Liver International最新文献

{"title":"Alterations in Primary Haemostasis in Patients With Liver Cirrhosis and Bacterial Infection.","authors":"Florentia Athanasaki, Larisa Vasilieva, Efthimia Pavlou, Stavros Formozis, Krystalia Dimitriou, Dimitra Krystallaki, Nikolaos Nektarios Karamanolis, Iliana Mani, Flora Kontopidou, Emilia Hadziyannis, Efrosyni Nomikou, Alexandra Alexopoulou","doi":"10.1111/liv.70649","DOIUrl":"10.1111/liv.70649","url":null,"abstract":"<p><strong>Background/aims: </strong>There is a controversy regarding hyporesponsiveness of platelet (PLT) aggregation in liver cirrhosis (LC). This study aimed to assess alterations in PLT aggregation and von Willebrand factor (vWF)-related parameters, as well as their prognostic role in bacterial infection (BI) superimposed on LC.</p><p><strong>Methods: </strong>PLT aggregation was assessed using thromboelastography PLT mapping assay. vWF antigen (vWF:Ag), vWF Ristocetin cofactor (vWF:RCo) and FVIII levels were also measured in patients with decompensated cirrhosis and BI (DC + BI), stable decompensated cirrhosis (SDC) and infection without LC (control group). The prognostic value of PLT aggregation was evaluated only in the DC + BI group.</p><p><strong>Results: </strong>Seventy-one patients were enrolled in the DC + BI, 38 in the SDC and 20 in the control group. Patients with DC + BI had significantly reduced PLT aggregation in response to adenosine diphosphate (ADP) compared with those with SDC (p = 0.042). Elevated vWF:Ag, vWF:RCo and FVIII levels accompanied impaired PLT aggregation_(ADP) (p = 0.002, p = 0.003 and p = 0.042, respectively). Within the DC + BI group, patients with organ failure exhibited lower PLT aggregation_(ADP). In survival analysis of the DC + BI group, non-survivors demonstrated reduced ADP-induced PLT aggregation, which showed high accuracy in predicting mortality (AUROC = 0.851). In a multivariate cox regression model including age, gender, MELD score and PLT aggregation_(ADP), age (p = 0.048), gender (p = 0.023) and PLT aggregation_(ADP) (p < 0.001) were independently associated with 30-day mortality.</p><p><strong>Conclusions: </strong>ADP-induced PLT aggregation is impaired in DC with infection in a stepwise manner according to infection severity and has prognostic implications, as it is associated with 30-day mortality. Elevated vWF:Ag, vWF:RCo and FVIII levels accompany PLT hyporesponsiveness.</p>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"46 5","pages":"e70649"},"PeriodicalIF":5.2,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147723169","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":"The MASLD Journey in the General Population: Linkage-to-Care and Patient-Reported Uptake of Fibrosis Risk Assessment.","authors":"Joo Hyun Oh, Jun-Hyuk Lee, Sang Bong Ahn, Eunjoo Kwon, Eileen L Yoon, Hyo Young Lee, Seon Cho, Dae Won Jun","doi":"10.1111/liv.70658","DOIUrl":"10.1111/liv.70658","url":null,"abstract":"<p><strong>Background & aims: </strong>Despite the growing burden of steatotic liver disease (SLD), real-world evidence on patient-reported post-diagnostic care pathways and fibrosis risk assessment remains limited. We aimed to describe the patient-reported care pathway from initial diagnosis to subsequent follow-up and fibrosis assessment among individuals with self-reported SLD, including those meeting at-risk criteria in a population-based survey sample.</p><p><strong>Methods: </strong>A web-based survey was conducted among Korean adults aged ≥ 19 years recruited from an established online research panel, using quota strata to approximate the national distribution of key demographics. Respondents completed a screening questionnaire; those who screened positive for self-reported physician-diagnosed or imaging-detected fatty liver/SLD proceeded to the full survey on post-diagnosis healthcare utilization and follow-up. Of 12 946 respondents with a valid screening questionnaire, 1000 individuals with self-reported SLD comprised the final analytic sample.