Hepatitis C virus clearance and less liver damage in patients with high cholesterol, low-density lipoprotein cholesterol and APOE ε4 allele

Table 1 Demographic and clinical characteristics of hepatitis C virus patients, n (%)

Variable	Chronic, n = 206	Clearance, n = 93	P value
Demographic and clinical data
Age, yr (mean ± SD) (range)	51.0 ± 12.0 (20-78)	47.1 ± 13.0 (21-74)	0.100
Female sex	123 (60)	48 (52)	0.236
Time of evolution, yr	18.0 ± 14.5	20.2 ± 15.6	0.156
BMI, kg/m2 (mean ± SD)	27.0 ± 6.0	28.0 ± 4.1	0.098
Normal weight	76 (36.4)	19 (19.3)	0.003
Overweight	87 (42.2)	51 (54.8)	0.042
Obesity	43 (20.8)	23 (24.7)	0.456
Glucose, mg/dL	105.6 ± 43.6	101.6 ± 33.0	0.46
HOMA-IR > 2.5	114 (55.4)	40 (43.0)	0.072
Type 2 diabetes	27 (13.1)	7 (7.5)	0.183
Biochemistry
AST, IU/L	74.2 ± 53.4	30.9 ± 14.4	< 0.001
ALT, IU/L	76.4 ± 66.7	31.5 ± 19.8	< 0.001
Lipid profile
Total cholesterol, mg/dL	148.1 ± 43.3	184.1 ± 43.1	< 0.001
LDL-c, mg/dL	83.7 ± 37.2	112.4 ± 35.4	< 0.001
Triglycerides, mg/dL	127.7 ± 61.3	168.2 ± 80.3	< 0.001
VLDL-c, mg/dL	25.8 ± 14.3	33.3 ± 15.8	0.001
HDL-c, mg/dL	39.7 ± 13.5	41.9 ± 17.7	0.766
Lipid abnormality
Hypercholesterolemia	20 (9.8)	30 (32.2)	< 0.001
High LDL-c	20 (9.7)	24 (25.8)	< 0.001
Hypertriglyceridemia	60 (29.1)	45 (48.3)	0.001
Hypoalphalipoproteinemia	85 (41.3)	44 (47.3)	0.328
Viral genotype
HCV genotype 1	138 (66.9)	Not determined	-
Non-genotype 1	68 (33.1)
Fibrosis stage1
F1	26 (29.5)	30 (62.5)	< 0.001
F2	19 (21.8)	11 (22.9)	0.883
F3	9 (10.3)	1 (2.1)	0.083
F4	33 (38.5)	6 (12.5)	0.002
Risk factors for HCV infection
Surgeries	144 (69.9)	62 (66.7)	0.164
Blood transfusion	119 (58)	36 (38.7)	0.169
Tattooing	49 (23.7)	19 (20.4)	0.375
Dental procedure	49 (23.7)	18 (19.3)	0.28
Sexual promiscuity	41 (19.9)	14 (15.0)	0.702
Acupuncture	28 (13.5)	8 (8.6)	0.464
Injection drug use	27 (13.1)	10 (10.7)	0.932
Body piercing	4 (1.9)	8 (8.6)	0.002

¹Liver damage was assessed in 87 chronic hepatitis C and 48 spontaneous clearance patients. BMI: Body mass index; HOMA-IR: Homeostatic model assessment insulin resistance; AST: Aspartate aminotransferase; ALT: Alanine aminotransferase.

Table 2  APOE allele distribution among the study population and stages of fibrosis in chronic hepatitis C patients, n (%)

	HCV-patients			Fibrosis stage in CHC patients4
	Chronic (n = 206)	Clearance (n = 93)	P value	F1-F2 (n = 49)	F3-F4 (n = 38)	P value
Genotypes
ε2ε2	2 (1.0)	0	-	0	0	-
ε2ε3	15 (7.4)	8 (8.6)	0.691	5 (10.5)	2 (5.3)	0.400
ε2ε4	2 (1.0)	0	-	0	0	-
ε3ε3	160 (77.5)	64 (68.8)	0.102	29 (59.2)	34 (89.5)	0.001
ε3ε4	26 (12.7)	19 (20.4)	0.080	14 (28.6)	1 (2.6)	0.001
ε4ε4	1 (0.5)	2 (2.2)	0.181	1 (2)	1 (2.6)	0.969
Alleles
ε2	21 (5.1)	8 (4.3)	0.674	4 (5.1)	2 (2.6)	0.603
ε3	361 (87.6)	155 (83.3)	0.158	78 (78.6)	70 (93.4)	0.0222
ε4	30 (7.3)	23 (12.4)	0.0421	16 (16.3)	4 (4)	0.0233
HWE	0.438	0.892	-	0.910	0.286	-

¹ε4 allele was associated with SC OR = 0.55, 95%CI: 0.31-0.98, P = 0.042.

²ε3 allele was associated with severe fibrosis (F3-F4) OR = 2.99, 95%CI: 1.13-7.87, P = 0.021.

