Direct-acting antiviral-based triple therapy on alpha-fetoprotein level in chronic hepatitis C patients

Table 1 Baseline demographic characteristics, classified by treatment

Baseline characteristics	Triple therapy (n = 88)	Dual therapy (n = 122)	P value
Age, yr	63 (53-68)	60 (52-65)	0.101
Male	37 (42.1)	52 (42.6)	0.933
Body weight, kg	56 (49-67)	58 (50-66)	0.782
Body mass index, kg/m2	22.7 (20.7-25.1)	22.8 (20.6-24.9)	0.859
Serum AFP level, ng/mL	4.5 (2.8-9.0)	4.0 (2.8-8.9)	0.677
Serum AFP level < 5 ng/mL	50 (56.8)	70 (57.4)	0.967
Serum AFP level 5-9.9 ng/mL	18 (20.5)	26 (21.3)
Serum AFP level ≥ 10 ng/mL	20 (20.7)	26 (21.3)
HCV RNA level, log10 IU/mL	6.5 (6.1-6.9)	6.3 (5.8-6.6)	0.010
HCV genotype 1a	1 (1.1)	3 (2.5)	0.476
HCV genotype 1b	87 (98.9)	119 (97.5)
Serum albumin, g/L	41 (38-43)	41 (39-43)	0.376
Alanine aminotransferase, U/L	46 (25-73)	51 (33-81)	0.176
Alanine aminotransferase ≥ 40 IU/L	49 (55.7)	78 (63.9)	0.228
γ-glutamyl-transpeptidase, U/L	39 (23-76)	37 (21-63)	0.199
Estimated glomerular filtration rate, mL/min per 1.73 m2	80 (68-94)	81 (71-94)	0.464
Total cholesterol, mg/dL	175 (153-192)	164 (146-192)	0.216
Triglycerides, mg/dL	94 (68-124)	79 (57-121)	0.070
Aspartate aminotransferase to platelet ratio index	0.86 (0.51-1.85)	0.76 (0.50-1.40)	0.306
White blood cell count, × 106/L	4780 (4038-5890)	4600 (3890-5645)	0.447
Hemoglobin level, g/L	137 (129-144)	135 (126-145)	0.319
Platelet count, × 109/L	156 (122-195)	178 (136-209)	0.040
Diabetes	10 (11.3)	7 (5.7)	0.144
Stage of fibrosis
F0-2	52 (81.2)	76 (90.5)	0.105
F3-4	12 (18.8)	8 (9.5)
Not determined, n	24	38
Previous treatment response
Naïve	25 (28.4)
Prior relapse	34 (38.6)
Prior NVR	27 (30.7)
Prior unknown response	2 (2.3)
IL28B SNP (rs8099917)
TT	49 (55.7)	73 (70.2)	0.113
TG/GG	39 (44.3)	31 (29.8)
Not determined, n	0	18

Data are presented at n (%) or as median (first- third quartiles) unless otherwise indicated. AFP: Alpha-fetoprotein; Dual therapy: Pegylated-interferon-α and ribavirin; HCV: Hepatitis C virus; IL28B: Interleukin 28B; NVR: Non-virological response; SNP: Single-nucleotide polymorphism; Triple therapy: Telaprevir-based therapy combined with pegylated-interferon-α and ribavirin.

Table 2 Sustained virological response rates n (%)

Group	Triple therapy		Dual therapy		P value
	n	SVR	n	SVR
All patients	88	75 (85.2)	122	52 (42.6)	< 0.001
Previous treatment response
Naïve/prior relapse	59	56 (94.9)
Prior NVR	27	17 (63.0)
Prior unknown response	2	2 (100)
IL28B SNP (rs8099917)
TT	49	48 (98.0)	73	45 (61.6)	< 0.001
TG/GG	39	27 (69.2)	31	1 (3.2)	< 0.001
Not determined, n	0	-	18	6 (33.3)	-
Stage of fibrosis
F0-2	52	48 (92.3)	76	43 (56.6)	< 0.001
F3-4	12	9 (75.0)	8	4 (50.0)	0.279
Not determined, n	24	18 (75.0)	38	5 (13.2)
Baseline HCV RNA level
≥ 6 log10 IU/mL	69	58 (84.1)	86	39 (45.3)	< 0.001
< 6 log10 IU/mL	19	17 (89.5)	36	23 (63.8)	0.032
Baseline platelet count
≥ 100 × 109/L	80	71 (88.8)	117	62 (53.0)	< 0.001
< 100 × 109/L	8	4 (50.0)	5	0 -	0.043
Baseline serum AFP level
< 10 ng/mL	68	63 (92.6)	96	49 (51.0)	< 0.001
≥ 10 ng/mL	20	12 (60.0)	26	3 (11.5)	< 0.001

Treatment response was analyzed by per-protocol analysis. AFP: Alpha-fetoprotein; Dual therapy: Pegylated-interferon-α and ribavirin; HCV: Hepatitis C virus; IL28B: Interleukin 28B; NVR: Non-virological response; SNP: Single-nucleotide polymorphism; Triple therapy: Telaprevir-based therapy combined with pegylated-interferon-α and ribavirin.

