Liver International最新文献

{"title":"Lactulose for Preventing Overt Hepatic Encephalopathy: Between Evidence and Unresolved Questions.","authors":"Lorenzo Ridola, Stefania Gioia, Silvia Nardelli","doi":"10.1111/liv.70820","DOIUrl":"10.1111/liv.70820","url":null,"abstract":"","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"46 8","pages":"e70820"},"PeriodicalIF":6.2,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13398014/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148579271","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to 'COVID-19 Vaccination Effectiveness and Clinical Outcomes in Chronic Liver Disease: A Nationwide Retrospective Cohort Study'.","authors":"","doi":"10.1111/liv.70801","DOIUrl":"10.1111/liv.70801","url":null,"abstract":"","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"46 8","pages":"e70801"},"PeriodicalIF":6.2,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13366441/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148437235","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Catecholamines Activate a Tumour Progression Program in Differentiated Tumour Hepatocytes.","authors":"Elise Lelou, Claudine Rauch, Hélène Dubois-Pot-Schneider, Marjorie Dufresne, Abolfazl Zekri Yazdi, Maelle Guillout, Luis Cano, Lise Desquilles, Nicolas Nesseler, Marc Bourgeois, Claude Bendavid, Julie Massart, Orlando Musso, Anne Corlu, Caroline Aninat","doi":"10.1111/liv.70775","DOIUrl":"10.1111/liv.70775","url":null,"abstract":"<p><strong>Background and aims: </strong>The sympathetic nervous system is involved in the progression and aggressiveness of several cancers, including hepatocellular carcinoma (HCC). However, the specific effects of sympathetic innervation and catecholamines on tumour hepatocyte behaviour remain poorly understood. In this study, we aimed to investigate the role of sympathetic fibres and catecholamines in the progression of HCC.</p><p><strong>Methods: </strong>The distribution of sympathetic nerves was mapped in 10 human HCC samples using multiplex immunofluorescence labeling. Adrenergic receptors (ADR) and enzymes involved in catecholamine degradation were assessed in three HCC (HepaRG, BC2, Huh-7) and one hepatoblastoma (HepG2) cell lines. The impact of catecholamines on gene and protein expression and metabolic pathways was assessed in differentiated HepaRG-hepatocytes, and the results were verified in primary human hepatocyte (PHH) cultures. The clinical relevance of the findings was evaluated in two transcriptomics datasets.</p><p><strong>Results: </strong>Abundant and tortuous sympathetic fibres were detected in non-tumour liver tissues adjacent to the HCC invasion front. Differentiated HepaRG-hepatocytes expressed both α₁- and β₂-ADR and metabolized catecholamines to normetanephrine, metanephrine, and vanillylmandelic acid. In these cells, catecholamine exposure activated inflammation, cell proliferation, and extracellular matrix remodelling pathways associated with retro-differentiation and primed epithelial-to-mesenchymal transition. The catecholamine-induced program was detected in aggressive, ECM/STEM HCC subclasses with poor patient prognosis.</p><p><strong>Conclusions: </strong>Catecholamines induce an aggressive phenotype in differentiated tumour hepatocytes localized at the invasive front, suggesting their involvement in cancer progression. Understanding the interplay between the sympathetic nervous system and HCC may offer novel therapeutic opportunities.</p>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"46 8","pages":"e70775"},"PeriodicalIF":6.2,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13342482/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148405212","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Viscoelastic Tests in Cirrhotic Patients Undergoing Invasive Procedures: A Systematic Review and Meta-Analysis of RCTs.","authors":"Andrea Boccatonda, Elena Campello, Angela Napolitano, Antonella Bray, Chiara Simion, Carla Serra, Fabio Piscaglia, Luca Spiezia, Paolo Simioni","doi":"10.1111/liv.70782","DOIUrl":"10.1111/liv.70782","url":null,"abstract":"<p><strong>Background and aims: </strong>Bleeding risk in cirrhotic patients undergoing invasive procedures is traditionally assessed using conventional coagulation tests, which poorly reflect the rebalanced haemostatic state of cirrhosis and often lead to unnecessary transfusions. Viscoelastic testing (VET) provides a global assessment of coagulation and may enable more rational transfusion strategies. We performed a systematic review and meta-analysis of randomised controlled trials (RCTs) to evaluate the efficacy and safety of VET-guided transfusion strategies in this setting.