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LETIM Robustly Predicts Immune Checkpoint Blockade Efficacy for Liver Cancer Patients Using Multiple Immune-Related Genesets LETIM使用多个免疫相关基因集稳健地预测肝癌患者免疫检查点阻断疗效。
IF 3.4 3区 医学 Q2 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2026-01-09 DOI: 10.1111/jgh.70232
Siqi Tang, Wenbin Xie, Zijie Wu, Jiawei Yang, Qiang Liu, Xiangdong Gao, Hong Tian, Wenbing Yao

Background and Aims

Immune checkpoint blockade (ICB) is an important liver cancer treatment but shows obvious variability in clinical response due to the tumor immune microenvironment (TIME) heterogeneity. Reliable models that identify TIME characteristics to predict potential beneficiaries remain lacking.

Methods

We analyzed single-cell RNA sequencing (scRNA-seq) data from ICB responsive and nonresponsive liver cancer patients to establish genesets with both intragroup stability and intergroup variability for immune cell status evaluation. These genesets were applied to bulk RNA sequencing (RNA-seq) data from large cohorts to score and construct an ICB response prediction model.

Results

The study identified immune-related genesets characterizing the influence of 21 immune cell types on ICB response. Using these genesets, we developed the Liver Cancer ExtraTrees Immune-response Model (LETIM). LETIM effectively predicted response by distinguishing TIME features. LETIM surpassed existing models in predictive performance and exhibited excellent generalizability in other large liver cancer sequencing cohorts (area under the receiver operating characteristic curve: 0.88–0.92).

Conclusions

Through comprehensive analysis of the effects of multiple immune cells on ICB response, LETIM achieved accurate prediction of ICB outcomes in liver cancer. Its cross-cohort applicability and robust predictive performance may support clinical translation to enable precision medicine and maximize patient benefits.

背景与目的:免疫检查点阻断(Immune checkpoint blockade, ICB)是一种重要的肝癌治疗方法,但由于肿瘤免疫微环境(TIME)的异质性,其临床反应存在明显的变异性。确定时间特征以预测潜在受益者的可靠模型仍然缺乏。方法:我们分析了来自ICB反应性和非反应性肝癌患者的单细胞RNA测序(scRNA-seq)数据,以建立具有组内稳定性和组间变异性的基因集,用于免疫细胞状态评估。这些基因集被应用于来自大型队列的大量RNA测序(RNA-seq)数据,以评分并构建ICB反应预测模型。结果:该研究鉴定了21种免疫细胞类型对ICB反应影响的免疫相关基因集。利用这些基因集,我们建立了肝癌外树免疫反应模型(LETIM)。LETIM通过识别时间特征有效预测响应。LETIM在预测性能上超越了现有模型,并在其他大型肝癌测序队列中表现出出色的通用性(受试者工作特征曲线下面积:0.88-0.92)。结论:LETIM通过综合分析多种免疫细胞对ICB应答的影响,能够准确预测肝癌患者的ICB结局。它的跨队列适用性和强大的预测性能可能支持临床翻译,以实现精准医学和最大化患者利益。
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引用次数: 0
Practice Guidelines for the Diagnosis and Treatment of Subepithelial Lesion Observed in Upper Gastrointestinal Endoscopy 上消化道内窥镜下上皮下病变的诊断和治疗实践指南。
IF 3.4 3区 医学 Q2 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2026-01-08 DOI: 10.1111/jgh.70225
Beom Jin Kim, Seung Joo Kang, Su Youn Nam, Chang Seok Bang, Byung-Hoon Min, Sung Eun Kim, Seung Young Kim, Hyunchul Lim, Chung Hyun Tae, Moon Won Lee, Seung Han Kim, Sang Hoon Kim, Jong Yeul Lee, Byung-Wook Kim, Jeong Seop Moon, Jong-Jae Park, Hwoon-Yong Jung, Korean College of Helicobacter and Upper Gastrointestinal Research

Subepithelial lesions (SELs) of the upper gastrointestinal tract are commonly detected during endoscopic examinations and encompass a broad spectrum of benign, potentially malignant, and malignant tumors. While most SELs are asymptomatic and incidentally found, accurate diagnosis remains challenging due to their subepithelial location, necessitating advanced imaging and tissue acquisition techniques. Endoscopic ultrasound (EUS) plays a crucial role in differentiating SELs, but its diagnostic accuracy remains limited. In response to the need for standardized clinical management, the Korean College of Helicobacter and Upper Gastrointestinal Research has developed evidence-based practice guidelines for the diagnosis and endoscopic treatment of SELs. These guidelines were established through a systematic review of existing literature and expert consensus, resulting in 11 key recommendations addressing diagnostic strategies, surveillance intervals, biopsy techniques, and indications for endoscopic or surgical resection.

