If the hemoglobin concentration declines to <8.5 g/dL, ribavirin should be discontinued. The boceprevir dose should never be reduced during ribavirin or interferon dose modifications. Additionally, if the discontinuation Doxorubicin of either interferon or ribavirin is required, all three treatments should be discontinued to prevent potential boceprevir resistance. A liver biopsy sample provides important information about the prognosis and the

urgency of treatment and excludes other forms of liver disease.13 The degree of fibrosis has also been shown to be an independent predictor of the response to therapy. In patients with HCV genotype 1 infections, the need for liver biopsy is less compelling because of the higher SVR rates observed with the addition of boceprevir to the standard of care. However, information about advanced fibrosis from a pretreatment liver biopsy sample may be used to predict the response

Z-VAD-FMK mw to therapy, even with the advent of newer direct-acting antiviral agents. Indeed, in the SPRINT-2 study, the SVR rates of patients with F3/F4 fibrosis in the boceprevir arms were only 41% to 52%. If a patient’s liver biopsy sample reveals mild fibrosis (F0-F2), there is a higher chance of SVR (67% in the SPRINT-2 study) with boceprevir-based treatment. A finding of minimal fibrosis may reduce the urgency of therapy, and the patient could await possible newer therapies. On the other hand, if the liver biopsy sample demonstrates cirrhosis, 48 weeks of treatment is recommended. The SVR rates for PR-treated HCV genotype 1 patients with the IL-28 CC genotype were more than 2-fold greater than the rates for patients with the CT or TT genotype.14-15 Data regarding the use of IL-28B with the addition of direct-acting antiviral agents to PR are emerging, and as the discovery of IL-28B occurred after the large phase 3 trials with telaprevir and boceprevir

had been initiated, we will need to wait for more complete data sets see more in naive patients. In the SPRINT-2 trial, IL-28 data were available for 62% of the patients (653/1048). The addition of boceprevir was associated with higher SVR rates for the patients with the IL-28 CT and TT genotypes (Supporting Fig. 1).16 Those with the IL-28 CC genotype had SVR rates comparable to those of the controls, but 88% of these individuals cleared the virus by week 8 and were eligible for short-term (28-week) therapy. Testing for IL-28 polymorphisms could be used for counseling patients. If a patient has the IL-28 CC genotype, he may require only 28 weeks of therapy instead of 48 weeks. If he has the IL-28 CT or TT genotype, the addition of boceprevir will substantially improve his chances of SVR in comparison with just PR therapy.