慢性乙型肝炎患者HBVDNA载量与肝组织炎症及纤维化程度的相关性分析

目的研究慢性乙型肝炎(CHB)患者血清HBV DNA载量与肝组织炎症及纤维化程度间的相关性。方法将169例CHB患者根据血清HBeAg分为HBeAg阳性组(110例)和HBeAg阴性组(59例),回顾性分析血清HBV DNA载量与肝组织病理炎症分级、纤维化分期之间关系。结果 HBeAg阳性组与HBeAg阴性组血清HBV DNA载量分别为(6.9±1.3)log10拷贝/ml和(4.7±1.8)log10拷贝/ml,两组比较差异有统计学意义(P=0.024)。HBeAg阳性组患者肝组织炎症活动度G1组为9例、G2组为80例、G3~4组为21例,其血清HBV DNA载量分别为(5.7±1.4)log10拷贝/ml、(6.4±1.8)log10拷贝/ml、(7.2±1.1)log10拷贝/ml,3组患者血清HBV DNA载量比较,差异无统计学意义(P=0.069)。肝组织纤维化程度S1组为28例、S2组为50例、S3~4组为32例,其血清HBV DNA载量分别为(6.9±1.1)log10拷贝/ml、(6.9±1.4)log10拷贝/ml、(6.8±4.2)log10拷贝/ml,3组患者血清HBV DNA载量比较,差异无统计学意义(P=0.079)。HBeAg阴性组患者肝组织炎症活动度G1组为6例、G2组为19例、G3~4组为34例,其血清HBV DNA载量分别为(2.2±1.9)log10拷贝/ml、(4.9±1.5)log10拷贝/ml、(5.4±1.8)log10拷贝/ml,3组患者血清HBV DNA载量比较,差异有统计学意义(P=0.014);肝组织纤维化程度S1组为12例、S2组为30例、S3~4组为17例,其血清HBV DNA载量分别为(2.6±4.1)log10拷贝/ml、(5.3±1.3)log10拷贝/ml、(5.6±1.7)log10拷贝/ml,3组血清HBV DNA载量比较,差异有统计学意义(P=0.026)。结论 HBeAg阳性CHB患者血清HBV DNA载量与肝组织炎症及纤维化程度无显著相关。HBeAg阴性CHB患者血清HBV DNA载量较高者,其肝组织炎症及纤维化程度较高。     

乙型肝炎相关性肝衰竭患者HBV DNA低水平复制及特异性抗体表达的临床意义

目的探讨乙型肝炎相关性肝衰竭患者血清HBV DNA低水平复制及HBV特异性抗体表达的相关因素及临床意义。方法收集2008年6月至2013年12月于天津市第二人民医院住院治疗的391例乙型肝炎相关性肝衰竭患者及394例慢性乙型肝炎患者的病历资料。比较乙型肝炎相关性肝衰竭与慢性乙型肝炎患者HBV DNA表达的不同及影响因素分析。根据HBV血清学标志物(HBV M)特异性表达的不同将肝衰竭患者分为特异性抗体阳性(指抗-HBs、抗-HBe和抗-HBc同时阳性)和特异性抗体阴性(无抗-HBs、抗-HBe和抗-HBc同时阳性)2组,分析2组患者HBV DNA水平的变化和生存情况。组间比较采用独立样本t检验或MannWhitney秩和检验,计数资料比较采用χ2检验。结果乙型肝炎相关性肝衰竭患者HBV DNA水平低于慢性乙型肝炎组,差异有统计学意义(Z=-16.469,P0.05);HBeAg阳性和阴性的肝衰竭患者HBV DNA水平均低于相应的慢性乙型肝炎患者,差异有统计学意义(Z分别为-11.665和-12.853,P0.05)。在391肝衰竭病例中,HBV特异性抗体阳性组29例(7.42%),死亡25例(86.21%),HBV特异性抗体阴性组362例(92.58%),死亡157例(43.37%),2组病死率差异有统计学意义(P0.05)。特异性抗体阳性组患者HBV DNA水平明显低于特异性抗体阴性组,差异有统计学意义(Z=-3.594,P0.05)。2组HBeAg阴性患者HBV DNA水平均低于HBeAg阳性患者,差异有统计学意义(Z分别为7.427和7.513,P0.05)。结论 HBV M表达形式及机体免疫状态的动态变化在乙型肝炎相关性肝衰竭的发生发展过程中起着一定作用,HBV DNA低水平复制系机体处于免疫清除期所致,而同时伴抗-HBs、抗-HBe、抗-HBc 3个抗体同时阳性则提示机体对HBV的超强免疫反应,致使病情恶化、发展迅速,病死率高。     

