Naples Prognostic Score is an Independent Prognostic Factor in Patients Undergoing Hepatectomy for Hepatocellular Carcinoma

Figures & data

Figure 1 Calculation of the Naples Prognostic Score.

Table 1 Comparisons of Clinical Characteristics Among the Three Groups According to Preoperative Naples Prognostic Score

Variables, %	Overall (N=476)	Group 1 (n=53)	Group 2 (n=297)	Group 3 (n=126)	P
Sex, male	409 (85.9)	45 (84.9)	256 (86.2)	108 (85.7)	0.520
Age, >60 years	182 (38.2)	23 (43.3)	108 (36.4)	51 (40.5)	0.967
ASA, > 2	58 (12.2)	1 (1.9)	42 (14.1)	15 (11.9)	0.042
Performance status, ≥ 1	113 (23.7)	10 (18.9)	62 (20.9)	41 (32.5)	0.024
HBV (+)	399 (83.8)	44 (83.0)	252 (84.8)	103 (81.7)	0.824
Cirrhosis	353 (74.2)	38 (71.7)	223 (75.1)	92 (73.0)	0.005
Portal hypertension	160 (33.6)	11 (20.8)	93 (31.3)	56 (44.4)	0.004
Child-Pugh, A/B	438 (92.0)/38 (8.0)	50 (94.3)/3 (5.7)	283 (95.3)/ 14 (4.7)	105 (83.3)/ 21 (16.7)	<0.001
PLT, ≥ 100*10^9/L	358 (75.2)	43 (81.1)	220 (74.1)	95 (75.4)	0.547
ALT, >40 U/L	143 (30.0)	15 (28.3)	98 (33.0)	30 (23.8)	0.162
AST, >40 U/L	176 (37.0)	19 (35.8)	104 (35.0)	53 (42.1)	0.383
COUNT, >2/ ≤2	220 (46.2)/256 (53.8)	6 (11.3)/47 (88.7)	119 (40.1)/178 (59.8)	95 (75.4)/31 (24.6)	<0.001
PNI, ≤44/ >44	130 (27.3)/346 (72.7)	2 (3.8)/51 (96.2)	50 (16.8)/247 (83.2)	78 (61.9)/48 (38.1)	<0.001
SIS, 0/1/2	168 (35.3)/196 (41.2)/112 (23.5)	50 (94.3)/2 (3.8)/1 (1.9)	116 (31.9)/159 (53.5)/22 (7.4)	2 (1.6)/35 (27.8)/89 (70.6)	<0.001
NLR,>2.96/≤2.96	124 (26.1)/352 (73.9)	3 (5.7)/50 (94.3)	47 (15.8)/250 (84.2)	74 (58.7)/52 (41.3)	<0.001
LMR,≤4.4/>4.4	197 (41.4)/279 (58.6)	2 (3.8)/51 (96.2)	83 (27.9)/214 (72.1)	112 (88.9)/14 (11.1)	<0.001
AFP, > 400 ug/L	115 (24.2)	9 (17.0)	72 (24.2)	34 (27.0)	0.361
Maximum tumor size > 5cm	170 (35.7)	17 (32.1)	101 (34.0)	52 (41.3)	0.305
Multiple tumors, 1/≥ 2	373 (78.4)/103 (21.6)	43 (81.1)/10 (18.9)	242 (81.5)/55 (18.5)	88 (69.8)/38 (30.2)	0.025
Resection margin, <1cm	122 (25.6)	8 (15.1)	85 (28.6)	29 (23.0)	0.085
Microscopic vascular	198 (41.6)	19 (35.8)	120 (40.4)	59 (46.8)	0.315
Satellite nodes	42 (8.8)	4 (7.5)	22 (7.4)	16 (12.7)	0.202
Poor differentiation	112 (23.5)	15 (28.3)	62 (20.9)	35 (27.8)	0.213
Operation time, >180 min	267 (56.1)	28 (52.8)	161 (54.2)	78 (69.1)	0.303
Intraoperative blood loss, > 600 mL	94 (19.7)	5 (9.4)	60 (20.2)	29 (23.0)	0.047
Blood transfusion	109 (22.9)	9 (17.0)	65 (21.9)	35 (27.8)	0.232

Abbreviations: ASA, physical Status classification system; HBV, hepatitis B virus; AFP, alpha fetoprotein; PLT, platelet count; ALT, alanine aminotransferase; AST, aspartate aminotransferase; SIS, systemic inflammation score; PNI, prognostic nutritional index; COUNT, controlling nutritional status; NPS, Naples prognostic score.

