{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T19:55:32Z","timestamp":1791489332577,"version":"4.3.4"},"reference-count":104,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2023,7,30]],"date-time":"2023-07-30T00:00:00Z","timestamp":1690675200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Alcohol effect hepatic lipid metabolism through various mechanisms, leading synergistically to an accumulation of fatty acids (FA) and triglycerides. Obesity, as well as dietary fat (saturated fatty acids (FA) versus poly-unsaturated fatty acids (PUFA)) may modulate the hepatic fat. Alcohol inhibits adenosine monophosphate activated kinase (AMPK). AMPK activates peroxisome proliferator activated receptor a (PPAR\u03b1) and leads to a decreased activation of sterol regulatory element binding protein 1c (SRABP1c). The inhibition of AMPK, and thus of PPAR\u03b1, results in an inhibition of FA oxidation. This \u00df-oxidation is further reduced due to mitochondrial damage induced through cytochrome P4502E1 (CYP2E1)-driven oxidative stress. Furthermore, the synthesis of FAs is stimulated through an activation of SHREP1. In addition, alcohol consumption leads to a reduced production of adiponectin in adipocytes due to oxidative stress and to an increased mobilization of FAs from adipose tissue and from the gut as chylomicrons. On the other side, the secretion of FAs via very-low-density lipoproteins (VLDL) from the liver is inhibited by alcohol. Alcohol also affects signal pathways such as early growth response 1 (Egr-1) associated with the expression of tumour necrosis factor \u03b1 (TNF \u03b1), and the mammalian target of rapamycin (mTOR) a key regulator of autophagy. Both have influence the pathogenesis of alcoholic fatty liver. Alcohol-induced gut dysbiosis contributes to the severity of ALD by increasing the metabolism of ethanol in the gut and promoting intestinal dysfunction. Moreover, pathogen-associated molecular patterns (PAMPS) via specific Toll-like receptor (TLR) bacterial overgrowth leads to the translocation of bacteria. Endotoxins and toxic ethanol metabolites enter the enterohepatic circulation, reaching the liver and inducing the activation of the nuclear factor kappa-B (NF\u03baB) pathway. Pro-inflammatory cytokines released in the process contribute to inflammation and fibrosis. In addition, cellular apoptosis is inhibited in favour of necrosis.<\/jats:p>","DOI":"10.3390\/life13081662","type":"journal-article","created":{"date-parts":[[2023,7,31]],"date-time":"2023-07-31T01:28:46Z","timestamp":1690766926000},"page":"1662","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Pathogenesis of Alcoholic Fatty Liver a Narrative Review"],"prefix":"10.3390","volume":"13","author":[{"given":"Helmut K.","family":"Seitz","sequence":"first","affiliation":[{"name":"Centre of Liver and Alcohol Associated Diseases, Ethianum Clinic, Faculty of Medicine, University of Heidelberg, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernardo","family":"Moreira","sequence":"additional","affiliation":[{"name":"Centre of Liver and Alcohol Associated Diseases, Ethianum Clinic, Faculty of Medicine, University of Heidelberg, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuela G.","family":"Neuman","sequence":"additional","affiliation":[{"name":"In Vitro Drug Safety and Biotechnology, Department of Pharmacology and Toxicology, Temerity Faculty of Medicine, University of Toronto, Banting Institute, Toronto, ON M5G 1L5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,7,30]]},"reference":[{"key":"ref_1","first-page":"1111","article-title":"Alcoholic Liver Disease","volume":"Volume 2","author":"Dancygier","year":"2010","journal-title":"Clinical Hepatology. Principle and Practice of Hepatobiliary Diseases"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1038\/s41572-018-0014-7","article-title":"Alcoholic liver disease","volume":"4","author":"Seitz","year":"2018","journal-title":"Nat. Rev. Dis. Prim."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.nut.2017.07.010","article-title":"An iso-\u03b1-acid-rich extract from hops (Humulus lupulus) attenuates acute alcohol-induced liver steatosis in mice","volume":"45","author":"Hege","year":"2018","journal-title":"Nutrition"},{"key":"ref_4","unstructured":"Hall, P. (1995). Alcoholic Liver Disease. Pathology and Pathogenesis, Edward Arnold. [2nd ed.]."