{"title":"Letter: Disappearing Microbe, Emerging Disease? Nuancing the Protective Effects of Helicobacter pylori Against Eosinophilic Oesophagitis. Authors' Reply","authors":"Irene Spinelli, Gianluca Ianiro","doi":"10.1111/apt.70099","DOIUrl":"10.1111/apt.70099","url":null,"abstract":"<p>We sincerely appreciate the constructive comments from Drs. Emanuele and Minoretti [<span>1</span>] on our meta-analysis of the potential protective role of <i>Helicobacter pylori</i> (<i>H. pylori</i>) infection against eosinophilic oesophagitis (EoE) [<span>2</span>], and are keen to address each point they raised.</p><p>The <i>cagA</i> protein has a well-known virulence effect in positive strains, and its enhancement of the Th1 response may play a role in reducing the Th2 response characteristic of EoE. Although a comparison of patients with <i>H. pylori</i> infection based on their <i>cagA</i> status would be of interest, we were unable to make this subgroup analysis due to the lack of availability of pertinent data in included studies.</p><p>We also acknowledge that the significant differences in the prevalence of <i>H. pylori</i> infection between Eastern and Western cohorts may be explained by region-specific confounders, which may be further depicted by regression models. However, we also highlight that the odds ratios in the two cohorts were almost equal (0.53 <i>v</i>. 0.52). This suggests that, regardless of the specific geographical prevalence of <i>H. pylori</i> infection, related mechanisms of protection are similar worldwide.</p><p>We agree with Drs. Emanuele and Minoretti that further evidence, arising from case–control studies nested within longitudinal birth cohorts and Mendelian randomisation studies, may clarify whether early <i>H. pylori</i> infection may be associated with a lower prevalence of EoE. However, we did not observe a significant odds reduction for EoE in paediatric patients infected with <i>H. pylori</i>. Possible explanations were the limited number of studies and the influence of genetic factors over environment [<span>2</span>]. However, this suggests that further evidence is needed to address the relationship between <i>H. pylori</i> and EoE in early life.</p><p>We are well aware that non-invasive biomarkers are an unmet need in EoE, and that its diagnosis and monitoring currently rely totally on upper endoscopy and histology. Several tests are emerging as potential candidates to monitor disease activity, but their application in clinical practice is still under validation [<span>3-5</span>]. In addition, omics technologies offer new insights into the genetic and immunologic mechanisms of EoE, but research is still nascent [<span>6, 7</span>].</p><p>Finally, incorporating the prevalence of <i>H. pylori</i> infection into ongoing EoE studies [<span>8-10</span>] would be of utmost interest because it could help clarify whether <i>H. pylori</i> plays a role in treatment response and whether it should be considered a factor in therapeutic decision-making.</p><p>We thank Drs. Emanuele and Minoretti for their careful analysis of our work and for their contribution to this important discussion.</p><p><b>Irene Spinelli:</b> conceptualization, investigation, methodology, data curation, resources, project administra","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"61 9","pages":"1575-1576"},"PeriodicalIF":6.6,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apt.70099","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143702857","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: Disappearing Microbe, Emerging Disease? Nuancing the Protective Effects of Helicobacter pylori Against Eosinophilic Oesophagitis","authors":"Enzo Emanuele, Piercarlo Minoretti","doi":"10.1111/apt.70075","DOIUrl":"10.1111/apt.70075","url":null,"abstract":"<p>We commend Spinelli et al. [<span>1</span>] for their comprehensive meta-analysis of 19 studies encompassing 1.7 million subjects, which substantially advances our understanding of <i>Helicobacter pylori</i> (Hp) infection's potential protective role against eosinophilic oesophagitis (EoE). Their findings demonstrate a notable 46% reduction in the odds of EoE development among Hp-exposed individuals. Notwithstanding the meticulous synthesis of existing data, several methodological refinements and research directions warrant consideration to further elucidate this intriguing epidemiological relationship.