Pub Date : 2024-01-01DOI: 10.1016/j.gastha.2024.03.003
Brenderia A. Cameron , Angela Z. Xue , Akshatha Kiran , Sean LaFata , Adolfo A. Ocampo , Justin McCallen , Christopher J. Lee , Stephanie A. Borinsky , Walker D. Redd , Cary C. Cotton , Swathi Eluri , Craig C. Reed , Evan S. Dellon
{"title":"Esophageal Candidiasis Is Strongly Associated With Treatment Response to Topical Steroids in Eosinophilic Esophagitis and Could Be a Marker of Adherence","authors":"Brenderia A. Cameron , Angela Z. Xue , Akshatha Kiran , Sean LaFata , Adolfo A. Ocampo , Justin McCallen , Christopher J. Lee , Stephanie A. Borinsky , Walker D. Redd , Cary C. Cotton , Swathi Eluri , Craig C. Reed , Evan S. Dellon","doi":"10.1016/j.gastha.2024.03.003","DOIUrl":"10.1016/j.gastha.2024.03.003","url":null,"abstract":"","PeriodicalId":73130,"journal":{"name":"Gastro hep advances","volume":"3 5","pages":"Pages 612-614"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772572324000335/pdfft?md5=0731ce43ce1c949729a4cb7381109574&pid=1-s2.0-S2772572324000335-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140276197","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}
Hemangiomas in the gastrointestinal tract are extremely rare, benign vascular tumors, known for their associated complication of bleeding. They are usually difficult to diagnose, despite the characteristic definition of radiolucent phleboliths on radiology and purplish, tannish brown nodule or polyp on endoscopy. Surgical resection is the treatment of choice. We describe a rare case of sigmoid colon cavernous hemangioma in a 49-year-old male who underwent colonoscopy for lower abdominal pain and revealed a large pedunculated polyp in the sigmoid colon measuring 1.7 cm in diameter. The hemangioma was completely resected endoscopically via hot snare with a favorable outcome.
{"title":"Endoscopic Resection of a Cavernous Hemangioma in the Sigmoid Colon: A Case Report","authors":"Noora Al-Khater , Mohamed Mohamed , Afra Juma , Faisal Abubaker , Sameer Ansari","doi":"10.1016/j.gastha.2023.12.008","DOIUrl":"10.1016/j.gastha.2023.12.008","url":null,"abstract":"<div><p>Hemangiomas in the gastrointestinal tract are extremely rare, benign vascular tumors, known for their associated complication of bleeding. They are usually difficult to diagnose, despite the characteristic definition of radiolucent phleboliths on radiology and purplish, tannish brown nodule or polyp on endoscopy. Surgical resection is the treatment of choice. We describe a rare case of sigmoid colon cavernous hemangioma in a 49-year-old male who underwent colonoscopy for lower abdominal pain and revealed a large pedunculated polyp in the sigmoid colon measuring 1.7 cm in diameter. The hemangioma was completely resected endoscopically via hot snare with a favorable outcome.</p></div>","PeriodicalId":73130,"journal":{"name":"Gastro hep advances","volume":"3 3","pages":"Pages 396-398"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772572323002042/pdfft?md5=29f814c67b73726d0fa9b6483f28ae0c&pid=1-s2.0-S2772572323002042-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139191243","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}
Pub Date : 2024-01-01DOI: 10.1016/j.gastha.2024.04.007
Background and Aims
Predicting the efficacy of molecular-targeted drugs (MTDs) is an unmet need in the treatment of ulcerative colitis (UC). Intestinal ultrasound (IUS) can be used to safely and repeatedly assess UC activity.
Methods
Thirty-eight patients who started MTD therapy for active UC and underwent IUS at baseline and 3 months after starting therapy were analyzed. Steroid-free clinical remission (SFCR) and endoscopic improvement (EI) at 6 months were defined as a Lichtiger index of ≤3 and Mayo endoscopic subscore of ≤1 while continuing the MTD without steroid induction or surgery. Sonographically estimated EI (SE-EI) at 3 months was assessed based on a Milan Ultrasound Criterion of ≤6.2 and Kyorin Ultrasound Criterion for UC (bowel wall thickness of <3.8 mm and submucosa index of <50%).
