Hepatology International最新文献

{"title":"Role of splenic hepatic elastography ratio in differentiating non-cirrhotic portal fibrosis and chronic liver disease in children and adolescents.","authors":"Piyush Upadhyay, Rajeev Khanna, Vikrant Sood, Bikrant Bihari Lal, Seema Alam","doi":"10.1007/s12072-024-10713-2","DOIUrl":"10.1007/s12072-024-10713-2","url":null,"abstract":"<p><strong>Background: </strong>Differentiation of Non-cirrhotic Portal Fibrosis (NCPF) from chronic liver disease (CLD) in children and adolescents with portal hypertension (PHT) is challenging especially in cases where liver stiffness measurement (LSM) and hepatic venous pressure gradient are higher. This objective of the current study was to evaluate the diagnostic accuracy of the splenic stiffness measurement (SSM)/LSM ratio in the diagnosis of NCPF.</p><p><strong>Methods: </strong>From January 2019 to December 2023, consecutive children and adolescents of 6 months to 18 years of age with PHT (CLD and NCPF) were prospectively enrolled. Transient elastography (TE) for SSM and LSM, upper gastrointestinal endoscopy (UGIE), liver biopsy/trans-jugular liver biopsy, abdominal imaging, and laboratory evaluation were done. The relationship of TE parameters for diagnosis of NCPF and CLD was evaluated. Receiver-operating characteristic (ROC) statistics were applied using R Studio-4.2.2 statistical software.</p><p><strong>Results: </strong>One hundred and forty seven with CLD and 27 patients with NCPF were evaluated. Median age was 10.0 (IQR 2.4-14.0) years; 68.4% were males. The AUROC of SSM/LSM ratio was better (0.992, 95%CI 0.982-1.0001) than LSM (0.945, 95%CI0.913-0.977) and SSM (0.626, 95%CI0.258-0.489) for the diagnosis of NCPF. SSM/LSM ratio cut-off of 3.67 predicted NCPF with an excellent sensitivity (100%), specificity (95.9%), and diagnostic accuracy (95.91%). The AUROC of SSM/LSM ratio was excellent and outperformed other TE parameters in the subgroups, i.e., LSM between 10 and 20 kPa (0.982, 95%CI 0.947-1.000), without clinically significant varices (CSV) (1.000, 95%CI 1.000-1.000) and with CSV (0.993, 95%CI 0.983-1.000). Diagnostic performance of SSM/LSM Ratio was better than LSM for discriminating NCPF from CLD using McNemar test (p = 0.01).</p><p><strong>Conclusion: </strong>The SSM/LSM ratio is an excellent tool in differentiating NCPF from CLD.</p>","PeriodicalId":12901,"journal":{"name":"Hepatology International","volume":" ","pages":"234-243"},"PeriodicalIF":5.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141787907","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Treatment of portal vein thrombosis in cirrhosis is associated with no survival advantage: a retrospective controlled study.","authors":"Abraham Z Cheloff, Luke J Bonanni, Joshua D Kirschenbaum, Naveena Luke, Jenny L Engelman, Joshua L Ross, Gabriel Fuligni, Patrick G Northup","doi":"10.1007/s12072-024-10734-x","DOIUrl":"10.1007/s12072-024-10734-x","url":null,"abstract":"<p><strong>Background and aims: </strong>Portal vein thrombosis (PVT) is associated with increased mortality post-transplant, but treatment of the clot is not definitively associated with improvement in mortality. We aimed to assess the effect of anticoagulation (AC), transjugular intrahepatic portosystemic shunt (TIPS), or best supportive care only (SCO) as treatment options in patients with PVT and cirrhosis.</p><p><strong>Methods: </strong>This was a retrospective controlled cohort study from a large urban health system. Patients with cirrhosis and PVT were identified and analyzed based on treatment provided (1) AC, (2) TIPS, and (3) SCO. Outcomes included patent portal vein at the end of follow-up and overall mortality.</p><p><strong>Results: </strong>150 patients on AC, 93 who underwent TIPS, and 172 who received SCO were analyzed. Final portal vein (PV) patency was not significantly different by treatment group in those with partial obstruction at presentation (p = 0.64), while any treatment improved final patency over SCO in those presenting with complete obstruction (p = 0.01). Rate of survival, transplant-free survival, and successful liver transplantation were not different between treatment groups.</p><p><strong>Conclusion: </strong>In our cohorts, treatment of PVT versus SCO showed no impact on survival in those presenting with partial obstruction of the PV. In those with complete obstruction, any treatment was more effective than SCO in achieving patency of the PV, but overall survival was no different. PVT may not be a pathologic mechanism that causes worsening of liver disease but may be an event in the progression that in itself is not directly responsible for worsening liver function.