Modern, simple breath testing for Helicobacter pylori
The Heliprobe® system by Kibion is a primary diagnostic tool for detecting the presence of Helicobacter pylori, and for eradication treatment follow-up.
The time from swallowing Helicap to getting a result is under 15 minutes making Heliprobe® the fastest Urea Breath Test available.
The compact size and simplicity of the system means breath tests can be conducted in your rooms with the results available right away.
The system comprises a capsule, a card for capturing the breath sample and the analyser unit. The HeliCap™ capsule contains labelled urea and is swallowed by the patient. The BreathCard contains a medium designed to trap the breath being tested. It includes an indicator window that changes colour when enough breath has been collected. The Heliprobe® analyser is a small, sturdy desktop sized unit with a simple interface.
Patients swallow a HeliCap™ capsule. After 10 minutes, the patient will breath into a BreathCard™ which holds the breath sample. The card is then placed into the Heliprobe® analyser and a button press initiates the analysis. After 250 seconds the result of the test is available.
With a sensitivity of 95% and specificity of 100% the Heliprobe™ delivers an outstanding level of accuracy1.
Backed by over a decade of research and development, with a proven track record of reliability Heliprobe® remains the instrument of choice by healthcare professionals worldwide.
[1] de Boer, W.A., C. van Alfen, J. Rydén. 2003. Validation of a new portable near patient ureas breath test; the Heliprobe® system. The European Helicobacter Study Group (EHSG) XVIth International Workshop, September 2003, Stockholm, Sweden.
What is Helicobacter pylori?
Helicobacter pylori is a bacterium which infects the lining of the stomach and is responsible for a high percentage of stomach and duodenal ulcers and is associated with stomach cancer and MALT lymphoma. Approximately 30% of the Australia population is thought to be infected with H. pylori with the percentage rising to approximately 40% for the over 60 age group.
People are usually infected in childhood and the infection can persist for many years, if not for life. It is thought that the bacterium is spread via person to person contact. It is common for H. pylori to be spread between family members. When a diagnosis of H. pylori infection is made, it is now advisable for immediate family members to be also breath tested and treated.
In order to cater to this increased need for routine screening, the Heliprobe® System provides a quick, simple diagnostic test which gastroenterologists and pathology laboratories can provide to patients for on-the-spot results.
How Heliprobe® works
Heliprobe® system was developed during the nineties by the Swedish company Noster System AB and was launched in 2001.
The Heliprobe™ System consists of three components; HeliCap™, BreathCard™ and Analyser. The system is designed to be usable in a doctor’s office and results are obtained on-site.
The patient swallows a capsule with C14 labelled urea. In the presence of Helicobacter pylori the urea is metabolised to carbon dioxide and ammonia by the urease enzyme produced by the bacteria.
H2N(14CO2)NH2O + H2O —(urease enzyme)—› 2NH3 + 14CO2
- On an empty stomach the patient swallows a HeliCap™ capsule with a glass of water.
- HeliCap™, containing 14C-labeled urea, disintegrates rapidly in the stomach and the 14C-urea is dissolved.
- In the presence of Helicobacter pylori, the 14C-urea is metabolized to carbon dioxide and ammonia by the enzyme urease, produced by Helicobacter pylori.
- The available 14C isotopes, now in the form of 14CO2, diffuse into the blood to be transported to the lungs, where it is exhaled in the breath to be captured during sampling. A positive answer offers conclusive evidence that the patient is infected with Helicobacter pylori.
- In the absence of Helicobacter pylori, the administered urea is absorbed in the gastrointestinal tract and subsequently voided.
Radioactivity
Although HeliCap™ is radioactive (14C, half life 5730 years), the radioactivity the patient is exposed to when swallowing a HeliCap™ (37kBq) is very small, significantly less than the dose given during a normal X-ray. There are studies that have investigated the level of radiation doses when performing a 14C-urea breath test. The conclusion is that the dose is very small and the risk is negligible.
