Changes in the Serum Hepcidin-to-ferritin Ratio with Erythroferrone after Hepatitis C Virus Eradication Using Direct-acting Antiviral Agents

Abstract

Objective Hepcidin is a master iron regulator hormone produced by the liver, but precise mechanism underlying its involvement in iron overload in hepatitis C virus (HCV) infection remains unclear. We investigated the serum hepcidin levels against iron overload before and after HCV eradication. Methods We prospectively investigated the iron metabolism characteristics in 24 patients with HCV genotype 1b infection before and after treatment. We also assessed the serum erythroferrone (ERFE) levels to investigate its association with iron metabolism changes. Patients were treated with Ledipasvir 90 mg and Sofosbuvir 400 mg once daily for 12 weeks and observed for 12 more weeks in order to evaluate their sustained virological response. Results Serum hepcidin levels at baseline were in the normal range, although serum ferritin levels were increased. After HCV eradication, both serum ferritin and hepcidin levels were significantly decreased at 24 weeks from baseline (p<0.001, p=0.006, respectively). However, the serum hepcidin-to-ferritin ratios were significantly increased (p<0.001). In addition, the serum ERFE levels were significantly decreased (p<0.001). Increases in the serum hepcidin-to-ferritin ratios were correlated with decreases in the serum ERFE levels (ρ=−0.422, p=0.039). Conclusion Serum hepcidin levels were relatively low against ferritin levels in HCV infection. However, after HCV eradication, the serum hepcidin-to-ferritin ratios were increased. These results indicate the improvement of inadequate hepcidin secretion against iron overload after HCV eradication. Downregulation of ERFE may have affected the improvement of iron metabolism.

Identification of Differentially Expressed Genes and Enriched Pathways in SARS-CoV-2/ COVID-19 using Bioinformatics Analysis

“…Similarly, GO enrichment analysis, many up and down-regulated genes may play a very key role in the progression of SARS-CoV-2 infection. Enriched genes such as IFNL4 [117], ZFP36 [118], CD274 [119], MIR21 [120], CYP1A1 [121], CMPK2 [122], C4A [123], SERPINE1 [124], CCRL2 [125], CD69 [126], FAH (fumarylacetoacetate hydrolase) [127], ERFE (erythroferrone) [128], SERINC5 [129], ADI1 [130], AP2M1 [131], PRIMPOL (primase and DNA directed polymerase) [132], BIRC5 [133] and TF (transferrin) [134] were responsible for the advancement of various viral infections, but these genes may be involved in the progression of SARS-CoV-2 infection. Enriched genes such as APOBEC3G [135], NLRC5 [136], PTX3 [137], FAP ( broblast activation protein alpha) [138] and CAT (catalase) [139] were linked with the development of in uenza viral infection, but these genes may be associated with progression of SARS-CoV-2 infection as well.…”

Bioinformatics analysis of expression profiling by high throughput sequencing for identification of potential key genes among SARS-CoV-2/COVID 19

“…Similarly, GO enrichment analysis, many up and down regulated genes may play a very key role in progression of SARS-CoV-2 infection. Enriched genes such as IFNL4 [116], ZFP36 [117], CD274 [118], MIR21 [119], CYP1A1 [120], CMPK2 [121], C4A [122], SERPINE1 [123], CCRL2 [124], CD69 [125], FAH (fumarylacetoacetate hydrolase) [126], ERFE (erythroferrone) [127], SERINC5 [128], ADI1 [129], AP2M1 [130], PRIMPOL (primase and DNA directed polymerase) [131], BIRC5 [132] and TF (transferrin) [133] were responsible for advancement of various viral infections, but these genes may be involved in progression of SARS-CoV-2 infection. Enriched genes such as APOBEC3G [134], NLRC5 [135], PTX3 [136], FAP ( broblast activation protein alpha) [137] and CAT (catalase) [138] were linked with development of in uenza viral infection, but these genes may be associated with progression of SARS-CoV-2 infection.…”

Male-specific Association between Iron and Lipid Metabolism Changes and Erythroferrone after Hepatitis C Virus Eradication

“…The suppression of hepcidin by ERFE promotes iron absorption from the intestine, resulting in increased iron storage (4,5). We previously reported an improvement in iron dysmetabolism associated with the reduction in the ERFE levels after HCV eradication (6). However, another study showed a correlation between increased LDL-C levels and interleukin-28B gene polymorphism after HCV eradication (7).…”