慢性乙型肝炎急性加重患者自然恢复和抗病毒过程中乙型肝炎表面抗原的动力学变化

目的 了解慢性乙型肝炎急性加重患者自然恢复和短期抗病毒干预过程中的乙型肝炎表面抗原定量(HBsAg)动力学变化趋势. 方法 慢性乙型肝炎急性加重接受恩替卡韦抗HBV治疗的39例患者为A组,未接受任何抗HBV治疗的22例患者为B组,分别在入院时(基线)、极期[终末期肝病模型(MELD)评分分值最高时]、恢复期(出院前)计算MELD评分,并检测HBV DNA载量和HBsAg定量,分别比较两组之间疾病三个时期的MELD评分、HBV DNA载量和HBsAg定量;并且进行同一组内三个时期之间的两两比较.两组间均数比较采用t检验,两组内均数的两两比较采用配对t检验的BONFERRONI法,计数资料(n＜40)采用Fisher精确概率法检验.结果 A组入院时、极期、恢复期HBsAg定量分别为(3.68±0.45)log10COI,(3.84±0.19)log10COI和(3.69±0.58) log10COI;B组HBsAg定量分别为(3.59±0.54) log10COI,(3.47±0.76)log10COI和(3.43±0.68)log10COI.A组和B组之间疾病三个时期MELD评分、HBV DNA载量和HBsAg定量比较,除A组HBV DNA极期和恢复期水平低于B组外(P值均＜0.05),其余差异均无统计学意义(P值均＞ 0.05).抗HBV治疗组中,MELD评分于基线和极期均高于恢复期水平(P=0.000),但基线和极期比较,差异无统计学意义(P=1.000);HBV DNA载量自基线、极期至恢复期逐渐下降,两两比较,差异均有统计学意义(P值均＜ 0.05);HBsAg定量三者之间两两比较,差异均无统计学意义(P值均＞ 0.05).非抗HBV治疗组中,MELD评分基线和极期均高于恢复期水平(P=0.000),但基线和极期比较,差异无统计学意义(P=1.000);HBV DNA载量基线和极期均高于恢复期水平(P值分别为0.000和0.003),但基线和极期比较,差异无统计学意义(P=0.619);HBsAg定量三者之间两两比较,差异均无统计学意义(P值均＞0.05). 结论 慢性乙型肝炎急性加重患者自然康复过程中,HBsAg定量没有变化;即使进行短期抗HBV治疗干预,HBsAg定量也不受影响.     

