{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T17:21:56Z","timestamp":1767892916242,"version":"3.49.0"},"reference-count":31,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2024,5,14]],"date-time":"2024-05-14T00:00:00Z","timestamp":1715644800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"UZ Brussel Foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Introduction: Tuberous sclerosis complex (TSC) is a genetic disease caused by pathogenetic variants in either the TSC1 or TSC2 genes. Consequently, the mechanistic target of the rapamycin complex 1 (mTORC1) pathway, a regulator of cell growth, metabolism, and survival, becomes inappropriately activated, leading to the development of benign tumors in multiple organs. The role of mTORC1 in lipid metabolism and liver steatosis in TSC patients has not been well-studied, and clinical data on liver involvement in this population are scarce. Methods: We conducted a retrospective, cross-sectional study to compare liver steatosis in TSC patients with age-, sex-, BMI-, and diabetes status-matched controls. Participants with a definite diagnosis of TSC were recruited from the TSC clinic at UZ Brussel. Liver steatosis was quantified using the fat signal fraction from in-phase and out-of-phase MRI, with a threshold of \u22655% defining the presence of steatosis. We also evaluated the prevalence of liver angiomyolipomata in the TSC group and analyzed risk factors for both liver steatosis and angiomyolipomata. Results: The study included 59 TSC patients and 59 matched controls. The mean fat signal fraction was 4.0% in the TSC group and 3.9% in the controls, showing no significant difference (two-tailed Wilcoxon signed ranks test, p = 0.950). Liver steatosis was observed in 15.3% of TSC patients compared to 23.7% of the controls, which was not statistically significant (two-tailed McNemar test, p = 0.267). Liver angiomyolipomata were identified in 13.6% of the TSC cohort. Conclusions: Our study, describing in detail the liver phenotype of TSC patients, did not reveal a significant difference in the prevalence of MRI-assessed liver steatosis in a large cohort of TSC patients compared to a closely matched control group.<\/jats:p>","DOI":"10.3390\/jcm13102888","type":"journal-article","created":{"date-parts":[[2024,5,14]],"date-time":"2024-05-14T06:28:12Z","timestamp":1715668092000},"page":"2888","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Prevalence of Liver Steatosis in Tuberous Sclerosis Complex Patients: A Retrospective Cross-Sectional Study"],"prefix":"10.3390","volume":"13","author":[{"given":"Tha\u00efs","family":"De Bock","sequence":"first","affiliation":[{"name":"Department of Nephrology and Arterial Hypertension, Universitair Ziekenhuis Brussel (UZ Brussel), Vrije Universiteit Brussel (VUB), 1090 Brussels, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5424-6300","authenticated-orcid":false,"given":"Carola","family":"Brussaard","sequence":"additional","affiliation":[{"name":"Department of Radiology, Universitair Ziekenhuis Brussel (UZ Brussel), Vrije Universiteit Brussel (VUB), 1090 Brussels, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Silke","family":"Fran\u00e7ois","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Universitair Ziekenhuis Brussel (UZ Brussel), Vrije Universiteit Brussel (VUB), 1090 Brussels, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karlien","family":"Fran\u00e7ois","sequence":"additional","affiliation":[{"name":"Department of Nephrology and Arterial Hypertension, Universitair Ziekenhuis Brussel (UZ Brussel), Vrije Universiteit Brussel (VUB), 1090 Brussels, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Seynaeve","sequence":"additional","affiliation":[{"name":"Department of Neurology, Universitair Ziekenhuis Brussel (UZ Brussel), Vrije Universiteit Brussel (VUB), 1090 Brussels, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Jansen","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neurology, Universitair Ziekenhuis Antwerpen (UZA), 2650 Antwerpen, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karl Martin","family":"Wissing","sequence":"additional","affiliation":[{"name":"Department of Nephrology and Arterial Hypertension, Universitair Ziekenhuis Brussel (UZ Brussel), Vrije Universiteit Brussel (VUB), 1090 Brussels, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0981-8621","authenticated-orcid":false,"given":"Peter","family":"Janssens","sequence":"additional","affiliation":[{"name":"Department of Nephrology and Arterial Hypertension, Universitair Ziekenhuis Brussel (UZ Brussel), Vrije Universiteit Brussel (VUB), 1090 Brussels, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,5,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"16035","DOI":"10.1038\/nrdp.2016.35","article-title":"Tuberous sclerosis complex","volume":"26","author":"Henske","year":"2016","journal-title":"Nat. Rev. Dis. Prim."