JHEP Reports最新文献

{"title":"STAT1 drives the immune landscape of murine Toll-like receptor 9-induced liver inflammation","authors":"Amber De Visscher ,&nbsp;Jarne Beliën ,&nbsp;Eline Bernaerts ,&nbsp;Marte Vandeput ,&nbsp;Bert Malengier-Devlies ,&nbsp;Fran Prenen ,&nbsp;Hanne Meers ,&nbsp;Liliana Sokol ,&nbsp;Tania Mitera ,&nbsp;Nele Berghmans ,&nbsp;Seray Anak ,&nbsp;Olivier Govaere ,&nbsp;Philippe Van den Steen ,&nbsp;Jochen Lamote ,&nbsp;Niels Vandamme ,&nbsp;Anna Bujko ,&nbsp;Charlotte L. Scott ,&nbsp;Carine H. Wouters ,&nbsp;Patrick Matthys","doi":"10.1016/j.jhepr.2025.101668","DOIUrl":"10.1016/j.jhepr.2025.101668","url":null,"abstract":"<div><h3>Background &amp; Aims</h3><div>Persistent activation of Toll-like receptor 9 (TLR9) has been implicated in eliciting a cytokine storm syndrome, leading to systemic and hepatic inflammation in mice and humans. This study investigates the unexplored role of STAT1, a transcription factor in pathogen-driven immune responses, in mediating TLR9-induced liver inflammation.</div></div><div><h3>Methods</h3><div>We compared clinical, histological, and laboratory characteristics (in total nine parameters) of TLR9-induced liver inflammation between wild-type (WT) mice and STAT1-deficient (<em>Stat1</em>^<em>-/-</em>) mice (n = 3–31 mice/condition depending on the parameter measured) and explored their hepatic immune landscape using single-cell CITE-sequencing (total of 36,585 CD45⁺ liver cells from four to eight mice/condition). Findings were validated by flow cytometry, treatment with biologicals, <em>ex vivo</em> cell culture, and exploration of publicly available patient datasets.</div></div><div><h3>Results</h3><div><em>Stat1</em>^<em>-/-</em> mice are protected against TLR9-induced inflammation as they do not develop the typical features seen in WT counterparts (<em>p</em> &lt;0.05–0.0001, depending on the parameter). This protection is associated with the absence of hepatic cycling CD38⁺CD8⁺ T cells, type 2 conventional dendritic cells, and monocytes transitioning into inflammatory macrophages. These cell populations exhibit elevated STAT1 expression and type I and II interferon (IFN) signatures, resembling immune profiles of patients with cytokine storm syndromes and liver inflammation. <em>Ex vivo</em>, type I and II IFNs induce the phenotype of cycling T cells and transitioning monocytes through STAT1 signaling. <em>In vivo</em>, simultaneous treatment with anti-type I and II IFN antibodies in CpG-injected WT mice provide protection against systemic and liver inflammation (<em>p</em> &lt;0.05–0.001 for five mice/condition).</div></div><div><h3>Conclusions</h3><div>Type I and II IFN-induced STAT1 activation drives TLR9-induced liver inflammation, and support further exploration of JAK1/2 inhibitors, which indirectly inhibit STAT1 activity, in patients with cytokine storm syndromes and other inflammatory liver disorders.</div></div><div><h3>Impact and implications</h3><div>Our study reveals that interferon-induced STAT1 signaling is a central mediator of both systemic and hepatic inflammation during a TLR9-induced cytokine storm. Based on these findings, we support the therapeutic use of JAK1/2 inhibitors, such as ruxolitinib and baricitinib, which indirectly suppress STAT1 activity, in patients with cytokine storm syndromes and inflammatory liver disorders to alleviate both systemic and hepatic symptoms. Notably, our data also highlight the promise of direct STAT1 inhibition as a more and potentially refined approach for intervention.</div></div>","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"8 2","pages":"Article 101668"},"PeriodicalIF":7.5,"publicationDate":"2025-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145922400","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":"Impact of LEAP-012 and EMERALD-1 in the management of HCC","authors":"Amit G. Singal ,&nbsp;Kirema Garcia-Reyes ,&nbsp;Robin K. Kelley ,&nbsp;Edward Kim","doi":"10.1016/j.jhepr.2025.101664","DOIUrl":"10.1016/j.jhepr.2025.101664","url":null,"abstract":"<div><div>The introduction of immune checkpoint inhibitors (ICIs) for hepatocellular carcinoma (HCC) has spurred interest in evaluating their use in earlier lines of therapy, including in combination with locoregional therapy for patients with intermediate-stage disease. Transarterial chemoembolisation (TACE) is believed to increase neoantigen release and local tumour PD-L1 expression, suggesting the potential for enhanced antitumour responses if combined with ICIs. The EMERALD-1 trial randomised 616 patients with Child-Pugh A-B7 and localised HCC (including 6-8% with Vp1-Vp2 vascular invasion) to durvalumab plus bevacizumab plus TACE, durvalumab plus placebo plus TACE, and placebo plus TACE. The primary endpoint, progression-free survival, was significantly longer with durvalumab plus bevacizumab plus TACE <em>vs.