Efficacy of direct-acting antiviral treatment for chronic hepatitis C: A single hospital experience

Table 1 Baseline demographics and patient characteristics

Parameter	Overall, n = 177	Genotype 1					Genotype 2 SOF/RBV n = 42
		IFN/TVR/RBV n = 5	IFN/SMV/RBV n = 11	DCV/ASV n = 43	LDV/SOF n = 66	OBV/PTV/r n = 10
Age, median1	67.8 (11.0)	62.9 (8.7)	60.2 (8.9)	72.7 (8.3)	66.0 (11.2)	70.9 (6.5)	67.5 (12.6)
> 65, n (%)	118 (66.7)	3 (60)	4 (36.4)	37 (88.1)	39 (59.0)	7 (70)	29 (67.4)
Sex, n (%)
Male	79 (44.6)	3 (60)	7 (63.6)	14 (32.6)	31 (47.0)	4 (40)	20 (47.6)
Female	98 (55.4)	2 (40)	4 (36.4)	29 (67.4)	35 (53.0)	6 (60)	22 (52.4)
HCV RNA, median Log10 LGE1	6.1 (0.8)	6.5 (0.56)	6.2 (1.1)	6.30 (0.5)	6.16 (0.6)	5.4 (0.9)	5.8 (0.9)
> 100000 IU/mL, n (%)	109 (61.6)	4 (80)	9 (81.8)	32 (76.2)	43 (0.7)	2 (20)	19 (45.2)
Cirrhosis present, n (%)
Yes	74 (41.8)	0 (0)	0 (0)	34 (79.0)	29 (44.0)	3 (30)	8 (18.6)
No	103 (58.2)	5 (100)	11 (100)	9 (20.1)	37 (56.0)	7 (70)	34 (81.4)
HCV treatment history, n (%)
Naïve	132 (74.6)	1 (20)	2 (18.2)	25 (58.1)	63 (95.5)	9 (90)	32 (76.2)
Prior IFN-based treatment	45 (25.4)	4 (80)	9 (81.8)	18 (41.8)	3 (4.5)	1 (1)	10 (23.8)
History of HCC, n (%)
Yes	26 (14.7)	1 (20)	0 (0)	19 (44.1)	3 (4.5)	0 (0)	3 (9)
No	151 (85.3)	4 (80)	11 (100)	24 (55.8)	63 (95.5)	10 (100)	39 (90.7)
Laboratory values
Baseline platelet count, mean (× 104/μL)1	15.1 (6.5)	15.4 (3.4)	15.1 (6.2)	11.5 (5.8)	15.5 (6.5)	18.0 (5.96)	17.6 (6.0)
Baseline ALT level, mean (IU/L)1	51.2 (37.3)	41.8 (9.7)	50.1 (50.5)	53.1 (27.8)	60.3 (45.2)	39.9 (26.8)	38.9 (28.6)
Baseline AFP level, mean (ng/mL)1	12.1 (17.6)	5.6 (1.6)	7.18 (9.1)	23.4 (27.2)	8.99 (11.6)	9.9 (11.6)	6.8 (6.9)

¹The standard deviation is given in parentheses. AFP: Alpha fetoprotein; ALT: Alanine aminotransferase; DCV/ASV: Daclatasvir/asunaprevir; HCV: Hepatitis C virus; IFN: Interferon; LDV/SOF: Ledipasvir/sofosbuvir; OBV/PTV/r: Ombitasvir/paritaprevir/ritonavir; RBV: Ribavirin; SMV: Simeprevir; TVR: Telaprevir.

Table 2 Baseline characteristics of IL28B and NS5A polymorphisms

	IFN/TVR/RBV n = 5	IFN/SMV/RBV n = 5
IL28B SNP (n)
rs8099917
T/T	4	1
T/G	1	2
G/G	0	1
rs11881222
A/A	4	1
A/G	0	2
G/G	1	1
rs88103142
T/T	4	1
T/C	1	2
C/C	0	1
NS5A aa701
Wild-type	3	0
Mutant	2	4
Competitive	0	1
NS5A aa911
Wild-type	3	0
Mutant	2	2
Competitive	0	3

¹aa HCV core amino acid. IFN: Interferon; RBV: Ribavirin; SMV: Simeprevil; TVR: Telaprevir.