恩替卡韦治疗后慢性乙型肝炎患者外周血T淋巴细胞表面程序性死亡受体1表达与HBeAg血清学转换的关系

目的 动态观察慢性乙型肝炎患者恩替卡韦抗病毒治疗后不同时期外周血T淋巴细胞(简称T细胞)表面程序性死亡受体1(PD-1)表达的变化,并探讨其与HBeAg血清学转换间的关系.方法 对20例HBeAg阳性慢性乙型肝炎患者予以恩替卡韦抗病毒治疗并随访51周,根据HBeAg是否发生血清学转换分为:HBeAg未转换组(14例),HBeAg转换组(6例).分别于治疗前(基线,T0)、治疗2～4周(T1)、治疗5～10周(T2)、治疗11～20周(T3)、治疗21～30周(T4)、治疗31～51周(T5)收集外周血,流式细胞术检测CD4+、CD8+T细胞表面PD-1的表达水平,实时荧光定量PCR检测血清HBV DNA载量,同时检测血清ALT水平.正态分布资料采用独立样本t检验,非正态分布者采用Mann-Whitney U检验比较组间差异,相关性分析采用Pearson相关分析.结果 治疗前两组患者血清HBV DNA载量分别为(7.54±0.67)log10拷贝/ml、(7.30±0.79)log10拷贝/ml(P＞0.05),ALT水平为(187.26±184.15)U/L、(272.17±215.07)U/L(P＞0.05),外周血CD4+T细胞表面PD-1表达水平为6.04%±3.71%6.77%±2.88%(P＞0.05),CD8+T细胞表面PD-1表达水平为6.39%±3.33%、8.88%±2.84%(P＞0.05).恩替卡韦抗病毒治疗后两组患者血清HBV DNA载量、ALT水平的下降与CD4+、CD8+T细胞表面PD-1表达的下调呈显著正相关(r=0.212,P=0.05;r=0.377,P＜0.01;r=0.279,P＜0.05;r=0.347,P＜0.01).在相同的随访时间段内,HBeAg转换组血清HBV DNA载量、ALT水平及外周血CD4+、CD8+T细胞表面PD-1表达的下降率均高于HBeAg未转换组,且两组间△ T0～T1、△T0～T2期HBV DNA的下降率及△T0～T2、△T0～T3期CD8+T细胞表面PD-1表达的下降率差异有统计学意义(分别为49.9%对比37.3%,56.7%对比47.4%,70.1%对比-4.2%,66.9%对比24.5%,P值均＜0.05).结论 HBeAg阳性慢性乙型肝炎患者经恩替卡韦抗病毒治疗后,外周血CD8+T细胞表面PD-1表达的快速下调与血清HBV DNA相似,可作为预测后期HBeAg血清学转换的指标之一.

Abstract：

Objective To observe longitudinally the expression of Programmed death 1 (PD-1) on peripheral blood T cells in chronic hepatitis B patients underwent antiviral treatment with entecavir (ETV)and to explore the relationship between PD-1 expression and HBeAg seroconversion.Methods Twenty HBeAg positive patients underwent antiviral treatment with ETV were followed up for 51 weels.14 patients remained HBeAg positive and 6 patients achieved HBeAg seroconversion.Peripheral blood was collected at six time points:T0:baseline,T1:2-4week;T2:5-10week;T3:11-20week;T4:21-30week:T5:31-51week.PD-1 expressions on T cells were assessed by flow cytometry.Serum HBV DNA loads were determined by real-time fluorescent quanttative polymerase chain reaction (PCR) and serum ALT levels were examined at the same time.Results At baseline,serum HBV DNA load of patients without HBeAg seroconversion and with HBeAg seroconversion were (7.54 ± 0.67) log10 copies/ml and (7.30 ± 0.79) log10 copies/ml(P ＞ 0.05),the ALT levels were (187.26 ± 184.15) U/L and (272.17 ± 215.07) U/L (P ＞ 0.05),PD-1 exprissions on CD4+ T cells were 6.04% ± 3.71% and 6.77% ± 2.88% (P ＞ 0.05),PD-1 exprissions on CD8+ T cells were 6.39% ± 3.33% and 8.88% ± 2.84% (P ＞ 0.05).After ETV treatment,serum HBV DNA loads and ALT levels both decreased gradually,which was positively correlated with PD-1 expressions on CD4+ and CD8+ T cells (r = 0.212,P = 0.05;r = 0.377,P ＜ 0.01;r = 0.279,P ＜ 0.05;r = 0.347,P ＜ 0.01 ).During the same monitoring period,the HBV DNA loads,ALT levels and PD-1 expressions on T cells of the patients with HBeAg seroconversion decreased significantly as compared with the patients without HBeAg seroconversion.Besides,the decrease of HBV DNA loads during period △ T0-T1 and △ T0-T2 and PD-1 expressions on CD8+ T cells during period △ T0-T2 and △ T0-T3 were significantly different between these two kinds of patients (49.9% vs 37.3%,P ＜ 0.05;56.7% vs 47.4%,P ＜ 0.05;70.1% vs -4.2%,P ＜ 0.05;66.9% vs 24.5%,P ＜ 0.05).Conclusion The rapid decrease of PD-1 expression on peripheral CD8+ T cells after antiviral treatment with ETV is positvely correlated with the decrease of serum HBV DNA loads and may be used as a predictive index for HBeAg seroconversion in HBeAg positive patients.     