},{"key":"ref_5","first-page":"689","article-title":"Sonographic course of alcoholic fatty liver by inter-observer and digital evaluation of liver echogenicity","volume":"45","author":"Simonis","year":"2007","journal-title":"Zeitschr. Gastroenterol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.1016\/j.jhep.2017.12.029","article-title":"Controlled attenuation parameter for the assessment of alcoholic hepatic steatosis: Biopsy-controlled diagnostic accuracy and role of detoxification","volume":"68","author":"Thiele","year":"2018","journal-title":"J. Hepatol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"842","DOI":"10.1136\/gutjnl-2021-324727","article-title":"Clomethiazole inhibits cytochrome P4502E1 and improves alcoholic liver disease","volume":"71","author":"Hohmann","year":"2022","journal-title":"Gut"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1016\/S0022-2275(20)40613-3","article-title":"Effects of ethanol on lipid metabolism","volume":"20","author":"Baraona","year":"1979","journal-title":"J. Lipid Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1111\/j.1530-0277.2008.00827.x","article-title":"Molecular mechanisms of alcoholic fatty liver","volume":"33","author":"Purohit","year":"2009","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Malnick, S.D.H., Alin, P., Somin, M., and Neuman, M.G. (2022). Fatty liver disease-alcoholic and non-alcoholic. Similar but different. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232416226"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1111\/hepr.12594","article-title":"Molecular basis of alcoholic fatty liver disease: From incidence to treatment","volume":"46","author":"Acco","year":"2016","journal-title":"Hepatol. Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"3492","DOI":"10.3748\/wjg.v18.i27.3492","article-title":"Multi-causality in fatty liver disease: Is there a rationale to distinguish between alcoholic and non-alcoholic origin","volume":"18","year":"2012","journal-title":"World J. Gastroenterol."},{"key":"ref_13","first-page":"52","article-title":"Do alcoholic calories count?","volume":"2","author":"Seitz","year":"2014","journal-title":"Front. Alcohol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"858","DOI":"10.1016\/0006-291X(70)90982-4","article-title":"Hepatic microsomal ethanol oxidizing system (MEOS) differentiation from alcohol dehydrogenase and NADPH oxidase","volume":"40","author":"Lieber","year":"1970","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Anzenbacher, P., and Zanger, U.M. (2012). Metabolism of Drugs and Other Xenobiotics, Wiley-VCH GmbH.","DOI":"10.1002\/9783527630905"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1451","DOI":"10.1172\/JCI105637","article-title":"Difference in hepatic metabolism of long-and medium chain fatty acids: The role of fatty acid chain length in the production of the alcoholic fatty liver","volume":"46","author":"Lieber","year":"1967","journal-title":"J. Clin. Investig."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"970292","DOI":"10.3389\/fphys.2022.970292","article-title":"The AMPK pathway in fatty liver disease","volume":"13","author":"Fang","year":"2022","journal-title":"Front. Physiol."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Zhong, Z., Ramshesh, V.K., Rehman, H., Liu, Q., Theruvath, T.P., Krishnasamy, Y., and Lemasters, J.J. (2014). Acute ethanol causes hepatic mitochondrial depolarization in mice: Role of ethanol metabolism. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0091308"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1074\/jbc.M008791200","article-title":"The transcriptional and DNA binding activity of peroxisome proliferator-activated receptor \u03b1 is inhibited by ethanol metabolism. A novel mechanism for the development of ethanol-induced fatty liver","volume":"276","author":"Galli","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"17756","DOI":"10.3748\/wjg.v20.i47.17756","article-title":"Pathogenesis of alcoholic liver disease: Role of oxidative metabolism","volume":"20","author":"Ceni","year":"2014","journal-title":"World J. Gastroenterol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"29342","DOI":"10.1074\/jbc.M202411200","article-title":"Ethanol induces fatty acid synthesis pathways by activation of sterol regulatory element-binding protein (SREBP)","volume":"277","author":"You","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1798","DOI":"10.1053\/j.gastro.2004.09.049","article-title":"The role of AMP-activated protein kinase in the action of ethanol in the liver","volume":"127","author":"You","year":"2004","journal-title":"Gastroenterology"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"41464","DOI":"10.18632\/oncotarget.6203","article-title":"Identification of cytochrome P4502E1 as critical mediator of alcohol effects on steatotic hepatocytes","volume":"6","author":"Mahli","year":"2015","journal-title":"Oncotarget"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1406","DOI":"10.1016\/j.freeradbiomed.2010.07.026","article-title":"Chronic alcohol-induced liver injury and oxidant stress are decreased in cytochrome P4502E1 knockout mice and restored in humanized cytochrome P4502E1 knock-in mice","volume":"49","author":"Lu","year":"2010","journal-title":"Free Radic Biol. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1483","DOI":"10.1002\/hep.22222","article-title":"Cytochrome P4502E1 contributes to ethanol-induced fatty liver in mice","volume":"47","author":"Lu","year":"2008","journal-title":"Hepatology"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1238","DOI":"10.1016\/j.freeradbiomed.2013.09.009","article-title":"CYP2E1 potentiates binge alcohol-induced gut leakiness, steatohepatitis and apoptosis","volume":"65","author":"Abdelmegeed","year":"2013","journal-title":"Free Radic. Biol. Med."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Harjum\u00e4ki, R., Pridgeon, C.S., and Ingelman-Sundberg, M. (2021). CYP2E1 in alcoholic and non-alcoholic liver injury. Roles of ROS, reactive intermediates and lipid overload. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22158221"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1524","DOI":"10.1016\/S0891-5849(01)00741-9","article-title":"Intoductional serial review: Alcohol, oxidative stress and cell injury","volume":"31","author":"Cederbaum","year":"2001","journal-title":"Free Radic. Biol. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1016\/j.redox.2017.09.018","article-title":"Impairment of Akt activity by CPY2E1-mediated oxidative stress is involved in chronic ethanol-induced fatty liver","volume":"14","author":"Zeng","year":"2018","journal-title":"Redox Biol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.cbi.2014.08.009","article-title":"Inhibition of cytochrome P4502E1 by chlormethiazole attenuated acute ethanol-induced fatty liver","volume":"222","author":"Chen","year":"2014","journal-title":"Chem. Biol. Interact."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1093\/alcalc\/agac068","article-title":"Effect of chlormethiazole vs. clorazepate on hepatic fat and serum transaminase activities in alcohol-associated liver disease: Results from a randomized, controlled phase II clinical trial","volume":"58","author":"Hohmann","year":"2023","journal-title":"Alcohol Alcohol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.tox.2017.01.016","article-title":"Alcoholic fatty liver is enhanced in CYP2A5 knockout mice: The role of the PPAR\u03b1-FGF21 axis","volume":"379","author":"Chen","year":"2017","journal-title":"Toxicology"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.abb.2018.09.012","article-title":"Nicotine enhances alcoholic fatty liver in mice: Role of CYP2A5","volume":"657","author":"Chen","year":"2018","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1294","DOI":"10.3390\/cimb44030087","article-title":"Molecular, Viral and Clinical Features of Alcohol- and Non-Alcohol-Induced Liver Injury","volume":"44","author":"Neuman","year":"2022","journal-title":"Curr. Issues Mol. Biol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1111\/j.1530-0277.2011.01607.x","article-title":"Ethanol-induced oxidative stress via CYP2E1 pathway disrupts adiponectin secretion from adipocytes","volume":"36","author":"Tang","year":"2012","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"850","DOI":"10.3181\/0902-MR-61","article-title":"Adinopectin: A key adipokine in alcoholic fatty liver","volume":"234","author":"You","year":"2009","journal-title":"Exp. Biol. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1002\/iub.124","article-title":"Adiponectin and alcoholic fatty liver disease","volume":"60","author":"Rogers","year":"2008","journal-title":"IUMBM Life"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1172\/JCI200317797","article-title":"The fat-derived hormone adiponectin alleviates alcoholic and non-alcoholic fatty liver diseases in mice","volume":"112","author":"Xu","year":"2001","journal-title":"J. Clin. Invest"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"998","DOI":"10.1016\/j.ajpath.2011.11.017","article-title":"Chronic alcohol exposure stimulates adipose tissue lipolysis in mice: Role of reverse triglyceride transport in the pathogenesis of alcoholic