New therapies against HCV: expected risks and challenges associated with their use in the liver transplant setting.

Current approaches to anti-viral therapy (AVT) in the setting of liver transplantation are based on the use of pegylated interferon in combination with ribavirin (PegIFN/RBV). Attempts to clear HCV pretransplant have been successful in about 15–20% of the patients with genotype 1 infection and about 20–35% with genotype 3 [1,2] Such patients usually have relatively lower MELD scores (<18) than many other patients listed for transplant. Despite this AVT is associated with an increased risk of serious bacterial infections [3]. Sustained viral response (SVR) pretransplant is associated with lack of viral recurrence post-transplant [1,2] Early post-transplant AVT is not thought to be useful due to lack of efficacy and poor tolerability [4,5]. The commencement of AVT is usually considered at about the 12-month mark based on protocol biopsies. Patients with either F2 or F1 with significant portal inflammation (stage P to 2) are usually considered for AVT6.-8. SVRs in the range of 20–30% for patients with HCV genotype 1 (G1) and 40–50% for patients with HCV G3 are obtained [6–8]. SVR post-transplant has been linked to both donor and recipient IL28 polymorphisms [9–11]. Achievement of SVR in the post-transplant setting is associated with improved survival compared to patients who do not achieve an SVR [6–8]. Given the importance of viral clearance in the pre and posttransplant setting, such results have been thought to be somewhat unsatisfactory and the liver transplant community has been eagerly awaiting new anti-HCV therapies.