Correlation between smoking habit and surgical outcomes on viral-associated hepatocellular carcinomas

Table 1 Clinicopathologic features of the hepatitis C virus-hepatocellular carcinoma and hepatitis B virus-hepatocellular carcinoma n (%)

	HCV (n = 273)	HBV (n = 68)	P value
Age (mean ± SD)	67.16 ± 8.56	57.15 ± 12.47	< 0.0001
Gender
Male	203 (74.36)	59 (86.76)	0.0300
Female	70 (25.64)	9 (13.24)
Smoking habit
Never	111 (40.66)	21 (30.88)	0.0715
Ex	74 (27.11)	15 (22.06)
Current	88 (32.23)	32 (47.06)
Alcohol abuse
(+)	63 (23.08)	22 (32.35)	0.1136
(-)	210 (76.92)	46 (67.65)
Diabetes mellitus
(+)	62 (22.71)	12 (17.65)	0.3647
(-)	211 (77.29)	56 (82.35)
BMI (mean ± SD)	22.49 ± 3.29	22.93 ± 3.80	0.3478
ICG R15 (%) (mean ± SD)	18.63 ± 9.03	13.31 ± 6.30	< 0.0001
AFP (ng/mL), Median (range)	26.2 (0, 29800)	31 (1, 271600)	0.0625
Tumor size (mean ± SD mm)	37.37 ± 25.62	49.72 ± 33.14	0.0052
Solitary/Multiple
Solitary	182 (66.67)	41 (60.29)	0.3230
Multiple	91 (33.33)	27 (39.71)
Vp
(+)	74 (27.11)	29 (42.65)	0.0125
(-)	199 (72.89)	39 (57.35)
T factor
T1/2	156 (57.14)	32 (47.06)	0.1347
T3/4	117 (42.86)	36 (52.94)

HCV: Hepatitis C virus; HBV: Hepatitis B virus.

Table 2 Univariate analysis results: Disease-free, overall and disease-specific survival after hepatic resection for hepatocellular carcinoma (hepatitis C virus, n = 273)

		DFS		OS		DSS
Characteristics	n	HR (95%CI)	P value	HR (95%CI)	P value	HR (95%CI)	P value
Age			0.9234		0.5143		0.7101
≤ 67	133	1		1		1
> 67	140	1.01381 (0.7665, 1.3409)		1.10679 (0.8159, 1.5015)		0.92155 (0.599, 1.4177)
Gender			0.5699		0.5110		0.2434
Female	70	1		1		1
Male	203	0.91269 (0.666, 1.2508)		1.12916 (0.786, 1.6221)		1.38366 (0.8019, 2.3876)
Smoking habit (Ex + current)			0.5978		0.1262		0.2147
Absent	111	1		1		1
Present	162	0.92696 (0.6994, 1.2286)		1.27849 (0.9332, 1.7516)		1.32797 (0.8483, 2.0788)
Smoking habit (current)			0.8864		0.0144		0.0483
Absent	185	1		1		1
Present	88	1.02258 (0.7527, 1.3892)		1.47783 (1.0808, 2.0207)		1.55795 (1.0033, 2.4192)
Alcohol abuse			0.0321		0.8232		0.7027
Absent	210	1		1		1
Present	63	0.68132 (0.4797, 0.9678)		0.95952 (0.6677, 1.3788)		0.90325 (0.5356, 1.5232)
Diabetes mellitus			0.3149		0.5259		0.9487
Absent	211	1		1		1
Present	62	1.18657 (0.85, 1.6564)		1.12207 (0.7861, 1.6017)		0.98302 (0.5831, 1.6572)
BMI			0.0270		0.2082		0.6409
≤ Median	137	1		1		1
> Median	136	0.72863 (0.5503, 0.9647)		0.82193 (0.6056, 1.1155)		0.9026 (0.5868, 1.3884)
ICG R15 (%)			0.0088		0.2391		0.6896
≤ Median	111	1		1		1
> Median	162	1.47199 (1.1021, 1.9659)		1.20672 (0.8825, 1.65)		1.09334 (0.7056, 1.6941)
AFP			0.2274		0.0402		0.1371
≤ Median	136	1		1		1
> Median	137	1.18795 (0.8981, 1.5713)		1.37689 (1.0144, 1.8689)		1.38776 (0.901, 2.1376)
Tumor size			0.0305		0.0019		0.0070
≤ Median	161	1		1		1
> Median	112	1.37235 (1.0303, 1.828)		1.63014 (1.1982, 2.2178)		1.81608 (1.1773, 2.8016)
Solitary/Multiple			0.0021		0.0001		0.1182
Solitary	182	1		1		1
Multiple	91	1.59365 (1.1835, 2.1459)		1.8536 (1.3563, 2.5332)		1.43932 (0.9115, 2.2728)
Vp			0.0767		0.0004		0.0177
Absent	199	1		1		1
Present	74	1.33528 (0.9695, 1.839)		1.81728 (1.3073, 2.5262)		1.76737 (1.104, 2.8294)
T12/T34			< 0.0001		0.0008		0.0315
T12	156	1		1		1
T34	117	1.81021 (1.3644, 2.4017)		1.68381 (1.2412, 2.2843)		1.60589 (1.0429, 2.4728)

DFS: Disease-free survival; OS: Overall survival; DSS: Disease-specific survival.

