Preoperative predictors of short-term survival after hepatectomy for multinodular hepatocellular carcinoma

Table 1 The baselines of clinical features at the time of diagnosis of hepatocellular carcinoma

Variable	mean/n
Age (yr)	50.16 ± 10.65 (range: 27-76)
Gender (male/female)	134:28
HBsAg-positive	156 (96.30%)
HCV-Ab positive	0
HBV-DNA
> 104/L	88 (140, 62.85%)
> 106/L	32 (140, 22.86%)
Child-Pugh score
5	148 (97.53%)
6	10 (2.47%)
TBIL (μmol/L)	15.76 ± 5.72 (range: 4.9-33)
DBIL (μmol/L)	5.51 ± 2.26 (range: 1.5-15.5)
IBIL (μmol/L)	10.28 ± 4.09 (range: 1-23)
ALB (g/L)	41.32 ± 3.59 (range: 32-53)
Prealbumin (mg/L)	217.73 ± 65.83(range:110-500)
PT > 13 s (n)	41(25.31%) (range: 10.4-17.6)
ALT > 44U/L (n)	48 (29.63%) (range: 12.9-235)
AST > 38 U/L (n)	88 (54.32%) (range: 12.8-207)
AFP > 20 μg/L	102 (62.96%) (range: 2.5-4537)
AFP > 400 μg/L	59 (36.42%)
Diabetes	14 (8.64%)
Cardiovascular hypertension	16 (9.88%)
History of smoke	50 (30.86%)
History of alcoholism	24 (14.81%)
History of other operations	20 (12.35%)
BCLC Staging
Stage A	44 (27.16%)
Stage B	118 (72.84%)
With Milan criteria	44 (27.16%)
With UCSF criteria	86 (53.09%)
TNM staging (6th, 2002 )
T2	103 (63.58%)
T3	59 (36.42%)
Total tumor size (cm)	7.58 ± 4.66 (range: 1.4-23)
The largest tumor size (cm)	5.37 ± 4.00 (range: 0.7-21)
Number of tumors
2	110
3	36
4	10
> 4	6
Serum creatinine (mmol/L)	68.65 ± 14.67 (range: 36-119)
Serum urea nitrogen (μmol/L)	5.86 ± 5.92 (range: 2.6-57)
WBC (× 109/L)	5.23 ± 1.69 (range: 1.66-11.6)
RBC (× 1012/L)	4.53 ± 0.52 (range: 3.3-6.59)
HGB (g/L)	142.8 ± 21.32 (range: 94-146)
PLT (× 109/L)	148.3 ± 75.93 (range: 31-476)
PLT < 100 × 109/L (n)	44 (27.16%)
Intraoperative transfusion	14 (8.64%)
Postoperative transfusion	6 (3.70%)
Death in 3 mo after operation	4 (2.47%)

HBsAg: Hepatitis B surface antigen; HBV: Hepatitis B virus; HCV: Hepatitis C virus; AFP: α fetoprotein; TBIL: Total bilirubin; DBIL: Direct bilirubin; IBIL: Indirect bilirubin; ALB: Albumin; PT: Prothrombin time; ALT: Alanine transaminase; AST: Aspartate aminotransferase; BCLC: Barcelona Clinic Liver Cancer; UCSF: University of California, San Francisco; WBC: White blood cell; RBC: Red blood cell; PLT: Platelet; HGB: Hematoglobulin; TNM: Tumor, nodes, metastasis.

Table 2 Univariate Cox analysis of potential prognostic factors

Variables	n	The 1-year survival rates %	P value
Age			< 0.001
> 40 yr	128	85.9
≤ 40 yr	34	64.7
Parameters of liver function
TBIL			< 0.001
> 17.1 μmol/L	49	58.33
≤ 17.1 μmol/L	113	91.22
ALB			0.530
< 35 g/L	8	75.00
≥ 35 g/L	154	81.82
GLB			0.565
> 30 g/L	79	79.48
≤ 30 g/L	83	83.33
Prealbumin			< 0.001
< 170 mg/L	33	58.3
≥170 mg/L	129	90.6
ALT			0.281
> 38 U/L	82	78.04
≤ 38 U/L	80	85.00
ALT			0.993
> 76 U/L	10	80.00
≤ 76 U/L	152	81.58
AST			0.001
> 38 U/L	88	75.00
≤ 38 U/L	74	89.21
AFU			0.004
> 40 U/L	31	64.31
≤ 40 U/L	131	85.89
ALP			0.001
> 129 U/L	27	58.33
≤ 129 U/L	135	85.50
GGT			< 0.001
> 64 U/L	82	65.00
≤ 64 U/L	80	97.56
PT			0.428
> 13 s	41	75.00
≤ 13 s	121	82.00
APTT			0.566
> 37 s	72	77.80
≤ 37 s	90	82.20
Parameters of blood test
WBC			0.389
< 4 × 109/L	35	76.5
≥ 4 × 109/L	127	82.5
PLT			< 0.001
< 100 × 109/L	44	59.1
≥100 × 109/L	118	89.7
Parameters of tumors
Total tumor size			0.010
> 5 cm	108	75.9
≤ 5 cm	54	92.6
Total tumor size			< 0.001
> 8 cm	54	66.7
≤ 8 cm	108	88.9
Largest tumor size			0.050
> 5 cm	58	72.41
≤ 5 cm	104	84.61
Largest tumor size			0.001
> 8 cm	22	54.54
≤ 8 cm	140	84.2
AFP			< 0.001
> 20 μg/L	102	72.00
≤ 20 μg/L	60	96.78
AFP			0.014
> 400 μg/L	59	72.41
≤ 400 μg/L	103	86.54
CA19-9			0.287
> 39 U/L	35	72.22
≤ 39 U/L	127	83.87
Location in same segment
Yes	20	80.00	0.924
No	142	81.96
Location in same lobe
Yes	34	88.2	0.238
No	128	79.7
Location in same hemiliver
Yes	74	83.8	0.530
No	88	79.5
Number of tumors			0.529
≤ 3	146	80.82
> 3	16	87.50
Parameters of hepatitis B
HBsAg			0.517
Positive	156	80.81
Negative	6	100.00
HBsAb			0.803
Positive	8	100.0
Negative	154	80.52
HBeAg
Positive	64	71.88	0.005
Negative	98	87.76
HBeAb
Positive	101	84.31	0.041
Negative	61	74.19
HBV-DNA1			0.228
> 104/L	88	79.54
≤ 104/L	50	88.00
HBV-DNA1			0.019
> 106/L	32	68.75
≤ 106/L	106	86.79

