JHEP Reports最新文献_第2页

Reply to: “Changing epidemiology of hepatocellular carcinoma in the Mediterranean area: A challenge for surveillance?” 回复：“地中海地区肝细胞癌流行病学的变化：监测的挑战？”

IF 9.5 1区医学

JHEP Reports Pub Date : 2025-05-01 DOI: 10.1016/j.jhepr.2025.101445

Margarita Sala , María Varela

引用次数: 0

Copyright and information 版权及资料

IF 9.5 1区医学

JHEP Reports Pub Date : 2025-05-01 DOI: 10.1016/S2589-5559(25)00119-3

引用次数: 0

Editorial Board page 编委会页面

IF 9.5 1区医学

JHEP Reports Pub Date : 2025-05-01 DOI: 10.1016/S2589-5559(25)00117-X

引用次数: 0

CD4 T cells and B cell help – when exhausted cells can still function CD4 T细胞和B细胞有帮助——当精疲力竭的细胞仍能正常工作

IF 9.5 1区医学

JHEP Reports Pub Date : 2025-04-23 DOI: 10.1016/j.jhepr.2025.101435

Jill Weisser, Tobias Boettler

引用次数: 0

Patient-derived organoids inform pharmacogenomic vulnerabilities in liver cancer 患者来源的类器官提示肝癌的药物基因组脆弱性

IF 9.5 1区医学

JHEP Reports Pub Date : 2025-04-22 DOI: 10.1016/j.jhepr.2025.101426

Alissa Michelle Wong , Hao Huang , Aikha Melissa Wong , Howard Ho Wai Leung , Winnie Wing Yan Cheung , Yin Kau Lam , Xiaofan Ding , Luyao Zhang , Clarice Chu , Yue Liu , Cecilia Ka Wing Chan , Anthony Wing Hung Chan , Kelvin Kwok Chai Ng , Xin Wang , Stephen Lam Chan , Nathalie Wong

{"title":"Patient-derived organoids inform pharmacogenomic vulnerabilities in liver cancer","authors":"Alissa Michelle Wong , Hao Huang , Aikha Melissa Wong , Howard Ho Wai Leung , Winnie Wing Yan Cheung , Yin Kau Lam , Xiaofan Ding , Luyao Zhang , Clarice Chu , Yue Liu , Cecilia Ka Wing Chan , Anthony Wing Hung Chan , Kelvin Kwok Chai Ng , Xin Wang , Stephen Lam Chan , Nathalie Wong","doi":"10.1016/j.jhepr.2025.101426","DOIUrl":"10.1016/j.jhepr.2025.101426","url":null,"abstract":"<div><h3>Background & Aims</h3><div>Patient-derived tumor organoids (PDTOs) are a reliable model for preclinical and translational studies. Despite positive retrospective correlations with patient response, challenges such as culture success, cost, standardization, and time constraints hinder their clinical utility in precision medicine. Here, we optimize PDTO establishment using growth factor-reduced media (GF-) to mitigate these challenges and (1) identify somatic variant indicators that can improve the therapeutic index of existing FDA-approved drugs against hepatocellular carcinoma (HCC), (2) elucidate synthetic lethal candidates against undruggable HCC driver mutations, and (3) assess the feasibility of PDTOs in personalized therapy.</div></div><div><h3>Methods</h3><div>We successfully established a panel of 23 PDTOs from patients with HCC undergoing curative hepatectomy using a protocol primarily based on growth factor-reduced medium. PDTOs were subjected to comprehensive analyses, including the identification of hallmark mutations, assessment of genomic heterogeneity, transcriptomic profiling, and histological characterization. A 100-drug repurposing screen was conducted on the PDTOs and organoids derived from adjacent non-tumoral and normal livers to explore tumor-specific drug responses. Pharmacogenomic analysis using elastic net was performed (cut-off <em>p</em> <0.05) and synthetic lethality links were subject to experimental validation. The clinical relevance of PDTOs in personalized therapy were investigated through two case studies.</div></div><div><h3>Results</h3><div>Our results reveal that GF-derived PDTOs mimic histology and genetic heterogeneity of HCC. Pharmacogenomic analysis showed that the majority of tested FDA-approved drugs were not associated with HCC driver mutations (<5%). In addition, non-canonical signaling from <em>CTNNB1</em> mutations were associated with ceritinib sensitivity (<em>p</em> <0.0001) via polypharmacological targeting of RPS6KA3. The PDTO case study showed clear benefit to patient survival by aiding clinical management.</div></div><div><h3>Conclusions</h3><div>Our findings underscore the utility of PDTOs established from minimal GF media in many facets of precision oncology advancements.</div></div><div><h3>Impact and implications</h3><div>Patient-derived tumor organoids are a reliable model for preclinical and translational studies. Despite positive retrospective correlations with patient response data, challenges such as culture success, cost, standardization, and time constraints hinder their clinical utility in guiding precision medicine. This study underscores the utility of patient-derived organoids established from growth factor-reduced media in many facets of precision oncology, showing for the first time in hepatocellular carcinoma, clear benefit to patient survival in a proof-of-concept case study.</div></div>","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"7 7","pages":"Article 101426"},"PeriodicalIF":9.5,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144270182","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Safety, efficacy, and outcomes of invasive coronary angiography in liver transplant candidates 有创冠状动脉造影在肝移植候选者中的安全性、有效性和结果

