Serum Pepsinogen Ⅰ and the Pepsinogen Ⅰ/Ⅱ Ratio as a Non-invasive Predictive marker for Autoimmune Metaplastic Atrophic Gastritis

Objective Autoimmune metaplastic atrophic gastritis (AMAG) is a chronic inflammatory disease characterized by autoimmune destruction of parietal cells, causing profound gastric body and fundus atrophy. AMAG is frequently overlooked or misdiagnosed in clinical practice. This study aimed to identify optimal cut-off values for serum pepsinogens (PGs) as a non-invasive diagnostic tool for AMAG in a retrospective cohort. Methods We retrospectively analyzed the clinical and laboratory data of 520 AMAG patients from our center and compared them with those of 223 control patients who underwent serum PG testing and esophagogastroduodenoscopy (EGD) for various indications during the same period. Results The AMAG cohort demonstrated a marked female predominance compared with controls (74.6% vs. 45.2%, p < 0.001), and 23.1% of patients were asymptomatic at diagnosis. Serological profiling showed that anti-parietal cell antibody was positive in 65.9% (309/469) of tested individuals, while anti-intrinsic factor antibody was detected in 39.1% (61/156). Gastric neuroendocrine tumors (NETs) were the most frequent neoplastic finding in AMAG (105 patients, 20.2%). Fasting gastrin-17 levels were significantly elevated in AMAG patients alongside markedly decreased pepsinogen I (PG I) and PG I/II ratio compared with controls (all p < 0.001). Receiver operating characteristic analysis identified PG I < 22.45 ng/mL (AUC: 0.964, 95% CI: 0.950–0.978; sensitivity: 88.9%, specificity: 96.0%) and PG I/II ratio < 2.25 (AUC: 0.957, 95% CI: 0.941–0.974; sensitivity: 89.6%, specificity: 95.1%) as optimal cut-offs for distinguishing AMAG from controls. The combined use of PG I < 22.45 ng/mL and PG I/II ratio < 2.25 achieved a specificity of 97.3% (95% CI: 94.2%–99.0%). Conclusions Serum PG I and the PG I/II ratio demonstrate good diagnostic performance for AMAG, with high specificity in particular. These biomarkers may serve as a useful non-invasive screening tool for AMAG.