Gastro hep advances最新文献

英文中文

Alcohol Relapse After Liver Transplantation: Risk Factors, Outcomes, and a Comparison of Risk Stratification Models 肝移植后酒精复发：危险因素、结果和风险分层模型的比较

Gastro hep advances

Pub Date : 2025-01-01 DOI: 10.1016/j.gastha.2024.09.005

Karen Young , Yuval A. Patel , Benson Hoffman , Sarah Peskoe , Shein-Chung Chow , Karli Erhart , Jennifer Jackson , Stephanie Garbarino

Background and Aims

Alcohol-related liver disease is a leading cause of liver transplantation (LT) in the United States; however, alcohol relapse remains a risk, and real-world assessment of relapse prediction scores is lacking. The primary aim of this study was to assess risk factors for alcohol relapse and compare effectiveness of pre-existing risk scores (e.g., Sustained Alcohol Use Post-Liver Transplant (SALT) and Harmful Alcohol Use Post-Liver Transplant (HALT) scores).

Methods

This was a retrospective chart review of 69 adults who underwent LT for alcohol-related liver disease at Duke University Hospital from January 1, 2018, to January 1, 2021. Outcome variables included relapse post-LT, severity of relapse, and graft dysfunction.

Results

Sixty-seven patients with a median follow-up time of 43 months were included. Eighteen (27%) experienced alcohol relapse. Of those, 16 (89%) had heavy alcohol use and 3 of those patients (17%) experienced graft dysfunction. Factors significantly associated with relapse included younger age, prior relapse, significant psychiatric comorbidities, alcohol use after cirrhosis diagnosis, shorter abstinence before LT listing, and prior alcohol treatment program. When applying SALT and HALT scores, the area under the curve was 0.69 (95% confidence interval 0.53–0.85) and 0.66 (95% confidence interval 0.50–0.81), respectively.

Conclusion

In our cohort, heavy alcohol use before transplantation and legal issues did not predict relapse, which are common components of prediction scores. Less than 5% of patients had graft dysfunction due to relapse, suggesting good graft outcomes. While the HALT and SALT scores were validated in our cohort, our finding of additional significant predictors of relapse, in addition to previously reported risk factors providing protective effect, suggests opportunity for further optimization of prediction scores.

背景和目的：在美国，酒精相关肝病是导致肝移植（LT）的主要原因之一；然而，酒精复发仍然是一种风险，而且缺乏对复发预测评分的真实世界评估。本研究的主要目的是评估酒精复发的风险因素，并比较已有风险评分（如肝移植后持续酒精使用评分（SALT）和肝移植后有害酒精使用评分（HALT））的有效性：这是一项回顾性病历审查，对象是2018年1月1日至2021年1月1日期间在杜克大学医院接受LT治疗酒精相关肝病的69名成人。结果变量包括LT后复发、复发严重程度和移植物功能障碍：共纳入 67 名患者，中位随访时间为 43 个月。18例（27%）患者复发酒精中毒。其中 16 人（89%）酗酒严重，3 人（17%）出现移植物功能障碍。与复发密切相关的因素包括：年龄较小、曾有复发、严重的精神并发症、肝硬化确诊后饮酒、LT 患者上市前戒酒时间较短、曾接受过酒精治疗项目。在应用SALT和HALT评分时，曲线下面积分别为0.69（95%置信区间0.53-0.85）和0.66（95%置信区间0.50-0.81）：在我们的队列中，移植前大量饮酒和法律问题并不能预测复发，而这是预测评分的常见组成部分。不到5%的患者因复发导致移植功能障碍，这表明移植结果良好。虽然HALT和SALT评分在我们的队列中得到了验证，但除了之前报道的具有保护作用的风险因素外，我们还发现了其他重要的复发预测因素，这为进一步优化预测评分提供了机会。

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引用次数: 0

Microfluidic Flow Promotes a Steatotic Phenotype in Induced Pluripotent Stem Cell–Derived Hepatocytes that is Influenced by Disease State of the Donor

Gastro hep advances

Pub Date : 2025-01-01 DOI: 10.1016/j.gastha.2024.100601

Ekta Minocha , Linan Jiang , Ashwani Kumar Gupta , Richard M. Green , Yitshak Zohar , Jason A. Wertheim

引用次数: 0

Adenosine Receptor 3 in Liver Cancer: Expression Variability, Epigenetic Modulation, and Enhanced Histone Deacetylase Inhibitor Effects

