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Prothrombin time predicts steroid response in severe alcohol-related hepatitis—Old wine in new bottle 凝血酶原时间可预测重度酒精相关性肝炎的类固醇反应--新瓶装旧酒。
IF 6 2区 医学
Liver International Pub Date : 2024-08-03 DOI: 10.1111/liv.15942
Mallikarjun Patil
{"title":"Prothrombin time predicts steroid response in severe alcohol-related hepatitis—Old wine in new bottle","authors":"Mallikarjun Patil","doi":"10.1111/liv.15942","DOIUrl":"10.1111/liv.15942","url":null,"abstract":"","PeriodicalId":18101,"journal":{"name":"Liver International","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2024-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141879002","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}
引用次数: 0
Racial and ethnic disparities in the natural history of alcohol-associated liver disease in the United States 美国酒精相关肝病自然病史中的种族和民族差异。
IF 6 2区 医学
Liver International Pub Date : 2024-08-03 DOI: 10.1111/liv.16023
Gustavo Ayares, Luis Antonio Díaz, Eduardo Fuentes-López, Francisco Idalsoaga, Thomas G. Cotter, Winston Dunn, Douglas Simonetto, Vijay H. Shah, Patrick S. Kamath, Jeffrey V. Lazarus, Ramon Bataller, Marco Arrese, Robert J. Wong, Ashwani K. Singal, Juan Pablo Arab
{"title":"Racial and ethnic disparities in the natural history of alcohol-associated liver disease in the United States","authors":"Gustavo Ayares,&nbsp;Luis Antonio Díaz,&nbsp;Eduardo Fuentes-López,&nbsp;Francisco Idalsoaga,&nbsp;Thomas G. Cotter,&nbsp;Winston Dunn,&nbsp;Douglas Simonetto,&nbsp;Vijay H. Shah,&nbsp;Patrick S. Kamath,&nbsp;Jeffrey V. Lazarus,&nbsp;Ramon Bataller,&nbsp;Marco Arrese,&nbsp;Robert J. Wong,&nbsp;Ashwani K. Singal,&nbsp;Juan Pablo Arab","doi":"10.1111/liv.16023","DOIUrl":"10.1111/liv.16023","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Outcomes in alcohol-associated liver disease (ALD) are influenced by several race and ethnic factors, yet its natural history across the continuum of patients in different stages of the disease is unknown.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We conducted a retrospective cohort study of U.S. adults from 2011 to 2018, using three nationally representative databases to examine potential disparities in relevant outcomes among racial and ethnic groups. Our analysis included logistic and linear regressions, along with competing risk analysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Black individuals had the highest daily alcohol consumption (12.6 g/day) while Hispanic participants had the largest prevalence of heavy episodic drinking (33.5%). In a multivariable-adjusted model, Hispanic and Asian participants were independently associated with a higher ALD prevalence compared to Non-Hispanic White interviewees (OR: 1.4, 95% CI: 1.1–1.8 and OR: 1.5 95% CI:1.1–2.0, respectively), while Blacks participants had a lower ALD prevalence (OR: .7 95% CI: .6–.9), and a lower risk of mortality during hospitalization due to ALD (OR: .83 95% CI: .73–.94). Finally, a multivariate competing-risk analysis showed that Hispanic ethnicity had a decreased probability of liver transplantation if waitlisted for ALD (SHR: .7, 95% CI: .6–.8) along with female Asian population (HR: .40, 95% CI: .26–.62).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>After accounting for key social and biological health determinants, the Hispanic population showed an increased risk of ALD prevalence, even with lower alcohol consumption. Additionally, Hispanic and Asian female patients had reduced access to liver transplantation compared to other enlisted patients.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2024-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/liv.16023","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141879003","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}
引用次数: 0
Dynamic pattern of postprandial bile acids in paediatric non-alcoholic fatty liver disease 儿科非酒精性脂肪肝患者餐后胆汁酸的动态模式。
IF 6 2区 医学
