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Single-cell transcriptomic insights into endosulfan-induced liver injury: Key pathways and inflammatory responses 单细胞转录组学洞察内啡肽诱导的肝损伤:关键途径和炎症反应
Q2 Medicine Pub Date : 2025-06-01 DOI: 10.1016/j.livres.2025.05.002
Pan Huang , Yunmeng Bai , Chaohua Zhou , Xiaoru Zhong , Ashok Iyaswamy , Peng Chen , Xu Wei , Wei Zhang , Chuanbin Yang , Jigang Wang

Background and aims

Environmental pollutants, particularly organochlorine insecticides like endosulfan (ENDO), are increasingly linked to liver toxicity and related diseases. Despite its widespread historical use, the mechanisms underlying ENDO-induced liver damage remain poorly understood. This study aims to elucidate the cellular and molecular mechanisms of ENDO-induced hepatotoxicity.

Methods

C57BL/6 mice were exposed to ENDO for two weeks. Single-cell RNA sequencing (scRNA-seq) was subsequently performed on mouse livers to explore ENDO-induced hepatotoxicity at the single-cell level. Differentially expressed genes (DEGs) across cell types and treatments were identified and then subjected to pathway enrichment to uncover key biological processes affected by ENDO. Transcription factor (TF) regulatory network, pseudotime trajectory, and cellular communication analysis were used to explore the molecular and cellular changes after ENDO exposure.

Results

ENDO not only caused direct hepatocyte injury but also activated hepatic stellate cells and lymphocytes, triggering inflammatory responses with upregulation of multiple key chemokines and cytotoxic genes. Additionally, ENDO exposure led to the recruitment and activation of myeloid cells, contributing to the inflammatory milieu. An increase in intercellular communication and changes to the hepatic microenvironment, especially the interaction between activated hepatic stellate cells and CD8+ T cells were observed, further implicating these processes in ENDO-induced liver damage.

