Association of interferon lambda-4 rs12979860 polymorphism with hepatocellular carcinoma in patients with chronic hepatitis C infection

Table 1 Sociodemographic and clinical features of chronic hepatitis C virus positive patients

Characteristics	Total, n = 305	Fibrosis, n = 53	Cirrhosis, n = 154	HCC, n = 98	P value
Age in yr	59.85 ± 8.83	57.89 ± 10.43	59.29 ± 8.43	61.78 ± 8.22	0.019
Male	144 (47.2)	20 (37.7)	67 (43.5)	57 (58.2)	0.024
Ethnicity, Caucasian	218 (71.5)	35 (66.1)	110 (71.4)	73 (74.5)	0.547
BMI in kg/m²	27.08 ± 4.85	26.39 ± 4.14	27.80 ± 5.39	26.34 ± 4.15	0.038
Level of education					0.366
Completed primary education or less	196 (62.0)	31 (56.6)	100 (62.3)	65 (64.3)
Secondary or higher education	102 (24.9)	20 (34.0)	51 (25.3)	31 (19.4)
Smoker	59 (19.3)	16 (30.2)	31 (20.1)	12 (12.2)	0.001
Alcohol consumption					0.004
No	260 (85.2)	49 (92.5)	137 (89.0)	74 (75.5)
Former	45 (14.8)	4 (7.5)	17 (11.0)	24 (24.5)
Illicit drug use					0.164
No	243 (79.7)	43 (81.1)	122 (79.2)	78 (79.6)
Yes	9 (3.0)	4 (7.5)	4 (2.6)	1 (1.0)
Former user	53 (17.4)	6 (1.1)	28 (18.2)	19 (19.4)
Coffee drinker	213 (69.8)	39 (73.6)	112 (72.7)	62 (63.3)	0.226
Age at infection of HCV in yr	27.43 ± 9.75	28.47 ± 9.12	27.48 ± 9.77	26.64 ± 10.26	0.735
Age at diagnosis of HCV in yr	49.11 ± 11.11	46.88 ± 12.99	49.17 ± 10.97	50.24 ± 10.11	0.223
HCV infection via blood transfusion	125 (41.0)	24 (45.3)	64 (41.6)	37 (37.8)	0.706
HCV-RNA as log10UI/mL	6.05 ± 0.86	-	6.11 ± 0.87	5.86 ± 0.78	0.141
HCV genotypes					0.060
1	124 (40.7)	-	86 (55.8)	38 (38.8)
2	7 (2.3)	-	4 (2.6)	3 (3.1)
3	112 (36.7)	-	61 (39.6)	51 (52.0)
Antiviral treatment	178 (58.4)	-	115 (74.7)	63 (64.3)	0.077
Diabetes	85 (27.9)	-	50 (32.5)	35 (35.7)	0.595
Steatosis	24 (7.9)	-	13 (8.4)	11 (11.2)	0.431
Ascites	66 (21.6)	-	31 (20.1)	35 (35.7)	0.005
Portal hypertension	146 (47.9)	-	72 (46.8)	74 (75.5)	< 0.001
Esophageal varices	156 (51.1)	-	91 (59.0)	65 (66.3)	0.231
Upper gastrointestinal bleeding	49 (16.0)	-	26 (16.9)	23 (23.5)	0.184
Spontaneous bacterial peritonitis	13 (4.3)	-	7 (4.5)	6 (6.1)	0.568
Hepatic encephalopathy	24 (7.9)	-	13 (8.4)	11 (11.2)	0.431
Child-Pugh					0.083
A	137 (44.9)	-	95 (61.7)	42 (42.9)
B	43 (14.1)	-	28 (18.2)	15 (15.3)
C	9 (3.0)	-	3 (1.9)	6 (6.1)
Number of tumors
1		-	-	62 (63.37)
2		-	-	17 (17.35)
≥ 3		-	-	18 (18.37)
Tumor size in cm		-	-	2.8 ± 1.81
Portal vein thrombosis		-	-	10 (10.20)
Extrahepatic metastases		-	-	7 (7.14)
Liver transplantation		-	-	47 (47.96)
Deaths	14 (4.59)	-	8 (5.19)	6 (6.12)	0.754

Characteristics expressed as number and percentage or mean ± SD. BMI: Body mass index; HCC: Hepatocellular carcinoma; HCV: Hepatitis C virus.