</p><p>First, stratification by Hp virulence factors and strain specificity could illuminate mechanistic insights. While the meta-analysis aggregated all Hp infections, growing evidence suggests strain-specific immunomodulatory effects—particularly cagA+ strains, which elicit more robust Th1 responses [<span>2</span>]. Subgroup analyses comparing cagA+ versus cagA− infections might reveal differential protection against EoE, as observed in other Th2-mediated conditions such as asthma [<span>3</span>]. Second, geographic heterogeneity warrants deeper exploration. Although Spinelli et al. [<span>1</span>] found comparable odds reductions in Eastern (odds ratio: 0.53) and Western (odds ratio: 0.52) cohorts, Hp infection prevalence diverged remarkably (43% vs. 14%, respectively). This paradox suggests region-specific confounders, such as genetic factors or endemic helminth infections synergising with Hp's immunoregulatory effects [<span>4</span>]. Regression models accounting for regional socioeconomic indices, sanitation standards and antibiotic stewardship could disentangle these interactions further. Third, temporality in the Hp–EoE relationship remains unresolved. The stronger inverse association in post-2019 studies (56% vs. 37% reduction) [<span>1</span>] is in accordance with EoE's rising incidence but raises questions about birth cohort effects [<span>5</span>]. Case–control studies nested within longitudinal birth cohorts could clarify whether early-life Hp acquisition may confer greater protection than adult exposure, as hypothesised for allergic diseases. Additionally, Mendelian randomisation studies using genetic variants as proxies for Hp susceptibility might better establish causality whilst minimising confounding [<span>6</span>]. Fourthly, the meta-analysis did not elaborate on mucosal cytokine profiles, transcriptomic alterations, or microbiome signatures associated with EoE and their potential modification by Hp infection. We further contend that non-invasive biomarkers of EoE, including autoantibodies and inflammatory mediators [<span>7</span>], warrant comprehensive investigation in relation to Hp. pylori status. Finally, within existing clinical trials involving EoE patients [<span>8-10</span>], it would be valuable to analyse the prevalence of Hp infection and to examine how it might influence therapeutic outcomes.</p><p>In con","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"61 9","pages":"1573-1574"},"PeriodicalIF":6.6,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apt.70075","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143703544","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: Chrononutrition and MASLD—Its About Time (Restricted Feeding)!","authors":"Hannah Mohr, Jonathan G. Stine","doi":"10.1111/apt.70078","DOIUrl":"10.1111/apt.70078","url":null,"abstract":"<p>The global obesity epidemic and the widespread adoption of a Westernised diet high in sugar and processed foods, alongside a sedentary lifestyle, have fueled the rise of metabolic dysfunction-associated steatotic liver disease (MASLD) [<span>1</span>]. Since an unhealthy lifestyle is central to MASLD development, effective lifestyle interventions remain essential for improving patient outcomes [<span>2</span>]. The Mediterranean diet (MD), rich in produce, whole grains and healthy fats like olive oil, while limiting red meat and processed foods, is widely recognized as a key dietary intervention [<span>3, 4</span>]. Adherence to MD has shown reduction in hepatic fat, improved insulin sensitivity, and slowed MASLD progression [<span>5, 6</span>]. However, barriers such as cost, accessibility, and cultural preferences hinder widespread adoption. As a result, alternative dietary strategies, such as time-restricted feeding (TRF), have gained attention. TRF limits food intake to a set daily window, typically 6 to 10 h, followed by fasting. Although TRF has demonstrated metabolic health benefits, particularly when paired with caloric restriction [<span>7</span>], its optimal implementation and impact on MASLD remain unclear, and it is not yet considered standard of care.</p><p>In the CHRONO-NAFLD study, Tsitsou et al. [<span>8</span>] explored the efficacy of a TRF + MD combination. The 12-week trial randomized 71 adults with MASLD and overweight/obesity into three groups: hypocaloric MD (control), hypocaloric MD + early TRF (8 AM–6 PM), and hypocaloric MD + late TRF (12 PM–10 PM). Dietary adherence was rigorously measured using self-reports verified by study personnel and reinforced via phone calls, with > 90% adherence in each group. The study boasted a high completion rate of 83%. All groups experienced significant reductions in body weight, body fat, and blood pressure, along with improvements in VCTE-measured liver fat and a modest trend toward reduced liver stiffness. Notably, the only between-group differences emerged in glycemic control, with improvements in insulin resistance and hemoglobin A1c observed in both TRF groups. However, these changes, while statistically significant, did not reach clinically meaningful thresholds (Figure 1).