A total of 192 patients died and 1 patient underwent liver transplantation. Variables independently associated with the outcome of death/liver transplantation are described in the table below. A total of 39 liver-related events occurred in 26 patients. Fibrosis stage 3 (HR 14.2 [95% CI 3.38, 59.68] p<0.001) and stage 4 (HR 51.5 [95% CI 9.87, 269.2]; p<0.001) as compared to stage 0 were the only variables independently associated with the outcome of liver-related events. Conclusions: Fibrosis stage but no other histological features or presence of NASH PARP inhibition is independently associated with overall death/liver transplantation and liver related events in patients with NAFLD. Disclosures: The following
people have nothing to disclose: Paul Angulo, David E. Kleiner, Sanne Dam-Larsen, Leon Adams, Bjornsson S. Einar, Phunchai Charatcharoenwit-thaya, Peter R. Mills, Jill C. Keach, Svanhildur
Haflidadottir, Flemming Bendtsen Background and aims: Mass spectrometry based metabolomics is used to identify new biomarkers related to alteration in organ metabolism. We have used this technique to analyse plasma samples of subjects with NAFLD and identify possible markers of severity of liver disease associated with metabolic dysfunction. Methods: We studied 54 subjects, 45 NAFLD with liver biopsy and 9 healthy control (CT) and measured plasma concentration profile AZD1208 of amino acids (AA) and fatty acid (FA) by GCMS. Data were correlated with NAS and fibrosis score, indexes of insulin resistance (IR) measured by tracers, LFTs, beta–hydroxybutyrate (BOH), ox-LDL, total antioxidative status (TAS), sRAGE, and adiponectin. We calculated: a) using tracer infusion, hepatic IR as endogenous glucose production × fasting insulin (HIR=EG-PxFPI), adipose tissue insulin resistance (AT-IR) as fasting lip-olysis × FPI; b) from fatty acid composition we calculated de novo lipogenesis index (DNL=16:0/18:2) and SCD1 activity as 16:1/16:0; c) from AA profile, the branched 上海皓元 chain concentrations (BCAA) and the ratio of glutamate/(glycine +serine), that is as an index of glutathione biosynthesis (GSH-I). Results: Compared to
controls, subjects with NAFLD had increased H-IR (118±10 vs. 56±7) and AT-IR (34±3 vs. 13±2), GSH-I (0.73±0.06 vs 0.33±0.09), DNL (1.17±0.05 vs 0.86±0.04) and SCD1 (0.10±0.01vs 0.08±0.01) indices compared to controls. GSH_I was increased proportionally to the severity of fibrosis (r=0.36 per trend, p<0.0001), ln(cholesterol) (r=0.39) and negatively with ln(sRAGE) (r=0.30) but not with TG liver content nor with NAS score, TAS, ox-LDL and adiponectin. DNL was increased proportionally to circulating ln(TG) (r=0.53), fat in biopsy (r=0.31) and both DNL and SCD-1 were increased with high fibrosis Fib1/2 and Fib3/4 (p<0.05). GSH-I, DNL and SCD1 were positively associated with the degree of AT-IR (r=0.28; r=0.41; r=0.43) and of H-IR(r=0.39; r=0.28; r=0.32).