Alimentary Pharmacology & Therapeutics最新文献

{"title":"Letter: Comparison of the Efficacy of Adjuvant PD-1 Inhibitor After Curative Resection for Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) Related HCC Versus Other Aetiologies","authors":"Jia-Yong Su, Kang Chen, Zhen Liu, Min Luo, Shao-Ping Liu, Jun-Jie Ou, Ze Su, Wen-Feng Li, Wen-Hai He, Ning Peng, Liang Ma, Bang-De Xiang, Jian-Hong Zhong","doi":"10.1111/apt.70102","DOIUrl":"https://doi.org/10.1111/apt.70102","url":null,"abstract":"<p>We read with substantial interest the study by Uluk et al. [<span>1</span>], which assessed the impacts of metabolic dysfunction-associated steatotic liver disease (MASLD) on long-term outcomes subsequent to curative surgery for hepatocellular carcinoma (HCC). Their retrospective investigation examines the novel MASLD and MetALD classifications among HCC patients who underwent curative surgery, further corroborated by body composition analysis. They discovered that patients with MASLD-related HCC exhibited shorter overall survival compared to patients with HCC of other aetiologies. Indeed, one previous study comparing patients with MASLD-related HCC to those with HCC of other aetiologies has also identified shorter overall survival in the MASLD-related HCC group [<span>2</span>]. However, some other findings indicate that patients suffering from HCC associated with MASLD may potentially experience extended recurrence-free and overall survival in comparison to those with HCC of alternative aetiologies [<span>3, 4</span>]. These discordant results emphasise the necessity for further investigations into the prognosis of MASLD-related HCC patients following curative resection.</p>\u0000<p>Immunotherapy is one of the main treatments for HCC in recent years. One study found that patients with MASLD-related advanced HCC receiving immune checkpoint inhibitors have a comparable prognosis to those with other aetiologies [<span>5</span>], while another study has indicated that patients with non-alcoholic steatohepatitis-related HCC may not obtain optimal benefits from immunotherapy [<span>6</span>]. Nowadays, no studies have reported whether MASLD affects the efficacy of adjuvant immunotherapy in patients with HCC after curative resection.</p>\u0000<p>A retrospective analysis was conducted on the medical data of patients who underwent adjuvant PD-1 therapy after curative resection within 10 medical centers of the GUIDANCE collaboration in China, spanning from January 16, 2019, to January 24, 2024. The patients were classified into the MASLD group and the non-MASLD group in accordance with the guideline [<span>7</span>]. The survival curves were estimated using the Kaplan–Meier method and compared by means of the log-rank test. A total of 409 patients were enrolled (most patients were enrolled after 2022), including 72 with MASLD-related HCC and 337 with HCC from other aetiologies. After a median follow-up period of 30.0 months (interquartile range: 21.4–44.1 months), no significant differences were found in the recurrence-free survival (hazard ratio 1.04, 95% confidence interval: 0.74–1.50; Figure 1A) and overall survival (hazard ratio 0.95, 95% confidence interval: 0.53–1.70; Figure 1B) between patients with MASLD-related HCC and those with HCC of other aetiologies.</p>\u0000<figure><picture>\u0000<source media=\"(min-width: 1650px)\" srcset=\"/cms/asset/4bcc863a-4612-4578-9463-c6c32cefc280/apt70102-fig-0001-m.jpg\"/><img alt=\"Details are in the caption following the image\" da","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"3 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143775991","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":"Therapeutic Sequences of Systemic Therapy After Atezolizumab Plus Bevacizumab for Hepatocellular Carcinoma: Real-World Analysis of the IMMUreal Cohort","authors":"Najib Ben Khaled, Valentina Zarka, Bernard Hobeika, Julia Schneider, Monika Rau, Alexander Weich, Hans Benno Leicht, Liangtao Ye, Ignazio Piseddu, Michael T. Dill, Arne Kandulski, Matthias Pinter, Ursula Ehmer, Peter Schirmacher, Jens U. Marquardt, Julia Mayerle, Enrico N. De Toni, Andreas Geier, Florian P. Reiter","doi":"10.1111/apt.70090","DOIUrl":"https://doi.org/10.1111/apt.70090","url":null,"abstract":"The introduction of several new