Acoustic radiation force impulse predicts long-term outcomes in a large-scale cohort: High liver cancer, low comorbidity in hepatitis B virus

Table 1 Baseline demographic features of the cohort

	HBV (n = 1064)	HCV (n = 507)	NBNC (n = 391)	P value	Missing rate
Demographics
Age (yr)	52.05 ± 10.90	58.69 ± 10.84	51.97 ± 13.10	< 0.0001 (2 & 3, 1 & 2)	0.00%
Male sex, n (%)	825 (77.5)	273 (53.8)	233 (59.6)	< 0.0001	0.00%
Weight (kg)	68.36 ± 12.30	64.53 ± 12.17	70.94 ± 14.09	< 0.0001 (2 & 3, 1 & 2, 1 & 3)	0.97%
Height (cm)	166.34 ± 7.62	161.67 ± 8.57	164.18 ± 8.75	< 0.0001 (2 & 3, 1 & 2, 1 & 3)	2.80%
BMI (kg/m2)	24.66 ± 3.62	24.58 ± 3.75	26.25 ± 4.23	< 0.0001 (2 & 3, 1 & 3)	3.47%
Lab data at ARFI study
Spleen index (cm2)	31.97 ± 14.47	33.63 ± 16.72	34.07 ± 16.05	0.0640 (1 & 3)	0.03%
Albumin (mg/dL)	4.345 ± 0.51	4.29 ± 0.51	4.43 ± 0.48	0.0040 (2 & 3)	42.15%
AST (U/L)	57.50 ± 102.16	62.46 ± 58.08	58.40 ± 50.72		1.12%
ALT (U/L)	75.05 ± 162.88	71.52 ± 69.61	83.46 ± 78.32		1.33%
Bilirubin (mg/dL)	0.93 ± 1.23	0.91 ± 1.19	0.92 ± 1.21		12.79%
Prothrombin time (INR)	1.10 ± 0.13	1.11 ± 0.21	1.06 ± 0.13	0.0040 (2 & 3, 1 & 3)	42.15%
Platelets (109/L)	177.86 ± 61.86	170.13 ± 60.19	218.96 ± 76.08	< 0.0001 (2 & 3, 1 & 3)	13.25%
FIB4	2.454 ± 2.720	3.31 ± 3.04	2.06 ± 2.13	< 0.0001 (2 & 3, 1 & 2)	23.35%
Mean ARFI (m/s)1	1.40 ± 0.46	1.60 ± 0.61	1.42 ± 0.62	< 0.0001 (2 & 3, 1 & 2)	0.00%
Stiffness status1				< 0.0001
Cirrhosis	331 (31.1)	163 (32.1)	78 (19.9)
Severe fibrosis	138 (13.0)	110 (21.7)	61 (15.6)
Moderate fibrosis	114 (10.7)	68 (13.4)	29 (7.4)
Mild or non-fibrosis	481(45.2)	166(32.7)	223(57.0)
Comorbidities
Hypertension	181 (17.0)	147 (29.0)	115 (29.4)	< 0.0001
Diabetes	119 (11.2)	103 (20.3)	76 (19.4)	< 0.0001
Heart failure	14 (1.3)	17 (3.4)	7 (1.8)	0.023
Atrial fibrillation	9 (0.8)	11 (2.2)	5 (1.3)	0.091
Myocardial infraction	12 (1.1)	5 (1.0)	2 (0.5)	0.567
Ischemic stroke	6 (0.6)	17 (3.4)	8 (2.0)	< 0.0001
Dyslipidemia	170 (16.0)	95 (18.7)	125 (32.0)	< 0.0001
Follow-up (year)
mean ± SD	4.59 ± 2.22	4.34 ± 2.35	3.13 ± 2.15	< 0.0001 (1 & 3, 2 & 3)
Median/IQR	4.54/3.59	3.97/3.88	2.61/3.23

¹Cutoff values according to reference 11.

ARFI: Acoustic radiation force impulse; FIB4: Fibrosis-4 index; BMI: Body mass index; HBV: Hepatitis B; HCV: Hepatitis C; NBNC: Non-hepatitis B, non-hepatitis C; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase.

