{"title":"Editorial: Combination Therapies for MASH : A Step Forward or More Complexity? Authors' Reply","authors":"Eric Lawitz, Linda Greenbaum","doi":"10.1111/apt.70510","DOIUrl":"https://doi.org/10.1111/apt.70510","url":null,"abstract":"","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"9 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145836125","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}
BACKGROUNDSteatotic liver disease (SLD) and cardiometabolic risk factors (CMRFs) are common in chronic hepatitis C (CHC). The risk of major adverse cardiovascular events (MACEs) after sustained virological response (SVR) remains elusive.AIMSThis study assessed the impact of CMRFs on cardiovascular outcomes in CHC patients with metabolic dysfunction-associated steatotic liver disease (MASLD) after achieving SVR.METHODSWe recruited SLD patients from the nationwide multicenter cohorts in Taiwan. Their CMRFs and fibrosis stage were assessed after SVR. Competing risk analyses, including Grey's method and Cox regression, were performed to estimate cardiovascular outcomes.RESULTSAmong 8755 patients, 624 developed MACEs during a mean follow-up of 3.9 years. The incidence of MACEs was significantly higher in patients with MASLD than in the simple SLD group (190.2 vs. 84.0 per 10,000 person-years, p < 0.001). Age, advanced fibrosis, chronic kidney disease (CKD), and CMRFs burden were independently associated with MACEs. The MACEs risk increased with CMRFs burden, with adjusted hazard ratios from 1.72 for one CMRF to 2.33 for ≥ four CMRFs. The risk was significantly higher in patients without advanced fibrosis or CKD than in their counterparts.CONCLUSIONSCMRFs burden, advanced fibrosis, and CKD predicted MACEs in CHC patients with MASLD after achieving SVR. CMRFs monitoring and management should be prioritised in high-risk patients.
背景：脂肪变性肝病（SLD）和心脏代谢危险因素（cmrf）在慢性丙型肝炎（CHC）中很常见。持续病毒学反应（SVR）后发生主要不良心血管事件（mace）的风险仍然难以捉摸。目的：本研究评估CMRFs对CHC合并代谢功能障碍相关脂肪变性肝病（MASLD）患者达到SVR后心血管结局的影响。方法：我们从台湾的全国性多中心队列中招募SLD患者。SVR后评估cmrf和纤维化分期。竞争风险分析，包括Grey's方法和Cox回归，用于估计心血管预后。结果8755例患者中，624例在平均3.9年的随访期间发生mace。MASLD患者的mace发生率显著高于单纯SLD组（190.2 vs 84.0 / 10000人年，p < 0.001）。年龄、晚期纤维化、慢性肾脏疾病（CKD）和CMRFs负担与mace独立相关。mace风险随着CMRF负担的增加而增加，调整后的风险比从1个CMRF的1.72增加到≥4个CMRF的2.33。无晚期纤维化或CKD患者的风险明显高于对照组。结论scmrfs负担、晚期纤维化和CKD可预测CHC合并MASLD患者在达到SVR后的mace。高危患者应优先监测和管理cmrf。
{"title":"Advanced Fibrosis and Cardiometabolic Risk Burden Increase Major Cardiovascular Events in Chronic Hepatitis C Patients With Steatotic Liver Disease After Viral Eradication.","authors":"Pei-Chien Tsai,Chung-Feng Huang,Ming-Lun Yeh,Yu-Ju Wei,Chih-Wen Wang,Tyng-Yuan Jang,Po-Cheng Liang,Yi-Hung Lin,Chia-Yen Dai,Jee-Fu Huang,Wan-Long Chuang,Ming-Lung Yu, ","doi":"10.1111/apt.70500","DOIUrl":"https://doi.org/10.1111/apt.70500","url":null,"abstract":"BACKGROUNDSteatotic liver disease (SLD) and cardiometabolic risk factors (CMRFs) are common in chronic hepatitis C (CHC). The risk of major adverse cardiovascular events (MACEs) after sustained virological response (SVR) remains elusive.AIMSThis study assessed the impact of CMRFs on cardiovascular outcomes in CHC patients with metabolic dysfunction-associated steatotic liver disease (MASLD) after achieving SVR.METHODSWe recruited SLD patients from the nationwide multicenter cohorts in Taiwan. Their CMRFs and fibrosis stage were assessed after SVR. Competing risk analyses, including Grey's method and Cox regression, were performed to estimate cardiovascular outcomes.RESULTSAmong 8755 patients, 624 developed MACEs during a mean follow-up of 3.9 years. The incidence of MACEs was significantly higher in patients with MASLD than in the simple SLD group (190.2 vs. 84.0 per 10,000 person-years, p < 0.001). Age, advanced fibrosis, chronic kidney disease (CKD), and CMRFs burden were independently associated with MACEs. The MACEs risk increased with CMRFs burden, with adjusted hazard ratios from 1.72 for one CMRF to 2.33 for ≥ four CMRFs. The risk was significantly higher in patients without advanced fibrosis or CKD than in their counterparts.CONCLUSIONSCMRFs burden, advanced fibrosis, and CKD predicted MACEs in CHC patients with MASLD after achieving SVR. CMRFs monitoring and management should be prioritised in high-risk patients.","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"184 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145830338","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}
