Verónica Segura, Ángela Ruiz-Carnicer, Ángeles Pizarro, Carmen González-Naranjo, Jacobo Díaz, Cristóbal Coronel-Rodríguez, Federico Argüelles-Arias, Marta Garzón-Benavides, Carolina Sousa, Isabel Comino
Faecal calprotectin is used to assess intestinal inflammation, but its role in monitoring mucosal healing in coeliac disease is unclear. This study followed 48 adults with coeliac disease on a gluten-free diet over 12 months, evaluating faecal calprotectin levels in correlation with anti-transglutaminase antibodies, gluten-free diet adherence by dietary questionnaires and histology. Although significant histological lesions (Marsh II-III) decreased from 24% to 10%, faecal calprotectin levels fluctuated without correlation to anti-transglutaminase, adherence or histological remission, and did not differentiate between lesion grades. Our findings underscore faecal calprotectin's unreliability in monitoring mucosal healing in adults with coeliac disease, highlighting the urgent need for alternative biomarkers.
{"title":"Limitations of Faecal Calprotectin in Detecting Histological Changes and Persistent Villous Atrophy in Patients With Coeliac Disease on a Gluten-Free Diet.","authors":"Verónica Segura, Ángela Ruiz-Carnicer, Ángeles Pizarro, Carmen González-Naranjo, Jacobo Díaz, Cristóbal Coronel-Rodríguez, Federico Argüelles-Arias, Marta Garzón-Benavides, Carolina Sousa, Isabel Comino","doi":"10.1111/apt.70114","DOIUrl":"https://doi.org/10.1111/apt.70114","url":null,"abstract":"<p><p>Faecal calprotectin is used to assess intestinal inflammation, but its role in monitoring mucosal healing in coeliac disease is unclear. This study followed 48 adults with coeliac disease on a gluten-free diet over 12 months, evaluating faecal calprotectin levels in correlation with anti-transglutaminase antibodies, gluten-free diet adherence by dietary questionnaires and histology. Although significant histological lesions (Marsh II-III) decreased from 24% to 10%, faecal calprotectin levels fluctuated without correlation to anti-transglutaminase, adherence or histological remission, and did not differentiate between lesion grades. Our findings underscore faecal calprotectin's unreliability in monitoring mucosal healing in adults with coeliac disease, highlighting the urgent need for alternative biomarkers.</p>","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143762663","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}
<p>Recent evidence suggests that air pollution also contributes to the development of metabolic dysfunction associated with steatosis liver disease (MASLD), progression of cirrhosis, incidence of hepatocellular carcinoma (HCC), and liver-related mortality beyond lung disease [<span>1-5</span>]. Particulate matter 2.5 (PM2.5) and NOx are the most extensively studied in liver disease. A meta-analysis investigating the association between air pollution and the incidence of MASLD and progression of cirrhosis showed that PM2.5, NOx, PM10, PM2.5–10, PM1, and air pollution from solid fuel combustion increased the risk of developing NAFLD and related cirrhosis [<span>3</span>]. Another systematic review on air pollution and HCC indicated that PM2.5 was also significantly associated with the incidence of HCC, whereas the associations with other air pollutants (nitrogen oxide (NOx)) and HCC and incidence of HCC and liver-related mortality remain inconclusive and require further research [<span>4</span>].</p><p>This study examines the association between air pollution and mortality in chronic hepatitis B (CHB) patients receiving nucleos(t)ide analog therapy, emphasising environmental exposures as a significant factor in liver disease progression. A significant finding of this study is the association between NOx exposure and increased mortality risk in CHB patients. Unlike prior research that predominantly examined metabolic disorders or HCC [<span>6, 7</span>], this study demonstrates that NOx levels exceeding 25.5 ppb are associated with a 2.5-fold increase in mortality risk among cirrhotic CHB patients. This finding underscores the necessity of incorporating environmental risk factors into liver disease management, particularly for high-risk populations. Furthermore, the study highlights the long-term impact of air pollution on CHB survival. Over a 10-year period, CHB patients residing in high NOx exposure regions exhibited a mortality rate of 37.6%, compared to 18.6% in lower-exposure areas. This contrast emphasises the need to include environmental factors in CHB treatment strategies. NOx exposure not only affects liver-related mortality but also increases overall mortality, highlighting the importance of a comprehensive approach to CHB care that mitigates environmental risks.</p><p>Another recent evidence suggests that certain populations may be more susceptible to the air pollution. Previous studies have reported that exposure to oxidative gaseous air pollutants is associated with an increase in liver fat content and the risk of developing MASLD, particularly showing a strong association in Hispanic participants [<span>8</span>]. This includes individuals with pre-existing liver conditions or those with genetic predispositions to liver cancer. A study conducted on 69 young adults from the Meta-AIR cohort examined the association between PNPLA3-I148M genotype, oxidative gaseous air pollutant exposure, and liver fat accumulation. After short-term expos
