Alimentary Pharmacology & Therapeutics最新文献

{"title":"Editorial: When and What to Ask—Capturing the Symptoms Experienced by Patients With PSC. Authors' Reply","authors":"Natassia Tan, Christopher Zampogna, Amanda J. Nicoll","doi":"10.1111/apt.70151","DOIUrl":"https://doi.org/10.1111/apt.70151","url":null,"abstract":"<p>We thank Professor Bowlus and Dr. Evon for their interest in our publication [<span>1</span>]. We agree that the development and validation of primary sclerosing cholangitis (PSC) specific patient reported outcome (PRO) measures are crucial as part of composite trial endpoints [<span>2</span>]. We are pleased that patient support organisations and academics are uniting to develop other PSC-specific PRO measures [<span>3, 4</span>], with further validation required to determine the best instrument for use in population-based studies and clinical trials [<span>5</span>].</p>\u0000<p>We took the opportunity to use the first validated PSC-PRO instrument by Younossi et al. [<span>6</span>] to describe PRO in an Australian cohort of participants with PSC, and as highlighted, participants overall reported low symptom scores in contrast with other studies [<span>1</span>]. This reflects the limitations of PSC-PRO, with only a 24-h recall period for PSC symptoms, which results in intermittent symptoms not being captured and contrasting findings between study cohorts [<span>5</span>]. The discrepancy in recall period with PSC and inflammatory bowel disease (IBD) symptoms using different PRO instruments might make interpretation challenging, and consideration needs to be made towards interrogating both PSC and IBD symptoms with one PRO instrument to determine if there is truly a correlation between bowel and cholestatic symptoms.</p>\u0000<p>The novel finding of a history of cholangitis being associated with reduced health-related quality of life is important, and emphasises the impact of intermittent symptoms that may not be captured in symptom-based questionnaires such as the simple cholestatic complaints score [<span>7</span>]. Our study only captured PSC and IBD symptoms at one timepoint, whereas repeated administration of PRO instruments with longitudinal follow-up may be more effective at capturing the frequency of recurrent cholangitis and other symptoms that fluctuate as seen in other population-based cohorts [<span>8, 9</span>]. The potential association between previous episodes of cholangitis and development of chronic mental stress, physical fatigue, or emotional distress due to recurrent hospitalisations, side effects of antibiotic use, invasive procedures, and loss of work and social productivity is underappreciated in the literature. As discussed by Prof Bowlus and Dr. Evon [<span>5</span>], the significant emotional burden of PSC is not a unique finding of our study [<span>8, 10</span>]. This publication should serve as a reminder to clinicians to screen for psychological distress, fatigue, and provide appropriate support when looking after individuals with PSC.</p>\u0000<p>We look forward to the further PSC-specific PRO instruments that are being developed and refined with patient input, as this is crucial in deciding what types of questions reflect the true effects of this disease on individual well-being. We hope that our publication has shone light ","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"120 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143831543","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: When and What to Ask—Capturing the Symptoms Experienced by Patients With PSC","authors":"Christopher L. Bowlus, Donna M. Evon","doi":"10.1111/apt.70127","DOIUrl":"https://doi.org/10.1111/apt.70127","url":null,"abstract":"<p>Despite advances throughout the field of hepatology, primary sclerosing cholangitis (PSC) remains one of the few liver diseases without an effective treatment other than liver transplantation to improve survival, symptoms or health-related quality of life (HRQOL). A major challenge for PSC clinical trials is the low frequency of events in non-cirrhotic patients. However, patients with PSC often experience symptoms including fatigue, pruritus, abdominal pain and sleep disturbances [<span>1</span>]. Valid PSC-specific patient-reported outcome (PRO) measures for use as trial endpoints would be a major advancement toward developing therapies that improve how patients feel and function.