首页 > 最新文献

Gastro hep advances最新文献

英文 中文
Esophageal Candidiasis Is Strongly Associated With Treatment Response to Topical Steroids in Eosinophilic Esophagitis and Could Be a Marker of Adherence 食管念珠菌病与嗜酸性粒细胞性食管炎患者对局部类固醇的治疗反应密切相关,并可作为坚持治疗的标志物
Pub Date : 2024-01-01 DOI: 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}
引用次数: 0
Endoscopic Resection of a Cavernous Hemangioma in the Sigmoid Colon: A Case Report 乙状结肠海绵状血管瘤的内窥镜切除术:病例报告
Pub Date : 2024-01-01 DOI: 10.1016/j.gastha.2023.12.008
Noora Al-Khater , Mohamed Mohamed , Afra Juma , Faisal Abubaker , Sameer Ansari

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.

胃肠道血管瘤是一种极为罕见的良性血管肿瘤,因其伴有出血并发症而闻名。尽管在放射学检查中可看到放射状的静脉结石,在内镜检查中可看到紫褐色或棕褐色的结节或息肉,但通常很难诊断。手术切除是首选的治疗方法。我们描述了一例罕见的乙状结肠海绵状血管瘤病例,患者为一名 49 岁男性,因下腹疼痛接受结肠镜检查,发现乙状结肠内有一个直径 1.7 厘米的巨大有蒂息肉。他因下腹疼痛接受结肠镜检查,发现乙状结肠内有一个直径 1.7 厘米的巨大有蒂息肉,通过热套管在内镜下完全切除了血管瘤,结果良好。
{"title":"Endoscopic Resection of a Cavernous Hemangioma in the Sigmoid Colon: A Case Report","authors":"Noora Al-Khater ,&nbsp;Mohamed Mohamed ,&nbsp;Afra Juma ,&nbsp;Faisal Abubaker ,&nbsp;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}
引用次数: 0
Early Sonographic Improvement Predicts Clinical Remission and Mucosal Healing With Molecular-Targeted Drugs in Ulcerative Colitis 分子靶向药物对溃疡性结肠炎的临床缓解和粘膜愈合具有早期声像图预示作用
Pub Date : 2024-01-01 DOI: 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.

背景和目的预测分子靶向药物(MTD)的疗效是治疗溃疡性结肠炎(UC)的一项尚未满足的需求。方法分析了38名开始接受MTD治疗的活动性UC患者,他们在基线和开始治疗3个月后接受了IUS检查。无类固醇临床缓解(SFCR)和6个月时的内镜改善(EI)定义为Lichtiger指数≤3和Mayo内镜子评分≤1,同时继续接受MTD治疗,无类固醇诱导或手术。结果31名患者在6个月时达到了SFCR(SFCR(+)组)。与 SFCR(-)组相比,SFCR(+)组在 3 个月时的肠壁厚度和肠壁血管改善情况明显更好。米兰超声标准和 UC-IUS 指数在 SFCR(+)组的改善程度也明显高于 SFCR(-)组。这些参数预测 SFCR 的曲线下面积约为 0.80。28 名患者在 6 个月时接受了结肠镜检查,其中 15 名患者达到了 EI。3 个月时的 SE-EI 与 6 个月时的 EI 显著相关。3个月时的SE-EI对6个月时的SFCR和EI的阳性预测值均为100%。结论3个月时的声像图改善可预测6个月时MTD治疗的临床和内镜疗效,这表明IUS监测对UC治疗具有纵向意义。
{"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 &lt;3.8 mm and submucosa index of &lt;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}
引用次数: 0
Algorithm Development and Early Performance Evaluation of a Next-Generation Multitarget Stool DNA Screening Test for Colorectal Cancer 下一代多靶点大便 DNA 大肠癌筛查检验的算法开发和早期性能评估
Pub Date : 2024-01-01 DOI: 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).

