{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,9]],"date-time":"2026-05-09T05:04:58Z","timestamp":1778303098040,"version":"3.51.4"},"reference-count":52,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2021,6,5]],"date-time":"2021-06-05T00:00:00Z","timestamp":1622851200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004271","name":"Sapienza Universit\u00e0 di Roma","doi-asserted-by":"publisher","award":["M_000106_11_AR__ATTILI_ATENEO"],"award-info":[{"award-number":["M_000106_11_AR__ATTILI_ATENEO"]}],"id":[{"id":"10.13039\/501100004271","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>In nonalcoholic steatohepatitis animal models, an increased lipid droplet size in hepatocytes is associated with fibrogenesis. Hepatocytes with large droplet (Ld-MaS) or small droplet (Sd-MaS) macrovesicular steatosis may coexist in the human liver, but the factors associated with the predominance of one type over the other, including hepatic fibrogenic capacity, are unknown. In pre-ischemic liver biopsies from 225 consecutive liver transplant donors, we retrospectively counted hepatocytes with Ld-MaS and Sd-MaS and defined the predominant type of steatosis as involving \u226550% of steatotic hepatocytes. We analyzed a donor Patatin-like phospholipase domain-containing protein 3 (PNPLA3) rs738409 polymorphism, hepatic expression of proteins involved in lipid metabolism by RT-PCR, hepatic stellate cell (HSC) activation by \u03b1-SMA immunohistochemistry and, one year after transplantation, histological progression of fibrosis due to Hepatitis C Virus (HCV) recurrence. Seventy-four livers had no steatosis, and there were 98 and 53 with predominant Ld-MaS and Sd-MaS, respectively. In linear regression models, adjusted for many donor variables, the percentage of steatotic hepatocytes affected by Ld-MaS was inversely associated with hepatic expression of Insulin Induced Gene 1 (INSIG-1) and Niemann-Pick C1-Like 1 gene (NPC1L1) and directly with donor PNPLA3 variant M, HSC activation and progression of post-transplant fibrosis. In humans, Ld-MaS formation by hepatocytes is associated with abnormal PNPLA3-mediated lipolysis, downregulation of both the intracellular cholesterol sensor and cholesterol reabsorption from bile and increased hepatic fibrogenesis.<\/jats:p>","DOI":"10.3390\/ijms22116100","type":"journal-article","created":{"date-parts":[[2021,6,6]],"date-time":"2021-06-06T23:59:55Z","timestamp":1623023995000},"page":"6100","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["The Propensity of the Human Liver to Form Large Lipid Droplets Is Associated with PNPLA3 Polymorphism, Reduced INSIG1 and NPC1L1 Expression and Increased Fibrogenetic Capacity"],"prefix":"10.3390","volume":"22","author":[{"given":"Flaminia","family":"Ferri","sequence":"first","affiliation":[{"name":"Department of Translational and Precision Medicine, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3164-1500","authenticated-orcid":false,"given":"Simone","family":"Carotti","sequence":"additional","affiliation":[{"name":"Laboratory of Microscopic and Ultrastructural Anatomy, CIR, University Campus Bio-Medico, 00128 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guido","family":"Carpino","sequence":"additional","affiliation":[{"name":"Department of Movement, Human and Health Sciences, Division of Health Sciences, University of Rome \u201cForo Italico\u201d, 00135 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Monica","family":"Mischitelli","sequence":"additional","affiliation":[{"name":"Department of Translational and Precision Medicine, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2378-0874","authenticated-orcid":false,"given":"Alfredo","family":"Cantafora","sequence":"additional","affiliation":[{"name":"Department of Translational and Precision Medicine, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonio","family":"Molinaro","sequence":"additional","affiliation":[{"name":"Wallenberg Laboratory, Department of Molecular and Clinical Medicine\/Wallenberg Laboratory, Institute of Medicine, University of Gothenburg and Sahlgrenska University Hospital, 413 45 Gothenburg, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9213-1494","authenticated-orcid":false,"given":"Maria Eva","family":"Argenziano","sequence":"additional","affiliation":[{"name":"Department of Translational and Precision Medicine, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9953-009X","authenticated-orcid":false,"given":"Simona","family":"Parisse","sequence":"additional","affiliation":[{"name":"Department of Translational and Precision Medicine, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6896-4509","authenticated-orcid":false,"given":"Alessandro","family":"Corsi","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8643-9211","authenticated-orcid":false,"given":"Mara","family":"Riminucci","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1487-3235","authenticated-orcid":false,"given":"Quirino","family":"Lai","sequence":"additional","affiliation":[{"name":"General Surgery and Organ Transplantation Unit, Department of Surgery, Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gianluca","family":"Mennini","sequence":"additional","affiliation":[{"name":"General Surgery and Organ Transplantation Unit, Department of