Pub Date : 2025-12-24DOI: 10.1136/gutjnl-2025-336902
Antonio Tursi,Giovanni Brandimarte,Francesco Di Mario,Wenjie Ma,Juozas Kupcinskas,Jaroslaw Regula,Giovanni Maconi,Peter Malfertheiner,Giovanni Barbara,Neil Stollman,Savvas Papagrigoriadis,Thomas Golda,Antonio Amato,Mauro Bafutto,Gabrio Bassotti,Gian A Binda,Sebastiano Biondo,Pellegrino Crafa,Dan Dumitrascu,Walter Elisei,Nicola Flor,Kok Ann Gwee,David James Humes,Takaomi Kessoku,Wolfgang Kruis,Adi Lahat,Angel Lanas,Atsushi Nakajima,Marcello Picchio,Robin C Spiller,Athena Adamopoulos,Carmelo Scarpignato
INTRODUCTIONColonic diverticulosis is the most common structural abnormality of the colon in developed countries, with an increasing global prevalence. Approximately 20-25% of affected individuals develop symptoms, collectively referred to as diverticular disease. Given its wide clinical spectrum, evolving pathophysiological insights and growing disease burden, updated guidance is essential.METHODSThis International Consensus, developed by 32 experts from 14 countries through a structured Delphi process based on the PICO framework and GRADE methodology, provides evidence-based recommendations across five domains: epidemiology and pathogenesis; clinical features; diagnosis; medical therapy; and surgical management.RESULTSKey statements define diverticulosis as the presence of diverticula without symptoms and diverticular disease as diverticula associated with symptoms or complications. High dietary fibre intake is protective whereas smoking, obesity and the use of non-steroidal anti-inflammatory drugs, corticosteroids, opioids or immunotherapy increase risk. Imaging is essential in suspected acute diverticulitis: ultrasound may be appropriate in experienced hands, while CT remains preferred for complicated cases. Diverticulosis itself requires no treatment. In symptomatic uncomplicated diverticular disease, dietary fibre, selected probiotics, mesalazine and rifaximin may help relieve symptoms. Routine antibiotic use is not recommended for acute uncomplicated diverticulitis, and elective surgery should be individualised, prioritising quality of life considerations over episode count.CONCLUSIONSThese Consensus statements aim to standardise and optimise the diagnosis, management and prevention of diverticular disease across diverse healthcare systems, while highlighting research priorities such as microbiome characterisation, genetic risk profiling and long-term outcomes of selective antimicrobial and surgical strategies.
{"title":"Revised version global guidelines on diverticular disease of the colon: the Fiesole Consensus report.","authors":"Antonio Tursi,Giovanni Brandimarte,Francesco Di Mario,Wenjie Ma,Juozas Kupcinskas,Jaroslaw Regula,Giovanni Maconi,Peter Malfertheiner,Giovanni Barbara,Neil Stollman,Savvas Papagrigoriadis,Thomas Golda,Antonio Amato,Mauro Bafutto,Gabrio Bassotti,Gian A Binda,Sebastiano Biondo,Pellegrino Crafa,Dan Dumitrascu,Walter Elisei,Nicola Flor,Kok Ann Gwee,David James Humes,Takaomi Kessoku,Wolfgang Kruis,Adi Lahat,Angel Lanas,Atsushi Nakajima,Marcello Picchio,Robin C Spiller,Athena Adamopoulos,Carmelo Scarpignato","doi":"10.1136/gutjnl-2025-336902","DOIUrl":"https://doi.org/10.1136/gutjnl-2025-336902","url":null,"abstract":"INTRODUCTIONColonic diverticulosis is the most common structural abnormality of the colon in developed countries, with an increasing global prevalence. Approximately 20-25% of affected individuals develop symptoms, collectively referred to as diverticular disease. Given its wide clinical spectrum, evolving pathophysiological insights and growing disease burden, updated guidance is essential.METHODSThis International Consensus, developed