steatosis","volume":"180","author":"Zhong","year":"2012","journal-title":"Am. J. Pathol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"237","DOI":"10.2174\/1874467208666150817111727","article-title":"Structure, function and metabolism of hepatic and adipose tissue lipid droplets: Implications in alcoholic liver disease","volume":"10","author":"Natarajan","year":"2017","journal-title":"Curr. Mol. Pharmacol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2066","DOI":"10.1053\/j.gastro.2005.02.065","article-title":"Early growth response-1 transcription factor is essential for ethanol-induced fatty liver injury in mice","volume":"128","author":"McMullen","year":"2005","journal-title":"Gastroenterology"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1740","DOI":"10.1053\/j.gastro.2010.07.041","article-title":"Autophagy reduces acute ethanol-induced hepatotoxicity and steatosis in mice","volume":"139","author":"Ding","year":"2010","journal-title":"Gastroenterology"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1301","DOI":"10.1111\/j.1530-0277.2012.01742.x","article-title":"Autophagy in alcohol-induced liver diseases","volume":"36","author":"Dolganiuc","year":"2012","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1002\/hep4.1063","article-title":"Ethanol-induced steatosis involves impairment of lipophagy, associated with reduced Dynamin2 activity","volume":"1","author":"Rasineni","year":"2017","journal-title":"Hepatol. Commun."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.redox.2014.10.002","article-title":"Intestinal CYP2E1: A mediator of alcohol-induced gut leakiness","volume":"3","author":"Forsyth","year":"2014","journal-title":"Redox Biol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"6161","DOI":"10.3748\/wjg.v27.i37.6161","article-title":"Significance of gut microbiota in alcoholic and non-alcoholic fatty liver diseases","volume":"27","author":"Sharma","year":"2021","journal-title":"World J. Gastroenterol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1016\/j.numecd.2012.02.007","article-title":"Gut--liver axis: The impact of gut microbiota on non alcoholic fatty liver disease","volume":"22","author":"Compare","year":"2012","journal-title":"Nutr Metab Cardiovasc Dis."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"742","DOI":"10.1016\/S0168-8278(00)80242-1","article-title":"Increased intestinal permeability to macromolecules and endotoxemia in patients with chronic alcohol abuse in different stages of alcohol-induced liver disease","volume":"32","author":"Parlesak","year":"2000","journal-title":"J. Hepatol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1008","DOI":"10.1053\/jhep.2000.19621","article-title":"Exacerbation of alcoholic liver injury by enteral endotoxin in rats","volume":"32","author":"Mathurin","year":"2000","journal-title":"Hepatology"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/S0168-8278(87)80003-X","article-title":"Endotoxemia in patients with alcoholic and non-alcoholic cirrhosis and in subjects with no evidence of chronic liver disease following acute alcohol excess","volume":"4","author":"Bode","year":"1987","journal-title":"J. Hepatol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1002\/hep.23009","article-title":"Endotoxemia and gut barrier dysfunction in alcoholic liver disease","volume":"50","author":"Rao","year":"2009","journal-title":"Hepatology"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1148","DOI":"10.2353\/ajpath.2006.050617","article-title":"Impairment of the intestinal barrier by ethanol involves enteric microflora and mast cell activation in rodents","volume":"168","author":"Ferrier","year":"2006","journal-title":"Am. J. Pathol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"G966","DOI":"10.1152\/ajpgi.00380.2011","article-title":"Colonic microbiome is altered in alcoholism","volume":"302","author":"Mutlu","year":"2012","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"2829","DOI":"10.1172\/JCI90562","article-title":"Intestinal fungi contribute to development of alcoholic liver disease","volume":"127","author":"Yang","year":"2017","journal-title":"J. Clin. Invest"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1002\/hep.30832","article-title":"Intestinal Fungal Dysbiosis and Systemic Immune Response to Fungi in Patients With Alcoholic Hepatitis","volume":"71","author":"Lang","year":"2020","journal-title":"Hepatology"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1314","DOI":"10.1007\/s12029-021-00748-1","article-title":"The Gut Microbiome and Hepatocellular Carcinoma","volume":"52","year":"2021","journal-title":"J Gastrointest Cancer."