systemic therapies in recent years has significantly altered the treatment landscape for advanced hepatocellular carcinoma. However, while the approval of the combination of atezolizumab and bevacizumab as the preferred first-line therapy over sorafenib represents progress, it has also raised uncertainties regarding optimal treatment sequencing for advanced disease.","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"37 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143776033","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: Comparing the Efficacy of Adjuvant PD–1 Inhibitor After Curative Resection for Metabolic Dysfunction-Associated Steatotic Liver Disease Related HCC Versus Other Aetiologies—Authors' Reply","authors":"Isabella Lurje, Deniz Uluk, Frank Tacke, Georg Lurje","doi":"10.1111/apt.70126","DOIUrl":"https://doi.org/10.1111/apt.70126","url":null,"abstract":"<p>We thank Su et al. for their interest in our study [<span>1</span>], which interrogated the role of hepatocellular carcinoma (HCC) aetiology on long-term outcomes following liver resection. In our work, we found that European patients with metabolic dysfunction-associated steatotic liver disease (MASLD)-related HCC had significantly shorter overall survival (OS) after liver resection compared to patients with HCC of other etiologies. Su et al. have raised a pertinent issue by discussing their recent findings in Asian patients receiving adjuvant anti-PD-1 immunotherapy, where no significant survival differences were observed between MASLD-related HCC and other aetiologies [<span>2</span>].</p>\u0000<p>As highlighted by Su et al. [<span>2</span>], several studies have reported better disease-free (DFS) and OS in patients with MASLD-related HCC after liver resection, which contrasts with the results of our study [<span>3</span>]. Discrepancies in outcomes may be attributable to variations in patient populations (Asian vs. European cohorts), tumour characteristics, severity of underlying liver disease, retrospective application of diagnostic criteria (e.g., alcohol intake) and adjuvant therapy. These variations emphasise the need for standardised prospective settings to address these questions.</p>\u0000<p>The investigation of MASLD-related HCC is especially crucial, as the underlying pathophysiology suggests distinct immune dynamics that may affect prognosis and response to therapy. Specifically, an autoreactive conventional dendritic cell (cDC1)-CD8 T-cell axis drives disease progression and cancerogenesis and can be stimulated through checkpoint inhibition in MASLD [<span>4, 5</span>]. A meta-analysis of published trials found that checkpoint inhibitor therapy (anti-PD-1 and anti-PD-L1, monotherapy or combination therapy) did not significantly improve survival in patients with advanced non-viral HCC. Interestingly, in patients with advanced HCC fulfilling metabolic dysfunction-associated steatohepatitis (MASH) criteria, survival outcomes were significantly worse with checkpoint inhibitor therapy compared to non-MASH-related HCC [<span>6</span>], suggesting that the immune microenvironment in MASLD-related HCC may differ from that in other HCC subtypes [<span>7</span>].</p>\u0000<p>Current European guidelines do not recommend adjuvant therapy after curative-intent HCC resection, due to insufficient evidence to support their long-term efficacy in Western cohorts [<span>8</span>]. The Imbrave050 trial recruited Western and Asian patients to receive Atezolizumab (anti-PD-L1) plus Bevacizumab (anti-VEGF) in an adjuvant setting. Despite encouraging initial results, long-term oncological outcomes were not significantly improved through combination immunotherapy [<span>9</span>]. However, emerging data from Asia are more promising. For instance, a recent phase II trial of sintilimab (anti-PD-1) as adjuvant treatment after resection of high-risk HCC demonstrated signi","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"58 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143776032","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":"Clinical Trial: Dose-Finding Study of Linaprazan Glurate, A Novel Potassium-Competitive Acid Blocker, Versus Lansoprazole for the Treatment of Erosive Oesophagitis","authors":"Prateek Sharma,&nbsp;Michael Vaezi,&nbsp;Peter Unge,&nbsp;Kjell Andersson,&nbsp;Kajsa Larsson,&nbsp;Ivan Popadiyn,&nbsp;Maria Rosenholm,&nbsp;Andras Rosztóczy,&nbsp;Elham Yektaei,&nbsp;David Armstrong","doi":"10.1111/apt.70109","DOIUrl":"10.1111/apt.70109","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Linaprazan glurate, a potassium-competitive acid blocker, is in development for the treatment of erosive oesophagitis and other acid-related diseases.