by 32 experts from 14 countries through a structured Delphi process based on the PICO framework and GRADE methodology, provides evidence-based recommendations across five domains: epidemiology and pathogenesis; clinical features; diagnosis; medical therapy; and surgical management.RESULTSKey statements define diverticulosis as the presence of diverticula without symptoms and diverticular disease as diverticula associated with symptoms or complications. High dietary fibre intake is protective whereas smoking, obesity and the use of non-steroidal anti-inflammatory drugs, corticosteroids, opioids or immunotherapy increase risk. Imaging is essential in suspected acute diverticulitis: ultrasound may be appropriate in experienced hands, while CT remains preferred for complicated cases. Diverticulosis itself requires no treatment. In symptomatic uncomplicated diverticular disease, dietary fibre, selected probiotics, mesalazine and rifaximin may help relieve symptoms. Routine antibiotic use is not recommended for acute uncomplicated diverticulitis, and elective surgery should be individualised, prioritising quality of life considerations over episode count.CONCLUSIONSThese Consensus statements aim to standardise and optimise the diagnosis, management and prevention of diverticular disease across diverse healthcare systems, while highlighting research priorities such as microbiome characterisation, genetic risk profiling and long-term outcomes of selective antimicrobial and surgical strategies.","PeriodicalId":12825,"journal":{"name":"Gut","volume":"7 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2025-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145823870","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}
BACKGROUNDPD-1 blockade has emerged as a promising approach for functional cure of chronic hepatitis B (CHB).OBJECTIVEThis study aimed to evaluate the safety profile of anti-PD-1 antibody (αPD-1), as well as its impact on hepatitis B surface antigen (HBsAg) and immune responses in a larger cohort of CHB patients.DESIGNIn this prospective, open-label study, virally suppressed patients with CHB on nucleos(t)ide analogue (NA) were assigned to receive either 24-week NA monotherapy (n=62) or αPD-1 (half-dose sintilimab) add-on therapy (n=59), with both groups subsequently receiving NA monotherapy for an additional 12-week observation period.RESULTS93.6% of adverse events (AEs) were grade 1 or 2. Elevations in alanine aminotransferase (ALT) and aspartate aminotransferase were the most common AEs, and they represented the only severe AEs. αPD-1 add-on therapy induced greater HBsAg reductions (mean decline: -0.720 vs -0.034 log10 IU/mL, p<0.001) and higher HBsAg loss rates (6.1% vs 0%, p=0.166) than NA monotherapy at week 24. Notably, significant HBsAg decline and seroclearance exclusively occurred in the initial 12 weeks of αPD-1 treatment. HBsAg levels did not rebound at 12 weeks after discontinuation of αPD-1 therapy. After αPD-1 therapy, the numbers of HBsAg-specific, HBpol-specific, HBx-specific and HBeAg/HBcAg-specific IFN-γ spots all increased (p<0.05), while frequencies of HBsAg-specific B cells remained stable. Furthermore, ALT elevation and enhanced HBsAg-specific T-cell responses following αPD-1 therapy correlated with HBsAg decline (p<0.05).CONCLUSIONSIn virally suppressed CHB patients on NA therapy, 24-week half-dose sintilimab treatment demonstrated a favourable safety profile. This regimen can facilitate HBsAg reduction and even HBsAg loss, while concurrently enhancing HBV-specific T-cell responses. These findings support αPD-1 as a potential therapeutic alternative for CHB.TRIAL REGISTRATION NUMBERNCT05769816.
