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Review
. 2017 Apr 5;130(7):866-871.
doi: 10.4103/0366-6999.202737.

Relationship between Hepatitis C Virus Infection and Iron Overload

Dong-Mei Zou  1 , Wan-Ling Sun  1
Affiliations
Review

Relationship between Hepatitis C Virus Infection and Iron Overload

Dong-Mei Zou et al. Chin Med J (Engl). .

Abstract

Objective: The aim of this study was to summarize the interactions between hepatitis C virus (HCV) infection and iron overload, and to understand the mechanisms of iron overload in chronic hepatitis C (CHC) and the role iron plays in HCV life cycle.

Data sources: This review was based on data in articles published in the PubMed databases up to January 28, 2017, with the keywords "hepatitis C virus", "iron overload", "iron metabolism", "hepcidin", "translation", and "replication".

Study selection: Articles related to iron metabolism, iron overload in patients with CHC, or the effects of iron on HCV life cycle were selected for the review.

Results: Iron overload is common in patients with CHC. The mechanisms involve decreased hepcidin levels caused by HCV through signal transducer and activator of transcription 3, mitogen-activated protein kinase, or bone morphogenetic protein/SMAD signaling pathways, and the altered expression of other iron-metabolism-related genes. Some studies found that iron increases HCV replication, while other studies found the opposite result. Most of the studies suggest the positive role of iron on HCV translation, the mechanisms of which involve increased expression levels of factors associated with HCV internal ribosome entry site-dependent translation, such as eukaryotic initiation factor 3 and La protein.

Conclusion: The growing literature demonstrates that CHC leads to iron overload, and iron affects the HCV life cycle in turn. Further research should be conducted to clarify the mechanism involved in the complicated interaction between iron and HCV.

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Conflict of interest statement

There are no conflicts of interest.

Figures

Figure 1
Figure 1
Relationship between HCV infection and iron overload. HCV reduces the levels of hepcidin, and elevates the levels of FPN, resulting in elevated iron absorbed by enterocytes and iron deposition in hepatocytes and macrophages. Although the role of iron in HCV replication is disputable, it is strongly suggested the positive effect of iron on HCV translation by increasing expression of both eIF3 and La protein, and changing the affinities of common cellular factors to HCV IRES. This positive effect can be partially inhibited by iron chelators. HCV: Hepatitis C virus; FPN: Ferroportin; SI: Serum iron; TS: Transferrin saturation; IRES: Internal ribosome entry site; eIF3: Eukaryotic initiation factor 3; ↑: Upregulated; ↓: Downregulated.
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