<p>Advanced chronic liver disease (ACLD) is characterised by excessive deposition of collagen within the hepatic interstitium, distortion of hepatic architecture and inflammation, culminating in impaired liver function and the development of portal hypertension (PH) [<span>1</span>]. In recent years, circulating biomarkers reflecting extracellular matrix (ECM) formation and degradation have been found not only to correlate with fibrosis stage but also with PH, systemic inflammation and even fibrosis regression, offering potential for disease staging and prognostication [<span>2, 3</span>]. However, most studies have focused either on pre-cirrhotic patients or on decompensated cirrhosis [<span>4, 5</span>]. Whether these markers can also predict disease severity and clinical outcomes in ACLD remains uncertain.</p> <p>In a single-centre prospective cohort study from Austria, Simbrunner et al. [<span>6</span>] evaluated a panel of ECM biomarkers in 232 individuals with compensated (cACLD) or decompensated (dACLD) disease undergoing hepatic venous pressure gradient (HVPG) measurement, alongside clinical characterisation and longitudinal follow-up for liver-related events (Figure 1).</p> <figure><picture> <source media="(min-width: 1650px)" srcset="/cms/asset/124ddc97-3f3a-4295-a7b6-37164c6dc8ea/apt70445-fig-0001-m.jpg"/><img alt="Details are in the caption following the image" data-lg-src="/cms/asset/124ddc97-3f3a-4295-a7b6-37164c6dc8ea/apt70445-fig-0001-m.jpg" loading="lazy" src="/cms/asset/96489215-df70-4c8a-a4e3-2e53ea918984/apt70445-fig-0001-m.png" title="Details are in the caption following the image"/></picture><figcaption> <div><strong>FIGURE 1<span style="font-weight:normal"></span></strong><div>Open in figure viewer<i aria-hidden="true"></i><span>PowerPoint</span></div> </div> <div>Matrix proteins as prognostic biomarkers in liver cirrhosis: Biomarkers for extracellular matrix (ECM) biogenesis—formation vs. degradation—are associated with clinical outcomes in individuals with advanced chronic liver disease (ACLD) in a single-centre observational study undergoing thorough assessment for portal hypertension, including hepatic venous pressure gradient (HVPG) measurement. Details can be found in the article by Simbrunner and colleagues in this issue. Figure was created with Biorender.</div> </figcaption> </figure> <p>Markers of collagen formation including Enhanced Liver Fibrosis (ELF) score, PRO-C3, PRO-C4, PRO-C6 and PRO-C18L and degradation (C3M and C4M) increased with clinical severity, liver stiffness and HVPG. Collagen formation showed only modest correlation with HVPG across the entire cohort. This relationship was more pronounced in patients with cACLD and diminished in the subgroup of dACLD. Through logistic regression, PRO-C4, PRO-C6, PRO-C18L and ELF identified patients at greater risk of liver-related events, particularly among those with cACLD. In multivariable models PRO-C4, C3M and C4M retained independent predictive value, althou
{"title":"Editorial: Extracellular Matrix Biomarkers Illuminate the Architecture of Portal Hypertension in End-Stage Liver Disease","authors":"Igor Spivak, Frank Tacke","doi":"10.1111/apt.70445","DOIUrl":"https://doi.org/10.1111/apt.70445","url":null,"abstract":"<p>Advanced chronic liver disease (ACLD) is characterised by excessive deposition of collagen within the hepatic interstitium, distortion of hepatic architecture and inflammation, culminating in impaired liver function and the development of portal hypertension (PH) [<span>1</span>]. In recent years, circulating biomarkers reflecting extracellular matrix (ECM) formation and degradation have been found not only to correlate with fibrosis stage but also with PH, systemic inflammation and even fibrosis regression, offering potential for disease staging and prognostication [<span>2, 3</span>]. However, most studies have focused either on pre-cirrhotic patients or on decompensated cirrhosis [<span>4, 5</span>]. Whether these markers can also predict disease severity and clinical outcomes in ACLD remains uncertain.</p>\u0000<p>In a single-centre prospective cohort study from Austria, Simbrunner et al. [<span>6</span>] evaluated a panel of ECM biomarkers in 232 individuals with compensated (cACLD) or decompensated (dACLD) disease undergoing hepatic venous pressure gradient (HVPG) measurement, alongside clinical characterisation and longitudinal follow-up for liver-related events (Figure 1).</p>\u0000<figure><picture>\u0000<source media=\"(min-width: 1650px)\" srcset=\"/cms/asset/124ddc97-3f3a-4295-a7b6-37164c6dc8ea/apt70445-fig-0001-m.jpg\"/><img alt=\"Details are in the caption following the image\" data-lg-src=\"/cms/asset/124ddc97-3f3a-4295-a7b6-37164c6dc8ea/apt70445-fig-0001-m.jpg\" loading=\"lazy\" src=\"/cms/asset/96489215-df70-4c8a-a4e3-2e53ea918984/apt70445-fig-0001-m.png\" title=\"Details are in the caption following the image\"/></picture><figcaption>\u0000<div><strong>FIGURE 1<span style=\"font-weight:normal\"></span></strong><div>Open in figure viewer<i aria-hidden=\"true\"></i><span>PowerPoint</span></div>\u0000</div>\u0000<div>Matrix proteins as prognostic biomarkers in liver cirrhosis: Biomarkers for extracellular matrix (ECM) biogenesis—formation vs. degradation—are associated with clinical outcomes in individuals with advanced chronic liver disease (ACLD) in a single-centre observational study undergoing thorough assessment for portal hypertension, including hepatic venous pressure gradient (HVPG) measurement. Details can be found in the article by Simbrunner and colleagues in this issue. Figure was created with Biorender.