Results
Thirty-one patients achieved SFCR at 6 months [SFCR(+) group]. The SFCR(+) group demonstrated significantly better improvement in bowel wall thickness and bowel wall vascularity at 3 months than the SFCR(−) group. The Milan Ultrasound Criterion and UC-IUS index also improved significantly more in the SFCR(+) than SFCR(−) group. The areas under the curve of these parameters for predicting SFCR were approximately 0.80. Colonoscopy was performed for 28 patients at 6 months, and 15 patients achieved EI. SE-EI at 3 months was significantly associated with achievement of EI at 6 months. The positive predictive values of SE-EI at 3 months for SFCR and EI at 6 months were 100%.
Conclusion
Sonographic improvements in 3 months predicted the clinical and endoscopic efficacy of MTD therapy at 6 months, suggesting the longitudinal significance of IUS monitoring for UC treatment.
{"title":"Early Sonographic Improvement Predicts Clinical Remission and Mucosal Healing With Molecular-Targeted Drugs in Ulcerative Colitis","authors":"","doi":"10.1016/j.gastha.2024.04.007","DOIUrl":"10.1016/j.gastha.2024.04.007","url":null,"abstract":"<div><h3>Background and Aims</h3><p>Predicting the efficacy of molecular-targeted drugs (MTDs) is an unmet need in the treatment of ulcerative colitis (UC). Intestinal ultrasound (IUS) can be used to safely and repeatedly assess UC activity.</p></div><div><h3>Methods</h3><p>Thirty-eight patients who started MTD therapy for active UC and underwent IUS at baseline and 3 months after starting therapy were analyzed. Steroid-free clinical remission (SFCR) and endoscopic improvement (EI) at 6 months were defined as a Lichtiger index of ≤3 and Mayo endoscopic subscore of ≤1 while continuing the MTD without steroid induction or surgery. Sonographically estimated EI (SE-EI) at 3 months was assessed based on a Milan Ultrasound Criterion of ≤6.2 and Kyorin Ultrasound Criterion for UC (bowel wall thickness of <3.8 mm and submucosa index of <50%).</p></div><div><h3>Results</h3><p>Thirty-one patients achieved SFCR at 6 months [SFCR(+) group]. The SFCR(+) group demonstrated significantly better improvement in bowel wall thickness and bowel wall vascularity at 3 months than the SFCR(−) group. The Milan Ultrasound Criterion and UC-IUS index also improved significantly more in the SFCR(+) than SFCR(−) group. The areas under the curve of these parameters for predicting SFCR were approximately 0.80. Colonoscopy was performed for 28 patients at 6 months, and 15 patients achieved EI. SE-EI at 3 months was significantly associated with achievement of EI at 6 months. The positive predictive values of SE-EI at 3 months for SFCR and EI at 6 months were 100%.</p></div><div><h3>Conclusion</h3><p>Sonographic improvements in 3 months predicted the clinical and endoscopic efficacy of MTD therapy at 6 months, suggesting the longitudinal significance of IUS monitoring for UC treatment.</p></div>","PeriodicalId":73130,"journal":{"name":"Gastro hep advances","volume":"3 6","pages":"Pages 703-710"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772572324000578/pdfft?md5=93f9f3a66f5b49b6aa4160db770bb924&pid=1-s2.0-S2772572324000578-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140760802","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}
Pub Date : 2024-01-01DOI: 10.1016/j.gastha.2024.05.002
Background and Aims
The multitarget stool DNA (mt-sDNA) assay is a noninvasive average-risk colorectal cancer (CRC) screening test. A new biomarker panel was developed for a next-generation test to improve specificity while maintaining/increasing sensitivity. We aimed first to establish an algorithm and cutoff for the next-generation mt-sDNA test and then to validate it using archived samples from the pivotal DeeP-C study (NCT01397747) of the first-generation test.