</p><p><strong>Methods: </strong>We systematically searched PubMed, Embase and Scopus from inception to 10 April 2026. RCTs comparing VET-guided versus standard-of-care transfusion strategies in cirrhotic patients undergoing invasive procedures were included. Primary outcome was procedure-related bleeding; secondary outcomes included transfusion requirements. Risk ratios (RRs) with 95% confidence intervals (CIs) were pooled using the Mantel-Haenszel method.</p><p><strong>Results: </strong>Six RCTs including 296 patients were analysed. Procedure-related bleeding was rare and did not differ between groups (RR 0.74, 95% CI 0.24-2.31; I² = 0%). In contrast, VET-guided strategies significantly reduced transfusion requirements, including any blood product transfusion (RR 0.33, 95% CI 0.26-0.44; I² = 56%), platelet transfusion (RR 0.20, 95% CI 0.13-0.32; I² = 40%), any fresh frozen plasma (FFP) exposure (RR 0.40, 95% CI 0.28-0.57; I² = 63%) and FFP-only transfusion (RR 0.22, 95% CI 0.10-0.46; I² = 81%).</p><p><strong>Conclusions: </strong>VET-guided transfusion strategies significantly reduce blood product utilisation without increasing bleeding risk in cirrhotic patients undergoing invasive procedures. These findings support a shift towards a physiology-based approach to haemostasis, with potential benefits for patient safety and resource optimisation.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov identifier: CRD420261382437.</p>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"46 8","pages":"e70782"},"PeriodicalIF":6.2,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148405276","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Machine Learning Predicts Treatment Response and Prognostic Pathways From Whole-Blood Transcriptome in Primary Biliary Cholangitis.","authors":"Hussain Syed, Ning Sun, Doaa Waly, Varinder Verma, Matthew Smith, David Shapiro, Mary Erickson, Kathy Siminovitch, Mark Swain, Mohammed S Osman, Andrew L Mason","doi":"10.1111/liv.70764","DOIUrl":"10.1111/liv.70764","url":null,"abstract":"<p><strong>Background and aims: </strong>Prognostic biomarkers that link disease progression and/or responses to therapeutic interventions in patients with primary biliary cholangitis (PBC) remain undefined. In this study, we used a machine learning (ML) approach with whole-blood transcriptomic data to predict clinical outcomes in response to obeticholic acid (OCA) and disease progression.</p><p><strong>Methods: </strong>We developed an ML model that incorporated whole-blood RNA-seq analyses using longitudinal samples from the POISE study (discovery cohort) and a prospective group of PBC patients who remained unchanged or progressed to liver transplantation/hepatic decompensation (independent validation cohort). The model identified 1200 candidate genes predictive of outcomes, which were investigated using pathway analysis. A genetic algorithm refined the panel to a 105-gene list that was trained on the POISE end-of-treatment cohort.</p><p><strong>Results: </strong>The algorithm's generalisability was tested by assessing the baseline POISE patients as responders or non-responders to OCA (AUROC 0.93) and independently validated by differentiating liver disease-related survival between progressors and non-progressors (AUROC 0.94). Pathway analysis of the ML candidate genes identified enrichment of FXR regulated genes, autoimmune disease-related inflammation, immune regulation, fibrosis and integrated stress response pathways as prognostically related to PBC. When we compared these ML-derived prognostic pathways with RNA-seq analysis of PBC versus healthy controls, the most relevant transcripts were those involved in the integrated stress response and metabolic remodelling in PBC.</p><p><strong>Conclusion: </strong>The ML-derived score links both prognostic and disease pathogenesis pathways and can be used in future studies to better understand the pathophysiology and management of PBC.