World Journal of Hepatology最新文献

{"title":"Effect of rapamycin nanoparticles in an animal model of primary biliary cholangitis.","authors":"Yu-Shu Yang, Xian-Rui Li, Zhi-Min Wang, Lin Zheng, Jin-Long Li, Xiao-Lin Cui, Yan-Biao Song, Jun-Ji Ma, Hui-Fang Guo, Li-Xia Gao, Xiao-Hui Zhou","doi":"10.4254/wjh.v17.i6.104073","DOIUrl":"10.4254/wjh.v17.i6.104073","url":null,"abstract":"<p><strong>Background: </strong>Primary biliary cholangitis (PBC) is a chronic autoimmune-mediated cholestatic liver disease. Nanoparticles encapsulating rapamycin (ImmTOR) suppress adaptive immune responses and induce the hepatic tolerogenic immune response.</p><p><strong>Aim: </strong>To investigate the effects of ImmTOR in PBC mouse models.</p><p><strong>Methods: </strong>PBC models were induced in C57BL/6 mice by two immunizations of 2-octynoic acid-coupled bovine serum albumin at two-week intervals, and polycytidylic acid every three days. The PBC mouse models were separated into the treatment group and the control group. The levels of alkaline phosphatase (ALP) and alanine aminotransferase in the mice were detected using an automatic biochemical analyzer. Liver and spleen mononuclear cells were analyzed by flow cytometry, and serum anti-mitochondrial antibodies (AMA) and the related cytokines were analyzed by enzyme-linked immunosorbent assay. Liver histopathology was examined by hematoxylin and eosin staining and scored.</p><p><strong>Results: </strong>After treatment with ImmTOR, the ALP level was significantly decreased (189.60 U/L ± 27.25 U/L <i>vs</i> 156.00 U/L ± 17.21 U/L, <i>P</i> < 0.05), the level of AMA was reduced (1.28 ng/mL ± 0.27 ng/mL <i>vs</i> 0.56 ng/mL ± 0.07 ng/mL, <i>P</i> < 0.001) and the expression levels of interferon gamma and tumor necrosis factor α were significantly decreased (48.29 pg/mL ± 10.84 pg/mL <i>vs</i> 25.01 pg/mL ± 1.49 pg/mL, <i>P</i> < 0.0001) and (84.24 pg/mL ± 23.47 pg/mL <i>vs</i> 40.66 pg/mL ± 14.65 pg/mL, <i>P</i> < 0.001). The CD4+ T lymphocytes, CD8+ T lymphocytes and B lymphocytes in the liver were significantly reduced, with statistically significant differences (24.21% ± 6.55% <i>vs</i> 15.98% ± 3.03%, <i>P</i> < 0.05; 9.09% ± 1.91% <i>vs</i> 5.49% ± 1.00%, <i>P</i> < 0.001; 80.51% ± 2.96% <i>vs</i> 75.31% ± 4.34%, <i>P</i> < 0.05). The expression of CD8+ T lymphocytes and B lymphocytes in the ImmTOR treatment group also decreased (9.09% ± 1.91% <i>vs</i> 5.49% ± 1.00%, <i>P</i> < 0.001; 80.51% ± 2.96% <i>vs</i> 75.31% ± 4.34%, <i>P</i> < 0.05). The liver pathology of PBC mice in the treatment group showed reduced inflammation and a decreased total pathology score, and the difference in the scores was statistically significant (4.50 ± 2.88 <i>vs</i> 1.75 ± 1.28, <i>P</i> < 0.05).</p><p><strong>Conclusion: </strong>ImmTOR can improve biochemistry and pathology of liver obvious by inhibiting the expression of CD8+ T cells and B cells, and reducing the titer of AMA.</p>","PeriodicalId":23687,"journal":{"name":"World Journal of Hepatology","volume":"17 6","pages":"104073"},"PeriodicalIF":2.5,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12210173/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144555001","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Future directions in prognostic modeling for dengue-induced severe hepatitis.","authors":"Chen Wang, Hong Hu, Yun Song, Yu-Gang Wang, Min Shi","doi":"10.4254/wjh.v17.i6.107299","DOIUrl":"10.4254/wjh.v17.i6.107299","url":null,"abstract":"<p><p>A study published by Teerasarntipan <i>et al</i> in the <i>World Journal of Gastroenterology</i> provides valuable insights into prognostic scoring for acute liver failure and in-hospital mortality in patients with dengue-induced severe hepatitis. Their findings validate the model for end-stage liver disease score as the most reliable predictor while demonstrating the utility of the simpler Easy Albumin-Bilirubin score. Despite these findings, current prognostic models face limitations in real-world clinical applications. This letter discusses the strengths and weaknesses of current prognostic models, proposes future directions for improving prognostic accuracy and clinical implementations. This letter also broadens the horizons of prognostic models for liver dysfunction caused by other viral infections.