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>To evaluate the 4-week healing rate and safety of four linaprazan glurate dosing regimens in patients with erosive oesophagitis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This double-blind, dose-finding study compared linaprazan glurate to lansoprazole. We included patients with endoscopically confirmed erosive oesophagitis (validated by a central review board) if they had Los Angeles (LA) grade C/D or LA grade A/B with partial response to at least 8 weeks of proton pump inhibitor therapy. Patients were randomised to 4 weeks of linaprazan glurate (25, 50, 75 or 100 mg twice daily) or lansoprazole (30 mg once daily), followed by 4 weeks of open-label lansoprazole.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Of 248 patients randomised, central review confirmed erosive oesophagitis in 182 at screening endoscopy. Across all doses, linaprazan glurate achieved a 4-week healing rate of 71.1% in intention-to-treat (ITT) analysis and 80.9% in per protocol (PP) analysis. In comparison, lansoprazole achieved healing rates of 60.6% (ITT) and 59.1% (PPS). The best performing linaprazan glurate dosing group outperformed lansoprazole by 28% in patients with LA grade A/B with partial PPI response and by more than 50% in patients with LA grade C/D.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Linaprazan glurate demonstrated high 4-week healing rates compared to lansoprazole, with a good safety profile, supporting its further development.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Trial Registration</h3>\u0000 \u0000 <p>ClinicalTrials.gov: NCT05055128; EudraCT: 2020-003319-91</p>\u0000 </section>\u0000 </div>","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"61 10","pages":"1590-1602"},"PeriodicalIF":6.6,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apt.70109","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143776034","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biopsy-Sparing Diagnosis of Coeliac Disease Based on Endomysial Antibody Testing and Clinical Risk Assessment","authors":"Stiliano Maimaris, Annalisa Schiepatti, Daniel Ignacio Conforme Torres, Roberta Muscia, Virginia Gregorio, Claudia Delogu, Ignazio Marzio Parisi, Michele Dota, Giovanni Arpa, Carolina Cicalini, Giulio Massetti, Chiara Scarcella, Paolo Minerba, Federico Biagi","doi":"10.1111/apt.70129","DOIUrl":"https://doi.org/10.1111/apt.70129","url":null,"abstract":"Interest in a biopsy-sparing diagnosis of coeliac disease in adults is growing.","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"37 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143776038","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: Lubiprostone Treatment for MASLD—Gender Imbalance and Blinding Considerations","authors":"Jiru Li,&nbsp;Qi-En Shen","doi":"10.1111/apt.70089","DOIUrl":"10.1111/apt.70089","url":null,"abstract":"&lt;p&gt;We read with great interest the studies by El-Kassas and their colleagues [&lt;span&gt;1&lt;/span&gt;]. This study provides valuable insights, demonstrating that Lubiprostone is well tolerated and effectively reduces liver fat content in patients with MASLD. However, we wish to highlight a few key considerations to enhance the interpretation of the findings and propose avenues for future research.