Gut最新文献

{"title":"Gut-peritoneal-multisystem axis in endometriosis.","authors":"Fatima El-Assaad, Emad M El-Omar","doi":"10.1136/gutjnl-2025-337490","DOIUrl":"https://doi.org/10.1136/gutjnl-2025-337490","url":null,"abstract":"","PeriodicalId":12825,"journal":{"name":"Gut","volume":" ","pages":""},"PeriodicalIF":25.8,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147769838","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}

{"title":"Reply to the letter to the editor from Gao and Liu regarding 'Non-invasive risk-based surveillance of hepatocellular carcinoma in patients with metabolic dysfunction-associated steatotic liver disease'.","authors":"Jimmy Che To Lai,Terry Cheuk-Fung Yip","doi":"10.1136/gutjnl-2026-339161","DOIUrl":"https://doi.org/10.1136/gutjnl-2026-339161","url":null,"abstract":"","PeriodicalId":12825,"journal":{"name":"Gut","volume":"1 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147753164","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}

{"title":"The UK experience with hepatitis B immunoglobulin use following liver transplantation: wide variation in practice despite evidence supporting cost-effective HBIG-free prophylaxis.","authors":"Almuthana Mohamed,Maria Guerra Veloz,Lindsay Greenland,Silke Francois,Gemma Botterill,Rachel Smith,Muhammad Salman,Lucy Turner,Alison Rowley,Stuart McPherson,Andrew Bathgate,Douglas Thorburn,William Gelson,Mark Aldersley,Patrick T F Kennedy,Kosh Agarwal,Ahmed M Elsharkawy","doi":"10.1136/gutjnl-2025-337965","DOIUrl":"https://doi.org/10.1136/gutjnl-2025-337965","url":null,"abstract":"INTRODUCTIONHepatitis B immunoglobulin (HBIG) and nucleos(t)ide analogues (NA) are standard prophylaxis against hepatitis B virus (HBV) recurrence after liver transplantation (LT). However, indefinite HBIG use, with variations in dosage and duration across LT centres, has recently been questioned. This study reviewed current HBV management practices and outcomes after LT across the UK.METHODSWe conducted a retrospective study of all HBV-related LTs in the UK (2010-2023) to review post-LT HBV prophylaxis, assess the impact of HBIG duration on HBV recurrence and overall survival and compare HBIG costs across protocols.RESULTSSignificant variation in protocols among LT centres was observed. The majority of the 273 patients were high risk for HBV recurrence (81.7%). After LT, 85% received HBIG regardless of the risk for HBV recurrence and 54.6% of patients continued HBIG treatment with a median duration of 119 days (IQR 10-344). A total of 14 patients (5.1%) experienced HBV recurrence within 12 months following LT. Our multivariate analysis indicated that triple immunosuppression following LT had a significantly increased risk of HBV recurrence. Survival rates at 1, 5 and 7 years after LT were 98.2%, 88.3% and 80.6%, respectively. In the Cox regression analysis, only lower HBIG IV doses during the first week after LT were associated with 7-year mortality.CONCLUSIONThere is a vast discrepancy in HBIG usage across the UK. HBIG doses after LT and the risk of HBV recurrence groups do not influence outcomes. HBIG maintenance-free prophylaxis is therefore a feasible and cost-effective option for most patients. Further prospective studies should verify these findings and support wider adoption of HBIG-free strategies.","PeriodicalId":12825,"journal":{"name":"Gut","volume":"26 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147753165","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}

