Helicobacter pylori (H. pylori) infection is one of the most common and persistent bacterial infections worldwide, with a wide variation of prevalence from 22% to 87%, especially in developing countries.1,2 The manifestations of H. pylori infection vary from asymptomatic to symptomatic. Disorders commonly caused by H. pylori infection are gastritis, peptic ulcer disease, gastric ulcers, and gastric cancer.3 In addition to gastroduodenal diseases, numerous studies have shown that H. pylori infection can cause disorders outside the gastrointestinal tract.4 Iron deficiency anemia is one of the most concerning disorders among extra-gastroduodenal disorders.4,5

Increasing evidence has reported an association between H. pylori infection and iron deficiency anemia (IDA).6–12 Many studies also found that eradication of H. pylori leads to improvement in iron deficiency anemia.6,12–14 This evidence indirectly supports the association between H. pylori infection and iron deficiency anemia. Given the association between H. pylori infection and iron deficiency anemia, several studies and guidelines suggest that H. pylori infection should be screened for and treated if detected in adults with unexplained iron deficiency anemia.6,14,15 The mechanism of H. pylori infection producing iron deficiency anemia has still been hypothesized. Blood loss due to bleeding from peptic ulcers, and hemorrhagic gastritis caused by H. pylori infection; inadequate iron absorption due to decreased levels of ascorbic acid and stomach acidity resulting from H. pylori chronic gastritis; and increased utilization of iron by H. pylori for their growth have been considered as mechanisms of iron deficiency anemia caused by H. pylori infection.4,5,16,17

However, some studies have reported that the association between H. pylori infection and iron deficiency anemia was not significant.18–20 Tseng et al even found no association between iron deficiency anemia and H. pylori infection and no improvement in iron deficiency anemia after H. pylori treatment.21 These findings suggest that the association between H. pylori infection and iron deficiency anemia is still conflicting due to differences in sampling method, the iron deficiency anemia criteria, and the prevalence of H. pylori infection in the study population among the studies.22 Iron deficiency anemia in individuals with H. pylori infection has not received much attention in Vietnam, although the prevalence of H. pylori infection in Vietnam is quite high at 70.3%1 and the proportion of anemia associated with iron deficiency among adults in Vietnam is high at 35.2%.23 This study aimed to determine the association between H. pylori infection and iron deficiency anemia to propose an approach to individuals infected with H. pylori.

This study aimed to determine the association between H. pylori infection and iron deficiency anemia. The study results showed that there was a significant association between H. pylori infection and anemia, and iron deficiency, and the rate of iron deficiency anemia in H. pylori-infected individuals was significantly higher than that in the H. pylori-uninfected individuals.

There was a significant relationship between H. pylori infection and iron deficiency in this study (aOR=2.12, 95% CI=1.05–4.25, P=.035). This finding is consistent with many previous studies.9,10,14,18,28–30 However, this present study found a discrepancy between changes in serum iron levels and serum ferritin levels in H. pylori-infected individuals. Both the serum iron and ferritin levels should be lower in the H. pylori-infected individuals compared to the H. pylori-uninfected ones due to iron deficiency related to H. pylori infection. However, only serum iron levels in H. pylori-positive individuals were significantly lower than those in H. pylori-negative individuals (59.4±42.1 μg/dL vs. 88.1±32.5 μg/dL, P<.001). In contrast, the median serum ferritin levels in the case group did not show significantly lower compared to the control group (103.5 [30.4–389.5] vs. 133.1 [56.6–224.1] (ng/mL), P=.623) in this study. This discrepancy was also reported in some studies.18,19,29,31 Hou et al. also noted no difference in serum ferritin levels between the H. pylori-infected group and the H. pylori-uninfected group (165.5 [109.80–272.75] vs. 186.10 [107.30–273.60], P=.903).20 Kishore et al. even noted that the serum ferritin level was higher in the H. pylori-infected group than in the H. pylori-uninfected group (536.82±117.0 ng/dL vs. 391.31±101.54 ng/dL, P<.001).32 This can be explained by the role of ferritin in the body which is a biomarker reflecting both the body's iron storage status and an inflammatory response. H. pylori infection causes a chronic inflammatory condition that increases ferritin levels, it consequently contributes to the normal or elevated serum ferritin levels despite iron deficiency arising from H. pylori infection.5,16,26,33

This study also found that the mean TSAT levels were less than 20% and the median ferritin levels were ≥100 ng/mL in H. pylori-infected individuals. High serum ferritin with low TSAT levels may imply dysutilization of iron for erythropoiesis.34 This condition can be caused by H. pylori infection which activates an inflammatory response mediated by Interleukin 6 leading to an increase in hepcidin. This substance binds ferroportin, a transmembrane protein found mainly in macrophages and enterocytes. This binding leads to cellular ferroportin internalization and degradation, subsequently decreasing iron availability for erythropoiesis. This is also a mechanism that contributes to the pathogenesis of anemia due to H. pylori infection.5

