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 LALactivity (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 cases (p = 0.296). When considering LAL-activity above and below 77 pmol/punch/h as a cut-off value, patients with reduced LAL-activity had a significant increase in necroinflammatory activity according to the METAVIR score (p = 0.040), and NAFLD activity score (NAS, p = 0.031) compared to cases with higher LAL-activity. Conclusion: Our findings suggest that reduced LAL-activity is associated with increased necroinflammatory activity and severity of the NAS. A better knowledge of the role of LAL may provide new insights into the pathogenesis and progression of MAFLD. (c) 2021 Elsevier Masson SAS. All rights reserved.

Automated summary

The study found that decreased LAL activity is associated with increased necroinflammatory activity and severity of the NAFLD activity score, providing new insights into the pathogenesis and progression of MAFLD.