Methods
Algorithm development and cross-validation included 3011 samples from 2 specimen collection studies (NCT03821948 and NCT03789162). The algorithm and cutoff were locked before validation. Validation test set samples included 57 CRC, 583 advanced precancerous lesions (APLs), and 7022 samples negative for CRC or APLs from the DeeP-C study, which prospectively enrolled average-risk, asymptomatic adults aged 50–84 years before screening colonoscopy. Next-generation biomarkers included methylated DNA markers ceramide synthase 4 gene, leucine-rich repeat-containing protein 4 gene, serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform gene, and zinc finger DHHC-type containing 1 gene (reference marker), and fecal hemoglobin. Primary validation end points were CRC sensitivity and specificity for the absence of advanced neoplasia. Secondary end points included APL sensitivity and specificity for non-neoplastic findings or negative colonoscopy.
Results
Cross-validation and best-fit results from algorithm development closely matched, confirming algorithm reliability and reproducibility. For the test set, next-generation mt-sDNA test sensitivity was 93.0% (95% confidence interval [CI], 83.0%–98.1%) for CRC and 48.4% (95% CI, 44.2%–52.5%) for APLs. Specificity was 88.5% (95% CI, 87.7%–89.2%) for the absence of advanced neoplasia and 90.4% (95% CI, 89.5%–91.2%) for the combination of non-neoplastic findings or negative colonoscopy.
Conclusion
Based on archived samples, the next-generation mt-sDNA test demonstrated promising CRC screening performance characteristics that will be further assessed in a prospective clinical validation study (BLUE-C; NCT04144738).
{"title":"Algorithm Development and Early Performance Evaluation of a Next-Generation Multitarget Stool DNA Screening Test for Colorectal Cancer","authors":"","doi":"10.1016/j.gastha.2024.05.002","DOIUrl":"10.1016/j.gastha.2024.05.002","url":null,"abstract":"<div><h3>Background and Aims</h3><p>The multitarget stool DNA (mt-sDNA) assay is a noninvasive average-risk colorectal cancer (CRC) screening test. A new biomarker panel was developed for a next-generation test to improve specificity while maintaining/increasing sensitivity. We aimed first to establish an algorithm and cutoff for the next-generation mt-sDNA test and then to validate it using archived samples from the pivotal DeeP-C study (NCT01397747) of the first-generation test.</p></div><div><h3>Methods</h3><p>Algorithm development and cross-validation included 3011 samples from 2 specimen collection studies (NCT03821948 and NCT03789162). The algorithm and cutoff were locked before validation. Validation test set samples included 57 CRC, 583 advanced precancerous lesions (APLs), and 7022 samples negative for CRC or APLs from the DeeP-C study, which prospectively enrolled average-risk, asymptomatic adults aged 50–84 years before screening colonoscopy. Next-generation biomarkers included methylated DNA markers ceramide synthase 4 gene, leucine-rich repeat-containing protein 4 gene, serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform gene, and zinc finger DHHC-type containing 1 gene (reference marker), and fecal hemoglobin. Primary validation end points were CRC sensitivity and specificity for the absence of advanced neoplasia. Secondary end points included APL sensitivity and specificity for non-neoplastic findings or negative colonoscopy.