Alimentary Pharmacology & Therapeutics最新文献

{"title":"Refining Prognosis in Cirrhosis Patients With Ascites: Impact of Acute vs. Non‐Acute Decompensation","authors":"Lucie Simonis, Lorenz Balcar, Anna Schedlbauer, Marta Tonon, Nikolaj Torp, Valeria Santori, Katharina Stopfer, Jan Embacher, Christian Sebesta, Leonie Hafner, Benedikt Silvester Hofer, Nina Dominik, Georg Kramer, Paul Thöne, Michael Trauner, Aleksander Krag, Salvatore Piano, Mattias Mandorfer, Thomas Reiberger, Georg Semmler","doi":"10.1111/apt.70302","DOIUrl":"https://doi.org/10.1111/apt.70302","url":null,"abstract":"BackgroundA more granular understanding of hepatic decompensation in cirrhosis has led to the classification of acute decompensation (AD) and non‐acute decompensation (NAD). In this study, we assessed differences in the clinical course of AD versus NAD in patients with ascites as the first decompensation event.Methods505 cirrhosis patients with ascites as first decompensation were included in this single‐center longitudinal cohort study and followed until further decompensation, orthotopic liver transplantation (OLT), or death. AD was defined as grade 3 ascites or ascites with spontaneous bacterial peritonitis (SBP) or acute‐kidney injury (AKI), while NAD was defined as grade 2 ascites. Hospitalisation was recorded.ResultsAmong 505 patients, 296 (58.6%) met the criteria for AD, with 216 (73.0%) requiring hospitalisation. NAD occurred in 209 (41.4%), with 107 (51.2%) requiring hospitalisation.During a median 4.4‐year follow‐up, further decompensation occurred in 65.1%, acute‐on‐chronic liver failure (ACLF) in 27.7%, 10.9% underwent OLT, and 51.1% died. Patients with AD had a higher incidence of further decompensation (at 12 months: 19% and 33%) and a higher risk of transplant‐free mortality (subdistribution hazard ratio [SHR]: 1.43 [95% CI: 1.12–1.82], <jats:italic>p</jats:italic> = 0.004) versus NAD.When stratified by hospitalisation, AD was associated with an increased risk of mortality only in cases requiring hospitalisation (SHR for hospitalised AD vs. non‐hospitalised NAD: 1.89, 95% CI: 1.35–2.65, <jats:italic>p</jats:italic> &lt; 0.001).Inflammation (C‐reactive protein) predicted transplant‐free mortality in AD (SHR per log‐change: 1.20 [95% CI: 1.02–1.41], <jats:italic>p</jats:italic> = 0.032) but not NAD.ConclusionsClassifying patients as AD versus NAD identified subgroups with different risks for further decompensation and transplant‐free mortality.","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"23 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144715677","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Emerging Trends in Patients Hospitalised With Cirrhosis—Aetiologies, Complications and Outcomes Compared to Other Chronic Health Conditions","authors":"Julian Pohl, Nirbaanjot Walia, Lukas Hofmann, Lena Wolters, Martin Schulz, Matthias Reinhardt, Brigitta Globke, Frank Tacke, Thomas Berg, Cornelius Engelmann","doi":"10.1111/apt.70287","DOIUrl":"https://doi.org/10.1111/apt.70287","url":null,"abstract":"BackgroundThe aetiologies, complications and overall burden of cirrhosis have undergone changes in recent years.AimsThis study aimed to assess the emerging trends in cirrhosis and its complications whilst also comparing them to other major chronic health conditions.MethodsThis retrospective study covering 2011–2022 was conducted at the Charité University Hospital Berlin and University Hospital Leipzig (validation cohort), Germany. ICD‐10 codes were used to identify patients with cirrhosis, its complications and comorbidities. Changes in demographics, aetiologies, complication rates and inpatient mortality were assessed. Trends were compared against major chronic health conditions.Results24,567 (Berlin) and 14,141 (Leipzig) inpatient admissions for cirrhosis were identified. Overall admission numbers have been decreasing; however, in‐hospital mortality and complication rates have been increasing. Alcohol‐related liver disease was persistently the most common cause of cirrhosis (42%). Mortality rates for admissions with variceal haemorrhage and gastrointestinal bleeding have increased from 15.53% and 10.53% in 2011 to 27.69% and 31.25% in 2022, respectively. Cirrhosis admissions had some of the highest rates of inpatient mortality (7.45%), despite being considerably younger and less comorbid than admissions with other chronic health conditions. Over time, the median age of admissions with other chronic diseases increased considerably more than admissions with cirrhosis. In the validation cohort, high inpatient mortality, increasing GI bleeding associated mortality, and complications rates were confirmed.ConclusionCirrhosis remains a significant clinical and public health challenge and is falling behind other major comorbidities with regard to inpatient outcomes. A focus on improved resource allocation and management options is warranted.","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"55 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144719468","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Network Meta‐Analysis: Comparative Efficacy of Biologics and Small Molecules in the Induction and Maintenance of Remission in Crohn's Disease","authors":"Mohammad Shehab, Fatema Alrashed, Abdulrahman Alrashidi, Amro Hassan, Christopher Ma, Neeraj Narula, Vipul Jairat, Miguel Regueiro, Talat Bessissow","doi":"10.1111/apt.70295","DOIUrl":"https://doi.org/10.1111/apt.70295","url":null,"abstract":"BackgroundAdvances in medical management of Crohn's disease (CD) have transformed therapeutic goals. Clinical and endoscopic remission are important endpoints.AimTo compare the efficacy of different advanced therapies in patients with CD.MethodsWe performed a literature search up to January 2025. We included phase 3 randomised controlled trials (RCTs) against placebo or an active comparator. The primary endpoint was induction and maintenance of clinical remission (CD Activity Index [CDAI] &lt; 150 points). Secondary endpoints included induction and maintenance of endoscopic remission (Simple Endoscopic Score for CD (SES‐CD) of ≤ 4 or CD Endoscopic Index of Severity (CDEIS) of ≤ 4). We performed network meta‐analysis (NMA) using the Frequentist method.ResultsWe included 39 studies. Induction of clinical remission analysis showed that infliximab combination with azathioprine ranked highest (93.2%), followed by guselkumab (88.6%) and adalimumab (76.9%). Guselkumab was superior to most interventions in inducing clinical remission. In maintenance of clinical remission, combination of infliximab and azathioprine ranked highest (75.7%) followed by mirikizumab (71.8%) and guselkumab (71.5%). There was no statistically significant difference between therapies in maintaining clinical remission. In induction of endoscopic remission, upadacitinib (88.5%) ranked highest, followed by risankizumab (73.7%) and guselkumab (73.4%). Guselkumab (74%) ranked highest in maintaining endoscopic remission, followed by adalimumab (67%) and mirikizumab (64%).ConclusionNovel IL‐23 inhibitors (such as mirikizumab, risankizumab and guselkumab) and anti‐TNFs (such as infliximab and adalimumab) ranked high in the induction of clinical and endoscopic remission. This highlights the potential of novel advanced therapies for CD.","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"63 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144715663","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Research Communication: Teriflunomide Does Not Affect Gluten‐Specific T‐Cell Activity in Coeliac Disease—A Randomised, Placebo‐Controlled Trial","authors":"Louise F. Risnes, Margit Brottveit, Ida Robertsen, Jostein Ibsen, Lars Aabakken, Marie K. Johannesen, Stine R. Lund, Siv K. B. Furholm, Siv E. H. Isaksen, Anders Åsberg, Ludvig M. Sollid, Knut E. A. Lundin","doi":"10.1111/apt.70301","DOIUrl":"https://doi.org/10.1111/apt.70301","url":null,"abstract":"Coeliac disease is an autoimmune disorder driven by gluten and managed through a strict gluten‐free diet. We tested teriflunomide, a drug known for its