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Caloric Restriction Is Associated With Enhanced Clinical Outcomes in Hospitalized Patients With Ulcerative Colitis 热量限制与溃疡性结肠炎住院患者的临床预后增强相关
Pub Date : 2025-11-07 DOI: 10.1016/j.gastha.2025.100842
Tomoyuki Nagai, Yoriaki Komeda, Saki Yoshida, Kohei Handa, Sho Masaki, Masashi Kono, Hajime Honjo, Shigenaga Matsui, Naoko Tsuji, Hiroshi Kashida, Masatoshi Kudo

Background and Aims

Ulcerative colitis (UC) is a chronic inflammatory bowel disease with a relapsing-remitting course that often requires hospitalization during flares. While prolonged fasting has traditionally led to high-calorie intravenous nutrition, excessive caloric intake may induce hyperglycemia, increase infection risk, and inhibit autophagy. This study aimed to evaluate the impact of a short-term, calorie-restricted regimen (≤400 kcal/day), designed to promote autophagy, on clinical outcomes in hospitalized patients with UC.

Methods

A retrospective analysis was conducted on 38 patients admitted for UC exacerbation between January 2022 and December 2024. Patients were categorized into a calorie-restricted group (≤400 kcal/day) or a standard nutrition group (>400 kcal/day) based on their total caloric intake. The calorie-restricted group received only intravenous fluids and noncaloric beverages. The primary endpoint was clinical remission at day 14, while secondary endpoints included the length of hospital stay and incidence of adverse events.

Results

The clinical remission at day 14 following treatment initiation was significantly higher in the calorie-restricted group (86% [12/14]) compared to the standard nutrition group (42% [10/24]) (P < .05). The mean duration of hospitalization was also significantly shorter in the calorie-restricted group (11.0 ± 3.3 days) compared to the standard nutrition group (22.1 ± 8.9 days) (P < .01). The calorie-restricted group experienced mild, transient adverse events but no serious complications. In contrast, the standard nutrition group experienced serious adverse events such as catheter-related infections and myocarditis.

Conclusion

Caloric restriction during hospitalization for UC exacerbation may be associated with increased clinical remission and a shorter hospital stay. That nutritional strategy offers a potentially novel and cost-effective approach distinct from conventional bowel rest. Further prospective, multicenter studies are warranted to validate these findings.
背景和目的溃疡性结肠炎(UC)是一种慢性炎症性肠病,病程复发缓解,经常需要住院治疗。虽然长期禁食传统上导致高热量静脉营养,但过量的热量摄入可能导致高血糖,增加感染风险,并抑制自噬。本研究旨在评估旨在促进自噬的短期卡路里限制方案(≤400 kcal/天)对UC住院患者临床结果的影响。方法对我院2022年1月至2024年12月收治的38例UC加重患者进行回顾性分析。根据患者的总热量摄入,将患者分为热量限制组(≤400千卡/天)和标准营养组(>;400千卡/天)。热量限制组只接受静脉输液和无热量饮料。主要终点是第14天的临床缓解,而次要终点包括住院时间和不良事件的发生率。结果在治疗开始后第14天,热量限制组的临床缓解率(86%[12/14])明显高于标准营养组(42% [10/24])(P < 0.05)。热量限制组的平均住院时间(11.0±3.3天)也明显短于标准营养组(22.1±8.9天)(P < 0.01)。卡路里限制组经历了轻微的、短暂的不良事件,但没有严重的并发症。相比之下,标准营养组经历了严重的不良事件,如导管相关感染和心肌炎。结论UC加重住院期间限制热量摄入可能与临床缓解增加和住院时间缩短有关。这种营养策略提供了一种潜在的新颖和具有成本效益的方法,与传统的肠道休息不同。需要进一步的前瞻性多中心研究来验证这些发现。
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引用次数: 0
Hepatitis B Surface Antigen Loss and Improved Clinical Outcomes in Asians with Chronic Hepatitis B Virus Infection 慢性乙型肝炎病毒感染的亚洲人乙型肝炎表面抗原丢失和改善的临床结果
Pub Date : 2025-11-06 DOI: 10.1016/j.gastha.2025.100844
Wallis Lau , Myriam Drysdale , Eleonora Morais , Luis Antunes , Loey Mak , Christopher Lee , Catarina Camarinha , Xiaohui Sun , Adrienne Y.L. Chan , May Lam , Vera Gielen , Dickens Theodore , Ian C.K. Wong , Iain A. Gillespie

Background and aims

Chronic hepatitis B virus (HBV) infection accounts for substantial disease burden and mortality due to liver complications. Hepatitis B surface antigen (HBsAg) loss is a key component of functional cure when assessing treatment efficacy. However, the impact of HBsAg loss on clinical outcomes deserves further exploration.

Methods

This population-based cohort study used electronic health record data from a territory-wide database in Hong Kong to identify patients with chronic HBV infection (2005–2019). The association between HBsAg loss and outcomes was assessed: compensated cirrhosis, decompensated liver disease (DLD), hepatocellular carcinoma (HCC), and all-cause mortality (ACM). A marginal structural model using inverse probability weighting was used to estimate hazard ratios (HRs; 95% confidence interval [CI]) adjusted for time-fixed and time-varying confounders. Health-care resource utilization before and after loss was evaluated.

Results

The study population comprised 71,077 patients accruing 348,379 person-years; 1639 (2.3%) experienced HBsAg loss, which occurred with a mean (standard deviation) of 74.63 (37.5) months after chronic HBV index date. HBsAg loss was associated with a reduced risk of DLD (74%; HR 0.26 [95% CI 0.08–0.83]), HCC (66%; 0.34 [0.19–0.61]), and ACM (26%; 0.74 [0.57–0.97]). The HR for compensated cirrhosis was 0.57 (0.30–1.14). Each additional month of HBsAg loss was associated with decreased risk of HCC and ACM. Of those experiencing HBsAg loss, cumulative probability of persistence at 24 and 60 months was 99% and 97%, respectively. Hospital admission, inpatient days, and drug prescribing were higher before HBsAg loss versus 6, 12, and 24 months post-HBsAg loss.