{"title":"Editorial: Air Pollution Associated With Mortality Among Chronic Hepatitis B Patients","authors":"Hyo Young Lee, Dae Won Jun","doi":"10.1111/apt.70062","DOIUrl":"10.1111/apt.70062","url":null,"abstract":"<p>Recent evidence suggests that air pollution also contributes to the development of metabolic dysfunction associated with steatosis liver disease (MASLD), progression of cirrhosis, incidence of hepatocellular carcinoma (HCC), and liver-related mortality beyond lung disease [<span>1-5</span>]. Particulate matter 2.5 (PM2.5) and NOx are the most extensively studied in liver disease. A meta-analysis investigating the association between air pollution and the incidence of MASLD and progression of cirrhosis showed that PM2.5, NOx, PM10, PM2.5–10, PM1, and air pollution from solid fuel combustion increased the risk of developing NAFLD and related cirrhosis [<span>3</span>]. Another systematic review on air pollution and HCC indicated that PM2.5 was also significantly associated with the incidence of HCC, whereas the associations with other air pollutants (nitrogen oxide (NOx)) and HCC and incidence of HCC and liver-related mortality remain inconclusive and require further research [<span>4</span>].</p><p>This study examines the association between air pollution and mortality in chronic hepatitis B (CHB) patients receiving nucleos(t)ide analog therapy, emphasising environmental exposures as a significant factor in liver disease progression. A significant finding of this study is the association between NOx exposure and increased mortality risk in CHB patients. Unlike prior research that predominantly examined metabolic disorders or HCC [<span>6, 7</span>], this study demonstrates that NOx levels exceeding 25.5 ppb are associated with a 2.5-fold increase in mortality risk among cirrhotic CHB patients. This finding underscores the necessity of incorporating environmental risk factors into liver disease management, particularly for high-risk populations. Furthermore, the study highlights the long-term impact of air pollution on CHB survival. Over a 10-year period, CHB patients residing in high NOx exposure regions exhibited a mortality rate of 37.6%, compared to 18.6% in lower-exposure areas. This contrast emphasises the need to include environmental factors in CHB treatment strategies. NOx exposure not only affects liver-related mortality but also increases overall mortality, highlighting the importance of a comprehensive approach to CHB care that mitigates environmental risks.</p><p>Another recent evidence suggests that certain populations may be more susceptible to the air pollution. Previous studies have reported that exposure to oxidative gaseous air pollutants is associated with an increase in liver fat content and the risk of developing MASLD, particularly showing a strong association in Hispanic participants [<span>8</span>]. This includes individuals with pre-existing liver conditions or those with genetic predispositions to liver cancer. A study conducted on 69 young adults from the Meta-AIR cohort examined the association between PNPLA3-I148M genotype, oxidative gaseous air pollutant exposure, and liver fat accumulation. After short-term expos","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"61 9","pages":"1545-1546"},"PeriodicalIF":6.6,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apt.70062","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143766588","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}
Matthew K. W. Chu, Alice S. Day, Lani Broad, Samuel P. Costello, Suzanne Edwards, Robert V. Bryant
<p>We appreciate the interest of Melton et al. in our systematic review and meta-analysis on the use of exclusive enteral nutrition (EEN) in the management of ulcerative colitis (UC) in adults [<span>1, 2</span>].</p><p>As Melton et al. described, while preclinical studies suggest that elemental diets may improve intestinal inflammation in UC-like murine models, these effects have not been consistently replicated in human clinical trials. As in Crohn's disease (CD), the mechanistic efficacy of EEN in UC remains uncertain. Luminal factors thought to contribute to intestinal inflammation, such as increased hydrogen sulphide levels, reduced short-chain fatty acids (SCFA), and decreased microbiota diversity, have paradoxically been observed with EEN [<span>3</span>]. However, these effects may be mitigated by incorporating fibre-containing EEN formulas, which provide substrates necessary for microbial carbohydrate fermentation, thereby mitigating potentially deleterious sequelae of EEN [<span>3</span>].</p><p>It is an important observation that most associations between EEN and microbial alterations stem from studies on CD. However, contemporary studies of EEN in UC provide some insights. In patients with acute severe UC (ASUC), EEN combined with standard-of-care (SOC) corticosteroid therapy significantly increased the abundance of beneficial bacteria, including <i>Faecalibacterium prausnitzii</i>, a species associated with immunomodulatory activity and SCFA production in the gut [<span>4, 5</span>]. In contrast, the abundance of <i>F. prausnitzii</i> is reduced in patients with CD undergoing EEN [<span>6</span>]. These findings raise the possibility that EEN modulates the microbiota and metabolome differently in UC and CD; this should be further investigated in future studies.</p><p>As we highlighted, the current literature on EEN in UC is scarce and heterogeneous. Establishing a consistent EEN protocol, selecting clinically meaningful endpoints, defining their timeframe, and monitoring adherence are all crucial in designing future EEN trials. We identified significant heterogeneity across prospective and retrospective studies. In the treatment of ASUC, outcomes and time points should align with international consensus guidelines [<span>7</span>]. Moreover, given the availability of effective therapies in ASUC, EEN should only be considered an adjunct to SOC [<span>7</span>]. Exploring postoperative outcomes in patients receiving EEN before colectomy for ASUC would also provide valuable insights, as improved nutrition—reflected by significantly higher serum albumin levels in EEN-treated patients—may enhance post-surgical recovery.</p><p>Further investigation is also warranted to assess EEN's efficacy in mild UC, given that only one prospective trial has evaluated efficacy in this cohort [<span>8</span>]. In this setting, longer treatment durations (four or more weeks) could be explored. However, unlike CD, where corticosteroids are the mainstay ther
