Pub Date : 2025-12-23DOI: 10.1097/hep.0000000000001631
Weikang Meng, Yuwei Sun
{"title":"Letter to the Editor: When locoregional therapy fails, how soon should we pivot?","authors":"Weikang Meng, Yuwei Sun","doi":"10.1097/hep.0000000000001631","DOIUrl":"https://doi.org/10.1097/hep.0000000000001631","url":null,"abstract":"","PeriodicalId":177,"journal":{"name":"Hepatology","volume":"12 1","pages":""},"PeriodicalIF":13.5,"publicationDate":"2025-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145807677","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}
Pub Date : 2025-12-22DOI: 10.1097/hep.0000000000001655
Jixu Guo,Shuiping Yu
{"title":"Letter to the Editor: The suggestion for additional clinical scores in decoding tumor heterogeneity in HCC.","authors":"Jixu Guo,Shuiping Yu","doi":"10.1097/hep.0000000000001655","DOIUrl":"https://doi.org/10.1097/hep.0000000000001655","url":null,"abstract":"","PeriodicalId":177,"journal":{"name":"Hepatology","volume":"22 1","pages":""},"PeriodicalIF":13.5,"publicationDate":"2025-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145801341","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}
Pub Date : 2025-12-22DOI: 10.1097/hep.0000000000001656
Zhi-Cheng Jin,Gao-Jun Teng
{"title":"Reply: The suggestion for additional clinical scores in decoding tumor heterogeneity in HCC.","authors":"Zhi-Cheng Jin,Gao-Jun Teng","doi":"10.1097/hep.0000000000001656","DOIUrl":"https://doi.org/10.1097/hep.0000000000001656","url":null,"abstract":"","PeriodicalId":177,"journal":{"name":"Hepatology","volume":"3 1","pages":""},"PeriodicalIF":13.5,"publicationDate":"2025-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145801340","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}
BACKGROUND AIMSNab-paclitaxel plus gemcitabine-cisplatin (Gem/Cis/nab-P) had promising efficacy in phase II trials for advanced biliary tract cancer (BTC) but failed to demonstrate superiority in phase III. We investigated Gem/Cis/nab-P efficacy and identified molecular subgroups with clinical benefit.APPROACH RESULTSThis prospective observational cohort study (NCT04871321) enrolled 119 patients with advanced BTC who received Gem/Cis/nab-P from July 2021 to December 2022. Of these, 108 were included in genomic and transcriptomic analyses of pretreatment tumor samples that met quality control criteria. Among 119 patients, 39.5% had intrahepatic cholangiocarcinoma, 37.0% extrahepatic cholangiocarcinoma, and 23.5% gallbladder cancer. Most patients had metastatic disease (68.9%). At a median follow-up of 23.7 months, the median progression-free survival was 8.3 months and median overall survival 19.8 months. Grade ≥3 treatment-related adverse events occurred in 70 patients (58.8%), and dose reduction was required in 99.2%. Frequent genetic alterations were TP53 (53.7%), KRAS (29.6%), and CDKN2A (20.4%), with TP53 mutations being significantly associated with worse outcomes. Transcriptomic analysis identified four molecular subtypes: cholangiocyte-like, stromal, metabolic, and inflammatory-proliferative. The cholangiocyte-like subtype, marked by increased cholangiocyte markers, had the most favorable prognosis. Stromal and metabolic subtypes showed moderate outcomes, characterized by a fibroblast-rich stroma with activated angiogenesis and enriched metabolic pathways, respectively. The inflammatory-proliferative subtype had the worst prognosis, with cell cycle and inflammatory activation, and an exhausted immune microenvironment.CONCLUSIONSThis study demonstrated the clinical activity of Gem/Cis/nab-P in advanced BTC and highlighted that biology-driven patient stratification based on genomic and transcriptomic features may provide important prognostic information.
{"title":"Biology-driven stratification of advanced biliary tract cancer treated with nab-paclitaxel plus gemcitabine-cisplatin: A prospective observational cohort study.","authors":"Seonjeong Woo,Beodeul Kang,Sung Hwan Lee,Jung Sun Kim,Haeyoun Kang,Seok Jeong Yang,Chansik An,Gwangil Kim,Gae Hoon Jo,Chang-Il Kwon,Min Je Sung,Suk Pyo Shin,Sanghoon Jung,Sohyun Hwang,Chan Kim,Hong Jae Chon","doi":"10.1097/hep.0000000000001650","DOIUrl":"https://doi.org/10.1097/hep.0000000000001650","url":null,"abstract":"BACKGROUND AIMSNab-paclitaxel plus gemcitabine-cisplatin (Gem/Cis/nab-P) had promising efficacy in phase II trials for advanced biliary tract cancer (BTC) but failed to demonstrate superiority in phase III. We investigated Gem/Cis/nab-P efficacy and identified molecular subgroups with clinical benefit.APPROACH RESULTSThis prospective observational cohort study (NCT04871321) enrolled 119 patients with advanced BTC who received Gem/Cis/nab-P from July 2021 to December 2022. Of these, 108 were included in genomic and transcriptomic analyses of pretreatment tumor samples that met quality control criteria. Among 119 patients, 39.5% had intrahepatic cholangiocarcinoma, 37.0% extrahepatic cholangiocarcinoma, and 23.5% gallbladder cancer. Most patients had metastatic disease (68.9%). At a median follow-up of 23.7 months, the median progression-free survival was 8.3 months and median overall survival 19.8 months. Grade ≥3 treatment-related adverse events occurred in 70 patients (58.8%), and dose reduction was required in 