Hepatology Communications最新文献

{"title":"Single-cell profiling reveals hepatic monocyte-derived macrophages heterogeneity during steatotic liver disease.","authors":"Haozhe Xu, Lu Yang, Peiyang Fang, Jie Sun, Xinjie Zhong, Wanqing Deng, Siqi Li, Longyang Zhou, Jinguo Fan, Dong Zhang, Guangyong Sun","doi":"10.1097/HC9.0000000000000928","DOIUrl":"10.1097/HC9.0000000000000928","url":null,"abstract":"<p><strong>Background: </strong>Monocyte-derived macrophages (MoMFs) play key roles in liver inflammation and fibrogenesis, with their heterogeneity affecting metabolic dysfunction-associated steatotic liver disease (MASLD) progression. However, current therapeutic strategies targeting macrophage-mediated inflammation have shown limited clinical efficacy in MASLD.</p><p><strong>Methods: </strong>We conducted single-cell RNA sequencing (scRNA-seq) of liver-infiltrating 7AAD-CD45+Ly6G-CD11bhiF4/80int MoMFs from NCD-fed and MCD-fed mice. Monocle 2 and CellChat analyses explored developmental trajectories and intercellular interactions, respectively.</p><p><strong>Results: </strong>Seven distinct clusters (c0-c6) with unique molecular signatures were identified. Beyond the classical CD206+ M2-polarized MoMFs, we identified 2 distinct subsets: CCR3+ (c3) MoMFs with enhanced pro-inflammatory and oxidative stress activities, and CCR7+ (c4) MoMFs with specialized antigen-presenting capacity in MASLD mouse livers. Although CCR2+ MoMFs are classically considered pro-inflammatory, our study revealed that the predominant CD14+CCR2+ (c0) MoMFs exhibit additional functional roles in fibrosis, lipid accumulation, and antigen presentation. Our pseudotime and in vitro data demonstrate that resident basal c1 MoMFs are phenotypically plastic, capable of acquiring CD14+/CCR7+ markers and transitioning toward c0-like and c4-like states, implying a potential intrahepatic origin for these subsets in diet-induced steatohepatitis. Notably, these MoMFs subsets and their dynamic changes during disease progression were conserved between the mouse models and human MASLD samples.</p><p><strong>Conclusions: </strong>Our study systematically characterized the heterogeneity and dynamic changes in intrahepatic MoMFs during MASLD progression. Resident c1 MoMFs are plastic and could be a local source for CD14+/CCR7+ subsets in MASLD without relying solely on bone marrow recruitment. These findings provide new insights into the therapeutic strategies that target macrophage-mediated inflammation in MASLD.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"10 5","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13120630/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147769994","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":"Prevalence and clinical impact of hepatic steatosis on autoimmune liver disease: A systematic review and meta-analysis.","authors":"Jarell Jie-Rae Tan, Ellina Lytvyak, Joo Wei Ethan Quek, Corrine Lee Singh, Yuan Jie Aidan Low, Shi Jie Ong, Mark Muthiah, Yu Jun Wong, Aldo J Montano-Loza","doi":"10.1097/HC9.0000000000000959","DOIUrl":"10.1097/HC9.0000000000000959","url":null,"abstract":"<p><strong>Background: </strong>The clinical impact of hepatic steatosis (HS) among patients with autoimmune liver disease (AILD) remains unclear. We aim to determine the prevalence of HS and its clinical impact on treatment response and outcomes in patients with AILD.</p><p><strong>Methods: </strong>We systematically searched 3 electronic databases until 17 December 2025, including all studies that reported the prevalence, clinical impact, and treatment response of AILD patients with concomitant HS. The temporal trend of HS prevalence was analyzed using a quasi-Poisson regression model, with annual percent changes (APC, %) calculated.