Annals of hepatology最新文献_第4页

Role of waist circumference, body mass index and high-sensitivity C-reactive protein in pediatric steatotic liver disease: A cross-sectional study 腰围、体重指数和高敏c反应蛋白在小儿脂肪变性肝病中的作用：一项横断面研究

IF 3.7 3区医学 Q2 GASTROENTEROLOGY & HEPATOLOGY

Annals of hepatology

Pub Date : 2025-01-01 DOI: 10.1016/j.aohep.2024.101759

Qiaoling Wu , Yongmei Peng , Chundan Gong

Introduction and Objectives

Relationships and interactions among waist circumference (WC), body mass index (BMI) and high-sensitivity C-reactive protein (hs-CRP) with steatotic liver disease (SLD) in children have rarely been studied as a whole. We aimed to investigate the association among WC, BMI and hs-CRP with SLD and its related metabolic indictors.

Materials and Methods

A total of 10,776 children aged 10–15 years were screened in our study. Anthropometric data, biochemical parameters and ultrasound assessments were collected. Metabolic indictors between children with and without SLD were compared. The correlation of waist circumference Z score (ZWC), body mass index Z score (ZBMI) and hs-CRP with SLD and its related metabolic indictors, and the interactive effect between ZWC with hs-CRP and ZBMI with hs-CRP upon SLD, respectively, was tested.

Results

A total of 543 children with normal BMI (n = 287) and high BMI (n = 256) were examined. Hs-CRP, ZWC and ZBMI were all found to significantly correlate with SLD and its related metabolic indexes. The interaction effect analysis showed that ZWC and male was independent risk factor of SLD with OR (95 %CI) of 23.431 (7.253, 75.697) and 7.927 (2.766,22.713), respectively, whereas the same effect wasn't found in ZBMI. The cut-off value of ZWC for the prediction of SLD was 1.494 and 1.541 in boys and girls, respectively.

Conclusions

Increased WC, BMI and hs-CRP exerts adverse effect in pediatric SLD and its related metabolic indictors. WC and male gender could be independent risk factors for SLD, and WC was a powerful index for the prediction of SLD in children aged 10–15 years.

前言与目的：目前很少对儿童腰围（WC）、体重指数（BMI）和高敏c反应蛋白（hs-CRP）与脂肪变性肝病（SLD）的关系和相互作用进行整体研究。我们旨在探讨WC、BMI和hs-CRP与SLD及其相关代谢指标的关系。材料与方法：本研究共筛选10,776名10-15岁儿童。收集人体测量数据、生化参数和超声评估。比较有无SLD患儿的代谢指标。检验腰围Z评分（ZWC）、体重指数Z评分（ZBMI）、hs-CRP与SLD及其相关代谢指标的相关性，以及ZWC与hs-CRP、ZBMI与hs-CRP对SLD的交互作用。结果：共检查BMI正常儿童（n=287）和BMI高儿童（n=256） 543例。Hs-CRP、ZWC、ZBMI均与SLD及其相关代谢指标显著相关。互作效应分析显示，ZWC和男性是SLD的独立危险因素，OR （95%CI）分别为23.431（7.253,75.697）和7.927(2.766,22.713)，而ZBMI无相同影响。ZWC预测男孩和女孩SLD的临界值分别为1.494和1.541。结论：WC、BMI、hs-CRP升高对儿童SLD及其相关代谢指标有不利影响。WC和男性性别可能是SLD的独立危险因素，WC是预测10-15岁儿童SLD的有力指标。

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引用次数: 0

An exploratory machine learning model for predicting advanced liver fibrosis in autoimmune hepatitis patients: A preliminary study 预测自身免疫性肝炎患者晚期肝纤维化的探索性机器学习模型：初步研究

IF 3.7 3区医学 Q2 GASTROENTEROLOGY & HEPATOLOGY

Annals of hepatology

Pub Date : 2025-01-01 DOI: 10.1016/j.aohep.2024.101754

Qinglin Wei , Wen Li , Shubei He , Hongbo Wu , Qiaoling Xie , Ying Peng , Xingyue Zhang

Introduction and Objectives

Advanced fibrosis is a crucial stage in the progression of autoimmune hepatitis (AIH), where fibrosis can either regress or advance. This study aims to leverage machine learning (ML) models for the assessment of advanced liver fibrosis in AIH patients using routine clinical features.

