Model: Adult male Long Evans rats were fed isocaloric liquid diets containing 0% or 26% (caloric content) ethanol (EtOH) for 8 weeks. In Weeks 3 through 8, rats were treated with NNK (2mg/kg) or vehicle by intraperito-neal (i.p.) injection, 3x/week, and in weeks 7 and 8, EtOH-fed rats were binge-administered EtOH (2g/kg) 3x/week; controls
were given saline. Results: Blood alcohol levels increased from 55-113 g/dL with chronic feeding to 188-229 g/dL 30 minutes after binge exposure. EtOH ± NNK cause steatohepatitis with hepatocellular necrosis, disruption of the hepatic cord architecture, focal ballooning degeneration, early fibrosis, mitochondrial cytopathy, and disrupted endoplasmic reticu-lum (ER). Severity of lesions was highest in the EtOH+ NNK group. Two-way ANOVA tests revealed that EtOH and NNK contributed to inhibition of insulin/IGF signaling through Akt PLX3397 and activation of pro-inflammatory cytokines; EtOH promoted lipid peroxidation; and Fluorouracil clinical trial NNK increased apoptosis. In addition, O6-Metylguanine adducts were only detected in NNK-ex-posed livers. Conclusion: Both alcohol and NNK contribute to the pathogenesis of ALD, including insulin/IGF resistance and inflammation. However, differential effects of EtOH and NNK on adduct formation in liver may modulate ALD progression among alcoholics who also smoke. Disclosures: The following people
have nothing to disclose: Valerie Zabala, Ming
Tong, Teresa Ramirez, Emine Yalcin, Silvia Balbo, Elizabeth Silbermann, Chetram Deochand, Stephen Hecht, Suzanne M. de la Monte Severe alcoholic hepatitis (AH) carries a mortality rate as a high as 80% at 6 months. Early identification of patients at high-risk of death is essential to optimize treatment and estimate prognosis. Our aim was to compare the performance of several validated prediction models in a prospective cohort of patients with severe AH living in the US. Methods: Patients hospitalized at a high volume liver transplant center and evaluated by a hepatologist for severe AH were prospectively identified from 1/2012 to 6/2014. The diagnosis of AH was based on clinical grounds and/or liver biopsy, MCE公司 with severe AH defined as a Maddrey’s discriminant function (DF) >32. Patient electronic medical records were reviewed for clinical data to calculate DF, Lille, model for end-stage liver disease (MELD), Glasgow alcoholic hepatitis score (GAHS) and Age, Bilirubin, INR, Creatinine (ABIC) scores at presentation. The primary outcomes of analysis were mortality or liver transplantation (LT) at 30-, 90- and 180 days from presentation. Results: Over the 2.5 year study period, 88 consecutive patients with severe AH were admitted or transferred to our liver service and prospectively evaluated. The median age was 47 years, 30% Hispanic or Black with near equal sex distribution.