</p>","PeriodicalId":23687,"journal":{"name":"World Journal of Hepatology","volume":"17 6","pages":"107299"},"PeriodicalIF":2.5,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12210175/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144555002","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hepatocyte-intrinsic innate immunity in hepatitis B virus infection: A focused review.","authors":"Ping Chen, Jing Zhao, Ning-Kai Chen, Zhi-Ying Chen","doi":"10.4254/wjh.v17.i6.104533","DOIUrl":"10.4254/wjh.v17.i6.104533","url":null,"abstract":"<p><p>Chronic hepatitis B virus (HBV) infection remains a major health burden worldwide. To establish a persistence infection, HBV needs to evade both adaptive and innate immune surveillance. Multiple mechanisms for adaptive immunity evasion have been established, but how HBV evades the innate surveillance is less clear. There are three types of host cells involving in the innate immune responses against HBV infection: Hepatocytes, hepatic nonparenchymal cells and conventional innate immune cells. Among these, hepatocytes are the only target cells that are susceptible to HBV infection and the only confirmed site where HBV replication takes place. This review focuses on the hepatocyte-intrinsic innate immunity; one of the earliest host defense responses. After entering hepatocytes, the viral components can be sensed by the cellular pattern recognition receptors. This triggers downstream antiviral responses capable of inhibiting viral replication and even degrading the viral DNA genome directly or indirectly. However, HBV has evolved a variety of sophisticated strategies to evade intracellular immune defense, resulting in the establishment of infection. Here, we provide insights into the mechanisms of the intrinsic innate immune response of hepatocytes and how HBV escapes these defense mechanisms. Hopefully, this will lay the foundation for the development of novel anti-HBV therapies.</p>","PeriodicalId":23687,"journal":{"name":"World Journal of Hepatology","volume":"17 6","pages":"104533"},"PeriodicalIF":2.5,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12210160/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144555004","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hope on the horizon: Emerging therapies for hepatitis D.","authors":"Zaigham Abbas, Minaam Abbas","doi":"10.4254/wjh.v17.i6.107963","DOIUrl":"10.4254/wjh.v17.i6.107963","url":null,"abstract":"<p><p>Current treatment options for hepatitis D are limited, with pegylated interferon-alpha (PEG-IFNα) being the only therapy available in the Asia-Pacific region. However, PEG-IFNα has limited efficacy and significant side effects. Pegylated interferon lambda acts on interferon-lambda (Type III) receptors predominantly expressed in hepatocytes. In 2023, bulevirtide was approved in the European Union and Russia for treating chronic hepatitis D. This drug works by binding to and inhibiting the sodium taurocholate co-transporting polypeptide receptor on liver cells, which is the primary entry point for the virus. Recently, several new drugs have entered various stages of development, offering hope for improved hepatitis D virus (HDV) management. Two more viral entry inhibitors are HH003 and tobevibart. Other agents include nucleic acid polymers (REP 2139-Mg), prenylation inhibitors (lonafarnib), and RNA interference-based therapies (elebsiran). Emerging trials are now considering combination therapies, such as SOLSTICE, a Phase 2 clinical trial evaluating tobevibart alone or combined with elebsiran. The combination dosed monthly achieved > 50% virologic and biochemical response at 24 weeks of therapy. The efficacy and safety of these drugs will further be evaluated in ECLIPSE 1, 2, and 3 trials. With these new treatments on the horizon, the prospects for improved HDV patient outcomes are promising.</p>","PeriodicalId":23687,"journal":{"name":"World Journal of Hepatology","volume":"17 6","pages":"107963"},"PeriodicalIF":2.5,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12210157/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144555005","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-term outcomes of early transjugular intrahepatic portosystemic shunts in patients with acute variceal bleeding and cirrhosis.","authors":"Xin Tang, Ju-Bo Liang, Chen Wang, Jia-Li Ma, Rong-Rong Jia, Yu-Gang Wang, Min Shi","doi":"10.4254/wjh.v17.i6.105578","DOIUrl":"10.4254/wjh.v17.i6.105578","url":null,"abstract":"<p><strong>Background: </strong>Early transjugular intrahepatic portosystemic shunts (TIPS) is a therapeutic option for acute variceal bleeding (AVB), offering a low risk of rebleeding. However, the long-term outcomes of early TIPS remain unclear.</p><p><strong>Aim: </strong>To evaluate the long-term outcomes for early TIPS compared with standard treatment in patients with cirrhosis and AVB.</p><p><strong>Methods: </strong>We retrospectively analyzed the clinical data of patients with AVB who underwent early TIPS or standard treatment between January 2014 and December 2023. The primary outcome was overall survival (OS).