Inflammatory markers as selection criteria of hepatocellular carcinoma in living-donor liver transplantation

Table 1 Clinical parameters of the study population n (%)

Parameter	Value
Mean age (yr)1	51.9 ± 6.9
Male	184 (82.1)
Diagnosis
Hepatitis B	197 (87.9)
Hepatitis C	13 (5.8)
Others	14 (6.3)
GRWR1	1.21 ± 0.27
Child pugh score1	8.2 ± 2.4
MELD score1	12.8 ± 7.6
AFP (ng/mL)1	183.4 ± 762.7
PIVKA-II (mAU/mL)1	206.5 ± 1118.7
C-reactive protein (mg/dL)1	1.36 ± 2.74
Neutrophil lymphocyte ratio1	3.47 ± 4.68
Pretransplant treatment for HCC	167 (74.6)
Tumor number1	2.6 ± 2.4
Maximum tumor size (cm)1	3.2 ± 3.1
Microvascular invasion	44 (21.3)
Edmondson-steiner grade (III-IV)	81 (42.9)
Within the milan criteria	133 (59.4)
Follow-up duration (mo)1	48.9 ± 37.3
	(median: 68, range: 6-139)

¹Values shown are mean ± SD except where stated otherwise. GRWR: Graft-to-recipient body weight ratio; MELD: Model for end-stage liver disease; AFP: Alpha-fetoprotein; PIVKA-II: Proteins induced by vitamin K antagonism or absence-II; HCC: Hepatocellular carcinoma.

Table 2 Disease-free survival and overall survival according to neutrophil-lymphocyte ratio and C-reactive protein

	Disease-free survival		Overall survival
	χ2	P value	χ2	P value
Neutrophil-lymphocyte ratio (n = 224)
NLR ≥ 1 (n = 195)	1.041	0.308	0.125	0.724
NLR ≥ 2 (n = 115)	2.938	0.087	2.777	0.096
NLR ≥ 3 (n = 70)	0.746	0.388	3.308	0.069
NLR ≥ 4 (n = 44)	1.132	0.287	5.301	0.021
NLR ≥ 5 (n = 34)	2.383	0.123	7.257	0.007
NLR ≥ 6 (n = 27)	3.497	0.049	8.799	0.003
NLR ≥ 7 (n = 22)	1.379	0.240	6.411	0.001
C-reactive protein (n = 145)
CRP ≥ 0.5 (n = 72)	1.359	0.244	4.032	0.045
CRP ≥ 1.0 (n = 42)	6.653	0.010	12.604	< 0.001
CRP ≥ 2.0 (n = 25)	6.974	0.008	6.728	0.009

NLR: Neutrophil-lymphocyte ratio; CRP: C-reactive protein.

Table 3 Clinicopathological characteristics according to Neutrophil-lymphocyte ratio and C-reactive protein n (%)

Parameters	NLR < 6	NLR≥6	P value	CRP < 1	CRP≥1	P value
	(n = 197)	(n = 27)		(n = 103)	(n = 42)
Mean age (yr)1	51.8 ± 7.0	52.2 ± 6.3	0.748	52.4 ± 6.9	52.4 ± 6.8	0.992
Male	164 (83.2)	20 (74.1)	0.243	81 (78.6)	35 (83.3)	0.522
Etiology (HBV)	172 (87.3)	25 (92.6)	0.345	90 (87.4)	37 (88.1)	0.991
GRWR1	1.20 ± 0.27	1.24 ± 0.30	0.495	1.21 ± 0.29	1.23 ± 0.26	0.777
Total bilirubin (g/dL)1	3.8 ± 6.8	11.1 ± 12.5	0.006	3.2 ± 5.8	11.5 ± 12.2	< 0.001
PT INR1	2.6 ± 15.3	1.7 ± 0.5	0.771	1.4 ± 0.3	6.6 ± 33.2	0.293
Child Pugh score1	7.9 ± 2.3	9.8 ± 2.2	< 0.001	7.8 ± 2.4	9.9 ± 1.9	< 0.001
MELD score1	11.7 ± 6.8	20.6 ± 8.8	< 0.001	10.9 ± 6.0	19.4 ± 8.9	< 0.001
AFP (ng/mL)1	142 ± 366	490 ± 1995	0.383	128 ± 381	346 ± 1593	0.389
NLR1	2.12 ± 1.19	13.3 ± 7.79	< 0.001	2.54 ± 2.71	6.15 ± 7.37	0.003
CRP (mg/dL)1	1.03 ± 2.13	3.55 ± 4.76	0.035	0.33 ± 0.29	3.87 ± 4.13	< 0.001
Tumor number1	2.5 ± 2.3	3.3 ± 2.8	0.162	2.7 ± 2.4	2.4 ± 2.1	0.352
Maximal tumor size1	3.10 ± 2.37	4.03 ± 6.13	0.441	2.9 ± 1.5	4.1 ± 5.8	0.475
Microvascular invasion (+)	38 (21.0)	6 (23.1)	0.800	20 (21.1)	6 (15.0)	0.225
E-S grade (III-IV)	94 (57.3)	14 (56.0)	0.901	38 (44.7)	17 (45.9)	0.415
Beyond the Milan criteria	69 (36.5)	14 (51.9)	0.125	39 (39.0)	15 (36.6)	0.899
Pretransplant locoregional treatment	146 (74.1)	21 (77.8)	0.682	81 (78.6)	30 (71.4)	0.352

