Impact of tacrolimus intra-patient variability in adverse outcomes after organ transplantation

Table 3 Tacrolimus intra-patient variability and liver transplantation: Main findings

Liver transplantation
Ref.	Sample size	Donor	Tac-IPV assessment	Outcome
Lieber et al[18], 2013	988	Not specified	SD	Non-adherence among liver transplant recipients is associated with increased risk of graft failure
Stuber et al[19], 2008	96	Not specified	SD	The SD has utility of monitoring routine tac blood levels in pediatric recipients for detecting non-adherence prior to clinical rejection
Venkat et al[32], 2008	101	Not specified	SD	Variations in tac blood levels is associated with an increased risk of late allograft rejection in pediatric recipients
Shemesh et al[33], 2017	400	Both living and deceased donor	SD; MLVI	MLVI predicts late acute rejection in pediatric liver transplantation recipients
de Oliveira et al[34], 2017	50	Both living and deceased donor	SD; MLVI	MLVI may be a nice indicator of the risk of medication non-adherence in child-age
Defrancq et al[35], 2019	41	Both living and deceased donor	CV	High Tac IPV may be associated with adverse patient outcomes. Also, there is some impact of biological factors on IPV and therapy adherence
Christina et al[36], 2014	150	Not specified	SD; MLVI	The MLVI is associated with and can predict rejection, possibly related to non-adherence in adult recipients
Del Bello et al[37], 2018	116	Deceased donor only	CV	Tac IPV could be useful to identify patients with a greater risk of graft rejection and pf developing de novo DSA after liver transplantation
Rayar et al[38], 2018	812	Deceased donor only	CV	High CV of Tac concentrations was found to be predictive of Tac-related toxicity and poorer survival
van der Veer et al[39], 2019	326	Both living and deceased donor	CV	High IPV in Tac exposure beyond 6 mo after liver transplantation was not associated with imune-mediated graft injury
Dopazo et al[40], 2022	140	Deceased donor only	CV	High IPV between the third and sixth months appears to be an early and independent predictor of poorer liver transplant outcomes
Kim et al[41], 2022	636	Both living and deceased donor	CV	High Tac IPV was associated with increased risks of overall mortality and HCC recurrence in liver transplantation recipients with HCC

SD: Standard deviation; CV: Coefficient of variation; MLVI: Medication level variability index; DSA: Donor-specific antibodies; HCC: Hepatocellular carcinoma.