Gastroenterol Res

Gastroenterology Research, ISSN 1918-2805 print, 1918-2813 online, Open Access

Article copyright, the authors; Journal compilation copyright, Gastroenterol Res and Elmer Press Inc

Journal website http://www.gastrores.org

Original Article

Volume 7, Number 5-6, December 2014, pages 123-130

Impact of Interleukin 28B Genotype on the Virological Responses in Chronic Hepatitis C Treatment

**Table 1.** Characteristics of Patients With Chronic Hepatitis C
BMI: body mass index; ALT: alanin aminotransferase; SD: standart deviation; CI: confidence interval. ^aLogarithmic transformation (base 10) was applied. Confidence intervals of geometric mean are computed using 1,000 bootstrap samples. ^bGenotypes were determined in 167 patients. ^c152 patients with liver biopsy, evaluated based on the Ishak score.
Gender, n (%)
Female	121 (65.1)
Male	65 (34.9)
Age (years), mean ± SD	55.6 ± 10
BMI (kg/m²), mean ± SD	27.3 ± 4.6
Normal weight (< 25 kg/m²), n (%)	55 (29.6)
Overweight (25-29.9 kg/m²), n (%)	95 (51.1)
Obese (≥ 30 kg/m²), n (%)	36 (19.4)
Viral load at baseline (IU/mL), geometric mean (95% CI)^a	854,053 (663,578 - 1,087,754)
< 400,000 (IU/mL), n (%)	56 (30.1)
≥ 400,000 (IU/mL), n (%)	130 (69.9)
Genotype, n (%)^b
Genotype 1b	145 (86.8)
Genotype 4	22 (13.2)
Baseline ALT levels (IU/L), median (first to third quartiles)	49.0 (34.0 - 69.0)
Liver necroinflammation^c, median (first to third quartiles)	5.5 (4.0 - 8.0)
Liver fibrosis^c, median (first to third quartiles)	2.0 (1.0 - 3.0)
Distribution of liver fibrosis, n (%)
Mild (Ishak staging score 0 - 2)	107 (70.5)
Moderate (Ishak staging score 3 - 4)	35 (23.0)
Severe (Ishak staging score 5 - 6)	10 (6.5)

Table 1. Characteristics of Patients With Chronic Hepatitis C

BMI: body mass index; ALT: alanin aminotransferase; SD: standart deviation; CI: confidence interval. ^aLogarithmic transformation (base 10) was applied. Confidence intervals of geometric mean are computed using 1,000 bootstrap samples. ^bGenotypes were determined in 167 patients. ^c152 patients with liver biopsy, evaluated based on the Ishak score.

Gender, n (%)

Female

121 (65.1)

Male

65 (34.9)

Age (years), mean ± SD

55.6 ± 10

BMI (kg/m²), mean ± SD

27.3 ± 4.6

Normal weight (< 25 kg/m²), n (%)

55 (29.6)

Overweight (25-29.9 kg/m²), n (%)

95 (51.1)

Obese (≥ 30 kg/m²), n (%)

36 (19.4)

Viral load at baseline (IU/mL), geometric mean (95% CI)^a

854,053 (663,578 - 1,087,754)

< 400,000 (IU/mL), n (%)

56 (30.1)

≥ 400,000 (IU/mL), n (%)

130 (69.9)

Genotype, n (%)^b

Genotype 1b

145 (86.8)

Genotype 4

22 (13.2)

Baseline ALT levels (IU/L), median (first to third quartiles)

49.0 (34.0 - 69.0)

Liver necroinflammation^c, median (first to third quartiles)

5.5 (4.0 - 8.0)

Liver fibrosis^c, median (first to third quartiles)

2.0 (1.0 - 3.0)

Distribution of liver fibrosis, n (%)

Mild (Ishak staging score 0 - 2)

107 (70.5)

Moderate (Ishak staging score 3 - 4)

35 (23.0)

Severe (Ishak staging score 5 - 6)

10 (6.5)