¹Values shown are mean ± SD. NLR: Neutrophil-lymphocyte ratio; CRP: C-reactive protein; HBV: Hepatitis B virus; GRWR: Graft-to-recipient body weight ratio; PT INR: Prothrombin time international normalized ratio; MELD: Model for end-stage liver disease; AFP: Alpha-fetoprotein; E-S grade: Edmondson grade.

Table 4 Prognostic factors for disease free survival and overall survival in the whole study population

	Disease free survival			Overall survival
	Univariate	Multivariate analysis		Univariate	Multivariate analysis
	P value	HR (95%CI)	P value	P value	HR (95%CI)	P value
Age ≥ 60	0.404			0.723
Male gender	0.196	2.086 (0.595-7.307)	0.250	0.411
Etiology (HBV)	0.977			0.775
GRWR ≥ 1.0	0.551			0.639
Child C	0.978			0.810
AFP ≥ 100	0.015	2.588 (1.187-5.645)	0.017	0.048	1.567 (0.822-2.987)	0.172
NLR ≥ 6	0.049	2.512 (0.987-6.391)	0.053	0.003	2.896 (1.399-5.996)	0.004
Pretransplant locoregional treatment	0.017	4.604 (1.074-19.740)	0.040	0.023	1.946 (0.804-4.713)	0.140
Tumor number ≥ 2	0.604			0.913
Tumor size ≥ 5 cm	< 0.001	6.014 (2.432-14.869)	< 0.001	0.001	2.206 (0.968-5.028)	0.060
Microvascular invasion (+)	0.024	1.369 (0.599-3.132)	0.456	0.074	1.554 (0.769-3.141)	0.220
E-S grade (III-IV)	0.172	1.040 (0.470-2.302)	0.923	0.082	1.371 (0.715-2.630)	0.342
CRP ≥ 1.0 (n = 145)	0.010			< 0.001

HBV: Hepatitis B virus; GRWR: Graft-to-recipient body weight ratio; AFP: Alpha-fetoprotein; NLR: Neutrophil lymphocyte ratio; E-S grade: Edmondson grade; CRP: C-reactive protein.

Table 5 Prognostic factors for disease free survival and overall survival in patients with hepatocelluar carcinoma according to the Milan criteria

	Disease free survival			Overall survival
	Univariate	Multivariate analysis		Univariate	Multivariate analysis
	P value	HR (95%CI)	P value	P value	HR (95%CI)	P value
Within the Milan criteria
AFP ≥ 100	0.475			0.471
NLR ≥ 6	0.541			0.037	2.509 (0.945-6.658)	0.065
Pretransplant locoregional treatment	0.193	2.126 (0.587-7.710)	0.251	0.257
Tumor number ≥ 2	0.764			0.459
Tumor size ≥ 5 cm	< 0.001	6.980 (1.497-32.535)	0.013	0.681
Microvascular invasion (+)	0.619			0.307
E-S grade (III-IV)	0.835			0.592
CRP ≥ 1.0 (n = 145)	0.797			0.054
Beyond the Milan criteria
AFP ≥ 100	0.058	3.619 (1.184-11.063)	0.024	0.082	2.456 (0.888-6.793)	0.083
NLR ≥ 6	0.034	3.973 (1.288-12.249)	0.016	0.045	4.685 (1.607-13.657)	0.005
Pretransplant locoregional treatment	0.096		0.972	0.086		0.971
Tumor number ≥ 2	0.001	0.429 (0.108-1.701)	0.228	0.016	0.493 (0.121-2.001)	0.322
Tumor size ≥ 5 cm	< 0.001	3.753 (0.901-15.626)	0.069	0.003	2.354 (0.587-9.449)	0.227
Microvascular invasion (+)	0.226			0.318
E-S grade (III-IV)	0.083	2.191 (0.697-6.884)	0.179	0.067	2.618 (0.895-7.651)	0.079
CRP ≥ 1.0 (n = 145)	0.004			0.001

HBV: Hepatitis B virus; GRWR: Graft-to-recipient body weight ratio; AFP: Alpha-fetoprotein; NLR: Neutrophil lymphocyte ratio; E-S grade: Edmondson grade; CRP: C-reactive protein.