Hepatology Communications最新文献

{"title":"The mechanistic insights behind the anticancer effects of statins in liver cancer.","authors":"Yiling Chen, Carmen Chak-Lui Wong","doi":"10.1097/HC9.0000000000000519","DOIUrl":"10.1097/HC9.0000000000000519","url":null,"abstract":"","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"8 9","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11371310/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142119675","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-term impact of scheduled regular endoscopic interventions for patients with primary sclerosing cholangitis.","authors":"Burcin Özdirik, Wilfried Veltzke-Schlieker, Jule Marie Nicklaus, Hilmar Berger, Daniel Schmidt, Silke Leonhardt, Volker Penndorf, Andreas Adler, Tobias Müller, Alexander Wree, Frank Tacke, Michael Sigal","doi":"10.1097/HC9.0000000000000494","DOIUrl":"10.1097/HC9.0000000000000494","url":null,"abstract":"<p><strong>Background: </strong>Primary sclerosing cholangitis (PSC) is associated with biliary obstructions that can require endoscopic retrograde cholangiopancreatography (ERCP). While the beneficial effects of ERCP are well documented, follow-up interventional strategies are less defined, and their long-term impact is debated.</p><p><strong>Methods: </strong>We evaluated the outcome of a scheduled program of ERCP-guided interventions that have been developed and implemented at our tertiary liver center for more than 20 years. Within our center, follow-up ERCPs were performed at regular intervals to treat previously detected morphological stenosis independent of clinical symptoms. We calculated the transplant-free survival (TFS) of patients who were enrolled in the scheduled ERCP program and compared it to patients who received follow-up ERCPs only on clinical demand. Moreover, we documented the occurrence of hepatic decompensation, recurrent cholangitis episodes, hepatobiliary malignancies, and endoscopy-related adverse events.</p><p><strong>Results: </strong>In our retrospective study, we included 201 patients with PSC who all received an ERCP. In all, 133 patients received scheduled follow-up ERCPs and 68 received follow-up ERCPs only on demand. The rates of TFS since initial diagnosis (median TFS: 17 vs. 27 y; P = 0.020) and initial presentation (median TFS: 16 vs. 11 y; P = 0.002) were higher in patients receiving scheduled versus on-demand ERCP. Subgroup analysis revealed that progression in cholangiographic findings between the first and second ERCP was associated with a poorer outcome compared to patients without progression (17 y vs. undefined; P = 0.021).</p><p><strong>Conclusion: </strong>In conclusion, we report the outcome data of a scheduled follow-up ERCP program for patients with PSC in an experienced high-volume endoscopy center. Our data suggest the initiation of multicenter randomized controlled prospective trials to explore the full potential of regular endoscopic follow-up treatment as a strategy to prevent disease progression in patients with PSC.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"8 9","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11371311/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142119673","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fatty acid synthesis is indispensable for Kupffer cells to eliminate bacteria in ALD progression.","authors":"Liuyu Xie, Beng Wu, Yuanyuan Fan, Ye Tao, Xiaoyong Jiang, Qing Li, Huaiping Zhu, Hua Wang, Chaojie Hu","doi":"10.1097/HC9.0000000000000522","DOIUrl":"10.1097/HC9.0000000000000522","url":null,"abstract":"<p><strong>Background: </strong>Dysregulated fatty acid metabolism is closely linked to the development of alcohol-associated liver disease (ALD). KCs, which are resident macrophages in the liver, play a critical role in ALD pathogenesis. However, the effect of alcohol on fatty acid metabolism in KCs remains poorly understood. The current study aims to investigate fatty acid metabolism in KCs and its potential effect on ALD development.</p><p><strong>Methods: </strong>Wild-type C57BL/6 mice were fed a Lieber-DeCarli ethanol liquid diet for 3 days. Then, the liver injury and levels of intrahepatic bacteria were assessed. Next, we investigated the effects and underlying mechanisms of ethanol exposure on fatty acid metabolism and the phagocytosis of KCs, both in vivo and in vitro. Finally, we generated KCs-specific Fasn knockout and overexpression mice to evaluate the impact of FASN on the phagocytosis of KCs and ethanol-induced liver injury.