IF 9.5 1区医学

JHEP Reports Pub Date : 2025-04-22 DOI: 10.1016/j.jhepr.2025.101428

Carme Ginard , Giulia Pagano , Salvatore Brugaletta , Annabel Blasi , Marta Sánchez-Ric , Ander Regueiro , Roger Pujol , Sergio Rodriguez-Tajes , Pablo Ruiz , Jordi Colmenero , Gonzalo Crespo

{"title":"Safety, efficacy, and outcomes of invasive coronary angiography in liver transplant candidates","authors":"Carme Ginard , Giulia Pagano , Salvatore Brugaletta , Annabel Blasi , Marta Sánchez-Ric , Ander Regueiro , Roger Pujol , Sergio Rodriguez-Tajes , Pablo Ruiz , Jordi Colmenero , Gonzalo Crespo","doi":"10.1016/j.jhepr.2025.101428","DOIUrl":"10.1016/j.jhepr.2025.101428","url":null,"abstract":"<div><h3>Background & Aims</h3><div>Invasive coronary angiography (ICA) with/without percutaneous coronary intervention (PCI) is recommended in liver transplant (LT) candidates at risk of silent coronary artery disease (CAD). The outcomes and safety of this approach have been scarcely analyzed in Europe.</div></div><div><h3>Methods</h3><div>This retrospective, single-center study included all patients assessed as LT candidates between July 2015 and December 2022. Outcomes before and after LT were compared between patients with and without ICA as part of pre-LT assessment. Findings and outcomes of ICA were recorded.</div></div><div><h3>Results</h3><div>A total of 912 patients were considered for LT, of whom 202 had an ICA. Patients with ICA more frequently presented contraindications for LT (<em>p</em> = 0.026). Severe (>70%) CAD was found in 29/202 cases (14%), and PCI was performed in 18 (9%). All patients received drug-eluting stents, and the duration of dual antiplatelet therapy (DAPT) was 1 month in 80%. Eight patients (4%) presented complications, which were more frequent in patients who received PCI (22%). One patient died from acute-on-chronic liver failure after post-DAPT bleeding. In the 516 patients who underwent transplantation, the incidence of cardiovascular events (CVEs) increased with the burden of CAD, from 11% in patients without ICA indication to 43% in patients with PCI (<em>p</em> <0.001), without differences in mortality (<em>p</em> = 0.529).</div></div><div><h3>Conclusions</h3><div>In a contemporary cohort of LT candidates, ICA was associated with a low incidence of complications, although some of these, related to DAPT, can be life-threatening. The burden of disease in ICA correlates with the incidence of post-LT CVEs, although this did not result in a higher mortality.</div></div><div><h3>Impact and implications</h3><div>Invasive coronary angiography (ICA) is performed in potential liver transplant (LT) candidates to identify severe coronary artery disease that may either be treated to permit LT or contraindicate LT if untreatable, but its safety and outcomes are not well defined. We show that ICA is associated with a low incidence of complications in LT candidates, although severe coronary artery disease requiring percutaneous treatment followed by dual antiplatelet therapy increased the risk of severe complications. In addition, ICA identifies patients with untreatable disease that can contraindicate LT. Finally, the higher the burden of disease on ICA, the higher the incidence of post-LT cardiovascular events, although this was not associated with increased post-LT mortality. These results support the use of ICA in LT candidates, although being aware of the potential risks is crucial for physicians and patients.</div></div>","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"7 7","pages":"Article 101428"},"PeriodicalIF":9.5,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144270183","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