上消化道上皮下病变(SELs)通常在内镜检查中发现,包括广泛的良性,潜在的恶性和恶性肿瘤。虽然大多数SELs无症状且偶然发现,但由于其位于上皮下,因此准确诊断仍然具有挑战性,需要先进的成像和组织采集技术。内镜超声(EUS)在诊断SELs中起着至关重要的作用,但其诊断准确性仍然有限。为了应对规范化临床管理的需要,韩国幽门螺杆菌和上消化道研究学院制定了以证据为基础的sel诊断和内镜治疗实践指南。这些指南是通过对现有文献和专家共识的系统回顾而建立的,产生了11项关键建议,涉及诊断策略、监测间隔、活检技术以及内窥镜或手术切除的指征。
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引用次数: 0
Shikonin Attenuates Liver Ischemia-Reperfusion Injury Through Direct Interaction With HMGB1 Protein 紫草素通过与HMGB1蛋白直接相互作用减轻肝脏缺血再灌注损伤。
IF 3.4 3区 医学 Q2 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2026-01-07 DOI: 10.1111/jgh.70200
Libang Zhang, Fang Liu, Pingping Shen, Xuewa Jiang, Richa Raj, Jian Zhang, Guolong Li

Background and Aim

Hepatic ischemia-reperfusion (IR) injury represents a critical clinical challenge characterized by excessive inflammation. HMGB1, known as a proinflammatory mediator released after liver IR injury, has been reported to worsen the damage and inflammation via a positive feedback loop. Herein, shikonin has been explored to alleviate hepatic IR injury through direct interaction with HMGB1.

Methods

The ligation on the hilum of the right liver lobe lasted for 90 min and then removed to induce hepatic IR injury in SD rats. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were determined. At the cellular level, HMGB1-induced NO release from RAW264.7 was assessed to test the inhibitory effect of shikonin. The surface plasmon resonance (SPR), saturation transfer difference nuclear magnetic resonance (STD-NMR), and molecular dynamics simulation were employed to study the interaction between shikonin and HMGB1.

Results

After administration of shikonin, the degree of liver IR damage in rats was attenuated significantly in a dose-dependent manner. In vitro, shikonin can effectively inhibit HMGB1 activation. Furthermore, mechanistic studies indicated that shikonin could directly bind to HMGB1. The results of 1H STD-NMR confirmed that shikonin interacted with HMGB1, and multiple protons in shikonin participated in the binding process. Notably, shikonin exhibits a selective binding affinity toward the I122 and L129-bearing region of HMGB1, which were supported by molecular dynamics simulation.

Conclusion

In general, our results suggest that shikonin is a promising natural candidate that directly targets HMGB1 to exert hepatoprotection for the development of clinical therapeutic anti-IR agents.

