Alimentary Pharmacology & Therapeutics最新文献

{"title":"Early Dynamics of Portal Pressure Gradient After TIPS Insertion Predict Mortality","authors":"P. A. Reuken, A. Franz, T. H. Wirtz, C. Ripoll, R. Aschenbach, U. Teichgräber, M. R. Pollmanns, M. Kiehntopf, S. Keil, C. Kuhl, P. C. Schulze, C. Trautwein, T. Bruns, A. Stallmach, A. Zipprich","doi":"10.1111/apt.18503","DOIUrl":"https://doi.org/10.1111/apt.18503","url":null,"abstract":"BackgroundTransjugular intrahepatic portosystemic shunt (TIPS) placement leads to a reduction in portal pressure and an improvement in survival in patients with recurrent and refractory ascites and variceal haemorrhage. Prediction of post‐TIPS survival is primarily determined by factors identified before the TIPS procedure, as data collected during or after TIPS implantation are limited. The aim of the study was to evaluate the influence of early hemodynamic changes after TIPS placement on survival, in order to refine post TIPS management.MethodsIn this prospective bicentric study, consecutive patients (<jats:italic>n</jats:italic> = 105) undergoing TIPS placement for ascites or variceal haemorrhage underwent measurement of portal pressure gradient (PPG) immediately at TIPS insertion (PPG0) and 24 h later (PPG24h) and the ΔPPG was calculated from PPG24h and PPG0 (ΔPPG = PPG24h‐PPG0). Kaplan–Meier survival analysis and uni‐ and multivariable regression analyses were conducted to identify survival predictors.ResultsPatients with lack of increased ΔPPG exhibited poorer 90‐day and 1‐year survival compared to patients with increased ΔPPG. This worse survival was independent of The Model for End‐Stage Liver Disease (MELD) score, Child‐Pugh score, bilirubin levels, creatinine and the Freiburg index of post‐TIPS survival (FIPS) &gt; 0.92. Among these patients with poorer outcome, elevated bilirubin (&gt; 25 μmol/L) further distinguished survivors from non‐survivors.ConclusionLack of increased ΔPPG post‐TIPS insertion identifies a high‐risk patient group with worse survival. We propose incorporating this second PPG measurement and determining ΔPPG into clinical practice to identify these patients early and tailor post‐TIPS patient care.","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"36 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142986270","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: Addressing Gaps in Hospital-Based Hepatitis C Screening—Insights and Recommendations","authors":"Zhen Deng,&nbsp;Lincheng Duan,&nbsp;Kai Wang","doi":"10.1111/apt.18460","DOIUrl":"10.1111/apt.18460","url":null,"abstract":"&lt;p&gt;We have carefully reviewed Ferrarese et al.'s study on the effectiveness of hospital-based hepatitis C virus (HCV) screening activities [&lt;span&gt;1&lt;/span&gt;]. This research offers crucial data for identifying HCV-infected patients beyond current national screening policies, and provides valuable insights for public health interventions. However, we propose several considerations and recommendations to enhance the study.&lt;/p&gt;&lt;p&gt;Firstly, the study does not sufficiently analyse patients' comorbid conditions. Hospitalised patients often have chronic diseases such as diabetes, metabolic syndrome or cardiovascular diseases, which increase HCV infection risk and influence treatment adherence and outcomes [&lt;span&gt;2, 3&lt;/span&gt;]. Stratified analysis by comorbidities could clarify the interplay between HCV infection and overall health, aiding in the development of targeted screening and treatment strategies.&lt;/p&gt;&lt;p&gt;Secondly, the research inadequately addresses patients' socioeconomic status (SES), a key factor affecting healthcare access and screening participation [&lt;span&gt;4, 5&lt;/span&gt;]. Individuals with low-income or education levels may encounter greater barriers due to financial constraints or lack of information [&lt;span&gt;6&lt;/span&gt;]. Collecting data on income, education and employment, and examining their impact on screening and treatment, would provide a more comprehensive understanding of how socioeconomic disparities impede HCV prevention and control.&lt;/p&gt;&lt;p&gt;Thirdly, while the study notes that 82.5% of hospitalised patients were not screened, it does not examine the specific characteristics of this unscreened group, such as age, gender, comorbidities or departmental distribution. This selection bias may limit the representativeness of the findings. We recommend a retrospective analysis of hospital records to identify traits of the unscreened population, enabling a more accurate assessment of HCV prevalence among hospitalised patients and the creation of more inclusive screening strategies.&lt;/p&gt;&lt;p&gt;Additionally, the study finds that female patients with positive viral loads are significantly older than males, while it does not explore the reasons for this gender disparity. This difference might relate to unique risk factors for disease progression in women or barriers to healthcare access. Future research should investigate this phenomenon to optimise screening and treatment approaches for female patients.