</p><p><strong>Results: </strong>A total of 37 patients with AVB underwent early TIPS, while 65 patients received standard treatment. Compared with the standard treatment group, the rates of uncontrolled bleeding or rebleeding in the early TIPS group were significantly lower (10.8% <i>vs</i> 50.8%, <i>P</i> < 0.001). Over a median follow-up of 46 months, no statistically significant differences were observed in terms of OS (<i>P</i> = 0.507). The presence of comorbidities was identified as an independent predictor of OS (adjusted hazard ratio = 3.81; 95% confidence interval: 1.16-12.46). Notably, new or worsening ascites occurred less frequently in the early TIPS group (13.5% <i>vs</i> 38.5%, <i>P</i> = 0.008). There was no significant difference in the rate of overt hepatic encephalopathy between the two groups (45.9% <i>vs</i> 36.9%, <i>P</i> = 0.372).</p><p><strong>Conclusion: </strong>While early TIPS is not associated with a long-term survival benefit compared with standard treatment for AVB, it is associated with reduced risks of rebleeding and ascites.</p>","PeriodicalId":23687,"journal":{"name":"World Journal of Hepatology","volume":"17 6","pages":"105578"},"PeriodicalIF":2.5,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12210172/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144555007","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MANPOWER study: Real-world post-hoc analysis assessing essential phospholipids for non-alcoholic fatty liver disease from the Russian registry.","authors":"Asad Izziddin Dajani, Branko Popovic, Caroline Amand, Sabine Tong, Kirill Maximovich Starostin, Victor Goncharuk","doi":"10.4254/wjh.v17.i6.103217","DOIUrl":"10.4254/wjh.v17.i6.103217","url":null,"abstract":"<p><strong>Background: </strong>Since non-alcoholic fatty liver disease (NAFLD) is associated with abnormal liver function tests, treatment recommendations aim to reduce the level of known markers of liver inflammation, such as alanine transaminase (ALT), aspartate transaminase (AST) and gamma-glutamyl transferase (GGT). Essential phospholipids (EPLs) have been shown to reduce levels of these liver enzymes and improve ultrasonographic features. While non-invasive diagnostic tests have been developed to stage inflammation, these tests were not specifically designed to evaluate patients with NAFLD. This highlights the need to describe the liver enzyme profile across the different levels of NAFLD severity for improved grading and staging of NAFLD.</p><p><strong>Aim: </strong>To describe liver enzyme profiles across NAFLD severity to inform a diagnostic staging algorithm and identify who may benefit from EPLs.</p><p><strong>Methods: </strong>This post-hoc analysis of the observational MANPOWER study included 2843 adult patients with newly diagnosed NAFLD. The primary endpoint was assessment of baseline liver enzyme profiles. Secondary endpoints were effectiveness of Essentiale^® (an EPL) on liver enzyme levels and ultrasonography findings across three definitions of NAFLD: (1) Statistical distribution of liver enzyme levels; (2) MANPOWER cut-offs; and (3) Presence of physician-diagnosed non-alcoholic steatohepatitis. The best performing algorithm was used to describe the risk factors and profiles associated with increased liver enzyme levels.</p><p><strong>Results: </strong>Of the 2843 patients included in this post-hoc analysis, most were female (62.2%), with a mean age of 48.4 years (SD 8.59 years). Overall, mean levels of ALT, AST and GGT increased with NAFLD severity for all three subgroups, with the rate of chronic comorbidities correlated with NAFLD severity. Across each subgroup of interest, Essentiale significantly reduced average liver enzyme levels and improved ultrasonography features, including diffuse liver hyperechogenicity and heterogeneous liver structure (<i>P</i> < 0.05), with greater benefit associated with increased severity. Compared with all algorithms tested, the algorithm based on the statistical distribution of liver enzymes displayed the highest accuracy, sensitivity and specificity for the grading and staging of NAFLD and could form the basis of a diagnostic algorithm.</p><p><strong>Conclusion: </strong>Liver enzyme profiles may identify NAFLD severity and allow monitoring of therapeutic response. Essentiale may improve liver enzyme levels and ultrasonography features. An algorithm could aid in the diagnosis/staging of NAFLD.