Long-Term Outcomes of Everolimus Therapy in De Novo Liver Transplantation: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Risk of nephrotoxicity in liver transplant patients on calcineurin inhibitors (CnIs) is a concern. Several controlled trials reported benefit of everolimus (EVR) in minimizing this risk when combined with a reduced CnI dose. BACKGROUND: To systematically review the efficacy and safety of EVR, alone or with reduced CnI dose, as compared to CnI alone post-liver transplantation. METHODS: We searched MEDLINE, Scopus, and the Cochrane Library for randomized controlled trials comparing EVR- and CnI-based regimens post-liver transplantation. Assessment of studies and data extraction were undertaken independently. RESULTS: Eight studies were selected, describing 769 patients. Cockcroft-Gault GFR was higher at one (P = .05), 3, and 5 years (P = .030) in patients on EVR compared to those receiving CnI therapy. The composite endpoint of efficacy failure was similar between the 2 arms after 1, 3, and 5 years of study. More patients discontinued EVR due to adverse effects in 1 year; however, no difference was noted after 3 or 5 years. A higher rates of proteinuria, peripheral edema, and incisional hernia occurred in patients on EVR. CONCLUSIONS: The analysis confirms noninferiority of EVR and reduced CnI combination. Combination regimen resulted in better renal function compared to standard CnI therapy.

The clinical consequences of utilizing donation after cardiac death liver grafts into hepatitis C recipients.

UNLABELLED: Chronic liver failure from hepatitis C virus (HCV) remains the leading indication for liver transplantation (LT). Donation after cardiac death (DCD) donors are becoming a more frequent source of liver grafts. Hepatitis C recipients of standard donation after brain death (DBD) allografts may have inferior long-term results, and more so when expanded criteria organs are used. Given the nature of DCD grafts, a focus on the consequences to HCV recipients is of major importance. We analyzed the graft outcomes in HCV and non-HCV liver transplant recipients of DCD grafts. RESULTS: 21 patients underwent LT using a DCD grafts (9 HCV, 12 non-HCV) the donor body mass index and age was similar in both groups. One non-HCV recipient was retransplanted for primary non-function (PNF 8%). Biliary complications occurred in 22% (2/9) of the HCV group, 50% (6/12) in the non-HCV group (p = 0.21). After a mean of 19 months follow up, excellent patient and graft survival was seen in the non-HCV recipients of DCD grafts (100 and 92%, respectively). These outcomes were numerically less in HCV recipients (78, 67%). In the HCV recipients of DCD grafts, 33% (3/9) suffered graft loss, two from fatal aggressive fibrosing cholestatic (FCH) HCV and one due to ischemic cholangiopathy. CONCLUSION: Although a statistically significant difference in patient/graft survival for HCV and non-HCV recipients of DCD organs was not shown, it is clear that more dire consequences exist for HCV recipients of DCD grafts, highlighting the need for larger data sets for evaluating this patient population.