Muster et al.1 investigated 18 subjects who received either 185 kBq or 37 kBq (14C) Urea. Elimination via breath and urine were examined up to 72 hours. Maximum recoveries of 14C were between 1 and 2 hours after ingestion. Overall elimination of 14C independent of the amount ingested (185 kBq vs 37 KBq) was ca 87 % in “high expirers” and ca 99% in “low expirers”. Long-term retention was low. When compared to daily exposure to natural sources of radiation which on average figure 3.7 kBq/day, then the remaining activity 3 days after ingestion of a HeliCap™ is not more and even less than the average natural daily exposition to radiation.
Leide-Svegborn et al.2 also conclude that the exposure from a test dose of 110 kBq in adults and of 55 kBq in children both correspond to about a day of natural radiation from the environment. The majority of (14C) excreted in urine was found in the first 24 hours, and peak expiration of (14C) occurred within the first hour after ingestion.
Further, exposure to radioactivity associated with the use of HeliCap™ is hundreds to thousands of times less than well accepted procedures performed in departments of radiology.
[1] Munster DJ, Chapman BA, Burt MJ, Dobbs BR, Allardyce RA, Bagshaw PF, Troughton WD, Cook HB. The fate of ingested 14C-urea in the breath test for Helicobacter pylori infection. Scand J Gastroenterol 1993; 28: 661-666
[2] S. Leide-Svegborn, K. Stenström, M. Olofsson et al., “Biokinetics and radiation doses for carbon-14 urea in adults and children undergoing the Helicobacter pylori breath test,” European Journal of Nuclear Medicine, vol. 26, no. 6, pp. 573–580, 1999.
Key Publications – Helicobacter pylori
M.J. 1996. The bacteria behind ulcers. Scientific American. Feb:104-107.
H. pylori is the cause of almost all cases of ulcer disease that are not related to medications. Nearly all patients with ulcers are infected by H. pylori, versus around 30% of age-matched control subjects in the USA. H. pylori infection and chronic gastritis increase the risk of developing a peptic ulcer by around 3 – 12 times within 10 – 20 years of infection. Antimicrobial medications can cure H. pylori infection and gastritis, markedly lowering the chances that ulcers will return.
Malfertheiner, P., F. Megraud, C.O’Morain, F. Bazzoli, E. El-Omar, D. Graham, R. Hunt, T. Rokkas, N. Vakil, and E.J. Kuipers, The European Helicobacter Study Group (EHSG). 2007. Current concepts in the management of Helicobacter pylori infection: The Maastricht III Consensus Report. Gut. 56:772-781.
Fifty experts from 26 countries, including primary care physicians, were involved in formulating the Maastricht III Consensus Report on the management of H. pylori infection. Eradication of H. pylori infection was recommended in patients with gastroduodenal diseases including peptic ulcer disease and low grade gastric, mucosa associated lymphoid tissue (MALT) lymphoma, atrophic gastritis, unexplained iron deficiency anaemia and chronic idiopathic thrombocytopenic purpure. Eradication of H. pylori is also recommended for first degree relatives of people with gastric cancer. Eradication of H. pylori infection was determined not to cause or exacerbate gastro-oesophageal reflux disease (GORD). Eradication of H. pylori infection may help prevent peptic ulcer in patients who are naïve users of non-steroidal anti-inflammatory drugs (NSAIDs). In primary care a test and treat strategy using a non-invasive test (e.g. urea breath test) is recommended in adult patients (< 45 years) with persistent dyspepsia.
Lee, S.Y. 2012. Future candidates for indications of Helicobacter pylori eradication: do the indications need to be revised? Journal of Gastroenterology and Hepatology. 27:200-211.
Beyond the currently accepted indications, a significant amount of new information about the eradication of H. pylori has emerged. It is recommended that future indications for H. pylori eradication should focus on reversible lesions such as certain types of acute gastritis including nodular gastritis, hypertrophic gastritis, Ménétrier’s disease, haemorrhagic gastritis and granulomatous gastritis. In addition, for chronic gastritis, closed-type atrophic gastritis and complete-type intestinal metaplasia appear to have improved reversibility after eradication of H. pylori, compared with open-type atrophic gastritis and incomplete-type intestinal metaplasia. Eradication of H. pylori can also be considered in patients younger than 40 years with a family history of gastric cancer, in patients on long-term medications that could cause bleeding or atrophy.
