The global prevalence of obesity has increased significantly in recent decades, raising serious public health concerns. This trend has profound implications for gastrointestinal and liver diseases, as excess body weight plays a key role in their development, progression, and associated complications. Obesity-related metabolic and inflammatory alterations increase the risk of illness and place a significant strain on health care systems, making weight management a clinical priority.
Weight loss has been shown to improve outcomes for many gastrointestinal and liver diseases. Benefits have been observed through lifestyle modifications, pharmacological interventions, and bariatric procedures. In particular, novel anti-obesity agents such as glucagon-like peptide-1 receptor agonists offer promising potential for sustained weight loss and disease modification.
This narrative review explores the impact of obesity on non-neoplastic gastrointestinal and liver diseases, the potential of intentional weight loss to mitigate its effects, and the efficacy of novel pharmacological therapies in managing obesity-related conditions.
{"title":"Effect of Weight Loss on Clinical Outcomes in Patients With Chronic Gastrointestinal and Liver Diseases","authors":"Nicola Pugliese , Matteo Spertino , Miriana Mercurio , Stefano Ciardullo , Gianluca Perseghin , Cesare Hassan , Roberto Vettor , Salvatore Petta , Alessio Aghemo","doi":"10.1016/j.cgh.2025.10.018","DOIUrl":"10.1016/j.cgh.2025.10.018","url":null,"abstract":"<div><div>The global prevalence of obesity has increased significantly in recent decades, raising serious public health concerns. This trend has profound implications for gastrointestinal and liver diseases, as excess body weight plays a key role in their development, progression, and associated complications. Obesity-related metabolic and inflammatory alterations increase the risk of illness and place a significant strain on health care systems, making weight management a clinical priority.</div><div>Weight loss has been shown to improve outcomes for many gastrointestinal and liver diseases. Benefits have been observed through lifestyle modifications, pharmacological interventions, and bariatric procedures. In particular, novel anti-obesity agents such as glucagon-like peptide-1 receptor agonists offer promising potential for sustained weight loss and disease modification.</div><div>This narrative review explores the impact of obesity on non-neoplastic gastrointestinal and liver diseases, the potential of intentional weight loss to mitigate its effects, and the efficacy of novel pharmacological therapies in managing obesity-related conditions.</div></div>","PeriodicalId":10347,"journal":{"name":"Clinical Gastroenterology and Hepatology","volume":"24 3","pages":"Pages 583-594"},"PeriodicalIF":12.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145382783","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}
Germline genetic factors influence the clinical features of colorectal cancer (CRC); however, these factors remain underexplored in Taiwan. This study aims to evaluate the pathogenicity of germline variants and investigate their associations with familial risk and early-onset CRC.
Methods
Whole exome sequencing of 600 Taiwanese patients with CRC was analyzed, assessing variant pathogenicity using American College of Medical Genetics and Genomics (ACMG) guidelines. Comparative analysis with 1492 controls identified candidate genes, and clinical features were correlated with genetic variants.
Results
We identified several novel candidate genes, including CCDC18 and CEP135. A total of 24 pathogenic variants in hereditary cancer genes were found in 5.2% of Taiwanese patients with CRC, with the highest prevalence observed in early-onset cases (8.2%). Notably, a novel stop-gain variant in POLD1 (p.Y594X) was detected in a 26-year-old patient, suggesting dysfunction of the polymerase catalytic domain. The risks associated with ATM (1.3%) and the MUTYH (c.850-2A>G) variant were also highlighted. Additionally, 25.5% of rare-risk variants were novel, with 41 candidate pathogenic variants linked to familial and early-onset CRC.
Conclusions
These findings improve our understanding of germline genetics in Taiwanese CRC, support better screening and management strategies, and highlight the need to expand Asian variant databases for improved risk assessment and care.