Liver International Pub Date : 2024-07-31 DOI: 10.1111/liv.16054
Jiating Huang, Hu Lin, A-Na Liu, Wei Wu, Anna Alisi, Rohit Loomba, Cuifang Xu, Wenqin Xiang, Jie Shao, Guanping Dong, Ming-Hua Zheng, Junfen Fu, Yan Ni
{"title":"Dynamic pattern of postprandial bile acids in paediatric non-alcoholic fatty liver disease","authors":"Jiating Huang,&nbsp;Hu Lin,&nbsp;A-Na Liu,&nbsp;Wei Wu,&nbsp;Anna Alisi,&nbsp;Rohit Loomba,&nbsp;Cuifang Xu,&nbsp;Wenqin Xiang,&nbsp;Jie Shao,&nbsp;Guanping Dong,&nbsp;Ming-Hua Zheng,&nbsp;Junfen Fu,&nbsp;Yan Ni","doi":"10.1111/liv.16054","DOIUrl":"10.1111/liv.16054","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Dysregulation of bile acids (BAs), as important signalling molecules in regulating lipid and glucose metabolism, contributes to the development of non-alcoholic fatty liver disease (NAFLD). However, static BA profiles during fasting may obscure certain pathogenetic aspects. In this study, we investigate the dynamic alterations of BAs in response to an oral glucose tolerance test (OGTT) among children with NAFLD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We recruited 230 subjects, including children with overweight/obesity, or complicated with NAFLD, and healthy controls. Serum BAs, 7-hydroxy-4-cholesten-3-one (C4) and fibroblast growth factor 19 (FGF19) were quantified during OGTT. Clinical markers related to liver function, lipid metabolism and glucose metabolism were assessed at baseline or during OGTT.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Findings</h3>\u0000 \u0000 <p>Conjugated BAs increased while unconjugated ones decreased after glucose uptake. Most BAs were blunted in response to glucose in NAFLD (<i>p</i> &gt; .05); only glycine and taurine-conjugated chenodeoxycholic acid (CDCA) and cholic acid (CA) were responsive (<i>p</i> &lt; .05). Primary BAs were significantly increased while secondary BAs were decreased in NAFLD. C4 and FGF19 were significantly increased while their ratio FGF19/C4 ratio was decreased in NAFLD. The dynamic pattern of CDCA and taurine-conjugated hyocholic acid (THCA) species was closely correlated with glucose (correlation coefficient <i>r</i> = .175 and −.233, <i>p</i> &lt; .05), insulin (<i>r</i> = .327 and −.236, <i>p</i> &lt; .05) and c-peptide (<i>r</i> = .318 and −.238, <i>p</i> &lt; .05). Among which, CDCA was positively associated with liver fat content in NAFLD (<i>r</i> = .438, <i>p</i> &lt; .05). Additionally, glycochenodeoxycholic acid (GCDCA), CDCA and THCA were potential biomarkers to discriminate paediatric NAFLD from healthy controls and children with obesity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>This study provides novel insights into the dynamics of BAs during OGTT in paediatric NAFLD. The observed variations in CDCA and HCA species were associated with liver dysfunction, dyslipidaemia and dysglycaemia, highlighting their potential roles as promising diagnostic and therapeutic targets in NAFLD.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141855909","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}
引用次数: 0
Machine learning uncovers manganese as a key nutrient associated with reduced risk of steatotic liver disease 机器学习发现锰是降低脂肪肝风险的关键营养素。
IF 6 2区 医学
Liver International Pub Date : 2024-07-31 DOI: 10.1111/liv.16055
Simon Schophaus, Kate Townsend Creasy, Paul-Henry Koop, Jan Clusmann, Julius Jaeger, Varnitha Punnuru, Alexander Koch, Christian Trautwein, Rohit Loomba, Tom Luedde, Kai Markus Schneider, Carolin V. Schneider
