Des-gamma-carboxy prothrombin as an important prognostic indicator in patients with small hepatocellular carcinoma

Table 1 Comparison of demographic and clinical data

Factor		Conforming to the criteria (n = 85)	Outside the criteria (n= 57)	P value
Age (yr)		65.0 ± 8.4	60.1 ± 12.7	0.007
Gender	Male	62 (73%)	44 (77%)	0.57
	Female	23 (27%)	13 (23%)
Child-Pugh score	Class A	71 (84%)	54 (95%)	0.04
	Class B	14 (16%)	3 (5%)
	Class C	0	0
Total bilirubin (mg/dL)		0.90 ± 0.55	0.74 ± 0.32	0.04
	< 1	42 (49%)	41 (72%)	0.008
	≥ 1	43 (51%)	16 (28%)
Albumin (g/dL)		3.7 ± 0.5	3.8 ± 0.50	0.04
	≤ 3.5	39 (46%)	14 (25%)	0.01
	>3.5	46 (54%)	43 (75%)
Prothrombin time (%)		83.0 ± 15.2	85.9 ± 17.6	0.30
	≤ 80	35 (41%)	25 (44%)	0.75
	> 80	50 (59%)	32 (56%)
Platelet count (× 104/mm3)		11.8 ± 6.3	17.5 ± 8.6	< 0.0001
	< 10	35 (41%)	13 (23%)	0.02
	≥ 10	50 (59%)	44 (77%)
ICG R15 (%)		19.8 ± 9.9	14.1 ± 1.2	0.0005
	< 15	26 (31%)	35 (61%)	0.0003
	≥ 15	59 (69%)	22 (39%)
Hepatitis virus	C positive	68 (80%)	26 (46%)	< 0.0001
	B positive	8 (10%)	15 (26%)	0.008
Tumor number	Single	77 (91%)	29 (51%)	< 0.0001
	Multiple	8 (9%)	28 (49%)
Tumor size (cm)		2.9 ± 1.2	7.6 ± 4.6	< 0.0001
	≤ 3	52 (61%)	5 (9%)	< 0.0001
	3-5	33 (39%)	11 (19%)
	> 5	0	41 (72%)
Histology	Well or moderately differentiated	68 (87%)	39 (71%)	0.02
	Poorly differentiated	10 (13%)	16 (29%)
Vascular invasion	Macroscopically positive	0	5 (8.8%)	0.005
	Microscopically positive	8 (10%)	18 (32%)	0.0008
TNM Staging by the LCSGJ1	I/II/III/IV-A	25/51/8/1	2/17/25/13	< 0.0001
	I+ II	76 (89%)	19 (33%)	< 0.0001
	III + IV-A	9 (11%)	38 (67%)
AFP (ng/mL)		933 ± 6610	31 473 ± 192 949	0.15
	AFP ≥ 20	52 (61%)	35 (61%)	0.98
	AFP ≥ 100	28 (33%)	26 (46%)	0.13
	AFP ≥ 200	16 (19%)	24 (42%)	0.003
	AFP ≥ 400	11 (13%)	23 (40 %)	0.0002
DCP (mAU/mL)		780 ± 4129	8168 ± 28 247	0.02
	DCP ≥ 40	45 (53%)	43 (75%)	0.007
	DCP ≥ 100	26 (31%)	36 (63%)	0.0001
	DCP ≥ 200	16 (19%)	30 (53%)	< 0.0001
	DCP ≥ 400	11 (13%)	27 (47%)	< 0.0001

¹Liver Cancer Study Group of Japan.

Table 2 Univariate analysis for recurrence-free and overall survivals in 142 patients undergoing hepatectomy for hepatocellular carcinoma

