Source University of California, San Francisco, California, San Francisco, USA.
PURPOSE OF REVIEW: The new standard-of-care treatment for genotype 1 hepatitis C virus infection is a combination of PEG-interferon (PEG-IFN), ribavirin (RBV) and a protease inhibitor - telaprevir or boceprevir. As triple therapy is not yet approved for use in decompensated cirrhotics and liver transplant recipients, we examine the efficacy and safety of PEG-IFN, RBV and protease inhibitors in nontransplant populations to inform the current and future treatment paradigms for transplant candidates and recipients.
RECENT FINDINGS: Protease inhibitor-based triple therapy is more efficacious than PEG-IFN and RBV in nontransplant genotype 1 patients, so sustained virologic response rates are predicted to be higher in waitlisted candidates and transplant recipients treated with protease inhibitor-triple therapy. Because of the need to use a backbone of PEG-IFN and RBV, tolerability of therapy will remain a major challenge. Anemia, a well recognized side-effect with PEG-IFN and RBV, will be especially common with protease inhibitor-triple therapy. Both protease inhibitors can modify the levels of drugs metabolized by the CYP3A/4 pathway, and in posttransplant patients, the protease inhibitors increase the levels of cyclosporine and tacrolimus, with the magnitude of the drug-drug interactions varying with protease inhibitor and type of calcineurin inhibitor (CNI).
SUMMARY: Given the complexities of treatment, it is best undertaken by experienced clinicians and only after a detailed discussion of risks-benefits with the patient. To maximize the benefit while minimizing risk, only Child-Turcott-Pugh A (CPT-A) cirrhotics should be considered for pretransplant protease inhibitor-triple therapy. For transplant recipients, very close monitoring and adjustment of CNI levels is critical during protease inhibitor-triple therapy. Cytopenias, especially anemia, will require aggressive management.