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Glycolysis converts glucose into pyruvate and supplies energy and intermediates, yet abnormal glycolytic flux during CLD progression accelerates disease development. Aerobic glycolysis drives liver cancer oncogenic programs and also contributes non-neoplastic roles in immune activation and inflammatory disorders. Key mediators like HIF-1α and PKM2 increase during steatohepatitis and liver fibrosis; pharmacologic PKM2 inhibition or ablation reduces hepatic inflammation and CLD progression. This review emphasizes glycolytic and non-glycolytic functions of PKM2 to support translation of glycolysis-targeted therapies.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/glycolysis-in-chronic-liver-diseases-mechanistic-insights-and-therapeutic-opportunities/383927/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/glycolysis-in-chronic-liver-diseases-mechanistic-insights-and-therapeutic-opportunities/383927.png","ImageObject",300,407,{"name":92,"@type":93},"Sarah ","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-29","2026-09-24",true,{"@type":102,"interactionType":103,"userInteractionCount":34},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What role does abnormal glycolytic flux play in chronic liver diseases?","Question",{"text":112,"@type":113},"Abnormal glycolytic flux during CLD development accelerates disease progression by altering the metabolic program of liver cells and immune-related inflammation.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"Why is aerobic glycolysis important in liver cancer?",{"text":117,"@type":113},"Aerobic glycolysis is a hallmark of liver cancer and supports oncogenic functions such as proliferation, invasion, metastasis, angiogenesis, immune escape, and drug resistance.",{"name":119,"@type":110,"acceptedAnswer":120},"How does PKM2 influence CLD progression and inflammation?",{"text":121,"@type":113},"Key mediators including HIF-1α and PKM2 are upregulated during steatohepatitis and liver fibrosis; pharmacological inhibition or ablation of PKM2 attenuates hepatic inflammation and CLD progression.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},383927,1790650667,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":34,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":145},962085320529,"https://ap-avatar.wpscdn.com/davatar_9964176cb1d06d4a9deccf72a44ae3dc","cells  \nReview  \nGlycolysis in Chronic Liver Diseases: Mechanistic Insights and Therapeutic Opportunities  \nHengdong Qu, Junli Liu, Di Zhang, Ruoyan Xie, Lijuan Wang and Jian Hong *  \nDepartment of Pathophysiology, School of Medicine, Jinan University, Guangzhou 510632, China;  \n[quhengdong@stu2021.jnu.edu.cn](quhengdong@stu2021.jnu.edu.cn) (H.Q.)  \n* [Correspondence: hongjian7@jnu.edu.cn](Correspondence: hongjian7@jnu.edu.cn)  \nCitation: Qu, H.; Liu, J.; Zhang, D.; Xie, R.; Wang, L.; Hong, J. Glycolysis in Chronic Liver Diseases:  \nMechanistic Insights and Therapeutic Opportunities. Cells 2023, 12, 1930 . [https://doi.org/10.3390/](https://doi.org/10.3390/)[ ](https://doi.org/10.3390/)cells12151930  \nAcademic Editor: Kuo Du  \nReceived: 1 June 2023  \nRevised: 17 July 2023  \nAccepted: 21 July 2023  \nPublished: 26 July 2023  \nCopyright: © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) .  \nAbstract: Chronic liver diseases (CLDs) cover a spectrum of liver diseases, ranging from nonalcoholic fatty liver disease to liver cancer, representing a growing epidemic worldwide with high unmet medical needs. Glycolysis is a conservative and rigorous process that converts glucose into pyruvate and sustains cells with the energy and intermediate products required for diverse biological activities. However, abnormalities in glycolytic flux during CLD development accelerate the disease progression. Aerobic glycolysis is a hallmark of liver cancer and is responsible for a broad range of oncogenic functions including proliferation, invasion, metastasis, angiogenesis, immune escape, and drug resistance. Recently, the non-neoplastic role of aerobic glycolysis in immune activation and inflammatory disorders, especially CLD, has attracted increasing attention. Several key mediators of aerobic glycolysis, including HIF-1􀀋 and pyruvate kinase M2 (PKM2), are upregulated during steatohepatitis and liver fibrosis. The pharmacological inhibition or ablation of PKM2 effectively attenuates hepatic inflammation and CLD progression. In this review, we particularly focused on the glycolytic and non-glycolytic roles of PKM2 in the progression of CLD, highlighting the translational potential of a glycolysis-centric therapeutic approach in combating CLD.  \nKeywords: chronic liver disease; glycolysis; HIF-1􀀋; metabolic reprogramming; immune activation; PKM2; therapeutic target  \n1. Introduction  \nChronic liver disease (CLD) encompasses a broad spectrum of liver diseases, ranging from viral hepatitis, alcoholic liver disease (ALD), and nonalcoholic fatty liver disease (NAFLD) to end-stage hepatic conditions including nonalcoholic steatohepatitis (NASH), liver fibrosis, hepatocellular carcinoma (HCC), and cholangiocarcinoma (CCA) [1] . Due to the growing prevalence of metabolic syndromes, including obesity and hyperlipidemia, NAFLD has become the most prevalent CLD, affecting more than 25% of the adult population worldwide [2] . Currently, there are no approved therapeutics for certain CLDs, such as NASH and liver fibrosis, which is partly limited by the lack of understanding of their complicated pathogenesis and druggable targets [3,4] .  \nLiver is the most vital organ for glucose homeostasis, where it generates glucose during fasting and reserves glucose postprandially [5,6] . During the progression of CLD, hepatocyte injury and chronic low-grade inflammation lead to metabolic dysfunction, which causes an excessive accumulation of lipids and aberrant activation of metabolic pathways in the liver, including enhanced aerobic glycolysis [7,8] . On one hand, aerobic glycolysis promotes the pro-inflammatory activation of immune cells, which perpetuates hepatic inflammation and liver injur","cbCairrrF0gqqQxE","https://ap.wps.com/l/cbCairrrF0gqqQxE","pdf",1941509,14,"English","# Introduction\n## Scope of CLD and metabolic drivers\n# Glycolytic Mediators and PK Isoforms\n## Pyruvate kinase as a glycolysis rate-limiting enzyme\n## PKM2’s role in aerobic glycolysis and transcriptional regulation","[{\"question\":\"What role does abnormal glycolytic flux play in chronic liver diseases?\",\"answer\":\"Abnormal glycolytic flux during CLD development accelerates disease progression by altering the metabolic program of liver cells and immune-related inflammation.\"},{\"question\":\"Why is aerobic glycolysis important in liver cancer?\",\"answer\":\"Aerobic glycolysis is a hallmark of liver cancer and supports oncogenic functions such as proliferation, invasion, metastasis, angiogenesis, immune escape, and drug resistance.\"},{\"question\":\"How does PKM2 influence CLD progression and inflammation?\",\"answer\":\"Key mediators including HIF-1α and PKM2 are upregulated during steatohepatitis and liver fibrosis; pharmacological inhibition or ablation of PKM2 attenuates hepatic inflammation and CLD progression.\"}]","Glycolysis in Chronic Liver Diseases: Mechanistic Insights and Therapeutic Opportunities | PDF",1790260316,35]