Alimentary Pharmacology & Therapeutics最新文献

{"title":"Editorial: Association of Antibiotic Exposure With Microscopic Colitis—Authors' Reply","authors":"Máté Szilcz, Jonas W. Wastesson, David Bergman, Kristina Johnell, Jonas F. Ludvigsson","doi":"10.1111/apt.70056","DOIUrl":"10.1111/apt.70056","url":null,"abstract":"<p>We thank Drs. Tome and Pardi for their editorial on our study examining the association between antibiotic exposure and microscopic colitis (MC) [<span>1</span>]. We appreciate their careful literature review and insightful discussion regarding potential confounding factors that may influence the observed relationship between drug exposures and MC.</p><p>As the editorial highlighted, studies investigating medications associated with MC have consistently encountered challenges in disentangling causation from confounding. We aimed to address this through a self-controlled design [<span>2</span>], in which cases acted as their own controls, thereby mitigating important confounders, such as genetic predisposition, that are difficult to account for in traditional cohort studies [<span>3</span>]. In studies where external controls are necessary, matching by clinical characteristics and healthcare engagement patterns can further reduce confounding, thereby strengthening causal inference. However, we acknowledge that detection bias remains a consideration. Patients experiencing gastrointestinal symptoms on certain medications (e.g., antibiotics) may be more likely to undergo endoscopic evaluation, thereby increasing MC detection.</p><p>Medication exposures often occur in combination, particularly in older adults. These combinations (e.g., antibiotics combined with non-steroidal anti-inflammatory drugs or proton pump inhibitors) may amplify gastrointestinal side effects. The interplay of multiple drugs further complicates the challenge of establishing a direct causal link between any single medication and MC. Future research should investigate the impact of polypharmacy on MC incidence and severity, ideally through prospective, longitudinal studies with a rigorous selection of control groups.</p><p>Looking ahead, comprehensive studies are needed to understand how various drugs alter the intestinal environment, contributing to MC development. One potential option is investigating the gut microbiome's role and how antibiotic-induced dysbiosis may prime the colonic mucosa for an aberrant immune response. Incorporating stool metagenomics, mucosal immunologic markers, and detailed pharmacokinetic/pharmacodynamic data into prospective studies could provide crucial insights into the pathophysiology of MC. Such investigations may pave the way for precision medicine approaches, enabling targeted interventions based on microbiome profiles, immune pathways, or genetic predispositions to prevent or mitigate MC in high-risk individuals [<span>4</span>].</p><p>Large-scale data analyses using real-world evidence and electronic health record-based pharmacoepidemiologic studies could help to identify at-risk subgroups effectively. This might include older adults with multiple comorbidities, individuals with specific genetic or immune backgrounds, or patients requiring complex drug regimens. By leveraging big data analytics, future research could move beyond broad assoc","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"61 9","pages":"1549-1550"},"PeriodicalIF":6.6,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apt.70056","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143485872","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: Lipidomics in MASLD and MetALD—Authors' Reply","authors":"Kai Markus Schneider, Carolin V. Schneider","doi":"10.1111/apt.70058","DOIUrl":"10.1111/apt.70058","url":null,"abstract":"<p>We appreciate the insightful editorial [<span>1</span>] highlighting the significance of our lipidomic findings for detecting higher alcohol consumption in steatotic liver disease (SLD) [<span>2</span>]. When looking at SLD on a population level, one key challenge is that MetALD remains so rare that it is likely underreported [<span>3</span>]. This raises concerns about misclassification, particularly in cohorts relying on self-reported alcohol intake [<span>4</span>]. Biomarkers such as carbohydrate-deficient transferrin (CDT) in serum or ethylglucuronid (ETG) may serve as objective measures of alcohol intake and could be particularly useful in individuals with advanced SLD [<span>5</span>], where accurate assessment of alcohol exposure is crucial for prognosis and management. While previous studies have demonstrated the utility of CDT in detecting chronic alcohol consumption, its role in distinguishing moderate drinkers from those with excessive intake in the setting of SLD remains uncertain [<span>6</span>].