Conclusions

This study provides new insights into the cellular and molecular mechanisms underlying liver injury induced by organochlorine insecticides like ENDO. Key genes and pathways involved in ENDO-associated liver toxicity have been identified at a single-cell resolution. These findings suggest that altered cellular communications and inflammatory responses may play pivotal roles in the pathogenesis of ENDO-induced liver injury.
背景和目的环境污染物,特别是硫丹(ENDO)等有机氯杀虫剂,与肝脏毒性和相关疾病的联系越来越紧密。尽管其历史上广泛使用,但内源性内毒素引起的肝损伤的机制仍然知之甚少。本研究旨在阐明内啡肽诱导肝毒性的细胞和分子机制。方法sc57bl /6小鼠暴露于ENDO 2周。随后对小鼠肝脏进行单细胞RNA测序(scRNA-seq),在单细胞水平上探索内啡肽诱导的肝毒性。鉴定不同细胞类型和处理方式的差异表达基因(DEGs),然后进行途径富集,以揭示受ENDO影响的关键生物过程。利用转录因子(TF)调控网络、伪时间轨迹和细胞通讯分析来探讨ENDO暴露后的分子和细胞变化。结果sendo不仅能直接损伤肝细胞,还能激活肝星状细胞和淋巴细胞,通过上调多种关键趋化因子和细胞毒基因引发炎症反应。此外,ENDO暴露导致骨髓细胞的募集和激活,有助于炎症环境。观察到细胞间通讯的增加和肝脏微环境的改变,特别是活化的肝星状细胞与CD8+ T细胞之间的相互作用,进一步暗示这些过程与内啡肽诱导的肝损伤有关。结论本研究为有机氯杀虫剂ENDO等致肝损伤的细胞和分子机制提供了新的认识。参与endo相关肝毒性的关键基因和途径已经在单细胞分辨率下被确定。这些发现表明,细胞通讯和炎症反应的改变可能在内啡肽诱导的肝损伤的发病机制中起关键作用。
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引用次数: 0
A simplified and reproducible ex vivo model of cold and ischemia-reperfusion injury 一种简化、可重复的体外冷缺血再灌注损伤模型
Q2 Medicine Pub Date : 2025-06-01 DOI: 10.1016/j.livres.2025.04.005
Lele Zhang , Mingjie Ding , Ying Zhu , Zhiping Yan , Wenzhi Guo
Both cold stress and ischemia-reperfusion injury significantly contribute to poor prognosis after liver transplantation (LT). However, limited animal models incorporating both stimuli hinder the advancement of transplant-related research. Here, a simplified and reproducible isolated perfused liver model is established to simulate the stresses experienced by livers maximally during transplantation. We provide a detailed protocol for a straightforward technique that requires 20–30 min for harvesting, 24–48 h for static cold storage (SCS), and 2 h for normothermic machine perfusion (NMP) to induce LT-like stresses in the liver. Hepatic injury from SCS and NMP (LT-like stresses) is evaluated using three types of parameters. The pH values and hepatic enzyme levels of cold preservation solutions and perfusate serve as dynamic indicators of hepatic injury. Bile production and portal venous resistance directly reflect liver function, whereas pathological analysis visually illustrates the location and extent of injury. This animal model eliminates the influence of hemodynamic and immune factors, yielding highly reproducible results, and is strongly recommended as a standardized animal model for inducing LT-like stresses.
冷应激和缺血再灌注损伤都是导致肝移植术后预后不良的重要因素。然而,结合这两种刺激的有限动物模型阻碍了移植相关研究的进展。为了最大限度地模拟肝脏在移植过程中所承受的压力,我们建立了一个简化的、可重复的离体灌注肝脏模型。我们为一种简单的技术提供了详细的方案,该技术需要20-30分钟的收获,24-48小时的静态冷藏(SCS), 2小时的恒温机器灌注(NMP)来诱导肝脏中的lt样应激。使用三种类型的参数评估SCS和NMP (lt样应激)引起的肝损伤。冷保存液和灌注液的pH值和肝酶水平是肝损伤的动态指标。胆汁分泌和门静脉阻力直接反映肝功能,而病理分析直观地说明损伤的位置和程度。该动物模型消除了血流动力学和免疫因素的影响,结果可重复性高,强烈推荐作为诱导lt样应激的标准化动物模型。
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引用次数: 0
National Protect Liver Day 2025 in China: Integrating Traditional Chinese Medicine and Western Medicine to Reverse Liver Cirrhosis 2025年全国护肝日:中西医结合防治肝硬化
Q2 Medicine Pub Date : 2025-06-01 DOI: 10.1016/j.livres.2025.03.002
Cuicui Shi, Jiangao Fan
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引用次数: 0
Non-coding RNAs in alcohol-associated liver disease 非编码rna在酒精相关肝病中的作用
Q2 Medicine Pub Date : 2025-06-01 DOI: 10.1016/j.livres.2025.04.007
Ge Zeng , Hui Gao , Yanchao Jiang , Nazmul Huda , Themis Thoudam , Zhihong Yang , Jing Ma , Jian Sun , Suthat Liangpunsakul
Non-coding RNAs (ncRNAs), encompassing microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), have emerged as critical regulators of gene expression and cellular function. In alcohol-associated liver disease (ALD), chronic alcohol consumption disrupts the expression and function of ncRNAs in the liver and circulation, contributing to the disease's pathogenesis and progression. Dysregulated ncRNAs influence key pathways involved in hepatocyte injury, lipid metabolism, inflammation, and hepatic stellate cell (HSC) activation, thereby exacerbating steatosis, inflammation, and fibrosis. Furthermore, extracellular vesicles play a pivotal role in mediating ncRNA-driven intercellular communication, amplifying liver damage and fibrosis. This review provides a comprehensive overview of the multifaceted roles of ncRNAs in ALD, with a focus on their mechanistic contributions to disease development and progression. Additionally, we discuss the potential of ncRNAs as diagnostic biomarkers and therapeutic targets, emphasizing their translational relevance in addressing the burden of ALD.
非编码rna (ncRNAs),包括微rna (miRNAs)、长链非编码rna (lncRNAs)和环状rna (circRNAs),已经成为基因表达和细胞功能的关键调节因子。在酒精相关性肝病(ALD)中,慢性饮酒会破坏肝脏和循环中ncrna的表达和功能,从而导致疾病的发病和进展。失调的ncrna影响肝细胞损伤、脂质代谢、炎症和肝星状细胞(HSC)活化的关键途径,从而加剧脂肪变性、炎症和纤维化。此外,细胞外囊泡在介导ncrna驱动的细胞间通讯、放大肝损伤和纤维化中发挥关键作用。这篇综述全面概述了ncrna在ALD中的多方面作用,重点是它们对疾病发生和进展的机制贡献。此外,我们讨论了ncrna作为诊断生物标志物和治疗靶点的潜力,强调了它们在解决ALD负担方面的翻译相关性。
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引用次数: 0
Stem cell-based therapeutic strategies for liver aging 基于干细胞的肝衰老治疗策略
Q2 Medicine Pub Date : 2025-06-01 DOI: 10.1016/j.livres.2025.04.003
Huan Niu , Yan-Nan Wang , Yu Ding , Yu-Qing Lin , Jian Qin , Jian-Cheng Wang
Aging is characterized by a gradual deterioration of the physiological integrity of cells, tissues, and organs, resulting in a decrease in the body’s physiological functions and an acceleration of the onset of age-related diseases, ultimately leading to death. The aging of the liver, which is a critical metabolic organ, is closely linked to various chronic liver diseases, such as hepatitis, liver fibrosis, and cirrhosis, and it exacerbates their prognosis and is a primary risk factor for their development at all stages. Therefore, a comprehensive understanding of the causes, mechanisms, and potential therapeutic targets associated with liver aging holds significant clinical importance for delaying or potentially reversing liver aging and for treating chronic liver diseases. Stem cells, which are potential anti-aging agents, present a promising and effective alternative for managing liver aging. In this review, we systematically assess the driving factors, characteristics, and underlying mechanisms of liver aging. We then discuss the current status of the use of stem cells to mitigate liver senescence and address related liver diseases. The review reveals that a stem cell-based approach represents a promising therapeutic strategy for combating liver aging and associated diseases.
衰老的特征是细胞、组织和器官的生理完整性逐渐退化,导致身体生理功能下降,与年龄有关的疾病加速发病,最终导致死亡。肝脏作为一种重要的代谢器官,其衰老与肝炎、肝纤维化、肝硬化等各种慢性肝病密切相关,并使其预后恶化,是其各阶段发展的主要危险因素。因此,全面了解与肝衰老相关的原因、机制和潜在的治疗靶点,对于延缓或潜在逆转肝衰老和治疗慢性肝病具有重要的临床意义。干细胞是一种潜在的抗衰老药物,是治疗肝脏衰老的一种有前途和有效的替代方法。在这篇综述中,我们系统地评估了肝脏衰老的驱动因素、特征和潜在机制。然后,我们讨论了目前使用干细胞来缓解肝脏衰老和解决相关肝脏疾病的现状。综述显示,干细胞为基础的方法代表了一个有前途的治疗策略,以对抗肝脏老化和相关疾病。
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引用次数: 0
Rhizoma Atractylodis Macrocephalae reduces HFD-induced MAFLD in mice through activated AMPK-mediated inhibition of fatty acid synthesis 白术通过激活ampk介导的脂肪酸合成抑制,降低小鼠hfd诱导的MAFLD
Q2 Medicine Pub Date : 2025-06-01 DOI: 10.1016/j.livres.2025.04.004
Ke Zheng , Ruishuo Zhang , Yijing Xin , Yuge Zhou , Jiacheng Lin , Weifan Huang , Fang Wang , Liu Yang , Xuehua Sun , Xiaoni Kong

