Alimentary Pharmacology & Therapeutics最新文献

{"title":"Frequency and Effectiveness of Dose Escalation and De-Escalation of Biologic Therapy in Inflammatory Bowel Disease: The RAINBOW-IBD Study of ENEIDA.","authors":"Cristina Rubín de Célix,Elena Ricart,M Dolores Martín-Arranz,Ruth de Francisco,Francisco Javier García-Alonso,Francisco Mesonero,Fernando Gomollón,Luisa de Castro,Laura Ramos,Santiago García-López,Lara Arias,Miriam Mañosa,Eva Iglesias,Xavier Calvet,Carles Suria Bolufer,María José Casanova,José Lázaro Pérez-Calle,Antonio Giordano,Mónica Sierra-Ausín,Isabel Vera,Mercè Navarro-Llavat,Rufo Lorente,Marta Piqueras,Montserrat Rivero,Jordi Guardiola,María Esteve,Ana Fuentes Coronel,Iago Rodríguez-Lago,Ángel Ponferrada-Díaz,Yolanda Ber,Carlos Tardillo,Lucía Márquez,Daniel Carpio,Carlos Taxonera,Fernando Bermejo,David Busquets,Blau Camps,Ana Gutiérrez,Mariana Fe García-Sepulcre,Manuel Barreiro-de Acosta,Ignacio Marín-Jiménez,José M Huguet,Luis Ignacio Fernández-Salazar,Jordina Jaó,Cristina Rodríguez-Gutiérrez,Carlos Martínez-Flores,Luis Bujanda,Alfredo J Lucendo,Eva Sesé,Pilar Robledo Andrés,Daniel Ginard,Pablo Vega,Joan Riera,Ramón Pajares,Manuel Van Domselaar,Pedro Almela,Teresa Martínez Pérez,Carmen Muñoz-Villafranca,Pilar Varela,Federico Argüelles-Arias,Pilar Nos,Guillermo Alcaín,Luis Hernández,Hipólito Fernández,Fernando Muñoz,Pau Gilabert,Victor Manuel Navas-López,Patricia Ramírez de la Piscina,Lidia Buendía Sánchez,Jesús Legido Gil,Gemma Valldosera,Rosa Ana Muñoz,Santiago Frago,Eugeni Domènech,María Chaparro,Javier P Gisbert","doi":"10.1111/apt.70312","DOIUrl":"https://doi.org/10.1111/apt.70312","url":null,"abstract":"BACKGROUNDReal-world data on dose escalation/de-escalation in inflammatory bowel disease (IBD) are scarce.AIMSTo assess the frequency, effectiveness and durability of escalation/de-escalation of infliximab, adalimumab, golimumab, vedolizumab and ustekinumab in IBD, and to identify factors influencing relapse and drug discontinuation and re-escalation efficacy.METHODSWe included patients from the ENEIDA registry of GETECCU who were exposed to biologics and analysed escalations/de-escalations. We assessed the impact of variables on durability, drug discontinuation and relapse after escalation/de-escalation.RESULTSOf 19,720 patients on biologics, 5096 (26%) underwent dose escalation. Frequency of escalation per patient-year was 5% (infliximab), 7% (adalimumab), 7% (golimumab), 10% (vedolizumab) and 12% (ustekinumab). Clinical remission was recaptured in 32%-49% of patients. Durability of escalation (24 months) ranged from 66% to 88%. Drug discontinuation was associated with previous biologic exposure and disease duration (infliximab), monotherapy (adalimumab) and ulcerative colitis (ustekinumab). There were 669 de-escalations. The frequency per patient-year was 6%, 9%, 5%, 6% and 3% for infliximab, adalimumab, golimumab, vedolizumab and ustekinumab. Maintenance of remission after de-escalation was observed in 75%-100%. Durability of de-escalation (12 months) was 82%-90%. Factors associated with relapse were biologic exposure (infliximab) and age at de-escalation (adalimumab). Re-escalation benefited most patients.CONCLUSIONSIn the long term, some patients with IBD need biologic escalation, which frequently recaptures durable clinical remission. De-escalation is feasible in some patients. Re-escalation is generally effective after relapse.","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"1 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144797258","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":"Temporal Trends in Medical and Surgical Management of Ulcerative Colitis in England: 2003-2020.","authors":"J Couch,K Thomas,T R Card,D J Humes","doi":"10.1111/apt.70319","DOIUrl":"https://doi.org/10.1111/apt.70319","url":null,"abstract":"BACKGROUNDThe medical management of ulcerative colitis (UC) is evolving. However, colectomy may be required in severe or refractory cases.AIMTo provide contemporary evidence on medication usage and surgery for UC.METHODSAn incident cohort of patients newly diagnosed with UC from 2003 to 2020 was identified using computerised health records. The cumulative incidence of colectomy and medication use was calculated using Kaplan-Meier methods and compared across 3 time periods. We calculated 90-day post-operative mortality using life tables. Cox regression was used to model the risks of surgery and mortality, adjusting for confounders.RESULTS39,198 subjects had an incident diagnosis of UC. 5-year cumulative incidence of elective colectomy reduced from 2.60% to 