Pub Date : 2025-12-16DOI: 10.1097/hep.0000000000001645
Xiao-Dong Zhou,Qin-Fen Chen,Qiong-Yue Fan,Seung Up Kim,Terry Cheuk-Fung Yip,Salvatore Petta,Atsushi Nakajima,Emmanuel Tsochatzis,Jérôme Boursier,Elisabetta Bugianesi,Hannes Hagström,Wah-Kheong Chan,Manuel Romero-Gomez,José Luis Calleja,Victor de Lédinghen,Laurent Castéra,Arun J Sanyal,George Boon-Bee Goh,Philip Noel Newsome,Jian-Gao Fan,Michelle Lai,Céline Fournier-Poizat,Hye Won Lee,Grace Lai-Hung Wong,Angelo Armandi,Ying Shang,Grazia Pennisi,Elba Llop,Masato Yoneda,Marc de Saint-Loup,Clemence M Canivet,Paloma Carrillo-Fernandez,Carmen Lara-Romero,Rocio Gallego-Durán,Amon Asgharpour,Kevin Kim-Jun Teh,Mandy Sau-Wai Chan,Huapeng Lin,Wen-Yue Liu,Giovanni Targher,Christopher D Byrne,Vincent Wai-Sun Wong,Ming-Hua Zheng,
BACKGROUNDCardio-kidney-metabolic (CKM) syndrome, a new framework integrating cardiovascular, renal, and metabolic dysfunction, remains inadequately characterized in metabolic dysfunction-associated steatotic liver disease (MASLD).OBJECTIVEWe investigated the relationships between CKM stages and liver fibrosis severity, progression, and the risk of liver-related events (LREs) in MASLD.DESIGNPatients with MASLD from the VCTE-Prognosis cohort were stratified according to CKM stages. Outcomes included the prevalence of advanced liver fibrosis (LSM ≥10 kPa), liver stiffness progression (≥20% increase and Baveno category upshift), and incident LREs. Associations were assessed using multivariable logistic regression and Cox proportional hazards models.RESULTSAmong 12,097 patients with MASLD, the prevalence of advanced liver fibrosis increased across CKM stages at baseline: 9.6% (CKM stage 0-1), 18.0% (CKM stage 2), and 31.6% (CKM stage 3-4). CKM stage 2 (adjusted-OR=1.663, 95%CI 1.444-1.915) and CKM stage 3-4 (adjusted-OR=2.575, 95%CI 2.109-3.144) were independently associated with advanced fibrosis. During a 4.5-year median follow-up, 716 patients (6.1%) experienced progression of liver stiffness and 352 patients (1.7%) developed LRE. Compared to CKM stage 0-1, the risk of liver stiffness progression was higher in CKM stage 2 (adjusted-HR=1.321, 95%CI 1.050-1.662; p=0.018) and CKM stage 3-4 (adjusted-HR=1.767, 95%CI 1.339-2.330; p<0.001). In contrast, only CKM stage 3-4 was significantly associated with an increased risk of LREs (adjusted-HR=1.975, 95%CI 1.245-3.133; p=0.004).CONCLUSIONCKM stages are independently associated with the severity and progression of liver fibrosis in MASLD. CKM stage 2 significantly increases liver stiffness progression without excess LRE risk, while CKM stage 3-4 confers the highest risk for liver-related outcomes.