</p><p><strong>Results: </strong>Using Bodipy493/503 to stain intracellular neutral lipids, we found significantly reduced lipid levels in KCs from mice fed an alcohol-containing diet for 3 days and in RAW264.7 macrophages exposed to ethanol. Mechanistically, alcohol exposure suppressed sterol regulatory element-binding protein 1 transcriptional activity, thereby inhibiting fatty acid synthase (FASN)-mediated de novo lipogenesis in macrophages both in vitro and in vivo. We show that genetic ablation and pharmacologic inhibition of FASN significantly impaired KC's ability to take up and eliminate bacteria. Conversely, KCs-specific Fasn overexpression reverses the impairment of macrophage phagocytosis caused by alcohol exposure. We also revealed that KCs-specific Fasn knockout augmented KCs apoptosis and exacerbated liver injury in mice fed an alcohol-containing diet for 3 days.</p><p><strong>Conclusions: </strong>Our findings indicate the crucial role of de novo lipogenesis in maintaining effective KCs phagocytosis and suggest a therapeutic target for ALD based on fatty acid synthesis in KCs.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"8 9","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11357694/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142055417","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex- and age-associated factors drive the pathophysiology of MASLD.","authors":"Ajay K Yadav, Justin J MacNeill, Aleksei Krylov, Nadia Ashrafi, Romana Ashrafi Mimi, Romil Saxena, Sheng Liu, Stewart F Graham, Jun Wan, Núria Morral","doi":"10.1097/HC9.0000000000000523","DOIUrl":"10.1097/HC9.0000000000000523","url":null,"abstract":"<p><strong>Background: </strong>Metabolic dysfunction-associated steatotic liver disease (MASLD) is strongly associated with obesity. Sex and age affect MASLD prevalence and pathophysiology. The use of animal models fed Western-style diets is vital for investigating the molecular mechanisms contributing to metabolic dysregulation and for facilitating novel drug target identification. However, the sex-associated and age-associated mechanisms underlying the pathophysiology remain poorly understood. This knowledge gap limits the development of personalized sex-specific and age-specific drug treatments.</p><p><strong>Methods: </strong>Young (7 wk) and aged (52 wk) male and female mice were fed a high-fat diet (HFD) or low-fat diet. Liver metabolome (>600 molecules) and transcriptome profiles were analyzed.</p><p><strong>Results: </strong>Male and female mice fed an HFD developed obesity, glucose intolerance, and hepatic steatosis. However, fasting blood glucose, insulin, and serum alanine aminotransferase levels were higher in males fed an HFD, indicating a more severe metabolic disease. In addition, males showed significant increases in liver diacylglycerides and glycosylceramides (known mediators of insulin resistance and fibrosis), and more changes in the transcriptome: extracellular matrix organization and proinflammatory genes were elevated only in males. In contrast, no major increase in damaging lipid classes was observed in females fed an HFD. However, aging affected the liver to a greater extent in females. Acylcarnitine levels were significantly reduced, suggestive of changes in fatty acid oxidation, and broad changes in the transcriptome were observed, including reduced oxidative stress response gene expression and alterations in lipid partitioning genes.</p><p><strong>Conclusions: </strong>Here, we show distinct responses to an HFD between males and females. Our study underscores the need for using both sexes in drug target identification studies, and characterizing the molecular mechanisms contributing to the MASLD pathophysiology in aging animals.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"8 9","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11357696/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142055320","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic variants associated with immune-mediated liver injury from checkpoint inhibitors.","authors":"Robert J Fontana, Yi-Ju Li, Vincent Chen, David Kleiner, Andrew Stolz, Joe Odin, Raj Vuppalanchi, Jiezhun Gu, Lily Dara, Huiman Barnhart","doi":"10.1097/HC9.0000000000000518","DOIUrl":"10.1097/HC9.0000000000000518","url":null,"abstract":"<p><strong>Background: </strong>The clinical features, liver histology, and genetic variants in 57 patients with moderate to severe immune-mediated liver injury from checkpoint inhibitors (ILICI) are presented.