1.30%, and emergency colectomy from 3.27% to 2.27% from 2003-2007 to 2015-2020. For elective surgery, adjusted hazard ratio (aHR) 0.44 and for emergency surgery, aHR 0.58 when 2015-2020 was compared to 2003-2007. Colectomy was less likely in women (elective aHR 0.74, emergency aHR 0.71) and emergency colectomy was less likely in those aged 40-59, aHR 0.86 than in those aged 18-39. Ninety-day mortality for elective and emergency surgery was 1.58% and 4.21%, respectively. Use of advanced therapies increased from 2% to 16% at 5 years from diagnosis when comparing 2003-2007 and 2015-2020.CONCLUSIONColectomy in the five years following diagnosis has declined, coinciding with an increased use of advanced therapies. Overall post-operative mortality is low. While the indication for colectomy may influence the risk of adverse outcomes, aggregate data provide a reassuring picture of current practice.","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"165 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144797200","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 on ‘Post-TIPS Overt Hepatic Encephalopathy Increases Long-Term but Not Short-Term Mortality in Cirrhotic Patients With Variceal Bleeding: A Large-Scale, Multicentre Real-World’","authors":"Silvia Nardelli,&nbsp;Francesco Vizzutti,&nbsp;Filippo Schepis,&nbsp;Manuela Merli,&nbsp;Simone Di Cola,&nbsp;Stefania Gioia,&nbsp;Oliviero Riggio","doi":"10.1111/apt.70134","DOIUrl":"10.1111/apt.70134","url":null,"abstract":"<p>We read with great interest the article published in <i>Alimentary Pharmacology &amp; Therapeutics</i> regarding the impact of post-TIPS overt hepatic encephalopathy (OHE) on long-term mortality in a retrospective cohort of cirrhotic patients with variceal bleeding [<span>1</span>]. In particular, multivariable competing risk analysis, adjusting for potential confounders, showed that the onset of post-TIPS OHE was an independent predictor of all-cause mortality beyond the 24-month follow-up period, but was not associated with short-term mortality. Furthermore, from the multivariable analysis, in addition to OHE, other predictors are associated with a higher risk of mortality, including age and MELD score. Therefore, especially with such long follow-up, it becomes difficult to discriminate the role of each single predictor since the effect is probably to be understood as additive, especially if they are non-collinear predictors.</p><p>Similarly to Hartl et al. [<span>2</span>], competing risk regression analysis revealed that early onset of post-TIPS OHE (within the first month) was significantly associated with higher long-term mortality risk (SHR: 2.390 [2.020–2.840], <i>p</i> &lt; 0.001). This result was not observed in our cohort [<span>3</span>]. Could this result be due, at least in part, to the high rate of stent dysfunction (27%–30% of patients) observed in the Chinese cohort? However, as previously described [<span>2, 3</span>] when dealing with time-sensitive variables such as the development of OHE after TIPS, authors should have used Landmark analysis to avoid immortal time bias [<span>4</span>] although it includes certain limitations such as the impact of when the landmark is chosen on the obtained results or reduced sample size [<span>5</span>].</p><p>Another point to be noted is that more than half of the patients enrolled by Xiang et al. had TIPS placed for emergency haemostasis. In our cohort, we decided to exclude these patients because preemptive TIPS is known to be associated with reduced mortality and an incidence of OHE similar to pharmacological and endoscopic combined treatments. Therefore, the inclusion of patients submitted to preemptive TIPS may have altered per se the impact of OHE on survival [<span>6</span>]. Moreover, regarding this, Xiang et al. observed that a higher proportion of patients with OHE had variceal bleeding, which may have been the trigger for HE and mortality.</p><p>As already observed by Kumar et al. [<span>7</span>], a deeper analysis of post-TIPS OHE, including time to onset, severity, precipitating factors and their correlation with mortality, would provide a clearer understanding of its impact on patient outcomes. In particular, the authors do not specify how many patients develop recurrent or persistent HE which, as already described [<span>8</span>], are those at highest risk of mortality and therefore deserve a separate analysis.