Mais Khasawneh, Vivek C. Goodoory, Cho Ee Ng, Alexander C. Ford, Christopher J. Black
Background Irritable bowel syndrome (IBS) is a common disorder characterised by recurrent abdominal pain and altered bowel habits. Although IBS is classified according to stool form, symptom patterns fluctuate over time, posing challenges for subtype‐based management. Aims To assess stability of IBS classification over 12 months using four approaches: stool form, most troublesome symptom, a seven‐cluster latent class analysis (LCA) incorporating gastrointestinal and psychological symptoms and a simplified LCA based on degree of psychological burden. Methods Participants were recruited from ContactME‐IBS, a national UK registry. Individuals meeting Rome IV criteria for IBS completed validated online questionnaires at baseline and 12 months assessing gastrointestinal and psychological symptoms. Participants were sub grouped according to the four classification methods, and stability between baseline and follow‐up was evaluated using Cohen's kappa statistic. Results Of 752 participants meeting Rome IV criteria at baseline, 352 completed 12‐month follow‐up, with 259 (73.6%) continuing to meet Rome IV criteria. The highest stability was observed for stool form‐based subtyping (κ = 0.60), particularly in IBS with diarrhoea (83% remained stable). Classification based on psychological burden showed similar stability (κ = 0.54). In contrast, subgrouping by most troublesome symptom (κ = 0.47) and the seven‐cluster LCA (κ = 0.37) demonstrated lower stability. Conclusion Different IBS classifications showed only moderate stability over 12 months, highlighting the fluctuating nature of the disorder. Stool form and psychological burden‐based systems were most stable, but no method fully captured IBS variability. Future work could develop dynamic models integrating gastrointestinal and psychological factors to better guide management.
{"title":"Stability of Classification Systems for Irritable Bowel Syndrome","authors":"Mais Khasawneh, Vivek C. Goodoory, Cho Ee Ng, Alexander C. Ford, Christopher J. Black","doi":"10.1111/apt.70503","DOIUrl":"https://doi.org/10.1111/apt.70503","url":null,"abstract":"Background Irritable bowel syndrome (IBS) is a common disorder characterised by recurrent abdominal pain and altered bowel habits. Although IBS is classified according to stool form, symptom patterns fluctuate over time, posing challenges for subtype‐based management. Aims To assess stability of IBS classification over 12 months using four approaches: stool form, most troublesome symptom, a seven‐cluster latent class analysis (LCA) incorporating gastrointestinal and psychological symptoms and a simplified LCA based on degree of psychological burden. Methods Participants were recruited from ContactME‐IBS, a national UK registry. Individuals meeting Rome IV criteria for IBS completed validated online questionnaires at baseline and 12 months assessing gastrointestinal and psychological symptoms. Participants were sub grouped according to the four classification methods, and stability between baseline and follow‐up was evaluated using Cohen's kappa statistic. Results Of 752 participants meeting Rome IV criteria at baseline, 352 completed 12‐month follow‐up, with 259 (73.6%) continuing to meet Rome IV criteria. The highest stability was observed for stool form‐based subtyping (κ = 0.60), particularly in IBS with diarrhoea (83% remained stable). Classification based on psychological burden showed similar stability (κ = 0.54). In contrast, subgrouping by most troublesome symptom (κ = 0.47) and the seven‐cluster LCA (κ = 0.37) demonstrated lower stability. Conclusion Different IBS classifications showed only moderate stability over 12 months, highlighting the fluctuating nature of the disorder. Stool form and psychological burden‐based systems were most stable, but no method fully captured IBS variability. Future work could develop dynamic models integrating gastrointestinal and psychological factors to better guide management.","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"50 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145822907","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}