</p><p>HDL might be a starting point to differentiate MASLD from MetALD but, while lipidomics has provided key discriminatory markers, the next logical step is integrating proteomics to refine the distinction between these subtypes further. Beyond biochemical markers, the interaction between alcohol intake in SLD and emerging pharmacological interventions remains an area of critical importance. With the advent of novel therapies for MASLD/MASH, including Resmetirom [<span>7</span>], GLP-1 receptor agonists [<span>8</span>] and agents targeting relevant metabolic pathways, for example, FGF21 [<span>9</span>], their potential interaction with alcohol metabolism warrants further scrutiny. Additionally, the interplay between lifestyle factors, genetic risk variants and alcohol consumption remains poorly understood. Given that alcohol intake is highly variable across populations, differs over time and is influenced by socioeconomic, cultural and behavioural factors, future studies should aim to integrate multiomic data, including lipidomics, proteomics and metabolomics, to dissect these complex interactions.</p><p>Moving forward, a comprehensive approach combining lipidomics, proteomics and metabolomics will be essential to uncover non-linear relationships that may remain hidden when analysing a single omics layer. We propose developing a multi-omics-based score to differentiate MASLD and MetALD more effectively, ultimately aiding in personalised risk assessment and therapeutic decisions.</p><p>Lastly, lipidomic differences between MASLD and MetALD further validate the new nomenclature's attempt to differentiate subgroups within SLD [<span>10</span>]. The distinct lipid profiles observed in MetALD—particularly the elevation of HDL-centric lipidomic markers and ketone body metabolites—suggest that these two entities are biologically distinct rather than merely reflecting a continuum of alcohol exposure. This supports the concept that the class","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"61 8","pages":"1410-1411"},"PeriodicalIF":6.6,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apt.70058","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143477833","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: Early Ileal Resection in Crohn's Disease Is Not Associated With Severe Long-Term Outcomes: The ERIC Study: Authors' Reply","authors":"Nathan Grellier, Julien Kirchgesner, Philippe Seksik","doi":"10.1111/apt.70052","DOIUrl":"10.1111/apt.70052","url":null,"abstract":"<p>We thank Drs. Kelm and Flemming for their insightful letter [<span>1</span>] regarding our article [<span>2</span>]. We appreciate their remarks and would like to address their questions.</p><p>First, we would like to clarify a crucial point regarding our findings in relation to the primary outcome. Contrary to what Drs. Kelm and Flemming suggested, we found no statistically significant difference between the early resection group (< 6 months) and the other groups (6 months–2 years and 2–5 years) for the risk of a second ileocecal resection. However, patients who underwent early ileocecal resection required fewer post-operative treatments and demonstrated less morphological recurrence, supporting early resection as an effective treatment to maintain remission.</p><p>Second, accumulating evidence supports early ileocecal resection as a valuable approach for maintaining long-term remission in Crohn's disease isolated to the terminal ileum [<span>3</span>]. The challenge lies in identifying a safe approach that minimises recurrence risk while potentially reducing the need for subsequent immunosuppressive therapies. However, the key issue remains the stratification of recurrence risk and the selection of optimal surgical candidates.</p><p>The two centres involved in our study conduct weekly multidisciplinary IBD board meetings. Decisions regarding surgery for patients with IBD were always preceded by these discussions. Addressing the question regarding decision-making criteria for surgery versus advanced therapy is challenging in a retrospective setting. However, considering surgical indications, 95% of patients in the early resection group had complicated disease, compared to 82% in the late resection group. This suggests that patients who had early resection underwent surgery primarily out of necessity due to abscess or obstruction. These surgeries took place before the LIRIC trial, which later established laparoscopic ileocecal resection as a viable option for uncomplicated localised ileal Crohn's disease. In addition, the use of advanced therapies for complicated diseases was less standardised in the study period than it is today [<span>4, 5</span>].