Conclusion

In this large population-based study with extended follow-up in Hong Kong, HBsAg loss was associated with reduced risk of DLD, HCC, and ACM.
背景和目的慢性乙型肝炎病毒(HBV)感染是由肝脏并发症引起的大量疾病负担和死亡率。乙型肝炎表面抗原(HBsAg)丢失是评估治疗效果时功能性治愈的关键组成部分。然而,HBsAg损失对临床结果的影响值得进一步探讨。方法本以人群为基础的队列研究使用来自香港全区数据库的电子健康记录数据来识别慢性HBV感染患者(2005-2019)。评估了HBsAg损失与结局之间的关系:代偿性肝硬化、失代偿性肝病(DLD)、肝细胞癌(HCC)和全因死亡率(ACM)。使用反概率加权的边际结构模型来估计经时间固定和时变混杂因素调整后的风险比(hr; 95%置信区间[CI])。评估损失前后的卫生保健资源利用情况。研究人群包括71,077例患者,累计348,379人年;1639例(2.3%)患者出现HBsAg损失,平均(标准差)为74.63(37.5)个月。HBsAg损失与DLD (74%; HR 0.26 [95% CI 0.08-0.83])、HCC(66%; 0.34[0.19-0.61])和ACM(26%; 0.74[0.57-0.97])的风险降低相关。代偿性肝硬化的HR为0.57(0.30-1.14)。每增加一个月的HBsAg损失与HCC和ACM的风险降低相关。在经历HBsAg损失的患者中,持续24个月和60个月的累积概率分别为99%和97%。与HBsAg丢失后6、12和24个月相比,HBsAg丢失前的住院率、住院天数和药物处方更高。结论:在香港进行的一项大规模人群随访研究中,HBsAg损失与DLD、HCC和ACM风险降低相关。
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引用次数: 0
Prevalence of Eosinophilic Esophagitis Among Ethnic Groups in a Private Vs a Safety Net-Hospital in Southern California 南加州私立医院与安全网医院种族间嗜酸性食管炎的患病率
Pub Date : 2025-10-31 DOI: 10.1016/j.gastha.2025.100840
Ibrahim Abboud , Susie Lee , Jordan Stellern , Andrew Cruz , Nicholas Placone , Jennifer Dodge , Collin Mayemura , Anisa Shaker , Edy Soffer

Background and Aims

Eosinophilic esophagitis (EoE) is rapidly increasing in incidence and prevalence. It is more prevalent among Whites as compared to Hispanics. The reasons for this disparity remain unclear. We aimed to compare EoE Prevalence between a private facility and a safety-net hospital, the latter treating a larger proportion of foreign-born Spanish-speaking patients, and to examine differences in prevalence among Hispanics across both facilities.

Methods

We conducted a retrospective cross-sectional study of adult patients who underwent upper endoscopy for dysphagia, food impaction, or EoE at 2 medical centers. The primary outcome was a diagnosis of EoE, based on clinical, endoscopic, and pathologic criteria. Logistic regression was employed to calculate adjusted odds ratios (ORs) for EoE.

Results

Of 1005 patients, a higher proportion of Hispanic (73.3% versus 19.7%) and Spanish-speaking patients (64.8% versus 7.6%) received care at the safety-net hospital. Overall, 70 (7.0%) patients were diagnosed with EoE, with a higher prevalence at the private versus safety-net hospital (10.5% versus 1.9%; P < .001). In a multivariable analysis, odds of EoE remained lower for Hispanic vs White patients (OR = 0.20, 95% CI (0.1–0.5), P < .01), after adjustment for hospital setting and primary language. Within the Hispanic subgroup, neither the hospital setting (OR = 1.90, 95% CI (0.3–13.9), P = .53) nor primary spoken language (OR = 0.56, 95% CI (0.1–4.1), P = .56) showed a significant association with EoE.

Conclusion

The prevalence of EoE was significantly higher among Whites than Hispanics. Among Hispanics, the prevalence of EoE was not influenced by hospital setting or primary language. These results suggest that intrinsic factors, including possible genetic influences, may contribute to the disparity in EoE prevalence between the 2 groups.
背景和目的嗜酸性食管炎(EoE)的发病率和患病率正在迅速上升。与西班牙裔相比,它在白人中更为普遍。造成这种差异的原因尚不清楚。我们的目的是比较私立医院和安全网医院之间的EoE患病率,后者治疗外国出生的西班牙语患者的比例更大,并检查两家医院中西班牙裔患者患病率的差异。方法:我们对2个医疗中心因吞咽困难、食物嵌塞或EoE接受上内镜检查的成年患者进行了回顾性横断面研究。主要结果是根据临床、内镜和病理标准诊断出EoE。采用Logistic回归计算EoE的校正优势比(ORs)。结果1005例患者中,西班牙裔患者(73.3%对19.7%)和西班牙语患者(64.8%对7.6%)在安全网医院接受治疗的比例较高。总体而言,70名(7.0%)患者被诊断为EoE,私立医院的患病率高于安全网医院(10.5%对1.9%;P < .001)。在多变量分析中,在调整了医院环境和主要语言后,西班牙裔患者与白人患者发生EoE的几率仍然较低(OR = 0.20, 95% CI (0.1-0.5), P < 0.01)。在西班牙裔亚组中,医院环境(OR = 1.90, 95% CI (0.3-13.9), P = 0.53)和主要口语(OR = 0.56, 95% CI (0.1-4.1), P = 0.56)均未显示与EoE有显著关联。结论白种人的EoE患病率明显高于西班牙裔。在西班牙裔人群中,EoE患病率不受医院环境或主要语言的影响。这些结果表明,内在因素,包括可能的遗传影响,可能导致两组之间EoE患病率的差异。
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引用次数: 0
Identification of Circulating MiR-4651 as Novel Biomarker for Metabolic Dysfunction–Associated Steatotic Liver Disease 循环MiR-4651作为代谢功能障碍相关脂肪变性肝病的新生物标志物的鉴定
Pub Date : 2025-10-30 DOI: 10.1016/j.gastha.2025.100839
Mélanie Kirchmeyer , Anthoula Gaigneaux , Florence A. Servais , Anita Arslanow , Claudia Rubie , Markus Casper , Matthias Glanemann , María L. Martínez-Chantar , Marcin Krawczyk , Frank Lammert , Iris Behrmann

