Role of IL-28B polymorphisms in virologic response to combined pegylated interferon and ribavirin therapy in genotype 4 chronic HCV infected patients with and without cirrhosis

Peer review under responsibility of Alexandria University Faculty of Medicine.

Available online 17 October 2014

Figures & data

Table 1 Demographic and biochemical features of patients included in this study.

Parameter	Group		Test of significance (p Value)
	Chronic HCV + cirrhosis (n = 30)	Chronic HCV (n = 30)
Age (years)	45.3 ± 7.7	49 ± 7.7	Z = 2.01 (0.045)
Female (N/%) (17/28.3)	8 (26.7)	9 (30)	X^2 = 0.08
Male (N/%) (43/71.7)	22 (73.3)	21 (70)	p = 0.774
BMI (kg/m^2)	28 ± 3.1	28.4 ± 2.9	Z = 0.75 (0.451)
AST(IU/L)	53 ± 23.7	47.3 ± 38.6	Z = 2.20 (0.028)
Alb (g/dl)	3.4 ± 0.4	4.1 ± 0.53	Z = 1.19 (0.233)
GGTP (IU/L)	60.6 ± 47.3	72.8 ± 92.5	Z = 0.34 (0.734)
TLC count (×10^3/mm^3)	4.50 ± 1.43	4.89 ± 1.61	Z = 0.98 (0.328)
Hb (g/dl)	12.7 ± 1.3	12.7 ± 1.6	Z = 0.26 (0.796)
Platelets (×10^3/mm^3)	179.8 ± 63	183.5 ± 60.1	Z = 0.18 (0.859)
INR	1.1 ± 0.1	1.1 ± 0.0	Z = 1.61 (0.107)
PT	13.06 ± 1.37	12.29 ± 0.41	Z = 1.82 (0.069)
PCR-HCV (×10^6 IU/ml)	1.3 ± 1.4	1.8 ± 3.4	Z = 0.03 (0.976)
AFP(ng/ml)	9.1 ± 22.1	10.6 ± 22.2	Z = 0.26 (0.796)
Schistosomal serology (N/%)
Negative (43/71.7)	17 (56.7)	26 (86.7)	X^2 = 6.65
Positive (17/28.3)	13 (43.3)	4 (13.3)	p = 0.010
Cholesterol (mg/dl)	149.4 ± 38.9	151.6 ± 30.6	Z = 0.40 (0.690)
HDL (mg/dl)	48.2 ± 18.2	53.9 ± 18.8	Z = 1.37 (0.171)
LDL (mg/dl)	78.9 ± 27.0	75.9 ± 29.8	Z = 0.53 (0.600)
IR	4.8 ± 10.2	2.4 ± 1.4	Z = 0.27 (0.784)
IL28B genotypes (N/%)
CC (18/30)	11 (36.7)	7 (23.3)	MCp = 0.471
CT (34/56.7)	16 (53.3)	18 (60)
TT (8/13.3)	3 (10)	5 (16.7)
SVR12 (N/%)
Responders (35/58.3)	12 (40)	23 (76.7)	X^2 = 8.5
Non responders (25/41.7)	18 (60)	7 (23.3)	p = 0.004
SVR24 (N/%)
Responders (38/63.3)	14 (46.7)	24 (80)	X^2 = 7.18
Non responders (22/36.7)	16 (53.3)	6 (20)	p = 0.007

Note: BMI: body mass index, (calculated as the square of height in meters divided by weight in kilograms), AST: aspartate aminotransferase, Alb: albumin, GGTP: gamma-glutamyl transpeptidase, TLC: total leukocytic count, Hb: hemoglobin, PT: prothrombin time, AFP: alpha fetoprotein, HDL: high-density lipoprotein, LDL: low-density lipoprotein, IR: insulin resistance, SVR12: sustained virologic response 12 weeks after the completion of HCV, SVR24: sustained virologic response 24 weeks after the completion of HCV therapy. Data are presented as mean ± SD unless otherwise indicated.

Table 2 Relationship between SVR12 and demographic and biochemical variables among both studied groups.