&lt;/p&gt;&lt;p&gt;Lastly, the study mentions that some patients were lost to follow-up after referral to local centres but does not suggest specific improvements for follow-up management. Loss to follow-up can severely impact treatment outcomes, particularly for foreign patients or those with limited medical resources. To address these issues comprehensively, we suggest integrating social work practices to enhance HCV screening and treatment effectiveness. Health education and outreach through community lectures and multilingual support can help high-risk groups understand th","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"61 5","pages":"915-916"},"PeriodicalIF":6.6,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apt.18460","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142987500","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: Addressing Gaps in Hospital-Based Hepatitis C Screening—Insights and Recommendations. Authors' Reply'","authors":"Alberto Ferrarese,&nbsp;Francesco Paolo Russo","doi":"10.1111/apt.18505","DOIUrl":"10.1111/apt.18505","url":null,"abstract":"&lt;p&gt;We would like to thank Dr Deng and colleagues for their valuable comments on our recently published work in this Journal [&lt;span&gt;1&lt;/span&gt;]. We would like to clarify a few aspects in the light of the hypotheses proposed in their recent commentary [&lt;span&gt;2&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;The authors noted that our paper did not adequately address the comorbidities of the 109 patients with a positive hepatitis C (HCV) viral load. For this study, we were able to obtain the ICD-9 discharge codes; however, these may only partially capture the patients' comorbidities and. The association between HCV infection and cardiovascular and metabolic disorders is well-described [&lt;span&gt;3&lt;/span&gt;]. However, we believe that patient comorbidities should not serve as a basis for stratifying individuals in an in-hospital screening campaign. Given the excellent safety profile of direct-acting antiviral agents, the presence of significant comorbidities does not substantially limit access to treatment. Moreover, a targeted screening approach is inconsistent with the universal in-hospital screening model we advocate, which seeks to identify the largest possible number of positive patients. This universal approach also has the potential to reduce socio-economic barriers and health inequalities, particularly in Italy, where the public healthcare system could, hopefully in the near future, support its implementation.&lt;/p&gt;&lt;p&gt;Dr Deng and colleagues pointed out that only 17.5% of all hospitalised patients underwent in-hospital screening during the calendar year 2022. We acknowledge that this is a potential limitation in our paper. However, the number of samples collected (&lt;i&gt;n&lt;/i&gt; = 11,355) is substantial and provides valuable epidemiological insights. As our study was designed prospectively, it was not possible to retrospectively include unscreened patients, particularly those who declined informed consent. The relatively low percentage of screened patients may likely reflect limited awareness of the issue among both patients and healthcare providers. In this regard, our study can serve as a starting point to raise awareness at multiple levels. The gender differences observed in our study could potentially be attributed to the higher life expectancy of women than of men in Italy, a trend that has remained consistent over the years [&lt;span&gt;4&lt;/span&gt;]. Additionally, it is well-established that men have a higher risk of disease progression to cirrhosis, which may explain why liver-related mortality has likely affected more men than women in previous decades [&lt;span&gt;5&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;Finally, the authors correctly observed that 61/109 (66%) patients were not treated at our centre. However, this does not necessarily indicate a loss to follow-up. In 15 cases (24.5%), antiviral treatment was postponed due to severe extra-hepatic comorbidities, 7 patients (11.4%) refused to start therapy and 4 (6.5%) died during the same hospitalisation. In only 5 cases (8.1%), the reason for treatment postponement could ","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"61 5","pages":"917-918"},"PeriodicalIF":6.6,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apt.18505","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142987144","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: Exclusive Enteral Nutrition in Adults With Ulcerative Colitis","authors":"Matthew K. W. Chu,&nbsp;Alice S. Day,&nbsp;Lani Broad,&nbsp;Samuel P. Costello,&nbsp;Suzanne Edwards,&nbsp;Robert V. Bryant","doi":"10.1111/apt.18495","DOIUrl":"10.1111/apt.18495","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Exclusive enteral nutrition (EEN) is an established dietary therapy for Crohn's disease but its role in ulcerative colitis remains unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>To investigate the efficacy of EEN in adults with active ulcerative colitis and compare variations in treatment protocols, safety, tolerability and adherence.