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1146\/annurev-genom-083118-015354","article-title":"Genetic Etiologies, Diagnosis, and Treatment of Tuberous Sclerosis Complex","volume":"20","author":"Salussolia","year":"2019","journal-title":"Annu. Rev. Genom. Hum. Genet."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"586","DOI":"10.1111\/jdv.13356","article-title":"Systemic effects of treatment with mTOR inhibitors in tuberous sclerosis complex: A comprehensive review","volume":"30","author":"Sadowski","year":"2016","journal-title":"J. Eur. Acad. Dermatol. Venereol."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Franz, D.N., Belousova, E., Sparagana, S., Bebin, E.M., Frost, M.D., Kuperman, R., Witt, O., Kohrman, M.H., Flamini, J.R., and Wu, J.Y. (2016). Long-Term Use of Everolimus in Patients with Tuberous Sclerosis Complex: Final Results from the EXIST-1 Study. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0158476"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1016\/S0140-6736(12)61767-X","article-title":"Everolimus for angiomyolipoma associated with tuberous sclerosis complex or sporadic lymphangioleiomyomatosis (EXIST-2): A multicentre, randomised, double-blind, placebo-controlled trial","volume":"381","author":"Bissler","year":"2013","journal-title":"Lancet"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1038\/s41581-024-00818-0","article-title":"Clinical practice recommendations for kidney involvement in tuberous sclerosis complex: A consensus statement by the ERKNet Working Group for Autosomal Dominant Structural Kidney Disorders and the ERA Genes & Kidney Working Group","volume":"20","author":"Mekahli","year":"2024","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Feng, J., Qiu, S., Zhou, S., Tan, Y., Bai, Y., Cao, H., Guo, J., and Su, Z. (2022). mTOR: A Potential New Target in Nonalcoholic Fatty Liver Disease. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23169196"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1542","DOI":"10.1016\/j.jhep.2023.06.003","article-title":"A multisociety Delphi consensus statement on new fatty liver disease nomenclature","volume":"79","author":"Rinella","year":"2023","journal-title":"J. Hepatol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1625","DOI":"10.1016\/j.jcmgh.2022.02.015","article-title":"Activation of Liver mTORC1 Protects Against NASH via Dual Regulation of VLDL-TAG Secretion and De Novo Lipogenesis","volume":"13","author":"Uehara","year":"2022","journal-title":"Cell. Mol. Gastroenterol. Hepatol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.cmet.2011.06.002","article-title":"Akt stimulates hepatic SREBP1c and lipogenesis through parallel mTORC1-dependent and independent pathways","volume":"14","author":"Yecies","year":"2011","journal-title":"Cell Metab."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1670","DOI":"10.1002\/hep.32651","article-title":"RNA helicase DEAD-box protein 5 alleviates nonalcoholic steatohepatitis progression via tethering TSC complex and suppressing mTORC1 signaling","volume":"77","author":"Zhang","year":"2023","journal-title":"Hepatology"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"eabf8271","DOI":"10.1126\/science.abf8271","article-title":"Inhibition of nonalcoholic fatty liver disease in mice by selective inhibition of mTORC1","volume":"376","author":"Gosis","year":"2022","journal-title":"Science"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1186\/s13023-017-0581-9","article-title":"Management of everolimus-associated adverse events in patients with tuberous sclerosis complex: A practical guide","volume":"12","author":"Davies","year":"2017","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1210\/endrev\/bnaa030","article-title":"Metabolic Consequences of Solid Organ Transplantation","volume":"42","author":"Bhat","year":"2021","journal-title":"Endocr. Rev."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e345","DOI":"10.1097\/TP.0000000000002916","article-title":"Incidence and Risks for Nonalcoholic Fatty Liver Disease and Steatohepatitis Post-liver Transplant: Systematic Review and Meta-analysis","volume":"103","author":"Saeed","year":"2019","journal-title":"Transplantation"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.pediatrneurol.2021.07.011","article-title":"Updated International Tuberous Sclerosis Complex Diagnostic Criteria and Surveillance and Management Recommendations","volume":"123","author":"Northrup","year":"2021","journal-title":"Pediatr. Neurol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1148\/radiol.2021204288","article-title":"Quantification of Liver Fat Content with CT and MRI: State of the Art","volume":"301","author":"Starekova","year":"2021","journal-title":"Radiology"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1038\/jhh.2013.140","article-title":"Apparent and true resistant hypertension: Definition, prevalence and outcomes","volume":"28","author":"Judd","year":"2014","journal-title":"J. Hum. Hypertens."