{"title":"Letter: Exclusive Enteral Nutrition in Ulcerative Colitis—The Path Ahead Needs Careful Consideration. Authors' Reply","authors":"Matthew K. W. Chu, Alice S. Day, Lani Broad, Samuel P. Costello, Suzanne Edwards, Robert V. Bryant","doi":"10.1111/apt.70121","DOIUrl":"10.1111/apt.70121","url":null,"abstract":"<p>We appreciate the interest of Melton et al. in our systematic review and meta-analysis on the use of exclusive enteral nutrition (EEN) in the management of ulcerative colitis (UC) in adults [<span>1, 2</span>].</p><p>As Melton et al. described, while preclinical studies suggest that elemental diets may improve intestinal inflammation in UC-like murine models, these effects have not been consistently replicated in human clinical trials. As in Crohn's disease (CD), the mechanistic efficacy of EEN in UC remains uncertain. Luminal factors thought to contribute to intestinal inflammation, such as increased hydrogen sulphide levels, reduced short-chain fatty acids (SCFA), and decreased microbiota diversity, have paradoxically been observed with EEN [<span>3</span>]. However, these effects may be mitigated by incorporating fibre-containing EEN formulas, which provide substrates necessary for microbial carbohydrate fermentation, thereby mitigating potentially deleterious sequelae of EEN [<span>3</span>].</p><p>It is an important observation that most associations between EEN and microbial alterations stem from studies on CD. However, contemporary studies of EEN in UC provide some insights. In patients with acute severe UC (ASUC), EEN combined with standard-of-care (SOC) corticosteroid therapy significantly increased the abundance of beneficial bacteria, including <i>Faecalibacterium prausnitzii</i>, a species associated with immunomodulatory activity and SCFA production in the gut [<span>4, 5</span>]. In contrast, the abundance of <i>F. prausnitzii</i> is reduced in patients with CD undergoing EEN [<span>6</span>]. These findings raise the possibility that EEN modulates the microbiota and metabolome differently in UC and CD; this should be further investigated in future studies.</p><p>As we highlighted, the current literature on EEN in UC is scarce and heterogeneous. Establishing a consistent EEN protocol, selecting clinically meaningful endpoints, defining their timeframe, and monitoring adherence are all crucial in designing future EEN trials. We identified significant heterogeneity across prospective and retrospective studies. In the treatment of ASUC, outcomes and time points should align with international consensus guidelines [<span>7</span>]. Moreover, given the availability of effective therapies in ASUC, EEN should only be considered an adjunct to SOC [<span>7</span>]. Exploring postoperative outcomes in patients receiving EEN before colectomy for ASUC would also provide valuable insights, as improved nutrition—reflected by significantly higher serum albumin levels in EEN-treated patients—may enhance post-surgical recovery.</p><p>Further investigation is also warranted to assess EEN's efficacy in mild UC, given that only one prospective trial has evaluated efficacy in this cohort [<span>8</span>]. In this setting, longer treatment durations (four or more weeks) could be explored. However, unlike CD, where corticosteroids are the mainstay ther","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"61 9","pages":"1579-1580"},"PeriodicalIF":6.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apt.70121","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143745075","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}
Erin R. Bonner, Werner Tschollar, Robert Anderson, Sulayman Mourabit
The cover image is based on the article Review Article: Novel Enzyme Therapy Design for Gluten Peptide Digestion Through Exopeptidase Supplementation by Erin R. Bonner et al., https://doi.org/10.1111/apt.70014
{"title":"Featured Cover","authors":"Erin R. Bonner, Werner Tschollar, Robert Anderson, Sulayman Mourabit","doi":"10.1111/apt.70117","DOIUrl":"https://doi.org/10.1111/apt.70117","url":null,"abstract":"<p>The cover image is based on the article <i>Review Article: Novel Enzyme Therapy Design for Gluten Peptide Digestion Through Exopeptidase Supplementation</i> by Erin R. Bonner et al., https://doi.org/10.1111/apt.70014 \u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"61 7","pages":"i"},"PeriodicalIF":6.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apt.70117","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143741327","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}
Donghee Kim, Pojsakorn Danpanichkul, Karn Wijarnpreecha, George Cholankeril, Aijaz Ahmed
Characterising the phenotypic features of individuals with metabolic dysfunction-associated steatotic liver disease (MASLD) can help identify high-risk subpopulations within this group. High-sensitivity troponin (hs-troponin) is a significant risk factor for future cardiovascular disease events.
