JHEP Reports最新文献

{"title":"Point-of-care ultrasound of the inferior vena cava for intravascular volume assessment during intravenous albumin infusion in patients with cirrhosis","authors":"Daniel Segna , Fabio Brazerol , Pompilia Radu , Gerard Angeles Fite , Jaime Bosch , Annalisa Berzigotti","doi":"10.1016/j.jhepr.2025.101559","DOIUrl":"10.1016/j.jhepr.2025.101559","url":null,"abstract":"<div><h3>Background & Aims</h3><div>Current guidelines recommend intravenous (i.v.) albumin for different indications in decompensated cirrhosis, but iatrogenic hypervolemia following i.v. albumin is increasingly reported. We aimed to characterize intravascular volume status using point-of-care ultrasound (POCUS) of the inferior vena cava (IVC) during passive leg raise (PLR) and i.v. albumin, potentially facilitating clinical management and adjustment of albumin dosage.</div></div><div><h3>Methods</h3><div>This prospective pilot cohort included patients with decompensated cirrhosis requiring i.v. albumin. We assessed changes in minimal and maximal IVC diameters (IVC<sup>min</sup> and IVC<sup>max</sup>, respectively) and collapsibility index (IVCCI) during PLR and after i.v. albumin. We defined severe intravascular volume overload as IVC<sup>max</sup> >2.1 cm and IVCCI <20%. Clinical outcomes were recorded until 3 months after POCUS.</div></div><div><h3>Results</h3><div>We included 81 measurements in 55 patients (70.9% men; median age 62 years; 58.2% alcohol-related cirrhosis; median Child-Pugh score 9 points; 89.1% paracentesis; median 40 g i.v. albumin; 5.5 L ascites)<strong>.</strong> We found a significant increase in IVC diameters both during PLR (change in mean [Δ] IVC<sup>min</sup> +20.7%, Δ IVC<sup>max</sup> +14.1%, <em>p</em> <0.01) and after i.v. albumin (Δ IVC<sup>min</sup> +58.8%, Δ IVC<sup>max</sup> +48.2%, <em>p</em> <0.01). There was a significant decrease in IVCCI during PLR (relative Δ -11.1%, <em>p</em> <0.01) and after i.v. albumin (relative Δ -18.0%, <em>p</em> <0.01). Potential severe intravascular volume overload occurred on 17 occasions (21%) after i.v. albumin, more frequently in women than in men (40% <em>vs.</em> 15.7%, <em>p</em> <0.01), and showed higher cumulative incidence rates in variceal bleeding after 1 (16.7% <em>vs.</em> 0%, <em>p</em> = 0.01) and 3 months (18.2% <em>vs.</em> 0%, <em>p</em> = 0.01).</div></div><div><h3>Conclusions</h3><div>Potential severe intravascular volume overload after i.v. albumin was detected in every fifth patient with decompensated cirrhosis. Thus, there is a need to develop strategies for individualizing volume management in patients with decompensated cirrhosis.</div></div><div><h3>Impact and implications</h3><div>Iatrogenic volume overload after albumin infusions in patients with cirrhosis is a potentially harmful side effect, but no policy for monitoring intravascular volume overload using non-invasive tools has been suggested so far. New-onset potential volume overload was detected in almost one out of five men and four out of 10 women and was associated with increases in N-terminal prohormone of brain natriuretic peptide, lower mean arterial pressure during albumin infusion, and higher serum sodium levels. Our results from this proof-of-concept study emphasize the need for larger prospective cohort studies to validate our findings and introduce strategies","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"7 11","pages":"Article 101559"},"PeriodicalIF":7.5,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145218820","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":"RAC1 as a novel therapeutic target for acute liver failure","authors":"Barbara Bueloni ,&nbsp;Esteban Fiore ,&nbsp;María José Cantero ,&nbsp;Lucia Lameroli ,&nbsp;Catalina Atorrasagasti ,&nbsp;Matías Ciarlantini ,&nbsp;Andrea Barquero ,&nbsp;Lucía Gandolfi Donadio ,&nbsp;Daiana Ganiewich ,&nbsp;Francisco Orozco ,&nbsp;Martín Fauda ,&nbsp;Julieta Comin ,&nbsp;Ali Canbay ,&nbsp;Juan Bayo ,&nbsp;Guillermo Mazzolini","doi":"10.1016/j.jhepr.2025.101547","DOIUrl":"10.1016/j.jhepr.2025.101547","url":null,"abstract":"<div><h3>Background &amp; Aims</h3><div>The Rho GTPase RAC1 regulates key processes in acute liver failure (ALF), including oxidative stress and inflammation. We aimed to evaluate the therapeutic potential of RAC1 inhibition in ALF.