Clinical relevance of increased serum preneoplastic antigen in hepatitis C-related hepatocellular carcinoma

Table 1 Characteristics of patients with hepatitis C virus-related hepatitis, cirrhosis, and hepatocellular carcinoma

	1: Hepatitis (n = 50)		2: Cirrhosis (n = 44)		3: HCC (n = 47)		1 vs 2	1 vs 3	2 vs 3
	Mean	SD	Mean	SD	Mean	SD	P value	P value	P value
Sex (male/female)	20/30		18/26		25/22		0.360	0.048	0.101
Age (yr)	70.2	(11.7)	71.8	(10.4)	75.3	(9.0)	0.558	0.018	0.102
Albumin (g/L)	4.2	(0.3)	3.7	(0.6)	3.7	(0.9)	< 0.001	< 0.001	0.962
AST (U/L)	44	(35)	46	(20)	60	(51)	0.056	0.033	0.861
ALT (U/L)	41	(42)	33	(20)	45	(48)	0.967	0.667	0.674
ALP (U/L)	259	(60)	345	(141)	362	(312)	0.001	0.084	0.212
Bilirubin total (mg/dL)	0.8	(0.4)	1.2	(0.7)	1.2	(1.1)	0.001	0.003	0.477
GTP (U/L)	46	(61)	47	(44)	105	(212)	0.186	0.001	0.078
Type IV collagen (ng/mL)	159	(69)	237	(88)	207	(94)	< 0.001	0.003	0.075

Results are shown as means with SD. Differences in mean values between each group were assessed with Mann–Whitney U tests, and differences in the sex ratio were assessed with χ² tests. HCC: Hepatocellular carcinoma; AST: Aspartate aminotransferase; ALT: Alanine aminotransferase ; ALP: Alkaline phosphatase; GTP: Glutamyl tranpeptidase.

Table 2 Sensitivity and specificity of preneoplastic antigen, α-fetoprotein, and des-γ-carboxy-prothrombin in patients with hepatitis C virus-related hepatocellular carcinoma

	(A) HCC vs hepatitis		(B) HCC vs hepatitis/cirrhosis
	Sensitivity (%)	Specificity (%)	Sensitivity (%)	Specificity (%)
PNA	63.8	78.0	63.8	66.0
AFP	61.7	88.0	61.7	75.5
DCP	61.7	94.0	61.7	83.0

The sensitivity and specificity of markers were determined to discriminate hepatocellular carcinoma patients from (A) hepatitis patients and (B) hepatitis and cirrhosis patients. The cut-off value for positivity was 5 ng/mL for preneoplastic antigen, 10 ng/mL for α-fetoprotein, and 40 mAU/mL for des-γ-carboxy-prothrombin. HCC: Hepatocellular carcinoma; PNA: Preneoplastic antigen; AFP: α-Fetoprotein; DCP: Des-γ-carboxy-prothrombin.

Table 3 Correlations of preneoplastic antigen, α-fetoprotein, and des-γ-carboxy-prothrombin with laboratory tests in patients with hepatitis C virus-related hepatocellular carcinoma

	PNA		AFP		DCP
	r	P value	r	P value	r	P value
Albumin	-0.173	0.245	-0.416	0.004	-0.339	0.020
AST	0.325	0.026	0.626	< 0.001	0.232	0.117
ALT	0.227	0.125	0.438	0.002	-0.038	0.799
ALP	0.582	< 0.001	0.459	0.001	0.302	0.039
Bilirubin	0.226	0.130	0.366	0.012	0.030	0.841
GTP	0.666	< 0.001	0.274	0.062	0.082	0.585
Type IV collagen	0.107	0.476	0.498	< 0.001	0.246	0.095

The correlation index (r) and 2-sided P value were calculated by Spearman’s correlation analysis. PNA: Preneoplastic antigen; AFP: α-Fetoprotein; DCP: Des-γ-carboxy-prothrombin; AST: Aspartate aminotransferase; ALT: Alanine aminotransferase; ALP: Alkaline phosphatase; GTP: Glutamyl tranpeptidase.

Table 4 Comparison of biochemical markers between preneoplastic antigen-high and preneoplastic antigen-low patients with hepatitis C virus-related hepatocellular carcinoma

	PNA-high patients (n = 23)		PNA-low patients (n = 24)
	Mean	SD	Mean	SD	P value
Albumin (g/L)	3.5	0.7	3.9	1.1	0.1348
AST (U/L)	73.2	58.6	47.0	36.1	0.0247
ALT (U/L)	58.3	61.8	31.7	18.9	0.3025
ALP (U/L)	463.4	393.2	264.2	135.9	0.0004
Bilirubin total (mg/dL)	1.4	1.4	1.0	0.7	0.6345
GTP (U/L)	183.2	278.7	31.0	12.5	< 0.0001
Type IV collagen (ng/mL)	225.2	104.3	189.4	76.3	0.2133

Hepatocellular carcinoma patients were divided into preneoplastic antigen-high and preneoplastic antigen-low groups using the median preneoplastic antigen value (8 ng/mL) as the cut-off. Results are shown as means with SD. Differences in mean values between each group were assessed with Mann–Whitney U tests. PNA: Preneoplastic antigen; AST: Aspartate aminotransferase; ALT: Alanine aminotransferase; ALP: Alkaline phosphatase; GTP: Glutamyl transpeptidase.