{"title":"Association of High-Sensitivity Troponins in Metabolic Dysfunction-Associated Steatotic Liver Disease With All-Cause and Cause-Specific Mortality","authors":"Donghee Kim, Pojsakorn Danpanichkul, Karn Wijarnpreecha, George Cholankeril, Aijaz Ahmed","doi":"10.1111/apt.70128","DOIUrl":"https://doi.org/10.1111/apt.70128","url":null,"abstract":"Characterising the phenotypic features of individuals with metabolic dysfunction-associated steatotic liver disease (MASLD) can help identify high-risk subpopulations within this group. High-sensitivity troponin (hs-troponin) is a significant risk factor for future cardiovascular disease events.","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"37 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143745535","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}
<p>We read with interest the study by Peraza and colleagues examining the role of the Simple Endoscopic Score for Crohn's Disease (SES-CD) in defining mild Crohn's disease (CD) and predicting the risk of disease progression [<span>1</span>].</p><p>SES-CD is a well-established endoscopic scoring system used to assess CD severity based on ulcer size, ulcerated surface, affected surface without ulceration and stenosis [<span>2</span>]. SES-CD correlates with the more extensive Crohn's Disease Endoscopic Index of Severity and faecal calprotectin [<span>3, 4</span>].</p><p>Peraza et al. performed a retrospective analysis of 177 patients with CD from three major referral centres. They concluded that SES-CD ≥ 7 is an independent predictor of disease progression [<span>1</span>]. However, several limitations require further consideration.</p><p>The median disease duration at the time of endoscopy was 17 years, meaning that many patients had already declared their risk of progression or non-progression. In a population-based study, the cumulative risk of developing stricturing and/or penetrating complications was approximately 50% at 20 years post-diagnosis [<span>5</span>]. Despite this extended disease duration in this study, one-third of patients had an SES-CD score of 0 in the absence of current immunomodulator or biologic therapy, bringing the diagnosis of CD into question. How many of these patients had previously been treated with medical therapy for CD? What proportion simply reflects patients with previous isolated terminal ileal aphthous ulcers or ileitis without other evidence for CD, as is commonly encountered in clinical settings? [<span>6</span>] Hence, the study population may represent a less complex cohort, contrary to the authors' claim of including a more complex patient population.</p><p>Among this cohort, 14% had stricturing and 4% had fistulising disease at baseline. These complications would already classify such patients as moderate-to-severe, having had progression of their disease, and eligible for medical therapy to prevent further complications [<span>7</span>]. Therefore, inclusion of these patients does little to guide management decisions, particularly given the potential discrepancy between endoscopic and transmural findings in some patients [<span>8</span>].</p><p>The authors highlighted the advantage of SES-CD in assessing ileal and colonic disease activity separately, noting that an SES-CD ≥ 7 was more predictive of disease progression in ileal and ileocolonic disease than in isolated colonic disease. However, the study did not differentiate patients with small bowel CD or assess the predictive utility of SES-CD in this subgroup. An SES-CD of 4–6 in a patient with isolated ileal CD requires at least one or more of large ulcers (> 5 mm), ulcerated surface > 10%, affected surface > 50%, or narrowing. Hence, these patients would no longer be regarded as having mild disease, as recognised by inclusion criteria for m
{"title":"Letter: The Simple Endoscopic Score for Predicting Crohn's Disease Progression—Not as Simple as It Sounds","authors":"Ziheng Calvin Xu, Ethan Tan, Mayur Garg","doi":"10.1111/apt.70108","DOIUrl":"10.1111/apt.70108","url":null,"abstract":"<p>We read with interest the study by Peraza and colleagues examining the role of the Simple Endoscopic Score for Crohn's Disease (SES-CD) in defining mild Crohn's disease (CD) and predicting the risk of disease progression [<span>1</span>].</p><p>SES-CD is a well-established endoscopic scoring system used to assess CD severity based on ulcer size, ulcerated surface, affected surface without ulceration and stenosis [<span>2</span>]. SES-CD correlates with the more extensive Crohn's Disease Endoscopic Index of Severity and faecal calprotectin [<span>3, 4</span>].</p><p>Peraza et al. performed a retrospective analysis of 177 patients with CD from three major referral centres. They concluded that SES-CD ≥ 7 is an independent predictor of disease progression [<span>1</span>]. However, several limitations require further consideration.</p><p>The median disease duration at the time of endoscopy was 17 years, meaning that many patients had already declared their risk of progression or non-progression. In a population-based study, the cumulative risk of developing stricturing and/or penetrating complications was approximately 50% at 20 years post-diagnosis [<span>5</span>]. Despite this extended disease duration in this study, one-third of patients had an SES-CD score of 0 in the absence of current immunomodulator or biologic therapy, bringing the diagnosis of CD into question. How many of these patients had previously been treated with medical therapy for CD? What proportion simply reflects patients with previous isolated terminal ileal aphthous ulcers or ileitis without other evidence for CD, as is commonly encountered in clinical settings? [<span>6</span>] Hence, the study population may represent a less complex cohort, contrary to the authors' claim of including a more complex patient population.</p><p>Among this cohort, 14% had stricturing and 4% had fistulising disease at baseline. These complications would already classify such patients as moderate-to-severe, having had progression of their disease, and eligible for medical therapy to prevent further complications [<span>7</span>]. Therefore, inclusion of these patients does little to guide management decisions, particularly given the potential discrepancy between endoscopic and transmural findings in some patients [<span>8</span>].</p><p>The authors highlighted the advantage of SES-CD in assessing ileal and colonic disease activity separately, noting that an SES-CD ≥ 7 was more predictive of disease progression in ileal and ileocolonic disease than in isolated colonic disease. However, the study did not differentiate patients with small bowel CD or assess the predictive utility of SES-CD in this subgroup. An SES-CD of 4–6 in a patient with isolated ileal CD requires at least one or more of large ulcers (> 5 mm), ulcerated surface > 10%, affected surface > 50%, or narrowing. Hence, these patients would no longer be regarded as having mild disease, as recognised by inclusion criteria for m","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"61 9","pages":"1585-1586"},"PeriodicalIF":6.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apt.70108","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143745537","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}
Peter J. Kahrilas, Laurie Keefer, Rena Yadlapati, Foteini Anastasiou, Joel J. Heidelbaugh, Colin W. Howden, Juan M. Mendive, Edoardo Vincenzo Savarino, Mihaela Udrescu, A. Pali S. Hungin
Background
Reflux-like symptoms and reflux oesophagitis are often perceived as having the same acid-related aetiology and responsiveness to antisecretory therapy. However, the frequency of residual symptom reporting on proton pump inhibitor (PPI) therapy suggests the two entities have some differential pathophysiological determinants requiring distinct management approaches.
