Gastro hep advances最新文献

{"title":"Gastric Acid Suppression Is Associated With Higher Rates of Colectomy in Patients With Inflammatory Bowel Disease","authors":"Aun R. Shah , Nurlan Aliyev , Zarak H. Khan , Rubab Ali , Mohammad Bilal","doi":"10.1016/j.gastha.2024.09.008","DOIUrl":"10.1016/j.gastha.2024.09.008","url":null,"abstract":"","PeriodicalId":73130,"journal":{"name":"Gastro hep advances","volume":"4 2","pages":"Article 100553"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11762160/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143049019","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}

{"title":"Comparative Efficacy of NAFLD Therapies and Biomarker Associations: A Meta-Analysis Based on Liver Fat Content","authors":"Haoxiang Zhu ,&nbsp;Ling Xu ,&nbsp;Yinhua Lv ,&nbsp;Juan Yang ,&nbsp;Jihan Huang ,&nbsp;Qingshan Zheng ,&nbsp;Guang Ji ,&nbsp;Lujin Li","doi":"10.1016/j.gastha.2024.100593","DOIUrl":"10.1016/j.gastha.2024.100593","url":null,"abstract":"<div><h3>Background and Aims</h3><div>This study aims to conduct a comprehensive quantitative analysis of various nonalcoholic fatty liver disease (NAFLD) therapeutics, utilizing magnetic resonance (MR)-detected liver fat content (LFC) as the efficacy endpoint, and to identify biomarkers correlated with changes in LFC based on published literature.</div></div><div><h3>Methods</h3><div>We performed a systematic search of public databases for placebo-controlled randomized trials on NAFLD up to September 29, 2023. A random-effects meta-analysis was employed to assess efficacy differences between drugs with various mechanisms and placebo. Initial Pearson correlation analysis explored the relationships between biomarkers and LFC. For biomarkers showing significant correlations with LFC, further modeling analysis was conducted to examine their relationship characteristics.</div></div><div><h3>Results</h3><div>Our analysis included 36 studies with 3222 subjects and 33 investigational drugs, which were categorized into 6 mechanistic groups. Drugs such as fibroblast growth factor agonists, and those targeting adipocytes, inflammation, or fibrosis, showed greater efficacy in reducing LFC compared to Resmetirom, which has an efficacy of reducing LFC by 5.2%. From the 121 biomarkers analyzed, alanine aminotransferase and aspartate aminotransferase demonstrated moderate correlations with LFC; specifically, changes of −5.9 U/L in alanine aminotransferase or −3.3 U/L in aspartate aminotransferase were associated with an additional 1% reduction in LFC.</div></div><div><h3>Conclusion</h3><div>The results of this study provide valuable insights for the clinical development of future NAFLD therapeutics, highlighting the efficacy of specific drug mechanisms and the potential of certain biomarkers as surrogate endpoints.</div></div>","PeriodicalId":73130,"journal":{"name":"Gastro hep advances","volume":"4 4","pages":"Article 100593"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143377538","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}

{"title":"Successful Endoscopic Retrograde Cholangiopancreatography for Management of Choledocholithiasis in a Patient With Situs Inversus Totalis: A Case Report and Literature Review","authors":"Bashayer Alrufayi ,&nbsp;Saad Almutairi ,&nbsp;Abbas Zagnoon","doi":"10.1016/j.gastha.2024.09.010","DOIUrl":"10.1016/j.gastha.2024.09.010","url":null,"abstract":"<div><div>Situs inversus totalis is a rare congenital disorder defined by the transposition of all viscera to the opposite side of the body. Because of this anatomical alteration, endoscopic retrograde cholangiopancreatography (ERCP) in such a population is significantly challenging.