Diagnostic value of alpha-fetoprotein and prothrombin induced by vitamin K absence-II in serum, bile, and feces in hepatocellular carcinoma

Table 1 Analysis of the diagnostic value of alpha-fetoprotein and prothrombin induced by vitamin K absence-II in serum, bile, and feces in hepatocellular carcinoma

Samples	Indicators	Cut-off value	Sensitivity (%)	Specificity (%)	AUC (95%CI)	P value
Serum	AFP, ng/mL	8.78	65.8	100.0	0.898 (0.859-0.938)	< 0.001
	PIVKA-II, mAU/mL	40.00	78.2	90.9	0.904 (0.866-0.942)	< 0.001
	CEA, ng/mL	5.00	10.5	100.0	0.621 (0.459-0.782)	0.159
	CA125, U/mL	35.00	7.6	66.7	0.506 (0.298-0.715)	0.940
	CA153, U/mL	31.3	1.9	100.0	0.628 (0.464-0.791)	0.137
	CA199, U/mL	37.00	11.4	100.0	0.604 (0.433-0.775)	0.225
Bile	AFP, ng/mL	1.32	61.2	100.0	0.859 (0.779-0.938)	< 0.001
	PIVKA-II, mAU/mL	59.50	35.9	80.0	0.526 (0.384-0.668)	0.725
	CEA, ng/mL	84.26	9.4	100.0	0.371 (0.179-0.563)	0.219
	CA125, U/mL	123.75	3.8	100.0	0.211 (0.048-0.374)	0.006
	CA153, U/mL	1.35	56.6	66.7	0.596 (0.407-0.786)	0.358
	CA199, U/mL	4.31	92.3	44.4	0.622 (0.394-0.850)	0.246
Feces	Fecal AFP, ng/mL	0.04	16.4	96.2	0.568 (0.452-0.684)	0.272
	Fecal PIVKA-II, mAU/mL	1469.20	5.7	96.2	0.402 (0.285-0.519)	0.115
	CEA, ng/mL	15001.00	0.0	100.0	0.431 (0.156-0.706)	0.659
	CA125, U/mL	23.25	6.9	100.0	0.297 (0.000-0.611)	0.195
	CA153, U/mL	1.85	17.2	100.0	0.522 (0.229-0.814)	0.890
	CA199, U/mL	8.64	62.1	75.0	0.575 (0.462-0.689)	0.659
Combination	Fecal AFP + fecal PIVKA-II	-0.0016	56.4	77.0	0.631 (0.514-0.748)	0.034
	Serum AFP + bile AFP	9.34	70.0	100.0	0.903 (0.843-0.964)	< 0.001
	Serum AFP + serum PIVKA-II	10.84	90.7	97.0	0.961 (0.940-0.983)	< 0.001
	Serum PIVKA-II + bile AFP	113.30	88.3	100.0	0.965 (0.933-0.996)	< 0.001
	Serum PIVKA-II + bile PIVKA-II	29.90	86.3	92.3	0.913 (0.860-0.967)	< 0.001
	Serum AFP + bile PIVKA-II	4.35	81.4	92.3	0.891 (0.827-0.956)	< 0.001
	Bile AFP+ bile PIVKA-II	1.09	60.2	100.0	0.871 (0.794-0.947)	< 0.001

AFP: Alpha-fetoprotein; AUC: Area under the curve; CA: Carbohydrate antigen; CEA: Carcinoembryonic antigen; CI: Confidence interval; PIVKA-II: Prothrombin induced by vitamin K absence-II.

