Gastro hep advancesPub Date : 2026-01-01Epub Date: 2026-05-12DOI: 10.1016/j.gastha.2026.100996
Julia Zanco, Aravinthan Vignarajah, Reza Arsanjani, Elizabeth J. Carey, Luis R. Scott, Dan Sorajja
{"title":"Direct Oral Anticoagulant Type and Dose in Atrial Fibrillation With Decompensated Cirrhosis: A Propensity-Matched Analysis","authors":"Julia Zanco, Aravinthan Vignarajah, Reza Arsanjani, Elizabeth J. Carey, Luis R. Scott, Dan Sorajja","doi":"10.1016/j.gastha.2026.100996","DOIUrl":"10.1016/j.gastha.2026.100996","url":null,"abstract":"","PeriodicalId":73130,"journal":{"name":"Gastro hep advances","volume":"5 8","pages":"Article 100996"},"PeriodicalIF":3.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13293670/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148347608","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Gastro hep advancesPub Date : 2026-01-01Epub Date: 2025-12-16DOI: 10.1016/j.gastha.2025.100865
Audy Meutia Ariana , Budi Widodo
{"title":"Recurrent Esophageal Stricture Following Caustic Injury From a Concentrated Herbal Preparation in a Resource-Limited Setting","authors":"Audy Meutia Ariana , Budi Widodo","doi":"10.1016/j.gastha.2025.100865","DOIUrl":"10.1016/j.gastha.2025.100865","url":null,"abstract":"<div><div>Caustic esophageal injury is a frequently overlooked health problem, despite its serious impact on patients’ quality of life. We report the case of a 24-year-old male from an island region of Indonesia who developed esophageal stricture after consuming a traditional herbal preparation with low potential of Hydrogen. Delayed endoscopy, due to limited facilities and financial constraints, further worsened the condition. The patient experienced recurrent dysphagia 6 months after dilation, necessitating conservative management with staged dilation and intralesional triamcinolone injection. This case highlights an unusual etiology, a multidimensional burden, and the need for effective therapeutic strategies and preventive health policies.</div></div>","PeriodicalId":73130,"journal":{"name":"Gastro hep advances","volume":"5 3","pages":"Article 100865"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146038873","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Gastro hep advancesPub Date : 2026-01-01Epub Date: 2026-09-03DOI: 10.1016/j.gastha.2026.101113
Anas Zaher, Ahmad Al-Qady, Lauren Adkins, Rawan Abu Tarbosh, Marah Khaleel, Lina Wahbeh, Omar Al-Radideh, Bashar J. Qumseya
{"title":"Systematic Review and Meta-Analysis of TissueCypher and p53 Immunohistochemistry for Risk Stratification in Barrett’s Esophagus","authors":"Anas Zaher, Ahmad Al-Qady, Lauren Adkins, Rawan Abu Tarbosh, Marah Khaleel, Lina Wahbeh, Omar Al-Radideh, Bashar J. Qumseya","doi":"10.1016/j.gastha.2026.101113","DOIUrl":"10.1016/j.gastha.2026.101113","url":null,"abstract":"<div><h3>Background and Aims</h3><div>Barrett's esophagus surveillance relies on subjective biopsy grading that misses fast progressors. Although the Tissue Systems Pathology-9 (TSP-9) test and p53 immunohistochemistry (IHC) have each been evaluated separately, no prior study has directly compared the 2 within a single analytic framework. We compared both biomarkers for predicting progression to high-grade dysplasia or esophageal adenocarcinoma.</div></div><div>Barrett's esophagus surveillance relies on subjective biopsy grading that misses fast progressors. Although the Tissue Systems Pathology-9 (TSP-9) test and p53 immunohistochemistry (IHC) have each been evaluated separately, no prior study has directly compared the 2 within a single analytic framework. We compared both biomarkers for predicting progression to high-grade dysplasia or esophageal adenocarcinoma.</div><div><h3>Methods</h3><div>PubMed, Embase, Cochrane, and Web of Science were searched through December 2025. Studies were included if they evaluated TSP-9 or p53 IHC in patients with non-dysplastic Barrett's esophagus, indefinite for dysplasia, or low-grade dysplasia and reported prognostic outcomes. Pooled sensitivity, specificity, negative predictive value (NPV), odds ratios, and hazard ratios (HRs) were estimated using random-effects models.</div></div><div>PubMed, Embase, Cochrane, and Web of Science were searched through December 2025. Studies were included if they evaluated TSP-9 or p53 IHC in patients with non-dysplastic Barrett's esophagus, indefinite for dysplasia, or low-grade dysplasia and reported prognostic outcomes. Pooled sensitivity, specificity, negative predictive value (NPV), odds ratios, and hazard ratios (HRs) were estimated using random-effects models.