Pub Date : 2024-08-09DOI: 10.1016/j.jhepr.2024.101185
Fabrizia Carli , Giuseppe Della Pepa , Silvia Sabatini , Antonio Vidal Puig , Amalia Gastaldelli
Metabolic dysfunction-associated steatotic liver disease/steatohepatitis (MASLD/MASH) is recognised as a metabolic disease characterised by excess intrahepatic lipid accumulation due to lipid overflow and synthesis, alongside impaired oxidation and/or export of these lipids. But where do these lipids come from? The main pathways related to hepatic lipid accumulation are de novo lipogenesis and excess fatty acid transport to the liver (due to increased lipolysis, adipose tissue insulin resistance, as well as excess dietary fatty acid intake, in particular of saturated fatty acids). Not only triglycerides but also other lipids are secreted by the liver and are associated with a worse histological profile in MASH, as shown by lipidomics. Herein, we review the role of lipid metabolism in MASLD/MASH and discuss the impact of weight loss (diet, bariatric surgery, GLP-1RAs) or other pharmacological treatments (PPAR or THRβ agonists) on hepatic lipid metabolism, lipidomics, and the resolution of MASH.
{"title":"Lipid metabolism in MASLD and MASH: From mechanism to the clinic","authors":"Fabrizia Carli , Giuseppe Della Pepa , Silvia Sabatini , Antonio Vidal Puig , Amalia Gastaldelli","doi":"10.1016/j.jhepr.2024.101185","DOIUrl":"10.1016/j.jhepr.2024.101185","url":null,"abstract":"<div><div>Metabolic dysfunction-associated steatotic liver disease/steatohepatitis (MASLD/MASH) is recognised as a metabolic disease characterised by excess intrahepatic lipid accumulation due to lipid overflow and synthesis, alongside impaired oxidation and/or export of these lipids. But where do these lipids come from? The main pathways related to hepatic lipid accumulation are <em>de novo</em> lipogenesis and excess fatty acid transport to the liver (due to increased lipolysis, adipose tissue insulin resistance, as well as excess dietary fatty acid intake, in particular of saturated fatty acids). Not only triglycerides but also other lipids are secreted by the liver and are associated with a worse histological profile in MASH, as shown by lipidomics. Herein, we review the role of lipid metabolism in MASLD/MASH and discuss the impact of weight loss (diet, bariatric surgery, GLP-1RAs) or other pharmacological treatments (PPAR or THRβ agonists) on hepatic lipid metabolism, lipidomics, and the resolution of MASH.</div></div>","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"6 12","pages":"Article 101185"},"PeriodicalIF":9.5,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142593365","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}
Pub Date : 2024-08-08DOI: 10.1016/j.jhepr.2024.101184
Joan Clària , Ferran Aguilar , Juan-José Lozano , Laura Jiménez-Gracia , Juan C. Nieto , Berta Romero-Grimaldo , Xavi Marcos-Fa , Emma Giarracco , Emmanuel Weiss , Jonel Trebicka , Inmaculada Hernàndez , Javier Fernandez , Mireia Casulleras , Cristina López-Vicario , Sinan Muldur , Alex Hopke , Alexandru Vlagea , Ana M. Aransay , Domenica Marchese , Mauro Bernardi , Richard Moreau
Background & Aims
Patients with acutely decompensated (AD) cirrhosis are immunocompromised and particularly susceptible to infections. This study investigated the immunomodulatory actions of albumin by which this protein may lower the incidence of infections.
Methods
Blood immunophenotyping was performed in 11 patients with AD cirrhosis and 10 healthy volunteers (HV). Bulk and single-cell RNA sequencing (scRNA-seq) and flow cytometry were performed in peripheral blood mononuclear cells (PBMCs) from 20 patients with AD cirrhosis and 34 HV exposed to albumin. Albumin’s effects on degranulation, phagocytosis, chemotaxis, and swarming of neutrophils from six patients with AD cirrhosis and nine HV were assessed by measuring myeloperoxidase enzymatic activity, the engulfment of fluorescent-labeled Escherichia coli and zymosan, and interactions of neutrophils with Candida albicans at single-cell resolution in microfluidic chambers, respectively. Whole blood RNA sequencing (RNA-seq) analyses were performed in 49 patients admitted for severe AD cirrhosis, of whom 30 received albumin during hospitalization.
