Alimentary Pharmacology & Therapeutics最新文献

{"title":"Clearance of Hepatitis C Viremia During Direct-Acting Antiviral Therapy Leads to Rapid Changes in Lipid and Lipoprotein Metabolism.","authors":"Zahra Sarrafan-Chaharsoughi,Varun Takyar,Sungyoung Auh,Gavin Nee,Ahmad Alawad,Brent S Abel,Devika Kapuria,Colleen Byrnes,Anna Wolska,David E Kleiner,Robert Shamburek,Alan T Remaley,Marc G Ghany","doi":"10.1111/apt.70130","DOIUrl":"https://doi.org/10.1111/apt.70130","url":null,"abstract":"BACKGROUND AND AIMSChronic hepatitis C virus (HCV) infection is associated with hypolipidemia. HCV eradication may, therefore, result in hyperlipidemia and increase cardiovascular disease (CVD) risk. We investigated the impact of HCV eradication on serum lipid and lipoprotein profiles and CVD risk during and following direct-acting antiviral (DAA) therapy.APPROACH AND RESULTSWe retrospectively analysed stored sera and plasma from 60 DAA-naïve patients, genotypes 1-4, treated with 12 weeks of sofosbuvir-velpatasvir. Serum lipids, apolipoproteins (apo), and a systemic inflammatory marker, GlycA, were measured serially beginning early on treatment and off treatment. Additionally, NMR LipoProfile analysis was performed on plasma samples. Expression of genes regulating lipid metabolism was assessed from paired liver biopsies obtained before and on treatment. Linear mixed models were used to examine changes in lipid and inflammatory markers; Framingham and ASCVD CVD risk scores were assessed before and after treatment. Decline in HCV viremia was associated with a rapid, significant increase in TChol, HDL-C, LDL-C, ApoA-1 and ApoB, and GlycA, improvement in ALT, hepatic inflammation, and steatosis but no change in glycemic control (HOMA-IR and HbA1c). Increase in TChol, LDL-C, and ApoB was associated with an increased SREBP1expression. Both ASCVD and Framingham risk scores were significantly increased at week 24 post treatment after adjusting for age (p < 0.0001).CONCLUSIONSerum lipids and lipoproteins rapidly increase with inhibition of viral replication during DAA therapy, an effect that may be mediated by genes affecting hepatic de novo lipogenesis. Based on lipid changes, HCV eradication may increase CVD risk, but this needs to be investigated prospectively.","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"35 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143945466","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: Different Risk of Acute Variceal Bleeding According to the Liver Disease Aetiology in Decompensated Cirrhosis Patients Receiving Carvedilol‐Based Primary Prophylaxis—May Insulin Resistance Unloose This Gordian Knot?","authors":"Mario Romeo, Fiammetta Di Nardo, Carmine Napolitano, Paolo Vaia, Alessandro Federico, Marcello Dallio","doi":"10.1111/apt.70192","DOIUrl":"https://doi.org/10.1111/apt.70192","url":null,"abstract":"&lt;p&gt;&lt;i&gt;Editors&lt;/i&gt;.&lt;/p&gt;\u0000&lt;p&gt;We enthusiastically read the brilliant research by Villanueva et al. which, by systematically reviewing randomised clinical trials (RCTs) comparing non-selective beta-blocker (NSBB) versus variceal band ligation (VBL) for primary acute variceal bleeding (AVB) prevention in cirrhotic patients presenting high-risk varices, revealed NSBBs significantly improved survival versus VBL, with no additional benefit noted of the combination strategy, exclusively in patients with compensated advanced chronic liver disease (cACLD), reporting, in contrast, a similar survival with both therapies in decompensated (dACLD) individuals [&lt;span&gt;1&lt;/span&gt;]. These findings remarked on a crucial need for personalised AVB-primary prophylaxis by adapting treatment to the clinical stage of cirrhosis [&lt;span&gt;1&lt;/span&gt;].&lt;/p&gt;\u0000&lt;p&gt;More recently, the “&lt;i&gt;CAVARLY trial&lt;/i&gt;” has demonstrated the superiority of the combination therapy (VBL-NSBB) to either strategy alone in preventing the first AVB in dACLD patients with high-risk varices [&lt;span&gt;2&lt;/span&gt;]. Interestingly, an elevated rate of events in the carvedilol arm (33.6%) was reported, and, notably, over half of the patients did not show a haemodynamic NSBB response [&lt;span&gt;2&lt;/span&gt;].