{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T00:57:03Z","timestamp":1784854623666,"version":"3.55.0"},"reference-count":33,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2015,11,25]],"date-time":"2015-11-25T00:00:00Z","timestamp":1448409600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Lysosomal Acid Lipase (LAL) is a key enzyme involved in lipid metabolism, responsible for hydrolysing the cholesteryl esters and triglycerides. Wolman Disease represents the early onset phenotype of LAL deficiency rapidly leading to death. Cholesterol Ester Storage Disease is a late onset phenotype that occurs with fatty liver, elevated aminotransferase levels, hepatomegaly and dyslipidaemia, the latter characterized by elevated LDL-C and low HDL-C. The natural history and the clinical manifestations of the LAL deficiency in adults are not well defined, and the diagnosis is often incidental. LAL deficiency has been suggested as an under-recognized cause of dyslipidaemia and fatty liver. Therefore, LAL activity may be reduced also in non-obese patients presenting non-alcoholic fatty liver disease (NAFLD), unexplained persistently elevated liver transaminases or with elevation in LDL cholesterol. In these patients, it could be indicated to test LAL activity. So far, very few studies have been performed to assess LAL activity in representative samples of normal subjects or patients with NAFLD. Moreover, no large study has been carried out in adult subjects with NAFLD or cryptogenic cirrhosis.<\/jats:p>","DOI":"10.3390\/ijms161226085","type":"journal-article","created":{"date-parts":[[2015,11,25]],"date-time":"2015-11-25T10:44:52Z","timestamp":1448448292000},"page":"28014-28021","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Does Lysosomial Acid Lipase Reduction Play a Role in Adult Non-Alcoholic Fatty Liver Disease?"],"prefix":"10.3390","volume":"16","author":[{"given":"Francesco","family":"Baratta","sequence":"first","affiliation":[{"name":"Department of Internal Medicine and Medical Specialities and Department of Anatomical, Histological, Forensic Medicine and Orthopedics Sciences-Sapienza University, Rome 00185, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6357-5213","authenticated-orcid":false,"given":"Daniele","family":"Pastori","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Medical Specialities and Department of Anatomical, Histological, Forensic Medicine and Orthopedics Sciences-Sapienza University, Rome 00185, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Licia","family":"Polimeni","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Medical Specialities and Department of Anatomical, Histological, Forensic Medicine and Orthopedics Sciences-Sapienza University, Rome 00185, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Tozzi","sequence":"additional","affiliation":[{"name":"Unit for Neuromuscular and Neurodegenerative Diseases, Children\u2019s Hospital and Research Institute \u201cBambino Ges\u00f9\u201d, Rome 00165, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Violi","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Medical Specialities, Sapienza University, Rome 00185, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9372-3923","authenticated-orcid":false,"given":"Francesco","family":"Angelico","sequence":"additional","affiliation":[{"name":"Department of Public Health and Infectious Diseases, Sapienza University, Policlinico Umberto I, I Clinica Medica, Viale del Policlinico 155, Rome 00161, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1199-8454","authenticated-orcid":false,"given":"Maria","family":"Del Ben","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Medical Specialities, Sapienza University, Rome 00185, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2015,11,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1111\/j.1365-2036.2011.04724.x","article-title":"Systematic review: The epidemiology and natural history of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in adults","volume":"34","author":"Vernon","year":"2011","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1007\/s00535-013-0758-5","article-title":"Mechanisms of hepatic triglyceride accumulation in non-alcoholic fatty liver disease","volume":"48","author":"Kawano","year":"2013","journal-title":"J. Gastroenterol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"20704","DOI":"10.3390\/ijms141020704","article-title":"Multiple hits, including oxidative stress, as pathogenesis and treatment target in non-alcoholic steatohepatitis (NASH)","volume":"14","author":"Takaki","year":"2013","journal-title":"Int. J. Mol. Sci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e113","DOI":"10.1038\/ctg.2015.43","article-title":"Similar reduction of cholesterol-adjusted vitamin e serum levels in simple steatosis and non-alcoholic steatohepatitis","volume":"6","author":"Pastori","year":"2015","journal-title":"Clin. Transl. Gastroenterol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1097\/01.TP.0000436723.59879.01","article-title":"Nonalcoholic fatty liver disease epidemic and its implications for liver transplantation","volume":"96","author":"Kemmer","year":"2013","journal-title":"Transplantation"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1002\/hep.23314","article-title":"Decreased survival of subjects with elevated liver function tests during a 28-year follow-up","volume":"51","author":"Soderberg","year":"2010","journal-title":"Hepatology"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1724","DOI":"10.3748\/wjg.v20.i7.1724","article-title":"Risk of cardiovascular, cardiac and arrhythmic complications in patients with non-alcoholic fatty liver disease","volume":"20","author":"Ballestri","year":"2014","journal-title":"World J. Gastroenterol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1190","DOI":"10.1093\/eurheartj\/ehr453","article-title":"Non-alcoholic fatty liver disease: A new and important cardiovascular risk factor?","volume":"33","author":"Bhatia","year":"2012","journal-title":"Eur. Heart J."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"S291","DOI":"10.1007\/s11739-012-0819-4","article-title":"Non-alcoholic fatty liver disease and cardiovascular disease: Epidemiological, clinical and pathophysiological evidences","volume":"7","author":"Baratta","year":"2012","journal-title":"Internal Emerg. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1016\/j.atherosclerosis.2009.10.011","article-title":"Circulating levels and hepatic expression of molecular mediators of atherosclerosis in nonalcoholic fatty liver disease","volume":"209","author":"Sookoian","year":"2010","journal-title":"Atherosclerosis"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1402","DOI":"10.1016\/j.amjcard.2015.02.032","article-title":"Relation of nonalcoholic fatty liver disease and framingham risk score to flow-mediated dilation in patients with cardiometabolic risk factors","volume":"115","author":"Pastori","year":"2015","journal-title":"Am. J. Cardiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1212","DOI":"10.2337\/dc06-2247","article-title":"Prevalence of nonalcoholic fatty liver disease and its association with cardiovascular disease among type 2 diabetic patients","volume":"30","author":"Targher","year":"2007","journal-title":"Diabetes Care"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1947","DOI":"10.1007\/s00125-008-1135-4","article-title":"Increased risk of cardiovascular disease in non-alcoholic fatty liver disease: Causal effect or epiphenomenon?","volume":"51","author":"Targher","year":"2008","journal-title":"Diabetologia"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1053\/jhep.2003.50161","article-title":"Nonalcoholic fatty liver, steatohepatitis, and the metabolic syndrome","volume":"37","author":"Marchesini","year":"2003","journal-title":"Hepatology"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"8341","DOI":"10.3748\/wjg.v20.i26.8341","article-title":"Modern approach to the clinical management of non-alcoholic fatty liver disease","volume":"20","author":"Polimeni","year":"2014","journal-title":"World J. Gastroenterol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"842","DOI":"10.1016\/S0016-5085(98)70599-2","article-title":"Steatohepatitis: A tale of two \u201chits\u201d?","volume":"114","author":"Day","year":"1998","journal-title":"Gastroenterology"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e000019","DOI":"10.1136\/bmjgast-2014-000019","article-title":"Systematic review of genetic association studies involving histologically confirmed non-alcoholic fatty liver disease","volume":"2","author":"Wood","year":"2015","journal-title":"BMJ Open Gastroenterol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1016\/j.ejim.2014.05.012","article-title":"Non-alcoholic fatty liver disease, metabolic syndrome and patatin-like phospholipase domain-containing protein3 gene variants","volume":"25","author":"Polimeni","year":"2014","journal-title":"Eur. J. Intern. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1111\/j.1365-2265.2012.04498.x","article-title":"Fatty liver and insulin resistance in children with hypobetalipoproteinemia: The importance of aetiology","volume":"79","author":"Fintini","year":"2013","journal-title":"Clin. Endocrinol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1016\/j.jhep.2013.04.016","article-title":"Hepatic cholesteryl ester accumulation in lysosomal acid lipase deficiency: Non-invasive identification and treatment monitoring by magnetic resonance","volume":"59","author":"Thelwall","year":"2013","journal-title":"J. Hepatol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"732","DOI":"10.1016\/j.numecd.2012.05.009","article-title":"Heterozygosity for lysosomal acid lipase E8SJM mutation and serum lipid concentrations","volume":"23","author":"Muntoni","year":"2013","journal-title":"Nutr. Metab. Cardiovasc. Dis."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/j.ymgme.2009.02.007","article-title":"Cholesteryl ester storage disease (CESD) due to novel mutations in the LIPA gene","volume":"97","author":"Pisciotta","year":"2009","journal-title":"Mol. Genet. Metab."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1230","DOI":"10.1016\/j.jhep.2013.02.014","article-title":"Cholesteryl ester storage disease: Review of the findings in 135 reported patients with an underdiagnosed disease","volume":"58","author":"Bernstein","year":"2013","journal-title":"J. Hepatol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.atherosclerosis.2014.04.003","article-title":"Lysosomal acid lipase deficiency\u2014An under-recognized cause of dyslipidaemia and liver dysfunction","volume":"235","author":"Reiner","year":"2014","journal-title":"Atherosclerosis"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.1111\/j.1365-2559.2011.04164.x","article-title":"Distinctive histopathological features that support a diagnosis of cholesterol ester storage disease in liver biopsy specimens","volume":"60","author":"Hulkova","year":"2012","journal-title":"Histopathology"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1016\/j.ymgme.2011.12.008","article-title":"Lysosomal lipase deficiency: Molecular characterization of eleven patients with wolman or cholesteryl ester storage disease","volume":"105","author":"Fasano","year":"2012","journal-title":"Mol. Genet. Metab."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"3","DOI":"10.3389\/fcell.2015.00003","article-title":"Lysosomal acid lipase: At the crossroads of normal and atherogenic cholesterol metabolism","volume":"3","author":"Dubland","year":"2015","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1381","DOI":"10.1152\/physrev.00047.2003","article-title":"Role of oxidative modifications in atherosclerosis","volume":"84","author":"Stocker","year":"2004","journal-title":"Physiol. Rev."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1430","DOI":"10.1161\/01.ATV.0000077207.49221.06","article-title":"Lysosomal enzymes are released from cultured human macrophages, hydrolyze LDL in vitro, and are present extracellularly in human atherosclerotic lesions","volume":"23","author":"Hakala","year":"2003","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1207","DOI":"10.1016\/j.cca.2012.03.019","article-title":"A new method for the measurement of lysosomal acid lipase in dried blood spots using the inhibitor lalistat 2","volume":"413","author":"Hamilton","year":"2012","journal-title":"Clin. Chim. Acta"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1093\/jb\/mvj137","article-title":"Overexpression of lysosomal acid lipase and other proteins in atherosclerosis","volume":"140","author":"Zschenker","year":"2006","journal-title":"J. Biochem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"750","DOI":"10.1016\/j.ebiom.2015.05.018","article-title":"Reduced lysosomal acid lipase activity in adult patients with non-alcoholic fatty liver disease","volume":"2","author":"Baratta","year":"2015","journal-title":"EBioMedicine"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1010","DOI":"10.1056\/NEJMoa1501365","article-title":"A phase 3 trial of sebelipase alfa in lysosomal acid lipase deficiency","volume":"373","author":"Burton","year":"2015","journal-title":"N. Engl. J. Med."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/16\/12\/26085\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T20:52:43Z","timestamp":1760215963000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/16\/12\/26085"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,11,25]]},"references-count":33,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2015,12]]}},"alternative-id":["ijms161226085"],"URL":"https:\/\/doi.org\/10.3390\/ijms161226085","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,11,25]]}}}