Hepatology Communications最新文献

{"title":"Hepatobiliary complications in patients with sickle cell disease: A 30-year review of 1009 patients.","authors":"Maya Deeb, Kristel K Leung, Richard Ward, Jordan J Feld, Kevin H M Kuo, Gideon M Hirschfield","doi":"10.1097/HC9.0000000000000712","DOIUrl":"https://doi.org/10.1097/HC9.0000000000000712","url":null,"abstract":"<p><strong>Background: </strong>Sickle cell disease (SCD) is the most common hemoglobinopathy. We aimed to identify the prevalence of hepatobiliary injury and its association with mortality in SCD.</p><p><strong>Methods: </strong>Patients with SCD followed at a dedicated clinic at our tertiary center were retrospectively evaluated with descriptive statistics. Correlations between hepatobiliary complications and SCD complications were expressed as ORs. To evaluate mortality predictors, log-rank testing was used for univariate analysis and Cox proportional hazards for multivariable analysis, with time-dependent covariates for biochemistry.</p><p><strong>Results: </strong>Between January 1990 and December 2020, 1009 patients with SCD were identified; 63.2% were HbSS. The median age at first clinic visit was 26.4 years (IQR: 18.9-37.1), 44.3% were male, and 62.6% were ever treated with hydroxyurea. The median follow-up was 4.8 years (IQR: 1.9-8.5); mortality was 8.9%. The most frequent hepatobiliary manifestations were cholelithiasis (n=431 [42.7%]) and iron overload (n=121; 12%). Chronic viral hepatitis was reported in only 18 patients. Twenty-nine patients (2.1%) had peak ALT> 2× upper limit of normal, 15 (2.3%) had peak ALP> 2× upper limit of normal, 97 (10.3%) had peak total bilirubin >103 μmol/L, (6.02 mg/dL), and 184 (18.2%) patients had elevated peak direct bilirubin. Hepatomegaly was reported in 37 patients (3.7%), while 24 patients (2.4%) were clinically cirrhotic. Five patients received a liver transplant. In an exploratory multivariate model, age (HR 1.08 [95% CI: 1.05-1.11]), ALT elevation (HR 1.52 [95% CI: 1.29-1.78]), and total bilirubin >103 μmol/L (HR 9.3 [95% CI: 3.95-21.9]) predicted mortality independently.</p><p><strong>Conclusions: </strong>Hepatobiliary complications are common in patients with SCD and require vigilance for identification.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"9 5","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12045543/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144018791","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":"Role of mitogens in normal and pathological liver regeneration.","authors":"Massoud Vosough, Bahare Shokouhian, Mohammad Amin Sharbaf, Roya Solhi, Zahra Heidari, Homeyra Seydi, Moustapha Hassan, Ezhilarasan Devaraj, Mustapha Najimi","doi":"10.1097/HC9.0000000000000692","DOIUrl":"https://doi.org/10.1097/HC9.0000000000000692","url":null,"abstract":"<p><p>The liver has a unique ability to regenerate to meet the body's metabolic needs, even following acute or chronic injuries. The cellular and molecular mechanisms underlying normal liver regeneration have been well investigated to improve organ transplantation outcomes. Once liver regeneration is impaired, pathological regeneration occurs, and the underlying cellular and molecular mechanisms require further investigations. Nevertheless, a plethora of cytokines and growth factor-mediated pathways have been reported to modulate physiological and pathological liver regeneration. Regenerative mitogens play an essential role in hepatocyte proliferation. Accelerator mitogens in synergism with regenerative ones promote liver regeneration following hepatectomy. Finally, terminator mitogens restore the proliferating status of hepatocytes to a differentiated and quiescent state upon completion of regeneration. Chronic loss of hepatocytes, which can manifest in chronic liver disorders of any etiology, often has undesired structural consequences, including fibrosis, cirrhosis, and liver neoplasia due to the unregulated proliferation of remaining hepatocytes. In fact, any impairment in the physiological function of the terminator mitogens results in the progression of pathological liver regeneration. In the current review, we intend to highlight the updated cellular and molecular mechanisms involved in liver regeneration and discuss the impairments in central regulating mechanisms responsible for pathological liver regeneration.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"9 5","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12045551/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144018805","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":"miR-27b-3p modulates liver sinusoidal endothelium dedifferentiation in chronic liver disease.","authors":"Laia Abad-Jordà, Ana Martínez-Alcocer, Sergi Guixé-Muntet, Nicholas J Hunt, Lara J Westwood, Juan José Lozano, Rocío Gallego-Durán, Victoria C Cogger, Anabel Fernández-Iglesias, Jordi Gracia-Sancho","doi":"10.1097/HC9.0000000000000700","DOIUrl":"https://doi.org/10.1097/HC9.0000000000000700","url":null,"abstract":"<p><strong>Background: </strong>During chronic liver diseases, LSECs undergo a dedifferentiation process contributing to the development of hepatic microvascular dysfunction. Although microRNAs (miRNAs) have been associated with chronic liver disease, their role as modulators of liver endothelial phenotype is mostly unknown. Therefore, the aim of this study was to analyze miRNAs as regulators of hepatic sinusoidal endothelial dysfunction in chronic liver disease to suggest novel and translatable therapeutic options for cirrhosis.