</p></div><div><h3>Results</h3><p>Cross-validation and best-fit results from algorithm development closely matched, confirming algorithm reliability and reproducibility. For the test set, next-generation mt-sDNA test sensitivity was 93.0% (95% confidence interval [CI], 83.0%–98.1%) for CRC and 48.4% (95% CI, 44.2%–52.5%) for APLs. Specificity was 88.5% (95% CI, 87.7%–89.2%) for the absence of advanced neoplasia and 90.4% (95% CI, 89.5%–91.2%) for the combination of non-neoplastic findings or negative colonoscopy.</p></div><div><h3>Conclusion</h3><p>Based on archived samples, the next-generation mt-sDNA test demonstrated promising CRC screening performance characteristics that will be further assessed in a prospective clinical validation study (BLUE-C; NCT04144738).</p></div>","PeriodicalId":73130,"journal":{"name":"Gastro hep advances","volume":"3 6","pages":"Pages 740-748"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772572324000682/pdfft?md5=f370e2134caedae468ba7504471851e7&pid=1-s2.0-S2772572324000682-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141045461","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}
Pub Date : 2024-01-01DOI: 10.1016/j.gastha.2024.08.004
Sophia R. Meyer , Charles J. Zhang , Max A. Garcia , Megan C. Procario , Sanghee Yoo , Amber L. Jolly , Sumin Kim , Jiho Kim , Kyusuk Baek , Roland D. Kersten , Robert J. Fontana , Jonathan Z. Sexton
Background and Aims
Drug-induced liver injury (DILI) is a major failure mode in pharmaceutical development. This study aims to address the limitations of existing preclinical models by assessing a high-throughput, microfluidic liver-on-a-chip system, termed “Curio Barrier Liver Chips,” and its capacity to recapitulate the effects of chronic hepatotoxic drug treatment through metabolic and phenotypic characterization.
Methods
Curio Barrier liver chips (Curiochips), fabricated in an 8 × 2 well configuration, were utilized to establish three dimensional liver organoid cultures. Human-induced pluripotent stem cells were differentiated into human liver organoids, and their viability, liver-specific functions, and pharmacological responses were assessed over 28 days.
Results
The Curiochips successfully maintained liver physiology and function, showing strong albumin secretion and cytochrome (CYP) P450 activities for 28 days. Unlike traditional models requiring millimolar drug concentrations to detect hepatotoxicity, this platform showed increased sensitivity for acetaminophen and fialuridine at micromolar concentrations. In situ differentiation of foregut spheroids to liver organoids was also achieved, further simplifying the establishment of liver chips. Furthermore, the chips demonstrated viability, function, and DILI responsiveness for 28 days, making this an improved model for studying idiosyncratic DILI with prolonged drug exposure and high-throughput capabilities compared to other available systems or primary human hepatocytes.
Conclusion
The Curiochips offer an advanced, miniaturized in vitro model for early-stage drug development and a sensitive, responsive, and cost-effective means to detect direct hepatotoxicity. Induced pluripotent stem cell liver organoids, in conjunction with the Curiochip, deliver a high-throughput platform with robust functionality and pharmacological responsiveness that make it a promising tool for improving the prediction and understanding of DILI risk prediction, especially with prolonged drug exposure. The model also opens new avenues for research in other chronic liver diseases.