</p><p><strong>Methods: </strong>Between 2010 and 2022, 57 high-causality ILICI cases were enrolled in the Drug-Induced Liver Injury Network. HLA and selected candidate gene variants were tested for association with ILICI risk compared to the general population and other DILI controls.</p><p><strong>Results: </strong>The 57 high-causality cases were attributed to pembrolizumab (16), ipilimumab (15), ipilimumab and nivolumab (13), and other immune checkpoint inhibitors (13) and occurred at a median of 72 days after the first infusion. Median age was 57.8 years, 66% male, and 89% were non-Hispanic Whites. At DILI onset, 53% had hepatocellular, 35% mixed, and 15% cholestatic, with younger patients more likely to have hepatocellular injury. The incidence of ANA, smooth muscle antibody, and elevated IgG levels was low (17%, 23%, and 0%), but corticosteroids were given to 86%. Microgranulomas and hepatic steatosis were seen in 54% and 46% of the 26 liver biopsies, respectively. The HLA alleles associated with autoimmune hepatitis were not over-represented, but 2 host immune response genes (EDIL3 and SAMA5A) and 3 other genes (GABRP, SMAD3, and SLCO1B1) were associated with ILICI (OR: 2.08-2.4, p<0.01).</p><p><strong>Conclusions: </strong>ILICI typically arises within 12 weeks of initiating immunotherapy and is self-limited in most cases. Genetic variants involved in host T-cell regulation and drug disposition were identified, implicating these pathways in the pathogenesis of ILICI. If validated, these findings could lead to improved diagnostic instruments and possible treatments for ILICI.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"8 9","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11357698/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142055418","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Population screening for cirrhosis.","authors":"Maja Thiele, Elisa Pose, Adrià Juanola, Jessica Mellinger, Pere Ginès","doi":"10.1097/HC9.0000000000000512","DOIUrl":"10.1097/HC9.0000000000000512","url":null,"abstract":"<p><p>In response to the growing health crisis of liver-related morbidity and mortality, screening for liver cirrhosis has emerged as a promising strategy for early detection and timely intervention. By identifying individuals with severe fibrosis or compensated cirrhosis, screening holds the promise of enhancing treatment outcomes, delaying disease progression, and ultimately improving the quality of life of affected individuals. Clinical practice guidelines from international scientific societies currently recommend targeted screening strategies, investigating high-risk populations with known risk factors of liver disease. While there is good evidence that screening increases case finding in the population, and a growing number of studies indicate that screening may motivate beneficial lifestyle changes in patients with steatotic liver disease, there are major gaps in knowledge in need of clarification before screening programs of cirrhosis are implemented. Foremost, randomized trials are needed to ensure that screening leads to improved liver-related morbidity and mortality. If not, screening for cirrhosis could be unethical due to overdiagnosis, overtreatment, increased health care costs, negative psychological consequences of screening, and futile invasive investigations. Moreover, the tests used for screening need to be optimized toward lower false positive rates than the currently used FIB-4 while retaining few false negatives. Finally, barriers to adherence to screening and implementation of screening programs need to be elucidated. This review provides a comprehensive overview of the current landscape of screening strategies for liver cirrhosis and the promises and pitfalls of current methods for early cirrhosis detection.