The association between childhood obesity and major adverse liver outcomes in adolescence and young adulthood 儿童肥胖与青春期和青年期主要不良肝脏结局之间的关系

IF 9.5 1区医学

JHEP Reports Pub Date : 2025-04-11 DOI: 10.1016/j.jhepr.2025.101425

Resthie R. Putri , Thomas Casswall , Pernilla Danielsson , Claude Marcus , Emilia Hagman

{"title":"The association between childhood obesity and major adverse liver outcomes in adolescence and young adulthood","authors":"Resthie R. Putri , Thomas Casswall , Pernilla Danielsson , Claude Marcus , Emilia Hagman","doi":"10.1016/j.jhepr.2025.101425","DOIUrl":"10.1016/j.jhepr.2025.101425","url":null,"abstract":"<div><h3>Background & Aims</h3><div>Paediatric obesity is associated with liver steatosis and injury. We aimed to investigate the association between paediatric obesity and the risk of major adverse liver outcomes (MALOs) during adolescence and adulthood.</div></div><div><h3>Methods</h3><div>A cohort study of children with overweight or obesity enrolled in the Swedish Childhood Obesity Treatment Register (1997–2020) was performed (n = 29,321). Controls from the general population matched by sex, birth year, and resident areas were obtained (n = 141,510). The individuals were followed from age 10 (or obesity treatment initiation) up to age 40. MALOs were defined as any occurrence of cirrhosis, hepatocellular carcinoma, oesophageal or gastric varices, portal hypertension, liver transplantation, ascites, liver failure, or liver-related mortality.</div></div><div><h3>Results</h3><div>During a median follow-up of 8.3 [Q1–Q3: 5.5–11.8] years, MALOs were identified in 77 individuals. The cumulative incidence of MALOs by age 40 was 1.14% in the obesity cohort and 0.52% in the control group. Childhood adiposity was associated with the risk of MALOs (hazard ratio 2.15, 95% CI 1.33–3.48, <em>p =</em> 0.002). Individuals who had childhood obesity and developed alcohol use disorder during follow-up had an even higher risk of MALOs than controls without alcohol use disorder (hazard ratio 7.64, 95% CI 2.73–21.47, <em>p</em> <0.001). Type 2 diabetes did not mediate the association between childhood obesity and MALOs (<em>p =</em> 0.54).</div></div><div><h3>Conclusions</h3><div>Paediatric obesity is associated with a two-fold increased risk of MALOs. However, the absolute risk of developing MALOs by age 40 remains low.</div></div><div><h3>Impact and implications</h3><div>Firstly, healthcare providers should recognise that the consequences of paediatric obesity are not limited to immediate health concerns but rather present a sustained consequence on liver health into adulthood. Secondly, our findings revealed that a substantial proportion of individuals with alcohol use disorder experienced onset during adolescence, significantly amplifying the risk of major adverse liver outcomes. This underscores the importance of incorporating routine assessment for alcohol use disorder within paediatric care, particularly during adolescence, to identify and mitigate this increased risk. Thirdly, while the incidence of major adverse liver outcomes up to age 40 remains low, we identify a population at increased risk. This could help to refine risk stratification and target interventions more effectively.</div></div>","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"7 7","pages":"Article 101425"},"PeriodicalIF":9.5,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144279214","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Temporal dichotomy of neutrophil function in acute liver injury and repair 急性肝损伤与修复中中性粒细胞功能的时间二分法

