Alterations in the Iron Homeostasis Network of Hepatocytes Caused by Hepatitis B Virus.

Abstract

It is unclear whether hepatitis B virus (HBV) itself causes iron metabolism disorder in patients with chronic hepatitis B (CHB). In this study, we investigated the effect of HBV on iron metabolism at the clinical and cellular levels to determine the pathogenesis of CHB. We enrolled 41 CHB patients and 20 healthy controls (HCs) in a retrospective study. Parameters of iron status included serum iron (SI), ferritin (SF), transferrin (TRF), soluble transferrin receptor (sTfR), transferrin saturation (TS), total iron-binding capacity (TIBC), unsaturated iron-binding capacity (UIBC), and hepcidin. Liver function indicators included serum alanine transaminase (ALT) and albumin. Furthermore, we investigated the correlations between iron markers and liver function indicators. Finally, the alterations in SF, TRF, transferrin receptor (TfR), and hepcidin expression were detected by RT-PCR, western blot, and cell immunofluorescence after HepG2 cells and Huh7 cells were transfected with the pSM2-HBV plasmid. We also measured these alterations between HepG2 cells and HepG2.215 cells. The significance of differences was analyzed by SPSS version 17.0. Compared with healthy controls, the CHB patients were more likely to have lower levels of serum hepcidin, TRF, sTfR, TIBC, and UIBC and higher levels of SI, SF, and TS (p < 0.05, all). In CHB patients, the levels of SI and SF correlated positively with ALT concentrations, and the serum hepcidin concentrations correlated positively with albumin concentrations (p < 0.05, all). The expression levels of ferritin, transferrin, and hepcidin mRNA and protein were significantly higher in HepG2.215 cells than in HepG2 cells, while expression levels of TfR were lower. The alterations in these iron markers in HepG2 and Huh7 cells that were transfected with pSM2-HBV plasmid were consistent with those in HepG2.215 cells. Serum iron markers tended to be abnormal in CHB patients. In hepatocytes, HBV promoted the expression of ferritin, transferrin, and hepcidin, while it inhibited the expression of TfR.