背景和目的:肝缺血再灌注损伤是一种严重的临床挑战,其特征是过度炎症。HMGB1是肝脏IR损伤后释放的促炎介质,有报道称其通过正反馈回路加重损伤和炎症。本研究探讨了紫草素通过与HMGB1直接相互作用减轻肝脏IR损伤的作用。方法:SD大鼠右肝门部结扎90 min后取出肝IR损伤。测定血清天冬氨酸转氨酶(AST)和丙氨酸转氨酶(ALT)。在细胞水平上,通过hmgb1诱导RAW264.7释放NO来检测紫草素的抑制作用。采用表面等离子体共振(SPR)、饱和转移差核磁共振(STD-NMR)和分子动力学模拟等方法研究了紫草素与HMGB1的相互作用。结果:紫草素给药后,大鼠肝脏IR损伤程度明显减轻,且呈剂量依赖性。在体外,紫草素能有效抑制HMGB1的激活。此外,机制研究表明,紫草素可以直接与HMGB1结合。1H STD-NMR结果证实了紫草素与HMGB1相互作用,并且紫草素中的多个质子参与了结合过程。值得注意的是,紫草素对HMGB1的I122和l129承载区具有选择性的结合亲和性,这一点得到了分子动力学模拟的支持。结论:总的来说,我们的研究结果表明,紫草素是一种有前景的直接靶向HMGB1发挥肝保护作用的天然候选药物,可用于临床治疗性抗ir药物的开发。
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引用次数: 0
Scissor-Type Knife Improves Trainee's Self-Completion of Endoscopic Submucosal Dissection for Early Gastric Cancer 剪刀型刀提高早期胃癌内镜下粘膜下解剖学员自我完成度。
IF 3.4 3区 医学 Q2 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2026-01-06 DOI: 10.1111/jgh.70216
Hayato Fukui, Osamu Dohi, Naoto Iwai, Mayuko Seya, Tomoko Ochiai, Junki Yumoto, Hiroki Mukai, Katsuma Yamauchi, Hajime Miyazaki, Takeshi Yasuda, Takuma Yoshida, Tsugitaka Ishida, Hiroaki Kitae, Ryohei Hirose, Toshifumi Doi, Ken Inoue, Naohisa Yoshida, Kazuhiko Uchiyama, Takeshi Ishikawa, Tomohisa Takagi, Hideyuki Konishi, Yoshito Itoh

Background

This retrospective study aimed to verify the efficacy of endoscopic submucosal dissection (ESD) using a scissor-type knife for early gastric cancer (EGC).

Methods

The patients who underwent ESD for EGC between April 2014 and March 2022 were enrolled. The primary endpoint of this study was to assess the efficacy of a scissor-type knife by comparing the self-completion rate of trainees between gastric ESD performed using a scissor-type knife (ESD-SC) and nonscissor devices (ESD-NS).

Results

Of the 903 lesions, 485 and 418 underwent ESD-SC and ESD-NS, respectively. The self-completion rate of trainees was significantly higher for ESD-SC than for ESD-NS (50.3 and 33.0%, respectively; p < 0.001). The procedure time was also significantly shorter for ESD-SC (50.0 vs. 66.5 min, respectively; p < 0.001). Intraoperative perforation rate was not significantly different (0.6% for ESD-SC and 1.4% for ESD-NS, respectively). In multivariate analyses, tumor located in the lower third of the stomach (odds ratio [OR] 1.93, 95% confidence interval [CI] 1.46–2.55, p < 0.001), tumor size ≤ 20 mm (OR 3.32, 95% CI 2.20–5.00, p < 0.001), and a scissor-type knife (OR 2.22, 95% CI 1.67–2.94, p < 0.001) were factors related to the self-completion rate of trainees for gastric ESD.

Conclusions

A scissor-type knife was associated with higher self-completion rates and shorter procedure times among trainees. Further prospective studies are needed to validate its clinical utility in ESD training.

背景:本回顾性研究旨在验证剪刀型刀内镜下粘膜下剥离术(ESD)治疗早期胃癌(EGC)的疗效。方法:选取2014年4月~ 2022年3月期间接受ESD治疗的EGC患者。本研究的主要终点是通过比较使用剪刀式刀(ESD- sc)和非剪刀式装置(ESD- ns)进行胃ESD的自我完成率来评估剪刀式刀的疗效。结果:903例病变中,分别有485例和418例接受了ESD-SC和ESD-NS治疗。静电放电- sc手术的自我完成率明显高于静电放电- ns手术(分别为50.3%和33.0%);p结论:剪刀型刀具有更高的自我完成率和更短的手术时间。需要进一步的前瞻性研究来验证其在ESD培训中的临床应用。
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引用次数: 0
Long-Term Outcomes of Surveillance Endoscopy After Endoscopic Resection for Early Esophageal Squamous Cell Carcinoma: A Multicenter Retrospective Study 早期食管鳞状细胞癌内镜切除后监测内镜的长期疗效:一项多中心回顾性研究。
IF 3.4 3区 医学 Q2 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2026-01-06 DOI: 10.1111/jgh.70226
Akira Dobashi, Toshiyuki Yoshio, Tatsunori Minamide, Machi Suka, Yosuke Kishi, Hiroyuki Ono, Kazuki Sumiyama

Background

Endoscopic surveillance is mandatory for patients who underwent endoscopic resection (ER) for esophageal squamous cell carcinoma (ESCC) to detect multiple ESCCs. This study aimed to evaluate whether the current surveillance system is appropriate from the viewpoint of the clinical course after ER.