</p><p><strong>Results: </strong>Overall, 44 studies, comprising 19,898 patients with autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), and primary sclerosing cholangitis (PSC) were included. The pooled prevalence of HS in patients with AIH, PBC, and PSC was 27.3%, 32.9%, and 21.6%, respectively. HS prevalence has significantly increased among PBC patients since 2010 (APC: +37.4%). While concomitant HS was associated with a higher risk of hepatic decompensation (OR: 1.6, 95% CI: 1.3-2.1, I2=0%) and hepatocellular carcinoma (OR: 1.8, 95% CI: 1.3-2.6, I2=0%) in patients with AIH, HS did not influence the clinical outcomes in patients with PBC. Treatment response in AIH and PBC was not influenced by concomitant HS. Available data on PSC with concomitant HS were insufficient to assess its association with clinical outcomes.</p><p><strong>Conclusions: </strong>AIH patients with concomitant HS had worse outcomes than those without HS; whereas HS did not influence the clinical outcomes in patients with PBC. Future research evaluating the impact of HS on PSC and overlap syndrome is much needed.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"10 5","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13120599/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147769979","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":"Arrb2 in hepatocytes promotes M2 macrophage polarization, ameliorates hepatic ischemia-reperfusion injury through upregulating metabolite 6-ketoLCA.","authors":"Xiao-Wen Wang, Wen-Jie Zheng, Hao-Qi Chen, Tao Huang, Yuan Zhang, Xi-Jing Yan, Wen-Chao Li, Long Zou, Jie-Zhong Wu, Wen-Feng Zhu, Qi-Wei Yang, Gen-Shu Wang, Kun-Peng Hu","doi":"10.1097/HC9.0000000000000916","DOIUrl":"10.1097/HC9.0000000000000916","url":null,"abstract":"<p><strong>Background: </strong>Hepatic ischemia-reperfusion injury (IRI) is an important factor affecting the prognosis of liver transplantation patients. The role of Arrb2 in liver injury is unclear. Our study aimed to determine the role of Arrb2 in hepatic IRI and to identify its underlying mechanisms.</p><p><strong>Methods: </strong>An analysis of clinical samples was conducted to assess the association between Arrb2 expression and the prognosis of liver transplantation. A 70% hepatic ischemia/reperfusion model in mice was established to verify the mechanism of Arrb2 in hepatocytes promoting M2 macrophage polarization in attenuating hepatic IRI by regulating 6-ketoLCA. A model of hypoxia/reoxygenation in vitro was established to investigate the molecular mechanism of 6-ketoLCA in promoting M2 macrophage polarization and pharmacological screening.</p><p><strong>Results: </strong>Arrb2 in hepatocytes has been shown to provide significant liver protection against hepatic IRI, primarily through promoting the polarization of liver macrophages to M2. Arrb2 remodels bile acids and upregulates 6-ketoLCA through Cyp7a1 in hepatocytes, promoting M2 polarization of macrophages, thereby alleviating hepatic IRI. Mechanistically, TGR5 plays a crucial role in promoting the induction of M2 polarization in macrophages by 6-ketoLCA. Pharmacological screening indicates that dutasteride enhances the activity of the Arrb2 promoter and upregulates Arrb2 expression in hepatocytes, thereby mitigating hepatic IRI.</p><p><strong>Conclusions: </strong>Arrb2 in hepatocytes attenuates hepatic IRI by promoting macrophages toward the M2 phenotype through bile acid. Moreover, dutasteride, a selective agonist of Arrb2, emerges as a promising targeted therapeutic agent for the clinical management of liver injury.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"10 5","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13120515/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147770019","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":"Integrated behavioral care in general hepatology increases alcohol use disorder treatment in veterans.","authors":"Ponni V Perumalswami, Brittany L Cornwell, Peter P Grau, Alyssa C Meyers, Mayank Jayaram, Sarosh Irani, Parnnate Wongsirisakul, Suthat Liangpunsakul, Arpan Patel, Dominick DePhilippis, Joseph Liberto, Benjamin R Szymanski, John F McCarthy","doi":"10.1097/HC9.0000000000000956","DOIUrl":"10.1097/HC9.0000000000000956","url":null,"abstract":"<p><strong>Background: </strong>Hepatology visits present an opportunity to engage patients with alcohol-associated liver disease in care. This quality improvement pilot integrated a behavioral health provider (BHP) into the hepatology clinic at one Veterans Health Administration site and assessed its impact on alcohol use disorder (AUD) treatment.