</p>\u0000<p>Tan et al. [<span>2</span>] present the first publication using the PSC-PRO instrument since its development in 2018 [<span>3</span>]. The PSC-PRO consists of two modules: Module 1, a 24-h recall of 12 PSC symptoms to produce a total symptom score, and Module 2, a 7-day recall of the impact of symptoms on seven HRQOL domains. The PSC-PRO was administered at one timepoint along with an IBD-specific PRO measure (SIBDQ) in those with IBD. Overall, participants reported low total symptom scores, contrasting other studies suggesting greater symptom prevalence [<span>1, 4, 5</span>]. For example, our recent study of 200 patients from seven academic medical centres found that 21% reported moderate to severe itch in the past 24 h on a numeric rating scale [<span>5</span>]. Like the Tan et al. study, IBD symptoms were strongly correlated with PSC symptoms, including itch. However, a closer examination of individual symptoms shown Tan et al.'s figure 1 reveals that about half of patients experienced physical and mental tiredness, difficulty concentrating, dark urine and itch. These findings suggest that summing of individual chronic and acute PSC symptoms into one total score may obfuscate symptom experiences and treatment impacts.</p>\u0000<p>Tan et al. also reported that cholangitis-related symptoms were rare during the 24-h recall period, implying that frequent administration of the PSC-PRO may be needed to capture episodic symptoms.</p>\u0000<p>Additionally, the association between a history of cholangitis and reduced HRQOL in six of seven domains is novel and warrants further understanding. Future research should elucidate whether recurrent cholangitis progressively worsens symptoms and HRQOL. Finally, the results from Module 2 suggest a significant toll on emotional health, underscoring the importance of psychological distress screening and referral to PSC support groups when indicated [<span>6</span>].</p>\u0000<p>Fortunately, several PSC-specific PRO measures are under development to provide a comprehensive assessment of PSC symptoms and HRQOL. Along with the PSC-PRO [<span>3</span>], the Simple Cholestatic Complaints Score (SCCS) [<span>7</span>] and the CLDQ-PSC [<span>8</span>] have been published. The <i>PSC Partners Seeking A Cure</i> organisation is partnering with US a","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"25 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143831541","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: Real-World Evidence of Upadacitinib—An Effective Induction Therapy for Crohn's Disease? Authors' Reply","authors":"Nicolas Richard, Mathurin Fumery","doi":"10.1111/apt.70149","DOIUrl":"https://doi.org/10.1111/apt.70149","url":null,"abstract":"<p>We thank Drs. Belinchon and Plevris for their editorial [<span>1</span>] on our article, which provides real-world data on the effectiveness and safety of upadacitinib induction therapy in Crohn's disease (CD) [<span>2</span>]. We fully agree with their valuable comments.</p>\u0000<p>The editorial rightly highlighted a few limitations of our study, including its retrospective design, short duration of follow-up and safety analysis constraints—all of which we have acknowledged. A longer follow-up of this cohort is ongoing, with the following objectives: (1) to confirm the effectiveness of upadacitinib as maintenance therapy in CD, (2) to assess the rate of mucosal healing achieved with this drug in real life, and (3) to provide longer term safety data. Encouragingly, reassuring safety data from the phase-3 U-ACTIVATE long-term extension trial were presented at the 2025 ECCO Congress; in over 1000 patient-years, there were two major adverse cardiovascular events (MACE), four venous thromboembolic events (VTE) and seven malignancies (excluding non-melanoma skin cancer) [<span>3</span>]. However, as patients in real-world practice may differ substantially from patients included in this study, further safety analyses regarding rare serious adverse events like VTE, MACE or malignancies are required. Studies based on medical-administrative databases could be a solution to address this problem. However, these studies are limited by lack of information regarding several factors that can influence the safety profile of a drug in inflammatory bowel diseases (IBDs), such as phenotype, disease activity and severity. ICARE-II, a prospective longitudinal observational multicentre cohort study promoted by GETAID in France, aims to evaluate the real-life safety of Janus kinase inhibitors (JAKi) as well as anti-IL23p19 and S1p modulators in IBD by including more than 6000 patients followed for a minimum of 4 years.