Table 3 Multivariate analyses for current smokers vs others (hepatitis C virus, n = 273)

Type	Characteristics	HR (95%CI)	P value
DFS	Smoking habit (current)	1.22892 (0.8736, 1.7287)	0.2364
	Age (67 < yr)	0.98815 (0.7442, 1.3121)	0.9343
	Gender (male)	0.9536 (0.6797, 1.338)	0.7833
	Alcohol abuse	0.55622 (0.3803, 0.8135)	0.0025
	BMI (median <)	0.70403 (0.5284, 0.9381)	0.0165
	ICG R15 (median <)	1.59531 (1.1763, 2.1635)	0.0027
	T factor (T3/4)	1.90638 (1.4279, 2.5452)	< 0.0001
OS	Smoking habit (current)	1.69259 (1.1844, 2.4187)	0.0039
	Age (67 < yr)	1.18434 (0.8668, 1.6182)	0.2880
	Gender (male)	1.01654 (0.687, 1.504)	0.9346
	Alcohol abuse	0.74612 (0.5061, 1.1)	0.1392
	BMI (median <)	0.89005 (0.6489, 1.2208)	0.4701
	ICG R15 (median <)	1.32015 (0.9524, 1.83)	0.0955
	T factor (T3/4)	1.74555 (1.2767, 2.3865)	0.0005
DSS	Smoking habit (current)	1.68394 (1.0201, 2.7798)	0.0416
	Age (67 < yr)	1.00555 (0.6464, 1.5644)	0.9804
	Gender (male)	1.25081 (0.6981, 2.2412)	0.4520
	Alcohol abuse	0.66203 (0.3796, 1.1547)	0.1462
	BMI (median <)	0.97081 (0.6206, 1.5185)	0.8967
	ICG R15 (median <)	1.18278 (0.7484, 1.8692)	0.4722
	T factor (T3/4)	1.67615 (1.0752, 2.613)	0.0226

DFS: Disease-free survival; OS: Overall survival; DSS: Disease-specific survival.

Table 4 Univariate analysis results: Disease-free, overall and disease-specific survival after hepatic resection for hepatocellular carcinoma (hepatitis B virus, n = 68)

		DFS		OS		DSS
Characteristics	n	HR (95%CI)	P value	HR (95%CI)	P value	HR (95%CI)	P value
Age			0.9417		0.8991		0.3769
≤ 67	54	1		1		1
> 67	14	0.97131 (0.445, 2.1202)		1.05615 (0.4541, 2.4565)		0.5123 (0.1162, 2.2588)
Gender			0.6063		0.1844		0.3363
Female	9	1		1		1
Male	59	1.28118 (0.4993, 3.2876)		2.64152 (0.6294, 11.0865)		2.70202 (0.3562, 20.4981)
Smoking habit (Ex + current)			0.8323		0.5660		0.9544
Absent	21	1		1		1
Present	47	0.93056 (0.478, 1.8115)		1.26612 (0.5656, 2.8343)		0.96953 (0.336, 2.7975)
Smoking habit (current)			0.4008		0.3620		0.8001
Absent	36	1		1		1
Present	32	1.30547 (0.7009, 2.4314)		1.38988 (0.6848, 2.8209)		1.13501 (0.4258, 3.0251)
Alcohol abuse			0.0183		0.0706		0.5674
Absent	46	1		1		1
Present	22	0.4139 (0.199, 0.861)		0.45823 (0.1966, 1.0679)		0.73339 (0.2534, 2.1228)
Diabetes mellitus			0.4682		0.6700		0.8752
Absent	56	1		1		1
Present	12	1.32065 (0.6229, 2.7999)		1.21513 (0.4959, 2.9773)		1.10618 (0.3141, 3.8962)
BMI			0.3087		0.9126		0.6383
≤ Median	33	1		1		1
> Median	35	1.3863 (0.7392, 2.6)		0.96125 (0.4746, 1.9468)		1.26746 (0.4718, 3.4046)
ICG R15 (%)			0.6240		0.8562		0.5468
≤ Median	49	1		1		1
> Median	19	0.83516 (0.4064, 1.7163)		1.07744 (0.4808, 2.4147)		1.38526 (0.4799, 3.9983)
AFP			0.0665		0.0015		0.0114
≤ Median	34	1		1		1
> Median	34	1.80218 (0.9606, 3.3809)		3.54578 (1.6235, 7.7443)		4.36412 (1.3942, 13.6606)
Tumor size			0.1252		0.2124		0.0585
≤ Median	28	1		1		1
> Median	40	1.67393 (0.8665, 3.2339)		1.61822 (0.7594, 3.4483)		3.37156 (0.9574, 11.8735)
Solitary/Multiple			0.0002		0.0001		0.0013
Solitary	41	1		1		1
Multiple	27	3.30417 (1.7552, 6.2201)		4.6829 (2.1913, 10.0073)		6.42975 (2.0644, 20.0257)
Vp			0.0598		0.0035		0.0362
Absent	39	1		1		1
Present	29	1.85208 (0.975, 3.5182)		2.94188 (1.4258, 6.07)		2.92487 (1.0717, 7.9823)
T12/T34			0.0042		0.0001		0.0019
T12	32	1		1		1
T34	36	2.60213 (1.3531, 5.0043)		5.55785 (2.3542, 13.1211)		10.58522 (2.3795, 47.0876)

