JHEP Reports最新文献

Rifaximin in the spotlight: Are we ready to target the microbiome? 利福昔明在聚光灯下：我们准备好瞄准微生物组了吗？

IF 9.5 1区医学

JHEP Reports Pub Date : 2025-05-01 DOI: 10.1016/j.jhepr.2025.101360

Florent Artru , Virginia Hernández-Gea

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Corrigendum to ‘Cholangiocarcinoma across England: Temporal changes in incidence, survival and routes to diagnosis by region and level of socioeconomic deprivation’ [JHEP Reports 6 (2024) 100983] “全英格兰胆管癌：按地区和社会经济剥夺水平的发病率、生存率和诊断途径的时间变化”的勘误表[JHEP报告6 (2024)100983]

IF 9.5 1区医学

JHEP Reports Pub Date : 2025-05-01 DOI: 10.1016/j.jhepr.2025.101326

Daniela Tataru , Shahid A. Khan , Roger Hill , Helen Morement , Kwok Wong , Lizz Paley , Mireille B. Toledano

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Reply to: “A comment on ” 回复到：“对…的评论”

IF 9.5 1区医学

JHEP Reports Pub Date : 2025-05-01 DOI: 10.1016/j.jhepr.2025.101333

Mi Na Kim

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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

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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

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Copyright and information 版权及资料

IF 9.5 1区医学

JHEP Reports Pub Date : 2025-04-01 DOI: 10.1016/S2589-5559(25)00088-6

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Editorial Board page 编委会页面

IF 9.5 1区医学

JHEP Reports Pub Date : 2025-04-01 DOI: 10.1016/S2589-5559(25)00085-0

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The dual role of TIGIT in regulatory and effector T cells in chronic liver disease 慢性肝病中TIGIT在调节性和效应性T细胞中的双重作用

IF 9.5 1区医学

JHEP Reports Pub Date : 2025-03-29 DOI: 10.1016/j.jhepr.2025.101405

Amber G. Bozward , Scott P. Davies , Rémi Fiancette , Grace E. Wootton , Sian Faustini , Hin Fai Kwok , Naomi Richardson , Sean M. Morris , Kayani Kayani , Gary Middleton , Ye H. Oo

{"title":"The dual role of TIGIT in regulatory and effector T cells in chronic liver disease","authors":"Amber G. Bozward , Scott P. Davies , Rémi Fiancette , Grace E. Wootton , Sian Faustini , Hin Fai Kwok , Naomi Richardson , Sean M. Morris , Kayani Kayani , Gary Middleton , Ye H. Oo","doi":"10.1016/j.jhepr.2025.101405","DOIUrl":"10.1016/j.jhepr.2025.101405","url":null,"abstract":"<div><h3>Background & Aims</h3><div>Effective control of chronic liver diseases (CLD) requires suppression of effector T cells by CD4<sup>+</sup>CD25<sup>+</sup>CD127<sup>low</sup> regulatory T cells (Tregs). This study investigated the role of TIGIT, a co-inhibitory receptor, in CLD by examining the phenotype, recruitment, localisation, and function of TIGIT<sup>+</sup>Tregs and how TIGIT augments Treg function. We also elucidated the function of TIGIT<sup>+</sup>effector T cells on hepatocytes.</div></div><div><h3>Methods</h3><div>Liver infiltrating (CLD explants n = 7, donor liver n = 4) and peripheral (CLD blood n = 22, healthy control blood n = 10) TIGIT<sup>+</sup>Tregs and TIGIT<sup>+</sup>effector T cells were phenotyped by flow cytometry, and their localisation was examined by immunohistochemistry. Phenotypic and functional changes in TIGIT<sup>+</sup>Tregs in response to TIGIT agonism and IL-2 supplementation were also assessed. TIGIT<sup>+</sup>effector T cell-induced primary hepatocyte apoptosis was investigated using co-culture experiments and blocking assays.</div></div><div><h3>Results</h3><div>TIGIT<sup>+</sup>Tregs were more suppressive towards CD4<sup>+</sup>T cells than TIGIT<sup>-</sup>Tregs (<em>p</em> = 0.04254), and their suppressive action was IL-10 dependent. TIGIT expression was highly enriched on intrahepatic Tregs compared to effector T cells (<em>p</em> <0.0001). TIGIT<sup>+</sup>Tregs and TIGIT<sup>+</sup>effector T cells expressed CXCR3 and VLA-4 and localised around hepatocytes which express TIGIT ligand, CD155. TIGIT<sup>+</sup>Tregs also exhibited significantly higher cytotoxic T lymphocyte-associated antigen-4 (CTLA-4; <em>p</em> = 0.0012), FoxP3 (<em>p</em> <0.0001), and CD39 (<em>p</em> <0.0001) expression than TIGIT<sup>-</sup>Tregs. TIGIT agonism upregulated FoxP3 and CTLA-4 on Tregs, reduced proliferation, and increased TNF-α expression. Supplementing TIGIT<sup>+</sup>Tregs with IL-2 further enhanced FoxP3 and CTLA-4 expression. In contrast, TIGIT<sup>+</sup>effector T cells displayed reduced cytotoxicity towards hepatocytes, which reversed upon TIGIT blockade.</div></div><div><h3>Conclusions</h3><div>TIGIT<sup>+</sup>Tregs are highly suppressive and can be enhanced in response to TIGIT agonism and IL-2 stimulation, demonstrating their translational therapeutic potential. However, TIGIT blockade on CD8<sup>+</sup>T cells induces hepatitis, caution is required when using anti-TIGIT therapy.</div></div><div><h3>Impact and implications</h3><div>We identified a highly suppressive subset of regulatory T cells in the liver, defined as TIGIT<sup>+</sup>CD39<sup>+</sup>CTLA-4<sup>+</sup>Tregs. TIGIT agonists and IL-2 enhanced the suppressive function of this cell subset. The TIGIT ligand, CD155, is expressed on inflamed hepatocytes, and TIGIT blockade in oncology could instigate checkpoint inhibitor induced liver injury (CHILI). These findings have implications for future therapy in liver disease.</div","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"7 6","pages":"Article 101405"},"PeriodicalIF":9.5,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144115799","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}