Saqr Alsakarneh, Omar Al Ta’ani, Madi Y. Mahmoud, Wing‐Kin Syn, James K. Ruffle, Qasim Aziz, Adam D. Farmer
Background Ehlers–Danlos syndrome (EDS) comprises inherited connective tissue disorders characterised by joint hypermobility, skin hyperextensibility and tissue fragility. It links to systemic comorbidities, including gastrointestinal (GI) disorders, but hitherto large‐scale data remain limited. We aimed to evaluate the prevalence of GI, systemic and psychological comorbidities in EDS patients versus propensity score‐matched controls, using a comprehensive research network database. Design This was a retrospective, propensity‐matched analysis (2005–2023) utilising the TriNetX network. We identified EDS patients (excluding Marfan's syndrome). Propensity score matching (1:1) generated balanced cohorts for age, sex and baseline characteristics. Comorbidities were analysed via prevalence rates and odds ratios (ORs) with 95% confidence intervals (CIs). Results Matched cohorts included 59,128 pairs. Among GI disorders, gastroesophageal reflux disease was most common in EDS (18.4%, OR 1.5, 95% CI 1.4–1.5, p < 0.001), followed by constipation (12.4%, OR 1.8, 95% CI 1.7–1.9, p < 0.001), irritable bowel syndrome (7.3%, OR 2.6, 95% CI 2.5–2.8, p < 0.001) and gastroparesis (4.7%, OR 8.2, 95% CI 7.3–9.2, p < 0.001). Psychiatric conditions showed heightened prevalence of anxiety (26.1%, OR 1.8, 95% CI 1.7–1.8, p < 0.001) and depression (18.7%, OR 1.3, 95% CI 1.2–1.3, p < 0.001). Systemic comorbidities included postural orthostatic tachycardia syndrome (13.2%, OR 899.7, 95% CI 483.8–1673.0, p < 0.001), chronic pain (7.9%, OR 7.0, 95% CI 6.4–7.6, p < 0.001), migraines (19.7%, OR 2.5, 95% CI 2.4–2.6, p < 0.001) and fibromyalgia (9.5%, OR 1.7, 95% CI 1.6–1.8, p < 0.001). Conclusion EDS patients exhibit heightened risk for GI, systemic and psychological comorbidities, highlighting the importance of multidisciplinary approaches for effective management.
背景Ehlers-Danlos综合征（EDS）包括遗传性结缔组织疾病，其特征是关节过度活动，皮肤过度伸展和组织脆弱。它与包括胃肠道（GI）疾病在内的全身性合并症有关，但迄今为止大规模的数据仍然有限。我们的目的是利用一个综合的研究网络数据库，评估EDS患者与倾向评分匹配对照的胃肠道、全身和心理合并症的患病率。这是一项回顾性的倾向匹配分析（2005-2023），利用TriNetX网络。我们确定了EDS患者（不包括马凡氏综合征）。倾向评分匹配（1:1）生成年龄、性别和基线特征的平衡队列。通过患病率和95%置信区间（ci）的优势比（ORs）分析合并症。结果匹配的队列包括59,128对。在胃肠道疾病中，胃食管反流病在EDS中最常见（18.4%,OR 1.5, 95% CI 1.4-1.5, p < 0.001），其次是便秘（12.4%,OR 1.8, 95% CI 1.7-1.9, p < 0.001），肠易激综合征（7.3%,OR 2.6, 95% CI 2.5-2.8, p < 0.001）和胃轻瘫（4.7%,OR 8.2, 95% CI 7.3-9.2, p < 0.001）。精神疾病显示焦虑（26.1%,OR 1.8, 95% CI 1.7-1.8, p < 0.001）和抑郁（18.7%,OR 1.3, 95% CI 1.2-1.3, p < 0.001）的患病率升高。全身性合并症包括体位性心动过速综合征（13.2%,OR 899.7, 95% CI 483.8-1673.0, p < 0.001）、慢性疼痛（7.9%,OR 7.0, 95% CI 6.4-7.6, p < 0.001）、偏头痛（19.7%,OR 2.5, 95% CI 2.4-2.6, p < 0.001）和纤维肌痛（9.5%,OR 1.7, 95% CI 1.6-1.8, p < 0.001）。结论EDS患者出现胃肠道、全身和心理合并症的风险较高，强调了多学科方法对有效治疗的重要性。
{"title":"Comprehensive Risk Profile of Gastrointestinal and Extra Articular Comorbidities in Ehlers–Danlos Syndrome: A Propensity‐Matched Analysis of 118,256 Individuals","authors":"Saqr Alsakarneh, Omar Al Ta’ani, Madi Y. Mahmoud, Wing‐Kin Syn, James K. Ruffle, Qasim Aziz, Adam D. Farmer","doi":"10.1111/apt.70506","DOIUrl":"https://doi.org/10.1111/apt.70506","url":null,"abstract":"Background Ehlers–Danlos syndrome (EDS) comprises inherited connective tissue disorders characterised by joint hypermobility, skin hyperextensibility and tissue fragility. It links to systemic comorbidities, including gastrointestinal (GI) disorders, but hitherto large‐scale data remain limited. We aimed to evaluate the prevalence of GI, systemic and