Tacrolimus-Based versus Cyclosporine-Based Immunosuppression in Hepatitis C Virus-Infected Patients after Liver Transplantation: A Meta-Analysis and Systematic Review

Abstract

BackgroundMost liver transplant recipients receive calcineurin inhibitors (CNIs), especially tacrolimus and cyclosporine, as immunosuppressant agents to prevent rejection. A controversy exists as to whether the outcomes of hepatitis C virus (HCV)-infected liver transplant patients differ based on the CNIs used. This meta-analysis compares the clinical outcomes of tacrolimus-based and cyclosporine-based immunosuppression, especially cases of HCV recurrence in liver transplant patients with end-stage liver disease caused by HCV infection.MethodsRelated articles were identified from the Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, Medline, and Embase. Meta-analyses were performed for the results of homogeneous studies.ResultsNine randomized or quasi-randomized controlled trials were included. The total effect size of mortality (RR = 0.98, 95% CI: 0.77–1.25, P = 0.87) and graft loss (RR = 1.05, 95% CI: 0.83–1.33, P = 0.67) showed no significant difference between the two groups irrespective of duration of immunosuppressant therapy after liver transplantation. In addition, the HCV recurrence-induced mortality (RR = 1.11, 95% CI: 0.66–1.89, P = 0.69), graft loss (RR = 1.62, 95% CI: 0.64–4.07, P = 0.31) and retransplantation (RR = 1.40, 95% CI: 0.48–4.09, P = 0.54), as well as available biopsies, confirmed that histological HCV recurrences (RR = 0.92, 95% CI: 0.71–1.19, P = 0.51) were similar.ConclusionThese results suggested no difference in posttransplant HCV recurrence-induced mortality, graft loss and retransplantation, as well as histological HCV recurrence in patients treated with tacrolimus-based and cyclosporine-based immunosuppresion.

Systematic Review and Meta-Analysis of Tacrolimus versus Ciclosporin as Primary Immunosuppression After Liver Transplant

“…Outcomes in the HCV subgroup analysis of graft loss were also in line with many individual RCTs and a 2014 meta-analysis by Liu and colleagues [14]. In terms of individual studies, Villamil et al .…”

“…and a 2014 analysis focusing specifically on patients with hepatitis C virus (HVC) [12–14]. However, many of these analyses include data from older trials of tacrolimus and ciclosporin, predating either the use of ciclosporin microemulsion or the more prevalent use of MMF as the antiproliferative agent in place of the anti-metabolite azathioprine.…”

A long‐term experience with expansion of Milan criteria for liver transplant recipients

“…While there are no models suggesting a percentage of recurrence‐free survival necessary to justify expansion criteria, this study had a 69% recurrence‐free survival at 5 years and 47% at 10 years, which was not statistically different from the 74% and 54% recurrence‐free survival observed at 5 and 10 years, respectively, in the MC group. Allograft survival can also be a potential issue in liver transplant recipients with history of HCC, as these patients require both chemotherapy and immunosuppression and there is a lack of standardization in the literature of which modalities are most advantageous . Our study demonstrated that allograft survival was not compromised using the expanded R4C, nor was it statistically different compared to the MC group, even when stratifying patients based on presence of pretransplant LRT.…”

“…Allograft survival can also be a potential issue in liver transplant recipients with history of HCC, as these patients require both chemotherapy and immunosuppression and there is a lack of standardization in the literature of which modalities are most advantageous. [20][21][22][23] This could, in part, be explained by the higher MELD score for R4C patients (25 vs 24, P = .001); however, further studies and investigations would need to be undertaken to fully explain this observation.…”

Liver Transplantation in Patients with Hepatitis C

“…The impact is most pronounced when high-intensity regimens are used to treat acute rejection, particularly with high-dose steroid boluses and anti-lymphocyte antibody preparations [11][12][13]. There are no convincing data to support the use of any specific induction or maintenance regimen, and it is likely that the choice of initial calcineurin inhibitor (tacrolimus or cyclosporine) does not significantly impact overall outcomes in HCV-positive liver transplant recipients [14].…”