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Mitochondrial dysfunction characterises the multigenerational effects of maternal obesity on MASLD 线粒体功能障碍是母亲肥胖对MASLD的多代影响的特征

IF 9.5 1区医学

JHEP Reports Pub Date : 2025-03-29 DOI: 10.1016/j.jhepr.2025.101404

Anneleen Heldens , Milton Antwi , Louis Onghena , Tim Meese , Yannick Gansemans , Joél Smet , Ellen Dupont , Xavier Verhelst , Sarah Raevens , Hans Van Vlierberghe , Arnaud Vanlander , Filip Van Nieuwerburgh , Lindsey Devisscher , Ruth De Bruyne , Anja Geerts , Sander Lefere

{"title":"Mitochondrial dysfunction characterises the multigenerational effects of maternal obesity on MASLD","authors":"Anneleen Heldens , Milton Antwi , Louis Onghena , Tim Meese , Yannick Gansemans , Joél Smet , Ellen Dupont , Xavier Verhelst , Sarah Raevens , Hans Van Vlierberghe , Arnaud Vanlander , Filip Van Nieuwerburgh , Lindsey Devisscher , Ruth De Bruyne , Anja Geerts , Sander Lefere","doi":"10.1016/j.jhepr.2025.101404","DOIUrl":"10.1016/j.jhepr.2025.101404","url":null,"abstract":"<div><h3>Background & Aims</h3><div>Although maternal obesity is an independent risk factor for metabolic dysfunction-associated steatotic liver disease (MASLD), the pathogenesis remains unclear. We aimed to evaluate the effect and mechanisms of multigenerational maternal Western diet (WD) on MASLD progression, and test drug candidates.</div></div><div><h3>Methods</h3><div>Female mice were fed WD from 8 weeks before breeding initiation with a normal chow (NC)-fed male, throughout pregnancy and lactation. Male offspring were weaned onto NC or WD and assessed at the age of 24 days, 10 weeks, and 16 weeks (n = 5–11 per group). Additionally, offspring from dams with hepatic insulin receptor knockout were evaluated (n = 9–12 per group). Serum fibroblast growth factor 21 (FGF21) and mitochondrial open reading frame of 12S rRNA-c (MOTS-c) were measured in adolescents with MASLD with or without a history of maternal obesity. The therapeutic efficacy of FGF21, semaglutide and an amylin analogue was assessed from 8 to 16 weeks of age (n = 8–12 per group).</div></div><div><h3>Results</h3><div>Starting from weaning age, maternal WD feeding aggravated body weight gain, insulin resistance, steatosis, and inflammation. Fibrosis was only observed in offspring exposed to maternal WD. Mechanistically, the latter exhibited reduced OXPHOS activity. Isolated maternal hepatic insulin resistance partially recapitulated offspring inflammation and fibrosis. Notably, OXPHOS was also downregulated in a transcriptomic dataset of maternal WD feeding in non-human primates. Serum FGF21 and MOTS-c correlated with MASLD severity and maternal obesity in adolescents. Particularly FGF21 treatment ameliorated steatohepatitis and mitochondrial function.</div></div><div><h3>Conclusions</h3><div>Maternal WD aggravates MASLD in male offspring starting from weaning age, with mitochondrial dysfunction contributing to disease severity. This was reversed by FGF21 agonism.</div></div><div><h3>Impact and implications</h3><div>The underlying mechanisms of maternal obesity contributing to metabolic dysfunction-associated steatotic liver disease (MASLD) severity in the offspring are not completely understood. Our study characterises the impact of multigenerational maternal Western diet on offspring MASLD development and identifies mitochondrial dysfunction as a contributor to disease severity. In this setting, pharmacological compounds targeting mitochondrial dysfunction appear to have the greatest therapeutic potential.</div></div>","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"7 6","pages":"Article 101404"},"PeriodicalIF":9.5,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144115798","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}

