Regulatory polymorphism of CXCL10 rs1439490 in seronegative occult hepatitis C virus infection

Table 1 Algorithm for evaluation of histological activity

Piecemeal necrosis	+	Lobular necrosis	=	Histological activity score
0 (none)		0 (none or mild)		0 (none)
0		1 (moderate)		1 (mild)
0		2 (severe)		2 (moderate)
1 (mild)		0, 1		1
1		2		2
2 (moderate)		0, 1		2
2		2		3 (severe)
3 (severe)		0, 1, 2		3

Table 2 Fibrosis scoring

Description	Score
No fibrosis	0
Stellate enlargement of portal tract but without septa formation	1
Enlargement of portal tract with rare septa formation	2
Numerous septa without cirrhosis	3
Cirrhosis	4

Table 3 Clinical characteristics of patients enrolled in this study n (%)

	Seronegative OCI patients (n = 103)	Seropositive CHC patients (n = 155)	P value
Gender			0.664
Male	58 (56.3)	83 (53.5)
Female	45 (43.7)	72 (46.5)
Age (yr)	52.16 ± 7.64	42.70 ± 9.15	< 0.001
ALT (IU/L)	61.13 ± 23.54	93.17 ± 55.39	< 0.001
GGT	56.31 ± 16.63	52.86 ± 15.69	0.093
BMI	23.73 ± 2.38	24.12 ± 2.36	0.192
HOMA-IR	2.39 ± 0.15	2.42 ± 0.18	0.219
Transfusion/surgery/tattoo history	8 (7.8)	26 (16.8)	0.027
Family history of HCV infection	29 (28.2)	19 (12.3)	< 0.001
Intrahepatic HCV RNA (log10 IU/mL)	3.19 ± 1.05	5.48 ± 1.49	< 0.001
HCV genotype			0.89
Genotype 1	66 (64.1)	98 (63.2)
Non-genotype 1	37 (35.9)	57 (36.8)
Fibrosis (Fibroscan)			0.317
F0-1	65 (63.1)	104 (67.1)
F2-4	38 (36.9)	51 (32.9)
METAVIR activity score	1.14 ± 0.34	1.69 ± 0.68	< 0.001
METAVIR fibrosis score	1.82 ± 0.98	1.87 ± 1.07	0.673

P < 0.05; ALT: Alanine aminotransferase; GGT: Gamma-glutamyl transpeptidase; BMI: Body mass index; HOMA-IR: Homeostasis model assessment of insulin resistance; HCV non-genotype 1: Other HCV genotypes except for genotype 1, including HCV 2-6 genotypes.

Table 4 IL-28B single nucleotide polymorphism rs12979860 and CXCL10 single nucleotide polymorphism G-201A, C-1513T in occult hepatitis C virus infection and chronic hepatitis C virus infection patients n (%)

	Seronegative OCI patients (n=103)	Seropositive CHC patients (n=155)	P value
IL-28BSNP rs12979860
C/C	97 (94.2%)	128 (82.6%)	0.009
Non-C/C	6 (5.8%)	27 (17.4%)
CXCL10 SNP rs1439490 (G-201A)
G/G	93 (90.4%)	116 (74.8%)	0.003
G/A	9 (8.7%)	35 (22.6%)
A/A	1 (0.9%)	4 (2.6%)
CXCL10 SNP rs1440802 (C-1513T)
C/C	26 (25.2%)	40 (25.8%)	0.733
C/T	54 (52.4%)	78 (50.3%)
T/T	23 (22.4%)	37 (23.9%)

P value: OCI group compared with CHC group; P < 0.05; IL-28BSNP rs12979860 non-C/C genotype included IL-28BSNP rs12979860 C/T + T/T genotypes. OCI: Occult hepatitis C virus infection; CHC: Chronic hepatitis C virus infection.

Table 5 CXCL10 single nucleotide polymorphism G-201A in occult hepatitis C virus infection and chronic hepatitis C virus infection patients with IL-28B rs12979860 C/C n (%)

	Seronegative OCI patients (n = 97)	Seropositive CHC patients (n = 128)	P value	OR (95%CI)
G/G	87 (89.7)	95 (74.2)	0.005	0.331 (0.154-0.711)
Non-G/G (G/A + A/A)	10 (10.3)	33(25.8)

P value: OCI group compared with CHC group; P < 0.05; OR: odds ratio; 95%CI: 95% confidence interval; CXCL10 rs1439490 non-G/G genotype included CXCL10 rs1439490 G/A + A/A genotypes. OCI: Occult hepatitis C virus infection; CHC: Chronic hepatitis C virus infection.

Table 6 Intrahepatic hepatitis C virus RNA, CXCL10 mRNA, and METAVIR scores of 8 seronegative occult hepatitis C virus infection patients who underwent a second liver biopsy

Patient ID	CXCL10G-201A SNP	Intrahepatic HCV RNA (log10 IU/mL)		Relative liver CXCL10 mRNA		METAVIRnecroinflammation score		METAVIRfibrosis scores
		Before	After	Before	After	Before	After	Before	After
1	G/G	2.17	(-)	1.20	0.80	1	0	0	0
2	G/G	3.57	(-)	0.95	0.90	1	0	1	1
3	G/G	2.72	(-)	0.74	0.63	1	1	1	1
4	G/G	5.08	(-)	1.31	0.94	1	0	1	0
5	G/G	2.83	(-)	1.42	0.64	1	0	0	0
6	G/G	1.97	(-)	1.06	0.83	2	1	1	1
7	G/G	4.64	(-)	1.03	0.70	2	0	2	1
8	G/G	2.94	(-)	1.26	0.71	1	1	3	1

SNP: Single nucleotide polymorphism; HCV: Hepatitis C virus.

Table 7 Intrahepatic hepatitis C virus RNA, CXCL10 mRNA, and METAVIR scores of 5 seropositive chronic hepatitis C virus infection patients who underwent a second liver biopsy

Patient ID	CXCL10G-201A SNP	Intrahepatic HCV RNA (log10 IU/mL)		Relative Liver CXCL10 mRNA		METAVIRnecroinflammation score		METAVIRfibrosis scores
		Before	After	Before	After	Before	After	Before	After
1	G/G	6.18	(-)	1.93	0.93	1	0	2	1
2	G/G	3.9	(-)	1.80	0.90	2	1	1	1
3	G/A	7.74	1.94	2.78	1.30	2	1	3	2
4	G/A	7.38	(-)	2.39	1.24	2	1	2	2
5	G/G	5.51	1.38	1.31	1.12	1	1	2	1

SNP: Single nucleotide polymorphism; HCV: Hepatitis C virus.

Table 8 Logistic regression analysis of factors associated with seronegative occult occurrence of hepatitis C virus

Variable	Univariate analysis			Multivariate analysis
	OR	95%CI	P value	OR	95%CI	P value
Age	1.15	1.11-1.19	< 0.001
Blood transfusion	0.39	0.17-0.92	0.031
Family history of HCV	3.66	1.85-7.25	< 0.001
Intrahepatic HCV RNA level	0.30	0.23-0.39	< 0.001
IL-28B C/C	0.29	0.12-0.74	0.009	0.28	0.11-0.71	0.008
CXCL10 G-201A G/G	0.32	0.15-0.68	0.003	0.31	0.15-0.66	0.002

P < 0.05; OR: Odds ratio