</p>\u0000<p>However, the 54% steroid-free clinical remission rate at Week 12 is promising, especially considering the highly refractory nature of this cohort. These results align with previous works on smaller cohorts [<span>4, 5</span>]. However, like other therapies, upadacitinib appears to face the same ‘therapeutic ceiling’, with response rates plateauing around 30%–60% [<span>6</span>]. The identification of predictors may be one way of breaking through this ceiling. In this regard, the identified phenotypic predictors, likely surrogates of disease severity, are insufficient. Further research into the mechanisms of resistance to JAKi therapy in CD is crucial to advancing beyond this limitation.</p>","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"75 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143827255","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: Methodological Considerations in Comparing Liver Outcomes of Glucagon-Like Peptide-1 Receptor and Sodium Glucose Cotransporter-2 Inhibitors","authors":"Cheng-Hsien Hung,&nbsp;Chun-Ting Lin,&nbsp;James Cheng-Chung Wei","doi":"10.1111/apt.70049","DOIUrl":"10.1111/apt.70049","url":null,"abstract":"<p>Editors,</p><p>We read with great interest the article titled ‘Glucagon-Like Peptide-1 Receptor Agonists and Liver Outcomes in Patients with MASLD and Type 2 Diabetes [<span>1</span>].’ This study provides valuable insights into the comparative liver-related outcomes of GLP-1 receptor agonists (GLP-1 RAs) and sodium glucose cotransporter 2 inhibitors (SGLT2is) in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) and type 2 diabetes (T2D). While we commend their work, we offer the following suggestions to enhance the robustness of their findings:</p><p>First, the study includes patients from 2010, whereas SGLT2 inhibitors were first introduced in 2013, with canagliflozin being the first approved drug in this class [<span>2</span>]. This timeline discrepancy introduces the potential for time-related bias, as early years of the study cohort predominantly include GLP-1 RA users. Such bias may affect the comparability of the two groups, particularly as advancements in MASLD management and diagnostic practices occurred during this period. A sensitivity analysis limiting the cohort to patients treated after 2013 would help clarify whether the observed differences are driven by this temporal imbalance.</p><p>Secondly, SGLT2 inhibitors are widely recognised for their cardiovascular benefits, particularly in heart failure [<span>3, 4</span>], and have been used to reduce the risk of cardiovascular death and hospitalisation in patients with heart failure. Heart failure is closely associated with liver disease through mechanisms such as hepatic congestion and is also linked to ischaemic injury.</p><p>Lastly, while propensity score matching effectively balances many baseline characteristics, unmeasured variables, such as lifestyle factors (e.g. diet and physical activity) and the concurrent use of hepatoprotective medications (e.g. silymarin [<span>5</span>]), remain unaddressed. These variables could significantly influence the observed outcomes. Performing sensitivity analyses to account for the potential impact of these unmeasured confounders would enhance the robustness and reliability of the study's findings.</p><p>In conclusion, while this study provides meaningful insights into liver outcomes associated with GLP-1 RAs and SGLT2is, addressing the aforementioned limitations would further strengthen the validity and clinical applicability of its conclusions.</p><p><b>Cheng-Hsien Hung:</b> writing – original draft. <b>Chun-Ting Lin:</b> writing – review and editing. <b>James Cheng-Chung Wei:</b> writing – original draft.</p><p>The authors declare no conflicts of interest.</p><p>This article is linked to Kuo et al paper. To view this article, visit https://doi.org/10.1111/apt.18502.