</em> TACE alone (hazard ratio [HR] 0.77, 95% CI 0.61–0.98) but not durvalumab plus TACE <em>vs.</em> TACE alone (HR 0.94, 95% CI 0.75–1.19). The LEAP-012 trial randomised 480 patients with Child-Pugh A and liver-localised HCC to lenvatinib plus pembrolizumab plus TACE <em>vs.</em> placebos plus TACE. Progression-free survival was significantly longer with lenvatinib plus pembrolizumab plus TACE <em>vs.</em> TACE alone (HR 0.66, 95% CI 0.51–0.84). Both trials demonstrated increased grade 3-4 treatment-related adverse events in the combination <em>vs.</em> TACE alone arms, including those resulting in treatment discontinuation. Early data from LEAP-012 suggested a trend toward overall survival benefit (HR 0.80, 95% CI 0.57–1.11), although this failed to achieve statistical significance on follow-up analyses. Neither trial has yet reported on other outcomes, including quality of life. Clinicians should emphasise individualised patient selection when deciding between TACE plus ICI <em>vs.</em> TACE alone in patients with HCC eligible for locoregional therapy.</div></div>","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"8 1","pages":"Article 101664"},"PeriodicalIF":7.5,"publicationDate":"2025-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145786928","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":"Practice changing RCT design and rationale: Abbreviated MRI plus AFP vs. ultrasound plus AFP for HCC surveillance in cirrhosis (PREMIUM study)","authors":"George N. Ioannou ,&nbsp;Tamar H. Taddei ,&nbsp;Beata M. Planeta ,&nbsp;Grant D. Huang ,&nbsp;Noel S. Weiss ,&nbsp;Timothy R. Morgan ,&nbsp;Jason A. Dominitz ,&nbsp;Ghassan K. Abou-Alfa ,&nbsp;Mustafa R. Bashir ,&nbsp;Michael V. Beheshti ,&nbsp;Amit G. Singal ,&nbsp;Cynthia A. Moylan ,&nbsp;Robin J. Boland ,&nbsp;Lynn F. Buchwalder ,&nbsp;Rajni L. Mehta ,&nbsp;Kimberly S. Hoisington ,&nbsp;Nhan V. Do ,&nbsp;Shari S. Rogal ,&nbsp;David E. Kaplan ,&nbsp;Jihane N. Benhammou ,&nbsp;Ifeyinwa Onyiuke","doi":"10.1016/j.jhepr.2025.101666","DOIUrl":"10.1016/j.jhepr.2025.101666","url":null,"abstract":"<div><div>Abdominal ultrasound every 6 months with or without serum alpha-fetoprotein (AFP) is recommended for hepatocellular carcinoma (HCC) screening in patients with cirrhosis. However, high-quality evidence demonstrating that this screening strategy reduces HCC-related mortality in cirrhosis is lacking. Dynamic contrast-enhanced abbreviated MRI (DCE aMRI) protocols for HCC screening have nearly identical performance to full multiphasic MRI (the gold standard for HCC diagnosis) and can be completed in under 15 min. PREMIUM is a multicentre randomised controlled trial comparing HCC screening by ultrasound+AFP every 6 months <em>vs.</em> DCE aMRI+AFP every 6 months for up to 8 years among patients with cirrhosis. Sponsored by and executed within the Department of Veterans Affairs (VA), participant recruitment began in November 2023. Eligible participants are Veterans aged 18-75 years with cirrhosis, high HCC risk, Child-Turcotte-Pugh (CTP) score ≤9, model for end-stage liver disease (MELD) score ≤20, and no MRI contraindications or life-threatening comorbidities. The DCE aMRI protocol consists of T1-weighted axial pre-contrast and DCE sequences (arterial, portal, and 5-minute delayed) following administration of extracellular gadolinium-based contrast agent, plus a T2-weighted sequence between portal and delayed phases. PREMIUM aims to randomise 4,700 participants (2,350 in each arm), who will undergo per-protocol imaging and follow-up for up to 8 years. The primary outcome is HCC-related mortality. Secondary outcomes include HCC stage at diagnosis, receipt of potentially curative HCC treatment, and all-cause mortality. The study is powered to detect at least a 35% relative reduction in HCC-related mortality in the aMRI+AFP arm <em>vs</em>. the ultrasound+AFP arm. If PREMIUM demonstrates reduced HCC-related mortality in the aMRI+AFP arm, it could provide the necessary evidence to recommend aMRI+AFP for HCC screening in patients with cirrhosis (<span><span>ClinicalTrials.gov</span><svg><path></path></svg></span> identifier: NCT05486572).</div><div>The PREMIUM Study is a registered clinical trial: NCT05486572.