Hepatology最新文献

{"title":"Reply: Reevaluating PCA and SCTransform usage in single-cell intrahepatic cholangiocarcinoma analysis.","authors":"Guangyu Fan,Xiaohong Han,Yuankai Shi","doi":"10.1097/hep.0000000000001480","DOIUrl":"https://doi.org/10.1097/hep.0000000000001480","url":null,"abstract":"","PeriodicalId":177,"journal":{"name":"Hepatology","volume":"20 1","pages":""},"PeriodicalIF":13.5,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144737399","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: HAF prevents hepatocyte apoptosis and progression to MASH and HCC through transcriptional regulation of the NF-κB pathway.","authors":"Karen Acuña-Pilarte,Ethan C Reichert,Yangsook Song Green,Lily M-T Halberg,Martin Golkowski,Kathleen M Maguire,Patrice N Mimche,Severin Donald Kamdem,Po-An Hu,Jillian Wright,Gregory S Ducker,Warren P Voth,Ryan M O'Connell,Sydney A McFarland,Erika Said Abu Egal,Amandine Chaix,Scott A Summers,Jordan W Reelitz,John Alan Maschek,James E Cox,Kimberley J Evason,Mei Yee Koh","doi":"10.1097/hep.0000000000001416","DOIUrl":"https://doi.org/10.1097/hep.0000000000001416","url":null,"abstract":"","PeriodicalId":177,"journal":{"name":"Hepatology","volume":"27 1","pages":""},"PeriodicalIF":13.5,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144737397","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":"Reply: Is fecal acetate a viable pan-etiological predictor of outcomes in HCC immunotherapy?","authors":"Pei-Chang Lee, Yi-Hsiang Huang","doi":"10.1097/hep.0000000000001482","DOIUrl":"https://doi.org/10.1097/hep.0000000000001482","url":null,"abstract":"","PeriodicalId":177,"journal":{"name":"Hepatology","volume":"27 1","pages":""},"PeriodicalIF":13.5,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144736791","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: Reevaluating PCA and SCTransform usage in single-cell intrahepatic cholangiocarcinoma analysis","authors":"Yoshiyasu Takefuji","doi":"10.1097/hep.0000000000001479","DOIUrl":"https://doi.org/10.1097/hep.0000000000001479","url":null,"abstract":"","PeriodicalId":177,"journal":{"name":"Hepatology","volume":"26 1","pages":""},"PeriodicalIF":13.5,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144737108","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":"E2F2 transcription factor promotes a cholestatic MASH phenotype by regulating hepatobiliary metabolism through miR-34a-5p","authors":"Maider Apodaka-Biguri, André L. Simão, Francisco González-Romero, Daniela Mestre, Pedro M. Rodrigues, Igor Aurrekoetxea, Beatriz Gómez-Santos, Xabier Buqué, Ane Nieva-Zuluaga, Mikel Ruiz de Gauna, Idoia Fernandez-Puertas, Paul Gomez-Jauregui, Natalia Sainz-Ramirez, Kendall Alfaro-Jiménez, Ane Ortiz-Palma, Estibaliz Castillero, Ainhoa Iglesias-Ara, Jone Mitxelena, Ainhoa Eriz, Ana M. Aransay, Juan-José Lozano, Jose J.G. Marin, Laura Izquierdo-Sanchez, Maria J. Perugorria, Luis Bujanda, Jesus M. Banales, César Martín, Lorena Mosteiro, Gaizka Errazti, Wing-Kin Syn, Luis Castaño, Ana M. Zubiaga, Rui E. Castro, Patricia Aspichueta","doi":"10.1097/hep.0000000000001461","DOIUrl":"https://doi.org/10.1097/hep.0000000000001461","url":null,"abstract":"Background &amp; Aims: Metabolic dysfunction-associated steatotic liver disease (MASLD) affects a heterogeneous group of patients. Among them, those with cholestatic profile show worse outcomes. Here, we investigated whether E2F2 is involved in MASLD-associated cholestasis and, if so, the role of miRNAs. Methods: <jats:italic toggle=\"yes\">E2f2</jats:italic>-knockout (<jats:italic toggle=\"yes\">E2f2</jats:italic> <jats:sup> -/- </jats:sup>) and wild-type (WT) mice were fed a choline-deficient high-fat diet (ChD-HFD) or a HFD after injection of diethylnitrosamine (DEN-HFD) to