The association between H. pylori infection and anemia was also recorded in this study with aOR=7.59, 95% CI=3.83–15.05 (P<.001). This result is in line with previous studies.11,20,35–37 In addition, this study found that the cases of microcytic hypochromic anemia which occurred predominantly in H. pylori-infected individuals had mean RDW values of more than 14%. These findings indicate that iron deficiency is likely to be a cause of anemia in H. pylori-infected people.16,33,38 The predominance of microcytic hypochromic anemia in the case group is not in agreement with some studies.13,20 These studies reported normocytic normochromic anemia arising from H. pylori-infected individuals. This could be explained that iron deficiency anemia is detected in an early stage in these studies, thus MCV and MCH indices are not much affected.16,26 In addition, coexisting vitamin B12 deficiency which is caused by gastritis due to H. pylori infection can result in anemia without microcytosis despite existing iron deficiency.13,26

There was no case of iron deficiency anemia found in the control group, so our study only compared the rate of iron deficiency anemia between the 2 groups with a chi-square test instead of using multivariate regression analysis to identify the association between them. This study noted that the rate of iron deficiency anemia in H. pylori-infected people was significantly higher than that in H. pylori-uninfected people (13% vs. 0%, χ2=16.05, P<.001). Furthermore, H. pylori infection significantly associated with iron deficiency and anemia were found in the present study as described above. Microcytic hypochromic anemia, a type of anemia caused by iron deficiency, predominated in the cases of anemia occurring in H. pylori-infected individuals as well. These findings suggest a potential relationship between H. pylori infection and iron deficiency anemia. The association between H. pylori infection and iron-deficiency anemia has also been demonstrated in previous studies.6,7,9,12 However, in this study, the ferritin levels did not show a significant difference between the H. pylori-infected group and the H. pylori-uninfected group, and the IQR of median ferritin levels in the case group was wider than that in the control group. Therefore, iron deficiency as the primary cause of anemia in H. pylori-infected patients has not been conclusively established. The anemia in individuals infected with H. pylori may be caused by iron deficiency, chronic H. pylori infection, or a combination of both in the present study. Further studies are needed to ascertain whether iron deficiency is the primary cause of anemia in H. pylori-infected individuals or not.

The exact mechanism of iron deficiency anemia in patients with H. pylori infection remains unclear. However, there are several mechanisms through which H. pylori infection results in iron deficiency anemia that have been investigated. First, gastritis caused by H. pylori infection leads to decreased levels of ascorbic acid and stomach acidity. These in turn contribute to decreased absorption of dietary iron and thus the pathogenesis of iron deficiency anemia.4,5,12 The CagA-positive H. pylori strains were presumed to have a relationship with reduced levels of ascorbic acid in the stomach.12 Second, H. pylori require iron for their growth, so bacteria will increase iron acquisition directly from the stomach’s contents, consequently reducing the iron amount available to the host.4,5,12H. pylori can directly acquire iron by sequestering lactoferrin from the gastric mucosa of the host through a receptor for lactoferrin in its membrane.5 Third, bleeding from peptic ulcers and hemorrhagic gastritis caused by H. pylori are other possible mechanisms that can cause or contribute to iron deficiency.4,5,12 Finally, the role of hepcidin as presented earlier which contributes to the dysutilization of iron for erythropoiesis is a possible explanation of iron deficiency anemia due to H. pylori infection.5 The mechanisms of H. pylori infection leading to iron deficiency anemia mentioned above also imply that iron deficiency anemia can occur in both symptomatic and asymptomatic H. pylori infections.5,12 This may be meaningful in clinical practice, the screening for iron deficiency anemia should be performed in persons infected with H. pylori regardless of their clinical manifestations.

To the best of our knowledge, this is the first study to identify the association between iron deficiency anemia and H. pylori infection in the Vietnamese population. However, this study had some limitations. Firstly, the sample size was relatively small as compared to previous studies, which may have affected the significance of the results. However, a sample size of 115 cases and 115 controls is still sufficient to yield meaningful results. Furthermore, the study was conducted using rigorous methods, with accurate data collection and appropriate statistical analysis. It was conducted at the University Medical Center, so the results can be considered valid for the study population. Secondly, the study did not test fecal occult blood for upper gastrointestinal bleeding to rule out cases of anemia due to blood loss, and measurement of sTfR (soluble transferrin receptor) has not yet been performed to distinguish between anemia caused by iron deficiency and anemia caused by chronic disease or inflammation. Finally, the study results just show the significant association between H. pylori infection and anemia; the cohort study is needed to identify whether H. pylori infection is a cause of iron deficiency anemia.

This study has shown a significant association between H. pylori infection and anemia, and iron deficiency. The relationship between H. pylori and iron deficiency anemia remains inconclusive and needs further studies. However, these results remain meaningful in the context that the prevalence of H. pylori infection is still high, and iron deficiency anemia is a health problem in Vietnam as well. The study results suggest that tests for iron deficiency anemia should be performed routinely in the management of individuals infected with H. pylori.

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