</p><p>Nevertheless, further prospective studies considering ","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"62 6","pages":"674-675"},"PeriodicalIF":6.7,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apt.70134","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144796858","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: Lymphocyte-To-Monocyte Ratio and Recompensation in PBC—A New Piece in an Incomplete Puzzle?","authors":"Adrielly Martins,&nbsp;Adriaan J. van der Meer","doi":"10.1111/apt.70266","DOIUrl":"10.1111/apt.70266","url":null,"abstract":"&lt;p&gt;The concept of recompensation has emerged as a meaningful outcome in patients with decompensated cirrhosis, reflecting the potential for clinical and biochemical improvement in selected patients [&lt;span&gt;1&lt;/span&gt;]. Although patients with decompensated cirrhosis may improve from symptom-directed therapies, such as diuretics and lactulose, successful clearance or suppression of the aetiology of liver disease is considered a prerequisite for long-term recovery of liver function. In primary biliary cholangitis (PBC), a rare chronic cholestatic liver disease that remains incurable short of liver transplantation, predictors of recompensation remain poorly defined and understudied.&lt;/p&gt;&lt;p&gt;Therefore, as presented in this issue of &lt;i&gt;Alimentary Pharmacology &amp; Therapeutics&lt;/i&gt;, Lin and colleagues report an interesting study assessing the prognostic value of the lymphocyte-to-monocyte ratio (LMR) in 401 patients with decompensated PBC-related cirrhosis [&lt;span&gt;2&lt;/span&gt;]. The most common initial decompensating event was ascites (62.3%), followed by variceal bleeding (24.4%) and hepatic encephalopathy (HE) (13.2%). Recompensation was defined using adapted Baveno VII criteria: UDCA response (ALP &lt; 1.67 × ULN after ≥ 12 months of therapy), resolution of decompensating events, and improved liver function (albumin &gt; 35 g/L, INR &lt; 1.5, bilirubin &lt; 34 μmol/L). In total, 105 patients (26.2%) achieved recompensation. Higher baseline LMR was linearly associated with increased likelihood of recompensation (HR: 1.45; 95% CI: 1.26–1.58), independent from other factors, with stable estimates in case of repeated measurements over time.&lt;/p&gt;&lt;p&gt;These findings underscore the potential of LMR as a simple, readily available, non-invasive biomarker that may reflect the immune-inflammatory milieu in PBC. Biologically, a higher LMR could suggest a more favourable immunologic profile, consistent with the understanding of immune dysregulation in PBC, where monocyte-driven inflammation and lymphocyte imbalances (e.g., Th1/Th17 predominance) are thought to contribute to progressive bile duct injury and fibrosis [&lt;span&gt;3-5&lt;/span&gt;]. However, LMR is influenced by a wide range of non-hepatic factors, including infections, comorbid autoimmune conditions, medications (e.g., corticosteroids), lifestyle exposures, and aging. Many of these are difficult to fully account for in retrospective analyses and clinical practice. As such, while LMR may be sensitive to shifts in immune tone, it lacks specificity, and its use as a solitary predictive marker warrants cautious interpretation.&lt;/p&gt;&lt;p&gt;Thus, while promising, several limitations of the presented study warrant consideration. The retrospective, single-centre design limits generalisability, as recompensation remains a subjective endpoint; it requires trials of diuretics and/or HE withdrawal. Variability in supportive management may also affect outcomes. Moreover, while the authors applied adapted Baveno VII criteria, etiological con","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"62 6","pages":"672-673"},"PeriodicalIF":6.7,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apt.70266","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144796855","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":"Efficacy and Safety of Vedolizumab and Tofacitinib (VETO) Combination Therapy in Refractory Ulcerative Colitis Unresponsive to Anti-TNF and a Second-Line Advanced Therapy: A Prospective Cohort Nested Within a Randomised Trial.","authors":"Pardhu Bharath Neelam,Dhanush Mekala,Rajender Patel,Rupa Banerjee","doi":"10.1111/apt.70309","DOIUrl":"https://doi.org/10.1111/apt.70309","url":null,"abstract":"BACKGROUNDManagement of refractory ulcerative colitis (UC) unresponsive to advanced therapies is challenging. Combination therapy is a potential strategy.AIMTo evaluate the safety and efficacy of vedolizumab and tofacitinib combination (VETO) therapy in patients with UC refractory to anti-TNF and unresponsive to either agent as monotherapy.METHODSWe prospectively recruited patients with moderate-to-severe disease