</p>","PeriodicalId":12901,"journal":{"name":"Hepatology International","volume":" ","pages":"191-198"},"PeriodicalIF":5.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142345523","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rheumatoid factor levels indicate cryoglobulinemia severity in hepatitis B e antigen-negative hepatitis B virus carriers: a 7-year prospective cohort study.","authors":"Jen-Wei Wu, Wei-Ting Chen, Chung-Guei Huang, Yung-Chang Chen, Chao-Wei Hsu, Rong-Nan Chien, Ming-Ling Chang","doi":"10.1007/s12072-024-10761-8","DOIUrl":"10.1007/s12072-024-10761-8","url":null,"abstract":"<p><strong>Background: </strong>The phenotype of cryoglobulinemia in hepatitis B virus (HBV) carriers remains elusive.</p><p><strong>Methods: </strong>A 7-year prospective cohort of 648 hepatitis B e antigen (HBeAg)-negative Taiwanese HBV carriers [males: 344 (53%)] was conducted.</p><p><strong>Results: </strong>Among 648, 189 (29.2%) had cryoglobulinemia, and 26 (4.0%) had cryoglobulinemic syndrome (CS). More females; higher levels of rheumatoid factor (RF), immunoglobulin M (IgM) and fibrosis-4 indices; higher proportions of proteinuria, hematuria and hepatocellular carcinoma; and lower levels of quantitative HBsAg, C3, C4 and eGFR were noted in patients with than in those without cryoglobulinemia. The associations were RF levels with cryoglobulinemia (cutoff > 12.55 IU/mL), and RF levels and baseline autoimmune diseases with CS. CS patients, symptomless cryoglobulinemia patients and patients without cryoglobulinemia had the highest, moderate, and lowest RF levels, respectively. A greater percentage of mixed cryoglobulins [IgG (2 +), IgM (2 +) and IgA (1 +)] was noted in cryoglobulinemia patients with than in those without CS (11.5% vs. 0.81%, p = 0.002). Among the 7 CS patients treated with nucleos(t)ide analogues (Nucs), cryoglobulinemia disappeared in 3 and symptoms improved in 5 during therapy. The CS prevalence was highest (6%) in patients with a baseline age of 31-40 years. Among the 26 CS patients, 23 (88.5%), 20 (76.9%), and 16 (61.5%) had peripheral neuropathy, articular and skin involvement, respectively. The cumulative incidences of major outcomes and mortality did not differ between patients with and without cryoglobulinemia.</p><p><strong>Conclusions: </strong>The prevalence rates of cryoglobulinemia and CS in HBeAg-negative HBV carriers were 29.2% and 4.0%, respectively. RF levels correlate with cryoglobulinemia severity. Mixed cryoglobulins of IgG (2 +), IgM (2 +) and IgA (1 +) are likely linked to CS, which might be alleviated by Nucs in some patients. The impact of cryoglobulinemia on long-term outcomes might be negligible.</p>","PeriodicalId":12901,"journal":{"name":"Hepatology International","volume":" ","pages":"118-130"},"PeriodicalIF":5.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142853937","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In response to \"Key considerations in portal vein thrombosis management\".","authors":"Patrick Northup, Abraham Cheloff, Luke Bonanni, Joshua Kirschenbaum, Naveena Luke, Jenny Engelman, Joshua Ross, Gabriel Fuligni","doi":"10.1007/s12072-024-10747-6","DOIUrl":"10.1007/s12072-024-10747-6","url":null,"abstract":"","PeriodicalId":12901,"journal":{"name":"Hepatology International","volume":" ","pages":"258"},"PeriodicalIF":5.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142638752","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chinese expert consensus on clinical management of hepatopathy-related thrombocytopenia (2023 edition).","authors":"Hang Yu, Hongli Yu, Yao Sun, Fu-Sheng Wang, Yinying Lu","doi":"10.1007/s12072-024-10755-6","DOIUrl":"10.1007/s12072-024-10755-6","url":null,"abstract":"<p><p>Hepatopathy-related thrombocytopenia refers to a reduction in platelet count caused by liver disease or its treatment. The incidence of this condition is correlated with the duration and severity of liver disease. The direct impact of thrombocytopenia on the clinical outcome of patients with liver disease is an increased risk of bleeding. In addition, the indirect effect involves delays or discontinuation of treatment due to the potential risk of bleeding. The pathophysiological mechanisms of hepatopathy-related thrombocytopenia include reduced platelet production, abnormal distribution, increased destruction or consumption, and so on. Current treatment strategies targeting different mechanisms include thrombopoietic agents, surgery, immunosuppressants, and platelet transfusion. However, their clinical application lacks standardization. The National Clinical Research Center for Infectious Diseases organized experts to discuss and develop this consensus to enhance the clinical management level of hepatopathy-related thrombocytopenia in China. The experts focused on aspects of diagnosis, classification, and choosing the best treatment plans based on the most recent research in the field.