Aims
To examine the complexities of reflux-like symptom pathophysiology and strategies that may be used to target contributing factors beyond acid reflux.
Methods
A panel of ten expert clinicians (primary care, gastroenterology and psychology) held a series of online meetings to share perspectives on the underlying contributors to, and management of, reflux-like symptoms when PPIs are ineffective or provide partial relief. This review summarises the agreed key themes that emerged from the expert discussions.
Results
While degradation of the anti-reflux barrier dominates in reflux oesophagitis, cognitive-affective, behavioural, and other psychosocial factors can play a major role in symptom persistence. These require individualised management strategies, beginning with education on the gut-brain connection and expectation setting with regard to PPI therapy. A detailed clinical history and patient-reported outcome tools that measure symptom burden and associated anxiety/hypervigilance can help guide management using brain-gut behavioural therapies, supported diet/lifestyle modification, diaphragmatic breathing, weight loss, and/or on-demand symptom control measures according to a patient's specific needs.
Conclusions
A paradigm shift in reflux-like symptom management is required such that acid suppression is viewed as one of several interventions that can be utilised as part of a phenotype-driven, individualised approach to care that acknowledges the multiple contributors to symptom burden.
{"title":"Review Article: Individualised Management of Reflux-Like Symptoms—Strategies Beyond Acid Suppression","authors":"Peter J. Kahrilas, Laurie Keefer, Rena Yadlapati, Foteini Anastasiou, Joel J. Heidelbaugh, Colin W. Howden, Juan M. Mendive, Edoardo Vincenzo Savarino, Mihaela Udrescu, A. Pali S. Hungin","doi":"10.1111/apt.70115","DOIUrl":"10.1111/apt.70115","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Reflux-like symptoms and reflux oesophagitis are often perceived as having the same acid-related aetiology and responsiveness to antisecretory therapy. However, the frequency of residual symptom reporting on proton pump inhibitor (PPI) therapy suggests the two entities have some differential pathophysiological determinants requiring distinct management approaches.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>To examine the complexities of reflux-like symptom pathophysiology and strategies that may be used to target contributing factors beyond acid reflux.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A panel of ten expert clinicians (primary care, gastroenterology and psychology) held a series of online meetings to share perspectives on the underlying contributors to, and management of, reflux-like symptoms when PPIs are ineffective or provide partial relief. This review summarises the agreed key themes that emerged from the expert discussions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>While degradation of the anti-reflux barrier dominates in reflux oesophagitis, cognitive-affective, behavioural, and other psychosocial factors can play a major role in symptom persistence. These require individualised management strategies, beginning with education on the gut-brain connection and expectation setting with regard to PPI therapy. A detailed clinical history and patient-reported outcome tools that measure symptom burden and associated anxiety/hypervigilance can help guide management using brain-gut behavioural therapies, supported diet/lifestyle modification, diaphragmatic breathing, weight loss, and/or on-demand symptom control measures according to a patient's specific needs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>A paradigm shift in reflux-like symptom management is required such that acid suppression is viewed as one of several interventions that can be utilised as part of a phenotype-driven, individualised approach to care that acknowledges the multiple contributors to symptom burden.</p>\u0000 </section>\u0000 </div>","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"61 9","pages":"1437-1446"},"PeriodicalIF":6.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apt.70115","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143745534","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}
Sarah Melton, Akhilesh Swaminathan, Jessica Fitzpatrick
<p>We read with interest the recent article by Chu et al. Meta-Analysis: Exclusive Enteral Nutrition in Adults With Ulcerative Colitis [<span>1</span>], which addresses the unresolved question of the efficacy of exclusive enteral nutrition (EEN) in the management of ulcerative colitis (UC).</p><p>Preclinical studies have previously demonstrated a significant reduction in colonic inflammation when using elemental diets in animal models mimicking UC [<span>2</span>]. However, these findings have seldom been replicated in human UC trials compared with Crohn's disease (CD), where EEN is an established therapy. These limitations may be due, in part, to existing studies combining patients with CD and UC, despite the significant pathophysiological differences between these conditions [<span>3</span>]. This heterogeneity can obscure disease-specific effects of EEN, particularly in UC. Furthermore, published studies have largely included cohorts with moderate-to-severe UC, acute severe UC or patients refractory to corticosteroids. These represent populations with a significant disease burden, and the efficacy of EEN on those with milder disease activity has not been clearly established. Additionally, there is significant heterogeneity in the duration of EEN (often 7–14 days of treatment in UC compared with 6–12 weeks in CD), follow-up and time to primary endpoints in these studies. Thus, it is unsurprising that positive findings have been sparsely seen in the published literature to date.