activity (Mayo score: 6-12). Patients were randomised to receive vedolizumab or tofacitinib. Non-responders were offered VETO therapy and followed for 24 weeks. The primary outcome was a combined clinical response and corticosteroid-free remission at week 24. Secondary outcomes included clinical response and remission at week 8, endoscopic remission at week 24 and incidence and severity of treatment-related adverse events.RESULTSOf 91 patients, 38 were randomised to vedolizumab and 40 to tofacitinib. Fourteen and 15, respectively, were non-responders to vedolizumab and tofacitinib; 24 received VETO with follow-up of 34 ± 16.1 weeks. Median second-line therapy duration before VETO was 21 weeks. Five non-responders received alternative interventions or were lost to follow-up. At week 8, 17 achieved clinical response and five achieved remission; three underwent colectomy. At week 24, response and corticosteroid-free remission were seen in 17 and 14, respectively; 7 achieved endoscopic remission. Mayo scores improved significantly (mean difference 5.33 ± 0.53; p < 0.01). Two patients developed pseudomembranous colitis that resolved with vancomycin. No severe adverse events occurred.CONCLUSIONVETO was effective and safe in patients with UC refractory to anti-TNF and second-line therapies, with over half achieving clinical remission by 24 weeks.","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"150 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144769618","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: HBV Integration: A Possible Key Driver in the Course of Patients With Chronic HBV Infection Under Viral Suppression","authors":"Hidenori Toyoda","doi":"10.1111/apt.70285","DOIUrl":"10.1111/apt.70285","url":null,"abstract":"&lt;p&gt;The development of hepatocellular carcinoma (HCC) and the disappearance of hepatitis B virus (HBV) surface antigen (HBsAg) are two main events that can occur in patients with chronic HBV infection that is successfully controlled by anti-HBV therapy. The integration of HBV may be a key driver of both of these events.&lt;/p&gt;&lt;p&gt;Gu et al. [&lt;span&gt;1&lt;/span&gt;] investigated the association between the metrics of HBV integration and HBsAg loss by anti-HBV therapy with nucleoside analogue (NUC) and peginterferon (PEG-IFN) using high through-put sequencing for detecting HBV integration. They found that a lower number of breakpoint types at baseline was related to a higher rate of HBsAg loss. In contrast, no association was found between HBsAg loss and the frequency of breakpoints. These results are novel and may provide insight into the association between low HBsAg or HBsAg loss and a reduced risk of developing HCC in patients undergoing anti-HBV therapy.&lt;/p&gt;&lt;p&gt;HBV-related HCC has a distinct type of development that is specific to HBV infection, which involves the development of HCC without advanced liver fibrosis or even with no fibrosis. HCCs with other etiologies usually develop only in patients with cirrhosis or advanced liver fibrosis. Liver function is ameliorated and liver fibrosis, which is the most important risk factor for developing HCC, is regressed in HBV-infected patients under viral suppression by anti-HBV therapy, thus reducing the risk of developing HCC. However, the risk of HCC from this type of development is not reduced with continuous suppression of HBV by anti-HBV therapy.&lt;/p&gt;&lt;p&gt;The integration of HBV into the human host genome is considered the main cause for this phenomenon. A higher number of breakpoint types may increase the likelihood of HBV integration at the site flanking host genes associated with hepatocarcinogenesis. Therefore, a higher number of breakpoint types could play a role in a decreased likelihood of HBsAg loss and increased risk of developing HCC. This possibility may explain, at least in part, the known clinical association between a lower HBsAg titre or HBsAg loss and a reduced risk of HCC in patients with HBV under viral suppression.