{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,28]],"date-time":"2026-03-28T18:38:50Z","timestamp":1774723130007,"version":"3.50.1"},"reference-count":103,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2023,7,15]],"date-time":"2023-07-15T00:00:00Z","timestamp":1689379200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>It is estimated that 25% of the world\u2019s population has non-alcoholic fatty liver disease. This disease can advance to a more severe form, non-alcoholic steatohepatitis (NASH), a disease with a greater probability of progression to cirrhosis and hepatocellular carcinoma (HCC). NASH could be characterized as a necro-inflammatory complication of chronic hepatic steatosis. The combination of factors that lead to NASH and its progression to HCC in the setting of inflammation is not clearly understood. The portal vein is the main route of communication between the intestine and the liver. This allows the transfer of products derived from the intestine to the liver and the hepatic response pathway of bile and antibody secretion to the intestine. The intestinal microbiota performs a fundamental role in the regulation of immune function, but it can undergo changes that alter its functionality. These changes can also contribute to cancer by disrupting the immune system and causing chronic inflammation and immune dysfunction, both of which are implicated in cancer development. In this article, we address the link between inflammation, microbiota and HCC. We also review the different in vitro models, as well as recent clinical trials addressing liver cancer and microbiota.<\/jats:p>","DOI":"10.3390\/pathogens12070940","type":"journal-article","created":{"date-parts":[[2023,7,17]],"date-time":"2023-07-17T01:06:36Z","timestamp":1689555996000},"page":"940","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["From Non-Alcoholic Fatty Liver Disease to Liver Cancer: Microbiota and Inflammation as Key Players"],"prefix":"10.3390","volume":"12","author":[{"given":"Avilene","family":"Rodr\u00edguez-Lara","sequence":"first","affiliation":[{"name":"Center of Biomedical Research, Institute of Nutrition and Food Technology \u201cJos\u00e9 Mataix\u201d, University of Granada, Avda. del Conocimiento s\/n., Armilla, 18016 Granada, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1048-2448","authenticated-orcid":false,"given":"Ascensi\u00f3n","family":"Rueda-Robles","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Food Science, Faculty of Pharmacy, University of Granada,18071 Granada, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7439-9817","authenticated-orcid":false,"given":"Mar\u00eda Jos\u00e9","family":"S\u00e1ez-Lara","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology I, School of Sciences, University of Granada, 18071 Granada, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5171-9408","authenticated-orcid":false,"given":"Julio","family":"Plaza-Diaz","sequence":"additional","affiliation":[{"name":"Children\u2019s Hospital Eastern Ontario Research Institute, Ottawa, ON K1H 8L1, Canada"},{"name":"Instituto de Investigaci\u00f3n Biosanitaria ibs.GRANADA, Complejo Hospitalario Universitario de Granada, 18014 Granada, Spain"},{"name":"Department of Biochemistry and Molecular Biology II, School of Pharmacy, University of Granada, 18071 Granada, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8476-9970","authenticated-orcid":false,"given":"Ana I.","family":"\u00c1lvarez-Mercado","sequence":"additional","affiliation":[{"name":"Center of Biomedical Research, Institute of Nutrition and Food Technology \u201cJos\u00e9 Mataix\u201d, University of Granada, Avda. del Conocimiento s\/n., Armilla, 18016 Granada, Spain"},{"name":"Instituto de Investigaci\u00f3n Biosanitaria ibs.GRANADA, Complejo Hospitalario Universitario de Granada, 18014 Granada, Spain"},{"name":"Department of Biochemistry and Molecular Biology II, School of Pharmacy, University of Granada, 18071 Granada, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,7,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1038\/s41575-020-00381-6","article-title":"Global epidemiology of NAFLD-related HCC: Trends, predictions, risk factors and prevention","volume":"18","author":"Huang","year":"2021","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_2","first-page":"167","article-title":"Pathogenesis and Prevention of Hepatic Steatosis","volume":"11","author":"Nassir","year":"2015","journal-title":"Gastroenterol. Hepatol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"262","DOI":"10.4093\/dmj.2012.36.4.262","article-title":"GLP-1 Receptor Agonist and Non-Alcoholic Fatty Liver Disease","volume":"36","author":"Lee","year":"2012","journal-title":"Diabetes Metab. J."