Surgery, Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gustavo","family":"Spadetta","sequence":"additional","affiliation":[{"name":"Department of Internal Anesthesiological and Cardiovascular Clinical Sciences, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesco","family":"Pugliese","sequence":"additional","affiliation":[{"name":"Department of Internal Anesthesiological and Cardiovascular Clinical Sciences, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Massimo","family":"Rossi","sequence":"additional","affiliation":[{"name":"General Surgery and Organ Transplantation Unit, Department of Surgery, Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sergio","family":"Morini","sequence":"additional","affiliation":[{"name":"Laboratory of Microscopic and Ultrastructural Anatomy, CIR, University Campus Bio-Medico, 00128 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eugenio","family":"Gaudio","sequence":"additional","affiliation":[{"name":"Department of Anatomical, Histological, Forensic Medicine and Orthopedics Sciences, Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0839-1961","authenticated-orcid":false,"given":"Stefano","family":"Ginanni Corradini","sequence":"additional","affiliation":[{"name":"Department of Translational and Precision Medicine, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.arcmed.2020.11.010","article-title":"Epidemiology, Pathogenesis, Diagnosis and Emerging Treatment of Nonalcoholic Fatty Liver Disease","volume":"52","author":"Makri","year":"2020","journal-title":"Arch. Med. Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1726","DOI":"10.1002\/hep.29546","article-title":"Nonalcoholic fatty liver disease incidence and impact on metabolic burden and death: A 20 year-community study","volume":"67","author":"Allen","year":"2018","journal-title":"Hepatology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"S40","DOI":"10.1038\/modpathol.3800680","article-title":"Pathology of fatty liver disease","volume":"20","author":"Brunt","year":"2007","journal-title":"Mod. Pathol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1002\/lt.23615","article-title":"Assessment of hepatic steatosis by transplant surgeon and expert pathologist: A prospective, double-blind evaluation of 201 donor livers","volume":"19","author":"Yersiz","year":"2013","journal-title":"Liver Transpl."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1111\/j.1440-1746.2011.06844.x","article-title":"Grade of deceased donor liver macrovesicular steatosis impacts graft and recipient outcomes more than the Donor Risk Index","volume":"27","author":"Kench","year":"2012","journal-title":"J. Gastroenterol. Hepatol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"273","DOI":"10.3109\/08941939.2011.586094","article-title":"Type of steatosis influences microcirculation and fibrogenesis in different rat strains","volume":"24","author":"Rosenstengel","year":"2011","journal-title":"J. Investig. Surg."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1177\/0023677212473717","article-title":"Gender and strain-specific differences in the development of steatosis in rats","volume":"47","author":"Palmes","year":"2013","journal-title":"Lab. Anim."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1038\/s41374-019-0315-9","article-title":"Automated computerized image analysis for the user-independent evaluation of disease severity in preclinical models of NAFLD\/NASH","volume":"100","author":"Bouzin","year":"2020","journal-title":"Lab. Invest."},{"key":"ref_9","first-page":"G726","article-title":"Liver-specific loss of Perilipin 2 alleviates diet-induced hepatic steatosis, inflammation, and fibrosis","volume":"310","author":"Najt","year":"2016","journal-title":"Am. J. Physiol. Liver Physiol."},{"key":"ref_10","first-page":"101115","article-title":"Hepatic lipid droplets: A balancing act between energy storage and metabolic dysfunction in NAFLD","volume":"10","author":"Mashek","year":"2020","journal-title":"Mol. Metab."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1016\/j.jhep.2008.01.016","article-title":"NASH Clinical Research Network. Relationship of steatosis grade and zonal location to histological features of steatohepatitis in adult patients with non-alcoholic fatty liver disease","volume":"48","author":"Chalasani","year":"2008","journal-title":"J. Hepatol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1016\/j.jhep.2010.11.021","article-title":"Presence and significance of microvesicular steatosis in nonalcoholic fatty liver disease","volume":"55","author":"Tandra","year":"2011","journal-title":"J. Hepatol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"467","DOI":"10.3389\/fmed.2020.00467","article-title":"Disturbances in Cholesterol Homeostasis and Non-alcoholic Fatty Liver Diseases","volume":"7","author":"Malhotra","year":"2020","journal-title":"Front. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2548154","DOI":"10.1155\/2018\/2548154","article-title":"Hypoxic Signaling and Cholesterol Lipotoxicity in Fatty Liver Disease Progression","volume":"31","author":"Tirosh","year":"2018","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"18548","DOI":"10.1038\/s41598-020-75604-6","article-title":"Molecular imaging analysis of microvesicular and macrovesicular lipid droplets in non-alcoholic fatty liver disease by Raman microscopy","volume":"29","author":"Minamikawa","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1111\/iep.12169","article-title":"Pathological characterization and morphometric analysis of hepatic lesions in SHRSP5\/Dmcr, an experimental non-alcoholic steatohepatitis model, induced by high-fat and high-cholesterol diet","volume":"97","author":"Horai","year":"2016","journal-title":"Int. J. Exp. Pathol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"3320","DOI":"10.1083\/jcb.201803153","article-title":"Lipid droplet size directs lipolysis and lipophagy catabolism in hepatocytes","volume":"218","author":"Schott","year":"2019","journal-title":"J. Cell Biol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"32443","DOI":"10.1073\/pnas.2011442117","article-title":"Direct lysosome-based autophagy of lipid droplets in hepatocytes","volume":"117","author":"Schulze","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.semcdb.2020.04.011","article-title":"Hepatic lipid droplet homeostasis and fatty liver disease","volume":"108","author":"Seebacher","year":"2020","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Dejgaard, S.Y., and Presley, J.F. (2021). Interactions of Lipid Droplets with the Intracellular Transport Machinery. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22052776"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"900","DOI":"10.1016\/j.bbalip.2018.06.018","article-title":"The role of PNPLA3 in health and disease","volume":"1864","author":"Pingitore","year":"2019","journal-title":"Biochim. Biophys. Acta Mol. Cell Biol. Lipids."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"15756","DOI":"10.1038\/s41598-017-15943-z","article-title":"PNPLA3 variant and portal\/periportal histological pattern in patients with biopsy-proven non-alcoholic fatty liver disease: A possible role for oxidative stress","volume":"7","author":"Carpino","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"4130","DOI":"10.1172\/JCI65179","article-title":"Chronic overexpression of PNPLA3I148M in mouse liver causes hepatic steatosis","volume":"122","author":"Li","year":"2012","journal-title":"J. Clin. Investig."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1111\/boc.201200036","article-title":"PNPLA3\/adiponutrin functions in lipid droplet formation","volume":"105","author":"Chamoun","year":"2013","journal-title":"Biol. Cell."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2427","DOI":"10.1002\/hep.30583","article-title":"PNPLA3, CGI-58, and Inhibition of Hepatic Triglyceride Hydrolysis in Mice","volume":"69","author":"Wang","year":"2019","journal-title":"Hepatology"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1002\/hep.27242","article-title":"Pnpla3I148M knockin mice accumulate PNPLA3 on lipid droplets and develop hepatic steatosis","volume":"61","author":"Smagris","year":"2015","journal-title":"Hepatology"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"4282","DOI":"10.1074\/jbc.M115.701094","article-title":"Differential Roles of Cell Death-inducing DNA Fragmentation Factor-\u03b1-like Effector (CIDE) Proteins in Promoting Lipid Droplet Fusion and Growth in Subpopulations of Hepatocytes","volume":"291","author":"Xu","year":"2016","journal-title":"J. Biol. Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"3245","DOI":"10.1111\/febs.14189","article-title":"A unifying mathematical model of lipid droplet metabolism reveals key molecular players in the development of hepatic steatosis","volume":"284","author":"Wallstab","year":"2017","journal-title":"FEBS J."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1007\/s00216-018-1506-8","article-title":"Mapping the triglyceride distribution in NAFLD human liver by MALDI imaging mass spectrometry reveals molecular differences in micro and macro steatosis","volume":"411","author":"Alamri","year":"2019","journal-title":"Anal. Bioanal. Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2427","DOI":"10.1111\/liv.14492","article-title":"Disruption of Plin5 degradation by CMA causes lipid homeostasis imbalance in NAFLD","volume":"40","author":"Ma","year":"2020","journal-title":"Liver Int."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1007\/s12263-014-0392-8","article-title":"Influence of dietary pattern, physical activity, and I148M PNPLA3 on steatosis severity in at-risk adolescents","volume":"9","author":"Nobili","year":"2014","journal-title":"Genes Nutr."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1186\/s12944-020-01207-9","article-title":"Independent and joint correlation of PNPLA3 I148M and TM6SF2 E167K variants with the risk of coronary heart disease in patients with non-alcoholic fatty liver disease","volume":"19","author":"Wu","year":"2020","journal-title":"Lipids Health Dis."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1130","DOI":"10.1111\/liv.14419","article-title":"PNPLA3 I148M gene variant and chronic kidney disease in type 2 diabetic patients with NAFLD: Clinical and experimental findings","volume":"40","author":"Mantovani","year":"2020","journal-title":"Liver Int."