Background and aims

Metabolic dysfunction-associated fatty liver disease (MAFLD) is a common chronic condition that can lead to cancer due to its complex pathogenesis. Therapeutic agents targeting AMP-activated protein kinase (AMPK) activation have been suggested as potential treatments for metabolic disorders such as metabolic dysfunction-associated steatohepatitis (MASH). Rhizoma Atractylodis Macrocephalae (RAM) has been clinically used to treat obesity-related health problems, but its therapeutic effects on MAFLD and the underlying mechanism remain unclear. Therefore, this study was conducted to evaluate the function and underlying mechanism of RAM in the treatment of MAFLD.

Methods

The effect of RAM decoction on MAFLD was evaluated using a high-fat diet (HFD)-induced MAFLD mouse model. In vitro studies were conducted using a palmitic acid/oleic acid-induced lipid accumulation model in the alpha mouse liver 12 cells and RAM-containing serum. The underlying mechanisms were elucidated through a combination of network pharmacology analysis, immunohistochemistry, western blotting, and polymerase chain reaction analysis.

Results

Administration of RAM decoction significantly reduced body weight gain in MAFLD mice without changing food intake. The weights of the liver and inguinal adipose tissues were also reduced after RAM treatment. Additionally, RAM administration decreased serum levels of alanine aminotransferase, aspartate transaminase, total cholesterol, triglyceride, low-density lipoprotein cholesterol, and glucose, while reducing lipid droplet accumulation in the liver tissues of MAFLD mice. The underlying mechanisms included the activation of the phosphorylation of AMPK and acetyl-CoA carboxylase (ACC), and inhibition of the expression of sterol regulatory element binding protein 1 (SREBP1). However, RAM did not alter the protein expression levels of peroxisome proliferator-activated receptor α and carnitine palmitoyltransferase-1α. Furthermore, the RAM-induced upregulation of phosphorylated AMPK, phosphorylated ACC, and SREBP1 expression, as well as the downregulation of fatty acid synthase expression, were reversed by using an AMPK inhibitor.