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We conducted a systematic search of MEDLINE, Embase, Cochrane CENTRAL, Emcare, CINAHL, Web of Science and trial registries for articles published from inception until July 21, 2024. We included all experimental and observational studies that described the use of EEN in adults with active ulcerative colitis. This review was registered on PROSPERO (CRD42022319584).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Of 3273 articles screened, we included 10 studies (334 adults). Overall, there was no difference between EEN and comparator for ulcerative colitis remission induction (median follow-up 14 days, risk ratio (RR) 1.15, 95% confidence interval (CI) 0.71–1.85; 2 studies). In acute severe ulcerative colitis, there was no difference between EEN and comparator for corticosteroid failure (RR 0.76, 95% CI 0.48–1.20; 2 studies) or risk of colectomy (RR 0.88, 95% CI 0.51–1.51, <i>n</i> = 2 studies) during index admission. The pooled discontinuation rate was 3% (95% CI 0–10; 9 studies). There was heterogeneity in trial design, methodology and assessment of outcomes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>EEN was well tolerated with low therapy discontinuation in adults with active ulcerative colitis. However, there is insufficient evidence to support the use of EEN as an adjunctive therapy to standard of care. Further, well-designed studies with reproducible methodology and endpoints are necessary to evaluate its effectiveness.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Registry Number for Systematic Review</h3>\u0000 \u0000 <p>PROSPERO 2022 CRD42022319584.</p>\u0000 </section>\u0000 </div>","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"61 5","pages":"756-775"},"PeriodicalIF":6.6,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apt.18495","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142987150","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":"Disparities in Alcohol-Associated Liver Disease Hospital Encounters Amongst a Texas-Based Cohort of Patients","authors":"Thomas G. Cotter,&nbsp;Ahmad Anouti,&nbsp;Bill Zhang,&nbsp;Elias D. Rady,&nbsp;Mausam Patel,&nbsp;Suraj Patel,&nbsp;Daniel J. Ellis,&nbsp;Sarah R. Lieber,&nbsp;Nicole E. Rich,&nbsp;Jacqueline G. O'Leary,&nbsp;Mack C. Mitchell,&nbsp;Amit G. Singal","doi":"10.1111/apt.18477","DOIUrl":"10.1111/apt.18477","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Alcohol-associated liver disease (ALD) disproportionately impacts men, racial and ethnic minorities, and individuals of low socioeconomic status; however, it's unclear how recent increases in ALD burden have impacted these disparities. We aimed to describe trends in racial, ethnic and socioeconomic disparities in alcohol-associated hospital encounters.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We conducted a retrospective cohort study of adult hospital encounters with alcohol-associated diagnoses from three health systems between January 2016 and December 2021. The cohort was divided into three eras: a ‘Historical Era,’ (Oct 2016—June 2018, used only for trends); ‘Era 1’ (July 2018—March 2020); and ‘Era 2’ (April 2020—December 2021). Kaplan Meier and Cox regression analyses were performed to identify factors associated with overall survival.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We identified 19,295 individuals with alcohol-associated encounters (44.7% White, 29.8% Hispanic, and 21.8% non-Hispanic Black (NHB) individuals), with a greater increase observed between eras 1 and 2 than the historical era and Era 1 (8.7% vs. 5.0%, <i>p</i> &lt; 0.01). By age and sex, the greatest increases in encounters were observed in the youngest and oldest females but only the oldest males. By race and ethnicity, Hispanic individuals had greater increases in encounters compared to Black and White individuals (14.8% vs. 7.5% and 6.3%, <i>p</i> &lt; 0.01). Older age (aSHR: 1.03, 95% CI: 1.03–1.0), higher MELD (aSHR: 1.08, 95% CI: 1.0–1.09), hepatic encephalopathy (aSHR: 1.42, 95% CI: 1.06–1.90), and hepatocellular carcinoma (HCC) (aSHR: 3.20, 95% CI: 2.29–4.49) were associated with increased mortality.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The highest increases of alcohol-associated encounters were observed amongst young Hispanic and NHB women, highlighting variation in trends by age, sex, race and ethnicity. These disparities merit further investigation to elucidate underlying mechanisms and develop tailored interventions to improve ALD burden and outcomes.