</div>\u0000</figcaption>\u0000</figure>\u0000<p>Markers of collagen formation including Enhanced Liver Fibrosis (ELF) score, PRO-C3, PRO-C4, PRO-C6 and PRO-C18L and degradation (C3M and C4M) increased with clinical severity, liver stiffness and HVPG. Collagen formation showed only modest correlation with HVPG across the entire cohort. This relationship was more pronounced in patients with cACLD and diminished in the subgroup of dACLD. Through logistic regression, PRO-C4, PRO-C6, PRO-C18L and ELF identified patients at greater risk of liver-related events, particularly among those with cACLD. In multivariable models PRO-C4, C3M and C4M retained independent predictive value, althou","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"361 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145796248","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 great interest the manuscript by Lu et al. who mapped the gaps in intestinal ultrasound (IUS) research [<span>1</span>]. Given the growing interest in this technology and its clinical application, we would like to congratulate the authors on their timely manuscript. However, we would like to emphasise that several of the gaps described by the authors are closing faster than the literature can track, and the emerging picture is more interesting than simple equivalence with endoscopy.</p><p>Standardisation is a concern the authors rightly emphasised. An international consensus of 35 experts has now codified IUS response and remission criteria for clinical trials, endorsing the Bowel Ultrasound Score (BUSS) for Crohn's disease and the Milan Ultrasound Criteria (MUC) for ulcerative colitis [<span>2</span>]. The 2025 ECCO-ESGAR-ESP-IBUS guidelines formally recommend validated imaging indices for monitoring [<span>3</span>]. The scaffolding, in other words, is largely built.</p><p>The deeper question is whether endoscopy itself sets the right benchmark. In ulcerative colitis, transmural healing independently predicted reduced relapse, yet the distinction between Mayo Endoscopic Subscore 0 and 1 did not [<span>4</span>]. Baseline MUC outperformed the Mayo score for predicting colectomy [<span>5</span>]. And ultrasound remission at week 12 was the sole independent predictor of sustained mucosal healing, carrying a 96% negative predictive value [<span>6</span>].</p><p>Crohn's disease tells a similar story. In a multicentre study, patients with sonographic inflammation despite clinical remission had higher corticosteroid use and reduced hospitalisation-free and surgery-free survival [<span>7</span>]. In another study by Castiglione et al., the authors found that transmural healing outperformed mucosal healing alone for 1-year clinical outcomes [<span>8</span>]. In a prospective study recently published in this journal, Yzet et al. followed patients who had already achieved complete endoscopic healing [<span>9</span>]. At 12 months, those with IUS transmural healing had a 2% relapse rate; those without, 33%. Absence of transmural healing was the only independent predictor of relapse.</p><p>The temporal resolution of IUS is equally striking. In the STARDUST trial, patients with sonographic response at week 4 achieved superior transmural healing at 48 weeks [<span>10</span>]. This timing enables treatment optimisation before endoscopic reassessment would typically occur.</p><p>Challenges remain: training pipelines are thin, access is uneven, and rectal imaging has real limitations. But the conversation has shifted. We are no longer simply asking whether IUS correlates with endoscopy. We are asking what transmural healing adds to mucosal healing and whether combining both perspectives might serve patients better than either alone.</p><p><b>Luisa Bertin:</b> methodology, validation, writing – original draft, investigation. <b>Edoardo Vincenzo Sa
{"title":"Letter: Intestinal Ultrasound: The Evidence Is Catching Up With the Technology","authors":"Luisa Bertin, Edoardo Vincenzo Savarino","doi":"10.1111/apt.70508","DOIUrl":"10.1111/apt.70508","url":null,"abstract":"<p>We read with great interest the manuscript by Lu et al. who mapped the gaps in intestinal ultrasound (IUS) research [<span>1</span>]. Given the growing interest in this technology and its clinical application, we would like to congratulate the authors on their timely manuscript. However, we would like to emphasise that several of the gaps described by the authors are closing faster than the literature can track, and the emerging picture is more interesting than simple equivalence with endoscopy.</p><p>Standardisation is a concern the authors rightly emphasised. An international consensus of 35 experts has now codified IUS response and remission criteria for clinical trials, endorsing the Bowel Ultrasound Score (BUSS) for Crohn's disease and the Milan Ultrasound Criteria (MUC) for ulcerative colitis [<span>2</span>]. The 2025 ECCO-ESGAR-ESP-IBUS guidelines formally recommend validated imaging indices for monitoring [<span>3</span>]. The scaffolding, in other words, is largely built.