</p>","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"61 10","pages":"1721-1722"},"PeriodicalIF":6.6,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apt.70049","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143827200","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: Real-World Evidence of Upadacitinib—An Effective Induction Therapy for Crohn's Disease?","authors":"C. Ramos-Belinchon, N. Plevris","doi":"10.1111/apt.70113","DOIUrl":"https://doi.org/10.1111/apt.70113","url":null,"abstract":"&lt;p&gt;To mitigate the progressive nature of Crohn's disease (CD), early introduction of advanced therapies is key [&lt;span&gt;1&lt;/span&gt;]. However, despite therapeutic advances, we continue to encounter a ‘therapeutic ceiling’ for all therapies [&lt;span&gt;2&lt;/span&gt;]. Ongoing development of new treatments is essential to allow patients the best chance of achieving normalisation of mucosal inflammation and, ultimately, quality of life.&lt;/p&gt;\u0000&lt;p&gt;Upadacitinib is an oral, selective Janus kinase (JAK)-1 inhibitor approved for the treatment of moderate-to-severe CD. The Phase 3 trials, U-EXCEL and U-EXCEED, demonstrated post-induction (Week 12) clinical remission (CDAI &lt; 150) rates of 49.5% and 38.9%, respectively. Adverse events included acne, anaemia and infections such as Herpes zoster [&lt;span&gt;3&lt;/span&gt;]. However, questions around generalisability remain. Many patients in real-world practice would not qualify for enrolment in these trials, while response rates to the drugs differ between those meeting versus not meeting inclusion criteria [&lt;span&gt;4&lt;/span&gt;]. Therefore, large real-world cohorts are needed to assess generalisability for clinical practice.&lt;/p&gt;\u0000&lt;p&gt;Richard et al. conducted a retrospective, multicentre study in 29 French GETAID centres to assess the effectiveness and safety of upadacitinib induction therapy in CD. The primary outcome was steroid-free clinical remission (SFCR) at Week 12, defined by a Harvey Bradshaw Index (HBI) &lt; 5 [&lt;span&gt;5&lt;/span&gt;]. More than 200 patients with moderate to severe disease were included. The cohort was highly refractory, with 95% having failed two or more biologics. SFCR was achieved in 54.3% of patients at Week 12. Body mass index ≤ 18.5 kg/m&lt;sup&gt;2&lt;/sup&gt; and HBI &gt; 7 were predictors of lower rates of SFCR at Week 12. Regarding safety, 7.6% experienced serious adverse events, the most common being CD exacerbations. There was one case of EBV-associated lymphoma.&lt;/p&gt;\u0000&lt;p&gt;This valuable nationwide study suggests that, even in a very refractory cohort of patients with CD, upadacitinib can achieve high remission rates as early as Week 12. Interestingly, no association was found between SFCR and the number of prior biologics. These results are similar to those seen by others, supporting the notion that upadacitinib works quickly and is also a good option for patients with prior biologic failure. A relevant aspect is also the identification of two phenotypic predictors associated with lower SFCR, although these are probably related to a more severe disease phenotype. Reassuringly, no cases of Herpes zoster, thromboembolic events, or major adverse cardiovascular events were reported.&lt;/p&gt;\u0000&lt;p&gt;Nevertheless, this study has several limitations, mainly its retrospective nature and short follow-up. The lack of endoscopic data also makes it difficult to gauge the true benefit of the drug in this refractory population, especially considering the disconnect between symptoms and mucosal inflammation in CD. Furthermore, the study is underpower","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"27 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143827310","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: Advancing Non-Invasive Assessment Tools for MASLD—A Focus on Disease Remission","authors":"Gong Feng,&nbsp;Na He,&nbsp;Hui Wang,&nbsp;Yi Liu","doi":"10.1111/apt.70050","DOIUrl":"10.1111/apt.70050","url":null,"abstract":"&lt;p&gt;We read with interest the article by Noureddin et al. on the use of non-invasive tests (NITs) to monitor patients with metabolic dysfunction-associated steatotic liver disease (MASLD) [&lt;span&gt;1&lt;/span&gt;]. While liver biopsy remains the gold standard for assessing MASLD severity, its invasive nature, high cost, procedural risks (e.g., bleeding, sampling variability) and patient discomfort limit its utility for repeated testing. Consequently, there is an urgent need for safe, cost-effective and reliable non-invasive tools to screen, stage and prognosticate MASLD. The review by Noureddin et al. addresses this gap by evaluating existing NITs and proposing stage-specific monitoring protocols.