Hepatology Communications最新文献

{"title":"Reply: Statins for the prevention of cirrhosis complications: An American emulation of the StatLiver trial.","authors":"Nina Kimer, Thit M Kronborg, Flemming Bendtsen","doi":"10.1097/HC9.0000000000000551","DOIUrl":"10.1097/HC9.0000000000000551","url":null,"abstract":"","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"8 11","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11524740/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142521763","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 influence of biophysical niche on tumor-associated macrophages in liver cancer.","authors":"Ying Zhang, Ying Rao, Jiahuan Lu, Jiyu Wang, Dai Fei Elmer Ker, Jingying Zhou, Dan Michelle Wang","doi":"10.1097/HC9.0000000000000569","DOIUrl":"10.1097/HC9.0000000000000569","url":null,"abstract":"<p><p>HCC, the most common type of primary liver cancer, is a leading cause of cancer-related mortality worldwide. Although the advancement of immunotherapies by immune checkpoint inhibitors (ICIs) that target programmed cell death 1 or programmed cell death 1-ligand 1 has revolutionized the treatment for HCC, the majority is still not beneficial. Accumulating evidence has pointed out that the potent immunosuppressive tumor microenvironment in HCC poses a great challenge to ICI therapeutic efficacy. As a key component in tumor microenvironment, tumor-associated macrophages (TAMs) play vital roles in HCC development, progression, and ICI low responsiveness. Mechanistically, TAM can promote cancer invasion and metastasis, angiogenesis, epithelial-mesenchymal transition, maintenance of stemness, and most importantly, immunosuppression. Targeting TAMs, therefore, represents an opportunity to enhance the ICI therapeutic efficacy in patients with HCC. While previous research has primarily focused on biochemical cues influencing macrophages, emerging evidence highlights the critical role of biophysical signals, such as substrate stiffness, topography, and external forces. In this review, we summarize the influence of biophysical characteristics within the tumor microenvironment that regulate the phenotype and function of TAMs in HCC pathogenesis and progression. We also explore the possible mechanisms and discuss the potential of manipulating biophysical cues in regulating TAM for HCC therapy. By gaining a deeper understanding of how macrophages sense and respond to mechanical forces, we may potentially usher in a path toward a curative approach for combinatory cancer immunotherapies.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"8 11","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11524744/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142521764","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":"A patient-centered approach to dietary supplements for patients with chronic liver disease.","authors":"Jennifer C Lai, Melinda Ring, Anand Dhruva, Gloria Y Yeh","doi":"10.1097/HC9.0000000000000552","DOIUrl":"10.1097/HC9.0000000000000552","url":null,"abstract":"<p><p>The use of dietary supplements by patients with chronic liver disease is prevalent and rising. Despite the known risks of dietary supplements, including hepatotoxicity, adulteration, and contamination, patients with chronic liver disease often turn to dietary supplements to support their liver and/or overall health but are not necessarily empowered with the information or guidance from their liver practitioner to do so. This article provides practitioners with a framework for balancing the risks and benefits of dietary supplements in patients with chronic liver disease, offering examples of independent resources and certifications to use this framework in clinical practice. We offer 3 common clinical scenarios to highlight how the use of this framework can improve communication and decision-making in clinical practice. By adapting principles from Integrative Medicine, this article advocates for a patient-centered approach to dietary supplements in patients with chronic liver disease, encouraging open dialogue between clinicians and their patients to facilitate informed decision-making and personalized care.