</p><p><strong>Methods: </strong>Global expression of miRNAs was determined in primary LSECs from healthy and cirrhotic patients (alcohol abuse) and rats (CCl4 inhalation). LSECs were transfected with the mimetic or inhibitor of dysregulated miRNAs or with quantum dot nano-complexes containing miR-27b-3p or negative control, and endothelial phenotype was analyzed by RNA sequencing, quantitative PCR, and western blot. Endothelial or mesenchymal phenotypes were analyzed in LSEC by RNA sequencing, followed by pathway analyses and gene deconvolution.</p><p><strong>Results: </strong>In all, 30 and 69 dysregulated miRNAs were identified in human and rat cirrhosis, respectively, of which 6 miRNAs were commonly dysregulated. Specific exogenous downregulation of miR-27b-3p was associated with the upregulation of target genes, suggesting a correlation between loss of miR-27b-3p and LSEC dedifferentiation. Finally, the expression of miR-27b-3p was efficiently and physiologically re-established in cirrhotic LSECs using nano-miR-27b-3p, leading to modulation of 1055 genes compared with the negative control, ultimately leading to inhibition of the endothelial-to-mesenchymal transition process observed in cirrhosis.</p><p><strong>Conclusions: </strong>Loss of miR-27b-3p expression contributes to LSECs dedifferentiation in cirrhosis. The use of nano-miR-27b-3p represents a new therapeutic option for hepatic diseases coursing with endothelial dysfunction.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"9 5","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12045533/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144007899","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":"Cellular communication networks in fibrosis: Insights from the MASLD pig model.","authors":"Kaiyi Zhang, Jiakun Miao, Juan Du, Yu Yang, Boce Xia, Huanqi Peng, Shuang Xu, Jiangao Fan, Yanfang Wang, Martine Schroyen, Shulin Yang","doi":"10.1097/HC9.0000000000000667","DOIUrl":"https://doi.org/10.1097/HC9.0000000000000667","url":null,"abstract":"<p><strong>Background: </strong>This research aims to reveal the cellular cross talk in fibrosis liver using transgenic pigs (TG) expressing humanized risk genes (PNPLA3I148M-GIPRdn-hIAPP) as a metabolic dysfunction-associated steatotic liver disease (MASLD) model.</p><p><strong>Methods and results: </strong>The study uses single-nucleus sequencing to reveal the differentiation and interaction characteristics of various cell populations in the liver during the development of MASLD. After 6 months of high-fat, high-sucrose diet induction, the model pigs exhibited obvious liver pathological features, including fat deposition, inflammatory cell aggregation, fibrosis, and blocked insulin signaling pathways, similar to PNPLA3 rs738409 C>G carriers. Single-nucleus RNA sequencing showed that pigs share a high correlation with human hepatic cell types and zonation. HSCs in TG pigs are more activated, showing enhancing fibrosis-related pathways and declining retinol metabolism. Pseudo-trajectory analysis revealed that over 90% of macrophages in TG liver differentiated to Fate 1 (CD68hi) with higher expression of major histocompatibility complex-II molecules, proinflammatory cytokines, phagosomes, and lysosomal-related genes. Active cell interactions were found between HSCs, endothelial cells, and Fate1 macrophages. Ligand and receptor interactions, including FGF23-FGFR, PDGFs-PDGFRs, EFNA1-EPHRs, and CXCL12-CXCR4/CXCR7, were predicted to involve in hepatic fibrosis in model pigs.</p><p><strong>Conclusions: </strong>The transgenic pig model of MASLD exhibits liver pathological features consistent with patients with MASLD. Our data supplemented the mechanism by which PNPLA3 mutations lead to hepatic steatosis, depicted a detailed atlas of hepatic profibrosis cellular network, and provided a reliable large animal model and data reference for MASLD drug development and precision treatment.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"9 5","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12045537/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143997856","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":"Treatment of alcohol use disorder in alcohol-associated liver disease: A meta-analysis.","authors":"Ashwani K Singal, Wanyu Zhang, Akshay Shetty, Arpan Patel, Shaikhoon Mohammed, Prabha Bhandari, Mohamed Abdallah, Vatsalya Vatsalya, Lorenzo Leggio, Maiying Kong","doi":"10.1097/HC9.0000000000000686","DOIUrl":"https://doi.org/10.1097/HC9.0000000000000686","url":null,"abstract":"<p><strong>Background: </strong>To examine alcohol use disorder (AUD) treatment in patients with alcohol-associated liver disease (ALD) on alcohol relapse and liver-related outcomes.