Hepatology最新文献

{"title":"Hepatic footprint of emerging antihyperglycemic therapies","authors":"P. Vineeth Daniel","doi":"10.1097/hep.0000000000001814","DOIUrl":"https://doi.org/10.1097/hep.0000000000001814","url":null,"abstract":"","PeriodicalId":177,"journal":{"name":"Hepatology","volume":"19 1","pages":"625-626"},"PeriodicalIF":13.5,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148754713","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":"Fellows’ Corner","authors":"Somaya Albhaisi","doi":"10.1097/hep.0000000000001795","DOIUrl":"https://doi.org/10.1097/hep.0000000000001795","url":null,"abstract":"","PeriodicalId":177,"journal":{"name":"Hepatology","volume":"463 1","pages":"629-630"},"PeriodicalIF":13.5,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148754708","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":"No prescription needed: Remote nutrition care linked to fewer liver events","authors":"Leandro Sierra, Juan Pablo Arab","doi":"10.1097/hep.0000000000001802","DOIUrl":"https://doi.org/10.1097/hep.0000000000001802","url":null,"abstract":"","PeriodicalId":177,"journal":{"name":"Hepatology","volume":"12 1","pages":"627-628"},"PeriodicalIF":13.5,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148754711","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":"Shear wave elastography demonstrates similar risk stratification performance to vibration-controlled transient elastography in FIB-4–based two-step algorithms for MASLD","authors":"Jaejun Lee, Hyun Yang, Si Hyun Bae, Sun Hong Yoo, Soon Woo Nam, Jiwoon Yoon, Jung Hyun Kwon, Soon Kyu Lee","doi":"10.1097/hep.0000000000001841","DOIUrl":"https://doi.org/10.1097/hep.0000000000001841","url":null,"abstract":"Background &amp; Aims: The role of shear wave elastography (SWE) in two-step MASLD risk stratification remains unclear. We compared SWE with vibration-controlled transient elastography (VCTE) using American Gastroenterological Association (AGA) and European Association for the Study of the Liver (EASL) algorithms. Approach &amp; Results: Patients with MASLD who underwent both VCTE and SWE during the same session between 2019 and 2025 were included. Risk stratification was performed using AGA- and EASL-based two-step approaches. The primary endpoint was liver-related events (LRE). Among 2,817 patients, the AGA-SWE algorithm classified 2,196, 140, and 481 patients as low-, intermediate-, and high-risk, respectively. Using the AGA-SWE algorithm, both intermediate- and high-risk groups showed increased risks of LREs compared with the low-risk group (subdistribution hazard ratio [sHR] 7.60 and 9.86, respectively). The EASL-SWE algorithm also stratified LRE risk relative to the low-risk group, with higher sHRs observed for the intermediate-low, intermediate-high, and high-risk groups (sHR 2.99, 10.83, and 18.87, respectively). The integrated time-dependent area under the curve through 60 months was 0.770 (95% confidence interval [CI]: 0.709, 0.827) and 0.775 (95% CI: 0.712, 0.835) for AGA-SWE and AGA-VCTE, respectively, and 0.804 (95% CI: 0.753, 0.849) and 0.805 (95% CI: 0.750, 0.852) for EASL-SWE and EASL-VCTE, respectively, with no significant differences between SWE and VCTE in either algorithm. No significant net reclassification improvement was observed between SWE- and VCTE-based AGA algorithms. SWE and VCTE demonstrated a strong correlation (Spearman’s ρ = 0.713, 95% CI: 0.691–0.735, <jats:italic toggle=\"yes\">p</jats:italic> &lt;0.001). Conclusions: SWE-based two-step risk stratification showed similar predictive performance to VCTE-based models for predicting LREs in MASLD, although these findings do not establish formal equivalence.","PeriodicalId":177,"journal":{"name":"Hepatology","volume":"13 1","pages":""},"PeriodicalIF":13.5,"publicationDate":"2026-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148728739","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":"Redefining obesity in the context of MASLD","authors":"Daniel Q. Huang, Norbert Stefan","doi":"10.1097/hep.0000000000001837","DOIUrl":"https://doi.org/10.1097/hep.0000000000001837","url":null,"abstract":"","PeriodicalId":177,"journal":{"name":"Hepatology","volume":"16 1","pages":""},"PeriodicalIF":13.5,"publicationDate":"2026-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148728716","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":"A First-in-Human study of AHB-137, an