{"title":"Machine learning uncovers manganese as a key nutrient associated with reduced risk of steatotic liver disease","authors":"Simon Schophaus,&nbsp;Kate Townsend Creasy,&nbsp;Paul-Henry Koop,&nbsp;Jan Clusmann,&nbsp;Julius Jaeger,&nbsp;Varnitha Punnuru,&nbsp;Alexander Koch,&nbsp;Christian Trautwein,&nbsp;Rohit Loomba,&nbsp;Tom Luedde,&nbsp;Kai Markus Schneider,&nbsp;Carolin V. Schneider","doi":"10.1111/liv.16055","DOIUrl":"10.1111/liv.16055","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Metabolic dysfunction-associated steatotic liver disease (MASLD) affects approximately 20%–30% of the general population and is linked to high-caloric western style diet. However, there are little data that specific nutrients might help to prevent steatosis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We analysed the UK Biobank (ID 71300) 24 h-nutritional assessments and investigated the association between nutrient intake calculated from food questionnaires and hepatic steatosis indicated by imaging or ICD10-coding. The effect of manganese (Mn) on subgroups with risk single nucleotide polymorphism carriage as well as the effect on metabolomics was investigated. All analyses are corrected for age, sex, body mass index, Townsend index for socioeconomic status, kcal, alcohol, protein intake, fat intake, carbohydrate intake, energy from beverages, diabetes, physical activity and for multiple testing.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We used a random forest classifier to analyse the feature importance of 63 nutrients and imaging-proven steatosis in a cohort of over 25 000 UK Biobank participants. Increased dietary Mn intake was associated with a lower likelihood of MRI-diagnosed steatosis. Subsequently, we conducted a cohort study in over 200 000 UK Biobank participants to explore the relationship between Mn intake and hepatic or cardiometabolic outcomes and found that higher Mn intake was associated with a lower risk of ICD-10 coded steatosis (OR = .889 [.838–.943], <i>p</i> &lt; .001), independent of other potential confounders.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our study provides evidence that higher Mn intake may be associated with lower odds of steatosis in a large population-based sample. These findings underline the potential role of Mn in the prevention of steatosis, but further research is needed to confirm these findings and to elucidate the underlying mechanisms.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11464189/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141855910","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}
引用次数: 0
Impaired HBsAg release and antiproliferative/antioxidant cell regulation by HBeAg-negative patient isolates reflects an evolutionary process HBeAg 阴性患者分离株的 HBsAg 释放和抗增殖/抗氧化细胞调节能力受损反映了一个进化过程。
IF 6 2区 医学
Liver International Pub Date : 2024-07-30 DOI: 10.1111/liv.16048
Michael Basic, Keerthihan Thiyagarajah, Mirco Glitscher, Anja Schollmeier, Qingyan Wu, Esra Görgülü, Pia Lembeck, Jannik Sonnenberg, Julia Dietz, Fabian Finkelmeier, Michael Praktiknjo, Jonel Trebicka, Stefan Zeuzem, Christoph Sarrazin, Eberhard Hildt, Kai-Henrik Peiffer
{"title":"Impaired HBsAg release and antiproliferative/antioxidant cell regulation by HBeAg-negative patient isolates reflects an evolutionary process","authors":"Michael Basic,&nbsp;Keerthihan Thiyagarajah,&nbsp;Mirco Glitscher,&nbsp;Anja Schollmeier,&nbsp;Qingyan Wu,&nbsp;Esra Görgülü,&nbsp;Pia Lembeck,&nbsp;Jannik Sonnenberg,&nbsp;Julia Dietz,&nbsp;Fabian Finkelmeier,&nbsp;Michael Praktiknjo,&nbsp;Jonel Trebicka,&nbsp;Stefan Zeuzem,&nbsp;Christoph Sarrazin,&nbsp;Eberhard Hildt,&nbsp;Kai-Henrik Peiffer","doi":"10.1111/liv.16048","DOIUrl":"10.1111/liv.16048","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The hepatitis B e antigen (HBeAg)-negative infection Phase 3 is characterized by no or minimal signs of hepatic inflammation and the absence of hepatic fibrosis. However, underlying molecular mechanisms leading to this benign phenotype are poorly understood.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Genotype A, B and D HBeAg-negative patient isolates with precore mutation G1896A from Phase 3 were analysed in comparison with respective HBeAg-positive rescue mutant and HBeAg-positive wild-type reference genomes regarding differences in viral replication, morphogenesis, infectivity and impact on NF-E2-related factor 2 (Nrf2)/antioxidant response element (ARE)-dependent gene expression and cellular kinome.