</p><p><strong>Results: </strong>The self-reported prevalence of physician-diagnosed or imaging-detected SLD was 23.7%. Most participants (79.9%) reported an incidental diagnosis during routine medical check-ups. Overall, 57.7% (577/1000) reported linkage-to-care, and 14.9% (86/577) of those reporting linkage-to-care also reported having undergone fibrosis assessment. Among those reporting no follow-up, the most commonly cited reason was the belief that SLD was not a serious condition. Among those reporting linkage-to-care, 68.8% (397/577) reported follow-up in primary clinics and 31.2% (180/577) in referral centres; patient-reported fibrosis assessment was 10.6% (42/397) and 24.4% (44/180), respectively. The at-risk subgroup comprised 61.9% (619/1000); 65.6% (406/619) reported linkage-to-care and 12.1% (75/619) reported fibrosis assessment. Patient-reported linkage-to-care was 55.5% in MASLD, 59.7% in MetALD and 65.2% in ALD.</p><p><strong>Conclusion: </strong>In this survey sample, most respondents with self-reported SLD reported an incidental diagnosis during medical check-ups, and patient-reported fibrosis assessment was uncommon, including among those meeting at-risk criteria.</p>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"46 5","pages":"e70658"},"PeriodicalIF":5.2,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13093470/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147722818","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":"Diagnostic and Prognostic Values of Bile Biomarkers for Malignant Biliary Stenosis.","authors":"E Gigante, V Untereiner, S Caruso, R Rhaiem, L Grados, C Boulagnon-Rombi, S Adam, G D Sockalingum, R Garnotel, G Thiefin","doi":"10.1111/liv.70637","DOIUrl":"https://doi.org/10.1111/liv.70637","url":null,"abstract":"<p><strong>Introduction: </strong>Differentiating between malignant and benign biliary strictures remains a clinical challenge because current diagnostic tools have limited sensitivity. The detection of tumour-related biomarkers directly in bile, which is in close contact with the lesion, may enhance diagnostic accuracy. This study aimed at evaluating the diagnostic and prognostic values of biliary concentrations of VEGF, PDGF-AA, IGF and MMPs in patients with extrahepatic cholangiocarcinoma (CCA), pancreatic ductal adenocarcinoma (PDAC), or benign obstruction.</p><p><strong>Methods: </strong>A total of 100 consecutive patients undergoing ERCP for obstructive jaundice were enrolled and categorised into benign (n = 48), CCA (n = 23) and PDAC (n = 29) groups. Bile samples collected during ERCP were analysed. The diagnostic and prognostic performance of several biomarkers was assessed and, when appropriate, their incremental diagnostic value was assessed in comparison with standard bile cytology.</p><p><strong>Results: </strong>Biliary concentrations of VEGF, MMP-1, MMP-2, MMP-7 and MMP-9 were significantly higher in malignant cases than in benign cases. VEGF demonstrated the best diagnostic accuracy (AUROC 0.86, sensitivity 87%, specificity 81%). MMP-1 and MMP-7 also showed good diagnostic values (AUROCs 0.79 and 0.81 respectively). In the multivariate analysis, VEGF was independently associated with the diagnosis of malignancy and PDAC, whereas both VEGF and MMP-2 were independently associated with CCA diagnosis. Using a predefined cut-off, bile VEGF showed a higher sensitivity than bile cytology, and their combination markedly reduced false-negative results. Regarding prognosis, higher PDGF-AA levels were independently associated with better survival rates.</p><p><strong>Conclusion: </strong>Biliary VEGF is a strong independent biomarker for the diagnosis of malignant biliary obstruction, both in PDAC and CCA. MMP-2 was independently associated with CCA diagnosis. PDGF-AA is a promising prognostic biomarker for malignant biliary strictures. These findings support the clinical potential of bile-based biomarkers for improving the diagnosis and assessing the prognosis of malignant biliary strictures.