pd -1阻断已成为慢性乙型肝炎（CHB）功能性治愈的一种有前景的方法。目的：本研究旨在评估抗pd -1抗体（αPD-1）的安全性，以及其对乙型肝炎表面抗原（HBsAg）和免疫应答的影响。在这项前瞻性、开放标签的研究中，对核苷类似物（NA）进行病毒抑制的CHB患者被分配接受24周NA单药治疗（n=62）或αPD-1（半剂量sintilimab）附加治疗（n=59），两组随后接受NA单药治疗额外12周观察期。结果93.6%的不良事件（ae）为1或2级。谷丙转氨酶（ALT）和天冬氨酸转氨酶升高是最常见的ae，也是唯一严重的ae。αPD-1附加治疗在第24周诱导HBsAg下降（平均下降：-0.720 vs -0.034 log10 IU/mL, p<0.001）和HBsAg损失率（6.1% vs 0%, p=0.166）高于NA单药治疗。值得注意的是，明显的HBsAg下降和血清清除率仅发生在αPD-1治疗的最初12周。停止αPD-1治疗12周后，HBsAg水平未出现反弹。αPD-1治疗后，hbsag特异性、hbpol特异性、hbx特异性和HBeAg/ hbcag特异性IFN-γ点数量均增加（p<0.05），而hbsag特异性B细胞频率保持稳定。此外，αPD-1治疗后ALT升高和HBsAg特异性t细胞反应增强与HBsAg下降相关（p<0.05）。结论在接受NA治疗的病毒性抑制CHB患者中，半剂量辛替单抗治疗24周具有良好的安全性。该方案可以促进HBsAg的减少甚至HBsAg的丢失，同时增强hbv特异性t细胞反应。这些发现支持αPD-1作为慢性乙型肝炎的潜在治疗选择。试验注册号05769816。
{"title":"Twenty-four-week anti-PD-1 antibody regimen promoted HBsAg reduction and concurrently enhanced HBV-specific T cell responses in patients with chronic hepatitis B.","authors":"Taiyu He,Min Chen,Maoying Liu,Li Zhang,Huidan Sun,Lu Zhang,Aoyi Li,Weiqun Zeng,Ning Ling,Xiaofeng Shi,Hua He,Mingli Peng,Dachuan Cai,Peng Hu,Dazhi Zhang,Yinghua Lan,Hong Ren","doi":"10.1136/gutjnl-2025-336655","DOIUrl":"https://doi.org/10.1136/gutjnl-2025-336655","url":null,"abstract":"BACKGROUNDPD-1 blockade has emerged as a promising approach for functional cure of chronic hepatitis B (CHB).OBJECTIVEThis study aimed to evaluate the safety profile of anti-PD-1 antibody (αPD-1), as well as its impact on hepatitis B surface antigen (HBsAg) and immune responses in a larger cohort of CHB patients.DESIGNIn this prospective, open-label study, virally suppressed patients with CHB on nucleos(t)ide analogue (NA) were assigned to receive either 24-week NA monotherapy (n=62) or αPD-1 (half-dose sintilimab) add-on therapy (n=59), with both groups subsequently receiving NA monotherapy for an additional 12-week observation period.RESULTS93.6% of adverse events (AEs) were grade 1 or 2. Elevations in alanine aminotransferase (ALT) and aspartate aminotransferase were the most common AEs, and they represented the only severe AEs. αPD-1 add-on therapy induced greater HBsAg reductions (mean decline: -0.720 vs -0.034 log10 IU/mL, p<0.001) and higher HBsAg loss rates (6.1% vs 0%, p=0.166) than NA monotherapy at week 24. Notably, significant HBsAg decline and seroclearance exclusively occurred in the initial 12 weeks of αPD-1 treatment. HBsAg levels did not rebound at 12 weeks after discontinuation of αPD-1 therapy. After αPD-1 therapy, the numbers of HBsAg-specific, HBpol-specific, HBx-specific and HBeAg/HBcAg-specific IFN-γ spots all increased (p<0.05), while frequencies of HBsAg-specific B cells remained stable. Furthermore, ALT elevation and enhanced HBsAg-specific T-cell responses following αPD-1 therapy correlated with HBsAg decline (p<0.05).CONCLUSIONSIn virally suppressed CHB patients on NA therapy, 24-week half-dose sintilimab treatment demonstrated a favourable safety profile. This regimen can facilitate HBsAg reduction and even HBsAg loss, while concurrently enhancing HBV-specific T-cell responses. These findings support αPD-1 as a potential therapeutic alternative for CHB.TRIAL REGISTRATION NUMBERNCT05769816.","PeriodicalId":12825,"journal":{"name":"Gut","volume":"261 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2025-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145823872","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}