HBeAg状态及乙型肝炎病毒载量对慢性重型乙型肝炎预后的影响

目的 探讨HBeAg状态及HBV DNA载量对慢性重型乙型肝炎预后的影响.方法 回顾分析2002年1月至2007年12月在南方医科大学南方医院住院的慢性重型乙型肝炎患者406例,研究HBeAg状态、HBV DNA载量对疾病预后的影响.计量资料采用t检验,率的比较采用X2检验.结果 406例重型肝炎患者中,HBeAg阳性208例,占51.2%,HBeAg阴性198例,占48.8%.HBeAg阳性组与HBeAg阴性组比较,两组间男女构成比、TBil峰值及平均凝血酶原活动度谷值差异均无统计学意义;HBeAg阴性组平均年龄(46.7±12.8)岁,显著高于HBeAg阳性组(38.3±13.5)岁(t=6.43,P＜0.01);HBeAg阴性组肝硬化患者占67.7%,亦显著高于HBeAg阳性组的45.7%(X2=19.97,P＜0.01);HBeAg阴性组好转率为32.3%,显著低于HBeAg阳性组的44.7%(X2=6.56,P＜0.05).在208例HBeAg阳性与198例HBeAg阴性患者中,均显示随着HBV DNA载量的升高,其好转率下降,呈显著负相关(X2=22.98,X2=26.04;均P＜0.01).结论 HBeAg阴性重型乙型肝炎较HBeAg阳性者预后差;无论HBeAg状态如何,HBV DNA载量越高,其预后越差.     

肝脂肪变对聚乙二醇干扰素α-2a治疗慢性乙型肝炎疗效的影响

目的 探讨肝脂肪变对慢性乙型肝炎(CHB)患者应用聚乙二醇干扰素α-2a(PEG-IFNα-2a)抗病毒疗效的影响.方法 对2005年至2009年经肝组织病理学检查确诊的应用PEG-IFNα-2a抗病毒治疗且资料齐全的50例CHB患者进行回顾性分析,依据病理学检测结果将其分为无脂变组(28例)、脂变组(轻度脂肪变21例、中度脂肪变1例).检测血常规、肝肾功能、空腹血糖、血脂,荧光定量PCR法检测HBV DNA载量(下限为500拷贝/rnl),采用电化学发光法检测HBV标志物(HBsAg、抗-HBs、HBeAg、抗-HBe)及甲状腺功能;分析比较两组患者治疗48周时的抗病毒疗效、不良反应情况.对数据中的计量资料采用t检验、计数资料采用x2检验进行统计学分析. 结果 无脂变组HBV DNA阴转率(＜500拷贝/ml)为42.9％,HBeAg/抗-HBe血清学转换率为31.6％,完全应答率39.3％;脂变组HBV DNA阴转率为40.9％,HBeAg/抗-HBe血清学转换率为33.3％,完全应答率40.9％,经x2检验(x2值分别为0.012,0.019,0.014,P值分别为0.600,0.560,0.568),未发现两组患者抗病毒治疗48周时的疗效差异存在统计学意义.两组患者抗病毒治疗后甘油三酯均较治疗前升高(无脂变组t=-2.164,P＜0.05;脂变组t=-2.863,P＜0.05);治疗后两组甘油三酯差异有统计学意义(t=2.412,P＜0.05). 结论 本研究未发现轻度肝脂肪变对CHB患者应用PEG-IFNα-2a抗病毒治疗48周时的疗效有明显影响.     