Conclusions

Through a combination of network pharmacology and experimental validation, we demonstrated that RAM may exert therapeutic effects on MAFLD by inhibiting lipid synthesis and activating phosphorylated AMPK pathways.
背景与目的代谢功能障碍相关脂肪性肝病(MAFLD)是一种常见的慢性疾病,由于其复杂的发病机制可导致癌症。靶向amp活化蛋白激酶(AMPK)活化的治疗剂已被认为是代谢紊乱(如代谢功能障碍相关脂肪性肝炎(MASH))的潜在治疗方法。巨头苍术已被临床用于治疗肥胖相关的健康问题,但其对MAFLD的治疗作用及其潜在机制尚不清楚。因此,本研究旨在探讨RAM在治疗mald中的作用及其机制。方法采用高脂饮食(HFD)诱导的mald小鼠模型,观察枳椇子煎剂对mald的影响。采用棕榈酸/油酸诱导的脂质积累模型在α小鼠肝12细胞和含ram的血清中进行了体外研究。通过网络药理学分析、免疫组织化学、免疫印迹和聚合酶链反应分析,阐明了其潜在的机制。结果在不改变食物摄取量的情况下,给予RAM煎剂可显著降低MAFLD小鼠的体重增加。RAM处理后肝脏和腹股沟脂肪组织的重量也有所减轻。此外,RAM降低了血清丙氨酸转氨酶、天冬氨酸转氨酶、总胆固醇、甘油三酯、低密度脂蛋白胆固醇和葡萄糖水平,同时减少了MAFLD小鼠肝组织中脂滴的积累。其潜在机制包括激活AMPK和乙酰辅酶a羧化酶(ACC)的磷酸化,抑制甾醇调节元件结合蛋白1 (SREBP1)的表达。然而,RAM没有改变过氧化物酶体增殖物激活受体α和肉碱棕榈酰转移酶-1α的蛋白表达水平。此外,ram诱导的磷酸化AMPK、磷酸化ACC和SREBP1表达的上调,以及脂肪酸合酶表达的下调,通过使用AMPK抑制剂被逆转。结论通过网络药理学和实验验证相结合,我们证明了RAM可能通过抑制脂质合成和激活磷酸化AMPK通路来发挥治疗MAFLD的作用。
{"title":"Rhizoma Atractylodis Macrocephalae reduces HFD-induced MAFLD in mice through activated AMPK-mediated inhibition of fatty acid synthesis","authors":"Ke Zheng ,&nbsp;Ruishuo Zhang ,&nbsp;Yijing Xin ,&nbsp;Yuge Zhou ,&nbsp;Jiacheng Lin ,&nbsp;Weifan Huang ,&nbsp;Fang Wang ,&nbsp;Liu Yang ,&nbsp;Xuehua Sun ,&nbsp;Xiaoni Kong","doi":"10.1016/j.livres.2025.04.004","DOIUrl":"10.1016/j.livres.2025.04.004","url":null,"abstract":"<div><h3>Background and aims</h3><div>Metabolic dysfunction-associated fatty liver disease (MAFLD) is a common chronic condition that can lead to cancer due to its complex pathogenesis. Therapeutic agents targeting AMP-activated protein kinase (AMPK) activation have been suggested as potential treatments for metabolic disorders such as metabolic dysfunction-associated steatohepatitis (MASH). Rhizoma Atractylodis Macrocephalae (RAM) has been clinically used to treat obesity-related health problems, but its therapeutic effects on MAFLD and the underlying mechanism remain unclear. Therefore, this study was conducted to evaluate the function and underlying mechanism of RAM in the treatment of MAFLD.</div></div><div><h3>Methods</h3><div>The effect of RAM decoction on MAFLD was evaluated using a high-fat diet (HFD)-induced MAFLD mouse model. <em>In vitro</em> studies were conducted using a palmitic acid/oleic acid-induced lipid accumulation model in the alpha mouse liver 12 cells and RAM-containing serum. The underlying mechanisms were elucidated through a combination of network pharmacology analysis, immunohistochemistry, western blotting, and polymerase chain reaction analysis.</div></div><div><h3>Results</h3><div>Administration of RAM decoction significantly reduced body weight gain in MAFLD mice without changing food intake. The weights of the liver and inguinal adipose tissues were also reduced after RAM treatment. Additionally, RAM administration decreased serum levels of alanine aminotransferase, aspartate transaminase, total cholesterol, triglyceride, low-density lipoprotein cholesterol, and glucose, while reducing lipid droplet accumulation in the liver tissues of MAFLD mice. The underlying mechanisms included the activation of the phosphorylation of AMPK and acetyl-CoA carboxylase (ACC), and inhibition of the expression of sterol regulatory element binding protein 1 (SREBP1). However, RAM did not alter the protein expression levels of peroxisome proliferator-activated receptor α and carnitine palmitoyltransferase-1α. Furthermore, the RAM-induced upregulation of phosphorylated AMPK, phosphorylated ACC, and SREBP1 expression, as well as the downregulation of fatty acid synthase expression, were reversed by using an AMPK inhibitor.</div></div><div><h3>Conclusions</h3><div>Through a combination of network pharmacology and experimental validation, we demonstrated that RAM may exert therapeutic effects on MAFLD by inhibiting lipid synthesis and activating phosphorylated AMPK pathways.</div></div>","PeriodicalId":36741,"journal":{"name":"Liver Research","volume":"9 2","pages":"Pages 157-168"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144331290","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
Anti-PD-1 synergizes with RFA to suppress abscopal tumors and induce durable memory against recurrence in HCC 抗pd -1与RFA协同抑制体外肿瘤并诱导抗HCC复发的持久记忆
Q2 Medicine Pub Date : 2025-06-01 DOI: 10.1016/j.livres.2025.05.003
Kai Lei , Shuang Li , Jiale Chen , Zebin Chen , Fang Wang , Xuezhen Zeng

Background and aims

Radiofrequency ablation (RFA) is the first-line treatment for early-stage hepatocellular carcinoma (HCC). However, recurrence after curative RFA remains a significant challenge for HCC patients. Although RFA induces an immune response, the anti-tumor effect is often limited by the immunosuppressive tumor microenvironment. Enhancing anti-tumor immunity is essential to improve treatment efficacy and prevent recurrence. In this study, we explore the efficacy and underlying mechanisms of the combination of RFA and anti-PD-1 in suppressing abscopal and recurrent tumors.