</p>","PeriodicalId":23687,"journal":{"name":"World Journal of Hepatology","volume":"17 6","pages":"103217"},"PeriodicalIF":2.5,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12210169/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144555009","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of zinc finger protein 71 in hepatocellular carcinoma: Methodological concerns, clinical relevance, and future directions.","authors":"Arunkumar Krishnan, Diptasree Mukherjee","doi":"10.4254/wjh.v17.i6.106573","DOIUrl":"10.4254/wjh.v17.i6.106573","url":null,"abstract":"<p><p>A recent study by Qin <i>et al</i> emphasized the potential of zinc finger protein 71 (ZNF71) as a promising biomarker for hepatocellular carcinoma (HCC). The authors offered valuable insights into the relationship between ZNF71 and various clinical and pathological stages of HCC. However, several limitations are required to be addressed to improve the findings. These limitations include concerns regarding patient selection, the generalizability of the results, and the necessity for functional validation to establish ZNF71's specific role in the progression of HCC. Furthermore, statistical issues related to multiple comparisons, confounding variables, and the inherent heterogeneity of high-throughput datasets warrant careful consideration. Future research should focus on multi-institutional cohorts, utilize <i>in vivo</i> models, and compare ZNF71 with established biomarkers to strengthen the clinical relevance of ZNF71.</p>","PeriodicalId":23687,"journal":{"name":"World Journal of Hepatology","volume":"17 6","pages":"106573"},"PeriodicalIF":2.5,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12210155/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144555012","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Human albumin infusion for reducing hyponatremia and circulatory dysfunction in liver cirrhosis: A meta-analysis update.","authors":"Hui-Juan Zhou, Zi-Qiang Li, Da-Er Dili, Qing Xie","doi":"10.4254/wjh.v17.i6.106418","DOIUrl":"10.4254/wjh.v17.i6.106418","url":null,"abstract":"<p><strong>Background: </strong>Liver cirrhosis is a progressive disease with high morbidity and mortality requiring effective management strategies to improve patient outcomes. Various therapies including albumin infusion, volume expanders (VEs), and vasoactive agents are used to manage patients with cirrhosis. Despite numerous clinical trials, a comprehensive meta-analysis comparing the effectiveness of albumin infusion against alternative treatments is limited. This study provides the current and comprehensive synthesis of evidence, offering key insights for optimizing therapeutic strategies in patients with liver cirrhosis.</p><p><strong>Aim: </strong>To systematically update available data on therapies of liver cirrhosis, we performed a meta-analysis to evaluate and compare the clinical efficacy of albumin infusion <i>vs</i> other VEs and vasoactive agents in patients with liver cirrhosis.</p><p><strong>Methods: </strong>A literature search from the PubMed and Embase databases (inception till June 2024) focused on hyponatremia (primary outcome) and various outcomes such as gastrointestinal bleeding, hepatic encephalopathy, severe infection, post-paracentesis-induced circulatory dysfunction (PICD), ascites reappearance, spontaneous bacterial peritonitis, hepatorenal syndrome, renal impairment, hospital stay, mortality, and safety was performed. The primary analysis pooled studies that compared albumin infusion with control. In the subgroup analysis, comparisons were made within the stratified treatment categories included in the control group.</p><p><strong>Results: </strong>Of the 2957 studies retrieved, 31 studies (27 randomized controlled trials and 4 observational studies) comprising 6255 patients were included. Albumin use was significant in reducing odds of hyponatremia [odds ratio (OR) = 0.67; 95% confidence interval (95%CI) = 0.53-0.85] and PICD (OR = 0.38; 95%CI = 0.20-0.71), whereas the reduction in severe infection (OR = 0.55; 95%CI = 0.28-1.07) did not reach statistical significance. In the subgroup analysis, albumin demonstrated a favorable improvement in lowering the incidence of hyponatremia vs inactive/standard medical therapy (OR = 0.54; 95%CI = 0.27-1.09). For PICD, albumin use was significant compared with other VEs (OR = 0.31; 95%CI = 0.11-0.85) but not with vasoconstrictors (OR = 0.63; 95%CI = 0.21-1.91). In the overall subgroup analysis, a significant reduction was observed in hyponatremia (OR = 0.67; 95%CI = 0.53-0.85) and PICD (OR = 0.38; 95%CI = 0.20-0.71).</p><p><strong>Conclusion: </strong>Human albumin has been shown to significantly reduce the incidence of hyponatremia and PICD in patients with liver cirrhosis, whereas its effect on severe infection remains suggestive but not statistically significant.