Patients and Methods

A total of 233 patients diagnosed with AIH and underwent liver biopsy were included in the discovery cohort. The dataset was randomly split into training and testing sets. Patients were categorized into groups with no/minimal/moderate fibrosis and advanced fibrosis. Six ML models were employed to identify the optimal model. Subsequently, the predictive capability of the best ML model was validated in an additional cohort (n = 33) and compared with conventional noninvasive fibrosis scores.

Results

Three key clinical features, including prothrombin time (PT), albumin (ALB), and ultrasound spleen thickness (UTST), were analyzed by least absolute shrinkage and selection operator (LASSO) regression. In the training set, the random forest (RF) model showed the highest diagnostic performance in predicting advanced fibrosis stage (AUC=0.951). In the testing cohort and validation cohort, the RF model maintained high accuracy (AUC = 0.863 and AUC = 0.843). Additionally, the random forest model outperformed the conventional noninvasive fibrosis scores.

Conclusions

ML models, particularly the RF model, can help improve the discrimination of advanced liver fibrosis in patients with AIH.

简介和目的：晚期纤维化是自身免疫性肝炎（AIH）进展的关键阶段，在此阶段纤维化可退可进。本研究旨在利用机器学习（ML）模型，利用常规临床特征评估AIH患者的晚期肝纤维化。患者和方法：共有233名确诊为AIH并接受肝活检的患者被纳入发现队列。数据集随机分为训练集和测试集。患者分为无/轻度/中度纤维化组和晚期纤维化组。采用6个ML模型来确定最优模型。随后，在另一个队列中验证了最佳ML模型的预测能力（n = 33），并与传统的非侵入性纤维化评分进行了比较。结果：采用最小绝对收缩和选择算子（LASSO）回归分析凝血酶原时间（PT）、白蛋白（ALB）和超声脾厚度（UTST） 3个关键临床特征。在训练集中，随机森林（RF）模型预测纤维化晚期的诊断性能最高（AUC=0.951）。在检验队列和验证队列中，RF模型保持较高的准确性（AUC = 0.863,AUC = 0.843）。此外，随机森林模型优于传统的非侵入性纤维化评分。结论：ML模型，尤其是RF模型有助于提高AIH患者晚期肝纤维化的鉴别能力。

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引用次数: 0

Challenges in the management of alcohol-associated liver disease in Latin America 拉丁美洲酒精相关肝病管理面临的挑战

IF 3.7 3区医学 Q2 GASTROENTEROLOGY & HEPATOLOGY

Annals of hepatology

Pub Date : 2025-01-01 DOI: 10.1016/j.aohep.2024.101748

Francisco Idalsoaga , Luis Antonio Diaz , Gustavo Ayares , Marco Arrese , Juan Pablo Arab

引用次数: 0

Integrated analyses and a novel nomogram for the prediction of significant fibrosis in patients 综合分析和一种预测患者显著纤维化的新nomogram。

IF 3.7 3区医学 Q2 GASTROENTEROLOGY & HEPATOLOGY

Annals of hepatology

Pub Date : 2025-01-01 DOI: 10.1016/j.aohep.2024.101744

Mengxin Lu , Shuai Tao , Xinyan Li , Qunling Yang , Cong Du , Weijia Lin , Shuangshuang Sun , Conglin Zhao , Neng Wang , Qiankun Hu , Yuxian Huang , Qiang Li , Yi Zhang , Liang Chen

Introduction and Objectives

This study aimed to explore the key genes involved in the pathophysiological process of liver fibrosis and develop a novel predictive model for noninvasive assessment of significant liver fibrosis patients.