</div><div><h3>Results</h3><div>Twenty-three studies (7 TSP-9, 16 p53 IHC; 6655 patients) met inclusion criteria. TSP-9 yielded a higher pooled HR (HR: 7.65; 95% confidence interval: 5.86–9.99) compared with p53 IHC (HR: 5.05; 95% confidence interval: 4.27–5.97). Sensitivities were comparable (TSP-9: 57.1% vs p53 IHC: 60.1%), while p53 IHC demonstrated higher specificity (91.5% vs 83.5%). Both biomarkers exhibited robust NPVs exceeding 90% (p53 IHC: 94.7%; TSP-9: 91.1%).</div></div><div>Twenty-three studies (7 TSP-9, 16 p53 IHC; 6655 patients) met inclusion criteria. TSP-9 yielded a higher pooled HR (HR: 7.65; 95% confidence interval: 5.86–9.99) compared with p53 IHC (HR: 5.05; 95% confidence interval: 4.27–5.97). Sensitivities were comparable (TSP-9: 57.1% vs p53 IHC: 60.1%), while p53 IHC demonstrated higher specificity (91.5% vs 83.5%). Both biomarkers exhibited robust NPVs exceeding 90% (p53 IHC: 94.7%; TSP-9: 91.1%).</div><div><h3>Conclusion</h3><div>Both TSP-9 and p53 IHC substantially outperform standard histology for risk stratification in Barrett's esophagus. The higher HR with TSP-9 may reflect its multiplexed approach. The strong NPV of both assays supports safely extending surveillance intervals in lo","PeriodicalId":73130,"journal":{"name":"Gastro hep advances","volume":"5 12","pages":"Article 101113"},"PeriodicalIF":3.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149161535","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Gastro hep advancesPub Date : 2026-01-01Epub Date: 2026-09-07DOI: 10.1016/j.gastha.2026.101107
Philip Vutien, Richard Li, Ravi Karkar, James Fogarty, Sean A. Munson, Sabrina Omer, Michael Yacoub, James Kashima, George N. Ioannou
{"title":"At-Home Critical Flicker Frequency Testing in Cirrhosis: A Feasibility Pilot Study Using the Novel Beacon Device","authors":"Philip Vutien, Richard Li, Ravi Karkar, James Fogarty, Sean A. Munson, Sabrina Omer, Michael Yacoub, James Kashima, George N. Ioannou","doi":"10.1016/j.gastha.2026.101107","DOIUrl":"10.1016/j.gastha.2026.101107","url":null,"abstract":"<div><h3>Background and Aims</h3><div>Critical flicker frequency (CFF) is a well-validated neurophysiologic screening test for minimal hepatic encephalopathy (MHE) in cirrhosis. We evaluated the feasibility and reliability of repeated at-home, self-administered CFF testing using a novel device (Beacon).</div></div><div>Critical flicker frequency (CFF) is a well-validated neurophysiologic screening test for minimal hepatic encephalopathy (MHE) in cirrhosis. We evaluated the feasibility and reliability of repeated at-home, self-administered CFF testing using a novel device (Beacon).</div><div><h3>Methods</h3><div>We enrolled 21 participants with cirrhosis. Each received a Beacon device and smartphone preloaded with an application to measure CFF using 2 protocols: (1) method of limits–descending (MOL-D) and (2) forced choice. Participants were instructed to complete ≥5 tests per week for 2 weeks, followed by ≥ 1 test per week for an additional 4 weeks. Outcomes included adherence, test duration, and longitudinal CFF trends to assess potential learning effects from repeated testing.</div></div><div>We enrolled 21 participants with cirrhosis. Each received a Beacon device and smartphone preloaded with an application to measure CFF using 2 protocols: (1) method of limits–descending (MOL-D) and (2) forced choice. Participants were instructed to complete ≥5 tests per week for 2 weeks, followed by ≥ 1 test per week for an additional 4 weeks. Outcomes included adherence, test duration, and longitudinal CFF trends to assess potential learning effects from repeated testing.</div><div><h3>Results</h3><div>Participants were predominantly male (76%) with a mean age of 52.2 years; 43% had alcohol-related liver disease and 38% had prior overt HE. Adherence (completing ≥70% of recommended measurements) was observed in 19 (90.5%) for daily and 16 participants (76.2%) for weekly testing. Median CFF was 42.9 Hz (interquartile range: 38.4–44.4) by MOL-D and 43.7 Hz (interquartile range: 41.7–45.8) by forced choice. Forced choice CFF was significantly lower in those with prior HE (median 40.7 Hz vs 44.9 Hz; <em>P</em> = .02), while MOL-D CFF did not differ by HE status (42.7 Hz vs 42.9 Hz; <em>P</em> = .44). CFF remained stable over time for both protocols (MOL-D: +0.01 Hz/day of testing, <em>P</em> = .67; forced choice: +0.03 Hz/day, <em>P</em> = .09). Forced choice testing required more time than MOL-D to complete (median 4.67 vs 2.48 minutes; <em>P</em> < .001).