Direct-acting antivirals failed to reduce the incidence of hepatocellular carcinoma occurrence in hepatitis C virus associated cirrhosis: A real-world study

Table 1 Baseline characteristics of the direct-acting antiviral agents treatment group (n = 236) and the non-antiviral treatment group (n = 118), n (%)

Variables	DAA treatment(n = 236)	Non-antiviral (n = 118)	t/Z/χ2	P value
Ages (yr)	55.01 ± 9.52	53.69 ± 10.07	1.208	0.228
Male	120 (50.85)	68 (57.63)	1.452	0.228
Cirrhosis (compensate)	187 (79.24)	90 (76.27)	0.407	0.524
Nonspecific liver nodules	191 (80.25)	100/18 (15.13)	0.782	0.377
Child-Pugh (A/B/C)	177/51/8	83/30/5	0.887	0.642
Genotype (1a/1b/2a/3a/3b/6a)	1/156/48/11/11/9	0/73/21/7/7/10	4.663	0.458
lg (HCV RNA) IU/mL	6 (5.6)	5 (4.6)	-2.191	0.028
Along with the disease
Diabetes	51 (21.61)	30 (25.42)	0.648	0.421
Fatty liver	52 (22.03)	13 (11.02)	6.370	0.012
Hypertension	50 (21.19)	23 (19.49)	0.138	0.710
FIB-4	5.27 (3.51, 8.16)	4.94 (2.30, 6.38)	-0.032	0.975
CEA (ng/mL)	3.27 (2.22, 4.86)	2.76 (1.45, 4.70)	-1.015	0.310
AFP (ng/mL)	9,28 (5.15, 19.60)	9.58 (4.27, 17.89)	-2.919	0.004
PIVKA-II (mAU/mL)	24 (18, 32)	24 (21, 35.5)	-1.190	0.234
PLT (109/L)	108.02 ± 61.66	110.66 ± 65.68	-0.342	0.733
CAP (dB/m)	232.76 ± 45.35	241.15 ± 53.59	-0.986	0.325
LSM (kPa)	26.15 ± 16.90	29.50 ± 16.61	-1.269	0.206

DAAs: Direct-acting antiviral agents; HCV RNA was calculated by denary logarithm expressed as lg (HCV RNA); FIB-4: The Fibrosis-4 index; ALBI: The albumin-Bilirubin score; CEA: Carcinoembryonic antigen; AFP: Alpha fetoprotein; PIVKA-II: Vitamin K Absence or Antagonist-II; PLT: Platelet; CAP: Controlled attenuation parameter; LSM: Liver stiffness measurement; PSM: Propensity score matching.

Table 2 Changes of laboratory parameters before and after sustained virologic response in the direct-acting antiviral agents treatment group (n = 236)

Variables	Before DAA	After DAA	t/Z/χ2	P value
ALT (U/L)	52 (34, 84.25)	20.5 (16, 32)	12.962	0
AST (U/L)	59.5 (40, 83.5)	26 (20.2, 39)	14.351	0
γ-GT (U/L)	58 (34.75, 108.5)	34 (23, 54)	8.691	0
ALP (U/L)	86 (65.75, 113.25)	83.9 (64, 115)	2.236	0.025
TP (g/L)	71.93 ± 8.23	73.62 ± 7.88	-2.267	0.024
ALB (g/L)	38.78 ± 6.22	42.93 ± 7.08	-6.755	0
TBIL (μmol/L)	18.6 (14.5, 27.5)	23.7 (13.3, 41)	-1.452	0.146
BUN (mmol/L)	4.98 ± 2.24	5.83 ± 3.70	-2.969	0.003
GLU (mmol/L)	6.34 ± 1.98	6.93 ± 2.44	-2.717	0.007
PT (s)	14.41 ± 2.16	14.30 ± 6.35	0.16	0.873
INR	1.27 ± 1.22	1.21 ± 0.56	0.444	0.557
WBC (109/L)	4.39 ± 1.69	4.93 ± 2.13	-3.066	0.002
RBC (1012/L)	4.14 ± 0.75	4.27 ± 0.79	-1.803	0.072
HGB (g/L)	130.33 ± 23.05	131.91 ± 25.07	-0.706	0.481
PLT (109/L)	108.20 ± 61.66	123.45 ± 65.98	-2.57	0.01
CEA (ng/mL)	3.3 (2.22, 4.89)	3.34 (2.3, 5.27)	-0.111	0.911
AFP (ng/mL)	9.38 (5.31, 19.67)	5.81 (3.6, 9.02)	9.683	0
PIVKA-II (mAU/mL)	24 (18,32)	28 (20,41)	-1.958	0.05
CAP (dB/m)	232.76 ± 45.35	239.56 ± 45.35	-2.062	0.04
LSM (kPa)	26.15 ± 16.90	20.55 ± 16.95	3.499	0.001

SVR: Sustained virologic response; DAA: Direct-acting antiviral agents; HCV RNA was calculated by denary logarithm expressed as lg (HCV RNA); CEA: Carcinoembryonic antigen; AFP: Alpha fetoprotein; PIVKA-II: Vitamin K Absence or Antagonist-II; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; γ-GT: γ-alanine transferase; ALP: Alkaline phosphatase; TP: Total protein; ALB: Albumin; TBIL: Total bilirubin; BUN: Renal function; GLU: Blood glucose; PT: Prothrombin time; INR: International standardized ratio of prothrombin time; WBC: White blood cell; RBC: Red blood cell; HGB: Hemoglobin; PLT: Platelet; CAP: Controlled attenuation parameter; LSM: Liver stiffness measurement.

Table 3 Factors of hepatocellular carcinoma occurrence in all patients with hepatitis C virus associated cirrhosis (n = 427)

Variables	Univariate			Multivariate
	HR	95%CI	P value	HR	95%CI	P value
DAA treated	0.478	0.245-0.933	0.03
Ages (yr)	1.052	1.019-1.087	0.002	1.089	1.033-1.147	0.002
Gender (M/F)	1.297	0.750-2.242	0.352
Cirrhosis (compensate/de)	2.312	1.271-4.207	0.006
nonspecific nodules (Y/N)	3.112	1.734-5.586	0
Child-Pugh (A/B/C)	2.184	1.416-3.367	0
Fatty liver	0.686	0.271-1.738	0.427
FIB-4	1.063	1.026-1.101	0.001
AFP (ng/mL)	0.994	0.981-1.008	0.419
AST (U/L)	1.005	0.999-1.010	0.126
ALB (g/L)	0.922	0.885-0.961	0
TIBL (μmol/L)	1.015	1.007-1.022	0
PT	1.23	1.083-1.398	0.001
PLT	0.992	0.986-0.997	0.005
LSM	1.038	1.018-1.058	0	1.043	1.022-1.065	0

HCC: Hepatocellular carcinoma; HR: Hazard ratio; DAA: Direct-acting antiviral agents; FIB-4: The Fibrosis-4 index; ALBI: The albumin-Bilirubin score; AFP: Alpha fetoprotein; AST: Aspartate aminotransferase; ALB: Albumin; TBIL: Total bilirubin; EOT: End of treatment; PLT: Platelet; PT: Prothrombin time; LSM: Liver stiffness measurement.