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Di Ciaula, A., Baj, J., Garruti, G., Celano, G., De Angelis, M., Wang, H.H., Di Palo, D.M., Bonfrate, L., Wang, D.Q.-H., and Portincasa, P. (2020). Liver Steatosis, Gut-Liver Axis, Microbiome and Environmental Factors. A Never-Ending Bidirectional Cross-Talk. J. Clin. Med., 9.","DOI":"10.3390\/jcm9082648"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1016\/j.bpg.2014.07.008","article-title":"Non-alcoholic fatty liver disease, obesity and the metabolic syndrome","volume":"28","author":"Dietrich","year":"2014","journal-title":"Best Prsct. Res. Clin. Gastroenterol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1097\/MCG.0000000000000116","article-title":"World Gastroenterology Organisation Global Guidelines: Nonalcoholic fatty liver disease and nonalcoholic steatohepatitis","volume":"48","author":"LaBrecque","year":"2014","journal-title":"J. Clin. Gastroenterol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"15080","DOI":"10.1038\/nrdp.2015.80","article-title":"Nonalcoholic fatty liver disease","volume":"1","author":"Brunt","year":"2015","journal-title":"Nat. Rev. Dis. Prim."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.4254\/wjh.v13.i9.1107","article-title":"Hepatocellular carcinoma in nonalcoholic fatty liver disease: A growing challenge","volume":"13","author":"Mattos","year":"2021","journal-title":"World J. Hepatol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1016\/j.jhep.2019.10.003","article-title":"The gut-liver axis in liver disease: Pathophysiological basis for therapy","volume":"72","author":"Albillos","year":"2020","journal-title":"J. Hepatol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1007\/7651_2021_389","article-title":"Differentiating between Tight Junction-Dependent and Tight Junction-Independent Intestinal Barrier Loss In Vivo","volume":"2367","author":"Abtahi","year":"2021","journal-title":"Methods Mol. Biol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"16795","DOI":"10.3748\/wjg.v20.i45.16795","article-title":"Microbiota and the gut-liver axis: Bacterial translocation, inflammation and infection in cirrhosis","volume":"20","author":"Giannelli","year":"2014","journal-title":"World J. Gastroenterol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1819","DOI":"10.1152\/physrev.00035.2018","article-title":"Metabolomics for Investigating Physiological and Pathophysiological Processes","volume":"99","author":"Wishart","year":"2019","journal-title":"Physiol. Rev."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"7866","DOI":"10.1039\/D0FO01890B","article-title":"Dietary choline, rather than betaine intake, is associated with hepatocellular carcinoma mortality","volume":"11","author":"Liu","year":"2020","journal-title":"Food Funct."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1743","DOI":"10.1016\/j.ajpath.2021.06.010","article-title":"Methionine- and Choline-Deficient Diet\u2013Induced Nonalcoholic Steatohepatitis Is Associated with Increased Intestinal Inflammation","volume":"191","author":"Matthews","year":"2021","journal-title":"Am. J. Pathol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1498","DOI":"10.1111\/jgh.15899","article-title":"The effect of increasing intestinal short-chain fatty acid concentration on gut permeability and liver injury in the context of liver disease: A systematic review","volume":"37","author":"Pohl","year":"2022","journal-title":"J. Gastroenterol. Hepatol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"e00131","DOI":"10.14309\/ctg.0000000000000131","article-title":"Altered Microbiota Diversity and Bile Acid Signaling in Cirrhotic and Noncirrhotic NASH-HCC","volume":"11","author":"Sydor","year":"2020","journal-title":"Clin. Transl. Gastroenterol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Thomas, C.E., Luu, H.N., Wang, R., Xie, G., Adams-Haduch, J., Jin, A., Koh, W.-P., Jia, W., Behari, J., and Yuan, J.-M. (2021). Association between Pre-Diagnostic Serum Bile Acids and Hepatocellular Carcinoma: The Singapore Chinese Health Study. Cancers, 13.","DOI":"10.3390\/cancers13112648"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Won, S.