背景与目的药物诱导的肝损伤(DILI)是药物开发中的一种主要失败模式。本研究旨在通过评估被称为 "Curio Barrier 肝芯片 "的高通量微流控肝芯片系统及其通过代谢和表型特征重现慢性肝毒性药物治疗效果的能力,解决现有临床前模型的局限性。结果Curio芯片成功地维持了肝脏的生理和功能,在28天内显示出强大的白蛋白分泌和细胞色素(CYP)P450活性。与需要毫摩尔药物浓度才能检测肝毒性的传统模型不同,该平台对微摩浓度的对乙酰氨基酚和非亚尿苷显示出更高的灵敏度。还实现了前肠球体到肝脏器官组织的原位分化,进一步简化了肝脏芯片的建立。此外,与其他可用的系统或原代人类肝细胞相比,这种芯片在 28 天内都表现出活力、功能和对 DILI 的反应能力,使其成为研究特异性 DILI 的改良模型,具有长时间药物暴露和高通量能力。诱导多能干细胞肝脏器官组织与 Curiochip 相结合,提供了一个功能强大、药理反应灵敏的高通量平台,使其成为一种很有前途的工具,可用于改善对 DILI 风险预测的预测和理解,尤其是在长期药物暴露的情况下。该模型还为其他慢性肝病的研究开辟了新途径。
{"title":"A High-Throughput Microphysiological Liver Chip System to Model Drug-Induced Liver Injury Using Human Liver Organoids","authors":"Sophia R. Meyer , Charles J. Zhang , Max A. Garcia , Megan C. Procario , Sanghee Yoo , Amber L. Jolly , Sumin Kim , Jiho Kim , Kyusuk Baek , Roland D. Kersten , Robert J. Fontana , Jonathan Z. Sexton","doi":"10.1016/j.gastha.2024.08.004","DOIUrl":"10.1016/j.gastha.2024.08.004","url":null,"abstract":"<div><h3>Background and Aims</h3><div>Drug-induced liver injury (DILI) is a major failure mode in pharmaceutical development. This study aims to address the limitations of existing preclinical models by assessing a high-throughput, microfluidic liver-on-a-chip system, termed “Curio Barrier Liver Chips,” and its capacity to recapitulate the effects of chronic hepatotoxic drug treatment through metabolic and phenotypic characterization.</div></div><div><h3>Methods</h3><div>Curio Barrier liver chips (Curiochips), fabricated in an 8 × 2 well configuration, were utilized to establish three dimensional liver organoid cultures. Human-induced pluripotent stem cells were differentiated into human liver organoids, and their viability, liver-specific functions, and pharmacological responses were assessed over 28 days.</div></div><div><h3>Results</h3><div>The Curiochips successfully maintained liver physiology and function, showing strong albumin secretion and cytochrome (CYP) P450 activities for 28 days. Unlike traditional models requiring millimolar drug concentrations to detect hepatotoxicity, this platform showed increased sensitivity for acetaminophen and fialuridine at micromolar concentrations. <em>In situ</em> differentiation of foregut spheroids to liver organoids was also achieved, further simplifying the establishment of liver chips. Furthermore, the chips demonstrated viability, function, and DILI responsiveness for 28 days, making this an improved model for studying idiosyncratic DILI with prolonged drug exposure and high-throughput capabilities compared to other available systems or primary human hepatocytes.</div></div><div><h3>Conclusion</h3><div>The Curiochips offer an advanced, miniaturized <em>in vitro</em> model for early-stage drug development and a sensitive, responsive, and cost-effective means to detect direct hepatotoxicity. Induced pluripotent stem cell liver organoids, in conjunction with the Curiochip, deliver a high-throughput platform with robust functionality and pharmacological responsiveness that make it a promising tool for improving the prediction and understanding of DILI risk prediction, especially with prolonged drug exposure. The model also opens new avenues for research in other chronic liver diseases.</div></div>","PeriodicalId":73130,"journal":{"name":"Gastro hep advances","volume":"3 8","pages":"Pages 1045-1053"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142538910","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}
Pub Date : 2024-01-01DOI: 10.1016/j.gastha.2023.06.014
Katerina Roma , Toni-Marie Chandler , Zahra Dossaji , Ankoor Patel , Kapil Gupta , Carlos D. Minacapelli , Vinod Rustgi , Robert Gish
Chronic hepatitis B virus (HBV) infection affects about 262 million people worldwide, leading to over 820,000 deaths each year primarily due to cirrhosis and hepatocellular carcinoma. The World Health Organization has pledged to eliminate HBV as a health threat by 2030, but currently, no countries are on track to achieve this goal. One of the barriers to HBV elimination is stigma, causing shame, denial, self-isolation, self-rejection, and depression leading to those with chronic HBV less likely to get tested or seek treatment and more likely to conceal their infection. Other barriers include limited access to care and complicated and restrictive clinical practice guidelines. Increasing public and political efforts are necessary to raise awareness, increase access to care, and change screening and treatment guidelines. The current guidance of the American Association for the Study of Liver Diseases (AASLD) recommends testing only if patients are considered at risk, but this has proven to be ineffective. We propose a simplified “test all and treat all” approach with a 5-line guideline for HBV infection. Universal screening and treatment of adults is cost-effective and can prevent transmission by effectively managing chronic HBV. All patients who are hepatitis B surface antigen (HBsAg) positive with detectable HBV-DNA should receive treatment until HBsAg is undetectable for 12 months, as HBV-DNA transmission via blood transfusion can occur even at low viral loads of 16 copies/mL, and mother-to-child transmission is still a risk even with passive-active immunoprophylaxis. Furthermore, clinical outcomes after HBsAg clearance are significantly better than the clinical outcomes of those who remain HBsAg positive.