Methods

This was a retrospective study conducted at a multicenter, high-volume center. Patients who underwent ER without additional therapy for ESCC with T1a pathology were included. The primary endpoints were the 3- and 5-year cumulative incidence of ESCC with invasion depth of the muscularis mucosa or deeper (index ESCC).

Results

A total of 378 patients were included in this analysis. The median observation period was 67.3 (range 24.1–104.3) months. In total, 375 patients underwent surveillance endoscopy with narrow band imaging (NBI), followed by Lugol chromoendoscopy (LCE). The numbers of patients with surveillance intervals of 6 months, 12 months, and irregular were 180, 133, and 65, respectively. There were 275 cases of multiple ESCCs, including 11 index ESCCs. The 3- and 5-year cumulative incidence rates of index ESCCs were 1.3% and 2.7%, respectively. Multiple ESCCs were diagnosed with higher Lugol voiding lesion grades and during 6-month rather than 12-month or irregular surveillance (p < 0.001). However, cox proportional hazards analysis showed no significant factors associated with the cumulative incidence of index ESCCs. No ESCC-related death occurred during the study period.

Conclusion

Surveillance endoscopy with NBI and LCE at intervals of 6–12 months can be acceptable, given the low cumulative incidence of index ESCCs and favorable prognosis.

背景:内镜下监测是食管鳞状细胞癌(ESCC)行内镜切除(ER)的患者必须进行的,以发现多发ESCC。本研究旨在从急诊后临床病程的角度评价目前的监测系统是否合适。方法:这是一项在多中心、高容量中心进行的回顾性研究。接受ER治疗但未接受额外治疗的伴有T1a病理的ESCC患者被纳入研究。主要终点是3年和5年ESCC的累积发病率,其浸润深度为肌层粘膜或更深(ESCC指数)。结果:本分析共纳入378例患者。中位观察期为67.3个月(24.1 ~ 104.3个月)。总共有375例患者接受了窄带成像(NBI)监测内窥镜检查,其次是Lugol色内窥镜检查(LCE)。监测间隔为6个月、12个月和不定期的患者分别为180例、133例和65例。多发性escc 275例,其中指数型escc 11例。指数escc的3年和5年累积发病率分别为1.3%和2.7%。在6个月而非12个月或不规则的监测期间,诊断出多发escc具有较高的Lugol排尿病变等级(p)。结论:考虑到指数escc的低累积发病率和良好的预后,NBI和LCE的监测内镜检查间隔为6-12个月是可以接受的。
{"title":"Long-Term Outcomes of Surveillance Endoscopy After Endoscopic Resection for Early Esophageal Squamous Cell Carcinoma: A Multicenter Retrospective Study","authors":"Akira Dobashi,&nbsp;Toshiyuki Yoshio,&nbsp;Tatsunori Minamide,&nbsp;Machi Suka,&nbsp;Yosuke Kishi,&nbsp;Hiroyuki Ono,&nbsp;Kazuki Sumiyama","doi":"10.1111/jgh.70226","DOIUrl":"10.1111/jgh.70226","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Endoscopic surveillance is mandatory for patients who underwent endoscopic resection (ER) for esophageal squamous cell carcinoma (ESCC) to detect multiple ESCCs. This study aimed to evaluate whether the current surveillance system is appropriate from the viewpoint of the clinical course after ER.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This was a retrospective study conducted at a multicenter, high-volume center. Patients who underwent ER without additional therapy for ESCC with T1a pathology were included. The primary endpoints were the 3- and 5-year cumulative incidence of ESCC with invasion depth of the muscularis mucosa or deeper (index ESCC).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 378 patients were included in this analysis. The median observation period was 67.3 (range 24.1–104.3) months. In total, 375 patients underwent surveillance endoscopy with narrow band imaging (NBI), followed by Lugol chromoendoscopy (LCE). The numbers of patients with surveillance intervals of 6 months, 12 months, and irregular were 180, 133, and 65, respectively. There were 275 cases of multiple ESCCs, including 11 index ESCCs. The 3- and 5-year cumulative incidence rates of index ESCCs were 1.3% and 2.7%, respectively. Multiple ESCCs were diagnosed with higher Lugol voiding lesion grades and during 6-month rather than 12-month or irregular surveillance (<i>p</i> &lt; 0.001). However, cox proportional hazards analysis showed no significant factors associated with the cumulative incidence of index ESCCs. No ESCC-related death occurred during the study period.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Surveillance endoscopy with NBI and LCE at intervals of 6–12 months can be acceptable, given the low cumulative incidence of index ESCCs and favorable prognosis.</p>\u0000 </section>\u0000 </div>","PeriodicalId":15877,"journal":{"name":"Journal of Gastroenterology and Hepatology","volume":"41 2","pages":"734-741"},"PeriodicalIF":3.4,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145911934","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
IgG4-Associated Autoimmune Hepatitis: a Systematic Review igg4相关自身免疫性肝炎:系统综述
IF 3.4 3区 医学 Q2 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2026-01-05 DOI: 10.1111/jgh.70213
Chun-Hsun Liao, Hsu-Hua Tseng, Ting-An Shen, Tzu-Chan Hong, Shih-Jer Hsu, Jia-Horng Kao, Chun-Jen Liu