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1016\/j.mric.2010.08.013","article-title":"Quantification of Liver Fat with Magnetic Resonance Imaging","volume":"18","author":"Reeder","year":"2010","journal-title":"Magn. Reson. Imaging Clin. N. Am."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1086\/316951","article-title":"Mutational Analysis in a Cohort of 224 Tuberous Sclerosis Patients Indicates Increased Severity of TSC2, Compared with TSC1, Disease in Multiple Organs","volume":"68","author":"Dabora","year":"2001","journal-title":"Am. J. Hum. Genet."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2212","DOI":"10.1016\/S0140-6736(20)32511-3","article-title":"Non-alcoholic fatty liver disease","volume":"397","author":"Powell","year":"2021","journal-title":"Lancet"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1002\/hep.28431","article-title":"Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence, incidence, and outcomes","volume":"64","author":"Younossi","year":"2016","journal-title":"Hepatology"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2041","DOI":"10.1111\/jgh.15156","article-title":"Global epidemiology of lean non-alcoholic fatty liver disease: A systematic review and meta-analysis","volume":"35","author":"Lu","year":"2020","journal-title":"J. Gastroenterol. Hepatol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"103967","DOI":"10.1016\/j.etap.2022.103967","article-title":"Valproic acid induced liver injury: An insight into molecular toxicological mechanism","volume":"95","author":"Ezhilarasan","year":"2022","journal-title":"Environ. Toxicol. Pharmacol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1053\/j.gastro.2015.04.043","article-title":"Liver Fibrosis, but No Other Histologic Features, Is Associated With Long-term Outcomes of Patients With Nonalcoholic Fatty Liver Disease","volume":"149","author":"Angulo","year":"2015","journal-title":"Gastroenterology"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.pediatrneurol.2017.09.012","article-title":"Liver Angiomyolipomas in Tuberous Sclerosis Complex\u2014Their Incidence and Course","volume":"78","author":"Sadowski","year":"2018","journal-title":"Pediatr. Neurol."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Kechaou, I., Cherif, E., Ben Hassine, L., and Khalfallah, N. (2014). Liver involvement in tuberous sclerosis. BMJ Case Rep., 2014.","DOI":"10.1136\/bcr-2013-201650"},{"key":"ref_28","first-page":"7","article-title":"Ruptured hepatic angiolipoma in tuberous sclerosis complex","volume":"381","author":"Huber","year":"1996","journal-title":"Langenbeck\u2019s Arch. Surg."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1111\/j.1399-0004.2012.01845.x","article-title":"Hepatic manifestations of tuberous sclerosis complex: A genotypic and phenotypic analysis","volume":"82","author":"Black","year":"2012","journal-title":"Clin. Genet."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Dabora, S.L., Franz, D.N., Ashwal, S., Sagalowsky, A., DiMario, F.J., Miles, D., Cutler, D., Krueger, D., Uppot, R.N., and Rabenou, R. (2011). Multicenter Phase 2 Trial of Sirolimus for Tuberous Sclerosis: Kidney Angiomyolipomas and Other Tumors Regress and VEGF- D Levels Decrease. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0023379"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1186\/s13023-015-0317-7","article-title":"Rapamycin and its analogues (rapalogs) for Tuberous Sclerosis Complex-associated tumors: A systematic review on non-randomized studies using meta-analysis","volume":"10","author":"Sasongko","year":"2015","journal-title":"Orphanet J. Rare Dis."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/13\/10\/2888\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:42:01Z","timestamp":1760107321000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/13\/10\/2888"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,14]]},"references-count":31,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2024,5]]}},"alternative-id":["jcm13102888"],"URL":"https:\/\/doi.org\/10.3390\/jcm13102888","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5,14]]}}}