Table 2 Analysis of the diagnostic efficacy of alpha-fetoprotein and prothrombin induced by vitamin K absence-II in serum alpha-fetoprotein or prothrombin induced by vitamin K absence-II negative group

Group	Indicators	Sensitivity (%)	AUC (95%CI)	P value
Serum AFP negative group	Serum PIVKA-II	75.3	0.887 (0.827-0.947)	< 0.001
	Bile AFP	13.9	0.657 (0.487-0.828)	0.079
	Bile PIVKA-II	38.9	0.537 (0.369-0.705)	0.679
	Fecal AFP	0.0	0.512 (0.347-0.649)	0.868
	Fecal PIVKA-II	4.3	0.386 (0.250-0.521)	0.105
Serum PIVKA-II negative group	Serum AFP	61.2	0.848 (0.765-0.931)	< 0.001
	Bile AFP	55.0	0.842 (0.714-0.969)	0.001
	Bile PIVKA-II	5.0	0.270 (0.088-0.452)	0.021
	Fecal AFP	6.0	0.561 (0.415-0.708)	0.418
	Fecal PIVKA-II	6.0	0.352 (0.214-0.491)	0.051
Both serum AFP and serum PIVKA-II negative group	Bile AFP	0.0	0.648 (0.426-0.871)	0.233
	Bile PIVKA-II	11.1	0.230 (0.018-0.441)	0.030
	Fecal AFP	18.2	0.483 (0.274-0.692)	0.872
	Fecal PIVKA-II	9.0	0.414 (0.209-0.619)	0.412

AFP: Alpha-fetoprotein; AUC: Area under the curve; CI: Confidence interval; PIVKA-II: Prothrombin induced by vitamin K absence-II.

Table 3 Analysis of the diagnostic efficacy of alpha-fetoprotein and prothrombin induced by vitamin K absence-II for hepatocellular carcinoma in different tumor stages, size and number subgroups

