Treatment of chronic hepatitis C in "difficult-to-treat" patients in the clinical setting

Abstract

The hepatitis C virus (HCV) was discovered in 1989 as the causative agent of posttransfusion non-A, non-B hepatitis (Choo et al., 1989).About 170million people are infected with HCV worldwide, with a reported prevalence ranging from 1% to 5% in most countries (Anonymous, World Health Organization, 1999). Most patients develop chronic infection that may progress to chronic liver disease, cirrhosis, and hepatocellular carcinoma (HCC) (Pawlotsky, 2006). With a prolonged natural history, the most efficacious therapeutic measure is the permanent clearance of the virus from the blood. Antiviral therapy for chronic hepatitis C (CHC) has dramatically advanced since the introduction of interferon-alpha (IFN-α) monotherapy in the early 1990s (Hoofnagle et al., 1986). IFN-α directly inhibits HCV replication (Neumann et al., 1998) and, through its immunomodulatory properties, may also accelerate the clearance of infected hepatocytes by the host immune system (Pawlotsky, 2006). The addition of the synthetic guanosine analogue ribavirin (RBV) to IFN-α regimens was a major breakthrough in anti-HCV therapy. Several landmark randomized trials (McHutchison et al., 1998; Poynard et al., 1998) demonstrated the superiority of combination therapy and led to the approval of the IFN-α/RBV combination as the standard treatment for CHC, as recommended by the European Association for the Study of the Liver (EASL) Consensus Conference on Hepatitis C in 1999. The principal clinical effect of RBV is to prevent relapses in patients who respond to the antiviral effect of IFN-α, probably by shortening the half-life of infected cells in the presence of IFN-α; however, the precise mechanisms underlying its action in CHC remain unclear (Pawlotsky, 2006). © 2008 Springer Science+Business Media, LLC.