背景和目的多靶点粪便 DNA(mt-sDNA)检测是一种无创的平均风险结直肠癌(CRC)筛查试验。为了提高特异性,同时保持/提高灵敏度,我们为下一代检测开发了一个新的生物标记物面板。我们的目标首先是为下一代mt-sDNA检验建立算法和临界值,然后使用第一代检验的关键性DeeP-C研究(NCT01397747)的存档样本对其进行验证。方法算法开发和交叉验证包括来自2项样本采集研究(NCT03821948和NCT03789162)的3011份样本。在验证前锁定了算法和截止值。验证测试集样本包括来自 DeeP-C 研究的 57 例 CRC、583 例晚期癌前病变 (APL) 和 7022 例 CRC 或 APL 阴性样本。下一代生物标记物包括甲基化DNA标记物神经酰胺合成酶4基因、富含亮氨酸重复蛋白4基因、丝氨酸/苏氨酸蛋白磷酸酶2A 56 kDa调节亚基γ异构体基因、锌指DHHC型含1基因(参考标记物)和粪便血红蛋白。主要验证终点是 CRC 对无晚期肿瘤的敏感性和特异性。结果交叉验证和算法开发的最佳拟合结果非常吻合,证实了算法的可靠性和可重复性。对于测试集,下一代 mt-sDNA 检测对 CRC 的灵敏度为 93.0%(95% 置信区间 [CI],83.0%-98.1%),对 APL 的灵敏度为 48.4%(95% 置信区间 [CI],44.2%-52.5%)。结论基于存档样本,下一代mt-sDNA检验显示出很好的CRC筛查性能特征,将在前瞻性临床验证研究(BLUE-C;NCT04144738)中进一步评估。
{"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}
引用次数: 0
Mycophenolate Mofetil-Induced Pneumatosis Intestinalis 霉酚酸酯诱发的肠道肺炎
Pub Date : 2024-01-01 DOI: 10.1016/j.gastha.2024.08.003
Daphne Moutsoglou , Byron P. Vaughn
{"title":"Mycophenolate Mofetil-Induced Pneumatosis Intestinalis","authors":"Daphne Moutsoglou ,&nbsp;Byron P. Vaughn","doi":"10.1016/j.gastha.2024.08.003","DOIUrl":"10.1016/j.gastha.2024.08.003","url":null,"abstract":"","PeriodicalId":73130,"journal":{"name":"Gastro hep advances","volume":"3 8","pages":"Page 1028"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142538837","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}
引用次数: 0
A High-Throughput Microphysiological Liver Chip System to Model Drug-Induced Liver Injury Using Human Liver Organoids 利用人体肝脏器官组织模拟药物性肝损伤的高通量微生理肝芯片系统
Pub Date : 2024-01-01 DOI: 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 ,&nbsp;Charles J. Zhang ,&nbsp;Max A. Garcia ,&nbsp;Megan C. Procario ,&nbsp;Sanghee Yoo ,&nbsp;Amber L. Jolly ,&nbsp;Sumin Kim ,&nbsp;Jiho Kim ,&nbsp;Kyusuk Baek ,&nbsp;Roland D. Kersten ,&nbsp;Robert J. Fontana ,&nbsp;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}
引用次数: 0
A Review of the Systemic Manifestations of Hepatitis B Virus Infection, Hepatitis D Virus, Hepatocellular Carcinoma, and Emerging Therapies 乙肝病毒感染、丁型肝炎病毒、肝细胞癌的系统性表现及新疗法的综述
Pub Date : 2024-01-01 DOI: 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.