{"title":"Cardiovascular-Kidney-Metabolic syndrome and the risk of liver fibrosis progression and liver-related events in MASLD.","authors":"Xiao-Dong Zhou,Qin-Fen Chen,Qiong-Yue Fan,Seung Up Kim,Terry Cheuk-Fung Yip,Salvatore Petta,Atsushi Nakajima,Emmanuel Tsochatzis,Jérôme Boursier,Elisabetta Bugianesi,Hannes Hagström,Wah-Kheong Chan,Manuel Romero-Gomez,José Luis Calleja,Victor de Lédinghen,Laurent Castéra,Arun J Sanyal,George Boon-Bee Goh,Philip Noel Newsome,Jian-Gao Fan,Michelle Lai,Céline Fournier-Poizat,Hye Won Lee,Grace Lai-Hung Wong,Angelo Armandi,Ying Shang,Grazia Pennisi,Elba Llop,Masato Yoneda,Marc de Saint-Loup,Clemence M Canivet,Paloma Carrillo-Fernandez,Carmen Lara-Romero,Rocio Gallego-Durán,Amon Asgharpour,Kevin Kim-Jun Teh,Mandy Sau-Wai Chan,Huapeng Lin,Wen-Yue Liu,Giovanni Targher,Christopher D Byrne,Vincent Wai-Sun Wong,Ming-Hua Zheng, ","doi":"10.1097/hep.0000000000001645","DOIUrl":"https://doi.org/10.1097/hep.0000000000001645","url":null,"abstract":"BACKGROUNDCardio-kidney-metabolic (CKM) syndrome, a new framework integrating cardiovascular, renal, and metabolic dysfunction, remains inadequately characterized in metabolic dysfunction-associated steatotic liver disease (MASLD).OBJECTIVEWe investigated the relationships between CKM stages and liver fibrosis severity, progression, and the risk of liver-related events (LREs) in MASLD.DESIGNPatients with MASLD from the VCTE-Prognosis cohort were stratified according to CKM stages. Outcomes included the prevalence of advanced liver fibrosis (LSM ≥10 kPa), liver stiffness progression (≥20% increase and Baveno category upshift), and incident LREs. Associations were assessed using multivariable logistic regression and Cox proportional hazards models.RESULTSAmong 12,097 patients with MASLD, the prevalence of advanced liver fibrosis increased across CKM stages at baseline: 9.6% (CKM stage 0-1), 18.0% (CKM stage 2), and 31.6% (CKM stage 3-4). CKM stage 2 (adjusted-OR=1.663, 95%CI 1.444-1.915) and CKM stage 3-4 (adjusted-OR=2.575, 95%CI 2.109-3.144) were independently associated with advanced fibrosis. During a 4.5-year median follow-up, 716 patients (6.1%) experienced progression of liver stiffness and 352 patients (1.7%) developed LRE. Compared to CKM stage 0-1, the risk of liver stiffness progression was higher in CKM stage 2 (adjusted-HR=1.321, 95%CI 1.050-1.662; p=0.018) and CKM stage 3-4 (adjusted-HR=1.767, 95%CI 1.339-2.330; p<0.001). In contrast, only CKM stage 3-4 was significantly associated with an increased risk of LREs (adjusted-HR=1.975, 95%CI 1.245-3.133; p=0.004).CONCLUSIONCKM stages are independently associated with the severity and progression of liver fibrosis in MASLD. CKM stage 2 significantly increases liver stiffness progression without excess LRE risk, while CKM stage 3-4 confers the highest risk for liver-related outcomes.","PeriodicalId":177,"journal":{"name":"Hepatology","volume":"13 1","pages":""},"PeriodicalIF":13.5,"publicationDate":"2025-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145760037","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 : 2025-12-16DOI: 10.1097/hep.0000000000001602
Michael Eiswerth,Juan Pablo Arab
{"title":"The roadMAP of how terlipressin reverses HRS-AKI.","authors":"Michael Eiswerth,Juan Pablo Arab","doi":"10.1097/hep.0000000000001602","DOIUrl":"https://doi.org/10.1097/hep.0000000000001602","url":null,"abstract":"","PeriodicalId":177,"journal":{"name":"Hepatology","volume":"14 1","pages":"2-3"},"PeriodicalIF":13.5,"publicationDate":"2025-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145760034","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 : 2025-12-15DOI: 10.1097/hep.0000000000001630
Marta Fortuny, Antonio De Rosa, Ignacio Roca, Dan Ouchi, Elisaul Suárez, Andrea Cadiz, Mario Matute-González, Andrew M. Moon, Jordi Rimola, Ferran Torres, Maria Reig
Background & Aims: Macrovascular invasion (MaVI) defines advanced-stage HCC and typically mandates systemic therapy, yet some guidelines advocate surgery or locoregional approaches. We conducted a systematic review and meta-analysis of overall survival (OS) in HCC with MaVI treated with approaches other than systemic therapy, enforcing stringent inclusion criteria to exclude studies lacking a minimal prognostic dataset and to improve cohort comparability. Approach & Results: PRISMA-guided methods were used (CRD420251051847). PubMed was searched (January-2008 to November-2024). Eligible studies reported OS for HCC with MaVI and provided baseline performance status and liver function; studies without adequate prognostic information were excluded. Data on OS at 1, 2, 3, and 5-year were extracted, and heterogeneity was assessed. Seventy-three