Validation of Hepatocellular Carcinoma Risk Prediction Models in Patients with Hepatitis B-Related Cirrhosis

Figures & data

Table 1 Baseline Characteristics of Patients with HBV-Related Cirrhosis

Parameters	Total (n=252)	Without HCC (n=204)	With HCC (n=48)	P-value
Age (year)	52.13±10.24	51.78±10.32	53.63±9.85	0.355
Male, n (%)	195 (77.3%)	161 (78.9%)	34 (70.8%)	0.228
Follow-up (month)	56.96±23.52	62.94±19.71	31.58±21.52	0.000*
BMI (kg/m^2)	24.2 (4.14)	24.27 (4.16)	24.19 (4.28)	0.569
HBV DNA (log10 IU/mL)	4.35 (2.85)	4.45 (2.88)	3.81 (2.68)	0.195
HBeAg(+), n (%)	89 (35.3%)	68 (33.3%)	21 (43.7%)	0.174
PLT, ×10^9/L	79 (62)	82 (67)	71 (41.5)	0.096
ALT, IU/L	36 (40.75)	36 (42.25)	34.5 (35.75)	0.801
AST, IU/L	45 (45.5)	45 (44.75)	44.5 (52)	0.944
Scr, μmol/L	78 (20)	78 (19.75)	79 (18.07)	0.889
TBIL, μmol/L	22 (23.63)	22.7 (25.08)	19.2 (17.33)	0.152
ALB, g/L	34.9 (11)	35.25 (11.53)	34.35 (10.1)	0.745
ALP, IU/L	90 (46)	88.5 (46.75)	95.5 (41.25)	0.871
GGT, IU/L	47 (57.75)	44.5 (58.5)	51 (57.25)	0.568
HDL,mmol/L	1.02 (0.53)	1.03 (0.55)	0.96 (0.46)	0.442
LDL,mmol/L	1.94 (1.09)	1.96 (1.06)	1.84 (1.1)	0.431
INR	1.19 (0.23)	1.18 (0.22)	1.26 (0.27)	0.259
AFP, ng/mL	4.97 (24.11)	4.31 (13.54)	21.86 (256.27)	<0.001*
Decompensation, n (%)	111 (44%)	85 (41.7%)	26 (54.1%)	0.117
VR at year 1, n (%)	187 (74.2%)	154 (75.7%)	33 (68.7%)	0.337
VB, n (%)	25 (9.9%)	17 (8.3%)	8 (16.6%)	0.082
ETV treatment, n (%)	108 (42.9%)	90 (44.1%)	18 (37.5%)	0.405
AASL-H	20 (4)	20 (5)	21 (3)	0.625
aMAP	63.74 (8)	63.16 (8.74)	64.78 (6.4)	0.205
CU-HCC	35 (20.5)	23.5 (20.5)	35 (20.75)	0.163
CAMD	16 (4)	16 (4)	16 (3)	0.266
mPAGE-B	14 (4)	14 (4)	15 (2)	0.009*
PAGE-B	18 (5)	18 (5)	19 (5)	0.041*
RWS-HCC	6 (2.5)	5.5 (2.5)	7 (1.87)	0.082
REAL-B	7 (2)	7 (2)	8 (2)	<0.001*
THRI	297 (69)	291.5 (69)	297 (77.25)	0.219

Note: *Statistically significant P values.

Abbreviations: AFP, alpha-fetoprotein; ALB, albumin; ALT, alanine amino transferase; AST, aspartate aminotransferase; ALP, alkaline phosphatase; BMI, body mass index; GGT, γ-glutamyl transpeptidase; HBeAg, hepatitis B e antigen; HCC, hepatocellular carcinoma; HDL, High-density lipoprotein cholesterol; INR, international normalized ratio; LDL, Low-density lipoprotein cholesterol; PLT, blood platelet; Scr, serum creatinine; TBIL, total bilirubin; VB, virologic breakthrough; VR, virologic response.