全球约有 2.62 亿人感染慢性乙型肝炎病毒(HBV),每年有超过 82 万人主要死于肝硬化和肝细胞癌。世界卫生组织承诺到 2030 年消除 HBV 对健康的威胁,但目前还没有任何国家有望实现这一目标。消除 HBV 的障碍之一是耻辱感,耻辱感会导致羞耻、否认、自我孤立、自我排斥和抑郁,从而导致慢性 HBV 感染者不太可能接受检测或寻求治疗,更有可能隐瞒自己的感染情况。其他障碍还包括获得治疗的机会有限,临床实践指南复杂且具有限制性。有必要加大公众和政治方面的努力,以提高人们的认识,增加获得医疗服务的机会,并改变筛查和治疗指南。美国肝病研究协会(AASLD)目前的指南建议,只有当患者被认为有风险时才进行检测,但事实证明这种做法效果不佳。我们建议采用简化的 "全部检测、全部治疗 "的方法,并针对 HBV 感染制定五线指南。对成人进行普遍筛查和治疗具有成本效益,并且可以通过有效管理慢性 HBV 防止传播。所有乙型肝炎表面抗原(HBsAg)阳性并可检测到 HBV-DNA 的患者都应接受治疗,直到 HBsAg 在 12 个月内检测不到为止,因为即使病毒载量低至 16 拷贝/毫升,HBV-DNA 也会通过输血传播,而且即使采取了被动积极的免疫预防措施,母婴传播仍然存在风险。此外,HBsAg 清除后的临床疗效明显优于 HBsAg 仍然阳性者。
{"title":"A Review of the Systemic Manifestations of Hepatitis B Virus Infection, Hepatitis D Virus, Hepatocellular Carcinoma, and Emerging Therapies","authors":"Katerina Roma ,&nbsp;Toni-Marie Chandler ,&nbsp;Zahra Dossaji ,&nbsp;Ankoor Patel ,&nbsp;Kapil Gupta ,&nbsp;Carlos D. Minacapelli ,&nbsp;Vinod Rustgi ,&nbsp;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}
引用次数: 0
Erratum Regarding Conflicts of Interest Statements in Previously Published Articles 关于以往发表文章中利益冲突声明的勘误
Pub Date : 2024-01-01 DOI: 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}
引用次数: 0
Gastric Adenocarcinoma Masquerading as Cannabis Hyperemesis Syndrome 伪装成大麻亢进综合征的胃腺癌
Pub Date : 2024-01-01 DOI: 10.1016/j.gastha.2023.11.014
Charles Altfillisch , Fortune Unegbu , Daniel Buckles
{"title":"Gastric Adenocarcinoma Masquerading as Cannabis Hyperemesis Syndrome","authors":"Charles Altfillisch ,&nbsp;Fortune Unegbu ,&nbsp;Daniel Buckles","doi":"10.1016/j.gastha.2023.11.014","DOIUrl":"10.1016/j.gastha.2023.11.014","url":null,"abstract":"","PeriodicalId":73130,"journal":{"name":"Gastro hep advances","volume":"3 2","pages":"Page 186"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772572323001899/pdfft?md5=a66f36dec9c16790c5ac80815555639d&pid=1-s2.0-S2772572323001899-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138626141","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}
引用次数: 0
Dynamics of Virological and Clinical Response Parameters of Bulevirtide Treatment for Hepatitis D: Real-World Data 布来韦肽治疗 D 型肝炎的病毒学和临床反应参数动态 - 真实世界的数据
Pub Date : 2024-01-01 DOI: 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.