BACKGROUNDHBV surface antigen (HBsAg) seroconversion indicates the clearance of HBV in patients with chronic HBV infection.OBJECTIVEWe aimed to investigate the predictive value of HBV RNA and HBV mutants on HBsAg seroconversion in patients with chronic HBV infection from childhood to adulthood.DESIGNWe recruited 700 children (409 males and 291 females) with initially hepatitis B e antigen (HBeAg)-positive chronic HBV infection. With the mean initial visit age of 7.28 years (95% CI 7.03 to 7.62 years), they were followed for 15 912 person-years at our institution. Serum samples collected after HBeAg seroconversion in HBeAg seroconverters were analysed for circulating HBV RNA, HBsAg, HBV core-related antigen, HBV DNA levels and the percentage of HBV mutants.RESULTS23 subjects (3.29%) experienced HBsAg seroconversion following antiviral therapy, while another 27 (3.86%) achieved spontaneous HBsAg seroconversion in this cohort. The annual probability of HBsAg seroconversion is 0.32% (95% CI 0.30% to 0.33%) per person-year across the entire cohort. After HBeAg seroconversion, the spontaneous annual HBsAg seroconversion rate is 0.47% (95% CI 0.42% to 0.51%) per person-year, and it rises to 1.30% (95% CI 1.10% to 1.51%) per person-year in subjects who had previously received antiviral agents before HBeAg seroconversion. Undetectable circulating HBV RNA and the percentage of A2131C mutants <10% after HBeAg seroconversion are significant predictors of HBsAg seroconversion in both univariate and multivariate survival analyses.CONCLUSIONIn this long-term chronic HBV cohort, we elucidated both the natural course and antiviral-related HBsAg seroconversion. Undetectable circulating HBV RNA and percentage of A2131C mutants <10% after HBeAg seroconversion are novel and independent predictors of HBsAg seroconversion.
背景：乙型肝炎病毒表面抗原（HBsAg）血清转化表明慢性乙型肝炎病毒感染患者的乙型肝炎病毒清除。目的探讨HBV RNA和HBV突变体对儿童期至成年期慢性HBV感染患者HBsAg血清转化的预测价值。我们招募了700名儿童（409名男性和291名女性），他们最初是乙型肝炎e抗原（HBeAg）阳性的慢性HBV感染。他们的平均初次就诊年龄为7.28岁（95% CI为7.03 ~ 7.62岁），在我们的机构随访了15912人年。对HBeAg血清转化后采集的血清样本进行循环HBV RNA、HBsAg、HBV核心相关抗原、HBV DNA水平和HBV突变体百分比的分析。结果23名受试者（3.29%）在抗病毒治疗后出现HBsAg血清转化，另外27名受试者（3.86%）实现了自发HBsAg血清转化。在整个队列中，HBsAg血清转换的年概率为每人年0.32% （95% CI 0.30%至0.33%）。HBeAg血清转化后，自发年HBsAg血清转化率为0.47% /人/年（95% CI 0.42% ~ 0.51%），在HBeAg血清转化前曾接受抗病毒药物治疗的受试者中，自发年HBsAg血清转化率上升至1.30% /人/年（95% CI 1.10% ~ 1.51%）。在单因素和多因素生存分析中，检测不到的循环HBV RNA和HBeAg血清转化后A2131C突变体的百分比<10%是HBsAg血清转化的重要预测因素。结论在这个长期慢性HBV队列中，我们阐明了自然病程和抗病毒相关的HBsAg血清转化。检测不到的循环HBV RNA和HBeAg血清转化后A2131C突变体百分比<10%是新的和独立的HBsAg血清转化预测因子。
{"title":"Circulating HBV RNA and HBsAg seroconversion in patients with chronic HBV infection: a long-term follow-up study starting from childhood in Taiwan.","authors":"Jia-Feng Wu,Chien-Ting Hsu,Chi-San Tai,Kai-Chi Chang,Chieh-Yu Chu,Yu-Chun Chiu,Huey-Ling Chen,Yen-Hsuan Ni,Mei-Hwei Chang","doi":"10.1136/gutjnl-2025-337123","DOIUrl":"https://doi.org/10.1136/gutjnl-2025-337123","url":null,"abstract":"BACKGROUNDHBV surface antigen (HBsAg) seroconversion indicates the clearance of HBV in patients with chronic HBV infection.OBJECTIVEWe aimed to investigate the predictive value of HBV RNA and HBV mutants on HBsAg seroconversion in patients with chronic HBV infection from childhood to adulthood.DESIGNWe recruited 700 children (409 males and 291 females) with initially hepatitis B e antigen (HBeAg)-positive chronic HBV infection. With the mean initial visit