Alimentary Tract
Clinical usefulness of serum pepsinogens I and II, gastrin-17 and anti-Helicobacter pylori antibodies in the management of dyspeptic patients in primary care

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Abstract

Background.

Several tests have been proposed for evaluating dyspeptic symptoms and their relationship to the underlying gastric disease. Serum pepsinogens and gastrin-17 are known to be useful biomarkers for the detection of gastric pathologies.

Aim.

To evaluate the capability of screening dyspeptic patients in the primary care by analyses of serum pepsinogens I (sPGI) and II (sPGII), gastrin-17 (sG-17) and the IgG anti-Helicobacter pylori antibodies (IgG-Hp).

Patients and methods.

Three hundred and sixty-two consecutive patients with dyspeptic symptoms (208 females, mean age 50.6 ± 16 years, range 18–88 years) referred by general practitioners for upper gastrointestinal endoscopy were enrolled. A blood sample was taken from each subject for IgG-Hp, sPGI, sPGII and sG-17 analyses.

Results.

Two hundred and eighty-seven patients had a complete screening; of these, 132 resulted positive for Hp infection. Patients with atrophic chronic gastritis showed significantly lower serum pepsinogen I levels and sPGI/sPGII ratio than patients with non-atrophic chronic gastritis. Moreover, by calculating the values of sPGI by sG-17 and sG-17 by sPGII/sPGI, subjects with atrophic chronic gastritis could be distinguished from those with non-atrophic chronic gastritis and from those with normal mucosa, respectively. sG-17 levels were found to be a useful biomarker for the detection of antral atrophic gastritis, while the combination of sPGI, the sPGI/sPGII ratio and sG-17 was found effective in identifying corpus atrophy.

Conclusion.

A panel composed of PGI, PGII, G-17 and IgG-Hp could be used as a first approach in the ‘test and scope’ and/or ‘test and treat’ strategy in the primary care management of dyspeptic patients.

Introduction

Approximately 25–40% of the general population has experienced dyspeptic symptoms [1], [2]. Management of these patients occurs at the primary care level, and as such, most patients are treated without confirmatory analyses [3], [4], [5]. H. pylori is known to be the causal agent for several gastroduodenal diseases [6], [7], [8], [9]. The infection is initially confined to the antrum, causing a superficial gastritis, which then progresses to pangastritis or corpus predominant gastritis, often developing into atrophy over several years [10]. Atrophic gastritis can be related to autoimmune diseases, although this is less frequent in Western Europe. Several diagnostic tests are performed to evaluate dyspeptic symptoms, including upper gastrointestinal endoscopy, radiography and testing for H. pylori infection [11], [12], [13], [14]. Endoscopy with biopsy remains the gold standard method for the diagnosis of most of the conditions associated with dyspepsia and provides information about H. pylori infection, the presence of atrophy, intestinal metaplasia or dysplasia, as well as their topographical distribution [15]. This invasive method is uncomfortable, distressing and very expensive. Current interests lie in finding rapid, reliable and inexpensive non-invasive tests for screening and monitoring patients with mild to moderate dyspeptic symptoms [16]. 13C-UBT and H. pylori stool antigen (HpSA) analyses are often used, but they do not offer information about the morphological status of gastric mucosa [17], [18].

Recently, the determination of serum pepsinogens I (sPGI) and II (sPGII), gastrin-17 (sG-17) and IgG anti-H. pylori antibodies (IgG-Hp) by ELISA has been proposed as a series of non-invasive markers for the assessment of both morphological and functional status of gastric mucosa in subjects with dyspeptic symptoms [19], [20]. PGI and PGII are both precursors of pepsin. PGI, exclusively secreted by oxyntic glands, is a specific marker of corpus secretion capacity. Conversely, PGII produced by all gastric glands (oxyntic, cardiac and pyloric) as well as duodenal (Brunner's) glands is strongly influenced by gastric inflammation [21], [22]. These precursors are secreted into the gastric lumen, but only a small amount, which is measurable, leaks into the blood stream. Gastrin-17 (G-17), produced exclusively in the antrum and secreted directly in the blood, represents a specific marker of G cell functionality [23]. Studies have shown that sPGI, sPGII and sG-17 levels are high in the presence of H. pylori related to non-atrophic chronic gastritis (NACG) [24], [25]. SPGI and sPGII concentrations are found to decrease significantly 2 months after a successful H. pylori cure [26], [27], [28]. Similarly, sPGI levels and the calculated value, sPGI·gastrin, are found to predict the presence of gastric cancer [29], [30], [31]. Indeed, sPGI and/or sPGI/sPGII levels are considered serological markers of atrophic body gastritis [32], [33], [34]. In the latter condition, G-17 levels are significantly high. Conversely in antral atrophy, they become very low due to the exiguity number of G cells [23].

The correlations between the above-mentioned variables and related histological patterns of gastritis could give a first selection of patients, who need an upper gastrointestinal endoscopy with multiple biopsies to identify precancerous gastric conditions or lesions [35].

The aim of the present study was to evaluate dyspeptic patients in the primary care by means of a panel of non-invasive serological tests (PGI, PGII, G-17 and IgG-Hp) and to establish the accuracy of these tests to identify patients with atrophic chronic gastritis (ACG) in whom gastroscopy and biopsy should be performed.

Section snippets

Patients

This study was conducted in two gastroenterological centres in Italy (in Belluno, located in the mountains of north-eastern Italy and in Parma, located on the agricultural plain in central Italy). The policy of ‘open access’ to endoscopy was adopted by each centre, to which general practitioners (GP) could directly refer patients for further investigation when needed.

After a series of meetings aimed at informing the GPs about the relevance of sPGI, sPGII, sG-17 and IgG-Hp analyses in the

Results

Seventy-five patients were excluded from the study because they were under therapy with proton pump inhibitors. Of the remaining 287 patients, 132 were positive for H. pylori infection (68 females, mean age 51.2 ± 16.1 years, range 19–83 years) and 155 were negative (mean age 48.0 ± 16.5 years, range 18–88 years). H. pylori-positive patients demonstrated significantly higher mean sPGI (120.6 ± 63.2 μg/L), sPGII (15.9 ± 1.0 μg/L) levels and IgG-Hp titres (73.1 ± 32.6 IU) than H. pylori-negative patients

Discussion

This study was aimed to validate a non-invasive test or panel of tests to evaluate, at the primary care level, patients with dyspeptic symptoms and to select subjects in whom gastroscopy with biopsy should be done. The relationship of sPGI, sPGII, sG-17 and IgG-Hp levels to histological gastric mucosal damage was assessed. It is well known that the GP must have a fast, reliable and inexpensive test to identify patients with dyspepsia who are in need of a more thorough, yet invasive and costly,

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