</p><p>As noted by Chu et al. [<span>1</span>], faecal calprotectin appears to reduce after 7 days of EEN in UC. This raises the question as to whether we can expect meaningful therapeutic responses to EEN with a longer duration of therapy and follow-up when most modern IBD trials assess primary endpoints at 26 or 52 weeks. Furthermore, the adjunctive role of EEN to the expanding armamentarium of advanced therapies available for UC has not been fully established. Future studies should carefully consider the duration of EEN, appropriate timepoints to assess important outcomes, and evaluate a combination of clinical, biochemical, sonographic and endoscopic responses to gain a more nuanced understanding of the utility of EEN in UC.</p><p>The unique composition of EEN also warrants consideration in UC. Standard EEN formulas are fibre-free, which has known implications for the gut microbiota and has been demonstrated to promote a more dysbiotic microbial environment in Crohn's disease [<span>4</span>]. A deeper understanding of the mechanism of action of EEN, and therefore how it contributes to reduction in CD-related inflammation, would further progress our understanding of the role for EEN in UC. Resistant starch, fructooligosaccharide and non-starch polysaccharide have been shown to have some beneficial effects in previous studies [<span>5</span>], and therefore, mechanistic studies should consider fibre-free vs. fibre-containing formulas to potentially optimise the therape
{"title":"Letter: Exclusive Enteral Nutrition in Ulcerative Colitis—The Path Ahead Needs Careful Consideration","authors":"Sarah Melton, Akhilesh Swaminathan, Jessica Fitzpatrick","doi":"10.1111/apt.70091","DOIUrl":"10.1111/apt.70091","url":null,"abstract":"<p>We read with interest the recent article by Chu et al. Meta-Analysis: Exclusive Enteral Nutrition in Adults With Ulcerative Colitis [<span>1</span>], which addresses the unresolved question of the efficacy of exclusive enteral nutrition (EEN) in the management of ulcerative colitis (UC).</p><p>Preclinical studies have previously demonstrated a significant reduction in colonic inflammation when using elemental diets in animal models mimicking UC [<span>2</span>]. However, these findings have seldom been replicated in human UC trials compared with Crohn's disease (CD), where EEN is an established therapy. These limitations may be due, in part, to existing studies combining patients with CD and UC, despite the significant pathophysiological differences between these conditions [<span>3</span>]. This heterogeneity can obscure disease-specific effects of EEN, particularly in UC. Furthermore, published studies have largely included cohorts with moderate-to-severe UC, acute severe UC or patients refractory to corticosteroids. These represent populations with a significant disease burden, and the efficacy of EEN on those with milder disease activity has not been clearly established. Additionally, there is significant heterogeneity in the duration of EEN (often 7–14 days of treatment in UC compared with 6–12 weeks in CD), follow-up and time to primary endpoints in these studies. Thus, it is unsurprising that positive findings have been sparsely seen in the published literature to date.</p><p>As noted by Chu et al. [<span>1</span>], faecal calprotectin appears to reduce after 7 days of EEN in UC. This raises the question as to whether we can expect meaningful therapeutic responses to EEN with a longer duration of therapy and follow-up when most modern IBD trials assess primary endpoints at 26 or 52 weeks. Furthermore, the adjunctive role of EEN to the expanding armamentarium of advanced therapies available for UC has not been fully established. Future studies should carefully consider the duration of EEN, appropriate timepoints to assess important outcomes, and evaluate a combination of clinical, biochemical, sonographic and endoscopic responses to gain a more nuanced understanding of the utility of EEN in UC.</p><p>The unique composition of EEN also warrants consideration in UC. Standard EEN formulas are fibre-free, which has known implications for the gut microbiota and has been demonstrated to promote a more dysbiotic microbial environment in Crohn's disease [<span>4</span>]. A deeper understanding of the mechanism of action of EEN, and therefore how it contributes to reduction in CD-related inflammation, would further progress our understanding of the role for EEN in UC. Resistant starch, fructooligosaccharide and non-starch polysaccharide have been shown to have some beneficial effects in previous studies [<span>5</span>], and therefore, mechanistic studies should consider fibre-free vs. fibre-containing formulas to potentially optimise the therape","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"61 9","pages":"1577-1578"},"PeriodicalIF":6.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apt.70091","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143745172","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}
Mario Frías, Eduardo Chicano-Gálvez, Antonio Rivero-Juárez, Ana Gordon, Diana Corona-Mata, José María Moyano, Ángela Peralbo-Molina, Ángela Camacho, Ignacio Pérez-Valero, María del Mar Malagón, Antonio Rivero
Liver steatosis (LS) is a condition that is characterised by hepatic fat accumulation unrelated to significant alcohol consumption. This study explored the serum proteomic profile associated with LS in people living with HIV (PLWH).