99.2%. Frequent genetic alterations were TP53 (53.7%), KRAS (29.6%), and CDKN2A (20.4%), with TP53 mutations being significantly associated with worse outcomes. Transcriptomic analysis identified four molecular subtypes: cholangiocyte-like, stromal, metabolic, and inflammatory-proliferative. The cholangiocyte-like subtype, marked by increased cholangiocyte markers, had the most favorable prognosis. Stromal and metabolic subtypes showed moderate outcomes, characterized by a fibroblast-rich stroma with activated angiogenesis and enriched metabolic pathways, respectively. The inflammatory-proliferative subtype had the worst prognosis, with cell cycle and inflammatory activation, and an exhausted immune microenvironment.CONCLUSIONSThis study demonstrated the clinical activity of Gem/Cis/nab-P in advanced BTC and highlighted that biology-driven patient stratification based on genomic and transcriptomic features may provide important prognostic information.","PeriodicalId":177,"journal":{"name":"Hepatology","volume":"361 1","pages":""},"PeriodicalIF":13.5,"publicationDate":"2025-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145785843","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}
Pub Date : 2025-12-19DOI: 10.1097/hep.0000000000001654
Harmeet Malhi,Gregory J Gores
{"title":"Discontinuing Letters to the Editor: Loss of utility and pertinence.","authors":"Harmeet Malhi,Gregory J Gores","doi":"10.1097/hep.0000000000001654","DOIUrl":"https://doi.org/10.1097/hep.0000000000001654","url":null,"abstract":"","PeriodicalId":177,"journal":{"name":"Hepatology","volume":"13 1","pages":""},"PeriodicalIF":13.5,"publicationDate":"2025-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145786204","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}
Pub Date : 2025-12-17DOI: 10.1097/hep.0000000000001653
Madhumita Premkumar, Kamal Kajal
{"title":"Reply to ‘Nuances in POCUS-guided hemodynamic assessment in cirrhosis’","authors":"Madhumita Premkumar, Kamal Kajal","doi":"10.1097/hep.0000000000001653","DOIUrl":"https://doi.org/10.1097/hep.0000000000001653","url":null,"abstract":"","PeriodicalId":177,"journal":{"name":"Hepatology","volume":"152 1","pages":""},"PeriodicalIF":13.5,"publicationDate":"2025-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145765246","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}
Pub Date : 2025-12-17DOI: 10.1097/hep.0000000000001652
Madalina-Gabriela Indre, Federico Ravaioli
{"title":"Response to: Beyond semantics—acknowledging diagnostic differences between NAFLD and MASLD","authors":"Madalina-Gabriela Indre, Federico Ravaioli","doi":"10.1097/hep.0000000000001652","DOIUrl":"https://doi.org/10.1097/hep.0000000000001652","url":null,"abstract":"","PeriodicalId":177,"journal":{"name":"Hepatology","volume":"17 1","pages":""},"PeriodicalIF":13.5,"publicationDate":"2025-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145765242","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}
Pub Date : 2025-12-17DOI: 10.1097/hep.0000000000001651
Magnus Holmer, Michael Ingre, Martti Färkkilä, Cyriel Ponsioen, Bregje Mol, Christoph Schramm, Trine Folseraas, Kristine Wiencke, Nora Cazzagon, Elisa Catanzaro, Antonio Molinaro, Emma Nilsson, Johan Vessby, Stergios Kechagias, Nils Nyhlin, Mårten Werner, Annika Bergquist
{"title":"Reply: Competing risk and surveillance thresholds for HCC in Patients with PSC","authors":"Magnus Holmer, Michael Ingre, Martti Färkkilä, Cyriel Ponsioen, Bregje Mol, Christoph Schramm, Trine Folseraas, Kristine Wiencke, Nora Cazzagon, Elisa Catanzaro, Antonio Molinaro, Emma Nilsson, Johan Vessby, Stergios Kechagias, Nils Nyhlin, Mårten Werner, Annika Bergquist","doi":"10.1097/hep.0000000000001651","DOIUrl":"https://doi.org/10.1097/hep.0000000000001651","url":null,"abstract":"","PeriodicalId":177,"journal":{"name":"Hepatology","volume":"153 1","pages":""},"PeriodicalIF":13.5,"publicationDate":"2025-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145765244","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}
Pub Date : 2025-12-17DOI: 10.1097/hep.0000000000001649
Giovani Schulte Farina, Jonathan Soldera
{"title":"Letter to the Editor: Beyond Semantics—Acknowledging diagnostic differences between NAFLD and MASLD","authors":"Giovani Schulte Farina, Jonathan Soldera","doi":"10.1097/hep.0000000000001649","DOIUrl":"https://doi.org/10.1097/hep.0000000000001649","url":null,"abstract":"","PeriodicalId":177,"journal":{"name":"Hepatology","volume":"5 1","pages":""},"PeriodicalIF":13.5,"publicationDate":"2025-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145765245","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}
Pub Date : 2025-12-17DOI: 10.1097/hep.0000000000001648
Abhilash Koratala, Eduardo R. Argaiz
{"title":"Nuances in POCUS-guided hemodynamic assessment in cirrhosis","authors":"Abhilash Koratala, Eduardo R. Argaiz","doi":"10.1097/hep.0000000000001648","DOIUrl":"https://doi.org/10.1097/hep.0000000000001648","url":null,"abstract":"","PeriodicalId":177,"journal":{"name":"Hepatology","volume":"93 1","pages":""},"PeriodicalIF":13.5,"publicationDate":"2025-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145765249","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}
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