Treatment with Interferon and Ribavirin

Abstract

The natural history of chronic hepatitis C virus (HCV) infection is one of disease progression with worsening liver fibrosis leading to the development of cirrhosis and related complications including portal hypertension, liver failure, and hepatocellular carcinoma. Eradication of HCV infection may prevent and/or reverse this process and thus the major goals of therapy are to reduce the incidence of cirrhosis, and subsequent liver failure and hepatocellular carcinoma. Interferon (IFN)-based therapies represent the cornerstone of treatment for chronic HCV infection. Since the early descriptions of the use of IFN therapy in the treatment of non-A, non-B hepatitis over 20 years ago, significant advances have occurred in the management of this disease. Over time treatment has sequentially evolved from IFN monotherapy, to combination therapy with ribavirin, to the use of pegylated IFN’s followed by the current standard of care utilizing the combination of pegylated IFN-α, administered as weekly subcutaneous injections, and ribavirin given orally (Fig. 10.1). Today, treatment success is measured by surrogate virological endpoints rather than clinical outcomes. Using the current standard of care, a sustained virological response (Fig. 10.3) can be achieved in approximately 50% of patients infected with genotype 1 and up to 80% in genotypes 2 and 3. Treatment outcomes are even better in those who achieve a virological response during the initial 12 weeks of therapy as discussed in Chap. 13. The ongoing and future development of direct-acting antiviral agents including HCV protease and polymerase inhibitors hold significant promise for enhanced treatment outcomes in the short to medium term.

This chapter details the progress of IFN-based therapies over the past two decades as a lead into the emerging new era of direct-acting antiviral agents. It is clear however that these novel compounds will most likely be approved initially in combination with IFN-based therapy thereby emphasizing the importance of IFN and ribavirin as the basis of treatment for chronic viral hepatitis C.