Hepatology International最新文献

{"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":"Burden, trends, and predictions of liver cancer in China, Japan, and South Korea: analysis based on the Global Burden of Disease Study 2021.","authors":"Si Yang, Yujiao Deng, Yi Zheng, Jing Zhang, Dongdong He, Zhijun Dai, Changcun Guo","doi":"10.1007/s12072-024-10763-6","DOIUrl":"https://doi.org/10.1007/s12072-024-10763-6","url":null,"abstract":"<p><strong>Background: </strong>Liver cancer (LC) is a major concern in the Asia-Pacific region, particularly in China, Korea, and Japan. In this study, we aimed to investigate the burden, trends, and predictions related to LC in these countries.</p><p><strong>Methods: </strong>Using data from the Global Burden of Disease Study 2021, the epidemiological characteristics [incidence, deaths, and disability-adjusted life-years (DALYs)] for LC were analysed and stratified by specific etiologies in China, Japan, and South Korea. We examined temporal trends in LC burden over the last 32 years and projected changes over the following 25 years. The risk factors associated with LC deaths and DALYs were also investigated.</p><p><strong>Results: </strong>In 2021, the highest LC-related incidence, mortality, and DALYs were recorded in China (196,637 incidents, 172,068 mortalities, and 4,890,023 DALYs), and the lowest in South Korea (18,642 incidents, 13,674 deaths, and 326,336 DALYs). South Korea recorded the highest age-standardized rates (ASRs) of incidence, mortality, and DALYs for LC (19.94 per 100,000, 14.53 per 100,000, and 354.57 per 100,000), and Japan the lowest (9.89, 7.29, and 145.74, respectively). From 1990 to 2021, LC incidents and deaths in the three countries increased, and the trends in ASRs decreased. LC incidents and deaths caused by five etiologies also increased in the past 32 years, and non-alcoholic steatohepatitis (NASH) was the largest increasing etiologies in China. Infections with hepatitis B virus remained the leading cause of LC in China and South Korea, while hepatitis C virus was the prevailing cause in Japan. High body mass index (BMI) was the most sharply increasing risk factor in China. Alcohol and drug use were the main risk factors for LC in South Korea and Japan, respectively. The LC burden in the three countries was projected to rise steadily between 2022 and 2046.</p><p><strong>Conclusions: </strong>LC remains a significant disease burden in China, Japan, and South Korea now and over the next 25 years. Regarding etiologies and risk factors, NASH and high BMI in China, alcohol use in South Korea, and drug use in Japan should receive significant attention.</p>","PeriodicalId":12901,"journal":{"name":"Hepatology International","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2025-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142970563","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":"Development of nomograms to predict outcomes for large hepatocellular carcinoma after liver resection.","authors":"Jianxing Zeng, Guixiang Chen, Jinhua Zeng, Jingfeng Liu, Yongyi Zeng","doi":"10.1007/s12072-024-10754-7","DOIUrl":"https://doi.org/10.1007/s12072-024-10754-7","url":null,"abstract":"<p><strong>Background: </strong>Large hepatocellular carcinoma (HCC) is difficult to resect and accompanied by poor outcome. The aim was to evaluate the short-term and long-term outcomes of patients who underwent liver resection for large HCC, eventually drawing prediction models for short-term and long-term outcomes.</p><p><strong>Methods: </strong>1710 large HCC patients were recruited and randomly divided into the training (n = 1140) and validation (n = 570) cohorts in a 2:1 ratio. Independent risk factors were identified by regression model and used to establish three nomograms for surgical risk, overall survival (OS), and recurrence-free survival (RFS) in the training cohort. Model performances were assessed by discrimination and calibration. The three models were also compared with six other staging systems.