title: Severe reduction of blood lysosomal acid lipase activity in cryptogenic cirrhosis: A nationwide multicentre cohort study.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: I Clinica Medica, Atherothrombosis Center, Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Italy; Department of Public Health and Infectious Diseases, Sapienza University of Rome, Italy. Electronic address: francesco.angelico@uniroma1.it.
authors.forename: Francesco
authors.initials: F
authors.lastname: Angelico
authors.affiliation: Gastroenterology Division, Department of Clinical Medicine, Sapienza University of Rome, Italy.
authors.forename: Stefano Ginanni
authors.initials: SG
authors.lastname: Corradini
authors.affiliation: I Clinica Medica, Atherothrombosis Center, Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Italy; Department of Anatomical, Histological, Forensic Medicine and Orthopedics Sciences - Sapienza University of Rome, Italy.
authors.forename: Daniele
authors.initials: D
authors.lastname: Pastori
authors.affiliation: Department of Pathophysiology and Transplantation, Ca' Granda Foundation IRCCS Maggiore Policlinico Hospital, University of Milan, Milan, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Fargion
authors.affiliation: Department of Pathophysiology and Transplantation, Ca' Granda Foundation IRCCS Maggiore Policlinico Hospital, University of Milan, Milan, Italy.
authors.forename: Anna Ludovica
authors.initials: AL
authors.lastname: Fracanzani
authors.affiliation: Hepatology Unit, Tor Vergata University, Rome, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Angelico
authors.affiliation: Department of Medical and Surgical Sciences, University of Bologna, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Bolondi
authors.affiliation: Unit for Neuromuscular and Neurodegenerative Diseases, Children's Hospital and Research Institute "Bambino Gesù", Rome, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Tozzi
authors.affiliation: Department of Internal Medicine, Ospedale di Arzignano, ULSS n.5 "Ovest Vicentino", Italy.
authors.forename: Pietro Luigi
authors.initials: PL
authors.lastname: Pujatti
authors.affiliation: I Clinica Medica, Atherothrombosis Center, Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Italy.
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Labbadia
authors.affiliation: First Department of Internal Medicine, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Italy.
authors.forename: Gino Roberto
authors.initials: GR
authors.lastname: Corazza
authors.affiliation: Department of Internal Medicine and Medical Specialties - DIBIMIS, School of Medicine, University of Palermo, Palermo, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Averna
authors.affiliation: Department of Medical and Surgical Sciences, University Magna Græcia of Catanzaro, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Perticone
authors.affiliation: Internal Medicine Unit, Giuseppe Mazzini Hospital, Teramo, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Croce
authors.affiliation: Internal Medicine and Hepatology Unit, Salerno University of Medicine, Salerno, Italy.
authors.forename: Marcello
authors.initials: M
authors.lastname: Persico
authors.affiliation: Internal Medicine and Hepatology Unit, Salerno University of Medicine, Salerno, Italy.
authors.forename: Tommaso
authors.initials: T
authors.lastname: Bucci
authors.affiliation: I Clinica Medica, Atherothrombosis Center, Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Italy; Department of Anatomical, Histological, Forensic Medicine and Orthopedics Sciences - Sapienza University of Rome, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Baratta
authors.affiliation: I Clinica Medica, Atherothrombosis Center, Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Italy.
authors.forename: Licia
authors.initials: L
authors.lastname: Polimeni
authors.affiliation: I Clinica Medica, Atherothrombosis Center, Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Del Ben
authors.affiliation: I Clinica Medica, Atherothrombosis Center, Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Violi
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D016009:Chi-Square Distribution; D015897:Comorbidity; D003430:Cross-Sectional Studies; D015536:Down-Regulation; D059788:Dried Blood Spot Testing; D005260:Female; D006801:Humans; D007558:Italy / Q000453:epidemiology; D016014:Linear Models; D008103:Liver Cirrhosis / Q000097:blood / Q000151:congenital* / Q000175:diagnosis / Q000201:enzymology / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010976:Platelet Count; D015995:Prevalence; D012307:Risk Factors; D002787:Sterol Esterase / Q000097:blood*
chemical_list: D015415:Biomarkers; C503451:LIPA protein, human; D002787:Sterol Esterase
keywords: Cryptogenic cirrhosis; Liver disease; Lysosomal acid lipase; Pathogenesis