Background and Aims

Metabolic dysfunction–associated steatotic liver disease (MASLD) affects >30% of adults and is becoming one of the leading causes of hepatocellular carcinoma (HCC). Reliable biomarkers are needed for the early diagnosis of HCC and detection of chronic liver diseases, like MASLD. Here we assessed the biomarker potential of circulating microRNAs in a cohort of patients genotyped for the risk allele of patatin-like phospholipase domain-containing protein 3 (PNPLA3), associated with increased susceptibility to chronic liver diseases.

Methods

The cohort comprised 70 MASLD patients (40 with simple steatosis, 9 with metabolic dysfunction–associated steatohepatitis (MASH), 21 with cirrhosis), 47 HCC patients (32 with cirrhosis), and 14 healthy controls. Serum levels of miR-122-5p, miR-146a-5p, miR-146b-5p, miR-21-5p, miR-335-5p, miR-433-3p, miR-4530, miR-4651, miR-526a2, and miR-873-5p were quantified using custom qPCR plates. Their suitability for prediction of MASLD (steatosis/MASH/cirrhosis) or HCC was assessed by receiver operating characteristic curve analyses.

Results

MiR-4651 and miR-21-5p were significantly reduced in sera from patients with MASLD, particularly in those with simple steatosis. Both microRNAs effectively distinguished MASLD patients with simple steatosis from healthy controls (area under the curve: 0.95 and 0.89, respectively). Moreover, miR-4651 emerged as the best predictor for differentiating “complicated” MASLD (i.e., MASH or cirrhosis) from simple steatosis; the predictive values could be increased by including additional parameters into the models (Fibroscan, thrombocytes, cytokines, or other miRNAs). miR-335-5p showed strong ability to differentiate HCC from healthy individuals (area under the curve: 0.86). The PNPLA3 p.I148M genotype was not associated with altered levels of microRNAs.

