POSTERSvitro after the cells were treated with Ad.Luc, Ad.IL-24, Ad.Bax or Ad.IL-24-Bax.The mechanism involved was also explored.A model using nude mice with liver tumors was used to evaluate the adenovirus' effects on tumor volume and cell apoptosis in vivo.Results: Ad.IL-24-Bax selectively suppressed growth of hepatocellular carcinoma cells but had little influence on the growth of normal hepatocytes in vitro.Ad.IL-24-Bax induced apoptosis in the hepatocellular carcinoma cells but not in normal hepatocytes.The Ad.IL-24-Bax had an enhanced ability to induce apoptosis and inhibit hepatocellular carcinoma cell growth when compared to Ad.IL-24 or Ad.Bax alone.The mechanism of this response may include the effect of the 10HRE/VEGF385 promoter and the synergistic effect of IL-24 and Bax.Ad.IL-24-Bax also suppressed tumor growth in nude mice and induced apoptosis.Conclusion: Ad.IL-24-Bax may be a useful tool for gene therapy in the treatment of hepatic cancer in clinical applications.

504 INSULIN RESISTANCE CONFERS A HIGHER RISK OF PORTAL HYPERTENSION, CIRRHOSIS AND EARLY MORTALITY TO ALCOHOLIC LIVER DISEASE PATIENTS E. Trepo, D. Degre, A. Lemmers, T. Gustot, A. Gerkens, S. Evrard, R. Ouziel, P. Deltenre, M. Adler, J. Deviere, C. Moreno. Department Gastroenterology, Hepatopancreatology and Digestive Oncology, Erasme Hospital, Laboratory of Experimental Gastroenterology, Universite Libre de Bruxelles, Brussels, Hopital de Jolimont, Haine-Saint-Paul, Belgium E-mail: christophe.moreno@erasme.ulb.ac.be

POSTERSviral load, and fibrosis stage remain significant predictors of SVR in BOC-based triple therapy but Week 4 response was the strongest predictor of SVR when added to the model.

Drug-induced liver damage is one of the most complex liver diseases due to its similar presentation to other acute or chronic liver processes, its potential severity and the absence of specific biomarkers to confirm diagnosis, which is based on clinical suspicion and exclusion of alternative causes. Because the drug development process fails to completely screen out hepatotoxic molecules and identify susceptible individuals, postmarketing pharmacovigilance remains essential. Hepatotoxicity registries are the ideal instrument for systematic and continual data collection, using preestablished criteria based on consensus. The present article briefly describes the contributions of the Spanish Hepatotoxicity Registry and those of other international registries. Hopefully, Latin American registries will be incorporated into existing initiatives, which will stimulate research and improve understanding of the complex mechanisms involved in this adverse reaction.

days) was compared through the analysis of the area under the ROC curve (AUROC).For the evaluation of prognostic stratification with the ABIC score the Kaplan-Meier method with log-rank test was used.To identify the independent prognostic factors for short-term mortality, a multivariate logistic regression analysis of variables associated with death was performed. Results:The overall mortality rate at 90 days was 50%.The AUROC for the different scores were: Maddrey's discriminant function 0.79; MELD score 0.83; Glasgow score 0.77 and ABIC score 0.82.The ABIC score allowed an accurate discrimination of 3 distinct prognosis subgroups with 14% (low risk), 50% (moderate risk) and 80% (high risk) mortality rate at 90 days (p < 0.001).The independent prognostic factors of 90-day mortality were: age, creatinine, bilirubin, leukocyte count and alcohol consumption >120 g/day.Importantly, the amount of alcohol consumption was an independent prognostic factor related with mortality (patients with >120 g/day had a 64% mortality rate at 90 days).The impact of alcohol consumption on mortality was particularly strong among patients with moderate risk of death (ABIC 6.71-8.99:30% vs 62% risk of death, p = 0.02). Conclusion:The ABIC score obtained at admission is useful for the prognostic stratification of patients with AH.An amount of alcohol consumption >120 g/day has a negative impact on patient mortality.Policies aimed at decreasing alcoholic consumption may have beneficial effects in patients with a high risk at developing AH.

Drug-induced liver injury (DILI) susceptibility has a potential genetic basis. We have evaluated possible associations between the risk of developing DILI and common genetic variants of the manganese superoxide dismutase (SOD2 Val16Ala) and glutathione peroxidase (GPX1 Pro200Leu) genes, which are involved in mitochondrial oxidative stress management. Genomic DNA from 185 DILI patients assessed by the Council for International Organizations of Medical Science scale and 270 sex- and age-matched controls were analyzed. The SOD2 and GPX1 genotyping was performed using polymerase chain reaction restriction fragment length polymorphism and TaqMan probed quantitative polymerase chain reaction, respectively. The statistical power to detect the effect of variant alleles with the observed odds ratio (OR) was 98.2% and 99.7% for bilateral association of SOD2 and GPX1, respectively. The SOD2 Ala/Ala genotype was associated with cholestatic/mixed damage (OR = 2.3; 95% confidence interval [CI] = 1.4-3.8; corrected P [Pc] = 0.0058), whereas the GPX1 Leu/Leu genotype was associated with cholestatic injury (OR = 5.1; 95%CI = 1.6-16.0; Pc = 0.0112). The presence of two or more combined risk alleles (SOD2 Ala and GPX1 Leu) was more frequent in DILI patients (OR = 2.1; 95%CI = 1.4-3.0; Pc = 0.0006). Patients with cholestatic/mixed injury induced by mitochondria hazardous drugs were more prone to have the SOD2 Ala/Ala genotype (OR = 3.6; 95%CI = 1.4-9.3; Pc = 0.02). This genotype was also more frequent in cholestatic/mixed DILI induced by pharmaceuticals producing quinone-like or epoxide metabolites (OR = 3.0; 95%CI = 1.7-5.5; Pc = 0.0008) and S-oxides, diazines, nitroanion radicals, or iminium ions (OR = 16.0; 95%CI = 1.8-146.1; Pc = 0.009). Conclusion: Patients homozygous for the SOD2 Ala allele and the GPX1 Leu allele are at higher risk of developing cholestatic DILI. SOD2 Ala homozygotes may be more prone to suffer DILI from drugs that are mitochondria hazardous or produce reactive intermediates. (HEPATOLOGY 2010;52:303-312)