacter pylori and autoimmune hepatitis

In a hospital-based study from England, antiHelicobacter pylori ( H.p ylori) IgG antibodies were found in 13.6 % of children presenting with recurrent abdominal pain; however, on endoscopy, only 64 % of them were found to have H. pylori gastritis [2]. We present an interesting association of H. pylori gastritis and autoimmune hepatitis in a 13-year-old patient. A 13-year-old girl was referred to our Centre with an acute onset of jaundice. There was no history of blood transfusion or recent exposure to drugs or toxins. Apart from jaundice and mild hepatomegaly, clinical examination was unremarkable. Her blood investigations showed a conjugated hyperbilirubinaemia of 71 lmol/l with ALT and AST levels of 572 IU/l and 909 IU/l respectively, a gamma-glutamyl transpeptidase activity of 52 IU/l and a slightly deranged clotting profile (INR 1.64). She had negative hepatitis A, B, C and Epstein Barr virus screens and normal serum coeruloplasmin and alpha-1-antitrypsin levels and phenotype. An autoantibody screen was positive for antinuclear and smooth muscle antibodies (a titre of 1:640 for both) and the antidouble stranded DNA antibody level was 10 IU/ml (normal value <7 IU/ml). A serum immunoglobulin (Ig) profile showed raised total IgG and IgA levels of 40.5 g/l (reference range 6.26–13.9 g/l) and 3.64 g/l (reference range 0.39–2.52 g/l) respectively. IgG subclasses showed elevated IgG1 and IgG3 of 36.8 g/l (reference range 3.47–9.93 g/l) and 1.27 g/l (reference range 0.23–1.17 g/l) respectively. Ultrasonographic examination of the liver was normal and there was no evidence of ascites. A liver biopsy and oesophagogastroduodenoscopy were performed under general anaesthesia. There was evidence of duodenitis in the duodenal bulb (markedly erythematous and oedematous mucosa with no evidence of ulceration) and CLO test, routine histopathology and culture all indicated H. pylori colonisation. The liver histopathology showed plasma cell, lymphocyte and eosinophil infiltration in the portal tracts with prominent interface hepatitis and evidence of hepatocyte necrosis, regeneration, fibrosis and rosette formation consistent with autoimmune hepatitis. Unfortunately, we were unable to do PCR for H. pylori on the liver biopsy. She was given antiH. pylori triple therapy (amoxicillin, metronidazole and omeprazole) for 2 weeks and started on steroid and azathioprine for autoimmune hepatitis. A few weeks later, she was much better. She had a negative urea-breath test indicating H. pylori eradication and her ALT and AST levels improved (62 and 60 IU/l respectively) with a normal bilirubin of 11 lmol/l. The prevalence of serum antibodies to non-gastric Helicobacter species was significantly higher in patients with autoimmune chronic liver disease than in healthy blood donors [4]. Infection with Helicobacter hepaticus causes chronic hepatitis and hepatocellular carcinoma (HCC) in mice and H. pylori genomic sequences have been demonstrated in the liver of patients with cirrhosis. In a small adult case-control study from Italy, seroprevalence of antibodies to H. pylori was higher in patients with HCC than in controls (78.2% compared to 54%, P <0.05) [3]. In another adult study from the same Centre, the prevalence of H. pylori antibodies was higher in patients with autoimmune hepatitis compared to controls, but the difference was not statistically significant (64.5% compared to 53.2%, P =0.3). In both studies, infection with H. pylori was not confirmed by endoscopy. As autoimmunity is a feature of H. pylori [1], larger studies are needed to examine the role of H. pylori in the aetiology of autoimmune hepatitis. W. El-Matary (&) AE A. M. Dalzell Gastroenterology Unit, Royal Liverpool Children’s NHS Trust, Alder Hey, Eaton Road, L12 2AP Liverpool, UK E-mail: welmatary@yahoo.com Tel.: +44-151-2284811 Fax: +44-151-2280383

Review article: 13C‐urea breath test in the diagnosis of Helicobacter pylori infection – a critical review

The urea breath test is a non-invasive, simple and safe test which provides excellent accuracy both for the initial diagnosis of Helicobacter pylori infection and for the confirmation of its eradication after treatment. Some studies have found no differences between urea breath test performed under non-fasting conditions. The simplicity, good tolerance and economy of the citric acid test meal probably make its systematic use advisable. The urea breath test protocol may be performed with relatively low doses (<100 mg) of urea: 75 mg or even 50 mg seem to be sufficient. With the most widely used protocol (with citric acid and 75 mg of urea), excellent accuracy is obtained when breath samples are collected as early as 10-15 min after urea ingestion. A unique and generally proposed cut-off level is not possible because it has to be adapted to different factors, such as the test meal, the dose and type of urea, or the pre-/post-treatment setting. Fortunately, because positive and negative urea breath test results tend to cluster outside of the range between 2 and 5 per thousand, a change in cut-off value within this range would be expected to have little effect on clinical accuracy of the test.

