08. Alcoholic liver disease, NAFLD and drug induced liver disease $255 patient had developed clinical signs of liver disease. However, among patients not treated with statins progression of liver fibrosis was more likely to occur (P < 0.005). Conclusions: Statins are safe in patients with persistent aminotransferase elevation because of NAFLD. Moreover, this study indicates that statins may have a positive effect on hepatic histology in patients with NAFLD. ~-9-~ CLINICAL SIGNIFICANCE OF HIGH SENSITIVITY C-REACTIVE PROTEIN (hs-CRP) IN NON-ALCOHOLIC FATTY LIVER DISEASE (NAFLD) T. Kogisol~ Y. Moriyoshi 1, H. Nagahara2. 1International Medical Center o f Japan, 1-21-1 Toyama, Shinjuku-ku, Tokyo, Japan," 2International University of Health and Welfare, 2600-1 Kitakanamaru Ootawara-shi, Tochigi, Japan Aims: High-sensitivity C-reactive protein (hs-CRP) assay has been devel- oped and identified a useful marker for prediction of coronary vascular diseases in metabolic syndrome (MS). The aim of this study is to inves- tigate whether hs-CRP correlates with progression of non-alcoholic fatty liver disease (NAFLD) by statistic analysis based on Akaike Information Criterion (AIC), which could assess the good fitness to the balance of adaptation and complexity of a model. Methods: 230 individuals (93 males and 137 females) who visited our hospital for dry dock of annual check up were analyzed. NAFLD was diagnosed by more than two technician and physician according to ul- trasonographic pattern. Serum CRP was measured as highly sensitive by latex agglutination assay. We excluded individuals who show positive in hepatitis viral markers and drinkers from this study. Results: NAFLD was diagnosed in 35.4% of males and 18.9% of fe- males. 7/33 (21.1%) of males and 3/24 (12.5%) of females in NAFLD were matched with MS based on Japanese criteria, while there were no MS patients in normal population. NAFLD showed high hs-CRP level in female (normal: NAFLD 0.45:1.47 mg/L, P < 0.05), whereas no significant difference in male subjects. AIC scoring system identified the significant factors for developing NAFLD; BMI (AIC 78.0), waist cir- cumference (68.8), body weight (66.0), TG (51.4), W/H ratio (50.2), hip circumference (47.8), HDL-C (40.4), and hs-CRP (20.8), FBS (18.3). These factors highly ranked by AIC in NAFLD were matched to that participated in MS. Thus, hs-CRP was the third highest factor in serum markers in AIC analysis of NAFLD, however, multiple logistic analysis could not indicate any risk factors of NAFLD. hs-CRP strongly correlated with serum markers such as triglyceride in females, and fasting blood glucose, HbAlc, and Waist/Hip ratio in males (R 0.41 0.56, P<0.05). Conclusions: FL is not a simple focal fat deposit disease in liver but a systemic disease, one of MS, because NAFLD had high complication rate with MS and high hs-CRP level, hs-CRP was a serum predictor of NAFLD according to AIC analysis, and we propose AIC as a useful analysis to evaluate NAFLD and MS. • PROGNOSTIC VALUE OF SOLUBLE ADHESION MOLECULES IN ALCOHOLIC LIVER DISEASE I.V. Korzh, I.E Fedotova, V.D. Nemtsova. Internal Medicine, Kharkov Medical University, Kharkov, Ukraine Background and Aims: Alcoholic liver disease damages critical functions in the liver. However, the mechanisms involved in hepatic dysfunction are obscure. Endothelial activation plays an active role in modifications of the circulatory status of cirrhotic patients. Soluble endothelial adhesion molecules, induced by pro-inflammatory cytokines, could be considered markers of endothelial activation. Their role in the natural history of alcoholic liver disease and portal hypertension has not been reported. Our aim was to analyze the prognostic value of soluble adhesion molecules in patients with alcoholic liver disease. Methods: We studied 53 patients with alcoholic liver disease and 27 healthy controls. Serum concentrations of soluble CD14, soluble