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Systemic Oxidative Stress Markers In Cirrhotic Patients With Hepatic Encephalopathy: Possible Connections With Systemic Ammoniemia

Cătălin Sfarti, Alin Ciobica, Ioana-Miruna Balmus, Ovidiu-Dumitru Ilie, Anca Trifan, Oana Petrea, Camelia Cojocariu, Irina Gîrleanu, Ana Maria Sîngeap, Carol Stanciu

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Background and objectives: Oxidative stress shows evidence of dysregulation in cirrhotic patients with hepatic encephalopathy (HE), although there are still controversies regarding the connections between oxidative stress and ammonia in these patients. The aim of this study was to evaluate the oxidative stress implication in overt HE pathogenesis of cirrhotic patients. Materials and Methods: We performed a prospective case-control study, which included 40 patients divided into two groups: group A consisted of 20 cirrhotic patients with HE and increased systemic ammoniemia, and group B consisted of 20 cirrhotic patients with HE and normal systemic ammoniemia. The control group consisted of 21 healthy subjects matched by age and sex. The activity of superoxide dismutase (SOD), glutathione peroxidase (GPx), malondialdehyde (MDA) levels (lipid peroxidation marker), and ammoniemia were evaluated. Results: We found a significant decrease in SOD and GPx activity and also a significant increase of MDA levels in cirrhotic patients with HE as compared to the healthy age-matched control group (1.35 ± 0.08 vs. 0.90 ± 0.08 U/mL, p = 0.002; 0.093 ± 0.06 vs. 0.006 ± 0.008 U/mL, p = 0.001; and 35.94 ± 1.37 vs. 68.90 ± 5.68 nmols/mL, p = 0.0001, respectively). Additionally, we found significant correlations between the main oxidative stress markers and the levels of systemic ammonia (r = 0.452, p = 0.005). Patients from group A had a significant increase of MDA as compared with those from group B (76.93 ± 5.48 vs. 50.06 ± 5.60 nmols/mL, p = 0.019). Also, there was a compensatory increase in the activity of both antioxidant enzymes (SOD and GPx) in patients with increased systemic ammoniemia (group A), as compared to HE patients from group B. Conclusions: Our results demonstrated a significant decrease in antioxidants enzymes activities (SOD and GPx), as well as a significant increase in MDA concentrations, adding new data regarding the influence of oxidative stress in HE pathogenesis in cirrhotic patients.