</p><p>The deeper question is whether endoscopy itself sets the right benchmark. In ulcerative colitis, transmural healing independently predicted reduced relapse, yet the distinction between Mayo Endoscopic Subscore 0 and 1 did not [<span>4</span>]. Baseline MUC outperformed the Mayo score for predicting colectomy [<span>5</span>]. And ultrasound remission at week 12 was the sole independent predictor of sustained mucosal healing, carrying a 96% negative predictive value [<span>6</span>].</p><p>Crohn's disease tells a similar story. In a multicentre study, patients with sonographic inflammation despite clinical remission had higher corticosteroid use and reduced hospitalisation-free and surgery-free survival [<span>7</span>]. In another study by Castiglione et al., the authors found that transmural healing outperformed mucosal healing alone for 1-year clinical outcomes [<span>8</span>]. In a prospective study recently published in this journal, Yzet et al. followed patients who had already achieved complete endoscopic healing [<span>9</span>]. At 12 months, those with IUS transmural healing had a 2% relapse rate; those without, 33%. Absence of transmural healing was the only independent predictor of relapse.</p><p>The temporal resolution of IUS is equally striking. In the STARDUST trial, patients with sonographic response at week 4 achieved superior transmural healing at 48 weeks [<span>10</span>]. This timing enables treatment optimisation before endoscopic reassessment would typically occur.</p><p>Challenges remain: training pipelines are thin, access is uneven, and rectal imaging has real limitations. But the conversation has shifted. We are no longer simply asking whether IUS correlates with endoscopy. We are asking what transmural healing adds to mucosal healing and whether combining both perspectives might serve patients better than either alone.</p><p><b>Luisa Bertin:</b> methodology, validation, writing – original draft, investigation. <b>Edoardo Vincenzo Sa","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"63 4","pages":"587-588"},"PeriodicalIF":6.7,"publicationDate":"2025-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apt.70508","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145796249","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}
<p>Bowel urgency (BU), the sudden or immediate need for a bowel movement, is one of the most bothersome symptoms experienced by patients with ulcerative colitis (UC) or Crohn's disease (CD), considerably diminishing quality of life (QoL) [<span>1</span>]. BU typically coincides with active disease and is associated with an increased risk of colectomy, corticosteroid use and hospitalisation [<span>2</span>]. However, persistent BU has also been reported by a subset of patients with UC absent signs of active disease [<span>3</span>]. Despite its importance to patients, BU has been historically sidelined in clinical studies, often buried within composite symptom scores. Focused attention on BU as a distinct therapeutic target has led to inconsistent, yet growing, availability of data on treatment efficacy specifically addressing this symptom.</p><p>Patel et al. [<span>4</span>] have provided a systematic review and meta-analysis on the efficacy of advanced therapies on BU in IBD within the randomised controlled trial (RCT) setting. While 44 studies were identified, the meta-analysis itself pooled data from 11 of these trials—specifically those that assessed BU as a discrete variable—absence or presence. This pooled analysis shows that anti-interleukin (IL)-23p19 agents (guselkumab, mirikizumab, risankizumab) and the JAK inhibitor upadacitinib are effective in inducing and maintaining BU remission—namely BU absence—compared to placebo, with risk ratios of 1.8 and 2.1, respectively.</p><p>The review finding, while welcomed, starkly exposes a major historical divide in our evidence. The inability to include pivotal therapies like anti-tumour necrosis factor (TNF), anti-integrin and anti-IL-12/23 agents reflects a prior deficiency in including more patient-centric metrics into regulatory and clinical efficacy assessments. We have no RCT level data on BU for our most-used advanced therapies. This evidence gap is most pronounced in CD and extends even to the newest advanced therapies, where available data are two RCTs for a single mechanism of action. This highlights a profound lapse in therapeutic evaluation concerning a patient cohort in which urgency, while less frequently reported than in UC, is a highly bothersome and life-altering symptom. The meta-analysis had to rely on studies that reported BU as a simple dichotomous variable. This binary metric, while allowing for a pooled analysis, lacks the granularity to detect partial yet clinically meaningful improvements, such as a patient moving from severe to mild urgency. It obscures our ability to detect more subtle, yet vital, differences in the absolute and relative efficacy across different therapeutic classes. Therefore, real-world evidence (RWE) from observational studies remains fundamental [<span>5, 6</span>]. Prospective RWE studies utilising validated scores are essential to capture clinically relevant degrees of improvement, enabling more nuanced comparisons of effectiveness of all available
