Liver insulin-like growth factor 2 methylation in hepatitis C virus cirrhosis and further occurrence of hepatocellular carcinoma

Table 1 Baseline characteristics in 94 patients with Child-Pugh A hepatitis C-related cirrhosis and defined methylation profile at the insulin growth factor 2 gene: distribution and prognostic value for the occurrence of hepatocellular carcinoma at 10 years in univariate analysis

		Patients (n = 94)	No HCC (n = 74)	HCC (n = 20)	HR (95% CI)	P
Gender	Female	39	32	7	1
	Male	55	42	13	1.38 (0.55-3.48)	0.49
Age (yr)		57.7 ± 13.7	56.0 ± 14.4	63.9 ± 8.0	1.05 (1.01-1.09)	0.01
BMI (kg/m2)		25.0 ± 4.8	25.1 ± 4.8	24.7 ± 4.8	1.00 (0.90-1.11)	0.96
BMI ≥ 30 kg/m2	No	80	64	16	1
	Yes	14	10	4	2.16 (0.72-6.51)	0.17
Diabetes	No	73	57	16	1
	Yes	21	17	4	1.00 (0.33-2.98)	0.99
Oesophageal	0 or I	78	63	15	1
Varices grade	II or III	16	11	5	2.47 (0.89-6.83)	0.08
Bilirubin (μmol/L)		15.1 ± 8.8	14.6 ± 8.3	17.2 ± 10.4	1.05 (1.00-1.10)	0.05
Albumin (g/L)		41.1 ± 5.7	41.1 ± 5.6	41.0 ± 6.3	0.98 (0.90-1.06)	0.59
Prothrombin (%)		84.1 ± 16.2	85.2 ± 15.9	79.7 ± 16.9	0.97 (0.95-1.00)	0.04
Platelets (× 103/mm3)		151 ± 61	155 ± 64	138 ± 51	1.00 (0.99-1.00)	0.29
ALAT (× ULN)		3.2 ± 2.5	3.2 ± 2.6	3.2 ± 1.8	0.97 (0.80-1.19)	0.80
ASAT (× ULN)		2.9 ± 2.1	2.8 ± 2.0	3.2 ± 2.5	1.10 (0.91-1.33)	0.33
GGT (× ULN)		2.8 ± 2.7	2.8 ± 2.9	2.7 ± 1.7	0.99 (0.84-1.16)	0.86
AFP (ng/mL)		16.4 ± 26.9	17.2 ± 29.2	13.3 ± 15.7	1.01 (0.99-1.02)	0.54
Knodell score		10.8 ± 2.2	10.6 ± 2.4	11.7 ± 2.4	1.23 (1.00-1.51)	0.06
Serum IGF2 (ng/mL)1		279.6 ± 114.3	291.4 ± 117.3	234.1 ± 92.1	0.99 (0.98-1.01)	0.08
Liver Igf2	U	13	9	4	7.64 (0.85-68.62)	0.07
Methylation profile	UM	64	49	15	3.98 (0.53-30.14)	0.18
(3 classes)	M	17	16	1	1

Continuous values are used for quantitative parameters. HR: Hazard ratio; CI: Confidence interval; HCC: Hepatocellular carcinoma; BMI: Body mass index; ALAT: Alanine amino-transferase; GGT: Gamma glutamyl transferase; ULN: Upper limit of normal; AFP: Alpha-foetoprotein; IGF2: Insulin-growth factor 2.

¹Performed in 63 patients.

Table 2 Baseline characteristics according to the methylation profile at the Igf2 locus (U, UM, and M, respectively, for hypomethylated, normal and hypermethylated patterns) in patients with Child-Pugh A hepatitis C-related cirrhosis

	U (n = 13)	UM (n = 64)	M (n = 17)	Asymptotic global P-value
Male gender (%)	7 (53.8%)	38 (59.4%	10 (58.8%)	0.934
Age (yr)	58.15 (16.71)	57.55 (13.00)	57.89 (14.41)	0.985
Alcohol (g/d)	43.08 (64.21)	22.28 (45.97)	38.24 (77.48)	0.551
Tobacco (Pack, yr)	3.8 (7.1)	6.1 (13.1)	5.7 (11.5)	0.981
BMI (kg/m2)	26.32 (5.18)	25.41 (4.97)	23.86 (4.04)	0.244
Diabetes (%)	2 (15.4%)	14 (21.9%)	4 (23.5%)	0.883
Platelets (× 103/mm3)	147.28 (64.46)	152.32 (63.71)	177.30 (127.43)	0.958
Prothrombin (%)	79.46 (17.81)	84.58 (16.59)	85.59 (13.28)	0.433
Albumin (g/L)	40.45 (4.96)	40.77 (6.27)	42.76 (3.40)	0.437
Bilirubin (μmol/L)	14.58 (9.66)	15.16 (8.85)	15.50 (8.45)	0.731
ALAT (× ULN)	3.23 (2.13)	3.23 (2.61)	3.14 (2.16)	0.961
AFP (ng/mL)	13.58 (11.24)	13.88 (18.57)	28.21 (51.52)	0.530
Serum IGF2 (ng/mL)1	249.64 (81.23)	276.32 (116.97)	321.55 (129.24)	0.393
OV grade II or III (%)	5 (38.5%)	9 (14.1%)	2 (11.8%)	0.084
Knodell score (mean, SD)	11.6 (1.8)	10.6 (2.3)	10.7 (2.5)	0.414
HCV genotype 12 (%)	7 (63.6%)	41 (78.8%)	8 (53.3%)	0.125

Quantitative variables are expressed as means (SD). BMI: Body mass index; ALAT: Alanine amino-transferase; ULN: Upper limit of normal; AFP: Alpha-foetoprotein; IGF2: Insulin growth factor 2; OV: Esophageal varices; HCV:hepatitis C virus.

¹Performed in 63 patients,

²known in 78 patients (11, 52, 15 patients respectively in U, UM and M groups).