Figure 1 Cumulative incidence rates of hepatocellular carcinoma (Kaplan–Meier curve).

Table 2 Univariate and Multivariate Analyses of Predictive Factors Associated with HCC

Parameters	Univariate Analysis
	HR (95% CI)	P value
Age (year)	1.025 (0.996 1.054)	0.089
Male, n (%)	0.707 (0.380 1.318)	0.276
BMI (kg/m^2)	1.042 (0.958 1.134)	0.336
HBV DNA (log10 IU/mL)	0.864 (0.719 1.039)	0.120
HBeAg(+), n (%)	1.462 (0.827 2.587)	0.192
PLT, ×10^9/L	0.997 (0.991 1.003)	0.261
ALT, IU/L	0.998 (0.995 1.001)	0.241
AST, IU/L	0.999 (0.997 1.002)	0.697
Scr, μmol/L	0.998 (0.991 1.006)	0.624
TBIL, μmol/L	0.995 (0.984 1.006)	0.369
ALB, g/L	0.989 (0.951 1.029)	0.588
INR	2.063 (1.140 3.733)	0.017*
ALP, IU/L	1.000 (0.993 1.007)	0.962
GGT, IU/L	1.000 (0.997 1.004)	0.885
HDL, mmol/L	0.680 (0.334 1.384)	0.287
AFP, ng/mL	1.002 (1.001 1.003)	0.000*
ETV treatment, n (%)	0.799 (0.445 1.433)	0.451
Decompensation, n (%)	1.862 (1.054 3.291)	0.032*
VB, n (%)	1.737 (0.813 3.713)	0.154
HBV-DNA positivity at year 1 of the treatment	1.463 (0.794 2.695)	0.222
Diabetes, n (%)	2.540 (1.358 4.217)	0.003*
Alcohol drinking, n (%)	1.883 (1.056 3.358)	0.032*
Multivariate analyses: Predictors of HCC
INR	2.771 (1.462 5.254)	0.002*
AFP, ng/mL	1.001 (1.000 1.003)	0.035*
Diabetes, n (%)	3.061 (1.542 6.077)	0.001*
Alcohol drinking, n (%)	2.250 (1.042 4.856)	0.039*

Note: *Statistically significant P values.

Abbreviations: AFP, alpha-fetoprotein; ALB, albumin; ALT, alanine amino transferase; AST, aspartate aminotransferase; ALP, alkaline phosphatase; BMI, body mass index; GGT, γ-glutamyl transpeptidase; HBeAg, hepatitis B e antigen; HCC, hepatocellular carcinoma; HDL, High-density lipoprotein cholesterol; INR, international normalized ratio; PLT, blood platelet; Scr, serum creatinine; TBIL, total bilirubin; VB, virologic breakthrough.

Table 3 Discrimination of the Prognostic Models

Parameters	1-Year tdROC (95% CI)	3-Year tdROC (95% CI)	5-Year tdROC (95% CI)
REAL-B	0.720 (0.523 0.917)	0.739 (0.628 0.851)	0.695 (0.597 0.792)
Aasl-hcc	0.674 (0.543 0.805)	0.568 (0.469 0.668)	0.524 (0.431 0.617)
aMAP	0.703 (0.527 0.879)	0.598 (0.487 0.709)	0.582 (0.483 0.681)
CAMD	0.644 (0.491 0.798)	0.647 (0.544 0.749)	0.582 (0.484 0.681)
CU-HCC	0.583 (0.421 0.744)	0.488 (0.376 0.599)	0.481 (0.384 0.579)
mPAGE-B	0.681 (0.515 0.847)	0.609 (0.500 0.717)	0.571 (0.474 0.667)
PAGE-B	0.660 (0.471 0.850)	0.599 (0.480 0.719)	0.564 (0.456 0.672)
RWS-HCC	0.670 (0.499 0.841)	0.679 (0.579 0.779)	0.667 (0.575 0.758)
THRI	0.664 (0.489 0.839)	0.581 (0.471 0.691)	0.574 (0.473 0.674)

Abbreviation: tdROC, time-dependent receiver operating characteristic.