Conclusion

Serum microRNAs, in particular miR-4651, may serve as additional biomarkers in patients with steatotic liver disease.
背景和目的代谢功能障碍相关的脂肪变性肝病(MASLD)影响了30%的成年人,并正在成为肝细胞癌(HCC)的主要原因之一。HCC的早期诊断和慢性肝病(如MASLD)的检测需要可靠的生物标志物。在这里,我们评估了一组患者中循环microrna的生物标志物潜力,这些患者基因分型为patatin样磷脂酶结构域蛋白3 (PNPLA3)的风险等位基因,与慢性肝病易感性增加相关。方法70例MASLD患者(40例合并单纯性脂肪变性,9例合并代谢功能障碍相关脂肪性肝炎,21例合并肝硬化),47例HCC患者(32例合并肝硬化),14例健康对照。使用定制的qPCR板定量检测miR-122-5p、miR-146a-5p、miR-146b-5p、miR-21-5p、miR-335-5p、miR-433-3p、miR-4530、miR-4651、miR-526a2和miR-873-5p的血清水平。通过受试者工作特征曲线分析评估其预测MASLD(脂肪变性/MASH/肝硬化)或HCC的适用性。结果smir -4651和miR-21-5p在MASLD患者血清中显著降低,特别是在单纯性脂肪变性患者中。这两种microrna都能有效地将单纯脂肪变性的MASLD患者与健康对照区分开来(曲线下面积分别为0.95和0.89)。此外,miR-4651成为区分“复杂”MASLD(即MASH或肝硬化)与单纯性脂肪变性的最佳预测因子;通过在模型中加入其他参数(纤维扫描、血小板、细胞因子或其他mirna),可以提高预测值。miR-335-5p表现出较强的区分健康人HCC的能力(曲线下面积:0.86)。PNPLA3 p.I148M基因型与microrna水平的改变无关。结论血清microrna,特别是miR-4651,可能作为脂肪变性肝病患者的额外生物标志物。
{"title":"Identification of Circulating MiR-4651 as Novel Biomarker for Metabolic Dysfunction–Associated Steatotic Liver Disease","authors":"Mélanie Kirchmeyer ,&nbsp;Anthoula Gaigneaux ,&nbsp;Florence A. Servais ,&nbsp;Anita Arslanow ,&nbsp;Claudia Rubie ,&nbsp;Markus Casper ,&nbsp;Matthias Glanemann ,&nbsp;María L. Martínez-Chantar ,&nbsp;Marcin Krawczyk ,&nbsp;Frank Lammert ,&nbsp;Iris Behrmann","doi":"10.1016/j.gastha.2025.100839","DOIUrl":"10.1016/j.gastha.2025.100839","url":null,"abstract":"<div><h3>Background and Aims</h3><div>Metabolic dysfunction–associated steatotic liver disease (MASLD) affects &gt;30% of adults and is becoming one of the leading causes of hepatocellular carcinoma (HCC). Reliable biomarkers are needed for the early diagnosis of HCC and detection of chronic liver diseases, like MASLD. Here we assessed the biomarker potential of circulating microRNAs in a cohort of patients genotyped for the risk allele of <em>patatin-like phospholipase domain-containing protein 3</em> (<em>PNPLA3</em>), associated with increased susceptibility to chronic liver diseases.</div></div><div><h3>Methods</h3><div>The cohort comprised 70 MASLD patients (40 with simple steatosis, 9 with metabolic dysfunction–associated steatohepatitis (MASH), 21 with cirrhosis), 47 HCC patients (32 with cirrhosis), and 14 healthy controls. Serum levels of miR-122-5p, miR-146a-5p, miR-146b-5p, miR-21-5p, miR-335-5p, miR-433-3p, miR-4530, miR-4651, miR-526a2, and miR-873-5p were quantified using custom qPCR plates. Their suitability for prediction of MASLD (steatosis/MASH/cirrhosis) or HCC was assessed by receiver operating characteristic curve analyses.</div></div><div><h3>Results</h3><div>MiR-4651 and miR-21-5p were significantly reduced in sera from patients with MASLD, particularly in those with simple steatosis. Both microRNAs effectively distinguished MASLD patients with simple steatosis from healthy controls (area under the curve: 0.95 and 0.89, respectively). Moreover, miR-4651 emerged as the best predictor for differentiating “complicated” MASLD (i.e., MASH or cirrhosis) from simple steatosis; the predictive values could be increased by including additional parameters into the models (Fibroscan, thrombocytes, cytokines, or other miRNAs). miR-335-5p showed strong ability to differentiate HCC from healthy individuals (area under the curve: 0.86). The <em>PNPLA3</em> p.I148M genotype was not associated with altered levels of microRNAs.</div></div><div><h3>Conclusion</h3><div>Serum microRNAs, in particular miR-4651, may serve as additional biomarkers in patients with steatotic liver disease.</div></div>","PeriodicalId":73130,"journal":{"name":"Gastro hep advances","volume":"5 2","pages":"Article 100839"},"PeriodicalIF":0.0,"publicationDate":"2025-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145736961","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Endohepatology: Evolving Indications, Challenges, Unmet Needs and Opportunities 内源性肝病:不断发展的适应症、挑战、未满足的需求和机遇
Pub Date : 2025-10-30 DOI: 10.1016/j.gastha.2025.100838
Akash Roy , Mithun Sharma , Anand V. Kulkarni , Sundeep Lakhtakia , Aniruddha Pratap Singh , Rakesh Kalapala , Gregory G. Ginsberg , D.Nageshwar Reddy , K. Rajender Reddy
Endohepatology provides a unison of 2 rapidly developing fields of hepatology and advanced endoscopy. Conventionally, endoscopy in liver disease was restricted primarily to the management of varices. However, multiple new domains have emerged in advanced endoscopy, driven mainly by endoscopic ultrasound (EUS), and as such find several applications in clinical hepatology. Robust data have emerged regarding EUS liver biopsy and the management of gastric varices, and are becoming the first line of care at experienced centers. EUS-guided portal pressure gradient and direct measurements appear to be an exciting frontier for portal pressure assessment. EUS shear wave elastography holds promise but needs standardization and comparison to well-established noninvasive surrogates. Endobariatrics opens up new avenues in optimizing comprehensive obesity management. Interesting crossroads emerge in liver transplantation, where endohepatology may provide a unique single setting investigation and therapeutic solution. Several other potential uses are emerging but need to be replicated across settings. While the advancements usher in excitement, several gaps in knowledge and pragmatic concerns remain with the application of endohepatology, which need to be balanced against patient safety and in optimizing outcomes.
内窥镜提供了肝病学和先进内窥镜两个快速发展领域的统一。传统上,肝脏疾病的内窥镜检查主要局限于静脉曲张的治疗。然而,在内镜超声(EUS)的推动下,先进的内窥镜检查出现了多个新的领域,并在临床肝病学中得到了一些应用。关于EUS肝活检和胃静脉曲张管理的可靠数据已经出现,并且正在成为经验丰富的中心的第一线护理。eus引导门静脉压力梯度和直接测量似乎是门静脉压力评估的一个令人兴奋的前沿。EUS横波弹性成像很有前景,但需要标准化和与已建立的无创替代品进行比较。内窥镜为优化肥胖综合管理开辟了新的途径。有趣的十字路口出现在肝移植中,其中内源性肝病学可能提供独特的单一设置研究和治疗方案。其他一些潜在的用途正在出现,但需要在不同的设置中进行复制。虽然这些进展令人兴奋,但内源性肝病学的应用在知识和实际问题上仍然存在一些差距,需要与患者安全和优化结果相平衡。
{"title":"Endohepatology: Evolving Indications, Challenges, Unmet Needs and Opportunities","authors":"Akash Roy ,&nbsp;Mithun Sharma ,&nbsp;Anand V. Kulkarni ,&nbsp;Sundeep Lakhtakia ,&nbsp;Aniruddha Pratap Singh ,&nbsp;Rakesh Kalapala ,&nbsp;Gregory G. Ginsberg ,&nbsp;D.Nageshwar Reddy ,&nbsp;K. Rajender Reddy","doi":"10.1016/j.gastha.2025.100838","DOIUrl":"10.1016/j.gastha.2025.100838","url":null,"abstract":"<div><div>Endohepatology provides a unison of 2 rapidly developing fields of hepatology and advanced endoscopy. Conventionally, endoscopy in liver disease was restricted primarily to the management of varices. However, multiple new domains have emerged in advanced endoscopy, driven mainly by endoscopic ultrasound (EUS), and as such find several applications in clinical hepatology. Robust data have emerged regarding EUS liver biopsy and the management of gastric varices, and are becoming the first line of care at experienced centers. EUS-guided portal pressure gradient and direct measurements appear to be an exciting frontier for portal pressure assessment. EUS shear wave elastography holds promise but needs standardization and comparison to well-established noninvasive surrogates. Endobariatrics opens up new avenues in optimizing comprehensive obesity management. Interesting crossroads emerge in liver transplantation, where endohepatology may provide a unique single setting investigation and therapeutic solution. Several other potential uses are emerging but need to be replicated across settings. While the advancements usher in excitement, several gaps in knowledge and pragmatic concerns remain with the application of endohepatology, which need to be balanced against patient safety and in optimizing outcomes.</div></div>","PeriodicalId":73130,"journal":{"name":"Gastro hep advances","volume":"5 2","pages":"Article 100838"},"PeriodicalIF":0.0,"publicationDate":"2025-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145737489","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Advancing Esophageal Disease Modeling: Microfluidic Platforms for Adult Tissue–Resident Stem Cell Culture and Differentiation 推进食管疾病建模:成体组织驻留干细胞培养和分化的微流控平台
Pub Date : 2025-10-23 DOI: 10.1016/j.gastha.2025.100837
Sara Hosseini-Farahabadi , Omar Abuhussein , Corina Stewart , Guang Gao , Tenanye Haglund , David Schaeffer , Fergal Donnellan , Frank McKeon , Wa Xian , Dermot Kelleher , Shane Duggan