IF 9.5 1区医学

JHEP Reports Pub Date : 2025-04-11 DOI: 10.1016/j.jhepr.2025.101417

Jennifer A. Cartwright , Philippe M.D. Potey , Eilidh Livingstone , Lara Campana , Philip J. Starkey Lewis , Magdalena E.M. Oremek , Naomi N. Gachanja , Giulia Rinaldi , Rhona E. Aird , Tak Yung Man , Anuruddika J. Fernando , Joanna P. Simpson , Natalie Z.M. Homer , Nicole Barth , Melisande Addison , Candice Ashmore-Harris , Maria Elena Candela , Alastair M. Kilpatrick , Matthieu Vermeren , Calum T. Robb , Adriano G. Rossi

{"title":"Temporal dichotomy of neutrophil function in acute liver injury and repair","authors":"Jennifer A. Cartwright , Philippe M.D. Potey , Eilidh Livingstone , Lara Campana , Philip J. Starkey Lewis , Magdalena E.M. Oremek , Naomi N. Gachanja , Giulia Rinaldi , Rhona E. Aird , Tak Yung Man , Anuruddika J. Fernando , Joanna P. Simpson , Natalie Z.M. Homer , Nicole Barth , Melisande Addison , Candice Ashmore-Harris , Maria Elena Candela , Alastair M. Kilpatrick , Matthieu Vermeren , Calum T. Robb , Adriano G. Rossi","doi":"10.1016/j.jhepr.2025.101417","DOIUrl":"10.1016/j.jhepr.2025.101417","url":null,"abstract":"<div><h3>Background & aims</h3><div>Acetaminophen (APAP)-induced acute liver injury (APAP-ALI) is the leading cause of acute liver failure-induced death, with host innate immune responses driving outcomes. Neutrophils are activated and increased in APAP-ALI and reported to contribute to liver damage. However, neutrophil dysfunction in patients with acute liver failure is associated with non-survival, and recent reports highlight their importance in hepatic repair. Neutrophil-targeted therapies for APAP-ALI are hampered by this controversy and a lack of time-dependent investigation.</div></div><div><h3>Methods</h3><div>Hepatic neutrophils were depleted at different times in a wild-type mouse model of APAP-ALI. <em>Fpr1</em><sup><em>-/-</em></sup> mice, with reduced neutrophil activation, were also used. The impact of neutrophil depletion was interrogated during hepatic injury and repair after APAP-ALI, using serum biochemistry, liver and blood flow cytometry, liver histopathology, immunohistochemistry, ELISA, and NanoString analysis.</div></div><div><h3>Results</h3><div>Neutrophils contributed both to hepatic damage and repair after APAP-ALI. Early liver necrosis was reduced by neutrophil depletion (34% to 23%, <em>p</em> = 0.0018, n ≥10) and by reducing neutrophil functions (39% to 29%, <em>p</em> = 0.0279, n ≥11). By contrast, late neutrophil depletion resulted in markedly reduced liver repair (persistent necrosis 17% to 30%, <em>p</em> = 0.016, and higher serum alanine aminotransferase [1,221 to 3,725 IU/l, <em>p</em> = 0.0007, n ≥10]) and hepatocyte proliferation (decreased minichromosomal maintenance 2+ hepatocytes, 3% to 1%, <em>p</em> = 0.025, n = 10). Late neutrophil depletion reduced proliferation, growth factors, and angiogenesis transcripts (Mik6 fold change [FC] -6.322, <em>p</em> = 0.002; Socs2 FC -2.91, <em>p</em> = 0.01; vascular endothelial growth factor A FC -1.48, <em>p</em> = 0.01; n = 3). Similar transcript changes were identified when preventing formylated peptide receptor 1-mediated neutrophil activation, along with reduced extracellular matrix remodeling (Col12a1, FC -1.99, <em>p</em> = 0.0001; n ≥5). Finally, depleting neutrophils resulted in a hepatic proinflammatory monocyte/macrophage phenotype during repair stages, with increased proinflammatory-related transcripts and reduced reparative transcripts.</div></div><div><h3>Conclusion</h3><div>Recruited neutrophils contribute not only to hepatic damage early in APAP-ALI, but also to hepatic repair through a variety of pathways, including extracellular matrix remodeling, angiogenesis, hepatocyte proliferation, and promotion of an anti-inflammatory monocyte/macrophage phenotype.</div></div><div><h3>Impact and implications</h3><div>Novel therapies are required for APAP-ALI to improve patient outcomes. Neutrophil products and functions are potential targets for future therapies, but current literature controversy and a lack of time-dependent studies hinder progression. This","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"7 7","pages":"Article 101417"},"PeriodicalIF":9.5,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144307750","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