&lt;/p&gt;\u0000&lt;p&gt;Unlike previous historical research [&lt;span&gt;3&lt;/span&gt;], in this trial, a significant proportion (~50%) of enrolled patients presented Metabolic dysfunction-Associated Steatotic Liver Disease (MASLD)-related cirrhosis, providing an updated snapshot of the current chronic liver disease (CLD) epidemiology.&lt;/p&gt;\u0000&lt;p&gt;Relevantly, type 2 diabetes mellitus (T2DM) and obesity have already been demonstrated to impair the haemodynamic response to NSBB, thus predisposing to overall hepatic decompensation [&lt;span&gt;4, 5&lt;/span&gt;]. However, the impact of CLD aetiology on first AVB remains unexplored in dACLD patients.&lt;/p&gt;\u0000&lt;p&gt;From July 2022 to April 2024, we consecutively enrolled and followed over 12 months, 76 (35 viral-related and 41 MASD-related) dACLD individuals presenting high-risk varices (IRB-prot0021377/i). Patients received carvedilol-based primary prophylaxis (32 MASLD; 28 viral-related), reserving VBL for NSBB-intolerant subjects (9 MASLD; 7 viral-related) [&lt;span&gt;6&lt;/span&gt;]. As in “&lt;i&gt;CAVARLY&lt;/i&gt;”, NSBB compliance was self-monitored by arterial pressure measurements and a diary.&lt;/p&gt;\u0000&lt;p&gt;A significantly higher rate of AVB was observed in MASLD compared to the viral-related group (HR: 2.806, &lt;i&gt;p&lt;/i&gt;: 0.027), specifically in the carvedilol-receiving patients. Interestingly, the Cox regression analysis (adjusted for sex, age, Child-Pugh, BMI, and endoscopic varices features) revealed T2DM (aHR: 2.541, &lt;i&gt;p&lt;/i&gt;: 0.001), Homeostasis Model Assessment for Insulin Resistance (aHR: 2.112, &lt;i&gt;p&lt;/i&gt; &lt; 0.0001), obesity (aHR: 1.781, &lt;i&gt;p&lt;/i&gt;: 0.002), and C-reactive protein (aHR: 1.72, &lt;i&gt;p&lt;/i&gt;: 0.001) as the variables significantly associated with this outcome (Figure 1).&lt;/p&gt;\u0000&lt;figure&gt;&lt;picture&gt;\u0000&lt;source media=\"(min-width: 1650px)\" srcset=\"/cms","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"10 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143940265","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: Selective FGFR1c/KLB Activation in MASH—A Mechanistic Dilemma?","authors":"Cuiyun Tao, Ye Liang, Jianghui Zeng","doi":"10.1111/apt.70166","DOIUrl":"https://doi.org/10.1111/apt.70166","url":null,"abstract":"<p>The Phase 2b trial of MK-3655 (NCT04583423) provides critical insights into fibroblast growth factor 21 (FGF21) pathway modulation, yet raises fundamental questions about therapeutic targeting strategies [<span>1</span>]. While the reported 26.1% placebo-adjusted liver fat reduction at 300 mg (<i>p</i> &lt; 0.05) aligns with early-phase FGF21 analogs [<span>2</span>], it falls substantially below the ≥ 40% reductions seen with efruxifermin [<span>3</span>] and pegozafermin [<span>4</span>] in comparable populations. This discrepancy underscores a key mechanistic consideration: does selective FGFR1c/KLB activation sufficiently replicate FGF21's pleiotropic effects?</p>\u0000<p>The trial's early termination limits histological interpretation, but the 17.6% MASH resolution rate at 300 mg versus 5.9% placebo (<i>p</i> = NS) suggests partial biological activity. However, the modest efficacy contrasts with dual FGFR1c/2c/3c activators showing 24%–26% MASH resolution rates [<span>3, 4</span>]. Preclinical models indicate FGFR1 primarily mediates metabolic effects through adipose tissue [<span>5</span>], but human data now suggest broader receptor engagement may be necessary for optimal hepatoprotection. This aligns with the 48% greater LFC reduction seen with pan-FGFR activator pegozafermin [<span>3</span>] versus MK-3655.</p>\u0000<p>The safety profile merits attention. While MK-3655 showed fewer gastrointestinal events than FGF21 analogs [<span>3, 4</span>], its 2.2%–4.3% blood pressure elevation mirrors class effects observed in SYMMETRY trial [<span>6</span>]. Paradoxical weight gain (+1.2 kg vs. placebo) contrasts with FGF21's catabolic profile, potentially reflecting incomplete β-Klotho receptor engagement or compensatory mechanisms.