Oxidative stress and antioxidant status in patients with autoimmune liver diseases

Figures & data

Table 1. Age, gender, BMI, dietary and lifestyle habits of patients and controls

	AC controls	AC patients	AIH controls	AIH patients
Gender (male/female)	(8/42)	(6/43)	(10/31)	(8/28)
Age (years)	54 ± 15	57 ± 14	49 ± 17	50 ± 15
BMI (kg/(h)^Citation2)	26 ± 4	26 ± 4	26 ± 3	26 ± 6
Smokers	33%	16%	18%	16%
Smoking (pack-years)	29 ± 24	29 ± 27	26 ± 50	27 ± 59
Alcohol consumption (1–7 drinks/week)	36%	24%	15%	16%
Meat consumption >4 times/week	35%	20%	30%	26%
Fruit consumption >7 times/week	55%	52%	65%	60%
Vegetables consumption >7 times/week	80%	53%	75%	80%

Values shown as percentages % or as mean ± SD.

BMI, body mass index.

Table 2. Markers of lipid peroxidation, protein oxidation, activities of oxidant enzymes and antioxidant defence in controls and AC group in relation to disease stage and treatment response

Parameters	Controls (n = 50)	AC patients (n = 49)	Cirrhotics with AC (n = 6)	Non-cirrhotics with AC (n = 43)	Naïve patients with AC (n = 9)	Treated patients with AC (n = 40)	Non-responders to treatment with AC (n = 9) (3 patients with cirrhosis)	Responders to treatment with AC (n = 31) (3 patients with cirrhosis)
8-Iso ng/mg creatinine (U)	1 (0.01–2.7)	1.8*** (0.2–3.7)	2.6*** (1.7–3.2)	1.8**** (0.2–3.7)	2.5** (2.2–3.4)	1.8**** (0.2–3.7)	2.1*** (0.6–3.2)	1.8**** (0.2–3.7)
Aldehydes μM (P)	0.3 (0.05–4.7)	1.2*** (0.1–3.8)	0.4 (0.1–1)	1.3*** (0.1–3.7)	2.1* (0.3–3.8)	0.9** (0.1–3.8)	0.3 (0.1–2.1)	1.7**** (0.2–3.8)
3-NT nM (P)	11 (1.5–20)	14** (1.3–70)	22 (1.8–50)	14 (1.3–70)	6.9 (2.5–20)	14 (1.3–70)	14 (1.9–40)	13 (1.3–70)
PC mg/mg protein (S)	1.6 (0.1–10)	4.1**** (0.01–21)	8.1**** (5.9–21)	3.7****/^+ (0.02–19)	5.4 (0.02–4.6)	4*** (0.02–21)	3.6*** (0.02–21)	4.2*** (0.14–15)
MPO U/10^6cells (L)	12 (1–142)	19 (1.3–511)	13 (2–39)	20 (1.3–511)	7 (1.3–65)	25** (1.3–511)	10 (1.3–511)	26 (2–245)
GSSG (GSH + GSSG) (WB)	5.1 (0.1–36)	14*** (0.2–92)	27** (1.5–75)	12 (0.2–92)	12 (0.2–71)	10** (0.2–92)	13 (0.2–92)	14 (0.4–71)
GSH μM (WB)	1101 (276–5409)	475**** (4–2743)	209**** (89–659)	495*** (4–2743)	258** (18–2743)	500**** (18–1872)	426**** (4–1400)	494** (18–1872)
Catalase kU/gHb (RC)	142 (50–449)	148 (11–504)	144 (79–265)	153 (11–504)	144 (28–430)	130 (11–504)	124** (14–294)	162 (11–504)
SOD kU/gHb (RC)	43 (8–68)	51*** (14–78)	52 (25–60)	50** (14–78)	46 (24–78)	51** (14–60)	52** (29–78)	50** (14–60)
GSH-Px U/gHb (RC)	3.6 (0.3–25)	4.9 (0.1–63)	7.8 (0.8–16)	3.4 (0.1–63)	3 (0.8–63)	3.5 (0.1–63)	3.4 (0.4–25)	3.7 (0.1–63)
Glutathione reductase U/gHb (RC)	1.6 (0.08–10)	2.6 (0.1–36)	2.9 (0.5–16)	2.6 (0.1–36)	3.3 (0.83–36)	2.6 (0.1–37)	2.7 (0.22–37)	2.6 (0.1–35)
AST U/l (S)	20 (12–44)	23 (12–100)	37* (19–100)	22 (12–48)	18 (15–30)	23 (12–100)	25 (15–100)	21 (12–39)
ALT U/l (S)	20 (11–57)	26** (6–86)	44 (12–58)	25** (6–86)	18 (6–31)	26** (6–86)	31** (12–86)	21 (6–50)
ALP U/l (S)	61 (32–96)	81**** (28–279)	130* (41–191)	79**** (28–279)	67 (41–120)	120**** (28–279)	127**** (46–279)	73 (28–117)
γ-GT U/l (S)	14 (5–44)	28**** (10–213)	71* (11–196)	27**** (10–213)	25 (12–75)	30**** (10–213)	52**** (13–213)	21 (10–37)
Bilirubin mg/dl (S)	0.5 (0.1–1)	0.6*** (0.23–1.7)	1.1** (0.53–1.7)	0.6** (0.23–1.6)	0.45 (0.26–1.6)	0.6**** (0.23–1.7)	0.7**** (0.23–1.7)	0.6 (0.29–1.1)
UDCA (duration of intake in months)		29 (1–168)	50 (12–168)	29 (1–91)		29 (1–168)	25 (2–91)	38 (1–168)

Values shown as medians with range. P values (<0.05) derived by the Mann–Whitney U test (*vs. control group, ⁺vs. cirrhotic group).