Background and aims

Classical organoid models of Barrett’s esophagus (BE) lack accessible luminal surfaces, tissue depth and tractable stem cell and immune cell components. Herein, we aimed to seed adult tissue-resident stem cells (ASC) with advanced organ-on-a-chip (OOAC) microfluidics to provide a platform upon which to study the immunobiology of BE and associated high grade dysplasia (HGD).

Methods

ASCs from BE and HGD and gastroesophageal junction (GEJ) were obtained using methods analogous to ground-state stem cell culture and conditional reprogramming. ASC differentiation was achieved on Transwells and flexible OOAC with tissues examined by immunohistochemistry and single-cell RNA sequencing gene expression analysis. Monocytic cell line THP1 was utilized in transmigration experiments.

Results

Monolayered ASCs exhibited colony formation, self-renewal and air–liquid interface-mediated differentiation resulting in 3D furrow formation, mucus production and cell types reflective of tissue of origin-foveolar, goblet, enterocyte-like. Levels of intestinal marker Trefoil Factor 3 were abundant in BE tissue, significantly lower in HGD and absent in GEJ. The gastric marker Gastrokine1 was only expressed in HGD- and GEJ-differentiated ASCs. Comparatively, tissues derived from OOAC displayed significantly enhanced villus-like structure, height, and prolonged survival (<19 days) when compared to Transwell-differentiated equivalents. Single-cell RNAseq analysis detected populations representative of stem cells, transit amplifying stem cells, early and late enterocytes, goblet and enteroendocrine cells and CXCL8 positive immunomodulatory cells in both systems. However, significantly higher levels of proliferating cells, terminal enterocyte-like, Goblet cells, and enteroendocrine-like cells were observed in BE-OOAC systems. THP1 cells were tracked under flow conditions in BE-OOAC and their transmigration through the endothelial layer was evident only in the presence of organoid tissue above.

Conclusion

These findings showed that OOACs offer more physiologically relevant environments, promote deeper cellular differentiation, and increased cellular tractability when seeded as ASCs rather than classical organoid aggregates.
背景和目的经典的Barrett食管(BE)类器官模型缺乏可接近的管腔表面、组织深度和可处理的干细胞和免疫细胞成分。在此,我们的目标是用先进的器官芯片(OOAC)微流体植入成体组织干细胞(ASC),为研究BE和相关的高级别发育不良(HGD)的免疫生物学提供一个平台。方法采用类似于基态干细胞培养和条件重编程的方法,从BE、HGD和胃食管交界处(GEJ)获得sscs。通过免疫组织化学和单细胞RNA测序基因表达分析,在Transwells和柔性OOAC上实现ASC分化。利用单核细胞系THP1进行传代实验。结果单层ASCs表现出集落形成、自我更新和气液界面介导的分化,导致三维沟形成、粘液产生和反映起源组织的细胞类型——凹泡样、杯状、肠细胞样。小肠标志物三叶因子3在BE组织中含量丰富,在HGD中显著降低,在GEJ中不存在。胃标记物Gastrokine1仅在HGD和gej分化的ASCs中表达。相比之下,与Transwell-differentiated equivalents相比,OOAC衍生的组织显示出明显增强的绒毛样结构、高度和延长的存活时间(19天)。单细胞RNAseq分析检测到两个系统中干细胞、转运扩增干细胞、早期和晚期肠细胞、杯状细胞和肠内分泌细胞以及CXCL8阳性免疫调节细胞的代表性群体。然而,在BE-OOAC系统中观察到明显更高水平的增殖细胞、终末肠细胞样细胞、杯状细胞和肠内分泌样细胞。在BE-OOAC的流动条件下追踪THP1细胞,只有在上面有类器官组织的情况下,THP1细胞才能通过内皮层迁移。这些发现表明,与传统的类器官聚集体相比,ooac作为ASCs种子提供了更多的生理相关环境,促进了更深层次的细胞分化,并增加了细胞的可亲和性。
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引用次数: 0
Impact of Mediterranean Fever Gene Mutations on Clinical Characteristics in Patients With Inflammatory Bowel Disease 地中海热基因突变对炎症性肠病患者临床特征的影响
Pub Date : 2025-10-22 DOI: 10.1016/j.gastha.2025.100836
Tomoya Nakamura , Kohei Wagatsuma , Yuki Hayashi , Hiromu Morikubo , Daisuke Saito , Masashi Idogawa , Masanori Nojima , Jun Miyoshi , Minoru Matsuura , Tadakazu Hisamatsu , Hiroshi Nakase

Background and Aims

The Mediterranean fever (MEFV) gene, which encodes a pyrin protein, is the causative gene of familial Mediterranean fever. Patients with inflammatory bowel disease (IBD) have a significantly higher frequency of MEFV mutations than healthy controls; however, the pathological significance of this difference remains unknown. This study investigated the relationship between MEFV mutations and the clinical characteristics of IBD and refractoriness in patients with a confirmed diagnosis of ulcerative colitis (UC) or Crohn's disease (CD).