</p>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"46 5","pages":"e70637"},"PeriodicalIF":5.2,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13100460/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147775476","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":"Albumin Restores Endothelial Cell Mitochondrial Morphology in Patients With Decompensated Cirrhosis.","authors":"Susan E Fischer, Rudmer J Postma, Roel Bijkerk, Annarein J C Kerbert, Anton Jan van Zonneveld, Minneke J Coenraad","doi":"10.1111/liv.70653","DOIUrl":"10.1111/liv.70653","url":null,"abstract":"<p><strong>Background & aims: </strong>Endothelial cell (EC) activation is a critical driver of disease progression in cirrhosis, contributing to acute decompensation (AD) and acute-on-chronic liver failure (ACLF). Although human albumin administration improves EC function in cirrhotic patients with hypoalbuminemia, its direct effects on ECs remain unclear. This ex vivo study investigates the impact of albumin on EC morphology and mitochondrial function upon exposure to plasma from patients with decompensated cirrhosis (DC).</p><p><strong>Methods: </strong>Human umbilical vein ECs were exposed to plasma from patients with DC and hypoalbuminemia (albumin < 30 g/L, n = 20), compensated cirrhosis (CC, > 30 g/L, n = 20), or healthy controls (HC, n = 20). Albumin was added to DC and HC plasma to reach physiological (~40 g/L) or supraphysiological levels. Mitochondrial function was assessed by measuring oxygen consumption rate (OCR) and reactive oxygen species (ROS) production. The effects of albumin on EC activation were tested using circulating factors elevated in DC (lipopolysaccharide (LPS), tumour necrosis factor-α (TNFα), bilirubin).</p><p><strong>Results: </strong>Mitochondrial morphology distinguished ECs exposed to DC plasma from those exposed to CC or HC plasma. Albumin supplementation shifted EC morphology towards a healthier phenotype. ECs exposed to DC plasma showed increased mitochondrial respiration without a concomitant increase in ROS production, which was normalised by albumin. Albumin had no significant effects on EC activation induced by circulating factors.</p><p><strong>Conclusions: </strong>Plasma from patients with DC and hypoalbuminemia induces EC morphological changes, particularly in mitochondria. Albumin mitigates these effects, suggesting a direct modulatory role on mitochondrial function and supporting its therapeutic potential in vascular dysfunction in cirrhosis.</p>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"46 5","pages":"e70653"},"PeriodicalIF":5.2,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13096249/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147729376","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":"Relapse After Treatment Withdrawal in Autoimmune Hepatitis: Biopsy-Guided Versus Clinically Guided Strategies-A Meta-Analysis.","authors":"Yongqi Dong, Dan Zhou, Leyu Zhou, Li Yang, Yi Shen","doi":"10.1111/liv.70642","DOIUrl":"10.1111/liv.70642","url":null,"abstract":"<p><p>Long-term immunosuppression in autoimmune hepatitis (AIH) carries substantial side effects, making treatment withdrawal an important consideration after sustained biochemical remission. Whether biopsy-guided withdrawal based on histological assessment reduces relapse compared with clinically guided withdrawal remains uncertain. We conducted a systematic review and meta-analysis to compare relapse rates between these two strategies. This meta-analysis followed PRISMA 2020. PubMed, Embase, Web of Science, Scopus and the Cochrane Library were searched from inception to identify studies reporting relapse after treatment withdrawal in AIH using biopsy-guided or clinically guided strategies. Pooled relapse rates were estimated using random-effects models of transformed proportions. Prespecified subgroup, sensitivity and meta-regression analyses evaluated the impact of relapse definitions, histological stringency and follow-up duration. Twelve studies (518 patients) were