Alimentary Pharmacology & Therapeutics最新文献

{"title":"Letter: A Prospective Study on the Prevalence of MASLD in Patients With Type 2 Diabetes and Hyperferritinaemia","authors":"Xiaojuan Liu, Xueru Huang, Mingsi Zhang, Tao Jiang, Guangji Zhang","doi":"10.1111/apt.18419","DOIUrl":"10.1111/apt.18419","url":null,"abstract":"<p>We were intrigued by the study conducted by Amangurbanova et al. [<span>1</span>], which examined the prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) in patients with type 2 diabetes mellitus (T2DM) and hyperferritinaemia. The authors proposed elevated serum ferritin as a potential biomarker for MASLD and significant fibrosis, while also elucidating the risk characteristics associated with MASLD and fibrosis in individuals with hyperferritinaemia. This pioneering work is commendable; however, certain limitations in the inclusion and exclusion criteria may affect the external validity of the findings.</p><p>One notable limitation is the restricted age range of 50–80 years, which may not adequately reflect the evolving epidemiology of MASLD. Recent evidence suggests a concerning trend of earlier disease onset. A nationwide study of 5.7 million Chinese adults found that the prevalence of severe liver steatosis (grade S3) peaked between ages 35 and 39 [<span>2</span>]. Additionally, paediatric NAFLD rates in Asian populations increased from 4.4% (2004–2010) to 7.1% (2011–2020) [<span>3</span>]. Alarmingly, a long-term follow-up study reported a rise in MASLD prevalence from 0.52% to 3.4% among children aged 5–8 years [<span>4</span>]. Including younger patients would provide a more accurate representation of contemporary disease patterns and enhance the generalisability of results.</p><p>Furthermore, we suggest refinements in the alcohol consumption exclusion criteria. While the authors defined significant alcohol intake as ≥ 14 drinks/week for men or ≥ 7 drinks/week for women over the past 2 years, the specific alcohol content per ‘standard drink’ was not provided. The definition of a standard drink varies internationally. For instance, in the United States, a standard drink is defined as 14 g of pure alcohol, while other countries, such as Switzerland (10–12 g) [<span>5</span>] and Luxembourg (12.8 g) [<span>6</span>], have different standards. Austria even defines a standard drink as 20 g [<span>7</span>]. Standardising alcohol content measurements is essential.</p><p>Lastly, we would like to highlight the impact of HFE mutations (the author has noting this is one of the limitations for this study). HFE mutations are prevalent in European populations, particularly among individuals of Northern European ancestry, with frequencies reaching up to 1:250 [<span>8</span>]. These mutations can disrupt iron homeostasis before clinical manifestations occur. Given that both hereditary hemochromatosis and metabolic dysfunction can elevate serum ferritin levels, distinguishing between these etiologies is crucial for accurate risk stratification and patient management [<span>9</span>]. Moreover, HFE mutations may independently influence liver fat accumulation and fibrosis progression [<span>10</span>], potentially confounding the relationship between hyperferritinaemia and MASLD.</p><p>Despite these limitations, the current st","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"61 5","pages":"929-930"},"PeriodicalIF":6.6,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apt.18419","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143125004","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: Clinical Trial Design Considerations for Hospitalised Patients With Ulcerative Colitis Flares and Application to Study Hyperbaric Oxygen Therapy in the NIDDK HBOT-UC Consortium","authors":"Brian C. Weiner","doi":"10.1111/apt.18450","DOIUrl":"10.1111/apt.18450","url":null,"abstract":"<p>Careful planning helps to get reliable results and avoids mistakes. The publication by Dulai et al. [<span>1</span>] shows the work involved in a major multicentre project to demonstrate the feasibility for a new treatment in an area sorely lacking in recent innovation. Hyperbaric oxygen (HBO) is purported to be helpful in management of severe inflammatory bowel disease (IBD) due to its known effect of increasing tissue oxygen levels [<span>2-4</span>].</p><p>Disadvantages associated with HBO include medical risk, logistics (awkwardness of treating constitutionally sick patients in a bariatric chamber), lack of standardisation of HBO, possible interaction with drugs and lack of insurance coverage. Important contraindications include pregnancy and pneumothorax [<span>5-7</span>].