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Hepatocyte-derived fibrinogen-like protein 1 (FGL-1) stimulates hepatocyte proliferation and also serves as a ligand for the inhibitory receptor LAG-3. This study characterizes FGL-1 and LAG-3 in AH patients and links them to disease state and 3-year clinical course. Patients showed increased hepatic FGL-1 mRNA, reduced hepatic LAG-3 mRNA, unchanged circulating sLAG-3, and diagnostic immune profiles associated with severity and mortality.",{"@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/the-fgl-1lag-3-axis-is-associated-with-disease-course-in-alcohol-associated-hepatitis-a-preliminary-report/405445/",{"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/the-fgl-1lag-3-axis-is-associated-with-disease-course-in-alcohol-associated-hepatitis-a-preliminary-report/405445.png","ImageObject",300,407,{"name":92,"@type":93},"Jiven","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-02","2026-09-28",true,{"@type":102,"interactionType":103,"userInteractionCount":52},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What is the main focus of this preliminary report on alcohol-associated hepatitis?","Question",{"text":112,"@type":113},"The report investigates how the FGL-1/LAG-3 axis relates to disease state and the clinical course in patients with alcohol-associated hepatitis.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How were FGL-1 and LAG-3 measured in alcohol-associated hepatitis patients?",{"text":117,"@type":113},"Hepatic gene expression was assessed by RNA sequencing, plasma FGL-1 and soluble LAG-3 were measured by ELISA, and LAG-3+CD8+ T cells were quantified using flow cytometry.",{"name":119,"@type":110,"acceptedAnswer":120},"What diagnostic associations were found with disease severity and mortality?",{"text":121,"@type":113},"Patients with the lowest plasma FGL-1 and the lowest frequency of LAG-3+CD8+ T cells at diagnosis had the highest disease severity and mortality.","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},405445,1791101836,{"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":52,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":44,"language":139,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":140,"faqs":141,"seo_title":142,"seo_description":67,"update_tm":143,"read_time":144,"preview_page_count":4},1099513958607,"https://ap-avatar.wpscdn.com/avatar/100002390cf8733938c?x-image-process=image/resize,m_fixed,w_180,h_180&k=1778829742770036399","Original Article JOURNAL OF CLINICAL AND EXPERIMENTAL HEPATOLOGY  \nThe FGL-1/LAG-3 Axis is Associated With Disease Course in Alcohol-associated Hepatitis: A Preliminary Report  \nLasse Pedersen * , Lotte L. Eriksen * , y , Frederik H. Brix * , Hendrik Vilstrup * , y , Bent Deleuran z , x ,  \nThomas D. Sandahl * , Sidsel Støy *  \n*Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark, y Department of Clinical Medicine, Aarhus University, Aarhus, Denmark, z Department of Rheumatology, Biomedicine, Aarhus University Hospital, Aarhus, Denmark and x Department of  \nBiomedicine, Aarhus University, Aarhus, Denmark  \nBackground: Alcohol-associated hepatitis (AH) has a short-term mortality rate of up to 40% primarily related to impaired hepatocyte regeneration and uncontrolled liver inflammation. The acute phase protein fibrinogen-like protein 1 (FGL-1) produced by hepatocytes stimulates hepatocyte proliferation by autocrine signaling. FGL-1 also is a ligand for the inhibitory T cell receptor lymphocyte activation gene 3 (LAG-3). In these ways, FGL-1 and LAG-3 have beneficial interactions that could be interrupted in AH. Aims: We aimed to characterize FGL-1 and LAG-3 in patients with AH and describe their relationship with the disease state and course. Methods: Thirty-two patients with AH were included at diagnosis and followed up for 3 years. We measured the hepatic gene expression ofFGL-1 and LAG-3 using RNA sequencing, plasma FGL-1 and soluble (s)LAG-3 using ELISA, and LAG-3+CD8+ T cells using flow cytometry. Healthy persons (HC) and patients with stable alcohol-associated cirrhosis served as controls. Results: At diagnosis ofAH, liver FGL-1 mRNA was increased when compared to HC, whereas plasma FGL-1 was unchanged. In contrast, liver LAG-3 mRNA was reduced in AH. Plasma sLAG- 3 levels and the frequency of LAG-3+CD8+ T cells were as in HC. However, those patients who had the lowest plasma FGL-1 and the lowest frequency of LAG-3+CD8+ T cells at diagnosis had the highest disease severity and mortality. Conclusions: Our data suggest that an impaired FGL-1/LAG-3 axis may be involved in the pathogenesis and course ofAH. (J CLIN EXP HEPATOL 2025;15:102424)  \nAlcohol-associated hepatitis  \nthreatening disease with a rate of up to 40% .1 The  \n(AH) is a lifesix-month mortality incidence of AH is  \nincreasing; however, no pharmacological treatment has shown convincing effects on clinical outcomes. Therefore, the key treatment remains careful supportive care and moderate hyperalimentation.2,3 The disease mechanisms are only partially understood. Acute alcohol-induced liver  \nKeywords: fibrinogen-like protein 1, lymphocyte activation gene 3, alcoholassociated liver disease, acute phase protein, checkpoint inhibitor Received: 27.11.2023; Accepted: 5.10.2024; Available online 10 October 2024 Address for correspondence: Sidsel Hyldgaard Støy, Department of Hepatology and Gastroenterology, Aarhus University Hospital, Palle Juul Jensens Boulevard 99, DK-8200 Aarhus N, Denmark. Tel.: +45 7845 3813.  \nE-mail: [sidsel.stoy@clin.au.dk](sidsel.stoy@clin.au.dk)  \nAbbreviations: AH: Alcoholic hepatitis; ALT: Alanine aminotransferase; ELISA: Enzyme-linked immunosorbent assay; FGL-1: Fibrinogen-like protein 1; GAHS: Glasgow Alcoholic Hepatitis Score; HC: Healthy Controls; HE: Hepatic encephalopathy; INR: international normalized ratio; LAG-3: Lymphocyte activation gene 3; MELD: Model of end-stage liver disease; MHCII: Major histocompatibility complex class II; NK cells: natural killer cells; PBMC: Peripheral Blood Mononuclear Cells; PD1: Programmed death receptor-1; SD: standard deviation; sFGL-1: soluble FGL-1; sLAG- 3: soluble LAG-3; TIM-3: T cell Immunoglobulin Mucin-3; Treg: Regulatory T cells  \n[https://doi.org/10.1016/j.jceh.2024.102424](https://doi.org/10.1016/j.jceh.2024.102424)  \ndamage results in uncontrolled inflammation of the liver, which involves both innate and adaptive immune cells, and this further exacerbates ","cbCaifqwe4H6pJE5","https://ap.wps.com/l/cbCaifqwe4H6pJE5","pdf",1001386,"English","# Background\n# Aims\n# Methods\n# Results\n# Conclusions","[{\"question\":\"What is the main focus of this preliminary report on alcohol-associated hepatitis?\",\"answer\":\"The report investigates how the FGL-1/LAG-3 axis relates to disease state and the clinical course in patients with alcohol-associated hepatitis.\"},{\"question\":\"How were FGL-1 and LAG-3 measured in alcohol-associated hepatitis patients?\",\"answer\":\"Hepatic gene expression was assessed by RNA sequencing, plasma FGL-1 and soluble LAG-3 were measured by ELISA, and LAG-3+CD8+ T cells were quantified using flow cytometry.\"},{\"question\":\"What diagnostic associations were found with disease severity and mortality?\",\"answer\":\"Patients with the lowest plasma FGL-1 and the lowest frequency of LAG-3+CD8+ T cells at diagnosis had the highest disease severity and mortality.\"}]","The FGL-1/LAG-3 Axis is Associated With Disease Course in Alcohol-associated Hepatitis: A Preliminary Report | PDF",1790560130,23]