¹There were only 138 patients received HBV-DNA examinations. GLB: Globulin; ALP: Alkaline phosphatase; AFU: α fucosidase; GGT: γ-glutamyl transpeptidase; PLT: Platelet; HBV: Hepatitis B virus; HBsAg: Hepatitis B surface antigen; HBeAg: Hepatitis B e antigen; HBsAb: Hepatitis B surface antibody; HBeAb: Hepatitis B e antibody; CA19-9: Carbohydrate antigen 19-9; PT: Prothrombin time; APTT: Activated partial thromboplastin time; TBIL: Total bilirubin; ALB: Albumin; ALT: Alanine transaminase; AST: Aspartate aminotransferase; WBC: White blood cell.

Table 3 Area under the receiver operating characteristics curves and cut-off points

Test variable(s)	Area	SE	Asym-ptotic Sig	Lower bound	Upper bound	Cut-off point 11	Cut-off point 22
TBIL	0.694	0.054	0.001	0.588	0.801	17.25	17.1
Prealbumin	0.817	0.043	< 0.001	0.099	0.266	170	170
AST	0.707	0.048	0.001	0.613	0.802	41.8	38
ALP	0.695	0.056	0.001	0.586	0.804	119.5	129
GGT	0.792	0.040	< 0.001	0.714	0.870	75.5	64
AFU	0.615	0.064	0.058	0.489	0.740	36	40
Total tumor size	0.693	0.057	0.001	0.581	0.805	8.1	8
AFP	0.626	0.050	0.037	0.528	0.725	32.6	20
PLT	0.721	0.058	< 0.001	0.166	0.393	92.5	100
Largest tumor size	0.597	0.064	0.089	0.472	0.722	5.9	6

¹The actual results defined by the ROC curves;

²The values adopted for multivariate analysis. AFP: α fetoprotein; TBIL: Total bilirubin; AST: Aspartate aminotransferase; PLT: Platelet; ALP: Alkaline phosphatase; AFU: α fucosidase; GGT: γ-glutamyl transpeptidase; Sig: Significance.

Table 4 Results of multivariate Cox analysis

Variables	β	SE	Sig	HR	95% CI for HR	Assigned points
Prealbumin < 170 mg/L	1.711	0.420	< 0.001	5.531	3.122-13.196	1
ALP > 129 U/L	1.132	0.420	0.005	3.252	1.413-7.480	1
AFP > 20 μg/L	2.014	0.792	0.011	7.477	1.419-31.234	2
Total tumor size > 8 cm	2.334	0.542	< 0.001	10.543	3.611-30.157	2
PLT < 100 × 109/L	2.310	0.484	< 0.001	9.937	3.770-26.121	2
GGT > 64 U/L	1.291	0.460	< 0.001	3.791	1.476-9.960	1

β: Partial regression coefficient; SE: Standard error; Sig: Significance; HR: Hazard ratio; CI: Confidence interval; AFP: α fetoprotein; PLT: Platelet; ALP: Alkaline phosphatase; GGT: γ-glutamyl transpeptidase.

Table 5 The comparison of surgical data and tumor biological characteristics between two groups n (%)

Variables	Group 1(n = 120)	Group 2(n = 42)	P value
Blood transfusion	6 (5.00)	8 (19.05)	0.010
Pringle time > 20 min	52 (43.33)	24 (57.14)	0.151
Liver cirrhosis	68 (56.67)	24 (57.14)	0.854
Type of liver cirrhosis			< 0.001
Small nodules	0 (0)	6 (25.00)
Large nodules	52 (76.47)	8 (33.33)
Mixed nodules	16 (23.53)	10 (41.65)
Differentiation of tumor			0.003
High differentiation (I-II)	30 (25.00)	2 (4.76)
Low differentiation (III-IV)	90 (75.00)	40 (95.23)
Microvascular invasion	16 (13.33)	18 (42.89)	< 0.001
Completed capsule of largest tumor			0.468
Yes	72 (60.00)	22 (52.38)
No	48 (40.00)	20 (47.62)