Gastro hep advances

Pub Date : 2025-01-01 DOI: 10.1016/j.gastha.2024.11.006

Louise Kaldjob-Heinrich , Sandro Nuciforo , Steffen Lemke , Aaron Stahl , Stefan Czemmel , Sepideh Babaei , Lauriane Blukacz , Marie-Anne Meier , Yizheng Zhang , Christian M. Schürch , Irene Gonzalez-Menendez , Pascal Woelffing , Nisar P. Malek , Veit Scheble , Sven Nahnsen , Manfred Claassen , Markus Templin , Hans Bösmüller , Markus H. Heim , Daniel Dauch , Michael Bitzer

Background and Aims

Primary liver cancer, including hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA), has low response rates to existing treatments, highlighting the urgent need for novel treatment options. Adenosine A3 receptor (ADORA3) signaling has emerged as a potential target. Namodenoson, an ADORA3 agonist, has shown promise in early clinical trials for HCC. However, further data are required to clarify ADORA3 expression patterns in liver cancer, mechanisms of action, and the potential for combination therapies to inform patient selection for future clinical trials.

Methods

Patient-derived tissue microarrays and RNA-sequencing were employed to investigate ADORA3 expression. Cellular responses to ADORA3 stimulation and combination treatments were studied in HCC and CCA cell lines and patient-derived organoids (PDOs). Genome-wide RNA-Seq analysis, mRNA analysis, and DigiWest protein profiling were performed.

Results

Tissue microarray analysis revealed higher ADORA3 expression in nonmalignant samples and a subset of tumors with weak or absent ADORA3 expression. This was supported by RNA sequencing data from The Cancer Genome Atlas and needle biopsy samples. Cell lines and PDOs exhibited antiproliferative effects with the ADORA3 agonist Namodenoson, confirmed by receptor dependency tests with specific antagonists and siRNA experiments. Genome-wide RNA-Seq analysis suggested chromatin remodeling events after ADORA3 stimulation. mRNA expression and DigiWest profiling identified downregulation of histone deacetylases and histone H3 modifications. Combination treatments with different ADORA3 agonists and histone deacetylase inhibitors significantly enhanced antiproliferative effects in almost all selected combinations, supported by investigations in PDOs.

Conclusion

ADORA3 expression varies considerably in HCC or CCA, ranging from high to absent receptor detection. This observation might help to identify patients for clinical studies. Additionally, Namodenoson’s epigenetic modulating activity suggests epigenetic drugs as promising candidates for combination treatment.

{"title":"Adenosine Receptor 3 in Liver Cancer: Expression Variability, Epigenetic Modulation, and Enhanced Histone Deacetylase Inhibitor Effects","authors":"Louise Kaldjob-Heinrich , Sandro Nuciforo , Steffen Lemke , Aaron Stahl , Stefan Czemmel , Sepideh Babaei , Lauriane Blukacz , Marie-Anne Meier , Yizheng Zhang , Christian M. Schürch , Irene Gonzalez-Menendez , Pascal Woelffing , Nisar P. Malek , Veit Scheble , Sven Nahnsen , Manfred Claassen , Markus Templin , Hans Bösmüller , Markus H. Heim , Daniel Dauch , Michael Bitzer","doi":"10.1016/j.gastha.2024.11.006","DOIUrl":"10.1016/j.gastha.2024.11.006","url":null,"abstract":"<div><h3>Background and Aims</h3><div>Primary liver cancer, including hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA), has low response rates to existing treatments, highlighting the urgent need for novel treatment options. Adenosine A3 receptor (ADORA3) signaling has emerged as a potential target. Namodenoson, an ADORA3 agonist, has shown promise in early clinical trials for HCC. However, further data are required to clarify ADORA3 expression patterns in liver cancer, mechanisms of action, and the potential for combination therapies to inform patient selection for future clinical trials.</div></div><div><h3>Methods</h3><div>Patient-derived tissue microarrays and RNA-sequencing were employed to investigate ADORA3 expression. Cellular responses to ADORA3 stimulation and combination treatments were studied in HCC and CCA cell lines and patient-derived organoids (PDOs). Genome-wide RNA-Seq analysis, mRNA analysis, and DigiWest protein profiling were performed.</div></div><div><h3>Results</h3><div>Tissue microarray analysis revealed higher ADORA3 expression in nonmalignant samples and a subset of tumors with weak or absent ADORA3 expression. This was supported by RNA sequencing data from The Cancer Genome Atlas and needle biopsy samples. Cell lines and PDOs exhibited antiproliferative effects with the ADORA3 agonist Namodenoson, confirmed by receptor dependency tests with specific antagonists and siRNA experiments. Genome-wide RNA-Seq analysis suggested chromatin remodeling events after ADORA3 stimulation. mRNA expression and DigiWest profiling identified downregulation of histone deacetylases and histone H3 modifications. Combination treatments with different ADORA3 agonists and histone deacetylase inhibitors significantly enhanced antiproliferative effects in almost all selected combinations, supported by investigations in PDOs.</div></div><div><h3>Conclusion</h3><div>ADORA3 expression varies considerably in HCC or CCA, ranging from high to absent receptor detection. This observation might help to identify patients for clinical studies. Additionally, Namodenoson’s epigenetic modulating activity suggests epigenetic drugs as promising candidates for combination treatment.</div></div>","PeriodicalId":73130,"journal":{"name":"Gastro hep advances","volume":"4 3","pages":"Article 100590"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143167833","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