{"title":"Editorial: Targeting Urgency in IBD—A Historical Divide","authors":"Daniele Noviello, Raja Atreya","doi":"10.1111/apt.70476","DOIUrl":"10.1111/apt.70476","url":null,"abstract":"<p>Bowel urgency (BU), the sudden or immediate need for a bowel movement, is one of the most bothersome symptoms experienced by patients with ulcerative colitis (UC) or Crohn's disease (CD), considerably diminishing quality of life (QoL) [<span>1</span>]. BU typically coincides with active disease and is associated with an increased risk of colectomy, corticosteroid use and hospitalisation [<span>2</span>]. However, persistent BU has also been reported by a subset of patients with UC absent signs of active disease [<span>3</span>]. Despite its importance to patients, BU has been historically sidelined in clinical studies, often buried within composite symptom scores. Focused attention on BU as a distinct therapeutic target has led to inconsistent, yet growing, availability of data on treatment efficacy specifically addressing this symptom.</p><p>Patel et al. [<span>4</span>] have provided a systematic review and meta-analysis on the efficacy of advanced therapies on BU in IBD within the randomised controlled trial (RCT) setting. While 44 studies were identified, the meta-analysis itself pooled data from 11 of these trials—specifically those that assessed BU as a discrete variable—absence or presence. This pooled analysis shows that anti-interleukin (IL)-23p19 agents (guselkumab, mirikizumab, risankizumab) and the JAK inhibitor upadacitinib are effective in inducing and maintaining BU remission—namely BU absence—compared to placebo, with risk ratios of 1.8 and 2.1, respectively.</p><p>The review finding, while welcomed, starkly exposes a major historical divide in our evidence. The inability to include pivotal therapies like anti-tumour necrosis factor (TNF), anti-integrin and anti-IL-12/23 agents reflects a prior deficiency in including more patient-centric metrics into regulatory and clinical efficacy assessments. We have no RCT level data on BU for our most-used advanced therapies. This evidence gap is most pronounced in CD and extends even to the newest advanced therapies, where available data are two RCTs for a single mechanism of action. This highlights a profound lapse in therapeutic evaluation concerning a patient cohort in which urgency, while less frequently reported than in UC, is a highly bothersome and life-altering symptom. The meta-analysis had to rely on studies that reported BU as a simple dichotomous variable. This binary metric, while allowing for a pooled analysis, lacks the granularity to detect partial yet clinically meaningful improvements, such as a patient moving from severe to mild urgency. It obscures our ability to detect more subtle, yet vital, differences in the absolute and relative efficacy across different therapeutic classes. Therefore, real-world evidence (RWE) from observational studies remains fundamental [<span>5, 6</span>]. Prospective RWE studies utilising validated scores are essential to capture clinically relevant degrees of improvement, enabling more nuanced comparisons of effectiveness of all available ","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"63 4","pages":"578-579"},"PeriodicalIF":6.7,"publicationDate":"2025-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apt.70476","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145752576","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}
Shiva Poola, MaryKate Kratzer, Kerry Sewell, Zikun Yang, Hans L. Tillmann
Background Hepatitis B virus (HBV) reactivation is a serious complication in patients receiving chronic immunosuppression. Anti‐CD20 agents such as Rituximab are considered high risk for HBV reactivation (> 10%); therefore, antiviral prophylaxis is recommended for all anti‐HBc positive patients. Some studies have suggested that patients with resolved HBV infection and higher hepatitis B surface antibody (anti‐HBs) titer have a higher level of protection against reactivation. Aim The purpose of this study was to systematically review the role of anti‐HBs titer on HBV reactivation in patients on rituximab while not on antiviral therapy/prophylaxis. Methods We systematically reviewed all studies that discussed HBV reactivation in patients on rituximab therapy with resolved HBV infection, defined as HBsAg negative and anti‐HBc positive, which discussed anti‐HBs titer. The search was conducted in PubMed, Embase via Elsevier, Scopus, and Cochrane CENTRAL inclusive July 2025. We evaluated the incidence of HBV reactivation from cohort studies that described anti‐HBs categorically based on anti‐HBs titer: ‘negative’ (titer < 10 iU/L), ‘10–100 iU/L’, or ‘> 100 iU/L’. Meta‐analysis statistics describe the proportion and risk difference for different anti‐HBs levels. Results The overall reactivation rate was 12.6%. There was a significant difference in HBV reactivation depending on titer: anti‐HBs negative 27.3% (51/195) (20.0%–36.0%), titer < 100 iU/L 13.8% (47/379) (8.8%–20.8%), and titer > 100 iU/L 3.5% (8/339) (1.8%–6.9%). Conclusions Those with anti‐HBs titer > 100 iU/L can be considered lower risk for HBV reactivation and may not require antiviral therapy, but monitoring with initiation of antiviral therapy if titer falls below 100 iU/L.
