Antioxidant and immunomodulatory effects of Viusid in patients with chronic hepatitis C

Table 1 Ingredients of Viusid

Malic acid	0.666 g	Ascorbic acid	0.020 g
Glycyrrhizic acid	0.033 g	Folic acid	66 mcg
Glucosamine	0.666 g	Cyanocobalamine	0.3 mcg
Arginine	0.666 g	Zinc sulfate	0.005 g
Glycine	0.333 g	Pyridoxal	0.6 mg
Calcium pantothenate	0.002 g

Table 2 Baseline characteristics

Variable	Viusid (n = 30)	Placebo (n = 30)	P value1
Age (yr)	49.3 ± 2.1	49.7 ± 2.2	0.90
Sex, n (%)
Male	10 (33)	16 (53)	0.19
Female	20 (67)	14 (47)
Body mass index (kg/m2)	25.3 ± 0.7	26.4 ± 0.7	0.28
HCV RNA > 600 000 IU/mL, n (%)	24 (80)	21 (70)	0.36
Genotype 1, n (%)	30 (100)	30 (100)	1.00
Ishak inflammation score	5.98 ± 3	5.88 ± 3	0.55
Ishak fibrosis score	1.88 ± 0.91	2.06 ± 1.8	0.68
ALT (IU/L)	66.9 ± 7.6	75.4 ± 8.4	0.45
AST (IU/L)	55.9 ± 7	65.8 ± 7.6	0.34
Fasting plasma glucose (mmol/L)	5.1 ± 0.14	5.8 ± 0.4	0.09
Alkaline phosphatase (mmol/L)	217.8 ± 12.8	221.1 ± 13.7	0.86
Creatinine (mmol/L)	80.4 ± 2.8	82.8 ± 3.6	0.59
Hemoglobin (g/L)	126.4 ± 1.4	131.3 ± 2.7	0.11
γ-glutamyltransferase (IU/L)	72.7 ± 13.5	84.1 ± 13.8	0.55
Bilirubin (mmol/L)	11.4 ± 1.4	14.1 ± 1.3	0.16
Albumin (g/L)	47.8 ± 0.5	47.6 ± 0.9	0.80
Uric acid (mmol/L)	257 ± 16.8	276 ± 13.4	0.37
IL-1α (pg/mL)	3.26 ± 0.7	3.09 ± 0.5	0.89
IL-1β (pg/mL)	3.7 ± 0.1	4 ± 0.1	0.29
IL-2 (pg/mL)	17.9 ± 2.3	19.9 ± 4.7	0.93
IL-6 (pg/mL)	2.5 ± 0.2	2.1 ± 0.3	0.35
IL-10 (pg/mL)	2.6 ± 0.6	2.8 ± 4.1	0.67
IL-12 (pg/mL)	7.5 ± 1.4	7.6 ± 1.2	0.92
IFN-γ (pg/mL)	1.92 ± 0.2	1.80 ± 0.1	0.63
TNF-α (pg/mL)	6.6 ± 0.2	6.9 ± 0.5	0.45
TNF-β (pg/mL)	8.5 ± 0.4	9.1 ± 0.6	0.58
Cathepsin L (ng/mL)	1.7 ± 0.1	1.7 ± 0.1	0.99
GM-CSF (pg/mL)	4.4 ± 0.1	4.3 ± 0.1	0.97
MDA (μmol/L)	0.97 ± 0.05	1.12 ± 0.09	0.17
4-hydroxyalkenals (μmol/L)	1.75 ± 0.09	1.92 ± 0.14	0.30
Cu/Zn SOD (U/mg Hb)	17.6 ± 1.1	18.7 ± 0.9	0.46
CAT (U/mg Hb)	235 ± 23.7	289 ± 21.8	0.09
GR (mU/mg Hb)	6.1 ± 0.7	6.9 ± 1.1	0.73
GPx (mU/mg Hb)	169 ± 11.6	176 ± 11.2	0.66
GSH (μmol/L)	26.3 ± 2.3	31.8 ± 3.2	0.16
MPO (ng/mL)	221 ± 6.6	221 ± 6.7	0.91
AOPP (μmol/L)	36.1 ± 5.4	26.2 ± 5.5	0.20