&lt;/p&gt;&lt;p&gt;Unfortunately, PEG-IFN is not routinely used as anti-HBV therapy in current clinical practice, and the prediction of HBsAg loss by PEG-IFN would have less clinical impact. Patients undergoing anti-HBV therapy with solely NUC could not achieve loss of HBsAg in this study. Whether viral suppression by NUC has a preventive effect on developing HCC without liver fibrosis is unknown. Additionally, whether PEG-IFN should be used for HBsAg loss and further reduction of the risk of HCC is unclear. It may be possible that the association between the HBsAg loss by PEG-IFN and a low risk of HCC was simply the two results from a lower number of breakpoint types of HBV integration. Further studies should investigate the associations between HBV integration metrics, HBsAg loss, and the risk o","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"62 9","pages":"948-949"},"PeriodicalIF":6.7,"publicationDate":"2025-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apt.70285","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144769656","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: HBV Integration—A Possible Key Driver on the Course of Patients With Chronic HBV Infection Under Viral Suppression. Authors' Reply","authors":"Qin Ning,&nbsp;Meifang Han","doi":"10.1111/apt.70321","DOIUrl":"10.1111/apt.70321","url":null,"abstract":"<p>We thank Dr. Toyoda for his insightful comments on our study [<span>1</span>]. We agree that a higher number of hepatitis B virus (HBV) integration breakpoint types is associated with a reduced likelihood of hepatitis B surface antigen (HBsAg) loss after pegylated interferon (Peg-IFN) therapy, potentially explaining why some patients do not achieve HBsAg clearance [<span>2</span>]. We also concur that HBV integration is a key driver of hepatocellular carcinoma (HCC) development [<span>3</span>].</p><p>Our study further found that the duration of prior nucleos(t)ide analogue (NUC) therapy (initiated upon hepatitis flares), along with alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, positively correlated with hepatocyte clonal expansion levels. This suggests that recurrent flares and prolonged inflammation promote clonal expansion, thereby increasing future HCC risk [<span>4</span>]. Crucially, NUC therapy does not fully eliminate HCC risk, especially in non-cirrhotic patients [<span>5</span>]. Therefore, patients with high breakpoint types or elevated clonal expansion warrant long-term HCC surveillance.</p><p>Even though the frequently integrated genes and associated signalling pathways observed in our NUC-experienced and virally suppressed chronic hepatitis B (CHB) patients differ from those previously reported in advanced HCC patients [<span>2, 3, 6</span>], the increased number of breakpoint types elevates the likelihood of HBV integration near oncogenes or tumour-related genes. This creates favourable conditions for widespread hepatocyte clonal expansion and consequently increases HCC risk [<span>3, 4</span>].</p><p>In fact, none of the patients in this study developed cirrhosis or HCC during treatment and follow-up. Future studies should extend the follow-up period to further investigate the relationship between HBV integration, HBsAg seroclearance and HCC development, as the precise molecular mechanisms remain complex.</p><p>We propose that Peg-IFN therapy suppresses viral replication and modulates immune responses (e.g., cytotoxic T lymphocytes activity) [<span>7</span>]. For NUC-experienced patients with low levels of HBsAg (&lt; 3000 IU/mL), sequential or combined Peg-IFN may improve functional cure rates [<span>7</span>]. Future research should prioritise investigating the relationship between HBV integration metrics, HBsAg loss and HCC risk in CHB patients, as seen in our ongoing OCEAN study. Given the challenges of obtaining liver tissue, developing non-invasive circulating biomarkers as surrogates for HBV integration also warrants exploration.</p><p><b>Qin Ning:</b> writing – original draft, writing – review and editing. <b>Meifang Han:</b> writing – original draft, writing – review and editing.</p><p>The authors declare no conflicts of interest.</p><p>This article is linked to Gu et al. papers. To view these articles, visit https://doi.org/10.1111/apt.70270 and https://doi.org/10.1111/apt.70285.</p>","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"62 9","pages":"950-951"},"PeriodicalIF":6.7,"publicationDate":"2025-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apt.70321","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144769621","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":"Impact of Frailty on the Prognosis of Patients With Liver Cirrhosis Undergoing Insertion of a TIPS","authors":"Martin Andreas Kabelitz, Simon Johannes Gairing, Anja Tiede, Eva Maria Schleicher, Liv Grete Ahl, Lea Wagner, Falko Zucker‐Reimann, Hannah Rieland, Jim Benjamin Mauz, Julia Weinmann‐Menke, Bernhard C. Meyer, Michael Bernhard Pitton, Heiner Wedemeyer, Peter Robert Galle, Lisa Sandmann, Benjamin Maasoumy, Christian Labenz","doi":"10.1111/apt.70315","DOIUrl":"https://doi.org/10.1111/apt.70315","url":null,"abstract":"Background