Prognostic value of the neutrophil-to-lymphocyte ratio for hepatocellular carcinoma patients with portal/hepatic vein tumor thrombosis

Table 1 Correlation between each neutrophil-to-lymphocyte ratio cut-off and overall survival of hepatocellular carcinoma patients with portal/hepatic vein tumor thrombosis using the Kaplan-Meier method

Cut-off value	Group	Cases	1-yr OS	2-yr OS	3-yr OS	5-yr OS	χ2	P value
1.0	NLR ≤ 1 vs > 1	5 vs 76	80.0% vs 46.9%	40.0% vs 27.7%	40.0% vs 19.0%	0.0% vs 17.3%	0.272	0.602
1.5	NLR ≤ 1.5 vs > 1.5	16 vs 65	80.0% vs 41.5%	46.7% vs 24.2%	26.7% vs 19.8%	6.7% vs 19.8%	1.575	0.210
2.0	NLR ≤ 2 vs > 2	28 vs 53	72.3% vs 37.3%	44.2% vs 20.7%	28.1% vs 17.8%	16.1% vs 17.8%	3.657	0.056
2.5	NLR ≤ 2.5 vs > 2.5	39 vs 42	64.5% vs 35.1%	39.2% vs 18.9%	25.2% vs 18.9%	16.8% vs 18.9%	3.935	0.047
2.6	NLR ≤ 2.6 vs > 2.6	42 vs 39	62.1% vs 35.4%	38.5% vs 17.7%	24.7% vs 17.7%	16.5% vs 17.7%	3.987	0.046
2.7	NLR ≤ 2.7 vs > 2.7	44 vs 37	59.1% vs 37.3%	36.6% vs 18.7%	23.6% vs 18.7%	15.7% vs 18.7%	2.254	0.133
2.8	NLR ≤ 2.8 vs > 2.8	49 vs 32	60.2% vs 32.7%	39.1% vs 13.1%	26.1% vs 13.1%	18.3% vs 13.1%	6.007	0.014
2.9	NLR ≤ 2.9 vs > 2.9	51 vs 30	59.8% vs 31.5%	39.5% vs 10.5%	26.3% vs 10.5%	18.4% vs 10.5%	7.227	0.007
3.0	NLR ≤ 3 vs > 3	53 vs 28	59.8% vs 32.1%	38.8% vs 10.7%	25.9% vs 10.7%	18.1% vs 10.7%	6.158	0.013
3.5	NLR ≤ 3.5 vs > 3.5	62 vs 19	56.7% vs 26.3%	34.4% vs 10.5%	23.7% vs 10.5%	17.2% vs 10.5%	2.843	0.092
4.0	NLR ≤ 4 vs > 4	66 vs 15	56.2% vs 20.0%	33.8% vs 6.7%	23.9% vs 6.7%	17.9% vs 6.7%	5.284	0.022
4.5	NLR ≤ 4.5 vs > 4.5	72 vs 9	51.1% vs 33.3%	30.7% vs 11.1%	21.7% vs 11.1%	16.3% vs 11.1%	1.724	0.189
5.0	NLR ≤ 5 vs > 5	75 vs 6	50.3% vs 33.3%	29.4% vs 16.7%	20.7% vs 16.7%	15.6% vs 16.7%	0.527	0.468

Table 2 Clinicopathological characteristics of the 81 hepatocellular carcinoma patients with portal/hepatic vein tumor thrombosis, n (%)