psychological comorbidities in EDS patients versus propensity score‐matched controls, using a comprehensive research network database. Design This was a retrospective, propensity‐matched analysis (2005–2023) utilising the TriNetX network. We identified EDS patients (excluding Marfan's syndrome). Propensity score matching (1:1) generated balanced cohorts for age, sex and baseline characteristics. Comorbidities were analysed via prevalence rates and odds ratios (ORs) with 95% confidence intervals (CIs). Results Matched cohorts included 59,128 pairs. Among GI disorders, gastroesophageal reflux disease was most common in EDS (18.4%, OR 1.5, 95% CI 1.4–1.5, <jats:italic>p</jats:italic> < 0.001), followed by constipation (12.4%, OR 1.8, 95% CI 1.7–1.9, <jats:italic>p</jats:italic> < 0.001), irritable bowel syndrome (7.3%, OR 2.6, 95% CI 2.5–2.8, <jats:italic>p</jats:italic> < 0.001) and gastroparesis (4.7%, OR 8.2, 95% CI 7.3–9.2, <jats:italic>p</jats:italic> < 0.001). Psychiatric conditions showed heightened prevalence of anxiety (26.1%, OR 1.8, 95% CI 1.7–1.8, <jats:italic>p</jats:italic> < 0.001) and depression (18.7%, OR 1.3, 95% CI 1.2–1.3, <jats:italic>p</jats:italic> < 0.001). Systemic comorbidities included postural orthostatic tachycardia syndrome (13.2%, OR 899.7, 95% CI 483.8–1673.0, <jats:italic>p</jats:italic> < 0.001), chronic pain (7.9%, OR 7.0, 95% CI 6.4–7.6, <jats:italic>p</jats:italic> < 0.001), migraines (19.7%, OR 2.5, 95% CI 2.4–2.6, <jats:italic>p</jats:italic> < 0.001) and fibromyalgia (9.5%, OR 1.7, 95% CI 1.6–1.8, <jats:italic>p</jats:italic> < 0.001). Conclusion EDS patients exhibit heightened risk for GI, systemic and psychological comorbidities, highlighting the importance of multidisciplinary approaches for effective management.","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"250 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145807674","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}
Scott Silvey, Nilang Patel, Jacqueline G. O'Leary, Timothy Morgan, John D. Markley, Sofia S. Jakab, Heather Patton, Shari Rogal, Jasmohan S. Bajaj
Background With changes in bacteriology and cirrhosis demographics, the impact of spontaneous bacterial peritonitis (SBP) on cirrhosis outcomes needs re‐evaluation. Aim Determine the importance of SBP on mortality and liver transplant (LT) across occurrence/recurrence and prophylaxis in a national cohort of Veterans with decompensated cirrhosis. Method Veterans admitted with their first hepatic decompensation between 2009 and 2019 were evaluated for SBP development, and use of primary/secondary SBP prophylaxis (PSPr/SSPr) to determine the associations between SBP and interaction with mortality and LT. Results 52,392 Veterans were included and followed for 7.51 ± 3.83 years, during which 77% died and 2.4% received LT. 16.7% developed one SBP episode, 2.3% two episodes and 0.8% ≥ 3 episodes. Patients on PSPr versus not showed a 24% higher mortality risk, those on SSPr versus not had a 5% increased mortality risk with first and 28% higher mortality risk with additional recurrences. SBPPr interacted with SBP episode number (1.4× PSPr and 1.76× for SSPr) for mortality but not LT. SBP cultures showed higher resistance with increasing SBP episodes (2nd vs. 1st: OR = 2.51, p < 0.001; ≥ 3 vs. 2nd: OR = 7.84, p < 0.001) and with SBPPr (PSPr vs. no prophylaxis: OR = 2.30; SSPr vs. no at first recurrence: OR = 3.70; SSPr vs. no at ≥ 2 recurrences: OR = 10.79, all p < 0.001). Despite documented resistance on PSPr, 82% of patients were continued on the same medication for SSPr, with similar rates of continuation after repeat infection while on SSPr. Conclusion In a national cohort of newly decompensated cirrhosis Veterans, SBP increased mortality, which worsened with recurrence. SBP prophylaxis (primary or secondary) showed an interaction with higher mortality but not LT. Antibiotic resistance increased with SBPPr, but culture results were not followed while resuming/initiating SBPPr. Novel strategies to prevent SBP recurrence and mortality are needed.
