To transplant or not to transplant recurrent hepatitis C and liver failure

In summary, re-OLT accounts for 10% of all OLTs performed and is associated with significantly increased resource use, and decreased survival compared with primary OLT. After transplantation into an HCV-infected recipient, infection of the allograft by HCV is invariable. As patients survive longer after liver transplantation, it is likely that allograft failure related to HCV recurrence will occur. Results of re-OLT for HCV are inferior to those of primary grafting, paralleling the results for retransplantation for other indications. Many studies have demonstrated that HCV infection significantly impairs patient and allograft survival after liver retransplantation, regardless of etiology of allograft failure. Patient survival rates with HCV infection are 57% to 65% at 1 year, as compared with 65% to 82% among patients without HCV infection. Experience with retransplantation is limited, however, and studies are difficult to interpret because of small sample sizes and lack of uniform definitions of survival, HCV recurrence, and allograft failure. Similar to outcomes after retransplantation for non-HCV related indications, the most common causes of death are sepsis and multi-organ failure. The high mortality associated with retransplantation has not universally been caused by recurrent disease, however recent studies have demonstrated that re-recurrent HCV occurs and the natural history is similar, if not more accelerated, after the second transplant. HCV infection may, in fact, increase mortality in a group of patients already predisposed to an inferior outcome. Preoperative serum creatinine and bilirubin have been consistently associated with survival after retransplantation and favorable results are attainable with strict selection criteria. The increasing use of expanded donor criteria, in particular, LRLT, raises important practical and ethical issues with regards to the HCV-positive transplant recipient and will become a challenge to the transplant community as a whole. With the donor morbidity and mortality associated with LRLT currently estimated at 32% and 0.3%, respectively, one must determine how much risk is acceptable to the donor in relation to the outcome in the recipient. This is especially true in HCV-infected recipients, in whom HCV re-recurrence may occur in the second allograft and lead to accelerated failure. LRLT, however, would not deplete the organ pool and would lead to the use of scarce cadaveric organs to patients who are awaiting primary liver transplantation. Despite inferior outcomes, a better tactic may be to consider retransplantation for recurrent HCV in those whose primary transplant was a LDLT, as the initial allograft did not deplete the donor pool. Given the shortage of donor organs and the increasing number of patients with HCV-induced allograft cirrhosis, identifying ways to improve allograft survival in HCV-infected patients represents an important focus for further research. Additional studies are needed to further explore the mechanisms underlying the reduction in survival and to identify which HCV-positive individuals are at greatest risk for poor survival. Studies are beginning to emerge that demonstrate that HCV recurrence can be modified with combination antiviral therapy and that the HCV virus can be eliminated. Additional longitudinal prospective studies are needed to assess the exact impact of HCV on survival after retransplantation, the effects of the newer immunosuppressive agents such as sirolimus and mycophenolate mofetil on HCV, the use of preemptive antiviral therapy on HCV eradication and fibrosis modification, and the appropriateness of expanded donor criteria. Until we have longer follow-up and greater experience with the HCV-positive recipient with allograft failure, retransplantation should be considered a viable option for highly selected patients, particularly in patients in whom renal failure and severe hyperbilirubinemia have not occurred.