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"8 9","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11357699/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142055319","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparison of blood-based liver fibrosis scores in the Mount Sinai Health System, MASLD Registry, and NHANES 2017-2020 study.","authors":"Robert Chen, Ben Omega Petrazzini, Girish Nadkarni, Ghislain Rocheleau, Meena B Bansal, Ron Do","doi":"10.1097/HC9.0000000000000515","DOIUrl":"10.1097/HC9.0000000000000515","url":null,"abstract":"<p><strong>Background: </strong>Liver fibrosis is a critical public health concern, necessitating early detection to prevent progression. This study evaluates the recently developed LiverRisk score and steatosis-associated Fibrosis Estimator (SAFE) score against established indices for prognostication and/or fibrosis prediction in 4diverse cohorts, including participants with metabolic dysfunction-associated steatotic liver disease (MASLD).</p><p><strong>Methods: </strong>We used data from the Mount Sinai Data Warehouse (32,828 participants without liver disease diagnoses), the Mount Sinai MASLD/MASH Longitudinal Registry (422 participants with MASLD), and National Health and Nutrition Examination Survey 2017-2020 (4133 participants representing the general population) to compare LiverRisk score, FIB-4 index, APRI, and SAFE score. Analyses included Cox proportional hazards regressions, Kaplan-Meier estimates, and classification metrics to evaluate performance in prognostication and fibrosis prediction.</p><p><strong>Results: </strong>In Mount Sinai Data Warehouse, LiverRisk score was significantly associated with future liver-related outcomes but did not significantly outperform FIB-4 or APRI for predicting any of the outcomes. In the general population, LiverRisk score and SAFE score outperformed FIB-4 and APRI in identifying fibrosis, but LiverRisk score underperformed among participants who were non-White or had type 2 diabetes. Among participants with MASLD, SAFE score outperformed FIB-4 and APRI in 1 of 2 cohorts, but there were generally few significant performance differences between all 4 scores.</p><p><strong>Conclusions: </strong>LiverRisk score does not consistently outperform existing predictors in diverse populations, and further validation is needed before adoption in settings with significant differences from the original derivation cohorts. It remains necessary to replicate the ability of these scores to predict liver-specific mortality, as well as to develop diagnostic tools for liver fibrosis that are accessible and substantially better than current scores, especially among patients with MASLD and other chronic liver conditions.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"8 9","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11357697/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142055416","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Erratum: Binge drinking at time of bariatric surgery is associated with liver disease, suicides, and increases long-term mortality.","authors":"","doi":"10.1097/HC9.0000000000000521","DOIUrl":"10.1097/HC9.0000000000000521","url":null,"abstract":"","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"8 9","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11340910/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142017276","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Age added to MELD or ACLF predicts survival in patients with alcohol-associated hepatitis declined for liver transplantation.","authors":"Stephanie M Rutledge, Rohit Nathani, Brooke E Wyatt, Erin Eschbach, Parth Trivedi, Stanley Kerznerman, Lily Chu, Thomas D Schiano, Leona Kim-Schluger, Sander Florman, Gene Y Im","doi":"10.1097/HC9.0000000000000514","DOIUrl":"10.1097/HC9.0000000000000514","url":null,"abstract":"<p><strong>Background: </strong>Severe alcohol-associated hepatitis (AH) that is nonresponsive to corticosteroids is associated with high mortality, particularly with concomitant acute-on-chronic liver failure (ACLF). Most patients will not be candidates for liver transplantation (LT) and their outcomes are largely unknown. Our aim was to determine the outcomes of these declined candidates and to derive practical prediction models for transplant-free survival applicable at the time of the waitlist decision.