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Diagnostic and prognostic role of LINC01767 in hepatocellular carcinoma. LINC01767 在肝细胞癌中的诊断和预后作用。
IF 2.5 Q2 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2024-06-27 DOI: 10.4254/wjh.v16.i6.932
Li Zhang, Tong-Xing Cui, Xiang-Zhi Li, Chong Liu, Wen-Qin Wang

Background: Hepatocellular carcinoma (HCC) is a primary contributor to cancer-related mortality on a global scale. However, the underlying molecular mechanisms are still poorly understood. Long noncoding RNAs are emerging markers for HCC diagnosis, prognosis, and therapeutic target. No study of LINC01767 in HCC was published.

Aim: To conduct a multi-omics analysis to explore the roles of LINC01767 in HCC for the first time.

Methods: DESeq2 Package was used to analyze different gene expressions. Receiver operating characteristic curves assessed the diagnostic performance. Kaplan-Meier univariate and Cox multivariate analyses were used to perform survival analysis. The least absolute shrinkage and selection operator (LASSO)-Cox was used to identify the prediction model. Subsequent to the validation of LINC01767 expression in HCC fresh frozen tissues through quantitative real time polymerase chain reaction, next generation sequencing was performed following LINC01767 over expression (GSE243371), and Gene Ontology/Kyoto Encyclopedia of Genes and Genomes/Gene Set Enrichment Analysis/ingenuity pathway analysis was carried out. In vitro experiment in Huh7 cell was carried out.

Results: LINC01767 was down-regulated in HCC with a log fold change = 1.575 and was positively correlated with the cancer stemness. LINC01767 was a good diagnostic marker with area under the curve (AUC) [0.801, 95% confidence interval (CI): 0.751-0.852, P = 0.0106] and an independent predictor for overall survival (OS) with hazard ratio = 1.899 (95%CI: 1.01-3.58, P = 0.048). LINC01767 nomogram model showed a satisfied performance. The top-ranked regulatory network analysis of LINC01767 showed the regulation of genes participating various pathways. LASSO regression identified the 9-genes model showing a more satisfied performance than 5-genes model to predict the OS with AUC > 0.75. LINC01767 was down-expressed obviously in tumor than para-tumor tissues in our cohort as well as in cancer cell line; the over expression of LINC01767 inhibit cell proliferation and clone formation of Huh7 in vitro.

Conclusion: LINC01767 was an important tumor suppressor gene in HCC with good diagnostic and prognostic performance.

背景:在全球范围内,肝细胞癌(HCC)是导致癌症相关死亡率的主要因素。然而,人们对其潜在的分子机制仍然知之甚少。长非编码 RNA 是新出现的 HCC 诊断、预后和治疗靶标。目的:进行多组学分析,首次探索 LINC01767 在 HCC 中的作用:方法:使用DESeq2软件包分析不同基因的表达。受体操作特征曲线评估了诊断性能。采用Kaplan-Meier单变量分析和Cox多变量分析进行生存分析。最小绝对收缩和选择算子(LASSO)-Cox用于确定预测模型。通过定量实时聚合酶链反应验证了LINC01767在HCC新鲜冰冻组织中的表达,随后进行了LINC01767过度表达的新一代测序(GSE243371),并进行了基因本体/京都基因和基因组百科全书/基因组富集分析/ingenuity通路分析。在 Huh7 细胞中进行了体外实验:结果:LINC01767在HCC中下调,对折变化=1.575,与癌症干性呈正相关。LINC01767 是一个很好的诊断标志物,其曲线下面积(AUC)为[0.801,95% 置信区间(CI):0.751-0.852,P = 0.0106],并且是总生存率(OS)的独立预测因子,其危险比为 1.899(95%CI:1.01-3.58,P = 0.048)。LINC01767提名图模型的表现令人满意。LINC01767的顶级调控网络分析显示了参与各种通路的基因的调控。LASSO回归发现,在预测OS方面,9基因模型的AUC>0.75,比5基因模型的AUC>0.75表现更佳。LINC01767在肿瘤组织和癌细胞系中的表达明显低于瘤旁组织;LINC01767的过度表达抑制了体外Huh7的细胞增殖和克隆形成:结论:LINC01767是HCC中一个重要的抑癌基因,具有良好的诊断和预后作用。
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引用次数: 0
Milestones to optimize of transjugular intrahepatic portosystemic shunt technique as a method for the treatment of portal hypertension complications. 优化经颈静脉肝内门体分流术作为治疗门脉高压并发症方法的里程碑。
IF 2.5 Q2 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2024-06-27 DOI: 10.4254/wjh.v16.i6.891
Dmitry Victorovich Garbuzenko

This editorial describes the milestones to optimize of transjugular intrahepatic portosystemic shunt (TIPS) technique, which have made it one of the main methods for the treatment of portal hypertension complications worldwide. Innovative ideas, subsequent experimental studies and preliminary experience of use in cirrhotic patients contributed to the introduction of TIPS into clinical practice. At the moment, the main achievement in optimize of TIPS technique is progress in the qualitative characteristics of stents. The transition from bare metal stents to extended polytetrafluoroethylene-covered stent grafts made it possible to significantly prevent shunt dysfunction. However, the question of its preferred diameter, which contributes to an optimal reduction of portal pressure without the risk of developing post-TIPS hepatic encephalopathy, remains relevant. Currently, hepatic encephalopathy is one of the most common complications of TIPS, significantly affecting its effectiveness and prognosis. Careful selection of patients based on cognitive indicators, nutritional status, assessment of liver function, etc., will reduce the incidence of post-TIPS hepatic encephalopathy and improve treatment results. Optimize of TIPS technique has significantly expanded the indications for its use and made it one of the main methods for the treatment of portal hypertension complications. At the same time, there are a number of limitations and unresolved issues that require further randomized controlled trials involving a large cohort of patients.