-M., Park, E., Jeong, J.-J., Ganesan, R., Gupta, H., Gebru, Y.A., Sharma, S., Kim, D.-J., and Suk, K.-T. (2021). The Gut Microbiota-Derived Immune Response in Chronic Liver Disease. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22158309"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Stolfi, C., Maresca, C., Monteleone, G., and Laudisi, F. (2022). Implication of Intestinal Barrier Dysfunction in Gut Dysbiosis and Diseases. Biomedicines, 10.","DOI":"10.3390\/biomedicines10020289"},{"key":"ref_20","first-page":"115","article-title":"Gut microbiota and metabolism","volume":"1","author":"Ilhan","year":"2018","journal-title":"Int. J. Med. Biochem."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"De Muynck, K., Vanderborght, B., Van Vlierberghe, H., and Devisscher, L. (2021). The Gut\u2013Liver Axis in Chronic Liver Disease: A Macrophage Perspective. Cells, 10.","DOI":"10.3390\/cells10112959"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2686","DOI":"10.1016\/j.ajpath.2017.08.015","article-title":"Acrolein disrupts tight junction proteins and causes endoplasmic reticulum stress-mediated epithelial cell death leading to intestinal barrier dysfunction and permeability","volume":"187","author":"Chen","year":"2017","journal-title":"Am. J. Pathol."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Vancells Lujan, P., Vi\u00f1as Esmel, E., and Sacanella Meseguer, E. (2021). Overview of non-alcoholic fatty liver disease (NAFLD) and the role of sugary food consumption and other dietary components in its development. Nutrients, 13.","DOI":"10.3390\/nu13051442"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Stromsnes, K., Correas, A.G., Lehmann, J., Gambini, J., and Olaso-Gonzalez, G. (2021). Anti-Inflammatory Properties of Diet: Role in Healthy Aging. Biomedicines, 9.","DOI":"10.3390\/biomedicines9080922"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1038\/s41392-022-00974-4","article-title":"Microbiota in health and diseases","volume":"7","author":"Hou","year":"2022","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"147","DOI":"10.3810\/pgm.2000.02.872","article-title":"Genetic liver disease in adults: Early recognition of the three most common causes","volume":"107","author":"Morrison","year":"2000","journal-title":"Postgrad. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1016\/j.cell.2011.02.013","article-title":"Hallmarks of cancer: The next generation","volume":"144","author":"Hanahan","year":"2011","journal-title":"Cell"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2097","DOI":"10.1007\/s11095-008-9661-9","article-title":"Cancer is a Preventable Disease that Requires Major Lifestyle Changes","volume":"25","author":"Anand","year":"2008","journal-title":"Pharm. Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"7204","DOI":"10.18632\/oncotarget.23208","article-title":"Inflammatory responses and inflammation-associated diseases in organs","volume":"9","author":"Chen","year":"2018","journal-title":"Oncotarget"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1038\/nature01322","article-title":"Inflammation and cancer","volume":"420","author":"Coussens","year":"2002","journal-title":"Nature"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1016\/j.cell.2010.01.025","article-title":"Immunity, inflammation, and cancer","volume":"140","author":"Grivennikov","year":"2010","journal-title":"Cell"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1007\/s13167-019-00194-x","article-title":"Chronic inflammation: Key player and biomarker-set to predict and prevent cancer development and progression based on individualized patient profiles","volume":"10","author":"Qian","year":"2019","journal-title":"EPMA J."},{"key":"ref_33","first-page":"217","article-title":"Chronic inflammation and cancer","volume":"16","author":"Shacter","year":"2002","journal-title":"Oncology"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1016\/S0140-6736(00)04046-0","article-title":"Inflammation and cancer: Back to Virchow?","volume":"357","author":"Balkwill","year":"2001","journal-title":"Lancet"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1126\/science.1232227","article-title":"Neutralizing tumor-promoting chronic inflammation: A magic bullet?","volume":"339","author":"Coussens","year":"2013","journal-title":"Science"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1007\/s12072-020-10113-2","article-title":"Transition rates to cirrhosis and liver cancer by age, gender, disease and treatment status in Asian chronic hepatitis B patients","volume":"15","author":"Liu","year":"2021","journal-title":"Hepatol. Int."