Sustained virologic response to direct-acting antiviral agents predicts better outcomes in hepatitis C virus-infected patients: A retrospective study

Table 1 Characteristics of the patients treated for hepatitis C virus infection with direct-acting antiviral agents according to the sustained virologic response and hepatocellular carcinoma development during follow up

Variable	All patients (n = 380)	No SVR (n = 18)	SVR (n = 362)	P value	No HCC (n = 363)	HCC (n = 17)	P value
General clinical characteristics
Age (yr)	60 ± 13	62 ± 10	59 ± 13	NS	59 ± 13	61 ± 9	NS
Male, n (%)	224 (58.9)	14 (77.8)	210 (58.0)	NS	213 (58.7)	11 (64.7)	NS
BMI (kg/m2)	24.9 ± 3.7	24.6 ± 2.7	24.9 ± 3.7	NS	24.9 ± 3.7	24.2 ± 3.2	NS
Alcohol use, n (%)	17 (4.5)	2 (11.1)	15 (4.1)	NS	16 (4.4)	1 (5.9)	NS
Diabetes, n (%)	48 (12.6)	4 (22.2)	44 (12.1)	NS	44 (12.1)	4 (23.5)	NS
Plasma creatinine (mg/dL)	0.86 ± 0.24	1.03 ± 0.42	0.86 ± 0.23	NS	0.86 ± 0.24	0.97 ± 0.30	NS
eGFR (mL/min/1.73 m2)	87 ± 25	91 ± 18	87 ± 25	NS	87 ± 25	86 ± 16	NS
HCV infection-related variables
HCV viremia (n × 103)	956 (203-2944)	297 (47-1442)	977 (219-3059)	0.033	967 (219-3049)	244 (36-1864)	NS
HIV coinfection, n (%)	8 (2.1)	0	8 (100)	-	8 (100)	0	-
Previous use of interferon, n (%)	137 (36.0)	7 (38.9)	130 (35.9)	NS	129 (35.5)	8 (47.1)	NS
Use of ribavirin association, n (%)	89 (23.4)	5 (27.8)	84 (23.2)	NS	84 (23.1)	5 (29.4)	NS
SVR, n (%)	362 (95.3)	-	362 (100)	-	355 (97.8)	10 (58.8)	< 0.001
Time to SVR (wk)	12 (12-13)	-	12 (12-13)	-	12 (12-12)	15 (13-23)	< 0.001
HCV relapse, n (%)	20 (5.3)	12 (66.7)	8 (2.2)	< 0.001	13 (3.6)	7 (41.2)	< 0.001
Mixed cryoglobulinemia, n (%)	35 (9.2)	4 (22.2)	31 (8.6)	NS	30 (8.3)	5 (29.4)	0.014
Liver structure and function variables
Metavir score	2.6 ± 1.2	3.7 ± 0.6	2.6 ± 1.2	< 0.001	2.6 ± 1.2	3.9 ± 0.3	< 0.001
Cirrhosis, n (%)	122 (32.1)	14 (77.8)	108 (29.8)	< 0.001	107 (29.5)	15 (88.2)	< 0.001
Plasma albumin (g/L)	41.0 ± 5.4	37.6 ± 6.3	41.2 ± 5.3	0.027	41.4 ± 5.4	38.7 ± 5.0	0.047
Plasma total bilirubin (g/dL)	0.79 ± 0.41	0.92 ± 0.50	0.78 ± 0.41	NS	0.78 ± 0.41	0.94 ± 0.47	NS
Plasma alpha-fetoprotein (ng/mL)	4.10 (2.87-7.10)	6.30 (5.20-8.70)	4.10 (2.75-7.05)	0.012	4.10 (2.70-6.80)	8.00 (4.95-10.80)	0.001
Platelet count (n × 103/mL)	167 ± 67	114 ± 67	170 ± 66	0.003	170 ± 66	98 ± 62	< 0.001
INR	1.05 ± 0.12	1.14 ± 0.19	1.04 ± 0.11	0.038	1.05 ± 0.11	1.17 ± 0.17	0.013
HCC-related variables
Previous HCC, n (%)	8 (2.1)	3 (16.7)	5 (1.4)	0.004	5 (1.4)	3 (17.6)	0.004
HCC, n (%)	17 (4.5)	10 (55.5)	7 (1.9)	< 0.001	-	17 (100)	-
Time to HCC (wk)	26 (17-65)	25 (12-57)	40 (25-63)	NS	-	26 (17-65)	-
Death, n (%)	8 (2.1)	3 (16.7)	5 (1.4)	0.004	4 (1.1)	4 (23.5)	< 0.001
Time to death (wk)	65.5 (50.5-126.8)	40 (28-79)	76 (55-150)	NS	65 (55-95)	79 (34-127)	NS