</p><p>As pointed out, we did not report perioperative morbidity or the potential impact of surgery on quality of life and post-operative digestive symptoms. These limitations are due to the retrospective nature of our study. Data in the immediate post-operative period were not collected comprehensively, and quality of life was not assessed systematically, particularly for patients who underwent surgery in the early 2000s. We acknowledge that surgery should only be considered when it is safe and associated with minimal adverse outcomes [<span>6</span>]. The main challenge for future studies will be to identify predictors of optimal quality of life after ileocecal resection, and the timing of surgery may be an important factor to consider. It remains to be addressed which patients will benefit mo","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"61 7","pages":"1262-1263"},"PeriodicalIF":6.6,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apt.70052","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143477869","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":"Meta-Analysis: Inverse Association Between Helicobacter pylori Infection and Eosinophilic Oesophagitis","authors":"Irene Spinelli,&nbsp;Serena Porcari,&nbsp;Chiara Esposito,&nbsp;William Fusco,&nbsp;Francesca Romana Ponziani,&nbsp;Cristiano Caruso,&nbsp;Edoardo Vincenzo Savarino,&nbsp;Antonio Gasbarrini,&nbsp;Giovanni Cammarota,&nbsp;Marcello Maida,&nbsp;Antonio Facciorusso,&nbsp;Gianluca Ianiro","doi":"10.1111/apt.70042","DOIUrl":"10.1111/apt.70042","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Exposure to <i>Helicobacter pylori</i> (<i>H. pylori</i>) has been associated with a decreased risk of eosinophilic oesophagitis (EoE).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>The aim of this study is to determine the association between <i>H. pylori</i> infection and EoE in this updated meta-analysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We searched MEDLINE, Scopus and ISI Web of Science, through to November 2024. We included studies reporting the status of <i>H. pylori</i> infection in patients with and without EoE or oesophageal eosinophilia (EE). We used a random-effects model to pool estimates.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We analysed 19 studies including 1.704.821 subjects. <i>H. pylori</i> infection was associated with a 46% lower risk of EoE/EE (OR: 0.54, 95% CI 0.43 to 0.67). Comparable findings were observed when subgrouping studies by location or design. There was a nonsignificant decrease in odds for EoE in paediatric patients exposed to <i>H. pylori</i> (OR 0.57, 95% CI 0.26 to 1.24), and in studies using serology to diagnose <i>H. pylori</i> (OR: 0.41, 95% CI 0.16 to 1.04). We found lower odds of EoE compared with the overall findings in studies that diagnosed <i>H. pylori</i> only by gastric biopsy (OR 0.43, 95% CI 0.25 to 0.74) and in those published after 2019 (OR 0.44, 95% CI 0.28 to 0.68).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Exposure to <i>H. pylori</i> was significantly associated with decreased odds of EoE/EE. As a stronger protective effect was found in more recent studies, the epidemiology of this association may evolve and deserve to be further monitored.</p>\u0000 </section>\u0000 </div>","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"61 7","pages":"1096-1109"},"PeriodicalIF":6.6,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apt.70042","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143477837","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: Lipidomics in MASLD and MetALD","authors":"Rajalakshmi Govalan,&nbsp;Vincent L. Chen","doi":"10.1111/apt.70047","DOIUrl":"10.1111/apt.70047","url":null,"abstract":"&lt;p&gt;Steatotic liver disease (SLD) includes the subtypes of metabolic dysfunction-associated steatotic liver disease (MASLD) and MASLD and increased alcohol intake (MetALD) [&lt;span&gt;1&lt;/span&gt;]. Differentiating MASLD from MetALD is crucial because of their distinct prognoses and management strategies [&lt;span&gt;2-4&lt;/span&gt;]. Advancements in the omics landscape—such as genomics, proteomics and metabolomics—may enhance our understanding of steatotic liver diseases [&lt;span&gt;5&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;Schneider