Alimentary Pharmacology & Therapeutics最新文献

{"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":"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}

{"title":"Letter: H. pylori Infection May Constitute a Risk Factor for Reflux Disease and Colonic Neoplasia-Authors' Reply.","authors":"Amnon Sonnenberg,Anna M Buchner,Ruth Kohen","doi":"10.1111/apt.70305","DOIUrl":"https://doi.org/10.1111/apt.70305","url":null,"abstract":"","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"19 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144693205","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":"Letter: H. pylori Infection May Constitute a Risk Factor for Reflux Disease and Colonic Neoplasia.","authors":"Jannis Kountouras,Christos Zavos,Elisabeth Vardaka,Evangelos Kazakos","doi":"10.1111/apt.70299","DOIUrl":"https://doi.org/10.1111/apt.70299","url":null,"abstract":"","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"90 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144693206","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":"Persistent Binge Drinking History Associated With Advanced Liver Fibrosis and All‐Cause Mortality in MetALD","authors":"Zhe‐Kun Xiong, Ru‐Tao Lin, Bi‐Wei Chen, Xin Xin, Tao‐Ying Deng, Qin‐Mei Sun, Yi‐Yang Hu, Li‐Ming Gan, Qin Feng","doi":"10.1111/apt.70286","DOIUrl":"https://doi.org/10.1111/apt.70286","url":null,"abstract":"BackgroundMetabolic dysfunction and alcohol‐related liver disease (MetALD) is characterised by the coexistence of metabolic dysfunction and moderate alcohol intake. In this population, the impact of specific drinking patterns and history, particularly persistent binge drinking (PBD) history, on disease severity and prognosis remains unclear.AimTo evaluate the association between a history of PBD and the risks of advanced fibrosis and all‐cause mortality in individuals with MetALD.MethodsWe analysed data from NHANES 1999–2016, including adults with MetALD. PBD is defined as having had a history of drinking ≥ 4 (women) or 5 (men) alcoholic beverages almost every day, based on ALQ150/151 questionnaires. Advanced fibrosis was defined as FIB‐4 &gt; 2.67, and mortality outcomes were obtained from the National Death Index. Multivariable logistic and Cox regression models were used to examine the associations between PBD and both liver fibrosis and all‐cause mortality, adjusting for alcohol intake and other confounders.ResultsAmong 865 individuals with MetALD, 326 (37.7%) reported a history of PBD. Compared to those without PBD, participants with PBD had a higher risk of advanced fibrosis (adjusted OR = 2.23, 95% CI: 1.12–4.45, <jats:italic>p</jats:italic> = 0.023). PBD was also associated with increased all‐cause mortality (adjusted HR = 1.48, 95% CI: 1.03–2.13, <jats:italic>p</jats:italic> = 0.035). A higher risk of overnight hospitalisation in PBD supports these findings (adjusted OR = 1.88, 95% CI: 1.15–3.06, <jats:italic>p</jats:italic> = 0.012).ConclusionPBD history is associated with increased risks of advanced fibrosis and mortality in MetALD. Clinical assessment should include an evaluation of drinking patterns and history, particularly persistent binge drinking.","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"98 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144677540","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":"Outcome After Surgery for Colon Cancer in a National Cohort of Patients With and Without Inflammatory Bowel Disease.","authors":"Erik Lundqvist,Karin Westberg,Sol Erika Boman,Ida H Myrberg,Åsa H Everhov,Pär Myrelid,Bengt Glimelius,Anna Martling,Caroline Nordenvall","doi":"10.1111/apt.70296","DOIUrl":"https://doi.org/10.1111/apt.70296","url":null,"abstract":"AIMSTo estimate the impact of inflammatory bowel disease on survival in a national cohort of patients following surgical resection for colon cancer, and to describe the surgical treatment of colon cancer in patients with inflammatory bowel disease.METHODSUsing the Colorectal Cancer Database, we included all patients ≥ 15 years of age with a diagnosis of stages I-III colon cancer treated with curative intent 2007-2021. We used Cox proportional hazards models to compare overall survival, recurrence-free survival and cancer-specific survival between patients with and without inflammatory bowel disease. Multivariable analyses were adjusted for sex, age, date of colon cancer surgery, Charlson Comorbidity Index and primary sclerosing cholangitis.RESULTSAmong 35,640 patients with colon cancer, 675 (1.9%) had inflammatory bowel