Alimentary Pharmacology & Therapeutics最新文献

{"title":"Editorial: Amino Acid Imbalance and Prognosis in Cirrhosis. Authors' Reply","authors":"Takao Miwa, Yuki Utakata, Masahito Shimizu","doi":"10.1111/apt.70990","DOIUrl":"10.1111/apt.70990","url":null,"abstract":"<p>We sincerely thank Iwadare and Kimura for their thoughtful Editorial and for their insightful discussion of our study [<span>1, 2</span>]. We greatly appreciate their perspective that amino acid imbalance may represent a metabolic dimension of prognosis that is not fully captured by conventional measures of liver functional reserves.</p><p>As highlighted in the Editorial, one of the important findings was that both lower branched-chain amino acid (BCAA) concentrations and higher tyrosine concentrations were independently associated with mortality, suggesting that the prognostic significance of the branched-chain amino acid-to-tyrosine ratio (BTR) is not attributable to a single component [<span>1</span>]. Although BTR has traditionally been used as an indicator of amino acid imbalance and nutritional status, BCAA and tyrosine may reflect distinct but complementary metabolic alterations in cirrhosis [<span>3</span>]. Reduced circulating BCAA concentrations may reflect altered skeletal muscle metabolism, nutritional impairment, and increased BCAA utilization in the setting of hyperammonaemia, whereas elevated tyrosine concentrations may be more closely related to impaired hepatic metabolism [<span>3-5</span>]. Indeed, both serum BCAA and tyrosine levels remained significant in their association with mortality after adjustment of skeletal muscle mass [<span>6</span>]. Thus, BTR may integrate metabolic information from both extrahepatic and hepatic compartments, while separate assessment of BCAA and tyrosine may provide further insight into the metabolic alterations underlying disease progression. Further studies incorporating detailed assessments of skeletal muscle, nutritional status, and ammonia metabolism are warranted to clarify the mechanisms underlying these associations.</p><p>We also fully agree that an independent association with mortality does not necessarily indicate incremental prognostic utility. Our study demonstrated that BTR and its individual components were associated with mortality independently of established clinical factors [<span>1</span>]; however, whether these biomarkers improve prognostic performance beyond conventional models remains to be established. Notably, in our cohort, the numbers of patients with BTR ≤ 4.4 were 140, 92, and 47 among those with Child–Pugh classes A, B, and C, respectively [<span>1</span>]. Thus, a substantial number of patients had a low BTR even when liver functional reserves were relatively preserved. Detailed evaluation of the clinical characteristics and subsequent outcomes of such patients may provide important insights into whether amino acid imbalance identifies a distinct metabolic risk that is not fully captured by conventional measures.</p><p>Another important point raised in the Editorial is the distinction between prognostic association and therapeutic efficacy. BCAA supplementation has been shown to improve amino acid imbalance and have beneficial effects on hepatic encephalopathy ","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"64 9","pages":"1314-1315"},"PeriodicalIF":6.8,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apt.70990","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149009906","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 Cardiometabolic Risk Factor Burden and Therapeutic Control on the Prognosis of Alcohol‐Related Hepatitis: A Biopsy‐Proven Cohort Study With External Multicentre Validation","authors":"Pablo Solís‐Muñoz,María de la Flor‐Robledo,Jorge Rivas‐Izquierdo,Joaquín Domínguez‐Humanes,Sergio Casiano‐Manzano,María Nogués‐Grajera,Miguel Fernández‐Bermejo,Zulianni Jiménez‐Colmenarez,Irene Ledo‐Mendoza,Daniel Martín‐Holgado,María Isabel Monge‐Romero,Elena García‐Martos,Elena García‐Abadía,Carmelo García‐Monzón,José Antonio Solís‐Herruzo","doi":"10.1111/apt.71022","DOIUrl":"https://doi.org/10.1111/apt.71022","url":null,"abstract":"ABSTRACT Background and Aims Cardiometabolic risk factors (CMRF) have traditionally been overlooked in alcohol‐related liver disease (ALD) and their prognostic impact in alcohol‐related hepatitis (AH) remains poorly defined. We evaluated the influence of CMRF burden and therapeutic control on complications and mortality in AH. Methods We prospectively enrolled 100 patients with biopsy‐proven AH. CMRF (obesity, hypertension, diabetes, hyper‐triglyceridaemia, low HDL cholesterol) and therapeutic control prior to admission were assessed. A cardiometabolic burden (CMB) score (0–10), incorporating CMRF number and control, was constructed. External validity was tested in an independent multicentre cohort of 332 patients with clinically diagnosed AH. Results In the primary cohort, patients with CMRF had higher 1‐year mortality than those without (48% vs. 25%, p  = 0.030) and more frequent in‐hospital complications. Clustered CMRF (≥ 3) independently predicted 1‐year mortality after adjustment for MELD, age and sex (HR = 4.1, 95% CI: 1.66–10, p  = 0.002). Increasing CMB scores (≥ 5) similarly associated with higher mortality (HR = 4.4, 95% CI: 1.76–11, p  = 0.002). These findings were reproduced