背景和目的入口抑制剂布来韦肽是治疗丁型肝炎病毒(HDV)感染患者的第一种特效药物。在临床试验中,约 80% 的患者在 1 年后丙氨酸氨基转移酶(ALT)恢复正常,约 60% 的患者出现病毒学应答,但人们对应答的动态变化以及治疗结果的临床预测因素知之甚少。我们报告了来自 15 名患者的单中心数据,并描述了应答动态、临床结果和治疗应答的预测因素。方法我们对本部门在 2020 年 10 月至 2022 年 8 月期间开始接受布来韦肽治疗的 15 名患者的回顾性数据进行了分析。根据我们的标准程序,每月对实验室参数进行控制;每 3 个月进行一次瞬态弹性成像,疗程为 12 个月。结果治疗 1 年后的治疗反应率与临床试验公布的数据相似。ALT正常化通常发生在治疗的第2-6个月,随后在≥6个月后出现病毒学应答。开始治疗时肝炎较严重的患者在治疗第一年出现应答的可能性较小。治疗≥1年后,三分之一的患者观察到HDV-RNA丢失。基线时的低体重指数和高甲胎蛋白可能是延迟治疗反应的预测因素。值得注意的是,转氨酶的下降先于病毒学应答。病毒载量和谷丙转氨酶水平较高的患者反应较慢,但无应答者(根据食品和药物管理局的标准分类)的病毒血症仍会减少。要确定布来韦肽单药治疗的最佳疗程,还需要更长的观察期。
{"title":"Dynamics of Virological and Clinical Response Parameters of Bulevirtide Treatment for Hepatitis D: Real-World Data","authors":"Alexander Killer ,&nbsp;Smaranda Gliga ,&nbsp;Carolin Lohr ,&nbsp;Christian Weigel ,&nbsp;Björn-Erik Ole Jensen ,&nbsp;Nadine Lübke ,&nbsp;Andreas Walker ,&nbsp;Jörg Timm ,&nbsp;Johannes Bode ,&nbsp;Tom Luedde ,&nbsp;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}
引用次数: 0
期刊
Gastro hep advances
全部 Acc. Chem. Res. ACS Applied Bio Materials ACS Appl. Electron. Mater. ACS Appl. Energy Mater. ACS Appl. Mater. Interfaces ACS Appl. Nano Mater. ACS Appl. Polym. Mater. ACS BIOMATER-SCI ENG ACS Catal. ACS Cent. Sci. ACS Chem. Biol. ACS Chemical Health & Safety ACS Chem. Neurosci. ACS Comb. Sci. ACS Earth Space Chem. ACS Energy Lett. ACS Infect. Dis. ACS Macro Lett. ACS Mater. Lett. ACS Med. Chem. Lett. ACS Nano ACS Omega ACS Photonics ACS Sens. ACS Sustainable Chem. Eng. ACS Synth. Biol. Anal. Chem. BIOCHEMISTRY-US Bioconjugate Chem. BIOMACROMOLECULES Chem. Res. Toxicol. Chem. Rev. Chem. Mater. CRYST GROWTH DES ENERG FUEL Environ. Sci. Technol. Environ. Sci. Technol. Lett. Eur. J. Inorg. Chem. IND ENG CHEM RES Inorg. Chem. J. Agric. Food. Chem. J. Chem. Eng. Data J. Chem. Educ. J. Chem. Inf. Model. J. Chem. Theory Comput. J. Med. Chem. J. Nat. Prod. J PROTEOME RES J. Am. Chem. Soc. LANGMUIR MACROMOLECULES Mol. Pharmaceutics Nano Lett. Org. Lett. ORG PROCESS RES DEV ORGANOMETALLICS J. Org. Chem. J. Phys. Chem. J. Phys. Chem. A J. Phys. Chem. B J. Phys. Chem. C J. Phys. Chem. Lett. Analyst Anal. Methods Biomater. Sci. Catal. Sci. Technol. Chem. Commun. Chem. Soc. Rev. CHEM EDUC RES PRACT CRYSTENGCOMM Dalton Trans. Energy Environ. Sci. ENVIRON SCI-NANO ENVIRON SCI-PROC IMP ENVIRON SCI-WAT RES Faraday Discuss. Food Funct. Green Chem. Inorg. Chem. Front. Integr. Biol. J. Anal. At. Spectrom. J. Mater. Chem. A J. Mater. Chem. B J. Mater. Chem. C Lab Chip Mater. Chem. Front. Mater. Horiz. MEDCHEMCOMM Metallomics Mol. Biosyst. Mol. Syst. Des. Eng. Nanoscale Nanoscale Horiz. Nat. Prod. Rep. New J. Chem. Org. Biomol. Chem. Org. Chem. Front. PHOTOCH PHOTOBIO SCI PCCP Polym. Chem.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1