JHEP Reports最新文献

IF 9.5 1区医学

JHEP Reports Pub Date : 2024-09-01 DOI: 10.1016/S2589-5559(24)00207-6

引用次数: 0

IF 9.5 1区医学

JHEP Reports Pub Date : 2024-09-01 DOI: 10.1016/S2589-5559(24)00210-6

引用次数: 0

AI-derived body composition parameters as prognostic factors in patients with HCC undergoing TACE in a multicenter study 一项多中心研究将 AI 衍生的身体成分参数作为接受 TACE 的 HCC 患者的预后因素

IF 9.5 1区医学

JHEP Reports Pub Date : 2024-08-01 DOI: 10.1016/j.jhepr.2024.101125

{"title":"AI-derived body composition parameters as prognostic factors in patients with HCC undergoing TACE in a multicenter study","authors":"","doi":"10.1016/j.jhepr.2024.101125","DOIUrl":"10.1016/j.jhepr.2024.101125","url":null,"abstract":"<div><h3>Background & Aims</h3><p>Body composition assessment (BCA) parameters have recently been identified as relevant prognostic factors for patients with hepatocellular carcinoma (HCC). Herein, we aimed to investigate the role of BCA parameters for prognosis prediction in patients with HCC undergoing transarterial chemoembolization (TACE).</p></div><div><h3>Methods</h3><p>This retrospective multicenter study included a total of 754 treatment-naïve patients with HCC who underwent TACE at six tertiary care centers between 2010–2020. Fully automated artificial intelligence-based quantitative 3D volumetry of abdominal cavity tissue composition was performed to assess skeletal muscle volume (SM), total adipose tissue (TAT), intra- and intermuscular adipose tissue, visceral adipose tissue, and subcutaneous adipose tissue (SAT) on pre-intervention computed tomography scans. BCA parameters were normalized to the slice number of the abdominal cavity. We assessed the influence of BCA parameters on median overall survival and performed multivariate analysis including established estimates of survival.</p></div><div><h3>Results</h3><p>Univariate survival analysis revealed that impaired median overall survival was predicted by low SM (<em>p <</em>0.001), high TAT volume (<em>p</em> = 0.013), and high SAT volume (<em>p</em> = 0.006). In multivariate survival analysis, SM remained an independent prognostic factor (<em>p</em> = 0.039), while TAT and SAT volumes no longer showed predictive ability. This predictive role of SM was confirmed in a subgroup analysis of patients with BCLC stage B.</p></div><div><h3>Conclusions</h3><p>SM is an independent prognostic factor for survival prediction. Thus, the integration of SM into novel scoring systems could potentially improve survival prediction and clinical decision-making. Fully automated approaches are needed to foster the implementation of this imaging biomarker into daily routine.</p></div><div><h3>Impact and implications:</h3><p>Body composition assessment parameters, especially skeletal muscle volume, have been identified as relevant prognostic factors for many diseases and treatments. In this study, skeletal muscle volume has been identified as an independent prognostic factor for patients with hepatocellular carcinoma undergoing transarterial chemoembolization. Therefore, skeletal muscle volume as a metaparameter could play a role as an opportunistic biomarker in holistic patient assessment and be integrated into decision support systems. Workflow integration with artificial intelligence is essential for automated, quantitative body composition assessment, enabling broad availability in multidisciplinary case discussions.</p></div>","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":null,"pages":null},"PeriodicalIF":9.5,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2589555924001290/pdfft?md5=8f81f815539c9b7127ef027a6c9b8f47&pid=1-s2.0-S2589555924001290-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141959515","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Editorial Board page 编辑委员会页面

IF 9.5 1区医学

JHEP Reports Pub Date : 2024-08-01 DOI: 10.1016/S2589-5559(24)00179-4

引用次数: 0

Copyright and information 版权和信息

IF 9.5 1区医学

JHEP Reports Pub Date : 2024-08-01 DOI: 10.1016/S2589-5559(24)00182-4

引用次数: 0

Metabolomics biomarkers of hepatocellular carcinoma in a prospective cohort of patients with cirrhosis 肝硬化患者前瞻性队列中的肝细胞癌代谢组学生物标志物