ability to alter T‐cell activity, in a phase 2a trial of 15 patients with coeliac disease. Participants received teriflunomide or placebo including a loading dose, followed by a 3‐day oral gluten challenge to monitor T‐cell responses. The main aim was to observe attenuation of gluten‐specific T‐cell activation markers after gluten exposure. We found no significant differences in T‐cell activity between groups, concluding that teriflunomide is ineffective as a non‐dietary treatment for coeliac disease.","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"107 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144715660","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial: LAMP Lights the Way-A Pragmatic Case for NUDT15 Screening Across Diverse Populations.","authors":"Swarup A V Shah,Devendra Desai","doi":"10.1111/apt.70260","DOIUrl":"https://doi.org/10.1111/apt.70260","url":null,"abstract":"","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"114 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144701324","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial: Polypharmacy in MASLD-An Overlooked Epidemic Disproportionately Affecting Women and Patients With Cirrhosis.","authors":"Mary Yue Wang,Terry Cheuk-Fung Yip","doi":"10.1111/apt.70307","DOIUrl":"https://doi.org/10.1111/apt.70307","url":null,"abstract":"","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"23 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144701325","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial: LAMP Lights the Way-A Pragmatic Case for NUDT15 Screening Across Diverse Populations-Authors' Reply.","authors":"Chris Roberts,James R Goodhand,Tariq Ahmad","doi":"10.1111/apt.70289","DOIUrl":"https://doi.org/10.1111/apt.70289","url":null,"abstract":"","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"20 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144701076","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Primary Sclerosing Cholangitis in the Absence of Inflammatory Bowel Disease Increases the Risk of Colorectal Cancer: A Multi-Centre Propensity Score Matched Analysis.","authors":"Saqr Alsakarneh,Razan Aburumman,Mohammad Bilal,Adam S Faye,Jana G Hashash,Aasma Shaukat","doi":"10.1111/apt.70303","DOIUrl":"https://doi.org/10.1111/apt.70303","url":null,"abstract":"INTRODUCTIONPatients with primary sclerosing cholangitis (PSC) and concomitant inflammatory bowel disease (IBD) are at increased risk of colorectal cancer (CRC). However, the risk of CRC in patients with PSC without IBD remains uncertain. We aimed to evaluate the risk of CRC in patients with PSC without a history of IBD using a large national database.METHODSWe conducted a retrospective cohort study using the TriNetX database to identify patients ≥ 18 years with PSC. Patients were then divided into two groups, PSC with IBD (PSC-IBD cohort) and PSC without IBD (PSC non-IBD cohort), and were matched with patients without a history of PSC or IBD (non-PSC/non-IBD group) by using 1:1 propensity score matching. The primary outcome was the risk of first diagnosis of CRC. With censoring applied, Kaplan-Meier analysis with hazard ratios (HRs) and 95% CIs was used to compare time-to-event rates at daily time intervals.RESULTSPSC patients without IBD were at increased risk of CRC compared to the non-PSC/IBD cohort (aHR = 2.91; 95% CI: 1.6-6.0). Patients with PSC and IBD exhibited a higher risk of CRC (aHR = 6.5; 95% CI: 3.78-11.2), especially among the UC cohort (aHR = 6.3; 95% CI: 3.2-12.4). Patients with PSC were at increased risk of various gastrointestinal malignancies (aHR = 10.5; 95% CI: 7.3-15; p < 0.0001), including hepatobiliary cancers, pancreatic cancer, and hepatocellular carcinoma.DISCUSSIONOur findings provide real-world evidence that PSC is an independent risk factor for colorectal cancer, even in the absence of concomitant IBD. These results support the need for further research to determine whether patients with isolated PSC may benefit from tailored CRC surveillance strategies.","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"27 