Hepatology最新文献

{"title":"Erratum: Insufficient radiofrequency ablation promotes hepatocellular carcinoma metastasis through N6-methyladenosine mRNA methylation-dependent mechanism.","authors":"Tianhong Su, Manling Huang, Junbin Liao, Shuibin Lin, Peng Yu, Jianhua Yang, Yuhong Cai, Shenghua Zhu, Lixia Xu, Zhenwei Peng, Sui Peng, Shuling Chen, Ming Kuang","doi":"10.1097/HEP.0000000000001257","DOIUrl":"https://doi.org/10.1097/HEP.0000000000001257","url":null,"abstract":"","PeriodicalId":177,"journal":{"name":"Hepatology","volume":"82 2","pages":"E35-E36"},"PeriodicalIF":12.9,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144663861","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multicenter, retrospective GUIDANCE001 study comparing transarterial chemoembolization with or without tyrosine kinase and immune checkpoint inhibitors as conversion therapy to treat unresectable hepatocellular carcinoma: Survival benefit in intermediate or advanced, but not early, stages.","authors":"Da-Long Yang, Lin Ye, Fan-Jian Zeng, Jie Liu, Hong-Bing Yao, Jun-Liang Nong, Shao-Ping Liu, Ning Peng, Wen-Feng Li, Pei-Sheng Wu, Chuang Qin, Ze Su, Jun-Jie Ou, Xiao-Feng Dong, Yi-He Yan, Teng-Meng Zhong, Xian-Shuang Mao, Ming-Song Wu, Yao-Zhi Chen, Guo-Dong Wang, Mian-Jing Li, Xue-Yao Wang, Fu-Quan Yang, Yong-Rong Liang, Shu-Chang Chen, Yong-Yu Yang, Kang Chen, Fu-Xin Li, Yong-Cheng Lai, Qing-Qing Pang, Xiu-Mei Liang, Xue-Mei You, Bang-De Xiang, Ya-Qun Yu, Liang Ma, Jian-Hong Zhong","doi":"10.1097/HEP.0000000000001229","DOIUrl":"10.1097/HEP.0000000000001229","url":null,"abstract":"<p><strong>Background and aims: </strong>Various conversion therapy options have become available to patients with unresectable HCC, but which conversion therapy is optimal for which type of patient is controversial. This study compared the efficacy and safety of TACE alone or combined with immune checkpoint and tyrosine kinase inhibitors.</p><p><strong>Approach and results: </strong>Data were retrospectively compared for patients with initially unresectable HCC who underwent conversion therapy consisting of TACE alone (n=459) or combined with immune checkpoint and tyrosine kinase inhibitors (n=343). Compared to the group that received TACE alone, the group that received triple conversion therapy showed significantly higher rates of overall survival (HR 0.43, 95%CI 0.35-0.53). In addition, triple therapy was associated with significantly longer median progression-free survival (15.9 vs. 8.0 mo, p <0.001). These results were confirmed in matched subsets of patients from each group. However, subgroup analysis confirmed the results only for patients with HCC in intermediate or advanced stages, not in an early stage. Those who received triple conversion therapy had a significantly higher rate of hepatectomy after conversion therapy (36.4 vs. 23.5%, p <0.001). Among those who underwent hepatectomy after conversion therapy, triple therapy was associated with a significantly higher rate of complete tumor response (32.1 vs. 11.1%, p <0.001). However, it was also associated with a significantly higher frequency of serious adverse events (35.6 vs. 27.0%, p =0.009).</p><p><strong>Conclusions: </strong>Combining TACE with immune checkpoint and tyrosine kinase inhibitors was associated with significantly better survival and conversion efficacy than TACE alone among patients with intermediate or advanced unresectable HCC.</p>","PeriodicalId":177,"journal":{"name":"Hepatology","volume":" ","pages":"357-369"},"PeriodicalIF":12.9,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143254230","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolic dysfunction-associated steatotic liver disease and the heart.","authors":"Stan Driessen, Sven M Francque, Stefan D Anker, Manuel Castro Cabezas, Diederick E Grobbee, Maarten E Tushuizen, Adriaan G Holleboom","doi":"10.1097/HEP.0000000000000735","DOIUrl":"10.1097/HEP.0000000000000735","url":null,"abstract":"<p><p>The prevalence and severity of metabolic dysfunction-associated steatotic liver disease (MASLD) are