Efficacy and safety of once daily tacrolimus compared to twice daily tacrolimus after liver transplantation

BACKGROUND Once daily tacrolimus regimen was found to exhibits similar bioavailability,safety and efficacy properties compared to twice-daily tacrolimus in kidney transplantation patients.AIM To compare the efficacy and safety of once-daily prolonged release tacrolimus compared to twice-daily tacrolimus in liver transplantation patients.METHODS MEDLINE,EMBASE,CENTRAL databases were searched for clinical trials until December 2020.Efficacy outcome measured as the rate of treatment failure indicated by biopsy-proven acute rejection,Serum creatinine,graft loss,or death.Two reviewers independently selected studies,collected data and assessed risk of bias.The results are reported as risk ratio with 95%confidence interval(CI)for dichotomous data.RESULTS Seven studies included with 965 patients.All the included studies were of moderate quality according to the risk of bias assessment using Cochrane Risk of Bias tool.Biopsy-proven acute rejection was reported in four studies,and pooled analysis of those studies indicated similar rejections in both twice daily and once daily tacrolimus groups(risk ratio:1.06,95%CI:0.84-1.34,n=758,I2=0%)and also we found no significant difference between both groups for renal outcome(serum creatinine;mean difference,0.001 mg/dL,95%CI:-0.042 to 0.043,n=846,I2=18.6%).Similarly,there was similar number of adverse events such as hypertension,headache,back pain,blood related disorders,infections and nausea observed in both groups.CONCLUSION The analysis findings confirm that both once daily and twice daily tacrolimus formulations are comparable in terms of efficacy and safety outcomes.

Early tacrolimus exposure does not impact long-term outcomes after liver transplantation

BACKGROUND Tacrolimus trough levels(TTL)during the first weeks after liver transplantation(LT)have been related with long-term renal function and hepatocellular carcinoma recurrence.Nevertheless,the significance of trough levels of tacrolimus during the early post-transplant period for the long-term outcome is under debate AIM To evaluate the effect of TTL during the first month on the long-term outcomes after LT.METHODS One hundred fifty-five LT recipients treated de novo with once-daily tacrolimus were retrospectively studied.Patients with repeated LT or combined transplantation were excluded as well as those who presented renal dysfunction prior to transplantation and/or those who needed induction therapy.Patients were classified into 2 groups according to their mean TTL within the first month after transplantation:≤10(n=98)and>10 ng/mL(n=57).Multivariate analyses were performed to assess risk factors for patient mortality.RESULTS Mean levels within the first month post-transplant were 7.4±1.7 and 12.6±2.2 ng/mL in the≤10 and>10 groups,respectively.Donor age was higher in the high TTL group 62.9±16.8 years vs 45.7±17.5 years(P=0.002)whilst mycophenolate-mofetil was more frequently used in the low TTL group 32.7%vs 15.8%(P=0.02).Recipient features were generally similar across groups.After a median follow-up of 52.8 mo(range 2.8-81.1),no significant differences were observed in:Mean estimated glomerular filtration rate(P=0.69),hepatocellular carcinoma recurrence(P=0.44),de novo tumors(P=0.77),new-onset diabetes(P=0.13),or biopsy-proven acute rejection rate(12.2%and 8.8%,respectively;P=0.50).Eighteen patients died during the follow-up and were evenly distributed across groups(P=0.83).Five-year patient survival was 90.5%and 84.9%,respectively(P=0.44),while 5-year graft survival was 88.2%and 80.8%,respectively(P=0.42).Early TTL was not an independent factor for patient mortality in multivariate analyses.CONCLUSION Differences in tacrolimus levels restricted to the first month after transplant did not result in significant differences in long-term outcomes of LT recipients.