</div></div><div>Participants were predominantly male (76%) with a mean age of 52.2 years; 43% had alcohol-related liver disease and 38% had prior overt HE. Adherence (completing ≥70% of recommended measurements) was observed in 19 (90.5%) for daily and 16 participants (76.2%) for weekly testing. Median CFF was 42.9 Hz (interquartile range: 38.4–44.4) by MOL-D and 43.7 Hz (interquartile range: 41.7–45.8) by forced choice. Forced choice CFF was significantly lower in those with prior HE (median 40.7 Hz vs 4","PeriodicalId":73130,"journal":{"name":"Gastro hep advances","volume":"5 12","pages":"Article 101107"},"PeriodicalIF":3.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149161644","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Gastro hep advancesPub Date : 2026-01-01Epub Date: 2026-02-06DOI: 10.1016/j.gastha.2026.100896
Jessica R. Allegretti, Alpesh N. Amin, Elizabeth L. Hohmann, AGA Harmonizing CDI Patient Care Roundtable Working Group, Erik R. Dubberke, Paul Feuerstadt, Monika Fischer, Stuart Johnson, Terra Ziporyn, Colleen Kelly
{"title":"Clostridioides difficile Infection: Harmonizing Patient Care","authors":"Jessica R. Allegretti, Alpesh N. Amin, Elizabeth L. Hohmann, AGA Harmonizing CDI Patient Care Roundtable Working Group, Erik R. Dubberke, Paul Feuerstadt, Monika Fischer, Stuart Johnson, Terra Ziporyn, Colleen Kelly","doi":"10.1016/j.gastha.2026.100896","DOIUrl":"10.1016/j.gastha.2026.100896","url":null,"abstract":"","PeriodicalId":73130,"journal":{"name":"Gastro hep advances","volume":"5 4","pages":"Article 100896"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147410004","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Fecal Bifidobacterium Serves as a Predictor of Postoperative Recurrence After Neoadjuvant Chemotherapy in Pancreatic Cancer","authors":"Ayaka Takaori , Tsukasa Ikeura , Daisuke Hashimoto , Motonobu Maruo , Masatoshi Ikeda , Takashi Ito , Koh Nakamaru , Masataka Masuda , Shinji Nakayama , Hidetaka Miyazaki , Kazuki Matsumura , So Yamaki , Tomoyo Yasuda , Masashi Kanai , Shohei Akagawa , Shoji Tsuji , Koichiro Higasa , Sohei Satoi , Makoto Naganuma","doi":"10.1016/j.gastha.2025.100779","DOIUrl":"10.1016/j.gastha.2025.100779","url":null,"abstract":"<div><h3>Background and Aims</h3><div>To date, neoadjuvant chemotherapy (NAC) is a well-accepted therapeutic strategy for patients with resectable (R) and borderline resectable (BR) pancreatic ductal adenocarcinoma (PDAC). We previously reported that the relative abundance of <em>Bifidobacterium</em> in the gut microbiota is associated with a more favorable pathological response to NAC in R/BR-PDAC. In the current study, we evaluated the association between pretreatment gut microbiota and postoperative prognosis in patients with R/BR-PDAC who underwent pancreatectomy after NAC.</div></div><div><h3>Methods</h3><div>In this prospective observational study, we analyzed 42 patients with R/BR-PDAC who underwent pancreatic resection following NAC with gemcitabine plus S-1 between 2020 and 2022 at Kansai Medical University Hospital. Stool samples were collected at PDAC diagnosis for microbiota analysis using 16S RNA gene sequences. In 19 genera accounting for ≥ 1% in relative abundance, the relationship between the microbiota profile and recurrence-free survival (RFS) and overall survival was examined using the Kaplan–Meier method and the Cox proportional hazards model.</div></div><div><h3>Results</h3><div>The median postoperative observation period was 24 months. During the observation period, 23 patients (55%) experienced recurrence, and 10 patients (24%) died of PDAC. RFS was significantly favorable in patients in the high-<em>Bifidobacterium</em> group (relative abundance ≥ 4%) compared to patients in the low-<em>Bifidobacterium</em> group (<4%). Furthermore, multivariable analysis revealed high-<em>Bifidobacterium</em> and pathological metastasis of lymph node were significantly associated with RFS (hazard ratio 0.37; 95% confidence interval 0.14–0.97, <em>P</em> = .042). Regarding overall survival, there was no significant association with gut microbiota, including <em>Bifidobacterium</em> genus (hazard ratio 0.23; 95% confidence interval 0.03–1.50), in the multivariable analysis.</div></div><div><h3>Conclusion</h3><div>The relative abundance of <em>Bifidobacterium</em> in the gut microbiota at diagnosis may be a predictor of postoperative recurrence in patients with R/BR-PDAC treated with NAC.</div></div>","PeriodicalId":73130,"journal":{"name":"Gastro hep advances","volume":"5 1","pages":"Article 100779"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145271182","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Gastro hep advancesPub Date : 2026-01-01Epub Date: 2025-12-01DOI: 10.1016/j.gastha.2025.100857