Association of Statin, Metformin, and Aspirin Use With Hepatocellular Carcinoma in the All of Us Research Program 他汀类药物、二甲双胍和阿司匹林与肝细胞癌的相关性研究

Gastro hep advances

Pub Date : 2025-01-01 DOI: 10.1016/j.gastha.2024.08.014

Erik Almazan , Raymond T. Chung

引用次数: 0

Impact of Order Set on Exocrine Pancreatic Insufficiency in Chronic Pancreatitis, Pancreatic Cancer, and Pancreatic Resection 顺序设置对慢性胰腺炎、胰腺癌和胰腺切除术中外分泌胰腺功能不全的影响。

Gastro hep advances

Pub Date : 2025-01-01 DOI: 10.1016/j.gastha.2024.08.019

Michael Ladna , Ishaan Madhok , Adnan Bhat , Nicole Ruiz , Jackson Brown , Jake Wilson , Peter Jiang , Robert Taylor , Mark Radetic , John George , Christopher Forsmark

Background and Aims

Enzyme insufficiency (EPI) is common in chronic pancreatitis (CP), pancreatic ductal adenocarcinoma (PDAC), and after pancreatic resection. 40%–50% of CP patients and 70%–80% of PDAC patients develop EPI. 1/3rd of these patients are prescribed Pancreatic enzyme replacement therapy (PERT), often at an inadequate dose, with evidence that this leads to increased morbidity and mortality. This study aimed to develop and implement an EPIC-based best practice alert (BPA) and smart set to improve the management of EPI.

Methods

A retrospective analysis of all patients with International Classification of Diseases codes for EPI, CP, and PDAC or CPT code for pancreatic resection from Feb-2018 to Feb-2021. Appropriate use of PERT was defined as ≥ 40,000 units of lipase with each meal. The BPA and smart set were implemented into the electronic medical record in Feb-2020. The BPA fired if the patient was already on PERT or if an order for PERT was placed and directed the clinician to the smart set which provided PERT formulations each prefilled to the minimum therapeutic dose of 40,000 units of lipase.

Results

A significant increase in the proportion of patients on minimum therapeutic dose of PERT from 61.9% to 72.9% (P ≤ .001). Ordering of pancreatic elastase, A1c, vitamin D, and dual X-ray absorptiometry increased from 20.4% to 29.9% (P < .001), 54.7%–62.1% (P = .001), 30.9%–48.1% (P < .001) and 10%–18% (P < .001), respectively. The BPA triggered a total of 30,838 times resulting in the smart being opened a total of 624 (2.02%) times over 24 months.

Conclusion

The BPA and smart set were associated with an improvement in the diagnosis and management of EPI and related complications in CP, PDAC, and s/p pancreatic resection.

背景与目的：酶功能不全（EPI）常见于慢性胰腺炎（CP）、胰腺导管腺癌（PDAC）和胰腺切除术后。40%-50%的CP患者和70%-80%的PDAC患者发生EPI。这些患者中有三分之一接受胰酶替代疗法（PERT），通常剂量不足，有证据表明这导致发病率和死亡率增加。本研究旨在开发和实施基于EPI的最佳实践警报（BPA）和智能集，以改善EPI的管理。方法：回顾性分析2018年2月至2021年2月期间所有使用EPI、CP和PDAC国际疾病分类代码或CPT胰腺切除术代码的患者。适当使用PERT的定义是每餐添加≥40000单位脂肪酶。2020年2月，双酚a和智能设备在电子病历中实施。如果病人已经在使用PERT，或者已经下了PERT的订单，BPA就会启动，并将临床医生引导到智能集，智能集提供了PERT配方，每个配方预先填充到最低治疗剂量的40,000单位脂肪酶。结果：接受最低治疗剂量PERT治疗的患者比例由61.9%显著增加至72.9% （P≤0.001）。胰弹性酶、糖化血红蛋白、维生素D和双x线吸收仪的排序分别从20.4%增加到29.9% （P < 0.001）、54.7%增加到62.1% （P = 0.001）、30.9%增加到48.1% （P < 0.001）和10%增加到18% （P < 0.001）。BPA在24个月内共触发30838次，导致智能手机被打开624次（2.02%）。结论：BPA和smart set与CP、PDAC和s/p胰腺切除术中EPI及相关并发症的诊断和管理改善有关。