</p><p><strong>Results: </strong>Platelet (PLT), gamma-glutamyl transpeptidase (GGT), albumin-bilirubin (ALBI) grade, blood transfusion and loss, resection margin, tumor size, and tumor number were established in a nomogram to evaluate surgical risk ( https://largehcc.shinyapps.io/largehcc-morbidity/ ). The model had a good prediction capability with a C-index of 0.764 and 0.773 in the training and validation cohorts. Alpha-fetoprotein (AFP), resection margin, tumor size, tumor number, microvascular invasion, Edmondson-Steiner grade, tumor capsular, and satellite nodules were considered to construct a prognostic nomogram to predict the 1-, 3- and 5-year OS ( https://largehcc.shinyapps.io/largehcc-os/ ). The C-index of the model was 0.709 and 0.702 for the training and validation cohorts. Liver cirrhosis, albumin (ALB), total bilirubin (TBIL), AFP, tumor size, tumor number, microvascular invasion, and tumor capsular were used to draw a prognostic nomogram to predict the 1-, 3- and 5-year RFS ( https://largehcc.shinyapps.io/largehcc-rfs/ ). The C-index of the model was 0.695 and 0.675 in the training and validation cohorts. The discrimination showed that the models had significantly better predictive performances than six other staging systems.</p><p><strong>Conclusions: </strong>Three novel nomograms were developed to predict short-term and long-term outcomes in patients with large HCC who underwent curative resection with adequate performance. These predictive models could help to design therapeutic interventions and surveillance for patients with large HCC.</p>","PeriodicalId":12901,"journal":{"name":"Hepatology International","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142931415","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":"Genetic predisposition of metabolic dysfunction-associated steatotic liver disease: a population-based genome-wide association study.","authors":"Shao-Wen Wang, Ching Wang, Yu-Ming Cheng, Chun-Yi Chen, Tsung-Han Hsieh, Chia-Chi Wang, Jia-Horng Kao","doi":"10.1007/s12072-024-10769-0","DOIUrl":"https://doi.org/10.1007/s12072-024-10769-0","url":null,"abstract":"<p><strong>Background/purpose: </strong>Although metabolic dysfunction-associated steatotic liver disease (MASLD) has been proposed to replace the diagnosis of non-alcoholic fatty liver disease (NAFLD) with new diagnostic criteria since 2023, the genetic predisposition of MASLD remains to be explored.</p><p><strong>Methods: </strong>Participants with data of genome-wide association studies (GWAS) in the Taiwan Biobank database were collected. Patients with missing data, positive for HBsAg, anti-HCV, and alcohol drinking history were excluded. MASLD was defined if having hepatic steatosis on ultrasound, plus at least one of cardiometabolic criteria. The Taiwan biobank used two genetic chips during the period of data collection: Taiwan biobank version 1 (TWBv1) as the initial chip and TWBv2 specifically designed for the Taiwanese population. TWBv2 was used as test group and TWBv1 as validation group. NAFLD fibrosis score (NFS) was used to assess the degree of liver fibrosis, and carotid plaques on duplex ultrasound were employed for the diagnosis of atherosclerosis.</p><p><strong>Results: </strong>In a total of 16,407 (mean age 55.35 ± 10.41; 29.6% males) participants, 6722 (41.0%) had MASLD. Eleven single-nucleotide polymorphisms (SNP) were identified to be associated with MASLD. Their functions were exonic in two and intronic in nine. They were related to the PNALA3, and SAMM50 genes located on chromosome 22. The linkage disequilibrium showed a high correlation with each other. Four SNPs of PNALA3 and SAMM50 genes had increased risk of MASLD and higher levels of AST/ALT. In addition, there was no association of these two genes with glucose metabolism, but better lipid profiles in SAMM50.</p><p><strong>Conclusions: </strong>This large GWAS study indicates that eleven SNPs of PNPLA3 and SAMM50 genes predispose the development of MASLD in Taiwanese population.</p>","PeriodicalId":12901,"journal":{"name":"Hepatology International","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2025-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142931416","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":"Metabolic (dysfunction)-associated fatty liver disease metrics and contributions: Correspondence.","authors":"Hinpetch Daungsupawong, Viroj Wiwanitkit","doi":"10.1007/s12072-024-10771-6","DOIUrl":"https://doi.org/10.1007/s12072-024-10771-6","url":null,"abstract":"","PeriodicalId":12901,"journal":{"name":"Hepatology International","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142894060","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":"Predictive model for HBsAg clearance rate in chronic hepatitis B patients treated with pegylated interferon α-2b for 48 weeks.","authors":"Zhili Tan, Nan Kong, Qiran Zhang, Xiaohong Gao, Jia Shang, Jiawei Geng, Ruirui You, Tao Wang, Ying Guo, Xiaoping Wu, Wenhong Zhang, Lihong Qu, Fengdi Zhang","doi":"10.1007/s12072-024-10764-5","DOIUrl":"https://doi.org/10.1007/s12072-024-10764-5","url":null,"abstract":"<p><strong>Background and aims: </strong>Chronic hepatitis B (CHB) is a major global health concern. This study aims to investigate the factors influencing hepatitis B surface antigen (HBsAg) clearance in CHB patients treated with pegylated interferon α-2b (Peg-IFNα-2b) for 48 weeks and to establish a predictive model.