DFS: Disease-free survival; OS: Overall survival; DSS: Disease-specific survival.

Table 5 Multivariate analyses for current smokers vs others (hepatitis B virus, n = 68)

Type	Characteristics	HR (95%CI)	P value
DFS	Smoking habit (current)	1.41417 (0.7413, 2.698)	0.2930
	Age (67 < yr)	0.9339 (0.4189, 2.0818)	0.8672
	Gender (male)	1.82154 (0.6845, 4.8477)	0.2298
	Alcohol abuse	0.37957 (0.1785, 0.8072)	0.0119
	Multiple tumor	3.18518 (1.6783, 6.045)	0.0004
OS	Smoking habit (current)	1.43613 (0.6865, 3.0045)	0.3365
	Age (67 < yr)	0.88873 (0.3727, 2.119)	0.7902
	Gender (male)	3.66949 (0.8392, 16.0457)	0.0842
	Alcohol abuse	0.38587 (0.1622, 0.9177)	0.0312
	Multiple tumor	4.91853 (2.2445, 10.7785)	0.0001
DSS	Smoking habit (current)	0.98786 (0.3539, 2.7572)	0.9814
	Age (67 < yr)	0.37251 (0.0808, 1.7181)	0.2055
	Gender (male)	3.89167 (0.4809, 31.4908)	0.2027
	Alcohol abuse	0.98786 (0.3539, 2.7572)	0.3991
	Multiple tumor	7.08829 (2.2387, 22.4436)	0.0009

DFS: Disease-free survival; OS: Overall survival; DSS: Disease-specific survival.

Table 6 Comparison of clinicopathological factors per current smoking status in the hepatitis C virus-related hepatocellular carcinoma and hepatitis B virus-related hepatocellular carcinoma patient group

	HCV (n = 273)			HBV (n = 68)
	Current (n = 88)	Never + Ex (n = 185)	P value	Current (n = 32)	Never + Ex (n = 36)	P value
Age (mean ± SD)	65.34 ± 7.82	68.02 ± 8.77	0.0153	53.66 ± 13.74	60.25 ± 10.46	0.0284
Gender (male/female)	81/7	122/63	< 0.0001	31/1	28/8	0.0204
Alcohol abuse (+/-)	35/53	28/157	< 0.0001	13/19	9/27	0.1692
Diabetes mellitus (+/-)	20/68	42/143	0.9964	5/27	7/29	0.6801
BMI (mean ± SD)	21.71 ± 2.74	22.87 ± 3.47	0.0031	23.01 ± 3.89	22.85 ± 3.77	0.8656
ICG R15 (%)	16.14 ± 7.24	19.81 ± 9.56	0.0005	12.54 ± 5.25	14.00 ± 7.11	0.3451
AFP (ng/mL), median (range)	20.5 (2, 29800)	29 (0, 19500)	0.4338	64.9 (1, 271600)	14.8 (2.4, 209900)	0.7995
Tumor size (mean ± SD mm)	39.25 ± 25.87	36.48 ± 25.52	0.4050	47.69 ± 29.26	51.53 ± 36.56	0.6369
Solitary/Multiple	60/28	122/63	0.7142	17/15	24/12	0.2546
Vp (+/-)	28/60	46/139	0.2271	13/19	16/20	0.7506
T factor (T12/T34)	48/40	108/77	0.5498	15/17	17/19	0.9772
Recurrence (+/-)	59/29	138/47	0.1934	20/12	20/16	0.5614

HCV: Hepatitis C virus; HBV: Hepatitis B virus; BMI: Body mass index; AFP: Alpha-fetoprotein.