</p><p>The researchers did not consider other possible mechanisms of the effects of oxygen on the clinical course of severe IBD. In patients with IBD who are sick enough to merit hospitalisation, there are symptoms consistent with ileus due to inflammation. These patients may have difficulty with oral intake, abdominal pain and distension and abnormal bowel habits. Prior HBO studies did not prominently report evidence of ileus, abdominal imaging or pre- and post- treatment bowel diameters. Therapeutic oxygen for gastrointestinal atony (TOGA) was reported by our group [<span>8</span>]. We performed a pilot study in patients with ileus or bowel obstruction. TOGA is a 6-h course of treatment with 100% oxygen via a non-rebreather mask at room air bariatric pressure. This creates a nitrogen gradient. Nitrogen is drawn out of the bowel and expired into the ambient atmosphere. This gradient led to a rapid decrease in the diameter of the bowel. Decreased bowel wall tension, improved blood flow and improved enteric muscle function are associated with this decrease in luminal diameter in ileus and bowel obstruction. We reported successful treatment in 10/11 medically refractory patients. 100% oxygen at 1 atm pressure may have similar effects in patients with IBD. Decreasing luminal diameter by driving out nitrogen from the lumen may improve blood flow to the inflamed tissue, thereby improving outcomes. Consider adding TOGA as an active control to your study design.</p><p><b>Brian C. Weiner:</b> conceptualization, investigation, writing – original draft, methodology, writing – review and editing, formal analysis.</p><p>Dr. Weiner holds a US patent on TOGA technology #11,771,855.</p><p>This article is linked to Dulai et al paper. To view this article, visit https://doi.org/10.1111/apt.18326.</p>","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"61 5","pages":"923-924"},"PeriodicalIF":6.6,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apt.18450","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143124384","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: Hepatotoxicity in Malignancies Under ICIs Treatment","authors":"Yue Zou,&nbsp;Zhengyu Zhang,&nbsp;Jianjun He","doi":"10.1111/apt.18442","DOIUrl":"10.1111/apt.18442","url":null,"abstract":"&lt;p&gt;We had the pleasure of reading the research article by Hung et al. [&lt;span&gt;1&lt;/span&gt;] We sincerely appreciate their meticulous work and significant contributions, and we hope to offer some constructive suggestions for future research.&lt;/p&gt;&lt;p&gt;Firstly, the article provides a comprehensive account of the patients' baseline data and outlines the baseline demographic characteristics of the study population, which is commendable. However, the authors have not adequately processed the data. It is clear that the hepatocellular carcinoma (HCC) cohort had significantly higher baseline alanine aminotransferase (ALT) levels and a greater proportion of hepatitis B surface antigen (HBsAg)-positive patients compared to the non-HCC cohort, indicating that the HCC group was more predisposed to liver events. This makes it difficult to accurately conclude that liver events were caused by immune checkpoint inhibitors (ICIs). Hence, we recommend the authors adopt a prospective study design to better control for variables, or use methods such as propensity score matching to minimise confounding bias [&lt;span&gt;2&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;Secondly, solely reporting HBsAg positivity is insufficient. HBsAg positivity indicates the presence of hepatitis B virus (HBV) infection but does not necessarily reflect the activity level of the virus. Higher levels of viral activity are often associated with more severe liver damage. We recommend including additional indicators, such as hepatitis B e antigen (HBeAg) status and HBV DNA levels, to provide a more comprehensive assessment of viral activity [&lt;span&gt;3&lt;/span&gt;]. Additionally, several critical confounding factors have not been considered, such as underlying comorbidities (e.g., diabetes, hypertension and fatty liver disease), concurrent treatments (e.g., chemotherapy and targeted therapy), tumour size and staging. A detailed analysis of these factors would further strengthen the reliability and robustness of the study's conclusions [&lt;span&gt;4&lt;/span&gt;]. Furthermore, the article identifies ALT &gt; 40 U/L as an independent risk factor for hepatitis flare following ICI therapy but does not delve into the specific causes of this abnormality, such as viral activity or immune-related damage. Comprehensive virological assessments, including the measurement of HBV DNA levels and HBeAg status, could provide greater clarity on whether the ALT elevation is driven by active viral replication.