</p><p><strong>Methods and results: </strong>Hepatologists across Veterans Health Administration facilities developed a workflow to refer patients with signs of unhealthy alcohol use to a BHP co-located in the hepatology clinic. Data during the first year of BHP integration (December 2022 to January 2024) were obtained through chart reviews and the Veterans Health Administration Corporate Data Warehouse. t tests and χ2 tests compared baseline characteristics and assessed the associations of referral status with receipt of evidence-based AUD treatments within 6 months of referral or index liver clinic appointment. Two hundred ninety-three patients with signs of unhealthy alcohol use were identified, representing 19.9% of all liver clinic patients engaged in care during the pilot. Of these, 86.4% had a prior mental health diagnosis, 79.2% had an AUD diagnosis, 57.7% had a positive AUDIT-C screen, 40.3% had an alcohol-associated liver disease diagnosis, and 71 patients (24% of patients with unhealthy alcohol use) were referred to the BHP. Referred patients were more likely to receive AUD psychotherapy and/or pharmacotherapy and had significantly more AUD pharmacotherapy fill days (35.2 vs. 10.3, p<0.001) but not AUD psychotherapy visits (5.2 vs. 3.2, p=0.172).</p><p><strong>Conclusions: </strong>Referral to a co-located BHP was associated with a higher likelihood of receiving AUD treatment and a greater amount of AUD treatment, but gaps in referral remain and need to be addressed. Integrating BHPs into general hepatology clinics may improve AUD treatment uptake, addressing an important gap in care.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"10 5","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13120633/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147770017","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":"Multi-threshold analysis of the ELF Test versus histology for prognostication of disease progression and regression in MASH.","authors":"Matthew F W Gee, Rachel Fonstad, Edward B De Vol, Chadwick Brown, Jordan J Feld, Keyur Patel, Arun J Sanyal","doi":"10.1097/HC9.0000000000000931","DOIUrl":"10.1097/HC9.0000000000000931","url":null,"abstract":"<p><strong>Background: </strong>Patients with metabolic dysfunction-associated steatohepatitis (MASH) with advanced fibrosis are at risk for progression to cirrhosis and clinical outcomes, but can also experience fibrosis regression. The aim of this study was to compare risk stratification by the Enhanced Liver Fibrosis (ELF) Test to histological staging to assess patients at risk of disease progression and those likely to experience histological regression.</p><p><strong>Methods: </strong>Using pooled data from 6 large placebo-controlled trials of 2710 patients with advanced fibrosis due to MASH, 4 analyses of ELF and fibrosis stage were performed to evaluate the association with the following events: (1) liver-related clinical outcomes; (2) progression from bridging fibrosis to cirrhosis; (3) regression from bridging fibrosis; (4) regression from cirrhosis. Significance was assessed by interval likelihood ratio (iLR), Cox proportional hazard ratio (HR), and area under the receiver operator characteristic curve (AUROC).</p><p><strong>Results: </strong>In 2304 participants (17.8 mo mean follow-up), there was a progressive rise in liver-related outcome risk with increasing baseline ELF score [<9.00 (0%), ≥9.00 to <9.80 (2%), ≥9.80 to <11.30 (4%), ≥11.30 to <12.80 (13%), ≥12.80 (40%)]. In 1414 patients with bridging fibrosis, increasing baseline ELF scores were associated with a higher risk of progression to cirrhosis [<9.80 (9%), ≥9.80 to <11.30 (18%), ≥11.30 (45%)] and a lower likelihood of histological regression. In 1690 patients with cirrhosis, increasing baseline ELF scores were associated with a lower likelihood of histological regression [<9.80 (33%), ≥9.80 to <11.30 (16%), ≥11.30 (6%)]. In all analyses, the ELF Test provided more detailed information than histology.