included. The pooled relapse rate after treatment withdrawal was 51.1%. Relapse rates were not significantly different between biopsy-guided (48.3%) and clinically guided withdrawal (56.3%; p = 0.604). Studies defining relapse by transaminase elevation alone reported higher relapse rates than those incorporating IgG elevation. Within biopsy-guided cohorts, stricter histological remission thresholds were associated with lower relapse rates and reduced heterogeneity.Relapse after treatment withdrawal in AIH remained common and did not differ significantly between biopsy-guided and clinically guided strategies. In the context of existing guideline recommendations, current evidence does not clearly support routine prewithdrawal liver biopsy in all patients with sustained biochemical remission. TRIAL REGISTRATION: PROSPERO registration number: 4202511295.</p>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"46 5","pages":"e70642"},"PeriodicalIF":5.2,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147729521","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":"Durvalumab-Tremelimumab in Advanced Hepatocellular Carcinoma: Real-World Data From the LOR-HCC (Lombardy Real-World HCC Group).","authors":"Andrea Casadei-Gardini, Lorenzo Canova, Federica Tosi, Silvia Camera, Elisa Bocchero, Pietro Pozzoni, Martina Torchio, Salvatore Corallo, Daniela Costantino, Annamaria Stagno, Giulia Grizzi, Rita Gengarle, Gianluca Tomasello, Nasim Ansarin, Mariangela Bruccoleri, Katia Bencardino, Mara Persano, Martina Pino, Alessia Riva, Sara Vavassori, Lorenzo Argiento, Chiara Mazzarelli, Massimo De Giorgio, Elena Rota Caremoli, Margherita Rimini, Tiziana Pressiani, Lorenza Rimassa, Massimo Iavarone","doi":"10.1111/liv.70640","DOIUrl":"10.1111/liv.70640","url":null,"abstract":"<p><strong>Background and aim: </strong>Dual immune checkpoint blockade with tremelimumab plus durvalumab (STRIDE) is an established first-line therapy for unresectable hepatocellular carcinoma (uHCC); however, real-world evidence on its safety, toxicity kinetics and liver function dynamics remains limited. We aimed to evaluate the tolerability and on-treatment changes in hepatic function and effectiveness in a multicentre cohort of patients treated with STRIDE in routine practice.</p><p><strong>Methods: </strong>We conducted a retrospective analysis of prospectively collected data from 115 consecutive patients with uHCC treated with STRIDE across 12 centres in Lombardy, Italy. Clinical, biochemical and radiological variables were recorded at baseline and throughout the therapy. Adverse events were graded per CTCAE v5.0, and Child-Pugh was used to assess hepatic functional evolution. The temporal toxicity patterns were evaluated using smoothed hazard functions. Progression-free survival (PFS), overall survival (OS) and competing-risk cumulative incidences of progression and death were examined.</p><p><strong>Results: </strong>The median follow-up was 8.9 months. More than 80% of the adverse events occurred within the first 2 months, and severe toxicities were infrequent. Child-Pugh deterioration from class A to B occurred in 7.8% of patients from baseline to day 28, increasing to 12.1% by day 56. PFS was 5.7 months; the median OS was not reached, with OS rates of 78.2% at 6 months and 53.3% at 18 months. Progression was the predominant early event, with a cumulative incidence of 49.2% at 6 months.</p><p><strong>Conclusions: </strong>In routine clinical practice, STRIDE shows reproducible effectiveness and a manageable safety profile, with an early and stabilising incidence of adverse events. Dynamic assessment of liver function shows that hepatic function declines modestly but is still clinically meaningful in affected patients.