Long-term immunosuppression after liver transplantation in real-life clinical practice: modifications and survival of therapy

Background. High long-term survival rates have been achieved in liver transplant recipients. However, personalised approaches are still needed for selecting and managing the initial immunosuppressive therapy regimen throughout the entire period of graft function.

Objective. To evaluate the outcomes of various immunosuppressive therapy regimens in liver recipients over a period of up to 20 years.

Material and methods. A retrospective cohort study was conducted using data from 173 patients who underwent 176 liver transplants between December 2004 and December 2021. The following immunosuppressive drugs were used: tacrolimus, steroids, mycophenolates, and everolimus, as monotherapy and in various combinations. Modifications to the initial regimen were studied in each patient over time, and the frequency with which various regimens were used at 1, 3, 5 and 10 years after transplantation was analyzed. Clinical observations were divided into two groups depending on whether steroids and/or mycophenolates were present (group 2, n=95) or absent (group 1, n=81) in the initial immunosuppression regimen.

Results. The median follow-up duration was 79.5 (58;120) (6–220) months, the total duration was 1355 patient-years. The initial immunosuppression regimen included: tacrolimus (100% of patients), mycophenolates (48% of patients), steroids (39% of patients), everolimus (8% of patients). Tacrolimus monotherapy was initially prescribed to 38% of patients. The regimens prescribed at discharge were modified at various times in 77 (44%) patients, in the 1st group in 14 (17.3%), in the 2nd group in 63 (66.3%), (p<0.05). The 10-year survival rate of the initial immunosuppression regimen was 89% in the 1st group, 33% in the 2nd group (p<0.05). Rejection was observed in 21.1% of cases in group 2 and 6.2% (n=5) in group 1 (p=0.004). Immune or unspecified graft dysfunction as a cause of death or retransplantation was significantly less common in group 1 than in group 2: 1 (1.2%) and 7 (7.4%), respectively (p=0.039). The average /CF level after 5 years in patients receiving tacrolimus monotherapy was 69.7±14.1 ml/min/1.73m², while in the combination therapy group it was 62.4±20.7 ml/min/1.73m² (p>0.05). SCF ≥ 60 ml/min/1.73m² was recorded in 76.9% and 48.3% of patients, respectively (p<0.01).

Conclusion. Tacrolimus monotherapy or its combination with everolimus are considered optimal for a selective group of adult liver transplant recipients. With careful selection, strict clinical and drug monitoring, these regimens are characterized by the best survival of therapy, minimal risk of rejection, rare development of late graft dysfunction, favorable safety profile in terms of side effects, in particular, nephrotoxicity.

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