{"title":"Differential intrahepatic integrated HBV DNA patterns between HBeAg-positive and HBeAg-negative chronic hepatitis B.","authors":"Daryl T-Y Lau, Elena S Kim, Zhili Wang, Wendy C King, David E Kleiner, Marc G Ghany, Yuanjie Liu, Raymond Chung, Richard K Sterling, Gavin Cloherty, Selena Y Lin, Hsin-Ni Liu, Ning Sun, Ying-Hsiu Su, Haitao Guo","doi":"10.1136/gutjnl-2025-337127","DOIUrl":"https://doi.org/10.1136/gutjnl-2025-337127","url":null,"abstract":"<p><strong>Background: </strong>Hepatitis B surface antigen (HBsAg) can be derived from intrahepatic covalently closed circular DNA (cccDNA) and integrated hepatitis B virus (HBV) DNA (iDNA).</p><p><strong>Objective: </strong>We evaluated the cccDNA and iDNA from liver tissues of 24 hepatitis B e antigen (HBeAg)(+) and 32 HBeAg(-) treatment-naive chronic hepatitis B (CHB) participants in the North American Hepatitis B Research Network.</p><p><strong>Design: </strong>For cccDNA analysis, DNA was heat-denatured and digested by plasmid-safe ATP-dependent DNase to remove relaxed circular DNA and iDNA before real-time polymerase chain reaction. For iDNA detection, total DNA was subjected to HBV hybridisation-targeted next generation sequencing assay for identification of the HBV-host junction sequences. Comparisons of HBV cccDNA and iDNA with other virological biomarkers were assessed.</p><p><strong>Results: </strong>Intrahepatic cccDNA, serum HBV DNA, HBV RNA, hepatitis B core related antigen and quantitative hepatitis B surface antigen were higher in HBeAg(+) CHB. Intrahepatic hepatitis B core antigen staining was present in 87% HBeAg(+) but only 13% HBeAg(-) samples (p<0.0001). HBsAg staining was frequent in over 85% in both groups. 23 (95.8%) HBeAg(+) participants had ≤50% iDNA whereas 25 (78.1%) HBeAg(-) participants had >50% iDNA of total HBV DNA in their livers. For HBeAg(+) CHB, the iDNA integration sites were random with only 15.9% localised to the direct repeat 2 (DR2)-DR1 region. For HBeAg(-) CHB, 52.4% of the iDNA integrations were clustered at DR2-DR1. Microhomology-mediated end joining patterns of double-stranded linear DNA HBV integration was more frequent in HBeAg(+) livers.</p><p><strong>Conclusion: </strong>HBeAg(-) CHB was associated with high HBsAg staining concentration despite low cccDNA levels suggesting that iDNA was the primary source of HBsAg. The high frequency of DR2-DR1 iDNA distribution in HBeAg(-) CHB suggests the selection advantage and clonal expansion of this integrant in the natural history of CHB.</p>","PeriodicalId":12825,"journal":{"name":"Gut","volume":" ","pages":""},"PeriodicalIF":25.8,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147769803","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}

{"title":"Clarifying the clinical role and implementation boundaries of the clinical-radiological model for TACE-treated hepatocellular carcinoma.","authors":"Shuang Shen,Guodong Yang,Xin Qiu","doi":"10.1136/gutjnl-2026-338921","DOIUrl":"https://doi.org/10.1136/gutjnl-2026-338921","url":null,"abstract":"","PeriodicalId":12825,"journal":{"name":"Gut","volume":"8 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147739036","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}

{"title":"Gastric microbiota-mediated immune remodelling in gastric cancer.","authors":"Jiuhe Gao,Harry Cheuk-Hay Lau,Gwenny Manel Fuhler,Jun Yu","doi":"10.1136/gutjnl-2026-338505","DOIUrl":"https://doi.org/10.1136/gutjnl-2026-338505","url":null,"abstract":"Increasing evidence indicates that the gastric microbiota plays crucial roles in regulating the tumour microenvironment (TME), influencing gastric tumourigenesis and progression. Several bacteria, including Streptococcus, Lactobacillus and Bacteroides, have shown robust immunomodulatory effects on TME. In this review, we summarise current understanding of the crosstalk between the gastric microbiota and TME in gastric cancer (GC). Functional alterations of the gastric microbiota from healthy mucosa to malignancy are delineated, with emphasis on the impacts of bacteria on different immune cell populations in gastric tumours, such as CD8+ T cells, macrophages, dendritic cells and regulatory T cells. The immunomodulatory roles of microbial metabolites and pathogen-associated molecular patterns in shaping immune cell infiltration, cytokine profiles and checkpoint molecule expression are also explored. While immune checkpoint blockade (ICB) has emerged as a promising treatment of various cancers, its efficacy in GC remains unsatisfactory due to the immunosuppressive gastric TME. We therefore evaluate the intricate interplays between the gastric microbiota and immunotherapy, and suggest potential microbiota-targeting strategies (eg, microbiota modulation, probiotics supplementation and combination therapies) to enhance antitumour immune response and boost ICB efficacy. We conclude by highlighting current challenges and providing future directions for microbiota research in GC. Overall, a deeper understanding of host-microbe interactions can provide promising avenues for precision medicine and the development of microbiota-targeting interventions against GC.","PeriodicalId":12825,"journal":{"name":"Gut","volume":"78 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147733752","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}