</p>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"46 5","pages":"e70640"},"PeriodicalIF":5.2,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13087547/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147699269","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":"Low-Dose Polystyrene Nanoplastics Alleviate High-Fat Diet-Induced Hepatic Injury via AMPK/mTOR-Mediated Lipophagy Activation.","authors":"Guoqin Luo, Zefen He, Yan Zhang, Baoxi Liu, Guangyu Yang, Weiwen Liu, Bing Huang, Qing Wang, Wenxue Li, Liping Chen","doi":"10.1111/liv.70635","DOIUrl":"10.1111/liv.70635","url":null,"abstract":"<p><strong>Background: </strong>Microplastics (MPs) or nanoplastics (NPs) are emerging environmental pollutants, but current studies predominantly focus on the hepatotoxicity of high-dose MPs, whereas the health effects of low-dose MPs under high-fat diet (HFD) conditions remain unclear. We aimed to investigate the hepatotoxicity induced by combined exposure to high-fat diet and low-dose microplastics.</p><p><strong>Methods: </strong>Male Wistar rats were administered a high-fat diet (HFD) without (HFD) or with polystyrene nanoparticles (PS-NPs) (HFD-NP) for consecutive 90 days. In vitro experiments were conducted using primary hepatocytes treated with PS-NPs and palmitic acid (PA) in the presence or absence of AMPK or an autophagy inhibitor for 24 h.</p><p><strong>Results: </strong>H&E staining revealed significant lipid accumulation, inflammation, and hepatic fibrosis in livers from HFD group, whereas no obvious pathological changes were observed in NP group. Notably, these effects were greatly diminished in HFD-NP group, compared with HFD group. In vitro experiments also showed that PS-NPs displayed no apparent effect on the viability of primary hepatocytes, while significantly alleviated palmitic acid (PA)-induced hepatocyte apoptosis and lipid droplet accumulation. These observations indicate that low-dose PS-NPs mitigate hepatotoxicity induced by HFD. Furthermore, hepatic lipid oxidation and utilization were enhanced in HFD-NP rats, suggesting that PS-NPs may modulate lipid metabolism upon HFD. Transcriptomic analysis revealed the mechanism might involve the activated AMPK signalling pathway and inhibited mTOR signalling pathway, important regulators for autophagy, implying the involvement of lipophagy in this process. Furthermore, in vitro experiments showed the inhibition of lipid droplet autophagy exacerbated HFD-induced hepatotoxicity.</p><p><strong>Conclusion: </strong>Our results indicate low-dose PS-NPs can activate the AMPK pathway and lipophagy, thereby alleviating liver injury through a stress adaptation response under high-fat diet conditions. Our findings elucidate the context-dependent interaction between microplastics and dietary patterns in liver diseases development and provide novel insights into the health effects of microplastics.</p>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"46 5","pages":"e70635"},"PeriodicalIF":5.2,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147654217","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":"The Prognostic and Biological Value of PGF-Based H&E Pathomics in Hepatocellular Carcinoma.","authors":"Long Chen, Xusheng Zhang, Kejun Liu, Weihu Ma, Ling Ding, Shicai Liang, Xuebo Wang, Bendong Chen","doi":"10.1111/liv.70655","DOIUrl":"https://doi.org/10.1111/liv.70655","url":null,"abstract":"<p><strong>Purpose: </strong>Placental growth factor (PGF) is associated with the progression of hepatocellular carcinoma (HCC), but current research on this relationship remains limited. This study aims to establish a pathomics model for predicting PGF expression levels in H&E-stained HCC sections, and to explore its prognostic relevance and underlying molecular mechanisms.</p><p><strong>Methods: </strong>Retrospective analysis utilised H&E images and clinical data from TCGA and an external cohort. Prognostic significance of PGF was assessed via survival analysis. Image segmentation employed the OTSU algorithm, followed by PyRadiomics-based feature extraction. Key features were selected using mRMR and RFE algorithms, with a gradient boosting machine (GBM) model constructed for PGF prediction. Model performance was validated through ROC and Precision-Recall (PR) curves, calibration analysis along with Brier score, and decision curve analysis. Prognostic stratification, Cox regression, and subgroup analyses were conducted for high/low pathomics score (PS: a continuous score derived from a machine learning model based on H&E image features to predict PGF expression) groups. Bioinformatics approaches identified differentially expressed genes (DEGs) and immune infiltration patterns.