Impact of IL28B and OAS gene family polymorphisms on interferon treatment response in Caucasian children chronically infected with hepatitis B virus

Table 1 Characteristics of hepatitis B e antigen-negative chronic hepatitis B children

Characteristic
n	52
Age (yr)
Median (range)	16 (4-18)
Gender
Female/male	16 (30.8)/36 (69.2)
Staging (F)
F0/F1/F2/F3	2 (3.9)/31 (59.6)/16 (30.7)/3 (5.8)
Grading (A)
A0/A1/A2	2 (3.9)/ 22 (42.3)/28 (53.8)
IL28B SNPs
rs12979860 CC/CT/TT	20 (38.5)/26 (50.0)/6 (11.5)
rs12980275 AA/AG/GG	24 (46.2)/24 (46.2)/4 (7.6)
rs8099917 TT/TG/GG	30 (57.7)/19 (36.5)/3 (5.8)
OAS SNPs
rs10849829 AA/AG/GG	19 (36.5)/27 (52.0)/6 (11.5)
rs1131476 AA/AG/GG	26 (50.0)/17 (32.7)/9 (17.3)
rs1293747 GG/GA/AA	32 (61.5)/17 (32.7)/3 (5.8)
rs2072136 GG/GA/AA	30 (57.7)/20 (38.5)/2 (3.8)
Baseline HBV DNA (IU/mL)
median (range), log	4.6 (3.4-8.0)
< 20000	31 (59.6)
Baseline ALT (U/L)
median (range)	42 (12-210)
< 40	14 (26.9)
At week 24 of treatment
HBV DNA < 100 (IU/mL)	32 (61.5)
ALT < 40 (U/L)	13 (25.0)
At the end of treatment
HBV DNA < 2000 (IU/mL)	39 (75.0)
ALT < 40 (U/L)	28 (53.9)
24 wk post-treatment
HBV DNA < 2000 (IU/mL)	27 (51.92)
ALT < 40 (U/L)	37 (71.15)
Partial response
< 2000 IU/mL HBV DNA or < 40 IU/L ALT	42 (80.8)
Complete response
< 2000 IU/mL HBV DNA with < 40 IU/L ALT	22 (42.3)

Data are presented as the number of patients (%) unless otherwise indicated.

Table 2 Impact of clinical and genetic factors on partial response in HBeAg-negative chronic hepatitis B children

Characteristic	PR,	No-PR,	P value	OR (95%CI)
	n = 42	n = 10
Age (yr)
Median (range)	16 (4-18)	16 (5-18)	0.803
Gender
Female	14 (33.3)	2 (20.0)	0.412
Staging (F)
F0-F1	26 (61.9)	7 (70.0)	0.729
Grading (A)
A0-A1	20 (47.6)	5 (50.0)	0.892
Baseline HBV DNA (IU/mL)
Median (range), log	4.1 (3.4-8.0)	5.9 (3.6-8.0)	0.017
< 20000	28 (66.7)	3 (30.0)	0.069
Baseline ALT (U/L)
Median (range)	44 (10-120)	63 (22-118)	0.003
< 40	13 (31.0)	1 (10.0)	0.207
IL28B rs12979860
CC	19 (45.2)	1 (10.0)	0.068
CT	20 (47.6)	6 (60.0)
TT	3 (7.2)	3 (30.0)	0.077
IL28B rs12980275
AA	23 (54.8)	1 (10.0)	0.014	10.9 (1.3-93.9)
AG	17 (40.6)	7 (70.0)
GG	2 (4.8)	2 (20.0)	0.163
IL28B rs8099917
TT	27 (64.2)	3 (30.0)	0.075
TG	13 (31.0)	6 (60.0)
GG	2 (4.8)	1 (10.0)	0.481
OASL rs10849829
AA	16 (38.1)	5 (50.0)	0.500
AG	20 (47.6)	5 (50.0)
GG	6 (14.3)	0 (0.0)	0.582
OAS1 rs1131476
AA	19 (45.2)	7 (70.0)	0.291
AG	15 (35.7)	2 (20.0)
GG	8 (19.1)	1 (10.0)	0.670
OAS2 rs1293747
GG	25 (59.5)	7 (70.0)	0.481
GA	15 (35.7)	2 (20.0)
AA	2 (4.8)	1 (10.0)	0.722
OAS3 rs2072136
GG	23 (54.8)	7 (70.0)	1.000
GA	17 (40.6)	3 (30.0)
AA	2 (4.8)	0 (0.0)	0.488

Data are presented as the number of patients (%) unless otherwise indicated.