</p>\u0000<p>This study crucially demonstrates that isolated FGFR1c activation achieves a partial therapeutic effect, challenging the sufficiency of ‘adipose-first’ strategies in MASH. Future development should explore whether multi-receptor agonists or combination therapies can optimise metabolic-liver crosstalk while maintaining favourable safety profiles.</p>","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"39 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143926637","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: Crohn's Disease With Latent Tuberculosis Infection or Intestinal Tuberculosis: Rapid Discrimination by Targeted Next-Generation Sequencing","authors":"Maryam Irshad, Shahzeen Irshad","doi":"10.1111/apt.70152","DOIUrl":"https://doi.org/10.1111/apt.70152","url":null,"abstract":"&lt;p&gt;We read with interest the study by Ye et al. [&lt;span&gt;1&lt;/span&gt;]. The authors demonstrated that targeted next-generation sequencing (tNGS) has high sensitivity (83%) and 100% specificity for detecting &lt;i&gt;Mycobacterium tuberculosis&lt;/i&gt; from fresh ulcer base biopsy samples, offering an alternative to conventional methods like acid-fast bacillus staining, TB-PCR, and histopathological examination. Given the diagnostic challenges in tuberculosis-endemic regions, this represents a potentially significant advancement in clinical gastroenterology.&lt;/p&gt;\u0000&lt;p&gt;The novelty of the study represents promising findings, but there are limitations.&lt;/p&gt;\u0000&lt;p&gt;First, the study was restricted to patients with positive Interferon Gamma Release Assay (IGRA) results. Since IGRA can yield false-negative results, especially in immunocompromised patients, this selection criterion may have excluded some patients with intestinal tuberculosis (ITB), thereby limiting generalizability [&lt;span&gt;2&lt;/span&gt;].&lt;/p&gt;\u0000&lt;p&gt;Second, the test missed 17% of true ITB cases. The authors attributed this to a low bacterial load in biopsy samples. However, particular patient-based factors such as immune suppression, prior antibiotic use, and variation in granuloma formation might also have played a role in the lower detection rate.&lt;/p&gt;\u0000&lt;p&gt;Third, the study was performed at a single institution and the sample size was small. These restrict the generalisability of the results as the specificity and sensitivity of a diagnosis may vary with respect to population, healthcare setting and endemic region. These factors may significantly influence the performance of tNGS, including variation of TB strain types, host immune responses and healthcare infrastructure. To establish such results prior to impulsive concretising of clinical use, a multicentre validation study with diverse patient cohorts and under diverse laboratory conditions would be necessary.&lt;/p&gt;\u0000&lt;p&gt;Although tNGS performs better than some conventional tests, the absence of the gold standard of TB culture limits direct comparison [&lt;span&gt;3&lt;/span&gt;]. Its real-life benefits are unknown without head-to-head assessments against diagnostics such as Xpert MTB/RIF (Xpert &lt;i&gt;M. tuberculosis&lt;/i&gt;/rifampicin) assay, a nucleic acid amplification test endorsed by the World Health Organization for detecting &lt;i&gt;M. tuberculosis&lt;/i&gt; complex and resistance to rifampicin in under 2 h [&lt;span&gt;4&lt;/span&gt;]. Moreover, histopathological data would be nullable, if based on biopsies performed on ulcer bases, which are very much subject to sampling error given the variable distribution of pathogens and difficulties in obtaining fresh tissue. Additional studies are needed to investigate whether larger numbers of biopsy sites or broader approaches to molecular techniques would increase sensitivity and feasibility.