Association of ITPA polymorphism with outcomes of peginterferon-α plus ribavirin combination therapy

Table 1 Baseline characteristics of patients

Baseline characteristics	ITPA polymorphism (rs1127354)		P value
	CA/AA (n = 37)	CC (n = 83)
Age (yr)	61 ± 8	59 ± 11	NS
Gender: male/female	18/19	37/46	NS
HCV RNA (log IU/mL)	6.2 ± 0.6	5.9 ± 0.5	NS
Hemoglobin (g/dL)	13.4 ± 1.5	13.8 ± 1.7	NS
WBC (× 103/μL)	4.7 ± 1.2	5.0 ± 1.5	NS
Platelet (× 104/μL)	18.0 ± 6.0	18.0 ± 7.0	NS
AST (IU/L)	56.8 ± 34.9	58.2 ± 42.3	NS
ALT (IU/L)	65.5 ± 40.0	68.4 ± 56.8	NS
GGT (IU/L)	56.1 ± 52.3	55.3 ± 49.4	NS
AFP (ng/mL)	5.3 ± 4.0	24.2 ± 61.8	NS
Staging: F1,2/F3,4	19/16	49/27	NS
IL28B: TT/TG + GG	29/8	53/30	NS

ITPA: Inosine triphosphatase; AST: Aspartate aminotransferase; ALT: Alanine aminotransferase; GGT: γ-glutamyl transpeptidase; AFP: α-fetoprotein; NS: Not significant; HCV: Hepatitis C virus; IL28B: Interleukin 28B.

Table 2 Sustained virological response rates according to total ribavirin dose in each inosine triphosphatase genotype

ITPA genotype (rs1127354)	Patients with > 60% total RBV dose	Patients with < 60% total RBV dose	Total
CA + AA	48.3% (14/29)	12.5% (1/8)	40.5% (15/37)
CC	58.5% (31/53)	20.0% (6/30)	44.6% (37/83)

Each group includes patients in whom treatment was withdrawn. RBV: Ribavirin; ITPA: Inosine triphosphatase.

Table 3 Virological response according to classification by inosine triphosphatase and interleukin 28B single-nucleotide polymorphisms n (%)

Virological response	IL28B: TT		IL28B: TG + GG
	CA + AA (n = 29)1	CC (n = 53)1	CA + AA (n = 8)1	CC (n = 30)1
RVR	3 (10.3)	10 (18.9)	0 (0.0)	4 (13.3)
RVR + EVR	18 (62.1)	35 (66.0)	1 (12.5)	8 (26.6)
SVR	13 (44.8)	29 (54.7)	2 (25.0)	8 (26.6)

¹Inosine triphosphatase (ITPA). SVR: Sustained virological response; RVR: Rapid virological response; EVR: Early virological response; IL28B: Interleukin 28B.

Table 4 Comparison of profile between sustained virological response and non-sustained virological response patients

Factors	SVR (n = 54)	non-SVR (n = 66)	P value
Age (yr)	57 ± 12	61 ± 9	< 0.05
Gender: male/female	21/33	33/33	NS
Body mass index (kg/m2)	23.5 ± 4.1	22.6 ± 3.3	NS
HCV RNA (log IU/mL)	5.9 ± 0.6	6.1 ± 0.6	< 0.05
Hemoglobin (g/dL)	13.7 ± 1.3	13.8 ± 1.8	NS
WBC (× 103/mL)	4.7 ± 1.3	5.1 ± 1.5	NS
Platelet (× 104/mL)	20 ± 7	17 ± 6	< 0.05
AST (IU/L)	46.2 ± 25.8	66.7 ± 47.1	NS
ALT (IU/L)	56.1 ± 33.3	75.1 ± 61.1	NS
GGT (IU/L)	39.8 ± 24.1	67.4 ± 61.2	NS
AFP (ng/mL)	8.3 ± 19.8	10.1 ± 24.2	NS
Staging: F1,2/F3,4	12/40	28/30	< 0.01
72 wk treatment: +/–	10/44	14/52	NS
Ribavirin dose (%)1	90 ± 35	76 ± 41	NS
ITPA: CC/CA + AA	38/16	45/21	NS
IL28B: TT/TG + GG	44/10	38/28	< 0.01

¹Percentage of ribavirin administration to the scheduled total dose of full-length treatment (48 or 72 wk). SVR: Sustained virological response; AST: Aspartate aminotransferase; ALT: Alanine aminotransferase; GGT: γ-glutamyl transpeptidase; AFP: α-fetoprotein; ITPA: inosine triphosphatase; NS: Not significant; HCV: Hepatitis C virus; IL28B: Interleukin 28B.

Table 5 Multivariate analysis for predictive factors associated with SVR

Factors	Category	95%CI	P value
HCV RNA (log IU/mL)	≥ 6.0: 1.0	1.42-10.95	0.008
	< 6.0: 3.94
IL28B (rs8099917)	TG + GG: 1.0	1.18-10.10	0.023
	TT: 3.46

HCV: Hepatitis C virus; IL28B: Interleukin 28B; SVR: Sustained virological response.