</div><div>Herein we report a case of a 50-year-old woman presented with epigastric and left upper quadrant pain. Preoperative examination revealed abnormal liver chemistries, situs inversus totalis, and multiple distal common bile duct stones with intrahepatic and extrahepatic bile duct dilatation on abdominal ultrasound. The patient underwent a successful ERCP to relieve biliary obstruction. It was performed while the patient was placed in a supine position with the endoscopist standing on the left side of the patient.</div><div>The major emphasis in ERCP is adjusting the patient and endoscopist positions during the procedure. The advantage of the supine position is that the endoscope could easily reach the pyloric ring and, after reaching the duodenum, the papilla could be reached without difficulty.</div></div>","PeriodicalId":73130,"journal":{"name":"Gastro hep advances","volume":"4 2","pages":"Article 100555"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11761330/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143049020","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}

{"title":"A Nonrandomized Pilot Study to Investigate the Acceptability and Feasibility of LivR Well: A Multifaceted 28-Day Home-Based Liver Optimization Program for Acute-on-Chronic Liver Failure","authors":"Natalie L.Y. Ngu ,&nbsp;Edward Saxby ,&nbsp;Thomas Worland ,&nbsp;Patricia Anderson ,&nbsp;Lisa Stothers ,&nbsp;Jo Hunter ,&nbsp;Alexander T. Elford ,&nbsp;Phil Ha ,&nbsp;Imogen Hartley ,&nbsp;Andrew Roberts ,&nbsp;Dean Seah ,&nbsp;George Tambakis ,&nbsp;Declan Connoley ,&nbsp;Anita Figredo ,&nbsp;Dilip Ratnam ,&nbsp;Danny Liew ,&nbsp;Benjamin Rogers ,&nbsp;William Sievert ,&nbsp;Sally Bell ,&nbsp;Suong Le","doi":"10.1016/j.gastha.2024.10.007","DOIUrl":"10.1016/j.gastha.2024.10.007","url":null,"abstract":"<div><h3>Background and Aims</h3><div>Acute-on-chronic liver failure (ACLF) has a 22%–74% 28-day mortality rate and 30%–40% 30-day readmission rate. We investigated the acceptability and feasibility of a multimodal community intervention for ACLF.</div></div><div><h3>Methods</h3><div>A single-arm nonrandomized pilot study of consecutive participants with ACLF was conducted in a tertiary health service. Participants received weekly medical and nursing reviews, dietetics, physiotherapy, pharmacy, social work, addiction medicine, and neuropsychiatry, where indicated. A digital platform included remote weight monitoring and online surveys. The primary outcome was acceptability/feasibility. Secondary outcomes included safety, mortality, readmission, liver disease severity, and costs.</div></div><div><h3>Results</h3><div>Fifty-nine patients were enrolled with median age 51 years (interquartile range (IQR): 45–59); majority alcohol etiology (74%),and median Model for End-Stage Liver Disease Sodium score 16 (IQR: 12–21). LivR Well was acceptable with low attrition (8 of 59), adherence to the program including home visits (mean 8.4 ± 4.2) and consultations (mean 2.4 ± 1.5) per patient. This was supported by positive feedback and themes identified through a qualitative subanalysis. Feasibility was demonstrated by recruitment rate of 4.94 patients/month and 86% completion. Mortality was lower than expected at 3%, 30-day readmission rate was 15%, and median Model for End-Stage Liver Disease Sodium score reduced to 15 (<em>P</em> = .01). Median 6-month costs reduced from $30,454 (IQR: $21,953–$65,657) to $17,657 ($4249–$42,876) (<em>P</em> = .009). The total 6-month health-care cost was $1,868,859 (95% confidence interval 1,081,821–2,655,897) compared to $2,518,227 (95% confidence interval 1,959,610–3,076,844).</div></div><div><h3>Conclusion</h3><div>LivR Well was acceptable, feasible, and safe with low short-term mortality and readmission rates. Health-care costs were reduced by 26% driven by a 40% reduction in 30-day readmission. Further evaluation includes a randomized controlled trial of LivR Well compared to standard care.</div></div>","PeriodicalId":73130,"journal":{"name":"Gastro hep advances","volume":"4 2","pages":"Article 100567"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11773469/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143061392","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}

