慢性乙型病毒性肝炎治疗新方法

就当前慢性乙肝治疗的新方法、新进展作一综述。     

Expression of type Ⅰ interferon in monocyte-derived dendritic cells after Toll like receptor 3 triggered in patients with chronic hepatitis B

Objective To detect the expression of type Ⅰ interferon in monocyte-derived dendritic cells(MoDCs)after Toll like receptor(TLR)3 triggered in patients with chronic hepatitis B(CHB),and to evaluate immune responses of CHB patients and its roles in the mechanisms of persistent infection of hepatitis B virus(HBV)and chronicity of hepatitis.Methods Peripheral blood mononuclear cells(PBMCs)were isolated and purified using magnetic beads(plasma was saved simultaneously)from 26 CHB patients and 18 healthy volunteers(HV).Dendritic cells(DCs)were induced and proliferated in a culture medium with recombinant human granulocyte macrophage colony stimulating factor(rhGM-CSF)and recombinant human interleukin(rhIL-4).EX3s were stimulated with Poly Ⅰ:C and the supernatants were collected at 0 h and 24 h after stimulation.Type Ⅰ interferon(IFN-α and IFN-β)in plasma and supernatants were examined by enzyme linked immunosorbent assay (ELISA).Results The levels of type Ⅰ interferon in plasma were not significantly different in groups of HV and CH B.IFN-α and IFN-β expressions in supernatants before Poly Ⅰ:C stimulation were(80.00±16.15)ng/L,(36.39±13.90)ng/L in CHB group and(76.76±15.90)ng/L,(37.14±13.68)ng/L in HV group,respectively.And there were no statistical differences between two groups(t=1.651,t=0.178;both P＞0.05).IFN-α expressions in supernatants at 24 h after stimulation in two groups were both higher than those before stimulation(at 0 h),but there were no statistical differences(t=1.534,t=1.243;both P＞0.05).IFN-β expressions in supernatants at 24 h after stimulation in HV group was(54.57±16.80)ng/L,which was significantly higher than that at 0 h(37.14±13.68)ng/L(t=4.061,P＜0.05).However,there was no significant difference at 24 h than tht at 0 h in CHB group(t=1.796,P＞0.05).At 24 h after stimulation.IFN-β level was(54.57±16.80)ng/L in HV group,which was significantly higher than that[(41.64±12.57)ng/L]in CHB group(t=2.921,P＜0.05).Conclusions Functions of MoDCs from CHB patients are impaired and MoDCs could not express type Ⅰ interferon normally.Expression of type Ⅰ interferon after TLR3 triggered in CHB patients is mainly IFN-β.     

Expression of type Ⅰ interferon in monocyte-derived dendritic cells after Toll like receptor 3 triggered in patients with chronic hepatitis B

Objective To detect the expression of type Ⅰ interferon in monocyte-derived dendritic cells(MoDCs)after Toll like receptor(TLR)3 triggered in patients with chronic hepatitis B(CHB),and to evaluate immune responses of CHB patients and its roles in the mechanisms of persistent infection of hepatitis B virus(HBV)and chronicity of hepatitis.Methods Peripheral blood mononuclear cells(PBMCs)were isolated and purified using magnetic beads(plasma was saved simultaneously)from 26 CHB patients and 18 healthy volunteers(HV).Dendritic cells(DCs)were induced and proliferated in a culture medium with recombinant human granulocyte macrophage colony stimulating factor(rhGM-CSF)and recombinant human interleukin(rhIL-4).EX3s were stimulated with Poly Ⅰ:C and the supernatants were collected at 0 h and 24 h after stimulation.Type Ⅰ interferon(IFN-α and IFN-β)in plasma and supernatants were examined by enzyme linked immunosorbent assay (ELISA).Results The levels of type Ⅰ interferon in plasma were not significantly different in groups of HV and CH B.IFN-α and IFN-β expressions in supernatants before Poly Ⅰ:C stimulation were(80.00±16.15)ng/L,(36.39±13.90)ng/L in CHB group and(76.76±15.90)ng/L,(37.14±13.68)ng/L in HV group,respectively.And there were no statistical differences between two groups(t=1.651,t=0.178;both P＞0.05).IFN-α expressions in supernatants at 24 h after stimulation in two groups were both higher than those before stimulation(at 0 h),but there were no statistical differences(t=1.534,t=1.243;both P＞0.05).IFN-β expressions in supernatants at 24 h after stimulation in HV group was(54.57±16.80)ng/L,which was significantly higher than that at 0 h(37.14±13.68)ng/L(t=4.061,P＜0.05).However,there was no significant difference at 24 h than tht at 0 h in CHB group(t=1.796,P＞0.05).At 24 h after stimulation.IFN-β level was(54.57±16.80)ng/L in HV group,which was significantly higher than that[(41.64±12.57)ng/L]in CHB group(t=2.921,P＜0.05).Conclusions Functions of MoDCs from CHB patients are impaired and MoDCs could not express type Ⅰ interferon normally.Expression of type Ⅰ interferon after TLR3 triggered in CHB patients is mainly IFN-β.     