studies met criteria [104 treatment arms;10,329 patients]. Despite rigorous identification process, substantial heterogeneity persisted for most modalities (I²>80%), precluding robust pooling. Transarterial-radioembolization (TARE) monotherapy was the only treatment with low heterogeneity (I²=0%) and showed a pooled 1-year OS of 34% (95%CI:2–48%). Apparent advantages of sequential strategies likely reflected confounding by indication and immortal-time bias, as only patients who lived long enough and were sufficiently fit proceeded through the full sequence. Data completeness declined beyond 12 months (missing OS: 0% at 1-year; 17.3% at 2-year; 32.7% at 3-year; 70.2% at 5-year). Conclusions: In HCC with MaVI, 1-year OS is the most comparable endpoint across modalities. This analysis identifies TARE as the only consistently reproducible option, showing a 1-year survival of 34%. In contrast, surgery and sequential therapies remain confounded by substantial heterogeneity. Accordingly, stratified head-to-head trials comparing alternative modalities against immunotherapy are warranted.
{"title":"Hepatocellular carcinoma with macrovascular invasion: Review and survival meta-analysis of initial local therapy using minimal prognostic criteria","authors":"Marta Fortuny, Antonio De Rosa, Ignacio Roca, Dan Ouchi, Elisaul Suárez, Andrea Cadiz, Mario Matute-González, Andrew M. Moon, Jordi Rimola, Ferran Torres, Maria Reig","doi":"10.1097/hep.0000000000001630","DOIUrl":"https://doi.org/10.1097/hep.0000000000001630","url":null,"abstract":"Background & Aims: Macrovascular invasion (MaVI) defines advanced-stage HCC and typically mandates systemic therapy, yet some guidelines advocate surgery or locoregional approaches. We conducted a systematic review and meta-analysis of overall survival (OS) in HCC with MaVI treated with approaches other than systemic therapy, enforcing stringent inclusion criteria to exclude studies lacking a minimal prognostic dataset and to improve cohort comparability. Approach & Results: PRISMA-guided methods were used (CRD420251051847). PubMed was searched (January-2008 to November-2024). Eligible studies reported OS for HCC with MaVI and provided baseline performance status and liver function; studies without adequate prognostic information were excluded. Data on OS at 1, 2, 3, and 5-year were extracted, and heterogeneity was assessed. Seventy-three studies met criteria [104 treatment arms;10,329 patients]. Despite rigorous identification process, substantial heterogeneity persisted for most modalities (I²>80%), precluding robust pooling. Transarterial-radioembolization (TARE) monotherapy was the only treatment with low heterogeneity (I²=0%) and showed a pooled 1-year OS of 34% (95%CI:2–48%). Apparent advantages of sequential strategies likely reflected confounding by indication and immortal-time bias, as only patients who lived long enough and were sufficiently fit proceeded through the full sequence. Data completeness declined beyond 12 months (missing OS: 0% at 1-year; 17.3% at 2-year; 32.7% at 3-year; 70.2% at 5-year). Conclusions: In HCC with MaVI, 1-year OS is the most comparable endpoint across modalities. This analysis identifies TARE as the only consistently reproducible option, showing a 1-year survival of 34%. In contrast, surgery and sequential therapies remain confounded by substantial heterogeneity. Accordingly, stratified head-to-head trials comparing alternative modalities against immunotherapy are warranted.","PeriodicalId":177,"journal":{"name":"Hepatology","volume":"7 1","pages":""},"PeriodicalIF":13.5,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145759710","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 : 2025-12-15DOI: 10.1097/hep.0000000000001639
Qi Ruan, Tao Chen, Minwoo Kim, Haotian Yang, Debottam Sinha, Yaowu He, Lez Burke, Lashith Wickramasuriya, Lu Cao, Weikang Yan, John Hooper, Haolu Wang, Kim Bridle, Janin Chandra, Darrell Crawford, Xiaowen Liang
Background and Aims: The poor response to current systemic treatments in liver cancer has been associated with the activation of cancer-associated fibroblasts (CAFs). Herein, we aimed to investigate the effects of chemotherapy on hepatic stellate cells (HSCs), the main origin of CAFs in liver cancer, and regulate HSC activation to improve treatment efficacy. Approach and Results: CAF subpopulations and alpha-smooth muscle actin (αSMA) expression were analysed using a single-cell RNA sequencing dataset and immunohistochemical staining in patients. αSMA expression was significantly increased as the proportion of CAFs enriched by COL1A1+ and ACTA2+ subpopulations in patients after transarterial chemoembolisation. In vitro experiments demonstrated that cisplatin activated HSCs through a paracrine effect of excessive reactive oxygen species (ROS) generated from tumour cells of hepatocellular carcinoma (HCC) and biliary tract cancer (BTC) origin. RNA sequencing revealed that the PI3K signalling pathway underlined the activation of HSCs in response to excessive ROS. This was further analysed in HCC mouse models on non-fibrotic and fibrotic livers. 