{"title":"Whole Exome Sequencing-identified Germline Variants Underlie High Familial Risk and Early-onset Colorectal Cancer in Taiwan","authors":"Yi-Chen Huang , Yen-Nien Chen , An-Ko Chung , Yu-An Chen , Pei-Lung Chen , Tang-Long Shen , Chien-Yu Chen , Han-Mo Chiu","doi":"10.1016/j.cgh.2025.07.040","DOIUrl":"10.1016/j.cgh.2025.07.040","url":null,"abstract":"<div><h3>Background & Aims</h3><div>Germline genetic factors influence the clinical features of colorectal cancer (CRC); however, these factors remain underexplored in Taiwan. This study aims to evaluate the pathogenicity of germline variants and investigate their associations with familial risk and early-onset CRC.</div></div><div><h3>Methods</h3><div>Whole exome sequencing of 600 Taiwanese patients with CRC was analyzed, assessing variant pathogenicity using American College of Medical Genetics and Genomics (ACMG) guidelines. Comparative analysis with 1492 controls identified candidate genes, and clinical features were correlated with genetic variants.</div></div><div><h3>Results</h3><div>We identified several novel candidate genes, including <em>CCDC18</em> and <em>CEP135</em>. A total of 24 pathogenic variants in hereditary cancer genes were found in 5.2% of Taiwanese patients with CRC, with the highest prevalence observed in early-onset cases (8.2%). Notably, a novel stop-gain variant in <em>POLD1</em> (p.Y594X) was detected in a 26-year-old patient, suggesting dysfunction of the polymerase catalytic domain. The risks associated with <em>ATM</em> (1.3%) and the <em>MUTYH</em> (c.850-2A>G) variant were also highlighted. Additionally, 25.5% of rare-risk variants were novel, with 41 candidate pathogenic variants linked to familial and early-onset CRC.</div></div><div><h3>Conclusions</h3><div>These findings improve our understanding of germline genetics in Taiwanese CRC, support better screening and management strategies, and highlight the need to expand Asian variant databases for improved risk assessment and care.</div></div>","PeriodicalId":10347,"journal":{"name":"Clinical Gastroenterology and Hepatology","volume":"24 3","pages":"Pages 835-846"},"PeriodicalIF":12.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144803745","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 : 2026-03-01Epub Date: 2025-04-30DOI: 10.1016/j.cgh.2025.02.017
Luis Antonio Diaz , Veeral Ajmera , Juan Pablo Arab , Daniel Q. Huang , Cynthia Hsu , Brian P. Lee , Alexandre Louvet , Maja Thiele , Federica Tavaglione , Monica Tincopa , Elisa Pose , Leon A. Adams , William Alazawi , Marco Arrese , Ramon Bataller , Ajay Duseja , Suthat Liangpunsakul , Michael R. Lucey , Philippe Mathurin , Jessica Mellinger , Rohit Loomba
Background & Aims
Metabolic dysfunction- and alcohol-associated liver disease (MetALD) is a recently defined entity for individuals with liver steatosis, metabolic dysfunction, and increased alcohol intake. However, the current definition of MetALD poses multiple challenges in clinical practice and research. In this Delphi consensus, we provide practical recommendations for the clinical assessment and management of MetALD to address current clinical challenges in MetALD.
Methods
We used a modified Delphi process, including 2 surveys involving a panel of 28 experts from 10 countries spanning 4 continents. We predefined consensus as requiring an ≥80% agreement.
Results
The panel reached consensus on 28 statements. Recommendations emphasize the importance of a comprehensive assessment of patients with presumed MetALD, including the quantification of alcohol intake using validated questionnaires and the use of objective biomarkers of alcohol use, such as phosphatidylethanol. The need to reassess metabolic risk factors and liver disease after a period of alcohol abstinence was highlighted to distinguish the primary driver of liver injury. Noninvasive tests were recommended to assess liver disease severity, whereas routine liver biopsy was deemed unnecessary unless other diagnoses were suspected. Comprehensive management strategies should involve multidisciplinary care focusing on lifestyle modifications, alcohol reduction or cessation, weight loss, and exercise. Finally, the panel identified significant gaps in knowledge, advocating for standardized research protocols, longitudinal studies, exploration of pathophysiological mechanisms to inform precision medicine approaches, and the validation of quantitative alcohol biomarkers for identifying MetALD.
Conclusions
This Delphi consensus provides clear recommendations for the clinical assessment and management of MetALD, addressing the unique challenges posed by this condition.