re- ceptors of tumor necrosis factor alpha and adhesion molecules ICAM-1 (intercellular adhesion molecule-l) and VCAM-1 (vascular cell adhesion molecule 1) as well as mean blood pressure, plasma renin activity, aldos- terone, vasopressin and norepinephrine concentrations were determined. Patients were followed up for a mean of 25.6 months. Results: Increased concentrations of soluble CD14, tumor necrosis factor receptors and ICAM-1 and VCAM-1 were detected in patients with alcoholic liver disease when compared with healthy controls. Tumor necrosis factor receptors and adhesion molecule concentrations were both significantly higher in advanced phases of cirrhosis (Child@ugh class C and B versus A). Eleven patients died as a related consequence of liver cirrhosis. Multivariate analysis demonstrated that Chil&Pugh score and serum levels of tumor necrosis factor receptor I and ICAM-1 were associated with mortality. Conclusions: In addition to the classic factor implicated in mortality (Chil&Pugh class), alterations in inflammation-related components and soluble adhesion molecules, as representatives of hemodynamic alterations, are of prognostic significance in patients with alcoholic liver disease. Regulation of adhesion molecules production may be a useful therapy for preventing liver dysfunction in alcoholic liver disease. ~9-~ MANGANESE SUPEROXIDE DISMUTASE OVEREXPRESSION PROTECTS AGAINST HEPATIC MITOCHONDRIAL DNA DEPLETION AFTER AN ACUTE ALCOHOL BINGE, YET AGGRAVATES MITOCHONDRIAL DNA DEPLETION AFTER CHRONIC ALCOHOL INTOXICATION IN MICE I. Larosche 1, P. Lett~ron 1, B. Fromenty 1, A. Abbey-Toby1, N. Vadrot 1, G. Feldmann 1, H. Van Remmen2, A. Richardson2, D. Pessayre 1, A. Mansouri 1. I INSERM U481, Facult~ de M~decine Xavier Bichat, Paris, France," ;Department of Cellular and Structural Biology, University of Texas Health Science Center at San Antonio, Texas, USA Background and Aims: Large doses of ethanol have been shown to cause oxidative damage to hepatic mitochondrial DNA (mtDNA) and to trigger acute mtDNA depletion in mice. However, the modulating role of manganese superoxide dismutase (MnSOD) has not been investigated yet. An optimal balance must exist between MnSOD and glutathione peroxidase-1; not enough MnSOD may cause excessive peroxynitrite formation, while overexpression of MnSOD may cause excessive hydroxyl radical (OH') formation. Both peroxynitrite and OH" may damage DNA. Furthermore, the optimal activity of MnSOD might differ in naive or in intoxicated animals due to the induction and/or inactivation of anti-oxidant enzymes. An answer to these questions might help understand recent controversies over the possible role of a genetic dimorphism increasing MnSOD activity in the susceptibility to alcoholic liver disease. Methods: We exposed 2-month old heterozygous knock out (MnSOD+/) mice, wild type (MnSOD+/+) mice, and overexpressing transgenic (Mn- SOD+++) mice to two different alcohol treatments. Acutely, mice received a single dose of ethanol (5 g/kg) by gastric intubation, and were sacrificed 2 and 24 hours later. Chronically, animals received 20% ethanol in their drinking water for 7 weeks. The effects of acute and chronic alcohol treat- ments on hepatic mtDNA levels were evaluated by slot-blot hybridization. Results: Two hours after an acute dose of ethanol, mtDNA levels decreased to 39%, 55% and 83% of control values in MnSOD+/ , MnSOD+/+ and MnSOD+++ mice, respectively. At 24 hours, mtDNA levels were still decreased in MnSOD+/ mice (74% of control), but were restored in MnSOD+/+ mice (117%) or MnSOD+++ mice (102%). In contrast, after 7 weeks of chronic alcohol treatment, mtDNA was unchanged in intoxicated MnSOD+/ and in wild type MnSOD+/+ mice, but was decreased to 53% of control level in intoxicated MnSOD+++ mice. Conclusions: MnSOD overexpression protects against hepatic mitochon- drial DNA depletion after an acute alcohol binge, yet aggravates mtDNA