Parameter	Chronic HCV with cirrhosis		p-Value	Chronic HCV without cirrhosis		p-Value
	Responders (n = 12)	Non-responders (n = 18)		Responders (n = 23)	Non-responders (n = 7)
Age (years)	43.1 ± 9.8	46.8 ± 5.8	0.106	48.4 ± 7.5	51.0 ± 8.5	0.446
BMI (kg/m^2)	27.2 ± 2.3	28.6 ± 3.6	0.363	27.7 ± 2.8	30.7 ± 1.9	0.015
Alb (g/dl)	4.2 ± 0.3	3.8 ± 0.4	0.018	4.1 ± 0.5	3.9 ± 0.7	0.507
GGTP (IU/L)	40.3 ± 29.0	74.2 ± 52.8	0.026	3.7 ± 96.9	67.0 ± 83.1	0.624
AST (IU/L)	51.9 ± 25.3	53.7 ± 23.3	0.932	51.2 ± 43.1	34.4 ± 11.6	0.508
TLC (×10^3/mm^3)	4.3 ± 1.1	4.6 ± 1.6	0.671	5.1 ± 1.5	4.2 ± 2.0	0.141
Hb (g/dl)	12.9 ± 1.5	12.5 ± 1.2	0.351	12.8 ± 1.7	12.3 ± 1.0	0.572
Platelets (×10^3/mm^3)	176.5 ± 54.7	181.9 ± 69.4	0.816	185.9 ± 65.5	175.6 ± 40.6	0.961
INR	1.0 ± 0.1	1.1 ± 0.1	0.029	1.0 ± 0.0	1.0 ± 0.0	0.499
PT	12.5 ± 0.8	13.5 ± 1.5	0.020	12.3 ± 0.4	12.2 ± 0.4	0.587
PCR-HCV (×10^6 IU/ml)	1722030.9 ± 1114642.4	1089318.8 ± 1480267.6	0.057	1112806.3 ± 1067043.9	4184974.9 ± 6605613.9	0.249
AFP (ng/ml) (mean ± SD)	4.1 ± 5.1	12.4 ± 28.1	0.028	8.0 ± 12.3	19.2 ± 41.4	0.731
Cholesterol (mg/dl)	152.3 ± 32.5	147.6 ± 43.4	0.687	154.3 ± 29.6	142.4 ± 34.4	0.364
HDL (mg/dl)	57.4 ± 23.1	42.0 ± 11.0	0.094	54.1 ± 20.8	53.3 ± 11.6	0.864
LDL (mg/dl)	73.8 ± 16.8	82.3 ± 32.1	0.485	79.2 ± 30.2	64.9 ± 28.0	0.229
IR	1.6 ± 0.7	6.9 ± 12.9	0.034	2.4 ± 1.4	2.3 ± 1.4	0.922
Male (N/%)	8 (36.4)	14 (63.6)	FETp = 0.678	15 (71.4)	6 (28.6)	FETp = 0.393
Female (N/%)	4 (50.0)	4 (50.0)		8 (88.9)	1 (11.1)
Schistosomal serology (N/%)
Negative	10 (58.8)	7 (41.2)	FET p = 0016.	20 (76.9)	6 (23.1)	FETp = 0.999
Positive	2 (15.4)	11 (84.6)		3 (75.0)	1 (25.0)
IL28B (N/%)
CC	6 (54.5)	5 (45.5)	MCP = 0.267	5 (71.4)	2 (28.6)	MCP = 0.591
CT	6 (37.5)	10 (62.5)		13 (72.2)	5 (27.8)
TT	0 (0.0)	3 (100)		5 (100)	0 (0.0)

Data are presented as mean ± SD unless otherwise indicated.

Table 3 Odds ratio of SVR12 depending on the patient group, BMI and schistosomal serology.

Factors affecting SVR12	p value	OR	95% CI
Cirrhotic group	0.016	6.39	1.41–28.87
BMI	0.001	19.07	3.15–115.66
Positive schistosomal serology	0.003	12.88	2.34–70.83
Model X^2 = 26.57 p = 0.000

OR: odds ratio, CI: confidence interval.

Table 4 Relationship between SVR24 and demographic and biochemical variables among both studied groups.

