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Page 4 of 7 Nouso et al. Hepatoma Res 2018;4:73 I http://dx.doi.org/10.20517/2394-5079.2018.93

Table 2. Diagnostic accuracy using different cut-offs
Variables (cut-off) Positive rate
NBNC-HCC ≤ 3 cm, ≤ 3 nodules DM
AFP (3.6 ng/mL)* 161 (79.3%) 74 (75.5%) 10 (9.4%)
(5 ng/mL) 138 (68.0%) 56 (57.1%) 5 (4.7%)
(10 ng/mL) 96 (47.3%) 29 (29.6%) 1 (0.94%)
DCP (25 mAU/mL)* 165 (81.3%) 71 (72.5%) 9 (8.5%)
(40 mAU/mL) 144 (70.9%) 53 (54.1%) 1 (0.94%)
(100 mAU/mL) 101 (49.8%) 25 (25.5%) 0
AST (30 IU/L)* 148 (72.9%) 66 (67.4%) 16 (15.1%)
(40 IU/L) 107 (52.7%) 45 (45.1%) 10 (9.4%)
(80 IU/L) 24 (11.8%) 6 (6.1%) 0
Combination** 198/203 (97.5%) 96/98 (98.0%) 29/106 (27.4%)
HCC with diabetes 66/67 (98.5%) 32/33 (97.0%) -
HCC without diabetes 132/136 (97.1%) 64/65 (98.5%) -
*Optimum value for detecting HCC; **combination of AST, AFP, and DCP; NBNC-HCC: nonB-nonC hepatocellular carcinoma; DM:
diabetes mellitus; AFP: alpha-fetoprotein; DCP: des-gamma-carboxy prothrombin; AST: aspartate aminotransferase; HCC: hepatocellular
carcinoma

A B

Figure 1. Distribution of marker-positive patients. Distribution of the patients positive for aspartate aminotransferase (AST), alpha-
fetoprotein (AFP), and des-gamma-carboxy prothrombin (DCP) in patients with nonB-nonC hepatocellular carcinoma (NBNC-HCC). The
majority (97.6%) of patients with NBNC-HCC showed elevations in AST, AFP and/or DCP over the selected cut-offs (A); distribution of
the three markers in patients with diabetes mellitus (B). One-fourth (27.4%) of the patients showed elevations in AST, AFP, and/or DCP
over the selected cut-offs

DISCUSSION
This study shows, for the first time, that a triple screen for serum AST, AFP, and DCP can be used to identify
patients at high risk for NBNC-HCC. Over 95% of patients with NBNC-HCC in this study showed eleva-
tions in AST (≥ 30 IU/L), AFP (≥ 3.6 ng/mL) and/or DCP (≥ 25 mAU/mL), regardless of the diabetic status.
In contrast, only one-fourth (27.4%) of DM patients without HCC showed elevations in AST, AFP, and/or
DCP. These patients can be considered to be at risk for developing HCC, meaning that this triple screening
method could be used to identify patients who need further testing using imaging.

AFP is an oncofetal protein originally recognized as an HCC tumor marker . There are many studies that
[19]
set the cut-offs at high level because most of the control subjects were active chronic viral hepatitis. As the
results, many of them showed low diagnostic abilities. Its sensitivity in HCC diagnosis increased to range
[9]
between 49% and 71% when using a lower cut-off of 20 ng/mL . However, AFP has not been considered a
tumor marker of choice in NBNC-HCC, as its elevation in this condition is less pronounced than that in
[17]
hepatitis virus-related HCC . Recently, AFP has also been identified as a marker of carcinogenic potential
of the liver. By using low cut-off (5 ng/mL), it can reliably predict development of HCC in chronic hepatitis C