12-parameter flow cytometry panel validated a significant increase in activated CAF subsets in tumours following cisplatin treatment. Alpelisib, an α-specific PI3K inhibitor, selectively targeted PI3K p110α and completely inhibited HSC activation induced by cisplatin. A marked decrease in fibrosis areas was achieved along with a significant reduction of tumour burden in murine HCC models. Conclusion: This study demonstrates a role of platinum-based chemotherapy on HSC activation in liver cancer. Selective targeting of PI3K p110α may provide a novel strategy to inhibit chemotherapy-induced HSC activation and improve treatment response.
{"title":"An α-specific PI3K inhibitor improves chemotherapy efficacy by inhibiting hepatic stellate cell activation in liver cancer","authors":"Qi Ruan, Tao Chen, Minwoo Kim, Haotian Yang, Debottam Sinha, Yaowu He, Lez Burke, Lashith Wickramasuriya, Lu Cao, Weikang Yan, John Hooper, Haolu Wang, Kim Bridle, Janin Chandra, Darrell Crawford, Xiaowen Liang","doi":"10.1097/hep.0000000000001639","DOIUrl":"https://doi.org/10.1097/hep.0000000000001639","url":null,"abstract":"Background and Aims: The poor response to current systemic treatments in liver cancer has been associated with the activation of cancer-associated fibroblasts (CAFs). Herein, we aimed to investigate the effects of chemotherapy on hepatic stellate cells (HSCs), the main origin of CAFs in liver cancer, and regulate HSC activation to improve treatment efficacy. Approach and Results: CAF subpopulations and alpha-smooth muscle actin (αSMA) expression were analysed using a single-cell RNA sequencing dataset and immunohistochemical staining in patients. αSMA expression was significantly increased as the proportion of CAFs enriched by COL1A1+ and ACTA2+ subpopulations in patients after transarterial chemoembolisation. <jats:italic toggle=\"yes\">In vitro</jats:italic> experiments demonstrated that cisplatin activated HSCs through a paracrine effect of excessive reactive oxygen species (ROS) generated from tumour cells of hepatocellular carcinoma (HCC) and biliary tract cancer (BTC) origin. RNA sequencing revealed that the PI3K signalling pathway underlined the activation of HSCs in response to excessive ROS. This was further analysed in HCC mouse models on non-fibrotic and fibrotic livers. 12-parameter flow cytometry panel validated a significant increase in activated CAF subsets in tumours following cisplatin treatment. Alpelisib, an α-specific PI3K inhibitor, selectively targeted PI3K p110α and completely inhibited HSC activation induced by cisplatin. A marked decrease in fibrosis areas was achieved along with a significant reduction of tumour burden in murine HCC models. Conclusion: This study demonstrates a role of platinum-based chemotherapy on HSC activation in liver cancer. Selective targeting of PI3K p110α may provide a novel strategy to inhibit chemotherapy-induced HSC activation and improve treatment response.","PeriodicalId":177,"journal":{"name":"Hepatology","volume":"20 1","pages":""},"PeriodicalIF":13.5,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145759681","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 AND AIMSLiver cirrhosis, a leading global cause of mortality, is marked by progressive fibrosis and immune dysregulation. Tissue-resident memory T (TRM) cells, particularly γδ T cells, are emerging as critical regulators of hepatic immunity; however, their role in fibrogenesis remains poorly understood.APPROACH AND RESULTSThrough single-cell RNA sequencing and flow cytometry, we show that CD69⁺CXCR6⁺ γδ T cells are enriched in healthy livers and produce IFN-γ and IL-2 but significantly depleted in cirrhotic tissue, correlating with disease severity. In a murine fibrosis model, CXCR6⁺ γδ T cells limited fibrosis progression by inducing hepatic stellate cell apoptosis via FasL-Fas signaling. Adoptive transfer of CXCR6⁺ γδ T cells significantly mitigated fibrosis, whereas CXCR6- γδ T cells showed no such effect.CONCLUSIONLiver-resident CD69⁺CXCR6⁺ γδ T cells constitute a protective immune subset that limit fibrosis development and progression. Enhancing the function or abundance of this population may offer a promising immunotherapeutic strategy for liver cirrhosis.