disease. Median age at colon cancer diagnosis was 68 years in patients with inflammatory bowel disease and 75 in those without; proportions of male sex were 55% and 49%, respectively. In patients with inflammatory bowel disease, surgical therapy was proctocolectomy in 10%, subtotal colectomy in 29% and segmental resection in 61%. From adjusted analyses, patients with inflammatory bowel disease had worse overall survival (HR = 1.38; 95% CI: 1.21-1.57), recurrence-free survival (HR = 1.33; 95% CI: 1.18-1.50) and cancer-specific survival (HR = 1.46; 95% CI: 1.23-1.73) than patients without.CONCLUSIONInflammatory bowel disease negatively influences the prognosis of colon cancer. Proctocolectomy was performed only in a minority of those with inflammatory bowel disease. Outcomes need to be improved in patients with inflammatory bowel disease developing colon cancer.","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"115 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144684113","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":"Appendectomy Is Not Associated With a Milder Clinical Course of Ulcerative Colitis: A Nationwide Danish Population-Based Study.","authors":"Anders Mark-Christensen,Eskild Bendix Kristiansen,Søren Laurberg,Rune Erichsen","doi":"10.1111/apt.70279","DOIUrl":"https://doi.org/10.1111/apt.70279","url":null,"abstract":"BACKGROUNDAppendectomy may have a beneficial effect on the course of ulcerative colitis (UC), but the association remains debated.AIMTo examine if appendectomy influences the clinical course of UC.METHODSWe identified all patients diagnosed with UC in Denmark from 1977 to 2017 from the Danish National Patient Registry. Patients who underwent appendectomy were matched for age, sex, calendar year and disease duration with up to 10 comparators with UC and no appendectomy. We compared UC-related admission rates, rates of initiating treatment with biologics, and colorectal resection rates between patients with UC with and without appendectomy.RESULTS22,098 patients with UC (2014 with and 20,084 without appendectomy) were followed for a median 10.3 years (interquartile range: 5.1-18.5). Hospitalisation rates were higher for those who underwent appendectomy of a normal appendix after UC (IRR = 1.11 (95% CI: 1.01-1.22)) and for those who underwent appendectomy for appendicitis before UC (IRR = 1.22 (95% CI: 1.15-1.31)). Appendectomy performed for appendicitis after UC was associated with a higher rate of colorectal resections 5-20 years after appendectomy (aHR5-10 years = 2.08 (95% CI: 1.03-4.17)), aHR10-20 years = 3.25 (95% CI: 1.31-8.08) and 5-10 years after appendectomy if not performed for appendicitis (aHR = 2.51 (1.01-6.23)). Rates of initiating treatment with biologics were comparable between patients with and without prior appendectomy.CONCLUSIONPatients with UC who underwent appendectomy did not experience a milder clinical course compared to those without appendectomy, regardless of underlying appendicitis.","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"11 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144669511","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":"Clinical and Genetic Associations in Cephalosporin-Induced Liver Injury: Insights From the Drug-Induced Liver Injury Network.","authors":"Raj Vuppalanchi,Yi-Ju Li,Don C Rockey,Dina Halegoua-DeMarzio,Robert J Fontana,Herbert L Bonkovsky,Christopher Koh,Joseph Odin,Huiman Barnhart,Jay H Hoofnagle, ","doi":"10.1111/apt.70284","DOIUrl":"https://doi.org/10.1111/apt.70284","url":null,"abstract":"INTRODUCTIONCephalosporins are widely prescribed antibiotics due to their efficacy and safety. Although rare, idiosyncratic drug-induced liver injury (DILI) has been reported with their use. Here, we characterise the clinical features and HLA associations of cephalosporin-related liver injury.METHODSBetween Jan 1, 2004, and Nov 2, 2022, a total of 2347 cases of DILI were enrolled in the DILIN study, of which 1854 were adjudicated as probable, highly likely, or definite. HLA sequencing was performed, and association with the risk of DILI was examined.RESULTS58 cases (3%) were attributed to different cephalosporins, including cefazolin (n = 40), cephalexin (n = 4), ceftriaxone (n = 3), cefdinir (n = 3), cefuroxime (n = 3), and five other individual agents. Clinical features included a self-limited course with a mixed or cholestatic biochemical pattern without hypersensitivity features occuring in 1 to 4 weeks. Most striking was the phenotype of cefazolin and other parenteral