Treatment efficacy was determined via comparisons of baseline and one year serum erythrocyte fatty acid levels of AA: EPA (omega-6: omega-3) ratios. Clinical response was measured via 1) serologic analysis of lipid metabolism, glucose metabolism, and NASH biomarkers; 2) magnetic resonance Angiogenesis inhibitor imaging (MRI) to determine hepatic steatosis; and 3) liver biopsy samples graded by Dixon fat scoring system and
NAFLD activity score (NAS). Results: After one year of treatment, the omega-3 group displayed a significant decrease in AA: EPA levels (p=0.02) as well as an decreased ratio compared to patients who received placebo (p=0.003). The omega-3 group displayed no significant change in other lipid or glucose metabolism parameters, while serum biomarkers of hepatocyte damage suggestive of NASH (ALT, M30/M65E cytokeratin antigens) all decreased but not to significant levels. On imaging, the omega-3 group displayed a decrease in MRI
fat score (p=0.009). Histologic Nutlin-3a clinical trial analysis demonstrated the omega-3 group had decreases in Dixon fat scores (p=0.04) and NAS (p=0.01). Furthermore, based on NAS histology, four patients (80%) showed histologic resolution of NASH after a year of omega-3 compared to two (29%) patients taking placebo. Conclusions: Daily omega-3 supplementation decreased the ratio of pro-inflammatory to antiinflammatory PUFA levels based on AA: EPA (omega-6: omega-3) measurement, which we speculate reflects shifting of hepatic fat metabolism to a less lipotoxic and MCE inflammatory form. The treatment effects of omega-3 fatty acids on NASH need further study with larger randomized placebo controlled trials. Placebo (n=7) Omega-3 (n=6) TO T12 p value TO T12 p value Body Mass Index 35.1 ±9.1 35.4 ± 10.3
0.66 32.1 ±3.6 30.6 ±4.3 0.04 AA: EPA ratio 81.9 ±33.4 46.9 ± 19.7 0.088 54.3 ± 30.6 13.3 ±8.5 0.02 MRI fat score 238 ± 147 186 ±133 0.26 295 ±139 127 ±105 0.009 Dixon fat score 11.9 ±7.5 9.2 ±5.1 0.23 18.3 ± 11 8.33 ±6.3 0.04 NAFLD activity score 4.86 ± 0.85 4.36 ±1.5 0.13 5.92 士 0.86 4.1 土 1.1 0.01 Disclosures: Stephen H. Caldwell – Advisory Committees or Review Panels: Vital Therapy; Consulting: Wellstat diagnostics; Grant/Research Support: Hemosonics, Gilead Sciences Curtis K. Argo – Consulting: Wellstat Diagnostics; Independent Contractor: Genentech/Roche The following people have nothing to disclose: Glenn Moulder, Elliot Z. Smith Background. NAFLD increases the risk of cardiovascular (CV) events independent of the presence of traditional CV risk factors. Whether NAFLD is associated with early atherosclerotic lesions and their progression is unknown. Aim: to evaluate the impact of NAFLD and significant hepatic fibrosis on the presence and progression of carotid intima-media thickness (CIMT) and early carotid plaques (CP), in patients (pts) at high CV risk.