</p><p><strong>Results: </strong>PGF expression was identified as an independent prognostic factor for poor survival in HCC (HR = 1.922, 95% CI: 1.217-3.036, p = 0.005). A pathomics model integrating seven PGF-associated features demonstrated strong predictive accuracy, achieving an AUC of 0.811 (95% CI: 0.749-0.873) in the training set, 0.747 (95% CI: 0.639-0.855) in the internal validation set, and 0.740 (95% CI: 0.632-0.849) in the external test set. Patients classified into the high-pathomics score (PS) subgroup had significantly poorer survival (HR = 1.667, 95% CI: 1.024-2.713, p = 0.040). Functional analysis of DEGs in high-PS tumours revealed enrichment in ribosome- and coagulation-related pathways, upregulation of the inflammatory gene HBEGF, and increased infiltration of γδT cells. Moreover, TP53 mutations were frequently observed in this subgroup, with a mutation rate exceeding 20%.</p><p><strong>Conclusion: </strong>PGF may serve as an independent prognostic biomarker in HCC. The developed pathomics model enables non-invasive PGF expression prediction through H&E image analysis. Mechanistically, PGF-associated molecular alterations involve inflammatory signalling, immune microenvironment remodelling, and frequent TP53 mutations, providing insights into HCC pathogenesis.</p>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"46 5","pages":"e70655"},"PeriodicalIF":5.2,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13106917/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147775491","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":"Farnesoid x Receptor Deficiency Promotes Hepatocytic Injury in Cyp2c70-Deficient Mice With a Human-Like Bile Acid Composition","authors":"Hilde D. de Vries,&nbsp;Jinxiao Li,&nbsp;Kirill Ustyantsev,&nbsp;Milaine V. Hovingh,&nbsp;Niels L. Mulder,&nbsp;Rick Havinga,&nbsp;Anna Palmiotti,&nbsp;Krisztina de Bruyn,&nbsp;Brecht Attema,&nbsp;Ellen Weersing,&nbsp;Rachel E. Thomas,&nbsp;Vincent W. Bloks,&nbsp;Eugene Berezikov,&nbsp;Martijn van Faassen,&nbsp;Henkjan J. Verkade,&nbsp;Jan Freark de Boer,&nbsp;Folkert Kuipers","doi":"10.1111/liv.70632","DOIUrl":"10.1111/liv.70632","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aims</h3>\u0000 \u0000 <p>Loss-of-function mutations in bile acid (BA)-activated farnesoid x receptor (<i>FXR</i>/<i>NR1H4</i>) cause severe neonatal liver pathology in humans, earlier referred to as progressive familial intrahepatic cholestasis type 5 (PFIC5). However, <i>Fxr</i>-deficient mice do not develop early-onset liver disease, possibly due to the predominance of hydrophilic muricholic acids (MCAs) in their BA pool. Mice lacking <i>Cyp2c70</i> display a human-like BA composition, lacking MCAs. This study aimed to evaluate whether <i>Fxr/Cyp2c70-</i>double knockout (DKO) mice recapitulate the pathophysiology of human FXR-deficiency.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>BA metabolism and liver pathology were assessed in wild-type (WT), <i>Fxr</i>-knockout (KO), <i>Cyp2c70</i>-KO and DKO mice of both sexes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p><i>Fxr</i>-deficiency markedly reduced the amounts of bile salt export pump (BSEP/ABCB11), but did not affect biliary BA secretion. DKO mice showed exacerbated hepatocytic injury and inflammation compared to <i>Fxr</i>-KO mice of both sexes. Surprisingly, despite higher alanine aminotransferase levels that indicate hepatocellular damage, female DKO mice showed much less liver fibrosis and ductular reactions than female <i>Cyp2c70</i>-KO mice. Gene Set Enrichment Analysis suggested that epithelial–mesenchymal transition was upregulated in <i>Cyp2c70</i>-KO livers compared to WT mice but downregulated particularly in livers of female DKO mice compared to <i>Cyp2c70</i>-KO. Biliary BA hydrophobicity was increased by the deletion of <i>Cyp2c70</i>, yet reduced by simultaneous absence of <i>Fxr</i> in female mice.