Diagnostic value of PIVKA-II and alpha-fetoprotein in hepatitis B virus-associated hepatocellular carcinoma

Table 1 Baseline characteristics of the study population (n = 1255)

	Non-cirrhotic CHB (n = 879)	Cirrhosis without HCC (n = 219)	HCC (n = 157)	P value
Age (yr)	45 (17-97)	54 (26-92)	57 (34-89)	0.0001
Gender (M:F)	549:330	151:68	124:33	0.0001
AFP (ng/mL)	2.5 (0.6-602.8)	3.3 (0.6-233.6)	55.9 (0.6-121000.0)	0.0001
PIVKA-II (mAU/mL)	23 (6-162)	19 (4-312)	202 (10-2000)	0.0001
INR	1.00 (0.84-3.24)	1.11 (0.92-2.38)	1.12 (0.79-8.93)	0.0001
Albumin (g/dL)	4.5 (2.3-5.3)	4.2 (0.5-5.2)	3.6 (2.0-5.2)	0.0001
Total bilirubin (mg/dL)	0.7 (0.2-19.2)	0.9 (0.2-18.9)	1.0 (0.3-14.7)	0.0001
ALT (IU/L)	26.5 (2-3112)	31 (8-886)	39 (6-1155)	0.1220
MELD score	7.1	10.1	9.9	0.0001
TNM stage n (%)	NA	NA
I			22 (14.0)
II			58 (36.9)
III			32 (20.4)
IV			45 (28.7)
Early HCC n (%)	NA	NA	46 (29.3)

Data are expressed as number or median (range). CHB: Chronic hepatitis B; HCC: Hepatocellular carcinoma; M: Male; F: Female; AFP: Alpha-fetoprotein; PIVKA-II: Prothrombin induced by vitamin K absence-II; INR: International normalized ratio; ALT: Alanine aminotransferase; MELD: Model for end-stage liver disease; TNM: Tumor-nodes-metastasis; NA: Not applicable.

Table 2 Comparision of baseline characteristics according to cutoff values of prothrombin induced by vitamin K absence-II (40 mAU/mL) and AFP (10 ng/mL)

	PIVKA-II < 40 AFP < 10	PIVKA-II≥40 AFP < 10	PIVKA-II < 40 AFP < 10	PIVKA-II≥40 AFP≥10	P value
Number	918	125	108	104
Age (yr)	47.9 (17-97)	48.4 (18-83)	51.4 (23-92)	55 (25-88)	0.0001
Gender (M:F)	578:340	97:28	67:41	82:22	0.0001
INR	1.0 (0.8-3.2)	1.0 (0.8-2.3)	1.1 (0.9-2.1)	1.13 (0.7-8.9)	0.0001
Albumin (g/dL)	4.5 (0.5-5.3)	2.9 (0.6-9.6)	3.8 (2-5.2)	3.5 (1.7-4.9)	0.0001
TB (mg/dL)	0.7 (0.2-18.9)	0.7 (0.2-19.2)	1.1 (0.2-17.3)	1.1 (0.3-14.7)	0.0001
ALT (IU/L)	25.4 (2-803)	30.1 (5-1664)	50 (9-1531)	43.4 (9-3112)	0.0001
MELD score	7.4	8.2	9.9	10.5	0.0001
LC, n (%)	188 (20.5)	42 (33.6)	50 (46.3)	89 (85.6)	0.0001
HCC, n (%)	21 (2.3)	30 (24)	20 (18.5)	86 (82.7)	0.0001

Data are expressed as number or median (range). PIVKA-II: Prothrombin induced by vitamin K absence-II; AFP: Alpha-fetoprotein; M: Male; F: Female; INR: International normalized ratio; TB: Total bilirubin; ALT: Alanine aminotransferase; MELD: Model for end-stage liver disease; LC: Liver cirrhosis; HCC: Hepatocellular carcinoma.

Table 3 Sensitivity and specificity of alpha-fetoprotein and prothrombin induced by vitamin K absence-II in differentiating hepatocellular carcinoma from nonmalignant chronic hepatitis B

	Sensitivity	Specificity	PPV	NPV
PIVKA-II (mAU/mL)
> 40
HCC vs CHB	73.9%	89.7%	50.7%	96.0%
HCC vs LC	73.9%	90.4%	84.7%	82.8%
> 100
HCC vs CHB	57.3%	98.8%	87.4%	94.2%
HCC vs LC	57.3%	96.8%	82.8%	76.0%
> 125
HCC vs CHB	56.1%	99.2%	90.7%	94.0%
HCC vs LC	56.1%	97.3%	93.6%	75.5%
> 150
HCC vs CHB	52.9%	99.4%	92.2%	93.6%
HCC vs LC	52.9%	97.3%	93.3%	74.2%
AFP (ng/mL)
> 10
HCC vs CHB	67.5%	90.3%	50.0%	95.1%
HCC vs LC	67.5%	82.6%	73.6%	78.0%
> 20
HCC vs CHB	59.9%	94.4%	60.3%	94.3%
HCC vs LC	59.9%	90.0%	81.0%	75.8%
> 200
HCC vs CHB	36.3%	99.3%	87.7%	91.6%
HCC vs LC	36.3%	99.1%	96.6%	68.5%
> 400
HCC vs CHB	29.9%	99.7%	94.0%	90.9%
HCC vs LC	29.9%	100.0%	100.0%	66.6%
Combination1
HCC vs CHB	75.2%	95.4%	69.8%	96.4%
HCC vs LC	75.2%	92.7%	88.1%	83.9%

¹Combination obtained from variable logAFP + 4.61logPIVKA-II. PPV: Positive predictive value; NPV: Negative predictive value; PIVKA-II: Prothrombin induced by vitamin K absence-II; HCC: Hepatocellular carcinoma; CHB: Chronic hepatitis B; LC: Liver cirrhosis; AFP: Alpha-fetoprotein.