IFIT1 polymorphisms predict interferon-α treatment efficiency for hepatitis B virus infection

Table 1 Patient charateristics

Patient characteristic	Total patient (n)
Total patient	225
Gender	225
Male	163 (72.4)
Female	62 (27.6)
Age	225
Median age (range)	26 (18-56)
Baseline ALT	225
Median (range)	150 (70-359)
Baseline AST	225
Median (range)	83 (30-294)
Baseline HBV DNA copies (log10IU/L)	225
Median (range)	7.36 (3.52-8.90)
HBV genotype	197
Type A	8 (4.1)
Type B	94 (47.7)
Type C	15 (7.6)
Type B + C	80 (40.6)
Virological response1	225
Response	83 (36.9)
Non-response	142 (63.1)
HBeAg seroconversion2	225
Response	61 (27.1)
Non-response	164 (72.9)
Combined response3	225
Response	35 (15.6)
Non-response	190 (84.4)
Sustained response4	225
Response	59 (26.2)
Non-response	166 (73.8)

¹Virological response was defined as serum HBV DNA level < 2000 IU/L at the end of the treatment;

²HBeAg seroconversion was defined as the loss of HBeAg and the presence of anti-HBe at the end of the treatment;

³Combined response was defined as the combination of HBeAg seroconversion and virological response, as well as the normalization of serum ALT at the end of the treatment;

⁴Sustained response was defined as the combined response at week 72 after the first dose of the treatment. ALT: Alanine aminotransferase; AST: Aspartate transaminase; HBV: Hepatitis B virus; HBeAg: Hepatitis B e antigen.

Table 2 Hepatitis B virus genotype and interferon-α treatment responses

HBV genotype	Total	Virological response1		HBeAg seroconversion2		Combined response3		Sustained response4
		R	%	R	%	R	%	R	%
Type A	8	3	37.5	1	12.5	1	12.5	1	12.5
Type B	94	42	44.7	38	40.4	19	20.2	37	39.4
Type C	15	10	66.7	5	33.3	5	33.3	6	40.0
Type B + C	80	22	27.5	11	13.8	7	8.8	10	12.5

¹Virological response was defined as serum HBV DNA level < 2000 IU/L at the end of the treatment;

²HBeAg seroconversion was defined as the loss of HBeAg and the presence of anti-HBe at the end of the treatment;

³Combined response was defined as the combination of HBeAg seroconversion and virological response, as well as the normalization of serum ALT at the end of the treatment;

⁴Sustained response was defined as the combined response at week 72 after the first dose of the treatment. HBV: Hepatitis B virus; R: Response; HBeAg: Hepatitis B e antigen.

Table 3 Association between clinical factors and responses

Patient characteristics	Virological response			HBeAg seroconversion			Combined response			Sustained response
	R	NR	P value1	R	NR	P value1	R	NR	P value1	R	NR	P value1
Gender			0.113			0.081			0.0272			0.204
Male	55	108		39	163		20	163		39	163
Female	28	34		22	62		15	62		20	63
Age			0.151			0.723			0.924			0.116
Baseline ALT			0.070			0.0202			0.391			0.181
Baseline AST			0.205			0.113			0.443			0.279
Baseline HBV DNA level			0.121			0.554			0.617			0.217
HBV genotype			0.0122			0.0012			0.0382			2.37 × 10-42
Type A	3	5		1	7		1	7		1	7
Type B	42	52		38	56		19	75		37	57
Type C	10	5		5	10		5	10		6	9
Type B + C	22	58		11	69		7	73		10	70

¹P value was calculated by χ² test or Student's t-test depending on which variables were analyzed;

²P < 0.05. ALT: Alanine aminotransferase; AST: Aspartate transaminase; HBV: Hepatitis B virus; R: Response; NR: Non-response; HBeAg: Hepatitis B e antigen.

Table 4 The association between single nucleotide polymorphisms and virological response by allele frequencies

SNP ID	Genotype	No./total1	%	P2	OR	95%CI
rs303218	A	75/242	0.31	0.0053	1 (Reference)
	G	87/198	0.44		0.57	0.39-0.85
rs303215	T	93/227	0.41	0.0453	1 (Reference)
	C	69/217	0.32		1.49	1.01-2.20
rs11203109	T	109/341	0.32	0.0203	1 (Reference)
	C	37/81	0.46		0.56	0.34-0.92
rs303212	C	93/284	0.33	0.0223	1 (Reference)
	T	65/148	0.44		0.62	0.41-0.94

¹Number indicated the patients who responsed in the same group;

²P value was calculated by univariable logistic regression analysis;

³P < 0.05. SNP: Single nucleotide polymorphism.

Table 5 The association between rs303218 and virological response

SNP ID	Genotype	Genetic model1	No./total2	%	χ2 test	Logistic regression analysis
					P value3	OR	95%CI	P value34
rs303218	A A		19/70	0.27	0.0223	1 (Reference)
	G A		37/102	0.36		0.77	0.38-1.55	0.467
	G G		25/48	0.52		0.40	0.18-0.91	0.0283
		Add				0.64	0.42-0.96	0.0323

¹The best fitting model was shown;

²Number indicated the patients who responsed in the same group;

³P < 0.05;

⁴P value was calculated by logistic regression analysis with adjustment of patient characteristics with P < 0.05 in univariate analysis (the adjusting covariate for virological response was HBV genotype). HBV: Hepatitis B virus.

Table 6 Stratified analyses of rs303218 and virological response

Variables	No./total1	rs303218
		OR	95%CI	P value2
Age (yr)
≤ 26	39/117	0.79	0.42-1.48	0.453
> 26	44/108	0.59	0.33-1.04	0.070
Gender
Male	55/163	0.53	0.32-0.88	0.0133
Female	28/62	1.03	0.46-2.31	0.947
Baseline ALT
≤ 150	38/113	0.38	0.20-0.74	0.0033
> 150	45/112	0.91	0.52-1.60	0.734
Baseline AST
≤ 83	34/114	0.31	0.16-0.61	0.0013
> 83	49/111	1.10	0.62-1.96	0.752
Baseline HBV DNA copies (log10 IU/mL)
≤ 7.36	47/113	0.86	0.49-1.52	0.611
> 7.36	36/112	0.47	0.25-0.88	0.0183
HBV genotype
Type B	42/94	0.74	0.42-1.31	0.304
Type C	10/15	2.19	0.36-13.51	0.397
Type B + C	22/80	0.41	0.19-0.86	0.0183

¹Number indicated the patients who responsed in the same group;

²P value was calculated by logistic regression analysis with adjustment of patient characteristics with P < 0.05 in univariate analysis in additive model (the adjusting covariate for virological response was HBV genotype);

³P < 0.05. ALT: Alanine aminotransferase; AST: Aspartate transaminase; HBV: Hepatitis B virus.