这篇社论介绍了经颈静脉肝内门体分流术(TIPS)技术优化的里程碑,该技术已成为全球治疗门静脉高压并发症的主要方法之一。创新理念、随后的实验研究以及在肝硬化患者中使用的初步经验促使 TIPS 进入临床实践。目前,优化 TIPS 技术的主要成就是支架质量特性的进步。从裸金属支架到加长型聚四氟乙烯覆盖支架移植物的过渡,使大大防止分流功能障碍成为可能。然而,支架的首选直径问题依然存在,即支架的直径应有助于最佳地降低门脉压力,同时又不会产生 TIPS 后肝性脑病的风险。目前,肝性脑病是 TIPS 最常见的并发症之一,严重影响其疗效和预后。根据认知指标、营养状况、肝功能评估等对患者进行仔细筛选,可降低 TIPS 术后肝性脑病的发生率,改善治疗效果。TIPS 技术的优化大大扩展了其适应症,使其成为治疗门静脉高压并发症的主要方法之一。与此同时,TIPS 还存在一些局限性和未解决的问题,需要进一步开展大规模患者群的随机对照试验。
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引用次数: 0
Successful treatment of severe hepatic impairment in erythropoietic protoporphyria: A case report and review of literature. 成功治疗红细胞生成性原卟啉症的严重肝功能损害:病例报告和文献综述。
IF 2.5 Q2 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2024-06-27 DOI: 10.4254/wjh.v16.i6.966
Tao Zeng, Shu-Ru Chen, Hao-Qiang Liu, Yu-Tian Chong, Xin-Hua Li

Background: Erythropoietic protoporphyria (EPP) is a rare genetic disorder stemming from ferrochelatase gene mutations, which leads to abnormal accumulation of protoporphyrin IX primarily in erythrocytes, skin, bone marrow and liver. Although porphyria-related severe liver damage is rare, its consequences can be severe with limited treatment options.

Case summary: This case study highlights a successful intervention for a 35-year-old male with EPP-related liver impairment, employing a combination of red blood cell (RBC) exchange and therapeutic plasma exchange (TPE). The patient experienced significant symptom relief and a decrease in bilirubin levels following multiple PE sessions and an RBC exchange.

Conclusion: The findings suggest that this combined approach holds promise for managing severe hepatic impairment in EPP.

背景:红细胞生成性原卟啉症(Erythropoietic protoporphyria,EPP)是一种罕见的遗传性疾病,源于铁螯合酶基因突变,导致原卟啉 IX 主要在红细胞、皮肤、骨髓和肝脏中异常积聚。虽然与卟啉症相关的严重肝损伤很少见,但其后果可能很严重,而且治疗方案有限。病例摘要:本病例研究重点介绍了对一名患有 EPP 相关肝损伤的 35 岁男性患者采取的成功干预措施,该措施采用了红细胞(RBC)交换和治疗性血浆交换(TPE)相结合的方法。经过多次治疗性血浆置换和一次红细胞置换后,患者的症状明显缓解,胆红素水平也有所下降:结论:研究结果表明,这种联合方法有望治疗 EPP 中的严重肝功能损害。
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引用次数: 0
Combined hepatocellular cholangiocarcinoma: A clinicopathological update 合并肝细胞性胆管癌:临床病理学最新进展
IF 2.4 Q3 Medicine Pub Date : 2024-05-27 DOI: 10.4254/wjh.v16.i5.766
M. Vij, Fadl H Veerankutty, A. Rammohan, Mohamed Rela
Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) is a rare primary liver cancer associated with an appalling prognosis. The diagnosis and management of this entity have been challenging to physicians, radiologists, surgeons, pathologists, and oncologists alike. The diagnostic and prognostic value of biomarkers such as the immunohistochemical expression of nestin, a progenitor cell marker, have been explored recently. With a better understanding of biology and the clinical course of cHCC-CCA, newer treatment modalities like immune checkpoint inhibitors are being tried to improve the survival of patients with this rare disease. In this review, we give an account of the recent developments in the pathology, diagnostic approach, and management of cHCC-CCA.
