Preoperative prognostic value of alfa-fetoprotein density in patients with hepatocellular carcinoma undergoing radiofrequency ablation

Figures & data

Figure 1. Flowchart for the patient selection and study design.

Table 1. Characteristics of the study patients.

Characteristic	All patients (n = 543)	Low AFP density group (n = 354)	High AFP density group (n = 189)	P value
Age (years)^a	56.54 ± 11.20	57.04 ± 11.10	55.61 ± 11.37	0.193
Gender				0.072
Male	468 (86.2)	312 (88.1)	156 (82.5)
Female	75 (13.8)	42 (11.9)	33 (17.5)
Etiology				0.016^b
HBV infection	469 (86.4)	296 (83.6)	173 (91.5)
HCV infection	27 (5.0)	18 (5.1)	9 (4.8)
Others	49 (9.0)	41 (11.6)	8 (4.2)
HBV-DNA (copies/mL)				0.124
<100	337 (62.1)	228 (64.4)	109 (57.7)
>100	206 (37.9)	126 (35.6)	80 (42.3)
PLT (×10^9/L)^a	126.0 (86.3–173.0)	132.0 (92.0–176.0)	119.0 (78.0–168.0)	0.008^b
ALB (g/L)^a	38.6 (35.2–42.1)	39.0 (35.6–42.1)	38.0 (34.9–42.4)	0.383
TBIL (μmol/L)^a	15.6 (11.1–22.4)	15.3 (11.0–20.6)	16.8 (11.4–24.6)	0.064
ALT (U/L)^a	32.0 (22.3–47.0)	31.5 (22.0–47.0)	33.0 (23.0–47.5)	0.459
AST (U/L)^a	34.0 (25.0–45.0)	33.0 (25.0–45.0)	35.0 (26.8–49.0)	0.160
γ-GGT (U/L)^a	52.0 (33.0–88.0)	50.0 (33.0–83.0)	57.0 (34.0–97.3)	0.195
AFP absolute (ng/mL)^a	18.1 (4.8–120.2)	6.7 (3.3–18.0)	221.7 (98.3–643.2)	<0.001^b
AFP density (ng/mL.cm^3)^a	2.8 (0.7–18.6)	1.0 (0.4–2.6)	44.5 (15.2–130.3)	<0.001^b
Child-pugh grade				0.122
A	509 (93.7)	336 (94.9)	173 (91.5)
B	34 (6.3)	18 (5.1)	16 (8.5)
ALBI grade				0.275
1	245 (45.1)	166 (46.9)	79 (41.8)
2	291 (53.6)	185 (52.3)	106 (56.1)
3	7 (1.3)	3 (0.8)	4 (2.1)
BCLC stage				<0.001^b
0	153 (28.2)	79 (22.3)	74 (39.2)
A	390 (71.8)	275 (77.7)	115 (60.8)
Tumor number				0.468
1	429 (79.0)	280 (79.1)	149 (78.8)
2	95 (17.5)	64 (18.1)	31 (16.4)
3	19 (3.5)	10 (2.8)	9 (4.8)
Maximum tumor diameter (cm)^a	2.4 (1.9-3.0)	2.5 (2.0-3.1)	2.1 (1.7-2.9)	<0.001^b

Otherwise indicated, data are numbers of patients, with percentages in parentheses. HBV: hepatitis B virus; HCV: hepatitis C virus; PLT: platelets; ALB: albumin; TBIL: total bilirubin; ALT: alanine aminotransferase; AST; aspartate aminotransferase; γ-GGT: γ-glutamyl transpeptidase; AFP: alpha-fetoprotein; ALBI grade: albumin-bilirubin grade; BCLC: Barcelona Clinic Liver Cancer.

^aData are mean ± standard deviation or medians, with interquartile range in parentheses.

^bStatistically significant.

Figure 3. Restricted cubic spline model for the association of AFP density with (a) overall survival (OS) and (b) progression-free survival (PFS). Shaded regions indicate 95% confidence bands for risk of outcomes as log function of AFP density. HR, hazard ratio.