{"title":"An Expert Consensus Delphi Panel in Metabolic Dysfunction- and Alcohol-associated Liver Disease: Opportunities and Challenges in Clinical Practice","authors":"Luis Antonio Diaz , Veeral Ajmera , Juan Pablo Arab , Daniel Q. Huang , Cynthia Hsu , Brian P. Lee , Alexandre Louvet , Maja Thiele , Federica Tavaglione , Monica Tincopa , Elisa Pose , Leon A. Adams , William Alazawi , Marco Arrese , Ramon Bataller , Ajay Duseja , Suthat Liangpunsakul , Michael R. Lucey , Philippe Mathurin , Jessica Mellinger , Rohit Loomba","doi":"10.1016/j.cgh.2025.02.017","DOIUrl":"10.1016/j.cgh.2025.02.017","url":null,"abstract":"<div><h3>Background & Aims</h3><div>Metabolic dysfunction- and alcohol-associated liver disease (MetALD) is a recently defined entity for individuals with liver steatosis, metabolic dysfunction, and increased alcohol intake. However, the current definition of MetALD poses multiple challenges in clinical practice and research. In this Delphi consensus, we provide practical recommendations for the clinical assessment and management of MetALD to address current clinical challenges in MetALD.</div></div><div><h3>Methods</h3><div>We used a modified Delphi process, including 2 surveys involving a panel of 28 experts from 10 countries spanning 4 continents. We predefined consensus as requiring an ≥80% agreement.</div></div><div><h3>Results</h3><div>The panel reached consensus on 28 statements. Recommendations emphasize the importance of a comprehensive assessment of patients with presumed MetALD, including the quantification of alcohol intake using validated questionnaires and the use of objective biomarkers of alcohol use, such as phosphatidylethanol. The need to reassess metabolic risk factors and liver disease after a period of alcohol abstinence was highlighted to distinguish the primary driver of liver injury. Noninvasive tests were recommended to assess liver disease severity, whereas routine liver biopsy was deemed unnecessary unless other diagnoses were suspected. Comprehensive management strategies should involve multidisciplinary care focusing on lifestyle modifications, alcohol reduction or cessation, weight loss, and exercise. Finally, the panel identified significant gaps in knowledge, advocating for standardized research protocols, longitudinal studies, exploration of pathophysiological mechanisms to inform precision medicine approaches, and the validation of quantitative alcohol biomarkers for identifying MetALD.</div></div><div><h3>Conclusions</h3><div>This Delphi consensus provides clear recommendations for the clinical assessment and management of MetALD, addressing the unique challenges posed by this condition.</div></div>","PeriodicalId":10347,"journal":{"name":"Clinical Gastroenterology and Hepatology","volume":"24 3","pages":"Pages 633-645.e4"},"PeriodicalIF":12.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143957072","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 : 2026-03-01Epub Date: 2026-02-20DOI: 10.1016/S1542-3565(26)00013-3
{"title":"Elsewhere in the AGA Journals","authors":"","doi":"10.1016/S1542-3565(26)00013-3","DOIUrl":"10.1016/S1542-3565(26)00013-3","url":null,"abstract":"","PeriodicalId":10347,"journal":{"name":"Clinical Gastroenterology and Hepatology","volume":"24 3","pages":"Pages A15-A18"},"PeriodicalIF":12.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146777355","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 : 2026-03-01Epub Date: 2025-08-07DOI: 10.1016/j.cgh.2025.07.042
Agnes H.Y. Ho, David Choi, Alex J. Mathew, Alexandra McDermott, Zachary Fine, Evan Fear, Natalie K. Choi, Russell D. Cohen, Sushila R. Dalal, Joel Pekow, Noa Krugliak Cleveland, David T. Rubin
Background & Aims
Upadacitinib (UPA) is approved for the treatment of moderately to severely active Crohn’s disease (CD) or ulcerative colitis (UC). Responders to UPA 45 mg daily (QD) may lose response (LOR) after transition to lower maintenance doses. We describe our real-world experience of LOR, reinduction, and subsequent maintenance with UPA 45 mg QD.
Methods
This is a prospective cohort study of patients with inflammatory bowel disease (IBD) treated with UPA between April 2022 and November 2023. Included patients responded to UPA induction, had LOR after dose reduction, and subsequently received reinduction therapy with 45 mg QD. Clinical, biochemical, radiologic, and endoscopic data were collected; comparative statistics and Kaplan-Meier survival were calculated.