Results
Compared with HV, patients with AD cirrhosis showed severe lymphopenia and defective neutrophil antimicrobial function. Bulk and scRNA-seq analyses revealed significantly (false discovery rate [FDR] <0.05) increased signatures related to B cells, myeloid cells, and CD4+ T cells in PBMCs incubated with albumin. Changes in the B cell population were confirmed by flow cytometry. Neutrophils exposed to albumin also exhibited augmented chemotactic and degranulation responses, enhanced phagocytosis, and increased pathogen-restrictive swarming. RNA-seq data analysis in patients who had received albumin revealed specific upregulation of signatures related to B cells and neutrophils together with transcriptional changes in CD4+ T cells (FDR <0.05).
Conclusions
The finding that albumin promotes the transcriptional reprogramming and expansion of the B cell compartment and improves neutrophil antimicrobial functions indicates mechanisms that may lower the incidence of infections in patients with severe AD cirrhosis receiving albumin therapy.
Impact and implications:
Patients with acutely decompensated cirrhosis receiving albumin as treatment have a lower incidence of infections. The reason for this protection is currently unknown, but the present study provides data that support the ability of albumin to boost the antimicrobial functions of immune cells in these patients. Moreover, these findings encourage the design of controlled clinical studies specifically aimed at investigating the effects of albumin administration on the immune system.
背景& 目的急性失代偿期（AD）肝硬化患者免疫力低下，特别容易受到感染。本研究调查了白蛋白的免疫调节作用，这种蛋白质可降低感染的发生率。方法对 11 名急性失代偿期肝硬化患者和 10 名健康志愿者（HV）进行了血液免疫分型。对暴露于白蛋白的 20 名 AD 肝硬化患者和 34 名健康志愿者的外周血单核细胞（PBMC）进行了大量和单细胞 RNA 测序（scRNA-seq）以及流式细胞术。通过在微流控室内以单细胞分辨率测量髓过氧化物酶的酶活性、荧光标记的大肠杆菌和齐莫散的吞噬作用以及中性粒细胞与白色念珠菌的相互作用，分别评估了白蛋白对 6 名 AD 型肝硬化患者和 9 名 HV 患者的中性粒细胞的脱颗粒、吞噬、趋化和成群作用的影响。结果与HV相比，AD肝硬化患者表现出严重的淋巴细胞减少和中性粒细胞抗菌功能缺陷。大量和scRNA-seq分析显示，与白蛋白培养的PBMCs中B细胞、骨髓细胞和CD4+ T细胞相关的特征显著增加（假发现率[FDR] <0.05）。流式细胞术证实了 B 细胞群的变化。暴露于白蛋白的中性粒细胞也表现出趋化和脱颗粒反应增强、吞噬能力增强以及病原体限制性蜂拥增加。对接受过白蛋白治疗的患者进行的 RNA-seq 数据分析显示，与 B 细胞和中性粒细胞相关的特征发生了特异性上调，CD4+ T 细胞的转录也发生了变化（FDR <0.05）。影响和意义：接受白蛋白治疗的急性失代偿期肝硬化患者的感染率较低。这种保护作用的原因目前尚不清楚，但本研究提供的数据支持了白蛋白增强这些患者免疫细胞抗菌功能的能力。此外，这些研究结果还鼓励设计临床对照研究，专门研究白蛋白对免疫系统的影响。
{"title":"Albumin reprograms the B cell transcriptional landscape and improves neutrophil antimicrobial function in patients with decompensated cirrhosis","authors":"Joan Clària , Ferran Aguilar , Juan-José Lozano , Laura Jiménez-Gracia , Juan C. Nieto , Berta Romero-Grimaldo , Xavi Marcos-Fa , Emma Giarracco , Emmanuel Weiss , Jonel Trebicka , Inmaculada Hernàndez , Javier Fernandez , Mireia Casulleras , Cristina López-Vicario , Sinan Muldur , Alex Hopke , Alexandru Vlagea , Ana M. Aransay , Domenica Marchese , Mauro Bernardi , Richard Moreau","doi":"10.1016/j.jhepr.2024.101184","DOIUrl":"10.1016/j.jhepr.2024.101184","url":null,"abstract":"<div><h3>Background & Aims</h3><div>Patients with acutely decompensated (AD) cirrhosis are immunocompromised and particularly susceptible to infections. This study investigated the immunomodulatory actions of albumin by which this protein may lower the incidence of infections.</div></div><div><h3>Methods</h3><div>Blood immunophenotyping was performed in 11 patients with AD cirrhosis and 10 healthy volunteers (HV). Bulk and single-cell RNA sequencing (scRNA-seq) and flow cytometry were performed in peripheral blood mononuclear cells (PBMCs) from 20 patients with AD cirrhosis and 34 HV exposed to albumin. Albumin’s effects on degranulation, phagocytosis, chemotaxis, and swarming of neutrophils from six patients with AD cirrhosis and nine HV were assessed by measuring myeloperoxidase enzymatic activity, the engulfment of fluorescent-labeled <em>Escherichia coli</em> and zymosan, and interactions of neutrophils with <em>Candida albicans</em> at single-cell resolution in microfluidic chambers, respectively. Whole blood RNA sequencing (RNA-seq) analyses were performed in 49 patients admitted for severe AD cirrhosis, of whom 30 received albumin during hospitalization.