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In comparison with reference genomes, the patient isolates are characterized by a lower intra- and extracellular hepatitis B surface antigen (HBsAg)-amount, and HBsAg-retention in the endoplasmic reticulum. Rescue of HBeAg expression increased HBsAg-amount but not its release. Expression of the isolated genomes is associated with a higher Nrf2/ARE-dependent gene expression as compared to reference genomes independent of HBeAg expression. Kinome analyses revealed a decreased activity of receptors involved in regulation of proliferative pathways for all patient isolates compared to the reference genomes. No specific conserved mutations could be found between all genomes from Phase 3.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>HBeAg-negative genomes from Phase 3 exhibit distinct molecular characteristics leading to lower HBsAg synthesis and release, enhanced oxidative stress protection and decreased activity of key kinases, triggering an antiproliferative stage, which might contribute to the lower probability of hepatocellular carcinoma. The observed differences cannot be associated with loss of HBeAg or specific mutations common to all analysed isolates, indicating the phenotype of Phase 3 derived genomes to be the result of a multifactorial process likely reflecting a conserved natural selection process.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/liv.16048","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141792861","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}
引用次数: 0
Correction to “integrin-linked kinase regulates endothelial cell nitric-oxide synthase expression in hepatic sinusoidal endothelial cells” 更正 "整合素连接激酶调节肝窦内皮细胞一氧化氮合酶的表达"。
IF 6 2区 医学
Liver International Pub Date : 2024-07-29 DOI: 10.1111/liv.15903
{"title":"Correction to “integrin-linked kinase regulates endothelial cell nitric-oxide synthase expression in hepatic sinusoidal endothelial cells”","authors":"","doi":"10.1111/liv.15903","DOIUrl":"10.1111/liv.15903","url":null,"abstract":"<p>Shafiei MS, Lui S, Rockey DC. Integrin-linked kinase regulates endothelial cell nitric-oxide synthase expression in hepatic sinusoidal endothelial cells. Liver Int. 2015 Apr;35(4):1213–1221. PMID: 24906011</p><p>The original version of this article, unfortunately contained a mistake. Since the publication of the article, the authors noticed errors in the beta-actin lanes of Figure 2A,C, and in the total AKT lane in Figure 6B. In the process of figure assembly, original images were inadvertently mislabeled and therefore used incorrectly. The revised figures can be found below. The authors apologize for the errors.</p><p>Figure legend for revised Figure 2.</p><p>Figure legend for revised Figure 6.</p>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/liv.15903","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141788572","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}
引用次数: 0
Network meta-analysis of adjuvant chemotherapy in biliary tract cancers: Setting the scene for new randomized evidence 胆道癌症辅助化疗的网络荟萃分析:为新的随机证据做好准备。
IF 6 2区 医学
Liver International Pub Date : 2024-07-29 DOI: 10.1111/liv.16047
Francesca Salani, Guglielmo Vetere, Daniele Rossini, Virginia Genovesi, Martina Carullo, Linda Bartalini, Valentina Massa, Laura Bernardini, Miriam Caccese, Silvia Cesario, Jessica Graziani, Giada Grelli, Francesco Mangogna, Caterina Vivaldi, Gianluca Masi, Lorenzo Fornaro