induce metabolic dysfunction-associated steatohepatitis (MASH). E2F2 was overexpressed in liver by AAV8. Cholestasis was induced by bile duct ligation or by a 3,5-diethoxycarbonyl-1,4-dihydrocollidine-enriched diet. microRNA sequencing was performed. Two biopsy-proven MASLD patient cohorts were used. Results: E2F2 deficiency resulted in increased synthesis and excretion of cholesterol, phosphatidylcholine and bile acids, reducing their storage in the liver while increasing their presence in feces. This was consistent with increased expression of genes involved in biliary lipid metabolism, reduced inflammation and fibrosis, and the generation of a distinct miRNA profile, thereby preventing MASH. Liver-specific induction of E2F2 <jats:italic toggle=\"yes\">in vivo</jats:italic> hampered the transcriptional program involved in biliary lipid metabolism and upregulated miR-34a-5p, which was downregulated in <jats:italic toggle=\"yes\">E2f2</jats:italic> <jats:sup> -/- </jats:sup> mice. The protective effects observed in <jats:italic toggle=\"yes\">E2f2</jats:italic> <jats:sup> -/- </jats:sup> mice were lost when a miR-34a-5p mimic was used. Hepatic miR-34a-5p levels were elevated in patients with advanced fibrosis, inflammation, steatosis score, cholelithiasis, and increased serum bile acids and biliary lipids. <jats:italic toggle=\"yes\">E2f2</jats:italic> deficiency conferred protection against cholestatic liver injury. Conclusions: E2F2 deficiency protects against MASH and cholestasis preventing cholesterol accumulation, fibrosis, and inflammation through modulation of miR-34a-5p, which could provide therapeutic benefits for patients with cholestatic-MASH.","PeriodicalId":177,"journal":{"name":"Hepatology","volume":"11 1","pages":""},"PeriodicalIF":13.5,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144719523","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":"Chiglitazar in MASLD with hypertriglyceridemia and insulin resistance: A phase II, randomized, double-blind, placebo-controlled study","authors":"Yameng Sun, Cuisong Wu, Guijie Xin, Bihui Zhong, Xiaofeng Wu, Yali Liu, Junping Shi, Qin Zhang, Yingren Zhao, Yufeng Gao, Yongning Xin, Yueyong Zhu, Lixian Wu, Xiaorong Mao, Jian Du, Jia Shang, Weiwei Sun, Jie Xu, Zujiang Yu, Yuemin Nan, Huiping Sheng, Yue Li, Huiying Rao, Chaohui Yu, Haixiang Cao, Bo Chen, Zhibin Li, Xiaoning Wu, Xiaofei Tong, Hong You","doi":"10.1097/hep.0000000000001475","DOIUrl":"https://doi.org/10.1097/hep.0000000000001475","url":null,"abstract":"Background and Aims: Metabolic dysfunction-associated steatotic liver disease (MASLD) can progress to severe forms such as metabolic dysfunction-associated steatohepatitis (MASH). Effective treatments for MASH are urgently needed. This study aimed to evaluate the efficacy and safety of chiglitazar, a PPAR pan-agonist, in MASLD with hypertriglyceridemia and insulin resistance. Approach and Results: In this phase II multicenter, randomized, double-blind and placebo-controlled study, 104 patients with MASLD with hypertriglyceridemia and insulin resistance were randomized 2:2:1 to receive 48 mg, 64 mg of chiglitazar, or placebo once daily for 18 weeks. The primary endpoint was the percentage change in liver fat content measured by magnetic resonance imaging proton density fat fraction (MRI-PDFF) at week 18. Chiglitazar significantly reduced liver fat content, with percentage change from baseline at week 18 of -28.1% (95% CI -37.5 to -18.7) in the 48 mg group and -39.5% (95% CI -49.0 to -30.0) in the 64 mg group, compared to -3.2% (95% CI -16.8 to 10.4) in placebo group. The differences compared to placebo were -24.9% (<jats:italic toggle=\"yes\">p</jats:italic>&lt;0.05) for the 48 mg group and -36.3% (<jats:italic