</div></div><div><h3>Methods</h3><div>Ingenuity Pathway Analysis and Gene Ontology analysis were performed on transcriptomic datasets from patients with ALF (GSE38941 and GSE80751). ALF was induced in mice using concanavalin A, acetaminophen, or D-galactosamine/lipopolysaccharide (n = 10-21/group). The RAC1 pharmacological inhibitor 1D-142 was used <em>in vivo</em> and <em>in vitro</em>. Hepatocytes and macrophages, from primary cultures and cell lines, were analyzed. RNA-sequencing data from ALF mouse livers (n = 3/group) were integrated with human datasets. Human liver explants (n = 6) were treated <em>in vitro</em> with 1D-142.</div></div><div><h3>Results</h3><div>RAC1 emerged as an upstream regulator correlating with immune activation and oxidative stress responses (<em>p &lt;</em>0.05) in human ALF samples. Administration of 1D-142 ameliorated liver injury in murine ALF models when administered at early or late stages post-injury (<em>p &lt;</em>0.05). 1D-142 treatment diminished reactive oxygen species formation (<em>p &lt;</em>0.01), inflammatory cell migration (<em>p &lt;</em>0.001), cytokine production (<em>p &lt;</em>0.05) and hepatocyte death (<em>p &lt;</em>0.05). Liver transcriptomics revealed that RAC1 inhibition modulated key dysregulated pathways in ALF. Human ALF liver explants treated with 1D-142 showed reduced necrosis (<em>p &lt;</em>0.05) and reduced expression of pro-inflammatory genes (<em>p &lt;</em>0.01).</div></div><div><h3>Conclusions</h3><div>RAC1 drives sterile inflammation and oxidative stress in ALF. Its pharmacological inhibition protects against liver injury in preclinical models and human explants, supporting RAC1 as a potential therapeutic target in ALF.</div></div><div><h3>Impact and implications</h3><div>Acute liver failure (ALF) is a life-threatening condition characterized by severe inflammation and oxidative stress for which there are limited treatment options. Our study provides strong scientific justification for targeting the RAC1 protein, demonstrating that its pharmacological inhibition with 1D-142 reduces liver injury, immune cell infiltration, and oxidative damage in murine models of ALF and in human liver explants. These findings identify RAC1 as a novel therapeutic target and provide translational support for its potential clinical application in ALF. RAC1-targeted therapy merits further studies in clinical settings.</div></div>","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"7 11","pages":"Article 101547"},"PeriodicalIF":7.5,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145218762","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":"Young-onset biliary tract cancers: Characteristics, treatment patterns, and patient outcomes","authors":"Thomas Pudlarz ,&nbsp;Anthony Turpin ,&nbsp;Natalia Soledad Tissera ,&nbsp;Marc Hilmi ,&nbsp;Leony Antoun ,&nbsp;Florian Castet ,&nbsp;Daniel Lopez-Valbuena ,&nbsp;Adrien Rousseau ,&nbsp;Matthieu Delaye ,&nbsp;Maximiliano Gelli ,&nbsp;Antoine Italiano ,&nbsp;Marine Valéry ,&nbsp;Anthony Tarabay ,&nbsp;Valérie Boige ,&nbsp;David Malka ,&nbsp;Eduardo García-Galea ,&nbsp;Gloria Castillo ,&nbsp;Tian V. Tian ,&nbsp;Antoine Hollebecque ,&nbsp;Cristina Smolenschi ,&nbsp;Alice Boilève","doi":"10.1016/j.jhepr.2025.101550","DOIUrl":"10.1016/j.jhepr.2025.101550","url":null,"abstract":"<div><h3>Background &amp; Aims</h3><div>The incidence of biliary tract cancers (BTC) among young individuals (≤50 years) is currently rising. We aimed to investigate the clinical, therapeutic and molecular characteristics and outcomes of young-onset BTC (YO-BTC).</div></div><div><h3>Methods</h3><div>Patients with histologically confirmed BTC treated at Gustave Roussy (France) and Vall d’Hebron Institute of Oncology (Spain) were categorized as YO-BTC (≤50 years old), average-onset (AO-BTC; 51-69 years old), and late-onset (LO-BTC; ≥70 years old). The primary endpoint was overall survival (OS). The secondary endpoint was the growth modulation index (GMI), <em>e.g</em>., the ratio of progression-free survival (PFS) with the targeted therapy line to the PFS of the n-1 line.</div></div><div><h3>Results</h3><div>Among 1,023 patients with BTC, 184 (18%) had YO-BTC, 561 (54.8%) had AO-BTC, and 278 (27.2%) had LO-BTC. Median OS in metastatic patients was longer in the YO group (22 months; 95% CI 18–26) than in the AO group (18 months; 95% CI 17–20; <em>p</em> = 0.010) or LO group (15 months; 95% CI 13–17; <em>p</em> &lt;0.001), despite a higher tumor burden in YO-BTC. <em>FGFR2</em> fusions were more frequent in YO-BTC (12% <em>vs</em>. 