</p><p><strong>Methods: </strong>This analysis is based on the \"OASIS\" project, a prospective real-world multicenter study in China. We included CHB patients who completed 48 weeks of Peg-IFNα-2b treatment. Patients were randomly assigned to a training set and a validation set in a ratio of approximately 4:1 by spss 26.0, and were divided into clearance and non-clearance groups based on HBsAg status at 48 weeks. Clinical data were analyzed using SPSS 26.0, employing chi-square tests for categorical data and Mann-Whitney U tests for continuous variables. Significant factors (p < 0.05) were incorporated into a binary logistic regression model to identify independent predictors of HBsAg clearance. The predictive model's performance was evaluated using ROC curve analysis.</p><p><strong>Results: </strong>We included 868 subjects, divided into the clearance group (187 cases) and the non-clearance group (681 cases). They were randomly assigned to a training set (702 cases) and a validation set (166 cases). Key predictors included female gender (OR = 1.879), lower baseline HBsAg levels (OR = 0.371), and cirrhosis (OR = 0.438). The final predictive model was: Logit(P) = 0.92 + Gender (Female) * 0.66 - HBsAg (log) * 0.96 - Cirrhosis * 0.88. ROC analysis showed an AUC of 0.80 for the training set and 0.82 for the validation set, indicating good predictive performance.</p><p><strong>Conclusion: </strong>Gender, baseline HBsAg levels, and cirrhosis are significant predictors of HBsAg clearance in CHB patients after 48 weeks of Peg-IFNα-2b therapy. The developed predictive model demonstrates high accuracy and potential clinical utility.</p>","PeriodicalId":12901,"journal":{"name":"Hepatology International","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142864065","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":"Global, regional, and national temporal trends in incidence and mortality for liver cancer due to hepatitis B, 1990-2021: a decomposition and age-period-cohort analysis for the Global Burden of Disease Study 2021.","authors":"Jinbo Li, Hongjing Bai, Ziyi Gao, Linying Gao, Weigang Wang, Yandi Li, Jia Lian, Tian Yao, Keke Wang, Ruigang Hao, Suping Wang, Yongliang Feng","doi":"10.1007/s12072-024-10765-4","DOIUrl":"https://doi.org/10.1007/s12072-024-10765-4","url":null,"abstract":"<p><strong>Objective: </strong>This study comprehensively assessed the burden of liver cancer due to hepatitis B (LCHB) from 1990 to 2021, analyzing temporal trends in disease burden and associations with age, period and birth cohort.</p><p><strong>Methods: </strong>Age-standardized incidence rate (ASIR), age-standardized mortality rate (ASMR) of LCHB from 1990 to 2021 were collected from the Global Burden of Disease (GBD) 2021. Joinpoint regression analysis estimated long-term trends. Age-period-cohort analysis evaluated the independent effects of age, period and cohort. Decomposition analysis elucidated the impact of population growth, aging and epidemiological changes on the burden.</p><p><strong>Results: </strong>Between 1990 and 2019, the ASIR and ASMR of LCHB witnessed an overall declining trend worldwide, with a notably higher burden in males compared to females. The highest ASIR and ASMR were observed in the middle socio-demographic index (SDI) region, while the lowest were in the low-middle SDI region, with substantial differences across countries. Age-period-cohort analysis revealed an initial increase in risk followed by a decline with advancing age, with the burden primarily affecting the elderly. Decomposition analysis indicated that population growth and aging were the primary drivers of the increase in incident cases and deaths.</p><p><strong>Conclusions: </strong>From 1990 to 2021, the ASIR and ASMR of LCHB decreased globally. However, population growth and aging contributed to an increase in the absolute numbers of incident cases and deaths. The risk burden increased with age, and favourable period and cohort effects were found in all SDI regions.</p>","PeriodicalId":12901,"journal":{"name":"Hepatology International","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142864054","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}