increasing. Physicians who treat patients with MASLD may acknowledge the strong coincidence with cardiometabolic disease, including atherosclerotic cardiovascular disease (asCVD). This raises questions on co-occurrence, causality, and the need for screening and multidisciplinary care for MASLD in patients with asCVD, and vice versa. Here, we review the interrelations of MASLD and heart disease and formulate answers to these matters. Epidemiological studies scoring proxies for atherosclerosis and actual cardiovascular events indicate increased atherosclerosis in patients with MASLD, yet no increased risk of asCVD mortality. MASLD and asCVD share common drivers: obesity, insulin resistance and type 2 diabetes mellitus (T2DM), smoking, hypertension, and sleep apnea syndrome. In addition, Mendelian randomization studies support that MASLD may cause atherosclerosis through mixed hyperlipidemia, while such evidence is lacking for liver-derived procoagulant factors. In the more advanced fibrotic stages, MASLD may contribute to heart failure with preserved ejection fraction by reduced filling of the right ventricle, which may induce fatigue upon exertion, often mentioned by patients with MASLD. Some evidence points to an association between MASLD and cardiac arrhythmias. Regarding treatment and given the strong co-occurrence of MASLD and asCVD, pharmacotherapy in development for advanced stages of MASLD would ideally also reduce cardiovascular events, as has been demonstrated for T2DM treatments. Given the common drivers, potential causal factors and especially given the increased rate of cardiovascular events, comprehensive cardiometabolic risk management is warranted in patients with MASLD, preferably in a multidisciplinary approach.</p>","PeriodicalId":177,"journal":{"name":"Hepatology","volume":" ","pages":"487-503"},"PeriodicalIF":12.9,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12266800/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139037210","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modulatory effects of CNNM4 on protein- l -isoaspartyl- O -methyltransferase repair function during alcohol-induced hepatic damage.","authors":"Irene González-Recio, Naroa Goikoetxea-Usandizaga, Claudia M Rejano-Gordillo, Carolina Conter, Rubén Rodríguez Agudo, Marina Serrano-Maciá, Leidy Estefanía Zapata-Pavas, Patricia Peña-Sanfélix, Mikel Azkargorta, Félix Elortza, José María Herranz, Álex Guillamon Thiery, Armando Raúl Guerra-Ruiz, Ramiro Jover, Unai Galicia-Garcia, César Martín, Ute Schaeper, Teresa C Delgado, Irene Díaz-Moreno, Antonio Díaz Quintana, Daniela Buccella, Rubén Nogueiras, JosepMaria Argemi, Matías A Ávila, Jordi Gratacós-Ginès, Paula Iruzubieta, Elisa Pose, Ramón Bataller, Javier Crespo, Luis Alfonso Martínez-Cruz, María Luz Martínez-Chantar","doi":"10.1097/HEP.0000000000001156","DOIUrl":"10.1097/HEP.0000000000001156","url":null,"abstract":"<p><strong>Background and aims: </strong>Alcohol-associated liver disease (ALD) is a leading cause of liver-related mortality worldwide, with limited treatment options beyond abstinence and liver transplantation. Chronic alcohol consumption has been linked to magnesium (Mg 2+ ) deficiency, which can influence liver disease progression. The mechanisms underlying Mg 2+ homeostasis dysregulation in ALD remain elusive. This study aimed to investigate the role of the Mg 2+ transporter Cyclin M4 (CNNM4) in ALD by analyzing its expression patterns in patients with ALD and preclinical animal models.</p><p><strong>Approach and results: </strong>In this study, CNNM4 is upregulated in the liver of both patients with ALD and animal models. CNNM4 overexpression triggers Mg 2+ homeostasis dysregulation, linked to ALD progression. We propose a novel therapeutic approach for ALD treatment using N -acetylgalactosamine silencing RNA technology to specifically modulate Cnnm4 expression in the liver, improving mitochondrial function and alleviating endoplasmic reticulum stress. Notably, silencing Cnnm4 restores protein isoaspartyl methyltransferase (PCMT1) activity, essential for repairing ethanol-induced protein damage. Enhancing mitochondrial activity through Cnnm4-dependent mechanisms increases S -adenosylmethionine levels, crucial for PCMT1 function, highlighting the interconnected roles of mitochondrial health and protein homeostasis in ALD treatment.