age of 7.28 years (95% CI 7.03 to 7.62 years), they were followed for 15 912 person-years at our institution. Serum samples collected after HBeAg seroconversion in HBeAg seroconverters were analysed for circulating HBV RNA, HBsAg, HBV core-related antigen, HBV DNA levels and the percentage of HBV mutants.RESULTS23 subjects (3.29%) experienced HBsAg seroconversion following antiviral therapy, while another 27 (3.86%) achieved spontaneous HBsAg seroconversion in this cohort. The annual probability of HBsAg seroconversion is 0.32% (95% CI 0.30% to 0.33%) per person-year across the entire cohort. After HBeAg seroconversion, the spontaneous annual HBsAg seroconversion rate is 0.47% (95% CI 0.42% to 0.51%) per person-year, and it rises to 1.30% (95% CI 1.10% to 1.51%) per person-year in subjects who had previously received antiviral agents before HBeAg seroconversion. Undetectable circulating HBV RNA and the percentage of A2131C mutants <10% after HBeAg seroconversion are significant predictors of HBsAg seroconversion in both univariate and multivariate survival analyses.CONCLUSIONIn this long-term chronic HBV cohort, we elucidated both the natural course and antiviral-related HBsAg seroconversion. Undetectable circulating HBV RNA and percentage of A2131C mutants <10% after HBeAg seroconversion are novel and independent predictors of HBsAg seroconversion.","PeriodicalId":12825,"journal":{"name":"Gut","volume":"4 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2025-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145785760","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}
BACKGROUNDChronic pancreatitis (CP) is a risk factor for pancreatic cancer, with inherited cases conferring a markedly increased risk. The underlying mechanisms driving malignant transformation by CP remain poorly understood.OBJECTIVECombining a recently developed mouse model of CP carrying the human carboxypeptidase A1 (CPA1) p.N256K mutation with the established KrasG12D pancreatic cancer model, we characterised mechanisms linking chronic inflammation to early pancreatic carcinogenesis.DESIGNWe crossed Cpa1 N256K mice (Cpa1) with Ptf1aCre;KrasLSL-G12D (KC). In Cre, Cpa1, KC and KC-Cpa1 mice, we performed phenotypical characterisation at five early time points and in an ageing cohort. Assessment of histology combined with both RNA-sequencing and single-cell RNA-sequencing was performed to analyse metaplasia, preneoplastic lesions and cellular heterogeneity.RESULTSKC-Cpa1 pancreata displayed a stark increase in remodelling, fibrosis and formation of metaplastic lesions as compared with KC. Cpa1N256K induced extensive plasticity in both the acinar and ductal compartment, including an early acinar-to-ductal metaplasia state in acinar cells characterised by an upregulation of endoplasmic reticulum stress markers and an inflammatory ductal phenotype (iDucts). We characterised the complex cell-cell communication networks underlying both pancreatic inflammation and early carcinogenesis, revealing disease-specific signalling between ductal cells, granulocytes and fibroblasts.CONCLUSIONSThe humanised KC-Cpa1 mouse model reveals the interplay of inflammation in hereditary CP and carcinogenesis. Cpa1N256K -induced plasticity in acinar and ductal cells, inflammation and cell-cell interaction networks cooperate with KrasG12D in early pancreatic carcinogenesis.