IF 9.5 1区医学

JHEP Reports Pub Date : 2024-08-01 DOI: 10.1016/j.jhepr.2024.101119

{"title":"Metabolomics biomarkers of hepatocellular carcinoma in a prospective cohort of patients with cirrhosis","authors":"","doi":"10.1016/j.jhepr.2024.101119","DOIUrl":"10.1016/j.jhepr.2024.101119","url":null,"abstract":"<div><h3>Background & Aims</h3><p>The effectiveness of surveillance for hepatocellular carcinoma (HCC) in patients with cirrhosis is limited, due to inadequate risk stratification and suboptimal performance of current screening modalities.</p></div><div><h3>Methods</h3><p>We developed a multicenter prospective cohort of patients with cirrhosis undergoing surveillance with MRI and applied global untargeted metabolomics to 612 longitudinal serum samples from 203 patients. Among them, 37 developed HCC during follow-up.</p></div><div><h3>Results</h3><p>We identified 150 metabolites with significant abundance changes in samples collected prior to HCC (Cases) compared to samples from patients who did not develop HCC (Controls). Tauro-conjugated bile acids and gamma-glutamyl amino acids were increased, while acyl-cholines and deoxycholate derivatives were decreased. Seven amino acids including serine and alanine had strong associations with HCC risk, while strong protective effects were observed for N-acetylglycine and glycerophosphorylcholine. Machine learning using the 150 metabolites, age, gender, and <em>PNPLA3</em> and <em>TMS6SF2</em> single nucleotide polymorphisms, identified 15 variables giving optimal performance. Among them, N-acetylglycine had the highest AUC in discriminating Cases and Controls. When restricting Cases to samples collected within 1 year prior to HCC (Cases-12M), additional metabolites including microbiota-derived metabolites were identified. The combination of the top six variables identified by machine learning (alpha-fetoprotein, 6-bromotryptophan, N-acetylglycine, salicyluric glucuronide, testosterone sulfate and age) had good performance in discriminating Cases-12M from Controls (AUC 0.88, 95% CI 0.83-0.93). Finally, 23 metabolites distinguished Cases with LI-RADS-3 lesions from Controls with LI-RADS-3 lesions, with reduced abundance of acyl-cholines and glycerophosphorylcholine-related lysophospholipids in Cases.</p></div><div><h3>Conclusions</h3><p>This study identified N-acetylglycine, amino acids, bile acids and choline-derived metabolites as biomarkers of HCC risk, and microbiota-derived metabolites as contributors to HCC development.</p></div><div><h3>Impact and implications:</h3><p>The effectiveness of surveillance for hepatocellular carcinoma (HCC) in patients with cirrhosis is limited. There is an urgent need for improvement in risk stratification and new screening modalities, particularly blood biomarkers. Longitudinal collection of paired blood samples and MRI images from patients with cirrhosis is particularly valuable in assessing how early blood and imaging markers become positive during the period when lesions are observed to obtain a diagnosis of HCC. We generated a multicenter prospective cohort of patients with cirrhosis under surveillance with contrast MRI, applied untargeted metabolomics on 612 serum samples from 203 patients and identified metabolites associated with risk of HCC development. Such","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":null,"pages":null},"PeriodicalIF":9.5,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S258955592400123X/pdfft?md5=73eb5310ef32b175ddc7625944e8c27e&pid=1-s2.0-S258955592400123X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141052568","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Non-ceruloplasmin copper and urinary copper in clinically stable Wilson disease: Alignment with recommended targets 临床稳定期威尔逊氏病患者的非血浆铜和尿铜：与推荐目标一致