Factor	Covariate (n)	Reference (n)	Recurrence-free survival			Overall survival
			HR	95% CI	P	HR	95% CI	P
Gender	Female (36)	Male (106)	1.00	0.63-1.58	0.99	1.26	0.73-2.18	0.42
Child-Pugh score	B (17)	A (125)	0.77	0.42-1.42	0.4	0.87	0.42-1.84	0.72
Total bilirubin (mg/dL)	≥ 1 (59)	< 1 (83)	1.14	0.76-1.70	0.53	1.13	0.68-1.87	0.64
Albumin (g/dL)	≤ 3.5 (53)	> 3.5 (89)	0.93	0.62-1.40	0.74	1.13	0.69-1.86	0.62
Prothrombin time (%)	≤ 80 (60)	> 80 (82)	1.34	0.89-2.01	0.16	1.31	0.79-2.16	0.30
Platelet (× 104/mm3)	< 10 (48)	≥ 10 (94)	0.92	0.61-1.40	0.71	0.82	0.49-1.39	0.47
ICG R15	≥ 15% (81)	< 15% (61)	0.94	0.63-1.40	0.76	0.79	0.48-1.31	0.36
Hepatitis C virus	Positive (94)	Negative (48)	1.24	0.80-1.93	0.33	0.87	0.52-1.48	0.62
Hepatitis B virus	Positive (23)	Negative (118)	0.99	0.58-1.70	0.97	1.39	0.74-2.62	0.30
Number of tumor	Multiple (36)	Single (106)	1.70	1.07-2.71	0.02	2.08	1.22-3.54	0.007
Size of tumor (cm)	> 5 (85)	≤ 5 (57)	1.37	0.86-2.17	0.18	2.00	1.08-3.70	0.03
Histology	Poor1 (26)	Well-mod2 (107)	1.70	1.01-2.85	0.04	1.81	0.90-3.65	0.10
Vascular invasion	Present (20)	Absent (113)	1.96	1.19-3.23	0.008	2.36	1.32-4.20	0.004
Stage by LCSGJ3	III + IV (47)	I+II (85)	1.99	1.29-3.06	0.001	2.86	1.71-4.76	< 0.0001
AFP (ng/mL)	≥ 20 (87)	< 20 (55)	1.71	1.11-2.62	0.01	1.90	1.09-3.33	0.02
	≥ 100 (54)	< 100 (88)	1.19	0.79-1.80	0.41	1.43	0.86-2.39	0.16
	≥ 200 (40)	< 200 (102)	1.06	0.68-1.66	0.07	1.25	0.73-2.16	0.41
	≥ 400 (34)	< 400 (108)	1.24	0.78-1.96	0.36	1.59	0.91-2.79	0.10
DCP (mAU/mL )	≥ 40 (88)	< 40 (54)	1.75	1.14-2.70	0.01	1.70	1.00-2.90	0.05
	≥ 100 (62)	< 100 (80)	1.86	1.23-2.80	0.003	1.82	1.10-3.00	0.02
	≥ 200 (46)	< 200 (96)	1.75	1.14-2.70	0.01	3.03	1.79-5.15	< 0.0001
	≥ 400 (38)	< 400 (104)	1.84	1.17-2.89	0.008	2.98	1.73-5.13	< 0.0001

n: Number of patients; HR: Hazard ratio; CI: Confidence interval.

¹Poorly differentiated;

²Well or moderately differentiated hepatocellular carcinoma;

³LCSGJ: Liver Cancer Study Group of Japan.

Table 3 Multivariate analysis for recurrence-free and overall survivals in 142 patients undergoing hepatectomy for hepatocellular carcinoma

Factor	Covariate (n)	Reference (n)	Recurrence-free survival			Overall survival
			HR	95%CI	P	HR	95% CI	P
Number of tumor	Multiple (36)	Single (106)	0.93	0.39-2.23	0.87	0.82	0.29-2.35	0.71
Size of tumor (cm)	> 5 (85)	≤ 5 (57)	0.93	0.51-1.82	0.82	1.00	0.41-2.42	1.00
Histology	Poor1 (26)	Well-mod2 (107)	1.14	0.63-2.05	0.67	0.73	0.33-1.61	0.44
Vascular invasion	Present (20)	Absent (113)	1.68	0.99-2.86	0.05	2.02	1.07-3.83	0.03
Stage by LCSGJ3	III+IV (47)	I+II (85)	1.72	0.73-2.69	0.22	2.24	0.78-6.45	0.13
AFP (ng/mL)	≥ 20 (87)	< 20 (55)	1.36	0.83-2.22	0.23	1.55	0.81-2.97	0.18
DCP (mAU/mL)	≥ 400 (38)	< 400 (104)	1.45	0.78-2.69	0.24	2.44	1.15-5.21	0.02

n: Number of patients; HR: Hazard ratio; CI; Confidence interval.

¹Poorly differentiated;

²Well or moderately differentiated hepatocellular carcinoma;

³LCSGJ: Liver Cancer Study Group of Japan.

Table 4 Univariate analysis for recurrence-free and overall survivals in 85 patients who met the criteria