</p>\u0000 </section>\u0000 </div>","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"61 6","pages":"988-999"},"PeriodicalIF":6.6,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apt.18477","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142988425","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":"Clinical Trial: Study to Investigate the Efficacy and Safety of the Alpha-2-Delta Ligand PD-217,014 in Patients With Irritable Bowel Syndrome","authors":"Lesley A. Houghton,&nbsp;Simiao Gao,&nbsp;Steven A. Gilbert,&nbsp;Benoit Coffin,&nbsp;Magnus Simren,&nbsp;Jeremy D. Gale,&nbsp;the A4451007 study investigators","doi":"10.1111/apt.18487","DOIUrl":"10.1111/apt.18487","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Despite the emergence of drugs to treat irritable bowel syndrome (IBS), improving abdominal pain can still be challenging. α₂δ ligands, such as gabapentin and pregabalin, are sometimes used off-label to tackle this problem. However, evidence for efficacy is limited, and no large-scale studies have been published.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>To study the efficacy of the α₂δ ligand PD-217,014 in IBS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This multi-centre, double-blind, randomised, placebo-controlled, parallel group study randomised participants with Rome II-defined IBS to 150 or 300 mg b.d. of PD-217,014 or placebo b.d. for 4 weeks. The primary efficacy endpoint was responder, defined as having adequate relief of abdominal pain/discomfort for ≥ 50% of the active treatment period. Key secondary endpoints were change from baseline in abdominal pain, bloating, stool frequency/consistency, and global assessment of IBS symptoms.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We randomised 330 participants [aged 19–73 years; 209 (65%) female] satisfying Rome II criteria, 322 (98%) were treated, and of whom 271 (84%) completed the study. In this study, 321 satisfied Rome IV criteria. Neither dose of PD-217,014 improved the percentage of participants reporting adequate relief of abdominal pain/discomfort compared with placebo, either using the Rome II-defined total cohort or Rome II and IV IBS bowel habit sub-types. There were similar observations for secondary endpoints, and no association between abdominal pain or anxiety levels at baseline with participant improvement. PD-217,014 was generally well tolerated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This first large, dose-ranging trial examining the efficacy of PD-217,014 showed no significant efficacy in participants with IBS or bowel habit sub-types, irrespective of their pain and anxiety levels.</p>\u0000 </section>\u0000 </div>","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"61 5","pages":"803-813"},"PeriodicalIF":6.6,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apt.18487","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142981739","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: HBeAg-Positive Chronic Hepatitis B With Low HBsAg Levels—Exploring Clinical Significance of preS2 Deletion Mutations","authors":"Ying-Nan Tsai,&nbsp;Yao-Chun Hsu","doi":"10.1111/apt.18480","DOIUrl":"10.1111/apt.18480","url":null,"abstract":"&lt;p&gt;Chronic hepatitis B virus (HBV) infection typically follows a natural history that includes phases of ‘immune tolerance’ and hepatitis B e antigen (HBeAg) clearance [&lt;span&gt;1&lt;/span&gt;]. HBeAg positivity usually indicates active replication and is associated with high viral load and elevated hepatitis B surface antigen (HBsAg) levels in patients with chronic hepatitis B (CHB) [&lt;span&gt;2&lt;/span&gt;]. However, the conventional phases cannot characterise all HBeAg-positive patients. A subset of these HBeAg-positive patients exhibit low HBsAg levels, accompanied by complex virological and immunological profiles, and tends to develop aggressive liver fibrosis and cirrhosis [&lt;span&gt;3, 4&lt;/span&gt;]. Additionally, different HBV genes and mutations are linked to diverse serological and clinical characteristics, including antigen seroconversion, response to antiviral treatment, vaccine escape, liver fibrosis status and the development of hepatocellular carcinoma (HCC) [&lt;span&gt;5&lt;/span&gt;]. The mechanisms underlying the clinical presentation of HBeAg-positive CHB with low HBsAg levels remain unclear.&lt;/p&gt;&lt;p&gt;In a recent study published in the journal, Chen et al. enrolled 171 treatment-naïve HBeAg-positive CHB patients with HBsAg concentrations below 1000 IU/mL, to investigate potential explanations by analysing their virological and immunological characteristics [&lt;span&gt;6&lt;/span&gt;]. Liver fibrosis severity was measured using non-invasive fibrosis indices. The results revealed that these patients had lower HBV DNA concentrations, higher rates of anti-HBs and anti-HBe positivity, elevated fibrosis scores and a predominance of genotype C. Moreover, there was a higher prevalence of viral quasispecies variants associated with the preS2 deletion. Notably, patients with preS2 deletion mutations exhibited higher fibrosis scores compared to both those infected with the wild-type virus, and HBeAg-positive CHB patients with high HBsAg concentration. They concluded that preS2 deletion mutants might enable HBV to evade host immunity and contribute to liver disease progression. These findings suggest that these patients warrant greater medical attention.