Table 3 Response during and after treatment with direct-acting antivirals

Response	Overall, n = 119	Genotype 1			Genotype 2 SOF + RBV n = 42
		DCV/ASV n = 43	LDV/SOF n = 66	OBV/PTV/r n = 10
HCV RNA < LLOQ during treatment1, n (%)	119 (100)	41 (100)	66 (100)	9 (90)3	42 (100)
HCV RNA < LLOQ after end of treatment1, n (%)	118 (98.3)	42 (97.6)	66 (100)	9 (90)3	42 (100)
SVR122, n (%)	109 (91.6)	35 (83.3)	64 (97)	9 (90)3	42 (100)
On-treatment failure, n (%)	1 (0.8)	1 (2.3)	0 (0)	0 (0)	0 (0)
Relapse, n (%)	8 (6.7)	6 (16.7)	2 (3)	0 (0)	0 (0)

¹LLOQ (lower limit of quantification) = 25 IU/ML;

²SVR: Sustained virologic response;

³One case lost to follow-up. DCV/ASV: Daclatasvir/asunaprevir; LDV/SOF: Ledipasvir/sofosbuvir; OBV/PTV/r: Ombitasvir/paritaprevir/ritonavir; RBV: Ribavirin.

Table 4 NS5A RASs and clinical course in patients with failure of DAAs

Patient No.	Sex	Age in yr	LC1	HCC2	Initial DAA	NS5A RASs			Second DAA	Second result
						Before DAA	After DAA (invader)	After DAA (cycleave)
1	Female	73	No	No	DCV/ASV	NA	Y93H L31F Q54H A92V	Y93 mutant L31 mutant	LDV/SOF/RBV	SVR
2	Female	77	Yes	Yes	DCV/ASV	NA	Y93H L31M Q24Q/R	Y93 mutant L31 mutant	LDV/SOF/RBV	Relapse
3	Female	71	Yes	No	DCV/ASV	NA	NA	Y93 wild-type L31mutant	LDV/SOF/RBV	SVR
4	Female	78	Yes	No	DCV/ASV	NA	NA	Y93 mutant L31 mutant	LDV/SOF/RBV	SVR
5	Male	74	Yes	Yes	DCV/ASV	NA	Y93H L31V Q54y Q62D	Y93 mutant L31 mutant	LDV/SOF	SVR
6	Female	83	Yes	Yes	DCV/ASV	Y93Y/H L31L	Y93H L31M L31V	Y93 mutant L31 wild-type	No	NA
7	Male	71	Yes	No	DCV/ASV	Y93Y L31L	NA	Y93 wild-type L31 mutant	DCV-TRIO	Undergoing
8	Female	66	No	No	LDV/SOF	Y93Y L31L	NA	Failure	Waiting	NA
9	Male	78	Yes	Yes	LDV/SOF	NA	NA	Failure	Waiting	NA

¹Diagnosed as cirrhosis;

²A history of curative treatment for hepatocellular carcinoma. DAA: Direct-acting antivirals; DCV/ASV: Daclatasvir/asunaprevir; DCV-TRIO: Daclatasvir/asunaprevir/beclabuvir; LDV/SOF: Ledipasvir/sofosbuvir; NA: Data not available; RAS: Resistance-associated substitution; RBV: Ribavirin; SVR: Sustained virologic response. Failure: Could not be detected.

Table 5 Multivariable logistic regression models for SVR in patients with DCV/ASV

	Odds ratio	95%CI	P-value
Model 1: All variables
Platelet count	0.00	-0.01-0.27	0.71
AFP level	0.00	-0.00-0.01	0.44
ALT level	0.00	-0.00-0.01	0.31
HCV RNA level	0.26	0.02-0.45	0.04a
Age	0.02	-0.01-0.04	0.14
Sex	-0.13	-0.39-0.12	0.28
Y93	0.23	-0.31-0.77	0.38
L31	-0.17	-1.05-0.70	0.68
History of HCC	-0.29	-0.68-0.92	0.13
Cirrhosis	-0.30	-0.38-0.26	0.67
Prior IFN	-0.15	-0.41-0.99	0.21
Model 2: Limited suspicious covariates
Age	0.00	-0.13-0.14	0.93
Y93	0.48	0.08-0.87	0.02a
L31	-0.42	-1.09-0.24	0.2
Cirrhosis	-0.15	-0.37-0.08	0.19

Model 1: The baseline model considered with all covariates obtained. Model 2: Limited to covariates suspected from Table 4.

^aP < 0.05 were considered statistically significant. AFP: Alpha fetoprotein; ALT: Alanine aminotransferase; HCC: Hepatocellular carcinoma; IFN: Interferon.