</p><p><strong>Methods: </strong>We analyzed a database of patients with severe AH who were hospitalized at a LT center from January 2012 to July 2021, using the National Death Index for those lacking follow-up. Clinical variables were analyzed based on the endpoints of mortality at 30, 60, 90, and 180 days. Logistic and Cox regression analyses were used for model derivation.</p><p><strong>Results: </strong>Over 9.5 years, 206 patients with severe AH were declined for LT, mostly for unfavorable psychosocial profiles, with a mean MELD of 33 (±8), and 61% with ACLF. Over a median follow-up of 521 (17.5-1368) days, 58% (119/206) died at a median of 21 (9-124) days. Of 32 variables, only age added prognostic value to MELD and ACLF grade. CLIF-C ACLF score and 2 new models, MELD-Age and ACLF-Age, had similar predictability (AUROC: 0.73, 0.73, 0.72, respectively), outperforming Lille and Maddrey's (AUROC: 0.63, 0.62). In internal cross-validation, the average AUROC was 0.74. ACLF grade ≥2, MELD score >35, and age >45 years were useful cutoffs for predicting increased 90-day mortality from waitlist decision. Only two patients initially declined for LT for AH subsequently underwent LT (1%).</p><p><strong>Conclusions: </strong>Patients with severe AH declined for LT have high short-term mortality and rare rates of subsequent LT. Age added to MELD or ACLF grade enhances survival prediction at the time of waitlist decision in patients with severe AH declined for LT.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"8 9","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11340926/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142017275","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GATA4 downregulation enhances CCL20-mediated immunosuppression in hepatocellular carcinoma.","authors":"N Jannah M Nasir, Samuel Chuah, Timothy Shuen, Aldo Prawira, Rebecca Ba, Mei Chee Lim, Joelle Chua, Phuong H D Nguyen, Chun J Lim, Martin Wasser, Sharifah N Hazirah, Tony K H Lim, Wei Qiang Leow, Tracy Jiezhen Loh, Wei Keat Wan, Yin Huei Pang, Gwyneth Soon, Peng Chung Cheow, Juinn Huar Kam, Shridhar Iyer, Alfred Kow, Yock Young Dan, Glenn K Bonney, Alexander Chung, Brian K P Goh, Pierce K H Chow, Salvatore Albani, Weiwei Zhai, John F Ouyang, Han Chong Toh, Valerie Chew","doi":"10.1097/HC9.0000000000000508","DOIUrl":"10.1097/HC9.0000000000000508","url":null,"abstract":"<p><strong>Background: </strong>Hepatocellular carcinoma (HCC) is a deadly cancer with a high global mortality rate, and the downregulation of GATA binding protein 4 (GATA4) has been implicated in HCC progression. In this study, we investigated the role of GATA4 in shaping the immune landscape of HCC.</p><p><strong>Methods: </strong>HCC tumor samples were classified into \"low\" or \"normal/high\" based on GATA4 RNA expression relative to adjacent non-tumor liver tissues. The immune landscapes of GATA4-low and GATA4-normal/high tumors were analyzed using cytometry by time-of-flight, bulk/spatial transcriptomic analyses and validated by multiplex immunofluorescence.</p><p><strong>Results: </strong>GATA4-low tumors displayed enrichment in exhausted programmed cell death protein 1+ T cells, immunosuppressive regulatory T cells, myeloid-derived suppressor cells, and macrophages, highlighting the impact of GATA4 downregulation on immunosuppression. Spatial and bulk transcriptomic analyses revealed a negative correlation between GATA4 and C-C Motif Chemokine Ligand 20 (CCL20) expression in HCC. Overexpressing GATA4 confirmed CCL20 as a downstream target, contributing to an immunosuppressive tumor microenvironment, as evidenced by increased regulatory T cells and myeloid-derived suppressor cells in CCL20-high tumors. Lastly, the reduced expression of GATA4 and higher expression of CCL20 were associated with poorer overall survival in patients with HCC, implicating their roles in tumor progression.</p><p><strong>Conclusions: </strong>Our study reveals that GATA4 downregulation contributes to an immunosuppressive microenvironment, driven by CCL20-mediated enrichment of regulatory T cells and myeloid-derived suppressor cells in HCC. These findings underscore the critical role of GATA4 reduction in promoting immunosuppression and HCC progression.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"8 9","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11340929/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142017277","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}