</p>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"46 8","pages":"e70764"},"PeriodicalIF":6.2,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13369844/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148447728","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The REACT Score and the Evolving Phenotypes of Decompensated Cirrhosis","authors":"Yolanda Sánchez-Torrijos,&nbsp;Javier Ampuero","doi":"10.1111/liv.70830","DOIUrl":"https://doi.org/10.1111/liv.70830","url":null,"abstract":"","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"46 9","pages":""},"PeriodicalIF":6.2,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148647792","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Steatosis in Cirrhosis: A Prognostic Marker for Liver-Related Outcomes in Metabolic-Dysfunction Associated Steatotic Liver Disease","authors":"Yiying Pei,&nbsp;Yayun Ren,&nbsp;Dean Tai,&nbsp;Hai-Yang Yuan,&nbsp;Ren-Yi Su,&nbsp;Muhammad Zulqarnain,&nbsp;Pavitratha Puspanathan,&nbsp;Sanjiv Mahadeva,&nbsp;Wei-Qiang Leow,&nbsp;Tony Lim,&nbsp;Chee-Kiat Tan,&nbsp;Pik-Eu Jason Chang,&nbsp;Ming-Hua Zheng,&nbsp;Chan Wah Kheong,&nbsp;George Boon Bee Goh","doi":"10.1111/liv.70828","DOIUrl":"https://doi.org/10.1111/liv.70828","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aims</h3>\u0000 \u0000 <p>The predictive ability of histological components in Metabolic Dysfunction Associated Steatotic Liver Disease (MASLD) has not been well studied. Here, we look at the ability of digital pathology through the components of qFIBs (qfibrosis, qInflammation, qBallooning, qSteatosis) in predicting the risk of Major Adverse Liver Outcomes (MALO).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method</h3>\u0000 \u0000 <p>235 liver biopsy images were retrieved, and the composite end point of MALO, including overall death, hepatic encephalopathy (HE), ascites, variceal haemorrhage and hepatocellular carcinoma (HCC), was studied in parallel with the Non-alcoholic Steatohepatitis Clinical Research Network (NASH-CRN) score and qFIBs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The predictive power of qFibrosis for MALOs (qF3/4 vs. qF0/1/2, HR 6.64, 95% CI 1.69–26.06, log rank <i>p</i>-value 0.001) was comparable to NASH-CRN (F3/4 vs. F0/1/2, HR 7.02, 95% CI 2.37–20.84, log rank <i>p</i>-value &lt; 0.001). Interestingly, a lower steatosis grade, rather than being a protective factor, correlated with poorer outcomes for both the qFIBs (qS0/1 vs. qS2/3 HR 17.24, 95% CI 3.12–95.32, log rank <i>p</i> value &lt; 0.001) and NASH-CRN (S0/1 vs. S2/3 HR 6.30, 95% CI 2.14–18.61, log rank <i>p</i> value &lt; 0.001). Lower qSteatosis scores of qS1 and below among the cirrhotic group (<i>n</i> = 35) also showed a six-fold higher risk of MALOs (&lt; 1.50 vs. ≥ 1.50, HR 6.40, 95% CI 1.08–37.92, log rank <i>p</i> value &lt; 0.011), likely due to the reduction of steatosis in the cachectic state of a patient with end stage liver disease. Samples with lower percentages of macro-vesicular vacuoles had a fourfold increased risk of MALOs (HR 4.41, 95% CI 1.06–18.43, log rank <i>p</i> value 0.017).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Lower steatosis grades in higher fibrosis stages correlate significantly with the occurrence of MALO. Our findings instigate exploration of the process of fat resorption in MASLD and its relation to outcomes.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"46 9","pages":""},"PeriodicalIF":6.2,"publicationDate":"2026-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148617280","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reassessing the Prognostic Value of Circulating Extracellular Vesicles in Cirrhosis","authors":"Yang Yang,&nbsp;Shuxiong Ge","doi":"10.1111/liv.70829","DOIUrl":"https://doi.org/10.1111/liv.70829","url":null,"abstract":"","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"46 9","pages":""},"PeriodicalIF":6.2,"publicationDate":"2026-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148617281","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Autophagy in MASLD: A Metabolic and Precision Medicine Perspective","authors":"Alessandra Cazzaniga,&nbsp;Silvia Frigo,&nbsp;Alessandro Cherubini,&nbsp;Eniada Rrapaj,&nbsp;Luca Valenti","doi":"10.1111/liv.70816","DOIUrl":"10.1111/liv.70816","url":null,"abstract":"<p>Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver condition worldwide and a major contributor to cirrhosis and hepatocellular carcinoma (HCC). While metabolic triggers such as obesity and insulin resistance are key drivers of MASLD, growing evidence has identified defects in intracellular quality control—namely impaired autophagy—as central mechanisms governing disease progression. Autophagy, including selective lipophagy and mitophagy, plays a crucial role in hepatic lipid turnover and mitochondrial homeostasis. In MASLD, disruption of these processes contributes to lipid accumulation and oxidative stress, leading to hepatocellular damage (ballooning), fibrogenesis, and HCC. Experimental studies linked impaired autophagic flux to liver injury, and emerging evidence from human genetics suggests that inter-individual inherited variation influences MASLD susceptibility by impairing autophagy. Specifically, main genetic MASLD modifiers such as the p.I148M variant of Patatin-like phospholipase domain-containing protein 3 (<i>PNPLA3</i>) and loss-of-function and hypomorphic variants in autophagy-related gene 7 (<i>ATG7</i>), a core autophagy gene, predispose to ballooning, fibrosis, and HCC. By outlining emerging therapies that restore autophagic flux and reduce steatosis, lipotoxicity, and fibrosis, we propose an integrated precision-medicine model based on genetics and autophagy dynamics biomarkers, offering a new framework for personalized therapeutics.</p>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"46 9","pages":""},"PeriodicalIF":6.2,"publicationDate":"2026-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/liv.70816","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148604147","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"p38 Inhibitor SB203580 Inhibits HEV Infection and Prevents HEV-Related Adverse Pregnancy Outcomes in a Pregnant Rabbit Model","authors":"Manyu Li,&nbsp;Wenjun Wan,&nbsp;Zeyu Song,&nbsp;Pengfei Wang,&nbsp;Wenwen Sun,&nbsp;Qiyu He,&nbsp;Haiwei Zhou","doi":"10.1111/liv.70811","DOIUrl":"https://doi.org/10.1111/liv.70811","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aims</h3>\u0000 \u0000 <p>Hepatitis E virus (HEV) infection during pregnancy can lead to severe adverse pregnancy outcomes including stillbirth, preterm birth, abortion, maternal death, and vertical transmission. Off-label use of ribavirin or pegylated interferon-α is proved effective for treating HEV infection, but they are both contraindicated for pregnant women. A safe and effective treatment against HEV infection during pregnancy is urgently needed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We used JEG-3 choriocarcinoma cells to investigate the p38-MAPK signalling pathway in HEV replication. The cells were treated with varying concentrations of SB203580, a selective p38-MAPK inhibitor. For in vivo validation, HEV-infected pregnant rabbits were treated with SB203580. HEV replication, cytokine secretion, apoptosis, and pathological changes were measured. The effects on pregnancy outcomes, including vertical transmission, were also monitored.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In this study, with a HEV-infected choriocarcinoma cell line, the JEG-3 cell model, we found that HEV infection significantly altered the expression patterns of the p38-MAPK signalling pathway. SB203580 can inhibit HEV replication and reduce the secretion of proinflammatory cytokines and apoptosis in vitro. Further in vivo validation with the HEV-infected pregnant rabbit model also revealed that SB203580 treatment during pregnancy significantly reduced the viral load in faeces and serum, the secretion of proinflammatory cytokines, and apoptosis in placental tissues. Most importantly, SB203580 is not only safe but can also effectively prevent HEV-related adverse pregnancy outcomes in pregnant rabbits and vertical transmission of HEV to pups.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>These results demonstrate that the p38 inhibitor SB203580 is an effective compound with potential as a therapeutic candidate against HEV infection during pregnancy.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"46 9","pages":""},"PeriodicalIF":6.2,"publicationDate":"2026-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148616181","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}