HBeAg阴性与阳性慢性乙型肝炎患者临床和病毒学特点分析

目的:回顾性分析HBeAg阴性和HBeAg阳性慢性乙型肝炎(CHB)患者在HBV DNA载量、肝功能及肝脏组织病理学方面的特点。方法:对60例CHB患者的临床资料,包括HBV DNA载量、肝功能及肝组织病理学检查结果进行回顾性分析。结果:60例患者中HBeAg阴性24例,占40.0%(24/60),平均年龄(48.3±7.7)岁;HBeAg阳性36例,占60.0%(36/60),平均年龄(27.7±9.1)岁,两者在平均年龄之间比较,差异有显著性意义(t=13.4,P<0.001)。HBeAg阴性与阳性患者的HBV DNA载量分别为(5.87±0.66)log拷贝/ml和(7.37±0.50)log拷贝/ml,两者之间比较,差异有显著性意义(t=13.6,P<0.001);ALT分别为(115.95±33.6)U/L和(172.2±84.20)U/L,两者之间比较,差异有显著性意义(t=4.81,P<0.001)。HBeAg阴性患者的肝组织炎症活动度分级(G)及纤维化分期(S)与HBeAg阳性者之间比较,差异无统计学意义(χ2值分别为2.53及1.27,P值分别为0.11及0.25)。结论:HBeAg阴性CHB患者的平均年龄高于HBeAg阳性者,HBV DNA载量及ALT值低于HBeAg阳性者,但HBeAg阴性CHB患者的肝脏组织病理学改变与HBeAg阳性者无差异。     

慢性乙型肝炎患者12周自发性HBV DNA水平变化分析

目的 分析慢性乙型肝炎患者12周内自发性HBV DNA水平下降情况.方法 回顾性分析2003-2005年未接受抗病毒药物治疗的慢性乙型肝炎患者12周内自发性HBV DNA水平下降情况,并根据患者基线ALT、总胆红素(TBil)水平进行分组,分析基线ALT、TBil对自发性HBVDNA水平下降的影响.两组间计量资料比较采用t检验或Wilcoxon符号秩和检验;多组数据均值比较采用方差分析;组间率的比较采用x2检验.结果 共收集213例慢性乙型肝炎患者,男性174例,女性39例,年龄18～65(33.0±10.0)岁.其中慢性乙型肝炎轻～中度124例,慢性乙型肝炎重度89例;12周时失访19例(8.92%).所有患者HBV DNA基线均值为(6.66±1.03)log10拷贝/ml,12周时为(5.98±1.53)log10拷贝/ml(P<0.01).慢性乙型肝炎重度患者基线时HBVDNA水平均值低于慢性乙型肝炎轻～中度患者,分别为(6.45±0.99)log10拷贝/ml与(6.81±1.04)log10拷贝/ml(P<0.05);但两组12周时HBV DNA水平均值及HBV DNA水平下降值的差异均无统计学意义.12周时HBV DNA≤3 log10拷贝/ml患者的基线ALT及TBil值高于HBVDNA>3 log10拷贝/ml组,但差异均无统计学意义.12周时HBV DNA水平下降值≥2 log10拷贝/ml与<2 log10拷贝/ml两组患者的基线ALT、TBil水平相近(P>0.05).基线ALT水平≤5倍正常值上限(ULN)与>5×ULN两组患者12周时HBV DNA水平均值及HBV DNA水平下降值的差异均无统计学意义;两组患者12周时HBV DNA≤3 log10拷贝/ml、HBV DNA水平下降值≥2 log10拷贝/ml的比例,差异也无统计学意义(P>0.05).基线时ALT≤5 × ULN及TBil≤5×ULN组HBV DNA水平均值高于其他3组(P<0.05),但12周时各组HBV DNA水平均值、HBV DNA下降值比较,差异无统计学意义. 结论 慢性乙型肝炎患者12周内存在一定程度的自发性HBV DNA水平下降,但肝脏炎症损伤程度与患者12周内自发性HBV DNA水平下降程度无明显的相关性.     