Methods

This retrospective cohort included 260 patients with UC and 131 patients with CD who visited Sapporo Medical University Hospital or Kyorin University Hospital from April 2021 to March 2023. Demographic and clinical data were collected, and blood samples were examined for MEFV mutations using next generation sequencing.

Results

Mutations of the MEFV gene were found in 60.8% of UC and 56.5% of CD patients. Two or more overlapping mutations were identified in 26.2% patients with UC and 19.8% patients with CD. In patients with IBD, mutations in exons 2 and 3 were associated with extraintestinal manifestations (EIMs), and the coexistence of exon 2 and 3 mutations further strengthened this association. G250R (P = .0096, odds ratio 3.49 [1.36–8.98]) and G304R (P = .039, odds ratio 2.62 [1.05–6.54]) in exon 2, and P373Q (P = .0016, odds ratio 7.86 [2.19–28.26]) in exons 3, were significantly associated with EIMs; when stratifying patients with IBD, this trend was observed in patients with UC, but not in those with CD.

Conclusion

The MEFV mutation rate was higher in Japanese patients with UC and CD than in healthy controls. MEFV mutations could influence EIMs in patients with IBD.
背景与目的地中海热(MEFV)基因是家族性地中海热的致病基因,该基因编码pyrin蛋白。炎症性肠病(IBD)患者的MEFV突变频率明显高于健康对照组;然而,这种差异的病理意义尚不清楚。本研究探讨了MEFV突变与确诊为溃疡性结肠炎(UC)或克罗恩病(CD)患者的IBD临床特征和难治性之间的关系。方法回顾性队列研究纳入2021年4月至2023年3月在札幌医科大学医院或高丽大学医院就诊的260例UC患者和131例CD患者。收集人口统计学和临床数据,并使用下一代测序检测血液样本是否有MEFV突变。结果60.8%的UC和56.5%的CD患者存在MEFV基因突变。在26.2%的UC患者和19.8%的CD患者中发现了两个或两个以上的重叠突变。在IBD患者中,外显子2和3的突变与肠外表现(EIMs)相关,外显子2和3突变的共存进一步加强了这种关联。外显子2的G250R (P = 0.0096,比值比3.49[1.36-8.98])、G304R (P = 0.039,比值比2.62[1.05-6.54])和外显子3的P373Q (P = 0.0016,比值比7.86[2.19-28.26])与EIMs显著相关;在对IBD患者进行分层时,这种趋势在UC患者中出现,而在CD患者中没有。结论日本UC和CD患者的MEFV突变率高于健康对照组。MEFV突变可能影响IBD患者的EIMs。
{"title":"Impact of Mediterranean Fever Gene Mutations on Clinical Characteristics in Patients With Inflammatory Bowel Disease","authors":"Tomoya Nakamura ,&nbsp;Kohei Wagatsuma ,&nbsp;Yuki Hayashi ,&nbsp;Hiromu Morikubo ,&nbsp;Daisuke Saito ,&nbsp;Masashi Idogawa ,&nbsp;Masanori Nojima ,&nbsp;Jun Miyoshi ,&nbsp;Minoru Matsuura ,&nbsp;Tadakazu Hisamatsu ,&nbsp;Hiroshi Nakase","doi":"10.1016/j.gastha.2025.100836","DOIUrl":"10.1016/j.gastha.2025.100836","url":null,"abstract":"<div><h3>Background and Aims</h3><div>The Mediterranean fever (<em>MEFV</em>) gene, which encodes a pyrin protein, is the causative gene of familial Mediterranean fever. Patients with inflammatory bowel disease (IBD) have a significantly higher frequency of <em>MEFV</em> mutations than healthy controls; however, the pathological significance of this difference remains unknown. This study investigated the relationship between <em>MEFV</em> mutations and the clinical characteristics of IBD and refractoriness in patients with a confirmed diagnosis of ulcerative colitis (UC) or Crohn's disease (CD).</div></div><div><h3>Methods</h3><div>This retrospective cohort included 260 patients with UC and 131 patients with CD who visited Sapporo Medical University Hospital or Kyorin University Hospital from April 2021 to March 2023. Demographic and clinical data were collected, and blood samples were examined for <em>MEFV</em> mutations using next generation sequencing.</div></div><div><h3>Results</h3><div>Mutations of the <em>MEFV</em> gene were found in 60.8% of UC and 56.5% of CD patients. Two or more overlapping mutations were identified in 26.2% patients with UC and 19.8% patients with CD. In patients with IBD, mutations in exons 2 and 3 were associated with extraintestinal manifestations (EIMs), and the coexistence of exon 2 and 3 mutations further strengthened this association. G250R (<em>P</em> = .0096, odds ratio 3.49 [1.36–8.98]) and G304R (<em>P</em> = .039, odds ratio 2.62 [1.05–6.54]) in exon 2, and P373Q (<em>P</em> = .0016, odds ratio 7.86 [2.19–28.26]) in exons 3, were significantly associated with EIMs; when stratifying patients with IBD, this trend was observed in patients with UC, but not in those with CD.</div></div><div><h3>Conclusion</h3><div>The <em>MEFV</em> mutation rate was higher in Japanese patients with UC and CD than in healthy controls. <em>MEFV</em> mutations could influence EIMs in patients with IBD.</div></div>","PeriodicalId":73130,"journal":{"name":"Gastro hep advances","volume":"5 2","pages":"Article 100836"},"PeriodicalIF":0.0,"publicationDate":"2025-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145736954","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Type 1 Autoimmune Pancreatitis in a Teenager With Ulcerative Colitis: A Case Report 1型自身免疫性胰腺炎合并溃疡性结肠炎1例报告
Pub Date : 2025-10-10 DOI: 10.1016/j.gastha.2025.100834
Jerry H. Rose , Michael J. Sikorski , Patrick W. Ruane , Dania Hudhud , Abdulhameed M. Al-Sabban
Type 2 autoimmune pancreatitis (AIP) is a recognized complication of ulcerative colitis (UC), whereas type 1 AIP—an immunoglobulin G4-related sclerosing pancreatitis—is uncommon in this patient population and typically presents in older males. We present a case of recurrent pancreatitis in an 18-year-old male with UC. Investigations revealed elevated immunoglobulin G4 levels and images demonstrating diffuse pancreatic strictures and parenchymal enlargement, consistent with type 1 AIP. The patient showed a favorable response to glucocorticoid therapy. This case highlights a potential new association between AIP and UC and emphasizes early recognition and treatment.
2型自身免疫性胰腺炎(AIP)是公认的溃疡性结肠炎(UC)的并发症,而1型AIP(免疫球蛋白g4相关的硬化性胰腺炎)在该患者群体中并不常见,通常出现在老年男性中。我们报告一例复发性胰腺炎在一个18岁的男性与UC。检查显示免疫球蛋白G4水平升高,图像显示弥漫性胰腺狭窄和实质肿大,与1型AIP一致。患者对糖皮质激素治疗反应良好。该病例强调了AIP和UC之间潜在的新关联,并强调了早期识别和治疗。
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引用次数: 0
Weight Change is Associated With Metabolic Liver Health in a General Population Extending Beyond Weight Loss Targets of International Guidelines 体重变化与超出国际指南减肥目标的一般人群的代谢性肝脏健康相关
Pub Date : 2025-10-10 DOI: 10.1016/j.gastha.2025.100831
Laurens A. van Kleef , Mesut Savas , Maurice Michel , Cyrielle Caussy , Jesse Pustjens , Adriaan G. Holleboom , Elisabeth F.C. van Rossum , Harry L.A. Janssen , Jörn M. Schattenberg , Willem P. Brouwer