</p><p>Importantly, this study has several strengths, including a well-characterized population, rigorous methodology, and validated dietary adherence measures assessing multiple clinically relevant outcomes. However, limitations include selection bias (84% of participants had moderate MD adherence at baseline) and most were physically active (> 600 MET-min/week). This limits generalisability, as the cohort was relatively homogenous and inclined toward MD consumption. Key confounders, such as meal composition and physical activity changes, were also not fully controlled. The study design also precluded distinguishing whether observed benefits stemmed from TRF itself or from caloric restriction.</p><p>In","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"61 9","pages":"1565-1566"},"PeriodicalIF":6.6,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apt.70078","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143713050","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}
Sofia Tsitsou, Magdalini Adamantou, Triada Bali, Aristi Saridaki, Kalliopi-Anna Poulia, Dimitrios S. Karagiannakis, Emilia Papakonstantinou, Evangelos Cholongitas
{"title":"Editorial: Chrononutrition and MASLD—It is About Time (Restricted Feeding)! Authors' Reply","authors":"Sofia Tsitsou, Magdalini Adamantou, Triada Bali, Aristi Saridaki, Kalliopi-Anna Poulia, Dimitrios S. Karagiannakis, Emilia Papakonstantinou, Evangelos Cholongitas","doi":"10.1111/apt.70107","DOIUrl":"10.1111/apt.70107","url":null,"abstract":"<p>We sincerely appreciate the opportunity to respond to the editorial by Mohr and Stine discussing our study on the effects of a 12-week Mediterranean-type time-restricted feeding (TRF) protocol in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) [<span>1, 2</span>]. We are grateful for their insightful commentary and for highlighting the strengths of our randomised controlled trial (RCT). Their analysis underscores the emerging role of chrononutrition in managing MASLD while also highlighting key questions regarding the independent contribution of TRF and caloric restriction to metabolic improvements. There is indeed a great need for studies that directly compare ad libitum TRF protocols with caloric restriction to evaluate their differentiative impact on several metabolic parameters. Most of the studies in MASLD have compared either ad libitum TRF protocols with the usual dietary habits of the participants or hypocaloric diets in both TRF and control groups, as in our study.</p><p>Our study was the first RCT that used the Mediterranean Diet (MD) as a control group, the gold standard for patients with MASLD [<span>3</span>]. The MD has been extensively documented as an effective intervention for MASLD [<span>4</span>]. Our study adds to this body of evidence by demonstrating that a hypocaloric MD, even over a short-term period, yields significant improvements in body weight, body fat, blood pressure and liver fat content [<span>1</span>]. Regarding the comment on the generalizability of the results [<span>2</span>], it is true that Greece is a Mediterranean country, and as described in previous studies, Greeks' adherence to the MD is moderate [<span>5</span>]. Our results [<span>1</span>] agree with these studies [<span>5</span>] and this may have enhanced our participants' adherence.</p><p>The TRF interventions (early or late) did not seem to improve the metabolic parameters mentioned above further in this population [<span>1</span>]. However, insulin resistance and haemoglobin A<sub>1c</sub> (HbA<sub>1c</sub>) were only improved in the early but not in the late TRF group. The reduction in HbA<sub>1c</sub> in the early TRF group (0.3% in total, 0.37% in those with T2DM under early TRF) in our study [<span>1</span>] was greater than in other similar studies, for example, 0.2% in the study by Wei et al. (early TRF + caloric restriction group) [<span>6</span>], whilst this grade of improvement has been associated with lower mortality in individuals with T2DM [<span>7</span>] and reduction in diabetic complications [<span>8</span>]. Prior studies suggest that aligning food intake with circadian rhythms and the light/dark cycle via TRF may enhance glucose metabolism independent of caloric restriction as humans are diurnal [<span>9</span>]. This is particularly relevant for MASLD patients, where insulin resistance is a pivotal driver of disease