Table 3 Serum alpha-fetoprotein level change at each testing point

Group	Triple therapySerum AFP level (ng/mL)					Dual therapySerum AFP level (ng/mL)
	n	At baseline	At end of treatment	At 24 wk after the end of treatment	P value1	n	At baseline	At end of treatment	At 24 wk after the end of treatment	P value1
All patients	88	8.8 ± 1.4	5.1 ± 0.4	4.4 ± 0.4	< 0.001	122	7.8 ± 0.9	6.2 ± 1.3	7.0 ± 1.5	0.316
Treatment outcome
SVR	75	7.8 ± 1.5	4.5 ± 0.4	3.5 ± 0.2	0.004	52	4.7 ± 0.6	3.1 ± 0.2	2.8 ± 0.2	< 0.001
Non-SVR	13	14.3 ± 2.3	8.3 ± 1.1	9.5 ± 1.2	0.007	70	10.2 ± 1.5	8.7 ± 2.2	10.1 ± 2.5	0.953
Baseline AFP level
≥ 10 ng/mL	20	24.8 ± 4.4	10.5 ± 1.0	8.9 ± 0.8	0.003	26	21.8 ± 3.0	17.1 ± 5.3	20.2 ± 6.4	0.701
< 10 ng/mL	68	4.1 ± 0.2	3.4 ± 0.2	3.1 ± 0.2	< 0.001	96	4.1 ± 0.2	3.2 ± 0.2	3.4 ± 0.2	< 0.001
Previous treatment response
Naïve/prior relapse	59	8.8 ± 1.9	4.8 ± 0.5	3.8 ± 0.3	0.007
Prior NVR	27	9.1 ± 1.5	5.5 ± 0.8	5.8 ± 0.9	< 0.001
IL28B SNP (rs8099917)
TT	49	6.2 ± 1.0	3.9 ± 0.4	3.6 ± 0.3	< 0.001	73	6.0 ± 0.7	3.7 ± 0.3	3.9 ± 0.3	< 0.001
TG/GG	39	12.0 ± 2.8	6.5 ± 0.8	5.5 ± 0.6	< 0.001	31	10.2 ± 1.6	8.8 ± 2.9	9.3 ± 2.2	0.520
Stage of fibrosis
F0-2	52	6.5 ± 1.4	4.2 ± 0.5	3.3 ± 0.3	0.014	76	6.0 ± 0.7	3.7 ± 0.3	4.3 ± 0.5	< 0.001
F3-4	12	12.2 ± 3.0	6.5 ± 0.8	6.8 ± 1.1	0.023	8	13.6 ± 3.2	9.2 ± 3.2	9.9 ± 3.8	0.284

¹Between baseline and 24 wk after the end of treatment. Treatment response was analyzed by per-protocol analysis. Data are expressed as mean ± SE. Dual therapy: Pegylated-interferon-α and ribavirin; IL28B: Interleukin 28B; NVR: Non-virological response; SNP: Single-nucleotide polymorphism; SVR: Sustained virological response; Triple therapy: Telaprevir-based therapy combined with pegylated-interferon-α and ribavirin; AFP: Alpha-fetoprotein.

Table 4 Alanine aminotransferase level change at each testing point

Group	Triple therapyALT level (U/L)					Dual therapyALT level (U/L)
	n	At baseline	At end of treatment	At 24 wk after the end of treatment	P value1	n	At baseline	At end of treatment	At 24 wk after the end of treatment	P value1
All patients	88	56.6 ± 4.1	25.9 ± 2.4	22.7 ± 1.8	< 0.001	122	64.1 ± 4.7	29.4 ± 4.0	35.3 ± 3.0	< 0.001
Treatment outcome
SVR	75	54.3 ± 4.3	25.4 ± 2.7	17.8 ± 1.1	< 0.001	52	74.0 ± 7.3	18.8 ± 1.6	14.9 ± 0.8	< 0.001
Non-SVR	13	69.8 ± 12.2	28.8 ± 3.8	50.6 ± 6.0	0.147	70	56.8 ± 4.9	37.4 ± 6.7	50.4 ± 4.3	0.169
Baseline ALT level
≥ 40 U/L	49	81.4 ± 5.1	32.9 ± 3.5	28.5 ± 2.8	< 0.001	78	84.3 ± 5.4	36.6 ± 5.9	40.0 ± 4.2	< 0.001
< 40 U/L	39	25.4 ± 1.2	17.1 ± 2.6	15.4 ± 1.3	< 0.001	44	28.3 ± 1.1	16.0 ± 1.7	26.8 ± 3.0	0.637
Previous treatment response
Naïve/Prior relapse	59	56.5 ± 5.2	25.5 ± 2.7	19.4 ± 1.5	< 0.001
Prior NVR	27	56.7 ± 7.5	21.0 ± 2.5	28.6 ± 4.5	< 0.001
IL28B SNP (rs8099917)
TT	49	56.9 ± 5.4	26.6 ± 3.8	17.4 ± 1.3	< 0.001	73	63.6 ± 5.4	18.9 ± 1.4	25.9 ± 2.4	< 0.001
TG/GG	39	56.2 ± 6.5	24.9 ± 2.6	29.2 ± 3.5	< 0.001	31	65.9 ± 9.4	38.8 ± 6.2	50.9 ± 5.2	0.073
Stage of fibrosis
F0-2	52	51.6 ± 5.2	23.1 ± 3.2	17.6 ± 1.5	< 0.001	76	63.4 ± 5.4	21.1 ± 1.7	25.4 ± 2.4	< 0.001
F3-4	12	68.8 ± 11.6	32.3 ± 5.6	27.5 ± 5.4	0.008	8	93.0 ± 25.8	34.8 ± 7.6	46.5 ± 11.8	0.172

¹Between baseline and 24 wk after the end of treatment. Treatment response was analyzed by per-protocol analysis. Data are expressed as mean ± SE. Dual therapy: Pegylated-interferon-α and ribavirin; IL28B: Interleukin 28B; NVR: Non-virological response; SNP: Single-nucleotide polymorphism; SVR: Sustained virological response; Triple therapy: Telaprevir-based therapy combined with pegylated-interferon-α and ribavirin; ALT: Alanine aminotransferase.