False Negative Urea Breath Tests with H2‐Receptor Antagonists: Interactions Between Helicobacter pylori Density and pH

We studied the effects of famotidine, sodium bicarbonate, and citric acid on the 13C-urea breath test (UBT). Helicobacter pylori-infected volunteers received a UBT, 40 mg of famotidine at bedtime, and a second UBT (pudding test meal, 648 mg NaHCO3 tablet then 125 mg of urea in 200 ml of water containing 650 mg of NaHCO3). Experiment 2 consisted of four UBTs. Two were standard citric acid UBTs with 75 mg of urea and 2 g citric acid and two were sequential bicarbonate-citric acid UBTs. Sequential UBTs consisted of administration of a 648 mg bicarbonate tablet with 50 g of Polycose in 200 ml of water. Five minutes later, 125 mg of 13C-urea was given in 75 ml of water containing 650 mg of NaHCO3. Breath samples were collected after 15 minutes. Then, to acutely acidify the stomach, 4 g of citric acid was given in 200 ml of water. A second breath sample was collected 15 minutes after the citric acid. The standard UBTs were done before and after 6 days of famotidine (40 mg b.i.d.). Sequential UBTs were done after 1 and 6 days of famotidine therapy. Gastric biopsies for histology, culture, and mucosal cytokines were assessed before and after 6 days of famotidine. Eighteen subjects participated, 10 in each experiment; seven had endoscopy with biopsy. Famotidine/ bicarbonate resulted an approximately 50% fall in UBT values (p = .021) with 10% becoming negative. The gastric pH increased from 5.1 +/- 0.5 to 6.7 +/- 0.2 (p = .03) although no pH value predicted the occurrence of false negative results. Under famotidine acid suppression, NaHCO3 reduced the delta over baseline (DOB) by 63% (p = .021). This was reversed with citric acid. Histology showed a H2-receptor antagonist-associated increase in the depth of gastric corpus inflammation. H2-receptor antagonists differ from proton pump inhibitors as high intragastric pH may cause a reduction in urease activity, unrelated to a reduced bacterial load and reversed by citric acid.

Studies regarding the mechanism of false negative urea breath tests with proton pump inhibitors

Objective The mechanism of false negative urea breath tests (UBTs) results among proton pump inhibitor (PPI) users is unknown. We studied the time course of PPI-associated negative UBT, the relation to Helicobacter pylori density, and whether gastric acidification would prevent false negative UBT results. Method In the UBT experiment, H. pylori–infected volunteers received omeprazole 20 mg b.i.d. for 13.5 days. UBTs with citric acid were done before, after 6.5 days of PPI, and 1, 2, 4, 7, and 14 days after therapy. In the culture and histology experiment, after a wash-out of >5 months, nine of the original subjects were rechallenged with omeprazole for 6.5 days. Antral and corpus biopsies for histology and culture were done before and 1 day after PPI administration. Results Thirty subjects (mean age 42 yr) were enrolled. UBTs were significantly reduced on day 6.5 ( p = 0.031); 10 subjects (33%) developed transient negative UBTs. The UBT recovered in all but one subject by the fourth day post-PPI and in all subjects by day 14. In the culture and histology experiment, upon PPI rechallenge, three of nine subjects (33%) had negative UBTs. H. pylori density, whether measured by culture or histology, decreased with PPI therapy; antral biopsies became histologically negative in five subjects and corpus biopsies in three subjects. Conclusion PPI-induced negative UBT results were related to the anti- H. pylori effect of the PPI. Acidification of the stomach did not prevent false negative UBT results. Three days is likely the minimum delay from stopping PPI until one should perform a test for active infection. A delay of 14 days is preferred.