progression [<span>10</span>]. That means that the differences in glucose me","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"61 9","pages":"1567-1568"},"PeriodicalIF":6.6,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apt.70107","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143713053","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: Cumulative Impact of Clinical Disease Activity, Biochemical Activity and Psychological Health on the Natural History of Inflammatory Bowel Disease During 8 Years of Longitudinal Follow-Up","authors":"Ben Massouridis, Akhilesh Swaminathan","doi":"10.1111/apt.70086","DOIUrl":"10.1111/apt.70086","url":null,"abstract":"<p>Inflammatory bowel disease (IBD) is a chronic inflammatory condition of the gastrointestinal tract, which has wide-ranging impacts for a patient. These can include severe gut symptoms, a period or lifetime of disability and significant effects on an individual's psychological health [<span>1, 2</span>]. Providing truly holistic care for a patient with IBD requires addressing both the inflammatory and noninflammatory burden of this debilitating disease.</p><p>Gut mucosal inflammation is a well-characterised contributor to the longitudinal course of IBD [<span>2</span>]. However, the impacts of the non-inflammatory burden on the longer term prognosis of IBD remain less certain. A recent study by Riggot et al. [<span>3</span>] explored this facet in a cohort of patients who were followed for 8 years. In this single-centre prospective cohort study, rates of IBD flares, glucocorticoid prescription, need for hospitalisation and/or intestinal resection were highest in those with clinical and biochemical disease activity with concomitant common mental health disorders. Of note, the presence of psychological comorbidity was associated with an increase in adverse outcomes even in individuals who were in biochemical disease remission at baseline assessment [<span>3</span>]. These findings reiterate the importance of considering brain–gut effects and the additive role of psychological morbidity on longer term IBD prognosis. However, the replication of such studies in ethnically and socioeconomically diverse cohorts is required to assess the impact of brain–gut effects in different populations living with IBD.</p><p>Screening for mental health issues is increasingly recognised as part of an integrated multidisciplinary approach to IBD care and is accepted by patients [<span>4, 5</span>]. The challenge, however, is in appropriately addressing these issues over the duration of the disease course to result in a sustained and meaningful improvement in long-term health outcomes. A previous meta-analysis of psychological therapies targeting the gut–brain axis in IBD has shown short-term improvements to psychological health and quality of life, but longer term benefits remain less clear [<span>6</span>]. Thus, appropriately identifying patients who are most likely to benefit from such therapies and finding a sustainable means to manage their psychological issues is a challenge for modern-day IBD practice. This is increasingly relevant given the rising costs of managing IBD and the increasing worldwide prevalence of this disease [<span>7, 8</span>].</p><p>Furthermore, aspects of IBD care such as medication adherence are also impacted by psychological health. Medication nonadherence in patients with IBD can result in uncontrolled disease and risk of disease-related complications, which are higher in patients with psychological health concerns [<span>9</span>]. Therefore, appropriately addressing these aspects of care may also help to improve medication adherence, p","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"61 10","pages":"1705-1706"},"PeriodicalIF":6.6,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apt.70086","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143672283","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}
Christy Riggott, Keeley M. Fairbrass, David J. Gracie, Alexander C. Ford