Table 2. Univariate analysis using Cox regression for overall survival and progress-free survival.

	Overall survival			Progress-free survival
Characteristic	Hazard ratio	95% CI	P value	Hazard ratio	95% CI	P value
Age (years), ≥65	1.826	1.366–2.442	<0.001^a	1.506	1.188–1.910	<0.001^a
Gender, Female	1.359	0.951–1.943	0.092	1.271	0.944–1.711	0.114
Etiology, non-HBV	0.855	0.570–1.283	0.449	1.014	0.728–1.413	0.934
HBV-DNA, >100	0.970	0.721–1.305	0.841	0.981	0.782–1.231	0.868
PLT (×10^9/L)	0.996	0.994–0.999	0.001^a	0.997	0.995–0.998	<0.001^a
ALB (g/L)	0.909	0.883–0.936	<0.001^a	0.948	0.927–0.970	<0.001^a
TBIL (μmol/L)	1.023	1.010–1.036	<0.001^a	1.013	1.003–1.023	0.013^a
ALT (U/L)	1.003	0.999–1.007	0.112	1.000	0.997–1.004	0.901
AST (U/L)	1.005	1.001–1.008	0.005^a	1.002	0.999–1.006	0.120
γ-GGT (U/L)	1.002	1.001–1.003	<0.001^a	1.001	1.000–1.002	0.024^a
AFP absolute (ng/mL)	1.000	1.000–1.001	<0.001^a	1.000	1.000–1.001	<0.001^a
AFP density, high	1.946	1.472–2.574	<0.001^a	1.569	1.252–1.967	<0.001^a
Child-pugh grade, B	2.268	1.379–3.733	0.001^a	1.718	1.123–2.628	0.013^a
ALBI grade
1	Ref
2	2.321	1.727–3.121	<0.001^a	1.740	1.385–2.186	<0.001^a
3	10.331	4.109–25.975	<0.001^a	2.994	1.218–7.360	0.017^a
Tumor number, >1	1.924	1.421–2.606	<0.001^a	1.864	1.454–2.389	<0.001^a
Total tumor volume (cm^3)	1.031	1.020–1.042	<0.001^a	1.037	1.028–1.046	<0.001^a
Maximum tumor diameter, ≥2	2.369	1.629–3.445	<0.001^a	2.171	1.647–2.862	<0.001^a

HBV: hepatitis B virus; PLT: platelets; ALB: albumin; TBIL: total bilirubin; ALT: alanine aminotransferase; AST: aspartate aminotransferase; γ-GGT: γ-glutamyl transpeptidase; AFP: alpha-fetoprotein; ALBI grade: albumin-bilirubin grade.

^aStatistically significant.

Table 3. Multivariate analysis using Cox regression for overall survival and progress-free survival.

	Overall survival			Progress-free survival
Characteristic	Hazard ratio	95% CI	P value	Hazard ratio	95% CI	P value
Age (years), ≥65	1.583	1.170–2.142	0.003^a	1.429	1.118–1.826	0.004^a
PLT\ (×10^9/L)	1.000	0.997–1.002	0.748	0.998	0.996–1.000	0.073
AST (U/L)	1.001	0.997–1.005	0.802	0.998	0.995–1.002	0.350
γ-GGT (U/L)	1.001	1.000–1.003	0.028^a	1.001	1.000–1.002	0.244
AFP density, high	1.742	1.309–2.319	<0.001^a	1.494	1.186–1.884	<0.001^a
Child-pugh grade, B	1.265	0.711–2.251	0.424	1.268	0.802–2.004	0.310
ALBI grade
1	Ref
2	1.929	1.384–2.688	<0.001^a	1.438	1.113–1.857	0.005^a
3	6.184	2.128–17.972	<0.001^a	2.199	0.844–5.728	0.107

PLT: platelets; AST: aspartate aminotransferase; γ-GGT; γ-glutamyl transpeptidase; AFP: alpha-fetoprotein; ALBI grade: albumin-bilirubin grade.

^aStatistically significant.