Bismuth-based quadruple therapy using a single capsule of bismuth biskalcitrate, metronidazole, and tetracycline given with omeprazole versus omeprazole, amoxicillin, and clarithromycin for eradication of helicobacter pylori in duodenal ulcer patients: a prospective, randomized, multicenter, north american trial

Objectives This multicenter, randomized, active-controlled trial assessed efficacy of bismuth-based quadruple therapy with omeprazole, bismuth biskalcitrate, metronidazole, and tetracycline (OBMT) using a single-triple capsule of BMT compared with triple therapy with omeprazole, amoxicillin, and clarithromycin (OAC) in treatment of patients with Helicobacter pylori infection and duodenal ulcers. Methods Patients with active duodenal ulcer or diagnosed within the past 5 yr and with infection documented by 13C-urea breath test plus histology or culture were randomly assigned to 10-day course of OBMT using a single-triple capsule containing bismuth biskalcitrate 140 mg, metronidazole 125 mg, and tetracycline 125 mg given as three capsules q.i.d. with omeprazole 20 mg b.i.d., or a 10-day course of OAC, omeprazole 20 mg plus amoxicillin 1 g plus clarithromycin 500 mg, all b.i.d. Eradication was confirmed by two negative urea breath tests at >1 month and >2 months after therapy. Results One hundred thirty-eight patients received OBMT and 137 OAC. Modified intent-to-treat eradication rates were 87.7% for OBMT and 83.2% for OAC (95% CI = −3.9%–12.8%; p = 0.29). OBMT eradicated 91.7% metronidazole-sensitive and 80.4% metronidazole-resistant strains ( p = 0.06). OAC eradicated 92.1% clarithromycin sensitive and 21.4% clarithromycin-resistant strains ( p < 0.001). Adverse events occurred in 58.5% of OBMT patients and 59.0% of OAC patients. Conclusions OBMT regimen using the single-triple capsule is as efficacious and well-tolerated as the widely used OAC regimen for H. pylori eradication. This OBMT therapy largely overcomes H. pylori metronidazole resistance, present in 40% of patients in this study.

Helicobacter pylori causes gastrointestinal hemorrhage in patients with congenital bleeding disorders

Helicobacter pylori (H. pylori) infection is associated with peptic ulcer disease and gastric cancer. The eradication of H. pylori is of special interest in patients with congenital bleeding disorders, for whom treatment of gastrointestinal hemorrhage with factor concentrates is costly. The prevalence of H. pylori varies between different populations and identification of high-risk subgroups may allow for more targeted screening and eradication of the infection. We performed a 5-year retrospective study of gastrointestinal bleeding, combined with screening and treatment for H. pylori and a long-term prospective follow-up in 168 Swedish and 23 Estonian patients with hemophilia or von Willebrand disease. The prevalence of seropositivity was lower in Sweden than in Estonia (28 versus 48%, p = 0.03), lower in native Swedes than in non-Nordic immigrants to Sweden (20 versus 76%, p = 0.0001) and lower in patients less than 40 years of age than older patients (16 versus 38%, p = 0.002). The incidence of gastrointestinal hemorrhages among the 35 Swedish patients with active H. pylori infection, confirmed by a urea breath test, was 6.0 per 100 patient-years before eradication therapy versus 1.7 during the prospective followup. A negative urea breath test one month after therapy always remained negative after one year. Screening, followed by treatment of all infected patients, yielded a reduction of direct costs over a 5-year period of 130 US-$ per screened patient. We conclude that screening and eradication therapy for infection with H. pylori in patients with congenital bleeding disorders is an effective and economic strategy.

Is Helicobacter pylori infection associated with chronic idiopathic urticaria?