Characteristic		Serum			Bile			Fecal supernatant
		Sensitivity (%)	AUC (95%CI)	P value	Sensitivity (%)	AUC (95%CI)	P value	Sensitivity (%)	AUC (95%CI)	P value
Tumor staging (CNLC)
Ia	AFP, ng/mL	65.1	0.900 (0.848-0.952)	< 0.001	46.5	0.805 (0.688-0.923)	< 0.001	11.1	0.555 (0.424-0.686)	0.419
	PIVKA-II, mAU/mL	63.5	0.835 (0.768-0.903)	< 0.001	18.6	0.383 (0.209-0.557)	0.180	12.7	0.466 (0.337-0.596)	0.620
Ib	AFP, ng/mL	63.8	0.898 (0.842-0.954)	< 0.001	67.5	0.882 (0.797-0.968)	< 0.001	18.8	0.571 (0.436-0.706)	0.316
	PIVKA-II, mAU/mL	91.3	0.960 (0.925-0.994)	< 0.001	41.9	0.609 (0.458-0.761)	0.211	0.0	0.333 (0.202-0.463)	0.018
II	AFP, ng/mL	71.0	0.878 (0.777-0.978)	< 0.001	66.7	0.874 (0.728-1)	0.003	27.3	0.607 (0.443-0.770)	0.207
	PIVKA-II, mAU/mL	80.6	0.929 (0.858-0.999)	< 0.001	55.6	0.652 (0.418-0.886)	0.222	0.0	0.392 (0.231-0.552)	0.200
III + IV	AFP, ng/mL	88.2	0.929 (0.818-1)	< 0.001	100.0	1.00 (1-1)	< 0.001	14.3	0.544 (0.296-0.792)	0.725
	PIVKA-II, mAU/mL	94.1	0.989 (0.966-1)	< 0.001	75.0	0.708 (0.453-0.963)	0.107	0.0	0.342 (0.095-0.587)	0.202
Tumor staging (BCLC)
0	AFP, ng/mL	80.0	0.924 (0.817-1)	< 0.001	50.0	0.850 (0.649-1)	0.036	16.7	0.644 (0.401-0.887)	0.277
	PIVKA-II, mAU/mL	40.0	0.679 (0.448-0.910)	0.09	0.0	0.267 (0.047-0.486)	0.162	50.0	0.622 (0.3-0.944)	0.359
A	AFP, ng/mL	59.0	0.884 (0.836-0.932)	< 0.001	57.3	0.837 (0.747-0.927)	< 0.001	15.5	0.560 (0.439-0.680)	0.351
	PIVKA-II, mAU/mL	77.6	0.900 (0.856-0.943)	< 0.001	33.3	0.505 (0.358-0.652)	0.953	4.1	0.398 (0.275-0.521)	0.111
B	AFP, ng/mL	77.1	0.926 (0.852-1)	< 0.001	64.3	0.900 (0.792-1)	< 0.001	21.7	0.614 (0.454-0.773)	0.173
	PIVKA-II, mAU/mL	82.9	0.932 (0.868-0.997)	< 0.001	28.6	0.557 (0.344-0.770)	0.600	4.3	0.390 (0.23-0.549)	0.186
C + D	AFP, ng/mL	87.5	0.941 (0.859-1)	< 0.001	90.0	0.967 (0.897-1)	< 0.001	0.0	0.516 (0.324-0.709)	0.865
	PIVKA-II, mAU/mL	91.7	0.985 (0.961-1)	< 0.001	80.0	0.747 (0.524-0.970)	0.040	0.0	0.360 (0.181-0.538)	0.148
Tumor diameter (cm)
d ≤ 2	AFP, ng/mL	73.8	0.898 (0.822-0.937)	< 0.001	62.5	0.817 (0.663-0.970)	0.003	16.7	0.547 (0.395-0.699)	0.549
	PIVKA-II, mAU/mL	52.4	0.792 (0.691-0.893)	< 0.001	43.8	0.575 (0.369-0.781)	0.477	6.7	0.347 (0.201-0.494)	0.051
2< d ≤ 5	AFP, ng/mL	60.2	0.912 (0.863-0.961)	< 0.001	57.8	0.841 (0.740-0.941)	< 0.001	12.3	0.581 (0.453-0.709)	0.223
	PIVKA-II, mAU/mL	75.7	0.887 (0.834-0.941)	< 0.001	33.3	0.542 (0.382-0.702)	0.627	6.2	0.435 (0.303-0.567)	0.330
5 < d ≤ 10	AFP, ng/mL	67.3	0.884 (0.814-0.955)	< 0.001	58.8	0.88 (0.785-0.976)	< 0.001	0.0	0.502 (0.346-0.658)	0.979
	PIVKA-II, mAU/mL	94.5	0.980 (0.952-1)	< 0.001	35.3	0.486 (0.311-0.661)	0.879	7.1	0.371 (0.222-0.520)	0.104
d > 10	AFP, ng/mL	72.0	0.874 (0.760-0.988)	< 0.001	87.5	0.950 (0.849-1)	< 0.001	35.3	0.689 (0.52-0.858)	0.038
	PIVKA-II, mAU/mL	96.0	0.993 (0.977-1)	< 0.001	37.5	0.508 (0.224-0.793)	0.949	0.0	0.362 (0.188-0.536)	0.130
Number of tumors
Single	AFP, ng/mL	65.6	0.901 (0.86-0.9441)	< 0.001	58.9	0.849 (0.765-0.934)	< 0.001	14.0	0.555 (0.435-0.674)	0.381
	PIVKA-II, mAU/mL	77.4	0.896 (0.856-0.937)	< 0.001	36.7	0.539 (0.394-0.683)	0.634	6.6	0.409 (0.289-0.529)	0.148
Multiple	AFP, ng/mL	66.7	0.883 (0.785-0.980)	< 0.001	76.9	0.923 (0.825-1)	< 0.001	31.6	0.651 (0.483-0.818)	0.087
	PIVKA-II, mAU/mL	83.3	0.954 (0.910-0.997)	< 0.001	30.8	0.441 (0.215-0.667)	0.596	0.0	0.358 (0.191-0.526)	0.108

AFP: Alpha-fetoprotein; AUC: Area under the curve; BCLC: Barcelona Clinic Liver Cancer staging system; CI: Confidence interval; CNLC: China liver cancer staging system; PIVKA-II: Prothrombin induced by vitamin K absence-II.