A 48-year-old woman with chronic NSAID use presents with epigastric pain and is found to have a gastric ulcer on endoscopy. Her serum gastrin level is 45 pg/mL (normal <100). Which finding best distinguishes NSAID-induced gastric ulcer from H. pylori–associated gastric ulcer?

## Distinguishing NSAID-Induced from H. pylori–Associated Gastric Ulcer **Key Point:** The single most reliable discriminator between NSAID-induced and H. pylori–associated gastric ulcers is the **presence or absence of H. pylori infection**—demonstrated by negative urease test, serology, and/or stool antigen in NSAID ulcers versus positive results in H. pylori ulcers. ### Pathophysiological Distinction **NSAID-Induced Ulcer:** - Direct mucosal injury via COX inhibition → ↓ PGE₂ and PGI₂ - Reduced mucus and bicarbonate secretion - Impaired mucosal blood flow - **H. pylori absent** (negative serology, urease test, stool antigen) - Acid secretion typically normal or low **H. pylori–Associated Ulcer:** - Chronic antral inflammation → increased gastrin release - Increased acid secretion (especially in duodenal ulcer; variable in gastric) - **H. pylori present** (positive urease test, serology, stool antigen, PCR) - Histology shows active chronic inflammation with organisms ### Comparison Table | Feature | NSAID Ulcer | H. pylori Ulcer | | --- | --- | --- | | **H. pylori status** | Absent (KEY) | Present (KEY) | | **Urease test** | Negative | Positive | | **Serology (IgG)** | Negative | Positive | | **Stool antigen** | Negative | Positive | | **Antral gastritis** | Minimal or absent | Marked (active chronic) | | **Acid secretion** | Normal or ↓ | ↑ (especially duodenal) | | **Ulcer location** | Antrum, lesser curve | Antrum, lesser curve (similar) | | **Risk factors** | NSAID, age, female | H. pylori exposure, ethnicity | **High-Yield:** The **absence of H. pylori** (negative urease test AND serology) is the gold-standard discriminator. In clinical practice, if an ulcer is found and H. pylori testing is negative, NSAID use (or rare causes like Zollinger–Ellison syndrome) must be considered. **Clinical Pearl:** A patient on chronic NSAIDs with a gastric ulcer and negative H. pylori serology confirms NSAID aetiology. Conversely, a patient with positive H. pylori serology and a gastric ulcer should be treated with eradication therapy, regardless of NSAID history. ### Why Location and Acid Are Not Discriminators Both NSAID and H. pylori ulcers commonly occur on the lesser curvature and antrum—location alone does not distinguish them. Acid secretion is also variable in gastric ulcers of both types (often normal or low). Only the **microbiological status** reliably separates the two. [cite:Harrison 21e Ch 297]