The Combination of Age, International Standardized Ratio, Albumin and γ-Glutamyl Transpeptidase (AIAG), Tumor Size and Alpha Fetoprotein (AFP) Stage as the Prognostic Model for Hepatitis B-Related Hepatocellular Carcinoma

Figures & data

Table 1 Basic Characteristics of Patients with Hepatitis B-Related Hepatocellular Carcinoma Stratified According to Level of the AIAG

Variables	Overall	AIAG		P
		≤0.91	>0.91
Sex
Male	394	282	112	0.937
Female	107	77	30
Age (years)	53.4±10.9	52.7±11.3	55.3±9.6	0.015
ALT (U/L)	35 (7–1315)	30 (7–1315)	53 (13–1068)	<0.001
AST (U/L)	38 (11–1247)	33 (11–1075)	54 (12–1247)	<0.001
GGT (U/L)	60 (3–1579)	52 (3–538)	89 (12–1579)	<0.001
TBIL (mol/L)	14(2–4312)	13(2–107)	18(3–4312)	<0.001
ALB (g/L)	40(19–72)	41(19–72)	34(19–51)	<0.001
INR	1.1(0.7–27.9)	1.0(0.7–1.2)	1.2((1.0–27.9)	<0.001
PLT (× 10^9/l)	141(31–575)	146(31–438)	117(37–575)	<0.001
AFP
>200ng/Ml	196	140	56	0.930
≤200ng/mL	266	189	77
Child–Pugh
A	457	349	108	<0.001
B	44	10	34
Ascites
Yes	48	31	17	0.387
No	412	291	121
Tumor size
>5cm	289	207	82	0.986
≤5cm	212	152	60
Tumor number
Multiple	65	46	19	0.856
Single	430	309	21
Cirrhosis
Yes	291	200	91	<0.001
No	210	160	50
BCLC
0	359	183	57	0.029
A/B	142	176	85

Abbreviations: AIAG, age, international standardized ratio, albumin, γ-glutamyl transpeptidase; ALT, alanine aminotransferase; AST, aspartate aminotransferase; GGT, γ-glutamyl transpeptidase; TBIL, total bilirubin; ALB, albumin; INR, international standardized ratio; PLT, platelet; AFP, α-fetoprotein; BCLC, Barcelona Clinic Liver Cancer.

Figure 1 Flow chart showing the inclusion process of eligible patients in the study.

Figure 2 Kaplan–Meier cumulative overall survival (A) and recurrence-free survival (B) curves of the study population.

Figure 3 Kaplan–Meier cumulative overall survival (A) and recurrence-free survival (B) curves of patients stratified according to the AIAG.

Table 2 Univariate Analysis of Factors Associated with Overall Survival and Recurrence-Free Survival of Patients with Hepatitis B-Related Hepatocellular Carcinoma

Variables	OS		RFS
	HR (95% CI)	P	HR (95% CI)	P
Sex (male/female)	1.024(0.697–1.504)	0.905	1.035(0.705–1.520)	0.861
ALT (U/L)	1.001(1.000–1.002)	0.038	1.001(1.000–1.002)	0.031
AST (U/L)	1.002(1.001–1.003)	<0.001	1.002(1.001–1.003)	<0.001
TBIL (ÿmol/L)	1.000(1.000–1.001)	0.015	1.000(1.000–1.001)	0.047
PLT (×10^9/L)	1.002(1.000–1.004)	0.020	1.002(1.000–1.004)	0.043
AFP:>200/≤200ng/mL	2.095(1.527–2.874)	<0.001	2.391(1.743–3.280)	<0.001
Child–Pugh: A/B	1.701(1.052–2.752)	0.030	1.550(0.959–2.505)	0.074
Ascites: yes/no	1.358(0.846–2.180)	0.205	1.450(0.904–2.323)	0.123
Tumor size	1.162(1.121–1.203)	<0.001	1.169(1.129–1.211)	<0.001
Tumor number: Multiple/single	1.321(1.058–1.649)	0.014	1.508(1.201–1.893)	<0.001
AIAG: >0.91/ ≤0.91	1.754(1.266–2.434)	0.001	1.693(1.222–2.346)	0.002
Cirrhosis: yes/no	0.730(0.531–1.003)	0.052	0.705(0.515–0.966)	0.029
BCLC:0-A/B	2.848(2.020–4.012)	<0.001	3.217(2.283–4.534)	<0.001