</div></div><div><h3>Results</h3><div>Compared with HV, patients with AD cirrhosis showed severe lymphopenia and defective neutrophil antimicrobial function. Bulk and scRNA-seq analyses revealed significantly (false discovery rate [FDR] <0.05) increased signatures related to B cells, myeloid cells, and CD4<sup>+</sup> T cells in PBMCs incubated with albumin. Changes in the B cell population were confirmed by flow cytometry. Neutrophils exposed to albumin also exhibited augmented chemotactic and degranulation responses, enhanced phagocytosis, and increased pathogen-restrictive swarming. RNA-seq data analysis in patients who had received albumin revealed specific upregulation of signatures related to B cells and neutrophils together with transcriptional changes in CD4<sup>+</sup> T cells (FDR <0.05).</div></div><div><h3>Conclusions</h3><div>The finding that albumin promotes the transcriptional reprogramming and expansion of the B cell compartment and improves neutrophil antimicrobial functions indicates mechanisms that may lower the incidence of infections in patients with severe AD cirrhosis receiving albumin therapy.</div></div><div><h3>Impact and implications:</h3><div>Patients with acutely decompensated cirrhosis receiving albumin as treatment have a lower incidence of infections. The reason for this protection is currently unknown, but the present study provides data that support the ability of albumin to boost the antimicrobial functions of immune cells in these patients. Moreover, these findings encourage the design of controlled clinical studies specifically aimed at investigating the effects of albumin administration on the immune system.</div></div>","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"6 11","pages":"Article 101184"},"PeriodicalIF":9.5,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142427448","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}
Pub Date : 2024-08-06DOI: 10.1016/j.jhepr.2024.101181
Parissa Tabrizian , Rebecca Marino , Pierce K.H. Chow
Immune checkpoint inhibitors (ICIs) have revolutionised the treatment landscape for advanced hepatocellular carcinoma (HCC). The combination of atezolizumab and bevacizumab has demonstrated efficacy, establishing a new standard of care for advanced HCC. Neoadjuvant studies have shown promising results with high response rates, increasing research into ICIs’ role. In the peri-operative setting, in addition to adjuvant and neo-adjuvant therapies, strategies for "downstaging" and "bridging" patients to liver transplantation (LT) are being investigated, broadening the eligible candidate pool. Furthermore, therapeutic advances have reshaped conversion strategies for hepatic resection, with emerging evidence indicating a role for adjuvant immunotherapy in patients at high risk of postoperative recurrence. In LT, concerns have arisen over the potential conflict between immunosuppression needs and the immune-enhancing effects of ICIs, with reports of severe rejection. However, liver-specific factors may lessen rejection risks, prompting exploration into the safety of pre-transplant ICI administration. Moreover, ongoing trials must prioritise patient selection and vigilant management protocols. Despite the remarkable progress in immunotherapy, the intricate molecular interactions within the tumour microenvironment and their implications on oncogenic pathways remain incompletely understood. This highlights the need for specialised expertise to effectively integrate immunotherapy into the surgical management of HCC. Key challenges include ensuring safety, optimising oncological outcomes, managing the risk of graft rejection in transplant recipients, and refining patient selection criteria. In this review, we aim to provide a comprehensive overview of the evolving role of immunotherapy in the surgical management of HCC, discussing the rationale for its application in both pre- and post-surgical contexts, leveraging current clinical experience, identifying potential limitations, and envisioning future applications. By integrating existing knowledge and highlighting areas for further investigation, this review seeks to inform clinical practice and guide future research endeavours.