Malfertheiner, P., F. Megraud, C.O’Morain, J. Atherton, A.T.R. Axon, F. Bazzoli, G. F. Gensini, J.P. Gisbert, D.Y. Graham, T. Rokkas, E. El-Omar, and E.J. Kuipers, The European Helicobacter Study Group (EHSG). 2012. Management of Helicobacter pylori infection – the Maastricht IV/ Florence Consensus Report. Gut. 61:646-664.
Forty-four experts from 24 countries were involved in formulating the Maastricht IV/ Florence Consensus Report, which included examination of diagnostic tests for H. pylori. The EHSG recommended that a test-and-treat strategy is appropriate for univestigated dyspepsia in populations where the H. pylori prevalence is high (≥ 20%). The main non-invasive tests that can be used for the test-and-treat strategy are urease breath tests and monoclonal stool antigen tests. Urea breath tests are also recommended as non-invasive tests for determining the success of eradication treatment. The time for testing the success of H. pylori eradication after the end of treatment should be at least 4 weeks.
HELIPROBE®
Hegedus, O., J. Rydén, A.-S. Rehnberg, S. Nilsson, and P.M. Hellström. 2002. Validated accuracy of a novel urea breath test for rapid Helicobacter pylori detection and in-office analysis. European Journal of Gastroenterology and Hepatology. 14:1-8.
The Heliprobe® system was validated against a conventional urea breath test system using β-scintilllation in 203 pre-treatment and 147 post-treatment patients. For pre-treatment detection full concordance was found between the two urea breath test systems, with 100% sensitivity and specificity (CI 95 – 100% and 97 – 100%, respectively) and b agreement (r = 0.80, CI 0.75 – 0.85; к = 1, CI 0.86 – 1.14; P < 0.0001). For post-treatment detection there was 100% sensitivity and specificity (CI 95 – 100% and 97 – 100%, respectively) and significant agreement (r = 0.48, CI 0.34 – 0.59; к = 1, CI 0.84 – 1.16; P < 0.0001). In addition, the use of encapsulated 14C-urea versus liquid form was validated (n = 37). The use of encapsulated 14C-urea did not change agreement between the urease breath test systems, with sensitivity and specificity remaining at 100% (CI 72 – 100% and 87 – 100%, respectively) with b agreement between the tests (r = 0.71, CI 0.50 – 0.84; к = 1, CI 0.68 – 1.32; P < 0.0001). It was concluded that the Heliprobe® system, with either liquid or encapsulated 14C-urea, was equi-efficacious to conventional urea breath tests, thus fulfilling its role as the non-invasive gold standard for detection of H. pylori.
de Boer, W.A., C. van Alfen, J. Rydén. 2003. Validation of a new portable near patient urea breath test; the Heliprobe® system. The European Helicobacter Study Group (EHSG) XVIth International Workshop, September 2003, Stockholm, Sweden.
Between April 2000 – January 2002 endoscoped patients biopsied for H. pylori also undertook urease breath tests using the Heliprobe® system. 107 patients participated, with 1 patient excluded due to an indeterminate result. In all patients 7 biopsies were taken, and combined biopsy results served as the gold standard. H. pylori prevalence was 39% by biopsy, and the Heliprobe® system provided sensitivity 95% (40/42) (95% CI 84-99) and specificity 100% (64/64) (95% CI 94-100). There were no adverse events, and it was noted that the Heliprobe® system was “easy to use”, “extremely reliable” and results were obtained within 20 minutes.
Öztürk, E., Z. Yeşilova, S. Ilgan, S. N. Arslan, A. Erdil, B. Celasun, M. Özgüven, K. Dağalp, Ö. Ovali, and H. Bayhan. 2003. A new, practical, low-dose 14C-urea breath test for the diagnosis of Helicobacter pylori infection: clinical validation and comparison with the standard method. European Journal of Nuclear Medicine and Molecular Imaging. 30:1458-1461.