{"title":"Hereditary chronic pancreatitis induced plasticity cooperates with mutant Kras in early pancreatic carcinogenesis.","authors":"Tanvi Vikrant Inamdar,Ferdinand Krannich,Nico Hesselbarth,Atul Verma,Teresa Vauti,Mariami Helena Jasaszwili,Ghanem El Kassem,Jasmine Hillmer,Tom Kaune,Michael Boettcher,Ivonne Regel,Heidi Griesmann,Irene Esposito,Markus Glaß,Monika Hämmerle,Patrick Michl,Helmut Laumen,Jonas Rosendahl","doi":"10.1136/gutjnl-2025-335947","DOIUrl":"https://doi.org/10.1136/gutjnl-2025-335947","url":null,"abstract":"BACKGROUNDChronic pancreatitis (CP) is a risk factor for pancreatic cancer, with inherited cases conferring a markedly increased risk. The underlying mechanisms driving malignant transformation by CP remain poorly understood.OBJECTIVECombining a recently developed mouse model of CP carrying the human carboxypeptidase A1 (CPA1) p.N256K mutation with the established KrasG12D pancreatic cancer model, we characterised mechanisms linking chronic inflammation to early pancreatic carcinogenesis.DESIGNWe crossed Cpa1 N256K mice (Cpa1) with Ptf1aCre;KrasLSL-G12D (KC). In Cre, Cpa1, KC and KC-Cpa1 mice, we performed phenotypical characterisation at five early time points and in an ageing cohort. Assessment of histology combined with both RNA-sequencing and single-cell RNA-sequencing was performed to analyse metaplasia, preneoplastic lesions and cellular heterogeneity.RESULTSKC-Cpa1 pancreata displayed a stark increase in remodelling, fibrosis and formation of metaplastic lesions as compared with KC. Cpa1N256K induced extensive plasticity in both the acinar and ductal compartment, including an early acinar-to-ductal metaplasia state in acinar cells characterised by an upregulation of endoplasmic reticulum stress markers and an inflammatory ductal phenotype (iDucts). We characterised the complex cell-cell communication networks underlying both pancreatic inflammation and early carcinogenesis, revealing disease-specific signalling between ductal cells, granulocytes and fibroblasts.CONCLUSIONSThe humanised KC-Cpa1 mouse model reveals the interplay of inflammation in hereditary CP and carcinogenesis. Cpa1N256K -induced plasticity in acinar and ductal cells, inflammation and cell-cell interaction networks cooperate with KrasG12D in early pancreatic carcinogenesis.","PeriodicalId":12825,"journal":{"name":"Gut","volume":"24 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2025-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145785758","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}
Pub Date : 2025-12-19DOI: 10.1136/gutjnl-2025-337514
Qingzhou Kong,Baobao Wang,Yueyue Li,Rui Ji,Yanqing Li
{"title":"Endoscopic gastroenterostomy for malignant gastric outlet obstruction: the need for reintervention is variable.","authors":"Qingzhou Kong,Baobao Wang,Yueyue Li,Rui Ji,Yanqing Li","doi":"10.1136/gutjnl-2025-337514","DOIUrl":"https://doi.org/10.1136/gutjnl-2025-337514","url":null,"abstract":"","PeriodicalId":12825,"journal":{"name":"Gut","volume":"4 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2025-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145786370","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}
Pub Date : 2025-12-19DOI: 10.1136/gutjnl-2024-333309
Sabela Lens,Alice R Burton,Jessica Davies,Maelle Locatelli,Mireia García-López,Anna Pocurull,Anna Jeffery-Smith,Nikolai Novikov,Simon P Fletcher,Xavier Forns,Sofía Pérez-Del-Pulgar,Mala K Maini
BACKGROUNDWithdrawal of prolonged nucleos(t)ide analogue (NA) treatment results in hepatitis B surface antigen (HBsAg) loss in some subjects with chronic hepatitis B (CHB), potentially revealing immune correlates of functional cure.OBJECTIVEWe investigated whether baseline or longitudinal changes in humoral immunity correlated with outcome of discontinuing prolonged NA treatment.DESIGNGlobal memory B cells (MBC) and T follicular helper cells (Tfh) were analysed by flow cytometry. HBs (small surface)/HBc (core)-MBC were quantified by ex-vivo bait staining and function assessed by cultured ELISpots (enzyme-linked immunosorbent spots). Immune parameters