Hepatology最新文献

{"title":"Letter to the Editor: Dynamics in liver stiffness to assess response in MASLD patients treated with resmetirom-One piece of the puzzle?","authors":"Georg Semmler, Maja Thiele, Thomas Reiberger, Mattias Mandorfer","doi":"10.1097/HEP.0000000000001265","DOIUrl":"10.1097/HEP.0000000000001265","url":null,"abstract":"","PeriodicalId":177,"journal":{"name":"Hepatology","volume":" ","pages":""},"PeriodicalIF":12.9,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143412588","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: AASLD Resmetirom Guidance.","authors":"Vincent L Chen, Timothy R Morgan, Yaron Rotman, Heather M Patton, Kenneth Cusi, Fasiha Kanwal, W Ray Kim","doi":"10.1097/HEP.0000000000001267","DOIUrl":"10.1097/HEP.0000000000001267","url":null,"abstract":"","PeriodicalId":177,"journal":{"name":"Hepatology","volume":" ","pages":""},"PeriodicalIF":12.9,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143412591","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":"Global burden of HBV-related liver disease: Primary liver cancer due to chronic HBV infection increased in over one-third of countries globally from 2000 to 2021","authors":"Pojsakorn Danpanichkul, Kwanjit Duangsonk, Vincent L. Chen, Preenapun Saokhieo, Disatorn Dejvajara, Banthoon Sukphutanan, Majd B. Aboona, Chawin Lopimpisuth, Yanfang Pang, Andrew F. Ibrahim, Michael B. Fallon, Daniel Q. Huang, Donghee Kim, Amit G. Singal, Ju Dong Yang, Bashar A. Aqel, Norah A. Terrault, Karn Wijarnpreecha","doi":"10.1097/hep.0000000000001260","DOIUrl":"https://doi.org/10.1097/hep.0000000000001260","url":null,"abstract":"Backgrounds &Aims: Hepatitis B virus (HBV)-related liver disease ranks as the seventh leading cause of mortality. Despite advances in prevention and treatment, global disparities in the burden of primary liver cancer (PLC) persist. We evaluate global trends in the prevalence, incidence, and death of HBV-related liver disease. Approach and Results: Data from the Global Burden of Disease Study 2021 evaluated acute HBV infection, HBV-related cirrhosis, and HBV-related liver cancer prevalence, incidence, and death. In 2021, there were 7.30 million cases of acute HBV, 283.64 million cases of HBV-related cirrhosis, and 288,110 cases of HBV-related PLC. HBV-related PLC accounted for 39% of the global incidence of PLC; Western Pacific had the highest rates for HBV-related PLC, with an incidence of 5.24 and a death rate of 4.38 per 100,000 population. Between 2000-2021, age-standardized incidence, prevalence, and death rates from HBV-related liver disease decreased; however, the incidence of HBV-related PLC rose in 65 countries from 2000 to 2021. In parallel, age-standardized prevalent rates from HBV-related PLC increased in Europe (Annual percent change [APC]: 0.77%, 95% confidence interval [CI] 0.72 to 0.81%) and the Americas (APC: 1.05%, 95%CI 1.00 to 1.10%). Conclusion: From 2000 to 2021, decreases in HBV-related liver disease incidence and prevalence were observed; however, more than one-third of countries showed an increase in the incidence of HBV-related PLC. These findings highlight the need for strengthened HBV treatment efforts to reduce the risk of liver cancer.","PeriodicalId":177,"journal":{"name":"Hepatology","volume":"30 1","pages":""},"PeriodicalIF":13.5,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143401656","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":"Erratum: Resmetirom therapy for metabolic dysfunction-associated steatotic liver disease: October 2024 updates to AASLD Practice Guidance","authors":"Vincent L. Chen, Timothy R. Morgan, Yaron Rotman, Heather M. Patton, Kenneth Cusi, Fasiha Kanwal, W. Ray Kim","doi":"10.1097/hep.0000000000001186","DOIUrl":"https://doi.org/10.1097/hep.0000000000001186","url":null,"abstract":"","PeriodicalId":177,"journal":{"name":"Hepatology","volume":"41 1","pages":""},"PeriodicalIF":13.5,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143401657","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 protein hyperSUMOylation halts cholangiocarcinoma progression by impairing cancer cell viability and tumor-stroma crosstalk","authors":"Irene Olaizola, Ainhoa Lapitz, Beatriz Val, Laura Izquierdo-Sanchez, Maite G. Fernandez-Barrena, Colm J. O’Rourke, Pui Y. Lee-Law, Andreea Gradinaru, Raul Jimenez-Agüero, Adelaida La Casta, Ioana Riaño, Rocio I.R. Macias, Jose J.G. Marin, Maria L. Martinez-Chantar, Matias A. Avila, Patricia Aspichueta, Jesper B. Andersen, Luke Boulter, Luis Bujanda, Pedro M. Rodrigues, Maria J. Perugorria, Jesus M. Banales","doi":"10.1097/hep.0000000000001259","DOIUrl":"https://doi.org/10.1097/hep.0000000000001259","url":null,"abstract":"Background