Findings from the study titled “Hepcidin/ferroportin expression levels involve efficacy of pegylated-interferon plus ribavirin in hepatitis C virus-infected liver,” published in the World Journal of Gastroenterology indicate that an over-accumulation of Iron is associated with liver damage by increasing oxidative stress and hepatitis C virus (HCV). Conversely, iron administration suppresses HCV replication in vitro.
Hepatitis C virus (HCV) is a major pathogen of chronic hepatitis and subsequent liver cirrhosis and hepatocellular carcinoma. Pegylated-interferon (PEG-IFN) plus ribavirin (RBV) combination therapy is an antiviral treatment for chronic hepatitis C because it can bring patients into sustained virological response (SVR) at a high rate. However, some relevant adverse events such as severe anemia still hinder the effect of the treatment by leading to dose reduction and cessation of treatment.
Iron is an essential biometal that is distributed to hemoglobin and is involved in oxygen transport. Liver iron overload is a well-described but not fully understood feature of HCV infection, which can induce liver damage by increasing oxidative stress. Absorbed iron is stored with ferritin and ferroportin excretes iron into blood. Hepcidin, a hepatic peptide hormone, is a primary regulator of systemic iron status by blocking iron release from villous cells into the blood through binding to and driving degradation of ferroportin. However, the association between HCV infection and iron metabolism remains poorly understood.
To further examine the relationship between the iron-metabolism-related gene expression profiles and efficacy of antiviral therapy in patients with chronic hepatitis C, Makoto Nakamuta from the Department of Gastroenterology and Clinical Research Center at the National Hospital Organization Kyushu Medical Center in Japan along with colleagues conducted an analysis of the hepatic expression profile of iron-metabolism-related genes in a total of 100 patients with choric hepatitis C (genotype1b, n = 50; genotype 2, n = 50). The researchers then evaluated the profile and its associations with virological response to a combined therapy of pegylated-interferon plus ribavirin.
The researchers used liver biopsy samples that were induced for a polymerase chain reaction for iron-metabolism-related genes and protein expression for ferroportin. As a control, normal liver tissue was obtained from 18 living donors of liver transplantation. Serum hepcidin level was measured with a specific spectrometry method.
The researchers found that a decreased expression of hepcidin and ferroportin in patients with sustained virological response indicates the importance of hepatocytic iron retention for viral response during pegylated-interferon plus ribavirin treatment.