5.7% AO and 4.3% LO; <em>p</em> = 0.038). Patients with YO-BTC received more targeted therapies as second or later lines (48%, 37%, and 29% for YO, AO, and LO; <em>p</em> = 0.020). Among patients receiving molecular-matched treatments, GMI &gt;1.33 was more frequent in YO-BTC (61.1%, 39.2%, and 33.3% for YO, AO, and LO; <em>p</em> = 0.044), although no differences in PFS or OS were observed.</div></div><div><h3>Conclusion</h3><div>Patients with YO-BTC have improved outcomes in the metastatic setting. The YO-BTC group is enriched for <em>FGFR2</em> fusions, highlighting opportunities for precision oncology-based approaches.</div></div><div><h3>Impact and implications</h3><div>The study underscores the scientific justification for investigating age-related differences in biliary tract cancers, revealing that patients with young-onset biliary tract cancer have improved survival outcomes and a higher prevalence of actionable molecular alterations, particularly <em>FGFR2</em> fusions. Physicians can apply these results by incorporating molecular profiling and targeted therapies earlier in the treatment plan for younger patients, potentially improving their prognosis and quality of life. However, it is crucial to consider the study's limitations, such as the retrospective design and potential selection bias, to avoid overgeneralization and ensure appropriate application of the findings in clinical practice and future research.</div></div>","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"7 11","pages":"Article 101550"},"PeriodicalIF":7.5,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145157138","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":"Epidemiology, comorbidities, treatments and outcomes of autoimmune liver diseases: A French nationwide study","authors":"Christophe Corpechot ,&nbsp;Pierre Hornus ,&nbsp;Mallory Cals ,&nbsp;Pierre Rinder ,&nbsp;Théo Marcille ,&nbsp;Amina Malek ,&nbsp;Karima Ben Belkacem ,&nbsp;Farid Gaouar ,&nbsp;Yasmina Chabane ,&nbsp;Pierre-Antoine Corret ,&nbsp;Paola Squarzoni ,&nbsp;Pierre-Antoine Soret ,&nbsp;Sara Lemoinne ,&nbsp;Olivier Chazouillères ,&nbsp;Angela Leburgue","doi":"10.1016/j.jhepr.2025.101546","DOIUrl":"10.1016/j.jhepr.2025.101546","url":null,"abstract":"<div><h3>Background &amp; Aims</h3><div>The epidemiology, clinical management, and prognosis of autoimmune liver diseases (AILDs) – including autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), and primary sclerosing cholangitis (PSC) – vary according to geography and time. This study aimed to provide a comprehensive evaluation of the burden of AILDs in a Western European country.</div></div><div><h3>Method</h3><div>A nationwide retrospective study was performed using the French national health data system from 2009 to 2019. AIH and PBC were identified via ICD-10 codes, while PSC was defined using composite criteria. Prevalence, incidence, geographic patterns, comorbidities, treatments, liver transplant, and standardized mortality ratio were assessed.</div></div><div><h3>Results</h3><div>A total of 30,255 AILD cases were identified, representing 5% of chronic liver disease cases. The prevalence per 100,000 inhabitants was 14.9 for AIH, 15.0 for PBC, and 4.2 for PSC. Geographic variation was observed, with significant regional clustering of AIH and PBC cases. The incidence of AIH increased significantly over time, whereas that of PBC and PSC declined. Patients with AILDs exhibited higher rates of diabetes and all-cause malignancies compared to the general population. Ursodeoxycholic acid was underprescribed in PBC, while corticosteroids were frequently overused in both PBC and PSC, and ursodeoxycholic acid in AIH. Liver transplantation was performed four times more often in PSC than in either AIH or PBC. All AILDs were associated with elevated 10-year standardized mortality ratios: 1.80 for AIH, 1.74 for PBC, and 2.59 for PSC.</div></div><div><h3>Conclusion</h3><div>These findings confirm the rising incidence of AIH – but not PBC or PSC – the non-random geographic distribution of AIH and PBC, a higher risk of diabetes and cancer across all AILDs, and persistent excess mortality despite current treatment options.