{"title":"CXCR6 defines a distinct resident state in γδ T cells for protecting from liver cirrhosis.","authors":"Jiahao Ji,Zhitao Chen,Wenjing He,Yanxu Chen,Dongmei Ye,Yingqian Zhong,Xiaomin Shi,Xiaojun Ouyang,Zhimin Zeng,Qianyu Ye,Xiaoshun He,Zhinan Yin,Jianlei Hao,Yifang Gao","doi":"10.1097/hep.0000000000001643","DOIUrl":"https://doi.org/10.1097/hep.0000000000001643","url":null,"abstract":"BACKGROUND AND AIMSLiver cirrhosis, a leading global cause of mortality, is marked by progressive fibrosis and immune dysregulation. Tissue-resident memory T (TRM) cells, particularly γδ T cells, are emerging as critical regulators of hepatic immunity; however, their role in fibrogenesis remains poorly understood.APPROACH AND RESULTSThrough single-cell RNA sequencing and flow cytometry, we show that CD69⁺CXCR6⁺ γδ T cells are enriched in healthy livers and produce IFN-γ and IL-2 but significantly depleted in cirrhotic tissue, correlating with disease severity. In a murine fibrosis model, CXCR6⁺ γδ T cells limited fibrosis progression by inducing hepatic stellate cell apoptosis via FasL-Fas signaling. Adoptive transfer of CXCR6⁺ γδ T cells significantly mitigated fibrosis, whereas CXCR6- γδ T cells showed no such effect.CONCLUSIONLiver-resident CD69⁺CXCR6⁺ γδ T cells constitute a protective immune subset that limit fibrosis development and progression. Enhancing the function or abundance of this population may offer a promising immunotherapeutic strategy for liver cirrhosis.","PeriodicalId":177,"journal":{"name":"Hepatology","volume":"38 1","pages":""},"PeriodicalIF":13.5,"publicationDate":"2025-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145728560","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 and Aims: Intrahepatic cholangiocarcinoma (iCCA) is a highly metastatic tumor type, and iCCA with intrahepatic metastasis is associated with poor prognosis. Previous studies have confirmed that the tumor microenvironment (TME) is closely related to tumor metastasis. However, the state of the TME during iCCA liver metastasis remains unknown. Approach and Results: We profiled 28 specimens from 16 patients with iCCA (with and without intrahepatic metastasis) using integrated single-cell and spatial transcriptomics, bulk RNA sequencing, whole-exome sequencing, and in vivo and in vitro functional experiments to characterize the specific TME changes during iCCA liver metastasis. we identified the metastatic tumor cells, COL3A1 + epithelial cells, and revealed that COL3A1 + epithelial cells-endothelial-to-mesenchymal transition cells crosstalk promoted tumor invasion by inducing mesenchymal transformation of endothelial cells, while COL3A1 + epithelial cells-VEGFA + CCL4 + neutrophils crosstalk promoted tumor colonization by forming neutrophil extracellular traps. Conclusions: We revealed the key biological mechanisms involved in the invasion and colonization phases of iCCA liver metastasis. Moreover, we provide valuable data for understanding iCCA liver metastasis and a possible avenue for the treatment of advanced iCCA.
