Impact of smoking habit on surgical outcomes in non-B non-C patients with curative resection for hepatocellular carcinoma

Table 1 Clinicopathologic features of the patients with non-B non-C hepatocellular carcinoma (n = 83)

Characteristic		n (%)
Age, yr (mean ± SD)		66.4 ± 11.6
Gender	Male	66 (79.5)
	Female	17 (20.5)
Alcohol abuse	(+)	19 (22.9)
	(-)	64 (77.1)
Smoking habit	Never	36 (43.4)
	Ex	23 (27.7)
	Current	24 (28.9)
Diabetes mellitus	(+)	29 (34.9)
	(-)	54 (65.1)
Obesity	(+)	26 (31.3)
	(-)	57 (68.7)
BMI (mean ± SD)		22.8 ± 4.50
Tumor size (mean ± SD mm)		65.2 ± 41.4
Solitary/Multiple	Solitary	52 (62.7)
	Multiple	31 (37.3)
Vp	(+)	32 (38.6)
	(-)	51 (61.4)
Background liver fibrosis1	F0	16 (19.5)
	F1	21 (25.6)
	F2	10 (12.2)
	F3	18 (22.0)
	F4	17 (20.7)
NASH1	(+)	10 (12.2)
	(-)	72 (87.8)

¹Noncancerous liver tissue was not available in one case (n = 82). NASH: Non-alcoholic steatohepatitis. Vp: Portal vein invasion.

Table 2 Univariate analyses for disease-free survival, overall survival and disease-specific survival after hepatic resection

	DFS		OS		DSS
	HR (95%CI)	P value	HR (95%CI)	P value	HR (95%CI)	P value
Age ( ≤ 70 yr)	0.777 (0.434-1.389)	0.3948	0.959 (0.529-1.739)	0.8915	0.757 (0.360-1.591)	0.4622
Gender (male)	0.742 (0.382-1.443)	0.3796	1.466 (0.653-3.291)	0.3537	1.351 (0.515-3.545)	0.5404
Occult HBV infection	1.052 (0.564-1.961)	0.8736	1.184 (0.628-2.232)	0.6009	1.328 (0.625-2.821)	0.4604
Alcohol abuse	0.700 (0.326-1.503)	0.3605	1.492 (0.749-2.969)	0.2549	1.489 (0.631-3.514)	0.3639
Smoking (Ex vs current)	0.405 (0.182-0.903)	0.0271	0.451 (0.215-0.945)	0.0349	0.299 (0.113-0.795)	0.0155
Smoking (Ex vs never)	0.680 (0.319-1.453)	0.3197	1.295 (0.597-2.807)	0.5132	0.905 (0.328-2.501)	0.848
Smoking (current vs never)	1.680 (0.874-3.230)	0.1199	2.869 (1.417-5.807)	0.0034	3.026 (1.315-6.968)	0.0092
Smoking (Ex + current vs never)	1.078 (0.606-1.920)	0.7976	1.926 (1.019-3.640)	0.0436	1.735 (0.804-3.745)	0.1604
Smoking (current vs other)	1.926 (1.047-3.544)	0.035	2.569 (1.397-4.724)	0.0024	3.144 (1.497-6.604)	0.0025
Diabetes mellitus	0.894 (0.474-1.685)	0.7285	1.715 (0.941-3.126)	0.0779	1.414 (0.665-3.008)	0.3681
Pathological NASH	1.222 (0.516-2.892)	0.649	1.076 (0.423-2.736)	0.8781	1.342 (0.465-3.873)	0.5863
Obesity	0.989 (0.535-1.828)	0.9714	1.049 (0.556-1.981)	0.8827	1.183 (0.549-2.549)	0.6673
Fibrosis	1.163 (0.699-1.936)	0.5608	1.004 (0.583-1.729)	0.9883	1.407 (0.742-2.670)	0.2956
Vp	2.428 (1.338-4.407)	0.0035	1.892 (1.042-3.436)	0.0362	1.918 (0.919-4.002)	0.0828
T factor (T3/4 vs T1/2)	3.220 (1.680-6.169)	0.0004	1.793 (0.984-3.268)	0.0565	2.222 (1.052-4.693)	0.0364
Multiple tumors	3.275 (1.784-6.014)	0.0001	2.009 (1.110-3.636)	0.0211	2.767 (1.329-5.761)	0.0065

Vp: Portal vein invasion; DFS: Disease-free survival; DSS: Disease-specific survival; HBV: Hepatitis B virus; NASH: Non-alcoholic steatohepatitis; OS: Overall survival.