Results
A total of 181 patients (79 CD, 83 UC, 6 IBD-Unclassified, 13 ileal pouch anal-anastomosis) responded to UPA 45 mg QD induction and were switched to a lower maintenance dose (30 mg QD, n = 180; 15 mg QD, n = 1), 46 (16 CD, 23 UC, 1 IBD- Unclassified, 6 ileal pouch anal-anastomosis) met the above criteria. They were followed for a median duration 93 weeks (interquartile range [IQR], 62–119 weeks). Relapse occurred at a median of 21 weeks (IQR, 8–46 weeks) after dose reduction. Dose escalation to 45 mg QD for a median of 13 weeks (IQR, 8–36 weeks) recaptured clinical response in 80.4%. Among patients who recaptured response, 19 again reduced to 30 mg or 15 mg. Over a median of 40 weeks (IQR, 22–59 weeks), 93.8% of patients on 45 mg QD maintained remission vs 21.1% who again dropped to 30 mg QD (P < .001). Disease extent and duration did not significantly predict response recapture. Acne/rosacea was the most common adverse event (39%); there were no serious adverse events.
Conclusions
Most patients with IBD who lose response to UPA when dose reduced in maintenance can be recaptured with 45 mg QD. Among these, continuing 45 mg QD for maintenance is effective, and appears safe.
{"title":"Real-world Experience of Upadacitinib Reinduction and High-dose Maintenance Therapy in Inflammatory Bowel Disease","authors":"Agnes H.Y. Ho, David Choi, Alex J. Mathew, Alexandra McDermott, Zachary Fine, Evan Fear, Natalie K. Choi, Russell D. Cohen, Sushila R. Dalal, Joel Pekow, Noa Krugliak Cleveland, David T. Rubin","doi":"10.1016/j.cgh.2025.07.042","DOIUrl":"10.1016/j.cgh.2025.07.042","url":null,"abstract":"<div><h3>Background & Aims</h3><div>Upadacitinib (UPA) is approved for the treatment of moderately to severely active Crohn’s disease (CD) or ulcerative colitis (UC). Responders to UPA 45 mg daily (QD) may lose response (LOR) after transition to lower maintenance doses. We describe our real-world experience of LOR, reinduction, and subsequent maintenance with UPA 45 mg QD.</div></div><div><h3>Methods</h3><div>This is a prospective cohort study of patients with inflammatory bowel disease (IBD) treated with UPA between April 2022 and November 2023. Included patients responded to UPA induction, had LOR after dose reduction, and subsequently received reinduction therapy with 45 mg QD. Clinical, biochemical, radiologic, and endoscopic data were collected; comparative statistics and Kaplan-Meier survival were calculated.</div></div><div><h3>Results</h3><div>A total of 181 patients (79 CD, 83 UC, 6 IBD-Unclassified, 13 ileal pouch anal-anastomosis) responded to UPA 45 mg QD induction and were switched to a lower maintenance dose (30 mg QD, n = 180; 15 mg QD, n = 1), 46 (16 CD, 23 UC, 1 IBD- Unclassified, 6 ileal pouch anal-anastomosis) met the above criteria. They were followed for a median duration 93 weeks (interquartile range [IQR], 62–119 weeks). Relapse occurred at a median of 21 weeks (IQR, 8–46 weeks) after dose reduction. Dose escalation to 45 mg QD for a median of 13 weeks (IQR, 8–36 weeks) recaptured clinical response in 80.4%. Among patients who recaptured response, 19 again reduced to 30 mg or 15 mg. Over a median of 40 weeks (IQR, 22–59 weeks), 93.8% of patients on 45 mg QD maintained remission vs 21.1% who again dropped to 30 mg QD (<em>P</em> < .001). Disease extent and duration did not significantly predict response recapture. Acne/rosacea was the most common adverse event (39%); there were no serious adverse events.</div></div><div><h3>Conclusions</h3><div>Most patients with IBD who lose response to UPA when dose reduced in maintenance can be recaptured with 45 mg QD. Among these, continuing 45 mg QD for maintenance is effective, and appears safe.</div></div>","PeriodicalId":10347,"journal":{"name":"Clinical Gastroenterology and Hepatology","volume":"24 3","pages":"Pages 763-771"},"PeriodicalIF":12.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144811886","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 : 2026-03-01Epub Date: 2025-06-13DOI: 10.1016/j.cgh.2025.05.016
Alvi H. Islam , Claudia Alvizuri , Hailemichael Desalegn , Emily Stephenson , Francisco Idalsoaga , Luis Antonio Diaz , John K. MacDonald , Gene Y. Im , Ashwani K. Singal , Vipul Jairath , Mohammad Qasim Khan , Juan Pablo Arab
Background & Aims
Alcohol-associated hepatitis (AH) is a severe form of alcohol-associated liver disease, with a short-term mortality of up to 50% within 3 months. The aim of this systematic review was to determine the optimal pharmacological treatment for severe AH that results in better survival outcomes.
