Ultimately, repeat liver transplantation may be considered in select patients with HCV recurrence and allograft failure. Although prior data have identified HCV infection as an independent predictor of mortality following retrans- plantation, more recent reports have described similar rates of survival in HCV and non-HCV recipients. A key factor associated with the observed improvement in outcomes related to retransplantation for recurrent HCV is patient selection. It is well recognized that the development of fibrosing cholestatic HCV is a major risk factor for severe recurrent disease following repeat transplantation with a negative impact on post-transplant survival. In a recent multicenter retrospective study that reported similar survival in HCV-infected and non-HCV patients listed for retransplantation, the most common reasons for not relisting potential candidates included rapid recurrence of HCV within 6 months and fibrosing cholestatic HCV. A recent review of the United Network for Organ Sharing database noted improved 1-year patient and graft survival in HCV-infected individuals undergoing repeat transplantation over subsequent study periods from 1994 to 2005. In this study, factors independently associated with an increased risk of mortality following retransplantation in patients with HCV included increased recipient age, MELD score greater than 25, retransplantation within 1 year of the first transplant, donor age 60 years or greater, and prolonged warm ischemia time. These findings emphasize the importance of not only patient selection, but also donor selection when considering repeat liver transplantation in patients with recurrent HCV.
Long-Term Strategies and Future Therapies
The development of post-liver transplantation comor- bidities, including obesity, hypertension, hyperlipidemia, diabetes mellitus, and renal insufficiency are of particular importance in patients with chronic HCV because they may greatly influence the course of recurrent disease. discount drugs
Post-transplant metabolic syndrome is common and may occur in up to one half of patients. Although components of metabolic syndrome are largely associated with immunosuppressive agents such as corticosteroids and calcineurin inhibitors, emerging data have revealed that HCV infection itself is a risk factor for its development. Recent studies have noted an increased incidence of insulin resistance and new onset diabetes mellitus within the first year in transplant recipients with HCV in contrast to non-HCV recipients. Consequently, the effects of insulin resistance in transplant recipients with HCV can be significant, as the development of insulin resistance has been linked to an increased risk of progressive liver disease and advanced allograft fibrosis. Efforts to minimize the development of post-transplant metabolic syndrome through steroid-free immunosuppression, minimization of calcineurin inhibitor therapy, and aggressive treatment of metabolic complications as they arise may become increasingly important in achieving optimal long-term clinical outcomes in HCV liver transplant recipients.
New investigational antiviral agents with selective activity against various phases of the HCV life cycle and replication, known as direct-acting antiviral (DAA) agents, will likely contribute greatly to the development of more effective treatment strategies against chronic HCV infection. These new agents include protease inhibitors, polymerase inhibitors, immune modulators, cyclophilin inhibitors, ribavirin analogues, and other molecules. Antiviral regimens involving the protease inhibitors telaprevir and boceprevir, in particular, have demonstrated significant improvements over combination PegIFN and RBV in phase II randomized clinical trials. Although DAA agents have not been studied in the transplant setting, they will likely have an important role in the treatment of HCV before or after transplantation, as they may potentially enhance the ability to achieve SVR with a shorter course of therapy. Additional treatment strategies involving CSA-based or steroid-sparing immunosuppression will require further prospective investigation. Other clinical tools, including the detection of specific genetic polymorphisms that are predictive of response to antiviral therapy (such as the IL-28B polymorphism), may also guide individualized treatment strategies in this population.