Abbreviations: OS, overall survival; RFS, recurrence-free survival; HR, hazard ratio; ALT, alanine aminotransferase; AST, aspartate aminotransferase; TBIL, total bilirubin; PLT, platelet; AFP, α-fetoprotein; AIAG, age, international standardized ratio, albumin, γ-glutamyl transpeptidase; BCLC, Barcelona Clinic Liver Cancer.

Figure 4 Kaplan–Meier cumulative overall survival (A) and recurrence-free survival (B) curves of patients stratified according to the BCLC stage.

Table 3 Multivariate Analysis of Factors Associated with Overall Survival and Recurrence-Free Survival of Patients with Hepatitis B-Related Hepatocellular Carcinoma

Variables	OS		RFS
	HR (95% CI)	P	HR (95% CI)	P
ALT (U/L)	0.998(0.995–1.001)	0.285	0.998(0.995–1.001)	0.289
AST (U/L)	1.003(1.000–1.006)	0.071	1.003(1.000–1.006)	0.095
TBIL (μmol/L)	1.000(1.000–1.001)	0.128	1.000(1.000–1.001)	0.346
PLT (× 10^9/l)	1.002(1.000–1.004)	0.048	1.001(0.999–1.004)	0.174
AFP:>200/≤200ng/mL	1.500(1.058–2.125)	0.023	1.769(1.253–2.498)	0.001
Child–Pugh: A/B	0.971(0.557–1.695)	0.918	1.000(0.580–1.722)	0.999
Tumor Size	1.107(1.049–1.168)	0.000	1.105(1.047–1.165)	0.000
Tumor number: Multiple/single	1.175(0.934–1.477)	0.168	1.355(1.069–1.719)	0.012
AIAG	3.471(1.302–9.251)	0.013	2.726(1.012–7.344)	0.047
BCLC:0-A/B	1.246(0.764–2.034)	0.378	1.364(0.839–2.215)	0.210

Abbreviations: OS, overall survival; RFS, recurrence-free survival; HR, hazard ratio; ALT, alanine aminotransferase; AST, aspartate aminotransferase; TBIL, total bilirubin; PLT, platelet; AFP, α-fetoprotein; AIAG, age, international standardized ratio, albumin, γ-glutamyl transpeptidase; BCLC, Barcelona Clinic Liver Cancer.

Table 4 Ranking of AUC of the Prognostic Systems

Rank	System	AUC	95% CI
1	AIAG+ tumor size+ AFP stage	0.728	0.676–0.769
2	AIAG+ tumor size	0.723	0.676–0.769
3	BCLC stage	0.654	0.602–0.705
4	AIAG+ AFP stage	0.608	0.555–0.662
5	AIAG	0.574	0.521–0.628

Abbreviations: AUC, area under curve; AIAG, age, international standardized ratio, albumin, γ-glutamyl transpeptidase; AFP, α-fetoprotein; BCLC Barcelona Clinic Liver Cancer.

Figure 5 ROC curves of the subgroups stratified according to the AIAG, tumor size and AFP.

Table 5 Ranking of Discriminatory Ability of the Prognostic Systems on the Basis of the Concordance Index

Rank	System	C Index	95% CI
1	AIAG+ tumor size+ AFP stage	0.710	0.669–0.751
2	AIAG+ tumor size	0.707	0.666–0.749
3	BCLC stage	0.636	0.598–0.673
4	AIAG+ AFP stage	0.611	0.564–0.658
5	AIAG	0.525	0.490–0.559

Abbreviations: CI, confidence interval; AIAG, age, international standardized ratio, albumin, γ-glutamyl transpeptidase; AFP, α-fetoprotein; BCLC, Barcelona Clinic Liver Cancer.