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Pediatric to adult care transfer in rare liver diseases: Recommendations based on insights from a European omnistakeholder event 罕见肝病的儿科到成人护理转移：基于欧洲全利益相关者事件见解的建议

IF 9.5 1区医学

JHEP Reports Pub Date : 2025-03-26 DOI: 10.1016/j.jhepr.2025.101403

Karsten Vanden Wyngaert , Janne Suykens , Deirdre Kelly , Isabel Goncalves , Ena Lindhart Thomsen , Jose Willemse , Zoe Mariño , João Madaleno , Jemma Day , Marianne Samyn , Mohamed Ali , Marianne Hørby Jørgensen , Eva Goossens , Johan De Munter , Anneloes Van Staa , Jo Wray , Panayiota Protopapa , Ansgar Lohse , Ruth De Bruyne

{"title":"Pediatric to adult care transfer in rare liver diseases: Recommendations based on insights from a European omnistakeholder event","authors":"Karsten Vanden Wyngaert , Janne Suykens , Deirdre Kelly , Isabel Goncalves , Ena Lindhart Thomsen , Jose Willemse , Zoe Mariño , João Madaleno , Jemma Day , Marianne Samyn , Mohamed Ali , Marianne Hørby Jørgensen , Eva Goossens , Johan De Munter , Anneloes Van Staa , Jo Wray , Panayiota Protopapa , Ansgar Lohse , Ruth De Bruyne","doi":"10.1016/j.jhepr.2025.101403","DOIUrl":"10.1016/j.jhepr.2025.101403","url":null,"abstract":"<div><h3>Background & Aims</h3><div>The transfer journey from pediatric to adult care services of young people with rare liver diseases poses significant challenges and is an underexplored research area. This study examined the critical aspects of, and opportunities for, transfer journey management for these young people in Europe.</div></div><div><h3>Methods</h3><div>In total, 72 individuals, representing 13 countries, participated in an omnistakeholder workshop on 17–18 March 2023. A standardized workshop methodology was used to discuss critical aspects and actions over nine focus sessions. The themes of these sessions were identified by engaging with healthcare providers, young people, and parents. Results (<em>i.e.</em> aspects receiving >25% of the votes) were ranked based on importance and validated by the European Reference Network of Hepatological Diseases (ERN RARE-LIVER) youth panel.</div></div><div><h3>Results</h3><div>Our findings revealed that the critical aspects of transfer journey management predominantly revolved around the transfer itself. Most of the critical aspects and actions were related to improving communication (<em>e.g.</em> allocating sufficient time, 81% of votes; giving consistent information, 43%; and discussing communication preferences, 100%), relational continuity (<em>e.g.</em> appointing a transition person to liaison between stakeholders, 79%), and management continuity (<em>e.g.</em> using a transfer document, 60%). Our results also underscored the importance of peer mentorship programs (100%), informing young people about the transfer process (85%), and implementing joint consultations (93%).</div></div><div><h3>Conclusions</h3><div>Current literature and guidelines on ‘transition’ might not fully address real-world challenges in rare liver diseases, particularly those concerning maintaining continuity of care during the actual transfer process. Future research should examine the effectiveness of strategies aimed at enhancing communication and continuity of care throughout the transfer journey, focusing on stakeholder experience.</div></div><div><h3>Impact and implications</h3><div>This international omnistakeholder workshop explored challenges and opportunities in managing transfer journeys for young people with rare liver diseases. By emphasizing practical implications (leading to actions), it provides a benchmark for improving transfer journeys worldwide, applicable to not only rare liver diseases, but possibly also common liver or other rare diseases. Our findings underscore the fundamental importance of the transfer itself in maintaining continuity of care. The critical aspects identified center around informative, relational, and management continuity of care and have been transformed into minimal criteria.</div></div>","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"7 6","pages":"Article 101403"},"PeriodicalIF":9.5,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144115630","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