</div></div>","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"8 2","pages":"Article 101666"},"PeriodicalIF":7.5,"publicationDate":"2025-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146034431","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":"Clinical practice and implications of biomarker testing in biliary tract cancer: An observational study","authors":"Sabrina Welland ,&nbsp;Ann-Kristin Zöller ,&nbsp;Ilektra A. Mavroeidi ,&nbsp;Aurelie Tomczak ,&nbsp;Christian Müller ,&nbsp;Dong Yawen ,&nbsp;Danmei Zhang ,&nbsp;Felix Keil ,&nbsp;Maria Pangerl ,&nbsp;Taotao Zhou ,&nbsp;Hossein Taghizadeh ,&nbsp;Sebastian Lange ,&nbsp;Maximilian N. Kinzler ,&nbsp;Kataryna Shmanko ,&nbsp;Maryam Barsch ,&nbsp;Carolin Zimpel ,&nbsp;Angela Djanani ,&nbsp;Henning Schulze-Bergkamen ,&nbsp;Julius Keyl ,&nbsp;Florian Lüke ,&nbsp;Arndt Vogel","doi":"10.1016/j.jhepr.2025.101635","DOIUrl":"10.1016/j.jhepr.2025.101635","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background &amp; Aims&lt;/h3&gt;&lt;div&gt;Biliary tract cancers (BTC) are aggressive malignancies with limited treatment options. Owing to the high frequency of actionable genomic alterations (GA) and the availability of targeted therapies, molecular testing has become increasingly important; however, its clinical implementation remains inconsistent. This study aimed to evaluate real-world molecular testing practices, characterize the BTC molecular landscape, and assess the prognostic and predictive relevance of selected GA.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;We retrospectively analyzed genomic and clinical data from 1,521 patients treated at 18 centers in Germany and Austria. A side-by-side comparison of clinical grade reports generated on two different sequencing platforms was performed for 90 patients.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;Twenty-four different NGS panels were used across 18 centers. A comparative analysis highlighted the significant variability in reports used to inform therapeutic decisions in clinical practice. Although there were substantial differences in the number of GA covered, the broader panels identified a similar number of actionable GA, indicating that key therapeutic targets are sufficiently represented. Integration with clinical data suggested that certain GA, such as &lt;em&gt;HER2&lt;/em&gt; amplifications (3%)&lt;em&gt;, BRAF&lt;/em&gt;&lt;sup&gt;&lt;em&gt;V600E&lt;/em&gt;&lt;/sup&gt; mutations (2%), and &lt;em&gt;FGFR2&lt;/em&gt; alterations (14%), may have prognostic significance beyond their predictive value. Patients with actionable alterations (610, 40%) that were treated accordingly (n = 204, 13%) had prolonged overall survival (31.8 months &lt;em&gt;vs.&lt;/em&gt; 22.8 months, &lt;em&gt;p&lt;/em&gt; &lt;0.01).&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;Standardized biomarker testing is crucial for effective integration of targeted therapies in the management of BTC. Our findings reinforce the value of targeted treatments and underscore the predictive and prognostic significance of selected GA.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Impact and implications&lt;/h3&gt;&lt;div&gt;Genomic profiling is recommended in patients with biliary tract cancers (BTC) but lacks harmonization across platforms and centers. By retrospectively analyzing genomic and clinical information from 1,521 patients with BTC diagnosed and treated at 18 centers in Germany and Austria, we provide real-world insights into the implementation of molecular profiling in BTC, highlighting variability in next generation sequencing-based testing and its impact on the detection of genomic alterations. Standardized molecular testing strategies will be key to enable the integration of more consistent and comparable genomic datasets across studies. Further, by elucidating the prognostic relevance of individual genomic alterations, our insights carry significant implications for interpreting single-arm clinical trials within genomically stratified patient cohorts and underscore the importance of randomized studies to delineate the benefit of targeted therapies.