Type of Pegylated Interferon Matters: Another Milestone in the Treatment of Hepatitis C Virus Infection

H C virus (HCV) infects 170 million people worldwide (1). The infection becomes chronic in 85%–90% of cases with potential to cause cirrhosis, end-stage liver disease, and hepatocellular carcinoma (HCC) (2). Treatment of HCV infection has evolved significantly over the last 20 years since the introduction of interferon-α in 1991. Initial studies using interferon were disappointing with response rates of less than 20%. Later, two important advances in the treatment of HCV infection, namely pegylation of interferon and introduction of ribavirin (RBV) in 2002, have revolutionized the treatment of HCV infection (3). Pegylation is a process in which a polyethylene glycol (PEG) moiety is attached to the molecules used for the treatment (4). This results in alteration of the pharmacokinetic, pharmacodynamic, and immunologic properties of the drug which in turn results in longer duration of action of the pegylated molecule allowing for using lower doses of the drug and better efficacy. Two pegylated molecules of interferon are pegylated interferon (PEG-IFN)-α2a (Pegasys) and -α2b (PegIntron). Both these molecules differ in terms of their physical characteristics and pharmacological properties (Table 1) (5). One of the major differences between these two molecules is that PEG-IFNα2b has a urethane bond which is unstable and is sensitive to hydrolysis. This results in release of interferon-α2b (the main therapeutic molecule) after injection of PEG-IFN-α2b. In contrast, PEGIFN-α2a with an amide bond is chemically stable and the entire intact molecule has therapeutic effects (5). PEG-IFN-α2a does not require any dose modification in the presence of renal insufficiency, in contrary to PEG-IFN-α2b which requires dose