Background

IgG4-associated autoimmune hepatitis (IgG4-AIH) is an emerging entity characterized by overlapping features of classical autoimmune hepatitis (AIH) and IgG4-related disease (IgG4-RD). However, significant heterogeneity in diagnostic criteria has obscured its true prevalence and clinical significance. This systematic review aimed to characterize the clinical, serological, and histopathological features of IgG4-AIH.

Methods

Following PRISMA guidelines, a systematic search was conducted across PubMed, Embase, and Web of Science. Study selection, data extraction, and quality assessment using Joanna Briggs Institute (JBI) tools were performed independently by two reviewers. A narrative synthesis was conducted.

Results

A total of 43 studies (11 cohort studies, 32 case reports and series) describing 185 patients were included. The cohort was predominantly of Asian origin and showed a female predominance. The most common autoantibody was antinuclear antibody (73%–78%), while serum IgG4 levels were highly variable but exceeded the 135-mg/dL threshold in all cases. Histopathologically, interface hepatitis and plasma cell infiltration were frequent features, and advanced fibrosis (Stages 3–4) was noted in approximately half the patients. Concurrent IgG4-RD was significantly more prevalent in case-based studies versus cohort studies (58% vs. 8.2%, respectively). Glucocorticoid therapy demonstrated high efficacy, with over 70% of patients achieving biochemical remission within three months.

Conclusion

This systematic review characterizes IgG4-AIH as a distinct clinical entity bridging classical AIH and IgG4-RD. Its unique clinical and pathological profile underscores the need for consensus diagnostic criteria and prospective studies to determine optimal management strategies and long-term outcomes.