{"title":"Meta‐Analysis: High anti‐ HBs Titers are Associated with Significantly Reduced Risk of Hepatitis B Virus Reactivation During Rituximab Treatment","authors":"Shiva Poola, MaryKate Kratzer, Kerry Sewell, Zikun Yang, Hans L. Tillmann","doi":"10.1111/apt.70490","DOIUrl":"https://doi.org/10.1111/apt.70490","url":null,"abstract":"Background Hepatitis B virus (HBV) reactivation is a serious complication in patients receiving chronic immunosuppression. Anti‐CD20 agents such as Rituximab are considered high risk for HBV reactivation (> 10%); therefore, antiviral prophylaxis is recommended for all anti‐HBc positive patients. Some studies have suggested that patients with resolved HBV infection and higher hepatitis B surface antibody (anti‐HBs) titer have a higher level of protection against reactivation. Aim The purpose of this study was to systematically review the role of anti‐HBs titer on HBV reactivation in patients on rituximab while not on antiviral therapy/prophylaxis. Methods We systematically reviewed all studies that discussed HBV reactivation in patients on rituximab therapy with resolved HBV infection, defined as HBsAg negative and anti‐HBc positive, which discussed anti‐HBs titer. The search was conducted in PubMed, Embase via Elsevier, Scopus, and Cochrane CENTRAL inclusive July 2025. We evaluated the incidence of HBV reactivation from cohort studies that described anti‐HBs categorically based on anti‐HBs titer: ‘negative’ (titer < 10 iU/L), ‘10–100 iU/L’, or ‘> 100 iU/L’. Meta‐analysis statistics describe the proportion and risk difference for different anti‐HBs levels. Results The overall reactivation rate was 12.6%. There was a significant difference in HBV reactivation depending on titer: anti‐HBs negative 27.3% (51/195) (20.0%–36.0%), titer < 100 iU/L 13.8% (47/379) (8.8%–20.8%), and titer > 100 iU/L 3.5% (8/339) (1.8%–6.9%). Conclusions Those with anti‐HBs titer > 100 iU/L can be considered lower risk for HBV reactivation and may not require antiviral therapy, but monitoring with initiation of antiviral therapy if titer falls below 100 iU/L.","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"20 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145746670","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 thank Drs. Noviello and Atreya for their thoughtful editorial accompanying our systematic review and meta-analysis on bowel urgency (BU) in inflammatory bowel disease (IBD) [<span>1, 2</span>]. We are pleased that the authors highlight the key message of our work: that BU represents a highly pertinent yet historically overlooked symptom for patients with IBD [<span>1, 2</span>]. We entirely agree that BU has long been under-represented in clinical trials despite its significant impact on patients' quality of life and functional status.</p><p>As the editorial mentions, our study demonstrates that several advanced IBD therapies can improve or resolve bowel urgency [<span>1</span>]. The benefit observed with IL-23p19 inhibitors (guselkumab, mirikizumab, and risankizumab) and the JAK inhibitor upadacitinib underscores that BU is clinically responsive to advanced therapies [<span>1</span>]. We see this as a rationale for considering BU more explicitly in developing treatment goals, particularly given the high value patients place on this symptom.</p><p>However, a key aim of our review was not only to summarise existing evidence but also to illuminate the extensive gaps that persist. We share the authors' concern that many pivotal trials of widely used advanced therapies, such as anti-TNFs, anti-integrins, and IL-12/23 inhibitors, did not include urgency as an endpoint [<span>2</span>]. As a result, our meta-analysis could include only a minority of available studies. This limits our ability to draw comparisons across the full therapeutic landscape.</p><p>We also agree that binary reporting of BU, while allowing synthesis of available data, is insufficient for capturing clinically important granularity in BU improvement. Patients often experience substantial benefits when urgency decreases in severity even if it is not fully resolved. Future research should thus adopt validated, granular measures of urgency to better capture patient experience.</p><p>For these reasons, we support the editorial's call for prospective real-world studies and systematic incorporation of urgency outcomes in future RCTs. We appreciate the editors' recognition of the importance of this topic and their support in bringing attention to a symptom that patients prioritise. It is our hope that the combination of emerging RCT data, improved measurement standards, and representative real-world evidence will together help close the historical gap in the study of bowel urgency.</p><p>Sincerely,</p><p>Purab Patel and Parul Tandon</p><p><b>Purab Patel:</b> writing – original draft, writing – review and editing, conceptualization. <b>Parul Tandon:</b> writing – review and editing, writing – original draft, conceptualization.</p><p>The authors have nothing to report.</p><p>This article is linked to Patel et al. papers. To view these articles, visit https://doi.org/10.1111/apt.70446 and https://doi.org/10.1111/apt.70476.</p><p>The data that support the findings of this study are avai