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"8 11","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11512633/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142499331","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":"Cholestatic insult triggers alcohol-associated hepatitis in mice.","authors":"Shengmin Yan, Zhen Lin, Michelle Ma, Ailar Arasteh, Xiao-Ming Yin","doi":"10.1097/HC9.0000000000000566","DOIUrl":"10.1097/HC9.0000000000000566","url":null,"abstract":"<p><strong>Background: </strong>Alcohol-associated hepatitis (AH) is a severe, potentially life-threatening form of alcohol-associated liver disease with limited therapeutic options. Existing evidence shows that biliary dysfunction and cholestasis are common in patients with AH and are associated with poorer prognosis. However, the role of cholestasis in the development of AH is largely unknown. We aimed to examine the hypothesis that cholestasis can be an important etiology factor for AH.</p><p><strong>Methods: </strong>To study the interaction of cholestasis and alcohol, chronically ethanol (EtOH)-fed mice were challenged with a subtoxic dose of α-naphthylisothiocyanate (ANIT), a well-studied intrahepatic cholestasis inducer. Liver injury was measured by biochemical and histological methods. RNAseq was performed to determine hepatic transcriptomic changes. The impact of inflammation was assessed using an anti-LY6G antibody to deplete the neutrophils and DNase I to degrade neutrophil extracellular traps.</p><p><strong>Results: </strong>ANIT synergistically enhanced liver injury following a 4-week EtOH feeding with typical features of AH, including increased serum levels of ALT, AST, and total bile acids, cholestasis, necrosis, neutrophil infiltration, and accumulation of neutrophil extracellular traps. RNAseq revealed multiple genes uniquely altered in the livers of EtOH/ANIT-treated mice. Analysis of differentially expressed genes suggested an enrichment of genes related to inflammatory response. Anti-LY6G antibody or DNase I treatment significantly inhibited liver damage in EtOH/ANIT-treated mice.</p><p><strong>Conclusions: </strong>Our results support the hypothesis that cholestasis can be a critical contributor to the pathogenesis of AH. A combined treatment of EtOH and ANIT in mice presents biochemical, histological, and molecular features similar to those found in patients with AH, suggesting that this treatment scheme can be a useful model for studying Alcohol-associated Cholestasis and Hepatitis (AlChoHep).</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"8 11","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11512636/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142499332","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 tyrosine kinase Yes1 is a druggable host factor of HEV.","authors":"Jil Alexandra Haase, Abarna Baheerathan, Xin Zhang, Rebecca Menhua Fu, Maximilian Klaus Nocke, Charlotte Decker, Viet Loan Dao Thi, Daniel Todt, Johan Neyts, Suzanne J F Kaptein, Eike Steinmann, Volker Kinast","doi":"10.1097/HC9.0000000000000553","DOIUrl":"10.1097/HC9.0000000000000553","url":null,"abstract":"<p><strong>Background: </strong>HEV is a positive-sense, single-stranded RNA virus of the Hepeviridae family. Although HEV accounts for more than 3 million symptomatic cases of viral hepatitis per year, specific anti-HEV therapy and knowledge about HEV pathogenesis are scarce.</p><p><strong>Methods: </strong>To gain a deeper understanding of the HEV infectious cycle and guide the development of novel antiviral strategies, we here used an RNAi mini screen targeting a selection of kinases, including mitogen-activated protein kinases, receptor tyrosine kinases, and Src-family kinases. Further, we used state-of-the-art HEV infection models, including primary human hepatocytes and athymic nude rats.</p><p><strong>Results: </strong>Upon knockdown of the Src-family kinase Yes1, a significant reduction of HEV susceptibility could be observed, suggesting an important role of Yes1 in the HEV infectious cycle. Selective inhibition of Yes1 kinase activity resulted in significant inhibition of HEV infection in hepatoma cells and primary human hepatocytes, as well as in a rat HEV in vivo model system. Subsequent analysis of Y1KI during the HEV infectious life cycle indicated a role of Yes1 kinase activity in the early onset of HEV infection.</p><p><strong>Conclusions: </strong>We identified the dependence of HEV on Yes1 signaling, which may contribute to the so far scarce knowledge of HEV's pathogenesis in the future. Moreover, we provide Y1KI as a novel antiviral drug candidate specifically targeting an HEV host factor.