New developments in the treatment of hepatitis C

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Abstract
Treatment of chronic hepatitis C virus (HCV) infection with interferon based therapies has been part of clinical practice for more than 10 years. While there have been incremental steps in improving sustained virological response (SVR), limited progress has been made in developing agents that eradicate the virus in all infected patients.1 The development of effective antiviral agents has been hindered by several key factors, including the genetic heterogeneity of HCV, lack of available culture systems or animal models, limited understanding of the mechanisms of action of current therapies, and the long delay between initiation of therapy and determination of virological response (48–72 weeks). Despite these limitations, progress has been made. The addition of oral ribavirin to standard interferon alfa-2b improved SVR for interferon monotherapy from 9% to 29% for genotype 1, and from 31% to 65% for genotypes 2–3. Peginterferons are the most recent additions to antiviral regimens and two molecules have been approved for the treatment of HCV as monotherapy and in combination with ribavirin. The process of pegylation involves linkage of interferon to repeating units of non-toxic polyethylene glycol (PEG). The size and linkage of the PEG determines many pharmacological and pharmacokinetic properties of the compound. Peginterferon alfa-2b utilises a 12 kDa PEG linked with a non-covalent bond. This PEG size results in more rapid subcutaneous absorption, wider volume of distribution, and predominantly renal clearance …