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Schwartz, B.E., Rajagopal, V., Smith, C., Cohick, E., Whissell, G., Gamboa, M., Pai, R., Sigova, A., Grossman, I., and Bumcrot, D. (2020). Discovery and Targeting of the Signaling Controls of PNPLA3 to Effectively Reduce Transcription, Expression, and Function in Pre-Clinical NAFLD\/NASH Settings. Cells, 9.","DOI":"10.3390\/cells9102247"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.molmet.2019.01.013","article-title":"Pnpla3 silencing with antisense oligonucleotides ameliorates nonalcoholic steatohepatitis and fibrosis in Pnpla3 I148M knock-in mice","volume":"22","author":"Ahnmark","year":"2019","journal-title":"Mol. Metab."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1016\/j.jhepr.2019.05.007","article-title":"Quantitative digital pathology reveals association of cell-specific PNPLA3 transcription with NAFLD disease activity","volume":"1","author":"Sandhu","year":"2019","journal-title":"JHEP Rep."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1002\/lt.21566","article-title":"Impact of donor graft steatosis on overall outcome and viral recurrence after liver transplantation for hepatitis C virus cirrhosis","volume":"15","author":"Ciria","year":"2009","journal-title":"Liver Transpl."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1259","DOI":"10.1097\/TP.0b013e318235a1ab","article-title":"Donor graft steatosis influences immunity to hepatitis C virus and allograft outcome after liver transplantation","volume":"92","author":"Subramanian","year":"2011","journal-title":"Transplantation"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1007\/s004240050525","article-title":"Noradrenaline and ATP decrease the secretion of triglyceride and apoprotein B from perfused rat liver","volume":"435","author":"Yamauchi","year":"1998","journal-title":"Pflugers Arch."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"578001","DOI":"10.3389\/fmed.2020.578001","article-title":"Hypoxia and Non-alcoholic Fatty Liver Disease","volume":"7","author":"Isaza","year":"2020","journal-title":"Front. Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"4443","DOI":"10.1096\/fj.10-159806","article-title":"Hypoxia-inducible protein 2 is a novel lipid droplet protein and a specific target gene of hypoxia-inducible factor-1","volume":"24","author":"Gimm","year":"2010","journal-title":"FASEB J."},{"key":"ref_42","first-page":"158738","article-title":"Regulation of lipid droplet homeostasis by hypoxia inducible lipid droplet associated HILPDA","volume":"1865","author":"Kersten","year":"2020","journal-title":"Biochim. Biophys. Acta Mol. Cell Biol. Lipids."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"15175","DOI":"10.1074\/jbc.M115.650184","article-title":"The Lipid Droplet Protein Hypoxia-inducible Gene 2 Promotes Hepatic Triglyceride Deposition by Inhibiting Lipolysis","volume":"290","author":"DiStefano","year":"2015","journal-title":"J. Biol. Chem."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"964","DOI":"10.1016\/j.bbalip.2012.03.004","article-title":"Niemann-Pick C1-Like 1 and cholesterol uptake","volume":"1821","author":"Wang","year":"2012","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1016\/j.cca.2020.05.042","article-title":"Emerging role of Insig-1 in lipid metabolism and lipid disorders","volume":"508","author":"Shuhui","year":"2020","journal-title":"Clin. Chim. Acta"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"296","DOI":"10.3904\/kjim.2017.194","article-title":"Ezetimibe decreased nonalcoholic fatty liver disease activity score but not hepatic steatosis","volume":"34","author":"Lee","year":"2019","journal-title":"Korean J. Intern. Med."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1002\/hep.26604","article-title":"Free cholesterol accumulation in hepatic stellate cells: Mechanism of liver fibrosis aggravation in nonalcoholic steatohepatitis in mice","volume":"59","author":"Tomita","year":"2014","journal-title":"Hepatology"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"15691","DOI":"10.1038\/ncomms15691","article-title":"Cellular senescence drives age-dependent hepatic steatosis","volume":"8","author":"Ogrodnik","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"5862985","DOI":"10.1155\/2019\/5862985","article-title":"Donor Small-Droplet Macrovesicular Steatosis Affects Liver Transplant Outcome in HCV-Negative Recipients","volume":"2019","author":"Ferri","year":"2019","journal-title":"Can. J. Gastroenterol. Hepatol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"806","DOI":"10.1002\/lt.21436","article-title":"Glial fibrillary acidic protein as an early marker of hepatic stellate cell activation in chronic and posttransplant recurrent hepatitis C","volume":"14","author":"Carotti","year":"2008","journal-title":"Liver Transpl."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1016\/0168-8278(95)80226-6","article-title":"Histological grading and staging of chronic hepatitis","volume":"22","author":"Ishak","year":"1995","journal-title":"J. Hepatol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/11\/6100\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:11:15Z","timestamp":1760163075000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/11\/6100"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6,5]]},"references-count":52,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2021,6]]}},"alternative-id":["ijms22116100"],"URL":"https:\/\/doi.org\/10.3390\/ijms22116100","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,6,5]]}}}