肝细胞胆管癌(cHCC-CCA)是一种罕见的原发性肝癌,预后极差。对于内科医生、放射科医生、外科医生、病理学家和肿瘤学家来说,这种疾病的诊断和治疗都是一项挑战。最近,人们开始探索生物标志物的诊断和预后价值,如免疫组化表达的 nestin(一种祖细胞标志物)。随着对 cHCC-CCA 的生物学和临床过程有了更好的了解,人们正在尝试采用免疫检查点抑制剂等新的治疗方式来改善这种罕见疾病患者的生存率。在这篇综述中,我们将介绍 cHCC-CCA 在病理学、诊断方法和治疗方面的最新进展。
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引用次数: 0
Presepsin as a biomarker of bacterial translocation and an indicator for the prescription of probiotics in cirrhosis 作为细菌转运生物标志物和肝硬化患者益生菌处方指标的前胃蛋白酶
IF 2.4 Q3 Medicine Pub Date : 2024-05-27 DOI: 10.4254/wjh.v16.i5.822
I. Efremova, R. Maslennikov, Elena Poluektova, O. Medvedev, Anna V Kudryavtseva, G. Krasnov, Maria Fedorova, Filipp Romanikhin, Maria Zharkova, O. Zolnikova, Gyunay Bagieva, V. Ivashkin
BACKGROUND The gut–liver axis and bacterial translocation are important in cirrhosis, but there is no available universal biomarker of cellular bacterial translocation, for which presepsin may be a candidate. AIM To evaluate the relationship of the blood presepsin levels with the state of the gut microbiota in cirrhosis in the absence of obvious infection. METHODS This study included 48 patients with Child–Pugh cirrhosis classes B and C and 15 healthy controls. The fecal microbiome was assessed using 16S rRNA gene sequencing. Plasma levels of presepsin were measured. A total of 22 patients received a probiotic (Saccharomyces boulardii ) for 3 months. RESULTS Presepsin levels were higher in patients with cirrhosis than in healthy individuals [342 (91-2875) vs 120 (102-141) pg/mL; P = 0.048]. Patients with elevated presepsin levels accounted for 56.3% of all included patients. They had lower levels of serum albumin and higher levels of serum total bilirubin and overall severity of cirrhosis as assessed using the Child–Pugh scale. Patients with elevated presepsin levels had an increased abundance of the main taxa responsible for bacterial translocation, namely Bacilli and Proteobacteria (including the main class Gammaproteobacteria and the minor taxa Xanthobacteraceae and Stenotrophomonas), and a low abundance of bacteria from the family Lachnospiraceae (including the minor genus Fusicatenibacter), which produce short-chain fatty acids that have a positive effect on intestinal barrier function. The presepsin level directly correlated with the relative abundance of Bacilli, Proteobacteria, and inversely correlated with the abundance of Lachnospiraceae and Propionibacteriaceae. After 3 months of taking the probiotic, the severity of cirrhosis on the Child–Pugh scale decreased significantly only in the group with elevated presepsin levels [from 9 (8-11) to 7 (6-9); P = 0.004], while there were no significant changes in the group with normal presepsin levels [from 8 (7-8) to 7 (6-8); P = 0.123]. A high level of presepsin before the prescription of the probiotic was an independent predictor of a greater decrease in Child–Pugh scores (P = 0.046), as well as a higher level of the Child–Pugh scale (P = 0.042), but not the C-reactive protein level (P = 0.679) according to multivariate linear regression analysis. CONCLUSION The level of presepsin directly correlates with the abundance in the gut microbiota of the main taxa that are substrates of bacterial translocation in cirrhosis. This biomarker, in the absence of obvious infection, seems important for assessing the state of the gut–liver axis in cirrhosis and deciding on therapy targeted at the gut microbiota in this disease.