背景:igg4相关自身免疫性肝炎(IgG4-AIH)是一种以经典自身免疫性肝炎(AIH)和igg4相关疾病(IgG4-RD)重叠特征为特征的新兴实体。然而,诊断标准的显著异质性掩盖了其真实患病率和临床意义。本系统综述旨在描述IgG4-AIH的临床、血清学和组织病理学特征。方法:遵循PRISMA指南,在PubMed, Embase和Web of Science上进行系统搜索。研究选择、数据提取和使用乔安娜布里格斯研究所(JBI)工具进行质量评估由两名审稿人独立完成。进行了叙事综合。结果:共纳入43项研究(11项队列研究,32例病例报告和系列研究),共185例患者。该队列主要是亚洲血统,并显示女性优势。最常见的自身抗体为抗核抗体(73% ~ 78%),血清IgG4水平变化较大,但均超过135 mg/dL阈值。组织病理学上,界面肝炎和浆细胞浸润是常见的特征,大约一半的患者出现晚期纤维化(3-4期)。并发IgG4-RD在基于病例的研究中比在队列研究中更为普遍(分别为58%和8.2%)。糖皮质激素治疗显示出很高的疗效,超过70%的患者在三个月内达到生化缓解。结论:本系统综述将IgG4-AIH定性为典型AIH和IgG4-RD之间的独特临床实体。其独特的临床和病理特征强调了共识诊断标准和前瞻性研究的必要性,以确定最佳的管理策略和长期结果。
{"title":"IgG4-Associated Autoimmune Hepatitis: a Systematic Review","authors":"Chun-Hsun Liao,&nbsp;Hsu-Hua Tseng,&nbsp;Ting-An Shen,&nbsp;Tzu-Chan Hong,&nbsp;Shih-Jer Hsu,&nbsp;Jia-Horng Kao,&nbsp;Chun-Jen Liu","doi":"10.1111/jgh.70213","DOIUrl":"10.1111/jgh.70213","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>IgG4-associated autoimmune hepatitis (IgG4-AIH) is an emerging entity characterized by overlapping features of classical autoimmune hepatitis (AIH) and IgG4-related disease (IgG4-RD). However, significant heterogeneity in diagnostic criteria has obscured its true prevalence and clinical significance. This systematic review aimed to characterize the clinical, serological, and histopathological features of IgG4-AIH.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Following PRISMA guidelines, a systematic search was conducted across PubMed, Embase, and Web of Science. Study selection, data extraction, and quality assessment using Joanna Briggs Institute (JBI) tools were performed independently by two reviewers. A narrative synthesis was conducted.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 43 studies (11 cohort studies, 32 case reports and series) describing 185 patients were included. The cohort was predominantly of Asian origin and showed a female predominance. The most common autoantibody was antinuclear antibody (73%–78%), while serum IgG4 levels were highly variable but exceeded the 135-mg/dL threshold in all cases. Histopathologically, interface hepatitis and plasma cell infiltration were frequent features, and advanced fibrosis (Stages 3–4) was noted in approximately half the patients. Concurrent IgG4-RD was significantly more prevalent in case-based studies versus cohort studies (58% vs. 8.2%, respectively). Glucocorticoid therapy demonstrated high efficacy, with over 70% of patients achieving biochemical remission within three months.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This systematic review characterizes IgG4-AIH as a distinct clinical entity bridging classical AIH and IgG4-RD. Its unique clinical and pathological profile underscores the need for consensus diagnostic criteria and prospective studies to determine optimal management strategies and long-term outcomes.</p>\u0000 </section>\u0000 </div>","PeriodicalId":15877,"journal":{"name":"Journal of Gastroenterology and Hepatology","volume":"41 2","pages":"443-453"},"PeriodicalIF":3.4,"publicationDate":"2026-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jgh.70213","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145906002","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Circulating Tumor Cells as Diagnostic and Therapeutic Biomarkers in Hepatocellular Carcinoma: Advancing Precision Oncology Through Liquid Biopsy 循环肿瘤细胞作为肝细胞癌诊断和治疗的生物标志物:通过液体活检推进精准肿瘤学。
IF 3.4 3区 医学 Q2 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2026-01-05 DOI: 10.1111/jgh.70197
Mutaz Jamal Al-khreisat, Munthar Kadhim-Abosaoda, Namim Abas Ibrahim, Ms Malathi.H, Priya Priyadarshini-Nayak, V. Sathiya-Priya, Gurjant Singh, Ashish Singh Chauhan

Circulating tumor cells (CTCs) are emerging as promising biomarkers in hepatocellular carcinoma (HCC), offering noninvasive insight into tumor biology, progression, and treatment response. Advances in enrichment and single-cell technologies have enabled the characterization of CTCs at genomic, transcriptomic, epigenetic, and proteomic levels. CTC detection correlates with tumor stage, vascular invasion, and alpha-fetoprotein levels, supporting their role in early diagnosis and staging. Specific surface markers such as epithelial cell adhesion molecule, GPC3, ASGPR, and stem cell–associated antigens like CD90 and CD133 help classify CTC subtypes with prognostic and therapeutic relevance. Mesenchymal and hybrid phenotypes, identified via epithelial-to-mesenchymal transition markers, are linked to recurrence and metastasis. Furthermore, CTCs provide a platform for companion diagnostics by reflecting mutational and resistance profiles, particularly in the context of targeted therapies and immune checkpoint inhibitors. Despite current limitations in standardization, sensitivity, and scalability, the integration of CTC analysis into clinical practice holds potential to enhance precision medicine strategies in HCC.

