**6. Iron-deficiency anemia**

*H. pylori* infection has also been linked to iron-deficiency anemia (IDA) [42–44]. Mechanisms that cause IDA may increase iron loss due to hemorrhagic gastritis, gastric cancer, peptic ulcers, iron utilization for bacterial growth, achlorhydria resulting in reduced iron uptake, and reduced secretion of ascorbic acid [45].

A meta-analysis comprising 15,183 patients from 20 studies found an association between *H. pylori* infection and IDA (odds ratio (OR) 2.22) [46]. They also found a greater effect of eradication therapy plus iron than iron supplements alone but with heterogeneous results. Adult IDA patients reacted more strongly to eradication than children and adolescents, and bismuth triple therapy seemed to be more effective than proton pump inhibitor (PPI) triple therapy. The authors do not recommend a population-based screening for *H. pylori* to prevent IDA [46].

On the other hand, Herschko et al. studied 160 patients with autoimmune gastritis, of whom 83 presented with IDA [47]. When stratifying by age, they found a decreasing prevalence of coexistent *H. pylori* infection with increasing age: 88% at age <20 years, 47% at 20–40 years, 38% at 41–60 years, and 13% at age >60 years. A possible explanation, which other authors also have mentioned, is that *H. pylori* demands an acidic environment to survive, which no longer exists in advanced atrophic anemia. This might suggest that *H. pylori* infection in autoimmune gastritis may represent an early phase of the disease in which an infectious process is gradually replaced by an autoimmune disease terminating in a burned-out infection and the irreversible destruction of gastric mucosa. This might explain why younger patients with IDA have a high prevalence of *H. pylori* infection [47].

The British Society of Gastroenterology recommends noninvasive testing and antibiotic treatment for *H. pylori* in patients with IDA and normal esophagogastroduodenoscopy and colonoscopy [48]. The American College of Gastroenterology also recommends testing for *H. pylori* in patients with unexplained IDA [49]. The association between IDA and *H. pylori* infection in the pediatric population is less studied and with heterogeneous results. ESPGHAN/ NASPGHAN guidelines propose that in children with refractory IDA where there is an indication for upper endoscopy, it might be considered taking biopsies to test for *H. pylori* [41].
