Importance of virological response in the early stage of telaprevir-based triple therapy for hepatitis C

Table 1 Patient characteristics

	All (n = 253)	SVR (n = 207)	Non-SVR (n = 46)	P value
Sex, male (%)	123 (48.6)	108 (52.2)	15 (32.6)	0.0153
Age (yr)	61 (12.5)	60 (12)	63.5 (11.25)	0.0340
Body mass index (kg/m2)	23.4 (3.9)	23.4 (3.9)	23.9 (3.8)	0.2198
Baseline HCV RNA (log10 IU/mL)	6.5 (0.9)	6.5 (0.9)	6.4 (0.7)	0.4468
IL28B SNP (rs8099917), TT/TG or GG (%)1	186/65 (74.1/25.9)	166/40 (80.6/19.4)	20/25 (44.4/55.6)	< 0.0001
ITPA SNP (rs1127354), CC/CA or AA (%)1	193/58 (76.9/23.1)	157/49 (76.2/23.8)	36/9 (80.0/20.0)	0.5802
Hemoglobin level (g/L)	138 (22)	140 (21)	134 (20)	0.0031
Platelet count (× 109/L)	157 (69)	159 (65)	129 (69)	0.0006
Serum albumin (g/L)	40 (6.0)	40 (6.0)	39 (5.0)	0.0143
Aspartate aminotransferase (U/L)	48 (42)	46 (43)	59 (34.5)	0.0350
Alanine aminotransferase (U/L)	54 (58)	53 (64)	58 (44)	0.4955
γ-glutamyl-transpeptidase (U/L)	40 (51)	39 (47)	46 (59)	0.1270
LDL-cholesterol (mg/dL)	95 (38)	98 (36)	75 (35)	< 0.0001
Ferritin (μg/L)	164.6 (232.3)	160.5 (223.2)	181.7 (253.9)	0.3583
Estimated glomerular filtration rate (mL/min per 1.73 m2)	79.4 (19.1)	79.7 (18.9)	77.7 (19.4)	0.6210
Response to previous PegIFN-α/RBV therapy				< 0.0001
Treatment naïve, n (%)	92 (36.4)	81 (39.4)	11 (23.9)
Prior relapse, n (%)	113 (44.7)	100 (48.1)	13 (28.3)
Prior non-response, n (%)	48 (19.0)	26 (12.5)	22 (44.8)
Liver histology
Stage, F0-2/F3-4 (%)	96/58 (62.3/37.7)	87/38 (69.6/30.4)	9/20 (31.0/69.0)	< 0.0001
Grade, A0-1/A2-3 (%)	54/100 (35.1/64.9)	45/80 (36.0/64.0)	9/20 (31.0/69.0)	0.614
Not determined, n	99	82	17

¹IL28B and ITPA SNPs were not available for only two patients (1.2%). Continuous variables are expressed as median (interquartile range). P value draws a comparison between SVR and non-SVR patients. SVR: Sustained virological response; HCV: Hepatitis C virus; IL28B: Interleukin 28B; SNP: Single-nucleotide polymorphism; ITPA: Inosine triphosphate pyrophosphatase; LDL: Low-density lipoprotein; PegIFN: Pegylated interferon; RBV: Ribavirin.

Table 2 Precision rate for the prediction of sustained virological response and non-sustained virological response in the early stage of telaprevir-based triple therapy

	Patients who achieved SVR/patients with VR, n	PPV (%)	Patients who did not achieve SVR/patients without VR, n	NPV (%)	Kappa coefficient (95%CI)
Week 1	14/14	100	45/222	20.3	0.03 (0.01-0.05)
Week 2	52/52	100	44/185	23.8	0.12 (0.08-0.16)
Week 3	113/124	91.1	33/109	30.3	0.22 (0.12-0.33)
Week 4	168/182	92.3	26/64	40.6	0.38 (0.24-0.51)
Week 6	202/228	88.6	14/17	82.4	0.44 (0.27-0.61)
Week 8	200/232	86.2	5/8	62.5	0.18 (0.02-0.34)
Week 12	198/234	84.6	1/1	100	-

PPV: Positive predictive value, the probability that a patient with a given on-treatment virological response (VR) will achieve sustained virological response (SVR); NPV: Negative predictive value, the probability that a patient without a given on-treatment VR will not achieve SVR.

Table 3 Factors contributing to sustained virological response

	Univariate analysis		Multivariable analysis
	OR	P value	OR (95%CI)	P value
Sex (male to female)	2.25	0.0153
Age (< 60 yr to ≥ 60 yr)	1.79	0.0822
IL28B SNPs (rs8099917) (TT to TG/GG)	5.19	< 0.0001	8.24 (2.81-26.8)	< 0.0001
Hemoglobin level (≥ 140 g/L to < 140 g/L)	2.13	0.0245
Platelet count (≥ 150 × 109/L to < 150 × 109/L)	3.21	0.0005
Serum albumin (> 35 g/L to ≤ 35 g/L)	2.51	0.0308
Aspartate aminotransferase (< 50 U/L to ≥ 50 U/L)	2.30	0.0123
LDL-cholesterol (≥ 95 mg/dL to < 95 mg/dL)	4.39	< 0.0001
Response to previous PegIFN-α/RBV therapy (naïve/relapse to non-response)	6.38	< 0.0001	3.29 (1.14-9.46)	0.0281
VR at week 6	31.1	< 0.0001	63.8 (10.8-563)	< 0.0001

P value draws a comparison between SVR and non-SVR patients. SVR: Sustained virological response; IL28B: Interleukin 28B; SNP: Single-nucleotide polymorphism; LDL: Low-density lipoprotein; PegIFN: Pegylated interferon; RBV: Ribavirin; VR: Virological response.