{"title":"Network meta-analysis of adjuvant chemotherapy in biliary tract cancers: Setting the scene for new randomized evidence","authors":"Francesca Salani,&nbsp;Guglielmo Vetere,&nbsp;Daniele Rossini,&nbsp;Virginia Genovesi,&nbsp;Martina Carullo,&nbsp;Linda Bartalini,&nbsp;Valentina Massa,&nbsp;Laura Bernardini,&nbsp;Miriam Caccese,&nbsp;Silvia Cesario,&nbsp;Jessica Graziani,&nbsp;Giada Grelli,&nbsp;Francesco Mangogna,&nbsp;Caterina Vivaldi,&nbsp;Gianluca Masi,&nbsp;Lorenzo Fornaro","doi":"10.1111/liv.16047","DOIUrl":"10.1111/liv.16047","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aims</h3>\u0000 \u0000 <p>The best adjuvant chemotherapy for resected biliary tract cancer (BTC) is under debate, with capecitabine supported by weak evidence. Aim of this network meta-analysis is to estimate the efficacy of different phase II/III regimens, comparing monotherapies (gemcitabine or fluoropyrimidines) head-to-head, against observation and combination regimens.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A comprehensive literature search was conducted on PubMed and EMBASE for phase II/III randomized clinical trials (RCTs) available as of December 2023, reporting hazard ratios (HRs) of overall survival (OS) and event-free survival (EFS). A frequentist framework employing a random-effects model was applied; treatment rankings were outlined according to <i>P</i>-score, based on direct and indirect evidence. Exploratory subgroup analyses for OS were also performed (primary site, resected margin status and nodal involvement).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Six RCTs (1979 total patients) were identified. Fluoropyrimidine monotherapy showed significantly better OS (HR .84 [.72–.97]) and EFS (HR .79 [.69–.91]) than observation, as any monotherapy did (HR .84 [.74–.96]; HR .79 [.70–.89]). In the head-to-head comparison for OS, only S1 confirmed to be superior to observation alone (HR .69 [.49–.98]) while fluoropyrimidines achieved the best <i>P</i> score (.81), similarly to any monotherapy (0.92). Combinations failed to prove superior to monotherapies with respect both to OS and EFS. Subgroup analyses were inconclusive due to results' inconsistency and limited sample size.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our work confirmed that adjuvant chemotherapy grants OS and EFS benefit for resected BTC patients. Fluoropyrimidines appeared the most effective option, confirming capecitabine as the preferred choice for the Western population.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/liv.16047","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141788574","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}
引用次数: 0
Differential HBV replicative markers and covalently closed circular DNA transcription in immune-active chronic hepatitis B with and without HBeAg 有 HBeAg 和无 HBeAg 的免疫活性慢性乙型肝炎中不同的 HBV 复制标记和共价闭合环状 DNA 转录。
IF 6 2区 医学
Liver International Pub Date : 2024-07-29 DOI: 10.1111/liv.16032
Hye Seon Kim, Jin Seoub Kim, Ji Min Kim, Ji Won Han, Soon Kyu Lee, Heechul Nam, Pil Soo Sung, Jung Hyun Kwon, Si Hyun Bae, Jong Young Choi, Seung Kew Yoon, Jeong Won Jang
{"title":"Differential HBV replicative markers and covalently closed circular DNA transcription in immune-active chronic hepatitis B with and without HBeAg","authors":"Hye Seon Kim,&nbsp;Jin Seoub Kim,&nbsp;Ji Min Kim,&nbsp;Ji Won Han,&nbsp;Soon Kyu Lee,&nbsp;Heechul Nam,&nbsp;Pil Soo Sung,&nbsp;Jung Hyun Kwon,&nbsp;Si Hyun Bae,&nbsp;Jong Young Choi,&nbsp;Seung Kew Yoon,&nbsp;Jeong Won Jang","doi":"10.1111/liv.16032","DOIUrl":"10.1111/liv.16032","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aims</h3>\u0000 \u0000 <p>Molecular processes driving immune-active chronic hepatitis B (CHB) with and without hepatitis B e antigen (HBeAg) remain incompletely understood. This study aimed to investigate expression profiles of serum and intrahepatic HBV markers and replicative activity of HBV in CHB patients with or without HBeAg.