{"title":"Spatiotemporal landscape of intrahepatic cholangiocarcinoma liver metastasis at the single-cell level","authors":"Ziyu Xun, Hao Wang, Zhengfeng Xuan, Kexu Xiong, Nan Zhang, Junyu Long, Huishan Sun, Yiran Li, Chengpei Zhu, Mingjian Piao, Ting Zhang, Longhao Zhang, Shuofeng Li, Chengjie Li, Jiongyuan Li, Boyu Sun, Zixiang Zhou, Shanshan Wang, Ziyue Huang, Kai Liu, Yang Tan, Xiaohua Shi, Xiaobo Yang, Hanping Wang, Ling Lu, Haitao Zhao","doi":"10.1097/hep.0000000000001641","DOIUrl":"https://doi.org/10.1097/hep.0000000000001641","url":null,"abstract":"Background and Aims: Intrahepatic cholangiocarcinoma (iCCA) is a highly metastatic tumor type, and iCCA with intrahepatic metastasis is associated with poor prognosis. Previous studies have confirmed that the tumor microenvironment (TME) is closely related to tumor metastasis. However, the state of the TME during iCCA liver metastasis remains unknown. Approach and Results: We profiled 28 specimens from 16 patients with iCCA (with and without intrahepatic metastasis) using integrated single-cell and spatial transcriptomics, bulk RNA sequencing, whole-exome sequencing, and in vivo and in vitro functional experiments to characterize the specific TME changes during iCCA liver metastasis. we identified the metastatic tumor cells, COL3A1 <jats:sup>+</jats:sup> epithelial cells, and revealed that COL3A1 <jats:sup>+</jats:sup> epithelial cells-endothelial-to-mesenchymal transition cells crosstalk promoted tumor invasion by inducing mesenchymal transformation of endothelial cells, while COL3A1 <jats:sup>+</jats:sup> epithelial cells-VEGFA <jats:sup>+</jats:sup> CCL4 <jats:sup>+</jats:sup> neutrophils crosstalk promoted tumor colonization by forming neutrophil extracellular traps. Conclusions: We revealed the key biological mechanisms involved in the invasion and colonization phases of iCCA liver metastasis. Moreover, we provide valuable data for understanding iCCA liver metastasis and a possible avenue for the treatment of advanced iCCA.","PeriodicalId":177,"journal":{"name":"Hepatology","volume":"1 1","pages":""},"PeriodicalIF":13.5,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145717479","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 : 2025-12-08DOI: 10.1097/hep.0000000000001638
Zhengtong Zhou,Hua Zhou
{"title":"Letter to the editor: Methodological considerations for ITH quantification and model integration.","authors":"Zhengtong Zhou,Hua Zhou","doi":"10.1097/hep.0000000000001638","DOIUrl":"https://doi.org/10.1097/hep.0000000000001638","url":null,"abstract":"","PeriodicalId":177,"journal":{"name":"Hepatology","volume":"6 1","pages":""},"PeriodicalIF":13.5,"publicationDate":"2025-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145704425","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 : 2025-12-08DOI: 10.1097/hep.0000000000001640
John F Dillon,Damien Leith,Paul Brennan
{"title":"Addressing the utility of a novel score for \"At-Risk\" MASH in those with significant obesity.","authors":"John F Dillon,Damien Leith,Paul Brennan","doi":"10.1097/hep.0000000000001640","DOIUrl":"https://doi.org/10.1097/hep.0000000000001640","url":null,"abstract":"","PeriodicalId":177,"journal":{"name":"Hepatology","volume":"29 1","pages":""},"PeriodicalIF":13.5,"publicationDate":"2025-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145704422","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 : 2025-12-08DOI: 10.1097/hep.0000000000001633