&lt;/p&gt;&lt;p&gt;Firstly, we would like to highlight the significant gender imbalance in the study's patient population. The patient group included a disproportionately high percentage of women, with 83% in the control group and 91% in the intervention group. Additionally, the mean age of the female patients in the intervention group (43.3 ± 9.1 years) was younger than that in the control group (47.0 ± 10.2 years). This age difference aligns with the menopausal transition, increasing oestrogen level variations between pre-menopausal and peri-menopausal women. Oestrogen plays a critical role in the progression of fatty liver disease [&lt;span&gt;2&lt;/span&gt;]. Postmenopausal women often experience a worsened clinical course of fatty liver due to the decline in oestrogen levels [&lt;span&gt;2, 3&lt;/span&gt;]. Given the age difference between the two groups of patients in this study, oestrogen levels may have differed significantly between the intervention and control groups, which may have exaggerated the actual effects of lubiprostone. A more refined approach might include monitoring oestrogen levels as part of a broader analysis of how these hormones influence the course of MASLD and treatment outcomes.&lt;/p&gt;&lt;p&gt;Secondly, while we commend the authors for employing a randomised, double-blind design, we note a potential limitation related to the drug's mechanism. Lubiprostone, as a laxative, is known to have a direct effect on bowel movements [&lt;span&gt;4&lt;/span&gt;]. In clinical practice, patients receiving laxatives are often able to infer their treatment group based on changes in gastrointestinal function, which may affect their perceptions of the drug's efficacy. Although the study reports that both the participants and caregivers were blinded to treatment allocation, the physiological response to lubiprostone may introduce a psychological bias. Therefore, in similar study designs, a dummy laxative (a drug with no physiological effect) could be introduced as a control group in the study to ensure that participants are not able to judge their group by their physiological response.&lt;/p&gt;&lt;p&gt;Finally, it is important to acknowledge the limitations in the study's inclusion criteria. All trial participants had liver enzymes under 40, which suggests that the study focused on individuals with mild liver steatosis and without overt steatohepatitis. MASLD is a progressive, chronic disease, and its management requires a long-term approach. The safety and tolerability of lubiprostone over extended periods remain uncertain, particularly in patients with co-morbid metabolic conditions [&lt;span&gt;5&lt;/span&gt;]. As such, we reco","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"61 10","pages":"1725-1726"},"PeriodicalIF":6.6,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apt.70089","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143776040","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Letter: Lubiprostone Treatment for MASLD—Gender Imbalance and Blinding Considerations. Authors' Reply","authors":"Mohamed El-Kassas,&nbsp;Hala Mostafa,&nbsp;Hongqun Liu,&nbsp;Samuel S. Lee","doi":"10.1111/apt.70132","DOIUrl":"10.1111/apt.70132","url":null,"abstract":"&lt;p&gt;We appreciate the comments of Drs. Li and Shen [&lt;span&gt;1&lt;/span&gt;] on our recent study [&lt;span&gt;2&lt;/span&gt;] investigating the effects of lubiprostone in metabolic dysfunction-associated steatotic liver disease (MASLD). Their concerns regarding gender imbalance and blinding considerations provide an opportunity to further clarify our study design and findings.&lt;/p&gt;&lt;p&gt;First, we acknowledge that our study population had a higher proportion of female participants, with 83% in the control group and 91% in the lubiprostone group. This gender distribution reflects real-world epidemiological patterns, where MASLD is increasingly prevalent among women, particularly in regions with high obesity and metabolic syndrome rates [&lt;span&gt;3&lt;/span&gt;]. Recent data from Egypt indicate that obesity prevalence in adults is among the highest globally, with significantly higher rates in females (49.5%) compared to males (29.5%) [&lt;span&gt;4&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;Secondly, while oestrogen may play a role in MASLD pathophysiology [&lt;span&gt;5&lt;/span&gt;], the randomization process in our study ensured an equal distribution of potential confounders across both groups. Furthermore, baseline characteristics—including BMI, lipid profiles, and liver enzymes—were comparable, minimising the likelihood that hormonal differences influenced our results. Future studies may benefit from stratified randomisation based on menopausal status or direct oestrogen level assessments to explore this aspect further.