</p><p><strong>Methods and results: </strong>Twenty-five eligible studies on 93,899 (33,834 AUD intervention) patients with ALD were analyzed. Data presented as HR, with a 95% CI. Of 14 studies in patients with ALD outside the liver transplantation (LT) setting, pooled data from 7 randomized controlled trials (RCTs) showed that AUD treatment reduces alcohol relapse by 73% (HR: 0.27, 95% CI: 0.15-0.46) with any treatment and by 77% (HR: 0.23, 95% CI:0.14-0.39) with medications in 5 RCTs on 322 (186 intervention) patients. AUD treatment from observational studies was associated with reduced readmission (5 studies) by 48% and decompensation (2 studies) by 52%, but not patient mortality (3 studies). Data showed moderate to high heterogeneity, without publication bias. Analysis of 8 observational studies on LT recipients showed that AUD treatment reduced alcohol relapse in the post-LT period by 59%, with 58% and 60% reduction using integrated and nonintegrated models, respectively. AUD treatment among LT recipients was associated with a reduction in patient mortality by 56% in 3 observational studies, but not in 2 RCTs (HR: 0.82, 95% CI: 0.38-1.79). Pooled data were homogeneous in the analysis of alcohol relapse but showed moderate heterogeneity in analyzing patient mortality.</p><p><strong>Conclusions: </strong>Available data on AUD treatment in patients with ALD improves abstinence and liver-related outcomes both outside and within LT settings. RCTs are needed to examine (a) medications in patients with ALD to examine the benefit of alcohol relapse and patient outcomes and (b) the benefit of integrated multidisciplinary treatment to manage the dual pathology (AUD and liver disease).</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"9 5","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12045530/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143997964","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":"Global patterns of utilization of noninvasive tests for the clinical management of metabolic dysfunction-associated steatotic liver disease.","authors":"Alina M Allen, Jeffrey V Lazarus, Naim Alkhouri, Mazen Noureddin, Vincent Wai-Sun Wong, Emmanuel A Tsochatzis, Leyla de Avila, Andrei Racila, Fatema Nader, Henry E Mark, Linda Henry, Maria Stepanova, Laurent Castera, Zobair M Younossi","doi":"10.1097/HC9.0000000000000678","DOIUrl":"https://doi.org/10.1097/HC9.0000000000000678","url":null,"abstract":"<p><strong>Background: </strong>Noninvasive tests (NITs) are used to risk-stratify metabolic dysfunction-associated steatotic liver disease. The aim was to survey global patterns of real-world use of NITs.</p><p><strong>Methods: </strong>A 38-item survey was designed by the Global NASH Council. Providers were asked about risks for advanced fibrosis, which NITs (cutoff values) they use to risk-stratify liver disease, monitor progression, and which professional guidelines they follow.</p><p><strong>Results: </strong>A total of 321 participants from 43 countries completed the survey (54% hepatologists, 28% gastroenterologists, and 18% other). Of the respondents, 85% would risk-stratify patients with type 2 diabetes, obesity (82%), or abnormal liver enzymes (73%). Among NITs to rule out significant or advanced fibrosis, transient elastography (TE) and fibrosis-4 (FIB-4) were most used, followed by NAFLD Fibrosis Score, Enhanced Liver Fibrosis, and magnetic resonance elastography. The cutoffs for ruling out significant fibrosis varied considerably between practices and from guidelines, with only 50% using TE <8 kPa, 65% using FIB-4 <1.30 for age <65, and 41% using FIB-4 <2.00 for age ≥65. Similar variability was found for ruling in advanced fibrosis, where thresholds of FIB-4 ≥2.67 and TE ≥10 kPa were used by 20% and 17%, respectively. To establish advanced fibrosis, 48% would use 2 NITs while 23% would consider 1 NIT, and 17% would confirm with liver biopsy. TE was used by >75% to monitor, and 66% would monitor (intermediate or high risk) annually. Finally, 65% follow professional guideline recommendations regarding NITs.</p><p><strong>Conclusions: </strong>In clinical practice, there is variability in NIT use and their thresholds. Additionally, there is suboptimal adherence to professional societies' guidelines.