IF 9.5 1区医学

JHEP Reports Pub Date : 2024-08-01 DOI: 10.1016/j.jhepr.2024.101115

{"title":"Non-ceruloplasmin copper and urinary copper in clinically stable Wilson disease: Alignment with recommended targets","authors":"","doi":"10.1016/j.jhepr.2024.101115","DOIUrl":"10.1016/j.jhepr.2024.101115","url":null,"abstract":"<div><h3>Background & Aims</h3><p>Wilson disease (WD) is caused by accumulation of copper primarily in the liver and brain. During maintenance therapy of WD with D-penicillamine, current guidelines recommend on-treatment ranges of urinary copper excretion (UCE) of 200-500 μg/24 h and serum non-ceruloplasmin-bound copper (NCC) of 50-150 μg/L. We compared NCC (measured by two novel assays) and UCE from patients with clinically stable WD on D-penicillamine therapy with these recommendations.</p></div><div><h3>Methods</h3><p>This is a secondary analysis of data from the Chelate trial (NCT03539952) that enrolled physician-selected patients with clinically stable WD on D-penicillamine maintenance therapy (at an unaltered dose for at least 4 months). We analyzed laboratory samples from the first screening visit, prior to interventions. NCC was measured by either protein speciation (NCC-Sp) using anion exchange high-performance liquid chromatography protein speciation followed by copper determination with inductively coupled plasma mass spectroscopy or as exchangeable copper (NCC-Ex). NCC-Sp was also analyzed in healthy controls (n = 75).</p></div><div><h3>Results</h3><p>In 76 patients with WD with 21.3±14.3 average treatment-years, NCC-Sp (mean±SD: 56.6±26.2 μg/L) and NCC-Ex (mean±SD: 57.9±24.7 μg/L) were within the 50-150 μg/L target in 61% and 54% of patients, respectively. In addition, 36% and 31%, respectively, were even below the normal ranges (NCC-Sp: 46-213 μg/L, NCC-Ex: 41-71 μg/L). NCC-Ex positively correlated with NCC-Sp (r<sup>2</sup> = 0.66, <em>p <</em>0.001) but with systematic deviation. UCE was outside the 200-500 μg/24 h target range in 58%. Only 14/69 (20%) fulfilled both the NCC-Sp and UCE targets. Clinical or biochemical signs of copper deficiency were not detected.</p></div><div><h3>Conclusion</h3><p>Clinically stable patients with WD on maintenance D-penicillamine therapy frequently have lower NCC-Sp or higher UCE than current recommendations without signs of overtreatment. Further studies are warranted to identify appropriate target ranges of NCC-Sp, NCC-Ex and UCE in treated WD.</p></div><div><h3>Impact and implications:</h3><p>Chelator treatment of patients with Wilson disease (WD) is currently guided by measurements of non-ceruloplasmin-bound copper (NCC) and 24 h urinary copper excretion (UCE) but validation is limited. In 76 adults with ≈21 years history of treated WD and clinically stable disease on D-penicillamine therapy, NCC was commonly found to be below normal values and recommended target ranges whether measured by protein speciation (NCC-Sp) or as exchangeable copper (NCC-Ex), while UCE values were above the recommended target range in 49%. Common wisdom would suggest overtreatment in these cases, but no clinical or biochemical signs of copper deficiency were observed. Exploratory analysis of liver enzymes suggested that NCC below levels seen in controls may be beneficial, while the relation to UCE was less cle","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":null,"pages":null},"PeriodicalIF":9.5,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2589555924001198/pdfft?md5=46cf07d4a9e83f01fd9dea261062796a&pid=1-s2.0-S2589555924001198-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141057679","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Good long-term outcomes of primary sclerosing cholangitis in childhood 儿童原发性硬化性胆管炎的长期良好疗效