Background and aims

Weight loss of ≥3%–10% is recommended in metabolic dysfunction–associated steatotic liver disease (MASLD) management, according to current guidelines. We investigated the associations between weight change and impaired metabolic liver health and focused on associations beyond these recommendations.

Methods

Adults from the National Health and Nutrition Examination Survey 2017–2020, with data on 1-year weight history, controlled attenuation parameter and/or liver stiffness measurement (LSM) were selected. Exclusion criteria were age ≥80 years, body mass index <18.5 kg/m2, excessive alcohol and viral hepatitis. Impaired metabolic liver health included MASLD (controlled attenuation parameter ≥275 dB/m with ≥1 cardiometabolic riskfactor), at-risk metabolic dysfunction–associated steatohepatitis (MASH) (FibroScan aspartate aminotransferase score ≥0.35) and LSM ≥8 kPa. Multivariate logistic regression models were adjusted for demographics and prior weight.

Results

We included 6802 individuals (aged 48 years [33–62], 48.9% male). MASLD was present in 42.2%, at-risk MASH in 6.5% and LSM ≥8 kPa in 9.1%. Over 1 year, 29% gained and 28% lost ≥3% weight. Compared to stable weight, weight gain ≥3% was associated with increased MASLD prevalence (adjusted odds ratio (aOR):1.78; 95% confidence interval (CI): 1.48–1.95), at-risk MASH (aOR: 1.78; 95% CI: 1.39–2.29) and LSM ≥8 kPa (aOR:1.48; 95%CI:1.19–1.84); whilst weight loss ≥ 3% was associated with reduced MASLD prevalence (aOR: 0.54; 95% CI: 0.47–0.62), at-risk MASH (aOR: 0.72; 95% CI: 0.55–0.94) and LSM ≥8 kPa (aOR: 0.62; 95% CI: 0.49–0.78). Results were consistent when weight loss was further categorized or when assessed as continuous variable without evidence for nonlinearity.

