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Vitamin E and Vitamin C Treatment Improves Fibrosis in Patients With Nonalcoholic Steatohepatitis

Nonalcoholic steatohepatitis (NASH) is one of the most common forms of liver disease and is frequently associated with clinical conditions such as obesity, type II diabetes mellitus, hyperlipidemia, and hypertension. Recent data suggest that the prevalence of this disease is increasing as the incidence of diabetes and obesity increase. Several studies have now demonstrated that this is not a benign condition: 7–17% of patients with NASH will progress to cirrhosis over time.

Based on present concepts of pathogenesis, oxidative stress likely is involved in the progression of disease from steatosis to NASH and potentially cirrhosis. It has been shown that chronic oxidative stress, generated through the oxidation of cytotoxic free fatty acids, can lead to upregu-lation of cytokines, induction of the liver cytochrome P450 enzyme 2E1, and depletion of hepatic antioxidant concentrations. In addition, enhanced lipid peroxidation leads to the generation of byproducts, such as 4-hy-droxynonenal and malonaldehyde, which have been shown to further enhance cytokine stimulation and are involved in hepatic stellate cell activation, leading to fibrogenesis and enhanced extracellular matrix protein deposition. Seki et al. have recently shown that lipid peroxidation products are elevated in NASH patients, occur more prominently in zone 3 of the liver parenchyma, and correlate directly with increasing necroinflammatory activity and fibrosis.