Diagnostic value of AFP-L3 and PIVKA-II in hepatocellular carcinoma according to total-AFP

Table 1 Demographics and laboratory test values of patients with benign liver disease and with hepatocellular carcinoma n (%)

	BLD (n = 78)	HCC (n = 90)	P value
Age (mean ± SD), yr	55.6 ± 12.5	59.7 ± 10.1	0.020
Male	51 (65.4)	64 (71.1)	0.506
Cause of disease
HBV	34 (43.6)	61 (67.8)	0.002
HCV	9 (11.5)	9 (10.0)	0.749
Alcohol	5 (6.4)	12 (13.3)	0.139
NANBNC	1 (1.3)	8 (8.9)	0.038
Benign mass	10 (12.8)
Others	19 (24.4)
AFP < 20 ng/mL	74 (94.9)	38 (42.2)
AFP 20-200 ng/mL	4 (5.1)	20 (22.2)
AFP > 200 ng/mL	0 (0)	32 (35.6)
Tumor stage
I/II/III/IVa/IVb		16 (17.8)/31 (34.4)/19 (21.1)/18 (20.0)/6 (6.7)
Tumor size
< 2/2-5/> 5 cm		25 (27.8)/33 (36.7)/32 (35.6)
Tumor number
Single/multiple		40 (44.4)/50 (55.6)
AFP level	6.9 ± 13.5	473.9 ± 746.0	< 0.001
(mean ± SD, ng/mL)
AFP-L3 level	2.3 ± 4.9	40.0 ± 35.7	< 0.001
(mean ± SD, %)
PIVKA-II level	20.0 ± 31.2	4469 ± 11 553.8	< 0.001
(mean ± SD, AU/L)

HBV: Hepatitis B virus; HCV: Hepatitis C virus; NANBNC: Non-hepatitis A, non-hepatitis B, non-hepatitis C virus; AFP: α-fetoprotein; PIVKA-II: Prothrombin induced by vitamin K absence-II; BLD: Benign liver disease; HCC: Hepatocellular carcinoma.

Table 2 Performance of α-fetoprotein, α-fetoprotein-L3 and prothrombin induced by vitamin K absence-II in detecting hepatocellular carcinoma in all patients and in subgroups according to total α-fetoprotein levels: Total α-fetoprotein

		Cut-off value	Sensitivity	Specificity
Entire group (n = 168, 90 HCC)	AFP	10 ng/mL	78.9%	84.6%
	AFP-L3	5%	82.2%	79.5%
		10%	67.8%	93.6%
	PIVKA-II	40 AU/L	62.2%	94.9%
	AFP-L3 or PIVKA-II	5% or 40 AU/L	94.4%	75.6%
		10% or 40 AU/L	84.4%	89.7%
AFP < 20 ng/mL (n = 112, 38 HCC)	AFP-L3	5%	71.1%	83.8%
		10%	47.4%	97.3%
	PIVKA-II	40 AU/L	57.9%	95.9%
	AFP-L3 or PIVKA-II	5% or 40 AU/L	92.1%	79.7%
		10% or 40 AU/L	78.9%	93.2%
AFP < 200 ng/mL (n = 136, 58 HCC)	AFP-L3	5%	74.1%	79.5%
		10%	56.9%	93.6%
	PIVKA-II	40 AU/L	62.1%	94.9%
	AFP-L3 or PIVKA-II	5% or 40 AU/L	93.1%	75.6%
		10% or 40 AU/L	82.8%	89.7%

AFP: α-fetoprotein; PIVKA-II: Prothrombin induced by vitamin K absence-II; HCC: Hepatocellular carcinoma.

Table 3 Sensitivity of α-fetoprotein-L3 and prothrombin induced by vitamin K absence-II according to the tumor characteristics in 38 hepatocellular carcinoma patients with α-fetoprotein < 20 ng/mL n (%)

	n	AFP-L3	PIVKA-II	AFP-L3 and PIVKA-II combined
		(> 5%)	(> 40 AU/L)	(> 5%, > 40 AU/L)
Tumor stage (UICC)
I	11	7 (63.6)	5 (45.5)	9 (81.8)
II	16	12 (75.0)	9 (56.3)	16 (100)
III	9	6 (66.7)	6 (66.7)	8 (88.9)
IVa	2	2 (100)	2 (100)	2 (100)
Tumor size
< 2 cm	15	7 (46.7)	6 (40.0)	13 (86.7)
2-5 cm	17	8 (47.1)	11 (64.7)	16 (94.1)
> 5 cm	6	3 (50.0)	5 (83.3)	6 (100)
Tumor number
Single	24	16 (66.7)	12 (50.0)	22 (91.7)
Multiple	14	11 (78.6)	10 (71.4)	13 (92.7)

AFP: α-fetoprotein; PIVKA-II: Prothrombin induced by vitamin K absence-II; UICC: International Union Against Cancer; HCC: Hepatocellular carcinoma.

Table 4 Stepwise multiple linear regression analysis using dependent variables α-fetoprotein-L3 and prothrombin induced by vitamin K absence-II

Variable	AFP-L3		PIVKA-II
	βcoefficient	P value	βcoefficient	P value
AFP	0.839	< 0.001		NS
Tumor size	0.190	0.002		NS
AST		NS	0.550	< 0.001
Total bilirubin		NS	0.336	< 0.001
Platelet		NS	0.566	0.001
Albumin		NS	-0.674	< 0.001

AFP: α-fetoprotein; PIVKA-II: Prothrombin induced by vitamin K absence-II; AST: Aspartate aminotransferase; NS: Not significant.