Figure 2 Curves comparisons of overall survival and recurrence free survival among each group (calculated by Log rank test). Group 1 (NPS = 0); Group 2 (NPS = 1 or 2), and Group 3 (NPS = 3 or 4), respectively. (A) Overall survival, (B) Recurrence-free survival.

Table 2 Univariable and Multivariable Cox Regression Analyses of Risk Factors Associated with Overall Survival for HCC After Hepatectomy

Variables	OR Comparison	UV OR (95% CI)	UV P	MV OR (95% CI)	MV P^a
Sex	Male vs Female	0.675 (0.461–0.990)	0.044	NS
Age	> 60 vs.≤ 60 years	1.022 (0.758–1.378)	0.886
ASA	> 2 vs ≤ 2	1.163 (0.757–1.788)	0.491
Performance status	≥1 vs 0	1.506 (1.087–2.088)	0.014	NS
HBV	Yes vs No	0.958 (0.651–1.411)	0.829
Cirrhosis	Yes vs No	1.172 (0.832–1.650)	0.364
Portal hypertension	Yes vs No	1.678 (1.252–2.249)	0.001	1.709 (1.257–2.325)	0.001
Child-Pugh	B vs A	1.340 (0.839–2.141)	0.220
PLT	< 100 vs ≥ 100*10^9/L	0.975 (0.740–1.351)	0.897
AST	> 40 vs ≤ 40 U/L	1.253 (0.923–1.700)	0.148
ALT	>40 vs ≤ 40 U/L	1.649 (1.233–2.207)	0.001	NS
AFP	> 400 vs ≤ 400 ug/L	2.255 (1.661–3.061)	<0.001	1.530 (1.102–2.125)	0.011
Maximum tumor size	> 5 vs ≤ 5 cm	1.464 (1.088–1.969)	0.012	1.387 (1.003–1.918)	0.048
Tumor number	Multiple vs Solitary	1.872 (1.348–2.598)	<0.001	1.638 (1.161–2.311)	0.005
Resection margin	< 1 vs ≥ 1 cm	1.582 (1.152–2.172)	0.005	1.217 (1.013–1.317)	0.036
Macroscopic vascular	Yes vs No	2.338 (1.740–3.139)	<0.001	1.706 (1.241–2.345)	0.001
Satellite nodes	Yes vs No	2.673 (1.773–4.030)	<0.001	2.229 (1.417–3.508)	0.001
Differentiation	Poor vs Moderate/Well	1.294 (0.926–1.809)	0.131
Anatomical resection	Yes vs No	1.183 (0.883–1.585)	0.259
Operation time	≥180 vs < 180 min	1.280 (0.952–1.721)	0.102
Intraoperative blood loss	> 600 vs ≤600 mL	2.115 (1.535–2.913)	<0.001	1.647 (1.120–2.422)	0.011
Blood transfusion	Yes vs No	1.892 (1.383–2.589)	<0.001
NPS	1	Reference		Reference
	2	2.085 (1.119–3.888)	0.021	1.958 (1.038–3.369)	0.038
	3	3.515 (1.855–6.662)	<0.001	2.608 (1.358–5.008)	0.004
SIS^b	0	Reference		Reference
	1	1.061 (0.740–1.522)	0.747	1.009 (0.623–1.301)	0.576
	2	2.123 (1.483–3.041)	<0.001	1.467 (1.013–2.123)	0.042
PNI	≤ 44 vs > 44	2.248 (1.670–3.025)	<0.001	1.436 (1.043–1.976)	0.026
COUNT	> 2 vs ≤2	1.507 (1.125–2.018)	0.006	1.237 (0.906–1.689)	0.181
NLR	>2.96 vs.≤2.96	1.638 (1.208–2.221)	0.001	1.376 (1.004–1.886)	0.047
LMR	≤4.4 vs >4.4	1.575 (1.177–2.109)	0.002	1.416 (1.052–1.906)	0.022

Notes: ^aThose variables found significant at P < 0.1 in univariable analyses were entered into multivariable logistic analyses. ^bTo avoid collinearity with NPS, SIS, PNI, COUNT, NLR and LMR were analyzed separately with other variables.

Abbreviations: HCC, hepatocellular carcinoma; HBV, hepatitis B virus; AFP, alpha-fetoprotein; PLT, platelet count; ALT, alanine aminotransferase; AST, aspartate aminotransferase; SIS, systemic inflammation score; PNI, prognostic nutritional index; COUNT, controlling nutritional status; NPS, Naples prognostic score. MV, multivariable; NA, not available; OR, odds ratio; UV, univariable.

