Severe reduction of blood lysosomal acid lipase activity in cryptogenic cirrhosis: A nationwide multicentre cohort study

Atherosclerosis. 2017 Jul:262:179-184. doi: 10.1016/j.atherosclerosis.2017.03.038. Epub 2017 Mar 31.

Abstract

Background and aims: Blood lysosomal acid lipase (LAL) is reduced in non-alcoholic steatohepatitis, which is the major cause of cryptogenic cirrhosis (CC); few data on LAL activity in CC do exist. We investigated LAL activity in a cohort of patients with liver cirrhosis.

Methods: This is a multicentre cohort study including 274 patients with liver cirrhosis of different aetiology from 19 centres of Internal Medicine, Gastroenterology and Hepatology distributed throughout Italy. Blood LAL activity (nmol/spot/h) was measured with dried blood spot extracts using Lalistat 2.

Results: Overall, 133 patients had CC, and 141 patients had cirrhosis by other causes (61 viral, 53 alcoholic, 20 alcoholic + viral, 7 autoimmune). Mean age was 64.2 ± 13.4 years, and 28.5% were women. Patients with CC were older compared to other aetiology-cirrhosis, with a lower Child-Turcotte-Pugh (CTP, p=0.003) and MELD (p=0.009) score, and a higher prevalence of cardio-metabolic risk factors and previous ischemic events. In the whole cohort, median LAL activity value was 0.58 nmol/spot/h, 0.49 and 0.65 in the groups of CC and known-aetiology cirrhosis, respectively (p=0.002). The difference remained significant after adjustment for white blood cells count (p=0.001). Multivariable linear regression analysis showed that CC (vs. known aetiology, Beta = -0.144, p=0.018), platelet count (Beta = 0.398, p < 0.001) and CTP score (Beta = -0.133, p=0.022) were associated with log-LAL activity. Similar results were found using MELD as covariate.

Conclusions: We found a marked reduction of LAL activity in patients with cryptogenic cirrhosis compared to the other known aetiologies. A prospective study will clarify the role of LAL in chronic liver diseases.

Keywords: Cryptogenic cirrhosis; Liver disease; Lysosomal acid lipase; Pathogenesis.

Publication types

  • Multicenter Study
  • Observational Study

MeSH terms

  • Aged
  • Biomarkers / blood
  • Chi-Square Distribution
  • Comorbidity
  • Cross-Sectional Studies
  • Down-Regulation
  • Dried Blood Spot Testing
  • Female
  • Humans
  • Italy / epidemiology
  • Linear Models
  • Liver Cirrhosis / blood
  • Liver Cirrhosis / congenital*
  • Liver Cirrhosis / diagnosis
  • Liver Cirrhosis / enzymology
  • Liver Cirrhosis / epidemiology
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Platelet Count
  • Prevalence
  • Risk Factors
  • Sterol Esterase / blood*

Substances

  • Biomarkers
  • LIPA protein, human
  • Sterol Esterase

Supplementary concepts

  • Cirrhosis, Cryptogenic