**Table 2.** Patients Characteristics in Each IL28B Genotype Subgroup
Variables	C/C (n = 42)	C/T (n = 98)	T/T (n = 46)	P
BMI: body mass index; ALT: alanin aminotransferase; SD: standart deviation; CI: confidence interval. ^aLogarithmic transformation (base 10) was applied. Confidence intervals of geometric mean are computed using 1,000 bootstrap samples. ^bGenotypes were determined in 167 patients. ^cCases with liver biopsy were evaluated based on Ishak score. ^d30 patients. ^e83 patients. ^f39 patients. Different superscripts in a row (x, y) indicate statistically significant difference between groups.
Age (years), mean ± SD	53.3 ± 11.2	55.7 ± 9.2	57.5 ± 10.2	0.147
Male, n (%)	17 (40.5)	31 (31.6)	17 (37)	0.571
BMI (kg/m²), mean ± SD	26.9 ± 4.3	27.7 ± 4.7	26.9 ± 4.6	0.446
Viral load at baseline (IU/mL), geometric mean (95% CI)^a	987,812 (571,056 - 1,811,751)	905,147 (648,435 - 1,296,846)	660,740 (406,456 - 1,055,059)	0.503
Patients with baseline viral load < 400,000 IU/mL, n (%)	18 (42.9)	21 (21.4)	16 (34.8)	0.020
Genotype 1b^b, n (%)	37 (97.4)	73 (83.9)	35 (83.3)	0.091
Genotype 4^b, n (%)	1 (2.6)	14 (16.1)	7 (16.7)
Baseline ALT levels (IU/L), median (first to third quartiles)	50.0 (34.0 - 83.0)^xy	44.0 (29.0 - 59.0)^x	57.5 (37.0-87.0)^y	0.006
Liver necroinflammation^c, median (first to third quartiles)	6.0 (4.0 - 6.0)	5.0 (4.0 - 8.0)	6.0 (4.0 - 8.0)	0.669
Liver fibrosis^c, median (first to third quartiles)	1.0 (1.0 - 2.0)^x	2.0 (1.0 - 3.0)^y	1.0 (1.0 - 3.0)^xy	0.023
Distribution of liver fibrosis, n (%)
Mild (Ishak staging score 0 - 2)	25 (83.3)^d	53 (63.9)^e	29 (74.4)^f	0.236
Moderate (Ishak staging score 3 - 4)	5 (16.7)^d	23 (27.7)^e	7 (17.9)^f
Severe (Ishak staging score 5 - 6)	0 (0.0)^d	7 (8.4)^e	3 (7.7)^f

Table 2. Patients Characteristics in Each IL28B Genotype Subgroup

Variables

C/C (n = 42)

C/T (n = 98)

T/T (n = 46)

BMI: body mass index; ALT: alanin aminotransferase; SD: standart deviation; CI: confidence interval. ^aLogarithmic transformation (base 10) was applied. Confidence intervals of geometric mean are computed using 1,000 bootstrap samples. ^bGenotypes were determined in 167 patients. ^cCases with liver biopsy were evaluated based on Ishak score. ^d30 patients. ^e83 patients. ^f39 patients. Different superscripts in a row (x, y) indicate statistically significant difference between groups.

Age (years), mean ± SD

53.3 ± 11.2

55.7 ± 9.2

57.5 ± 10.2

0.147

Male, n (%)

17 (40.5)

31 (31.6)

17 (37)

0.571

BMI (kg/m²), mean ± SD

26.9 ± 4.3

27.7 ± 4.7

26.9 ± 4.6

0.446

Viral load at baseline (IU/mL), geometric mean (95% CI)^a

987,812 (571,056 - 1,811,751)

905,147 (648,435 - 1,296,846)

660,740 (406,456 - 1,055,059)

0.503

Patients with baseline viral load < 400,000 IU/mL, n (%)

18 (42.9)

21 (21.4)

16 (34.8)

0.020

Genotype 1b^b, n (%)

37 (97.4)

73 (83.9)

35 (83.3)

0.091

Genotype 4^b, n (%)

1 (2.6)

14 (16.1)

7 (16.7)

Baseline ALT levels (IU/L), median (first to third quartiles)

50.0 (34.0 - 83.0)^xy

44.0 (29.0 - 59.0)^x

57.5 (37.0-87.0)^y

0.006

Liver necroinflammation^c, median (first to third quartiles)

6.0 (4.0 - 6.0)

5.0 (4.0 - 8.0)

6.0 (4.0 - 8.0)

0.669

Liver fibrosis^c, median (first to third quartiles)