Yanyu Zhang,Yehao Zhang,Tingting Hu
{"title":"Letter to the Editor: Timing shapes adjuvant PD-1 efficacy after hepatectomy in HCC.","authors":"Yanyu Zhang,Yehao Zhang,Tingting Hu","doi":"10.1097/hep.0000000000001633","DOIUrl":"https://doi.org/10.1097/hep.0000000000001633","url":null,"abstract":"","PeriodicalId":177,"journal":{"name":"Hepatology","volume":"6 1","pages":""},"PeriodicalIF":13.5,"publicationDate":"2025-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145704419","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 : 2025-12-05DOI: 10.1097/hep.0000000000001634
Nasir Hussain,Rodrigo V Motta,Usha Gungabissoon,Linda Casillas,Sumanta Mukherjee,Andrea Ribeiro,Megan M Mclaughlin,Kaitlin Hagan,Khushpreet Bhandal,Penelope Rogers,Martine Walmsley,James Ferguson,Andreas E Kremer,Emma L Culver,Palak Trivedi
BACKGROUNDDrug development in primary sclerosing cholangitis (PSC) is challenging, giving orphan disease status and variable rates of disease progression. A potential route for new therapies is through attenuation of symptoms. However, the epidemiology of symptomatic presentations and how they inherently fluctuate over time is not known.APPROACH AND RESULTSWe conducted a prospective, multicentre study (trial registration: ISRCTN:15518794) to quantify the prevalence, intensity and variability of pruritus in PSC. Participants underwent face-to-face symptom assessment through the itch numerical rating scale (NRS) and 5D-itch tool. Clinical, radiological and biochemical factors associated with pruritus intensity were determined, alongside the impact on health-related quality-of-life (EQ-5D 5L and chronic liver disease questionnaires [CLDQ]) over 12-week intervals (up to 48+/-4 weeks). In all, 220 patients participated, of whom n=116 reported pruritus, with n=56 scoring NRS worst itch ≥4. Median 5D-itch was greater in people with cirrhosis (11.0 vs 8.0), transient elastography readings >8.0 kPa (9.5 vs 5.0) and a history of ascending cholangitis (11.0 vs 7.0) (p<0.01; all). 5D-itch correlated positively with serum bilirubin, ALP, ALT and AST; and negatively with CLDQ and EQ-5D 5L. In patients scoring NRS≥4, 61.5% reported persistent pruritus intensity over 48 weeks. Reciprocally, 46.2% experienced a spontaneous ≥2 point reduction in NRS without the addition of a new anti-pruritic agent.CONCLUSIONOne in 4 PSC patients experience moderate-severe pruritus, with greater symptom intensity in those with advanced disease. Our dataset is able to serve as a reference tool to aid future interventional study design, with regards anti-pruritus therapies in PSC.
原发性硬化性胆管炎（PSC）的药物开发具有挑战性，具有孤儿病状态和疾病进展率的差异性。一种潜在的新疗法是通过减轻症状。然而，症状表现的流行病学以及它们如何随时间固有波动尚不清楚。方法和结果我们进行了一项前瞻性、多中心研究（试验注册：ISRCTN:15518794），以量化PSC患者瘙痒的患病率、强度和变异性。通过瘙痒数值评定量表（NRS）和5d -瘙痒工具对参与者进行面对面的症状评估。研究确定了与瘙痒强度相关的临床、放射学和生化因素，以及对健康相关生活质量（EQ-5D - 5L和慢性肝病问卷[CLDQ]）的影响，时间间隔为12周（最长为48+/-4周）。共纳入220例患者，其中n=116例报告瘙痒，n=56例评分NRS最严重瘙痒≥4。肝硬化（11.0 vs 8.0）、瞬时弹性图读数>8.0 kPa （9.5 vs 5.0）和升性胆管炎史（11.0 vs 7.0）患者的中位5D-itch更大（p<0.01；全部）。5D-itch与血清胆红素、ALP、ALT、AST呈正相关；与CLDQ、eq - 5d5l呈负相关。在NRS评分≥4的患者中，61.5%报告持续瘙痒强度超过48周。相反，46.2%的患者在没有添加新的止痒剂的情况下，NRS自发降低≥2点。结论1 / 4的PSC患者出现中重度瘙痒，晚期患者症状强度更大。我们的数据集可以作为参考工具，帮助未来的介入性研究设计，关于PSC的抗瘙痒治疗。
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