toggle=\"yes\">p</jats:italic>&lt;0.001) for the 64 mg group. Chiglitazar also significantly improved liver injury-related biomarkers such as ALT, AST and γ-GT. Liver fibrosis indicators, lipid parameters, insulin resistance and metabolic syndrome, showed improved trend. Both doses of chiglitazar were well tolerated, with most adverse events being mild to moderate. Conclusion: Chiglitazar significantly reduced liver fat content in MASLD with hypertriglyceridemia and insulin resistance, with a dose-dependent effect and favorable safety profile.","PeriodicalId":177,"journal":{"name":"Hepatology","volume":"20 1","pages":""},"PeriodicalIF":13.5,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144719524","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":"NEK7 induced phosphorylation of EGFR on serine 1070 drive the acquired lenvatinib resistance in hepatocellular carcinoma.","authors":"Qibo Huang,Weijian Wang,Qianyun Ge,Dafeng Xu,Renshun Dong,Ruizhi Chang,Xing Wu,Jie Mo,Chen Su,Deng Ning,Qiumeng Liu,Huifang Liang,Guihua Wang,Jin Chen,Xifeng Fu,Xiaoping Chen,Junnan Liang,Bixiang Zhang","doi":"10.1097/hep.0000000000001474","DOIUrl":"https://doi.org/10.1097/hep.0000000000001474","url":null,"abstract":"BACKGROUND AND AIMSLenvatinib is recognized as a first-line therapy for inoperable hepatocellular carcinoma (HCC) patients. Growing evidence indicates that the lenvatinib resistance can be acquired in HCC cells via kinase rewiring.APPROACH AND RESULTSWe established acquired lenvatinib resistance organoids and HCC cell lines. NIMA-related coiled-coil kinase 7 (NEK7) was identified as an HCC lenvatinib acquired resistance gene by kinase CRISPR-Cas9 genetic screen. Functional analyses demonstrate that NEK7 enhanced lenvatinib resistance in HCC and NEK7 knock down or knock out display the anti-tumor effects in acquired lenvatinib HCC cells and organoids. Mechanistically, NEK7 binds to EGFR, leading to the phosphorylation of EGFR (Endothelial growth factor receptor) specifically at the serine 1070 residue, which contributes to the activation of MAPK (Mitogen-activated protein kinase) and PI3K/AKT (Phosphoinositide 3-kinase/Akt) signaling pathways. Consistently, designed inhibitory peptides targeting domain from amino acids 979 to 1099 were proved to inhibit phosphorylation of EGFR S1070 site and therapeutically inhibit anti-tumor of acquired lenvatinib resistance HCC.CONCLUSIONSOur results unveil insights into the acquired lenvatinib resistance mechanism that NEK7 phosphorylates EGFR at S1070 to promote acquired lenvatinib resistance in HCC.","PeriodicalId":177,"journal":{"name":"Hepatology","volume":"98 1","pages":""},"PeriodicalIF":13.5,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144684295","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":"Causes of mortality among patients with early-stage hepatocellular carcinoma","authors":"Karim Seif El Dahan, Darine Daher, Nicole E. Rich, Anish J. Nayak, Caroline Ankoma-Sey, Rajalakshmi Govalan, Megha B. Bhongade, Emily Molina, Eunice Amador, Hannah Pitts, Prasun K. Jalal, Fasiha Kanwal, Neehar D. Parikh, Amit G. Singal","doi":"10.1097/hep.0000000000001471","DOIUrl":"https://doi.org/10.1097/hep.0000000000001471","url":null,"abstract":"Background: Early detection of hepatocellular carcinoma (HCC) can reduce cancer-related mortality; however, there are often competing risks from comorbid conditions, including cirrhosis. Understanding causes of death among patients with early-stage HCC can inform strategies to improve surveillance effectiveness. Methods: We conducted a retrospective cohort study of patients with early-stage HCC (BCLC stages 0/A) at four U.S. health systems between 2008 and 2022. We defined the primary cause of death as HCC-related, liver-related (non-HCC), and death from other causes. We used multivariable and Fine-Gray analysis, with liver transplant as a competing outcome, to identify factors associated with mortality. Results: Among 1,336 patients with early-stage HCC, 598 (44.8%) died during a median follow-up of 32.4 months – 220 (37%) HCC-related, 114 (19%) liver-related, and 179 (30%) from other causes. Median time to death was similar between the groups: 24 (95%CI 22-31), 19 (95%CI 15-23), and 23 (95%CI 19-27) months for HCC-related, liver-related, and other causes of mortality, respectively. Curative treatment was associated with reduced HCC-related (HR 0.34; 95%CI 0.23-0.48) and liver-related mortality (HR 0.23; 95%CI 0.14-0.38). Predictors of HCC-related mortality included AFP &gt;20 ng/mL (HR 2.19; 95%CI 1.59-3.03), and tumor diameter &gt;3 cm (HR 1.69; 95%CI 1.20-2.37). Liver-related mortality was associated with MASLD etiology (HR 1.99; 95%CI 1.09-3.65), Child-Pugh B cirrhosis (HR 2.64; 95%CI 1.58-4.42), and ALBI grade 2 (vs. grade 1: HR 2.47; 95%CI 1.21-5.06). Conclusion: Cause of death varies among patients with early-stage HCC, although HCC-related death remains the most common cause. Efforts are needed to optimize curative treatment effectiveness among patients with early-stage HCC to reduce cancer-related mortality.","PeriodicalId":177,"journal":{"name":"Hepatology","volume":"115 1","pages":""},"PeriodicalIF":13.5,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144684767","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":"Distinctive hemodynamic phenotype in Fontan-type circulation patients with distal esophageal varices.","authors":"Luis Téllez,María Toledano,María Álvarez,Elvira Garrido-Lestache,Elena Garrido,Antonio Guerrero,Jesús Donate,Lorenzo Canova,María Torres,Cristian Perna,María Jesús Del Cerro,Agustín Albillos","doi":"10.1097/hep.0000000000001472","DOIUrl":"https://doi.org/10.1097/hep.0000000000001472","url":null,"abstract":"BACKGROUND AIMSEsophageal varices (EV) are common in adults with Fontan-type circulation and may arise via distinct hemodynamic mechanisms depending on their anatomic location. We aimed to determine the prevalence, anatomical distribution and hemodynamic correlates of EV in this population.APPROACH RESULTSIn this prospective cohort study, 114 consecutive adults with Fontan-type circulation underwent combined hepatic and cardiac catheterization, esophagogastroduodenoscopy, and liver biopsy. Patients were classified by endoscopic findings into those with and without EV, and the EV cohort was further stratified by location (proximal or distal). EV were present in 36.8% (95% CI, 27.9-45.8%), including 28.9% with distal EV and 17.5% with proximal EV. Over a median follow-up of 48.9 months (IQR, 27.1-85.5), only one variceal bleeding event occurred. Patients with distal EV exhibited the highest cardiac index and pulmonary, systemic and hepatic venous pressures, as well as the lowest systemic vascular resistance (all p<0.01). Severe hepatic fibrosis was more frequent in this group (87.9%) than in patients without EV (33.8%) or those with proximal EV (25.0%). Non-invasive fibrosis markers (liver stiffness, FIB-4, Forns index, FonLiver risk score) were significantly elevated in patients with distal EV (all p<0.05), despite similar biochemical profiles.CONCLUSIONDistal EV are frequent and characterize a distinct hemodynamic phenotype, featuring elevated Fontan pathway pressures, severe hepatic fibrosis, portal hypertension, and a hyperdynamic circulatory state.","PeriodicalId":177,"journal":{"name":"Hepatology","volume":"155 1","pages":""},"PeriodicalIF":13.5,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144684173","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}