Low levels of Lysosomal Acid Lipase (LAL) activity increases necroinflammation in adult patients with biopsy-proven metabolic associated fatty liver disease.

INTRODUCTION AND OBJECTIVE: Metabolic associated fatty liver disease (MAFLD), characterized by intra-hepatic fat accumulation, will soon be the leading cause of end-stage liver disease. Lysosomal Acid Lipase (LAL) is a key enzyme in lipid metabolism. We investigated its activity in patients with biopsy-proven MAFLD. METHODS: Prospective cross-sectional study in patients with biopsy-proven MAFLD. Blood LAL-activity (pmol/punch/h) was measured with dried blood spot extracts using Lalistat 2. Demographic, clinical, and laboratory data were collected. RESULTS: 101 adult patients were recruited. Among them, 11.9% had a diagnosis of MAFLD without steatohepatitis and 88.1% had MAFLD with steatohepatitis. The median of LAL-activity in patients with MAFLD was 76.8 pmol/punch/h. MAFLD patients with steatohepatitis showed an increase in gamma-glutamyl transferase (p = 0.042), insulin (p = 0.001), homeostatic model assessment for insulin resistance (HOMA-IR, p = 0.001) and advanced liver fibrosis (p  < 0.001), compared to cases of mafld without steatohepatitis. there was no statistical difference in lal-activity between the (p =" 0.040)," when considering above and below 77 pmol punch h as a cut-off value, patients with reduced had significant increase necroinflammatory activity according metavir score nafld (nas, p =" 0.031)" higher lal-activity. conclusion: our findings suggest that is associated increased severity nas. a better knowledge role lal may provide new insights into pathogenesis progression mafld.< div>