{"title":"Large Language Models Outperform Traditional Natural Language Processing Methods in Extracting Patient-Reported Outcomes in Inflammatory Bowel Disease","authors":"Perseus V. Patel ,&nbsp;Conner Davis ,&nbsp;Amariel Ralbovsky ,&nbsp;Daniel Tinoco ,&nbsp;Christopher Y.K. Williams ,&nbsp;Shadera Slatter ,&nbsp;Behzad Naderalvojoud ,&nbsp;Michael J. Rosen ,&nbsp;Tina Hernandez-Boussard ,&nbsp;Vivek Rudrapatna","doi":"10.1016/j.gastha.2024.10.003","DOIUrl":"10.1016/j.gastha.2024.10.003","url":null,"abstract":"<div><h3>Background and Aims</h3><div>Patient-reported outcomes (PROs) are vital in assessing disease activity and treatment outcomes in inflammatory bowel disease (IBD). However, manual extraction of these PROs from the free-text of clinical notes is burdensome. We aimed to improve data curation from free-text information in the electronic health record, making it more available for research and quality improvement. This study aimed to compare traditional natural language processing (tNLP) and large language models (LLMs) in extracting 3 IBD PROs (abdominal pain, diarrhea, fecal blood) from clinical notes across 2 institutions.</div></div><div><h3>Methods</h3><div>Clinic notes were annotated for each PRO using preset protocols. Models were developed and internally tested at the University of California, San Francisco, and then externally validated at Stanford University. We compared tNLP and LLM-based models on accuracy, sensitivity, specificity, positive, and negative predictive value. In addition, we conducted fairness and error assessments.</div></div><div><h3>Results</h3><div>Interrater reliability between annotators was &gt;90%. On the University of California, San Francisco test set (n = 50), the top-performing tNLP models showcased accuracies of 92% (abdominal pain), 82% (diarrhea) and 80% (fecal blood), comparable to GPT-4, which was 96%, 88%, and 90% accurate, respectively. On external validation at Stanford (n = 250), tNLP models failed to generalize (61%–62% accuracy) while GPT-4 maintained accuracies &gt;90%. Pathways Language Model-2 and Generative Pre-trained Transformer-4 showed similar performance. No biases were detected based on demographics or diagnosis.</div></div><div><h3>Conclusion</h3><div>LLMs are accurate and generalizable methods for extracting PROs. They maintain excellent accuracy across institutions, despite heterogeneity in note templates and authors. Widespread adoption of such tools has the potential to enhance IBD research and patient care.</div></div>","PeriodicalId":73130,"journal":{"name":"Gastro hep advances","volume":"4 2","pages":"Article 100563"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11772946/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143061557","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}

{"title":"Plasma Circulating Metabolites Associated With Steatotic Liver Disease and Liver Enzymes: A Multiplatform Population-Based Study","authors":"Yasir J. Abozaid ,&nbsp;Ibrahim Ayada ,&nbsp;Laurens A. van Kleef ,&nbsp;Neil J. Goulding ,&nbsp;Jessica S. Williams-Nguyen ,&nbsp;Robert C. Kaplan ,&nbsp;Robert J. de Knegt ,&nbsp;Lynne E. Wagenknecht ,&nbsp;Nicholette D. Palmer ,&nbsp;Nicholas J. Timpson ,&nbsp;Jill M. Norris ,&nbsp;Yii-Der Ida Chen ,&nbsp;M. Arfan Ikram ,&nbsp;Willem Pieter Brouwer ,&nbsp;Mohsen Ghanbari","doi":"10.1016/j.gastha.2024.09.006","DOIUrl":"10.1016/j.gastha.2024.09.006","url":null,"abstract":"<div><h3>Background and Aims</h3><div>Steatotic liver disease (SLD) is the most common chronic liver disease strongly associated with metabolic dysfunction, but its pathogenesis remains incompletely understood. Exploring plasma circulating metabolites may help in elucidating underlying mechanisms and identifying new biomarkers for SLD.