</p>","PeriodicalId":12901,"journal":{"name":"Hepatology International","volume":" ","pages":"70-86"},"PeriodicalIF":5.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143189132","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gut microbes associated with functional cure of chronic hepatitis B.","authors":"Takashi Honda, Masatoshi Ishigami, Yoji Ishizu, Norihiro Imai, Takanori Ito, Kenta Yamamoto, Shinya Yokoyama, Hisanori Muto, Yosuke Inukai, Asuka Kato, Asako Murayama, Sachiyo Yoshio, Tetsuya Ishikawa, Mitsuhiro Fujishiro, Hiroki Kawashima, Takanobu Kato","doi":"10.1007/s12072-025-10776-9","DOIUrl":"https://doi.org/10.1007/s12072-025-10776-9","url":null,"abstract":"<p><strong>Background and aims: </strong>Hepatitis B virus (HBV) is prevalent worldwide and is difficult to eradicate. Current treatment strategies for chronic hepatitis B ultimately seek to achieve functional cure (FC); however, the factors contributing to FC remain unclear. We aimed to investigate the gut microbiota profiles of patients with chronic hepatitis B who achieved FC.</p><p><strong>Methods: </strong>Among 105 HBeAg-negative patients with chronic hepatitis B, 70 were enrolled, after excluding patients with cirrhosis or hepatocellular carcinoma and those receiving nucleoside analogs. The gut microbiota of patients who achieved FC was assessed and compared with that of patients with high-titer of HBV DNA (HBV DNA ≥ 3.3 log IU/mL) or low-titer of HBV DNA (HBV DNA < 3.3 log IU/mL). Furthermore, we used cell culture-generated HBV (HBVcc) as a model for HBV infection to evaluate the effects of short-chain fatty acids (SCFAs) produced by the identified bacteria.</p><p><strong>Results: </strong>There was no difference in the alpha or beta diversity of the gut microbiota between the FC group and the other groups. However, compared with the other groups, the FC group presented a greater relative abundance of bacteria that produce SCFAs, especially butyrate. In vitro studies demonstrated that 1.0 mM butyrate reduces HBsAg production in HBVcc-infected cells. Furthermore, butyrate administration was most effective at the post-HBV infection stage.</p><p><strong>Conclusions: </strong>Our findings suggest that butyrate-producing bacteria contribute to FC in HBeAg-negative patients with chronic hepatitis B through butyrate-mediated inhibition of HBV production.</p>","PeriodicalId":12901,"journal":{"name":"Hepatology International","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143046568","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Non-canonical Wnt signaling pathway activated NFATC3 promotes GDF15 expression in MASH: prospective analyses of UK biobank proteomic data.","authors":"Hao Wang, Xiaoqian Xu, Lichen Shi, Cheng Huang, Yameng Sun, Hong You, Jidong Jia, You-Wen He, Yuanyuan Kong","doi":"10.1007/s12072-024-10775-2","DOIUrl":"https://doi.org/10.1007/s12072-024-10775-2","url":null,"abstract":"<p><strong>Background: </strong>Our previous research demonstrated that growth differentiation factor 15 (GDF15) exhibited superior predictive capability for metabolic dysfunction-associated steatohepatitis (MASH) development with an AUC of 0.86 at 10 years before disease diagnosis. However, the specific pathways and molecular mechanisms associated with GDF15 expression during MASH development remain to be fully investigated in humans.</p><p><strong>Methods: </strong>A nested case-control study comprising a MASH group of 78 individuals and three age- and sex-matched control groups (156 metabolic dysfunction-associated steatosis, 78 viral hepatitis, and 156 normal liver controls) was conducted. The baseline levels of GDF15-related transcription factors and upstream signaling pathways associated with the identified transcription factors were analysed prospectively.