</div></div><div><h3>Impact and implications</h3><div>The true burden of autoimmune liver diseases (AILDs) remains inadequately characterized. In this extensive study conducted in France, based on health insurance and hospital records collected between 2009 and 2019, we characterized the epidemiology, comorbidities, treatments and outcomes of autoimmune hepatitis, primary biliary cholangitis and primary sclerosing cholangitis. We confirm the rising incidence of AIH, the non-random geographic distribution of both autoimmune hepatitis and primary biliary cholangitis, the elevated risk of diabetes and cancer, and a persistently increased mortality across all AILDs – most notably in primary sclerosing cholangitis, where both excess mortality and the need for liver transplantation is higher than in other AILDs. These findings highlight the persistent gaps and unmet needs in the management of AILDs.</div></div>","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"7 11","pages":"Article 101546"},"PeriodicalIF":7.5,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145218761","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":"Mildly elevated liver lipid content is characterised by reduced insulin sensitivity","authors":"Nelli Tuomola ,&nbsp;Eleni Rebelos ,&nbsp;Aino Latva-Rasku ,&nbsp;Marco Bucci ,&nbsp;Heidi Immonen ,&nbsp;Virva Saunavaara ,&nbsp;Saara Laine ,&nbsp;Tanja Sjöros ,&nbsp;Taru Garthwaite ,&nbsp;Juho R.H. Raiko ,&nbsp;Lilian Fernandes Silva ,&nbsp;Kirsi A. Virtanen ,&nbsp;Jarna C. Hannukainen ,&nbsp;Mika Ala-Korpela ,&nbsp;Kari K. Kalliokoski ,&nbsp;Ilkka H.A. Heinonen ,&nbsp;Pirjo Nuutila ,&nbsp;Miikka-Juhani Honka","doi":"10.1016/j.jhepr.2025.101535","DOIUrl":"10.1016/j.jhepr.2025.101535","url":null,"abstract":"<div><h3>Background &amp; Aims</h3><div>Recently, a new cut-off of ≤1.85% was proposed for normal liver lipid content based on a large population trial. In that study, people having liver lipid between 1.86% and the currently used magnetic resonance spectroscopy-specific upper limit of 5.56% had lower insulin sensitivity (higher homeostatic model assessment for insulin resistance [HOMA-IR]) when compared with people with ≤1.85% of liver lipid. We aimed to build upon these findings by evaluating differences in tissue-specific insulin sensitivity between individuals having low (LL; ≤1.85%) or mildly elevated (MEL; &gt;1.85% and ≤5.56%) liver lipids.</div></div><div><h3>Methods</h3><div>Combining data from previous studies, 202 White European individuals without diabetes were included in this cross-sectional study. Liver lipids were measured with magnetic resonance spectroscopy. Endogenous glucose production (EGP; N = 96) was measured by hyperinsulinaemic–euglycaemic clamp combined with [¹⁸F]fluorodeoxyglucose positron emission tomography, and adipose tissue insulin resistance by the product of fasting free fatty acids and insulin (N = 197). Serum metabolites were measured using nuclear magnetic resonance metabolomics (N = 152).</div></div><div><h3>Results</h3><div>The MEL group had higher EGP during hyperinsulinemia (2.7 [-0.4; 7.5] <em>vs.</em> -0.2 [-4.3; 5.3] μmol/kg/min, <em>p</em> = 0.041) and higher adipose tissue insulin resistance at fasting (28.4 [16.6; 37.5] <em>vs.</em> 17.6 [9.6; 26.9] pmol/L × mmol/L, <em>p</em> = 0.037) compared with the LL group. In addition, serum triglycerides and branched-chain amino acids were elevated (false discovery rate &lt;0.05) compared with the LL group.</div></div><div><h3>Conclusions</h3><div>People with MEL had lower hepatic and adipose tissue insulin sensitivity and adverse changes in metabolites when compared with people with LL. These findings support a lower upper limit for normal liver lipids in White Europeans. In addition, the data indicate that impaired suppression of EGP during hyperinsulinaemia and insulin resistance of lipolysis are early features in the cascade of systemic insulin resistance.</div></div><div><h3>Impact and implications</h3><div>It has long been known that a substantially increased liver lipid content is connected to an increase in cardiovascular risk factors. From the perspective of both researchers and clinicians, it is important to know that even slightly elevated liver lipid content is associated with many adverse metabolic changes. Further research is needed to confirm if intervening early in the development of fatty liver with lifestyle intervention and, if necessary, drug treatment at an early stage, provide benefit for the prevention of metabolic diseases in the future.