Patients and Methods

Differentially expressed genes (DEGs) were identified using the Limma package. The hub genes were explored using the CytoHubba plugin app and validated in GEO datasets and cell models. Furthermore, serum LTBP2 was measured in liver fibrosis (LF) patients with biopsy-proven by ELISA. All patients' clinical characteristics and laboratory results were analyzed. Finally, multivariate logistic regression analysis was used to construct the model for visualization by nomogram. Area under the receiver operating characteristic curve (AUROC) analysis, calibration curves, and decision curve analysis (DCA) certify the accuracy of the nomogram.

Results

RNA sequencing was performed on the liver tissues of 66 biopsy-proven HBV-LF patients. After multiple analyses and in vitro simulation of HSC activation, LTBP2 was found to be the most associated with HSC activation regardless of the causes. Serum LTBP2 expression was measured in 151 patients with biopsy, and LTBP2 was found to increase in parallel with the fibrosis stage. Multivariate logistic regression analysis showed that LTBP2, PLT and AST levels were demonstrated as the independent prediction factors. A nomogram that included the three factors was tabled to evaluate the probability of significant fibrosis occurrence. The AUROC of the nomogram model was 0.8690 in significant fibrosis diagnosis.

Conclusions

LTBP2 may be a new biomarker for liver fibrosis patients. The nomogram showed better diagnostic performance in patients.

前言与目的：本研究旨在探索肝纤维化病理生理过程中涉及的关键基因，并建立一种新的无创评估肝纤维化患者的预测模型。患者和方法：采用Limma试剂盒对差异表达基因（deg）进行鉴定。使用CytoHubba插件应用程序对中心基因进行了探索，并在GEO数据集和细胞模型中进行了验证。此外，通过ELISA检测经活检证实的肝纤维化（LF）患者血清LTBP2。分析所有患者的临床特征和实验室结果。最后，采用多元逻辑回归分析构建模型，并进行nomogram可视化分析。接收机工作特性曲线（AUROC）下面积分析、校准曲线和决策曲线分析（DCA）证明了nomogram的准确性。结果：对66例活检证实的HBV-LF患者的肝组织进行了RNA测序。经过多次分析和体外模拟HSC激活后，我们发现LTBP2与HSC激活的相关性最大，无论其原因如何。在151例活检患者中检测血清LTBP2表达，发现LTBP2与纤维化分期平行增加。多因素logistic回归分析显示，LTBP2、PLT和AST水平是独立的预测因素。将包含这三个因素的图列出来，以评估发生显著纤维化的可能性。图模型诊断显著纤维化AUROC为0.8690。结论：LTBP2可能是肝纤维化患者新的生物标志物。该图对患者的诊断效果较好。

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引用次数: 0

Lipocalin-2 silencing alleviates sepsis-induced liver injury through inhibition of ferroptosis Lipocalin-2沉默通过抑制铁下垂减轻败血症诱导的肝损伤。

IF 3.7 3区医学 Q2 GASTROENTEROLOGY & HEPATOLOGY

Annals of hepatology

Pub Date : 2025-01-01 DOI: 10.1016/j.aohep.2024.101756

Yuping Li , Lu Li , Yuming Zhang , Qi Yun , Ruoli Du , Hongwei Ye , Zhenghong Li , Qin Gao

Introduction and Objectives

Liver plays a key role in sepsis, a systemic inflammatory response syndrome caused by infection. Ferroptosis is involved in sepsis-induced liver injury. We aimed to assess the changes in ferroptosis in cecal ligation and puncture (CLP)-induced septic mice, and determine the role of lipocalin-2 (LCN2) in liver ferroptosis.

Materials and Methods

CLP was used to induce sepsis in mice. The morphological changes in liver tissues and mitochondrial structure were observed using hematoxylin and eosin staining and transmission electron microscopy. The levels of serum alanine transaminase, aspartate aminotransferase, superoxide dismutase, and malondialdehyde were detected using the corresponding kits. The changes of reactive oxygen species level in liver tissues were detected using dihydroethidium as a fluorescence probe. LCN2, cysteine-glutamate reverse transport system, and dihydroorotate dehydrogenase protein levels in the liver were detected by western blotting. The ferroptosis inhibitor ferrostatin-1 (Fer-1), iron chelator dexrazoxane (DXZ), iron-dextran, and LCN2 knockdown studies were performed to determine role of ferroptosis and LCN2 in liver injury during sepsis.