&lt;/p&gt;&lt;p&gt;Additionally, Li and Shen raise concerns regarding the potential for participants to infer their treatment allocation due to lubiprostone's well-documented gastrointestinal effects. While we recognise that laxatives may induce a noticeable physiological response [&lt;span&gt;6&lt;/span&gt;], our study adhered to a rigorous double-blind design in which both patients and healthcare providers were unaware of group allocation. Importantly, patient-reported outcomes were not a primary endpoint, reducing the potential for subjective bias. Although the suggestion of incorporating a dummy laxative as a control arm is theoretically appealing, it presents ethical and logistical challenges, including potential confounding effects. That said, future trials incorporating validated blinding assessment tools could provide additional reassurance regarding the robustness of blinding procedures.&lt;/p&gt;&lt;p&gt;Finally, our trial focused on MASLD patients without advanced fibrosis, with liver enzyme levels below 40 U/L. This was an intentional design choice to examine lubiprostone's effects on hepatic steatosis in a relatively homogenous population. We agree that studying patients with more severe MASLD, including those with elevated ALT and significant fibrosis, is crucial. The long-term safety of lubiprostone, particularly in patients with metabolic comorbidities, warrants further study in larger, multi-centre trials with extended follow-up periods.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Mohamed El-Kassas:&lt;/b&gt; conceptualization, writing – original draft, writing – revi","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"61 10","pages":"1727-1728"},"PeriodicalIF":6.6,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apt.70132","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143776037","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial: Obesity and Outcomes on Advanced Therapy in Ulcerative Colitis—The Fat of the Matter","authors":"Anish J. Kuriakose Kuzhiyanjal,&nbsp;Jimmy K. Limdi","doi":"10.1111/apt.70097","DOIUrl":"10.1111/apt.70097","url":null,"abstract":"&lt;p&gt;The increasing prevalence of obesity worldwide poses a major threat to global health [&lt;span&gt;1&lt;/span&gt;]. The body mass index (BMI) of individuals with inflammatory bowel disease (IBD) has also undergone an upward shift, with 15%–40% of adult patients reported to be obese and 20%–40% in the overweight category [&lt;span&gt;2&lt;/span&gt;]. Obesity contributes to an inflammatory state through adipokines and various pro-inflammatory cytokines, sparking curiosity about the potential role of obesity in IBD pathogenesis, its natural history, and impact on medical and surgical management [&lt;span&gt;2&lt;/span&gt;]. A recent study demonstrated that obese patients with IBD had a higher risk of having active disease and disease-related relapse compared to patients with a normal BMI, an effect stronger in ulcerative colitis (UC) than Crohn's disease(CD) [&lt;span&gt;3&lt;/span&gt;]. Additionally, obesity is associated with accelerated drug clearance, increased central volume of distribution, and unfavourable pharmacokinetics [&lt;span&gt;2, 4&lt;/span&gt;]. A pooled meta-analysis demonstrated that obesity was associated with higher odds of anti-TNF failure in UC (but not CD) but there are virtually no data on the efficacy of other biologic therapies on IBD outcomes [&lt;span&gt;5&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;Adding to our understanding, Desai et al. report a retrospective cohort study, utilising the TriNetX database, of the impact of obesity on the efficacy of advanced therapies in UC, assessing a composite outcome of corticosteroid use, change in advanced therapy, or colectomy within 2 years among IBD patients with obesity (BMI ≥ 30 kg/m&lt;sup&gt;2&lt;/sup&gt;) to non-overweight and non-obese individuals (BMI 18.5–24.9 kg/m&lt;sup&gt;2&lt;/sup&gt;) [&lt;span&gt;6&lt;/span&gt;]. They identified an increased risk of the composite outcome in obese IBD patients receiving anti-TNF agents, vedolizumab, ustekinumab, and Janus Kinase inhibitors (JAK-i). The increased risk extended to the overweight cohort (BMI 25–29.9 kg/m&lt;sup&gt;2&lt;/sup&gt;) in vedolizumab and anti-TNF treated patients, but not ustekinumab and JAK-i.