Reduced lysosomal acid lipase activity in adult patients with non-alcoholic fatty liver disease

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 subanalysis on 35 patients with biopsy-proven non-alcoholic steatohepatitis (NASH) was performed. Median LAL activitywas 1.15 (0.95–1.72) inHS. It was significantly reduced inNAFLD [0.78 (0.61–1.01), p b 0.001 vs. HS]. A further reduction was observed in the subgroup of NASH [0.67 (0.51–0.77), p b 0.001 vs. HS]. Patients with LAL activity below median had higher values of serumtotal cholesterol (p b 0.05) and LDL-c (p b 0.05), and increased serum liver enzymes (ALT, p b 0.001; AST, p b 0.01; GGT, p b 0.01). At multivariable logistic regression analysis, factors associatedwith LAL activity belowmedian 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.