Protease inhibitor use for chronic hepatitis C infection in prior null responders and recurrent hepatitis C infection post liver transplant

Chronic hepatitis C (CHC) remains a significant medical and economic burden in Canada, affecting nearly 1% of the population. In 2007, it was estimated that 242,000 Canadians had chronic HCV infection and about 7,000 new infections occurred. Of those with chronic infection,15% to 25% will develop progressive liver disease, end stage liver disease, hepatocellular carcinoma or will require liver transplant. Hepatitis C is the principal cause of death from liver disease and the leading indication for liver transplantation. Recurrence of HCV occurs in more than 95% of patients after liver transplantation. Boceprevir (BOC) and telaprevir (TP) are two NS3 protease inhibitors (PI) indicated for the treatment of CHC genotype 1 infection. They have shown statistically significant improvement of the SVR rate in patients with CHC who are treatment nav̐e or failed to respond to prior standard PR therapy. However, the comparative effectiveness and safety of triple therapy of BOC or TP plus PR compared with standard PR therapy alone in patients who are prior null responder (defined as less than 2 log10 HCV RNA reduction after 12 weeks of PR therapy) or patients who have recurrent HCV after liver transplantation were not well established. The addition of PI to the established PR regimen may provide another opportunity for patients who have had a null response to prior PR therapy. It is therefore important to ascertain the efficacy of PI-PR triple therapy in this population. The use of BOC or TP in the post-transplant setting in patients with genotype 1 HCV disease has been limited. It has been indicated that drug-drug (PI and immunosuppressive agents) interactions remain a significant clinical issue. The aim of this review is to evaluate the effective and safety evidence of BOC or TP-containing triple therapy regimens in the treatment of the above special populations.