At a Glance

Gastritis is the common term used to refer gastric mucosa inflammation, one of the main causes of dyspepsia, a very common symptom caused by several organic or functional diseases. It presents as chronic or recurrent epigastric pain, upper abdominal fullness and feeling full earlier than expected during eating, and loss of appetite. It can be accompanied by bloating, belching, nausea, or heartburn.

Gastritis is caused by different exogenous and/or endogenous factors, and it is usually classified as acute or chronic, according to the length of symptoms and functional diseases.

There are two categories of gastritis:

Acute gastritis, which is generally linked to alcohol abuse, NSAIDs consumption, acute chemical or irritant injury, bile reflux and systemic infections, as well as H. pylori infection. Most acute gastritis is self-limiting 7-15 days after pathogen and/or injury removal.

Chronic gastritis is classified into two subtypes: nonatrophic and atrophic.

Chronic nonatrophic gastritis: Antrum of the stomach is primarily involved.

Chronic atrophic type A gastritis: Autoimmune pathogenesis usually involving gastric body and fundus.

Chronic atrophic type B gastritis: Commonly H. pylori-associated and involving gastric antrum at the beginning with possible evolution to pan-gastritis as the disease progresses.

What Tests Should I Request to Confirm My Clinical Dx? In addition, what follow-up tests might be useful?

Since the majority of chronic gastritis worldwide (more than 90%) is caused by H. pylori infection and the H. pylori “test and treat” strategy has been recommended for the management of dyspeptic patients without alarm symptoms, H. pylori infection diagnosis is recommended (see H. pylori).

To obtain insights into the severity and extension of gastric mucosa inflammation, the request of the so-called “GastroPanel” is suggested. GastroPanel is a biochemical integrated test that might support the clinical suspicion of gastritis. It is based on the measurement in serum of pepsinogens A and C (PGA and PGC), Gastrin-17 (G-17), and anti-H. pylori antibodies all entering in a classification algorithm analysis.(Table 1)

Table 1
  PGA PGC PGA/PGC G-17 Anti-H. pylori
Normal mucosa Normal Normal Normal Normal Normal
Corpus atrophic gastritis Low Normal Low High Normal or high in the presence of H. pylori infection
Pan-atrophic gastritis Low Low Normal or low Low Normal or high in the presence of H. pylori infection
Non-atrophic gastritis High High Normal or low Normal or high Normal or high in the presence of H. pylori infection

They are pepsin proenzymes measurable in the sera: PGA (also called PGI, produced by the gastric corpus) and PGC (also called PGII, produced by the gastric corpus and antrum). Their serum levels reflect parietal cell mass, and, consequently, reduced levels in serum are an index of the presence of gastric mucosa atrophy. Conversely, inflammation enhances serum pepsinogens levels. High serum PGA can be considered a marker of nonatrophic gastritis, subclinical marker of duodenal ulcer and of any eventual complication, as well as marker of possible recurrence of peptic ulcer. Conversely, low PGA serum levels (<25 pg/mL) are a marker of severe atrophic gastritis, and, when associated with high serum G-17 and PGC levels, results in a low PGA/PGC ratio, testified corpus atrophy, and a risk condition for gastric cancer.

Fasting G-17

G-17 is a 17-aminoacids form of gastrin produced by antral G cells. Its fasting level increases in case of gastric antrum inflammation and/or when gastric acid secretion is low. H. pylori infection, as well as chronic therapy with proton pump inhibitors (PPIs) may induce a slight G-17 increase, whereas, in the presence of atrophy of the corpus mucosa with consequent hypo- or a-chloridrya, serum levels increase much more.

Anti-H. pylori antibodies

Anti-H. pylori antibodies of the IgG class are used in the algorithm as marker of infection (see H. pylori).

The classification algorithm analysis uses the subsequent four parameters to identify patients without gastritis or patients with different biochemical patterns of gastritis:

Normal mucosa: All parameters fall within the reference interval (i.e., 30-150 ug/L for PGA, 3-20 ug/L for PGC, 1-10 pmol/L for G-17, and <30 EIU for anti-H. pylori antibodies). The high negative predictive value of a normal test result (>90%) allows clinicians to avoid further invasive and eventually expensive diagnostic procedures.

H. pylori-associated non atrophic gastritis: PGC shows a relatively greater increase than PGA, resulting in a significant decrease of PGA/PGC ratio. In particular, PGC levels increase according to the severity of gastric mucosa inflammation either in antrum or corpus. G-17 levels could be normal or slightly high. Anti-H. pylori antibodies are elevated.

Nonatrophic gastritis: Both pepsinogens increase. G-17 levels could be normal or slightly high. Anti-H. pylori antibodies are negative.