循环肿瘤细胞(CTCs)正在成为肝细胞癌(HCC)中有前途的生物标志物,为肿瘤生物学、进展和治疗反应提供了无创的见解。富集和单细胞技术的进步使ctc在基因组学、转录组学、表观遗传学和蛋白质组学水平上的表征成为可能。CTC检测与肿瘤分期、血管侵犯和甲胎蛋白水平相关,支持其在早期诊断和分期中的作用。特异性表面标志物,如上皮细胞粘附分子、GPC3、ASGPR和干细胞相关抗原如CD90和CD133,有助于对CTC亚型进行分类,并具有预后和治疗相关性。间充质和杂交表型,通过上皮到间充质转化标记确定,与复发和转移有关。此外,ctc通过反映突变和耐药概况,特别是在靶向治疗和免疫检查点抑制剂的背景下,为伴随诊断提供了一个平台。尽管目前在标准化、敏感性和可扩展性方面存在局限性,但将CTC分析整合到临床实践中具有增强HCC精准医疗策略的潜力。
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引用次数: 0
Comment on: “Man Plus Machine: A Randomized Control Trial of Artificial Intelligence Including the Impact of Adjunctive Polyp Detection Techniques” 评论:“人加机器:包括辅助息肉检测技术影响的人工智能随机对照试验”。
IF 3.4 3区 医学 Q2 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2026-01-05 DOI: 10.1111/jgh.70230
Elettra Merola, Giovanni Mario Pes, Maria Pina Dore
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引用次数: 0
The Spleen Promotes Liver Sinusoidal Endothelial Cell Angiogenesis by Stimulating the TGFβ/Smad2/3 Pathway Through GDF15 脾脏通过GDF15刺激TGFβ/Smad2/3通路促进肝窦内皮细胞血管生成
IF 3.4 3区 医学 Q2 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2026-01-05 DOI: 10.1111/jgh.70233
Xi Deng, Na Huang, Ke Du, Hailong Zhang, Ziwei Du, Yudan Fan, Mengchen Zhu, Pengfei Liu, Yanhua Mu, Zongfang Li

Background and Aims

Liver sinusoidal endothelial cells (LSECs) are crucial nonparenchymal cells involved in liver fibrosis progression. Liver fibrosis develops from various chronic liver diseases, with pathological progression associated with the spleen. However, the precise mechanism by which the spleen influences LSECs during fibrosis is not fully understood. This study investigated the spleen's effect on LSEC angiogenesis and its underlying mechanisms using animal and cellular experiments.

Methods

Splenectomy or sham operations were performed on carbon tetrachloride (CCl4)–induced liver fibrosis mice and oil-treated control mice. Intraoperative spleen serum, peripheral serum from hepatitis B cirrhosis patients pre- and post-splenectomy, and normal human peripheral serum were collected and used to treat cultured LSECs. LSEC proliferation, migration, and tubule formation were then assessed. Active serum cytokines were identified by cytokine array analysis, and activated signaling pathways in LSECs were investigated through functional experiments.

Results

The spleen promoted LSEC angiogenesis in fibrotic mice. Compared to peripheral serum, spleen serum from cirrhotic patients significantly enhanced LSEC proliferation, migration, and tubule formation. Growth differentiation factor 15 (GDF15) was elevated in spleen serum and promoted LSEC angiogenesis. In vitro, GDF15 induced Smad2/3 phosphorylation in LSECs. Furthermore, inhibition of Smad3 phosphorylation attenuated the pro-angiogenic effects of spleen serum or GDF15 on LSECs.

Conclusion

The spleen promotes LSEC angiogenesis by activating the TGFβ/Smad2/3 pathway through GDF15 in serum.

