Severe reduction of blood lysosomal acid lipase activity in cryptogenic cirrhosis: A nationwide multicentre cohort study. (July 2017)

• Record Type: Journal Article
• Authors: Violi, Francesco; Angelico, Francesco; Pastori, Daniele; Baratta, Francesco; Del Ben, Maria; Polimeni, Licia; Labbadia, Giancarlo; Basili, Stefania; Raparelli, Valeria; Napoleone, Laura; Corradini, Stefano Ginanni; Ferri, Flaminia; Monica, Pellone; Mischitelli, Monica; Lucia, Parlati; Tozzi, Giulia; D'Amico, Jessica; Colzi, Marina; Andreozzi, Paola; Perticone, Francesco; Caroleo, Benedetto; Corazza, Gino Roberto; Michela, Masotti; Gaetano, Bergamaschi; Sacerdoti, David; Brocco, Silvia; Angelico, Mario; Santopaolo, Francesco; Francioso, Simona; Pujatti, Pietro Luigi; Faedo, Alessandra; Andriulli, Angelo; Ippolito, Antonio M.; Bolondi, Luigi; Tovoli, Francesco; Fargion, Silvia; Fracanzani, Anna Ludovica; Davì, Giovanni; Di Michele, Dario; Croce, Giuseppe; Averna, Maurizio; Giammanco, Antonina; Persico, Marcello; Bucci, Tommaso; Iuliano, Luigi; Ciacciarelli, Marco; Angelico, Francesco; Corradini, Stefano Ginanni; Pastori, Daniele; Fargion, Silvia; Fracanzani, Anna Ludovica; Angelico, Mario; Bolondi, Luigi; Tozzi, Giulia; Pujatti, Pietro Luigi; Labbadia, Giancarlo; Corazza, Gino Roberto; Averna, Maurizio; Perticone, Francesco; Croce, Giuseppe; Persico, Marcello; Bucci, Tommaso; Baratta, Francesco; Polimeni, Licia; Del Ben, Maria; Violi, Francesco;
• Is Part Of: Atherosclerosis. Volume 262(2017)
• Page Start: 179
• Page End: 184
• Publication Date: 2017-07
• Subjects: Lysosomal acid lipase -- Cryptogenic cirrhosis -- Pathogenesis -- Liver disease; CESD cholesterol ester storage disease -- CTP Child-Turcotte-Pugh -- LAL lysosomal acid lipase -- NAFLD non-alcoholic fatty liver disease -- NASH non-alcoholic steatohepatitis -- MACCE major cardiovascular and cerebrovascular events -- MELD Model for End-stage Liver Disease; Arteriosclerosis -- Periodicals; Electronic journals; 616.136
• DOI: 10.1016/j.atherosclerosis.2017.03.038
• Languages: English
• ISSNs: 0021-9150

Abstract

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. Highlights: Cryptogenic cirrhosis is the evolution of non-alcoholic steatohepatitis (NASH). Lysosomal acid lipase (LAL) activity is reduced in patients with NASH. We found a marked reduction of LAL activity in patients with liver cirrhosis. Patients with cryptogenic cirrhosis showed a more severe reduction of LAL. LAL activity reduction was correlated with severity of liver disease.