Atrophic gastritis: A common feature of corpus atrophy is a very low PGA serum level (≤ 25 ug/L).Type A autoimmune gastritis is characterized by hypochlorhydria or achlorhydria resulting from parietal cell destruction secondary to autoantibodies that recognize the H+/K+ATPase of the parietal cells. PGA decreases more than PGC, and, consequently, PGA/PGC ratio is very low, whereas G-17 serum level increases as normal response to high intragastric pH. Anti-H. pylori antibodies may or may not be present, according to the presence or absence of infection. Type B is a multifocal chronic atrophic gastritis in which also G-17 can result low because of gastric antrum involvement. Most of these forms of gastritis are H. pylori related, and anti-H. pylori antibodies are usually high.

Are There Any Factors That Might Affect the Lab Results? In particular, does your patient take any medications – OTC drugs or Herbals – that might affect the lab results?

Use of PPIs raises serum levels of G-17 and pepsinogens and may cause false-positive results. Therapy should be discontinued at least 15 days before both tests. Gastrin and intragastric pH, in fact, form a feed-back control mechanism in which hypochlorhydria enhances the gastrin release from antral G cells, and G-17 itself stimulates acid output from parietal cells in the gastric corpus. Gastrins are also trophic hormones and persistently high serum levels result in hyperplasia and hyperthophy of the gastric mucosa with a consequent increase in pepsinogens release.

Fasting is requested for the GastroPanel test (eating may increase serum G-17 levels).

What Lab Results Are Absolutely Confirmatory?

Urea breath test or H. pylori stool antigen testing are confirmatory of H. pylori infection. Biopsy makes the definitive diagnosis possible.

What Tests Should I Request to Confirm My Clinical Dx? In addition, what follow-up tests might be useful?

The following tests should be ordered:

Post-prandial G-17 (with 250 Kcal of protein): Although post-pranadial G-17 is suggested to be a more sensitive index than fasting G-17, meal is not easy to standardize both in the same laboratory and even more so among different laboratories. Furthermore, for the patient, post-prandial G-17 determination is more cumbersome than fasting G-17.

Complete blood count (CBC): CBC is indicated to diagnose anemia. Iron deficiency anemia may be a sign of chronic bleeding or of impaired nonemic iron absorption. Parietal cell destruction could lead to reduced intrinsic factor and, consequently, to vitamin B12 deficiency and pernicious anemia. In about 60% of these patients, intrinsic factor autoantibodies are also found.

Follow-up of H. pylori eradication therapy: Serum PGC decreases earlier (2 months after successful therapy) than anti-H. pylori antibodies, and it is considered a more reliable index of resolution of gastric mucosa inflammation. Anti-H. pylori antibodies would return into normal range approximately 6-12 months after a successful eradication therapy.

Additional Issues of Clinical Importance

The presence of gastrointestinal bleeding, difficulty swallowing, unintentional weight loss, and persistent vomiting are suggestive of peptic ulcer disease or malignancy (alarm symptoms) and would necessitate urgent further instrumental investigations (EGDS).

In case of low pepsinogens, as well as positive findings of antiparietal cells and/or anti-intrinsic factor autoantibodies, request EGDS with appropriate multiple biopsies to characterize the extension and degree of gastric mucosa atrophy, which are directly correlated with cancer risk. Moreover, H. pylori has been classified by the International Agency for Research on Cancer (IARC) as type I carcinogen, and eradication therapy is recommended when the infection is diagnosed.

Patients with low serum fasting G-17 level but normal serum PGA and post-prandial G-17 levels are generally hypersecretors, and high gastric acid increases the risk of gastroesophageal reflux disease (GERD) and its complications (e.g., Barret’s esophagus).

High serum gastrin levels could also indicate the presence of a Zollinger Ellison syndrome, a rare disorder caused by neoplastic production of the hormone and, consequently, gastric acid hypersecretion with peptic ulcer disease and persistent diarrhea. Provocative tests (e.g., secretin test) are useful for establishing whether a patient has a gastrinoma, which usually develops in the duodenum, the pancreas, or abdominal lymph nodes, but which can also develop in distant sites. Gastrinoma can occur as a component of multiple endocrine neoplasia type 1 (MEN1) syndrome or can occur in isolation.

Errors in Test Selection

Other causes of epigastric pain may be related to food intolerance, food allergy, celiac disease, angina abdominis, acute or chronic pancreatitis, choledocolithiasis, and other conditions that should be suspected by the clinician on the basis of an accurate evaluation of symptoms and on proper laboratory and/or imaging and/or endoscopic tests.

Errors in Interpretation of Test Results

Anti-H. pylori antibodies remain high for months, even after a successful eradication therapy. A high value might erroneously be interpreted as indicative of persistent infection when clinical data are not collected.

Some H. pylori strains (e.g., those CagA negative) are low immunogenic. In these cases, a low value of anti-H. pylori antibodies might be erroneously interpreted as indicative of the absence of H. pylori infection.

Low serum pepsinogens could reflect the presence of a small stomach, especially in children.