1948-LB: Effect of N-Acetyl Cysteine on Thrombo-inflammation in Children with Metabolic Dysfunction–Associated Steatotic Liver Disease

Background: Obesity (OB)-related pro-thrombo-inflammatory state sets the basis for cardiometabolic disease including type 2 diabetes (T2D) and metabolic dysfunction-associated steatotic liver disease (MASLD) in children. The aims were to explore in children with OB and MASLD (i) the role of gamma prime (γ′) fibrinogen (GPF), a novel marker of thrombo-inflammation, and selected metabolic parameters and (ii) the effect of N-acetyl cysteine (NAC) on GPF and metabolic parameters. Methods: 16-week randomized, double-blind, placebo-controlled trial of oral NAC treatment. Participants (n=13) with OB (BMI-percentile>95) and MASLD (NAS Score >2) were randomized to one of the two groups of NAC (600mg NAC/day or 1200mg NAC/day) and placebo. GPF, leptin, spexin, glucose, insulin and body composition were measured. Data on high-sensitivity c-reactive protein (hs-CRP), interleukin-6 (IL-6), liver enzymes, liver fat fraction (LFF) and liver stiffness (LS) were previously reported. Because of the small sample size and that the response to both doses of NAC was similar, merged data of the two intervention groups were used for statistical analysis, which included 2-sample t-test and analysis of covariance (ANCOVA). Results: GPF was elevated (p=0.01) in those with MASLD vs normal weight (NW) and OB [GPF data from age and sex matched children with NW and OB from our previous study]. Leptin was higher and spexin lower in MASLD. GPF and leptin decreased (p=0.01 and 0.03) and spexin increased (p=0.02) in response to NAC treatment. Substantial decrease in liver enzymes, LFF, and LS were previously reported. Conclusion: 16-week NAC treatment led to improvements in the pro-thrombo-inflammatory state present in children with OB and MASLD along with beneficial liver outcomes. Further investigation on the role of thrombo-inflammation in children with MASLD, particularly in those with T2D is warranted because of the higher incidence and severity of MASLD in those with T2D.