et al. explored lipidomic differences between MASLD and MetALD using the UK Biobank to identify lipidomic biomarkers to reliably distinguish these two steatotic liver disease phenotypes [&lt;span&gt;6&lt;/span&gt;]. They analysed data from 40,534 individuals with magnetic resonance imaging (MRI) liver scans, of whom 11,217 had SLD, as well as detailed data on alcohol consumption and cardiometabolic comorbidities. Among these participants, nuclear magnetic resonance spectroscopy lipidomic profiles were available for 6055 cases (5539 MASLD, 462 MetALD and 53 alcohol-related liver disease), and the authors examined 250 plasma lipidomic and metabolomic parameters. MetALD participants had significantly elevated high-density lipoprotein (HDL)-centric lipidomic markers compared with MASLD, and other top discriminatory metabolites include acetoacetate, 3-hydroxybutyrate, apolipoprotein A1 and phosphatidylcholines. These markers exhibited a stable association with alcohol consumption during their sensitivity analysis, and Mendelian randomisation identified a causal relationship between alcohol consumption and levels of several of these metabolites.&lt;/p&gt;&lt;p&gt;This study utilised a large cohort with well-characterised liver phenotypes and a comprehensive array of lipidomic and metabolomic biomarkers. Furthermore, Mendelian randomisation offers a robust approach to infer causal relationships, mitigating biases often seen in observational studies, lending credence to the argument that alcohol consumption distinctly alters lipid profiles. The study is not without limitations. There was a temporal disconnect between the lipidomic data collection and liver MRI scans. In UK Biobank, lipidomic specimens were nearly all collected in 2006–2010 (some were collected in 2012–2013), whereas MRI scans were done in 2014 or later. This potentially obscures the temporal dynamics of lipid changes. The authors attempted to mitigate this by performing a sensitivity analysis in the subset of participants with two metabolomic profiles to show that HDL profiles remained largely stable over time. Also, the study relies on self-reported alcohol consumption; alcohol biomarkers that distinguish MASLD and MetALD, as some of the authors of this study recently showed [&lt;span&gt;7&lt;/span&gt;], may serve as the basis for defining future MetALD cohorts. Finally, the cohort's predominantly European ancestry limits the generalisability of the findings to other populations.&lt;/p&gt;&lt;p&gt;The study highlights the complex link between alcohol co","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"61 8","pages":"1408-1409"},"PeriodicalIF":6.6,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apt.70047","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143477902","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: ‘Early Ileal Resection in Crohn's Disease Is Not Associated With Severe Long-Term Outcomes: The ERIC Study’","authors":"Matthias Kelm,&nbsp;Sven Flemming","doi":"10.1111/apt.70013","DOIUrl":"10.1111/apt.70013","url":null,"abstract":"&lt;p&gt;We read with interest the article by Grellier et al. [&lt;span&gt;1&lt;/span&gt;]. The authors clearly demonstrated that early surgical intervention is not only accompanied by significantly reduced rates of ileal re-resection, but also with reduced requirement for postoperative immunosuppressive therapy. In addition, the risk of morphological recurrence revealed by endoscopy or radiology was also significantly lower.&lt;/p&gt;&lt;p&gt;Based on these data, the study strongly strengthens the available evidence towards primary surgical therapy in patients suffering from complicated or uncomplicated (i.e., isolated) ileocecal Crohn's disease, in line with previously published prospective and retrospective data [&lt;span&gt;2-5&lt;/span&gt;]. Given this growing evidence, surgeons specialised in inflammatory bowel disease (IBD) need to advocate strongly for a primary surgical approach for patients with isolated ileocecal Crohn's disease. However, treatment strategies for patients with IBD are complex and include different specialties. Therefore, multidisciplinary IBD boards should always discuss individual treatment strategies. These boards comprising gastroenterologists, gastrointestinal surgeons, radiologists, pathologists and psychologists ensure that patients receive personalised and evidence-based therapy. It would be helpful if the authors could provide information about the use of IBD boards in the study before therapy was initiated and which criteria were used for decision-making to perform early or late resection. Furthermore, it would be interesting if there were any differences in short-term outcomes regarding postoperative morbidity.