Results

Ferroptosis levels increased in the liver tissues of CLP-induced septic mice. Both Fer-1 and DXZ suppressed ferroptosis and attenuated liver injury following sepsis challenge, whereas iron-dextran increased ferroptosis and liver injury in mice with sepsis. LCN2 knockdown suppressed ferroptosis and reduced oxidative stress in the liver.

Conclusions

Ferroptosis inhibition attenuates septic liver injury. LCN2 knockdown alleviates sepsis-induced liver injury by inhibiting ferroptosis and reducing oxidative stress.

简介和目的：肝脏在败血症中起关键作用，败血症是一种由感染引起的全身炎症反应综合征。铁下垂与败血症引起的肝损伤有关。我们旨在评估盲肠结扎和穿刺（CLP）诱导的脓毒症小鼠铁下垂的变化，并确定脂钙素-2 （LCN2）在肝脏铁下垂中的作用。材料与方法：用CLP诱导小鼠脓毒症。采用苏木精染色、伊红染色及透射电镜观察大鼠肝脏组织形态及线粒体结构变化。采用相应试剂盒检测血清丙氨酸转氨酶、天冬氨酸转氨酶、超氧化物歧化酶和丙二醛水平。用二氢乙啶作为荧光探针，检测肝脏组织中活性氧水平的变化。western blotting检测肝脏中LCN2、半胱氨酸-谷氨酸逆向运输系统和二氢酸脱氢酶蛋白水平。通过对铁中毒抑制剂铁他汀-1 （fer1）、铁螯合剂dexrazoxane （DXZ）、铁葡聚糖和LCN2敲低研究来确定铁中毒和LCN2在脓毒症期间肝损伤中的作用。结果：clp诱导的脓毒症小鼠肝组织中铁下垂水平升高。铁-1和DXZ均能抑制脓毒症小鼠的铁下垂和肝损伤，而铁葡聚糖则会增加脓毒症小鼠的铁下垂和肝损伤。LCN2敲低可抑制铁下垂，降低肝脏氧化应激。结论：铁下垂抑制可减轻脓毒性肝损伤。LCN2敲低可通过抑制铁下垂和降低氧化应激减轻败血症所致的肝损伤。

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引用次数: 0

One-stop shop endoscopy for patients with biliary pancreatitis: A Jack of all trades? 胆道性胰腺炎患者的一站式内窥镜检查：多面手？

IF 3.7 3区医学 Q2 GASTROENTEROLOGY & HEPATOLOGY

Annals of hepatology

Pub Date : 2025-01-01 DOI: 10.1016/j.aohep.2024.101752

Łukasz Krupa , Frank Lammert , Marcin Krawczyk

引用次数: 0

Racial and ethnic disparities in alcohol-associated liver disease hospitalizations in Brazil before and after the COVID-19 pandemic COVID-19大流行前后巴西酒精相关肝病住院的种族和民族差异

IF 3.7 3区医学 Q2 GASTROENTEROLOGY & HEPATOLOGY

Annals of hepatology

Pub Date : 2025-01-01 DOI: 10.1016/j.aohep.2024.101742

Daniel L Heringer , Gabriel P.A. Costa , Jeremy Weleff , Victor Rodrigues , Shreya Sengupta , Akhil Anand

Introduction and Objectives

The COVID-19 pandemic has resulted in a greater incidence of alcohol-associated liver disease (ALD) and simultaneously magnified health-related inequalities. We evaluated the impact of race and ethnicity on ALD-related hospitalizations in Brazil.

Materials and Methods

An interrupted time series analysis was used to estimate ALD-related hospitalization in public hospitals in Brazil. Monthly hospitalization rates for 34 consecutive months before and after the point of interruption (March 2020) were calculated using the Sistema de Informações Hospitalares database across four ethnic groups: Black, Pardo, Black, and Pardo combined, and Others (White and Unknown Ethnicity).