Methods
MEDLINE, EMBASE, and CENTRAL were searched through February 16, 2025, for randomized controlled trials (RCTs) of medical therapy for adults with severe AH. The primary outcome was mortality at 28 days. Secondary outcomes included mortality at 90 days, adverse events, the incidence of hepatorenal syndrome, acute kidney injury or infections, and liver transplantation rates. Pooled risk ratios (RRs) and 95% confidence intervals (CIs) were calculated for each outcome. GRADE was used to assess certainty of evidence.
Results
Fifty-two RCTs (5121 participants) were included in the review. A survival benefit at 28 days was observed for corticosteroids over placebo (RR, 0.62; 95% CI, 0.41‒0.95), for corticosteroids plus N-acetylcysteine over corticosteroids alone (RR, 0.35; 95% CI, 0.16‒0.78), for granulocyte colony-stimulating factor combined plus pentoxifylline over pentoxifylline alone (RR, 0.27; 95% CI, 0.13‒0.54), and metadoxine combined with corticosteroids over corticosteroids alone (RR, 0.47; 95% CI, 0.25‒0.90) or pentoxifylline (RR, 0.50; 95% CI, 0.26‒0.96). The certainty of evidence ranged from very low to moderate.
Conclusions
Low certainty evidence supports the efficacy of corticosteroids as first line therapy for eligible patients with severe AH. The certainty of the evidence supporting other therapies ranges from low to moderate. Further studies are needed to confirm these benefits.
{"title":"Pharmacological Strategies for the Management of Severe Alcohol-associated Hepatitis: A Systematic Review and Meta-Analysis","authors":"Alvi H. Islam , Claudia Alvizuri , Hailemichael Desalegn , Emily Stephenson , Francisco Idalsoaga , Luis Antonio Diaz , John K. MacDonald , Gene Y. Im , Ashwani K. Singal , Vipul Jairath , Mohammad Qasim Khan , Juan Pablo Arab","doi":"10.1016/j.cgh.2025.05.016","DOIUrl":"10.1016/j.cgh.2025.05.016","url":null,"abstract":"<div><h3>Background & Aims</h3><div>Alcohol-associated hepatitis (AH) is a severe form of alcohol-associated liver disease, with a short-term mortality of up to 50% within 3 months. The aim of this systematic review was to determine the optimal pharmacological treatment for severe AH that results in better survival outcomes.</div></div><div><h3>Methods</h3><div>MEDLINE, EMBASE, and CENTRAL were searched through February 16, 2025, for randomized controlled trials<span><span> (RCTs) of medical therapy for adults with severe AH. The primary outcome was mortality at 28 days. Secondary outcomes included mortality at 90 days, adverse events, the incidence of </span>hepatorenal syndrome<span>, acute kidney injury or infections, and liver transplantation rates. Pooled risk ratios (RRs) and 95% confidence intervals (CIs) were calculated for each outcome. GRADE was used to assess certainty of evidence.</span></span></div></div><div><h3>Results</h3><div>Fifty-two RCTs (5121 participants) were included in the review. A survival benefit at 28 days was observed for corticosteroids over placebo (RR, 0.62; 95% CI, 0.41‒0.95), for corticosteroids plus <em>N</em><span>-acetylcysteine over corticosteroids alone (RR, 0.35; 95% CI, 0.16‒0.78), for granulocyte colony-stimulating factor combined plus pentoxifylline over pentoxifylline alone (RR, 0.27; 95% CI, 0.13‒0.54), and metadoxine combined with corticosteroids over corticosteroids alone (RR, 0.47; 95% CI, 0.25‒0.90) or pentoxifylline (RR, 0.50; 95% CI, 0.26‒0.96). The certainty of evidence ranged from very low to moderate.</span></div></div><div><h3>Conclusions</h3><div>Low certainty evidence supports the efficacy of corticosteroids as first line therapy for eligible patients with severe AH. The certainty of the evidence supporting other therapies ranges from low to moderate. Further studies are needed to confirm these benefits.</div></div>","PeriodicalId":10347,"journal":{"name":"Clinical Gastroenterology and Hepatology","volume":"24 3","pages":"Pages 606-620"},"PeriodicalIF":12.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144279041","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 : 2026-02-26DOI: 10.1016/j.cgh.2026.02.015
Joana Camões Neves, Tiago Leal, Samuel Fernandes, Diogo Couto Sousa, André Silva Neves, Margarida Cristiano, Francisco Portela, Catarina Costa, Rita Ferreira, Margarida Portugal, Raquel Oliveira, Madalina Gututui, António Bastos, Pedro Barros Santos, Ana Rita Silva, Plácido Gomes, José Damasceno, Andreia Guimarães, Patrícia Vaz Conde, Sofia Mendes, João Soares, Bruno Arroja, Raquel Gonçalves, Dalila Costa
Background and aims: Ulcerative colitis (UC) has increasingly been recognized as a progressive disease. However, unlike Crohn's disease (CD), evidence in UC has not demonstrated a clear benefit of early biologic therapy (BT), and disease progression has not been formally evaluated. We aimed to assess whether early intervention improves UC outcomes, particularly in preventing disease progression.
