Reduced Lysosomal Acid Lipase Activity in Adult Patients With Non-alcoholic Fatty Liver Disease

•LAL activity is significantly reduced in adult patients with NAFLD, compared to healthy subjects.•Patients with NASH disclose the lowest value of LAL activity.•Patients with LAL activity below median have a significant elevation of serum liver enzymes and a worse lipid profile.•Low LAL activity is associated with metabolic syndrome and lower statin use.

Non-alcoholic fatty liver disease (NAFLD) is characterized by intra-hepatic fat accumulation and mechanisms involved in its pathogenesis are not fully explained. Lysosomal Acid Lipase (LAL) is a key enzyme in lipid metabolism. We investigated its activity in patients with fatty liver.LAL activity (nmol/spot/h) was measured in 100 adult healthy subjects (HS) and in 240 NAFLD patients. A sub-analysis on 35 patients with biopsy-proven non-alcoholic steatohepatitis (NASH) was performed.Median LAL activity was 1.15 (0.95–1.72) in HS. It was significantly reduced in NAFLD [0.78 (0.61–1.01), p < 0.001 vs. HS]. A further reduction was observed in the subgroup of NASH [0.67 (0.51–0.77), p < 0.001 vs. HS]. Patients with LAL activity below median had higher values of serum total cholesterol (p < 0.05) and LDL-c (p < 0.05), and increased serum liver enzymes (ALT, p < 0.001; AST, p < 0.01; GGT, p < 0.01). At multivariable logistic regression analysis, factors associated with LAL activity below median were ALT (OR: 1.018, 95% CI 1.004–1.032, p = 0.011) and metabolic syndrome (OR: 2.551, 95% CI 1.241–5.245, p = 0.011), whilst statin use predicted a better LAL function (OR: 0.464, 95% CI 0.248–0.866, p = 0.016).Our findings suggest a strong association between impaired LAL activity and NAFLD. A better knowledge of the role of LAL may provide new insights in NAFLD pathogenesis.