unconjugated antisense oligonucleotide, in healthy subjects and patients with chronic hepatitis B","authors":"Edward J. Gane, Yao-Chun Hsu, Chi-Yi Chen, Shyamasundaran Kottilil, Eric Lawitz, Ira M. Jacobson, Paul Yien Kwo, Lung-Yi Mak, Wai-Kay Seto, Joel V. Chua, Di Zhao, Tingting Lu, Bingxia Lu, Xiao Qiu, Yilei Wen, Yeming Pan, Mingyue Chen, Miao Wang, Chen Yang, Audrey H. Lau, Chengyong Yang, Guofeng Cheng, Wan-Long Chuang, Christian Schwabe, Man-Fung Yuen","doi":"10.1097/hep.0000000000001835","DOIUrl":"https://doi.org/10.1097/hep.0000000000001835","url":null,"abstract":"Background &amp; Aims: AHB-137 is a novel ASO targeting a conserved region near the 3′ end of all HBV mRNA. This first-in-human phase 1 study evaluated the safety, tolerability, pharmacokinetics (PK), and antiviral efficacy in healthy subjects and chronic hepatitis B (CHB) patients. Methods: Forty healthy subjects were randomized into four placebo-controlled single ascending dose (100-450 mg, 6:2 AHB-137:placebo) cohorts and one multiple-dose (MD; 300 mg, 6:2) cohort receiving four weekly subcutaneous doses with a Day 4 loading dose (5 doses). Twenty-four virally suppressed, HBeAg-negative CHB patients on stable nucleos(t)ide analogue therapy were enrolled: four in an open-label 300-mg MD cohort (5 doses) and 20 in two placebo-controlled 300-mg MD cohorts (4:1, stratified by baseline HBsAg), receiving an additional loading dose on Day 11 (6 doses). Results: Treatment-related adverse events occurred in 73% of healthy subjects and 71% of CHB patients and were primarily mild or moderate injection-site reactions and headaches. No treatment-related serious adverse events, discontinuations, or deaths were observed. PK profiles showed rapid absorption (T <jats:sub>max</jats:sub> 2.96-5.50 h), dose-proportional exposure, no significant accumulation, long terminal half-life (150-220 h), and minimal renal excretion. In CHB patients, AHB-137 treatment led to a rapid HBsAg decline (mean 0.7-1.0 log <jats:sub>10</jats:sub> IU/mL). HBsAg loss (&lt;0.05 IU/mL) for at least one timepoint was observed in three patients, including two with baseline HBsAg &lt;1 IU/mL and one with baseline HBsAg &lt;1.5 IU/mL. Conclusions: In this Phase 1 study, AHB-137 demonstrated an acceptable safety profile, predictable PK, and rapid and prolonged HBsAg reductions, supporting further evaluation of dosing and treatment duration in CHB.","PeriodicalId":177,"journal":{"name":"Hepatology","volume":"21 1","pages":""},"PeriodicalIF":13.5,"publicationDate":"2026-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148726432","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":"Liver-on-a-Chip: Applications for clinical modeling of liver disease using microscale systems","authors":"Nina M. Brooks, Anna Peczak, Robert E. Schwartz","doi":"10.1097/hep.0000000000001829","DOIUrl":"https://doi.org/10.1097/hep.0000000000001829","url":null,"abstract":"Liver-on-a-chip (LOC) systems are tunable, microscale environments that can incorporate additional layers of physiologic complexity in comparison to 2D cell culture. LOCs are an <jats:italic toggle=\"yes\">in vitro</jats:italic> adjunct and potential alternative to <jats:italic toggle=\"yes\">in vivo</jats:italic> animal models that utilize human-derived cells, typically embedded in a synthetic device containing natural or engineered materials. This enables LOC models to exhibit a high level of customization per organ, disease, or condition. LOCs typically contain dynamic flow to cells embedded in a series of microchannels within the device. This perturbation aims to recreate mechanobiological forces seen <jats:italic toggle=\"yes\">in vivo</jats:italic> and encourage cell-to-cell interactions in a 3D environment. These models have proven to be particularly advantageous in modeling organs with complex spatial zonation, such as the liver, as oxygen and nutrient gradients can more accurately be represented under these dynamic conditions. LOC systems have also been proposed to improve the accuracy of drug toxicity screening for clinical applications because they employ human-derived cells in more physiologically relevant conditions. This review will first discuss fabrication techniques and considerations when recreating biological microenvironments. Next, the advances of LOC systems and applications for modeling liver disease and infection will be explored. Finally, current