{"title":"Editorial: Targeting Urgency in IBD—A Historical Divide. Authors' Reply","authors":"Parul Tandon, Purab Patel","doi":"10.1111/apt.70494","DOIUrl":"10.1111/apt.70494","url":null,"abstract":"<p>We thank Drs. Noviello and Atreya for their thoughtful editorial accompanying our systematic review and meta-analysis on bowel urgency (BU) in inflammatory bowel disease (IBD) [<span>1, 2</span>]. We are pleased that the authors highlight the key message of our work: that BU represents a highly pertinent yet historically overlooked symptom for patients with IBD [<span>1, 2</span>]. We entirely agree that BU has long been under-represented in clinical trials despite its significant impact on patients' quality of life and functional status.</p><p>As the editorial mentions, our study demonstrates that several advanced IBD therapies can improve or resolve bowel urgency [<span>1</span>]. The benefit observed with IL-23p19 inhibitors (guselkumab, mirikizumab, and risankizumab) and the JAK inhibitor upadacitinib underscores that BU is clinically responsive to advanced therapies [<span>1</span>]. We see this as a rationale for considering BU more explicitly in developing treatment goals, particularly given the high value patients place on this symptom.</p><p>However, a key aim of our review was not only to summarise existing evidence but also to illuminate the extensive gaps that persist. We share the authors' concern that many pivotal trials of widely used advanced therapies, such as anti-TNFs, anti-integrins, and IL-12/23 inhibitors, did not include urgency as an endpoint [<span>2</span>]. As a result, our meta-analysis could include only a minority of available studies. This limits our ability to draw comparisons across the full therapeutic landscape.</p><p>We also agree that binary reporting of BU, while allowing synthesis of available data, is insufficient for capturing clinically important granularity in BU improvement. Patients often experience substantial benefits when urgency decreases in severity even if it is not fully resolved. Future research should thus adopt validated, granular measures of urgency to better capture patient experience.</p><p>For these reasons, we support the editorial's call for prospective real-world studies and systematic incorporation of urgency outcomes in future RCTs. We appreciate the editors' recognition of the importance of this topic and their support in bringing attention to a symptom that patients prioritise. It is our hope that the combination of emerging RCT data, improved measurement standards, and representative real-world evidence will together help close the historical gap in the study of bowel urgency.</p><p>Sincerely,</p><p>Purab Patel and Parul Tandon</p><p><b>Purab Patel:</b> writing – original draft, writing – review and editing, conceptualization. <b>Parul Tandon:</b> writing – review and editing, writing – original draft, conceptualization.</p><p>The authors have nothing to report.</p><p>This article is linked to Patel et al. papers. To view these articles, visit https://doi.org/10.1111/apt.70446 and https://doi.org/10.1111/apt.70476.</p><p>The data that support the findings of this study are avai","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"63 4","pages":"580-581"},"PeriodicalIF":6.7,"publicationDate":"2025-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apt.70494","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145752560","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}
Maria de Brito Nunes,Matthias Knecht,Jonas Schropp,Reiner Wiest,Jaume Bosch,Annalisa Berzigotti
BACKGROUND AND STUDY AIMPost-banding ulcer bleeding (PBUB) is an understudied complication of endoscopic band ligation (EBL) used in the prevention and treatment of oesophageal variceal bleeding (VB). The aim of this study is to investigate the incidence, mortality and risk factors of PBUB.METHODSRetrospective cohort study conducted at the university hospital of Bern (Switzerland). It included patients with cirrhosis and oesophageal varices who underwent prophylactic or urgent EBL for VB between 1 January 2018 and 31 December 2022.RESULTSIn total, 206 patients with cirrhosis, who underwent 630 sessions of EBL, were included. The incidence rate of PBUB was 17.5% (95% CI, 12.7%-23.5%), considering the total number of patients, and 6.8% (95% CI, 5.0%-9.2%) considering the total of EBL procedures. Urgent EBL (SHR: 2.78, 95% CI: 1.29-6.00, p = 0.009) and elevated creatinine (SHR: 1.04, 95% CI: 1.01-1.07, p = 0.024) were independent risk factors for PBUB on multivariate analysis. PBUB required blood product transfusions in 88.1% of events (95% CI, 73.6%-95.5%) and hospitalisation at the intensive care unit in 74.4% of events, with a median hospital stay of 2 days (range: 1-34 days). In patients with PBUB, the short-term mortality during hospitalisation was 19%, and long-term mortality at 52 weeks was 64%.CONCLUSIONSPatients with cirrhosis undergoing urgent EBL or those with elevated creatinine levels are at increased risk of PBUB. Due to the high mortality associated with PBUB, identifying high-risk patients and implementing preventive strategies is essential for improving patient outcomes.