{"title":"A Review of the Systemic Manifestations of Hepatitis B Virus Infection, Hepatitis D Virus, Hepatocellular Carcinoma, and Emerging Therapies","authors":"Katerina Roma , Toni-Marie Chandler , Zahra Dossaji , Ankoor Patel , Kapil Gupta , Carlos D. Minacapelli , Vinod Rustgi , Robert Gish","doi":"10.1016/j.gastha.2023.06.014","DOIUrl":"10.1016/j.gastha.2023.06.014","url":null,"abstract":"<div><p>Chronic hepatitis B virus (HBV) infection affects about 262 million people worldwide, leading to over 820,000 deaths each year primarily due to cirrhosis and hepatocellular carcinoma. The World Health Organization has pledged to eliminate HBV as a health threat by 2030, but currently, no countries are on track to achieve this goal. One of the barriers to HBV elimination is stigma, causing shame, denial, self-isolation, self-rejection, and depression leading to those with chronic HBV less likely to get tested or seek treatment and more likely to conceal their infection. Other barriers include limited access to care and complicated and restrictive clinical practice guidelines. Increasing public and political efforts are necessary to raise awareness, increase access to care, and change screening and treatment guidelines. The current guidance of the American Association for the Study of Liver Diseases (AASLD) recommends testing only if patients are considered at risk, but this has proven to be ineffective. We propose a simplified “test all and treat all” approach with a 5-line guideline for HBV infection. Universal screening and treatment of adults is cost-effective and can prevent transmission by effectively managing chronic HBV. All patients who are hepatitis B surface antigen (HBsAg) positive with detectable HBV-DNA should receive treatment until HBsAg is undetectable for 12 months, as HBV-DNA transmission via blood transfusion can occur even at low viral loads of 16 copies/mL, and mother-to-child transmission is still a risk even with passive-active immunoprophylaxis. Furthermore, clinical outcomes after HBsAg clearance are significantly better than the clinical outcomes of those who remain HBsAg positive.</p></div>","PeriodicalId":73130,"journal":{"name":"Gastro hep advances","volume":"3 2","pages":"Pages 276-291"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S277257232300105X/pdfft?md5=a4580b16e4bb44ab1318e603aee179d8&pid=1-s2.0-S277257232300105X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48876277","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}
Pub Date : 2024-01-01DOI: 10.1016/j.gastha.2024.02.002
{"title":"Erratum Regarding Conflicts of Interest Statements in Previously Published Articles","authors":"","doi":"10.1016/j.gastha.2024.02.002","DOIUrl":"https://doi.org/10.1016/j.gastha.2024.02.002","url":null,"abstract":"","PeriodicalId":73130,"journal":{"name":"Gastro hep advances","volume":"3 3","pages":"Page 301"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772572324000190/pdfft?md5=d17f32241d16c4b526c91e6806ac00b3&pid=1-s2.0-S2772572324000190-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139992663","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}
Pub Date : 2024-01-01DOI: 10.1016/j.gastha.2024.01.001
Alexander Killer , Smaranda Gliga , Carolin Lohr , Christian Weigel , Björn-Erik Ole Jensen , Nadine Lübke , Andreas Walker , Jörg Timm , Johannes Bode , Tom Luedde , Hans H. Bock
Background and Aims
The entry inhibitor bulevirtide represents the first specific treatment for hepatitis-D virus (HDV)-infected patients. In clinical trials, around 80% of patients achieve normalization of alanine aminotransferase (ALT) with about 60% virological response after 1 year, but little is known about the dynamics of responses and clinical predictors of treatment outcomes. We report our single-center data from 15 patients and describe response dynamics, clinical outcomes, and predictive factors for treatment response.