</p><p><strong>Conclusions: </strong>These findings shed light on the dysregulation of Mg 2+ homeostasis in ALD, providing a promising therapeutic approach targeting CNNM4. N -acetylgalactosamine si Cnnm4 therapy boosts the repair processes of ethanol-damaged proteins through the upregulation of PCMT1 activity.</p>","PeriodicalId":177,"journal":{"name":"Hepatology","volume":" ","pages":"388-404"},"PeriodicalIF":12.9,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12266796/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142783524","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Navigating the \"specific etiology\" steatohepatitis category: Evaluation and management of nonalcohol/nonmetabolic dysfunction-associated steatohepatitis.","authors":"Mohammad Qasim Khan, Sara Hassan, Blanca C Lizaola-Mayo, Mamatha Bhat, Kymberly D Watt","doi":"10.1097/HEP.0000000000000674","DOIUrl":"10.1097/HEP.0000000000000674","url":null,"abstract":"","PeriodicalId":177,"journal":{"name":"Hepatology","volume":" ","pages":"504-521"},"PeriodicalIF":12.9,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71519818","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Human T cells engineered with an HLA-A2-restricted murine T-cell receptor targeting glypican 3 effectively control human hepatocellular carcinoma in mice.","authors":"Enric Vercher, Ángela Covo-Vergara, Enrique Conde, Mercedes Hernández-Rueda, Edurne Elizalde, Uxua Mancheño, Javier Glez-Vaz, Ibon Tamayo-Uria, Maritza R García-García, Marta Ferrer-Roig, Javier Marañón-Lopez, David Repáraz, Marta Ruiz, Ascensión López-Díaz de Cerio, Susana Inogés, Mercedes Iñarrairaegui, Juan J Lasarte, Bruno Sangro, Pablo Sarobe, Sandra Hervas-Stubbs","doi":"10.1097/HEP.0000000000001175","DOIUrl":"10.1097/HEP.0000000000001175","url":null,"abstract":"<p><strong>Background and aims: </strong>Glypican-3 (GPC3) is a promising target for T-cell therapy in HCC. While chimeric antigen receptor (CAR) T cells targeting GPC3 have demonstrated therapeutic efficacy, their effectiveness is limited by challenges such as low persistence and shedding of surface GPC3. Natural T-cell receptors (TCRs) may serve as an alternative, though identifying GPC3-specific TCRs within the endogenous repertoire is difficult.</p><p><strong>Approach and results: </strong>We immunized human leucocyte antigen-A2 (HLA-A2) transgenic mice with an adenovirus expressing human GPC3, identifying a panel of TCRs that recognize the GPC3(522-530) epitope. We cloned 3 murine GPC3-TCRs (TCR-A, TCR-B, and TCR-C) and engineered primary human T cells (TCR-T). TCR-T cells effectively recognized GPC3 + HLA-A2 + human HCC cells, with recognition diminished by GPC3 silencing and HLA-A2 blockade. TCR-B-T and TCR-C-T cells showed the highest reactivity, with TCR-B-T cells exhibiting superior effector functions, proliferative capacity, and therapeutic efficacy in xenograft HCC models. Notable, TCR-B-T cells outperformed second-generation 41BB GPC3-specific CAR-T cells, attributed to lower exhaustion, enhanced proliferation, greater effector function, and improved resilience. Furthermore, mixed dosing of CAR-T and TCR-B-T cells was significantly more effective than staggered dosing of the same cell type, suggesting potential synergistic effects.</p><p><strong>Conclusions: </strong>Transgenic TCRs join forces with CARs, expanding the arsenal of GPC3-targeting receptors for HCC T-cell therapy.