Validation of the PAGE-B score to predict hepatocellular carcinoma risk in caucasian chronic hepatitis B patients on treatment

Table 1 Demographic and follow-up characteristics of study population

	n = 742
Age, yr ± SE	45.0 ± 0.5
Gender, male n (%)	472 (63.6)
Follow-up, mo ± SE	54.7 ± 1.2
Diabetes mellitus, n (%)	116 (15.7)
HBeAg positivity, n (%)	171 (23.0)
Cirrhosis, n (%)	161 (21.7)
NA(s) before ETV/TDF, n (%)	162 (21.8)
Antiviral treatment (ETV/TDF), n (%)	240 (32.3)/502(67.7)
MVR, n (%)	633 (85.3)
Hepatic flare, n (%)	25 (3.4)
ALT normalization at 6 mo, n (%)	620 (85.9)
Virological response at 6 mo, n (%)	597 (85.4)
PAGE-B score ± SE	11.1 ± 0.2
PAGE-B score-risk groups, n (%)
Low	281 (37.9)
Moderate	341 (46)
High	120 (16.2)
HCC cases during follow up, n (%)	26 (3.5)

HBeAg: Hepatitis B e antigen; ALT: Alanine transaminase; ETV: Entecavir; HCC: Hepatocellular carcinoma; MVR: Maintained virological response; NA(s): Nucleos(t)ide analogue(s); TDF: Tenofovir disoproxil fumarate; SE: Standard error of mean.

Table 2 Comparison of baseline characteristics of patients with and without hepatocellular carcinoma

	Patients with HCC	Patients without HCC	P value
Age (yr) mean ± SE	57.8 ± 2.3	44.5 ± 0.5	< 0.001
Male gender, n (%)	24 (92.3)	448 (62.6)	0.004
Cirrhosis, n (%)	16 (61.5)	145 (20.3)	< 0.001
Diabetes mellitus, n (%)	8 (32)	108(15.1)	0.043
Antiviral treatment (ETV/TDF), n (%)	10 (38.5)/16 (61.5)	230 (32.1)/486 (67.9)	0.642
Laboratory (mean ± SE)
HBeAg positivity, n (%)	6 (23.1)	165 (23.0)	1.000
ALT (IU/L)	92.9 ± 25.7	98.3 ± 5.7	0.856
Albumin (g/dL)	3.9 ± 0.1	4.1 ± 0.0	0.014
Total bilirubin (mg/dL)	0.9 ± 0.1	1.0 ± 0.1	0.709
AFP (ng/mL)	23.3 ± 9.6	5.2 ± 0.4	< 0.001
INR	1.1 ± 0.0	1.1 ± 0.0	0.143
Platelet (10³/mL)	128.8 ± 8.6	203.5 ± 2.5	< 0.001
HBV-DNA (log IU/mL)	5.4 ± 0.3	5.5 ± 0.1	0.859

ALT: Alanine transaminase; AFP: Alpha-fetoprotein; ETV: Entecavir; HCC: Hepatocellular carcinoma; SE: Standard error of mean; TDF: Tenofovir disoproxil fumarate; HBeAg: Hepatitis B e antigen; INR: International normalized ratio; HBV: Hepatitis B virus.

Table 3 Risk factors associated with the risk of hepatocellular carcinoma development

	Univariate analysis, OR (95% CI)	P value	Multivariate analysis, OR (95% CI)	P value
Age (per yr increase)	1.1 (1.0-1.1)	< 0.001	1.1 (1.0-1.1)	< 0.001
Gender (male vs female)	7.2 (1.7-30.6)	0.004	8.9 (1.1-70.7)	0.038
Platelet1 (103/mL)	1.0 (1.0-1.0)	< 0.001	1.0 (1.0-1.0)	< 0.001
AFP (ng/mL)	1.0 (1.0-1.0)	< 0.001	1.0 (1.0-1.0)	0.141
HBeAg status (positive vs negative)	1.0 (0.4-2.5)	1.000
Diabetes mellitus (yes vs no)	2.7 (1.1-6.3)	0.043	0.6 (0.2-1.7)	0.308
NA(s) before ETV/TDF (yes vs no)	2.0 (0.9-4.5)	0.143
Cirrhosis1 (yes vs no)	6.3 (2.8-14.2)	< 0.001	3.1 (1.1-8.2)	0.026
Antiviral treatment (ETV vs TDF)	0.8 (0.3-1.7)	0.642
MVR (no vs yes)	0.6 (0.2-1.4)	0.253
ALT normalization at month 6 (no vs yes)	0.4 (0.2-0.9)	0.043	0.2 (0.1-0.7)	0.009
ALT normalization at month 12 (no vs yes)	0.4 (0.2-1.0)	0.101
Virological response at month 6 (no vs yes)	0.8 (0.3-1.9)	0.622
Virological response at month 6 (no vs yes)	0.7 (0.2-2.2)	0.530

¹Cirrhosis and platelet count were analyzed separately among with other independent variables in logistic regression model as they showed collinearity.

AFP: Alpha-fetoprotein; HBeAg: Hepatitis B e antigen; CI: Confidence interval; ETV: Entecavir; MVR: Maintained virological response; NA(s): Nucleos(t)ide analogue(s); TDF: Tenofovir disoproxil fumarate.