Methods
Retrospective data from 15 patients have been analyzed at our department who started treatment with bulevirtide between 10/2020 and 08/2022. According to our standard procedures, laboratory parameters were controlled monthly; transient elastography was performed every 3 months, and the treatment duration was 12 months.
Results
Treatment response rates after 1 year of treatment were similar to published data from clinical trials. ALT normalization usually occurs between months 2–6 of treatment, followed by a virological response after ≥6 months. Patients with more severe hepatitis at the start of treatment were less likely to respond in the first year of treatment. Loss of HDV-RNA was observed in one-third of patients after ≥1 year of treatment. Low body mass index and high alpha-fetoprotein at baseline were possible predictors of a delayed treatment response.
Conclusion
Bulevirtide is a safe treatment option for HDV, leading to a fast hepatological response. Of note, decrease in transaminases precedes virological response. Patients with high viral load and ALT levels respond slower, but nonresponders (as classified by Food and Drug Administration criteria) still show a reduction in viremia. Longer observation periods are required to determine the optimal duration of bulevirtide monotherapy.
{"title":"Dynamics of Virological and Clinical Response Parameters of Bulevirtide Treatment for Hepatitis D: Real-World Data","authors":"Alexander Killer , Smaranda Gliga , Carolin Lohr , Christian Weigel , Björn-Erik Ole Jensen , Nadine Lübke , Andreas Walker , Jörg Timm , Johannes Bode , Tom Luedde , Hans H. Bock","doi":"10.1016/j.gastha.2024.01.001","DOIUrl":"10.1016/j.gastha.2024.01.001","url":null,"abstract":"<div><h3>Background and Aims</h3><p>The entry inhibitor bulevirtide represents the first specific treatment for hepatitis-D virus (HDV)-infected patients. In clinical trials, around 80% of patients achieve normalization of alanine aminotransferase (ALT) with about 60% virological response after 1 year, but little is known about the dynamics of responses and clinical predictors of treatment outcomes. We report our single-center data from 15 patients and describe response dynamics, clinical outcomes, and predictive factors for treatment response.</p></div><div><h3>Methods</h3><p>Retrospective data from 15 patients have been analyzed at our department who started treatment with bulevirtide between 10/2020 and 08/2022. According to our standard procedures, laboratory parameters were controlled monthly; transient elastography was performed every 3 months, and the treatment duration was 12 months.</p></div><div><h3>Results</h3><p>Treatment response rates after 1 year of treatment were similar to published data from clinical trials. ALT normalization usually occurs between months 2–6 of treatment, followed by a virological response after ≥6 months. Patients with more severe hepatitis at the start of treatment were less likely to respond in the first year of treatment. Loss of HDV-RNA was observed in one-third of patients after ≥1 year of treatment. Low body mass index and high alpha-fetoprotein at baseline were possible predictors of a delayed treatment response.</p></div><div><h3>Conclusion</h3><p>Bulevirtide is a safe treatment option for HDV, leading to a fast hepatological response. Of note, decrease in transaminases precedes virological response. Patients with high viral load and ALT levels respond slower, but nonresponders (as classified by Food and Drug Administration criteria) still show a reduction in viremia. Longer observation periods are required to determine the optimal duration of bulevirtide monotherapy.</p></div>","PeriodicalId":73130,"journal":{"name":"Gastro hep advances","volume":"3 3","pages":"Pages 353-360"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772572324000013/pdfft?md5=8474f0a7ece90d3db7212decf80fdefe&pid=1-s2.0-S2772572324000013-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139395740","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}