Table 2 Allele and genotype frequencies of interferon lambda-4 rs12979860 polymorphism in patients with hepatitis C virus-associated liver diseases and healthy control subjects

rs12979860	Control, n = 260	Total patients, n = 305	Fibrosis, n = 53	Cirrhosis, n = 154	HCC, n = 98	P value
						Fibrosis vs Control	Cirrhosis vs Control	HCC vs Control	Fibrosis vs Cirrhosis	Cirrhosis vs HCC
Allele						0.047	< 0.001	0.010	0.708	0.618
C	345 (66.3)	331 (54.3)	59 (55.7)	163 (52.9)	109 (55.6)
T	175 (33.7)	279 (45.7)	47 (44.3)	145 (47.1)	87 (44.4)
Genotype						0.113	< 0.001	0.002	0.541	0.665
CC	115 (44.2)	76 (24.9)	16 (30.2)	36 (23.4)	24 (24.5)
CT	115 (44.2)	179 (58.7)	27 (50.9)	91 (59.1)	61 (62.2)
TT	30 (11.6)	50 (16.4)	10 (18.9)	27 (17.5)	13 (13.3)

Variables expressed as number (percentage). HCC: Hepatocellular carcinoma; HCV: Hepatitis C virus.

Table 3 Genetic models of association between interferon lambda-4 rs12979860 polymorphism and hepatitis C virus-associated liver diseases

rs12979860	Fibrosis vs Control		Cirrhosis vs Control		HCC vs Control		Fibrosis vs Cirrhosis		Cirrhosis vs HCC
	OR (95%CI)	P value	OR (95%CI)	P value	OR (95%CI)	P value	OR (95%CI)	P value	OR (95%CI)	P value
Codominant model
CC	1.00 (Ref.)	-	1.00 (Ref.)	-	1.00 (Ref.)	-	1.00 (Ref.)	-	1.00 (Ref.)	-
CT	1.69 (0.82-3.54)	0.126	2.53 (1.55-4.15)	< 0.001	2.54 (1.44-4.56)	0.001	1.50 (0.67-3.28)	0.277	1.01 (0.52-1.95)	0.986
TT	2.40 (0.87-6.27)	0.053	2.88 (1.44-5.77)	0.001	2.08 (0.86-4.83)	0.068	1.20 (0.43-3.45)	0.702	0.72 (0.28-1.80)	0.447
T allele dominant model
CC	1.00 (Ref.)	-	1.00 (Ref.)	-	1.00 (Ref.)	-	1.00 (Ref.)	-	1.00 (Ref.)	-
CT + TT	1.83 (0.94-3.71)	0.061	2.60 (1.63-4.19)	< 0.001	2.45 (1.42-4.31)	0.001	1.42 (0.66-2.97)	0.325	0.94 (0.50-1.79)	0.840

CI: Confidence interval; HCC: Hepatocellular carcinoma; HCV: Hepatitis C virus; OR: Odds ratio; Ref.: Reference.

Table 4 Distribution of the interferon lambda-4 rs12979860 genotypes based on the clinical features of patients with hepatocellular carcinoma, n = 98

		Genotypes		Codominant model	T allele dominant model
Variable	CC, n = 24	CT, n = 61	TT, n = 13	P value	P value
HCV genotypes				0.052	0.017
1	3 (14.3)	27 (46.6)	8 (61.5)		0.004
2	1(4.8)	2 (3.4)	-
3	17 (81.0)	29 (50.0)	5 (38.5)		0.007
Diabetes	10 (41.7)	19 (31.1)	6 (46.2)	0.463	0.484
Steatosis	1(4.2)	8 (13.3)	2 (16.7)	0.409	0.195
Ascites	10 (41.7)	20 (32.8)	5 (41.7)	0.679	0.511
Portal hypertension	17 (70.8)	48 (78.7)	9 (75.0)	0.741	0.469
Esophageal varices	17 (70.8)	39 (63.9)	9 (75.0)	0.682	0.646
Upper gastrointestinal bleeding	8 (33.3)	10 (16.4)	5 (41.7)	0.075	0.201
Spontaneous bacterial peritonitis	1 (4.2)	5 (8.2)	-	0.500	0.636
Hepatic encephalopathy	3 (12.5)	2 (3.3)	3 (25.0)	0.030	0.383
Child-Pugh				0.209	0.156
A	8 (61.5)	26 (63.4)	8 (88.9)
B	2 (15.4)	12 (29.3)	1 (11.1)
C	3 (23,1)	3 (7.3)	-
Number of tumors				0.325	0.684
1	17 (70.8)	39 (65.0)	6 (46.2)
2	3 (12.5)	12 (20.0)	2 (15.4)
≥ 3	4 (16.7)	9 (15.0)	5 (38.5)
Portal vein thrombosis	4 (16.7)	4 (6.6)	2 (16.7)	0.286	0.238
Extrahepatic metastases	1 (4.2)	5 (8.6)	1 (7.7)	0.780	0.487

Variables expressed as number (percentage). HCC: Hepatocellular carcinoma; HCV: Hepatitis C virus.