&lt;/d","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"8 1","pages":"Article 101635"},"PeriodicalIF":7.5,"publicationDate":"2025-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145682308","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":"Progressive fibrosis in human MASLD is associated with spatially linked transcriptomic signatures of metabolic reprogramming and senescence","authors":"Hani Vu ,&nbsp;Yuliangzi Sun ,&nbsp;Zherui Xiong ,&nbsp;Xiao Tan ,&nbsp;Daniel Radford-Smith ,&nbsp;Andrew Causer ,&nbsp;Alex M. Dickens ,&nbsp;Tuulia Hyötyläinen ,&nbsp;Ilia Evstafev ,&nbsp;Matej Oresic ,&nbsp;Christian Nefzger ,&nbsp;Eoin D. O’Sullivan ,&nbsp;Matthew J. Watt ,&nbsp;Grant A. Ramm ,&nbsp;Andrew Clouston ,&nbsp;Katharine M. Irvine ,&nbsp;Quan H. Nguyen ,&nbsp;Elizabeth E. Powell","doi":"10.1016/j.jhepr.2025.101657","DOIUrl":"10.1016/j.jhepr.2025.101657","url":null,"abstract":"<div><h3>Background &amp; Aims</h3><div>Granular detail about the location and nature of liver cell interactions and the metabolic, inflammatory and fibrogenic pathways driving progressive fibrosis in metabolic dysfunction-associated steatotic liver disease (MASLD) is needed to identify novel therapeutic targets.</div></div><div><h3>Methods</h3><div>We generated Visium spatial transcriptomic data from 33 human liver biopsies across the spectrum of MASLD. Gene expression data were overlaid with histological annotations to integrate spatial molecular and histopathological information, enabling interrogation of disease progression. Differential gene expression, pathway, cellular deconvolution and ligand-receptor interaction analyses were conducted for each annotated anatomical category, with specific protein expression validated using immunohistochemistry staining.</div></div><div><h3>Results</h3><div>Unsupervised clustering based on gene expression data classified the annotated spots into two main clusters enriched for fibro-inflammatory <em>vs</em>. parenchymal regions. Transcriptomic cellular deconvolution aligned well with manually annotated histopathological features. Fibrotic regions were enriched for genes involved in extracellular matrix/receptor interactions and inflammatory pathways (Benjamini-Hochberg adjusted <em>p</em> values &lt;0.05), underscoring known pathological mechanisms. We also identified immunoglobulin gene induction in late-stage fibrosis, which was spatially associated with a senescence signature, as has previously been reported in aging tissues. Dynamic changes in metabolic gene expression from early to late fibrosis were observed, suggesting MASLD progression is accompanied by a decline in normal liver metabolic function and reprogramming of metabolic fuel utilisation from oxidative to glycolytic metabolism, which may be both a cause and a consequence of senescence.</div></div><div><h3>Conclusions</h3><div>Taken together, our valuable discovery dataset highlights the complex crosstalk between metabolic perturbations and inflammation underpinning fibrosis progression in MASLD.</div></div><div><h3>Impact and implications</h3><div>Metabolic dysfunction-associated steatotic liver disease (MASLD) has a complex pathogenesis driven by cell and matrix interactions in inflammatory niches. In this study, we identify a senescence signature in fibroinflammatory regions, characterised by high immunoglobulin expression and associated with a shift from oxidative to glycolytic metabolism. We identify spatially co-expressed ligand-receptor pairs, including senescence-associated factors, correlated with progressive fibrosis. This discovery dataset highlights the complex crosstalk between metabolic perturbations and inflammation underpinning fibrosis progression in MASLD and lays the groundwork for future research into the role of senescence in MASLD.</div></div>","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"8 2","pages":"Article 101657"},"PeriodicalIF":7.5,"publicationDate":"2025-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145814289","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":"Extending the Baveno VII definition of recompensation to autoimmune hepatitis: Considerations regarding treatment timing and response criteria","authors":"Benedikt S. Hofer ,&nbsp;Lukas Burghart ,&nbsp;Thomas Reiberger ,&nbsp;Albert F. Stättermayer","doi":"10.1016/j.jhepr.2025.101667","DOIUrl":"10.1016/j.jhepr.2025.101667","url":null,"abstract":"","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"8 2","pages":"Article 101667"},"PeriodicalIF":7.5,"publicationDate":"2025-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146034366","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":"Impact of SGLT2i and GLP-1RA on liver-related events in patients with MASLD and type 2 diabetes: A network meta-analysis","authors":"Lu Li ,&nbsp;Xianhua Mao ,&nbsp;Chi Ho Lee ,&nbsp;David Tak Wai Lui ,&nbsp;Rex Wan-Hin Hui ,&nbsp;Lung-Yi Mak ,&nbsp;Man-Fung Yuen ,&nbsp;Ka Shing Cheung ,&nbsp;Wai-Kay Seto","doi":"10.1016/j.jhepr.2025.101661","DOIUrl":"10.1016/j.jhepr.2025.101661","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background &amp; Aims&lt;/h3&gt;&lt;div&gt;Glucose-lowering drugs (GLDs) including glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium–glucose cotransporter 2 inhibitors (SGLT2is) have been broadly evaluated in patients with coexisting metabolic dysfunction-associated steatotic liver disease (MASLD) and type 2 diabetes (T2D). However, their comparative efficacy in reducing the risk of liver-related events remains unclear. Thus, we aim to simultaneously compare the efficacy of different GLDs for patients with MASLD and T2D.