</p>","PeriodicalId":177,"journal":{"name":"Hepatology","volume":" ","pages":"326-343"},"PeriodicalIF":12.9,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12266797/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142724400","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunogenomics of cholangiocarcinoma.","authors":"Virag Gehl, Colm J O'Rourke, Jesper B Andersen","doi":"10.1097/HEP.0000000000000688","DOIUrl":"10.1097/HEP.0000000000000688","url":null,"abstract":"<p><p>The development of cholangiocarcinoma spans years, if not decades, during which the immune system becomes corrupted and permissive to primary tumor development and metastasis. This involves subversion of local immunity at tumor sites, as well as systemic immunity and the wider host response. While immune dysfunction is a hallmark of all cholangiocarcinoma, the specific steps of the cancer-immunity cycle that are perturbed differ between patients. Heterogeneous immune functionality impacts the evolutionary development, pathobiological behavior, and therapeutic response of these tumors. Integrative genomic analyses of thousands of primary tumors have supported a biological rationale for immune-based stratification of patients, encompassing immune cell composition and functionality. However, discerning immune alterations responsible for promoting tumor initiation, maintenance, and progression from those present as bystander events remains challenging. Functionally uncoupling the tumor-promoting or tumor-suppressing roles of immune profiles will be critical for identifying new immunomodulatory treatment strategies and associated biomarkers for patient stratification. This review will discuss the immunogenomics of cholangiocarcinoma, including the impact of genomic alterations on immune functionality, subversion of the cancer-immunity cycle, as well as clinical implications for existing and novel treatment strategies.</p>","PeriodicalId":177,"journal":{"name":"Hepatology","volume":" ","pages":"522-539"},"PeriodicalIF":12.9,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136395447","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Erratum: Effects of trientine and penicillamine on intestinal copper uptake: A mechanistic 64 Cu PET/CT study in healthy humans.","authors":"Frederik Teicher Kirk, Ditte Emilie Munk, Eugene Scott Swenson, Adam Michael Quicquaro, Mikkel Holm Vendelbo, Michael L Schilsky, Peter Ott, Thomas Damgaard Sandahl","doi":"10.1097/HEP.0000000000001367","DOIUrl":"10.1097/HEP.0000000000001367","url":null,"abstract":"","PeriodicalId":177,"journal":{"name":"Hepatology","volume":" ","pages":"E37"},"PeriodicalIF":12.9,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144148747","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Erratum: Multicenter, retrospective GUIDANCE001 study comparing transarterial chemoembolization with or without tyrosine kinase and immune checkpoint inhibitors as conversion therapy to treat unresectable hepatocellular carcinoma: Survival benefit in intermediate or advanced, but not early, stages.","authors":"Da-Long Yang, Lin Ye, Fan-Jian Zeng, Jie Liu, Hong-Bing Yao, Jun-Liang Nong, Shao-Ping Liu, Ning Peng, Wen-Feng Li, Pei-Sheng Wu, Chuang Qin, Ze Su, Jun-Jie Ou, Xiao-Feng Dong, Yi-He Yan, Teng-Meng Zhong, Xian-Shuang Mao, Ming-Song Wu, Yao-Zhi Chen, Guo-Dong Wang, Mian-Jing Li, Xue-Yao Wang, Fu-Quan Yang, Yong-Rong Liang, Shu-Chang Chen, Yong-Yu Yang, Kang Chen, Fu-Xin Li, Yong-Cheng Lai, Qing-Qing Pang, Xiu-Mei Liang, Xue-Mei You, Bang-De Xiang, Ya-Qun Yu, Liang Ma, Jian-Hong Zhong","doi":"10.1097/HEP.0000000000001401","DOIUrl":"10.1097/HEP.0000000000001401","url":null,"abstract":"","PeriodicalId":177,"journal":{"name":"Hepatology","volume":" ","pages":"E40"},"PeriodicalIF":12.9,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144493278","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Letter to the Editor: Can we assess the diagnostic accuracy of 2D-SWE for liver fibrosis staging in MASLD?","authors":"Agostino Colli,Mirella Fraquelli,Giovanni Casazza","doi":"10.1097/hep.0000000000001470","DOIUrl":"https://doi.org/10.1097/hep.0000000000001470","url":null,"abstract":"","PeriodicalId":177,"journal":{"name":"Hepatology","volume":"14 1","pages":""},"PeriodicalIF":13.5,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144669540","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}