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"8 11","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11495762/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142667334","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":"Serum levels of total bile acids are associated with an increased risk of HCC in patients with cirrhosis.","authors":"Hashem B El-Serag, Aaron P Thrift, Hao Duong, Jing Ning, Saira Khaderi, Amit G Singal, Sumeet K Asrani, Jorge A Marrero, Hannah Powell, Kinza Rizwan, Omar Najjar, Christopher I Amos, Michelle Luster, Abeer Al-Sarraj, Emad Salem, Michael E Scheurer, Jagpreet Chhatwal, Salma Kaochar, Fasiha Kanwal","doi":"10.1097/HC9.0000000000000545","DOIUrl":"10.1097/HC9.0000000000000545","url":null,"abstract":"<p><strong>Background: </strong>Previous studies have reported higher circulating bile acid levels in patients with HCC compared to healthy controls. However, the association between prediagnostic bile acid levels and HCC risk among patients with cirrhosis is unclear.</p><p><strong>Methods: </strong>We measured total BA (TBA) concentration in serum samples collected from a prospective cohort of patients with cirrhosis who were followed until the development of HCC, death, or last study date. Competing risk proportional hazard-adjusted models were used to estimate the association between tertiles of serum TBA levels and the risk of developing HCC. We quantified the incremental predictive value of serum bile acid when added to a previously validated clinical model.</p><p><strong>Results: </strong>We analyzed data from 940 patients with cirrhosis, of whom 68 patients progressed to HCC during 3406 person-years of follow-up. Higher baseline serum TBA level was significantly associated with an increased risk of developing HCC with an adjusted HR of 3.69 (95% CI = 1.85-7.37) for the highest versus lowest tertile. TBA levels significantly increased predictive ability for progression to HCC at 2 years of follow-up; the c statistic increased from 0.74 to 0.80 (p < 0.001). There was evidence for a significant interaction between TBA level and hepatitis C (p = 0.04).</p><p><strong>Conclusions: </strong>In a large prospective cohort study, the prediagnostic serum level of TBAs was associated with a significant increase in the risk of developing HCC among patients with multi-etiology cirrhosis. The TBA-associated risk was additive to that of established demographic and clinical predictors.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"8 11","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11469875/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142800578","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":"Zinc supplementation to improve prognosis in patients with compensated advanced chronic liver disease: a multicenter, randomized, double-blind, placebo-controlled clinical trial.","authors":"Juan Bañares, Laia Aceituno, Lourdes Ruiz-Ortega, Mònica Pons, Juan G Abraldes, Joan Genescà","doi":"10.1097/HC9.0000000000000524","DOIUrl":"10.1097/HC9.0000000000000524","url":null,"abstract":"<p><p>Zinc homeostasis could play a role in compensated advanced chronic liver disease, and its supplementation has been linked to improvement in liver function, a decrease of hepatic complications, and reduction in HCC incidence. Compensated advanced chronic liver disease encompasses a heterogeneous group of patients with variable risks of clinically significant portal hypertension and clinical events. The ANTICIPATE model is a validated model for stratifying these risks. Our aim is to demonstrate that zinc administration can reduce the rate and risk of presenting clinical events (first decompensation, HCC, death, and liver transplantation). This study protocol describes an ongoing phase III, national, multicenter, randomized, double-blind clinical trial that will enroll 300 patients to receive either the trial treatment (zinc acexamate) or placebo. An inclusion period of 42 months is planned, with a minimum follow-up of 2 years. Our principal hypothesis is that zinc could modify the natural history of patients with compensated advanced chronic liver disease, with an overall improvement in prognosis.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"8 11","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11469812/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142406335","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":"Impact of racial, ethnic, and socioeconomic disparities on presentation and survival of HCC: A multicenter study.","authors":"Nicole E Rich, Patricia D Jones, Hong Zhu, Tanushree Prasad, Amy Hughes, Sandi Pruitt, Caitlin C Murphy, Karim Seif-El-Dahan, Darine Daher, Gloria Figueroa, Stephanie Castaneda, Lisa Quirk, Michael Gonzales, Osiris Carranza, Samantha Bourque, Nargis Baset, Adam C Yopp, Amit G Singal","doi":"10.1097/HC9.0000000000000477","DOIUrl":"10.1097/HC9.0000000000000477","url":null,"abstract":"<p><strong>Background: </strong>Racial and ethnic disparities have been reported for HCC prognosis, although few studies fully account for clinically important factors and social determinants of health, including neighborhood socioeconomic status.