&lt;/p&gt;&lt;p&gt;Inherent limitations posed by the retrospective design notwithstanding (no claims data, hospitalisation or external provider data from the nature of the database used, smaller sample sizes for ustekinumab and JAK-I), this study adds credence through its sobering observation that obesity and high BMI in UC are consistently and negatively associated with the undesirable outcomes studied.&lt;/p&gt;&lt;p&gt;It also raises important questions. The use of BMI as a measure of obesity limits the ability to differentiate visceral adipose tissue (VAT) from subcutaneous fat, with distinct metabolic and immunological profiles [&lt;span&gt;7&lt;/span&gt;]. Prospective studies should explore volumetric analysis of VAT to correlate with IBD outcomes and better adjustment of confounders such as smoking, steroid use and disease activity. The potential for wide variation in the timing of BMI measurements and confounding by smoking, steroid use, and disease activity blur our understanding of","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"61 10","pages":"1709-1710"},"PeriodicalIF":6.6,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apt.70097","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143776036","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial: Obesity and Outcomes on Advanced Therapy in Ulcerative Colitis—The Fat of the Matter: Authors' Reply","authors":"Aakash Desai,&nbsp;Priya Sehgal","doi":"10.1111/apt.70125","DOIUrl":"10.1111/apt.70125","url":null,"abstract":"&lt;p&gt;We appreciate the editorial by Kuzhiyanjal et al. [&lt;span&gt;1&lt;/span&gt;] As obesity becomes increasingly prevalent among individuals with IBD, its clinical implications continue to gain relevance [&lt;span&gt;2&lt;/span&gt;]. Obesity has been associated with a more severe phenotype of IBD, characterised by increased disease activity and suboptimal treatment response. We propose that this relationship is primarily driven by visceral adiposity, which refers to the hormonally and metabolically active fat deposited around the viscera. Visceral, as opposed to subcutaneous, adiposity may be the key player behind adverse outcomes in patients with obesity and IBD. Visceral fat can promote a pro-inflammatory state mediated by adipocyte-derived cytokines such as leptin, TNF-alpha, and IL-6 [&lt;span&gt;3&lt;/span&gt;]. In a prospective study, visceral adiposity was associated with decreased rates of corticosteroid-free and endoscopic remission [&lt;span&gt;4&lt;/span&gt;]. Visceral adiposity has also been associated with decreased time between IBD flares in both Crohn's disease and ulcerative colitis [&lt;span&gt;5&lt;/span&gt;]. Furthermore, visceral adiposity has been associated with increased risk of surgery among patients on anti-TNF-α therapy, stricturing in Crohn's disease, and post-operative mortality following ileocolonic resection [&lt;span&gt;6, 7&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;We explored the impact of obesity (BMI ≥ 30 kg/m&lt;sup&gt;2&lt;/sup&gt;) on outcomes in ulcerative colitis; elevated BMI was associated with the composite outcome of corticosteroid use, change in advanced therapy, or colectomy within 2 years across several different advanced therapies including anti-TNF agents, vedolizumab, ustekinumab and Janus kinase inhibitors (JAKi) [&lt;span&gt;8&lt;/span&gt;]. Given the confines of a database study, BMI was the only possible measure of obesity. In keeping with prior studies, we hypothesized that BMI may serve as a surrogate measure for visceral adiposity, as patients with increased visceral fat probably exhibit higher BMI. BMI is also convenient in routine clinical practice. However, it remains an imperfect measure, and its association with adverse IBD outcomes is inconsistent. For instance, in a multi-centre cohort study, of patients with IBD starting a new biologic therapy, BMI was not associated with hospitalisation, IBD-related surgery, or serious infection [&lt;span&gt;9&lt;/span&gt;]. Additionally, in a pooled analysis of four clinical trials (ACCENT-1, SONIC, ACT-1, and −2), there was no significant association between BMI and clinical remission, clinical response, or mucosal healing in Crohn's disease or ulcerative colitis [&lt;span&gt;10&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;We