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Refolo, M.G., Messa, C., Guerra, V., Carr, B.I., and D\u2019alessandro, R. (2020). Inflammatory Mechanisms of HCC Development. Cancers, 12.","DOI":"10.3390\/cancers12030641"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1038\/nature07205","article-title":"Cancer-related inflammation","volume":"454","author":"Mantovani","year":"2008","journal-title":"Nature"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1055\/s-0039-3399562","article-title":"Neutrophil Extracellular Traps and Liver Disease","volume":"40","author":"Hilscher","year":"2020","journal-title":"Semin. Liver Dis."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1007\/s00428-022-03330-7","article-title":"Neutrophil extracellular traps enriched with IL-1\u03b2 and IL-17A participate in the hepatic inflammatory process of patients with non-alcoholic steatohepatitis","volume":"481","author":"Arelaki","year":"2022","journal-title":"Virchows Arch."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1038\/s41572-020-00240-3","article-title":"Hepatocellular carcinoma","volume":"7","author":"Llovet","year":"2021","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Kotsiliti, E., Leone, V., Schuehle, S., Govaere, O., Li, H., Wolf, M.J., Horvatic, H., Bierwirth, S., Hundertmark, J., and Inverso, D. (J. Hepatol., 2023). Intestinal B cells license metabolic T-cell activation in NASH microbiota\/antigen-independently and contribute to fibrosis by IgA-FcR signalling, J. Hepatol., online ahead of print.","DOI":"10.1016\/j.jhep.2023.04.037"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2410","DOI":"10.1002\/hep.31845","article-title":"Cancer Risk in Patients with Biopsy-Confirmed Nonalcoholic Fatty Liver Disease: A Population-Based Cohort Study","volume":"74","author":"Simon","year":"2021","journal-title":"Hepatology"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1566","DOI":"10.1097\/MEG.0000000000001681","article-title":"The association of nonalcoholic steatohepatitis and hepatocellular carcinoma","volume":"32","author":"Asfari","year":"2020","journal-title":"Eur. J. Gastroenterol. Hepatol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"808","DOI":"10.1002\/hep.31014","article-title":"Effect of Metabolic Traits on the Risk of Cirrhosis and Hepatocellular Cancer in Nonalcoholic Fatty Liver Disease","volume":"71","author":"Kanwal","year":"2020","journal-title":"Hepatology"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1002\/hep.30858","article-title":"Diabetes Is Associated with Increased Risk of Hepatocellular Carcinoma in Patients with Cirrhosis from Nonalcoholic Fatty Liver Disease","volume":"71","author":"Yang","year":"2020","journal-title":"Hepatology"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1016\/j.jhep.2011.09.020","article-title":"Obesity, inflammation, and liver cancer","volume":"56","author":"Sun","year":"2012","journal-title":"J. Hepatol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"456","DOI":"10.4239\/wjd.v6.i3.456","article-title":"Oxidative stress, insulin resistance, dyslipidemia and type 2 diabetes mellitus","volume":"6","author":"Tangvarasittichai","year":"2015","journal-title":"World J. Diabetes"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1736","DOI":"10.1016\/j.clnu.2017.06.027","article-title":"Dietary Inflammatory Index and liver status in subjects with different adiposity levels within the PREDIMED trial","volume":"37","author":"Cantero","year":"2018","journal-title":"Clin. Nutr."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1002\/iid3.391","article-title":"Inflammation initiates a vicious cycle between obesity and nonalcoholic fatty liver disease","volume":"9","author":"Luo","year":"2021","journal-title":"Immun. Inflamm. Dis."