370 IS ALANINE AMINOTRANSFERASE A SURROGATE MARKER OF SEVERE HEPATOCYTE APOPTOSIS IN PATIENTS WITH NON-ALCOHOLIC FATTY LIVER DISEASE

Apoptosis and oxidative injury are recognized as the most important causes of hepatocyte injury in non-alcoholic fatty liver disease (NAFLD). We aimed to search for the association between serum alanine aminotransferase (ALT) levels and hepatocyte apoptosis and oxidative stress parameters in NAFLD. Fifty patients (24 male / 26 female, mean age: 47.3 ± 10.1 years) with biopsy-proven NAFLD were studied. While ALT was in normal range in 24 subjects, it was elevated in 26. Upper range of normal was set to 19 U/L for women and 30 U/L for men. While non-alcoholic fatty liver (NAFL) denotes simple steatosis, nonalcoholic steatohepatitis (NASH) denotes the presence of inflammation, ballooned hepatocytes and fibrosis. Liver oxidative stress was estimated on the basis of tissue gluthathione concentration, and superoxide dismutase (SOD), and malondialdehyde (MDA) activities in tissue and serum specimens. Immunohistochemistry was performed for activated caspase 3 and 8, nuclear factor kB (NF-kB), antiapoptotic Bcl-2 protein, and tumor necrosis factor receptor (TNF-sRp55). The mean caspase 3 and 8 activity scores, oxidative stress parameters, mean necroinflammatory grade and prevalence of severe fibrosis were comparable across the groups with normal versus elevated ALT. Only patients with NASH had significantly higher caspase 3 and 8 activity, and serum MDA levels than those with NAFL (54.81±18.06, 39.81±27.43, p=0.04; 49.62±17.66, 26.17±15.03, p=0.03, and 5.09±0.77, 3.58±0.50, p= 0.049, respectively). Multiple regression analysis revealed that ALT elevation was not a risk factor for advanced necroinflammatory grade and fibrosis (OR:0.99, p=0.74, CI: 0.991.00, and OR:0.99, p=0.71, CI:0.98-1.00, respectively). Area under the receiver operating characteristic curve (AUROC) did not show any significant sensitivity and specificity for discriminative power of ALT (according to the upper limits above) for the necroinflammatory and fibrosis severity (AUROC 0.49; 95 % CI: 0.57-0.91, and AUROC 0.43; 95 % CI: 0.190.67, and respectively). In conclusion, we demonstrated that apoptosis and oxidative stress are the main events contributing to disease progression in NAFLD and serum ALT values do not correlate well with the parameters of these injurious processes or the severity of resultant histological changes.