</div></div><div><h3>Methods</h3><div>We examined cross-sectionally the association between plasma metabolites and SLD as well as liver enzymes using data from 4 population-based cohort studies (Rotterdam study, Avon Longitudinal Study of Parents and Children, The Insulin Resistance Atherosclerosis Family Study, and Study of Latinos). Metabolites were assessed in the Nightingale platform (n = 225 metabolites) by nuclear magnetic resonance spectroscopy and in the Metabolon platform (n = 991 metabolites) by ultra-high-performance liquid chromatography-mass spectrometry. Serum levels of liver enzymes (alanine aminotransferase, aspartate aminotransferase, and gamma-glutamyl transpeptidase) were measured and SLD was diagnosed by ultrasound or computed tomography scan. Logistic and linear regression models were performed per cohort and meta-analyzed. A false discovery rate &lt; 0.05 was considered as significant threshold.</div></div><div><h3>Results</h3><div>Several metabolites were significantly associated with SLD and liver enzymes, of which 21 metabolites were associated with both traits. The most significant associations were observed with phenylalanine, triglycerides in (high-density lipoprotein, intermediate-density lipoprotein, and small low-density lipoprotein), fatty acid (FA) ratios of (18:2 linoleic acid-to-total FA, omega 6 FA-to-total FA, and polyunsaturated FA-to-total FA) from the Nightingale and glutamate and sphingomyelin from the Metabolon platform. Other associated metabolites were mainly involved in lipid, amino acid, carbohydrates, and peptide metabolism.</div></div><div><h3>Conclusion</h3><div>Our study indicates a landscape of circulating metabolites associated with SLD. The identified metabolites may contribute to a better understanding of the metabolic pathways underlying SLD and hold promising for potential biomarkers in early diagnosis and monitoring of the disease.</div></div>","PeriodicalId":73130,"journal":{"name":"Gastro hep advances","volume":"4 2","pages":"Article 100551"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11772964/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143061559","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}

{"title":"Initial Diagnostic Strategies for Helicobacter Pylori in Patients With Bleeding Peptic Ulcers Undergoing Endoscopy: A Cost-Effectiveness Analysis","authors":"Michael G. Artin ,&nbsp;Josephine Soddano ,&nbsp;Sheila D. Rustgi ,&nbsp;Zainab Aziz ,&nbsp;Francesca Lim ,&nbsp;Jeong Yun Yang ,&nbsp;Myles A. Ingram ,&nbsp;John T. Nathanson ,&nbsp;John Y. Kao ,&nbsp;Chin Hur","doi":"10.1016/j.gastha.2024.100602","DOIUrl":"10.1016/j.gastha.2024.100602","url":null,"abstract":"<div><h3>Background and Aims</h3><div>Helicobacter pylori (H. pylori) is a major cause of peptic ulcer disease (PUD) and upper gastrointestinal bleeding. Testing for and eradication of H. pylori reduces the risk of future PUD-related complications including readmission for gastrointestinal bleeding. Our aim was to determine the most cost-effective testing strategy for H. pylori in patients hospitalized with bleeding peptic ulcers.</div></div><div><h3>Methods</h3><div>We developed a Markov cohort model to compare the following 6 H. pylori testing strategies: no testing, histology, rapid urease test, stool antigen test, urea breath test (UBT), and serology. Histology and rapid urease test require biopsies, while stool antigen test, UBT, and serology do not. We assumed a 17% H. pylori prevalence in patients admitted with bleeding ulcers. Model outcomes included hospitalizations for rebleeds, number needed to treat to avoid another hospitalization, life expectancy, total cost, quality-adjusted life years, and incremental cost-effectiveness ratios.