1.0 (1.0 - 2.0)^x

2.0 (1.0 - 3.0)^y

1.0 (1.0 - 3.0)^xy

0.023

Distribution of liver fibrosis, n (%)

Mild (Ishak staging score 0 - 2)

25 (83.3)^d

53 (63.9)^e

29 (74.4)^f

0.236

Moderate (Ishak staging score 3 - 4)

5 (16.7)^d

23 (27.7)^e

7 (17.9)^f

Severe (Ishak staging score 5 - 6)

0 (0.0)^d

7 (8.4)^e

3 (7.7)^f

**Table 3.** Distribution of IL28B rs12979860 C/T Genotypes and Alleles in Patients With Sustained Virologic Response and Non-Responder
	IL28B	SVR (n = 83), n (%)	Non-response (n = 103), n (%)	P	OR (95% CI)
SVR: sustained virologic response; OR: odds ratio; CI: confidence interval.
rs12979860 alleles	C	98 (59)	84 (41)	< 0.001	-
T	68 (41)	122 (59)	< 0.001
rs12979860 genotypes	CC	28 (66.7)	14 (33.3)	0.001	1
CT	42 (42.9)	56 (57.1)		0.38 (0.18 - 0.80)
TT	13 (28.3)	33 (71.7)		0.20 (0.08 - 0.49)

Table 3. Distribution of IL28B rs12979860 C/T Genotypes and Alleles in Patients With Sustained Virologic Response and Non-Responder

IL28B

SVR (n = 83), n (%)

Non-response (n = 103), n (%)

OR (95% CI)

SVR: sustained virologic response; OR: odds ratio; CI: confidence interval.

rs12979860 alleles

98 (59)

84 (41)

< 0.001

68 (41)

122 (59)

< 0.001

rs12979860 genotypes

28 (66.7)

14 (33.3)

0.001

42 (42.9)

56 (57.1)

0.38 (0.18 - 0.80)

13 (28.3)

33 (71.7)

0.20 (0.08 - 0.49)

**Table 4.** Relationship Between IL28B Genotype and Response to Treatment Rates
Variables, n (%)	C/C (n = 42)	C/T (n = 98)	T/T (n = 46)	P
RVR: rapid virological response; cEVR: complete early virological response; EVR: early virological response; pEVR: partial early virological response; ETR: end-of-treatment response; SVR: sustained virological response; PR: partial response; NR: null response. ^aFive patients were not evaluated for RVR.
RVR	23 (54.8)	39 (41.9)^a	18 (39.1)	0.216
cEVR	37 (88.1)	57 (58.2)	22 (47.8)	< 0.001
EVR (cEVR + pEVR)	41 (97.6)	71 (72.4)	29 (63.0)	< 0.001
ETR	38 (90.5)	61 (62.2)	26 (56.5)	0.001
SVR	28 (66.7)	42 (42.9)	13 (28.3)	0.001
Relapse	11 (26.2)	20 (20.4)	14 (30.4)	0.400
PR	1 (2.4)	8 (8.2)	3 (6.5)	0.443
NR	1 (2.4)	25 (25.5)	16 (34.8)	0.001
Breakthrough	1 (2.4)	3 (3.1)	0 (0.0)	0.495

Table 4. Relationship Between IL28B Genotype and Response to Treatment Rates

Variables, n (%)

C/C (n = 42)

C/T (n = 98)

T/T (n = 46)

RVR: rapid virological response; cEVR: complete early virological response; EVR: early virological response; pEVR: partial early virological response; ETR: end-of-treatment response; SVR: sustained virological response; PR: partial response; NR: null response. ^aFive patients were not evaluated for RVR.

RVR

23 (54.8)

39 (41.9)^a

18 (39.1)

0.216

cEVR

37 (88.1)

57 (58.2)

22 (47.8)

< 0.001

EVR (cEVR + pEVR)

41 (97.6)

71 (72.4)

29 (63.0)

< 0.001

ETR

38 (90.5)

61 (62.2)

26 (56.5)

0.001

SVR

28 (66.7)

42 (42.9)

13 (28.3)

0.001

Relapse

11 (26.2)

20 (20.4)

14 (30.4)

0.400

1 (2.4)

8 (8.2)

3 (6.5)

0.443

1 (2.4)

25 (25.5)

16 (34.8)

0.001

Breakthrough

1 (2.4)

3 (3.1)

0 (0.0)

0.495