},{"key":"ref_51","first-page":"4712","article-title":"Insulin Regulation of Human Hepatic Growth Hormone Receptors: Divergent Effects on Biosynthesis and Surface Translocation1","volume":"85","author":"Leung","year":"2000","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1038\/nrc1387","article-title":"Insulin-like growth factors and neoplasia","volume":"4","author":"Pollak","year":"2004","journal-title":"Nat. Rev. Cancer"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1541","DOI":"10.1007\/s00018-019-03011-w","article-title":"The links between the gut microbiome and non-alcoholic fatty liver disease (NAFLD)","volume":"76","author":"Safari","year":"2019","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1007\/s12029-019-00311-z","article-title":"Microbiome Dysbiosis and Predominant Bacterial Species as Human Cancer Biomarkers","volume":"51","author":"Shirazi","year":"2020","journal-title":"J. Gastrointest. Cancer"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1159\/000508328","article-title":"Gut Microbiota Dysbiosis Drives the Development of Colorectal Cancer","volume":"102","author":"Fan","year":"2021","journal-title":"Digestion"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1554","DOI":"10.21037\/tlcr-20-156","article-title":"Microbiota dysbiosis in lung cancer: Evidence of association and potential mechanisms","volume":"9","author":"Xu","year":"2020","journal-title":"Transl. Lung Cancer Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1016\/j.bbcan.2019.04.001","article-title":"The power of small changes: Comprehensive analyses of microbial dysbiosis in breast cancer","volume":"1871","author":"Parida","year":"2019","journal-title":"Biochim. Biophys. Acta Rev. Cancer"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/j.hbpd.2019.01.002","article-title":"Relationship between intestinal microbial dysbiosis and primary liver cancer","volume":"18","author":"Zhang","year":"2019","journal-title":"Hepatobiliary Pancreat. Dis. Int."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"104479","DOI":"10.1016\/j.micpath.2020.104479","article-title":"Oral microbial community analysis of the patients in the progression of liver cancer","volume":"149","author":"Li","year":"2020","journal-title":"Microb. Pathog."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1014","DOI":"10.1136\/gutjnl-2017-315084","article-title":"Gut microbiome analysis as a tool towards targeted non-invasive biomarkers for early hepatocellular carcinoma","volume":"68","author":"Ren","year":"2019","journal-title":"Gut"},{"key":"ref_61","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_62","doi-asserted-by":"crossref","first-page":"1047570","DOI":"10.3389\/fimmu.2022.1047570","article-title":"Akkermansia muciniphila suppressing nonalcoholic steatohepatitis associated tumorigenesis through CXCR6+ natural killer T cells","volume":"13","author":"Li","year":"2022","journal-title":"Front. Immunol."},{"key":"ref_63","first-page":"116","article-title":"Gut microbiota characterization in Egyptian patients with hepatocellular carcinoma post-chronic hepatitis C virus genotype 4 infection","volume":"11","author":"Montasser","year":"2021","journal-title":"J. Appl. Pharm. Sci."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"4232","DOI":"10.1002\/cam4.3045","article-title":"Liver cirrhosis contributes to the disorder of gut microbiota in patients with hepatocellular carcinoma","volume":"9","author":"Zheng","year":"2020","journal-title":"Cancer Med."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"e00182","DOI":"10.1097\/HC9.0000000000000182","article-title":"A gut bacterial signature in blood and liver tissue characterizes cirrhosis and hepatocellular carcinoma","volume":"7","author":"Effenberger","year":"2023","journal-title":"Hepatol. Commun."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1126\/science.aaa4972","article-title":"Cancer and the microbiota","volume":"348","author":"Garrett","year":"2015","journal-title":"Science"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1038\/s41467-020-20422-7","article-title":"Gut microbiota impact on the peripheral immune response in non-alcoholic fatty liver disease related hepatocellular carcinoma","volume":"12","author":"Behary","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"4973589","DOI":"10.1155\/2021\/4973589","article-title":"Dysbiosis of Gut Microbiota Promotes Hepatocellular Carcinoma Progression by Regulating the Immune Response","volume":"2021","author":"Zhang","year":"2021","journal-title":"J. Immunol. Res."