IF 9.5 1区医学

JHEP Reports Pub Date : 2024-08-01 DOI: 10.1016/j.jhepr.2024.101123

{"title":"Good long-term outcomes of primary sclerosing cholangitis in childhood","authors":"","doi":"10.1016/j.jhepr.2024.101123","DOIUrl":"10.1016/j.jhepr.2024.101123","url":null,"abstract":"<div><h3>Background & Aims</h3><p>Primary sclerosing cholangitis (PSC) is a rare progressive liver disease associated with inflammatory bowel disease (IBD). It is usually diagnosed in adults but can also present in children. Data on long-term outcomes of pediatric PSC are limited. Our aim was to study the natural history of pediatric PSC in Sweden.</p></div><div><h3>Methods</h3><p>This is a cohort study, including all children (<18 years), diagnosed with PSC between January 2000 and December 2015 at the Pediatric Liver Unit at Karolinska University Hospital, Stockholm. Patients were followed until liver transplantation, death or last date of follow-up (August 2021).</p></div><div><h3>Results</h3><p>We identified 124 children with a median age of 14 (1.9–17.8) years at PSC diagnosis. Sixty percent were boys, 93% had IBD. Median follow-up time was 13 years (5.7–21.6). Overall event-free survival in the cohort was 91% (95% CI 0.84–0.95) at 5 years and 77% (95% CI 0.68–0.84) at 10 years after diagnosis. Autoimmune hepatitis (AIH) was present in 31% (n = 39). Portal hypertension developed in 13% (n = 16), biliary complications in 24% (n = 30), cholangiocarcinoma (CCA) in 0.8% (n = 1), while 13% (n = 16) underwent liver transplantation and three patients died. Transplant-free survival was 91% after 10 years. Individuals with a high SCOPE index at diagnosis had a 2.3-fold increased risk of requiring liver transplantation (hazard ratio 2.35, 95% CI 1.18–4.66, c-statistics = 0.70). Patients with an additional diagnosis of autoimmune hepatitis had slightly higher risk of reaching transplantation during follow-up (hazard ratio 2.85, 95% CI 1.06–7.67, <em>p</em> = 0.038).</p></div><div><h3>Conclusions</h3><p>Children diagnosed with PSC have a good prognosis during the first decade after diagnosis. A high SCOPE index at diagnosis was associated with a less favorable outcome.</p></div><div><h3>Impact and implications:</h3><p>Data on long-term outcome in pediatric primary sclerosing cholangitis bridging over to adulthood is limited. There is a great need among children with primary sclerosing cholangitis and their parents for more knowledge about the natural history of this disease and what they can expect from the future. We hope that the data presented in this study may help counsel health professionals, young individuals and families affected by this disease.</p></div>","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":null,"pages":null},"PeriodicalIF":9.5,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2589555924001277/pdfft?md5=237b31cbbeaa0ee743f239cbe1482beb&pid=1-s2.0-S2589555924001277-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141959510","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Association of physical activity, including amount and maintenance, with the risk of HCC among patients with type 2 diabetes 体育锻炼（包括运动量和维持时间）与 2 型糖尿病患者罹患肝癌风险的关系

IF 9.5 1区医学

JHEP Reports Pub Date : 2024-07-03 DOI: 10.1016/j.jhepr.2024.101166

{"title":"Association of physical activity, including amount and maintenance, with the risk of HCC among patients with type 2 diabetes","authors":"","doi":"10.1016/j.jhepr.2024.101166","DOIUrl":"10.1016/j.jhepr.2024.101166","url":null,"abstract":"<div><h3>Background & Aims</h3><p>We investigated the association of physical activity (PA) levels and changes with the risk of hepatocellular carcinoma (HCC) in patients with type 2 diabetes.</p></div><div><h3>Methods</h3><p>Patients with type 2 diabetes who had undergone health examinations in 2009 and 2011 were enrolled. In total, 1,439,152 patients were included in the analysis. The level of PA was classified as inactive (<500 metabolic equivalent task [MET]-min/week), moderately active (500-1,500 MET-min/week), and active (≥1,500 MET-min/week). Change in PA was categorized as persistently inactive PA, newly active PA, active PA quitter, and persistently active PA according to change of PA between 2009 and 2011.</p></div><div><h3>Results</h3><p>During a median of 5.2 years of follow-up, 22,686 patients developed HCC. Compared to the inactive group, the risk of HCC was significantly lower in the moderately active (adjusted hazard ratio [aHR] 0.96, 95% CI 0.93–0.99), and active (aHR 0.95, 95% CI 0.91–0.99) groups. The patients in the persistently active PA group had a significantly lower risk of HCC than those in the persistently inactive PA group (aHR 0.91, 95% CI 0.84–0.98).</p></div><div><h3>Conclusions</h3><p>Physical activity exhibited a dose-responsive preventive effect against HCC in patients with diabetes.</p></div><div><h3>Impact and implications:</h3><p>Our study investigated the impact of physical activity (PA) levels and changes on the risk of hepatocellular carcinoma (HCC) in patients with type 2 diabetes. PA was associated with a dose-responsive preventive effect against HCC. Patients in the persistently active PA group had a significantly lower risk of HCC than those in the persistently inactive PA group, while newly active patients and PA quitters had similar risks to the persistently inactive group. Our study highlighted the importance of maintaining regular PA as a preventive strategy against HCC.</p></div>","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":null,"pages":null},"PeriodicalIF":9.5,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2589555924001708/pdfft?md5=82d7f0076ab976d25246af14a7e68c2f&pid=1-s2.0-S2589555924001708-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141709059","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Surrogate markers of bile duct disease progression in primary sclerosing cholangitis – A prospective study with repeated ERCP examinations 原发性硬化性胆管炎胆管疾病进展的替代标记物--一项通过重复 ERCP 检查进行的前瞻性研究