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"699253","DOI":"10.3389\/fphys.2021.699253","article-title":"Dynamic Changes of the Fungal Microbiome in Alcohol Use Disorder","volume":"12","author":"Hartmann","year":"2021","journal-title":"Front. Physiol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1830693","DOI":"10.1080\/19490976.2020.1830693","article-title":"Therapeutic manipulation of gut microbiota by polysaccharides of Wolfiporia cocos reveals the contribution of the gut fungi-induced PGE2 to alcoholic hepatic steatosis","volume":"12","author":"Sun","year":"2020","journal-title":"Gut Microbes"},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Couch, R.D., Dailey, A., Zaidi, F., Navarro, K., Forsyth, C.B., Mutlu, E., Engen, P.A., and Keshavarzian, A. (2015). Alcohol induced alterations to the human fecal VOC metabolome. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0119362"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1685","DOI":"10.1016\/j.dld.2019.05.025","article-title":"Are presepsin and resistin better markers for bacterial infection in patients with decompensated liver cirrhosis?","volume":"51","author":"Fischer","year":"2019","journal-title":"Dig. Liver Dis."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"594150","DOI":"10.3389\/fimmu.2020.594150","article-title":"Role of metabolic endotoxemia in systemic inflammation and potential interventions","volume":"11","author":"Mohammad","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"11336","DOI":"10.1074\/jbc.M116.773291","article-title":"The let-7\/Lin28 axis regulates activation of hepatic stellate cells in alcoholic liver injury","volume":"292","author":"McDaniel","year":"2017","journal-title":"J. Biol. Chem."},{"key":"ref_63","first-page":"367","article-title":"Severity of liver injury in experimental alcoholic liver disease. Correlation with plasma endotoxin, prostaglandin E2, leukotriene B4, and thromboxane B2","volume":"142","author":"Nanji","year":"1993","journal-title":"Am. J. Pathol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1224","DOI":"10.1002\/hep.22470","article-title":"The critical role of toll-like receptor (TLR) 4 in alcoholic liver disease is independent of the common TLR adapter MyD88","volume":"48","author":"Hritz","year":"2008","journal-title":"Hepatology"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"27526","DOI":"10.1074\/jbc.M114.602383","article-title":"Regulation of the extrinsic apoptotic pathway by microRNA-21 in alcoholic liver injury","volume":"289","author":"Francis","year":"2014","journal-title":"J. Biol. Chem."},{"key":"ref_66","first-page":"2205","article-title":"The differing effects of acute and chronic alcohol on gastric and intestinal permeability","volume":"89","author":"Keshavarzian","year":"1994","journal-title":"Am. J. Gastroenterol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"G385","DOI":"10.1152\/ajpgi.00111.2018","article-title":"Knockout of microRNA-21 attenuates alcoholic hepatitis through the VHL\/NF-\u03baB signaling pathway in hepatic stellate cells","volume":"315","author":"Wu","year":"2018","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1002\/hep.30036","article-title":"Hepatocellular Carcinoma Is Associated with Gut Microbiota Profile and Inflammation in Nonalcoholic Fatty Liver Disease","volume":"69","author":"Ponziani","year":"2019","journal-title":"Hepatology"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1111\/nure.12027","article-title":"Ethanol metabolism and its effects on the intestinal epithelial barrier","volume":"71","author":"Elamin","year":"2013","journal-title":"Nutr. Rev."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1016\/j.alcohol.2010.07.008","article-title":"The effects of ethanol administration on brush border membrane glycolipids in rat intestine","volume":"44","author":"Grewal","year":"2010","journal-title":"Alcohol"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1002\/hep.24018","article-title":"Enteric dysbiosis associated with a mouse model of alcoholic liver disease","volume":"53","author":"Yan","year":"2011","journal-title":"Hepatology"},{"key":"ref_72","first-page":"4","article-title":"Metagenomic analyses of alohol induced pathogenic alterations in the intestinal microbiome and the Effect of Lactobacillus rhamnosus GG treatment","volume":"8","author":"Feng","year":"2013","journal-title":"PLoS ONE"},{"key":"ref_73","first-page":"223","article-title":"The Gastrointestinal microbiome: Alcohol effects on the composition of intestinal microbiota","volume":"37","author":"Engen","year":"2015","journal-title":"Alcohol. Res."