*0.1 > P > 0.05, **/⁺P ≤ 0.05, ***P ≤ 0.01, ****P ≤ 0.001. GSSG/(GSH + GSSG) was expressed as %.

U, urine; P, plasma; S, serum; WB, whole blood; L, leucocytes; RC, red blood cells; UDCA, ursodeoxycholic acid.

Table 3. Markers of lipid peroxidation, protein oxidation, activities of oxidant enzymes and antioxidant defence in controls and AIH group in relation to disease stage and treatment response

Parameters	Controls (n = 41)	AIH patients (n = 36)	Cirrhosis (n = 10)	No cirrhosis (n = 26)	Non-responders to treatment (n = 10) (4 patients with cirrhosis)	Responders to treatment (n = 23) (6 patients with cirrhosis)
8-Iso ng/mg creatinine (U)	1 (0.02–3)	1.3*** (0.01–8.5)	2.6** (0.4–8.5)	0.9 (0.01–5)	0.9 (0.01–8.5)	1.2 (0.4–4.2)
Aldehydes μM (P)	0.3 (0.05–4.7)	1.7**** (0.2–7.9)	3**** (0.18–7.8)	1.7**** (0.17–6.6)	1.7*** (0.2–7.9)	0.8**** (0.2–7)
3-NT nM (P)	9 (1.5–20)	12*** (1.6–100)	12 (2.3–48)	15 (1.64–100)	6.5 (2.1–100)	12 (1.6–48)
PC mg/mg protein (S)	1.8 (0.1–9.9)	1.8* (0.1–14)	3.8*** (0.6–15)	1.5^+ (0.15–6.8)	6.7** (0.14–14)	1.9 (0.5–6.3)
MPO U/10^6cells (l)	12 (1–141)	10.5 (1.2–463)	11.5 (1.5–87)	10.5 (1.2–462)	9.7 (1.2–463)	12 (1.5–160)
GSSG/(GSH + GSSG) (WB)	4.3 (0.2–15)	9.5** (0.1–93)	8.6 (1.4–85)	12.4 (0.1–93)	6.7** (0.3–93)	7.9** (0.1–85)
GSH μM (WB)	1135 (293–5409)	512*** (51–5541)	293**** (51–5541)	511***^/++ (88–2977)	519**** (88–5541)	800** (51–1033)
Catalase kU/gHb (RC)	146 (40–449)	173 (5–772)	147 (5–320)	215** (22–772)	236*** (5–772)	148 (17–409)
SOD kU/gHb (RC)	44 (8–68)	48 (13–59)	37 (16–59)	47 (13–59)	24 (13–59)	45 (13–59)
GSH-Px U/gHb (RC)	3.6 (0.3–25)	8.6** (0.6–36)	7 (2.2–32)	8.8** (0.6–35)	8.9** (1.6–36)	8.9*** (0.6–33)
Glutathione reductase U/gHb (RC)	2.4 (0.1–10)	2.1 (0.08–36)	2.2 (0.08–36)	2.3 (0.08–8.9)	2.6 (0.1–36)	2.3 (0.2–8)
AST U/l (S)	20 (12–30)	25*** (10–117)	29* (10–65)	25** (10–117)	52*** (18–117)	23 (10–49)
ALT U/l (S)	18 (9–29)	25*** (10–160)	23** (10–81)	26*** (12–160)	56 **** (20–160)	20 (10–43)
ALP U/l (S)	61 (32–91)	61 (26–320)*	64 (49–136)*	60 (26–320)*	106*** (30–300)	61 (26–116)
γ-GT U/l (S)	13 (5.2–27)	22.5**** (8–277)	21** (8–170)	23**** (8–277)	35**** (12–240)	15 (8–69)
Bilirubin mg/dl (S)	0.5 (0.1–1)	0.7*** (0.3–1.96)	1*** (0.3–1.96)	0.6** (0.2–1.32)	0.68*** (0.3–1.96)	0.5 (0.3–1)
Prednisolone (duration of intake in months)		30 (1–114)	54 (11–101)	13 (1–114)	16 (1–58)	36 (3–114)
MMF (duration of intake in months)		26 (1–94)	41 (11–84)	16 (1–94)	16 (1–60)	30 (3–94)

Values shown as medians with range. P values (<0.05) derived by the Mann–Whitney U test (*vs. control group, ⁺vs. cirrhotic group).

*0.1 > P > 0.05, **P ≤ 0.05, ***^/+P ≤ 0.01, ****^/++P ≤ 0.001. GSSG/(GSH + GSSG) was expressed as %.

U, urine; P, plasma; S, serum; WB, whole blood; L, leucocytes; RC, red blood cells; MMF, mycophenolate mofetil.

Figure 1. Markers of oxidative stress in controls and AC patients according to Ludwig's stage. Levels of 3-NT (A), PC (B), isoprostane (C), aldehydes (D), oxidized/total GSH ratio (E), and reduced glutathione (F). The results are expressed as median, interquartile range, and range. P values refer to the comparison between each stage to controls (Mann–Whitney U test).

Figure 2. Products of oxidative stress injury products in controls and AIH patients according to the stage of fibrosis. Products of lipid (A) and protein (B) oxidation. The results are expressed as median, interquartile range, and range. P values refer to the comparison between each stage to controls (Mann–Whitney U test).

Lindor KD, Gershwin ME, Poupon R, Kaplan M, Bergasa NV, Heathcote EJ; American Association for Study of Liver Diseases. Primary biliary cirrhosis. Hepatology 2009;50:291–308.

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