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引用次数: 0

Nucleos(t)ide Analog Treatment Discontinuation in Chronic Hepatitis B Virus Infection: A Systematic Literature Review 慢性乙型肝炎病毒感染停止核苷类似物治疗：系统文献综述。

Gastro hep advances

Pub Date : 2025-01-01 DOI: 10.1016/j.gastha.2024.08.015

Robert Gish , Kosh Agarwal , Anadi Mahajan , Supriya Desai , Saifuddin Kharawala , Rob Elston , Joyeta Das , Stuart Kendrick , Vera Gielen

Background and Aims

The aim of this systematic literature review (SLR) was to examine outcomes and associated predictors following nucleos(t)ide analog (NA) treatment cessation in adult patients with chronic hepatitis B virus infection.

Methods

The SLR was conducted according to PRISMA methodology. All included studies were quality assessed using appropriate scales or checklists.

Results

The SLR identified 145 studies. Cumulative rates of clinical relapse (40 studies), virological relapse (53 studies), biochemical relapse (10 studies) and retreatment events (14 studies) post NA cessation varied widely across studies (clinical relapse: 40%–65%, virological relapse: 75%–94%, biochemical relapse: 63%–73%, retreatment rates: 30%–78% at 24 and 144 weeks, respectively). Significant predictors with adequate evidence of clinical relapse included older age, male gender, and higher hepatitis B surface antigen (HBsAg) and hepatitis B virus DNA at baseline and end of treatment. HBsAg loss was reported in 25 studies, with overall median HBsAg loss rates ranging from 2% at 24 weeks (5 studies) to 11% at 192 weeks (2 studies) post NA cessation. There was adequate evidence for lower HBsAg level at baseline and end of treatment as a significant and consistent predictor of HBsAg loss.

Conclusion

There is considerable heterogeneity among studies of NA cessation. Data are currently incomplete to provide strong recommendations for NA cessation or to identify patients who may benefit most from this approach in clinical practice. Further studies are required to provide clearer guidelines, and tools to assess and monitor patients who may benefit from NA treatment cessation.

背景和目的：本系统文献综述（SLR）的目的是研究成人慢性乙型肝炎病毒感染患者停止核苷类似物（NA）治疗后的结局和相关预测因素。方法：采用PRISMA方法进行单反成像。所有纳入的研究均采用适当的量表或检查表进行质量评估。结果：SLR识别了145项研究。NA停用后的累积临床复发率（40项研究）、病毒学复发率（53项研究）、生化复发率（10项研究）和再治疗事件（14项研究）在研究中差异很大（临床复发率：40%-65%，病毒学复发率：75%-94%，生化复发率：63%-73%，再治疗率：30%-78%，分别为24周和144周）。有充分临床复发证据的重要预测因素包括：年龄较大、男性、基线和治疗结束时较高的乙型肝炎表面抗原（HBsAg）和乙型肝炎病毒DNA。25项研究报告了HBsAg损失，总体中位HBsAg损失率从停用NA后24周的2%（5项研究）到192周的11%（2项研究）不等。有充分的证据表明，基线和治疗结束时较低的HBsAg水平是HBsAg损失的重要和一致的预测因子。结论：NA停止的研究存在相当大的异质性。目前的数据不完整，无法提供强有力的建议，也无法确定在临床实践中哪些患者可能从这种方法中获益最多。需要进一步的研究来提供更清晰的指南和工具来评估和监测可能从NA治疗停止中受益的患者。

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引用次数: 0

Family History of Eosinophilic Esophagitis or Other Eosinophilic Gastrointestinal Disease Is Not Associated With Response to Topical Steroids in Eosinophilic Esophagitis

