Monday, 24 July 2017

False Positive and False Negative Results in Diagnosis of Helicobacter Pylori Infection Can be Avoided by A Panel of Serum Biomarkers

Helicobacter pylori (HP) management (including diagnosis and therapy) has been exhaustively reviewed in several reports. These reports are unanimous in that several clinical conditions seriously hamper the diagnostic value of the two most commonly used HP tests: 13C-Urea Breath Test (UBT) and Stool Antigen test (SAT), both false-negative and false-positive results being not uncommon. Basically, these false-negative results are due to decreased bacterial loads in the stomach mucosa, and include the following clinical conditions: 1) use of PPI medication; 2) use of antibiotics; 3) bleeding peptic ulcer; 4) atrophic gastritis (AG; with or without intestinal metaplasia); 5) gastric cancer; 6) MALT lymphoma, and 7) partial gastrectomy. Since the late 1990’s, it has been well established that UBT also gives false-positive results in cases where urease-producing bacterial species are colonizing an acid-free stomach due to AG or a long term use of proton pump inhibitors (PPI). It is to be emphasized that neither UBT nor SAT (or HP serology) is capable of diagnosing AG, caused by HP infection or autoimmune disease, thus missing the patients at high risk for important clinical sequels of AG: I) gastric cancer (GC), ii) esophageal cancer, iii) vitamin-B12 deficiency (due to malabsorption), and iv) malabsorption of calcium, iron, magnesium and certain medicines.

The understanding on the important role played by Helicobacter pylori (HP) infection in pathogenesis of gastric cancer (GC) and peptic ulcer disease has increased progressively since the discovery of the bacteria in 1984 by Marshall and Warren. According to the current concepts, GC develops from HP-infection through precursor lesions of progressively increasing severity: mild, moderate and severe atrophic gastritis (AG), ac companied by intestinal metaplasia (IM) and dysplasia. This sequence of events is generally known as the Correa cascade, and estimated to be involved in around 50% of GC cases, particularly the intestinal type of GC . In parallel with the increased understanding of the pathogenetic mechanisms, also the management of HP- infection has undergone substantial development during the past decade.

In this context, management also covers the complex topics related to the diagnosis of HP-infections. Much of this favorable development can be attributed to the European Helicobacter Study Group that took its first initiative in 1996 in Maastricht to gather dedicated experts in the field to review and discuss all relevant clinical data to arrive at recommendations for the clinical management of HP infection. Since then, these Maastricht conferences have been repeated every 4-5 years. Each of these conferences has yielded a Consensus Report, the latest being the 4th in order, published in 2012. Attempts to standardize HP management (diagnosis and treatment) within countries have led to several national guidelines. In all these reports, considerable attention has been paid to different diagnostic methods available for HP detection, also including comprehensive review of the advantages and limitations of each technique and their utility in different settings, all based on updated literature.  

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