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This study recruited 111 untreated immune-active CHB (60 HBeAg-positive and 51 HBeAg-negative) patients and quantified intrahepatic covalently closed circular DNA (cccDNA), pre-genomic RNA (pgRNA), total HBV DNA (tDNA), and replicative intermediates as well as serum HBV markers (HBV DNA, hepatitis B surface antigen, hepatitis B core-related antigen). Correlations between HBV markers and clinico-virological factors influencing expression levels of HBV markers were analysed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Levels of all serum markers and intrahepatic cccDNA/tDNA as well as cccDNA transcriptional activity and virion productivity were significantly reduced in HBeAg-negative patients compared to those in HBeAg-positive patients. Additionally, correlations between intrahepatic cccDNA/pgRNA and serum markers were impaired in HBeAg-negative individuals. Aminotransferase levels were positively correlated with cccDNA transcriptional activity in HBeAg-positive patients, but not in HBeAg-negative patients. Notably, among HBeAg-positive patients, there was a progressive decline in pgRNA level, transcriptional activity, and serum HBV markers as liver fibrosis advanced, which was not observed in HBeAg-negative patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>HBeAg loss is correlated with diminished intrahepatic HBV reservoirs and cccDNA transcription, leading to decreased serum HBV marker levels. Circulating HBV markers are not reliable indicators of intrahepatic HBV replicative activity for HBeAg-negative patients. Our findings reveal distinct disease phenotypes between immune-active CHB with and without HBeAg, highlighting the need to establish optimal surrogate biomarkers that can accurately mirror intrahepatic viral activity to aid in decision-making for antiviral therapy for immune-active CHB.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141788573","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}
引用次数: 0
Effect of midodrine on HVPG in advanced chronic liver disease and acute-on-chronic liver failure—A pilot study 米多君对晚期慢性肝病和急性慢性肝衰竭患者 HVPG 的影响--一项试验研究。
IF 6 2区 医学
Liver International Pub Date : 2024-07-24 DOI: 10.1111/liv.16033
Chitranshu Vashishtha, Ankit Bhardwaj, Ankur Jindal, Manoj Kumar, Shiv Kumar Sarin
{"title":"Effect of midodrine on HVPG in advanced chronic liver disease and acute-on-chronic liver failure—A pilot study","authors":"Chitranshu Vashishtha,&nbsp;Ankit Bhardwaj,&nbsp;Ankur Jindal,&nbsp;Manoj Kumar,&nbsp;Shiv Kumar Sarin","doi":"10.1111/liv.16033","DOIUrl":"10.1111/liv.16033","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aims</h3>\u0000 \u0000 <p>Nonselective beta-blockers (NSBB) are the mainstay for treatment of portal hypertension (PH), but require caution in decompensated cirrhosis (DC) or acute-on-chronic liver failure (ACLF) with hypotension, hyponatremia, acute kidney injury (AKI) or type 2 hepatorenal syndrome (HRS). Midodrine is oral, rapidly acting, α1-adrenergic agonist. We evaluated acute effects of midodrine on hepatic venous pressure gradient (HVPG) in DC and ACLF with contraindications to NSBB.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Patients of DC (<i>n</i> = 30) with grade III ascites and serum sodium (Na) &lt;130/systolic blood pressure (SBP) &lt;90/type II HRS (group I) and ACLF patients (<i>n</i> = 30) with Na &lt;130/SBP &lt;90/AKI (group II) were included. HVPG was done at baseline and repeated 3 h after 10 mg midodrine. Primary outcome was HVPG response (reduction by &gt;20% or to &lt;12 mmHg).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In group I, midodrine significantly reduced HVPG (19.2 ± 4.6 to 17.8 ± 4.2, <i>p</i> = .02) and heart rate (HR) (86.3 ± 11.6 to 77.9 ± 13.1, <i>p</i> &lt; .01) and increased mean arterial pressure (MAP) (74.1 ± 6.9 to 81.9 ± 6.6 mmHg, <i>p</i> &lt; .01). In group II also, midodrine reduced HVPG (19.1 ± 4.1 to 17.0 ± 4.2) and HR (92.4 ± 13.7 to 84.6 ± 14.1) and increased MAP (85.4 ± 7.3 to 91.2 ± 7.6 mmHg), <i>p</i> &lt; .01 for all. HVPG response was achieved in 3/30 (10%) in group I and 8/30 (26.7%) in group II. On logistic regression analysis, prerenal AKI (OR 11.04, 95% CI 1.83–66.18, <i>p</i> &lt; .01) and increase in MAP (OR 1.22, 95% CI 1.03–1.43, <i>p</i> = .02) were independent predictors of response. Increase in MAP by 8.5 mmHg with midodrine had best cut-off with AUROC of .76 for response.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>In decompensated cirrhosis and ACLF patients with contraindications to NSBB, midodrine is useful in decreasing HVPG. Dose of midodrine should be titrated to increase MAP atleast by 8.5 mmHg.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141752058","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}