{"title":"Afamin and Apolipoprotein F Associated With Liver Steatosis From People Living With HIV: A Discovery Study","authors":"Mario Frías, Eduardo Chicano-Gálvez, Antonio Rivero-Juárez, Ana Gordon, Diana Corona-Mata, José María Moyano, Ángela Peralbo-Molina, Ángela Camacho, Ignacio Pérez-Valero, María del Mar Malagón, Antonio Rivero","doi":"10.1111/apt.70119","DOIUrl":"https://doi.org/10.1111/apt.70119","url":null,"abstract":"Liver steatosis (LS) is a condition that is characterised by hepatic fat accumulation unrelated to significant alcohol consumption. This study explored the serum proteomic profile associated with LS in people living with HIV (PLWH).","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"72 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143737073","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}
Tarek Hassanein, Andrew P. Keaveny, Parvez Mantry, Mitchell Shiffman, Michael Leise, Kamran Qureshi, Alastair D. Smith, Michael P. McRae, Joanne C. Imperial, Gregory T. Everson
<p>In our previous publications in Alimentary Pharmacology & Therapeutics [<span>1, 2</span>], we highlighted the diagnostic performance of the disease severity index (DSI) derived from the oral cholate challenge test [<span>3-5</span>] (HepQuant DuO) to rule out large oesophageal varices (LEV) and other significant lesions of portal hypertension. In these publications, two criteria were evaluated: (1) using DSI ≤ 18.3 alone and (2) using DSI ≤ 24 or < 25 with platelet count > 135,000 μL<sup>−1</sup>. The sensitivity cut-off for rule-out of LEV was based on Baveno VII criteria for miss rate < 5% (sensitivity > 95%) [<span>6</span>]. The diagnostic performance for DSI ≤ 18.3 was previously reported [<span>1, 2</span>], but the diagnostic performance of DSI with platelet count was not. Table 1 shows the combination of DSI ≤ 18.3 or DSI ≤ 24 with PLT > 135,000 μL<sup>−1</sup> for the HepQuant DuO test. The HepQuant DuO test had miss rates < 5% (sensitivity > 95%), negative predictive values (NPV) > 99% and negative likelihood ratios (NLR) ≤ 0.08. Specificity was 63.8% for LEV and 58.3% for all significant lesions of portal hypertension.</p><div><header><span>TABLE 1. </span>Diagnostic performance (95% CI) of the combination of DSI ≤ 18.3 with DSI ≤ 24 and platelet count > 135,000 μL<sup>−1</sup> from the oral cholate challenge test (HepQuant DuO) to rule out of large oesophageal varices (LEV) and all portal hypertensive lesions (defined as oesophageal varices needing treatment, LEV, large gastric varices or severe portal hypertensive gastropathy).</header><div tabindex="0"><table><thead><tr><td></td><th>Large oesophageal varices</th><th>All portal hypertensive lesions</th></tr></thead><tbody><tr><td>Sensitivity (%)</td><td>95.9 (86.0, 99.5)</td><td>97.2 (85.5, 99.9)</td></tr><tr><td>Specificity (%)</td><td>63.8 (58.9, 68.5)</td><td>58.3 (51.1, 65.2)</td></tr><tr><td>Positive likelihood ratio</td><td>2.65 (2.30, 3.05)</td><td>2.33 (1.96, 2.77)</td></tr><tr><td>Negative likelihood ratio</td><td>0.06 (0.02, 0.25)</td><td>0.05 (0.01, 0.33)</td></tr><tr><td>Prevalence (%)</td><td>10.8 (8.1, 14.1)</td><td>15.3 (11.0, 20.6)</td></tr><tr><td>Positive predictive value (%)</td><td>24.4 (21.8, 27.1)</td><td>29.7 (26.2, 33.4)</td></tr><tr><td>Negative predictive value (%)</td><td>99.2 (97.1, 99.8)</td><td>99.1 (94.4, 99.9)</td></tr><tr><td>Miss rate (%)</td><td>4.1</td><td>2.8</td></tr><tr><td>EGDs avoided (%)</td><td>57.3</td><td>49.8</td></tr></tbody></table></div><div></div></div><p>From this analysis, we conclude that the combined criteria of DSI ≤ 18.3 with DSI ≤ 24 plus platelet count > 135,000 μL<sup>−1</sup> may be sufficient to rule out LEV and aid the decision to avoid endoscopy (EGD) (Table 1). When used in combination, the diagnostic performance for LEV is maintained with a low miss rate (4.1%) but a much higher likelihood to avoid endoscopy (57.3%). The
