On behalf of the authors of the article titled, “Relationship between Hepatitis C Virus Infection and Iron Overload,” we appreciate Prof. Ponzetto and Prof. Figura for their comments on our review. As mentioned in the letter, Helicobacter pylori may present in patients with liver cirrhosis and hepatocellular carcinoma, and worsen the prognosis,[1,2] therefore we agree with them that testing for presence of H. pylori should be conducted in all patients with chronic hepatitis, no matter how the hepatitis is caused.
In our review, the relationship between hepatitis C virus infection and iron overload was focused, while iron overload may also happen in patients with other chronic infection, H. pylori infection might be included. The presence of H. pylori in the gastric mucosa is associated with chronic active gastritis, which may lead to the development of peptic ulcer, gastric carcinoma and even gastric lymphoma.[3]
Iron is an essential micronutrient for virtually all organisms, including H. pylori, which has a repertoire of high affinity iron-uptake system. The iron homeostasis in H. pylori is regulated by Ferric Uptake Regulator protein. In H. pylori, some iron-uptake systems are constitutively expressed and iron uptake is not down-regulated in iron-replete conditions.[4] These results suggest it is potentially possible that iron overload would happen, related to H. pylori infection, in theory. So far, few cases of iron overload in patients with H. pylori infection have been reported, while the link between H. pylori infection and the development of host iron deficiency is clearly illustrated.[5] Therefore, to confirm the relationship between body total iron load and H. pylori infection, more studies are needed.
REFERENCES
- 1.Wang L, Zollinger T, Zhang J. Association between Helicobacter pylori infection and liver cancer mortality in 67 rural Chinese counties. Cancer Causes Control. 2013;24:1331–7. doi: 10.1007/s10552-013-0211-3. doi: 10.1007/s10552-013-0211-3. [DOI] [PubMed] [Google Scholar]
- 2.Leone N, Pellicano R, Brunello F, Cutufia MA, Berrutti M, Fagoonee S, et al. Helicobacter pylori seroprevalence in patients with cirrhosis of the liver and hepatocellular carcinoma. Cancer Detect Prev. 2003;27:494–7. doi: 10.1016/j.cdp.2003.07.004. doi: 10.1016/j.cdp.2003.07.004. [DOI] [PubMed] [Google Scholar]
- 3.Atherton JC, Blaser MJ. Coadaptation of Helicobacter pylori and humans: Ancient history, modern implications. J Clin Invest. 2009;119:2475–87. doi: 10.1172/JCI38605. doi: 10.1172/JCI38605. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Pich OQ, Merrell DS. The ferric uptake regulator of Helicobacter pylori: A critical player in the battle for iron and colonization of the stomach. Future Microbiol. 2013;8:725–38. doi: 10.2217/fmb.13.43. doi: 10.2217/fmb.13.43. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Flores SE, Aitchison A, Day AS, Keenan JI. Helicobacter pylori infection perturbs iron homeostasis in gastric epithelial cells. PLoS One. 2017;12:e0184026. doi: 10.1371/journal.pone.0184026. doi: 10.1371/journal.pone.0184026. [DOI] [PMC free article] [PubMed] [Google Scholar]