and Rationale: Cholangiocarcinoma (CCA) includes a diverse group of biliary malignancies with poor prognosis. Alterations in post-translational modifications contribute to disrupted protein dynamics, cellular disturbances, and disease. This study investigates the role of protein SUMOylation in cholangiocarcinogenesis and its potential as a therapeutic target. Approach and Results: Analysis of CCA tumors from four patient cohorts and CCA cell lines, revealed increased expression of the SUMOylation machinery genes <jats:italic toggle=\"yes\">SAE1</jats:italic> and <jats:italic toggle=\"yes\">UBE2I</jats:italic>, regardless of the tumor’s molecular profile, resulting in elevated levels of SUMO1-conjugated proteins. Higher <jats:italic toggle=\"yes\">SAE1</jats:italic> and <jats:italic toggle=\"yes\">UBE2I</jats:italic> levels were both indicative of unfavorable clinical outcomes. Deregulated SUMOylated proteins in CCA, mostly linked to cell proliferation, survival, and homeostasis, were identified through immunoprecipitation and mass spectrometry. Genetic (<jats:italic toggle=\"yes\">UBE2I</jats:italic>-knockdown) and pharmacological (ML792 and SAMe) inhibition of SUMOylation effectively suppressed tumorigenesis in subcutaneous and oncogene-driven CCA models, reducing the presence of cancer-associated fibroblasts (CAFs) and increasing the recruitment of anti-tumor immune cells. <jats:italic toggle=\"yes\">In vitro</jats:italic>, targeting SUMOylation induced CCA cell death and reduced cell proliferation, colony formation, and spheroid growth. Importantly, ML792 and SAMe did not adversely affect normal human cholangiocytes. Moreover, co-culture of wild-type or <jats:italic toggle=\"yes\">UBE2I</jats:italic>-knockdown CCA cells with CAFs revealed that depleting SUMOylation in CCA cells impaired CAF cell growth and altered their protein secretome, ultimately disrupting CCA growth through a regulatory feedback loop. Conclusion: Aberrant SUMOylation drives CCA progression by enhancing cell survival, proliferation, and shaping the tumor microenvironment. Targeting SUMOylation shows potential in inhibiting CCA growth, representing a promising therapeutic strategy.","PeriodicalId":177,"journal":{"name":"Hepatology","volume":"79 5 Pt 1 1","pages":""},"PeriodicalIF":13.5,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143385131","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":"Aptamer-directed, nanovesicle-mediated targeting of undruggable molecules in preclinical cholangiocarcinoma models","authors":"Mincheng Yu, Jack W. Sample, Irene K. Yan, Shohei Takaichi, Jennifer L. Tomlinson, Emilien J. Loeuillard, Ryan D. Watkins, Nathan W. Werneburg, Amro M. Abdelrahman, Danielle Carlson, Hendrien Kuipers, Meina Cai, Enis H. Ozmert, Brooke Kimball, Jinchun Yang, Sumera I. Ilyas, Gregory J. Gores, Tushar Patel, Rory L. Smoot","doi":"10.1097/hep.0000000000001256","DOIUrl":"https://doi.org/10.1097/hep.0000000000001256","url":null,"abstract":"Background and Aims: Cholangiocarcinoma (CCA) is an aggressive malignancy arising from the biliary epithelium with limited therapeutic options and poor long-term survival rates. To address the limitations in CCA treatment, we investigated cell-targeted nanovesicles as a delivery platform for transcriptome-targeting therapeutics. Approach &amp; Results: Milk-derived nanovesicles (MNVs) were loaded with short interfering RNAs targeting YAP, the downstream effector of the Hippo pathway; LCK, an upstream regulator of YAP; and tafazzin, a protein critical for the integrity of the inner mitochondrial membrane. These transcriptome-targeting nanovesicles (tMNVs) were decorated with a lipid-coupled RNA aptamer to epithelial cell adhesion molecule (EpCAM), including a tracking fluorophore. <jats:italic toggle=\"yes\">In vitro</jats:italic> studies were conducted using multiple CCA cell lines. <jats:italic toggle=\"yes\">In vivo</jats:italic> studies were performed using C57BL/6 and NOD/SCID mice to evaluate delivery and efficacy in both an immunocompetent syngeneic murine and a patient-derived xenograft (PDX) model. We demonstrated that tMNVs were selectively taken up by liver tumor cells, which was augmented by the incorporation of a targeting aptamer, and that MNVs loaded with siRNA effectively downregulated target gene expression, both <jats:italic toggle=\"yes\">in vitro</jats:italic> and <jats:italic toggle=\"yes\">in vivo</jats:italic>. Downstream effects of target gene inhibition were observed, including downregulation of YAP-TEAD target genes and an increase in reactive oxygen species production at the mitochondrial level. Administration of tMNVs targeting YAP, LCK, and tafazzin