{"title":"Letter: Enhancing the Diagnostic Performance of the Oral Cholate Challenge Test: Implications for Avoidance of Potentially Unnecessary Endoscopy","authors":"Tarek Hassanein, Andrew P. Keaveny, Parvez Mantry, Mitchell Shiffman, Michael Leise, Kamran Qureshi, Alastair D. Smith, Michael P. McRae, Joanne C. Imperial, Gregory T. Everson","doi":"10.1111/apt.70116","DOIUrl":"https://doi.org/10.1111/apt.70116","url":null,"abstract":"<p>In our previous publications in Alimentary Pharmacology & Therapeutics [<span>1, 2</span>], we highlighted the diagnostic performance of the disease severity index (DSI) derived from the oral cholate challenge test [<span>3-5</span>] (HepQuant DuO) to rule out large oesophageal varices (LEV) and other significant lesions of portal hypertension. In these publications, two criteria were evaluated: (1) using DSI ≤ 18.3 alone and (2) using DSI ≤ 24 or < 25 with platelet count > 135,000 μL<sup>−1</sup>. The sensitivity cut-off for rule-out of LEV was based on Baveno VII criteria for miss rate < 5% (sensitivity > 95%) [<span>6</span>]. The diagnostic performance for DSI ≤ 18.3 was previously reported [<span>1, 2</span>], but the diagnostic performance of DSI with platelet count was not. Table 1 shows the combination of DSI ≤ 18.3 or DSI ≤ 24 with PLT > 135,000 μL<sup>−1</sup> for the HepQuant DuO test. The HepQuant DuO test had miss rates < 5% (sensitivity > 95%), negative predictive values (NPV) > 99% and negative likelihood ratios (NLR) ≤ 0.08. Specificity was 63.8% for LEV and 58.3% for all significant lesions of portal hypertension.</p>\u0000<div>\u0000<header><span>TABLE 1. </span>Diagnostic performance (95% CI) of the combination of DSI ≤ 18.3 with DSI ≤ 24 and platelet count > 135,000 μL<sup>−1</sup> from the oral cholate challenge test (HepQuant DuO) to rule out of large oesophageal varices (LEV) and all portal hypertensive lesions (defined as oesophageal varices needing treatment, LEV, large gastric varices or severe portal hypertensive gastropathy).</header>\u0000<div tabindex=\"0\">\u0000<table>\u0000<thead>\u0000<tr>\u0000<td></td>\u0000<th>Large oesophageal varices</th>\u0000<th>All portal hypertensive lesions</th>\u0000</tr>\u0000</thead>\u0000<tbody>\u0000<tr>\u0000<td>Sensitivity (%)</td>\u0000<td>95.9 (86.0, 99.5)</td>\u0000<td>97.2 (85.5, 99.9)</td>\u0000</tr>\u0000<tr>\u0000<td>Specificity (%)</td>\u0000<td>63.8 (58.9, 68.5)</td>\u0000<td>58.3 (51.1, 65.2)</td>\u0000</tr>\u0000<tr>\u0000<td>Positive likelihood ratio</td>\u0000<td>2.65 (2.30, 3.05)</td>\u0000<td>2.33 (1.96, 2.77)</td>\u0000</tr>\u0000<tr>\u0000<td>Negative likelihood ratio</td>\u0000<td>0.06 (0.02, 0.25)</td>\u0000<td>0.05 (0.01, 0.33)</td>\u0000</tr>\u0000<tr>\u0000<td>Prevalence (%)</td>\u0000<td>10.8 (8.1, 14.1)</td>\u0000<td>15.3 (11.0, 20.6)</td>\u0000</tr>\u0000<tr>\u0000<td>Positive predictive value (%)</td>\u0000<td>24.4 (21.8, 27.1)</td>\u0000<td>29.7 (26.2, 33.4)</td>\u0000</tr>\u0000<tr>\u0000<td>Negative predictive value (%)</td>\u0000<td>99.2 (97.1, 99.8)</td>\u0000<td>99.1 (94.4, 99.9)</td>\u0000</tr>\u0000<tr>\u0000<td>Miss rate (%)</td>\u0000<td>4.1</td>\u0000<td>2.8</td>\u0000</tr>\u0000<tr>\u0000<td>EGDs avoided (%)</td>\u0000<td>57.3</td>\u0000<td>49.8</td>\u0000</tr>\u0000</tbody>\u0000</table>\u0000</div>\u0000<div></div>\u0000</div>\u0000<p>From this analysis, we conclude that the combined criteria of DSI ≤ 18.3 with DSI ≤ 24 plus platelet count > 135,000 μL<sup>−1</sup> may be sufficient to rule out LEV and aid the decision to avoid endoscopy (EGD) (Table 1). When used in combination, the diagnostic performance for LEV is maintained with a low miss rate (4.1%) but a much higher likelihood to avoid endoscopy (57.3%). The","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"52 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143734412","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}