The Resolution of Severe Iron-Deficiency Anemia After Successful Eradication of Helicobacter pylori in Teenagers

**Background:** Helicobacter pylori infection is associated with iron-deficiency anemia (IDA), particularly in children and adolescents. Meta-analyses report a pooled odds ratio of 1.33 for IDA in H. pylori-infected individuals. The Maastricht V/Florence Consensus and pediatric guidelines recommend H. pylori eradication for recurrent or refractory IDA when other causes are excluded. However, the mechanisms in children remain unclear because, unlike adults, infected Japanese children typically lack significant gastric atrophy or reduced acid secretion. Increased iron demand during adolescent growth spurts and sports activities may synergize with H. pylori infection. Long-term follow-up data (>6 months) after eradication are scarce.

**Methods:** Seven H. pylori-infected patients (12–16 years old; 2 female, 5 male) with recurrent (n=5), refractory (n=1), or both recurrent and refractory (n=1) IDA were referred to Tohoku University Hospital. Five participated in intensive sports. All underwent esophagogastroduodenoscopy (EGD) with gastric biopsies, ¹³C-urea breath test, and hematological evaluation. Baseline median values: hemoglobin 6.3 g/dL (range 5.3–8.3), serum iron 9 μg/dL (range 5–30), serum ferritin 1.5 ng/mL (range 0.9–6.8). No patient had hemorrhagic lesions on EGD. All had chronic gastritis without significant atrophy (median atrophy grade 0 in antrum and corpus) or intestinal metaplasia. Patients received a 7-day lansoprazole-based triple regimen (amoxicillin + clarithromycin or metronidazole) plus oral sodium ferrous citrate (50–100 mg/day iron) for 1–4 months post-eradication. Hematological data were compared at baseline, 2–3 months post-eradication, and at final follow-up (median 20 months, range 9–76 months) using paired t-tests.

**Key Results:** Successful eradication was confirmed by negative ¹³C-urea breath test in all patients. At 2–3 months post-eradication, hemoglobin (median 12.5 g/dL, range 10.8–14.2) significantly increased from baseline (P < 0.001). Serum iron (median 95 μg/dL, range 55–205) and ferritin (median 12.1 ng/mL, range 8.9–23.9) also significantly increased (P < 0.005 and P < 0.001, respectively). At final follow-up (median 20 months after stopping iron), hemoglobin remained significantly higher than at 2–3 months (median 14.2 g/dL, range 10.8–16.1; P < 0.05). Serum iron (median 102 μg/dL, range 76–239; P = 0.93) and ferritin (median 29.3 ng/mL, range 3.9–102.1; P = 0.15) were maintained at similar levels. No patient had recurrence of IDA.

**Clinical Implications:** This study provides long-term evidence that H. pylori eradication leads to sustained normalization of iron indices in adolescents with recurrent or refractory IDA, even after iron supplementation is discontinued. The absence of hemorrhagic lesions or gastric atrophy suggests H. pylori itself—not blood loss or hypochlorhydria—is central to IDA pathogenesis in this population. Increased iron demand from growth spurts and sports activities likely plays a synergistic role. Limitations include the small sample size (n=7), lack of a control group, no data on menstrual bleeding in the 2 female patients, and no routine duodenal biopsy (though celiac disease is rare in Japan). Despite these limitations, the findings support H. pylori testing and eradication in adolescents with unexplained recurrent or refractory IDA.