</div></div><div><h3>Results</h3><div>Compared to no testing, UBT resulted in a gain of 0.02 quality-adjusted life years, total cost savings of $2140 per patient, and 1675 hospitalizations avoided per 10,000 patients per year. Additionally, the number needed to treat to avoid an additional hospitalization over 35 years was 167. UBT was the preferred strategy as it was both less costly and more effective than no testing.</div></div><div><h3>Conclusion</h3><div>Our findings suggest that UBT is the cost-effective strategy to identify H. pylori in patients admitted with PUD. Noninvasive H. pylori testing at the point of care or during inpatient admission should be considered, as it presents limited risk to patients and offers potential clinical benefits.</div></div>","PeriodicalId":73130,"journal":{"name":"Gastro hep advances","volume":"4 4","pages":"Article 100602"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143237940","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}

{"title":"Ulcerative Colitis Preceding Asymptomatic Wilson’s Disease: A Case Report and Literature Review","authors":"Jun Kunizaki ,&nbsp;Yuko Yoto ,&nbsp;Yoshinobu Nagaoka ,&nbsp;Akira Ishii ,&nbsp;Tomoe Kazama ,&nbsp;Kohei Wagatsuma ,&nbsp;Noriyuki Akutsu ,&nbsp;Aki Ishikawa ,&nbsp;Toju Tanaka ,&nbsp;Shintaro Sugita ,&nbsp;Takeshi Tsugawa ,&nbsp;Hiroshi Nakase","doi":"10.1016/j.gastha.2024.09.003","DOIUrl":"10.1016/j.gastha.2024.09.003","url":null,"abstract":"<div><div>An 11-year-old girl with quiescent ulcerative colitis had sustained elevation of liver enzymes. Although she had no clinical symptoms suggestive of Wilson’s disease, such as Kayser–Fleischer rings, laboratory data showed decreased serum copper and ceruloplasmin levels and increased urinary copper excretion. Genetic testing showed pathogenic variants in <em>ATP7B</em> allele 1: c.2004_2006delGAT (p. Met668del) and allele 2: c.1708-5T&gt;G. After starting copper chelators, her liver function normalized, and she maintained clinical and endoscopic remission of ulcerative colitis. Mutations or defective functions of <em>ATP7B</em> lead to hepatic dysfunction and intestinal inflammation.</div></div>","PeriodicalId":73130,"journal":{"name":"Gastro hep advances","volume":"4 1","pages":"Article 100548"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11714711/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142959718","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}

{"title":"Hepatitis Delta Virus Testing, Prevalence, and Liver-Related Outcomes Among US Veterans With Chronic Hepatitis B","authors":"Robert J. Wong ,&nbsp;Zeyuan Yang ,&nbsp;Janice H. Jou ,&nbsp;Binu V. John ,&nbsp;Joseph K. Lim ,&nbsp;Ramsey Cheung","doi":"10.1016/j.gastha.2024.10.015","DOIUrl":"10.1016/j.gastha.2024.10.015","url":null,"abstract":"<div><h3>Background and Aims</h3><div>Hepatitis delta virus (HDV) infection in patients with chronic hepatitis B (CHB) is associated with worse liver-related outcomes. We aim to comprehensively evaluate HDV testing, diagnosis, and liver-related outcomes among a national cohort of US Veterans with CHB.</div></div><div><h3>Methods</h3><div>US Veterans with CHB from 2010 to 2023 were evaluated to determine trends in HDV testing (anti-HDV antibody, HDV RNA) and proportion positive among those tested. HDV positive patients were 1:2 propensity score matched to CHB patients who were HDV negative to evaluate incidence (per 100,000 person-years) of cirrhosis, hepatic decompensation, or hepatocellular carcinoma using competing risks Nelson-Aalen methods for estimating cumulative hazards.</div></div><div><h3>Results</h3><div>Among the 27,548 CHB patients identified, 16.1% completed HDV testing, among whom 3.25% (n = 144) were positive. After excluding patients with cirrhosis or HCC at baseline, 71 patients with HDV (median follow-up 5.3 years, interquartile range 2.5–7.6) were propensity score matched to 140 CHB patients without HDV (median follow-up 4.5 years, interquartile range 2.6–8.1). Compared to CHB patients without HDV, those with concurrent HDV had significantly greater incidence of cirrhosis (4.39 vs 1.30 per 100,000 person-years, <em>P</em> &lt; .01) and hepatic decompensation (2.18 vs 0.41 per 100,000 person-years, <em>P</em> = .01).