&lt;/p&gt;&lt;p&gt;From a surgical point of view, we would like to emphasise that all patients were operated on before 2012, where an open approach was more common than minimally invasive surgery. It can be presumed that, today, perioperative results of ileocecal resection would be even better with reduced morbidity, faster recovery and improved postoperative quality of life due to modern surgical and non-surgical approaches [&lt;span&gt;6&lt;/span&gt;]. In addition to these obvious therapeutic advantages for early surgery, evaluation of differences for therapeutic strategies regarding quality of life and healthcare-related costs should also be considered during short- and long-term follow-up. It would have been interesting to include patient aspects by collecting data about differences in quality of life since this is the most relevant patient-related outcome measure. Unfortunately, this very important issue is often neither the primary endpoint nor even reported in IBD-treatment studies.&lt;/p&gt;&lt;p&gt;In conclusion, we congratulate Grellier et al. for their study since the results improve our current evidence about primary treatment options in ileocecal Crohn's disease. However, despite growing evidence, there is still a great need for prospective, randomised studies respecting patient-centred outcome measures to ensure that all requirements of the complexity and heterogene","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"61 7","pages":"1260-1261"},"PeriodicalIF":6.6,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apt.70013","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143477834","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: Association of Antibiotic Exposure With Microscopic Colitis","authors":"June Tome,&nbsp;Darrell S. Pardi","doi":"10.1111/apt.70043","DOIUrl":"10.1111/apt.70043","url":null,"abstract":"&lt;p&gt;Soon after microscopic colitis (MC) was first described, reports emerged of cases that appeared to be due to the use of certain medications. As case reports accumulated, the topic gained further attention. At one point, a sophisticated imputation score was created in an attempt to assess the likelihood of causality of a particular drug or drug class as a cause of MC with the conclusion that eight drugs or drug classes had a high likelihood of inducing MC and seven had an intermediate risk [&lt;span&gt;1&lt;/span&gt;]. Combinations of these drugs, such as non-steroidal anti-inflammatory drugs (NSAIDs) together with proton pump inhibitors (PPIs), may exacerbate the risk [&lt;span&gt;2-4&lt;/span&gt;]. In addition to drug-induced MC scoring systems, various other clinical predictive models have been proposed to identify patients unlikely to have MC and in whom colon biopsies can potentially be avoided. More recently, immune checkpoint inhibitors used in oncology have also been associated with the development of MC [&lt;span&gt;5&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;A meta-analysis of 12 case–control studies demonstrated modest odds ratios suggesting that exposure to NSAIDs, PPIs, SSRIs and aspirin was associated with the incidence of MC [&lt;span&gt;6&lt;/span&gt;]. However, several studies evaluating this association demonstrated that the risk was significantly mitigated when controls with diarrhoea—rather than healthy subjects—were used for comparison [&lt;span&gt;7, 8&lt;/span&gt;] indicating that the association with some of these medications was not causative but, rather, due to the medications exacerbating diarrhoea and thereby bringing milder cases to medical attention.&lt;/p&gt;&lt;p&gt;Szilcz and colleagues have reported a modest association with antibiotic use and the development of MC in a large national case–control study of older adults in Sweden [&lt;span&gt;9&lt;/span&gt;]. To control for detection bias, they also performed an analysis of the association between antibiotic use and normal colon biopsies. In this control group, the association with antibiotic exposure was even stronger indicating that the observed association with MC was probably due to detection bias. Similar to the studies discussed above, these results reinforce the need to consider the control group when studying associations between drug exposure and the development of MC.