Results

A total of 84,787 ALD-related hospitalizations were recorded during the study period. The mean age of hospitalized patients was 53 years (SD=12.5); 83.6% were male. Immediately after the start of the pandemic, there was a statistically significant decrease in monthly ALD-related hospitalization rates for the whole population and for all ethnic groups. Subsequently, compared to pre-pandemic rates, there was a statistically significant trend increase in the referred hospitalization rates for the total population (0.065, 95% CI= 0.045 to 0.085, p<0.01), black population (0.0028, 95% CI= 0.006 to 0.050, p<0.05), pardo population (0.077, 95% CI= 0.063 to 0.090, p<0.01), and for black and pardo combined population (0.066, 95% CI= 0.053 to 0.079, p<0.01); however, the increase in hospitalization rates among the Others population (0.059, 95% CI= -0,014 to 0.133, p>0.1) was not statistically significant.

Conclusions

The pandemic impacted ALD-related monthly hospitalization rates and disproportionately impacted Black and Pardo populations in Brazil.

前言和目标：2019冠状病毒病（COVID-19）大流行导致酒精相关性肝病（ALD）发病率上升，同时也加剧了与健康相关的不平等现象。我们评估了种族和民族对巴西阿尔茨海默病相关住院的影响。材料和方法：采用中断时间序列分析估计巴西公立医院与ald相关的住院情况。使用Sistema de Informações Hospitalares数据库计算中断点（2020年3月）前后连续34个月的每月住院率，涵盖四个种族群体：黑人、帕尔多人、黑人和帕尔多人组合，以及其他（白人和未知种族）。结果：研究期间共记录了84,787例与ald相关的住院治疗。住院患者平均年龄53岁（SD=12.5）；83.6%为男性。在大流行开始后，全体人口和所有族裔群体每月与老年痴呆症相关的住院率在统计上都有显著下降。随后，与大流行前的比率相比，总人口的转诊住院率有统计学上显著的上升趋势（0.065,95% CI= 0.045 ~ 0.085, p0.1），但无统计学意义。结论：大流行影响了与阿尔茨海默病相关的每月住院率，并不成比例地影响了巴西的黑人和帕尔多人口。

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引用次数: 0

Free fatty acid-induced DDX3 inhibits autophagy via miR-141 upregulation in diet-induced MASLD mice model system 在饮食诱导的MASLD小鼠模型系统中，游离脂肪酸诱导的DDX3通过上调miR-141抑制自噬。

IF 3.7 3区医学 Q2 GASTROENTEROLOGY & HEPATOLOGY

Annals of hepatology

Pub Date : 2025-01-01 DOI: 10.1016/j.aohep.2024.101758

Md. Musa Hossain , Amit K. Mishra , Ajay K. Yadav , Md. Ismail , Teja Naveen Sata , Amrendra K. Sah , Arnab Banik , Gopal Sharma , Senthil K. Venugopal

Introduction and Objectives

Metabolic dysfunction-associated steatotic liver disease (MASLD) is one of the primary causes of chronic liver disease and may lead to liver cirrhosis and hepatocellular carcinoma. Recent reports suggested that DEAD-box RNA helicase (DDX3) acts as a sensor of free fat accumulation and may modulate the pathogenesis via miRNAs. Hence, we hypothesized that DDX3 might modulate MASLD progression via miRNA-141-mediated inhibition of Sirt-1 and autophagy.

Materials and Methods

RNA and total protein were isolated from free fatty acid-treated HepG2 cells or CDAA-fed C57BL/6 mice (6 mice per group) for 6, 18, 32, or 54 weeks. The cells were transfected with DDX3 or miR-141 or siRNA to DDX3, and Western blots for autophagy markers were performed.

Results

The FFAs induced the DDX3 and miRNA-141 expression, while downregulating Sirt-1, beclin-1, Atg7, and LC3-II. Overexpression of DDX3 resulted in increased miRNA-141. Overexpression of DDX3 or miRNA-141 downregulated Sirt-1 expression and autophagy marker proteins, while these effects were reversed with siRNA to DDX3. The expression of both DDX3 and miRNA-141 was significantly increased, while autophagy markers were downregulated in CDAA-fed mice.