{"title":"Editorial: Cumulative Impact of Clinical Disease Activity, Biochemical Activity and Psychological Health on the Natural History of Inflammatory Bowel Disease During 8 Years of Longitudinal Follow-Up. Authors' Reply","authors":"Christy Riggott, Keeley M. Fairbrass, David J. Gracie, Alexander C. Ford","doi":"10.1111/apt.70100","DOIUrl":"10.1111/apt.70100","url":null,"abstract":"<p>We would like to thank Drs Massouridis and Swaminathan for their editorial dealing with our article and welcome this opportunity for further discussion [<span>1, 2</span>]. Bi-directionality of gut–brain axis communications has been highlighted consistently in inflammatory bowel disease (IBD), with both a high prevalence of symptoms of common mental disorders (CMD) and an association between the presence of these symptoms and future adverse disease outcomes [<span>3</span>]. Although poor psychological health is most apparent during periods of disease activity, the prevalence of symptoms compatible with a CMD remains twice that of the general population even in quiescent disease, suggesting factors beyond inflammatory burden contribute to their development [<span>1, 3</span>]. Furthermore, a recently published longitudinal follow-up study examining trajectories of these symptoms in patients with IBD demonstrates that abnormal anxiety and depression scores persist in almost half of patients, suggesting poor psychological health is a constant for many patients [<span>4</span>]. Psychological health may, therefore, be an important therapeutic target in IBD.</p><p>A biopsychosocial model of care is advocated for patients with irritable bowel syndrome (IBS), including access to brain–gut behavioural therapies and gut–brain neuromodulators to manage the associated symptoms [<span>5, 6</span>]. With the current lack of focus on psychological health in IBD management guidelines, holistic care models are yet to translate to routine IBD care. A substantial barrier to the implementation of such models is a lack of informative research. Few randomised controlled trials (RCTs) have assessed the effects of brain–gut behavioural therapies or gut–brain neuromodulators in patients with IBD with pre-existing psychological co-morbidity, who are the patient group most likely to benefit from the addition of such therapies [<span>7</span>]. In addition, identifying patients with symptoms of a CMD may be difficult given the time-sensitive nature of routine IBD care, where the focus is on managing inflammatory burden. Model-based clustering techniques incorporating measures of psychological and gastrointestinal symptom severity have identified clusters of patients with IBD and high psychological symptom burden, and could serve in clinical practice to identify subgroups of patients who may experience a benefit from brain–gut behavioural therapies or gut–brain neuromodulators [<span>8</span>]. Furthermore, one quarter of patients with IBD with endoscopically quiescent disease also report symptoms that are compatible with IBS [<span>9</span>]. Such patients, if identified in clinical practice, may also be best managed with brain–gut behavioural therapies or gut–brain neuromodulators, similar to the paradigm in IBS.</p><p>Finally, as suggested, replication of this research is required in ethnically and socioeconomically diverse cohorts [<span>2</span>]. In fact, the unde","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"61 10","pages":"1707-1708"},"PeriodicalIF":6.6,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apt.70100","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143672419","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}
Shamim Joudaki, Olamide Oladipupo, Isabel Carbery, Marco Vincenzo Lenti, Christian P. Selinger
{"title":"Meta-Analysis: Pregnancies With Inflammatory Bowel Disease Complicated by Intrahepatic Cholestasis of Pregnancy","authors":"Shamim Joudaki, Olamide Oladipupo, Isabel Carbery, Marco Vincenzo Lenti, Christian P. Selinger","doi":"10.1111/apt.70096","DOIUrl":"10.1111/apt.70096","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Inflammatory Bowel Disease (IBD) requires maintenance of remission during pregnancy to avoid poor maternal and fetal outcomes. Intrahepatic cholestasis of pregnancy (ICP) could also increase these risks.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>To examine the prevalence of ICP in pregnancies with IBD and associations with thiopurine exposure.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>An electronic search of MEDLINE, EMBASE, and EMBASE Classic databases using search terms for IBD and ICP from inception to 10th September 2024 was performed. Studies involving pregnant adults with a confirmed diagnosis of IBD reporting ICP were included. Prevalence and event numbers for ICP were pooled using a random effects model.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We identified two case reports, a case series of eight cases, and three cohort studies. Pooled prevalence of ICP in 1603 pregnancies with IBD was 3% (95% confidence interval [CI] 1.0%–7.0%). One cohort study reported that the prevalence of ICP in IBD was significantly higher compared to the general population (odds ratio [OR] 3.08 [95% CI 1.11–8.56], <i>p</i> = 0.039). Meta-analysis showed that thiopurine exposure was associated with an increased risk of ICP, OR 6.65 [95% CI 3.10–14.25]. One cohort study showed that, compared to non-IBD controls, the incidence of ICP was increased in thiopurine exposed pregnancies (OR 7.55 [95% CI 2.52–22.57] <i>p</i> < 0.001) but not in non-exposed pregnancies (OR 1.41 [95% CI 0.40–4.92], <i>p</i> = 0.75).