背景 肠道-肝脏轴和细菌转运在肝硬化中非常重要,但目前还没有细胞细菌转运的通用生物标志物,而前胰蛋白酶可能是一种候选生物标志物。目的 评估肝硬化患者在无明显感染的情况下,血液中前胰蛋白酶水平与肠道微生物群状态的关系。方法 本研究纳入了 48 名 Child-Pugh 肝硬化 B 级和 C 级患者以及 15 名健康对照者。采用 16S rRNA 基因测序法对粪便微生物群进行了评估。对血浆中的前胃蛋白酶水平进行了测定。共有 22 名患者接受了为期 3 个月的益生菌(布拉氏酵母菌)治疗。结果 肝硬化患者的前蛋白酶水平高于健康人 [342 (91-2875) vs 120 (102-141) pg/mL;P = 0.048]。前蛋白水平升高的患者占所有纳入患者的 56.3%。他们的血清白蛋白水平较低,血清总胆红素水平较高,根据 Child-Pugh 分级法评估的肝硬化总体严重程度也较高。前体蛋白水平升高的患者体内负责细菌转运的主要类群,即杆菌和蛋白菌(包括主要的伽马蛋白菌类和次要的黄杆菌科和 Stenotrophomonas 类)的数量增加,而产生对肠道屏障功能有积极影响的短链脂肪酸的漆树科细菌(包括次要的 Fusicatenibacter 属)的数量较少。前体蛋白水平与芽孢杆菌、蛋白杆菌的相对丰度直接相关,而与拉赫诺斯皮拉菌科和丙酸杆菌科的丰度成反比。服用益生菌 3 个月后,Child-Pugh 评分表中的肝硬化严重程度仅在前胰蛋白酶水平升高组有显著下降[从 9 (8-11) 降至 7 (6-9); P = 0.004],而在前胰蛋白酶水平正常组没有显著变化[从 8 (7-8) 降至 7 (6-8); P = 0.123]。根据多变量线性回归分析,在处方益生菌前,高水平的前胃蛋白酶是 Child-Pugh 评分下降幅度更大(P = 0.046)以及 Child-Pugh 量表水平更高(P = 0.042)的独立预测因素,但不是 C 反应蛋白水平(P = 0.679)的独立预测因素。结论 前胃蛋白酶的水平与肠道微生物群中作为肝硬化细菌转运底物的主要类群的丰度直接相关。在没有明显感染的情况下,这一生物标志物似乎对评估肝硬化患者肠道-肝脏轴的状态以及决定针对该疾病肠道微生物群的治疗非常重要。
{"title":"Presepsin as a biomarker of bacterial translocation and an indicator for the prescription of probiotics in cirrhosis","authors":"I. Efremova, R. Maslennikov, Elena Poluektova, O. Medvedev, Anna V Kudryavtseva, G. Krasnov, Maria Fedorova, Filipp Romanikhin, Maria Zharkova, O. Zolnikova, Gyunay Bagieva, V. Ivashkin","doi":"10.4254/wjh.v16.i5.822","DOIUrl":"https://doi.org/10.4254/wjh.v16.i5.822","url":null,"abstract":"BACKGROUND\u0000 The gut–liver axis and bacterial translocation are important in cirrhosis, but there is no available universal biomarker of cellular bacterial translocation, for which presepsin may be a candidate.\u0000 AIM\u0000 To evaluate the relationship of the blood presepsin levels with the state of the gut microbiota in cirrhosis in the absence of obvious infection.\u0000 METHODS\u0000 This study included 48 patients with Child–Pugh cirrhosis classes B and C and 15 healthy controls. The fecal microbiome was assessed using 16S rRNA gene sequencing. Plasma levels of presepsin were measured. A total of 22 patients received a probiotic (Saccharomyces boulardii ) for 3 months.\u0000 RESULTS\u0000 Presepsin levels were higher in patients with cirrhosis than in healthy individuals [342 (91-2875) vs 120 (102-141) pg/mL; P = 0.048]. Patients with elevated presepsin levels accounted for 56.3% of all included patients. They had lower levels of serum albumin and higher levels of serum total bilirubin and overall severity of cirrhosis as assessed using the Child–Pugh scale. Patients with elevated presepsin levels had an increased abundance of the main taxa responsible for bacterial translocation, namely Bacilli and Proteobacteria (including the main class Gammaproteobacteria and the minor taxa Xanthobacteraceae and Stenotrophomonas), and a low abundance of bacteria from the family Lachnospiraceae (including the minor genus Fusicatenibacter), which produce short-chain fatty acids that have a positive effect on intestinal barrier function. The presepsin level directly correlated with the relative abundance of Bacilli, Proteobacteria, and inversely correlated with the abundance of Lachnospiraceae and Propionibacteriaceae. After 3 months of taking the probiotic, the severity of cirrhosis on the Child–Pugh scale decreased significantly only in the group with elevated presepsin levels [from 9 (8-11) to 7 (6-9); P = 0.004], while there were no significant changes in the group with normal presepsin levels [from 8 (7-8) to 7 (6-8); P = 0.123]. A high level of presepsin before the prescription of the probiotic was an independent predictor of a greater decrease in Child–Pugh scores (P = 0.046), as well as a higher level of the Child–Pugh scale (P = 0.042), but not the C-reactive protein level (P = 0.679) according to multivariate linear regression analysis.