limitations and advances for implementing LOC devices into clinical and commercial settings will be examined.","PeriodicalId":177,"journal":{"name":"Hepatology","volume":"46 1","pages":""},"PeriodicalIF":13.5,"publicationDate":"2026-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148703423","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":"Hepatocyte hnRNPK preserves mitochondrial integrity to restrain liver injury and fibrosis","authors":"Qian Peng, Sujuan Wang, Yufeng Zhang, Yangjun Luo, Beiwu Lan, Nan Wang, Wei Jiao, Zhiqin Xie, Yaming Yuan, Wei Duan, Huijuan Sun, Ping Yang, Zhigang Li, Yewei Ji, Yufei Gao, Ben Zhou, Lifeng Yang, Yongfang Jiang, Ming Lu, Ying Feng, Zhangsen Zhou","doi":"10.1097/hep.0000000000001836","DOIUrl":"https://doi.org/10.1097/hep.0000000000001836","url":null,"abstract":"Background &amp; Aims: Liver fibrosis is a global health issue with unclear unified drivers. The RNA-binding protein hnRNPK is critical for hepatic homeostasis, but its role in chronic fibrosis remains undefined. This study investigated hnRNPK-mediated splicing dysregulation in liver fibrosis and its therapeutic potential. Approach &amp; Results: We mapped hepatocellular hnRNPK expression across a broad spectrum of human and murine fibrotic etiologies. Mechanistic insights were obtained by integrating snRNA-seq, hepatocyte-specific alternative splicing profiling, untargeted and spatial metabolomics, and 3D mitochondrial reconstruction using AT-SEM. We identified reduced hepatocellular hnRNPK abundance as a conserved hallmark of liver fibrosis across distinct pathogenic insults, including MASH, ALD, HBV, and DILI. Hepatocyte-specific <jats:italic toggle=\"yes\">Hnrnpk</jats:italic> ablation in mice induced aberrant <jats:italic toggle=\"yes\">Opa1</jats:italic> splicing, specifically promoting exon 4b inclusion. This disrupted the balance of OPA1 isoforms, depleting L-OPA1 and driving severe mitochondrial fragmentation characterized by distinct “spheroid” ultrastructures. This loss of mitochondrial integrity triggered HSC activation through the cytosolic mtDNA-cGAS-STING pro-inflammatory signaling cascade and the mitochondria-containing pellet. Notably, restoring the hnRNPK- <jats:italic toggle=\"yes\">Opa1</jats:italic> axis via AAV-mediated overexpression of <jats:italic toggle=\"yes\">Hnrnpk</jats:italic> or the <jats:italic toggle=\"yes\">Opa1</jats:italic> -Δ4b isoform (lacking exon 4b), together with pharmacological promotion of mitochondrial fusion, effectively arrested and regressed established liver fibrosis in multiple murine models. Conclusions: Our findings establish the loss of hnRNPK as a central, unifying mechanism in liver fibrogenesis. By governing the <jats:italic toggle=\"yes\">Opa1</jats:italic> splicing axis, hnRNPK maintains mitochondrial integrity and prevents the pro-inflammatory signaling and secretome that fuel HSC activation. Targeting this RNA-mitochondria axis represents a potent, etiology-independent therapeutic strategy for chronic liver disease.","PeriodicalId":177,"journal":{"name":"Hepatology","volume":"15 1","pages":""},"PeriodicalIF":13.5,"publicationDate":"2026-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148703424","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":"BEACON-HCC: Best evidence and north american consensus on treatment allocation for hepatocellular carcinoma.","authors":"Amit G Singal, Vatche G Agopian, Laura A Dawson, Anthony El-Khoueiry, Richard S Finn, Karim Halazun, Julie K Heimbach, Robin Katie Kelley, Edward Kim, Laura Kulik, Neil Mehta, Mishal Mendiratta-Lala, Jeffrey Meyer, Neehar D Parikh, Anjana Pillai, Riad Salem, Gonzalo Sapisochin, Parissa Tabrizian, Adam Yopp, Mark Yarchoan","doi":"10.1097/HEP.0000000000001834","DOIUrl":"https://doi.org/10.1097/HEP.0000000000001834","url":null,"abstract":"<p><strong>Background: </strong>Hepatocellular carcinoma (HCC) remains a major cause of cancer-related mortality. Optimal treatment decisions are challenging, and existing treatment allocation frameworks may not fully reflect the evolving therapeutic landscape or contemporary clinical practices in North America.