and AimsFrailty is associated with a poorer prognosis of patients awaiting liver transplantation. Data on the impact of frailty on prognosis after transjugular intrahepatic portosystemic shunt (TIPS)‐insertion in patients with cirrhosis and the influence of TIPS on longitudinal changes in frailty are lacking.MethodsWe retrospectively analysed data of 123 prospectively recruited patients with cirrhosis in Mainz and Hannover prior to elective TIPS insertion and monitored them for death/liver transplantation or post‐TIPS overt hepatic encephalopathy (OHE). Patients underwent testing with the Liver Frailty Index (LFI) prior to TIPS insertion as well as 1, 3 and 6 months after TIPS placement.ResultsMedian LFI prior to TIPS insertion was 4.32 (interquartile range: 3.78–4.88). 53% of patients who were frail at baseline and still alive at 6 months improved to prefrail status within 6 months of TIPS insertion. Higher LFI and younger age were associated with a decrease in LFI within 6 months. During follow‐up, 40 patients developed post‐TIPS OHE and 30 patients died or received a liver transplantation. There was no significant association between LFI as a metric variable and post‐TIPS OHE or liver transplantation/death. However, patients with LFI values in the lowest quartile had a significantly better transplantation‐free survival.ConclusionsTIPS insertion seems to improve physical functioning, as indicated by a decreasing LFI, but only in patients with a poor performance in LFI prior to TIPS. Conducting LFI prior to elective TIPS insertion can identify those with an excellent prognosis. However, frailty should not be considered a contraindication for TIPS.Trial Registration<jats:ext-link xmlns:xlink=\"http://www.w3.org/1999/xlink\" xlink:href=\"http://clinicaltrials.gov\">ClinicalTrials.gov</jats:ext-link> identifier: NCT05466669 and NCT04801290","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"11 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144763259","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: Toward Safer Pain Management in IBD—Lessons From Prescription Patterns","authors":"Shabari Shenoy,&nbsp;Laurie Keefer","doi":"10.1111/apt.70263","DOIUrl":"10.1111/apt.70263","url":null,"abstract":"&lt;p&gt;Pain is reported by roughly two-thirds of patients with inflammatory bowel disease (IBD) [&lt;span&gt;1&lt;/span&gt;]. Chronic pain impairs quality of life and psychosocial wellbeing, and increases pain medication use [&lt;span&gt;2&lt;/span&gt;]. Acetaminophen/paracetamol, NSAIDs and opioids are commonly used in practice but are associated with adverse effects and outcomes [&lt;span&gt;3&lt;/span&gt;]. Despite this, data on the prevalence and scope of pain medication use in IBD remain limited. This editorial discusses the timely and relevant study by Baillie et al. [&lt;span&gt;4&lt;/span&gt;] which explored trends in pain and sedative medication use in IBD in the UK.&lt;/p&gt;&lt;p&gt;Using Clinical Practice Research Datalink-GOLD, the authors filled a much-needed gap in our understanding, particularly in Europe, of global prescription and co-prescription patterns of benzodiazepines, Z drugs (non-benzodiazepine hypnotics acting at the benzodiazepine receptors, commonly prescribed for sleep difficulties) and gabapentinoids for pain management in IBD and identified risk factors for harm. They examined prescriptions of 4901 patients over a 5-year follow-up period, focusing on opioid potency and chronicity, and the use of benzodiazepines and Z drugs. Between 2010 and 2019, chronic prescription of strong and weak opioids, gabapentin and Z drugs increased, while benzodiazepine prescriptions declined. Co-prescriptions, especially with gabapentinoids, also increased. Chronic prescribing of strong opioids was most common in Crohn's disease. Older age of diagnosis, female sex, current smoking, anxiety/depression and fibromyalgia prior to diagnosis were significantly associated with long-term and co-prescribing patterns.