</p><p><strong>Conclusions: </strong>The ELF Test adds risk strata that are significantly different from fibrosis staging for the prediction of clinical events and histological changes, thereby improving risk stratification.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"10 5","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13120574/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147770034","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":"Liver transplantation is the major determinant of ≥10-year survival in patients with hepatocellular carcinoma.","authors":"Mohammad Saeid Rezaee-Zavareh, Joseph C Ahn, Hyunseok Kim, Michael Luu, Walid Ayoub, Alexander Kuo, Hirsh Trivedi, Yun Wang, Aarshi Vipani, Tsuyoshi Todo, Georgios Voidonikolas, Justin A Steggerda, Steven A Wisel, Todd V Brennan, Cristina Ferrone, Irene K Kim, Kambiz Kosari, Nicholas Nissen, Neehar D Parikh, Amit G Singal, Ju Dong Yang","doi":"10.1097/HC9.0000000000000951","DOIUrl":"10.1097/HC9.0000000000000951","url":null,"abstract":"<p><strong>Background: </strong>Hepatocellular carcinoma (HCC) has a poor long-term prognosis due to high recurrence and cirrhosis-related mortality, even after potentially curative treatments such as liver transplantation (LT), surgical resection, or ablation. This study aimed to identify factors associated with ≥10-year survival in HCC patients.</p><p><strong>Methods: </strong>A retrospective cohort study was conducted among HCC patients diagnosed between 2004 and 2022 using the National Cancer Database. Multivariable Cox regression was used to identify predictors of overall survival, and logistic regression was used to identify predictors of ≥10-year survival.</p><p><strong>Results: </strong>Among 249,600 HCC patients, 177,585 (71.2%) died within 5 years, 8613 (3.5%) died at 5-10 years, 54,988 (22.0%) were alive with <10 years of follow-up, and 8219 (3.3%) survived ≥10 years. LT, resection, and ablation were performed in 6.6%, 9.3%, and 11% of patients, respectively. Compared with ablation as the reference group, LT [adjusted odds ratio (aOR) 11.96, 95% confidence interval (CI): 11.27-13.29] and resection (aOR: 2.83, 95% CI: 2.57-3.08) increased the odds of ≥10-year survival, while non-curative treatments reduced the odds compared with ablation (aOR: 0.50, 95% CI: 0.47-0.55). Cox regression results were consistent with the logistic model, confirming the association. Decision tree analysis confirmed LT as the dominant determinant of long-term survival. Black individuals were associated with lower odds of ≥10-year survival (aOR: 0.88, 95% CI: 0.820-0.96) and decreased likelihood of receiving LT (aOR: 0.73, 95% CI: 0.55-0.96).</p><p><strong>Conclusions: </strong>LT offers the best chance of ≥10-year survival in HCC. Ensuring equitable access is essential, especially for Black patients who have lower transplant rates and worse outcomes.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"10 5","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13120506/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147769981","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":"Lumican-TLR4 interaction accelerates hepatic fibrosis by activating hepatic stellate cells.","authors":"Yongqiang Xiong, Huanhuan Zhang, Ao Wang, Yaqian Cui, Jiaxi Ye, Leiming Jin, Mengsha Lin, Qianhui Zhang, Guang Liang, Wu Luo, Weiwei Zhu, Xiang Hu","doi":"10.1097/HC9.0000000000000948","DOIUrl":"10.1097/HC9.0000000000000948","url":null,"abstract":"<p><strong>Background: </strong>Lumican expression is associated with liver fibrosis across various etiologies. However, its precise role and underlying mechanisms in liver fibrosis remain unclear.</p><p><strong>Methods: </strong>Lumican knockout (Lum KO) mice were generated, and liver fibrosis was induced using bile duct ligation (BDL) and carbon tetrachloride (CCl4) to investigate the in vivo role of Lumican. Proteomic analyses and target validation were performed to elucidate the mechanisms by which Lumican contributes to liver fibrosis.