&lt;/p&gt;&lt;p&gt;In conclusion, this study provides valuable insights into the risk of liver events in HCC patients receiving ICI therapy. Future research should strive to thoroughly elucidate the mechanisms underlying liver events associated with ICI treatment, optimise clinical management strategies and improve the safety and effectiveness of patient care.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Yue Zou:&lt;/b&gt; writing – review and editing, writing – original draft. &lt;b&gt;Zhengyu Zhang:&lt;/b&gt; writing – review and editing, writing – original draft. &lt;b&gt;Jianjun He:&lt;/b&gt; investigation, conceptualization.&lt;/p&gt;&lt;p&gt;The aut","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"61 5","pages":"931-932"},"PeriodicalIF":6.6,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apt.18442","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143125001","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":"Review Article: Surrogate Endpoints to Assess Treatment Efficacy in Disorders of Gut–Brain Interaction of Lower Gastrointestinal Tract","authors":"Michael Camilleri,&nbsp;Alexander C. Ford","doi":"10.1111/apt.18527","DOIUrl":"10.1111/apt.18527","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Surrogate endpoints such as laboratory parameters that are not direct measurements of, but predict, clinical benefit are approved by regulatory agencies for initial proof of efficacy. No surrogate endpoints are approved for disorders of gut–brain interaction.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>To assess the correlation of scintigraphic colonic transit (CT) with response rates according to patient-reported symptom-based endpoints (composite/global symptoms, abdominal pain or stool frequency/consistency) in irritable bowel syndrome (IBS) or chronic idiopathic constipation (CIC).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We reviewed available data from, randomised controlled trials (RCTs) reporting effects on CT at 24 h and 48 h with drug versus placebo and extracted the difference in the proportions responding to drug or placebo, using rates from individual RCTs or from meta-analyses when more than one RCT existed for a drug. We analysed associations between differences (drug vs. placebo) in CT and in response rates using Spearman correlation. Additional analyses of CT at 24 h with composite/global symptom or pain endpoints were performed with exclusion of alosetron (the only drug slowing CT).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>CT at 24 h correlated significantly with composite/global symptom endpoints (Rs = −0.755, <i>p</i> = 0.021). CT correlated with stool frequency or consistency (at 24 h, Rs = 0.506, <i>p</i> = 0.074; at 48 h, Rs = 0.631, <i>p</i> = 0.026). CT at 24 h did not correlate with abdominal pain (Rs = −0.054, <i>p</i> = 0.843). With the exclusion of alosetron data, CT at 24 h was non-significantly correlated with the composite/global symptom endpoint (Rs = −0.667, <i>p</i> = 0.073), but not with abdominal pain (Rs = 0.377, <i>p</i> = 0.419).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Scintigraphic CT measurement fulfils the expectation of a surrogate endpoint for symptom-based outcomes, particularly in IBS-D or IBS-C and CIC.</p>\u0000 </section>\u0000 </div>","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"61 6","pages":"950-958"},"PeriodicalIF":6.6,"publicationDate":"2025-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143076903","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":"Impact of GLP‐1 Receptor Agonists on Alcohol‐Related Liver Disease Development and Progression in Alcohol Use Disorder","authors":"Chia‐Chih Kuo, Chun‐Hsien Li, Min‐Hsiang Chuang, Po‐Yu Huang, Hsing‐Tao Kuo, Chih‐Cheng Lai","doi":"10.1111/apt.70007","DOIUrl":"https://doi.org/10.1111/apt.70007","url":null,"abstract":"Background and AimsGlucagon‐like peptide‐1 receptor agonists (GLP‐1RAs) have shown promise in reducing alcohol consumption, but their impact on clinical outcomes in patients with alcohol use disorder (AUD) remains unclear. We investigated the association between GLP‐1RAs and the development and progression of alcohol‐related liver disease (ArLD) in patients with AUD.MethodsUsing the TriNetX Research Network, we conducted two retrospective cohort studies comparing GLP‐1RAs versus dipeptidyl peptidase‐4 inhibitors (DPP‐4is) in patients with type 2 diabetes. The first cohort included patients with AUD but without ArLD (<jats:italic>n</jats:italic> = 7132 after propensity score matching), while the second comprised patients with established ArLD (<jats:italic>n</jats:italic> = 1896 after matching). Primary outcomes were incident ArLD