Ruona Ebiai , Jasmine McNair , Sameera Shuaibi , Adil Memon , Anshuman Desai , Lisa Birdsall Fort , Leo Seoane , Nigel Girgrah , George Therapondos
{"title":"Unrecognized Fibrosis Risk in MASLD: A Real-World Analysis and the Case for AI-Augmented Stratification","authors":"Ruona Ebiai , Jasmine McNair , Sameera Shuaibi , Adil Memon , Anshuman Desai , Lisa Birdsall Fort , Leo Seoane , Nigel Girgrah , George Therapondos","doi":"10.1016/j.gastha.2025.100857","DOIUrl":"10.1016/j.gastha.2025.100857","url":null,"abstract":"<div><h3>Background and Aims</h3><div>Current fibrosis risk stratification in metabolic dysfunction–associated steatotic liver disease (MASLD) relies on provider-initiated noninvasive testing and referral, making it vulnerable to variability in awareness, documentation, and follow-through. We aimed to quantify care gaps associated with this provider-dependent approach and explore opportunities for artificial intelligence to improve MASLD detection and management.</div></div><div><h3>Methods</h3><div>We performed a retrospective analysis of all adults undergoing abdominal ultrasound in 2024 at Ochsner Health’s South Shore campuses. Natural language processing identified reports with hepatic steatosis, and patients with at least 1 cardiometabolic risk factor were included. Fibrosis-4 index (FIB-4) scores were calculated from recent laboratory data (within 6 months of ultrasound) using age-adjusted thresholds to classify patients as low, indeterminate, or high fibrosis risk. Management was defined as hepatology referral for high- or indeterminate-risk patients and documentation of a primary care provider for low-risk patients requiring reassessment.</div></div><div><h3>Results</h3><div>Among 14,814 adults with ultrasound in 2024, 3052 (20.6%) met the MASLD criteria. Based on age-adjusted FIB-4, 15.2% were high risk, 18.0% indeterminate, and 66.0% low risk for advanced fibrosis. Of 465 high-risk patients, only 33.5% had hepatology referrals, leaving 309 (10.1% of the MASLD cohort) without appropriate specialty evaluation. Among 549 indeterminate-risk patients, 58.7% lacked referral for secondary assessment. In the low-risk group, 224 (7.3%) had no documented primary care provider for follow-up, and 24 (0.8%) lacked sufficient laboratory data for FIB-4 calculation. Overall, 28.0% of the MASLD cohort had a critical, moderate, or monitoring care gap.</div></div><div><h3>Conclusion</h3><div>Significant gaps persist in MASLD fibrosis risk stratification and management, largely reflecting system-level coordination failures rather than access barriers. Artificial intelligence–driven workflows integrated into the electronic health record could automate steatosis detection, calculate FIB-4 scores, flag care gaps, and prompt risk-stratified referrals or reassessments, offering a scalable solution to standardize MASLD management and improve outcomes.</div></div>","PeriodicalId":73130,"journal":{"name":"Gastro hep advances","volume":"5 3","pages":"Article 100857"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145981463","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Gastro hep advancesPub Date : 2026-01-01Epub Date: 2025-08-05DOI: 10.1016/j.gastha.2025.100762
Jaimie Anderson , Wojciech Blonski , Joy Gaziano , Camille Thélin , Rebecca Klam , Samuel Slone , Rene L. Utianski , John Jacobs