&lt;/p&gt;&lt;p&gt;Therefore, accumulating evidence linking medication use to the development of MC indicates that the association for many drugs may be more confounded than causal [&lt;span&gt;10&lt;/span&gt;]. This observation has important implications for understanding the underlying pathophysiological mechanisms underpinning the development of MC. However, the implications for clinicians caring for these patients are less clear. Specifically, if a patient is being evaluated for diarrhoea, whether they have biopsy-proven MC or not, a careful review of their medication list, including over-the-counter medications, is essential. If any drug might be temporally associated with the onset of diarrhoea, consideration ","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"61 9","pages":"1547-1548"},"PeriodicalIF":6.6,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apt.70043","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143470475","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 Incident Type 2 Diabetes and Prediabetes in Patients With Direct Acting Antiviral-Induced Cure of Hepatitis C Virus Infection","authors":"Yu-Ping Chang,&nbsp;Ji-Yuh Lee,&nbsp;Chi-Yi Chen,&nbsp;Wei-Yu Kao,&nbsp;Chih-Lin Lin,&nbsp;Sheng-Shun Yang,&nbsp;Yu-Lueng Shih,&nbsp;Cheng-Yuan Peng,&nbsp;Fu-Jen Lee,&nbsp;Ming-Chang Tsai,&nbsp;Shang-Chin Huang,&nbsp;Tung-Hung Su,&nbsp;Tai-Chung Tseng,&nbsp;Chun-Jen Liu,&nbsp;Pei-Jer Chen,&nbsp;Jia-Horng Kao,&nbsp;Chen-Hua Liu","doi":"10.1111/apt.70029","DOIUrl":"10.1111/apt.70029","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Data regarding the risk of incident type 2 diabetes (T2D) and prediabetes among patients with hepatitis C virus (HCV) achieving direct-acting antivirals (DAAs)-induced sustained virologic response (SVR₁₂) remains limited.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A total of 1079 patients, including 589 with normoglycemia and 490 with prediabetes, who underwent biannual fasting glucose and glycosylated haemoglobin (HbA1c) assessment for a median post-SVR₁₂ follow-up of 5.5 years, were enrolled. We reported the crude (cIRs) and age-standardised incidence rates (ASIRs) of T2D and prediabetes. Factors associated with incident T2D and prediabetes were assessed using the Cox proportional hazards models.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The cIRs of T2D and prediabetes were 1.18 and 8.99 per 100 person-years of follow-up (PYFU), respectively. Additionally, the ASIRs of T2D and prediabetes were 1.09 (95% CI: 0.76–1.53) and 8.47 (95% CI: 7.23–9.90) per 100 PYFU. Prediabetes (adjusted hazard ratio [aHR]: 4.71; 95% confidence interval (CI): 2.55–8.70, <i>p</i> &lt; 0.001), body mass index (BMI) per kg/m² increase (aHR: 1.17; 95% CI: 1.09–1.26, <i>p</i> &lt; 0.001) and liver stiffness measurement (LSM) per kPa increase (aHR: 1.05; 95% CI: 1.02–1.09, <i>p</i> = 0.001) were associated with a higher risk of incident T2D. Age per year increase (aHR: 1.02; 95% CI: 1.01–1.03, <i>p</i> &lt; 0.001) was associated with a higher risk of incident prediabetes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The incidence rates of T2D and prediabetes remain substantial among patients after HCV eradication. Lifestyle modification, drug therapy and regular monitoring of glycemic status are crucial for patients at risk of developing T2D and prediabetes following HCV clearance.</p>\u0000 </section>\u0000 </div>","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"61 9","pages":"1508-1518"},"PeriodicalIF":6.6,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143463042","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: A Phase 2b Study to Evaluate the Efficacy and Safety of MK-3655 in Individuals With Pre-Cirrhotic MASH","authors":"Annaswamy Raji,&nbsp;Ira Gantz,&nbsp;Michael Crutchlow,&nbsp;Heather Flynn,&nbsp;Lianzhe Xu,&nbsp;Anthony J. Rodgers,&nbsp;Radha Krishnan,&nbsp;Matthew L. Rizk,&nbsp;Shuai Hu,&nbsp;Keith D. Kaufman,&nbsp;Samuel S. Engel,&nbsp;MK-3655 P001 Study Group","doi":"10.1111/apt.70038","DOIUrl":"10.1111/apt.70038","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Fibroblast growth factor 21 (FGF21) is a metabolic regulator with demonstrated efficacy for the treatment of metabolic dysfunction-associated steatohepatitis (MASH). FGF21 signals through ‘c’ isoforms of the FGF receptors (FGFR) 1–3 and the co-receptor β-klotho.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>We report the safety and efficacy of MK-3655, a monoclonal antibody that binds β-klotho and selectively activates the FGFR1c/β-klotho co-receptor complex, in patients with pre-cirrhotic MASH.