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World J Gastroenterol. Aug 14, 2019; 25(30): 4172-4180
Published online Aug 14, 2019. doi: 10.3748/wjg.v25.i30.4172
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
Francesco Baratta, Daniele Pastori, Domenico Ferro, Giovanna Carluccio, Francesco Violi, Maria Del Ben, Department of Internal Medicine and Medical Specialties, Sapienza - University of Rome, Rome 00155, Italy
Giulia Tozzi, Hepatogastroenterology and Nutrition Unit - Pediatric Department, Bambino Gesù Children’s Hospital, Rome 00156, Italy
Francesco Angelico, Department of Public Health and Infectious Disease, Sapienza - University of Rome, Rome 00161, Italy
Author contributions: All authors equally contributed to this paper with conception and design of the study, literature review and analysis, drafting, critical revision and editing, and final approval of the final version.
Conflict-of-interest statement: No potential conflicts of interest. No financial support.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Francesco Angelico, MD, Associate Professor, I Clinica Medica, Department of Public Health and Infectious Diseases, Sapienza University of Rome, viale del Policlinico 155, Rome 00161, Italy. francesco.angelico@uniroma1.it
Telephone: +39-6-49977777 Fax: +39-6-49972309
Received: April 8, 2019
Peer-review started: April 8, 2019
First decision: May 30, 2019
Revised: June 20, 2019
Accepted: July 2, 2019
Article in press: July 3, 2019
Published online: August 14, 2019
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.

Keywords: Non-alcoholic fatty liver disease, Non-alcoholic steatohepatitis, Lysosomal acid lipase, Cirrhosis, Wolman disease, Cholesterol ester storage disease

Core tip: Reduced lysosomal acid lipase (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. A less severe and non-genetic reduction of LAL activity has been reported in children and adults with non-alcoholic fatty liver disease (NAFLD). Patients with NAFLD show a significant, progressive reduction of LAL activity from simple steatosis to non-alcoholic steatohepatitis and cryptogenic cirrhosis. In the future, modulation of LAL activity may become a possible new therapeutic target for patients with more advanced forms of NAFLD and represent a possible new marker of disease severity.