{"title":"Multidisciplinary Assessment and Management of Functional Dysphagia","authors":"Jaimie Anderson , Wojciech Blonski , Joy Gaziano , Camille Thélin , Rebecca Klam , Samuel Slone , Rene L. Utianski , John Jacobs","doi":"10.1016/j.gastha.2025.100762","DOIUrl":"10.1016/j.gastha.2025.100762","url":null,"abstract":"<div><div>Functional dysphagia (FD), a type of functional esophageal disorder, is characterized by difficulty passing solid and/or liquid food through the esophagus, without underlying mucosal, luminal, or major motility diseases, as defined by the Rome IV criteria. It is also a type of functional gastrointestinal disorder (FGID), which are disorders of gut-brain interaction (DGBI). The underlying mechanism is thought to involve a complex interaction between the gut and central nervous system (CNS), where altered gut signaling may lead to visceral hypersensitivity, while CNS dysregulation may cause hyper-vigilance, potentially contributing to motor disturbances.</div><div>There is no standardized approach to the evaluation of FD and historically, it has been considered a diagnosis of exclusion. There is also no standardized treatment algorithm, and most FD treatments are garnered from other FGIDs. As our field gains a deeper appreciation of FGIDs, it is also clear that the management of suspected FD patients requires a multidisciplinary approach. This narrative review not only 1) provides an overview of FD including its definition, epidemiology, pathophysiology, clinical characteristics, associated disorders, multidisciplinary assessment, and treatment, but also 2) details our unique multidisciplinary approach to FD patients from the perspective of gastroenterologists, speech-language pathologists (SLPs), and GI psychologists at the Joy McCann Culverhouse Center for Swallowing Disorders at the University of South Florida (USF CSD).</div></div>","PeriodicalId":73130,"journal":{"name":"Gastro hep advances","volume":"5 1","pages":"Article 100762"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145270543","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Gastro hep advancesPub Date : 2026-01-01Epub Date: 2025-08-25DOI: 10.1016/j.gastha.2025.100769
Nanci Santos-Ferreira , Xin Zhang , Laura Corneillie , Jana Van Dycke , Winston Chiu , Claire Montpellier , Johan Neyts , Laurence Cocquerel , Suzanne J.F. Kaptein , Joana Rocha-Pereira
{"title":"Proliferative Cell Targeting and Epithelial Cell Turnover Fuels Hepatitis E Virus Replication in Human Intestinal Enteroids","authors":"Nanci Santos-Ferreira , Xin Zhang , Laura Corneillie , Jana Van Dycke , Winston Chiu , Claire Montpellier , Johan Neyts , Laurence Cocquerel , Suzanne J.F. Kaptein , Joana Rocha-Pereira","doi":"10.1016/j.gastha.2025.100769","DOIUrl":"10.1016/j.gastha.2025.100769","url":null,"abstract":"<div><h3>Background and Aims</h3><div>Hepatitis E virus (HEV) is a leading pathogen causing acute viral hepatitis globally. While HEV is primarily spread fecal-orally, the role of the gut in HEV pathogenesis remains largely unexplored, including how HEV disseminates from gut to liver, and whether the gut is an HEV reservoir. We here aimed to illuminate HEV biology in the gut using human intestinal enteroids (HIEs).</div></div><div><h3>Methods</h3><div>Three strategies were explored to establish an HEV-HIE model – three-dimensional (3D) HIEs, two-dimensional HIEs in transwell, and HEV RNA-electroporated HIEs. HEV particles produced by electroporated HIEs were characterized by western blot and gradient centrifugation. The intestinal tropism of HEV was investigated through confocal fluorescent microscopy and gene expression analysis.</div></div><div><h3>Results</h3><div>HEV infection in 3D-HIEs and two-dimensional-HIEs showed limited replication, whereas HIEs electroporation led to a sustained increase in the release of nonenveloped infectious virions. These virions could reinfect new 3D-HIEs, yielding a ∼2 log<sub>10</sub> increase in HEV RNA over time. In electroporated HIEs, high expression of the infectious open reading frame 2 capsid form was observed in the supernatant. Importantly, 70% of all HEV-infected cells were identified as proliferative cells (leucine-rich-repeat-containing G-protein-coupled receptor 5 intestinal stem cells and transit-amplifying progenitor cells). Open reading frame 2 staining was also observed in absorptive enterocytes, goblet, and enteroendocrine cells.</div></div><div><h3>Conclusion</h3><div>Overall, we established a robust HEV-HIE model that yields high titers of infectious nonenveloped virions. Proliferative cells and the fast intestinal epithelial cell turnover are important features that facilitate efficient HEV replication, and likely also its dissemination. This study suggests that the gut is an HEV reservoir, capable of producing some of the nonenveloped HEV shed in the feces.</div></div>","PeriodicalId":73130,"journal":{"name":"Gastro hep advances","volume":"5 1","pages":"Article 100769"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145270548","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}