	NLR ≤ 2.9 (n = 51)	NLR > 2.9 (n = 30)	P value
Age in years	48.49 ± 1.52	48.47 ± 2.28	0.993
Gender			0.292
Male	48 (94.1)	30 (100.0)
Female	3 (5.9)	0 (0.0)
HBsAg status			0.281
Negative	3 (5.9)	0 (0.0)
Positive	45 (88.2)	30 (100.0)
Unknown	3 (5.9)	0 (0.0)
Preoperative HBV DNA			0.025
< 1 × 103	19 (37.3)	4 (13.3)
≥ 1 × 103	23 (45.1)	19 (63.3)
Unknown	9 (17.6)	7 (23.3)
Preoperative AFP level			0.038
< 400 ng/mL	19 (37.3)	5 (16.7)
≥ 400 ng/mL	30 (58.8)	25 (83.3)
Unknown	2 (3.9)	0 (0.0)
Preoperative ALT level (U/L)	41 (10-713)	42.5 (21-146.5)	0.697
Preoperative Hgb level (g/L)	147.79 ± 2.43	148.52 ± 4.37	0.884
Preoperative PLT level (109/L)	185.84 ± 12.73	201.97 ± 13.97	0.417
Preoperative Child-Pugh score			0.017
Child A (5)	21 (41.2)	7 (23.3)
Child A (6)	22 (43.1)	14 (46.7)
Child B (7)	4 (7.8)	5 (16.7)
Child B (8)	1 (2.0)	2 (6.7)
Child B (9)	0 (0.0)	1 (3.3)
Unknown	3 (5.9)	1 (3.3)
Preoperative ICGR15 (%)	6.42 ± 0.79	5.37 ± 0.94	0.404
Number of tumors			0.474
Solitary	28 (54.9)	14 (46.7)
Multiple	23 (45.1)	16 (53.3)
Maximum diameter of tumor (cm)	8.93 ± 0.58	11.88 ± 0.80	0.003
Uni/bilobular disease			0.414
Unilobular disease	48 (94.1)	26 (86.7)
Bilobular disease	3 (5.9)	4 (13.3)
Adjacent organ invasion			0.722
Negative	32 (62.7)	20 (66.7)
Positive	19 (37.3)	10 (33.3)
Operative procedure			0.215
Minor	45 (88.2)	23 (76.7)
Major	6 (11.8)	7 (23.3)
Total occlusion time of the hepatic inflow (min)	17.89 ± 1.58	18.18 ± 2.53	0.918
Total operative time (min)	168.43 ± 7.19	205.00 ± 13.77	0.011
Blood loss (mL)	579.41 ± 61.82	891.67 ± 171.61	0.095
Blood transfusion (mL)			0.061
No	33 (64.7)	13 (43.3)
Yes	18 (35.3)	17 (56.7)
Surgical margin			0.002
≤ 1 cm	33 (64.7)	25 (83.3)
> 1 cm	18 (35.3)	1 (3.3)
Unknown	0 (0.0)	4 (13.3)
Histological grade of tumor cells			0.958
I-II	19 (37.3)	11 (36.7)
III-IV	32 (62.7)	19 (63.3)
Postoperative complication			0.792
Negative	42 (82.4)	24 (80.0)
Positive	9 (17.6)	6 (20.0)
Postoperative hospital stay (d)	11 (8-28)	11.5 (8-83)	0.468

NLR: Neutrophil-to-lymphocyte ratio.

Table 3 Patterns of recurrence and postoperative treatments in the patients of the two groups, n (%)

	NLR ≤ 2.9	NLR > 2.9	P value
Recurrence	n = 51	n = 30	1.000
Negative	3 (5.9)	1 (3.3)
Positive	39 (76.5)	23 (76.7)
Unknown	9 (17.6)	6 (20)
Recurrence pattern	n = 39	n = 23	0.832
Intrahepatic only	26 (66.7)	15 (65.2)
Extrahepatic only	2 (5.1)	2 (8.7)
Both	11 (28.2)	6 (26.1)
Treatments	n = 51	n = 30
TACE	23	15
Hepatectomy	2	0
PMCT	4	0
Systemic chemotherapy	3	2
RFA	5	0
PEI	2	0
CIK	0	2
TAI	1	1
Sorafenib	0	1
Radiotherapy	1	0
Sealed source radiotherapy	1	2
Traditional Chinese medicine	4	0
Supportive care only	21	12

Some patients accepted more than one type of treatment. NLR: Neutrophil-to-lymphocyte ratio; TACE: Transarterial chemoembolization; PMCT: Percutaneous microwave tumor coagulation therapy.

