Summary and Introduction
Summary
Hepatitis C virus (HCV) is a major cause of chronic hepatitis and hepatic fibrosis, and chronic infection can frequently progress to cirrhosis, end-stage liver disease and hepatocellular carcinoma. Treatment with pegylated interferons (INFs) plus ribavirin has been shown to be more effective than pegylated INFs alone or standard INFs with or without ribavirin. The early response of HCV to treatment with peg-INF has been used to predict treatment outcomes in infected patients, emphasizing the importance of viral kinetics and genotyping in their treatment. Mathematic modelling of viral dynamics has shown the importance of optimal doses of drug, with early virologic response at week 12 predictive of sustained virologic response. Maintaining INF concentration above a therapeutically effective level is necessary to prevent viral rebound and subsequent treatment failure. Once-weekly dosing with peg-INF-α2a, which has a longer half-life than other forms of INF, plus daily dosing with ribavirin, has been shown to be effective in reducing viral load.
Introduction
Hepatitis C virus (HCV) is a common infectious agent worldwide, affecting approximately 170 million persons, including 3-4 million people in the United States.[1,2] In some cases, HCV-related liver disease progresses to cirrhosis, end-stage liver disease or hepatocellular carcinoma.[3-7] An estimated 8000-10 000 HCV-related deaths occur in the United States each year.[8]
Current therapy for patients with HCV consists of combination of pegylated interferon (IFN) plus ribavirin.[4] Clinical trials have shown that more than 50% of HCV-infected patients receiving pegylated IFN and ribavirin achieve a sustained viral response (SVR), defined as undetectable HCV RNA in the blood 24 weeks after completion of therapy.[9-11]
Viral kinetic modelling has provided important insights into the life cycle of HCV, the antiviral effects of IFN and the relative resistance of certain populations to IFN therapy. Most recently, viral kinetic analysis has provided information about how ribavirin impacts HCV treatment.
Viral kinetic principles are used in clinical practice to identify patients who are unlikely to achieve an SVR, based on early virologic response (EVR) at week 12 of therapy. Kinetic models have been developed to predict nonresponse at even earlier time points. In the future, viral kinetics might be used to optimize therapy for patients with reduced response rates, such as those with genotype 1 infection and high virus levels, and African-Americans. Viral kinetics will also be important in evaluating the antiviral efficacy of new agents that are in development for the treatment of HCV.