³ε4 allele was associated with mild fibrosis (F1-F2) OR = 0.091, 95%CI: 0.01-0.75, P = 0.020.

⁴Liver damage was assessed in 87 chronic hepatitis C patients. CHC: Chronic hepatitis C; HWE: Hardy-Weinberg Equilibrium.

Table 3 Effect of APOE alleles on lipid profile and lipid abnormalities of hepatitis C virus patients

	Chronic			Clearance
	E2 (n = 19)	E3 (n = 160)	E4 (n = 27)	E2 (n = 8)	E3 (n = 64)	E4 (n = 21)
Lipid profile
TC, mg/dL	140.6 ± 34.1	150.9 ± 45.7	158.3 ± 45.5	142.7 ± 40.3	184.3 ± 41.43	188.9 ± 424
TG, mg/dL	134.4 ± 78.4	130.2 ± 59.6	114.2 ± 53.4	151.2 ± 81.6	169.1 ± 81.1	165.8 ± 79.4
HDL-c, mg/dL	36.9 ± 7.7	38.8 ± 12.9	45.9 ± 17.61	34.7 ± 6.5	42.6 ± 21.1	42.0 ± 9.7
VLDL-c, mg/dL	24.3 ± 11.4	26.7 ± 15.3	22.1 ± 10.0	30.1 ± 16.7	33.2 ± 15.7	33.1 ± 15.9
LDL-c, mg/dL	82.6 ± 29.2	85.6 ± 38.2	98.7 ± 43.5	77.7 ± 29.0	110.1 ± 33.15	121.6 ± 34.76
Lipid abnormalities, n (%)
Hypercholesterolemia	1 (5.3)	13 (8.1)	6 (22.2)2	0	19 (29.6)	8 (38.1)
Hypertriglyceridemia	7 (36.8)	43 (26.9)	6 (22.2)	3 (37.5)	26 (40.6)	9 (42.8)
Hypoalphalipoproteinemia	10 (52.6)	75 (46.9)	9 (33.3)	7 (87.5)	30 (46.9)	10 (47.6)
High LDL-c	1 (5.3)	14 (8.7)	5 (18.5)	0	12 (18.7)	7 (33.3)

¹E4 vs E3, P = 0.033;

²E4 vs E3, P = 0.024;

³E3 vs E2, P = 0.018;

⁴E4 vs E2, P = 0.014;

⁵E3 vs E2, P = 0.012;

⁶E4 vs E2, P = 0.005. E2: ε2ε2 + ε2ε3 + ε2ε4; E3: ε3ε3; E4: ε3ε4 + ε4ε4. TC: Total cholesterol; TG: Triglycerides; Hchol: Hypercholesterolemia; HTG: Hypertriglyceridemia; HALP: Hypoalphalipoproteinemia.

Table 4 Logistic regression analysis of variables associated with spontaneous hepatitis C virus clearance

Variable	Univariate			Multivariate
	OR	95%CI	P value	OR	95%CI	P value
AST, IU/L	1.058	1.040-1.076	< 0.001
ALT, IU/L	1.04	1.026-1.054	< 0.001	1.037	1.019-1.056	< 0.001
LDL-c, mg/dL	0.981	0.973-0.988	< 0.001	0.977	0.963-0.992	0.002
Total cholesterol, mg/dL	0.983	0.977-0.989	< 0.001
Triglycerides, mg/dL	0.993	0.989-0.996	< 0.001	0.992	0.986-0.999	0.027
VLDL-c, mg/dL	0.97	0.953-0.987	0.001
Age, (yr)	1.024	1.003-1.045	0.023
BMI, kg/m2	0.962	0.913-1.013	0.138	0.874	0.790-0.966	0.008
Female, sex	1.358	0.833-2.213	0.22
HDL-c, mg/dL	0.994	0.977-1.011	0.481

Hosmer and Lemeshow test: Chi-square = 4.53, P = 0.806. Only significant variables (P < 0.2) in the univariate analysis were introduced in the multivariate analysis when P < 0.05 was significant. AST: Aspartate aminotransferase; ALT: Alanine aminotransferase; LDL-c: Low-density lipoprotein cholesterol; VLDL-c: Very low-density lipoprotein cholesterol; BMI: Body mass index; HDL-c: High density-lipoprotein cholesterol; OR: Odds ratio; CI: Confidence interval.

Table 5 Receiver operating characteristic analysis of variables associated with spontaneous hepatitis C virus clearance

Variable	Cutoff	AUC	P value	Sensitivity, %	Specificity, %	PPV	NPV
ALT, IU/L	50.5	.79	< 0.001	62%	83%	88%	52%
LDL-c, mg/dL	101.5	.72	< 0.001	60.7%	78%	79%	58%
Triglycerides, mg/dL	117.5	.64	< 0.001	69%	55%	78%	42%
BMI, kg/m2	26.6	.59	0.018	63%	54%	76%	38.7%

PPV: Positive predictive value; NPV: Negative predictive value; AUC: Area under the curve; ALT: Alanine transaminase; LDL-c: Low-density lipoprotein cholesterol; BMI: Body mass index.