</div></div><div><h3>Clinical Trials Registration</h3><div>The study has been registered at <span><span>ClinicalTrials.gov</span><svg><path></path></svg></span> (NCT03310502).</div></div>","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"7 11","pages":"Article 101535"},"PeriodicalIF":7.5,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145218824","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":"Kinase suppressor of Ras 1 (KSR1) promotes liver carcinogenesis via activation of the RAS/RAF/MEK/ERK signaling pathway","authors":"Hyuk Moon,&nbsp;Hyunjung Park,&nbsp;Sangjik Lee,&nbsp;Soyun Lee,&nbsp;Mihyeon Jun,&nbsp;Jaehun Lee,&nbsp;Jiyeon Baek,&nbsp;Hyerin Park,&nbsp;Jieun Bang,&nbsp;Simon Weonsang Ro","doi":"10.1016/j.jhepr.2025.101536","DOIUrl":"10.1016/j.jhepr.2025.101536","url":null,"abstract":"<div><h3>Background &amp; Aims</h3><div>Mutations in the RAS and RAF genes are frequently observed in various human cancers, leading to persistent activation of the RAS/RAF/MEK/ERK signaling pathway and driving tumorigenesis. Intriguingly, hepatocellular carcinoma (HCC) reveals rare mutations in <em>RAS</em> and <em>RAF</em>, despite frequent activation of the RAS/RAF/MEK/ERK signaling. Here, we identify kinase suppressor of Ras 1 (KSR1) as a pivotal player in pathway activation and tumorigenesis in the liver.</div></div><div><h3>Methods</h3><div>Gene expression data from human cancers were analyzed using publicly available databases. HCC cell lines stably expressing KSR1 were established to evaluate RAS/RAF/MEK/ERK signaling activity. Liver cancer was induced in C57BL/6 male mice via hydrodynamic tail vein injection. Tumor-bearing livers were formalin-fixed and processed for H&amp;E staining and immunohistochemistry.</div></div><div><h3>Results</h3><div>KSR1 expression was frequently upregulated in human HCC (n = 366, <em>p</em> &lt;0.001) and strongly associated with activation of the RAS/RAF/MEK/ERK signaling pathway (n = 50, <em>p</em> &lt;0.001). Ectopic expression of KSR1 led to increased phosphorylation of MEK1/2 and ERK1/2 in HCC cells and murine livers, confirming activation of the signaling pathway. Overexpression of KSR1 in murine livers in conjunction with P53 inactivation or c-Myc overexpression led to the development of HCC, which exhibited activated RAS/RAF/MEK/ERK signaling (n = 10 mice per group). Notably, the degrees of MEK phosphorylation and tumorigenesis in the liver induced by KSR1 overexpression were equivalent to those by an activated RAF, the bona fide kinase of MEK1/2. Intriguingly, liver tumors induced by activated RAS or RAF were efficiently suppressed by KSR1 knockdown or pharmacological inhibition of KSR1 (n = 10, <em>p</em> &lt;0.01), highlighting the potential of KSR1 as a therapeutic target for cancers driven by pathway activation.</div></div><div><h3>Conclusions</h3><div>Overexpression of KSR1 activates the RAS/RAF/MEK/ERK signaling pathway and drives hepatic tumorigenesis in the absence of mutations in <em>RAS</em> or <em>RAF</em>.</div></div><div><h3>Impact and implications</h3><div>Our findings identify kinase suppressor of Ras 1 (KSR1) as an oncogenic driver in the liver and a key activator of the RAS/RAF/MEK/ERK signaling pathway. This study enhances our understanding of the role that scaffold proteins play in promoting oncogenic signaling cascades. The successful use of a pharmacological inhibitor of KSR to suppress <em>in vivo</em> tumor growth driven by RAS or RAF highlights the potential of KSR1 as a druggable target.</div></div>","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"7 11","pages":"Article 101536"},"PeriodicalIF":7.5,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145134883","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":"Isolation and immortalization of human portal vein endothelial cells: A novel research tool for studying splanchnic vasculature","authors":"Aina Anton ,&nbsp;Sarah Shalaby ,&nbsp;Júlia Campalans ,&nbsp;Annabel Blasi ,&nbsp;Yiliam Fundora ,&nbsp;Rosa Montañés ,&nbsp;Héctor García-Calderó ,&nbsp;Lixin Sun ,&nbsp;Joana Codina ,&nbsp;Josepmaria Argemí ,&nbsp;Olga Tura-Ceide ,&nbsp;Joan Carles García-Pagán ,&nbsp;Genís Campreciós ,&nbsp;Virginia Hernández-Gea","doi":"10.1016/j.jhepr.2025.101543","DOIUrl":"10.1016/j.jhepr.2025.101543","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background &amp; Aims&lt;/h3&gt;&lt;div&gt;Cirrhosis profoundly impacts extrahepatic vasculature, particularly altering the portal venous system, leading to increased portal pressure, portosystemic collaterals, and portal vein thrombosis, which heightens morbidity and reduces survival in liver disease. Although intrahepatic vascular changes in cirrhosis are well studied, molecular insights into extrahepatic alterations in the splanchnic region remain limited owing to the inaccessibility of the human portal vein and suboptimal preclinical models. Here, we aim to isolate, characterize, and immortalize primary human portal vein endothelial cells (PVECs) to enhance understanding of pathophysiological changes during liver disease and establish a platform for future drug testing.