&lt;/p&gt;&lt;p&gt;Extrapolating findings from this retrospective study should be approached cautiously. Potential confounding factors, such as host genetics or environmental influences, [&lt;span&gt;7, 8&lt;/span&gt;] may contribute to fibrosis or immune modulation and were not fully accounted for in this study. It remains unclear whether preS2 deletion mutations arise as a result of liver disease progression, or alternatively, causally contribute to it. Moreover, in vitro experiments may not fully replicate the intricate host immune interactions occurring in vivo and disease progression. To further clarify the role of preS2 deletions in the natural history of CHB, prospective cohort studies that longitudinally track the emergence of preS2 deletions are needed to establish a clear temporal association with clinical outcomes such as fibrosis progression or HCC. Ad","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"61 5","pages":"899-900"},"PeriodicalIF":6.6,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apt.18480","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142981740","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: HBeAg-Positive Chronic Hepatitis B With Low HBsAg Levels—Exploring Clinical Significance of preS2 Deletion Mutations. Authors' Reply","authors":"Yuxin Chen,&nbsp;Rui Huang,&nbsp;Chao Wu,&nbsp;Yong Liu","doi":"10.1111/apt.18504","DOIUrl":"10.1111/apt.18504","url":null,"abstract":"&lt;p&gt;We thank Drs Tsai and Hsu for their insightful editorial on our recent study [&lt;span&gt;1, 2&lt;/span&gt;]. Despite hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) patients with low hepatitis B surface antigen (HBsAg) levels constituting only a small proportion of CHB patients, it still deserves our attention because of its unique clinical characteristics and its potential close association with advanced disease progression [&lt;span&gt;3&lt;/span&gt;]. For the first time, we showed that these patients had a greater proportion of quasispecies mutations introduced by preS2 deletion, which were associated with increased liver fibrosis scores. However, because of the limitations of the study, several points merit further discussion.&lt;/p&gt;&lt;p&gt;First, as Drs Tsai and Hsu noted, our study is limited by the retrospective design. Prospective studies with a long-term follow-up could provide valuable insight into the clinical outcome of these patients and clarify the impact of preS2 deletion mutations on CHB progression. Given the elevated risk of liver fibrosis and cirrhosis for these patients, our next data highlighted the prompt initiation of antiviral therapy for these patients with CHB. In our study, 23 HBeAg-positive CHB patients with low HBsAg levels received antiviral treatment by nucleos(t)ide analogues (NAs). After 24 weeks of antiviral treatment, serum HBV DNA levels were undetectable in 95.7% (22/23) of patients, and serum alanine transaminase (ALT) levels normalised in all patients. After 48 weeks, although no patient achieved HBeAg seroconversion, all maintained undetectable serum HBV DNA levels and ALT levels remained within the normal range. Despite the limited sample size, these findings suggest that NAs are effective in suppressing viral replication in these patients. However, the long-term trajectory of liver disease in these patients following therapy remains uncertain and requires further investigation.&lt;/p&gt;&lt;p&gt;Second, the role of preS2 deletion mutations as a cause or a consequence of liver disease progression remains unclear. We speculate that the preS2 deletion mutations resulted from the interaction between the host immunity and the virus, reflecting the host immune pressure. This is further supported by the findings that the mutated strains induced weaker host immune responses, and that the deletion regions were localised in complex alpha helix regions and immune response epitopes. However, further prospective cohort studies, cytological studies and animal experiments are needed to validate this hypothesis. Humanised mouse models are particularly important for understanding the pathogenesis of HBV, including virus–host dynamics and immune responses [&lt;span&gt;4&lt;/span&gt;]. However, current HBV mouse models face limitations, such as lacking a fully functional human immune system and failing to replicate human-specific virus–host interactions [&lt;span&gt;5&lt;/span&gt;]. These limitations underscore the need for cautious interpretation of results and further","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"61 5","pages":"901-902"},"PeriodicalIF":6.6,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apt.18504","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142981662","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":"Baseline Drug Clearance Predicts Outcomes in Children With Inflammatory Bowel Disease Treated With Vedolizumab: Results From the VedoKids Prospective Multicentre Study","authors":"Ronen Stein,&nbsp;Dan Turner,&nbsp;Séamus Hussey,&nbsp;Aysha Kawasmi,&nbsp;Oren