Methods

We established a bilateral subcutaneous HCC mouse model and performed complete RFA on the right-flank tumor. Anti-PD-1 or anti-IgG was administered post-RFA. Tumor growth, immune cell profiles, and molecular pathways were assessed using flow cytometry, immunohistochemistry staining, RNA-sequencing, and Western blot. Chemokines released by the tumor were detected by ELISA. An in vivo tumor rechallenge experiment was performed after a complete tumor regression to evaluate the immune memory induced by the RFA+anti-PD-1 treatment.

Results

RFA combined with anti-PD-1 significantly suppressed abscopal tumor growth and prolonged survival. Compared with RFA monotherapy, the infiltration of CD8+T cells and dendritic cells was significantly increased in the combined treatment group, while PMN-MDSCs were markedly reduced. Mechanistically, the chemokine signaling pathway and JAK-STAT signaling pathway were activated in the tumor of the RFA+anti-PD-1 group with upregulation of CXCL10 to recruit CD8+T cells. In addition, the combination therapy induced durable immune memory that inhibited rechallenge tumor outgrowth.

Conclusions

Our study discovered that RFA combined with anti-PD-1 induced anti-tumor immunity to inhibit abscopal tumors and durable immune memory to prevent recurrence, suggesting RFA+anti-PD-1 as a potential therapeutic strategy for multifocal HCC and preventing recurrence.
背景与目的射频消融(RFA)是早期肝细胞癌(HCC)的一线治疗方法。然而,治疗性RFA后的复发仍然是HCC患者面临的一个重大挑战。虽然RFA可诱导免疫应答,但其抗肿瘤作用往往受到肿瘤微环境免疫抑制的限制。增强抗肿瘤免疫是提高治疗效果和预防复发的关键。在这项研究中,我们探讨了RFA和抗pd -1联合抑制体外肿瘤和复发肿瘤的疗效和潜在机制。方法建立小鼠双侧皮下肝癌模型,对右侧肿瘤行完全射频消融。rfa后给予抗pd -1或抗igg。使用流式细胞术、免疫组织化学染色、rna测序和Western blot评估肿瘤生长、免疫细胞谱和分子通路。ELISA法检测肿瘤释放的趋化因子。在肿瘤完全消退后进行体内肿瘤再挑战实验,评估RFA+抗pd -1治疗诱导的免疫记忆。结果rfa联合抗pd -1治疗可显著抑制体外肿瘤生长,延长生存期。与RFA单药治疗相比,联合治疗组CD8+T细胞和树突状细胞的浸润明显增加,PMN-MDSCs明显减少。机制上,RFA+抗pd -1组肿瘤通过上调CXCL10募集CD8+T细胞,激活趋化因子信号通路和JAK-STAT信号通路。此外,联合治疗诱导持久的免疫记忆,抑制肿瘤的再挑战生长。结论我们的研究发现,RFA联合抗pd -1可诱导抗肿瘤免疫抑制体外肿瘤和持久免疫记忆,防止复发,提示RFA+抗pd -1可能是多灶性HCC的治疗策略,可预防复发。
{"title":"Anti-PD-1 synergizes with RFA to suppress abscopal tumors and induce durable memory against recurrence in HCC","authors":"Kai Lei ,&nbsp;Shuang Li ,&nbsp;Jiale Chen ,&nbsp;Zebin Chen ,&nbsp;Fang Wang ,&nbsp;Xuezhen Zeng","doi":"10.1016/j.livres.2025.05.003","DOIUrl":"10.1016/j.livres.2025.05.003","url":null,"abstract":"<div><h3>Background and aims</h3><div>Radiofrequency ablation (RFA) is the first-line treatment for early-stage hepatocellular carcinoma (HCC). However, recurrence after curative RFA remains a significant challenge for HCC patients. Although RFA induces an immune response, the anti-tumor effect is often limited by the immunosuppressive tumor microenvironment. Enhancing anti-tumor immunity is essential to improve treatment efficacy and prevent recurrence. In this study, we explore the efficacy and underlying mechanisms of the combination of RFA and anti-PD-1 in suppressing abscopal and recurrent tumors.</div></div><div><h3>Methods</h3><div>We established a bilateral subcutaneous HCC mouse model and performed complete RFA on the right-flank tumor. Anti-PD-1 or anti-IgG was administered post-RFA. Tumor growth, immune cell profiles, and molecular pathways were assessed using flow cytometry, immunohistochemistry staining, RNA-sequencing, and Western blot. Chemokines released by the tumor were detected by ELISA. An <em>in vivo</em> tumor rechallenge experiment was performed after a complete tumor regression to evaluate the immune memory induced by the RFA+anti-PD-1 treatment.</div></div><div><h3>Results</h3><div>RFA combined with anti-PD-1 significantly suppressed abscopal tumor growth and prolonged survival. Compared with RFA monotherapy, the infiltration of CD8<sup>+</sup>T cells and dendritic cells was significantly increased in the combined treatment group, while PMN-MDSCs were markedly reduced. Mechanistically, the chemokine signaling pathway and JAK-STAT signaling pathway were activated in the tumor of the RFA+anti-PD-1 group with upregulation of CXCL10 to recruit CD8<sup>+</sup>T cells. In addition, the combination therapy induced durable immune memory that inhibited rechallenge tumor outgrowth.</div></div><div><h3>Conclusions</h3><div>Our study discovered that RFA combined with anti-PD-1 induced anti-tumor immunity to inhibit abscopal tumors and durable immune memory to prevent recurrence, suggesting RFA+anti-PD-1 as a potential therapeutic strategy for multifocal HCC and preventing recurrence.</div></div>","PeriodicalId":36741,"journal":{"name":"Liver Research","volume":"9 2","pages":"Pages 132-143"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144331288","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
Insights into the coexistence of Wilson’s disease and chronic hepatitis B: A retrospective propensity score matched study for improving clinical practice 肝豆状核变性和慢性乙型肝炎共存的见解:一项改善临床实践的回顾性倾向评分匹配研究
Q2 Medicine Pub Date : 2025-06-01 DOI: 10.1016/j.livres.2024.12.003
Jiahui Pang , Shuru Chen , Yingfu Zeng, Yutian Chong, Weiqiang Gan, Xinhua Li

