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.

Severe reduction of blood lysosomal acid lipase activity in cryptogenic cirrhosis: A nationwide multicentre cohort study / F. Angelico, S.G. Corradini, D. Pastori, S. Fargion, A.L. Fracanzani, M. Angelico, L. Bolondi, G. Tozzi, P.L. Pujatti, G. Labbadia, G.R. Corazza, M. Averna, F. Perticone, G. Croce, M. Persico, T. Bucci, F. Baratta, L. Polimeni, M. Del Ben, F. Violi. - In: ATHEROSCLEROSIS. - ISSN 0021-9150. - 262(2017 Jul), pp. 179-184. [10.1016/j.atherosclerosis.2017.03.038]

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

S. Fargion;A.L. Fracanzani;
2017

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.
Cryptogenic cirrhosis; Liver disease; Lysosomal acid lipase; Pathogenesis; Aged; Biomarkers; Chi-Square Distribution; Comorbidity; Cross-Sectional Studies; Down-Regulation; Dried Blood Spot Testing; Female; Humans; Italy; Linear Models; Liver Cirrhosis; Male; Middle Aged; Multivariate Analysis; Platelet Count; Prevalence; Risk Factors; Sterol Esterase; Cardiology and Cardiovascular Medicine
Settore MED/09 - Medicina Interna
lug-2017
31-mar-2017
Centro per lo studio e la cura delle malattie metaboliche del fegato
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/557353
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