Ledder,&nbsp;Jeremiah Levine,&nbsp;James Markowitz,&nbsp;Manar Matar,&nbsp;Esther Orlanski-Meyer,&nbsp;Richard K. Russell,&nbsp;Ron Shaoul,&nbsp;Anat Yerushalmy-Feler,&nbsp;Diane R. Mould,&nbsp;Maire A. Conrad","doi":"10.1111/apt.18484","DOIUrl":"10.1111/apt.18484","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The pharmacokinetics of biologic agents can differ between children and adults with inflammatory bowel disease (IBD), often necessitating modified paediatric dosing strategies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>To define the exposure–response relationship of vedolizumab in the paediatric IBD VedoKids cohort including the effect of baseline clearance on deep biochemical remission (normal C-reactive protein [CRP]/erythrocyte sedimentation rate [ESR] and steroid-free remission) at 30 weeks, and to use population pharmacokinetic models to find the best matches between adult and paediatric pharmacokinetic profiles.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We sought a pharmacokinetic model on 312 serum vedolizumab concentrations from 129 children, assisted by a published adult model as a Bayesian prior. We employed the model for exposure–response evaluation and for investigating doses in paediatric patients to match the adult exposure at the labelled dose.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>At Week 30, 104/129 (81%) children (53% female and 47% Crohn disease) remained on vedolizumab, of whom 39 (31%) in the exposure-response evaluation were in deep biochemical remission. Increased baseline drug clearance was associated with lower deep biochemical remission rates at Week 30 based on ESR/CRP (OR 0.47 [95% CI 0.2–1.05, <i>p</i> = 0.08]) and calprotectin &lt; 100 μg/g (OR 0.13 [95% CI 0.1–0.79, <i>p</i> &lt; 0.05]). Higher weight and lower serum albumin were associated with increased clearance (<i>p</i> &lt; 0.001). Simulation models found that, for children ≤ 30 kg, tiered fixed dosing regimens best matched adult drug concentrations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Drug clearance was strongly influenced by serum albumin. Baseline clearance predicted deep biochemical remission at Week 30. Further investigation is needed to better understand optimal dosing strategies—especially for lower-weight children receiving vedolizumab.</p>\u0000 </section>\u0000 </div>","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"61 6","pages":"1000-1010"},"PeriodicalIF":6.6,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apt.18484","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142981661","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 of Placebo-Treated Patients: Dropout Rates From Treatment in MASH Randomised Controlled Trials","authors":"Matheus Souza,&nbsp;Marcio J. M. Amaral,&nbsp;Luan C. V. Lima,&nbsp;Cristiane Alves Villela-Nogueira","doi":"10.1111/apt.18498","DOIUrl":"10.1111/apt.18498","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Dropout is common and affects the statistical power and randomization balance of randomised controlled trials (RCTs).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>To estimate the dropout rate in RCTs of metabolic dysfunction-associated steatohepatitis (MASH) and to examine factors associated with dropout in placebo-treated participants.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>PubMed and Cochrane databases were searched for phase 2–4 MASH RCTs with placebo arms through November 24, 2024. Dropout was defined as the attrition of patients included in the intention-to-treat analysis but did not complete treatment. RCTs were qualitatively reviewed to assess the expected and observed dropouts. Generalised linear mixed model was used to estimate pooled dropout rates.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Sixty RCTs with 3230 placebo-treated participants with MASH were analysed. Thirty-three RCTs reported the dropout rate used to estimate the effect size. Of these, 60.6%, 36.4%, and 3.0% had an expected dropout rate that was higher, lower, and similar, respectively, than the observed dropout rate in the placebo arm. Overall, the dropout rate was 11.06% (95% confidence interval [CI] 9.07 to 13.42), with a higher rate in phase 3–4 trials than in phase 2 trials. The corresponding rates due to adverse events, loss to follow-up and patient choice were 2.41% (95% CI 1.67 to 3.48), 1.79% (95% CI 1.06 to 2.99) and 4.06% (95% CI 2.97 to 5.53), respectively. Meta-regression determined that the dropout rate increased with longer treatment duration.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Placebo dropout in MASH RCTs is significant, mainly due to patient choice. Factors such as trial phase and treatment duration should be considered when calculating sample size in future clinical trials.</p>\u0000 </section>\u0000 </div>","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"61 5","pages":"776-786"},"PeriodicalIF":6.6,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142975244","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}