Background and aims

Early and accurate diagnosis of the coexistence of Wilson’s disease (WD) and chronic hepatitis B (CHB) presents a significant challenge for clinicians. The objective of this study was to retrospectively analyse the characteristics of such patients to improve clinical practice and provide a reference for clinical management.

Methods

From January 2011 to December 2022, 35 patients with concurrent CHB and WD (CHB + WD group) were identified. A total of 127 patients with CHB (CHB group) and 168 patients with WD (WD group) were included in the control group between January 2016 and December 2021. Propensity score matching (PSM) was performed to balance the baseline values between groups. The Kaplan–Meier (K–M) survival analysis and log-rank test were performed to compare the prognoses.

Results

In the cohort of 35 patients with concurrent CHB and WD, 74.3% of patients (26 patients) faced a substantial delay of up to 10 years (range: 0–40 years) in WD diagnosis following their CHB diagnosis. Twenty-three (65.7%) patients had cirrhosis at the time of WD diagnosis, and 26 (74.3%) patients experienced liver failure. The levels of serum copper and uric acid were lower in patients in the CHB + WD group than in those in the CHB group. Patients in the CHB + WD group presented higher alanine transaminase and total bile acid levels compared to those in the WD group. K–M survival analysis indicated that patients with CHB and WD had poorer outcomes than those with CHB alone; however, the outcomes were similar to those of individuals with WD alone. The optimal cut-point of serum ceruloplasmin (CP) in identifying WD in CHB patients was 0.10 g/L before PSM and after PSM.

