Association between the early high level of serum tacrolimus and recurrence of hepatocellular carcinoma in ABO-incompatible liver transplantation

Table 1 Univariate and multivariate Cox-regression analyses of factors associated with graft survival

	Univariate		Multivariate
	HR (95%CI)	P value	HR (95%CI)	P value
Tacrolimus level, post-LT 16 wk	0.82 (0.68-0.99)	0.040		NS
Tacrolimus level, post-LT 24 wk	0.71 (0.52-0.96)	0.029	0.75 (0.56-0.99)	0.048
AMR	6.01 (2.17-16.68)	0.001	5.41 (1.44-20.40)	0.013

HR: Hazard ratio; 95%CI: 95% confidence interval; AMR: Antibody mediated rejection; NS: Not significant.

Table 2 Cox-regression analyses for factors associated with graft survival in recipients without and with hepatocellular carcinoma

	Non-HCC				HCC
	Univariate		Multivariate		Univariate		Multivariate
	HR (95%CI)	P value	HR (95%CI)	P value	HR (95%CI)	P value	HR (95%CI)	P value
B cell crossmatching, positive					0.19 (0.05-0.73)	0.016		NS
Tacrolimus level, post-LT 24 week	0.42 (0.23-0.88)	0.019	0.46 (0.23-0.91)	0.026
AMR	3.39 (0.70-16.36)	0.099		NS	11.33 (2.88-44.57)	0.001	63.20 (6.49-614.78)	< 0.001
HCC recurrence					5.31 (1.48-19.02)	0.010	20.72 (2.48-173.32)	0.005

HR: Hazard ratio; 95%CI: 95% confidence interval; HCC: Hepatocellular carcinoma; LT: Liver transplantation; AMR: Antibody mediated rejection; NS: Not significant.

Table 3 Cox-regression analyses for factors associated with HCC recurrence in recipients with hepatocellular carcinoma

	Univariate		Multivariate
	HR (95%CI)	P value	HR (95%CI)	P value
AFP > 200	4.07 (1.32-12.53)	0.014		NS
B-cell crossmatching, positive	0.29 (0.08-1.08)	0.065		NS
HLA-C mismatching	0.36 (0.12-1.11)	0.066		NS
Tacrolimus level, post-LT 4 wk	1.28 (1.00-1.65)	0.046	1.37 (1.04-1.80)	0.024
Over Milan – preoperative radiologic	13.11 (3.54-48.55)	< 0.001	8.61 (1.97-37.70)	0.004
Over Milan – pathologic	6.69 (2.05-21.83)	0.002		NS

HR: Hazard ratio; 95%CI: 95% confidence interval; AFP: Alpha-fetoprotein; HLA: Human leukocyte antigen; LT: Liver transplantation; NS: Not significant.

Table 4 Comparison of patients’ characteristics between low and high tacrolimus level groups at 4 wk liver transplantation before and after propensity-score matching

	Before matching			After matching
	Low FK 4wk, n = 34	High FK 4wk, n = 13	P value	Low FK 4wk, n = 12	High FK 4wk, n = 12	P value
Male gender	31 (91.2)	9 (69.2)	0.152	10 (83.3)	8 (66.7)	0.637
Age (yr)	57.0 (54.0; 62.0)	54.0 (46.0; 59.0)	0.103	54.0 (52.5; 58.5)	54.0 (46.0; 62.0)	0.862
AFP (ng/mL)	9.6 (3.2; 31.0)	17.5 (12.0; 28.8)	0.216	15.3 (3.5; 40.0)	16.5 (10.2; 263.8)	0.713
PIVKA (mAU/mL)	20.5 (12.0; 119.0)	16.0 (13.0; 26.0)	0.625	21.5 (14.5; 87.5)	15.0 (12.5; 62.5)	0.506
MELD	9.0 (7.0; 14.0)	8.0 (7.0; 10.0)	0.234	7.5 (4.5;12.2)	7.0 (4.5; 8.0)	0.62
ACR	4 (11.8)	3 (23.1)	0.606	3 (25.0)	2 (16.7)	1
AMR	2 (5.9)	1 (7.7)	1	2 (16.7)	1 (8.3)	1
Biliary complication	14 (41.2)	5 (38.5)	1	6 (50.0)	5 (41.7)	1
Hepatic artery thrombosis	1 (2.9)	1 (7.7)	1	1 (8.3)	1 (8.3)	1
mTOR inhibitor	8 (23.5)	5 (38.5)	0.51	3 (27.3)	3 (27.3)	1
Radiologic over Milan	8 (23.5)	7 (53.8)	0.1	2 (16.7)	6 (50.0)	0.194
Pathologic over Milan	10 (29.4)	5 (38.5)	0.806	3 (25.0)	4 (33.3)	1
Downstaging treatment	14 (41.2)	5 (38.5)	1	4 (33.3)	4 (33.3)	1
Tumor largest size, cm	1.5 (0.0; 3.2)	3.0 (1.6; 4.5)	0.174	1.8 (0.0; 2.3)	2.5 (0.8; 4.0)	0.331
Tumor number	1.0 (0.0; 2.0)	1.0 (1.0; 2.0)	0.303	1.0 (0.0; 1.5)	1.0 (0.5; 2.5)	0.336

Data are given as n (%) or median (quartile). FK: Tacrolimus; AFP: Alpha-fetoprotein; PIVKA: Protein-induced by vitamin K; MELD: Model for end-stage liver disease; ACR: Acute cellular rejection; AMR: Antibody-mediated rejection.