Issues in selecting HCV-infected candidates for anti-viral treatment.

Abstract

The recent approval of two protease inhibitors (telaprevir and boceprevir) and the resultant increase in the sustained virological response (SVR) rate when either of these drugs is added to pegylated interferon (PEG-IFN) and ribavirin (RBV) have led to a flurry of patients with hepatitis C virus (HCV) infection seeking treatment. Some of these patients had been diagnosed with HCV for several years and had been hesitant to receive treatment with PEG-IFN and RBV because of the low SVR rate, the high frequency of adverse events, and the need for injections. Others would have been suitable candidates for PEG-IFN and RBV treatment but were fortunate to have early-stage liver disease and were advised that they could afford to wait until a more efficacious and/or better tolerated treatment became available. Still others had gone through one or more courses of interferon (IFN)-based therapy but had failed to achieve SVR or could not tolerate the side effects of PEG-IFN and RBV. This article focuses on patients with an HCV genotype 1 infection because telaprevir and boceprevir have not been approved for other HCV genotypes. Patients with conditions for which telaprevir and boceprevir have not been approved are also not discussed (Table 1). Table 2 summarizes the factors that need to be considered in determining whether a patient should be started on HCV treatment now. Because the new standard of HCV therapy includes PEG-IFN and RBV, patients with contraindications to these drugs should not be started on treatment now. A key factor to the success of triple therapy is the patient’s ability to adhere to the complex treatment regimen. Telaprevir and boceprevir need to be administered every 8 hours with a snack, and in the case of telaprevir, the snack should contain 20 g of fat to facilitate absorption. Low trough concentrations of telaprevir have been shown to increase the risk of drug resistance. 1 Therefore, treatment should be started only for patients who are motivated and are able to comply with the treatment regimen. In comparison with Caucasians, African Americans have significantly lower SVR rates with PEG-IFN and RBV dual therapy. The addition of a protease inhibitor to PEG-IFN and RBV increases the SVR rate 2,3 (Fig. 1). Although the SVR rates for African Americans are still lower than those for Caucasians, the improved response to triple therapy has increased the enthusiasm of physicians and patients alike for pursuing HCV treatment. In comparison with unfavorable genotypes (CT and TT), a favorable interleukin-28B (IL-28B) genotype (rs12979860 CC) is associated with a 2-fold higher rate of SVR to treatment with PEG-IFN and RBV. 4 The addition of telaprevir or boceprevir to PEG-IFN and RBV has a minimal impact on the SVR rate of patients with a favorable IL-28B genotype, but there is a 2- to 3-fold increase in the SVR rate of patients with unfavorable IL-28B genotypes 5,6 (Fig. 2). Testing for the IL-28B genotype has very little role in determining whether treatment should be recommended, but in countries with a high prevalence of favorable IL-28B genotypes and limited resources, IL28B genotyping may help in identifying patients who would derive the greatest benefit from triple therapy. Not all patients with chronic HCV will progress to cirrhosis; therefore, previous guidelines recommended the initiation of treatment only in patients at risk of progressive liver disease. An assessment of the liver disease stage has been an integral part of the pretreatment evaluation. The improved SVR rate with triple therapy has raised the question whether HCV treatment should be recommended for all patients, including those with minimal or no fibrosis. Patients with