Table 4 Univariate and multivariate analyses of factors affecting overall survival

Variables	Univariate analysis for OS			Multivariate analysis for OS
	HR	95%CI	P value	HR	95%CI	P value
NLR > 2.9	1.969	1.190-3.259	0.008	1.866	1.048-3.322	0.034
Age ≤ 50 yr	1.532	0.913-2.569	0.106
Female	2.035	0.625-6.623	0.238
HBsAg (+)	1.055	0.327-3.402	0.929
HBV-DNA > 1 × 103	1.258	0.709-2.234	0.432
AFP ≥ 400 ng/mL	2.026	1.163-3.527	0.013	1.863	1.024-3.392	0.042
ALT ≤ 40 U/L	1.122	0.684-1.839	0.649
Hgb > 130 g/L	1.964	0.987-3.909	0.054
PLT > 100 × 109/L	1.168	0.467-2.916	0.740
Child A	1.090	0.564-2.106	0.798
ICGR15 ≤ 10%	1.642	0.746-3.610	0.218
Multiple tumors	1.676	1.022-2.748	0.041	1.084	0.627-1.876	0.772
Maximum diameter of tumor > 5 cm	1.869	0.973-3.593	0.061
Bilobular disease	2.764	1.153-6.628	0.023	3.292	1.215-8.918	0.019
Adjacent organ invaded	1.268	0.756-2.127	0.369
Major hepatectomy	1.145	0.597-2.195	0.683
Pringle maneuver	1.937	0.950-3.952	0.069
Operation time > 180 min	1.352	0.819-2.233	0.238
Intraoperative blood loss > 1000 mL	1.721	0.957-3.096	0.070
Intraoperative blood transfusion	1.485	0.901-2.448	0.121
Surgical margin ≤ 1 cm	1.868	1.024-3.408	0.042	1.195	0.596-2.394	0.616
Histologic grade III-IV	1.220	0.736-2.020	0.440
Postoperative complication	1.467	0.807-2.667	0.209
Postoperative hospital stay ≤ 10 d	1.078	0.646-1.798	0.774

NLR: Neutrophil-to-lymphocyte ratio; OS: Overall survival; HBV: Hepatitis B virus; AFP: Alpha fetoprotein; ALT: Alanine aminotransferase; PLT: Platelet.

Table 5 Univariate and multivariate analyses of factors affecting disease-free survival

Variables	Univariate analysis for DFS			Multivariate analysis for DFS
	HR	95%CI	P value	HR	95%CI	P value
NLR > 2.9	1.720	1.017-2.907	0.043	1.553	0.850-2.837	0.153
Age ≤ 50 yr	1.424	0.842-2.409	0.188
Female	1.593	0.384-6.610	0.522
HBsAg (+)	1.314	0.407-4.249	0.648
HBV-DNA > 1 × 103	1.426	0.772-2.634	0.257
AFP ≥ 400 ng/mL	2.099	1.196-3.684	0.010	1.732	0.954-3.146	0.071
ALT ≤ 40 U/L	1.272	0.771-2.098	0.346
Hgb > 130 g/L	2.629	1.266-5.460	0.010	2.051	0.940-4.476	0.071
PLT ≤ 100 × 109/L	1.147	0.413-3.186	0.793
Child B	1.254	0.631-2.492	0.518
ICGR15 ≤ 10%	2.470	1.052-5.796	0.038	2.134	0.870-5.236	0.098
Multiple tumors	1.189	0.709-1.992	0.512
Maximum diameter of tumor > 5 cm	1.865	0.944-3.686	0.073
Bilobular disease	1.778	0.753-4.199	0.189
Adjacent organ not invaded	1.119	0.659-1.899	0.677
Major hepatectomy	1.253	0.635-2.474	0.516
Pringle maneuver	1.922	0.933-3.960	0.076
Operation time ≤ 180 min	1.067	0.638-1.785	0.805
Intraoperative blood loss > 1000 mL	1.854	1.012-3.396	0.046	1.258	0.649-2.437	0.497
Intraoperative blood transfusion	1.655	0.972-2.817	0.064
Surgical margin ≤ 1 cm	1.492	0.827-2.690	0.183
Histologic grade I-II	1.083	0.648-1.808	0.761
Postoperative complication	1.173	0.608-2.264	0.634
Postoperative hospital stay > 10 d	1.041	0.616-1.759	0.882

NLR: Neutrophil-to-lymphocyte ratio; DFS: Disease-free survival; HBV: Hepatitis B virus; AFP: Alpha fetoprotein; ALT: Alanine aminotransferase; PLT: Platelet.