in the AUD cohort and hepatic decompensation in the ArLD cohort.ResultsIn the AUD cohort (median follow‐up: 63.2 months), GLP‐1RA users showed significantly lower risks of developing ArLD compared to DPP‐4i users (incidence rate: 6.0 vs. 8.7 per 1000 person‐years; HR: 0.62, 95% CI: 0.44–0.87, <jats:italic>p</jats:italic> = 0.006). GLP‐1RAs were also associated with reduced risks of all‐cause mortality (HR: 0.53, <jats:italic>p</jats:italic> &lt; 0.001). In the ArLD cohort (median follow‐up: 28.2 months), GLP‐1RA users demonstrated lower risks of hepatic decompensation (incidence rate: 39.5 vs. 51.4 per 1000 person‐years; HR: 0.66, 95% CI: 0.51–0.85, <jats:italic>p</jats:italic> = 0.001) and all‐cause mortality (HR: 0.53, <jats:italic>p</jats:italic> &lt; 0.001) compared to DPP‐4i users.ConclusionsGLP‐1RAs were associated with reduced risks of developing and progressing ArLD in patients with AUD, suggesting potential therapeutic benefits in this population.","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"12 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143072538","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":"Editorial: Autoimmune Hepatitis—Could It Be as Easy as Vitamin D?","authors":"Jessica K. Dyson","doi":"10.1111/apt.18524","DOIUrl":"10.1111/apt.18524","url":null,"abstract":"&lt;p&gt;Despite increasing knowledge regarding pathogenesis and risk factors in autoimmune hepatitis (AIH), there is still significant morbidity and mortality associated with both the disease and its treatments.&lt;/p&gt;&lt;p&gt;Here, Kilani et al. [&lt;span&gt;1&lt;/span&gt;] examine the impact of vitamin D levels on AIH outcomes, stratifying by deficiency, insufficiency and normal levels. This builds on previous work showing links between vitamin D deficiency and worse outcomes in AIH (treatment non-response, fibrosis progression, liver-related mortality and liver transplantation [LT] [&lt;span&gt;2&lt;/span&gt;] and chronic liver disease [CLD]) [&lt;span&gt;3, 4&lt;/span&gt;]. Crucially, there is also data in AIH to suggest that vitamin D may ameliorate disease progression and improve outcomes [&lt;span&gt;5-7&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;The powerful headline findings are that vitamin D deficient AIH patients have significantly increased all-cause mortality/hospitalizations, critical care admissions, decompensated cirrhosis, acute liver failure and LT at 1 year, as compared to those with normal levels (&lt;i&gt;n&lt;/i&gt; = 1288 both groups). Those with vitamin D insufficiency had increased all-cause mortality/hospitalizations but no significant differences in liver-related outcomes.&lt;/p&gt;&lt;p&gt;Utilising the TriNetX research network for propensity score matching (PSM) enabled inclusion of 118 million patients with data about demographics, healthcare utilization and outcomes and adjustment for potential confounding factors (age, race, socio-economic factors, immunosuppressive (IS) therapy, comorbidities and other CLDs) [&lt;span&gt;8&lt;/span&gt;]. However, while 39,426 patients were identified, only 7043 had documented vitamin D testing and treatment and a further 5401 were lost to keep similarity between records. The reason for exclusion depending on IS therapy is unclear. We, therefore, immediately introduce the risk of population bias. This, combined with the retrospective nature of the study, necessitates caution with interpretation of results.&lt;/p&gt;&lt;p&gt;Key limitations are the single vitamin D measurement performed throughout the analysis, patient inclusion only from the time of measurement and a short follow-up period of 1 year. We cannot, therefore, understand the dynamics of identified relationships.&lt;/p&gt;&lt;p&gt;The laboratory parameter findings are less striking than hard outcomes. By 1 year, only AST and bilirubin were statistically higher in vitamin D-deficient patients with no significant differences for insufficiency patients. We lack data on disease duration, IS changes during follow-up and are unable to assess disease activity (IgG levels unavailable).&lt;/p&gt;&lt;p&gt;The subgroup analyses about vitamin D replacement showed only that deficient patients who didn't receive replacement had increased all-cause mortality/ICU admissions. It is unclear whether patients were on replacement at time of vitamin D measurement (i.e. replacement was insufficient) or if treatment was commenced when low levels were found.