HCV: Hepatitis C virus; SVR: Sustained virologic response; HCC: Hepatocellular carcinoma; BMI: Body mass index; eGFR: Estimated glomerular filtration rate; NS: Not significant; INR: International standardized ratio; HIV: Human immunodeficiency virus.

Table 2 Cox’s proportional hazards analysis for the combined endpoint of hepatocellular carcinoma occurrence or death from any cause

	Univariate analysis		Multivariate analysis
Variable	HR (95%CI)	P value	HR (95%CI)	P value
Age (yr)	1.003 (0.968-1.040)	0.862	1.008 (0.958-1.060)	0.760
Male (no/yes)	1.334 (0.538-3.308)	0.534	2.492 (0.683-9.089)	0.167
HCV viremia (log n)	0.811 (0.698-0.944)	0.007	0.808 (0.666-0.980)	0.030
Cirrhosis (no/yes)	9.259 (2.705-31.70)	< 0.001	3.392 (0.861-13.37)	0.081
Platelet count (n × 104/mL)	0.806 (0.735-0.885)	< 0.001	0.910 (0.831-0.996)	0.041
eGFR (10 mL/min/1.73 m2)	0.935 (0.780-1.122)	0.473	0.774 (0.596-1.005)	0.055
Mixed cryoglobulinemia (no/yes)	4.522 (1.822-11.23)	0.001	3.460 (1.035-11.56)	0.044
SVR (no/yes)	0.035 (0.015-0.084)	< 0.001	0.070 (0.025-0.194)	< 0.001

HCV: Hepatocellular C virus; SVR: Sustained virologic response; HR: Hazard ratio; CI: Confidence interval; eGFR: Estimated glomerular filtration rate.

Table 3 Multi-state Cox-Markov stratified hazards model for transitions in Figure 1

Variable	HR	95%CI	P value
Transition 1→2
Age (yr)	0.997	0.989-1.005	0.493
Male (no/yes)	0.789	0.615-1.013	0.062
HCV viremia (log n)	0.983	0.940-1.029	0.470
Cirrhosis (no/yes)	0.521	0.404-0.672	< 0.001
Mixed cryoglobulinemia (no/yes)	0.755	0.520-1.098	0.141
Platelet count (n × 104/mL)	1.019	1.002-1.036	0.026
eGFR (10 mL/min/1.73 m2)	1.003	0.998-1.008	0.235
Transition 1→3
Age (yr)	0.975	0.912-1.043	0.466
Male (no/yes)	2.040	0.249-16.74	0.507
HCV viremia (log n)	0.771	0.589-1.009	0.058
Cirrhosis (no/yes)	5.704	0.620-52.51	0.124
Mixed cryoglobulinemia (no/yes)	5.633	1.022-31.05	0.047
Platelet count (n × 104/mL)	0.928	0.981-1.005	0.229
eGFR (10 mL/min/1.73 m2)	1.007	0.970-1.045	0.726
Transition 2→3
Age (yr)	1.019	0.945-1.098	0.625
Male (no/yes)	3.613	0.692-18.88	0.128
HCV viremia (log n)	0.972	0.715-1.321	0.857
Cirrhosis (no/yes)	2.720	0.479-15.44	0.259
Mixed cryoglobulinemia (no/yes)	5.982	1.217-29.41	0.028
Platelet count (n × 104/mL)	0.958	0.935-0.982	< 0.001
eGFR (10 mL/min/1.73 m2)	0.948	0.915-0.985	0.005

HCV: Hepatitis C virus; HR: Hazard ratio; CI: Confidence interval; eGFR: Estimated glomerular filtration rate.