assessed at end-of-treatment (EOT), 12 and 48 weeks after treatment withdrawal (and at 4-8 years in a subset) were correlated with intrahepatic and longitudinal serum viral markers and alanine transaminase (ALT).RESULTSIndividuals on prolonged NA had comparable frequencies of HBc-MBC and HBs-MBC, although the latter were PD-1hi and functionally defective. Following treatment withdrawal, increases in class-switched HBc-MBC were frequently temporally linked with hepatic flares. Subjects achieving HBsAg loss had an increase in activated global MBC detectable at EOT that become more marked by week 48, accompanied by significant increases in plasmablasts. HBs-MBC in those with HBsAg loss showed significant reductions in PD-1, trends to increased activation (CD71) and function and a more robust correlation with Tfh, compared with HBsAg persistence. MBC changes were maintained 4-8 years after HBsAg seroconversion.CONCLUSIONDifferences in global and HBs-specific B cell immunity associate with HBsAg loss, whereas HBc-MBC temporally associates with flares, following withdrawal of prolonged NA treatment. Our results underscore the need to further explore the potential of B cell targets for monitoring and enhancing HBV functional cure in larger cohorts.
{"title":"Tracking B cell immunity during perturbation of hepatitis B infection induced by treatment withdrawal.","authors":"Sabela Lens,Alice R Burton,Jessica Davies,Maelle Locatelli,Mireia García-López,Anna Pocurull,Anna Jeffery-Smith,Nikolai Novikov,Simon P Fletcher,Xavier Forns,Sofía Pérez-Del-Pulgar,Mala K Maini","doi":"10.1136/gutjnl-2024-333309","DOIUrl":"https://doi.org/10.1136/gutjnl-2024-333309","url":null,"abstract":"BACKGROUNDWithdrawal of prolonged nucleos(t)ide analogue (NA) treatment results in hepatitis B surface antigen (HBsAg) loss in some subjects with chronic hepatitis B (CHB), potentially revealing immune correlates of functional cure.OBJECTIVEWe investigated whether baseline or longitudinal changes in humoral immunity correlated with outcome of discontinuing prolonged NA treatment.DESIGNGlobal memory B cells (MBC) and T follicular helper cells (Tfh) were analysed by flow cytometry. HBs (small surface)/HBc (core)-MBC were quantified by ex-vivo bait staining and function assessed by cultured ELISpots (enzyme-linked immunosorbent spots). Immune parameters assessed at end-of-treatment (EOT), 12 and 48 weeks after treatment withdrawal (and at 4-8 years in a subset) were correlated with intrahepatic and longitudinal serum viral markers and alanine transaminase (ALT).RESULTSIndividuals on prolonged NA had comparable frequencies of HBc-MBC and HBs-MBC, although the latter were PD-1hi and functionally defective. Following treatment withdrawal, increases in class-switched HBc-MBC were frequently temporally linked with hepatic flares. Subjects achieving HBsAg loss had an increase in activated global MBC detectable at EOT that become more marked by week 48, accompanied by significant increases in plasmablasts. HBs-MBC in those with HBsAg loss showed significant reductions in PD-1, trends to increased activation (CD71) and function and a more robust correlation with Tfh, compared with HBsAg persistence. MBC changes were maintained 4-8 years after HBsAg seroconversion.CONCLUSIONDifferences in global and HBs-specific B cell immunity associate with HBsAg loss, whereas HBc-MBC temporally associates with flares, following withdrawal of prolonged NA treatment. Our results underscore the need to further explore the potential of B cell targets for monitoring and enhancing HBV functional cure in larger cohorts.","PeriodicalId":12825,"journal":{"name":"Gut","volume":"9 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2025-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145785759","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}
Pub Date : 2025-12-18DOI: 10.1136/gutjnl-2025-335398
Wolfgang Marx,Chao Suo,Thusharika Dissanayaka,Suzan Maleki,Liam Nguyen,Nikolaj Travica,Mohammadreza Mohebbi,Mojtaba Lotfaliany,Murat Yucel,Amelia J McGuinness,Michael Berk,Hajara Aslam,Felice N Jacka