\u0000 CONCLUSION\u0000 The level of presepsin directly correlates with the abundance in the gut microbiota of the main taxa that are substrates of bacterial translocation in cirrhosis. This biomarker, in the absence of obvious infection, seems important for assessing the state of the gut–liver axis in cirrhosis and deciding on therapy targeted at the gut microbiota in this disease.","PeriodicalId":23687,"journal":{"name":"World Journal of Hepatology","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2024-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141098355","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
Current concepts in the management of non-cirrhotic non-malignant portal vein thrombosis 治疗非肝硬化非恶性门静脉血栓的当前理念
IF 2.4 Q3 Medicine Pub Date : 2024-05-27 DOI: 10.4254/wjh.v16.i5.751
Adam J Willington, Dhiraj Tripathi
Non-cirrhotic non-malignant portal vein thrombosis (NCPVT) is an uncommon condition characterised by thrombosis of the portal vein, with or without extension into other mesenteric veins, in the absence of cirrhosis or intra-abdominal malignancy. Complications can include intestinal infarction, variceal bleeding and portal biliopathy. In this article, we address current concepts in the management of NCPVT including identification of risk factors, classification and treatment, and review the latest evidence on medical and interventional management options.
非肝硬化性非恶性门静脉血栓形成(NCPVT)是一种不常见的疾病,其特点是在没有肝硬化或腹腔内恶性肿瘤的情况下,门静脉血栓形成,并伴有或不伴有其他肠系膜静脉的扩展。并发症包括肠梗死、静脉曲张出血和门静脉胆汁淤积症。在这篇文章中,我们将阐述目前治疗 NCPVT 的理念,包括识别风险因素、分类和治疗,并回顾有关药物和介入治疗方案的最新证据。
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引用次数: 0
Hepatitis C virus eradication in people living with human immunodeficiency virus: Where are we now? 在人类免疫缺陷病毒感染者中根除丙型肝炎病毒:我们现在在哪里?
IF 2.4 Q3 Medicine Pub Date : 2024-05-27 DOI: 10.4254/wjh.v16.i5.661
A. Spera, Pasquale Pagliano, Valeria Conti
Hepatitis C virus (HCV)/human immunodeficiency virus (HIV) co-infection still involves 2.3 million patients worldwide of the estimated 37.7 million living with HIV, according to World Health Organization. People living with HIV (PLWH) are six times greater affected by HCV, compared to HIV negative ones; the greater prevalence is encountered among people who inject drugs and men who have sex with men: the risk of HCV transmission through sexual contact in this setting can be increased by HIV infection. These patients experience a high rate of chronic hepatitis, which if left untreated progresses to end-stage liver disease and hepatocellular carcinoma (HCC) HIV infection increases the risk of mother to child vertical transmission of HCV. No vaccination against both infections is still available. There is an interplay between HIV and HCV infections. Treatment of HCV is nowadays based on direct acting antivirals (DAAs), HCV treatment plays a key role in limiting the progression of liver disease and reducing the risk of HCC development in mono- and coinfected individuals, especially when used at an early stage of fibrosis, reducing liver disease mortality and morbidity. Since the sustained virological response at week 12 rates were observed in PLWH after HCV eradication, the AASLD has revised its simplified HCV treatment algorithm to also include individuals living with HIV. HCV eradication can determine dyslipidemia, since HCV promotes changes in serum lipid profiles and may influence lipid metabolism. In addition to these apparent detrimental effects on the lipid profile, the efficacy of DAA in HCV/HIV patients needs to be considered in light of its effects on glucose metabolism mediated by improvements in liver function. The aim of the present editorial is to describe the advancement in HCV treatment among PLWH.