</p><p><strong>Methods: </strong>We conducted a retrospective multicenter cohort study of patients newly diagnosed with HCC from January 2010 through August 2018 at 4 large health systems in the United States. We used multivariable logistic regression and cause-specific Cox proportional hazard models to identify factors associated with early-stage HCC presentation and overall survival.</p><p><strong>Results: </strong>Of 2263 patients with HCC (37.6% non-Hispanic White, 23.5% non-Hispanic Black, 32.6% Hispanic, and 6.4% Asian/other), 42.0% of patients presented at an early stage (Barcelona Clinic Liver Cancer stage 0/A). In fully adjusted models, there were persistent Black-White disparities in early-stage presentation (OR: 0.63, 95% CI: 0.45-0.89) but not Hispanic-White disparities (OR: 0.93, 95% CI: 0.70-1.24). Median survival was 16.2 (IQR: 5.8-36.8) months for White patients compared to 15.7 (IQR: 4.6-34.4) months for Hispanic, 10.0 (IQR: 2.9-29.0) months for Black, and 9.5 (IQR: 3.4-31.9) months for Asian/other patients. Black-White disparities in survival persisted after adjusting for individual demographics and clinical factors (HR: 1.30, 95% CI: 1.09-1.53) but were no longer observed after adding HCC stage and treatment (HR: 1.05, 95% CI: 0.88-1.24), or in fully adjusted models (HR: 0.97, 95% CI: 0.79-1.18). In fully adjusted models, Hispanic-White (HR: 0.87, 95% CI: 0.73-1.03) and Asian/other-White (HR: 0.85, 95% CI: 0.63-1.15) differences in survival were not statistically significant, although patients in high-SES neighborhoods had lower mortality (HR: 0.69, 95% CI: 0.48-0.99).</p><p><strong>Conclusions: </strong>In a multicenter cohort of patients with HCC, racial and ethnic differences in HCC prognosis were explained in part by differences in tumor stage at diagnosis and neighborhood SES. These data inform targets to intervene and reduce disparities.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"8 11","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11469814/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142817856","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":"Concordance of MASLD and NAFLD nomenclature in youth participating in the TARGET-NASH real-world cohort.","authors":"Cristian Sanchez-Torres, Ana Ramirez Tovar, Kelsey Chatman, Heather L Morris, Feng Yu, Andrea R Mospan, Anna Mae Diehl, Daniel H Leung, Preeti Viswanathan, James E Squires, Sirish Palle, Miriam B Vos","doi":"10.1097/HC9.0000000000000546","DOIUrl":"10.1097/HC9.0000000000000546","url":null,"abstract":"","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"8 11","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11469899/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142464076","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":"Infections in decompensated cirrhosis: Pathophysiology, management, and research agenda.","authors":"Jessica Ferguson Toll, Elsa Solà, Maria Alejandra Perez, Salvatore Piano, Alice Cheng, Aruna K Subramanian, W Ray Kim","doi":"10.1097/HC9.0000000000000539","DOIUrl":"10.1097/HC9.0000000000000539","url":null,"abstract":"<p><p>Bacterial infections in patients with cirrhosis lead to a 4-fold increase in mortality. Immune dysfunction in cirrhosis further increases the risk of bacterial infections, in addition to alterations in the gut microbiome, which increase the risk of pathogenic bacteria. High rates of empiric antibiotic use contribute to increased incidence of multidrug-resistant organisms and further increases in mortality. Despite continous advances in the field, major unknowns regarding interactions between the immune system and the gut microbiome and strategies to reduce infection risk and improve mortality deserve further investigation. Here, we highlight the unknowns in these major research areas and make a proposal for a research agenda to move toward improving disease progression and outcomes in patients with cirrhosis and infections.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"8 10","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11458171/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142371729","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}