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144693260","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Research Communication: Combination Therapy of Upadacitinib With Infliximab, Risankizumab, Ustekinumab or Vedolizumab for Refractory Crohn's Disease: A Descriptive Case Series","authors":"Rahul S. Dalal, Lindsay M. Clarke, Heidy J. Cabral, Alexander D. Carlin, Grace B. Hardwick, Jessica R. Allegretti","doi":"10.1111/apt.70298","DOIUrl":"https://doi.org/10.1111/apt.70298","url":null,"abstract":"Combining two advanced therapies may improve outcomes in Crohn's disease (CD) refractory to monotherapy. We conducted a descriptive case series of 27 patients with CD who initiated combination therapy with upadacitinib and infliximab (<jats:italic>n</jats:italic> = 1), risankizumab (<jats:italic>n</jats:italic> = 17), ustekinumab (<jats:italic>n</jats:italic> = 3) or vedolizumab (<jats:italic>n</jats:italic> = 6). At 12 weeks, 24 achieved clinical response and 9 achieved steroid‐free remission. At 52 weeks, these rates were 15/20 and 11/20, respectively. Endoscopic response and extraintestinal manifestation improvement were frequently observed. Adverse events occurred in 13 patients, leading to treatment discontinuation in three. Combining upadacitinib with a biologic appeared effective and safe, warranting further investigation in prospective studies.","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"25 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144701537","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bradycardia and Other Arrhythmias in Patients With Hepatorenal Syndrome-Acute Kidney Injury Following Terlipressin Treatment: A Pooled Analysis of Three North American Phase III Clinical Studies.","authors":"Jasmohan S Bajaj,Paul Kwo,Stephen Chris Pappas,Jacqueline G O'Leary,Khurram Jamil,Sanaz Cardoza,Florence Wong","doi":"10.1111/apt.70297","DOIUrl":"https://doi.org/10.1111/apt.70297","url":null,"abstract":"BACKGROUNDTerlipressin is the FDA-approved systemic vasoconstrictor therapy for hepatorenal syndrome-acute kidney injury (HRS-AKI)-a rapidly progressive renal failure occurring in patients with decompensated cirrhosis and ascites. Bradycardia, a known effect of terlipressin, as well as other arrhythmias, has previously been reported in terlipressin-treated patients.AIMTo assess terlipressin-related cardiac adverse events (AEs) in patients with HRS-AKI.METHODSThree North American-centric Phase III, randomised, placebo-controlled studies (OT-0401, REVERSE, CONFIRM) were pooled in the largest-to-date prospective database. Cardiac AEs were reported by the investigators for each trial and retrospectively analysed.RESULTSBradycardia was the only cardiac AE reported more frequently in terlipressin-treated patients compared with placebo (6.3% [22/349] vs. 0.8% [2/249]). In the terlipressin group, no bradycardia AEs were serious, 4.5% (1/22) of patients required a dose interruption, 9.1% (2/22) required a dose reduction, and none discontinued treatment due to bradycardia. The incidences of other arrhythmia AEs were similar in both treatment groups (terlipressin: 7.4% [26/349]; placebo 8.8% [22/249]). The incidence of atrial fibrillation serious AEs (SAEs) was low (terlipressin: 0.9% [3/349]; placebo: 1.6% [4/249]). There were no AE reports of torsades de pointes, while a QT interval prolongation was reported in two patients.CONCLUSIONSIn a pooled analysis, bradycardia was observed in 6% of terlipressin-treated patients but rarely required a dose interruption or reduction. Arrhythmia SAE incidences were low and similar in both treatment groups. Routine intensive cardiac monitoring for the detection of arrhythmias may not be necessary during terlipressin administration.TRIAL REGISTRATIONOT-0401: NCT00089570, REVERSE: NCT01143246 and CONFIRM: NCT02770716.","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"19 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144693224","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}