The Index sAGP is Valuable for Distinguishing Atypical Hepatocellular Carcinoma from Atypical Benign Focal Hepatic Lesions

Figures & data

Figure 1 Flowchart of patient selection.

Abbreviations: FHL, focal hepatic lesion; AFP, alpha-fetoprotein; aHCC, atypical hepatocellular carcinoma; aBFHL, atypical benign focal hepatic lesion.

Table 1 Demographic and Clinical Characteristics of the Patients

	Result [Mean ± SD, n (%) or M (IQR)]				P
	n	aHCC	n	aBFHL
Age (years)	224	56.0 ± 10.2	178	46.8 ± 11.5	< 0.001^a
Sex	224		178		< 0.001^b
Male		204 (91.1)		61 (34.3)
Female		20 (8.9)		117 (65.7)
Blood tests
WBC (*10^9/L)	224	5.0 (3.9–6.4)	178	5.2 (4.1–6.4)	0.332^c
RBC (*10^12/L)	224	4.5 ± 0.6	178	4.5 ± 0.5	0.816^a
HGB (g/L)	224	140.0 (128.0–151.8)	178	131.0 (122.0–142.3)	< 0.001^c
PLT (*10^9/L)	224	155.2 ± 80.0	178	221.6 ± 72.0	< 0.001^a
NEUT (*10^9/L)	224	2.8 (2.1–3.7)	178	3.0 (2.3–3.9)	0.308^c
LYM (*10^9/L)	224	1.5 ± 0.7	178	1.7 ± 0.5	0.044^a
MON (*10^9/L)	224	0.4 (0.3–0.5)	178	0.4 (0.3–0.5)	0.031^c
ALB (g/L)	224	41.4 (38.1–44.3)	178	44.2 (41.7–46.3)	< 0.001^c
TBIL (μmol/L)	224	13.7 (9.3–17.5)	178	9.4 (7.0–12.5)	< 0.001^c
DBIL (μmol/L)	224	3.8 (2.9–6.1)	178	2.4 (1.7–3.4)	< 0.001^c
ALT (U/L)	224	31.0 (23.0–45.0)	178	16.0 (11.0–27.0)	< 0.001^c
AST (U/L)	224	34.5 (27.0–49.8)	178	20.7 (18.0–25.3)	< 0.001^c
GGT (U/L)	224	48.5 (28.0–88.8)	178	21.0 (14.0–34.0)	< 0.001^c
ALP (U/L)	224	100.5 (81.3–127.0)	178	76.0 (59.8–94.3)	< 0.001^c
PA (g/L)	143	210.3 ± 69.7	107	268.7 ± 72.6	< 0.001^a
CR (μmol/L)	224	74.2 ± 15.4	178	62.3 ± 14.4	< 0.001^a
BUN (mmol/L)	224	5.4 ± 1.5	178	5.0 ± 1.4	0.004^a
PT (s)	221	11.8 (11.1–12.7)	178	10.9 (10.4–11.6)	< 0.001^c
APTT (s)	221	28.4 (26.3–32.5)	178	27.6 (25.3–29.8)	< 0.001^c
FBG (g/L)	221	2.5 (2.1–3.2)	173	2.4 (2.1–2.9)	0.198^c
AFP (ng/mL)	224	8.6 (3.2–42.6)	178	2.4 (1.6–3.4)	< 0.001^c
Child-Pugh grade	221		178		0.004^b
A		209 (94.6)		175 (98.3)
B		12 (5.4)		2 (1.1)
C		0 (0.0)		1 (0.6)

Notes: ^aStudent’s t-test. ^bPearson’s Chi-squared test. ^cMann–Whitney U-test.

Abbreviations: aHCC, atypical hepatocellular carcinoma; aBFHL, atypical benign focal hepatic lesions; WBC, white blood cell; RBC, red blood cell; HGB, hemoglobin; PLT, platelet; LYM, lymphocyte; MON, monocyte; NEUT, neutrophil; ALB, albumin; TBIL, total bilirubin; DBIL, direct bilirubin; ALT, alanine aminotransaminase; AST, aspartate aminotransaminase; GGT, γ-glutamyltransferase; ALP, alkaline phosphatase; PA, prealbumin; CR, creatinine; BUN, blood urea nitrogen; PT, prothrombin time; APTT, activated partial thromboplastin time; FBG, fibrinogen; AFP, alpha fetoprotein.