BackgroundChronic idiopathic urticaria (CIU) is one of the most frequent skin diseases, however its causes remain unknown in the vast majority of cases. There is increasing evidence for systemic effects of gastric Helicobacter pylori infection, which may result in extra gastrointestinal disorders. Although CIU can result from several causes, a possible relationship between chronic urticaria and Helicobacter pylori has been recently suggested ObjectiveThe aim of this study is to determine the prevalence of Helicobacter pylori infection in a series of patients with CIU, and measure the effectiveness of eradication therapy on the skin disease MethodWe assess Helicobacter pylori infection by 13C urea breath test (UBT) in 21 CIU patients. Amoxicillin, clarithromycin, and omeprazole were given to infected patients for seven days. The results of therapy were assessed by urea breath test one month after therapy. Urticaria and gastrointestinal symptoms were assessed on enrolment and for six months after eradication ResultsPrevalence of Helicobacter pylori infection was of 71.4 % (15/21). There were no differences concerning age (31.83 vs. 33.82 years) and duration of symptoms (38.40 vs. 35.38 months) in patients with respectively positive and negative UBT. Helicobacter pylori eradication rate was of 80% (12/14). Three patients had clinical improvement with total resolution of urticaria starting immediately after eradication therapy, being able to completely withdrawn antihistamine and corticosteroids therapy without complaints. In relation to the rest of the patients, these three had smaller duration of urticaria disease (14.3 vs. 43.7 months; p = 0.038) and greater titters in the UBT results (42.39 vs. 25.81; p = 0.073) DiscussionAlthough some authors found convincing evidence of the involvement of Helicobacter pylori as one possible cause of chronic urticaria, our results have failed to confirm the existence of this etiological association. The most remarkable finding was that those patients who had clinical remission of disease were the ones with greater UBT titters suggesting a role for the amount of colonization by Hp in the pathogenesis of urticaria disease

Quadruple therapy for symptomatic spontaneous duodenal ulcer disease

AIMTo investigateHelicobacter pylori eradication in duodenal ulcer patients with a new regimen, lansoprazole 30 mg daily for one or four weeks plus twice daily tetracycline 500 mg, clarithromycin 250 mg,...

Posttreatment follow-up of Helicobacter pylori infection using a stool antigen immunoassay.

The Helicobacter pylori stool antigen enzyme immunoassay (HpSA) was evaluated during posttreatment follow-up of patients in a country with a very high prevalence of H. pylori infection. From among 273 dyspeptic individuals (18 to 55 years) initially recruited from a shantytown in Lima, Peru, 238 participants who met the inclusion criteria and were suspected to be H. pylori positive based on (14)C urea breath test (UBT) results underwent endoscopy. Participants with endoscopy-proven infections received standard eradication therapy and were monitored by UBT and HpSA at 1 month following treatment and at 3-month intervals for 9 months posttreatment. A second endoscopy was performed if UBT results showed evidence of treatment failure or H. pylori recurrence. Biopsy results were considered the "gold standard" in all analyses. Among patients who underwent endoscopy, HpSA had a pretreatment sensitivity of 93%. Two-hundred thirty patients completed the treatment regimen, of whom 201 (93%) were considered to have had successful treatment outcomes based on a negative follow-up UBT. Thirty-two patients with UBT-defined treatment failures or H. pylori recurrences at any point during the 9-month follow-up underwent a second endoscopy. In the posttreatment setting, HpSA had an overall sensitivity of 73% and a specificity of 67%. Agreement between UBT and HpSA diminished throughout the follow-up. Among 14 participants in whom HpSA remained positive at 1 month following treatment despite UBT evidence of treatment success, 12 (86%) became HpSA negative within 3 months posttreatment. Although this study confirmed the validity of the HpSA in the initial assessment of dyspeptic patients, the test demonstrated a reduced overall accuracy in the detection of treatment failures and H. pylori recurrences during 9 months of posttreatment follow-up. Furthermore, in some patients it may take up to 3 months after successful eradication for antigen shedding to diminish to levels within the negative HpSA range.

Negative effect of ranitidine on the results of urea breath test for the diagnosis of Helicobacter pylori

OBJECTIVES: In analogy with proton pump inhibitors, H2- antagonists may also be responsible for false-negative results on urea breath test for the detection of Helicobacter pylori. In this study we assessed the frequency and duration of false-negative urea breath tests in patients given different doses of ranitidine. METHODS: A total of 120 consecutive dyspeptic patients infected with H. pylori on the basis of concomitant positive results of CLO-test, histology and urea breath test were recruited for this prospective, open, parallel-group study performed in an urban university gastroenterological clinic. They were randomized to receive an acute treatment with either ranitidine 300 mg once a day in the evening, ranitidine 300 mg once a day in the morning, ranitidine 150 mg b.i.d., or ranitidine 300 mg b.i.d. for 14 days. The urea breath test was performed on day 14 while patients were still taking ranitidine, and on day 21, 1 wk after completion of therapy. The test was repeated on day 28 in those patients who were still negative on day 21. Duplicate breath samples were collected after ingestion of 75 mg 13C-urea plus citric acid. A δ value >5‰ was considered positive. RESULTS: Of 118 patients infected with H. pylori, 15 (13%) had a negative urea breath test on day 14. The false-negative results were equally distributed among the four groups of ranitidine dosage. Nine of these patients reverted to positive at 7 days and the remaining six at 14 days after completion of therapy. CONCLUSIONS: Our study shows that ranitidine negatively affects the results of urea breath testing, independent of the given dosage. Patients undergoing this examination for H. pylori diagnosis should discontinue use of H2-antagonists 2 wk before testing.