¹P values are for the comparison between Viusid and placebo; Plus-minus values are mean ± SE of mean; For all laboratory measures and for continuous demographics: P value Mann-Whitney U-test; Proportions: Percentage, P value χ². HCV: Hepatitis C virus; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; IL: Interleukin; IFN: Interferon; TNF: Tumor necrosis factor; GM-CSF: Granulocyte-macrophage colony-stimulating factor; MDA: Malondialdehyde; Cu/Zn SOD: Copper/Zinc superoxide dismutase; CAT: Catalase; GR: Glutathione reductase; GPx: Glutathione peroxidase; GSH: Glutathione; MPO: Myeloperoxidase; AOPP: Advanced oxidation protein products.

Table 3 Patients’ baseline oxidative stress parameters and outcome at 6 mo

Variable	Viusid (n = 30)				Placebo (n = 30)				P value1
	Before treatment	After treatment	Change	P value	Before treatment	After treatment	Change	P value
MDA (μmol/L)	0.97 ± 0.05	0.29 ± 0.05	-0.68 ± 0.08	< 0.001	1.12 ± 0.09	0.76 ± 0.08	-0.36 ± 0.12	0.002	0.001
4-hydroxyalkenals (μmol/L)	1.75 ± 0.09	0.53 ± 0.06	-1.22 ± 0.1	< 0.001	1.92 ± 0.14	1.39 ± 0.13	-0.53 ± 0.2	0.01	0.001
Cu/Zn SOD (U/mg Hb)	17.6 ± 1.1	3.26 ± 0.4	-14.3 ± 1.2	< 0.001	18.7 ± 0.9	3.44 ± 0.39	-15.3 ± 1.04	< 0.001	0.71
CAT (U/mg Hb)	235 ± 23.7	17.6 ± 2.3	-217.4 ± 24	< 0.001	289 ± 21.8	21 ± 2.7	-268 ± 22	< 0.001	0.13
GR (mU/mg Hb)	6.1 ± 0.7	11 ± 1.1	4.9 ± 1.3	< 0.001	6.9 ± 1.1	12 ± 1.2	5.1 ± 1.6	0.001	0.97
GPx (mU/mg Hb)	169 ± 11.6	147 ± 12	-22 ± 17	0.20	176 ± 11.2	136 ± 16	-40 ± 19	0.05	0.87
GSH (μmol/L)	26.3 ± 2.3	16.4 ± 1.9	-9.9 ± 3	0.002	31.8 ± 3.2	19.8 ± 2.5	-12 ± 4.1	0.005	0.69
MPO (ng/mL)	221 ± 6.6	123 ± 12.9	-98 ± 14.2	< 0.001	221 ± 6.7	115 ± 22	-106 ± 23.2	< 0.001	0.61
AOPP (μmol/L)	36.1 ± 5.4	48.4 ± 13.7	12.3 ± 11.2	0.39	26.2 ± 5.5	35.9 ± 7.6	9.7 ± 9.3	0.30	0.57

¹P values are for the comparison between groups (change from baseline). Plus-minus values are mean ± SE of mean; Continuous parameters were analyzed using the Wilcoxon signed-ranks test and the Wilcoxon rank-sum tests were used for treatment group comparisons.