&lt;/p&gt;&lt;p&gt;While the longitudinal follow-up and large sample size are key strengths of the study, the lack of data on indications for prescription and co-prescription limits interpretation. While concerns around dependence and overdose with co-prescriptions are valid, the benefits of reducing opioid use through cautious gabapentinoid co-prescriptions should not be overlooked [&lt;span&gt;5, 6&lt;/span&gt;]. Furthermore, there is no data on the use of adjuvant therapies such as neuromodulators, antispasmodics, or lifestyle interventions often used in North America to reduce chronic opioid use [&lt;span&gt;2, 7&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;Pain management in IBD is challenging due to its relapsing–remitting course often leading to persistent chronic pain [&lt;span&gt;7&lt;/span&gt;]. Effective pain management (Table 1) requires an understanding of its underlying mechanisms. Distinguishing visceral pain from gut inflammation versus centrally-mediated neuropathic or functional pain is essential. It is also important to consider common co-existing painful conditions such as irritable bowel syndrome and psychosocial drivers of pain [&lt;span&gt;8, 9&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;While the decline in chronic benzodiazepine prescription is encouraging, the increase in the chronic prescriptions of opioids, gabapentinoids and Z drugs is concerning due to risks of dependenc","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"62 7","pages":"749-751"},"PeriodicalIF":6.7,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apt.70263","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144763341","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: Toward Safer Pain Management in IBD—Lessons From Prescription Patterns. Authors' Reply","authors":"Samantha Baillie,&nbsp;Jonathan Blackwell,&nbsp;Richard Pollok","doi":"10.1111/apt.70304","DOIUrl":"10.1111/apt.70304","url":null,"abstract":"<p>We welcome the editorial in response to our work on pain and sedative medication use in inflammatory bowel disease (IBD) [<span>1, 2</span>]. Chronic pain remains one of the most challenging and under-managed aspects of living with IBD, despite therapeutic advances in inflammation control over the past decade.</p><p>The need for effective, safer alternatives to opioids is clear. Neuromodulators including selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), and tricyclic antidepressants (TCAs)—have been increasingly used in clinical practice to target the central pain mechanisms of the gut-brain axis [<span>3</span>]. These agents offer a plausible pharmacological alternative in IBD based on their success in other chronic pain syndromes, such as irritable bowel syndrome (IBS), fibromyalgia, and neuropathic pain.</p><p>However, the current evidence base for the use of neuromodulators in IBD-specific pain remains limited and mixed [<span>4</span>]. Intermittent and continuous neuromodulator use is associated with similar or higher rates of corticosteroid use, respectively, which may be attributable to a more severe disease phenotype in individuals requiring neuromodulator prescriptions [<span>5</span>]. TCAs may modestly improve global well-being in individuals with inactive or mild disease, and their established efficacy in IBS may have relevance for patients with IBD-IBS overlap [<span>3, 4</span>] In a cohort study, neuromodulator use in IBD was associated with higher corticosteroid use, and more frequent emergency department visits and hospitalisations, although not IBD-related complications [<span>6</span>]. Notably, neuromodulator use was also linked to a reduced risk of surgery. In a systematic review and meta-analysis of 11 studies, neuromodulators significantly improved depressive symptoms and quality of life in individuals with IBD compared to placebo [<span>7</span>]. While SNRIs may improve anxiety-related symptoms, their impact on pain in this population has not been formally studied.</p><p>Pain symptoms persist even in endoscopic remission, and patients consistently rate pain and fatigue among their most burdensome symptoms. Improving symptom control is essential to holistic care and aligns with the broader goals of treat-to-target strategies, which now extend beyond inflammation alone [<span>8</span>]. Alongside developing new advanced therapies for treating inflammation, a well-designed randomised controlled trial of neuromodulators for IBD-related pain should be a research priority, given the potential for neuromodulators to reduce opioid reliance and improve quality of life.</p><p>A further consideration is the potential role of psychological interventions in managing pain and related symptoms in IBD. These approaches have shown potential in recent IBD studies, for example self-directed cognitive behavioural therapy in a sub-population with coexistent IBS in the recently conducte","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"62 7","pages":"752-753"},"PeriodicalIF":6.7,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apt.70304","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144763253","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}