DHCR7 inhibition ameliorates MetALD and HCC in mice and human 3D liver spheroids 抑制DHCR7可改善小鼠和人三维肝球体的MetALD和HCC

IF 9.5 1区医学

JHEP Reports Pub Date : 2025-04-05 DOI: 10.1016/j.jhepr.2025.101415

Gen Yamamoto , Raquel Carvalho-Gontijo Weber , Wonseok Lee , Vivian Zhang , Haeum Jang , Sadatsugu Sakane , Xiao Liu , Hyun Young Kim , David A. Brenner , Na Li , Tatiana Kisseleva

{"title":"DHCR7 inhibition ameliorates MetALD and HCC in mice and human 3D liver spheroids","authors":"Gen Yamamoto , Raquel Carvalho-Gontijo Weber , Wonseok Lee , Vivian Zhang , Haeum Jang , Sadatsugu Sakane , Xiao Liu , Hyun Young Kim , David A. Brenner , Na Li , Tatiana Kisseleva","doi":"10.1016/j.jhepr.2025.101415","DOIUrl":"10.1016/j.jhepr.2025.101415","url":null,"abstract":"<div><h3>Background & Aims</h3><div>Metabolic dysfunction and alcohol-associated liver disease (MetALD) results in the development of liver steatosis, inflammation, fibrosis, and hepatocellular carcinoma (HCC). <em>De novo</em> lipogenesis and cholesterol synthesis play an important role in the pathogenesis of MetALD. DHCR7 (7-dehydrocholesterol reductase) regulates the last stages of cholesterol production.</div></div><div><h3>Methods</h3><div>We investigated whether targeting DHCR7 can ameliorate the development of MetALD and HCC using experimental models and 3D human liver spheroids.</div></div><div><h3>Results</h3><div>Here, we demonstrate that partial genetic ablation of the <em>Dhcr7</em> gene and pharmacological blockade of DHCR7 activity with the AY9944 inhibitor suppresses hepatic steatosis (↓ lipid area, n = 15; <em>p</em> <0.001), inflammation (↓ F4/80, n = 6; <em>p</em> <0.01), fibrosis (↓ Sirius red, n = 6; <em>p</em> <0.01), and HCC (↓ AFP/YAP, n = 6; <em>p</em> <0.01) in diethylnitrosamine (DEN)-challenged high-fat diet (HFD) + ethanol (EtOH)-fed mice treated with AY9944 compared with control mice. To translate our findings, the effect of DHCR7 was tested using 3D human liver spheroids, which mimicked MetALD and MetALD-HCC. MetALD liver spheroids were composed of primary human hepatocytes, non-parenchymal cells, and hepatic stellate cells. In contrast, in MetALD-HCC spheroids, the HCC cell line HepG2 was used instead of hepatocytes. Therapeutic administration of AY9944 inhibited inflammation (↓ <em>TNF</em>, <em>p</em> <0.05) and fibrosis in MetALD spheroids (↓ <em>ACTA2</em>, <em>p</em> <0.001; <em>COL1A1</em>, <em>p</em> <0.05; <em>TIMP1</em>, <em>p</em> <0.01; <em>SERPINE1</em>, <em>p</em> <0.05). In turn, dsiRNA-based knockdown of DHCR7 reduced HepG2 proliferation (↓ <em>PCNA</em>, <em>p</em> <0.05; <em>CCNE</em>, <em>p</em> <0.05) and expression of MetALD-HCC markers (↓ <em>AFP</em>, <em>p</em> <0.05; <em>GPC3</em>, <em>p</em> <0.05; <em>YAP</em>, <em>p</em> <0.01).</div></div><div><h3>Conclusions</h3><div>Our data demonstrate that targeting DHCR7 can become a strategy for the treatment of MetALD and HCC.</div></div><div><h3>Impact and implications</h3><div>This study demonstrates the critical role of <em>de novo</em> lipogenesis and cholesterol synthesis in the pathogenesis of metabolic dysfunction and alcohol-associated liver disease (MetALD) and its progression to hepatocellular carcinoma (HCC). Our findings identified that the upregulation of DHCR7 contributes to the pathogenesis of MetALD and its inhibition suppresses hepatic steatosis, inflammation, fibrosis, and tumor proliferation. These findings are significant for researchers and clinicians, as they establish that genetic and pharmacological inhibition of DHCR7 is effective in both experimental models and translational 3D human liver spheroids. The results uncover the translational potential of DHCR7-targeted therapies fo","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"7 7","pages":"Article 101415"},"PeriodicalIF":9.5,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144221015","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Identification of pediatric MASLD using insulin resistance indices 应用胰岛素抵抗指标鉴别小儿MASLD

