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. VioliLAL-Cirrhosis Collaborative Research Group

Research output: Contribution to journalArticle

7 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)179-184
Number of pages6
JournalAtherosclerosis
Volume262
DOIs
Publication statusPublished - Jul 1 2017

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Sterol Esterase
Multicenter Studies
Cohort Studies
Cytidine Triphosphate
Fibrosis
Gastroenterology
Liver Cirrhosis
Cryptogenic Cirrhosis
Fatty Liver
Internal Medicine
Platelet Count
Leukocyte Count
Italy
Liver Diseases
Linear Models
Chronic Disease
Regression Analysis
Prospective Studies

Keywords

  • 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/congenital/diagnosis/enzymology/epidemiology
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Platelet Count
  • Prevalence
  • Risk Factors
  • Sterol Esterase/blood
  • Cryptogenic cirrhosis
  • Liver disease
  • Lysosomal acid lipase
  • Pathogenesis

Cite this

Severe reduction of blood lysosomal acid lipase activity in cryptogenic cirrhosis: A nationwide multicentre cohort study. / Angelico, F.; Corradini, S. G.; Pastori, D.; Fargion, S.; Fracanzani, A. L.; Angelico, M.; Bolondi, L.; Tozzi, G.; Pujatti, P. L.; Labbadia, G.; Corazza, G. R.; Averna, M.; Perticone, F.; Croce, G.; Persico, M.; Bucci, T.; Baratta, F.; Polimeni, L.; Ben, M. Del; Violi, F.; Group, LAL-Cirrhosis Collaborative Research.

In: Atherosclerosis, Vol. 262, 01.07.2017, p. 179-184.

Research output: Contribution to journalArticle

Angelico, F, Corradini, SG, Pastori, D, Fargion, S, Fracanzani, AL, Angelico, M, Bolondi, L, Tozzi, G, Pujatti, PL, Labbadia, G, Corazza, GR, Averna, M, Perticone, F, Croce, G, Persico, M, Bucci, T, Baratta, F, Polimeni, L, Ben, MD, Violi, F & Group, LAL-CCR 2017, 'Severe reduction of blood lysosomal acid lipase activity in cryptogenic cirrhosis: A nationwide multicentre cohort study', Atherosclerosis, vol. 262, pp. 179-184. https://doi.org/S0021-9150(17)30141-7 [pii]
Angelico, F. ; Corradini, S. G. ; Pastori, D. ; Fargion, S. ; Fracanzani, A. L. ; Angelico, M. ; Bolondi, L. ; Tozzi, G. ; Pujatti, P. L. ; Labbadia, G. ; Corazza, G. R. ; Averna, M. ; Perticone, F. ; Croce, G. ; Persico, M. ; Bucci, T. ; Baratta, F. ; Polimeni, L. ; Ben, M. Del ; Violi, F. ; Group, LAL-Cirrhosis Collaborative Research. / Severe reduction of blood lysosomal acid lipase activity in cryptogenic cirrhosis: A nationwide multicentre cohort study. In: Atherosclerosis. 2017 ; Vol. 262. pp. 179-184.
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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.",
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author = "F. Angelico and Corradini, {S. G.} and D. Pastori and S. Fargion and Fracanzani, {A. L.} and M. Angelico and L. Bolondi and G. Tozzi and Pujatti, {P. L.} and G. Labbadia and Corazza, {G. R.} and M. Averna and F. Perticone and G. Croce and M. Persico and T. Bucci and F. Baratta and L. Polimeni and Ben, {M. Del} and F. Violi and Group, {LAL-Cirrhosis Collaborative Research}",
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TY - JOUR

T1 - Severe reduction of blood lysosomal acid lipase activity in cryptogenic cirrhosis: A nationwide multicentre cohort study

AU - Angelico, F.

AU - Corradini, S. G.

AU - Pastori, D.

AU - Fargion, S.

AU - Fracanzani, A. L.

AU - Angelico, M.

AU - Bolondi, L.

AU - Tozzi, G.

AU - Pujatti, P. L.

AU - Labbadia, G.

AU - Corazza, G. R.

AU - Averna, M.

AU - Perticone, F.

AU - Croce, G.

AU - Persico, M.

AU - Bucci, T.

AU - Baratta, F.

AU - Polimeni, L.

AU - Ben, M. Del

AU - Violi, F.

AU - Group, LAL-Cirrhosis Collaborative Research

N1 - LR: 20180129; CI: Copyright (c) 2017; JID: 0242543; 0 (Biomarkers); EC 3.1.1.13 (LIPA protein, human); EC 3.1.1.13 (Sterol Esterase); Cirrhosis, Cryptogenic; OTO: NOTNLM; 2017/01/30 00:00 [received]; 2017/03/22 00:00 [revised]; 2017/03/29 00:00 [accepted]; 2017/04/12 06:00 [pubmed]; 2018/01/30 06:00 [medline]; 2017/04/12 06:00 [entrez]; ppublish

PY - 2017/7/1

Y1 - 2017/7/1

N2 - 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.

AB - 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.

KW - Aged

KW - Biomarkers/blood

KW - Chi-Square Distribution

KW - Comorbidity

KW - Cross-Sectional Studies

KW - Down-Regulation

KW - Dried Blood Spot Testing

KW - Female

KW - Humans

KW - Italy/epidemiology

KW - Linear Models

KW - Liver Cirrhosis/blood/congenital/diagnosis/enzymology/epidemiology

KW - Male

KW - Middle Aged

KW - Multivariate Analysis

KW - Platelet Count

KW - Prevalence

KW - Risk Factors

KW - Sterol Esterase/blood

KW - Cryptogenic cirrhosis

KW - Liver disease

KW - Lysosomal acid lipase

KW - Pathogenesis

U2 - S0021-9150(17)30141-7 [pii]

DO - S0021-9150(17)30141-7 [pii]

M3 - Article

VL - 262

SP - 179

EP - 184

JO - Atherosclerosis

JF - Atherosclerosis

SN - 0021-9150

ER -