&lt;/p&gt;&lt;p&gt;However, while the review thoroughly examines disease progression, the assessment of disease remission is equally important. Recent studies, particularly a study by Feng et al., have expanded our understanding of MASLD's natural history, emphasising the reversibility of fibrosis, fluctuations in inflammation and steatosis and even recompensation in patients with decompensated cirrhosis [&lt;span&gt;2, 3&lt;/span&gt;]. These findings underscore the importance of developing tools that can assess not only disease progression but also remission. The approval of resmetirom—the first drug for metabolic dysfunction-associated steatohepatitis (MASH) with significant fibrosis—has accelerated demand for non-invasive remission assessment tools [&lt;span&gt;4&lt;/span&gt;]. Replacing liver biopsy with validated, non-invasive methods to assess the histological resolution of MASLD is a critical frontier in MASLD research [&lt;span&gt;4-6&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;Recent research on histological remission and related NITs has begun to shed light on this essential aspect of MASLD management. For instance, Raverdy et al. evaluated NITs for fibrosis monitoring post-bariatric surgery, and Loomba et al. developed the MASH Histological Remission Index [&lt;span&gt;5, 7&lt;/span&gt;]. Furthermore, Loomba et al. also identified associations between baseline metabolic markers (e.g., triglycerides, alanine aminotransferase changes) and histological outcomes [&lt;span&gt;8&lt;/span&gt;]. However, critical gaps persist. Most studies focus narrowly on fibrosis improvement or MASH remission, with limited data on their long-term impact on liver-related outcomes. Few have examined the synergistic effects of combined fibrosis reversal and MASH remission, and existing tools lack validation across diverse populations (e.g., varying demographics, comorbidities), raising concerns about generalisability. Large-scale, multicentre, longitudinal studies are essential to address these limitations [&lt;span&gt;5, 7&lt;/span&gt;]. To advance non-invasive tools for MASLD remission, a multipronged approach is necessary for (1) optimising existing methods by refining protocols, thresholds and multimodal integration; (2) identifying novel biomarkers through mechanistic research at genetic and metabolic levels; (3) validating tools across diverse populations and disease stages an","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"61 10","pages":"1723-1724"},"PeriodicalIF":6.6,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apt.70050","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143827258","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 Impact of Antispasmodic Use on Abdominal Pain and Opioid Use in Inflammatory Bowel Disease: A Population-Based Study","authors":"Chachrit Khunsriraksakul, Olivia Ziegler, Dajiang Liu, Audrey S. Kulaylat, Matthew D. Coates","doi":"10.1111/apt.70147","DOIUrl":"https://doi.org/10.1111/apt.70147","url":null,"abstract":"Patients with inflammatory bowel disease (IBD) are often prescribed antispasmodics for chronic abdominal pain. Large-scale data regarding efficacy and impact on clinical outcomes are lacking.","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"40 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143819974","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: Association Between Viral Replication Activity and Postoperative Recurrence of HBV-Related Hepatocellular Carcinoma","authors":"Sifu Yang","doi":"10.1111/apt.70136","DOIUrl":"https://doi.org/10.1111/apt.70136","url":null,"abstract":"&lt;p&gt;We read with interest the article by Heo et al. [&lt;span&gt;1&lt;/span&gt;] on the association between viral replication activity and postoperative recurrence of HBV-related HCC. While the study provides valuable insights, there are several areas for improvement to strengthen the conclusions.