The Predictive Value And Mechanism Of Hepcidin On The Antiviral Effect Of Pegylated-interferon-α In The Treatment Of Chronic Hepatitis B

Background Hepcidin（HEPC）is the master iron regulator hormone coding by hepcidin antimicrobial peptide（HAMP）gene in liver.The association of serum HEPC level with the effect of pegylated interferon therapy in patients with chronic hepatitis C infection has been studied.However,the association of serum HEPC level with the effect of pegylated interferon treatment in patients with chronic hepatitis B（CHB）infection is yet to be elucidated.Our study aims to investigate the predictive value of HEPC expression levels on the curative effect of pegylated interferon α（PEG-IFN-α）therapy in patients with CHB and its mechanism.Methods A total of 47 patients with CHB who accepted PEG-IFN-α treatment were enrolled in our study.The serum level of HEPC was detected by ELISA.The dynamic changes in serum HEPC levels and its relationship with serum HBs Ag and HBV DNA level throughout the treatment in patients with CHB were analyzed.ROC curve was conducted to analyze the predictive value of HEPC level on the antiviral effect of pegylated-interferon-α in the treatment of chronic hepatitis B.RT-PCR,immunofluorescence cell staining and western blotting were used to analyze the alteration of HEPC level and antiviral proteins expression in Hep G2.2.15 cells which were treated with PEG-IFN-α.Hep G2.2.15 cells were used as cell model to investigate the potential mechanism.Results During PEG-IFN-α treatment,high levels of early on-treatment serum HEPC were observed in patients who achieved a decline in HBs Ag >1 log10 IU/m L or HBV DNA >1 log10 IU/m L.ROC curve was conducted to analyze the predictive cut-off value of HEPC for HBs Ag decline >1 log10 IU/m L was 239 pg/m L,which the sensitivity and specificity were 72.73% and 70.97%,respectively;the predictive cutoff value of HEPC for the decline in HBV DNA >1 log10 IU/m L was 190.4 pg/m L,which the sensitivity and specificity were 72.73% and 61.11%,respectively.In vitro,RT-PCR analysis indicated that HEPC gene expression level was increased and immunofluorescence cell staining analysis indicated that HEPC protein expression level was increased in Hep G2.2.15 cells which treated with PEG-IFN-α.Furthermore,the level of antiviral proteins in Hep G2.2.15 cells co-treated with HEPC and PEG-IFN-α were higher than those treated with PEG-IFN-α alone and the level of antiviral proteins in Hep G2.2.15 cells transfected with overexpression plasmid of HEPC were higher than those transfected with silence-HEPC RNA,which both indicated that HEPC had a synergistic effect on the expression of antiviral protein induced by PEGIFNα treatment.Conclusions In patients infected with CHB,higher early on-treatment HEPC levels indicate higher possibility of HBs Ag decline and HBV DNA decline during PEG-IFN-α treatment.High serum HEPC levels predict better antiviral effect of PEG-IFN-α in the treatment of chronic hepatitis B,which may be related to the synergistic effect of HEPC on the expression of antiviral protein induced by PEG-IFN-α treatment.