Impact of hepatitis C virus core mutations on the response to interferon-based treatment in chronic hepatitis C

Table 1 Demographic, clinical and virological characteristics of study patients n (%)

Characteristics	Total	IL28B CC	IL28B non-CC	P value
	n = 108	n = 19	n = 89
Age (yr), median	53.5 (22.0-68.3)	48.2 (22.1-66.4)	53.8 (22.1-68.3)	0.137
Female	64 (59.3)	8 (42.1)	56 (62.9)	0.094
Residence urban	78 (72.2)	17 (87.5)	61 (68.5)	0.090
Baseline ALT (mg/dL), median	76.5 (16-890)	103 (16-890)	74 (17-256)	0.031
Baseline HCV-RNA (log10IU/mL), median	6.1 (4.15-7.3)	6.2 (4.15-7.2)	6.1 (4.15-7.3)	0.333
Mild/moderate fibrosis	38 (58.5)	9 (69.23)	29 (55.8)	0.470
Absence of core mutations - DW	13 (12.0)	6 (31.6)	7 (7.9)	0.011
RVR (%)	14 (13.0)	7 (36.8)	7 (7.9)	0.003
EVR (%)	43 (39.8)	16 (84.2)	27 (30.3)	< 0.001
SVR (%)	42 (38.9)	17 (89.5)	25 (28.1)	< 0.001

HCV: Hepatitis C virus; DW: Double wild-type; SVR: Sustained virological response; EVR: Early virological response; RVR: Rapid virologic response.

Table 2 Patients characteristics related to core mutation type, univariate analysis

Characteristics	Patients withDW-type infectionn = 13	Patients with R70Q/H and/or L91Msubstitutions n =95	Patients withL91M substitutionn = 40	Patients with R70Q/H substitution n = 8	P value1
Age (yr)	51.5	53.6	53.3	50	a = 0.607
median	(29.1-66.54)	(22.1-68.3)	(24.4-67.3)	(33.8-58.8)	b = 0.694
					c = 0.860
Gender	7 (53.8)	57 (60)	22 (55)	5 (62.5)	a = 0.767
Female (%)					b = 1.000
					c = 1.000
Residence	11 (84.6)	67 (70.5)	33 (82.5)	5 (62.5)	a = 0.509
Urban (%)					b = 1.000
					c = 0.325
Baseline ALT (mg/dL)	94	76	78	67	a = 0.592
median	(3-235)	(16-890)	(17-890)	(54-197)	b = 0.849
					c = 1.000
Baseline HCV-RNA (log10IU/mL), median	6.25	6.05	6.05	6.3	a = 0.966
	(4.15-6.9)	(4.15-7.3)	(4.1-7.3)	(5.2-7.1)	b = 1.000
					c = 0.414
Mild/moderate fibrosis (F1 + F2, %)	4 (57.1)	34 (58.6)	14 (58.3)	4 (57.14)	a = 0.881
					b = 0.925
					c = 0.283
IL28B CC (%)	6 (46.2)	13 (13.7)	8 (20.0)	1 (12.5)	a = 0.011
					b = 0.080
					c = 0.174
RVR (%)	6 (46.2)	8 (8.4)	4 (10.0)	0 (0.0)	a = 0.002
					b = 0.009
					c = 0.005
EVR (%)	10 (76.9)	33 (34.7)	15 (37.5)	3 (37.5)	a = 0.005
					b = 0.024
					c = 0.164
SVR (%)	10 (76.9)	32 (33.7)	15 (37.5)	2 (25.0)	a = 0.005
					b = 0.024
					c = 0.032

¹P value symbols a, b, c: cases from each category type of viral substitutions (columns 3, 4, 5) vs cases without viral mutation [double wild-type (DW)-type - column 2]. HCV: Hepatitis C virus; SVR: Sustained virological response; EVR: Early virological response; RVR: Rapid virologic response.

Table 3 Predictive factors for sustained virological response, univariate analysis n (%)

Variable	SVR n = 42	No SVR n = 66	P value
Age (yr), median	48.1 (22.1-68.3)	54.7 (22.1-67.3)	< 0.001
Female gender	22 (52.4)	42 (63.6)	0.246
Urban residence (%)	37 (88.1)	41 (62.1)	0.004
Baseline ALT (mg/dL), median	79 (16-890)	75 (17-231)	0.688
Baseline HCV-RNA, median	6.2 (4.15-7.3)	6.2 (4.8; 7.3)	0.167
Mild/moderate fibrosis	18 (75.0)	20 (48.8)	0.107
IL28B type CC (%)	17 (40.5)	2 (3.0)	< 0.001
Absence of core mutations - DW	10 (23.8)	3 (4.5)	0.005
Presence of any core mutation, (%)	32 (76.2)	63 (95.5)	0.005
Viral mutation in core 91 only (%)	15 (60.0)	25 (84.3)	0.024
Viral mutation in core 70 only (%)	2 (16.7)	6 (66.7)	0.032
RVR (%)	13 (31.0)	1 (1.5)	< 0.001
EVR (%)	37 (88.1)	6 (9.1)	< 0.001

HCV: Hepatitis C virus; DW: Double wild-type; SVR: Sustained virological response; EVR: Early virological response; RVR: Rapid virologic response.

Table 4 Multivariate analysis on independent predictive factors for sustained virological response

Variable	Adjusted OR	95%CI	P value
Age (< 50 yr)	0.976	0.967-0.986	< 0.001
Absence of core mutations	4.710	1.10-21.30	0.04
IL28B polymorphism	19.200	4.05-91.40	< 0.001