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;We searched PubMed, EMBASE, Cochrane Library and Web of Science for observational studies from inception to April 2025. We evaluated the comparative efficacy of six GLDs, including GLP-1RAs, SGLT2is, dipeptidyl peptidase-4 inhibitors, metformin, sulfonylureas, and thiazolidinediones using pairwise meta-analysis and Bayesian network meta-analysis. We assessed overall and individual liver-related events, including the development of cirrhosis, decompensation and hepatocellular carcinoma (HCC), with treatments ranked via SUCRA (surface under the cumulative ranking) scores.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;Twelve studies involving 737,408 patients with MASLD and diabetes were analyzed. Both GLP-1RAs and SGLT2is, when compared to non-GLP-1RA and non-SGLT2i controls, were significantly associated with reduced risk for overall liver-related events (hazard ratio [HR] 0.79, 95% CI 0.70-0.90, and HR 0.75, 95% CI 0.63-0.88, respectively). Similar results were also observed for HCC and liver decompensation (HRs 0.74-0.81). In individuals with obesity, a greater risk reduction was observed for GLP-1RAs (HR 0.74, 95% CI 0.56-0.99) but not for SGLT2is. GLP-1RAs also outperformed SGLT2is in non-Asian populations (HR 0.91, 95% CI 0.83-0.99). Network meta-analysis identified GLP-1RAs and SGLT2is (SUCRA 90%/80%, respectively) as the most effective for risk reduction, with significantly greater efficacy than other GLDs (HRs 0.75-0.79).&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions&lt;/h3&gt;&lt;div&gt;GLP-1RAs and SGLT2is were associated with reduced risks of liver-related events in patients with MASLD and T2D. GLP-1RAs showed superior benefit in individuals with obesity and in non-Asian populations, supporting a personalized approach to treatment selection.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Impact and implications&lt;/h3&gt;&lt;div&gt;The long-term liver-related efficacy of different glucose-lowering drugs (GLDs) in patients with coexisting metabolic dysfunction-associated steatotic liver disease and type 2 diabetes remains unclear, despite a higher lifetime risk of advanced liver disease in this population. We evaluated the comparative efficacy of six GLDs by pairwise meta-analysis and Bayesian network meta-analysis, demonstrating GLP-1RAs and SGLT2is may be among the most effective GLDs for reducing liver-related events, with GLP-1RAs appearing particularly beneficial for patients with obesity. These findings support a personalized approach to tr","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"8 1","pages":"Article 101661"},"PeriodicalIF":7.5,"publicationDate":"2025-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145786929","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 to: “Predicting the need for early TIPS in patients with cirrhosis and ascites: More art than science”","authors":"Lorenz Balcar ,&nbsp;Marta Tonon ,&nbsp;Joan Valls ,&nbsp;Thomas Reiberger ,&nbsp;Juan Carlos García-Pagán ,&nbsp;Georg Semmler ,&nbsp;Salvatore Piano","doi":"10.1016/j.jhepr.2025.101583","DOIUrl":"10.1016/j.jhepr.2025.101583","url":null,"abstract":"","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"7 11","pages":"Article 101583"},"PeriodicalIF":7.5,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145462781","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 TIGIT to improve outcomes in advanced HCC","authors":"Anthony C. Bejjani ,&nbsp;Sasan Roayaie ,&nbsp;Richard S. Finn","doi":"10.1016/j.jhepr.2025.101552","DOIUrl":"10.1016/j.jhepr.2025.101552","url":null,"abstract":"","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"7 11","pages":"Article 101552"},"PeriodicalIF":7.5,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145462775","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)00337-4","DOIUrl":"10.1016/S2589-5559(25)00337-4","url":null,"abstract":"","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"7 11","pages":"Article 101655"},"PeriodicalIF":7.5,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145462777","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}