</p><p><strong>Methods: </strong>Using a modified Delphi process, a multidisciplinary panel of 20 North American experts in hepatology, medical oncology, surgery, radiology, and radiation oncology developed a consensus-based treatment framework for HCC, termed the BEACON-HCC system. The framework was informed by current evidence and expert opinion through iterative discussion and voting. In a pilot study using 29 real-world patient cases, we assessed concordance between external expert recommendations and BEACON-HCC recommendations and Barcelona Clinic Liver Cancer (BCLC) 2025 treatment recommendations.</p><p><strong>Results: </strong>The BEACON-HCC treatment allocation framework diverges from prior frameworks by incorporating nuanced clinical features such as degree of intrahepatic tumor burden and vascular invasion, and adverse tumor prognostic markers, to align treatment allocation with tumor biology and therapeutic potential. Key innovations include the incorporation of emerging modalities such as external beam radiation therapy (EBRT), transarterial radioembolization (TARE), and systemic-locoregional combination therapies. In the pilot exercise, expert treatment decisions showed 96.6% concordance with BEACON-HCC recommendations and 72.4% concordance with BCLC recommendations.</p><p><strong>Conclusions: </strong>BEACON-HCC is a consensus-based framework for treatment allocation that incorporates the expanding range of therapeutic options available to patients in the North American HCC population. Expert treatment decisions showed a high concordance with the BEACON-HCC system; further validation using empiric clinical data is planned through the HCC-Live Consortium.</p>","PeriodicalId":177,"journal":{"name":"Hepatology","volume":" ","pages":""},"PeriodicalIF":18.0,"publicationDate":"2026-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148682869","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":"With no lysine kinase 1 in hepatic stellate cells promotes mouse and human liver fibrosis through glycolytic triosephosphate isomerase 1.","authors":"Zeba Firdaus, Shalil Khanal, Alexander M Washington, Jasper K Solverson, Luke C Doskey, Yang Xiao, Mehdi Yaqubi, David Pereyra, Julie Heimbach, Timuçin Taner, Eugene W Krueger, Chou-Long Huang, Vijay H Shah, Patrick P Starlinger, Gina L Razidlo, Matthew J Schellenberg, Enis Kostallari","doi":"10.1097/HEP.0000000000001833","DOIUrl":"10.1097/HEP.0000000000001833","url":null,"abstract":"<p><strong>Background and aims: </strong>Liver fibrosis and cirrhosis are major global health burdens with limited treatments. Activated HSCs drive fibrosis through increased proliferation, migration, collagen deposition and glycolysis. The aim of this study is to elucidate the signaling events that lead to enhanced glycolysis, subsequent HSC activation, and liver fibrosis.</p><p><strong>Approach and results: </strong>Utilizing a phospho-kinase array, we identified with no lysine kinase 1 (WNK1) as a new kinase in primary human HSCs activated by the profibrotic PDGF-B. PDGF-mediated glycolysis in HSCs was attenuated by the WNK1 selective inhibitor, WNK-IN-11, as measured by live-cell metabolic assay, Glifon-300 fluorescence, Glucose-Glo assay, and glucose transporter 1 immunofluorescence. To understand how WNK1 promotes glycolysis, we employed chemical genetics where an engineered WNK1 carrying threonine 301 to glycine mutation (WNK1 T301G ) mutant with a modified ATP pocket accommodated a specific ATP-γ-S analogue to thio-phosphorylate its substrates. Thio-phosphorylated proteins were analyzed by mass spectrometry, which identified the glycolytic protein, triosephosphate isomerase 1 (TPI1), as a novel WNK1 direct substrate. TPI1 interacted with WNK1 in condensates, membrane-less phase separation structures. Condensate disruption and knockdown of TPI1 or WNK1 reduced HSC proliferation and migration in vitro. In vivo, pharmacological or genetic WNK1 inhibition significantly attenuated liver fibrosis in carbon tetrachloride and high-fat, choline-deficient, L -amino acid diet mouse models. Finally, WNK1 inhibition reduced fibrogenesis ex vivo in human precision-cut liver slices.</p><p><strong>Conclusions: </strong>These findings identify WNK1 as a previously unrecognized kinase that promotes HSC activation and liver fibrosis via TPI1-mediated glycolysis, highlighting the WNK1-TPI1 axis as a potential therapeutic target.</p>","PeriodicalId":177,"journal":{"name":"Hepatology","volume":" ","pages":""},"PeriodicalIF":18.0,"publicationDate":"2026-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148676508","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}