&lt;/p&gt;\u0000&lt;p&gt;In summary, while Ye et al. have provided meaningful insights into the potential of tNGS for rapidly distinguishing ITB from Crohn's disease with latent tuberculosis inf","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"7 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143926635","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: Are Antispasmodics Truly Ineffective in IBD? Considerations on Nuanced Interpretation and Stratified Analysis","authors":"Haoxun Mao, Sheng Li","doi":"10.1111/apt.70168","DOIUrl":"https://doi.org/10.1111/apt.70168","url":null,"abstract":"","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"228 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143920320","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: Are Antispasmodics Truly Ineffective in IBD? Considerations on Nuanced Interpretation and Stratified Analysis. Authors' Reply","authors":"Chachrit Khunsriraksakul, Olivia Ziegler, Dajiang Liu, Audrey S. Kulaylat, Matthew D. Coates","doi":"10.1111/apt.70186","DOIUrl":"https://doi.org/10.1111/apt.70186","url":null,"abstract":"&lt;p&gt;We appreciate the opportunity to respond to the comments submitted by Mao et al. [&lt;span&gt;1&lt;/span&gt;] relating to our article [&lt;span&gt;2&lt;/span&gt;]. They provided thoughtful commentary about the strengths and weaknesses of our study, and we agree with several concerns and recommendations that they shared. For example, they highlighted the potential limitations of relying upon ICD-10 codes to assess the abdominal pain status of each patient, including the lack of ‘granularity’ in data related to pain severity, frequency and chronicity. Mao et al. also pointed out that this investigation was not able to necessarily discern between individuals with quiescent or active inflammatory bowel disease (IBD), and appropriately concluded that this made it difficult to determine why patients in this study were receiving antispasmodics, and whether particular sub-cohorts (e.g., those with quiescent IBD and concomitant irritable bowel syndrome (IBS)) would demonstrate better outcomes after receiving these therapies. Additionally, they noted that almost two thirds of the patients included in our study did not report a racial identity. They also mentioned that there was a lack of information about participant socioeconomic status and education level. We appreciate all of these criticisms, and agree that they are all worthy of consideration. Indeed, as stated in our Discussion, there are important issues directly related to the use of retrospectively abstracted claims data that limit the inferences that can be made about this topic. In our Conclusions, we advocated for follow-on prospective studies to help address the limitations noted above.&lt;/p&gt;\u0000&lt;p&gt;Despite these concerns, we believe this study is important for several reasons. It is the first large-scale study investigating the clinical impact of antispasmodics in IBD. While there were potential limitations related to data type and quality, the database utilised has served as one of the largest and most comprehensive sources of information in the world for population-based studies and includes data from a wide variety of healthcare centres located around the world [&lt;span&gt;3&lt;/span&gt;]. Thus, it is likely that the associated study cohort provided a ‘real-world’ assessment of antispasmodic provision and its impact in IBD. As stated above, Mao et al. suggested that antispasmodic use is more likely to be successful in patients with quiescent IBD who exhibit visceral hypersensitivity or IBS. It is important to note that there is no definitive evidence in IBD to support this statement. This is, in fact, one of the reasons we undertook this study. However, even if that statement is eventually determined to be accurate, previous investigations demonstrate that, when healthcare providers believe that patients with IBD are in remission, many harbour unrecognised inflammation and other factors (unrelated to IBS or visceral hypersensitivity) that may contribute to abdominal pain [&lt;span&gt;4, 5&lt;/span&gt;]. Thus, identifying the optimal targe","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"3 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143920814","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":"Diabetes