Epidermal growth factor and transforming growth factor alpha in duodenal ulcer and non-ulcer dyspepsia patients before and after Helicobacter pylori eradication

Background: Epidermal growth (EGF) and transforming growth factor alpha (TGF alpha) are potent gastric secretory inhibitors, mitogens, and mucosal protectors, bur the impact of Helicobacter pylori infection on their mucosal expression and luminal release has not been clarified. Methods: In this study, gene and immunoreactive and immunohistochemical expressions of EGF and TGF alpha were assessed in the gastric mucosa of 15 H. pylori-negative healthy normals,in 22 H. pylori-positive duodenal ulcer patients (DU) and in 24 H. pylori-positive non-ulcer dyspepsia patients (NUD). All studies in DU and NUD patients were repeated after 2 weeks of triple therapy (amoxicillin + clarithromycin + omeprazole) and 4 weeks and 2 years later. Results: Immunohistochemical expression of EGF and TGF alpha in H. pylori-positive DU and NUD was significantly higher than in H. pylori-negative normals, and this increase persisted at 2 and 4 weeks after therapy but normalized 2 years later. EGF mRNA was detected in the gastric mucosa of H. pylori-positive DU before and at 2 and 4 weeks after H. pylori eradication, but it was not found 2 years after the eradication of H. pylori or in gastric mucosa of H. pylori-negative control subjects. TGF alpha mRNA was detected in the gastric mucosa independently of H. pylori status, with the stronger expression observed in the gastric mucosa of H. pylori-positive DU and NUD before eradication than after this procedure. Plasma gastrin, which was significantly increased in H. pylori-positive DU, normalized already after 2 weeks of triple therapy. The eradication rate as determined by histology after triple therapy reached 86.3% in DU patients and 90.5% in NUD patients. Two years after the eradication the H. pylori reinfection rate was 4.5% among DU patients and 4.2% among NUD. Treatment of DU patients with triple therapy resulted in complete ulcer healing. Conclusions: 1) Chronic H. pylori infection and resulting antral gastritis are associated with increased plasma gastrin and increased mucosal cell proliferation, probably due to enhanced expression of EGF and TGF alpha, and 2) the H. pylori eradication results in a decrease in plasma gastrin, but the increase in gastric TGF alpha and EGF content is sustained, suggesting that they may be involved in ulcer healing.