A preliminary investigation on the possible association between diminished copper availability and non-alcoholic fatty liver disease in epileptic patients treated with valproic acid

Figures & data

Table I. Results obtained in the patients treated with valproic acid in monotherapy according to its ceruloplasmin-specific oxidase activity.

	Specific oxidase activity <333(U/g)	Specific oxidase activity ≥333(U/g)
n (males/females)	28 (18/10)	47 (21/26)
VPA Css (mg/L)	63.2 ± 4.0 (67.9)	63.5 ± 2.7 (60.4)
VPA dose (mg/24h)	1170.0 ± 93.1 (1200.0)	1241.9 ± 86.1 (1000.0)
Specific oxidase activity (U/g)	278.5 ± 6.8 (276.1)^a	430.5 ± 13.0 (405.4)
Copper/ceruloplasmin ratio (μg/mg)	3.2 ± 0.1 (3.2)^a	3.9 ± 0.1 (3.8)
Glucose (mg/dL)	94.5 ± 5.1 (89.0)	88.4 ± 2.0 (87.5)
Cholesterol (mg/dL)	191.0 ± 10.2 (199.0)	175.5 ± 8.2 (171.0)
Triglycerides (mg/dL)	134.5 ± 13.2 (108.0)	107.7 ± 8.9 (99.0)
GGT (U/L)	31.6 ± 8.8 (12.6)	17.2 ± 2.5 (10.0)
ALP (U/L)	161.2 ± 11.3 (132.0)	162.1 ± 3.7 (143.0)
ChE (U/L)	7061.6 ± 407.4 (7250.0)	7005.9 ± 229.4 (7050.0)
AST(U/L)	14.6 ± 1.1 (13.5)	16.7 ± 1.9 (13.0)
ALT(U/L)	19.2 ± 1.6 (20.0)	22.1 ± 3.9 (14.5)
AST/ALT ratio	0.8 ± 0.1 (0.8)	0.9 ± 0.1 (0.7)
CRP (mg/L)	3.4 ± 1.2 (1.4)	6.6 ± 2.6 (1.4)
APRI score	0.37 ± 0.06(0.30)	0.35 ± 0.05(0.30)
FIB-4 score	0.89 ± 0.12(0.80)	0.84 ± 0.12(0.60)

^aSignificance: P < 0.01.

Table II. Results obtained in the patients treated with valproic acid in polytherapy according to its ceruloplasmin-specific oxidase activity.

	Specific oxidase activity<333(U/g)	Specific oxidase activity ≥333(U/g)
n (males/females)	10 (7/3)	16 (10/6)
VPA Css (mg/L)	49.4 ± 4.1 (48.1)	49.1 ± 6.3 (41.5)
VPA dose (mg/24h)	1900.0 ± 362.5 (1500.0)	1733.3 ± 244.5 (1500.0)
Specific oxidase activity (U/g)	256.0 ± 19.5 (279.8)^b	454.3 ± 18.0 (439.3)
Copper/ceruloplasmin ratio (μg/mg)	3.3 ± 0.2 (3.2)^a	3.9 ± 0.2 (3.9)
Glucose (mg/dL)	85.4 ± 1.7 (86.0)	98.9 ± 7.8(87.5)
Cholesterol (mg/dL)	215.4 ± 19.6 (194.0)	222.8 ± 23.5 (209.0)
Triglycerides (mg/dL)	126.8 ± 17.6 (130.5)	130.2 ± 25.0 (102.0)
GGT (U/L)	65.0 ± 19.3 (50.5)	70.6 ± 18.2 (44.0)
ALP (U/L)	145.2 ± 21.1 (147.0)	201.2 ± 34.1 (164.5)
ChE (U/L)	7198.6 ± 845.9 (7308.0)	7638.0 ± 798.0 (7147.0)
AST(U/L)	17.6 ± 4.4 (14.5)	15.9 ± 1.7 (15.0)
ALT(U/L)	27.4 ± 9.2 (19.0)	21.1 ± 3.1 (16.0)
AST/ALT ratio	0.8 ± 0.1 (0.7)	0.9 ± 0.1 (0.8)
CRP (mg/L)	38.7 ± 26.0 (8.9)	27.0 ± 14.7 (4.9)
APRI score	0.33 ± 0.07(0.30)	0.25 ± 0.04 (0.20)
FIB-4 score	0.69 ± 0.12(0.70)	0.63 ± 0.15 (0.50)

^aSignificance: P < 0.05.

^bSignificance: P < 0.001.

Figure 1. Distribution of the APRI score (A) and FIB-4 score (B) in males (•) and females (○) controls and patients treated with valproic acid in monotherapy (VPAM) and polytherapy (VPAP). The dashed lines correspond to the cut-off values for absence (APRI <0.5; FIB-4 <1.45) or presence of significant liver fibrosis (APRI>1.5; FIB-4 >3.25).