Lysosomal acid lipase activity and liver fibrosis in the clinical continuum of non-alcoholic fatty liver disease

Liver Int. 2019 Dec;39(12):2301-2308. doi: 10.1111/liv.14206. Epub 2019 Aug 21.

Abstract

Background and aims: Recent evidence showed a reduced activity of the lysosomal acid lipase (LAL) in patients with non-alcoholic fatty liver disease (NAFLD) and cryptogenic cirrhosis (CC). However, the relationship between LAL activity and liver fibrosis has never been investigated.

Methods: Cross-sectional study including 575 outpatients referred for the management of cardio-metabolic and liver disease. The absence of liver fibrosis was defined by a FIB-4 < 1.30 and NAFLD fibrosis score (NFS) <-1.455. LAL activity was measured with dried blood spot technique.

Results: Overall, 515 patients had a diagnosis of NAFLD (454 NAFL and 61 biopsy-proven NASH) and 60 of CC. The value of LAL activity progressively decreased from healthy subjects to NAFL/NASH patients to CC (P < .001). LAL activity was reduced by 10% in patients with NAFL, by 20% in NASH and by 50% in CC. The prevalence of CC decreased across the tertiles of LAL activity: 22.2% in the lowest, 4.6% in the intermediate and 0.5% in the highest tertile. In NAFLD patients, 69.9% had a FIB4 < 1.30, and 43.1% a NFS <-1.455. Multivariate logistic regression analysis showed that Log (LAL activity) was associated with FIB-4 < 1.30 (Odds ratio [OR] 2.19 95% confidence interval [CI] 1.33-3.62, P = .002) and NFS < -1.455 (OR 2.43, 95% CI 1.51-3.91, P < .001) after adjustment for confounding factors.

Conclusions: We found a progressive reduction of LAL activity according to liver disease severity. LAL activity was inversely associated with markers of liver fibrosis in patients with NAFLD.

Keywords: NAFLD; cryptogenic cirrhosis; liver fibrosis; lysosomal acid lipase.

MeSH terms

  • Adult
  • Aged
  • Cross-Sectional Studies
  • Female
  • Humans
  • Liver Cirrhosis / enzymology*
  • Male
  • Middle Aged
  • Non-alcoholic Fatty Liver Disease / enzymology*
  • Non-alcoholic Fatty Liver Disease / pathology
  • Sterol Esterase / metabolism*

Substances

  • LIPA protein, human
  • Sterol Esterase