IF 9.5 1区医学

JHEP Reports Pub Date : 2024-07-02 DOI: 10.1016/j.jhepr.2024.101161

{"title":"Surrogate markers of bile duct disease progression in primary sclerosing cholangitis – A prospective study with repeated ERCP examinations","authors":"","doi":"10.1016/j.jhepr.2024.101161","DOIUrl":"10.1016/j.jhepr.2024.101161","url":null,"abstract":"<div><h3>Background & Aims</h3><p>Validated prognostic tools for estimating short-term bile duct disease progression in primary sclerosing cholangitis (PSC) are lacking. We evaluated the predictive value of serum and biliary biochemistry for the progression of bile duct disease in PSC using repeated endoscopic retrograde cholangiopancreatography (ERCP) examinations to identify surrogate markers for more personalized surveillance.</p></div><div><h3>Methods</h3><p>We conducted a prospective analysis including patients with PSC who underwent ERCP for confirmation of diagnosis, monitoring of disease progression, or dysplasia surveillance. ERCP findings were scored, and dilatation was performed if a dominant stricture was diagnosed or if a cytology brush could not be passed. Bile samples were aspirated for biliary IL8 and calprotectin. We analysed optimal cut-off values and AUCs for 20 laboratory markers and evaluated their association with the time to an ERCP score increase of ≥2 points or first dilatation, whichever came first. Of the 1,002 patients, 653 had ≥2 ERCP examinations and ≥3 years of follow-up. After excluding patients with PSC-overlap syndrome or initial dilatation, 398 patients were included.</p></div><div><h3>Results</h3><p>Of the patients included, 62% had mild or moderate and 38% had advanced bile duct disease. During follow-up, 41% of patients demonstrated progression of disease. Biliary calprotectin (AUC 0.76; 95% CI 0.69 to 0.82) and IL8 (AUC 0.76; 95% CI 0.69 to 0.84) were the only variables that demonstrated predictive value for disease progression and/or need for dilatation.</p></div><div><h3>Conclusions</h3><p>Biliary calprotectin and IL8 are promising surrogate markers for identifying patients with PSC at risk of progression and determining the timing for subsequent imaging. Conventional liver function tests may not be sensitive or specific enough to monitor PSC progression, particularly in the short term.</p></div><div><h3>Impact and implications:</h3><p>Validated prognostic tools for estimating short-term bile duct disease progression in primary sclerosing cholangitis are lacking. In this prospective study, based on sequential endoscopic retrograde cholangiopancreatography examinations, biliary calprotectin and IL8 levels turned out to be more sensitive for predicting bile duct progression than traditional liver function tests, such as alkaline phosphatase, in the short term. These findings could lead to more personalized patient surveillance and improve clinical practice by providing a more accurate method for monitoring disease progression and treatment responses. Additionally, these markers have potential as surrogate endpoints in clinical drug trials. The limitation is that measurement of biliary IL8 and calprotectin requires endoscopic retrograde cholangiopancreatography with bile sampling.</p></div>","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":null,"pages":null},"PeriodicalIF":9.5,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2589555924001654/pdfft?md5=0ad0d27919dde85a6417e4efc125f0bd&pid=1-s2.0-S2589555924001654-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141714887","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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