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p><i>Fxr/Cyp2c70</i>-DKO mice exhibit more severe hepatocytic injury than <i>Fxr</i>-KO mice, mirroring the clinical phenotype of FXR deficiency. These data highlight the importance of studying the aetiology of cholestatic liver diseases in the context of a human-like BA composition.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"46 5","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13064423/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147639070","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":"Prognostication of Liver Disease Patients via the WFUMB ‘Rule-of-4’ Algorithm Using SSI-2D-SWE-Based Liver Stiffness Measurement","authors":"Christian Sebesta,&nbsp;Georg Kramer,&nbsp;Nina Dominik,&nbsp;Benedikt S. Hofer,&nbsp;Lorenz Balcar,&nbsp;Paul Thöne,&nbsp;Mathias Jachs,&nbsp;Lukas Hartl,&nbsp;Benedikt Simbrunner,&nbsp;Till Schöchtner,&nbsp;Friedrich Haimberger,&nbsp;Nicolas Balutsch,&nbsp;Albert F. Stättermayer,&nbsp;Michael Trauner,&nbsp;Mattias Mandorfer,&nbsp;Thomas Reiberger,&nbsp;David J. M. Bauer","doi":"10.1111/liv.70614","DOIUrl":"10.1111/liv.70614","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The World Federation for Ultrasound in Medicine and Biology (WFUMB) guidance update 2024 proposed a ‘rule-of-4’ using ARFI liver stiffness measurement (LSM) to stratify the risk of decompensation events. This rule identifies advanced chronic liver disease (ACLD) at a threshold of ≥ 13 kPa and indicates a high probability of clinically significant portal hypertension (CSPH) above 21 kPa.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We prospectively enrolled 187 patients undergoing same-day SSI-2D-LSM (Aixplorer SuperSonic Imagine) and hepatic venous pressure gradient (HVPG) measurement. Patients were stratified into three LSM groups &lt; 13 kPa, 13–21 kPa and &gt; 21 kPa and followed for decompensation events for 1 year (Y1).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The cohort comprised 31 (16.6%) patients with LSM &lt; 13 kPa (non-ACLD); 33 (17.6%) LSM 13–21 kPa (ACLD) and 123 (65.8%) LSM &gt; 21 kPa (high CSPH probability). The corresponding median HVPG values were 5 [IQR: 3–7] vs. 10 [7–14] vs. 17 [13–21] mmHg, respectively, and the corresponding CSPH prevalence was 6.5%, 54.5% and 91.9%. In ROC analysis to predict CSPH, SSI-2D-LSM demonstrated high accuracy (AUC: 0.83). Validating the new WFUMB extension of the ‘rule-of-4’, the recommended &gt; 21 kPa threshold identified CSPH with a specificity of 80.0% and a PPV of 83.1%. In competing risk analysis, the Y1-decompensation rate was 0%, 10% and 24.7% of patients in the &lt; 13 kPa, 13–21 kPa and &gt; 21 kPa groups, respectively. For prediction of Y1-decompensation risk in the compensated ACLD (cACLD) subgroup, HVPG demonstrated the highest predictive accuracy (AUC: 0.92), while SSI-2D-LSM (AUC: 0.75) performed similarly to vibration-controlled transient elastography (VCTE: AUC: 0.77; AUC-comparison: <i>p</i> = 0.837).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The WFUMB ‘rule-of-4’ for ARFI-LSM allows for accurate and point-of-care non-invasive risk stratification of patients with liver disease. Specifically, the short-term risk of decompensation starts at SSI-2D-LSM ≥ 13 kPa and becomes considerable at SSI-2D-LSM &gt; 21 kPa (indicating high CSPH probability). These findings support the broader implementation of ARFI-LSM for risk assessment in clinical routine.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"46 5","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13063207/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147639016","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}