Conclusions

The present study emphasizes the importance of clinicians being vigilant for concurrent CHB and WD diagnoses, as delays in WD diagnosis may adversely affect patient outcomes. CHB patients with serum CP below 0.10 g/L are highly recommended to screen for WD.
背景与目的早期准确诊断肝豆状核变性(WD)和慢性乙型肝炎(CHB)的共存是临床医生面临的一个重大挑战。本研究的目的是回顾性分析此类患者的特点,以改善临床实践,为临床管理提供参考。方法2011年1月至2022年12月,选取35例CHB合并WD患者(CHB + WD组)。2016年1月至2021年12月,共纳入127例CHB患者(CHB组)和168例WD患者(WD组)作为对照组。采用倾向评分匹配(PSM)来平衡各组之间的基线值。采用Kaplan-Meier (K-M)生存分析和log-rank检验比较预后。结果在35例合并CHB和WD的患者队列中,74.3%的患者(26例)在CHB诊断后WD诊断面临长达10年(范围:0-40年)的实质性延迟。23例(65.7%)患者在WD诊断时已出现肝硬化,26例(74.3%)患者出现肝功能衰竭。CHB + WD组患者血清铜和尿酸水平低于CHB组。CHB + WD组患者的丙氨酸转氨酶和总胆汁酸水平高于WD组。K-M生存分析表明,合并CHB和WD的患者预后比单独患有CHB的患者差;然而,结果与单独患有WD的个体相似。诊断CHB患者WD的最佳切割点是PSM前和PSM后血清铜蓝蛋白(CP)为0.10 g/L。本研究强调了临床医生警惕慢性乙型肝炎和WD同时诊断的重要性,因为WD诊断的延迟可能会对患者的预后产生不利影响。强烈建议血清CP低于0.10 g/L的慢性乙型肝炎患者进行WD筛查。
{"title":"Insights into the coexistence of Wilson’s disease and chronic hepatitis B: A retrospective propensity score matched study for improving clinical practice","authors":"Jiahui Pang ,&nbsp;Shuru Chen ,&nbsp;Yingfu Zeng,&nbsp;Yutian Chong,&nbsp;Weiqiang Gan,&nbsp;Xinhua Li","doi":"10.1016/j.livres.2024.12.003","DOIUrl":"10.1016/j.livres.2024.12.003","url":null,"abstract":"<div><h3>Background and aims</h3><div>Early and accurate diagnosis of the coexistence of Wilson’s disease (WD) and chronic hepatitis B (CHB) presents a significant challenge for clinicians. The objective of this study was to retrospectively analyse the characteristics of such patients to improve clinical practice and provide a reference for clinical management.</div></div><div><h3>Methods</h3><div>From January 2011 to December 2022, 35 patients with concurrent CHB and WD (CHB + WD group) were identified. A total of 127 patients with CHB (CHB group) and 168 patients with WD (WD group) were included in the control group between January 2016 and December 2021. Propensity score matching (PSM) was performed to balance the baseline values between groups. The Kaplan–Meier (K–M) survival analysis and log-rank test were performed to compare the prognoses.</div></div><div><h3>Results</h3><div>In the cohort of 35 patients with concurrent CHB and WD, 74.3% of patients (26 patients) faced a substantial delay of up to 10 years (range: 0–40 years) in WD diagnosis following their CHB diagnosis. Twenty-three (65.7%) patients had cirrhosis at the time of WD diagnosis, and 26 (74.3%) patients experienced liver failure. The levels of serum copper and uric acid were lower in patients in the CHB + WD group than in those in the CHB group. Patients in the CHB + WD group presented higher alanine transaminase and total bile acid levels compared to those in the WD group. K–M survival analysis indicated that patients with CHB and WD had poorer outcomes than those with CHB alone; however, the outcomes were similar to those of individuals with WD alone. The optimal cut-point of serum ceruloplasmin (CP) in identifying WD in CHB patients was 0.10 g/L before PSM and after PSM.</div></div><div><h3>Conclusions</h3><div>The present study emphasizes the importance of clinicians being vigilant for concurrent CHB and WD diagnoses, as delays in WD diagnosis may adversely affect patient outcomes. CHB patients with serum CP below 0.10 g/L are highly recommended to screen for WD.</div></div>","PeriodicalId":36741,"journal":{"name":"Liver Research","volume":"9 2","pages":"Pages 169-177"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144331291","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
Patients with chronic hepatitis B under nucleos(t)ide analog therapy with Omicron BA.5 infection: A retrospective study in South China 慢性乙型肝炎核苷类似物治疗伴欧米克隆ba5感染:华南地区回顾性研究
Q2 Medicine Pub Date : 2025-03-01 DOI: 10.1016/j.livres.2024.11.003
Peipei Wang , Junjian Chen , Dabiao Chen , Ziying Lei , Zhishuo Mo , Ying Zhang

Background and aims

Clinical data regarding patients with chronic hepatitis B (CHB) after Omicron BA.5 infection are currently limited. This study aimed to assess the clinical characteristics of patients with CHB and Omicron BA.5 infection in South China.

Methods

This retrospective study was conducted from January to March 2023 in a cohort of 485 healthy individuals and 553 patients with CHB. Clinical features, encompassing COVID-19-related symptoms, levels of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies, vaccination status, liver functions, and virological markers of hepatitis B virus (HBV) infection were measured.

Results

COVID-19-related symptom patterns were similar in both groups, except for fever, which was notably less prevalent (85.4% vs. 90.4%, P = 0.047) among patients with CHB who experienced a significantly shorter duration of fever (median 2.2 (25th–75th percentile, 1.0–3.0) days vs. 2.3 (1.0–3.0) days, P = 0.048) and a shorter time for symptom relief (9.2 (5.0–14.0) vs. 11.1 (5.0–14.0) days, P = 0.015). The levels of SARS-CoV-2 antibodies were comparable between the two groups but increased after booster vaccinations. In patients with CHB, globulin (GLB) and hepatitis B envelope antibody levels were significantly increased after Omicron BA.5 infection, regardless of nucleos(t)ide analog regimens comparing entecavir (ETV) with tenofovir (TFV). Patients with CHB treated with TFV had significantly higher levels of SARS-CoV-2 antibodies than those treated with ETV (1065.1 (346.9–1188.5) COI vs. 765.5 (24.5–1119.1) COI, P = 0.025).

