Reduced lysosomal acid lipase activity: A new marker of liver disease severity across the clinical continuum of non-alcoholic fatty liver disease?

Francesco Baratta, Daniele Pastori, Domenico Ferro, Giovanna Carluccio, Giulia Tozzi, Francesco Angelico, Francesco Violi, Maria Del Ben

Research output: Contribution to journalReview article

Abstract

Lysosomal acid lipase (LAL) plays a key role in intracellular lipid metabolism. Reduced LAL activity promotes increased multi-organ lysosomal cholesterol ester storage, as observed in two recessive autosomal genetic diseases, Wolman disease and Cholesterol ester storage disease. Severe liver steatosis and accelerated liver fibrosis are common features in patients with genetic LAL deficiency. By contrast, few reliable data are available on the modulation of LAL activity in vivo and on the epigenetic and metabolic factors capable of regulating its activity in subjects without homozygous mutations of the Lipase A gene. In the last few years, a less severe and non-genetic reduction of LAL activity was reported in children and adults with non-alcoholic fatty liver disease (NAFLD), suggesting a possible role of LAL reduction in the pathogenesis and progression of the disease. Patients with NAFLD show a significant, progressive reduction of LAL activity from simple steatosis to non-alcoholic steatohepatitis and cryptogenic cirrhosis. Among cirrhosis of different etiologies, those with cryptogenic cirrhosis show the most significant reductions of LAL activity. These findings suggest that the modulation of LAL activity may become a possible new therapeutic target for patients with more advanced forms of NAFLD. Moreover, the measurement of LAL activity may represent a possible new marker of disease severity in this clinical setting.

Original languageEnglish
Pages (from-to)4172-4180
Number of pages9
JournalWorld Journal of Gastroenterology
Volume25
Issue number30
DOIs
Publication statusPublished - Aug 14 2019

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Sterol Esterase
Liver Diseases
Fatty Liver
Cholesterol Ester Storage Disease
Wolman Disease
Non-alcoholic Fatty Liver Disease
Inborn Genetic Diseases
Cholesterol Esters
Lipase
Lipid Metabolism
Epigenomics
Liver Cirrhosis
Disease Progression
Fibrosis
Mutation

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Reduced lysosomal acid lipase activity : A new marker of liver disease severity across the clinical continuum of non-alcoholic fatty liver disease? / Baratta, Francesco; Pastori, Daniele; Ferro, Domenico; Carluccio, Giovanna; Tozzi, Giulia; Angelico, Francesco; Violi, Francesco; Del Ben, Maria.

In: World Journal of Gastroenterology, Vol. 25, No. 30, 14.08.2019, p. 4172-4180.

Research output: Contribution to journalReview article

Baratta, Francesco ; Pastori, Daniele ; Ferro, Domenico ; Carluccio, Giovanna ; Tozzi, Giulia ; Angelico, Francesco ; Violi, Francesco ; Del Ben, Maria. / Reduced lysosomal acid lipase activity : A new marker of liver disease severity across the clinical continuum of non-alcoholic fatty liver disease?. In: World Journal of Gastroenterology. 2019 ; Vol. 25, No. 30. pp. 4172-4180.
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abstract = "Lysosomal acid lipase (LAL) plays a key role in intracellular lipid metabolism. Reduced LAL activity promotes increased multi-organ lysosomal cholesterol ester storage, as observed in two recessive autosomal genetic diseases, Wolman disease and Cholesterol ester storage disease. Severe liver steatosis and accelerated liver fibrosis are common features in patients with genetic LAL deficiency. By contrast, few reliable data are available on the modulation of LAL activity in vivo and on the epigenetic and metabolic factors capable of regulating its activity in subjects without homozygous mutations of the Lipase A gene. In the last few years, a less severe and non-genetic reduction of LAL activity was reported in children and adults with non-alcoholic fatty liver disease (NAFLD), suggesting a possible role of LAL reduction in the pathogenesis and progression of the disease. Patients with NAFLD show a significant, progressive reduction of LAL activity from simple steatosis to non-alcoholic steatohepatitis and cryptogenic cirrhosis. Among cirrhosis of different etiologies, those with cryptogenic cirrhosis show the most significant reductions of LAL activity. These findings suggest that the modulation of LAL activity may become a possible new therapeutic target for patients with more advanced forms of NAFLD. Moreover, the measurement of LAL activity may represent a possible new marker of disease severity in this clinical setting.",
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AU - Carluccio, Giovanna

AU - Tozzi, Giulia

AU - Angelico, Francesco

AU - Violi, Francesco

AU - Del Ben, Maria

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AB - Lysosomal acid lipase (LAL) plays a key role in intracellular lipid metabolism. Reduced LAL activity promotes increased multi-organ lysosomal cholesterol ester storage, as observed in two recessive autosomal genetic diseases, Wolman disease and Cholesterol ester storage disease. Severe liver steatosis and accelerated liver fibrosis are common features in patients with genetic LAL deficiency. By contrast, few reliable data are available on the modulation of LAL activity in vivo and on the epigenetic and metabolic factors capable of regulating its activity in subjects without homozygous mutations of the Lipase A gene. In the last few years, a less severe and non-genetic reduction of LAL activity was reported in children and adults with non-alcoholic fatty liver disease (NAFLD), suggesting a possible role of LAL reduction in the pathogenesis and progression of the disease. Patients with NAFLD show a significant, progressive reduction of LAL activity from simple steatosis to non-alcoholic steatohepatitis and cryptogenic cirrhosis. Among cirrhosis of different etiologies, those with cryptogenic cirrhosis show the most significant reductions of LAL activity. These findings suggest that the modulation of LAL activity may become a possible new therapeutic target for patients with more advanced forms of NAFLD. Moreover, the measurement of LAL activity may represent a possible new marker of disease severity in this clinical setting.

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