NK cells in hepatitis C: role in disease susceptibility and therapy

Hepatitis C is caused by infection with the hepatitis C virus (HCV), a single-stranded RNA virus, which was first described in 1989. Hepatitis C is a major global health burden with approximately 150 million people chronically infected worldwide. Chronic HCV infection is a main cause of liver cirrhosis and hepatocellular carcinoma. Current treatment of hepatitis C is based on the administration of peg-IFN-α and ribavirin. However, this therapy can be associated with severe side effects. The role of NK cells in the pathogenesis of acute and chronic liver disease in HCV infection has only been studied in recent years, but those studies indicate an important role for this cell type. NK cells are a major component of the innate arm of the immune system. We summarize the current knowledge on NK cell phenotype and function in acute and chronic HCV infection. Moreover, we discuss the role of NK cells in IFN-α-based antiviral therapy. Understanding the mode of function and role of NK cells during HCV infection and therapy will become even more important in the near future, when new IFN-α-free treatment regimens become available.