HBsAg与抗-HBs同时阳性的慢性乙型肝炎患者临床特点分析

目的分析HBsAg与抗-HBs同时阳性的现象及其临床特点,并探讨其产生的原因。方法收集2011年2月-2014年2月东南大学附属第二医院体检者2260例,其中被诊断为慢性乙型肝炎的患者830例。采用化学发光微粒子免疫分析法筛选HBsAg与抗-HBs同时阳性的患者188例,分为HBeAg阳性组(n=101)和HBeAg阴性组(n=87)。同时选取200例HBsAg阳性、抗-HBs阴性者作为对照,其中HBeAg阳性组80例,HBeAg阴性组120例。检测HBV血清学标志物、肝功能、病毒载量并结合临床进行分析。计数资料组间比较采用χ2检验。结果 HBV血清学标志物在HBsAg与抗-HBs双阳性情况下共有5种模式,其中以HBsAg、抗-HBs、HBeAg及抗-HBc阳性,且抗-HBe阴性多见,占47.9%(90/188),肝功能指标总异常率为69.1%(130/188),HBV DNA总阳性率为56.9%(107/188)。HBeAg阳性的2组HBV DNA均存在高水平复制,其中HBsAg与抗-HBs双阳性组HBV DNA阳性率与对照组比较,差异无统计学意义(χ2=2.632,P0.05);HBeAg阴性组中,HBsAg与抗-HBs双阳性组HBV DNA定量1×105IU/ml的比例与对照组比较,差异有统计学意义(χ2=10.740,P0.05)。对HBV S区进行测序分析发现,测序的80例HBsAg与抗-HBs双阳性患者中有27例患者的HBV S区发生变异,突变率33.7%,且S区变异位点主要有P29L、S61L、P62L、I126T/S、Q129N、M133K、F134L、G145R/K、L175S和L186H等。结论 HBsAg与抗-HBs同时阳性者在乙型肝炎患者中有一定比例,其主要原因可能是病毒株变异所致。这种情况并不代表疾病好转,且抗-HBs出现并不一定能完全有效清除HBsAg,病毒DNA往往存在持续复制,需引起重视。     

浙南地区HBV基因型分布特征及其与慢性乙型肝炎患者血清HBV DNA水平和HBeAg表达的关系

目的分析浙南地区慢性乙型肝炎患者HBV基因型分布特征,探讨不同基因型与患者血清中HBV DNA水平及HBeAg表达的关系。方法收集2011年6月-2012年3月161例就诊的HBV DNA阳性患者血清标本,采用型特异性引物PCR方法对HBV进行基因分型并用实时荧光定量PCR方法测量HBV DNA含量(拷贝/ml)和ELISA方法检测HBeAg;对HBV DNA含量进行对数转换使其符合正态分布后,运用χ2检验分析基因型与HBeAg阳性率的关系,t检验分析B、C基因型患者HBV DNA水平的差异。结果 161例患者中,B型41例,占25.5%;C型118例,占73.3%;BC混合型2例,占1.2%。C型患者HBV DNA水平和HBeAg阳性率分别为(5.84±1.40)log10拷贝/ml和64.4%,高于B型的(5.49±1.33)log10拷贝/ml和53.7%,但差异均无统计学意义(P0.05)。结论浙南地区HBV基因型以C型为主,B型次之。C基因型HBV DNA水平与HBeAg阳性率均高于B基因型,肝硬化的发生与C基因型HBV密切相关。     