世界卫生组织称,在全球约 3770 万艾滋病毒感染者中,仍有 230 万患者同时感染丙型肝炎病毒(HCV)和人类免疫缺陷病毒(HIV)。与艾滋病毒阴性感染者相比,艾滋病毒感染者的丙型肝炎病毒感染率是后者的六倍;注射毒品者和男男性行为者的丙型肝炎病毒感染率更高:在这种情况下,艾滋病毒感染会增加通过性接触传播丙型肝炎病毒的风险。这些患者的慢性肝炎发病率很高,如果不及时治疗,会发展为终末期肝病和肝细胞癌(HCC)。 艾滋病毒感染会增加母婴垂直传播 HCV 的风险。目前还没有针对这两种感染的疫苗。艾滋病病毒和丙型肝炎病毒感染之间存在相互作用。目前,HCV 的治疗以直接作用抗病毒药物(DAAs)为主,HCV 治疗在限制肝病进展、降低单发和合并感染者发生 HCC 的风险方面发挥着关键作用,尤其是在肝纤维化的早期阶段使用,可降低肝病死亡率和发病率。由于在根除 HCV 后的艾滋病毒感染者中观察到第 12 周的持续病毒学应答率,AASLD 修订了其简化的 HCV 治疗算法,将艾滋病毒感染者也纳入其中。根除 HCV 可导致血脂异常,因为 HCV 会促使血清脂质谱发生变化,并可能影响脂质代谢。除了这些对血脂谱的明显不利影响外,DAA 对 HCV/HIV 患者的疗效还需要考虑到其通过改善肝功能对糖代谢的影响。本社论旨在介绍艾滋病毒/艾滋病感染者的 HCV 治疗进展。
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引用次数: 0
Ornithine aspartate effects on bacterial composition and metabolic pathways in a rat model of steatotic liver disease 天冬氨酸鸟氨酸对脂肪肝大鼠模型中细菌组成和代谢途径的影响
IF 2.4 Q3 Medicine Pub Date : 2024-05-27 DOI: 10.4254/wjh.v16.i5.832
Elisa Carolina Lange, P. H. Rampelotto, Larisse Longo, Laura Bainy Rodrigues de Freitas, Carolina Uribe-Cruz, Mario Reis Alvares-da-Silva
BACKGROUND Metabolic-dysfunction associated steatotic liver disease (MASLD) is a hepatic manifestation of metabolic syndrome. Studies suggest ornithine aspartate (LOLA) as drug therapy. AIM To analyze the influence of LOLA intake on gut microbiota using a nutritional model of MASLD. METHODS Adult male Sprague Dawley rats were randomized into three groups: Control (10 rats fed with a standard diet), MASLD (10 rats fed with a high-fat and choline-deficient diet), and LOLA (10 rats receiving 200 mg/kg/d LOLA, after the 16th week receiving high-fat and choline-deficient diet). After 28 wk of the experiment, animals were euthanized, and feces present in the intestine were collected. Following fecal DNA extraction, the V4 region of the 16S rRNA gene was amplified followed by sequencing in an Ion S5™ system. RESULTS Alpha and beta diversity metrics were comparable between MASLD and LOLA. 3 OTUs were differentially abundant between MASLD and LOLA, which belong to the species Helicobacter rodentium , Parabacteroides goldsteinii , and Parabacteroides distasonis . The functional prediction provided two different metabolic profiles between MASLD and LOLA. The 9 pathways differentially abundant in MASLD are related to a change in energy source, adenosine/purine nucleotides degradation as well as guanosine and adenosine deoxyribonucleotides biosynthesis. The 14 pathways differentially abundant in LOLA are associated with four major metabolic functions primarily influenced by L-aspartate, including tricarboxylic acid cycle pathways, purine/guanosine nucleotides biosynthesis, pyrimidine ribonucleotides biosynthesis and salvage as well as lipid IVA biosynthesis. CONCLUSION Although LOLA had no influence on alpha and beta diversity in this nutritional model of MASLD, it was associated with changes in specific gut microbes and their related metabolic pathways.