{"title":"Post-Banding Ulcer Bleeding After Endoscopic Ligation: Incidence, Risk Factors and Outcomes in Patients With Cirrhosis.","authors":"Maria de Brito Nunes,Matthias Knecht,Jonas Schropp,Reiner Wiest,Jaume Bosch,Annalisa Berzigotti","doi":"10.1111/apt.70495","DOIUrl":"https://doi.org/10.1111/apt.70495","url":null,"abstract":"BACKGROUND AND STUDY AIMPost-banding ulcer bleeding (PBUB) is an understudied complication of endoscopic band ligation (EBL) used in the prevention and treatment of oesophageal variceal bleeding (VB). The aim of this study is to investigate the incidence, mortality and risk factors of PBUB.METHODSRetrospective cohort study conducted at the university hospital of Bern (Switzerland). It included patients with cirrhosis and oesophageal varices who underwent prophylactic or urgent EBL for VB between 1 January 2018 and 31 December 2022.RESULTSIn total, 206 patients with cirrhosis, who underwent 630 sessions of EBL, were included. The incidence rate of PBUB was 17.5% (95% CI, 12.7%-23.5%), considering the total number of patients, and 6.8% (95% CI, 5.0%-9.2%) considering the total of EBL procedures. Urgent EBL (SHR: 2.78, 95% CI: 1.29-6.00, p = 0.009) and elevated creatinine (SHR: 1.04, 95% CI: 1.01-1.07, p = 0.024) were independent risk factors for PBUB on multivariate analysis. PBUB required blood product transfusions in 88.1% of events (95% CI, 73.6%-95.5%) and hospitalisation at the intensive care unit in 74.4% of events, with a median hospital stay of 2 days (range: 1-34 days). In patients with PBUB, the short-term mortality during hospitalisation was 19%, and long-term mortality at 52 weeks was 64%.CONCLUSIONSPatients with cirrhosis undergoing urgent EBL or those with elevated creatinine levels are at increased risk of PBUB. Due to the high mortality associated with PBUB, identifying high-risk patients and implementing preventive strategies is essential for improving patient outcomes.","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"44 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145710838","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}
Mattias Mandorfer, Mathias Jachs, Tânia Carvalho, Thomas Reiberger
<p>We would like to thank Drs. Zhu and Li for their editorial [<span>1</span>], which discusses key findings of our study [<span>2</span>] and addresses important points.</p> <p>First, our results do not support the clinical application of ICG-R15 as a non-invasive test (NIT) for clinically significant portal hypertension, as it was outperformed by liver stiffness measurement and ANTICPATE±NASH and did not even come close to the performance of a vibration-controlled transient elastography (VCTE) model that additionally considers spleen stiffness measurement at 100 Hz (SSM; i.e., NICER [<span>3</span>]). Even in a scenario in which elastography was unavailable, VITRO score (von Willebrand factor antigen/platelet count ratio) would be the preferred NIT for diagnosing CSPH in cACLD [<span>4</span>], as the latter showed a numerically higher area under the receiver operating characteristic curve versus ICG-R15. While the limited diagnostic utility of ICG-R15 for CSPH in cACLD seems to come as no real surprise for Drs. Zhu and Li [<span>1</span>], it is important to mention that previous work on ICG-R15 determined via venous blood sampling drew a more optimistic picture. Furthermore, a bicentric study from China [<span>5</span>] became available after the publication of our work, in which ICG-R15 by PDD showed an AUROC for CSPH > 0.85 in both the derivation and validation cohorts. However, the prevalence of CSPH was considerably lower (42%–46%) than in our study (62%) [<span>2</span>] and more than one fourth of patients did not have cACLD as defined by LSM ≥ 10 kPa, suggesting the inclusion of less advanced patients who are easier to classify [<span>6</span>]. All things considered, LSM by VCTE as well as platelet count remain the mainstay of the non-invasive diagnosis of CSPH and may be better complemented by SSM [<span>3</span>] or VITRO [<span>7</span>], rather than ICG-R15 by PDD.