&lt;/p&gt;&lt;p&gt;We are still to understand whethe","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"61 6","pages":"1065-1066"},"PeriodicalIF":6.6,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apt.18524","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143072536","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":"Chronic Use of Proton Pump Inhibitors Is Associated With Reduced 30-Day Mortality From Acute Pancreatitis.","authors":"Maya Fischman, Adi Elias, Amir Klein, Yaron Cohen, Zaher S Azzam, Itai Ghersin","doi":"10.1111/apt.18523","DOIUrl":"https://doi.org/10.1111/apt.18523","url":null,"abstract":"<p><p>Proton pump inhibitors (PPIs) decrease pancreatic exocrine secretions. There has been interest in the impact of their short-term in-hospital administration on acute pancreatitis (AP) outcomes. It is unknown whether long-term use affects AP outcomes. We investigated the association between chronic PPI use and short-term AP outcomes. We included all (2308) patients admitted with a primary diagnosis of AP (625 on chronic PPI use) between January 2008 and June 2021 and evaluated any association between chronic PPI use and 30-day all-cause mortality by univariate logistic regression. Compared to non-users, patients on chronic PPIs were older (p < 0.001) and had a higher Charlson Comorbidity Index score (p < 0.001). Mortality rates at 30 days were 1.5% in chronic PPI users and 4.6% in non-users (OR 0.33; 95% CI, 0.16-0.6; p < 0.001).</p>","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143062566","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":"Editorial: Baseline Drug Clearance Predicts Outcomes in Children With Inflammatory Bowel Disease Treated With Vedolizumab","authors":"Courtney Bartel,&nbsp;Phillip Minar","doi":"10.1111/apt.18519","DOIUrl":"10.1111/apt.18519","url":null,"abstract":"&lt;p&gt;The pharmacokinetics of IBD biologics in children differ from adults. Differences are thought to be related to physiological (e.g., differences in body surface area and a higher rate of hypoalbuminemia), developmental (immature immune processing and higher prevalence of anti-drug antibody formation) and disease-related (e.g., severity and extent of inflammation) factors [&lt;span&gt;1, 2&lt;/span&gt;]. Therapeutic drug monitoring (TDM), both reactive and proactive, has become a cornerstone for managing children with IBD, and higher biologic concentrations are often needed to achieve and sustain response [&lt;span&gt;3&lt;/span&gt;]. For instance, standard vedolizumab dosing (300 mg [or 10 mg/kg for &lt; 30 kg patients] every 8 weeks) was predicted to achieve maintenance target concentrations in fewer than 50% of paediatric patients, whereas dosing every 4 weeks was predicted to meet targets in 85%–100% [&lt;span&gt;4&lt;/span&gt;]. In the HUBBLE trial, a phase II paediatric study, vedolizumab was effective and safe, and drug exposure increased in a dose-proportional manner, but no clear dose–response relationship was observed [&lt;span&gt;5&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;In a &lt;i&gt;post hoc&lt;/i&gt; analysis, Stein et al. utilised data from the VedoKids study, a multicentre cohort of 129 children, to examine the association between baseline (pre-treatment) drug clearance, trough drug concentrations during early therapy and deep biochemical remission at Week 30 [&lt;span&gt;6&lt;/span&gt;]. Their primary aim was to evaluate baseline drug clearance as a predictor of deep biochemical remission at Week 30 (defined by normalised CRP and ESR and clinical remission). While they did not find a statistically significant association for this primary aim, increased baseline drug clearance was negatively associated with achieving a faecal calprotectin &lt; 100 μg/g and &lt; 250 μg/g at Week 30 in the subset with available data. Importantly, Week 2, Week 6 and Week 14 trough concentrations were strongly associated with deep biochemical remission, offering valuable guidance for future dosing guidelines. Finally, the pharmacokinetic model parameter estimates were similar to adult studies, while patient weight, serum albumin and prior biologic use (although confounded) influenced vedolizumab clearance.&lt;/p&gt;&lt;p&gt;This study underscores the critical importance of proactive TDM in children with IBD to identify altered vedolizumab clearance early and optimise future dosing to enhance clinical outcomes. However, some limitations warrant consideration. Most patients had received at least one biologic before starting vedolizumab, indicating a more refractory cohort. The lack of endoscopic data limits the ability to link drug concentrations or baseline clearance to mucosal healing, a critical therapeutic goal. Furthermore, while baseline drug clearance is an important pharmacokinetic measure, the study did not demonstrate clear advantages over trough concentrations, which were more strongly associated with deep biochemical remission.