Oxidative stress, immunological and cellular hypoxia biomarkers in hepatitis C treatment-naïve and cirrhotic patients.

ABSTRACT

INTRODUCTION: Hepatitis C virus (HCV) is the main cause of chronic liver disease, with calamitous complications. Its highest rate is recorded in Egypt. This study investigated whether oxidative stress, immunological chaos and cellular hypoxia are implicated in the pathophysiology of the disease. MATERIAL AND METHODS: This cross-sectional study aimed to evaluate the changes in blood oxidative stress, cellular hypoxia/angiogenesis and cellular immunological biomarkers in hospital-diagnosed treatment-naïve HCV-infected Upper Egyptian chronic liver disease patients vs. healthy controls (n = 40). The consecutively included patients comprised 120 with normal serum enzymes (HCV-NE) and 130 with high serum enzymes (HCV-HE), along with 120 cirrhotic patients. RESULTS: Oxidative stress biomarkers - malondialdehyde (MDA), total peroxides and oxidative stress index (OSI) - were significantly lower in controls vs. each of the patient groups. Cirrhotic patients presented the highest levels. However, total antioxidants (TAO) showed non-significant differences among the four groups. The cellular hypoxia/angiogenesis biomarkers - lactate, vascular endothelial cell growth factor (VEGF) and its soluble receptor 1 (sVEGFR1) - vs. controls were massively increased in patient groups. VEGF was lowest while sVEGFR1 was highest among cirrhotic patients. Immunological biomarkers, - granulocyte/monocyte-colony stimulating factor (GM-CSF) and total immunoglobulin G (IgG) - were massively increased in patient groups vs. controls. GM-CSF was lowest in HCV-HE and IgG was highest in cirrhotic patients. sVEGFR1 correlated with the progression towards cirrhosis. CONCLUSIONS: Oxidative stress is implicated in the progress of HCV infection with marked induction of cellular hypoxia and dysfunctional angiogenesis, and a futile immunological reaction. sVEGFR1 level correlated with progression towards HCV-induced liver fibrosis.