in the external cohort, where ≥ 3 CMRF predicted 1‐year mortality (HR = 3.0, 95% CI: 1.97–4.7, p  < 0.001). Furthermore, ≥ 3 CMRF independently predicted 1‐year mortality beyond MELD and Lille response in treated patients (HR = 2.6, 95% CI: 1.46–4.5, p  = 0.001). Conclusions Clustered (≥ 3) and poorly controlled CMRF significantly impair survival and increase complication rates in AH. These findings, confirmed in an independent multicentre cohort, support integrating systematic cardiometabolic evaluation into routine clinical ALD management.","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"20 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149088874","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":"Review Article: Fibrosis‐4 Index in Steatotic Liver Disease—Past, Present and Future","authors":"Kriti Soni,Vinay Jahagirdar,Omar Albhaisi,Richard K. Sterling,Juan Pablo Arab,Hanna Blaney,Luis Antonio Díaz","doi":"10.1111/apt.71037","DOIUrl":"https://doi.org/10.1111/apt.71037","url":null,"abstract":"ABSTRACT Background Steatotic liver disease (SLD) is highly prevalent, and fibrosis stage is the strongest determinant of liver‐related outcomes, hepatocellular carcinoma and mortality. Liver biopsy remains the reference standard for staging, but it is invasive, subject to sampling and observer variability. These limitations have accelerated the use of noninvasive tests (NITs) across various settings. Aims This review summarizes the past, present and future of the Fibrosis‐4 (FIB‐4) index in SLD. Methods We reviewed the development of serum‐based fibrosis assessment, validation of FIB‐4 across SLD subtypes, its incorporation into clinical pathways, real‐world performance and potential role in precision therapy and longitudinal risk assessment. Results Initially derived in patients with HIV/hepatitis C coinfection using age, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and platelet count, FIB‐4 has since been validated across SLD populations. FIB‐4 generally provides moderate discrimination for advanced fibrosis and high negative predictive value (NPV) when used with dual thresholds and age‐adjusted cutoffs. Modern care pathways operationalize FIB‐4 as the first‐line triage test, followed by transient elastography or another second line test for indeterminate or elevated results, with specialty referral and selective biopsy reserved for diagnostic uncertainty or discordant testing. Conclusions In the precision therapy era, FIB‐4 remains a scalable front‐door test but should not serve as a stand‐alone selector for drug eligibility; confirmatory staging is required to identify F2–F3 disease and exclude cirrhosis. Future directions include trajectory‐based monitoring, integration with elastography and multi‐analyte biomarkers, and selective layering of genetic risk to refine prognosis in intermediate and high‐risk strata.","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"480 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149088876","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: Interpreting HLA ‐A*11:01 and Persistent HDV Viraemia in the Context of Host, Viral and Treatment Heterogeneity","authors":"Jiachen Lin, Jianzhi Bao","doi":"10.1111/apt.71040","DOIUrl":"https://doi.org/10.1111/apt.71040","url":null,"abstract":"","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"23 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149086987","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 Trial: Dupilumab Improves Eosinophilic Oesophagitis Outcomes Versus Placebo Regardless of Comorbidities or Treatment History in a Randomised Clinical Trial","authors":"Evan S. Dellon, Marc E. Rothenberg, Jonathan M. Spergel, Albert J. Bredenoord, Antonella Cianferoni, Changming Xia, Margee Louisias, Allen Radin","doi":"10.1111/apt.71001","DOIUrl":"https://doi.org/10.1111/apt.71001","url":null,"abstract":"Background Patients with eosinophilic oesophagitis (EoE) can present with differing disease characteristics, treatment resistance, and associated type 2 inflammatory comorbidities. We assessed the efficacy of dupilumab in subgroups of patients with EoE from the LIBERTY EoE TREET study across a range of demographics, characteristics, treatments, and comorbidities. Methods Patients were categorised by subgroups based on weight (&lt; 60 kg or ≥ 60 kg), body mass index (&lt; 18.5 kg/m <jats:sup>2</jats:sup> , ≥ 18.5 to &lt; 30 kg/m <jats:sup>2</jats:sup> , ≥ 30 kg/m <jats:sup>2</jats:sup> ), disease duration before study entry (&lt; 5 years, ≥ 5 to &lt; 10 years, ≥ 10 years), history of type 2 inflammatory comorbidities (with/without asthma, allergic rhinitis, atopic dermatitis, or food allergy), history of elimination diet, concurrent elimination diet, concurrent proton pump inhibitor use, and prior oesophageal dilation. Outcomes were analysed post hoc and included the proportion of patients achieving ≤ 6 eosinophils per high‐power field (eos/hpf) and change from baseline in Dysphagia Symptom Questionnaire (DSQ) and total Endoscopic Reference Score (EREFS). Results At Week 24, dupilumab treatment increased the proportion of patients achieving histological remission (peak eosinophil count ≤ 6 eos/hpf) versus placebo in all subgroups. At Week 52, improvements were maintained with continued dupilumab treatment. Improvements were also observed through Week 52 