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;PVECs (n = 12) and inferior cava vein (ICV, n = 9) endothelial cells (ECs) were isolated from human portal vein or ICV, obtained during hepatic transplantation, using trypsinization, mechanical scratching, and FACS. EC identity was confirmed through characterization of gene and protein marker expression as well as functional assays assessing angiogenic capacity (tube formation), migratory ability (wound closure), and acetylated low-density lipoprotein uptake. PVECs were immortalized (iPVECs) with lentiviral particles expressing the SV40 large T-antigen.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;Isolated PVECs confirmed classical endothelial morphology and functionality, expressing hallmark proteins and functions. PVECs exhibited a distinct transcriptomic profile from ICVEC and systemic ECs, enriched in pathways for vascular remodeling and stress response. iPVECs retained endothelial identity and preserved the PVEC-specific transcriptomic traits across more than 20 passages.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions&lt;/h3&gt;&lt;div&gt;We successfully isolated, characterized, and immortalized PVECs, creating a novel tool to study splanchnic vascular diseases. These cells retain transcriptomic uniqueness distinct from systemic venous ECs, enabling investigation of vascular dysfunction mechanisms in liver disease and supporting translational research.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Impact and implications&lt;/h3&gt;&lt;div&gt;Portal hypertension and vascular complications are major drivers of morbidity in cirrhosis, yet extrahepatic vascular mechanisms remain poorly understood due to limited access to human portal vein tissue and inadequate models. By isolating, characterizing, and immortalizing primary human portal vein endothelial cells, we establish the first renewable, disease-relevant platform for studying splanchnic vascular biology. These immortalized portal vein endothelial cells preserve endothelial identity and transcriptomic signatures distinct from systemic venous cells, providing unique insights into vascular remodeling and stress responses in liver disease. This resource enables mechanistic discovery and drug testing aimed at improving outcomes in portal hypertension and related c","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"7 10","pages":"Article 101543"},"PeriodicalIF":7.5,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145155329","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":"Editorial Board page","authors":"","doi":"10.1016/S2589-5559(25)00207-1","DOIUrl":"10.1016/S2589-5559(25)00207-1","url":null,"abstract":"","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"7 8","pages":"Article 101528"},"PeriodicalIF":7.5,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144841361","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":"Copyright and information","authors":"","doi":"10.1016/S2589-5559(25)00210-1","DOIUrl":"10.1016/S2589-5559(25)00210-1","url":null,"abstract":"","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"7 8","pages":"Article 101531"},"PeriodicalIF":7.5,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144841363","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":"Targeting fibrosis and steatohepatitis through the metabolism – results from the ESSENCE trial","authors":"Maurice Michel ,&nbsp;Jörn M. Schattenberg","doi":"10.1016/j.jhepr.2025.101492","DOIUrl":"10.1016/j.jhepr.2025.101492","url":null,"abstract":"","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"7 9","pages":"Article 101492"},"PeriodicalIF":7.5,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144749591","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}