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Phase 2b, randomised, multicenter, double-blind, placebo-controlled, parallel-group study in patients with pre-cirrhotic MASH (NAS ≥ 4 and MASH CRN fibrosis score Stage 2 or 3). Participants were randomised 1:1:1:1 to receive MK-3655 50 mg, 100 mg, 300 mg, or matching placebo subcutaneously every 4 weeks. The primary endpoint was MASH resolution without worsening of fibrosis by histology at Week 52. An interim analysis (IA) of liver fat content (LFC) was planned once ≥ 25 participants per treatment group completed an MRI-PDFF assessment at Week 24.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among 183 participants, mean BMI was 33.4 kg/m², mean LFC was 18.1%, and 52.5% had type 2 diabetes. At the IA, the differences from placebo in relative reduction from baseline in LFC were assessed as insufficient for continuation of the trial. Among participants with Week 24 LFC assessment, percent relative reductions from baseline (LS mean difference vs. placebo) for MK-3655 50 mg (<i>N</i> = 33), 100 mg (<i>N</i> = 36), and 300 mg (<i>N</i> = 31), were 19.1%, 19.0%, and 26.1%, respectively. MK-3655 was generally well tolerated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>In patients with pre-cirrhotic MASH, treatment with MK-3655 resulted in a modest reduction in LFC at 24 weeks.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Clinical Trial Number</h3>\u0000 \u0000 <p>EudraCT: 2019-003048-63; NCT: 04583423.</p>\u0000 </section>\u0000 </div>","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"61 7","pages":"1152-1162"},"PeriodicalIF":6.6,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apt.70038","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143470466","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":"Air Pollution Associated With Mortality Among Chronic Hepatitis B Patients Treated With Nucleotide/Nucleoside Analogues","authors":"Tyng-Yuan Jang,&nbsp;Yu-Ting Zeng,&nbsp;Po-Cheng Liang,&nbsp;Chih-Da Wu,&nbsp;Yu-Ju Wei,&nbsp;Pei-Chien Tsai,&nbsp;Ming-Yen Hsieh,&nbsp;Yi-Hung Lin,&nbsp;Meng-Hsuan Hsieh,&nbsp;Chih-Wen Wang,&nbsp;Jeng-Fu Yang,&nbsp;Ming-Lun Yeh,&nbsp;Chung-Feng Huang,&nbsp;Wan-Long Chuang,&nbsp;Jee-Fu Huang,&nbsp;Ya-Yun Cheng,&nbsp;Chia-Yen Dai,&nbsp;Pau-Chung Chen,&nbsp;Ming-Lung Yu","doi":"10.1111/apt.70019","DOIUrl":"10.1111/apt.70019","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aims</h3>\u0000 \u0000 <p>Air pollution is associated with advanced liver fibrosis in patients with chronic liver diseases, including chronic hepatitis B (CHB). This study aimed to investigate the association between air pollution and mortality in patients with CHB treated with nucleotide/nucleoside analogues.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We enrolled 697 patients with CHB treated with nucleotide/nucleoside analogues and analysed the incidence and risk factors for mortality. Daily air pollutant concentrations were estimated from the year before enrolment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>All-cause mortality showed an annual incidence of 1.1/100 person-years after a follow-up period of 3798.1 person-years. Factors with the strongest association with all-cause mortality were liver cirrhosis (hazard ratio [HR]/95% confidence interval [CI]: 3.95/1.69–9.23; <i>p</i> = 0.02), age ([HR]/CI: 1.07/1.03–1.17, <i>p</i> &lt; 0.001) and pre-treatment gamma-glutamyl transferase (GGT) levels (HR/CI: 1.004/1.001–1.006, <i>p</i> = 0.004). Among patients with cirrhosis, the factors associated with all-cause mortality were age (HR/CI: 1.08/1.04–1.12, <i>p</i> &lt; 0.001), pre-treatment GGT levels (HR/CI: 1.004/1.001–1.008, <i>p</i> = 0.01), platelet count (HR/CI: 0.988/0.977–0.998, <i>p</i> = 0.02) and NO_x concentration (per unit increment, ppb) (1.045/1.001–1.091; <i>p</i> = 0.046). The best NO_x cut-off value for predicting all-cause mortality in patients with cirrhosis was 25.5 ppb (AUROC 0.63; <i>p</i> = 0.03). NO_x levels &gt; 25.5 ppb were associated with a higher incidence of mortality in patients with cirrhosis (HR/CI:2.49/1.03–6.02; <i>p</i> = 0.04).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Air pollution influences all-cause mortality in patients with CHB receiving nucleotide/nucleoside analogue therapy. Long-term NO_x exposure may increase liver-related mortality in patients with chronic hepatitis B and cirrhosis receiving nucleotide/nucleoside analogue treatment.</p>\u0000 </section>\u0000 </div>","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"61 9","pages":"1458-1466"},"PeriodicalIF":6.6,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143447762","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}