&lt;/p&gt;\u0000&lt;p&gt;First, relying solely on baseline HBV DNA levels to assess postoperative recurrence risk has a fundamental flaw. Baseline data are static, while viral activity is dynamic. The study did not account for the effects of postoperative antiviral therapy, viral suppression stability, or immune environment changes, leading to biased conclusions. For instance, the “highest risk with moderate baseline viral load” in non-cirrhotic patients might reflect a critical state of postoperative suppression, where moderate viral loads are caught between incomplete suppression and immune activation [&lt;span&gt;2&lt;/span&gt;]. Surgical stress may also cause temporary viral rebound, which, if not monitored continuously, may be misinterpreted as baseline levels. Moreover, previous studies suggest that viral suppression at 6 months post-surgery is a more reliable predictor than baseline levels [&lt;span&gt;3&lt;/span&gt;]. If sustained suppression eliminates baseline differences, static viral load risk stratification would lose clinical relevance, weakening the conclusions and potentially leading to clinical misjudgments.&lt;/p&gt;\u0000&lt;p&gt;Second, although the study conducted a competing risk analysis, it did not detail the specific causes of death or liver transplantation (e.g., liver failure vs. non-liver-related factors), which could significantly affect the interpretation of recurrence risk. If death or liver transplantation was related to liver disease, it could impact the accuracy of recurrence risk assessment because these factors may be linked to HBV replication activity and HCC recurrence. The lack of clarification could confuse the direct effect of death or transplantation on recurrence, leading to biased competing risk analysis results and affecting the study's conclusion.&lt;/p&gt;\u0000&lt;p&gt;Third, some recurrences were diagnosed using imaging (CT or MRI) instead of pathological confirmation, which could lead to missed micro-lesions or misdiagnosis of benign nodules. While imaging is effective in most cases, smaller lesions or atypical nodules may be missed, potentially overestimating or underestimating recurrence rates and affecting the study's reliability [&lt;span&gt;4&lt;/span&gt;].&lt;/p&gt;\u0000&lt;p&gt;Finally, the median follow-up of 4.9 years may not be long enough to fully capture late recurrences (&gt; 5 years), particularly in non-cirrhotic patients. HCC recurrence in non-cirrhotic patients may be related to the “field effect,” where chronic HBV infection induces persistent liver inflammation and microenvironmental changes. This process may take longer to manifest its carcinogenic effects [&lt;span&gt;5&lt;/span&gt;]. A follow-up period that is too short may fail to capture late recurrences driven by chronic inflammation and viral activity, th","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"14 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143813900","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":"Real‐World Effectiveness and Safety of Mirikizumab Induction Therapy in Patients With Ulcerative Colitis: A Multicentre Retrospective Observational Study","authors":"Yasuhiro Takagi, Toshiyuki Sato, Takanori Nishiguchi, Akira Nogami, Masataka Igeta, Soichi Yagi, Maiko Ikenouchi, Mikio Kawai, Koji Kamikozuru, Yoko Yokoyama, Toshihiko Tomita, Hirokazu Fukui, Masayuki Fukata, Taku Kobayashi, Shinichiro Shinzaki","doi":"10.1111/apt.70140","DOIUrl":"https://doi.org/10.1111/apt.70140","url":null,"abstract":"BackgroundIn randomised controlled trials, mirikizumab achieved clinical remission and improved outcomes of patients with moderate to severe ulcerative colitis (UC). However, there is currently no real‐world evidence for mirikizumab.AimTo evaluate the real‐world effectiveness and safety of mirikizumab.MethodsIn a retrospective cohort study among three facilities, we included patients with UC who first received mirikizumab between June 2023 and April 2024. The primary outcome was the change in the partial Mayo score (PMS) from week 0 to 12. Secondary outcomes included changes in serum C‐reactive protein (CRP) and leucine‐rich α2‐glycoprotein (LRG) levels from week 0 to 12; clinical remission rate (PMS &lt; 2 with rectal bleeding subscore of 0), CRP remission rate (&lt; 3.0 mg/L), and LRG remission rate (&lt; 12.7 μg/mL) at week 12; and adverse events during induction therapy.ResultsWe included 52 patients. Median (interquartile range) PMS decreased from week 0 to 12 (5 [3–6] to 2 [0–3], <jats:italic>p</jats:italic> &lt; 0.001). CRP and LRG levels also decreased (CRP: 3.8 [0.9–7.3] to 1.8 [0.5–4.0] mg/L, <jats:italic>p</jats:italic> = 0.015; LRG: 20.1 [16.3–23.2] to 15.9 [12.8–23.2] μg/mL, <jats:italic>p</jats:italic> = 0.014). Rates of clinical remission, CRP remission, and LRG remission at week 12 were 44.2%, 67.3%, and 27.3%, respectively. There were no adverse events leading to permanent discontinuation of mirikizumab or death.ConclusionThis real‐world study demonstrated the short‐term effectiveness and safety of mirikizumab in patients with UC.","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"39 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143813458","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: Meta-Analysis Critique: Refining the Association Between Helicobacter pylori and Eosinophilic Oesophagitis. Authors' Reply","authors":"Irene Spinelli,&nbsp;Gianluca Ianiro","doi":"10.1111/apt.70135","DOIUrl":"10.1111/apt.70135","url":null,"abstract":"<p>We appreciate the insightful comments from Dr. Rahman [<span>1</span>] regarding our meta-analysis [<span>2</span>] and welcome this opportunity for further discussion.</p><p><i>Helicobacter pylori</i> (<i>H. pylori</i>) prevalence is influenced by socioeconomic and environmental factors such as diet, healthcare access and living conditions, all of which could independently affect the risk of developing eosinophilic esophagitis (EoE) [<span>3, 4</span>]. Failing to adjust for these confounding factors may result in an overestimation or misinterpretation of the association between <i>H. pylori</i> and EoE. A multivariate adjustment for these potential confounders could provide a clearer understanding of how <i>H. pylori</i> may contribute to the risk of EoE, offering more accurate insights into this potential connection.</p><p>We are aware that the setting in which participants are recruited could also play a significant role in introducing bias [<span>5</span>]. A sensitivity analysis, comparing symptomatic hospital patients with individuals with milder disease, would be a valuable approach to better understand how this influences results, providing a more accurate assessment of the relationship between <i>H. pylori</i> and the outcome of interest. We were not able to make this analysis due to the unavailability of pertinent data in included studies.</p><p>Longitudinal data are essential to clarify whether <i>H. pylori</i> infection contributes to the development of EoE or whether EoE treatments affect the ability to detect <i>H. pylori</i>. Long-term studies would help to establish whether <i>H. pylori</i> infection precedes EoE onset or whether the relationship is more complex, influenced by the treatments for EoE [<span>6</span>]. This would refine our understanding of the role <i>H. pylori</i> plays in the development of EoE.</p><p>Finally, relying solely on visual assessments of funnel plots may not always provide a clear picture of bias, and quantitative methods such as Egger's test could provide more rigorous insights [<span>7</span>]. Incorporating unpublished data is helpful to reduce this bias and improve the overall robustness of the study's findings. Future work should certainly focus on addressing these gaps.</p><p>We thank Dr. Rahman [<span>1</span>] for the opportunity to clarify these points.</p><p><b>Irene Spinelli:</b> conceptualization, investigation, writing – original draft, methodology, writing – review and editing, formal analysis, project administration, data curation, resources. <b>Gianluca Ianiro:</b> validation, visualization, supervision, conceptualization, writing – review and editing, formal analysis, resources, data curation.</p><p>This article is linked to Spinelli et al papers. To view these articles, visit https://doi.org/10.1111/apt.70042 and https://doi.org/10.1111/apt.70122.</p>","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"61 10","pages":"1731-1732"},"PeriodicalIF":6.6,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apt.70135","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143814037","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}