Conclusions

These results confirmed that FFA-induced DDX3 induced the expression of miRNA-141, which in turn targeted Sirt-1 and decreased autophagy.

简介和目的：代谢功能障碍相关脂肪变性肝病（MASLD）是慢性肝病的主要病因之一，可导致肝硬化和肝细胞癌。最近的报道表明，DEAD-box RNA解旋酶（DDX3）作为游离脂肪积累的传感器，可能通过mirna调节发病机制。因此，我们假设DDX3可能通过mirna -141介导的Sirt-1和自噬的抑制来调节MASLD的进展。材料和方法：从游离脂肪酸处理的HepG2细胞或cdaa喂养的C57BL/6小鼠（每组6只）中分离RNA和总蛋白，时间分别为6、18、32和54周。用DDX3或miR-141或siRNA转染DDX3细胞，进行自噬标记物的Western blot检测。结果：FFAs诱导DDX3和miRNA-141表达，下调Sirt-1、beclin-1、Atg7和LC3-II。过表达DDX3导致miRNA-141升高。DDX3或miRNA-141的过表达下调了Sirt-1的表达和自噬标记蛋白，而将siRNA加入DDX3后，这些作用被逆转。cdaa喂养小鼠DDX3和miRNA-141的表达均显著升高，而自噬标志物表达下调。结论：这些结果证实了ffa诱导的DDX3诱导miRNA-141的表达，miRNA-141反过来靶向Sirt-1，减少自噬。

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引用次数: 0

Tumor-associated macrophages contribute to cholangiocarcinoma progression and chemoresistance through activation of ID1 肿瘤相关巨噬细胞通过激活 ID1 促进了胆管癌的发展和化疗耐药性。

IF 3.7 3区医学 Q2 GASTROENTEROLOGY & HEPATOLOGY

Annals of hepatology

Pub Date : 2025-01-01 DOI: 10.1016/j.aohep.2024.101773

Yinghao Guo , Shuangda Miao , Yun Jin, Qi Li, Yihang Wang, Xiaoxiao Zhang, Jiangtao Li

Introduction and Objectives

Tumor-associated macrophages (TAM) can influence both cancer growth and chemoresistance, but the specific mechanisms involved in these processes in cholangiocarcinoma (CCA) are unclear.

Materials and Methods

We explored the distribution of TAM in CCA samples by multiplex immunofluorescence staining and tested the effects of TAM on CCA in vitro and in vivo. We then investigated the mechanisms underlying these effects using the Luminex assay, RNA sequencing, western blotting, flow cytometry, and co-immunoprecipitation.

Results

The infiltration of TAM was strongly increased in the cholangiocarcinoma tumor microenvironment. Oncostain M (OSM) secreted by TAM increased the proliferation and chemotherapeutic resistance of CCA cells both in vitro and in vivo. The results of transcriptome sequencing analysis, Western blot analysis, and immunofluorescence staining confirmed that OSM can promote Yap nuclear translocation and its subsequent formation of complexes with SMADs to upregulate the expression of inhibitor of DNA binding 1 (ID1).

Conclusions

TAM promotes CCA progression and chemoresistance through activating OSM-Yap-ID1.

简介和目的：肿瘤相关巨噬细胞（TAM）可以影响肿瘤生长和化疗耐药，但在胆管癌（CCA）中参与这些过程的具体机制尚不清楚。材料与方法：采用多重免疫荧光染色法研究TAM在CCA样品中的分布，并在体外和体内检测TAM对CCA的影响。然后，我们使用Luminex测定、RNA测序、western blotting、流式细胞术和共免疫沉淀研究了这些作用的机制。结果：胆管癌肿瘤微环境中TAM的浸润明显增加。TAM分泌的Oncostain M （OSM）在体外和体内均能增加CCA细胞的增殖和化疗耐药性。转录组测序分析、Western blot分析和免疫荧光染色结果证实，OSM可以促进Yap核易位及其随后与SMADs形成复合物，上调DNA结合抑制剂1 （inhibitor of DNA binding 1, ID1）的表达。结论：TAM通过激活OSM-Yap-ID1促进CCA进展和化疗耐药。