{"title":"Liver resection and transplantation in the era of checkpoint inhibitors","authors":"Parissa Tabrizian , Rebecca Marino , Pierce K.H. Chow","doi":"10.1016/j.jhepr.2024.101181","DOIUrl":"10.1016/j.jhepr.2024.101181","url":null,"abstract":"<div><div>Immune checkpoint inhibitors (ICIs) have revolutionised the treatment landscape for advanced hepatocellular carcinoma (HCC). The combination of atezolizumab and bevacizumab has demonstrated efficacy, establishing a new standard of care for advanced HCC. Neoadjuvant studies have shown promising results with high response rates, increasing research into ICIs’ role. In the peri-operative setting, in addition to adjuvant and neo-adjuvant therapies, strategies for \"downstaging\" and \"bridging\" patients to liver transplantation (LT) are being investigated, broadening the eligible candidate pool. Furthermore, therapeutic advances have reshaped conversion strategies for hepatic resection, with emerging evidence indicating a role for adjuvant immunotherapy in patients at high risk of postoperative recurrence. In LT, concerns have arisen over the potential conflict between immunosuppression needs and the immune-enhancing effects of ICIs, with reports of severe rejection. However, liver-specific factors may lessen rejection risks, prompting exploration into the safety of pre-transplant ICI administration. Moreover, ongoing trials must prioritise patient selection and vigilant management protocols. Despite the remarkable progress in immunotherapy, the intricate molecular interactions within the tumour microenvironment and their implications on oncogenic pathways remain incompletely understood. This highlights the need for specialised expertise to effectively integrate immunotherapy into the surgical management of HCC. Key challenges include ensuring safety, optimising oncological outcomes, managing the risk of graft rejection in transplant recipients, and refining patient selection criteria. In this review, we aim to provide a comprehensive overview of the evolving role of immunotherapy in the surgical management of HCC, discussing the rationale for its application in both pre- and post-surgical contexts, leveraging current clinical experience, identifying potential limitations, and envisioning future applications. By integrating existing knowledge and highlighting areas for further investigation, this review seeks to inform clinical practice and guide future research endeavours.</div></div>","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"6 11","pages":"Article 101181"},"PeriodicalIF":9.5,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142427463","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}
Pub Date : 2024-08-01DOI: 10.1016/j.jhepr.2024.101125
Lukas Müller , Aline Mähringer-Kunz , Timo Alexander Auer , Uli Fehrenbach , Bernhard Gebauer , Johannes Haubold , Benedikt Michael Schaarschmidt , Moon-Sung Kim , René Hosch , Felix Nensa , Jens Kleesiek , Thierno D. Diallo , Michel Eisenblätter , Hanna Kuzior , Natascha Roehlen , Dominik Bettinger , Verena Steinle , Philipp Mayer , David Zopfs , Daniel Pinto Dos Santos , Roman Kloeckner
Background & Aims
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).
Methods
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.
Results
Univariate survival analysis revealed that impaired median overall survival was predicted by low SM (p <0.001), high TAT volume (p = 0.013), and high SAT volume (p = 0.006). In multivariate survival analysis, SM remained an independent prognostic factor (p = 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.
Conclusions
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.
Impact and implications:
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.