Factor	Covariate (n)	Reference (n)	Recurrence-free survival			Overall survival
			HR	95% CI	P	HR	95% CI	P
Gender	Female (23)	Male (62)	0.81	0.44-1.48	0.48	0.91	0.43-1.94	0.81
Child-Pugh score	B (14)	A (71)	0.83	0.43-1.61	0.58	1.06	0.46-2.43	0.89
Total bilirubin (mg/dL)	≥ 1 (43)	< 1 (42)	1.37	0.82-2.30	0.23	1.77	0.83-3.79	0.14
Albumin (mg/dL)	≤ 3.5 (39)	> 3.5 (46)	0.92	0.55-1.52	0.74	0.56	0.28-1.09	0.09
Prothrombin time (%)	≤ 80 (35)	> 80 (50)	1.25	0.75-2.08	0.40	0.82	0.42-1.61	0.56
Platelet (× 104/mm3)	< 10 (35)	≥ 10 (50)	1.05	0.63-1.76	0.84	0.98	0.50-1.92	0.95
ICG R15	≥ 15% (59)	< 15% (26)	1.37	0.79-2.38	0.27	1.51	0.70-3.26	0.29
Hepatitis C virus	Positive (68)	Negative (17)	1.42	0.75-2.70	0.28	1.46	0.60-3.52	0.40
Hepatitis B virus	Positive (8)	Negative (76)	0.63	0.25-1.57	0.32	0.56	0.13-2.34	0.43
Number of tumor	Multiple (8)	Single (77)	1.12	0.48-2.61	0.79	1.29	0.50-3.36	0.60
Size of tumor (cm)	> 3 (33)	≤ 3 (52)	1.08	0.64-1.81	0.78	1.27	0.63-2.56	0.50
Histology	Poor1 (10)	Well-mod2 (68)	1.32	0.56-3.11	0.53	3.03	0.89-10.29	0.08
Vascular invasion	Present (8)	Absent (75)	0.96	0.38-2.06	0.77	0.88	0.31-2.54	0.82
Stage by LCSGJ3	III + IV (9)	I+II (76)	1.41	0.64-3.12	0.39	1.80	0.74-4.35	0.20
AFP (ng/mL)	≥ 20 (52)	< 20 (33)	1.47	0.87-2.49	0.15	1.50	0.75-3.02	0.25
	≥ 100 (28)	< 100 (57)	0.77	0.42-1.39	0.39	0.80	0.36-1.75	0.57
	≥ 200 (16)	< 200 (69)	0.53	0.25-1.13	0.10	0.50	0.18-1.42	0.20
	≥ 400 (11)	< 400 (74)	0.57	0.23-1.43	0.23	0.53	0.13-2.21	0.38
DCP (mAU/mL )	≥ 40 (45)	< 40 (40)	1.73	1.03-2.92	0.04	1.46	0.75-2.82	0.27
	≥ 100 (26)	<100 (59)	1.67	0.96-2.91	0.07	1.71	0.83-3.50	0.14
	≥ 200 (16)	< 200 (69)	1.69	0.84-3.40	0.14	5.81	2.56-13.16	< 0.0001
	≥ 400 (11)	< 400 (74)	2.41	1.12-5.18	0.02	5.71	2.38-13.70	< 0.0001

n: Number of patients; HR: Hazard ratio; CI: Confidence interval.

¹Poorly differentiated;

²Well or moderately differentiated hepatocellular carcinoma;

³LCSGJ: Liver Cancer Study Group of Japan.

Table 5 Multivariate analysis for recurrence-free and overall survivals in 85 patients who met the criteria

Factor	Covariate (n)	Reference (n)	Recurrence-free survival			Overall survival
			HR	95% CI	P	HR	95% CI	P
Number of tumor	Multiple (8)	Single (77)	0.66	0.06-7.45	0.74	0.46	0.006-35.08	0.72
Histology	Poor1 (10)	Well-mod2 (68)	0.70	0.24-2.01	0.51	0.37	0.07-2.12	0.27
Vascular invasion	Present (8)	Absent (75)	1.04	0.44-2.46	0.93	0.96	0.31-2.99	0.95
Stage by LCSGJ3	III + IV (9)	I+II (76)	1.90	0.17-21.28	0.60	3.97	0.05-333.33	0.53
AFP (ng/mL)	≥ 20 (52)	< 20 (33)	1.28	0.71-2.29	0.41	1.20	0.54-2.66	0.66
DCP (mAU/mL)	≥ 400 (11)	< 400 (74)	3.32	1.20-9.17	0.02	1.20	2.98-50.00	0.0005

n: Number of patients; HR: Hazard ratio; CI: Confidence interval.

¹Poorly differentiated;

²Well or moderately differentiated hepatocellular carcinoma;

³LCSGJ: Liver Cancer Study Group of Japan.

Table 6 Multivariate analysis for recurrence-free and overall survivals in 57 patients who did not meet the criteria

Factor	Covariate (n)	Reference (n)	Recurrence-free survival			Overall survival
			HR	95% CI	P	HR	95% CI	P
Gender	Female (13)	Male (44)	1.35	0.56-3.25	0.50	2.35	0.90-6.17	0.08
Number of tumor	Multiple (28)	Single (29)	0.84	0.32-2.25	0.73	0.72	0.24-2.20	0.57
Histology	Poor1 (16)	Well-mod2 (39)	1.14	0.47-2.76	0.76	0.61	0.21-1.73	0.35
Vascular invasion	Present (18)	Absent (38)	2.97	1.17-7.58	0.02	3.92	1.38-11.24	0.01
Stage by LCSGJ3	III + IV (38)	I+II (19)	1.65	0.57-4.78	0.36	1.92	0.52-7.09	0.33
AFP (ng/mL)	≥ 20 (35)	< 20 (22)	1.58	0.59-4.22	0.36	1.85	0.52-6.54	0.34
DCP (mAU/mL)	≥ 400 (27)	< 400 (30)	0.79	0.35-1.79	0.58	2.29	0.35-2.29	0.83

n: Number of patients; HR: Hazard ratio; CI: Confidence interval.

¹Poorly differentiated;

²Well or moderately differentiated hepatocellular carcinoma;

³LCSGJ: Liver Cancer Study Group of Japan.