Figure 2 Time-dependent area under the receiver operating characteristic curves (AUROCs) for predicting hepatocellular carcinoma development; (A) time-dependent AUROCs for predicting hepatocellular carcinoma development at 1 year; (B) time-dependent AUROCs for predicting hepatocellular carcinoma development at 3 years; (C) time-dependent AUROCs for predicting hepatocellular carcinoma development at 5 years.

Figure 3 Cumulative incidence rates of hepatocellular carcinoma based on the REAL-B score.

Table 4 Changes in Factors Constituting HCC Prediction Model

Parameters	Baseline (n=252)	1 year of NA Therapy (n=252)	P-value
PLT, ×10^9/L	79 (62)	85.5 (64.25)	0.570
ALT, IU/L	36 (40.75)	26 (20.75)	<0.001*
AST, IU/L	45 (45.5)	35 (21.75)	<0.001*
Scr, μmol/L	78 (20)	82 (22)	0.003*
TBIL, μmol/L	22 (23.63)	19.6 (18.08)	0.178
ALB, g/L	34.9 (11)	38.5 (11.38)	<0.001*
ALP, IU/L	90 (46)	83.5 (55.75)	0.541
GGT, IU/L	47 (57.75)	33.5 (37.5)	<0.001*
HDL,mmol/L	1.02 (0.53)	1.01 (0.48)	0.946
LDL,mmol/L	1.94 (1.09)	2.01 (1.06)	0.422
INR	1.19 (0.23)	1.17 (0.24)	0.572
AFP, ng/mL	4.97 (24.13)	4.12 (7.11)	0.010*
HBV-DNA(log10 IU/mL)	4.35 (2.85)	0 (2)	<0.001*
AASL-HCC	20 (4)	20 (4)	0.030*
aMAP	63.74 (8)	69.97 (7.43)	0.093
CU-HCC	35 (20.5)	20.5 (20)	0.010*
CAMD	16 (4)	16 (4)	1.000
mPAGE-B	14 (4)	14 (4)	0.062
PAGE-B	18 (5)	18 (6)	0.748
RWS-HCC	6 (2.5)	5.5 (2.5)	0.385
REAL-B	7 (2)	7 (2)	0.733
THRI	297 (69)	297 (69)	0.777

Note: *Statistically significant P values.

Abbreviations: AFP, alpha-fetoprotein; ALB, albumin; ALT, alanine amino transferase; AST, aspartate aminotransferase; ALP, alkaline phosphatase; BMI, body mass index; GGT, γ-glutamyl transpeptidase; HCC, hepatocellular carcinoma; HDL, High-density lipoprotein cholesterol; INR, international normalized ratio; LDL, Low-density lipoprotein cholesterol; NA, nucleos(t)ide analogs; PLT, blood platelet; Scr, serum creatinine; TBIL, total bilirubin.

Table 5 Changes in Prediction Model of HCC

Parameters	Baseline (n=48)	1 Year of NA Therapy (n=48)	P-value
AASL-HCC	21 (3)	21 (2.75)	0.573
aMAP	64.78 (6.4)	65.04 (5.61)	0.889
CU-HCC	35 (20.75)	29.25 (20)	0.766
CAMD	16 (3)	16 (3)	1.000
mPAGE-B	15 (2)	15 (3)	0.832
PAGE-B	19 (5)	19 (5)	0.691
RWS-HCC	7 (1.87)	6.25 (2.5)	0.181
REAL-B	8 (2)	8 (2)	0.561
THRI	297 (77.25)	297 (69)	0.787

Abbreviation: NA, nucleos(t)ide analogs.