背景& 目的最近发现，身体成分评估（BCA）参数是肝细胞癌（HCC）患者的相关预后因素。方法这项回顾性多中心研究纳入了2010-2020年间在6个三级医疗中心接受TACE治疗的754例未经治疗的HCC患者。对腹腔组织成分进行了基于人工智能的全自动三维容积定量分析，以评估干预前计算机断层扫描上的骨骼肌体积（SM）、总脂肪组织（TAT）、肌内和肌间脂肪组织、内脏脂肪组织和皮下脂肪组织（SAT）。BCA 参数根据腹腔切片数进行归一化处理。我们评估了BCA参数对中位总生存期的影响，并进行了包括既定生存期估计值在内的多变量分析。结果单变量生存期分析显示，低SM（p <0.001）、高TAT体积（p = 0.013）和高SAT体积（p = 0.006）可预测中位总生存期受损。在多变量生存分析中，SM 仍是一个独立的预后因素（p = 0.039），而 TAT 和 SAT 容量则不再具有预测能力。SM的这种预测作用在BCLC B期患者的亚组分析中得到了证实。因此，将 SM 纳入新型评分系统可能会改善生存预测和临床决策。影响和意义：身体成分评估参数，尤其是骨骼肌体积，已被确定为许多疾病和治疗的相关预后因素。在这项研究中，骨骼肌体积被确定为接受经动脉化疗栓塞术的肝细胞癌患者的独立预后因素。因此，骨骼肌体积作为一种元参数，可在患者整体评估中发挥机会性生物标志物的作用，并可整合到决策支持系统中。与人工智能相结合的工作流程对于自动、定量的身体成分评估至关重要，可广泛应用于多学科病例讨论。
{"title":"AI-derived body composition parameters as prognostic factors in patients with HCC undergoing TACE in a multicenter study","authors":"Lukas Müller , Aline Mähringer-Kunz , Timo Alexander Auer , Uli Fehrenbach , Bernhard Gebauer , Johannes Haubold , Benedikt Michael Schaarschmidt , Moon-Sung Kim , René Hosch , Felix Nensa , Jens Kleesiek , Thierno D. Diallo , Michel Eisenblätter , Hanna Kuzior , Natascha Roehlen , Dominik Bettinger , Verena Steinle , Philipp Mayer , David Zopfs , Daniel Pinto Dos Santos , Roman Kloeckner","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":"6 8","pages":"Article 101125"},"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}
Pub Date : 2024-08-01DOI: 10.1016/j.jhepr.2024.101119
<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
{"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":"6 8","pages":"Article 101119"},"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}
Pub Date : 2024-08-01DOI: 10.1016/j.jhepr.2024.101115
<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
{"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":"6 8","pages":"Article 101115"},"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}
Pub Date : 2024-08-01DOI: 10.1016/j.jhepr.2024.101123
Anna Jerregård Skarby , Thomas Casswall , Annika Bergquist , Lina Lindström
Background & Aims
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.
Methods
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).
Results
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, p = 0.038).
Conclusions
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.
Impact and implications:
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.
背景& 目的原发性硬化性胆管炎（PSC）是一种罕见的进行性肝病，与炎症性肠病（IBD）有关。它通常在成人中确诊，但也可在儿童中出现。有关小儿 PSC 长期预后的数据非常有限。方法这是一项队列研究，包括2000年1月至2015年12月期间在斯德哥尔摩卡罗林斯卡大学医院小儿肝病科确诊为PSC的所有儿童（18岁）。对患者进行了随访，直至肝移植、死亡或最后随访日期（2021 年 8 月）。结果我们发现 124 名儿童确诊为 PSC，中位年龄为 14（1.9-17.8）岁。其中60%为男孩，93%患有IBD。中位随访时间为 13 年（5.7-21.6）。确诊后 5 年和 10 年的总体无事件生存率分别为 91% (95% CI 0.84-0.95) 和 77% (95% CI 0.68-0.84)。31%的患者（n = 39）患有自身免疫性肝炎（AIH）。13%的患者（16人）出现门静脉高压，24%的患者（30人）出现胆道并发症，0.8%的患者（1人）出现胆管癌（CCA），13%的患者（16人）接受了肝移植，3名患者死亡。10年后无移植生存率为91%。诊断时SCOPE指数较高的患者需要进行肝移植的风险增加了2.3倍（危险比2.35，95% CI 1.18-4.66，c统计量=0.70）。在随访期间，附加诊断为自身免疫性肝炎的患者接受移植手术的风险略高（危险比 2.85，95% CI 1.06-7.67，p = 0.038）。结论：确诊为原发性硬化性胆管炎的儿童在确诊后的前十年预后良好，而确诊时SCOPE指数高则预后较差。原发性硬化性胆管炎患儿及其家长非常需要更多地了解这种疾病的自然病史以及他们对未来的预期。我们希望本研究中提供的数据能够为医疗专业人员、年轻人和受此病影响的家庭提供帮助。
{"title":"Good long-term outcomes of primary sclerosing cholangitis in childhood","authors":"Anna Jerregård Skarby , Thomas Casswall , Annika Bergquist , Lina Lindström","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":"6 8","pages":"Article 101123"},"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}
Pub Date : 2024-07-23DOI: 10.1016/j.jhepr.2024.101169
