TACROLIMUS was linked to lower mortality, fewer episodes of acute rejection and less hypertension than ciclosporin during the first year after liver transplantation, according to a meta-analysis of randomised controlled trials. However, the immunosuppressant was also tied to a markedly higher risk of post-transplantation diabetes mellitus (PTDM).
Liver transplant recipients require lifelong immunosuppression to prevent the immune system from attacking the transplanted organ. Calcineurin inhibitors (CNIs), including tacrolimus and ciclosporin, have formed the backbone of post-transplant immunosuppression for more than four decades.
Survival Gains Balanced Against Diabetes Risk
At 12 months, survival was higher in patients treated with tacrolimus. Across 12 studies, 89.7% of patients receiving tacrolimus survived compared with 86.3% of those treated with ciclosporin. The relative risk for mortality with ciclosporin versus tacrolimus was 1.31.
Acute rejection was also less common with tacrolimus. Rejection occurred in 24.6% of tacrolimus-treated patients compared with 28.3% in the ciclosporin arm. Researchers noted that six studies defined rejection as treated biopsy-proven acute rejection, while others also included clinically suspected rejection requiring treatment.
Hypertension rates favoured tacrolimus as well. Around one-quarter of tacrolimus recipients developed hypertension within 12 months, compared with nearly one-third of those receiving ciclosporin.
The trade-off was a substantially greater incidence of PTDM. More than one in five patients receiving tacrolimus developed PTDM, versus 13.5% in the ciclosporin group. PTDM refers to diabetes developing after transplantation, often requiring glucose-lowering therapy.
No Clear Difference in Graft Loss
The meta-analysis did not identify a significant difference in graft loss between the two drugs after one year, although the researchers reported considerable heterogeneity between studies.
Common causes of death included sepsis leading to multiple organ failure, hepatic artery thrombosis and recurrence of primary liver disease.
Investigators also highlighted gaps in the evidence base. Reporting of renal function was considered insufficient for meta-analysis, despite chronic kidney disease remaining a recognised long-term complication of calcineurin inhibitor therapy. Some included studies also used drug levels higher than those currently prescribed in routine practice.
While tacrolimus demonstrated advantages across several one-year outcomes, treatment decisions after liver transplantation remain individualised. Patients may have differing predispositions to complications such as PTDM, hypertension or chronic kidney disease, which could influence both immunosuppressive choice and clinical outcomes.
The findings broadly align with earlier meta-analyses published in 2006 and 2016, although the latest review strengthens evidence supporting tacrolimus for reducing acute rejection during the first year after liver transplantation.
Reference
Ruijter BN et al. Tacrolimus de novo versus ciclosporin after liver transplantation: an updated meta-analysis and systematic review. J Liver Transpl. 2026;DOI:10.1016/j.liver.2026.100350.
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