Conclusion

The prevalence of impaired metabolic liver health decreased with weight loss. Greater reported weight loss was associated with lower observed risks. Hence, we should recommend losing weight beyond the currently recommended targets to further reduce the risk of advanced liver disease.
背景和目的根据目前的指南,在代谢功能障碍相关脂肪变性肝病(MASLD)的治疗中,推荐体重减轻≥3%-10%。我们调查了体重变化与代谢性肝脏健康受损之间的关系,并关注了这些建议之外的关联。方法选取2017-2020年全国健康与营养调查中具有1年体重史、控制衰减参数和/或肝硬度测量(LSM)数据的成年人。排除标准为年龄≥80岁、体重指数≥18.5 kg/m2、过量饮酒和病毒性肝炎。代谢性肝脏健康受损包括MASLD(控制衰减参数≥275 dB/m,伴有≥1个心脏代谢危险因素)、高危代谢功能障碍相关脂肪性肝炎(MASH) (FibroScan天冬氨酸转氨酶评分≥0.35)和LSM≥8 kPa。根据人口统计学和先验权重调整多变量logistic回归模型。结果纳入6802例患者,年龄48岁[33-62],男性48.9%。MASLD占42.2%,高危MASH占6.5%,LSM≥8 kPa占9.1%。在1年内,29%的人体重增加,28%的人体重减轻≥3%。与稳定体重相比,体重增加≥3%与MASLD患病率增加相关(调整优势比(aOR):1.78;95%置信区间(CI): 1.48 - 1.95)、高危MASH (aOR: 1.78; 95%CI: 1.39-2.29)和LSM≥8 kPa (aOR:1.48; 95%CI: 1.19-1.84);而体重减轻≥3%与MASLD患病率降低(aOR: 0.54; 95% CI: 0.47-0.62)、高危MASH (aOR: 0.72; 95% CI: 0.55-0.94)和LSM≥8 kPa (aOR: 0.62; 95% CI: 0.49-0.78)相关。当体重下降被进一步分类或被评估为连续变量而没有非线性证据时,结果是一致的。结论代谢性肝脏健康受损的发生率随体重减轻而降低。报告的体重减轻越多,观察到的风险就越低。因此,我们应该建议在目前推荐的目标之外减肥,以进一步降低晚期肝病的风险。
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引用次数: 0
Plasma Fibulin-5 as a Novel Marker for Advanced Fibrosis in Chronic Hepatitis C 血浆纤维蛋白-5作为慢性丙型肝炎晚期纤维化的新标志物
Pub Date : 2025-10-10 DOI: 10.1016/j.gastha.2025.100827
Yutaka Yasui , Misako Sato-Matsubara , Masaru Enomoto , Tsutomu Matsubara , Mana Kosugi , Kirara Inoue , Truong Huu Hoang , Hideto Yuasa , Hideki Fujii , Atsuko Daikoku , Yoshihiro Ikura , Etsushi Kawamura , Sawako Uchida-Kobayashi , Akihiro Tamori , Norifumi Kawada

Background and Aims

Despite remarkable advances in the treatment of viral hepatitis, liver fibrosis sometimes persists after viral eradication. The accumulation of elastic fiber is associated with unfavorable clinical outcomes. We aimed to clarify the utility of plasma fibulin-5 (FBLN5), a component of elastic fibers, in assessing liver fibrosis in patients with chronic hepatitis.

Methods

We reviewed 90 patients with chronic hepatitis C who underwent liver biopsy. Using immunohistochemistry and in situ hybridization, we investigated the localization of FBLN5 and its correlation with α-smooth muscle actin (αSMA). We then analyzed mRNA and protein expression in human hepatic stellate cells (HHSteCs) and primary mouse stellate cells. Lastly, we evaluated the utility of plasma FBLN5 for predicting liver fibrosis in patients with hepatitis C.

Results

Immunohistochemical analysis revealed a correlation between the quantity of FBLN5 and αSMA (r = 0.65) as well as FBLN5 and fibrosis stage (r = 0.30). FBLN5 was localized to areas enriched for αSMA-positive cells. In situ hybridization confirmed the colocalization of FBLN5 mRNA with αSMA and desmin-positive cells. Single nuclear RNA-sequencing analysis revealed that FBLN5 expression is predominantly expressed in the hepatic stellate cell/fibroblast cluster in other etiology, and the expression level was higher in cirrhotic livers. FBLN5 was overexpressed in cultured HHSteCs in response to 2.0 μg/mL transforming growth factor-β1 (P < .001), with increased FBLN5 concentration in the medium of transforming growth factor-β1-treated activated HHSteC. FBLN5 upregulation was also confirmed in primary-cultured mouse stellate cells. Finally, plasma FBLN5 levels increased with fibrosis progression in patients with chronic hepatitis C (P < .001).

Conclusion

FBLN5 may represent the activation of hepatic stellate cells, and plasma FBLN5 levels have the potential to predict advanced fibrosis, especially in fibrosis related to elastic fibers.
背景和目的尽管病毒性肝炎的治疗取得了显著进展,但肝纤维化有时在病毒根除后仍然存在。弹性纤维的积累与不良的临床结果有关。我们旨在阐明血浆纤维蛋白-5 (FBLN5)在评估慢性肝炎患者肝纤维化中的效用,FBLN5是弹性纤维的一种成分。方法对90例慢性丙型肝炎患者行肝活检。采用免疫组织化学和原位杂交技术,研究FBLN5的定位及其与α-平滑肌肌动蛋白(αSMA)的相关性。然后,我们分析了人肝星状细胞(HHSteCs)和小鼠原代星状细胞mRNA和蛋白的表达。最后,我们评估了血浆FBLN5在预测丙型肝炎患者肝纤维化中的效用。结果免疫组化分析显示FBLN5与αSMA (r = 0.65)以及FBLN5与纤维化分期(r = 0.30)之间存在相关性。FBLN5定位于α sma阳性细胞富集的区域。原位杂交证实FBLN5 mRNA与αSMA和desmin阳性细胞共定位。单核rna测序分析显示,FBLN5在其他病因中主要表达于肝星状细胞/成纤维细胞簇,在肝硬化中表达水平较高。在2.0 μg/mL转化生长因子-β1的作用下,FBLN5在培养的HHSteC中过表达(P < .001),且在转化生长因子-β1处理的活化HHSteC培养基中FBLN5浓度升高。在原代培养的小鼠星状细胞中也证实了FBLN5的上调。最后,慢性丙型肝炎患者血浆FBLN5水平随着纤维化进展而升高(P < 0.001)。结论FBLN5可能代表肝星状细胞的活化,血浆FBLN5水平具有预测晚期纤维化的潜力,特别是与弹性纤维相关的纤维化。
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引用次数: 0
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Gastro hep advances
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