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"9 5","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12045536/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144006023","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":"The impact of liver transplantation on endpoint selection in alcohol-associated hepatitis trials.","authors":"Suthat Liangpunsakul, William B Krebs, Allison J Kwong, Paul Y Kwo, Robert S Brown, WeiQi Lin, Norman L Sussman","doi":"10.1097/HC9.0000000000000709","DOIUrl":"https://doi.org/10.1097/HC9.0000000000000709","url":null,"abstract":"<p><strong>Background: </strong>Alcohol-associated hepatitis (AH) is a serious liver disease caused by heavy alcohol consumption with severe cases exhibiting a 90-day mortality rate of ~30%. No drugs have been approved for AH, and regulatory approval currently requires evidence of improved survival. The lack of effective drug therapies and high mortality rates have fueled interest in early liver transplantation (LT), which has a survival rate that exceeds 90%. However, LT is resource-intensive and is available only in expert centers, where most AH trials are conducted. As a result, LT is overrepresented in recent AH studies, leading to confounding and unresolved questions regarding valid endpoints in therapeutic AH trials.</p><p><strong>Methods: </strong>We propose methodological approaches to address the inclusion of LT in AH trials, supported by power calculations and data from the AHFIRM trial, a 300-patient multicenter study completed in late 2023. We demonstrate the impact of effect size, trial size, and statistical methods on trial design and interpretation.</p><p><strong>Results: </strong>Effect size plays a crucial role in power calculations. While 90-day survival is the most efficient endpoint, competing risk analysis, primary stratum analysis, and win ratio are valuable tests for assessing the role of LT. The combined endpoint of death or LT is the least efficient method and requires the largest trial population to achieve statistical significance. We recommend using multiple statistical methods with adjustments for multiplicity.</p><p><strong>Conclusions: </strong>The adoption of early LT complicates the assessment of new therapies for AH. Statistical methods and endpoints are critical in power calculations and when assessing the efficacy of new therapeutic agents. We recommend mortality as the primary analysis complemented by hierarchical secondary analyses that avoid problems of multiplicity.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"9 5","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12045545/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143990675","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":"Single-cell landscape of peripheral immune cells in MASLD/MASH.","authors":"Agnes Anna Steixner-Kumar, Diana Santacruz, Tobias Geiger, Werner Rust, Dennis Böttner, Oliver Krenkel, Ehsan Bahrami, George Okafo, Thomas F E Barth, Mark Haenle, Wolfgang Kratzer, Patrycja Schlingeloff, Julian Schmidberger, Heike Neubauer, Alec Dick, Markus Werner, Eric Simon","doi":"10.1097/HC9.0000000000000643","DOIUrl":"https://doi.org/10.1097/HC9.0000000000000643","url":null,"abstract":"<p><strong>Background: </strong>Metabolic dysfunction-associated steatotic liver disease (MASLD) progresses to metabolic dysfunction-associated steatohepatitis (MASH) and is a major cause of liver cirrhosis. Although liver inflammation is the hallmark feature of MASH versus MASLD, the involvement of the peripheral immune cell compartments in disease progression is poorly understood, and single-cell profiles of peripheral immune cells in MASLD/MASH are not known.</p><p><strong>Methods: </strong>Patients with MASLD/MASH and healthy volunteers have been prospectively enrolled in a cross-sectional study. Patients have been histologically stratified and further characterized by liver bulk RNA sequencing (RNA-Seq). Peripheral immune cells from patients and control blood samples have been comprehensively profiled using bulk and single RNA-Seq.</p><p><strong>Results: </strong>Twenty-two patients with fibrosis stage less than F3 have been histologically stratified into patients with low, medium, and high disease activity scores (NAFLD activity score [NAS]). In contrast to fibrosis, the NAS group correlated with noninvasive imaging readouts and blood biomarkers of liver damage and inflammation (ALT, AST). The prevalence of type 2 diabetes and obesity increased with the NAS stage. Bulk RNA-seq profiling of patient liver biopsies revealed gene signatures that were positively and negatively associated with NAS. Known marker genes for liver fibrosis where upregulated on RNA level. Blood bulk RNA-seq showed only moderate differences in patients versus healthy controls. In contrast, single-cell analysis of white blood cells revealed multiple alterations of immune (sub-)populations, including an increased abundance of immature B cells and myeloid suppressor cells in patients with MASLD/MASH as compared to healthy controls.</p><p><strong>Conclusions: </strong>The study gives new insights into the pathophysiology of MASLD/MASH already manifesting relatively early in peripheral immune cell compartments. This opens new avenues for the development of new biomarker diagnostics and disease therapies.