Table 4 Patients’ baseline cytokine values and outcome at 6 mo

Variable	Viusid (n = 30)				Placebo (n = 30)				P value1
	Before treatment	After treatment	Change	P value	Before treatment	After treatment	Change	P value
IL-1α (pg/mL)	3.26 ± 0.7	2.61 ± 0.3	-0.60 ± 0.8	0.04	3.09 ± 0.5	6.62 ± 2.3	3.53 ± 2.4	0.04	0.04
IL-1β (pg/mL)	3.7 ± 0.1	2.9 ± 0.1	-0.8 ± 0.1	< 0.001	4 ± 0.1	3 ± 0.1	-1 ± 0.2	< 0.001	0.24
IL-2 (pg/mL)	17.9 ± 2.3	11.3 ± 0.2	-6.5 ± 2.2	< 0.01	19.9 ± 4.7	12.1 ± 0.8	-7.8 ± 3.9	0.04	0.39
IL-6 (pg/mL)	2.5 ± 0.2	2.1 ± 0.2	-0.4 ± 0.3	0.14	2.1 ± 0.3	2 ± 0.2	-0.1 ± 0.3	0.71	0.24
IL-10 (pg/mL)	2.6 ± 0.6	8.3 ± 4.1	5.7 ± 4	0.04	2.8 ± 4.1	4.1 ± 0.1	1.3 ± 0.2	0.09	0.01
IL-12 (pg/mL)	7.5 ± 1.4	5.1 ± 0.9	-2.4 ± 1.1	0.04	7.6 ± 1.2	6.2 ± 1.5	-1.4 ± 1.4	0.34	0.29
IFN-γ (pg/mL)	1.92 ± 0.2	2.89 ± 0.4	0.97 ± 0.5	< 0.001	1.80 ± 0.1	1.68 ± 0.1	-0.11 ± 0.2	0.70	< 0.0001
TNF-α (pg/mL)	6.6 ± 0.2	7.1 ± 0.4	0.45 ± 0.4	0.26	6.9 ± 0.5	16.2 ± 3.4	9.3 ± 3.1	< 0.01	0.001
TNF-β (pg/mL)	8.5 ± 0.4	5.4 ± 0.1	-3.1 ± 0.5	< 0.001	9.1 ± 0.6	6.3 ± 1.2	-2.8 ± 1.2	0.03	0.21
Cathepsin L (ng/mL)	1.7 ± 0.1	2.9 ± 0.2	1.2 ± 0.2	< 0.001	1.7 ± 0.1	3.1 ± 0.2	1.4 ± 0.2	< 0.001	0.16
GM-CSF (pg/mL)	4.4 ± 0.1	4.6 ± 0.1	0.2 ± 0.2	0.24	4.3 ± 0.1	4.6 ± 0.1	0.3 ± 0.2	0.11	0.60

¹P values are for the comparison between groups (change from baseline). Plus-minus values are mean ± SE of mean; Continuous parameters were analyzed using the Wilcoxon signed-ranks test and the Wilcoxon rank-sum tests were used for treatment group comparisons.

Table 5 Patients’ baseline characteristics and outcome at 6 mo

Variable	Viusid (n = 30)			Placebo (n = 30)			P value1
	Before treatment	After treatment	P value	Before treatment	After treatment	P value
Body mass index (kg/m2)	25.6 ± 0.7	25.7 ± 0.7	0.92	26 ± 0.7	27.2 ± 0.6	0.08	0.12
Hemoglobin (g/L)	125.8 ± 1.4	125.2 ± 2.1	0.74	132.2 ± 2.7	135.6 ± 3.1	0.09	0.13
Alkaline phosphatase (mmol/L)	217.2 ± 12	206.1 ± 15	0.49	217.1 ± 13	211.4 ± 13	0.69	0.80
ALT (IU/L)	67.6 ± 7.6	65.1 ± 9.9	0.68	67.7 ± 8.4	63.5 ± 6	0.38	0.82
AST (IU/L)	56 ± 7	57.7 ± 9.1	0.81	62.7 ± 7.6	53.9 ± 6.5	0.11	0.24
Fasting plasma glucose (mmol/L)	5 ± 0.1	4.8 ± 0.2	0.17	5.6 ± 0.4	5.4 ± 0.5	0.69	0.91
Creatinine (mmol/L)	79.4 ± 2.8	75.7 ± 2.4	0.06	83.3 ± 3.6	77.7 ± 3	0.17	0.67
γ-glutamyltransferase (IU/L)	72.7 ± 13	40.8 ± 6.1	0.001	84.1 ± 14	74.4 ± 10	0.56	0.002
Albumin (g/L)	47.4 ± 0.5	46.6 ± 0.8	0.43	46.5 ± 0.9	46.1 ± 1	0.72	0.79
Bilirubin (mmol/L)	12.1 ± 0.08	11.9 ± 0.07	0.91	13.8 ± 0.07	14.3 ± 0.08	0.79	0.67
Uric acid (mmol/L)	257 ± 16.8	198 ± 13.8	0.01	276 ± 13.4	267 ± 18	0.66	0.04

¹P values are for the comparison between groups (change from baseline). Values are expressed as mean ± SE of mean; Continuous parameters were analyzed using the Wilcoxon signed-ranks test and the Wilcoxon rank-sum tests were used for treatment group comparisons.