in patients who switched from placebo to dupilumab at Week 24. Similar results were observed for change from baseline in DSQ and EREFS. Conclusions Dupilumab treatment improved histological, symptomatic, and endoscopic outcomes versus placebo in patients with EoE, regardless of demographics, disease characteristics, treatment history, or type 2 inflammatory disease comorbidities. Trial Registration ClinicalTrials.gov identifier: NCT03633617","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"13 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149086989","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: Reactivation Risk Estimates in\u0000 HBsAg\u0000 ‐Negative Patients—Definitional, Serological, and Reporting Considerations. Authors' Reply","authors":"Kazuya Okushin,Kazuhiko Ikeuchi,Takeya Tsutsumi,Hiroshi Yotsuyanagi","doi":"10.1111/apt.71038","DOIUrl":"https://doi.org/10.1111/apt.71038","url":null,"abstract":"","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"36 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149088875","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: Host Innate Immunity Reaches the Clinic—The Laboratory of Genetics and Physiology Protein 2 ( LGP2 ) Q425R Variant and Severity of Chronic Hepatitis Delta","authors":"Edoardo G. Giannini, Andrea Pasta","doi":"10.1111/apt.71039","DOIUrl":"https://doi.org/10.1111/apt.71039","url":null,"abstract":"","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"15 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149087316","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: Dupilumab in Eosinophilic Oesophagitis Has Consistent Effectiveness Across Clinical Histories and Atopic Comorbidities—What Comes Next?","authors":"Pierfrancesco Visaggi","doi":"10.1111/apt.71015","DOIUrl":"https://doi.org/10.1111/apt.71015","url":null,"abstract":"","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"11 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149086988","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":"The TOP ‐ GERD Trial: Comparative Efficacy of Tegoprazan Versus Pantoprazole in the Treatment of Erosive Oesophagitis in a Non‐Asian Population","authors":"José M. Remes‐Troche, Luis Raúl Valdovinos‐García, C. Prakash Gyawali, José Luis Vargas‐Basurto, Carlos Alberto Reyes‐Medina, Gisselle Vanessa González‐Hernández, A. Rafael Bernal Mendez, H. H. Barragán Cordova, Pablo Thomas‐Dupont, Peter Grube‐Pagola","doi":"10.1111/apt.71032","DOIUrl":"https://doi.org/10.1111/apt.71032","url":null,"abstract":"Background Potassium‐competitive acid blockers provide rapid and sustained acid suppression, but tegoprazan has not been studied in non‐Asian populations. Aim To compare the efficacy and safety of tegoprazan 50 mg once daily with pantoprazole 40 mg once daily for healing erosive oesophagitis and improving reflux symptoms. Methods In this multicentre, randomized, double‐blind, active‐controlled trial, Mexican adults with Los Angeles grade B–D erosive oesophagitis received tegoprazan or pantoprazole for 4 weeks. The primary outcome was superior endoscopic healing at week 4. Secondary outcomes included early symptom response, complete symptom resolution, changes in symptom severity, health‐related quality of life, and adverse events. Results Seventy participants were randomized and 64 completed treatments. In the intention‐to‐treat population, endoscopic healing occurred in 88.9% receiving tegoprazan and 79.4% receiving pantoprazole ( <jats:italic>p</jats:italic> = 0.33). In the per‐protocol population, healing occurred in 100% and 84.4%, respectively ( <jats:italic>p</jats:italic> = 0.053). Among participants with Los Angeles grade C or D oesophagitis, per‐protocol healing rates were 100% with tegoprazan and 68.8% with pantoprazole ( <jats:italic>p</jats:italic> = 0.04). During the first treatment week, at least 50% symptom improvement occurred in 84.4% and 31.3%, respectively ( <jats:italic>p</jats:italic> &lt; 0.001), and complete symptom resolution was more frequent with tegoprazan from day 1. Symptom severity and health‐related quality of life improved in both groups. Adverse events were infrequent, mild, and unrelated to treatment. Conclusions There was a nonsignificant 9.5% difference in the primary intention‐to‐treat 4‐week healing endpoint between tegoprazan and pantoprazole. Tegoprazan provided faster symptom improvement, while the per‐protocol findings and the higher healing rate observed in the exploratory severe oesophagitis subgroup were encouraging and warrant further investigation. (ClinicalTrials.gov Identifier: NCT06991348).","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"36 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2026-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149086723","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: Does Adherence‐Selected Follow‐Up Establish the Benefit‐Harm Balance of Population Coeliac Disease Screening? Authors' Reply","authors":"Iida Ahonen, Kalle Kurppa, Laura Kivelä, Juha Taavela","doi":"10.1111/apt.71036","DOIUrl":"https://doi.org/10.1111/apt.71036","url":null,"abstract":"","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"7 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2026-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149086733","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}