</p><p><strong>Results: </strong>The significantly higher level of nuclear factor of activated T cells 3 (NFATC3), a transcription factor for GDF15, was identified in the circulation in MASH patients compared to controls. Expression of the non-canonical Wnt signaling pathway that is upstream of NFATC3, and its related proteins CTHRC1, FRZB, SFRP1, and SFRP4, were highest in the MASH group, suggesting a non-canonical Wnt signaling/NFATC3/GDF-15 cascade in MASH disease pathogenesis. A predictive model for MASH development based on four biomarkers (CTHRC1, FRZB, NFATC3, and GDF15) showed an AUC of 0.90 at 10 years. A protein-clinical model that included these four circulating proteins and BMI yielded an AUC of 0.93 at 10 years.</p><p><strong>Conclusions: </strong>Non-canonical Wnt signaling pathway may activate NFATC3 to promote GDF15 expression in MASH disease pathogenesis. These molecular mechanisms provide novel insights for developing targeted therapies that could modulate the non-canonical Wnt/NFATC3/GDF15 cascade to prevent/treat MASH.</p>","PeriodicalId":12901,"journal":{"name":"Hepatology International","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143004514","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antibiotic prophylaxis to prevent infection in patients with Child-Pugh A cirrhosis with upper gastrointestinal bleed: an open label randomised controlled trial.","authors":"Anany Gupta, Samagra Agarwal, Sanchit Sharma, Srikanth Gopi, Deepak Gunjan, Anoop Saraya","doi":"10.1007/s12072-024-10767-2","DOIUrl":"https://doi.org/10.1007/s12072-024-10767-2","url":null,"abstract":"<p><strong>Background and aims: </strong>Although beneficial in reducing the risk of bacterial infections in patients with advanced decompensated cirrhosis after upper gastrointestinal (GI) bleed, the utility of prophylactic antibiotics in those with Child-Pugh A cirrhosis is not known. We studied if prophylactic antibiotics can be withheld in this cohort.</p><p><strong>Methods: </strong>This was a single-centre, open-label randomised-controlled-trial with non-inferiority design. Patients of Child-Pugh A cirrhosis with upper-GI bleed and hemodynamic stability were randomised to receive either no prophylactic antibiotics (test-group) or ceftriaxone [standard of care (SOC)] for 72 h alongside standard medical management. The primary outcome was infection at day-5 in both arms. Secondary outcomes included failure to control bleed, mortality at day-5, and at 6 weeks.</p><p><strong>Results: </strong>Eligible patients (n = 180; mean age 45.1 ± 13.1 years, 76.9% males; median MELDNa 9 [interquartile-range: 7-12]) of predominant non-viral etiology (alcohol: 43.4%; non-alcoholic steatohepatitis: 21.7%) were randomised, of whom outcomes could be reliably assessed for 172 and 140 patients at 5-day and 6-week follow-up, respectively. Rate of day-5 infections in test-group [7.0% (95% CI 2.8-15.1%)] was non-inferior to SOC arm [11.6% (95% CI 6.02-20.8%); absolute risk difference: -4.7% (95% CI -13.3% to 4.0%; non-inferior at 10% margin)]. Spontaneous bacterial peritonitis following post-bleed ascites was the most common site of infection in both groups (10/16; 66.7%). Rates of failure to control bleed [0% vs 4.9; absolute-risk-difference: -4.6% (95% CI -9.1% to 0.2%)], day-5 mortality [0% vs 2.5%; absolute-risk-difference: -2.3% (-5.5% to 0.9%)], and 6-week mortality [1.4% vs 2.5%; absolute-risk-difference: -1.6% (-6.5% to 3.2%)] were comparable in both arms.</p><p><strong>Conclusion: </strong>Among patients with Child-Pugh A cirrhosis with hemodynamic stability, withholding prophylactic antibiotics after upper GI bleed was not associated with increased risk of post-bleed infections.</p>","PeriodicalId":12901,"journal":{"name":"Hepatology International","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142921232","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cell-free DNA methylation-based inflammation score as a marker for hepatocellular carcinoma among people living with HIV.","authors":"Kyeezu Kim, Yinan Zheng, Brian T Joyce, Drew R Nannini, Jun Wang, Yishu Qu, Claudia A Hawkins, Edith Okeke, Olufunmilayo A Lesi, Lewis R Roberts, Demirkan B Gursel, Fatimah B Abdulkareem, Alani S Akanmu, Mary J Duguru, Pantong Davwar, David Paul Nyam, Rahmat A Adisa, Godwin Imade, Jian-Jun Wei, Masha Kocherginsky, Kwang-Youn Kim, Wasiu L Adeyemo, Emuobor Odeghe, Firas H Wehbe, Chad Achenbach, Atiene Sagay, Folasade Ogunsola, Robert L Murphy, Lifang Hou","doi":"10.1007/s12072-024-10768-1","DOIUrl":"https://doi.org/10.1007/s12072-024-10768-1","url":null,"abstract":"<p><strong>Background: </strong>People living with the human immunodeficiency virus (HIV) are at a greater risk of developing hepatocellular carcinoma (HCC), potentially due to the stimulation of inflammation by HIV infection. Inflammation-related DNA methylation signatures obtained in liquid biopsy, such as circulating cell-free DNA (cfDNA), may serve as promising minimally invasive biomarkers that can inform diagnosis of HCC.