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1016\/j.jhep.2019.09.029","article-title":"The Candida albicans exotoxin candidalysin promotes alcohol-associated liver disease","volume":"72","author":"Chu","year":"2020","journal-title":"J. Hepatol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"830","DOI":"10.1136\/gutjnl-2015-310585","article-title":"Intestinal microbiota contributes to individual susceptibility to alcoholic liver disease","volume":"65","author":"Llopis","year":"2016","journal-title":"Gut"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1053\/j.gastro.2014.09.014","article-title":"Supplementation of saturated long-chain fatty acids maintains intestinal eubiosis and reduces ethanol-induced liver injury in mice","volume":"148","author":"Chen","year":"2015","journal-title":"Gastroenterology"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1016\/j.ajpath.2015.11.017","article-title":"Saturated and Unsaturated Dietary Fats Differentially Modulate Ethanol-Induced Changes in Gut Microbiome and Metabolome in a Mouse Model of Alcoholic Liver Disease","volume":"186","author":"Kirpich","year":"2016","journal-title":"Am. J. Pathol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1509","DOI":"10.1194\/jlr.R900007-JLR200","article-title":"Bile acids as regulatory molecules","volume":"50","author":"Hylemon","year":"2009","journal-title":"J. Lipid Res."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1283","DOI":"10.1016\/j.jhep.2012.01.019","article-title":"Bacterial translocation and changes in the intestinal microbiome in mouse models of liver disease","volume":"56","author":"Fouts","year":"2012","journal-title":"J. Hepatol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/j.cld.2015.10.012","article-title":"Nonalcoholic Fatty Liver Disease and the Gut Microbiome","volume":"20","author":"Boursier","year":"2016","journal-title":"Clin. Liver Dis."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"E4485","DOI":"10.1073\/pnas.1415174111","article-title":"Intestinal permeability, gut-bacterial dysbiosis, and behavioral markers of alcohol-dependence severity","volume":"111","author":"Leclercq","year":"2014","journal-title":"Proc. Nat. Acad. Sci. USA"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1016\/j.alcohol.2008.08.006","article-title":"Probiotics restore bowel flora and improve liver enzymes in human alcohol-induced liver injury: A pilot study","volume":"42","author":"Kirpich","year":"2008","journal-title":"Alcohol"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"945","DOI":"10.1016\/j.jhep.2008.02.015","article-title":"Effect of probiotic treatment on deranged neutrophil function and cytokine responses in patients with compensated alcoholic cirrhosis","volume":"48","author":"Stadlbauer","year":"2008","journal-title":"J. Hepatol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"2185","DOI":"10.1016\/j.ajpath.2020.08.014","article-title":"Kupffer Cells: Inflammation pathways and cell- cell interactions in Alcohol-associated liver disease","volume":"190","author":"Slevin","year":"2020","journal-title":"Am. J. Pathol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1749","DOI":"10.1016\/S0140-6736(14)60121-5","article-title":"Liver cirrhosis","volume":"383","author":"Tsochatzis","year":"2014","journal-title":"Lancet"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"k2817","DOI":"10.1136\/bmj.k2817","article-title":"Mortality due to cirrhosis and liver cancer in the United States, 1999-2016: Observational study","volume":"362","author":"Tapper","year":"2018","journal-title":"BMJ"},{"key":"ref_87","first-page":"307","article-title":"Alcoholic liver disease. Practice Guideline Committee of the American Association for the Study of Liver Diseases; Practice Parameters Committee of the American College of Gastroenterology","volume":"51","author":"Dasarathy","year":"2010","journal-title":"Hepatology"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.4065\/76.10.1021","article-title":"Pathogenesis, diagnosis, and treatment of alcoholic liver disease","volume":"76","author":"Menon","year":"2001","journal-title":"Mayo Clin. Proc."