新的诊断技术在肝病中的应用

近年来，人们运用诊断技术，特别是分子生物学技术诊断肝脏疾病。现就一些新的核酸检测技术、肝活检技术和血清标记物的临床应用做一总结。     

艾滋病合并多重感染一例

患者,男,33岁。因反复高热2月余入院。患者2个月来反复出现发热,体温最高达40℃,在外院查血白细胞2．7×10~9/L,中性粒细胞0．68,先后给予“头孢哌酮、左氧氟沙星、青霉素、头孢曲松”等多种抗菌药物治疗,用药后体温能降至正常,但停药后再次发热,如此反复多次。1周前患者再次出现高热,伴咳嗽,咳黄脓痰,自服抗生素药效不佳。入院体检：体温38．3℃,血压110/70 mm Hg(1mm Hg= 0．133 kPa),皮肤、黏膜未见皮疹、出血点,全身浅表淋巴结未及,咽无充血,扁桃体无充血肿大。颈软,两肺呼吸音粗,     

DNA 甲基化修饰在乙肝病毒持续感染相关肝病中的研究现状

乙型肝炎病毒（Hepatitis B virus,HBV）为双链 DNA 嗜肝病毒,其感染在世界范围内流行。目前全球约有近4亿 HBV慢性感染者,其中我国约占一亿。而每年更有近100万人死于HBV 感染所致的肝衰竭、肝硬化及原发性肝癌［1］。但迄今为止,HBV 感染慢性化、其持续感染所致的肝硬化及原发性肝癌的具体机制尚未明了,这也是改善 HBV 慢性感染相关疾病高死亡率的主要难点。     

细胞自噬在HBV慢性化感染中的研究现状

正1细胞自噬概述细胞自噬是真核细胞特有的生命现象,是细胞利用溶酶体降解胞内衰老细胞器、长寿命蛋白和内吞物质的过程,其降解产物可被循环再利用[1,2]。生理状态下,大多数组织细胞有一个基础水平的自噬,以维持细胞内蛋白质代谢平衡及内环境稳态,当细胞遭遇压力如饥饿、生长因子缺乏、胞内蛋白质蓄积、病毒感染、氧化应激、内质网应     

表观遗传学对乙型肝炎病毒复制的调节

全球有4亿多人感染了乙型肝炎病毒(HBV),慢性HBV感染仍是造成终末期肝病(肝硬化和肝细胞肝癌)最主要的原因[1-2].一旦形成慢性感染,人体便很难有效清除HBV.HBV在肝细胞内不断利用自身和宿主蛋白酶合成稳定的共价闭合环状DNA(covalently closed circular DNA,cccDNA)寄生于肝细胞核内,使得现有抗病毒药物难以根治HBV感染[3].近年来,研究者们发现HBV复制与许多非免疫调控机制有关,如HBV利用自噬系统促进自身复制[4-5].表观遗传学作为重要的转录后调节机制也受到关注,其中的cccDNA甲基化、miRNA、组蛋白修饰均参与了HBV基因表达的调控[6-13].通过进一步研究表观遗传学对HBV调控的机制,可能为揭示HBV感染慢性化原因、研发新的抗病毒药物治疗靶点提供思路.以下,我们分别就miRNA、cccDNA甲基化、组蛋白乙酰化对HBV调节机制的研究进展进行综述.     

自身免疫性胰腺炎所致反复肝功能异常1例

患者,男,52岁。因"胸痛5月余,反复中上腹不适伴黄疸3月余。"于2012年2月6日入复旦大学附属华山医院感染科住院治疗。患者2011年8月底无明显诱因下出现胸痛,不伴咳嗽、咳痰、咯血、呼吸困难等。9月1日至当地医院就诊,行胸部增强CT提示"两肺多发结节,双侧肺门、纵膈、右腋下淋巴结肿大"。于2011年10月11日在上海某三甲医院行胸腔     

血吸虫感染鼠血清SEAIC水平与肝脏病变关系的动态观察

采用分离纯化的兔抗ＳＥＡ－ＩｇＧ以生物素－亲和素放大系统，用ＣａｐｔｕｒｅＥＬＩＳＡ方法检测感染血吸虫鼠血清中抗ＳＥＡ循环免疫复合物（ＳＥＡＩＣ）水平在感染后各周的动态变化；并在观察肝脏病变的同时，采用图像分析技术，动态测定各周肝内虫卵肉芽肿的直径和面积。结果表明，血清ＳＥＡＩＣ在感染后４ｗｋ即可检出，６－７ｗｋ时达高峰，以后有所下降，但至实验观察结束时（１２ｗｋ）仍维持在较高水平。感染后４ｗｋ，肝组织内发现虫卵，但到５ｗｋ时尚未形成虫卵肉芽肿病变，至６ｗｋ时，肝内形成巨大的虫卵结节，其直径和面积于７ｗｋ时达高峰，此后逐渐下降，其动态变化与血清ＳＥＡＩＣ水平的动态变化相吻合，表明血清ＳＥＡＩＣ水平的高低可以作为反映肝脏病变程度的指标，并提示ＳＥＡＩＣ在日本血吸虫病的免疫发病机理中可能起重要作用。