Methods: We conducted a retrospective multicenter study (11 centers) including adult UC patients with at least 5-years of follow-up (FU). Early intervention was defined as BT initiation within ≤12 months of diagnosis. The primary outcome was UC progression, defined as a composite endpoint including proximal disease extension, colonic structural changes (stenosis or tubularization) and dysplasia/cancer. Secondary outcomes included clinical endpoints: hospitalizations, surgery and corticosteroid use.
Results: A total of 236 patients were included, 28.8% (n=68) with early BT [median FU: 6.9 (5.8-8.8) years]. Late BT initiation (23.2% vs 5.9%) independently predicted the composite outcome of progression (HR 4.39; 95% CI 1.57-12.29; p=0.005). Assessing each outcome separately, early BT was associated with a reduced risk of proximal extension (28.6% vs 0.0%; p=0.001). In multivariable Cox regression, late BT initiation (13.1% vs 2,9%) was an independent predictor of colonic structural damage (HR 4.83; 95% CI 1.14-20.58; p=0.033). No differences in clinical outcomes were observed.
Conclusion: Starting BT early in the disease course may reduce the long-term risk of disease progression, reshaping the window of opportunity in UC.
背景和目的：溃疡性结肠炎（UC）越来越被认为是一种进行性疾病。然而，与克罗恩病（CD）不同，UC的证据尚未显示早期生物治疗（BT）的明确益处，疾病进展尚未正式评估。我们的目的是评估早期干预是否能改善UC的预后，特别是在预防疾病进展方面。方法：我们进行了一项回顾性多中心研究（11个中心），包括至少5年随访（FU）的成年UC患者。早期干预定义为诊断≤12个月内开始BT。主要终点是UC进展，定义为复合终点，包括近端疾病扩展、结肠结构改变（狭窄或管状化）和不典型增生/癌症。次要结局包括临床终点：住院、手术和皮质类固醇使用。结果：共纳入236例患者，28.8% （n=68）为早期BT[中位FU: 6.9（5.8-8.8）年]。晚开始BT （23.2% vs 5.9%）独立预测进展的综合结果（HR 4.39; 95% CI 1.57-12.29; p=0.005）。单独评估每个结果，早期BT与近端延伸风险降低相关（28.6% vs 0.0%; p=0.001）。在多变量Cox回归中，晚BT起始（13.1% vs 2.9%）是结肠结构损伤的独立预测因子（HR 4.83; 95% CI 1.14-20.58; p=0.033）。临床结果未见差异。结论：在疾病过程中早期开始BT可能降低疾病进展的长期风险，重塑UC的机会之窗。
{"title":"EARLY INTERVENTION PREVENTS DISEASE PROGRESSION IN ULCERATIVE COLITIS - A MULTICENTER RETROSPECTIVE STUDY.","authors":"Joana Camões Neves, Tiago Leal, Samuel Fernandes, Diogo Couto Sousa, André Silva Neves, Margarida Cristiano, Francisco Portela, Catarina Costa, Rita Ferreira, Margarida Portugal, Raquel Oliveira, Madalina Gututui, António Bastos, Pedro Barros Santos, Ana Rita Silva, Plácido Gomes, José Damasceno, Andreia Guimarães, Patrícia Vaz Conde, Sofia Mendes, João Soares, Bruno Arroja, Raquel Gonçalves, Dalila Costa","doi":"10.1016/j.cgh.2026.02.015","DOIUrl":"https://doi.org/10.1016/j.cgh.2026.02.015","url":null,"abstract":"<p><strong>Background and aims: </strong>Ulcerative colitis (UC) has increasingly been recognized as a progressive disease. However, unlike Crohn's disease (CD), evidence in UC has not demonstrated a clear benefit of early biologic therapy (BT), and disease progression has not been formally evaluated. We aimed to assess whether early intervention improves UC outcomes, particularly in preventing disease progression.</p><p><strong>Methods: </strong>We conducted a retrospective multicenter study (11 centers) including adult UC patients with at least 5-years of follow-up (FU). Early intervention was defined as BT initiation within ≤12 months of diagnosis. The primary outcome was UC progression, defined as a composite endpoint including proximal disease extension, colonic structural changes (stenosis or tubularization) and dysplasia/cancer. Secondary outcomes included clinical endpoints: hospitalizations, surgery and corticosteroid use.