</p><p><strong>Results: </strong>Lumican is predominantly expressed in hepatic stellate cells (HSCs) and promotes their activation. Lumican deficiency attenuates liver fibrosis progression in mice following BDL and CCl4 administration. Proteomic analysis identified Lumican as a ligand of toll-like receptor 4 (TLR4). Lumican directly binds to TLR4, activating downstream SMAD3-mediated pro-fibrotic signaling pathways, thereby promoting HSC activation and contributing to liver fibrosis development.</p><p><strong>Conclusions: </strong>Lumican plays a critical role in HSC activation and liver fibrosis progression via the Lumican-TLR4-SMAD3 axis, highlighting it as a potential therapeutic target for anti-fibrotic intervention.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"10 5","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13120511/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147769987","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":"Rapamycin-modified novel tolerogenic dendritic cells induce liver graft tolerance through MHC-II+CD8+ regulatory T cells.","authors":"Lin Zhou, Yang Zhao, Jing Wang, Qing Chen, Ya-Nan Jia, Li-Chao Pan, Han-Xuan Wang, Hong-Wei Yang, Qiang He, Xian-Liang Li, Ren Lang, Guo-Sheng Du","doi":"10.1097/HC9.0000000000000942","DOIUrl":"10.1097/HC9.0000000000000942","url":null,"abstract":"<p><strong>Background: </strong>Inducing transplant tolerance to achieve long-term graft survival without immunosuppression remains a central objective in liver transplantation.</p><p><strong>Methods: </strong>Using a rat liver transplantation model, we evaluated the effects of infusing rapamycin-modified tolerogenic dendritic cells (Rapa-tolDCs) on graft survival and tolerance induction. Underlying molecular and cellular mechanisms were investigated through activation and inhibition experiments to assess the generation, signaling pathways, and suppressive functions of regulatory T and B cell populations.</p><p><strong>Results: </strong>Infusion of Rapa-tolDCs induced donor-specific tolerance and markedly prolonged graft survival (median survival time of 65 days, maximum of 102 days). Mechanistically, Rapa-tolDCs, characterized by low expression of Siglec1 and Spp1, functioned independently of the PI3K-mTOR pathway and promoted the differentiation and proliferation of CD8+CD45RClow/- regulatory T cells (CD8+CD45RClow/- Tregs). We identified that these Tregs acquired MHC-II molecules from donor cells via trogocytosis, becoming immune chimeric cells that predominantly secreted interleukin-10 (IL-10) to mediate immune suppression. The generation of these MHC-II+CD8+ Tregs was regulated by the Wnt5a/Fzd4/RhoD signaling axis. Furthermore, elevated levels of Foxp3+ Tregs and IL-10+ Bregs were found to contribute to prolonged graft survival following Rapa-tolDC infusion.</p><p><strong>Conclusions: </strong>These findings delineate a complete mechanistic pathway from cell therapy to donor-specific tolerance and provide a foundational strategy for clinical tolerance induction and post-transplant immunomodulation.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"10 5","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13090084/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147728920","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":"Deficiency of ZFP36L1 and ZFP36L2 impairs liver homeostasis and initiates cholestatic liver injury.","authors":"Rahul Kumar, Perry J Blackshear, Sonika Patial, Yogesh Saini","doi":"10.1097/HC9.0000000000000933","DOIUrl":"10.1097/HC9.0000000000000933","url":null,"abstract":"<p><strong>Background: </strong>RNA-binding proteins, Zinc Finger Protein 36-Like 1 (ZFP36L1) and Zinc Finger Protein 36-Like 2 (ZFP36L2), post-transcriptionally regulate the expression of a large number of genes involved in various cellular processes. However, specific or redundant functions of ZFP36L1 and ZFP36L2 in liver homeostasis have never been explored. Here, we hypothesized that ZFP36L1 and ZFP36L2 are functionally redundant in the liver, and their combined deficiency would stabilize their direct mRNA targets, which would alter liver homeostasis.</p><p><strong>Methods: </strong>We generated combined liver-specific ZFP36L1-deficient and ZFP36L2-deficient mice (L1/L2dKO) and compared their liver homeostatic parameters with flox control (L1/L2FLX) mice. We performed detailed analyses of liver histology, serum biomarkers of liver injury, liver transcriptome, bile flow rate, and biliary total bile acid (TBA) excretion.