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引用次数: 0

The role of inflammasomes in hepatocellular carcinoma: Mechanisms and therapeutic insights 炎性小体在肝细胞癌中的作用：机制和治疗见解。

IF 3.7 3区医学 Q2 GASTROENTEROLOGY & HEPATOLOGY

Annals of hepatology

Pub Date : 2025-01-01 DOI: 10.1016/j.aohep.2024.101772

Valentina Arrè , Roberto Negro , Gianluigi Giannelli

Hepatocellular carcinoma is among the most frequent forms of primary liver cancer and develops within a context of chronic inflammation, frequently associated with a multitude of risk factors, including viral infections, metabolic dysfunction-associated fatty liver disease, metabolic dysfunction-associated steatohepatitis and liver fibrosis. The tumor microenvironment is crucial for the progression of HCC, as immune cells, tumor-associated fibroblasts and hepatic stellate cells interact to promote chronic inflammation and tumor spread. Inflammasomes, the multiprotein complexes that launch the innate immune response, emerge as important mediators in the pathogenesis of HCC. Among others, the inflammasome Nucleotide-binding oligomerization domain, Leucine rich Repeat (NLR) and Pyrin (NLRP) 3 (NLRP3), and absent in melanoma 2 (AIM2), exhibit a dual role in HCC background. It has been reported that they can exert oncosuppressive functions by triggering the inflammatory death of cancer cells. Vice versa, chronic activation contributes to the development of a pro-tumorigenic environment, thus supporting tumor growth. In addition, other inflammasomes such as Nucleotide-binding oligomerization domain, Leucine rich Repeat (NLR) and Pyrin (NLRP) 6 and 12 (NLRP6 and NLRP12, respectively) regulate HCC onset and progression, although more experimental evidence is required. This review focuses on the molecular mechanisms underpinning the inflammasome's contribution to the onset, progression and spread of HCC. Moreover, we will explore the potential therapeutic approaches currently under investigation, which aim to improve the efficacy and reduce the side effects of the treatments currently available. Targeting inflammasomes may be a promising therapeutic strategy for the treatment of HCC, offering new opportunities to improve patient prognosis.

肝细胞癌是原发性肝癌最常见的形式之一，在慢性炎症的背景下发展，通常与多种危险因素相关，包括病毒感染、代谢功能障碍相关的脂肪性肝病、代谢功能障碍相关的脂肪性肝炎和肝纤维化。肿瘤微环境对HCC的进展至关重要，因为免疫细胞、肿瘤相关成纤维细胞和肝星状细胞相互作用，促进慢性炎症和肿瘤扩散。炎性小体是一种启动先天免疫反应的多蛋白复合物，是HCC发病过程中的重要介质。其中，炎症小体核苷酸结合寡聚化结构域，亮氨酸富重复序列（NLR）和Pyrin (NLRP) 3 (NLRP3)，在黑色素瘤2 （AIM2）中缺失，在HCC背景中表现出双重作用。据报道，它们可以通过引发癌细胞的炎症性死亡来发挥抑癌功能。反之亦然，慢性激活有助于促进致瘤环境的发展，从而支持肿瘤生长。此外，其他炎症小体如核苷酸结合寡聚化结构域、富亮氨酸重复序列（NLR）和Pyrin (NLRP) 6和12（分别为NLRP6和NLRP12）调节HCC的发生和进展，尽管还需要更多的实验证据。本文综述了炎症小体在HCC发病、进展和扩散过程中的分子机制。此外，我们将探索目前正在研究的潜在治疗方法，旨在提高现有治疗方法的疗效并减少副作用。靶向炎性小体可能是HCC治疗的一种有前景的治疗策略，为改善患者预后提供了新的机会。

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引用次数: 0