</p><p><strong>Results: </strong>A total of 236 patients were included, 28.8% (n=68) with early BT [median FU: 6.9 (5.8-8.8) years]. Late BT initiation (23.2% vs 5.9%) independently predicted the composite outcome of progression (HR 4.39; 95% CI 1.57-12.29; p=0.005). Assessing each outcome separately, early BT was associated with a reduced risk of proximal extension (28.6% vs 0.0%; p=0.001). In multivariable Cox regression, late BT initiation (13.1% vs 2,9%) was an independent predictor of colonic structural damage (HR 4.83; 95% CI 1.14-20.58; p=0.033). No differences in clinical outcomes were observed.</p><p><strong>Conclusion: </strong>Starting BT early in the disease course may reduce the long-term risk of disease progression, reshaping the window of opportunity in UC.</p>","PeriodicalId":10347,"journal":{"name":"Clinical Gastroenterology and Hepatology","volume":" ","pages":""},"PeriodicalIF":12.0,"publicationDate":"2026-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147321207","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 : 2026-02-26DOI: 10.1016/j.cgh.2026.02.018
Remo Panaccione, Julián Panés, Laurent Peyrin-Biroulet, Jean-Frédéric Colombel, James O Lindsay, Filip Baert, Raja Atreya, Séverine Vermeire, Toshimitsu Fujii, Elena Dubcenco, Justin Klaff, Benjamin Duncan, Smitha Suravaram, Irina Fish, Ana P Lacerda, Ramona Vladea, Sharanya Ford, Saajan Shah, Samuel I Anyanwu, David T Rubin
Background and aims: Upadacitinib (UPA) is an oral, reversible Janus kinase inhibitor approved for the treatment of ulcerative colitis (UC) and Crohn's disease (CD). We assessed the long-term safety of UPA in both inflammatory bowel disease (IBD) entities.
Methods: Safety from 6 UC/CD trials assessed UPA 45 mg (UPA45) once daily (QD) induction, UPA 15 mg and 30 mg (UPA 15/30 QD) maintenance/long-term extension (LTE) doses, and rescue therapy (UPA30 QD). Adverse events (AEs) were reported as events per 100 patient-years (E/100 PY).
Results: Overall, 2118 patients received placebo (PBO, n=725) or UPA45 (n=1393) induction; 1419 received PBO (n=468), UPA15 (n=471), or UPA30 (n=480) maintenance/LTE During maintenance/LTE, UPA cumulative exposure was 5149.3 patient-years (N=1910). Median treatment duration was 8.7 (IQR: 8.0-12.0) weeks for UPA45 induction; median maintenance/LTE treatment duration was 58.1 (IQR: 30.4-164.0) weeks for UPA15 and 130.9 (IQR: 39.4-175.1) for UPA30. AE incidence was comparable between UPA and PBO during induction and maintenance/LTE; AEs leading to study drug discontinuation and serious or severe AEs were lower with UPA. During maintenance/LTE, rates (UPA15/30 vs PBO) of venous thromboembolic events (0.3/0.4 vs 0 E/100 PY), gastrointestinal perforations (0.4/<0.1 vs 0.8 E/100 PY), and AEs leading to death (0.2/<0.1 vs 0 E/100 PY) were low. Herpes zoster, neutropenia, lymphopenia, creatine phosphokinase elevation, hepatic disorder, and COVID-19 were higher across UPA groups vs PBO; COVID-19 and herpes zoster were among the most common AEs during maintenance.