Mellitus in Patients With Autoimmune Hepatitis: Frequency, Risk Factors and Effect on Outcome","authors":"Sarah Flatley, Selena Dixon, Eleanor Pilsworth, Asha Dube, Barbara Hoeroldt, Laura Harrison, Dermot Gleeson","doi":"10.1111/apt.70188","DOIUrl":"https://doi.org/10.1111/apt.70188","url":null,"abstract":"BackgroundTreatment for autoimmune hepatitis (AIH) includes corticosteroids, which are associated with the development of diabetes mellitus (DM). Reported new‐onset DM rates in patients with AIH have varied, and predisposing factors and prognostic implications are inadequately characterised.AimTo identify the frequency and predisposing factors for DM in AIH and its association with disease progression and mortality.MethodsRetrospective/prospective single‐centre study of 494 patients with AIH presenting 1987–2023, 466 receiving corticosteroids (454 prednisolone, 12 budesonide) and followed for (median (range) 9 (0–36) years).ResultsForty‐seven patients (10%) already had DM at AIH diagnosis. New‐onset DM subsequently developed in another 59 (13%). In those receiving prednisolone, new‐onset DM incidence was 8% ± 1% after 1 year and 14% ± 2% after 10 years (14‐ and 3‐fold higher than expected population rate), and was independently associated with older age, non‐Caucasian ethnicity, higher initial prednisolone dose, higher BMI at diagnosis and more weight gain after 2 years of follow‐up. New‐onset DM usually persisted despite stopping prednisolone.New‐onset DM and DM at any time were independently associated with all‐cause death/transplantation rate, along with previously established risk factors (older age, cirrhosis, lower ALT at diagnosis and failure of early ALT normalisation). New‐onset DM and DM at any time were also independently associated with cirrhosis development. Similar associations of new‐onset DM and DM at any time with liver‐related death/transplantation were significant on univariate but not multivariate analysis.ConclusionNew‐onset DM occurred in 13% of patients with AIH, was related to older age, non‐Caucasian ethnicity, higher prednisolone dose, higher BMI at diagnosis and weight gain; and was an independent predictor of all‐cause death/transplantation and of cirrhosis development, underlining the need to minimise steroid burden in AIH.","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"20 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143920319","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: Is Enteric Neuropathy Absent in Hypermobility Spectrum Disorders/Hypermobile Ehlers-Danlos Syndrome?","authors":"Caitlin Green,&nbsp;Anne Maitland,&nbsp;Steven A. Kautz,&nbsp;Russell Norris,&nbsp;Sunil Patel,&nbsp;Amol Sharma","doi":"10.1111/apt.70142","DOIUrl":"10.1111/apt.70142","url":null,"abstract":"&lt;p&gt;We commend Sweerts et al. for their largest-to-date investigation using antroduodenal manometry (ADM) in 50 patients with hypermobility spectrum disorders (HSD) and hypermobile Ehler-Danlos Syndrome (hEDS) compared to 189 non-HSD/hEDS patients [&lt;span&gt;1&lt;/span&gt;]. ADM, a labour-intensive and technically challenging procedure, comes the closest to the gold standard of histopathological evaluation of full-thickness tissue specimens for diagnosing enteric myopathy or neuropathy. Key findings of the study were similar rates of antroduodenal dysmotility and delayed gastric emptying, but less enteric dysmotility in HSD/hEDS patients. As discussed, malnutrition was highly prevalent with 76% of HSD/hEDS patients receiving enteral (62%) or parenteral (13%) support. In contrast, the non-HSD/hEDS comparator group had nearly double the proportion of patients not receiving enteral or parenteral nutrition, suggesting differences in meal tolerability. The ADM protocol employed in this study only allowed a ‘one shot’ assessment of enteric function via a single meal. While logistical and technical challenges exist, 24-h recordings present more opportunities to detect enteric motility between meals, in response to multiple meals, in response to a non-meal stimulus through promotility agents, and diurnal variation [&lt;span&gt;2&lt;/span&gt;]. The conclusion of a lower prevalence of enteric dysmotility in the HSD/hEDS cohort based on a single meal challenge in patients with poor meal tolerability during ADM may be premature.