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"9 5","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12014121/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144007961","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":"Single-cell RNA sequencing reveals a reprogramming of hepatic immune cells and a protective role for B cells in MASH-driven HCC.","authors":"Haiguang Wang, Adam Herman, Fanta Barrow, Amal Abdel-Ghani, Micah Draxler, Gavin Fredrickson, Preethy Parthiban, Davis M Seelig, Sayeed Ikramuddin, Xavier S Revelo","doi":"10.1097/HC9.0000000000000668","DOIUrl":"https://doi.org/10.1097/HC9.0000000000000668","url":null,"abstract":"<p><strong>Background: </strong>HCC, the most common form of liver cancer, is one of the leading causes of cancer-related deaths worldwide. Although the immune system plays a crucial role in liver cancer pathogenesis, the immune landscape within metabolic dysfunction-associated steatohepatitis-driven HCC remains poorly understood.</p><p><strong>Methods: </strong>In this study, we used the high-fat, high-carbohydrate diet fed major urinary protein-urokinase-type plasminogen activator mouse model of metabolic dysfunction-associated steatohepatitis-driven HCC. We performed single-cell RNA sequencing on intrahepatic immune cells to characterize their heterogeneity and gene expression profiles. Additionally, we examined the role of B cells in antitumor immunity by depleting B cells in μMT mice and analyzing the effects on liver cancer progression.</p><p><strong>Results: </strong>Our analysis revealed significant shifts in intrahepatic immune cell populations, including B cells, T cells, and macrophages that undergo transcriptional reprogramming, suggesting altered roles in tumor immunity. Notably, an expanded subset of activated B cells in HCC mice showed an antitumor B cell gene expression signature associated with increased survival of patients with liver cancer. Consistently, B cell-deficient mice showed exacerbated liver cancer progression, a substantial reduction in intrahepatic lymphocytes, and impaired CD8+ T cell activation, suggesting that intrahepatic B cells may promote antitumor immunity by enhancing T cell responses.</p><p><strong>Conclusions: </strong>Our findings reveal a complex immune reprogramming within the metabolic dysfunction-associated steatohepatitis-driven HCC microenvironment and underscore a protective role for B cells in liver cancer. These results highlight B cells as potential targets for immunomodulatory therapies in HCC.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"9 5","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12014033/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144001758","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":"Health economic outcomes of a minimal monitoring approach to providing HCV therapy.","authors":"Benjamin P Linas, Michelle Weitz, Tannishtha Pramanick, Mark Sulkowski, Laura M Smeaton, Sandra W Cardoso, Sunil Solomon","doi":"10.1097/HC9.0000000000000579","DOIUrl":"https://doi.org/10.1097/HC9.0000000000000579","url":null,"abstract":"<p><strong>Background: </strong>The ACTG A5360 trial demonstrated that HCV treatment without planned on-treatment monitoring is safe and effective. We report the health economic outcomes of MINMON.</p><p><strong>Methods: </strong>A5360 was a 5-country, single-arm trial providing sofosbuvir/velpatasvir to people with HCV infection with no planned clinic visits between treatment initiation and week 24 sustained virologic response (SVR) evaluation. Trial records included planned/and most unplanned lab tests and visits. Participants completed a 4-week recall questionnaire at weeks 0, 24, 48, and 72 reporting hospital nights, emergency department visits, and ambulatory visits. We tabulated consumption and multiplied units of consumption by country-specific cost. We report the cost and cost per SVR of MINMON (2020 US$) from program and health sector perspectives. Sensitivity analyses compared MINMON costs to the standard of care (SoC). We consulted in-country experts to develop country-specific SoC treatment protocols and used micro-costing to estimate their costs. We compare the cost/SVR in MINMON with that of the simulated SoC, varying the expected SVR with the SoC.</p><p><strong>Results: </strong>MINMON cost/SVR (program perspective) varied by country from $1692/SVR (Thailand) to $27,632/SVR (United States). The cost/SVR (health sector perspective) ranged from $6273/SVR (South Africa) to $123,974/SVR (United States) MINMON had a lower cost/SVR than SoC across broad assumptions about SVR proportions, especially in low- and middle-income countries. In the United States-, MINMON had an appealing cost per cure compared to the SoC, unless retention on treatment fell below the SoC.</p><p><strong>Conclusions: </strong>MINMON is a cost-saving strategy for HCV treatment, particularly in low- and middle-income country settings.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"9 5","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12014070/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143990510","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}