</p><p><strong>Results: </strong>We demonstrated that the combined liver-specific deficiency of ZFP36L1 and ZFP36L2 in mice (L1/L2dKO) results in spontaneous cholestatic liver injury, which was characterized by elevated hepatic and serum levels of TBAs and liver injury biomarkers, including ALP, ALT, and AST, presence of bile infarcts followed by marked inflammation, cellular proliferation, and fibrosis. To determine the impact of deficiency of ZFP36L1 and ZFP36L2 on the liver transcriptome and their relevance to cholestatic liver injury, RNA sequencing of whole livers of L1/L2dKO and L1/L2FLX mice was performed, which showed significant perturbation of ZFP36L1/ZFP36L2 target genes associated with cholestasis in L1/L2dKO mice. In addition, L1/L2dKO mice exhibited reduced bile flow rate and decreased biliary TBA excretion. Subsequent analyses revealed impaired bile canalicular morphogenesis by postnatal day 7, as evidenced by F-actin and zonula occludens-1 staining patterns.</p><p><strong>Conclusions: </strong>Our findings demonstrate beneficial roles of ZFP36L1 and ZFP36L2 in maintaining liver homeostasis.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"10 5","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13090052/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147728958","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":"Radioembolization (90Y) achieves higher response rates and reduces progression risk compared with DEB-TACE in hepatocellular carcinoma.","authors":"Kelley Núñez, Navid Hasani, Julie Cronan, Juan Gimenez, Ari Cohen, Tyler Sandow, Paul Thevenot","doi":"10.1097/HC9.0000000000000935","DOIUrl":"10.1097/HC9.0000000000000935","url":null,"abstract":"<p><strong>Background: </strong>Drug-eluting bead transarterial chemoembolization (DEB-TACE) and yttrium-90 (90Y) radioembolization are approved therapies to treat hepatocellular carcinoma (HCC). Several randomized controlled trials and propensity score-matched studies (PSM) have been conducted to compare these 2 treatments; many utilized 90Y standard dosimetry (<200 Gy), which produced inferior outcomes compared with modern-day 90Y personalized dosimetry, which yields tumor doses exceeding 205 Gy.</p><p><strong>Purpose: </strong>This study utilized PSM between DEB-TACE and 90Y with personalized dosimetry to compare treatment and patient outcomes in Barcelona Clinic Liver Cancer (BCLC) A-B HCC.</p><p><strong>Methods: </strong>This retrospective study included 258 patients with unresectable BCLC A-B stage HCC treated with DEB-TACE or 90Y as the initial treatment approach from 2015 to 2024. PSM was performed (90Y:DEB-TACE), matching for tumor burden and alpha-fetoprotein levels at diagnosis. The primary endpoint was target response rate with secondary endpoints of overall response, target retreatment rate (TTR), target and overall time-to-progression (TTP), and overall survival (OS).</p><p><strong>Results: </strong>Overall, 90Y achieved significantly higher target complete (CR) and objective response (OR) rates compared with DEB-TACE (71% vs. 33% and 88% vs. 58%), respectively. In multifocal disease, target CR rates were higher following 90Y (68% vs. 13%). 90Y also yielded a longer duration of CR with a 1-year target retreatment rate of 12% compared with 40% with DEB-TACE. This translated into a longer target TPP (p=0.030) with 90Y, although overall TPP and OS were similar between treatment modalities. In multifocal disease, 90Y generated superior response rates as well as target (p=0.007) and overall TTP (p=0.015).</p><p><strong>Conclusions: </strong>90Y with personalized dosimetry achieved higher response rates and extended the duration of complete responses compared with DEB-TACE. 90Y was also more effective at treating multifocal disease.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"10 5","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13090074/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147728938","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}