</div></div><div><h3>Conclusion</h3><div>Among a national cohort of US Veterans with CHB, low rates of HDV testing were observed. This is concerning given that patients with concurrent HDV infection had &gt;3 times and &gt;5 times greater risks of cirrhosis and hepatic decompensation, respectively, compared to CHB patients without HDV, highlighting the importance of timely HDV diagnosis and treatment.</div></div>","PeriodicalId":73130,"journal":{"name":"Gastro hep advances","volume":"4 3","pages":"Article 100575"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143167817","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}

{"title":"Multiomic Sequencing Reveals Distinctive Gene Expression and Epigenetic Alterations Associated With Primary Sclerosing Cholangitis Development in Treatment-Naïve Pediatric Ulcerative Colitis","authors":"Alejandra Rodriguez-Sosa ,&nbsp;Ololade Lawal ,&nbsp;Ciaran McDonnell ,&nbsp;Luke Grant ,&nbsp;John O’Brien ,&nbsp;Muhammad Ali ,&nbsp;Ian Stephens ,&nbsp;Grainne Kirwan ,&nbsp;Flavia Genua ,&nbsp;Alexander Kel ,&nbsp;Anna Dominik ,&nbsp;Roisin Stack ,&nbsp;Gregory Yochum ,&nbsp;Michael McDermot ,&nbsp;Glen Doherty ,&nbsp;Seamus Hussey ,&nbsp;Sudipto Das","doi":"10.1016/j.gastha.2024.11.002","DOIUrl":"10.1016/j.gastha.2024.11.002","url":null,"abstract":"<div><h3>Background and Aims</h3><div>Primary sclerosing cholangitis (PSC) is a progressive cholestatic disease with up to 80% of patients also suffering from ulcerative colitis (PSC-UC). The difficulty in the diagnosis along with the increased risk for developing cancer represents a clinical challenge. Furthermore, the precise molecular factors regulating the phenotype of this disease subtype remain unknown.</div></div><div><h3>Methods</h3><div>We applied methyl-capture sequencing and mRNA sequencing to colonic mucosal biopsies from 3 groups of treatment-naïve children at diagnosis from the Determinants and Outcomes in CHildren and AdolescentS study: UC (n = 10), PSC-UC (n = 10), and healthy controls (n = 10).</div></div><div><h3>Results</h3><div>Differential gene expression between UC and PSC-UC showed significantly higher gene expression changes in PSC-UC patients when compared to UC. Specifically, expression of these genes was regulated by master transcriptional regulators (NLRP3, DLL1) and transcription factors (RELA, Myogenin, and FOXO1), which are shown to regulate expression of inflammatory response and immune-associated genes in PSC-UC patients exclusively. Differential methylation analysis between PSC-UC and UC demonstrated &gt;2000 differentially methylated regions with a large proportion of them enriched in gene promoter and enhancer regions. We further show no difference in epigenetic age between PSC-UC and UC. Finally, we identify KLHL17 as hypomethylated and upregulated in PSC-UC patients.</div></div><div><h3>Conclusion</h3><div>Our study, for the first time, identifies distinct gene expression and DNA methylation alterations that differentiate UC from PSC-UC at diagnosis in treatment-naïve pediatric patients. We show the gene expression differences observed between PSC-UC and UC are modulated by intricate molecular mechanisms involving master transcriptional regulator-mediated signaling through transcription factors. These findings suggest the potential utility of these molecular markers as predictive biomarkers for PSC development in UC at an early stage of development. Further validation in larger patient cohorts is warranted.</div></div>","PeriodicalId":73130,"journal":{"name":"Gastro hep advances","volume":"4 3","pages":"Article 100586"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143167818","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}