&lt;/p&gt;&lt;p&gt;Delayed gastric emptying was present in 85% of the HSD/hEDS cohort. While validated symptom scores for gastroparesis and/or functional dyspepsia were not captured, the corresponding predominant symptom was a cardinal gastroparesis symptom in most patients (nausea/vomiting &gt; 50% and abdominal pain and excessive fullness ~25% of HSD/hEDS group), projected to meet diagnostic criteria for gastroparesis. In gastroparesis overall (i.e., not limited to HSD/hEDS), constipation remains understudied and poorly understood from a pathophysiological standpoint. Fifty-eight percent of patients with gastroparesis have moderate to very severe constipation, and the severity of constipation symptoms correlates with the severity of gastroparesis symptoms [&lt;span&gt;3&lt;/span&gt;]. Based on our clinical observations and the lack of use of a prospective stool diary in this study, constipation was probably underreported by HSD/hEDS participants. Underlying rectal evacuation disorders are key drivers of pathophysiology in severe constipation and are present in 60%–75% of patients with HSD/hEDS undergoing anorectal manometry [&lt;span&gt;4, 5&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;While the prevalence of enteric dysmotility or neuropathy in HSD/hEDS remains unclear, more than half of HSD/hEDS patients have associated postural orthostatic tachycardia syndrome and dysautonomia [&lt;span&gt;6&lt;/span&gt;]. Transauricular vagal nerve stimulation targeting dysautonomia is promising for functional dyspepsia, also highly preva","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"61 11","pages":"1843-1844"},"PeriodicalIF":6.6,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apt.70142","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143915079","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: Is Enteric Neuropathy Absent in Hypermobility Spectrum Disorders/Hypermobile Ehler–Danlos Syndrome? Authors' Reply","authors":"Kim W. E. Sweerts,&nbsp;Zlatan Mujagic,&nbsp;Daniel Keszthelyi,&nbsp;José M. Conchillo","doi":"10.1111/apt.70157","DOIUrl":"10.1111/apt.70157","url":null,"abstract":"<p>We appreciate the interest and comments of Dr. Green and colleagues on our article about antroduodenal motility in patients with hypermobility spectrum disorders/hypermobile Ehlers–Danlos syndrome (HSD/hEDS) [<span>1, 2</span>].</p><p>They commented on the high frequency of food intolerance in the HSD/hEDS population resulting in a high prevalence of enteral and parenteral feeding, and the possible role of enteric dysmotility regarding this problem. Enteric dysmotility is often thought to be the underlying cause of food intolerance. However, in our study, enteric dysmotility was present less often (but not entirely absent) in the HSD/hEDS group with gastrointestinal symptoms compared to the control group despite the greater need for enteral/parenteral nutrition in the HSD/hEDS group.</p><p>Regarding the duration of antroduodenal manometry (ADM) protocols, we also see the added value of 24-h recordings. However, given the invasive nature and feasibility of 24-h measurements, we also see major challenges. Furthermore, two recent studies showed that shorter ADM studies of 4 or 7.5 h are reliable for evaluation of enteric motility [<span>3, 4</span>].</p><p>Our findings suggest that enteric dysmotility is not the main cause for gastrointestinal complaints in the HSD/hEDS population. A broader view on the pathophysiological mechanism underlying gastrointestinal symptoms in HSD/hEDS patients is necessary. Visceral hypersensitivity should be explored further in this context: it is well described in relation to disorders of gut-brain interaction and contributes significantly to symptom generation in response to normal physiological stimuli, such as food [<span>5</span>]. This phenomenon can be translated to patients with HSD/hEDS, who can exhibit characteristics of central sensitisation and enhanced pain perception, possibly linked to autonomic dysfunction [<span>6</span>]. Additionally, dietary habits and psychological comorbidities including disordered eating must be included in this broader framework because psychiatric problems such as eating disorders are not uncommon within the HSD/hEDS population [<span>7, 8</span>].