Conclusions: Long-term, UPA was generally well tolerated. This integrated analysis supports the favorable safety profile of UPA and treatment decisions for patients with IBD.
{"title":"Long-term Safety of Upadacitinib in Patients with Inflammatory Bowel Disease: Integrated Analysis of Phase 2/3 Studies.","authors":"Remo Panaccione, Julián Panés, Laurent Peyrin-Biroulet, Jean-Frédéric Colombel, James O Lindsay, Filip Baert, Raja Atreya, Séverine Vermeire, Toshimitsu Fujii, Elena Dubcenco, Justin Klaff, Benjamin Duncan, Smitha Suravaram, Irina Fish, Ana P Lacerda, Ramona Vladea, Sharanya Ford, Saajan Shah, Samuel I Anyanwu, David T Rubin","doi":"10.1016/j.cgh.2026.02.018","DOIUrl":"https://doi.org/10.1016/j.cgh.2026.02.018","url":null,"abstract":"<p><strong>Background and aims: </strong>Upadacitinib (UPA) is an oral, reversible Janus kinase inhibitor approved for the treatment of ulcerative colitis (UC) and Crohn's disease (CD). We assessed the long-term safety of UPA in both inflammatory bowel disease (IBD) entities.</p><p><strong>Methods: </strong>Safety from 6 UC/CD trials assessed UPA 45 mg (UPA45) once daily (QD) induction, UPA 15 mg and 30 mg (UPA 15/30 QD) maintenance/long-term extension (LTE) doses, and rescue therapy (UPA30 QD). Adverse events (AEs) were reported as events per 100 patient-years (E/100 PY).</p><p><strong>Results: </strong>Overall, 2118 patients received placebo (PBO, n=725) or UPA45 (n=1393) induction; 1419 received PBO (n=468), UPA15 (n=471), or UPA30 (n=480) maintenance/LTE During maintenance/LTE, UPA cumulative exposure was 5149.3 patient-years (N=1910). Median treatment duration was 8.7 (IQR: 8.0-12.0) weeks for UPA45 induction; median maintenance/LTE treatment duration was 58.1 (IQR: 30.4-164.0) weeks for UPA15 and 130.9 (IQR: 39.4-175.1) for UPA30. AE incidence was comparable between UPA and PBO during induction and maintenance/LTE; AEs leading to study drug discontinuation and serious or severe AEs were lower with UPA. During maintenance/LTE, rates (UPA15/30 vs PBO) of venous thromboembolic events (0.3/0.4 vs 0 E/100 PY), gastrointestinal perforations (0.4/<0.1 vs 0.8 E/100 PY), and AEs leading to death (0.2/<0.1 vs 0 E/100 PY) were low. Herpes zoster, neutropenia, lymphopenia, creatine phosphokinase elevation, hepatic disorder, and COVID-19 were higher across UPA groups vs PBO; COVID-19 and herpes zoster were among the most common AEs during maintenance.</p><p><strong>Conclusions: </strong>Long-term, UPA was generally well tolerated. This integrated analysis supports the favorable safety profile of UPA and treatment decisions for patients with IBD.</p>","PeriodicalId":10347,"journal":{"name":"Clinical Gastroenterology and Hepatology","volume":" ","pages":""},"PeriodicalIF":12.0,"publicationDate":"2026-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147321182","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 : 2026-02-24DOI: 10.1016/j.cgh.2026.02.016
Manuel Luis Rodríguez-Perálvarez, Antonio Manuel Gómez-Orellana, Emmanuel A. Tsochatzis
{"title":"Reply: Toward More Equitable Liver Allocation: Optimizing the GEMA-AI Model for the Chinese Context","authors":"Manuel Luis Rodríguez-Perálvarez, Antonio Manuel Gómez-Orellana, Emmanuel A. Tsochatzis","doi":"10.1016/j.cgh.2026.02.016","DOIUrl":"https://doi.org/10.1016/j.cgh.2026.02.016","url":null,"abstract":"","PeriodicalId":10347,"journal":{"name":"Clinical Gastroenterology and Hepatology","volume":"1 1","pages":""},"PeriodicalIF":12.6,"publicationDate":"2026-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147278819","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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