{"title":"Universal ESD for Barrett's neoplasia: the T1b '\"limbo'\" and risk of overtreatment.","authors":"Na Li,Shuai Zhang,Liqun Zhang,Xiaohui Jiang,Xuejiao Fan","doi":"10.1136/gutjnl-2026-338214","DOIUrl":"https://doi.org/10.1136/gutjnl-2026-338214","url":null,"abstract":"","PeriodicalId":12825,"journal":{"name":"Gut","volume":"127 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147731347","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}

{"title":"Letter to the editor regarding: Lai, Jimmy Che-To, et al \"Non-invasive risk-based surveillance of hepatocellular carcinoma in patients with metabolic dysfunction-associated steatotic liver disease\".","authors":"Wei Gao,Chen Liu","doi":"10.1136/gutjnl-2026-339053","DOIUrl":"https://doi.org/10.1136/gutjnl-2026-339053","url":null,"abstract":"","PeriodicalId":12825,"journal":{"name":"Gut","volume":"283 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147731706","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}

{"title":"CD48+ tumour-associated macrophages: novel immunotherapeutic targets in hepatocellular carcinoma.","authors":"Xiaolu Zhang,Natascha Roehlen","doi":"10.1136/gutjnl-2026-338840","DOIUrl":"https://doi.org/10.1136/gutjnl-2026-338840","url":null,"abstract":"","PeriodicalId":12825,"journal":{"name":"Gut","volume":"68 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147731348","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}

{"title":"Norepinephrine promotes tumour cell aggressiveness and NK cell ferroptosis via ADRB2 in intrahepatic cholangiocarcinoma with perineural invasion.","authors":"Xian-Long Meng,Jia-Cheng Lu,Yi-Xiao Zhang,Pei Pu,Xiao-Jun Guo,Tao Zhu,Zhi-Qiang Hu,Lei Yu,Qi-Man Sun,Qiang Gao,Jian Zhou,Jia Fan,Yi Chen,Xiao-Yong Huang,Guo-Ming Shi","doi":"10.1136/gutjnl-2025-337595","DOIUrl":"https://doi.org/10.1136/gutjnl-2025-337595","url":null,"abstract":"BACKGROUNDSympathetic signalling plays a critical role in the initiation and progression of various malignancies. However, its specific contribution to intrahepatic cholangiocarcinoma (iCCA) remains poorly understood.OBJECTIVEThis study aimed to investigate the effects and underlying mechanisms of sympathetic signalling on tumour and immune cells, and to explore the potential efficacy of targeting sympathetic pathways in iCCA characterised by perineural invasion (PNI).DESIGNSingle-cell RNA sequencing was employed to elucidate the impact of PNI on iCCA. In vivo and in vitro experiments were conducted to decipher the molecular mechanisms. Preclinical models were used to investigate the therapeutic potential of targeting sympathetic signalling.RESULTSTyrosine hydroxylase-positive sympathetic nerve fibres were detected in PNI+ iCCA, accompanied by elevated norepinephrine (NE). We constructed an atlas of PNI+ iCCA at single-cell transcriptional level, characterised by MDK overexpression and reduced infiltration of CD56dimCD16+ natural killer (NK) cells. Mechanistically, NE was found to upregulate MDK expression via the ADRB2/PI3K-AKT/p65 axis, thereby promoting tumour progression of PNI+ iCCA. Furthermore, NE might induce NK cell ferroptosis by triggering an imbalance in glutamate/cysteine metabolism in PNI+ iCCA via ADRB2. Loss of sympathetic innervation in mice reduced NE concentrations and MDK expression, while increasing NK cell infiltration and inhibiting tumour growth. Preliminary results suggested that blockers of β-adrenergic receptors suppressed iCCA progression.CONCLUSIONThis study uncovers a novel neuro-immune-tumour axis in iCCA and provides a mechanistic rationale for targeting β-adrenergic signalling as a possible therapeutic strategy for PNI+ iCCA.","PeriodicalId":12825,"journal":{"name":"Gut","volume":"73 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147726024","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}