},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"(2012). EASL clinical practical guidelines: Management of alcoholic liver disease. J. Hepatol., 57, 399\u2013420.","DOI":"10.1016\/j.jhep.2012.04.004"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1016\/j.jhep.2017.03.031","article-title":"Alcohol use disorders and the burden of chronic hepatitis C in France, 2008-2013: A nationwide retrospective cohort study","volume":"67","author":"Schwarzinger","year":"2017","journal-title":"J. Hepatol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1016\/j.ebiom.2016.04.023","article-title":"Ethnicity matters: A systematic review and meta-analysis of the non-linear relationship between alcohol consumption and prevalence and incidence of hepatic steatosis","volume":"8","author":"Roerecke","year":"2016","journal-title":"EBioMedicine"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1111\/j.1465-3362.2009.00153.x","article-title":"Alcohol as a risk factor for liver cirrhosis-a systematic review and meta-analysis","volume":"29","author":"Rehm","year":"2010","journal-title":"Drug Alcohol Rev."},{"key":"ref_93","first-page":"106","article-title":"Alcohol drinking pattern and risk of alcoholic liver cirrhosis: A prospective cohort study","volume":"62","author":"Kjaer","year":"2015","journal-title":"J. Hepatol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1093\/aje\/kwg184","article-title":"Wine, liquor, beer, and mortality","volume":"158","author":"Klatsky","year":"2003","journal-title":"Am. J. Epidemiol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1245","DOI":"10.1056\/NEJM199505113321901","article-title":"Alcohol consumption and mortality among women","volume":"332","author":"Fuchs","year":"1995","journal-title":"N. Engl. J. Med."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.1002\/hep.510230513","article-title":"Prediction of risk of liver disease by alcohol intake, sex, and age: A prospective population study","volume":"23","author":"Becker","year":"1996","journal-title":"Hepatology"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"868","DOI":"10.1053\/jhep.2002.32101","article-title":"Lower risk for alcohol-induced cirrhosis in wine drinkers","volume":"35","author":"Becker","year":"2002","journal-title":"Hepatology"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/S0009-9120(02)00275-8","article-title":"A comparison of the anticarcinogenic properties of four red wine polyphenols","volume":"35","author":"Soleas","year":"2002","journal-title":"Clin. Biochem."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/S0009-9120(02)00397-1","article-title":"Absorption of three wine-related polyphenols in three different matrices by healthy subjects","volume":"36","author":"Goldberg","year":"2003","journal-title":"Clin. Biochem."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"1032","DOI":"10.1021\/jf011149c","article-title":"Method for the gas chromatographic assay with mass selective detection of trichloro compounds in corks and wines applied to elucidate the potential cause of cork taint","volume":"50","author":"Soleas","year":"2002","journal-title":"J. Agric. Food Chem."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"759","DOI":"10.3390\/nu4070759","article-title":"Wine, beer, alcohol and polyphenols on cardiovascular disease and cancer","volume":"4","author":"Arranz","year":"2012","journal-title":"Nutrients"},{"key":"ref_102","doi-asserted-by":"crossref","unstructured":"Visioli, F., Panaite, S.A., and Tom\u00e9-Carneiro, J. (2020). Wine\u2019s Phenolic Compounds and Health: A Pythagorean View. Molecules, 25.","DOI":"10.3390\/molecules25184105"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"e1770","DOI":"10.6061\/clinics\/2020\/e1770","article-title":"Alcohol and sudden unexpected death in epilepsy: Do not pop the cork","volume":"75","author":"Scorza","year":"2020","journal-title":"Clinics"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1093\/qjmed\/hcu247","article-title":"High alcohol consumption and the risk of renal damage: A systematic review and meta-analysis","volume":"108","author":"Cheungpasitporn","year":"2015","journal-title":"QJM"}],"container-title":["Life"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-1729\/13\/8\/1662\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:22:43Z","timestamp":1760127763000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-1729\/13\/8\/1662"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,7,30]]},"references-count":104,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2023,8]]}},"alternative-id":["life13081662"],"URL":"https:\/\/doi.org\/10.3390\/life13081662","relation":{},"ISSN":["2075-1729"],"issn-type":[{"value":"2075-1729","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,7,30]]}}}