cephalosporins given as a single dose with the onset of jaundice, fatigue, and itching 1 to 3 weeks later. In the total cohort, HLA-A*02:01 was significantly associated with an increased risk of cephalosporin-induced liver injury (OR: ~2.5-2.7, P < 0.0001). The association was strongest with cefazolin, with carrier frequencies of 85% vs. 38% in those with DILI from other drugs.CONCLUSIONSCephalosporins can cause self-limited, mixed/cholestatic hepatitis that arises after a short course of therapy with a latency of up to 3 weeks with cefazolin. Cephalosporin-induced liver injury is associated with the HLA-A*02:01 allele, which is linked to more severe liver injury at the onset of illness.","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"65 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144669332","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: JAK to JAK—Navigating Intra-Class JAK Inhibitor Switching in Inflammatory Bowel Disease. Authors' Reply","authors":"Mathieu Uzzan,&nbsp;David Laharie,&nbsp;Julien Kirchgesner","doi":"10.1111/apt.70292","DOIUrl":"10.1111/apt.70292","url":null,"abstract":"<p>We thank Clough et al. for their editorial, which highlights the importance of the real-world data we generated on intra-class Janus kinase inhibitors (JAKi) switching [<span>1, 2</span>]. It is also important to note that this strategy may be of interest for patients with difficult-to-treat inflammatory bowel disease (IBD), although most currently available evidence assessed the switch from tofacitinib to upadacitinib [<span>3</span>]. Various studies, including ours, confirm the potential benefit of this approach, with approximately one in two patients achieving clinical remission after the induction phase. Similarly, the safety profile appears acceptable in patients previously exposed to multiple lines of immunomodulators.</p><p>There is less evidence supporting intra-class JAKi switching for sequences other than tofacitinib-to-upadacitinib in IBD. However, studies including rheumatoid arthritis have provided evidence to support cycling to another JAKi in case of inadequate response to a first JAKi besides tofacitinib [<span>4</span>].</p><p>Additionally, switching in patients intolerant to a first-line JAKi could be considered. Indeed, the safety profiles of the three available JAKi differ [<span>5</span>], and both safety and efficacy appear to be dose-related and intercorrelated. Therefore, a second-line JAKi could be proposed after discontinuation of a first-line JAKi that was effective but poorly tolerated. For instance, switching to tofacitinib or filgotinib could be an option in a patient receiving upadacitinib that is effective for colonic inflammatory activity but associated with severely burdensome acne. Acne is more frequent with upadacitinib than other JAKi [<span>6</span>].</p><p>As we emphasised in our paper, all intra-class switching strategies within the JAKi class should be carefully considered; future studies will be necessary to support the various potential approaches.</p><p><b>Mathieu Uzzan:</b> writing – original draft, conceptualization. <b>David Laharie:</b> writing – review and editing. <b>Julien Kirchgesner:</b> writing – review and editing.</p><p>M.U. declares counselling, boards or fees for AbbVie, Amgen, Celltrion, Pfizer, Owkin, Janssen, Lilly, Takeda. D.L. declares counselling, boards, transports or fees from Abbvie, Alfasigma, Amgen, Celltrion, Ferring, Janssen, Lilly, Medac, MSD, Pfizer, Sandoz, Takeda. J.K. received lecture fees from Janssen and Lilly, and consulting fees from Roche, Pfizer, Janssen, Abbvie, Takeda, Lilly, and Gilead.</p><p>This article is linked to Osty et al. papers. To view these articles, visit https://doi.org/10.1111/apt.70199 and https://doi.org/10.1111/apt.70226.</p>","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"62 4","pages":"460-461"},"PeriodicalIF":6.6,"publicationDate":"2025-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apt.70292","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144664228","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial on 'Prevalence and Predictors of Symptoms of Anxiety or Depression at Diagnosis in Patients With Inflammatory Bowel Disease: An Inception Cohort'. Authors' Reply.","authors":"Christy Riggott, David J Gracie, Alexander C Ford","doi":"10.1111/apt.70293","DOIUrl":"https://doi.org/10.1111/apt.70293","url":null,"abstract":"","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144657961","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}