&lt;/p&gt;&lt;p&gt;The fin","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"61 6","pages":"1063-1064"},"PeriodicalIF":6.6,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apt.18519","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143072537","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: Alpha2-Delta Ligands in Irritable Bowel Syndrome","authors":"Andrea Shin","doi":"10.1111/apt.18528","DOIUrl":"10.1111/apt.18528","url":null,"abstract":"&lt;p&gt;Irritable bowel syndrome (IBS) is a highly prevalent disorder of gut–brain interaction associated with increased healthcare spending and reduced quality of life. IBS subtypes are defined by bowel patterns, but abdominal pain is a hallmark feature. Few IBS pharmacotherapies specifically target pain. Among these therapies are neuromodulators, particularly tricyclic antidepressants (TCAs), which are recognised for their effects on visceral and central pain. Multiple studies, including a large randomised trial, have demonstrated that TCAs improve global symptoms and pain in IBS [&lt;span&gt;1&lt;/span&gt;]. However, responses are variable and may be limited for some due to a lack of efficacy or adverse effects, highlighting a need for novel therapies.&lt;/p&gt;&lt;p&gt;Houghton et al. [&lt;span&gt;2&lt;/span&gt;] presented the results of a multi-centre phase II trial examining the efficacy of an investigational alpha&lt;sub&gt;2&lt;/sub&gt;-delta ligand, PD-217014, for the treatment of abdominal pain in IBS. The study was conducted from 2004 to 2005 and patients were identified using Rome II criteria, with 321 also meeting Rome IV criteria. Results showed no significant differences between active treatment and placebo for the primary and secondary endpoints pertaining to patient-reported abdominal pain, bloating, bowel habits, and global symptoms in both the Rome II- and Rome IV-defined cohorts. Baseline pain, anxiety and depression did not influence treatment responses.&lt;/p&gt;&lt;p&gt;Other alpha&lt;sub&gt;2&lt;/sub&gt;-delta ligands, such as pregabalin and gabapentin, are commonly used to treat pain disorders due to their anti-nociceptive effects [&lt;span&gt;3&lt;/span&gt;]. Studies in IBS populations have suggested that response rates may vary according to IBS subtype, dosing scheme and treatment duration with more promising results reported in patients with IBS-D and in studies with longer treatment periods. Thus, the efficacy of alpha&lt;sub&gt;2&lt;/sub&gt;-delta ligands may be influenced by treatment protocols and patient-specific characteristics [&lt;span&gt;4, 5&lt;/span&gt;]. Similarly, preclinical studies of PD-217014 found baseline visceral hypersensitivity to be a predictor of response [&lt;span&gt;6&lt;/span&gt;], which may be present in many but not all patients with IBS. Although Houghton et al. did not find baseline pain severity to affect treatment response, abdominal pain is a subjective experience. Moreover, while pain is correlated with visceral hypersensitivity, it can also be affected by central processing, psychosocial variables, sex hormones and environmental factors [&lt;span&gt;7-9&lt;/span&gt;]. Multiple processes including immune activation, barrier dysfunction, the gut microbiota, neurotransmitter- and peptide-mediated mechanisms, dysregulation of the hypothalamic–pituitary–adrenal axis and the endocannabinoid system may further contribute to visceral sensitisation [&lt;span&gt;10&lt;/span&gt;]. Thus, pain-modifying agents may exhibit variable degrees of efficacy across individuals with IBS in whom common symptoms can arise from a complex combination of i","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"61 6","pages":"1067-1068"},"PeriodicalIF":6.6,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apt.18528","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143056317","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":"Risk of Variceal Bleeding in Patients Receiving Atezolizumab–Bevacizumab Treatment for Hepatocellular Carcinoma","authors":"Kanghee Park, Hye Won Lee, Euichang Kim, Won-Mook Choi, Danbi Lee, Ju Hyun Shim, Kang Mo Kim, Young-Suk Lim, Han Chu Lee, Changhoon Yoo, Baek-Yeol Ryoo, Seungbong Han, Jonggi Choi","doi":"10.1111/apt.18526","DOIUrl":"https://doi.org/10.1111/apt.18526","url":null,"abstract":"Real-world data on the variceal bleeding (VB) risk in patients receiving atezolizumab–bevacizumab (Atezo–Bev) treatment remain limited. This study aimed to assess the risk of VB and identify risk factors in patients with advanced hepatocellular carcinoma (HCC) receiving Atezo–Bev treatment.","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"23 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143050832","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}