</p> <p>Importantly, our results emphasise that for predicting first hepatic decompensation, hepatic (dys)function should not be neglected, as it is the second key prognostic indicator [<span>8</span>] besides CSPH evaluated by minimally invasive [<span>9</span>] or non-invasive methods [<span>6</span>]. However, whether ICG-R15 by PDD adds clinically meaningful information to that provided by simple tests of hepatic (dys)function such as serum albumin remains to be determined [<span>10</span>], as the low number of events in the cACLD group precluded multivariate analyses.</p> <p>Second, we would like to point out that all assessments in our study were performed in clinically stable outpatients, indicating that ICG-R15 but also other parameters reflect an individual patient's steady state rather than fluctuations, as observed in patients with acute decompensation or acute-on-chronic liver failure. This is an important aspect, as the purpose of the study was not to predict the course of a hospitalisation due to acute decompensation, but rather to investigate whether I
{"title":"Editorial: ICG-R15 by PDD—A Simple Dynamic Tool for Refining Risk Stratification in Compensated Advanced Chronic Liver Disease. Authors' Reply","authors":"Mattias Mandorfer, Mathias Jachs, Tânia Carvalho, Thomas Reiberger","doi":"10.1111/apt.70493","DOIUrl":"https://doi.org/10.1111/apt.70493","url":null,"abstract":"<p>We would like to thank Drs. Zhu and Li for their editorial [<span>1</span>], which discusses key findings of our study [<span>2</span>] and addresses important points.</p>\u0000<p>First, our results do not support the clinical application of ICG-R15 as a non-invasive test (NIT) for clinically significant portal hypertension, as it was outperformed by liver stiffness measurement and ANTICPATE±NASH and did not even come close to the performance of a vibration-controlled transient elastography (VCTE) model that additionally considers spleen stiffness measurement at 100 Hz (SSM; i.e., NICER [<span>3</span>]). Even in a scenario in which elastography was unavailable, VITRO score (von Willebrand factor antigen/platelet count ratio) would be the preferred NIT for diagnosing CSPH in cACLD [<span>4</span>], as the latter showed a numerically higher area under the receiver operating characteristic curve versus ICG-R15. While the limited diagnostic utility of ICG-R15 for CSPH in cACLD seems to come as no real surprise for Drs. Zhu and Li [<span>1</span>], it is important to mention that previous work on ICG-R15 determined via venous blood sampling drew a more optimistic picture. Furthermore, a bicentric study from China [<span>5</span>] became available after the publication of our work, in which ICG-R15 by PDD showed an AUROC for CSPH > 0.85 in both the derivation and validation cohorts. However, the prevalence of CSPH was considerably lower (42%–46%) than in our study (62%) [<span>2</span>] and more than one fourth of patients did not have cACLD as defined by LSM ≥ 10 kPa, suggesting the inclusion of less advanced patients who are easier to classify [<span>6</span>]. All things considered, LSM by VCTE as well as platelet count remain the mainstay of the non-invasive diagnosis of CSPH and may be better complemented by SSM [<span>3</span>] or VITRO [<span>7</span>], rather than ICG-R15 by PDD.</p>\u0000<p>Importantly, our results emphasise that for predicting first hepatic decompensation, hepatic (dys)function should not be neglected, as it is the second key prognostic indicator [<span>8</span>] besides CSPH evaluated by minimally invasive [<span>9</span>] or non-invasive methods [<span>6</span>]. However, whether ICG-R15 by PDD adds clinically meaningful information to that provided by simple tests of hepatic (dys)function such as serum albumin remains to be determined [<span>10</span>], as the low number of events in the cACLD group precluded multivariate analyses.</p>\u0000<p>Second, we would like to point out that all assessments in our study were performed in clinically stable outpatients, indicating that ICG-R15 but also other parameters reflect an individual patient's steady state rather than fluctuations, as observed in patients with acute decompensation or acute-on-chronic liver failure. This is an important aspect, as the purpose of the study was not to predict the course of a hospitalisation due to acute decompensation, but rather to investigate whether I","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"29 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145718450","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}
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：