Parameter	Chronic HCV with cirrhosis		p-Value	Chronic HCV without cirrhosis		p-Value
	Responders (n = 14)	Non-responders(n = 16)		Responders (n = 24)	Non-responders(n = 6)
Age (years)	44.1 ± 9.0	46.4 ± 6.5	0.337	49.3 ± 7.6	48.0 ± 8.7	0.815
BMI (kg/m^2)	28.2 ± 2.7	27.9 ± 3.6	0.506	28.8 ± 2.7	26.7 ± 3.3	0.186
Alb (g/dl)	4.1 ± 0.4	3.8 ± 0.4	0.132	4.1 ± 0.5	4.0 ± 0.6	0.406
GGTP (IU/L)	32.6 ± 17.6	85.2 ± 51.8	0.001	72.3 ± 102.2	71.7 ± 39.4	0.169
AST (IU/L)	53.1 ± 28.2	52.8 ± 19.9	0.901	50.0 ± 42.7	36.5 ± 8.2	0.917
TLC (×10^3/mm^3)	4.6 ± 1.8	4.4 ± 1.1	0.917	4.7 ± 1.7	5.6 ± 1.4	0.213
Hb (g/dl)	12.4 ± 1.2	12.9±.4	0.454	12.8 ± 1.7	12.4 ± 1.3	0.604
Platelets (×10^3/mm^3)	175.4 ± 52.2	183.6 ± 72.6	0.835	182.3 ± 58.8	188.3 ± 71.0	0.795
PT	12.4 ± 0.8	13.7 ± 1.5	0.001	12.2 ± 0.4	12.6 ± 0.5	0.036
INR	1.0 ± 0.1	1.1 ± 0.1	0.000	1.0 ± 0.0	1.1 ± 0.0	0.058
PCR-HCV (×10^6 IU/ml)	1801612.1 ± 1743753.6	940596.3 ± 763112.5	0.212	1977492.3 ± 3780153.0	1238258.8 ± 1115577.7	0.717
AFP (ng/ml)	3.3 ± 2.7	14.2 ± 29.7	0.010	5.6 ± 7.3	30.9 ± 44.7	0.062
Cholesterol (mg/dl)	158.1 ± 38.0	141.8 ± 39.2	0.339	158.1 ± 29.7	125.5 ± 18.7	0.022
HDL (mg/dl)	57.3 ± 21.8	40.2 ± 9.2	0.019	52.8 ± 20.6	58.3 ± 9.2	0.222
LDL (mg/dl)	75.9 ± 24.8	1.5 ± 29.4	0.708	81.2 ± 29.9	54.5 ± 19.3	0.038
IR	2.0 ± 1.4	7.2 ± 13.7	0.096	2.3 ± 1.4	2.5 ± 1.4	0.678
Male (N/%)	9 (40.9)	13 (59.1)	FETp = 0.417	16 (76.2)	5 (23.8)	FETp = 0.400
Female (N/%)	5 (62.5)	3 (37.5)		8 (88.9)	1 (11.1)
Schistosomal serology (N/%)
Negative	13 (76.5)	4 (23.5)	FETp = 0.000	23 (88.5)	3 (11.5)	FETp = 0.018
Positive	1 (7.7)	12 (92.3)		1 (25.0)	3 (75.0)
IL28B (N/%)
CC	9 (81.8)	2 (18.2)	MCP = 0.009	7 (100.0)	0 (0.0)	MCP = 0.372
CT	4 (25.0)	12 (75.0)		13 (72.2)	5 (27.8)
TT	1 (33.3)	2 (66.7)		4 (80.0)	1 (20.0)

Data are presented as mean ± SD unless otherwise indicated.

Table 5 Odds ratio of SVR24 depending on the patient group, type of polymorphism of IL28B and schistosomal serology.

Factors affecting SVR24	p value	OR	95% CI
Cirrhotic group	0.020	11.40	1.46–88.84
CT	0.043
CC	0.384	2.99	0.25–35.24
TT	0.064	0.03	0.00–1.22
Positive schistosomal serology	0.001	132.25	7.34–2383.52
Model X^2 = 46.43	p = 0.000

OR: odds ratio, CI: confidence interval.