引用次数: 0
AI-powered prediction of HCC recurrence after surgical resection: Personalised intervention opportunities using patient-specific risk factors 手术切除后 HCC 复发的人工智能预测:利用患者特异性风险因素的个性化干预机会。
IF 6 2区 医学
Liver International Pub Date : 2024-07-24 DOI: 10.1111/liv.16050
Seid Miad Zandavi, Christy Kim, Thomas Goodwin, Cynthuja Thilakanathan, Maryam Bostanara, Anna Camille Akon, Daniel Al Mouiee, Sasha Barisic, Ammar Majeed, William Kemp, Francis Chu, Marty Smith, Kate Collins, Vincent Wai-Sun Wong, Grace Lai-Hung Wong, Jason Behary, Stuart K. Roberts, Kelvin K. C. Ng, Fatemeh Vafaee, Amany Zekry
{"title":"AI-powered prediction of HCC recurrence after surgical resection: Personalised intervention opportunities using patient-specific risk factors","authors":"Seid Miad Zandavi,&nbsp;Christy Kim,&nbsp;Thomas Goodwin,&nbsp;Cynthuja Thilakanathan,&nbsp;Maryam Bostanara,&nbsp;Anna Camille Akon,&nbsp;Daniel Al Mouiee,&nbsp;Sasha Barisic,&nbsp;Ammar Majeed,&nbsp;William Kemp,&nbsp;Francis Chu,&nbsp;Marty Smith,&nbsp;Kate Collins,&nbsp;Vincent Wai-Sun Wong,&nbsp;Grace Lai-Hung Wong,&nbsp;Jason Behary,&nbsp;Stuart K. Roberts,&nbsp;Kelvin K. C. Ng,&nbsp;Fatemeh Vafaee,&nbsp;Amany Zekry","doi":"10.1111/liv.16050","DOIUrl":"10.1111/liv.16050","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Hepatocellular carcinoma (HCC) recurrence following surgical resection remains a significant clinical challenge, necessitating reliable predictive models to guide personalised interventions. In this study, we sought to harness the power of artificial intelligence (AI) to develop a robust predictive model for HCC recurrence using comprehensive clinical datasets.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Leveraging data from 958 patients across multiple centres in Australia and Hong Kong, we employed a multilayer perceptron (MLP) as the optimal classifier for model generation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Through rigorous internal cross-validation, including a cohort from the Chinese University of Hong Kong (CUHK), our AI model successfully identified specific pre-surgical risk factors associated with HCC recurrence. These factors encompassed hepatic synthetic function, liver disease aetiology, ethnicity and modifiable metabolic risk factors, collectively contributing to the predictive <i>synergy</i> of our model. Notably, our model exhibited high accuracy during cross-validation (.857 ± .023) and testing on the CUHK cohort (.835), with a notable degree of confidence in predicting HCC recurrence within accurately classified patient cohorts. To facilitate clinical application, we developed an online AI digital tool capable of real-time prediction of HCC recurrence risk, demonstrating acceptable accuracy at the individual patient level.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our findings underscore the potential of AI-driven predictive models in facilitating personalised risk stratification and targeted interventions to mitigate HCC recurrence by identifying modifiable risk factors unique to each patient. This model aims to aid clinicians in devising strategies to disrupt the underlying carcinogenic network driving recurrence.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/liv.16050","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141752057","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}
引用次数: 0
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