Conclusions

No significant exacerbation of COVID-19 symptoms was observed in conjunction with the efficacy of COVID-19 booster vaccinations. There were no notable alterations in liver functions except for GLB. HBV reactivation, as evidenced by increased HBV DNA, was observed among patients with CHB after Omicron BA.5 infection. These changes were not affected by ETV versus TFV administration; however, TFV resulted in a significant increase in SARS-CoV-2 antibody levels. Further studies are required to improve care and therapeutics for patients with CHB who contracted COVID-19.
背景和目的目前关于慢性乙型肝炎(CHB)患者感染Omicron BA.5后的临床资料有限。本研究旨在评估华南地区慢性乙型肝炎患者和Omicron BA.5感染的临床特征。方法本研究于2023年1月至3月在485名健康人和553名慢性乙型肝炎患者中进行回顾性研究。测量临床特征,包括covid -19相关症状、严重急性呼吸综合征冠状病毒2 (SARS-CoV-2)抗体水平、疫苗接种状况、肝功能和乙型肝炎病毒(HBV)感染病毒学标志物。结果两组患者中与scovd -19相关的症状模式相似,但CHB患者发热明显较低(85.4%比90.4%,P = 0.047),发热持续时间明显较短(中位数为2.2(25 - 75个百分点,1.0-3.0)天,P = 0.048),症状缓解时间较短(9.2(5.0-14.0)比11.1(5.0-14.0)天,P = 0.015)。两组之间的SARS-CoV-2抗体水平相当,但在加强疫苗接种后增加。在CHB患者中,球蛋白(GLB)和乙型肝炎包膜抗体水平在Omicron BA.5感染后显著升高,无论采用哪种核苷(t)类似物方案比较恩替卡韦(ETV)和替诺福韦(TFV)。用TFV治疗的CHB患者的SARS-CoV-2抗体水平明显高于用ETV治疗的CHB患者(1065.1 (346.9-1188.5)COI vs 765.5 (24.5-1119.1) COI, P = 0.025)。结论COVID-19加强疫苗接种后无明显症状加重。除GLB外,其他肝功能无明显改变。在感染欧米克隆BA.5后的CHB患者中观察到HBV再激活,证明HBV DNA升高。这些变化不受ETV和TFV管理的影响;然而,TFV导致SARS-CoV-2抗体水平显著升高。需要进一步的研究来改善感染COVID-19的慢性乙型肝炎患者的护理和治疗方法。
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引用次数: 0
An 82-year-old recipient of split liver transplantation worldwide: A case report 全球一例82岁肝移植受者:1例报告
Q2 Medicine Pub Date : 2025-03-01 DOI: 10.1016/j.livres.2024.12.004
Xiao Feng , Binsheng Fu , Qing Yang , Kaining Zeng , Huimin Yi , Shuhong Yi , Yang Yang
Split liver transplantation (SLT) has become an indispensable method for expanding the donor liver pool. However, advanced age in recipients can have significant adverse effects on prognosis. We report the case of an 82-year-old man with chronic liver failure and polycystic liver disease who underwent in vivo split right triple lobe donor liver transplantation on October 29, 2021. The patient made a remarkable recovery and was discharged 1 month after surgery. To date, he has been followed up for 32 months, with favorable laboratory and imaging test results, and no significant abnormalities or complications. Currently, this patient may be the oldest SLT recipient in the world. With comprehensive preoperative evaluation, optimized surgical techniques, and individually tailored postoperative care, older adults can safely undergo SLT. Therefore, advanced age should not be considered an absolute contraindication for this procedure.
劈裂肝移植已成为扩大供肝池不可缺少的一种方法。然而,高龄受者对预后有明显的不良影响。我们报告一例患有慢性肝功能衰竭和多囊性肝病的82岁男性患者于2021年10月29日接受了活体右三叶供肝移植。患者恢复良好,术后1个月出院。到目前为止,他已经随访了32个月,实验室和影像学检查结果良好,没有明显的异常或并发症。目前,这名患者可能是世界上年龄最大的SLT受体。通过全面的术前评估、优化的手术技术和个性化的术后护理,老年人可以安全地接受SLT。因此,高龄不应被视为该手术的绝对禁忌症。
{"title":"An 82-year-old recipient of split liver transplantation worldwide: A case report","authors":"Xiao Feng ,&nbsp;Binsheng Fu ,&nbsp;Qing Yang ,&nbsp;Kaining Zeng ,&nbsp;Huimin Yi ,&nbsp;Shuhong Yi ,&nbsp;Yang Yang","doi":"10.1016/j.livres.2024.12.004","DOIUrl":"10.1016/j.livres.2024.12.004","url":null,"abstract":"<div><div>Split liver transplantation (SLT) has become an indispensable method for expanding the donor liver pool. However, advanced age in recipients can have significant adverse effects on prognosis. We report the case of an 82-year-old man with chronic liver failure and polycystic liver disease who underwent <em>in vivo</em> split right triple lobe donor liver transplantation on October 29, 2021. The patient made a remarkable recovery and was discharged 1 month after surgery. To date, he has been followed up for 32 months, with favorable laboratory and imaging test results, and no significant abnormalities or complications. Currently, this patient may be the oldest SLT recipient in the world. With comprehensive preoperative evaluation, optimized surgical techniques, and individually tailored postoperative care, older adults can safely undergo SLT. Therefore, advanced age should not be considered an absolute contraindication for this procedure.</div></div>","PeriodicalId":36741,"journal":{"name":"Liver Research","volume":"9 1","pages":"Pages 74-78"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143679007","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
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Liver Research
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