</p><p><strong>Methods: </strong>Using data from 249 individuals with HIV (114 individuals with normal liver conditions, 69 with fibrosis, 30 with cirrhosis, and 36 with HCC), we constructed a cfDNA methylation-based inflammation score (inflammation-DNAm score) based on 54 CpGs previously associated with circulating C-reactive protein concentrations. Associations of DNAm scores with HCC were assessed using multivariable logistic regression models. Receiver operating characteristic analysis was conducted to assess the performance of discriminating HCC between the inflammation-DNAm score and alpha-fetoprotein (AFP), one of the current screening biomarkers.</p><p><strong>Results: </strong>A higher inflammation-DNAm score was associated with a 29% increase in the odds of HCC (OR = 1.29, 95% CI = 1.01-1.65). The association remained consistent in the models adjusted for cellular origin proportions. The DNAm score exhibited superior performance in discriminating HCC from controls (AUC = 0.94, 95% CI = 0.90-0.98), compared to AFP (AUC = 0.68, 95% CI = 0.51-0.85).</p><p><strong>Conclusions: </strong>Our findings suggest that cfDNA methylation-based biomarkers may aid in the detection of HCC in people living with HIV, a population at high-risk of developing HCC.</p>","PeriodicalId":12901,"journal":{"name":"Hepatology International","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142864051","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeted APT8(16-34) obtained by cell-SELEX and its internalization with miR-23-5p into activated hepatic stellate cells.","authors":"Xue Yang, Lu Huang, Li-Qing Yang, Si-Yuan Wu, Ling Huang, Jiao-Jiao Wang, Bo-Tao Li, Ying Wang, Xiao-Lian Wang, Yi-Ran Ni, Rui-Tao Zhang, Yan-Qiong Zhang, Hong-Bing Zhang, Bo-Qing Zhang, Lan Ma, Jiang-Feng Wu, Chuan-Lin Jiang","doi":"10.1007/s12072-024-10760-9","DOIUrl":"https://doi.org/10.1007/s12072-024-10760-9","url":null,"abstract":"<p><strong>Background: </strong>The activation of hepatic stellate cells play a pivotal role in the pathogenesis of hepatic fibrosis. However, the current lack of specifically identified targets on these cells poses a significant challenge in developing targeted delivery tools for effective anti-hepatic fibrosis therapeutics in clinical practice.</p><p><strong>Methods: </strong>Cell-systematic evolution of ligands by exponential enrichment method was conducted on HSC-T6 cell line to screen out activated hepatic stellate cell-specific aptamers. The specificity of the selected aptamers in targeting hepatic stellate cells was confirmed after truncation optimization. Furthermore, the optimal aptamer was conjugated with miR-23b-5p via C6 linkage to evaluate the targeting specificity of this complex and assess its potential in downregulating liver fibrosis-related proteins and slowing down the progression of liver fibrosis.</p><p><strong>Results: </strong>The present study successful identified 11 highly enriched single-stranded DNA sequences (APT1-11) that specifically target activated hepatic stellate cells. Subsequent affinity detection and optimization truncation led to the selection of APT8(16-34), which effectively targeted activated hepatic stellate cells both in vivo and in vitro. Moreover, when conjugated with miR-23b-5p, APT8(16-34) also exhibited internalization ability into activated hepatic stellate cells. The delivered cargo miR-23b-5p by APT8 (16-34) effectively targeted to mRNA, leading to translational inhibition and subsequent downregulation of related proteins.</p><p><strong>Conclusions: </strong>We have identified APT8 (16- 34), which exhibits specific targeting and internalization capabilities into activated hepatic stellate cells. Moreover, when conjugated with miR-23b-5p, APT8 (16-34) also internalizes into activated hepatic stellate cells, enabling miR-23b-5p exert their respective functions.</p>","PeriodicalId":12901,"journal":{"name":"Hepatology International","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142828380","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}