One year follow-up of patients after successful helicobacter pylori eradication therapy

The aim of this study was to investigate the Helicobacter pylori (Hp) status of patients who underwent successful eradication therapy 1 year prior to the study and to evaluate their current symptoms. Methods: all of the patients were initially evaluated by oesophago-gastro-bulboscopy and the Hp status was determined by at least two different methods [rapid urease test, histology or urea breath test (UBT)]. The Hp infection was treated with a 1-week triple therapy protocol, and the UBT was repeated 4–6 weeks later. We invited back 110 patients who had negative post-eradication UBT results 12±3 months prior to the study period. UBT was repeated and a questionnaire was completed about the previous and present complaints and medication. Results: 80 of the 110 patients (73%) came back for the follow-up. Twenty five patients had peptic ulcer disease, 36 patients had gastritis or duodenitis without erosive lesions, and 19 patients had erosive form of gastritis or duodenitis initially. All of the patients except one in the erosive gastritis group had negative control UBT 1 year after the eradication, which means 1.25% recurrence rate within 1 year. The eradication therapy completely revealed the symptoms of 16 patients in the ulcer group (64%), 13 patients in the gastroduodenitis group (36%, P=0.03 vs. ulcer patients), 10 patients with erosive gastroduodenitis (52%), but this was only temporary. One year after the eradication therapy seven of the ulcer patients (28%), 11 patients with gastroduodenitis (31%) and seven patients with erosive gastroduodenitis (37%) were symptom-free. Most of the patients had epigastric pain (44%), heartburn (43%) and/or abdominal distension (33%). Nine ulcer patients (36%), 10 patients with gastroduodenitis (28%) and five patients with erosive gastroduodenitis (26%) were taking H 2-blockers regularly. Conclusion: the 1-month post-eradication UBT was probable true negative in all of the evaluated cases, since 79 patients (98.75%) were also negative after 1 year. The Hp recurrence rate is very low (1.25%) in a 1-year period. The symptoms were relieved shortly after eradication therapy in the majority of patients with ulcer disease or erosive lesions. However, significantly smaller portion of the patients with gastroduodenitis became symptom-free. Only about one third of the treated patients remained symptom-free 1 year after the eradication.

Interpreting the 13C-urea breath test among a large population of young children from a developing country.

The 13C-urea breath test is a noninvasive tool for the diagnosis of gastric Helicobacter pylori infection. However, it has not been validated in young children from the developing world, where infection is very common. 13C urea breath tests were performed on 1532 occasions on 247 Gambian infants and children aged from 3 to 48 mo. The means and variances of the separate sub-populations of 13C enrichment results contained within the overall dataset were estimated by a Genstat procedure using the EM algorithm, thereby identifying a cut-off value to discriminate positive from negative results. To illustrate the appropriateness of this calculated cut-off value, 13C urea breath tests were performed upon a small group of 14 patients aged 6 to 28 mo undergoing diagnostic upper endoscopy. Fixed gastric antral biopsies were examined to identify H. pylori. Two subpopulations were identified within the large dataset. A cut-off value of 5.47 delta per thousand relative to Pee Dee Belemnite limestone above baseline at 30 min identified 95% of the normally distributed negative sub-population and 99.4% of the log normal distributed positive sub-population. Comparison with endoscopic data confirmed that this cut-off value was appropriate for this population, as 7/7 children without H. pylori on their gastric biopsies had negative urea breath tests, and 6/7 children with gastric H. pylori colonization had positive urea breath tests. These findings confirm the value of the urea breath test as a diagnostic tool in young children from developing countries. They also offer a way to calculate the most appropriate cut-off value for use in different populations and the likelihood that it will correctly assign any value into the appropriate sub-population, without the need for endoscopy.