Table 3 Impact of clinical and genetic factors on partial response in HBeAg-negative chronic hepatitis B children

Characteristic	CR,	No-CR,	P value	OR (95%CI)
	n = 22	n = 30
Age (yr)
Median (range)	16 (12-18)	17 (4-18)	0.141
Gender
Female	8 (36.4)	8 (26.7)	0.454
Staging (F)
F0-F1	14 (63.6)	19 (63.3)	0.942
Grading (A)
A0-A1	10 (45.5)	15 (50.0)	0.746
Baseline HBV DNA (IU/mL)
Median (range), log	4.6 (3.4-8.0)	4.7 (3.5-8.0)	0.671
< 20000	14 (63.6)	17 (56.7)	0.613
Baseline ALT (U/L)
Median (range)	43 (10-110)	48 (17-126)	0.116
< 40	8 (36.3)	6 (20.0)	0.189
IL28B rs12979860
CC	8 (36.4)	12 (40.0)	0.790
CT	14 (63.6)	12 (40.0)
TT	0 (0.0)	6 (20.0)	0.033	NA
IL28B rs12980275
AA	11 (50.0)	13 (43.3)	0.634
AG	11 (50.0)	13 (43.3)
GG	0 (0.0)	4 (13.4)	0.128
IL28B rs8099917
TT	15 (68.2)	15 (50.0)	0.190
TG	7 (31.8)	12 (40.0)
GG	0 (0.0)	3 (10.0)	0.253
OASL rs10849829
AA	5 (22.7)	16 (53.3)	0.026	0.26 (0.07-0.88)
AG	14 (63.6)	11 (36.7)
GG	3 (13.6)	3 (10.0)	0.685
OAS1 rs1131476
AA	10 (45.5)	16 (53.3)	0.575
AG	8 (36.4)	9 (30.0)
GG	4 (18.1)	5 (16.7)	0.887
OAS2 rs1293747
GG	14 (63.6)	18 (60.0)	0.253
GA	8 (36.4)	9 (30.0)
AA	0 (0.0)	3 (10.0)	0.790
OAS3 rs2072136
GG	15 (68.2)	15 (50.0)	1.000
GA	6 (27.3)	14 (46.7)
AA	1 (4.5)	1 (3.3)	0.190

Data are presented as the number of patients (%) unless otherwise indicated. NA: Not applicable.

Table 4 Association of OAS haplotypes with treatment response

Haplotype	CR	No-CR	P value	OR (95%CI)	PR	No-PR	P value	OR (95%CI)
A A A A	0.11	0.16	0.402	0.60 (0.18-1.98)	0.16	0.00	0.041	NA
A A G A	0.03	0.05	0.473	0.47 (0.06-3.78)	0.05	0.00	0.283	NA
A A G G	0.17	0.35	0.031	0.35 (0.13-0.92)	0.21	0.57	0.002	0.21 (0.07-0.61)
A G G G	0.24	0.12	0.156	2.11 (0.74-6.00)	0.17	0.13	0.543	1.55 (0.37-6.48)
G A G G	0.28	0.03	0.0003	11.96 (2.38-59.97)	0.16	0.05	0.173	3.91 (0.48-31.8)
G G G G	0.05	0.17	0.046	0.24 (0.05-1.06)	0.15	0.05	0.194	3.70 (0.45-30.25)

Data are presented as the haplotype frequency; NA: Not applicable.