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Patients with IBD have a higher risk of ICP compared to the general population. Thiopurine exposure in patients with IBD is associated with an increased risk of ICP. Clinicians should monitor pregnant patients with IBD exposed to thiopurines for symptoms of ICP.</p>\u0000 </section>\u0000 </div>","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"61 9","pages":"1430-1436"},"PeriodicalIF":6.6,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143666372","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}
R. Parker, A. Taylor, R. Dukes, B. Wilks, A. Hinkson, D. Burn, I. A. Rowe
{"title":"Risk Factors for Liver Disease Cluster Geographically: A Precision Public Health Analysis of a UK City","authors":"R. Parker, A. Taylor, R. Dukes, B. Wilks, A. Hinkson, D. Burn, I. A. Rowe","doi":"10.1111/apt.70088","DOIUrl":"10.1111/apt.70088","url":null,"abstract":"<p>These data describe the distribution of risk factors for liver disease in Leeds, a large city in the UK. Anonymised, unlinked data were aggregated to lower super output areas by the Leeds GP data extraction programme for deprivation, obesity, diabetes and alcohol use. Incident liver disease was quantified from coding of hospital admissions. Alcohol use, deprivation and obesity were associated with LD. Risk factors clustered together geographically. Liver blood tests were more frequently done in areas of low-disease prevalence. These results illustrate health inequalities and support public health policies to reduce incident liver disease.</p>","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"61 10","pages":"1697-1702"},"PeriodicalIF":6.6,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apt.70088","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143653518","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: Predictors of Corticosteroid Response in Alcohol-Related Hepatitis","authors":"Ewan Forrest, Richard Parker, Mark Thursz","doi":"10.1111/apt.70074","DOIUrl":"10.1111/apt.70074","url":null,"abstract":"<p>We read with interest the observational study by Idalsoaga et al. [<span>1</span>], which analysed a group of 289 patients treated with corticosteroids for alcohol-related hepatitis (AH). Models to determine response to corticosteroid therapy were assessed. It found that the Lille-7 score was the best-performing model, although none of the tested models had a high degree of discrimination. Determining response to corticosteroids for AH is important in order to abbreviate treatment in those not deriving benefit and so avoid corticosteroid-related complications. A dynamic model is one which looks at a change in variables after exposure to corticosteroids to determine their effectiveness. This is certainly true of the Lille model, which includes change in bilirubin from baseline (pre-treatment) to either Day 4 or Day 7 of treatment. However, the authors have also tested the trajectory of serum bilirubin (TSB), the neutrophil-to-lymphocyte ratio (NLR) and the change in NLR (Delta NLR), none of which have been proposed as indicators of response to already initiated corticosteroid therapy.</p><p>The TSB was originally described to categorise the trajectory of bilirubin before exposure to corticosteroids [<span>2</span>]. Therefore, it is a characteristic of a patient pre-treatment and not a dynamic model reflecting the response to already initiated corticosteroid treatment. If the authors wished to look at the change in bilirubin after exposure to corticosteroids, they should have used either ‘early change in bilirubin’ (ECBL) [<span>3</span>], or the percentage change in bilirubin over 1 week [<span>4</span>].</p><p>Similarly, the NLR has only been described as a baseline characteristic to identify those likely to benefit from corticosteroid treatment compared with those not receiving such treatment. The NLR has never been advocated as a simple prognostic or dynamic model, but as a baseline variable with a narrow ‘window’ (between 5 and 8) to predict improved outcomes with corticosteroid treatment [<span>5</span>]. This was demonstrated in 789 patients enrolled in the STOPAH trial and validated in a separate group of 237 patients. As there is a ‘window’ of NLR which identifies those who may benefit from corticosteroids, it is to be expected that it would perform poorly when analysed as a linear prognostic score. Its value can only be determined by comparing treated with untreated patients, which the current study does not assess. Delta NLR has never previously been suggested as a model to assess corticosteroid treatment in AH, and the well-recognised effects of corticosteroids upon circulating leucocytes will make this difficult to interpret.