Georg Semmler , Lorenz Balcar , Benedikt Simbrunner , Lukas Hartl , Mathias Jachs , Michael Schwarz , Benedikt Silvester Hofer , Laurenz Fritz , Anna Schedlbauer , Katharina Stopfer , Daniela Neumayer , Jurij Maurer , Sophie Gensluckner , Bernhard Scheiner , Elmar Aigner , Michael Trauner , Thomas Reiberger , Mattias Mandorfer
<div><h3>Background & Aims</h3><div>The LiverRisk score has been proposed as a blood-based tool to estimate liver stiffness measurement (LSM), thereby stratifying the risk of compensated advanced chronic liver disease (cACLD, LSM ≥10 kPa) and liver-related events in patients without known chronic liver disease (CLD). We aimed to evaluate its diagnostic/prognostic performance in tertiary care.</div></div><div><h3>Methods</h3><div>Patients referred to two hepatology outpatient clinics (cohort I, n = 5,897; cohort II, n = 1,558) were retrospectively included. Calibration/agreement of the LiverRisk score with LSM was assessed, and diagnostic accuracy for cACLD was compared with that of fibrosis-4 (FIB-4)/aspartate aminotransferase-to-platelet ratio index (APRI). The prediction of hepatic decompensation and utility of proposed cut-offs were evaluated.</div></div><div><h3>Results</h3><div>In cohort I/II, mean age was 48.3/51.8 years, 44.2%/44.7% were female, predominant etiologies were viral hepatitis (51.8%)/metabolic dysfunction-associated steatotic liver disease (63.7%), median LSM was 6.9 (IQR 5.1–10.9)/5.8 (IQR 4.5–8.8) kPa, and 1,690 (28.7%)/322 (20.7%) patients had cACLD.</div><div>Despite a moderate correlation (Pearson’s r = 0.325/0.422), the LiverRisk score systematically underestimated LSM (2.93/1.80 points/kPa lower), and range of agreement was wide, especially at higher values.</div><div>The diagnostic accuracy of the LiverRisk score for cACLD (area under the receiver operator characteristics curve [AUROC] 0.757/0.790) was comparable to that of FIB-4 (AUROC 0.769/0.813) and APRI (AUROC 0.747/0.765). The proposed cut-off of 10 points yielded an accuracy of 74.2%/81.2%, high specificity (91.9%/93.4%), but low negative predictive value (76.6%/84.5%, Cohen’s κ = 0.260/0.327).</div><div>In cohort I, 208 (3.5%) patients developed hepatic decompensation (median follow-up 4.7 years). The LiverRisk score showed a reasonable accuracy for predicting hepatic decompensation within 1–5 years (AUROC 0.778–0.832). However, it was inferior to LSM (AUROC 0.847–0.901, <em>p</em> <0.001) and FIB-4 (AUROC 0.898–0.913, <em>p</em> <0.001). Similar to the strata of other non-invasive tests, the proposed LiverRisk groups had distinct risks of hepatic decompensation.</div></div><div><h3>Conclusions</h3><div>The LiverRisk score did not improve the diagnosis of cACLD or prediction of hepatic decompensation in the tertiary care setting.</div></div><div><h3>Impact and implications</h3><div>The LiverRisk score has been proposed as a non-invasive tool to estimate liver stiffness measurement and thus the risk of compensated advanced chronic liver disease and liver-related events. As automatic implementation into lab reports is being discussed, the question of its applicability outside of opportunistic screening in the general population arises. In two large cohorts of patients referred to hepatology outpatient clinics, the LiverRisk score did not accurately pred