Gastro hep advances

Pub Date : 2025-01-01 DOI: 10.1016/j.gastha.2024.11.001

Angela Z. Xue , Sean S. LaFata , Timothy S. Gee , Hannah L. Thel , Brenderia A. Cameron , Akshatha Kiran , Adolfo A. Ocampo , Justin McCallen , Christopher J. Lee , Stephanie A. Borinsky , Walker D. Redd , Trevor S. Barlowe , Rayan N. Kaakati , Cary C. Cotton , Swathi Eluri , Craig C. Reed , Evan S. Dellon

引用次数: 0

Perindopril-Induced Collagenous Colitis: Case Report and Literature Review

Gastro hep advances

Pub Date : 2025-01-01 DOI: 10.1016/j.gastha.2024.09.009

Eddy Fares, Weam El Hajj, Stéphane Nahon, Gilles Macaigne

We report the first case of collagenous colitis attributed to perindopril use, in a 90-year-old woman. The patient developed diarrhea with hypokalemia, 3 weeks after perindopril was introduced in her medications for uncontrolled hypertension. Significant thickening of the basal epithelial membrane (up to 80 μm) was found on random colon biopsies. Diarrhea resolved within 3 days after perindopril withdrawal. Four months later, left colon biopsies revealed a normalization of the basal membrane thickness. The intrinsic imputability of perindopril as the causative agent of microscopic colitis is considered to be reasonable by the French accountability technique. There was no rechallenge test conducted.

我们报告了第一例因使用培哚普利而导致胶原性结肠炎的病例，患者是一名 90 岁的妇女。患者在服用培哚普利治疗未控制的高血压3周后出现腹泻和低钾血症。随机结肠活检发现基底上皮膜明显增厚（达 80 μm）。停用培哚普利后，腹泻在 3 天内缓解。四个月后，左结肠活检显示基底膜厚度恢复正常。根据法国的问责技术，认为培哚普利作为显微镜下结肠炎致病因子的内在不可归责性是合理的。没有进行再挑战试验。

引用次数: 0

A Comprehensive Assessment of Liver Transplant Trends and Outcomes Among Adults With Steatotic Liver Disease in the U.S.

Gastro hep advances

Pub Date : 2025-01-01 DOI: 10.1016/j.gastha.2024.100609

Shyam Patel , Sohil Patel , Wei Zhang , Ashwani K. Singal , Ramsey Cheung , Robert J. Wong

Background and Aims

Steatotic liver disease (SLD) is the leading indication for liver transplantation (LT) among U.S. adults. We aim to provide comprehensive updates of LT trends and outcomes among adults with SLD, highlighting racial, ethnic, and sociodemographic disparities.

Methods

Using data from the 2010 to 2023 United Network for Organ Sharing registry, we performed a retrospective cohort study evaluating LT waitlist trends, waitlist outcomes, and post-LT survival among 65,675 adults with SLD. Disparities in LT outcomes were evaluated using adjusted competing risks analyses.

Results

From 2014 to 2023, there was an increasing proportion of Hispanics, women, and younger adults with SLD listed for LT. For Hispanics, this was driven by metabolic dysfunction–associated steatohepatitis (MASH); 19.9% of MASH wait-listings in 2023 were Hispanics. For women and younger adults (18–39 years), this was driven by alcohol-associated liver disease (ALD); 30.9% and 16.4% of ALD-related wait-listings in 2023 were women and younger adults, respectively. Women (vs men) had greater waitlist removal risk (subdistribution hazard ratio (sHR) 1.12, 95% confidence interval (CI) 1.07–1.18) and lower likelihood of LT receipt (sHR 0.87, 95% CI, 0.85–0.90). Ethnic minorities had worse outcomes, particularly Hispanics, who had a 37% higher risk of waitlist removal (sHR 1.37, 95% CI, 1.30–1.45) and 16% lower likelihood of LT receipt (sHR 0.86, 95% CI, 0.82–0.87) vs non-Hispanic whites. Disparities in post-LT survival were also observed.

Conclusion

In 2023, nearly one-quarter of MASH liver transplant waitlist registrants were Hispanics. Approximately half and 1 in 6 ALD waitlist registrants were women and younger adults, respectively. These concerning trends are amplified by the disparities in LT outcomes observed among women and ethnic minorities.

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引用次数: 0

What Are TikTok Users Saying About Colorectal Cancer? An Examination of Content, Quality, and Emerging Themes TikTok用户对结直肠癌有什么看法？内容，质量和新兴主题的检查。

Gastro hep advances

Pub Date : 2025-01-01 DOI: 10.1016/j.gastha.2024.08.013

Bharathi Selvan, Melissa M. Tran, Christine O’Connell, Julius M. Wilder

引用次数: 0

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