Table 3 Multivariate analyses for current smokers vs other (age, gender, Vp, T factor in, P = 0.2)

Type	Label	HR (95%CI)	P value
DFS	Smoking (current vs other)	1.897 (0.888-4.054)	0.0985
	Age ( ≤ 70 yr)	0.627 (0.330-1.191)	0.1535
	Gender (male)	0.611 (0.279-1.337)	0.2176
	Vp	2.656 (1.145-6.165)	0.0229
	T factor (T3/4 vs T1/2)	1.574 (0.537-4.609)	0.4083
	Multiple tumors	1.930 (0.807-4.614)	0.1394
	Alcohol abuse	0.547 (0.228-1.310)	0.1755
OS	Smoking (current vs other)	2.807 (1.349-5.840)	0.0058
	Age ( ≤ 70 yr)	1.189 (0.603-2.346)	0.6177
	Gender (male)	1.362 (0.555-3.343)	0.4999
	Vp	3.069 (1.377-6.839)	0.0061
	T factor (T3/4 vs T1/2)	0.532 (0.187-1.512)	0.2364
	Multiple tumors	1.830 (0.760-4.405)	0.1774
DSS	Smoking (current vs other)	3.133 (1.307-7.512)	0.0105
	Age ( ≤ 70 yr)	0.988 (0.424-2.302)	0.9775
	Gender (male)	1.406 (0.463-4.271)	0.5478
	Vp	2.756 (1.095-6.935)	0.0313
	T factor (T3/4 vs T1/2)	0.610 (0.167-2.233)	0.4555
	Multiple tumors	2.476 (0.797-7.693)	0.1169
	Pathological NASH	2.320 (0.689-7.811)	0.1741

DFS: Disease-free survival; DSS: Disease-specific survival; OS: Overall survival; Vp: Portal vein invasion.

Table 4 Comparison of current smoking status and clinicopathological factors (n = 83)

	Current (n = 24)	Never + Ex (n = 59)	P value
Age, yr (mean ± SD)	59.4 ± 12.0	69.3 ± 10.2	0.0002
Gender (male/female)	22/2	44/15	0.0803
Alcohol abuse (+/-)	10/14	9/50	0.0188
Diabetes mellitus (+/-)	8/16	21/38	0.8448
Obesity (+/-)	6/18	20/39	0.6024
ICG R15 (%)	11.7 ± 1.8	14.8 ± 1.2	0.1235
Tumor size (mean ± SD mm)	68.4 ± 44.0	63.9 ± 40.6	0.6724
Solitary/Multiple	10/14	42/17	0.023
Vp (+/-)	9/15	23/36	0.8998
T factor (T12/T34)	10/24	33/26	0.3329
AFP (mean ± SD)	4450 ± 14563.6	3235 ± 13042	0.6442
Fibrosis (F12/F34, n = 82)	11/13	36/22	0.2224
Recurrence (+/-)	16/8	32/27	0.3362
Therapy for recurrent tumor (+/-)1	14/2	27/5	0.7724
TAE only	11	14
Surgical resection	1	5
Ablation	1	2
Chemotherapy	1	3
Multiple therapy2	0	3
Tumor-related death (%)	13 (54.2)	17 (28.8)	0.0293
Other cause of death (%)	5 (20.8)	11 (18.6)	0.8187

¹Comparison restricted in recurrent case;

²Two cases of TAE + operation and one case of TAE + ablation. ICG R15: Indocyanine green retention rate at 15 min; TAE: Transcatheter arteriography embolization; Vp: Portal vein invasion.