{"title":"Diagnostic and prognostic performance of the LiverRisk score in tertiary care","authors":"Georg Semmler , Lorenz Balcar , Benedikt Simbrunner , Lukas Hartl , Mathias Jachs , Michael Schwarz , Benedikt Silvester Hofer , Laurenz Fritz , Anna Schedlbauer , Katharina Stopfer , Daniela Neumayer , Jurij Maurer , Sophie Gensluckner , Bernhard Scheiner , Elmar Aigner , Michael Trauner , Thomas Reiberger , Mattias Mandorfer","doi":"10.1016/j.jhepr.2024.101169","DOIUrl":"10.1016/j.jhepr.2024.101169","url":null,"abstract":"<div><h3>Background & Aims</h3><div>The LiverRisk score has been proposed as a blood-based tool to estimate liver stiffness measurement (LSM), thereby stratifying the risk of compensated advanced chronic liver disease (cACLD, LSM ≥10 kPa) and liver-related events in patients without known chronic liver disease (CLD). We aimed to evaluate its diagnostic/prognostic performance in tertiary care.</div></div><div><h3>Methods</h3><div>Patients referred to two hepatology outpatient clinics (cohort I, n = 5,897; cohort II, n = 1,558) were retrospectively included. Calibration/agreement of the LiverRisk score with LSM was assessed, and diagnostic accuracy for cACLD was compared with that of fibrosis-4 (FIB-4)/aspartate aminotransferase-to-platelet ratio index (APRI). The prediction of hepatic decompensation and utility of proposed cut-offs were evaluated.</div></div><div><h3>Results</h3><div>In cohort I/II, mean age was 48.3/51.8 years, 44.2%/44.7% were female, predominant etiologies were viral hepatitis (51.8%)/metabolic dysfunction-associated steatotic liver disease (63.7%), median LSM was 6.9 (IQR 5.1–10.9)/5.8 (IQR 4.5–8.8) kPa, and 1,690 (28.7%)/322 (20.7%) patients had cACLD.</div><div>Despite a moderate correlation (Pearson’s r = 0.325/0.422), the LiverRisk score systematically underestimated LSM (2.93/1.80 points/kPa lower), and range of agreement was wide, especially at higher values.</div><div>The diagnostic accuracy of the LiverRisk score for cACLD (area under the receiver operator characteristics curve [AUROC] 0.757/0.790) was comparable to that of FIB-4 (AUROC 0.769/0.813) and APRI (AUROC 0.747/0.765). The proposed cut-off of 10 points yielded an accuracy of 74.2%/81.2%, high specificity (91.9%/93.4%), but low negative predictive value (76.6%/84.5%, Cohen’s κ = 0.260/0.327).</div><div>In cohort I, 208 (3.5%) patients developed hepatic decompensation (median follow-up 4.7 years). The LiverRisk score showed a reasonable accuracy for predicting hepatic decompensation within 1–5 years (AUROC 0.778–0.832). However, it was inferior to LSM (AUROC 0.847–0.901, <em>p</em> <0.001) and FIB-4 (AUROC 0.898–0.913, <em>p</em> <0.001). Similar to the strata of other non-invasive tests, the proposed LiverRisk groups had distinct risks of hepatic decompensation.</div></div><div><h3>Conclusions</h3><div>The LiverRisk score did not improve the diagnosis of cACLD or prediction of hepatic decompensation in the tertiary care setting.</div></div><div><h3>Impact and implications</h3><div>The LiverRisk score has been proposed as a non-invasive tool to estimate liver stiffness measurement and thus the risk of compensated advanced chronic liver disease and liver-related events. As automatic implementation into lab reports is being discussed, the question of its applicability outside of opportunistic screening in the general population arises. In two large cohorts of patients referred to hepatology outpatient clinics, the LiverRisk score did not accurately pred","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"6 11","pages":"Article 101169"},"PeriodicalIF":9.5,"publicationDate":"2024-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141839051","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}
扫码关注我们
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号