IF 9.5 1区医学

JHEP Reports Pub Date : 2025-04-03 DOI: 10.1016/j.jhepr.2025.101419

Kyungchul Song , Eunju Lee , Hye Sun Lee , Young Hoon Youn , Su Jung Baik , Hyun Joo Shin , Hyun Wook Chae , Ji-Won Lee , Yu-Jin Kwon

{"title":"Identification of pediatric MASLD using insulin resistance indices","authors":"Kyungchul Song , Eunju Lee , Hye Sun Lee , Young Hoon Youn , Su Jung Baik , Hyun Joo Shin , Hyun Wook Chae , Ji-Won Lee , Yu-Jin Kwon","doi":"10.1016/j.jhepr.2025.101419","DOIUrl":"10.1016/j.jhepr.2025.101419","url":null,"abstract":"<div><h3>Background & Aims</h3><div>We investigated the triglyceride-to-high density lipoprotein (HDL) ratio (TG/HDL), triglyceride–glucose index (TyG), single-point insulin sensitivity estimator (SPISE), and metabolic score for insulin resistance (METS-IR) as potential predictors of pediatric metabolic dysfunction-associated steatotic liver disease (MASLD) by addressing the limited research on insulin-resistance markers in this population.</div></div><div><h3>Methods</h3><div>This cross-sectional study included data from 1,150 and 260 youths from the National Health and Nutrition Examination Survey (NHANES) and a real-world clinic, respectively. Hepatic steatosis was assessed using transient elastography and abdominal sonography. Logistic regression analysis was performed using MASLD as the dependent variable. Receiver operating characteristic (ROC) curves were used to evaluate predictability.</div></div><div><h3>Results</h3><div>The MASLD group had higher TG/HDL, TyG, METS-IR, and obesity proportions but lower SPISE than the normal group in both NHANES and real-world data. All markers were significantly related to MASLD in logistic regression analyses, even after adjusting for age and sex, in both the NHANES and real-world clinic data (all <em>p</em> <0.001). The areas under the ROC curves (AUCs) for SPISE and METS-IR were 0.91 and 0.91 in the total group, 0.92 and 0.92 in the male group, and 0.90 and 0.89 in the female group, respectively—all higher than those for TG/HDL and TyG in the NHANES dataset (all <em>p</em> <0.001). In the real-world clinical data, the AUCs of SPISE and METS-IR were significantly higher than those of TG/HDL and TyG in the total and male groups (all <em>p</em> <0.001). In the female group, the AUC for SPISE was significantly higher than that for TG/HDL or TyG.</div></div><div><h3>Conclusions</h3><div>METS-IR and SPISE are effective, non-invasive markers for predicting pediatric MASLD, which offer valuable tools for early detection and improved clinical management.</div></div><div><h3>Impact and implications</h3><div>The increasing prevalence of pediatric metabolic dysfunction-associated steatotic liver disease (MASLD) and its strong association with cardiometabolic risk factors underscore the need for effective early detection tools. Our study demonstrates that single-point insulin sensitivity estimator (SPISE) and metabolic score for insulin resistance (METS-IR) are superior, non-invasive markers for predicting MASLD in children and adolescents, with validated cut-off values applicable to both population-based and real-world clinical settings. These findings are particularly relevant for clinicians and healthcare policymakers, as they provide practical, easily accessible screening tools derived from routine laboratory tests, aiding in the early identification and risk stratification of pediatric MASLD. However, given the study’s retrospective design and variations in diagnostic methods across datasets, fu","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"7 7","pages":"Article 101419"},"PeriodicalIF":9.5,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144205555","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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