Table 3 Univariable and Multivariable Cox Regression Analyses of Risk Factors Associated with Recurrence-Free Survival for HCC After Hepatectomy

Variables	HR Comparison	UV HR (95% CI)	UV P	MV HR (95% CI)	MV P^a
Sex	Male vs Female	0.917 (0.664–1.266)	0.597
Age	> 60 vs.≤ 60 years	1.044 (0.829–1.315)	0.751
ASA	> 2 vs ≤ 2	1.263 (0.909–1.757)	0.164
Performance status	≥1 vs 0	1.207 (0.927–1.572)	0.163
HBV	Yes vs No	1.034 (0.763–1.401)	0.829
Cirrhosis	Yes vs No	1.395 (1.065–1.828)	0.016	NS
Portal hypertension	Yes vs No	1.275 (1.008–1.612)	0.043	1.131 (1.006–1.439)	0.044
Child-Pugh	B vs A	1.048 (0.695–1.581)	0.822
PLT	< 100 vs ≥ 100*10^9/L	1.021 (0.789–1.321)	0.024	NS
AST	> 40 vs ≤ 40 U/L	1.417 (1.117–1.789)	0.004	NS
ALT	>40 vs ≤ 40 U/L	1.671 (1.331–2.099)	<0.001	1.592 (1.187–2.137)	0.002
AFP	> 400 vs ≤ 400 ug/L	1.985 (1.546–2.548)	<0.001	1.492 (1.134–1.963)	0.004
Maximum tumor size	> 3 vs ≤ 3 cm	1.346 (1.066–1.699)	0.013	1.371 (1.074–1.750)	0.011
Tumor number	Multiple vs Solitary	1.614 (1.241–2.099)	<0.001	1.532 (1.164–2.016)	0.002
Resection margin	<1 vs ≥1 cm	1.611 (1.257–2.064)	<0.001	1.521 (1.178–1.964)	0.001
Macroscopic vascular	Yes vs No	2.082 (1.645–2.621)	<0.001	1.540 (1.193–1.986)	0.001
Satellite nodes	Yes vs No	2.604 (1.833–3.700)	<0.001	1.802 (1.222–2.657)	0.003
Differentiation	Poor vs Moderate/Well	1.361 (1.047–1.768)	0.021	NS
Anatomical resection	Yes vs No	0.963 (0.768–1.207)	0.741
Operation time	≥180 vs < 180 min	1.279 (1.017–1.610)	0.036	NS
Intraoperative blood loss	> 600 vs ≤600 mL	1.626 (1.240–2.132)	<0.001	NS
Blood transfusion	Yes vs No	1.863 (1.448–2.397)	<0.001	NS
NPS	0	Reference		Reference
	1	1.823 (1.196–2.806)	0.005	2.014 (1.299–3.124)	0.002
	2	2.414 (1.539–3.786)	<0.001	2.002 (1.262–3.175)	0.003
SIS^b	0	Reference		Reference
	1	1.247 (0.953–1.631)	0.108	1.086 (0.826–1.429)	0.555
	2	1.746 (1.301–2.343)	<0.001	1.335 (0.979–1.821)	0.068
PNI	≤ 44 vs > 44	1.933 (1.523–2.454)	<0.001	1.351 (1.214–2.068)	0.019
COUNT	> 2 vs ≤2	1.185 (0.964–1.487)	0.139	0.976 (0.754–1.239)	0.789
NLR	>2.96 vs.≤2.96	1.419 (1.107–1.818)	0.006	1.371 (1.052–1.787)	0.020
LMR	≤4.4 vs >4.4	1.271 (1.012–1.596)	0.039	1.045 (0.902–1.428)	0.126

Notes: ^aThose variables found significant at P < 0.1 in univariable analyses were entered into multivariable logistic analyses. ^bTo avoid collinearity with NPS, SIS (including PNI, COUNT, NLR and LMR) was analyzed separately with other variables.

Abbreviations: HCC, hepatocellular carcinoma; HBV, hepatitis B virus; AFP, alpha-fetoprotein; PLT, platelet count; ALT, alanine aminotransferase; AST, aspartate aminotransferase; SIS, systemic inflammation score; PNI, prognostic nutritional index; COUNT, controlling nutritional status; NPS, Naples prognostic score. MV, multivariable; NA, not available; HR, hazard ratio; UV, univariable.

Figure 3 (A) Compared the predictive ability of postoperative overall survival at 5-year by time-dependent ROCs between the NPS scores and the other indicators. (B) Compared time-dependent AUCs between the NPS scores and the other indicators.

Abbreviations: ROCs, receiver operating characteristic curves; AUCs, areas under the curves; NPS, Naples prognostic score; SIS, systemic inflammation score; PNI, prognostic nutritional index; NLR, neutrophil-lymphocyte ratio; LMR, lymphocyte-monocyte ratio; COUNT, controlling nutritional status.