</p>","PeriodicalId":23687,"journal":{"name":"World Journal of Hepatology","volume":"17 6","pages":"106418"},"PeriodicalIF":2.5,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12210167/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144555006","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chromatin accessibility module identified by single-cell sequencing underlies the diagnosis and prognosis of hepatocellular carcinoma.","authors":"Xiao-Li Xi, Yi-Dong Yang, Hui-Ling Liu, Jie Jiang, Bin Wu","doi":"10.4254/wjh.v17.i6.107329","DOIUrl":"10.4254/wjh.v17.i6.107329","url":null,"abstract":"<p><strong>Background: </strong>Hepatocellular carcinoma (HCC) is notorious for its aggressive progression and dismal prognosis, with chromatin accessibility dynamics emerging as pivotal yet poorly understood drivers.</p><p><strong>Aim: </strong>To dissect how multilayered chromatin regulation sustains oncogenic transcription and tumor-stroma crosstalk in HCC, we combined multiomics single cell analysis.</p><p><strong>Methods: </strong>We integrated single-cell RNA sequencing and paired single-cell assay for transposase-accessible chromatin with sequencing data of HCC samples, complemented by bulk RNA sequencing validation across The Cancer Genome Atlas, Liver Cancer Institute, and GSE25907 cohorts. Cell type-specific chromatin architectures were resolved <i>via</i> ArchR, with regulatory hubs identified through peak-to-gene linkages and coaccessibility networks. Functional validation employed A485-mediated histone 3 lysine 27 acetylation suppression and small interfering RNA targeting <i>DGAT1</i>.</p><p><strong>Results: </strong>Malignant hepatocytes exhibited expanded chromatin accessibility profiles, characterized by increased numbers of accessible peaks and larger physical regions despite reduced peak intensity. Enhancer-like peaks enriched in malignant regulation, forming long-range hubs. Eighteen enhancer-like peak-related genes showed tumor-specific overexpression and diagnostic accuracy, correlating with poor prognosis. Intercellular coaccessibility analysis revealed tumor-stroma symbiosis <i>via</i> shared chromatin states. Pharmacological histone 3 lysine 27 acetylation inhibition paradoxically downregulated <i>DGAT1</i>, the hub gene most strongly regulated by chromatin accessibility. <i>DGAT1</i> knockdown suppressed cell proliferation.</p><p><strong>Conclusion: </strong>Multilayered chromatin reprogramming sustains HCC progression through tumor-stroma crosstalk and <i>DGAT1</i>-related oncogenic transcription, defining targetable epigenetic vulnerabilities.</p>","PeriodicalId":23687,"journal":{"name":"World Journal of Hepatology","volume":"17 6","pages":"107329"},"PeriodicalIF":2.5,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12210165/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144555096","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Machine learning to identify potential biomarkers for sarcopenia in liver cirrhosis.","authors":"Qian-Yu Liang, Jun Wang, Yun-Feng Yang, Kai Zhao, Rui-Li Luo, Ye Tian, Feng-Xia Li","doi":"10.4254/wjh.v17.i6.105332","DOIUrl":"10.4254/wjh.v17.i6.105332","url":null,"abstract":"<p><strong>Background: </strong>The prevalence of sarcopenia progressively increases with as liver function deteriorates. Muscle wasting has been shown to independently predict adverse outcomes in liver cirrhosis patients.</p><p><strong>Aim: </strong>To screen effective biomarkers for sarcopenia in liver cirrhosis.</p><p><strong>Methods: </strong>Untargeted metabolomics were performed on serum from 62 liver cirrhosis patients, including 41 with sarcopenia and 21 without sarcopenia. Candidate metabolite biomarkers were screened based on three machine-learning algorithms. The diagnostic or predictive value of potential biomarkers was evaluated by drawing receiver operating characteristic curves.</p><p><strong>Results: </strong>A total of 60 differential metabolites between cirrhotic sarcopenia and the non-sarcopenia group were identified. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis revealed differential metabolites primarily involved in glycerophospholipid metabolism, alpha-linolenic acid metabolism, retrograde endocannabinoid signaling, and choline metabolism in cancer. Finally, four potential biomarkers were screened through machine learning algorithms, namely N-Acetylcarnosine, 2-Stearylcitrate, CerP (d18:1/12:0), and 3-Methyl-alpha-ionylacetate. Among these, N-Acetylcarnosine can provide better diagnostic accuracy.</p><p><strong>Conclusion: </strong>This study unveiled different plasma metabolic profiles of liver cirrhosis patients with and without sarcopenia. These valuable biomarkers have the potential to improve the prognosis of liver patients with cirrhosis by early detection or prediction of sarcopenia.</p>","PeriodicalId":23687,"journal":{"name":"World Journal of Hepatology","volume":"17 6","pages":"105332"},"PeriodicalIF":2.5,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12210171/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144555008","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}