Several factors including ITPA polymorphism influence ribavirin-induced anemia in chronic hepatitis C

Table 1 Baseline profiles of the study population (mean ± SD)

Variable	Overall cohort (n = 561)	Derivation group (n = 374)	Confirmatory group (n = 187)
Demographic feature
Age (yr)	59.1 ± 10.9	59.1 ± 10.8	59.5 ± 11.3
Sex (female/male)	302/259	201/173	101/86
Weight (kg)	59.8 ± 11.4	59.9 ± 11.5	58.5 ± 10.9
BMI (kg/m2)	23.2 ± 3.3	23.2 ± 3.4	23.2 ± 3.2
Height (cm)	160.3 ± 9.0	160.4 ± 9.1	158.5 ± 8.7
BSA (m2)	1.62 ± 0.18	1.62 ± 0.18	1.59 ± 0.18
Laboratory data
ALT (IU/L)	63 ± 54	63 ± 56	58 ± 47
GGT (IU/L)	58 ± 63	56 ± 60	58 ± 72
Albumin (g/dL)	4.1 ± 0.4	4.1 ± 0.4	4.1 ± 0.3
Creatinine (mg/dL)	0.70 ± 0.16	0.70 ± 0.17	0.70 ± 0.17
WBC count (× 103/mL)	5.0 ± 1.5	5.0 ± 1.5	5.1 ± 1.4
Hemoglobin (g/dL)	13.7 ± 1.5	13.7 ± 1.5	13.8 ± 1.3
Platelet count (× 104/mL)	16.7 ± 5.7	16.5 ± 5.7	17.0 ± 6.2
Estimated calculation value
Ccr (mL/min)	91.8 ± 27.9	91.6 ± 28.0	87.9 ± 25.6
GFR (mL/min/1.73 m2)	77.5 ± 16.8	79.6 ± 17.0	78.2 ± 15.9
CL/F (L/h)	11.3 ± 5.4	11.2 ± 5.3	10.9 ± 5.1
Liver histopathology
Stage of fibrosis 0-1/2/3-4	221/131/161	146/89/107	75/42/54
Grade of inflammation 1/2/3	267/222/19	170/156/14	97/66/5
SNP genotype
rs1127354 CC/CA/AA	431/114/16	289/75/10	142/39/6
rs6051702 AA/AC/CC	388/158/15	260/104/10	128/54/5
Treatment
Ribavirin dosage (mg/kg/d)	11.4 ± 1.5	11.3 ± 1.9	11.4 ± 1.9
Peg-IFN α-2a/-2b	82/479	52/322	30/157
Virology
Viral load (log10 IU/mL)	6.2 ± 0.8	6.2 ± 0.8	6.2 ± 0.8

BMI: Body mass index; BSA: Body surface area; ALT: Alanine transaminase; GGT: γ glutamyl transpeptidase; WBC: White blood cell; GFR: Glomerular filtration rate; SNP: Single nucleotide polymorphism; Peg-IFN: Pegylated interferon.

Table 2 Time-course changes in hemoglobin concentration from baseline

	Week 2 of treatment	Week 4 of treatment
Overall cohort
mean (SD), g/dL	-1.12 (1.13)	-2.31 (1.39)
Median (25th–75th quartile), g/dL	-1.05 (-1.8 to -0.3)	-2.3 (-3.2 to -1.3)
Derivation group
mean (SD), g/dL	-1.09 (1.11)	-2.27 (1.40)
Median (25th–75th quartile), g/dL	-1.0 (-1.8 to -0.3)	-2.3 (-3.1 to -1.3)
Confirmatory group
mean (SD), g/dL	-1.18 (1.17)	-2.33 (1.37)
Median (25th–75th quartile), g/dL	-1.1 (-1.95 to -0.4)	-2.3 (-3.3 to -1.35)

Table 3 Pretreatment variables influencing significant hemoglobin decline in the derivation group

Variable	P value		OR (95% CI)
	Univariate analysis	Multivariate analysis
Age (yr)	0.110
Sex (female vs male)	0.0163
Weight (kg)	5.18 × 10-3
BMI	5.93 × 10-3
Height (cm)	0.153
BSA (m2)	0.0139
ALT (IU/L)	0.114
GGT (IU/L)	0.118
Albumin (g/dL)	6.88 × 10-3
Creatinine (mg/dL)	4.71 × 10-4
WBC count (× 103/mL)	0.147
Hemoglobin (g/dL)	7.75 × 10-8	1.29 × 10-9	1.89 (1.54-2.32)
Platelet count (× 104/mL)	0.558
Ccr (mL/min)	0.140
GFR (mL/min/1.73 m2)	5.69 × 10-4	6.46 × 10-4	0.959 (0.942-0.977)
CL/F (L/h)	0.814
Stage of fibrosis	0.641
Grade of inflammation	0.570
rs1127354 (CC vs CA/AA)	8.04 × 10-10	1.60 × 10-7	28.26 (8.10-98.62)
rs6051702 (AA vs AC/CC)	0.372
RBV dosage (mg/kg/d)	0.419
Peg-IFN α (2a vs 2b)	0.360
Viral load (log10 IU/mL)	0.355

BMI: Body mass index; BSA: Body surface area; ALT: Alanine transaminase; GGT: γ glutamyl transpeptidase; WBC: White blood cell; GFR: Glomerular filtration rate; SNP: Single nucleotide polymorphism; Peg-IFN: Pegylated interferon; OR: Odds ratio; CI: Confidence interval.