</p><p>In conclusion, we agree that further research is warranted to elucidate the gastrointestinal manifestations of HSD/hEDS, with particular emphasis on food intolerances. However, we advocate for a more comprehensive approach that addresses gastric and enteric dysmotility but also encompasses factors such as visceral hypersensitivity, autonomic dysfunction, dietary habits and psychological factors.</p><p><b>Kim W. E. Sweerts:</b> writing – original draft. <b>Zlatan Mujagic:</b> writing – review and editing. <b>Daniel Keszthelyi:</b> writing – review and editing. <b>José M. Conchillo:</b> writing – review and editing.</p><p>This article is linked to Sweerts et al. paper. To view this article, visit, https://doi.org/10.1111/apt.18471 and https://doi.org/10.1111/apt.70142.</p>","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"61 11","pages":"1845-1846"},"PeriodicalIF":6.6,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apt.70157","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143915078","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":"The Effectiveness of Medical Therapies for Joint, Skin and Eye Extraintestinal Manifestations in IBD—An Umbrella Review","authors":"Olga M. Nardone,&nbsp;Nurulamin M. Noor,&nbsp;Aniruddh Prabhu,&nbsp;Alessandra Lim,&nbsp;Anirudh Krishnakumar,&nbsp;Abdulaziz Alajmi,&nbsp;Yuhong Yuan,&nbsp;Vipul Jairath,&nbsp;Maria Manuela Estevinho,&nbsp;Virginia Solitano","doi":"10.1111/apt.70181","DOIUrl":"10.1111/apt.70181","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Extraintestinal manifestations (EIMs) occur commonly in patients with inflammatory bowel disease (IBD), affecting joints, skin, eyes and other organs, and contributing to morbidity and long-term disability.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>To synthesise evidence from systematic reviews (SRs) on the effectiveness and safety of medical treatments for IBD EIMs in IBD of joints, skin and eyes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>For this umbrella review, we searched three databases for relevant SRs published until May 30, 2024. Two independent reviewers performed screening, data extraction and quality appraisal (AMSTAR-2).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Ten, 12 and six SRs, respectively, provided data on medical therapies for articular, dermatological and ocular manifestations. Anti-TNF therapy showed high response rates for axial (59.1%–61.8%) and peripheral arthritis (73.4%–81.2%). The lowest improvement was in patients treated with vedolizumab for joint manifestations. Ustekinumab was effective for arthralgia and psoriatic arthritis, but not for axial spondylarthritis. High heterogeneity of response was reported for anti-TNF, vedolizumab, ustekinumab and tofacitinib (21%–100%) depending on the dermatological manifestation. No SRs evaluated IL-23 p40 antagonists or other oral small molecules. The incidence of new ocular EIMs was 1% for vedolizumab and ustekinumab. Anti-TNF agents were effective for most ocular EIM cases. Ustekinumab improved ocular symptoms in 55%–59%. Safety data were limited, with evidence certainty ranging from moderate to low.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Evidence for medical therapies for joint, skin and eye EIMs in IBD is heterogeneous and of low quality. Further research is needed, including a multidisciplinary approach and novel and practical methods for endpoint evaluation.</p>\u0000 </section>\u0000 </div>","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"61 12","pages":"1854-1871"},"PeriodicalIF":6.6,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apt.70181","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143915186","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}