{"title":"Spontaneous Bacterial Peritonitis Is Associated With High Mortality, Which Interacts With Antibiotic Prophylaxis in a National Cirrhosis Cohort","authors":"Scott Silvey, Nilang Patel, Jacqueline G. O'Leary, Timothy Morgan, John D. Markley, Sofia S. Jakab, Heather Patton, Shari Rogal, Jasmohan S. Bajaj","doi":"10.1111/apt.70498","DOIUrl":"https://doi.org/10.1111/apt.70498","url":null,"abstract":"Background With changes in bacteriology and cirrhosis demographics, the impact of spontaneous bacterial peritonitis (SBP) on cirrhosis outcomes needs re‐evaluation. Aim Determine the importance of SBP on mortality and liver transplant (LT) across occurrence/recurrence and prophylaxis in a national cohort of Veterans with decompensated cirrhosis. Method Veterans admitted with their first hepatic decompensation between 2009 and 2019 were evaluated for SBP development, and use of primary/secondary SBP prophylaxis (PSPr/SSPr) to determine the associations between SBP and interaction with mortality and LT. Results 52,392 Veterans were included and followed for 7.51 ± 3.83 years, during which 77% died and 2.4% received LT. 16.7% developed one SBP episode, 2.3% two episodes and 0.8% ≥ 3 episodes. Patients on PSPr versus not showed a 24% higher mortality risk, those on SSPr versus not had a 5% increased mortality risk with first and 28% higher mortality risk with additional recurrences. SBPPr interacted with SBP episode number (1.4× PSPr and 1.76× for SSPr) for mortality but not LT. SBP cultures showed higher resistance with increasing SBP episodes (2nd vs. 1st: OR = 2.51, <jats:italic>p</jats:italic> < 0.001; ≥ 3 vs. 2nd: OR = 7.84, <jats:italic>p</jats:italic> < 0.001) and with SBPPr (PSPr vs. no prophylaxis: OR = 2.30; SSPr vs. no at first recurrence: OR = 3.70; SSPr vs. no at ≥ 2 recurrences: OR = 10.79, all <jats:italic>p</jats:italic> < 0.001). Despite documented resistance on PSPr, 82% of patients were continued on the same medication for SSPr, with similar rates of continuation after repeat infection while on SSPr. Conclusion In a national cohort of newly decompensated cirrhosis Veterans, SBP increased mortality, which worsened with recurrence. SBP prophylaxis (primary or secondary) showed an interaction with higher mortality but not LT. Antibiotic resistance increased with SBPPr, but culture results were not followed while resuming/initiating SBPPr. Novel strategies to prevent SBP recurrence and mortality are needed.","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"182 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145801022","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}
Marco Vincenzo Lenti, Giovanni Santacroce, Antonio Di Sabatino
{"title":"Editorial: The Hidden Burden—Stigmatisation in Inflammatory Bowel Disease","authors":"Marco Vincenzo Lenti, Giovanni Santacroce, Antonio Di Sabatino","doi":"10.1111/apt.70478","DOIUrl":"https://doi.org/10.1111/apt.70478","url":null,"abstract":"","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"11 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145801021","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>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}
We read with great interest the manuscript by Lu et al. who mapped the gaps in intestinal ultrasound (IUS) research [1]. 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.
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 [2]. The 2025 ECCO-ESGAR-ESP-IBUS guidelines formally recommend validated imaging indices for monitoring [3]. The scaffolding, in other words, is largely built.
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 [4]. Baseline MUC outperformed the Mayo score for predicting colectomy [5]. And ultrasound remission at week 12 was the sole independent predictor of sustained mucosal healing, carrying a 96% negative predictive value [6].
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 [7]. In another study by Castiglione et al., the authors found that transmural healing outperformed mucosal healing alone for 1-year clinical outcomes [8]. In a prospective study recently published in this journal, Yzet et al. followed patients who had already achieved complete endoscopic healing [9]. 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.
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 [10]. This timing enables treatment optimisation before endoscopic reassessment would typically occur.
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.
{"title":"Letter: Intestinal Ultrasound: The Evidence Is Catching Up With the Technology","authors":"Luisa Bertin, Edoardo Vincenzo Savarino","doi":"10.1111/apt.70508","DOIUrl":"https://doi.org/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>\u0000<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>\u0000<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>\u0000<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>\u0000<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>\u0000<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>","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"1 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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