Transient elastography and fibrosis-4 index as predictors of hepatocellular carcinoma in hepatitis C virus patients with sustained virological response

Table 1 Baseline demographic and clinical characteristics of the included hepatitis C virus sustained virological response patients (n = 425), mean ± SD/n (%)

Variables
Age, years	61 ± 10.2
Female sex	277 (65.2)
White non-Hispanic	240 (56.5)
Type 2 diabetes mellitus	156 (36.7)
BMI, kg/m2	27.98 ± 5.24
AST, U/L, median IQR	70 (45-108)
ALT, U/L, median IQR	86 (54-135)
Albumin, g/dL, median IQR	3.8 (3.5-4.1)
Total bilirubin, mg/dL, median IQR	0.7 (0.5-1)
INR, median IQR	1.1 (1-1.2)
Alpha-fetoprotein, ng/mL, median IQR	8.2 (4.7-15)
Pre-T F3	137 (32.2)
Pre-T F4	265 (67.8)
CSPH	85 (20)
Previous decompensation	15 (3.5)
LSM, kPa, median IQR	15 (11.8-23.2)
FIB-4 index, median IQR	2.94 (1.89-4.85)
Platelets, × 109/L	165 ± 71
Time of follow-up, months	48 ± 23
HCC	26 (6)
Time until HCC since EOT, months
≥ 12	9 (34.6)
≥ 24	17 (65.4)

IQR: Interquartile range; Pre-T: Pre-treatment; BMI: Body mass index; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; INR: International normalized ratio; CSPH: Clinically significant portal hypertension; LSM: Liver stiffness measure; FIB-4: Fibrosis-4; EOT: End of treatment; HCC: Hepatocellular carcinoma.

Table 2 Comparative demographic, clinical, liver stiffness measure, and fibrosis-4 index analysis according to hepatocellular carcinoma development (n = 425), mean ± SD/n (%)

Variables	People without incident HCC (n = 399)	People with incident HCC (n = 26)	P value
Age, years	60.8 ± 10.3	64.8 ± 6.0	0.004
Female sex	261 (65.4)	16 (61.5)	0.68
BMI, kg/m2	28.0 ± 5.3	26.9 ± 3.2	0.36
Type 2 diabetes mellitus	144 (36)	12 (46)	0.30
Pre-T platelets, 109/L	168 ± 71	113 ± 44	< 0.001
Pre-T AST, U/L, median IQR	70 (45-110)	101 (62-123)	0.04
Pre-T ALT, U/L, median IQR	88 (55-139)	102 (52-126)	0.85
Pre-T albumin, g/dL, median IQR	3.8 (3.5-4.1)	3.4 (3.1-3.9)	0.007
Pre-T LSM, kPa, median IQR	14.6 (11.8-22.2)	24.5 (14.2-34.6)	< 0.001
Pre-T FIB-4, median IQR	2.83 (1.84-4.6)	5.86 (4.37-9.15)	< 0.001
1yr-EOT-platelets, 109/L	178 ± 69	138 ± 37	0.005
1-year-EOT AST, median IQR	24 (20-31)	29 (31-39)	0.03
1-year-EOT ALT, median IQR	25 (19-33)	25 (19-32)	0.78
1-year-EOT albumin, median IQR	4.1 (3.9-4.4)	3.8 (3.7-4.3)	0.02
1-year-EOT LSM, kPa, median IQR	11.9 (7.8-18.8)	20.1 (13.9-35.5)	< 0.001
1-year-EOT FIB-4, median IQR	1.75 (1.22-2.63)	3.02 (2.3-5.3)	< 0.001

IQR: Interquartile range; Pre-T: Pre-treatment; BMI: Body mass index; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; LSM: Liver stiffness measure; FIB-4: Fibrosis-4; 1-year-EOT: One year after the end of treatment; HCC: Hepatocellular carcinoma.

Table 3 Cox regression models regarding pre-treatment liver stiffness measure and fibrosis-4 index as continuous or categorical variables

Covariates	HR (95%CI)	P value
Model 3a: LSM, kPa
Sex (male)	1.42 (0.63-3.2)	0.39
Pre-treatment LSM, kPa	1.05 (1.02-1.07)	< 0.001
Pre-treatment age, years	1.06 (1.01-1.11)	0.10
Model 3b: LSM ≥ 20 kPa
Sex (male)	0.72 (0.32-1.63)	0.43
Pre-treatment LSM ≥ 20 kPa	0.2 (0.08-0.47)	< 0.001
Pre-treatment age, years	1.06 (1.01-1.11)	0.02
Model 3c: FIB-4 index
Sex (male)	1.41 (0.57-3.49)	0.45
Pre-treatment age, years	1.06 (1.01-1.11)	0.22
Pre-treatment FIB-4 index	1.13 (1.05-1.21)	< 0.001
Model 3d: FIB-4 index ≥ 3.25
Sex (male)	1.81 (0.49-2.82)	0.71
Pre-treatment age, years	1.06 (1-1.11)	0.034
Pre-treatment FIB-4 index ≥ 3.25	7.79 (2.31-26.32)	< 0.001

HR: Hazard ratio; CI: Confidence interval; LSM: Liver stiffness measure; FIB-4: Fibrosis-4.

Table 4 Cox regression models regarding post-treatment liver stiffness measure and fibrosis-4 index as continuous or categorical variables

Covariates	HR (95%CI)	P value
Model 4a: LSM, kPa
Sex (male)	1.17 (0.57-2.42)	0.66
1-year-EOT LSM, kPa	1.04 (1.01-1.06)	< 0.001
Age at 1-year-EOT, years	1.04 (0.99-1.08)	0.05
Model 4b: LSM ≥ 20 kPa
Sex (male)	1.45 (0.71-2.95)	0.30
1-year-EOT LSM ≥ 20 kPa	4.49 (2.19-9.19)	< 0.001
Age at 1-year-EOT, years	1.04 (1.003-1.085)	0.03
Model 4c: FIB-4 index
Sex (male)	1.10 (0.60-2.01)	0.30
Age at 1-year-EOT, years	1.040 (1.002-1.080)	0.04
1-year-EOT FIB-4 index	1.16 (1.06-1.28)	< 0.001
Model 4d: FIB-4 index ≥ 3.25
Sex (male)	1.15 (0.63-2.09)	0.63
Age at 1-year-EOT, years	1.03 (0.99-1.07)	0.07
1-year-EOT FIB-4 index ≥ 3.25	3.14 (1.65-6.00)	< 0.001

HR: Hazard ratio; CI: Confidence interval; LSM: Liver stiffness measure; 1-year-EOT: One year after the end of treatment; FIB-4: Fibrosis-4.