agree with Kuzhiyanjal et al. in that future studies examining the true impact of the relationship between obesity and IBD disease activity should utilise both BMI and visceral adiposity. It would be prudent to establish a relationship between these two exposure variables and the outcomes of disease activity—ideally endoscopic and histologic. Furthermore, studies should be carried out ","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"61 10","pages":"1711-1712"},"PeriodicalIF":6.6,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apt.70125","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143778636","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial: ‘Risk-Adapted Starting Ages of Colorectal Cancer Screening for People With Diabetes or Metabolic Syndrome’","authors":"James Turvill","doi":"10.1111/apt.70106","DOIUrl":"10.1111/apt.70106","url":null,"abstract":"&lt;p&gt;In 2019, at a symposium at the Royal College of Physicians in London, I first heard ‘FIT’ and ‘democratisation’ used in the same sentence [&lt;span&gt;1&lt;/span&gt;]. What was being discussed was how the objectivity of a faecal immunochemical test (FIT) result could be applied across age, sex, symptoms and signs and other laboratory tests to identify a personalised and so fixed, or equitable, colorectal cancer (CRC) risk. Perhaps other risk factors, such as ethnicity and one's index of multiple deprivation might also be in the offing with FIT [&lt;span&gt;2&lt;/span&gt;]. The paper by Seum et al. takes us into a new space [&lt;span&gt;3&lt;/span&gt;]. However one defines or identifies people with diabetes or metabolic syndrome, evidence suggests that CRC is commoner at any given age in this population. The authors make the case that, should equity underpin screening, the age at which those with diabetes or metabolic syndrome enter CRC screening programmes should be reduced [&lt;span&gt;4&lt;/span&gt;]. Is this the beginning of a new conversation? Where should we go from here?&lt;/p&gt;&lt;p&gt;Clearly, simplicity is key to the establishment of screening programmes. The logistics of identifying people with diabetes and, particularly, metabolic syndrome would be challenging. Where would one stop? For every cohort with an easily defined risk, are there not many others with inflammatory conditions, prior diseases and treatments, family and environmental factors that shift CRC risk? The Bowel Cancer Screening Programme (BCSP) in England has entered this space by bringing people with Lynch syndrome into its programme [&lt;span&gt;5&lt;/span&gt;]. These people have different risk profiles and, unlike others, are not expected to provide a FIT to ‘qualify’ for colonoscopy. The targeted lung health check drifts away from ‘screening’ [&lt;span&gt;6&lt;/span&gt;]. Here, those aged 55–74 with a smoking history are targeted for CT of the thorax (and upper abdomen). Clearly, there is a continuum between the seemingly contrived ‘indifference’ of screening and the ‘targeted approach’.&lt;/p&gt;&lt;p&gt;Then there is the population we serve. Recognising how powerful the BCSP has been in identifying people with stage I and II CRC, has not the wide disparity in uptake in, for example, Yorkshire and Humber (the region I serve) arguably added to inequity and so been ‘undemocratic’? [&lt;span&gt;7&lt;/span&gt;] Colleagues have been talking about the socio-technical elements of the implementation of medical devices [&lt;span&gt;8&lt;/span&gt;]. There are perhaps similarities in these interventions that might help in untangling this problem in screening. Rather than expecting people to embrace CRC screening equitably and spontaneously across society, the social arrangements that deliver, mediate and support screening need to be considered explicitly and deliberately. Encouraging engagement with CRC screening is one thing. The other might be to shift the FIT threshold in favour of those communities that are struggling. Let them see that they are valued. As a gastroenterologist and CRC ","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"61 10","pages":"1713-1714"},"PeriodicalIF":6.6,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apt.70106","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143766584","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}