inhibited CCA growth and further synergized with chemotherapy in two preclinical CCA models. Conclusions: Herein, we show that aptamer-directed, nanovesicle-mediated targeting of YAP, LCK, and tafazzin potentiates chemosensitivity in two CCA models when delivered using aptamer-guided milk-derived nanovesicles.","PeriodicalId":177,"journal":{"name":"Hepatology","volume":"3 1","pages":""},"PeriodicalIF":13.5,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143385164","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":"Letter to the Editor: Hepatic decompensation is the major driver of mortality in hepatocellular carcinoma patients treated with atezolizumab plus bevacizumab: The impact of successful antiviral treatment","authors":"Qingran Liu, Jinpeng Li, Hua Chen, Jinlong Song","doi":"10.1097/hep.0000000000001215","DOIUrl":"https://doi.org/10.1097/hep.0000000000001215","url":null,"abstract":"","PeriodicalId":177,"journal":{"name":"Hepatology","volume":"60 1","pages":""},"PeriodicalIF":13.5,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143385165","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":"Identifying the sweet spot in portal pressure reduction with TIPS","authors":"Louise China, David Patch","doi":"10.1097/hep.0000000000001258","DOIUrl":"https://doi.org/10.1097/hep.0000000000001258","url":null,"abstract":"","PeriodicalId":177,"journal":{"name":"Hepatology","volume":"55 1","pages":""},"PeriodicalIF":13.5,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143258628","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":"Coil or Plug-Assisted Retrograde transvenous obliteration (CARTO/PARTO) for treating portal hypertensive variceal bleeding: A multi-center, real-world 10-year retrospective study","authors":"Edward Wolfgang Lee, Sammy Saab, Navid Eghbalieh, Peng-xu Ding, Ung Bae Jeon, Joon Young Ohm, Ronnie C. Chen, Man-Deuk Kim, Kichang Han, Dong Jae Shim, Jong Soo Shin, Anirudh Mirakhur, Chien-An Liu, Jonathan Park, Frank Hao, Man Wong, Antonio Moreno, Jasleen Singh, Fady Kaldas, Douglas G. Farmer, Juan Gonzalez-Abraldes","doi":"10.1097/hep.0000000000001255","DOIUrl":"https://doi.org/10.1097/hep.0000000000001255","url":null,"abstract":"Background &amp; Aims: CARTO and PARTO are well-accepted treatment for gastric variceal (GV) bleeding. However, long-term (&gt;2 years) clinical outcomes have yet to be studied. In this study, we investigated long-term clinical outcomes, including overall survival (OS) in 10 years Methods: We performed a multi-national, multi-center, retrospective study of CARTO/PARTO in GV treatments between 05/2012 and 07/2024. The primary study outcomes were a long-term OS and prognostic factors of CARTO/PARTO. The secondary outcomes were long-term clinical/technical success, complications, clinical changes including portal hypertensive symptoms. Results: A total of 311 patients (41% female; 69% CARTO) from 13 centers in five countries were included. The cumulative 1-, 3-, 5-, 7-, and 10-year OS rates were 98, 80, 68, 52, and 33%, respectively, with a median OS of 99 months. Prophylactic CARTO/PARTO showed a better OS than CARTO/PARTO for active bleeding (<jats:italic toggle=\"yes\">p</jats:italic>=0.00035). The independent prognostic factors of OS were having high pre-MELD, concurrent HCC, treating GOV2, history of esophageal variceal bleeding, high pre-TBili, and ammonia levels. Notably, a high pre-MELD score &gt;27 had a significantly higher mortality rate (92.6%) than a lower pre-MELD score (<jats:italic toggle=\"yes\">p</jats:italic>&lt;0.001). The overall cumulative 1-, 3-, 5-, 7-, and 10-year recurrent GV bleeding rates were 0.9, 3.2, 4.0, 4.5, and 5.4%, respectively. The overall technical and clinical success rates were 96.5% and 95.3%, respectively, with a 4.5% major complication rate over 10 years. Conclusions: CARTO and PARTO have excellent long-term survival and clinical outcomes. However, these are negatively affected by high MELD scores, concomitant HCC, and coexisting esophageal varices.","PeriodicalId":177,"journal":{"name":"Hepatology","volume":"12 1","pages":""},"PeriodicalIF":13.5,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143192074","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: Interpreting the 100% disease control rate of Sin-Bev-RT in HCC with PVTT","authors":"Zelong Liu, Meiyan Zhu, Zhenwei Peng","doi":"10.1097/hep.0000000000001230","DOIUrl":"https://doi.org/10.1097/hep.0000000000001230","url":null,"abstract":"","PeriodicalId":177,"journal":{"name":"Hepatology","volume":"55 1","pages":""},"PeriodicalIF":13.5,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143192075","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}