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Hepatitis C virus (HCV) affects about 170 million people worldwide and is the most common chronic blood borne infection in the United States. Since the advent of blood screening protocols in the early 1990s, injection drug use has become the leading cause of infection. Hepatitis C can have both hepatic and nonhepatic manifestations of infection. Hepatic manifestations include hepatic fibrosis, cirrhosis, liver cancer, and liver failure. The standard treatment for chronic HCV is combination therapy with pegylated interferon-α and ribavirin. Although pegylated interferon and ribavirin has been used against HCV for close to a decade, advances in therapy have centered on doses and treatment durations. There has been increasing interest in applying on-treatment response or viral kinetics to predict antiviral response rates and shape therapeutic intervention. Protease inhibitors are a promising adjuvant to combination therapy, but their efficacy and safety are still under investigation.

In the last decade, hepatitis C virus (HCV) kinetics has become an important clinical tool for the optimization of therapy with pegylated-interferon-α (PEG-IFN) and ribavirin (RBV). Mathematical models have generated important insights into HCV pathogenesis, HCV-host dynamics, as well as IFN and RBV modes of action. Clinical trials with direct-acting antiviral agents (DAAs) against various steps of the HCV-life cycle have revealed new viral-kinetic patterns that have not been observed with (PEG)-IFN+RBV. Very recently, studies have shown that single nucleotide polymorphisms (SNPs) in the interleukin-28B (IL28B) gene region were associated with race/ethnicity, and with response to PEG-IFN+RBV. Here, we review our current knowledge of HCV kinetics and related mathematical models during (PEG)-IFN+RBV and/or DAA-based therapies, HCV pathogenesis, and the role of IL28B polymorphism on early HCV kinetics. Better understanding of the mode of actions of drugs and viral kinetics may help to develop new, individualized therapeutic regimens that include DAAs in combination with PEG-IFN+RBV. [ABSTRACT FROM AUTHOR]

Treatment for hepatitis C is aimed at eliminating the virus and thus preventing the development of cirrhosis. The effectiveness of antiviral therapy with pegylated interferon and ribavirin is based upon inhibition of viral replication and successful viral clearance while maintaining minimal toxicity. The treatment of hepatitis C has evolved to a response-guided paradigm based on viral kinetic response. Using response-guided therapy, duration of therapy as short as 12–16 weeks may be adequate for those with genotypes 2 or 3, and 24 weeks may be sufficient for those with genotype 1 and low viral load who achieve rapid virologic response. On the other hand, extension of therapy beyond 48 weeks may be beneficial for those with genotype 1 and slow response or in the setting of high pretreatment viral load who do not achieve rapid virologic response by reducing relapse. As new viral kinetic data emerge with pegylated interferon and ribavirin, the tailoring of HCV treatment will allow shorter durations of therapy in some, and a greater chance of sustained response in others treated for longer durations. These paradigms will require further refinement in the era of direct-acting antiviral therapies. [ABSTRACT FROM AUTHOR]