背景和目的:肝窦内皮细胞(LSECs)是参与肝纤维化进展的重要非实质细胞。肝纤维化发生于多种慢性肝病,病理进展与脾相关。然而,脾脏在纤维化期间影响LSECs的确切机制尚不完全清楚。本研究通过动物实验和细胞实验探讨脾脏对LSEC血管生成的影响及其潜在机制。方法:对四氯化碳(CCl4)诱导的肝纤维化小鼠和油处理小鼠分别行脾切除术或假手术治疗。收集术中脾血清、乙型肝炎肝硬化患者脾切除术前后外周血血清和正常人外周血血清,用于培养LSECs。然后评估LSEC的增殖、迁移和小管形成。通过细胞因子阵列分析鉴定活性血清细胞因子,并通过功能实验研究LSECs中激活的信号通路。结果:脾脏促进纤维化小鼠LSEC血管生成。与外周血清相比,肝硬化患者的脾血清显著增强LSEC的增殖、迁移和小管形成。脾血清中生长分化因子15 (GDF15)升高,促进LSEC血管生成。在体外,GDF15诱导LSECs中Smad2/3磷酸化。此外,抑制Smad3磷酸化可减弱脾血清或GDF15对LSECs的促血管生成作用。结论:脾脏通过血清GDF15激活TGFβ/Smad2/3通路,促进LSEC血管生成。
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引用次数: 0
An Integrated Systematic Review and Meta-Analysis From the Bloodstream to Identify Potential Biomarkers for ALD, MASLD, and HCC Without a Viral Background 一项来自血液的综合系统评价和荟萃分析,以确定没有病毒背景的ALD、MASLD和HCC的潜在生物标志物。
IF 3.4 3区 医学 Q2 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2026-01-02 DOI: 10.1111/jgh.70228
Karina González-García, Cecilia Zertuche-Martínez, Itayetzi Reyes-Avendaño, Edilburga Reyes-Jiménez, Pablo Muriel, Saúl Villa-Treviño, Jaime Arellanes-Robledo, Rafael Baltiérrez-Hoyos, Verónica Rocío Vásquez-Garzón

Chronic non-viral liver diseases (CNVLD), including alcohol-related liver disease (ALD) and metabolic dysfunction–associated steatotic liver disease (MASLD), have increased in prevalence, surpassing viral hepatitis as the main cause of hepatocellular carcinoma (HCC) in the last decade; thus, the identification of bloodstream biomarkers is essential for early diagnosis, risk stratification, and monitoring progression. This study aimed to systematically integrate and compare proteomic evidence from blood-based studies to identify differentially expressed proteins (DEPs) associated with ALD, MASLD, and HCC of non-viral etiology, to prioritize them as candidates for shared biomarkers and diagnostics for each disease. A systematic review was conducted, followed by a qualitative meta-analysis to identify DEPs bloodstream biomarkers. Biomarkers were compared across diseases to detect overlaps. Functional enrichment, network, and topological analyses were used to evaluate their biological relevance. We identified 16 diagnostic biomarkers for ALD, 53 for MASLD, and 8 for HCC. Four biomarkers were shared among ALD and MASLD, two among ALD and HCC, and two among MASLD and HCC. Functional analyses indicated platelet dysfunction and coagulation pathway alterations in ALD; lipid metabolism dysregulation in MASLD; and a combination of these processes in HCC patients. Network analysis highlighted key biomarkers with potential diagnostic and prognostic applications. The identified biomarkers reflect both shared and disease-specific molecular mechanisms in the progression of CNVLD toward HCC. Their consistent presence across independent studies supports their potential integration into diagnostic and prognostic panels, particularly in the context of the rising prevalence of ALD and MASLD worldwide.

慢性非病毒性肝病(CNVLD),包括酒精相关肝病(ALD)和代谢功能障碍相关脂肪变性肝病(MASLD),患病率增加,在过去十年中超过病毒性肝炎成为肝细胞癌(HCC)的主要原因;因此,血液生物标志物的识别对于早期诊断、风险分层和监测进展至关重要。本研究旨在系统地整合和比较来自血液研究的蛋白质组学证据,以鉴定与ALD、MASLD和非病毒病因的HCC相关的差异表达蛋白(DEPs),并优先考虑它们作为每种疾病的共享生物标志物和诊断候选物。进行了系统评价,随后进行了定性荟萃分析,以确定DEPs血液生物标志物。通过比较不同疾病的生物标志物来发现重叠。功能富集、网络和拓扑分析用于评估它们的生物学相关性。我们确定了16种ALD的诊断性生物标志物,53种用于MASLD, 8种用于HCC。ALD和MASLD共有4个生物标志物,ALD和HCC共有2个,MASLD和HCC共有2个。功能分析提示ALD患者血小板功能障碍及凝血途径改变;MASLD中脂质代谢失调;以及这些过程在HCC患者中的结合。网络分析强调了具有潜在诊断和预后应用的关键生物标志物。鉴定的生物标志物反映了CNVLD向HCC发展的共同和疾病特异性分子机制。它们在独立研究中的一致存在,支持了它们可能被纳入诊断和预后小组,特别是在全球ALD和MASLD患病率上升的背景下。
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Journal of Gastroenterology and Hepatology
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