The Heliprobe® system correctly identified 48 of 48 H. pylori-positive patients and 19 of 25 H. pylori-negative patients, with a sensitivity of 100%, specificity of 76%, positive predictive values of 88%, negative predictive value of 100% and accuracy of 91%. In comparison, the standard urea breath test system correctly identified 48 of 48 H. pylori-positive patients and 20 of 25 H. pylori-negative patients, with a sensitivity of 100%, specificity of 80%, positive predictive values of 90%, negative predictive value of 100% and accuracy of 93%. The CLO test identified 26 of 32 H. pylori-positive patients and 12 of 16 H. pylori-negative patients, with a sensitivity of 81%, specificity of 75%, positive predictive values of 86%, negative predictive value of 66% and accuracy of 79%.
Borody, T.J., A.R. Wettstein, J. Campbell, M. Torres, L. Hills, K. Herdman, G. Pang, and S. Ramrakha. 2008. Rapid and superior diagnosis of H. pylori infection by 14C-urea Heliprobe™ test versus the PYtest®. May 2008. Digestive Diseases Week, San Diego, California, USA.
The Heliprobe™ system was validated against the PYtest® using 119 consecutive patients (58 males, 61 females, mean age 48.9 +/- 12.5 years and 49.3 +/- 12.6 years, respectively) with dyspeptic symptons undergoing gastroscopy. Patients were randomised to the two systems at baseline then followed up at 10-12 days and re-tested in a cross-over fashion. H. pylori infection was confirmed by biopsy tests including rapid urease test (RUT) and histology. H. pylori infection was diagnosed by histology and RUT in 49 (41%) of patients. Heliprobe® detected infection in 49 (41%) and PYtest in 44 (37%) of patients. Comparing Heliprobe® and PYtest, using RUT and histology as standards, sensitivity was 98% (CI 89-99%) versus 86% (CI 73-94%) (P=0.0001), and specificity was 100% (CI 94-100%) versus 97% (CI 89-99%). Positive predictive values for Heliprobe® versus PYtest were 100% (CI 93-100%) versus 96% (CI 86-99%), negative predictive value were 98% (CI 92-99%) versus 97% (CI 89-99%) and accuracy 99% (CI 95-100%) versus 93% (CI 87-97%) (P=0.0001). Kappa test results showed ber agreement with the reference standard for Heliprobe® (к = 0.97) than for PYtest (к = 0.810) (P=0.0001).
14C urea breath tests in CHILDREN
Leide-Svegborn, K. Stenström, M. Oloffson, S. Mattsson L.-E. Nilsson, B. Nilsson, et al. 1999. Biokinetics and radiation doses for carbon-14 urea in adults and children undergoing the Helicobacter pylori breath test. European Journal of Nuclear Medicine. 26:573-580.
For children aged 7-14 years, dose values per unit of administered carbon-14 are similar to those of adults. Thus it was concluded that there is no reason for restrictions on performing a normal carbon-14 breath test on children in this age bracket.
Gunnarsson, M., S. Leide-Svegborn, K. Stenström, G. Skog, L.-E. Nilsson, R. Hellborg, and S. Mattsson. 2002. No radiation protection reasons for restrictions on 14C urea breath tests in children. The British Journal of Radiology. 75:982-986.
Using 55 kBq the effective dose to a 3-year old child was determined to be 6 µSv for a H. pylori-negative child and 20 µSv for a H. pylori-positive child. This dose is of the same magnitude as a few days of natural background radiation. Therefore it was concluded that there is no reason for restrictions on performing a normal carbon-14 breath test on children aged 3 – 7 years.
14C urea breath tests in
PREGNANT WOMEN
Bentur, Y., D. Matsui, and G. Koren. 2009. Safety of 14C-UBT for diagnosis of Helicobacter pylori infection in pregnancy. Canadian Family Physician. 55:479-480.
Radiation exposure of a foetus from the dose of 14C given as part of the urea breath test (UBT) to a pregnant woman is at least a thousand times lower than the dose considered terratogenic. Frequent voiding can substantially reduce the radiation-absorbed dose to the urinary bladder wall. In the event of inadvertent exposure during pregnancy, the pregnant woman should be reassured given the low foetal radiation dose.