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"e16165","DOI":"10.1200\/JCO.2021.39.15_suppl.e16165","article-title":"Association of gut microbiota and metabolites with tumor response to immune checkpoint inhibitors in patients with unresectable hepatocellular carcinoma","volume":"39","author":"Lee","year":"2021","journal-title":"J. Clin. Oncol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"S484","DOI":"10.1016\/j.annonc.2022.05.110","article-title":"MO5-4 Potential roles of gut microbiome in patients with hepatocellular carcinoma treated with immune checkpoint inhibitors","volume":"33","author":"Su","year":"2022","journal-title":"Ann. Oncol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1111\/liv.15466","article-title":"Association of gut microbiome and primary liver cancer: A two-sample Mendelian randomization and case\u2013control study","volume":"43","author":"Ma","year":"2023","journal-title":"Liver Int."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1016\/j.cmet.2017.09.008","article-title":"Improvement of insulin sensitivity after lean donor feces in metabolic syndrome is driven by baseline intestinal microbiota composition","volume":"26","author":"Kootte","year":"2017","journal-title":"Cell Metab."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1053\/j.gastro.2012.06.031","article-title":"Transfer of Intestinal Microbiota From Lean Donors Increases Insulin Sensitivity in Individuals with Metabolic Syndrome","volume":"143","author":"Vrieze","year":"2012","journal-title":"Gastroenterology"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"e9302","DOI":"10.15252\/emmm.201809302","article-title":"The role of the microbiome in NAFLD and NASH","volume":"11","author":"Kolodziejczyk","year":"2019","journal-title":"EMBO Mol. Med."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"105608","DOI":"10.1016\/j.phrs.2021.105608","article-title":"Liver organoid as a 3D in vitro model for drug validation and toxicity assessment","volume":"169","author":"Brooks","year":"2021","journal-title":"Pharmacol. Res."},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Blidisel, A., Marcovici, I., Coricovac, D., Hut, F., Dehelean, C.A., and Cretu, O.M. (2021). Experimental models of hepatocellular carci-noma\u2014A preclinical perspective. Cancers, 13.","DOI":"10.3390\/cancers13153651"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1111\/liv.14094","article-title":"Experimental models to unravel the molecular pathogenesis, cell of origin and stem cell properties of cholan-giocarcinoma","volume":"39","author":"Vicent","year":"2019","journal-title":"Liver Int."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1363","DOI":"10.1016\/j.celrep.2018.07.001","article-title":"Organoid Models of Human Liver Cancers Derived from Tumor Needle Biopsies","volume":"24","author":"Nuciforo","year":"2018","journal-title":"Cell Rep."},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Maier, C.F., Zhu, L., Nanduri, L.K., K\u00fchn, D., Kochall, S., Thepkaysone, M.-L., William, D., Gr\u00fctzmann, K., Klink, B., and Betge, J. (2021). Patient-derived organoids of cholangiocarcinoma. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22168675"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"2100327","DOI":"10.1002\/mabi.202100327","article-title":"Bioprinting of Human Liver-Derived Epithelial Organoids for Toxicity Studies","volume":"21","author":"Bouwmeester","year":"2021","journal-title":"Macromol. Biosci."},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Gunti, S., Hoke, A.T., Vu, K.P., and London, N.R. (2021). Organoid and spheroid tumor models: Techniques and applications. Cancers, 13.","DOI":"10.3390\/cancers13040874"},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Massa, A., Varamo, C., Vita, F., Tavolari, S., Peraldo-Neia, C., Brandi, G., Rizzo, A., Cavalloni, G., and Aglietta, M. (2020). Evolution of the Experimental Models of Cholangiocarcinoma. Cancers, 12.","DOI":"10.3390\/cancers12082308"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1111\/bcpt.13587","article-title":"3D human liver spheroids for translational pharmacology and toxicology","volume":"130","author":"Lauschke","year":"2022","journal-title":"Basic Clin. Pharmacol. Toxicol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"166","DOI":"10.3389\/fcell.2020.00166","article-title":"Modeling cell communication in cancer with organoids: Making the complex simple","volume":"8","author":"Fiorini","year":"2020","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"De Siervi, S., and Turato, C. (2023). Liver Organoids as an In Vitro Model to Study Primary Liver Cancer. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24054529"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1387","DOI":"10.1038\/s42003-021-02910-8","article-title":"Towards organoid culture without Matrigel","volume":"4","author":"Kozlowski","year":"2021","journal-title":"Commun. Biol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"6","DOI":"10.3389\/fphar.2018.00006","article-title":"Three-Dimensional in Vitro Cell Culture Models in Drug Discovery and Drug Repositioning","volume":"9","author":"Langhans","year":"2018","journal-title":"Front. Pharmacol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"33","DOI":"10.3389\/fmolb.2020.00033","article-title":"Is it time to start transitioning from 2D to 3D cell culture?","volume":"7","author":"Jensen","year":"2020","journal-title":"Front. Mol. Biosci."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.addr.2014.06.005","article-title":"Matrigel: From discovery and ECM mimicry to assays and models for cancer research","volume":"79","author":"Benton","year":"2014","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1038\/s41698-020-0121-2","article-title":"3D bioprinting for reconstituting the cancer microenvironment","volume":"4","author":"Datta","year":"2020","journal-title":"npj Precis. Oncol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"101015","DOI":"10.1016\/j.tranon.2021.101015","article-title":"3D Bioprinted cancer models: Revolutionizing personalized cancer therapy","volume":"14","author":"Augustine","year":"2021","journal-title":"Transl. Oncol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1007\/s13206-020-4201-8","article-title":"Recent Advances in 3D Bioprinted Tumor Microenvironment","volume":"14","author":"Bae","year":"2020","journal-title":"BioChip J."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1038\/nature11826","article-title":"In vitro expansion of single Lgr5+ liver stem cells induced by Wnt-driven regeneration","volume":"494","author":"Huch","year":"2013","journal-title":"Nature"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1186\/s13578-022-00890-8","article-title":"Liver organoids: An in vitro 3D model for liver cancer study","volume":"12","author":"Dong","year":"2022","journal-title":"Cell Biosci."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1007\/s13770-021-00357-w","article-title":"Liver Organoids: Formation Strategies and Biomedical Applications","volume":"18","author":"Zhu","year":"2021","journal-title":"Tissue Eng. Regen. Med."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1016\/j.cell.2014.11.050","article-title":"Long-Term Culture of Genome-Stable Bipotent Stem Cells from Adult Human Liver","volume":"160","author":"Huch","year":"2015","journal-title":"Cell"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"188350","DOI":"10.1016\/j.bbcan.2020.188350","article-title":"Application of organoids in translational research of human diseases with a particular focus on gastrointestinal cancers","volume":"1873","author":"Nguyen","year":"2020","journal-title":"Biochim. Biophys. Acta (BBA)-Rev. Cancer"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"2228","DOI":"10.1136\/gutjnl-2019-319256","article-title":"Liver organoids: From basic research to therapeutic applications","volume":"68","author":"Prior","year":"2019","journal-title":"Gut"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1186\/s13568-021-01314-5","article-title":"Anti-tumor effect of polysaccharide from Pleurotus ostreatus on H22 mouse Hepatoma ascites in-vivo and hepatocellular carcinoma in-vitro model","volume":"11","author":"Khinsar","year":"2021","journal-title":"AMB Express"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"S63","DOI":"10.1016\/S1590-8658(13)60173-5","article-title":"Bifidobacterium longum up-regulates PPAR-gamma and PPAR-alpha levels in HepG2 hepatic cancer cell line","volume":"45","author":"Cianflone","year":"2013","journal-title":"Dig. Liver Dis."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1038\/nrgastro.2013.182","article-title":"The genetics of NAFLD","volume":"10","author":"Anstee","year":"2013","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"4079","DOI":"10.3748\/wjg.v22.i16.4079","article-title":"Nonalcoholic fatty liver disease as a multi-systemic disease","volume":"22","author":"Fotbolcu","year":"2016","journal-title":"World J. Gastroenterol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1517\/13543784.14.1.29","article-title":"Recent advances in the treatment of non-alcoholic fatty liver disease","volume":"14","author":"Mendes","year":"2005","journal-title":"Expert Opin. Investig. 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