Hepcidin Expression in the Liver: Relatively Low Level in Patients with Chronic Hepatitis C

Abstract

Patients with chronic hepatitis C frequently have serum and hepatic iron overload, but the mechanism is unknown. Recently identified hepcidin, exclusively synthesized in the liver, is thought to be a key regulator for iron homeostasis and is induced by infection and inflammation. This study was conducted to determine the hepatic hepcidin expression levels in patients with various liver diseases. We investigated hepcidin mRNA levels of liver samples by real-time detection-polymerase chain reaction; 56 were hepatitis C virus (HCV) positive, 34 were hepatitis B virus (HBV) positive, and 42 were negative for HCV and HBV (3 cases of autoimmune hepatitis, 7 alcoholic liver disease, 13 primary biliary cirrhosis, 9 nonalcoholic fatty liver disease, and 10 normal liver). We analyzed the relation of hepcidin to clinical, hematological, histological, and etiological findings. Hepcidin expression levels were strongly correlated with serum ferritin (P < 0.0001) and the degree of iron deposit in liver tissues (P < 0.0001). Hepcidin was also correlated with hematological parameters (vs. hemoglobin, P = 0.0073; vs. serum iron, P = 0.0012; vs. transferrin saturation, P < 0.0001) and transaminase levels (P = 0.0013). The hepcidin-to-ferritin ratio was significantly lower in HCV + patients than in HBV + patients (P = 0.0129) or control subjects (P = 0.0080). In conclusion, hepcidin expression levels in chronic liver diseases were strongly correlated with either the serum ferritin concentration or degree of iron deposits in the liver. When adjusted by either serum ferritin values or hepatic iron scores, hepcidin indices were significantly lower in HCV + patients than in HBV + patients, suggesting that hepcidin may play a pivotal role in the pathogenesis of iron overload in patients with chronic hepatitis C.

Determinants of Hepcidin in Patients on Maintenance Hemodialysis: Role of Inflammation

“…A similar observation has been reported in patients with various liver diseases. Fujita et al [14] demonstrated that the serum ferritin level had a strong positive correlation with the hepatic level of hepcidin mRNA expression. In cultured cell models, a direct relation between ferritin and hepcidin expression in hepatocytes has not been demonstrated so far.…”

Molecular mechanism of iron metabolism and overload in chronic hepatitis C

“…22 Hepcidin was lower in CHC patients than in CHB patients. 23 Hepcidin and TfR2 may play a role in the pathogenesis of iron overload in CHC patients. Decreased hepcidin levels and increased TfR2 levels contribute to delivery of iron to hepatocytes from macrophage iron stores and intestinal mucosa.…”

A novel monoclonal antibody immunoassay for the detection of human serum hepcidin

“…The peptide HRSKAbuGMC was used as antigen for the production of monoclonal antibodies. Among the generated antibodies, mHK(8) and mHK (9) showed the best antigen recognition and were chosen for further evaluation and characterization. In dot blot and Western blot assays, both antibodies specifically detected the antigen HRSKAbuGMC as well as synthetic hepcidin.…”

“…3 Immunofluorescence staining with the monoclonal antibodies mHK(8) and mHK (9). Immunofluorescence staining of human liver tissues using the monoclonal antibodies mHK(8), mHK (9) (Fig.…”

“…The resulting excessive intestinal iron absorption leads to iron accumulation in the liver, the pancreas, and the heart [7] and subsequent organ damage (e.g., liver cirrhosis, hepatocellular carcinoma, diabetes mellitus, and cardiac diseases; see also reference [8]). Chronic liver diseases (such as alcoholic liver disease or hepatitis C; see reference [9]) are also accompanied by inadequately low hepcidin production; the consequent iron overload accelerates the disease development. On the other hand, hepcidin is an established acutephase protein, and its inflammation-induced elevation is thought to contribute to anemia of chronic diseases [10,11].…”