背景 代谢功能障碍相关性脂肪性肝病(MASLD)是代谢综合征的一种肝脏表现。研究建议将天门冬氨酸鸟氨酸(LOLA)作为药物治疗。目的 利用 MASLD 营养模型分析摄入 LOLA 对肠道微生物群的影响。方法 将成年雄性 Sprague Dawley 大鼠随机分为三组:对照组(10 只大鼠以标准饮食喂养)、MASLD 组(10 只大鼠以高脂肪和胆碱缺乏饮食喂养)和 LOLA 组(10 只大鼠摄入 200 mg/kg/d LOLA,第 16 周后摄入高脂肪和胆碱缺乏饮食)。实验 28 周后,对动物实施安乐死,并收集肠道中的粪便。提取粪便 DNA 后,扩增 16S rRNA 基因的 V4 区域,然后在 Ion S5™ 系统中进行测序。结果 MASLD 和 LOLA 的α和β多样性指标相当。有 3 个 OTU 在 MASLD 和 LOLA 中含量不同,它们分别属于啮齿类螺旋杆菌、金色副杆菌和远端副杆菌。功能预测提供了 MASLD 和 LOLA 两种不同的代谢概况。在 MASLD 中含量不同的 9 条途径与能量来源变化、腺苷/嘌呤核苷酸降解以及鸟苷和腺苷脱氧核苷酸生物合成有关。在 LOLA 中含量不同的 14 条途径与主要受 L-天门冬氨酸影响的四大代谢功能有关,包括三羧酸循环途径、嘌呤/鸟苷酸核苷酸的生物合成、嘧啶核糖核苷酸的生物合成和挽救以及脂质 IVA 的生物合成。结论 虽然 LOLA 对 MASLD 营养模型中的α和β多样性没有影响,但它与特定肠道微生物及其相关代谢途径的变化有关。
{"title":"Ornithine aspartate effects on bacterial composition and metabolic pathways in a rat model of steatotic liver disease","authors":"Elisa Carolina Lange, P. H. Rampelotto, Larisse Longo, Laura Bainy Rodrigues de Freitas, Carolina Uribe-Cruz, Mario Reis Alvares-da-Silva","doi":"10.4254/wjh.v16.i5.832","DOIUrl":"https://doi.org/10.4254/wjh.v16.i5.832","url":null,"abstract":"BACKGROUND\u0000 Metabolic-dysfunction associated steatotic liver disease (MASLD) is a hepatic manifestation of metabolic syndrome. Studies suggest ornithine aspartate (LOLA) as drug therapy.\u0000 AIM\u0000 To analyze the influence of LOLA intake on gut microbiota using a nutritional model of MASLD.\u0000 METHODS\u0000 Adult male Sprague Dawley rats were randomized into three groups: Control (10 rats fed with a standard diet), MASLD (10 rats fed with a high-fat and choline-deficient diet), and LOLA (10 rats receiving 200 mg/kg/d LOLA, after the 16th week receiving high-fat and choline-deficient diet). After 28 wk of the experiment, animals were euthanized, and feces present in the intestine were collected. Following fecal DNA extraction, the V4 region of the 16S rRNA gene was amplified followed by sequencing in an Ion S5™ system.\u0000 RESULTS\u0000 Alpha and beta diversity metrics were comparable between MASLD and LOLA. 3 OTUs were differentially abundant between MASLD and LOLA, which belong to the species Helicobacter rodentium , Parabacteroides goldsteinii , and Parabacteroides distasonis . The functional prediction provided two different metabolic profiles between MASLD and LOLA. The 9 pathways differentially abundant in MASLD are related to a change in energy source, adenosine/purine nucleotides degradation as well as guanosine and adenosine deoxyribonucleotides biosynthesis. The 14 pathways differentially abundant in LOLA are associated with four major metabolic functions primarily influenced by L-aspartate, including tricarboxylic acid cycle pathways, purine/guanosine nucleotides biosynthesis, pyrimidine ribonucleotides biosynthesis and salvage as well as lipid IVA biosynthesis.\u0000 CONCLUSION\u0000 Although LOLA had no influence on alpha and beta diversity in this nutritional model of MASLD, it was associated with changes in specific gut microbes and their related metabolic pathways.","PeriodicalId":23687,"journal":{"name":"World Journal of Hepatology","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2024-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141098410","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
Gestational diabetes mellitus may predispose to metabolic dysfunction-associated steatotic liver disease 妊娠糖尿病可能易导致代谢功能障碍相关性脂肪肝
IF 2.4 Q3 Medicine Pub Date : 2024-05-27 DOI: 10.4254/wjh.v16.i5.860
C. Milionis, Ioannis Ilias, E. Koukkou
The development of type 2 diabetes mellitus is a major contributing factor to the worldwide health burden of metabolic dysfunction-associated steatotic liver disease (MASLD). Insulin resistance, subclinical inflammation, dyslipidemia, obesity, and hypertension are all factors in this reciprocal interaction that contribute to the development of MASLD, which includes hepatocellular carcinoma, advanced fibrosis/cirrhosis, and non-alcoholic steatohepatitis (NASH). A new risk factor for MASLD/NASH that affects the course of the disease independently throughout life is gestational diabetes mellitus (GDM). Women with a history of GDM had a higher chance of developing NASH, according to a recent study that used a large-scale database. Although the precise etiology is yet unknown, temporary disruption of pancreatic beta cell activity during pregnancy may set off systemic inflammation, affecting distant organs including the liver. Early screening and management strategies are crucial in mitigating MASLD progression and preventing adverse cardiovascular events in affected individuals.