BACKGROUNDFermented foods are a promising yet underexplored intervention for influencing brain function and mental health through the gut-brain axis.OBJECTIVEThe objective of this study was to evaluate the impact of a dairy product fermented with probiotic bacteria on aspects of brain structure and function.DESIGNIn a triple-blind, randomised, placebo-controlled trial, 40 healthy women aged 18-55 years were randomised to consume either 130 g per day of a fermented probiotic yoghurt or a placebo for 8 weeks. The primary outcome was the between-group differential change from baseline to week 8 in left hippocampal metabolites, measured using magnetic resonance spectroscopy. Secondary outcomes included changes in brain structure and function, faecal microbiome composition and functional potential, mental health, gastrointestinal symptoms, memory and blood markers of oxidative stress and inflammation.RESULTSThere was a between-group difference in the change in average left hippocampal glutathione concentration (mean difference in change: -0.49; 95% CI -0.95 to -0.04), as well as brain volume in the hippocampus and nucleus accumbens, although these results did not withstand correction for multiple comparisons. There were between-group differences in the change in average functional connectivity between the left hippocampus and left frontal pole. There was also a significant between-group change in gut microbiome beta diversity. There were no differences in other secondary measures.CONCLUSIONThis study provides preliminary evidence that a probiotic fermented dairy product can modulate hippocampal-related outcomes.TRIAL REGISTRATION NUMBERACTRN12622000622707.
{"title":"Effects of a probiotic fermented dairy product on hippocampal metabolites, structure and function: an 8-week randomised, placebo-controlled trial in healthy women.","authors":"Wolfgang Marx,Chao Suo,Thusharika Dissanayaka,Suzan Maleki,Liam Nguyen,Nikolaj Travica,Mohammadreza Mohebbi,Mojtaba Lotfaliany,Murat Yucel,Amelia J McGuinness,Michael Berk,Hajara Aslam,Felice N Jacka","doi":"10.1136/gutjnl-2025-335398","DOIUrl":"https://doi.org/10.1136/gutjnl-2025-335398","url":null,"abstract":"BACKGROUNDFermented foods are a promising yet underexplored intervention for influencing brain function and mental health through the gut-brain axis.OBJECTIVEThe objective of this study was to evaluate the impact of a dairy product fermented with probiotic bacteria on aspects of brain structure and function.DESIGNIn a triple-blind, randomised, placebo-controlled trial, 40 healthy women aged 18-55 years were randomised to consume either 130 g per day of a fermented probiotic yoghurt or a placebo for 8 weeks. The primary outcome was the between-group differential change from baseline to week 8 in left hippocampal metabolites, measured using magnetic resonance spectroscopy. Secondary outcomes included changes in brain structure and function, faecal microbiome composition and functional potential, mental health, gastrointestinal symptoms, memory and blood markers of oxidative stress and inflammation.RESULTSThere was a between-group difference in the change in average left hippocampal glutathione concentration (mean difference in change: -0.49; 95% CI -0.95 to -0.04), as well as brain volume in the hippocampus and nucleus accumbens, although these results did not withstand correction for multiple comparisons. There were between-group differences in the change in average functional connectivity between the left hippocampus and left frontal pole. There was also a significant between-group change in gut microbiome beta diversity. There were no differences in other secondary measures.CONCLUSIONThis study provides preliminary evidence that a probiotic fermented dairy product can modulate hippocampal-related outcomes.TRIAL REGISTRATION NUMBERACTRN12622000622707.","PeriodicalId":12825,"journal":{"name":"Gut","volume":"27 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145777425","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}
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：