</p><p>In conclusion, Idalsoag and colleagues have identified the Lille score at Day 7 as the most useful model to determine response in those who have already started corticosteroids. However, their study has not been designed to investigate TSB or NLR as useful pre-treatment characteristics of patients. These","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"61 9","pages":"1569-1570"},"PeriodicalIF":6.6,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apt.70074","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143660566","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}
Francisco Idalsoaga, Luis Antonio Díaz, Ramon Bataller, Juan Pablo Arab
{"title":"Letter: Predictors of Corticosteroid Response in Alcohol-Related Hepatitis—Authors' Reply","authors":"Francisco Idalsoaga, Luis Antonio Díaz, Ramon Bataller, Juan Pablo Arab","doi":"10.1111/apt.70095","DOIUrl":"10.1111/apt.70095","url":null,"abstract":"<p>Severe alcohol-associated hepatitis (AH) is a condition that bears a high short-term mortality [<span>1</span>], and corticosteroids are currently the only available therapy for patients with this disease [<span>2</span>]. However, given the well-documented adverse effects associated with corticosteroid use, it is clinically relevant to identify patients who will benefit the most from this treatment [<span>3</span>]. In our recent study [<span>4</span>], through a multinational analysis, we evaluated the performance of different dynamic models (defined as those using laboratory data from at least two time-points) to predict 30- and 90-day mortality in patients with severe AH. Our results revealed that the Lille day 7 score (Lille-7) was the most accurate model for predicting both 30-day and 90-day mortality. The Lille day 4 score (Lille-4) and the Trajectory of serum bilirubin (TSB) also demonstrated moderate predictive value. Interestingly, no significant differences were found when comparing Lille-7, Lille-4 and TSB.</p><p>We appreciate the letter from Forrest et al. regarding our paper and their comments on the prognostic utility of the delta neutrophil-to-lymphocyte ratio (NLR) in patients with AH [<span>5</span>]. Although the original study by Forrest et al. [<span>6</span>], on the neutrophil-to-lymphocyte ratio (NLR) was primarily designed to identify patients who were likely to benefit from corticosteroid treatment, the use of delta NLR has been explored in multiple disease scenarios with significant inflammatory components, such as AH [<span>7</span>]. In fact, its utility has been assessed in various contexts, including living donor liver transplantation and graft survival [<span>8</span>], as well as its association with increased mortality in patients with hepatocellular carcinoma [<span>9</span>]. Furthermore, a study conducted in France that included 116 patients with cirrhosis admitted to the ICU found that the use of delta NLR was also an independent predictor of mortality at 28 days [<span>10</span>]. However, when specifically evaluated in AH in our study, this score did not demonstrate predictive power for mortality at 30 or 90 days, particularly in patients receiving corticosteroids.</p><p>The use of TSB as a predictor of mortality had been validated in AH, specifically in patients before corticosteroid treatment [<span>11</span>]. In our study, when using this model as a dynamic score during the use of steroids, it was useful to predict mortality at 30 and 90 days. Interestingly, no significant differences were observed when comparing TSB to Lille-7, and it also demonstrated comparable performance to Lille-4. Both TSB and Lille-4 are valuable tools for risk stratification in patients with severe AH. Thus, although Lille-7 remains the most validated dynamic score, shortening the assessment period to 4 days may have a good discriminatory ability, reducing unnecessary exposure to corticosteroids. Finally, there is a clear ne","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"61 9","pages":"1571-1572"},"PeriodicalIF":6.6,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apt.70095","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143660551","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}