2 型糖尿病是导致代谢功能障碍相关性脂肪性肝病(MASLD)这一全球健康负担的主要因素。胰岛素抵抗、亚临床炎症、血脂异常、肥胖和高血压都是导致 MASLD(包括肝细胞癌、晚期肝纤维化/肝硬化和非酒精性脂肪性肝炎(NASH))发生的相互影响的因素。妊娠期糖尿病(GDM)是MASLD/NASH的一个新的风险因素,它会独立影响疾病的终生进程。根据最近一项使用大型数据库进行的研究,有妊娠糖尿病史的妇女患 NASH 的几率更高。虽然确切的病因尚不清楚,但妊娠期间胰腺β细胞活动的暂时性中断可能会引发全身性炎症,影响包括肝脏在内的远处器官。早期筛查和管理策略对于减轻 MASLD 的进展和预防受影响人群的不良心血管事件至关重要。
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引用次数: 0
Role of incretins and glucagon receptor agonists in metabolic dysfunction-associated steatotic liver disease: Opportunities and challenges. 胰高血糖素和胰高血糖素受体激动剂在代谢功能障碍相关性脂肪肝中的作用:机遇与挑战。
IF 2.4 Q3 Medicine Pub Date : 2024-05-27 DOI: 10.4254/wjh.v16.i5.731
Chencheng Xie, Naim Alkhouri, Mohamed A Elfeki

Metabolic dysfunction-associated steatotic liver disease (MASLD) has become the most common chronic liver disease worldwide, paralleling the rising pandemic of obesity and type 2 diabetes. Due to the growing global health burden and complex pathogenesis of MASLD, a multifaceted and innovative therapeutic approach is needed. Incretin receptor agonists, which were initially developed for diabetes management, have emerged as promising candidates for MASLD treatment. This review describes the pathophysiological mechanisms and action sites of three major classes of incretin/glucagon receptor agonists: glucagon-like peptide-1 receptor agonists, glucose-dependent insulinotropic polypeptide receptor agonists, and glucagon receptor agonists. Incretins and glucagon directly or indirectly impact various organs, including the liver, brain, pancreas, gastrointestinal tract, and adipose tissue. Thus, these agents significantly improve glycemic control and weight management and mitigate MASLD pathogenesis. Importantly, this study provides a summary of clinical trials analyzing the effectiveness and safety of incretin receptor agonists in MASLD management and provides an in-depth analysis highlighting their beneficial effects on improving liver function, hepatic steatosis, and intrahepatic inflammation. There are emerging challenges associated with the use of these medications in the real world, particularly adverse events, drug-drug interactions, and barriers to access, which are discussed in detail. Additionally, this review highlights the evolving role of incretin receptor agonists in MASLD management and suggests future research directions.

代谢功能障碍相关性脂肪性肝病(MASLD)已成为全球最常见的慢性肝病,与此同时,肥胖症和 2 型糖尿病的发病率也在不断上升。由于代谢相关性脂肪性肝病对全球健康造成的负担日益加重,且发病机制复杂,因此需要一种多方面的创新治疗方法。最初开发用于糖尿病治疗的内分泌受体激动剂已成为治疗 MASLD 的有前途的候选药物。本综述介绍了三大类增量素/胰高血糖素受体激动剂的病理生理机制和作用部位:胰高血糖素样肽-1受体激动剂、葡萄糖依赖性促胰岛素多肽受体激动剂和胰高血糖素受体激动剂。胰岛素和胰高血糖素直接或间接影响多个器官,包括肝脏、大脑、胰腺、胃肠道和脂肪组织。因此,这些药物能明显改善血糖控制和体重管理,减轻 MASLD 的发病机制。重要的是,本研究总结了分析增量素受体激动剂在MASLD治疗中的有效性和安全性的临床试验,并深入分析了这些药物对改善肝功能、肝脂肪变性和肝内炎症的有益作用。本综述详细讨论了在现实世界中使用这些药物所面临的新挑战,特别是不良事件、药物间相互作用和使用障碍。此外,本综述还强调了增量素受体激动剂在 MASLD 治疗中不断演变的作用,并提出了未来的研究方向。
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引用次数: 0
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World Journal of Hepatology
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