Table 2 Reported Derived Indexes for the Diagnosis of Atypical Hepatocellular Carcinoma

Indexes	Result [M (IQR)]				P	AUROC (95% CI)
	n	aHCC	n	aBFHL
NLR	224	1.92 (1.47–2.60)	178	1.86 (1.37–2.51)	0.286	0.531 (0.474–0.588)
PLR	224	95.77 (69.94–134.66)	178	135.42 (102.63–176.94)	< 0.001	0.694 (0.643–0.746)
LMR	223	3.75 (2.75–4.92)	178	4.38 (3.43–5.98)	< 0.001	0.628 (0.574–0.683)
SII	224	259.58 (167.01–425.72)	178	394.68 (290.17–553.68)	< 0.001	0.666 (0.613–0.719)
GGT/ALT	224	1.66 (0.96–2.53)	178	1.27 (0.99–1.98)	0.014	0.572 (0.516–0.627)
GGT/AST	224	1.39 (0.89–2.11)	178	0.95 (0.69–1.50)	< 0.001	0.626 (0.571–0.681)
GGT/ALP	224	0.46 (0.30–0.83)	178	0.29 (0.20–0.45)	< 0.001	0.700 (0.649–0.751)
GPR	224	0.38 (0.19–0.74)	178	0.10 (0.07–0.17)	< 0.001	0.853 (0.814–0.892)
FAR	221	0.06 (0.05–0.08)	173	0.05 (0.05–0.07)	0.002	0.591 (0.536–0.647)
FPR	141	0.01 (0.01–0.02)	107	0.01 (0.01–0.01)	< 0.001	0.682 (0.616–0.747)

Abbreviations: aHCC, atypical hepatocellular carcinoma; aBFHL, atypical benign focal hepatic lesions; AUROC, area under the receiver operating characteristic curve; CI, interval confidence; NLR, neutrophil to lymphocyte ratio; PLR, platelet to lymphocyte ratio; LMR, lymphocyte to monocyte ratio; SII, systemic immune inflammatory index; ALT, alanine aminotransaminase; AST, aspartate aminotransaminase; GGT, γ-glutamyltransferase; ALP, alkaline phosphatase; GPR, γ-glutamyltransferase to platelet ratio; FPR, fibrinogen to prealbumin ratio; FAR, fibrinogen to albumin ratio.

Figure 2 Receiver operating characteristic curves of derived indexes reported previously for the diagnosis of atypical hepatocellular carcinoma. (A) Inflammation-related derived indexes; (B) Liver function-related derived indexes.

Abbreviations: NLR, neutrophil-to-lymphocyte ratio; PLR, platelet-to-lymphocyte ratio; LMR, lymphocyte-to-monocyte ratio; SII, systemic immune inflammatory index; ALT, alanine aminotransaminase; AST, aspartate aminotransaminase; GGT, γ-glutamyltransferase; ALP, alkaline phosphatase; GPR, γ-glutamyltransferase-to-platelet ratio; FPR, fibrinogen-to-prealbumin ratio; FAR, fibrinogen-to-albumin ratio.

Figure 3 Diagnostic performance of sAGP, AGP, GPR, and AFP in differentiating atypical hepatocellular carcinoma from atypical benign focal hepatic lesion. (A) Receiver operating characteristic curves; (B) Diagnostic validity metrics.

Abbreviations: AUROC, area under the receiver operating characteristic curve; CI, confidence interval; sAGP, (standardized α-fetoprotein + standardized γ-glutamyltransferase) to standardized platelet count ratio; AGP, (α-fetoprotein + γ-glutamyltransferase) to platelet count ratio; GPR, γ-glutamyltransferase-to-platelet ratio; AFP, α-fetoprotein; SEN, sensitivity; SPE, specificity; ACC, accuracy; PPV, positive predictive value; NPV, negative predictive value; PLR, positive likelihood ratio; NLR, negative likelihood ratio.

Figure 4 Receiver operating characteristic curves and diagnostic validity metrics of sAGP in the diagnosis of aHCC subgroups. (A) Early BCLC stage (0/A) aHCC vs aBFHL; (B) Early TNM stage (I) aHCC vs aBFHL; (C) Small aHCC (tumor diameter < 3 cm) vs aBFHL; (D) AFP-negative aHCC (AFP < 20 ng/mL) vs aBFHL.

Abbreviations: AUROC, area under the receiver operating characteristic curve; CI, confidence interval; sAGP, (standardized α-fetoprotein + standardized γ-glutamyltransferase) to standardized platelet count ratio; GPR, γ-glutamyltransferase-to-platelet ratio; AFP, α-fetoprotein; SEN, sensitivity; SPE, specificity; ACC, accuracy; PPV, positive predictive value; NPV, negative predictive value; PLR, positive likelihood ratio; NLR, negative likelihood ratio.