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基于肝脏类器官系统探讨布乐韦肽抑制丁型肝炎病毒复制的体外研究
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作者 沈乐而 陈金梅 +2 位作者 郭庆鑫 田璐瑛 陈小华 《中华传染病杂志》 CAS CSCD 北大核心 2024年第3期160-166,共7页
目的构建丁型肝炎病毒(HDV)感染的肝脏类器官系统,并探讨钠离子-牛磺胆酸共转运蛋白(NTCP)受体抑制剂布乐韦肽对HDV复制的抑制作用。方法将由诱导多能干细胞(iPSC)分化的肝细胞样细胞(HLC)接种于倒置胶体晶体聚乙二醇支架(ICC),构建肝... 目的构建丁型肝炎病毒(HDV)感染的肝脏类器官系统,并探讨钠离子-牛磺胆酸共转运蛋白(NTCP)受体抑制剂布乐韦肽对HDV复制的抑制作用。方法将由诱导多能干细胞(iPSC)分化的肝细胞样细胞(HLC)接种于倒置胶体晶体聚乙二醇支架(ICC),构建肝脏类器官系统。质粒转染人肝癌细胞(HuH7)后,收获细胞上清中的HDV颗粒,同时提取HepG2.2.15细胞上清液中的乙型肝炎病毒(HBV)颗粒,将HBV和HDV颗粒共同感染肝脏类器官,构建HDV感染的肝脏类器官,同时以未感染HDV的肝脏类器官作为阴性对照组。采用免疫荧光法在激光共聚焦显微镜下观察肝脏类器官单元的结构及丁型肝炎抗原(HDAg)和乙型肝炎表面抗原(HBsAg)的表达。蛋白质印迹法检测肝脏类器官中NTCP和HDAg的蛋白质水平。布乐韦肽Pre组为感染HDV前在肝脏类器官中加入布乐韦肽进行预处理,布乐韦肽Post组为感染24h后加入布乐韦肽,IFN-α组为感染24h后加入α干扰素,并设未经药物处理的空白对照组,比较4组的HDV复制情况。采用实时荧光定量聚合酶链反应(RT-qPCR)检测iPSC分化过程中Nanog同源框(NANOG)、性别决定区Y框(SOX)2、SOX17、叉头框蛋白A2(FOXA2)、肝细胞核因子4α(HNF-4α)、白蛋白、甲胎蛋白、NTCP的mRNA相对表达量,以及药物干预后4组HDV mRNA表达量。统计学分析采用两独立样本t检验。结果iPSC分化为HLC的21d内,NANOG的mRNA表达量逐渐下降,SOX17、FOXA2的表达量先升后降,HNF-4α、白蛋白、甲胎蛋白、NTCP的表达量逐渐升高。iPSC中NTCP的蛋白质水平为0.118±0.003,低于HLC的1.315±0.073,差异有统计学意义(t=11.92,P<0.001)。HDV感染后肝脏类器官中HDAg的蛋白质水平高于未感染HDV的阴性对照组(1.284±0.128比0.157±0.040),差异有统计学意义(t=23.27,P<0.001)。感染第14天激光共聚焦显微镜下观察到三维球体结构,HDAg与HBsAg高表达。用药干预后第3天,分别与空白对照组(1.000±0.077) 展开更多
关键词 丁型肝炎 布乐韦肽 诱导多能干细胞 肝脏类器官 丁型肝炎病毒感染
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Management of autoimmune hepatitis induced by hepatitis delta virus
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作者 Eleni Gigi Vasileios Lagopoulos Aris Liakos 《World Journal of Gastroenterology》 SCIE CAS 2024年第8期799-805,共7页
Approximately 12-72 million people worldwide are co-infected with hepatitis B virus(HBV)and hepatitis delta virus(HDV).This concurrent infection can lead to several severe outcomes with hepatic disease,such as cirrhos... Approximately 12-72 million people worldwide are co-infected with hepatitis B virus(HBV)and hepatitis delta virus(HDV).This concurrent infection can lead to several severe outcomes with hepatic disease,such as cirrhosis,fulminant hepatitis,and hepatocellular carcinoma,being the most common.Over the past few decades,a correlation between viral hepatitis and autoimmune diseases has been reported.Furthermore,autoantibodies have been detected in the serum of patients co-infected with HBV/HDV,and autoimmune features have been reported.However,to date,very few cases of clinically significant autoimmune hepatitis(AIH)have been reported in patients with HDV infection,mainly in those who have received treatment with pegylated interferon.Interestingly,there are some patients with HBV infection and AIH in whom HDV infection is unearthed after receiving treatment with immunosuppressants.Consequently,several questions remain unanswered with the challenge to distinguish whether it is autoimmune or“autoimmune-like”hepatitis being the most crucial.Second,it remains uncertain whether autoimmunity is induced by HBV or delta virus.Finally,we investigated whether the cause of AIH lies in the previous treatment of HDV with pegylated interferon.These pressing issues should be elucidated to clarify whether new antiviral treatments for HDV,such as Bulevirtide or immu-nosuppressive drugs,are more appropriate for the management of patients with HDV and AIH. 展开更多
关键词 Autoimmune hepatitis Hepatitis delta virus bulevirtide PREDNISOLONE
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Bulevirtide治疗慢性丁型肝炎研究现状和面临的挑战
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作者 鲁晓擘 王晓忠 《中华肝脏病杂志》 CAS CSCD 北大核心 2022年第10期1026-1028,共3页
2020年7月,bulevirtide获批用于成人代偿期慢性丁型肝炎的治疗;近年来,多项研究评估了bulevirtide用于治疗慢性丁型肝炎的安全性和有效性,现对此进行简要综述并提出目前面临的挑战。
关键词 慢性丁型肝炎 bulevirtide 有效性 安全性 挑战
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Cautious optimism in anticipation of hepatitis B curative therapies
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作者 Alla Turshudzhyan Micheal Tadros 《World Journal of Virology》 2022年第4期212-215,共4页
Despite relative effectiveness of current hepatitis B therapies,there is still no curative agents available.The new emerging approaches hold promise to achieve cure and loss of hepatitis B surface antigen.Studies or c... Despite relative effectiveness of current hepatitis B therapies,there is still no curative agents available.The new emerging approaches hold promise to achieve cure and loss of hepatitis B surface antigen.Studies or clinical trials investigating new therapies remain small and either focus on patients with low viral load and without hepatotoxic injury or patients with hepatitis D co-infection,which makes it challenging to assess their effectiveness and side effect profile in hepatitis B population. 展开更多
关键词 Hepatitis B Hepatitis B virus Hepatitis B virus entry inhibitor bulevirtide Transcription activator-like effector nucleases Zinc-finger nucleases Clustered regularly interspaced short palindromic repeats-associated 9 Nucleocapsid assembly modulators Hepatitis B virus transcription inhibitors Hepatitis B surface antigen release inhibitors
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