Table 2 Cancers and mortality in different groups

	HBV	HCV	NBNC	P value
Total cases	1064	507	391
Female	239 (22.5)	234 (46.2)	158 (40.4)	< 0.027
Follow years before enrollment	-2.65 ± 3.98	-2.78 ± 5.56	-3.30 ± 6.25	< 0.001 (3 & 1, 3 & 2)
Cancers, pre-enrollment
HCC	150 (14.1)	42 (8.3)	20 (5.1)	< 0.001
Non-HCC cancer	36 (3.4)	30 (5.9)	39 (10.0)	< 0.001
Colon cancer	9 (0.8)	3 (0.6)	6 (1.5)	NS
Breast cancer	1 (0.1)	9 (1.8)	17 (4.3)	< 0.0011
Hematology cancers	3 (0.3)	4 (0.8)	2 (0.5)	NS
Follow years before enrollment	-2.76 ± 4.55	-3.57 ± 5.18	-3.22 ± 4.40	NS
Cancers, post-enrollment
HCC	43 (4.0)	19 (3.7)	5 (1.3)	0.033
Non-HCC tumor	21 (2.2)	14 (2.8)	12 (3.1)	NS
Colon cancer	2 (0.1)	3 (0.6)	1 (0.3)	NS
Breast cancer	2 (0.2)	0 (0.0)	1 (0.3)	NS
Hematology cancers	6 (0.6)	0 (0.0)	1 (0.5)	NS
Prostate cancer	2 (0.1)	1 (0.2)	1 (0.3)	NS
Follow years after enrollment	2.43 ± 1.86	2.51 ± 1.86	2.25 ± 2.00	NS
Mortality total	72 (6.8)	41 (8.1)	21 (5.4)	NS
HCC	35 (3.3)	13 (2.6)	4 (1.0)2	0.057
Non-HCC cancers	16 (1.5)	8 (1.6)	7 (1.8)2	NS
Liver disease	6 (0.6)	7 (1.4)	6 (1.5)	NS
Non-liver disease	15 (1.4)	13 (2.6)	4 (1.0)	NS
Follow years after enrollment	2.59 ± 1.96	2.69 ± 1.99	2.00 ± 1.87	NS

¹Female only.

²P = 0.027.

Remark: Different cancers on the same patient were counted separately. HCC: Hepatocellular carcinoma; HBV: Hepatitis B; HCV: Hepatitis C; NBNC: Non-hepatitis B, non-hepatitis C; NS: Not significant.

Table 3 Logistic regression for hepatocellular carcinoma diagnosed before enrollment

	Univariate analysis	Multivariate analysis		95%CI
	P value	P value	Hazard ratio	Lower	Upper
Male	< 0.001	0.000	3.399	2.150	5.373
Etiology	< 0.001	0.000	-	-	-
HBV		0.000	4.009	2.219	7.241
HCV		0.169	1.644	0.810	3.335
Age, yr	< 0.001	0.000	1.047	1.029	1.066
ALT	0.243	0.001	0.993	0.989	0.997
AST	0.010	0.000	1.012	1.007	1.017
Bilirubin	0.170	0.729	0.980	0.875	1.098
Platelet	0.138	0.035	1.003	1.000	1.005
Spleen index	0.060	0.811	1.001	0.990	1.013
BMI	0.015	0.076	0.956	0.910	1.005
ARFI	< 0.001	0.010	1.556	1.110	2.181
Interferon therapy	0.011	0.012
Pre-enrollment		0.618	1.204	0.581	2.496
Post-enrollment		0.004	0.211	0.073	0.617
Oral anti-virus agents	0.041	0.181
Pre-enrollment		0.168	1.721	0.795	3.728
Post-enrollment		0.156	0.667	0.381	1.167
Pre- and post-enrollment		0.527	1.534	0.408	5.773
Hypertension	< 0.001	0.000	2.551	1.702	3.824
Diabetes mellitus	< 0.001	0.031	1.618	1.044	2.508
Dyslipidemia	< 0.001	0.000	0.358	0.207	0.620
Ischemic stroke	0.341	0.884	1.097	0.317	3.794

1481/1962 (75.5%) with complete data; cases (hepatocellular carcinoma), n = 189. HBV: Hepatitis B; HCV: Hepatitis C; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; BMI: Body mass index; ARFI: Acoustic radiation force impulse.

Table 4 Cox’s regression analysis for hepatocellular carcinoma occurring after enrollment

	Univariate analysis	Multivariate analysis		95%CI
	P value	P value	Hazard ratio	Lower	Upper
Male	0.005	0.009	20.796	1.293	6.045
Etiology	0.019	0.057
HBV		0.023	40.473	1.232	16.245
HCV		0.150	20.670	0.701	10.173
Age (yr)	< 0.001	0.094	10.028	0.995	1.061
ALT (U/L)	0.188	0.211	0.994	0.985	1.003
AST (U/L)	0.605	0.449	10.005	0.993	1.017
Bilirubin (mg/dL)	0.962	0.326	0.772	0.460	1.295
Platelet (109/L)	< 0.001	0.041	0.993	0.986	1.000
Spleen index (cm2)	0.019	0.169	10.012	0.995	1.030
BMI	0.334	0.524	0.973	0.894	1.059
ARFI (m/s)	< 0.001	0.000	20.775	10.624	4.742
Interferon therapy	0.814	0.943
Pre-enrollment		0.734	0.772	0.174	3.435
Post-enrollment		0.914	0.949	0.366	2.459
Oral anti-virus therapy	0.0174	0.086
Pre-enrollment		0.977	10.031	0.134	7.948
Post-enrollment		0.029	20.105	10.080	4.102
Pre- and post-enrollment		0.110	30.362	0.758	14.903
Hypertension	0.001	0.211	10.554	0.778	3.104
Diabetes mellitus	0.002	0.304	10.460	0.710	3.006
Ischemic stroke	0.305	0.971	00.000	0.000	1.46E+269
Dyslipidemia	0.233	0.065	10.920	0.960	3.840

1274/1749 (72.8%) with complete data, 49 cases (hepatocellular carcinoma). HBV: Hepatitis B; HCV: Hepatitis C; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; BMI: Body mass index; ARFI: Acoustic radiation force impulse.