Follow up after successful eradication of Helicobacter pylori: symptoms and reinfection.

The important long-term outcomes after Helicobacter pylori eradication are the proportion of patients with continuing symptoms, and the rate of recrudescence of the infection. Patients with proven H. pylori infection prior to treatment and a negative urea breath test at least 4 weeks after completing treatment were invited to return for a further urea breath test and a questionnaire. There were 167 patients and the mean interval since the post-treatment urea breath test was 16 months. The endoscopic diagnoses were duodenal ulcer 72, duodenitis 17, gastric ulcer 26, normal or oesophagitis 52. The ethnic groups were European 86, Maori 25, Pacific Island 28 and other ethnic groups 28. Ten patients (6%) had a positive urea breath test at follow up. The proportion of patients showing recrudescence of H. pylori was related to the delta value (delta) of the post-treatment urea breath test: delta 0-2, five of 146 (3.4%); delta 2-3, two of 18 (11%); and delta 3-4, three of five (60%). A symptom questionnaire was given to 147/157 patients with a persistently negative breath test; 60 had no symptoms, 31 had heartburn, 30 had epigastric pain, 15 had both heartburn and epigastric pain, and 11 had nausea or other symptoms. There were fewer symptoms in patients with gastric ulcer (GU) compared with patients with duodenal ulcer (DU) and non-ulcer patients. Twenty-four patients (16%) were taking H2-antagonists (including seven DU and five GU), 15 were taking antacids and four were taking omeprazole. There was no difference in medication use between diagnostic groups. Eighteen of the 46 patients (39%) with heartburn stated that this was a new symptom. Heartburn was a common symptom for duodenal ulcer patients after eradication (24/74, 32%). A second urea breath test 6-12 months after eradication is required to definitely prove eradication. Patients with a breath test delta value of 2-4 should have a repeat urea breath test.

Clarithromycin for the Eradication of Helicobacter Pylori

Helicobacter pylori infection has proven to be extraordinarily difficult to eradicate. Antimicrobial monotherapies have been particularly disappointing, with most eradication rates in the range of 0-15%. Clarithromycin has potential advantages over other macrolides to which H. pylori is susceptible because of its acid stability and solubility at low pH. We evaluated clarithromycin therapy (250 mg four times daily for 14 days) in 12 H. pylori-infected patients. The 13C-urea breath test was used to evaluate the effectiveness of therapy. Eradication was defined as a negative urea breath test 4-6 weeks after the end of treatment. Suppression of H. pylori was demonstrated in 11 of 12 patients (92%) by a negative urea breath test 2 days after start of treatment. H. pylori was eradicated in five (42%) of 12 patients. Adverse events were intermittent and mild. Clarithromycin is the first antimicrobial agent that appears to offer promise as monotherapy for the eradication of H. pylori.

A sensitive and specific serologic test for detection of Campylobacter pylori infection

Campylobacter pylori has been associated with gastritis, duodenal ulcer, gastric ulcer, and nonulcer dyspepsia. Evidence that C. pylori may be the causative agent or at least a major contributory factor in peptic ulcer disease has generated intense interest in the development of reliable methods for detecting C. pylori infections. We have developed a specific and sensitive enzyme-linked immunosorbent assay (ELISA) that detects serum immunoglobulin G antibodies directed against high molecular weight cell-associated proteins (HM-CAP) of C. pylori. In a blinded fashion we tested sera from 300 individuals and found that all of 147 HM-CAP ELISA-negative individuals were also negative for C. pylori, as documented by a negative urea breath test; also, 151 of 153 C. pylori-positive (by urea breath test) individuals were HM-CAP ELISA-positive. Campylobacter pylori was cultured from the two ELISA-negative but infected patients and these isolates did possess HM-CAP antigens, showing that these two individuals had failed to seroconvert. Thus, the specificity and positive predictive value of the HM-CAP ELISA were each 100%; the sensitivity of the assay was 98.7%, and the negative predictive value was 98.6%. The HM-CAP ELISA and the urea breath test both proved valuable for detecting C. pylori infection, the urea breath test being a more direct method whereas the ELISA is less expensive and easier to perform. Furthermore, the results of a serologic test such as the HM-CAP ELISA would not be influenced by recent ingestion of bismuth compounds or antimicrobial therapy, which might suppress C. pylori and cause a transient false-negative result in the urea breath test.