Maternal knowledge of the risk of vertical transmission and offspring acquisition of hepatitis B

Introduction and objectivesUniversal vaccination at birth and in infancy is key to the elimination of chronic hepatitis B infection. We aimed to assess hepatitis B immune-prophylaxis and perinatal transmission knowledge, in a large and ethnically diverse cohort of previously pregnant North American women, chronically infected with hepatitis B.Materials and methodsThe Hepatitis B Research Network (HBRN) is comprised of 28 Clinical Centers in the United States and Canada. Female cohort participants were administered a questionnaire to assess: (1) their assertion of knowledge regarding HBV prophylaxis at birth, testing, and diagnosis of hepatitis B in their children, and (2) the percentage of affirmative to negative responses for each of the HBV-related interventions her child may have received. The relationship between asserted knowledge, actions taken and maternal demographics were assessed.ResultsA total of 351 mothers with 627 children born in or after 1992 were included. Median age at enrollment was 39.8 years. Mothers were mostly foreign-born with the largest percentage from Asia (73.4%) and Africa (11.7%). Of the 627 children, 94.5% had mothers who asserted that they knew whether their child had received HBIG or HBV vaccine at birth, for 88.8% of the children, their mothers indicated that they knew if their child was tested for HBV and for 84.5% of children, their mothers knew if the child was diagnosed with HBV infection. Among children whose mothers asserted knowledge of their HBV management, 95.3% were reported to have received HBIG or HBV vaccine, 83.4% of children were said to have been tested for HBV, and 4.8% of children were said to have been diagnosed with HBV. Younger maternal age was the only factor significantly associated with higher percentage of children for whom mothers reported knowledge of testing (p = 0.02) or diagnosis of HBV (p = 0.02).ConclusionsWhile high percentages of North American children had mothers asserting knowledge of HBV prophylaxis and testing, knowledge gaps remain, with mothers of 5.5–15.5% of children lacking knowledge of key components of the HBV prevention and diagnosis in the perinatal setting. Targeted education of HBsAg-positive mothers may aid in closing this gap and reducing vertical transmission.     

Advances in treatment and prevention of hepatitis B

Chronic hepatitis B(CHB) continues to contribute to worldwide morbidity and mortality significantly. Scientists, clinicians, pharmaceutical companies, and health organizations have dedicated substantial Intellectual and monetary resources to finding a cure, increasing immunization rates, and reducing the global burden of CHB. National and international health-related organizations including the center for disease control, the national institute of health, the American Association for the study of liver disease(AASLD), The European association for the study of the Liver(EASL), The Asia Pacific association for the study of the Liver(APASL) and the world health organization release periodic recommendations for disease prevention and treatment. Our review of the most recent guidelines by EASL, AASLD, APASL, and Taiwan Association for the Study of the Liver revealed that an overwhelming majority of cited studies were published before 2018. We reviewed Hepatitis B-related literature published 2018 onwards to identify recent developments and current barriers that will likely direct future efforts towards eradicating hepatitis B. The breakthrough in our understanding of the hepatitis B virus life cycle and resulting drug development is encouraging with significant room for further progress. Data from high-risk populations, most vulnerable to the devastating effects of hepatitis B infection and reactivation remain sparse. Utilization of systems approach, optimization of experimental models, identification and validation of next-generation biomarkers, and precise modulation of the human immune response will be critical for future innovation. Within the foreseeable future, new treatments will likely complement conventional therapies rather than replace them. Most Importantly, pragmatic management of CHB related population health challenges must be prioritized to produce real-world results.     

拉米夫定治疗慢性乙型肝炎病人的长期疗效

通过多中心,承机,双盲,安慰剂对照的临床试验,研究拉米夫定（ｌａｍｉｖｕｄｉｎｅ）对慢性乙型肝炎（乙肝）病人的疗效和安全性。方法随机选择３２２例慢性乙肝病拉米夫定治疗（１００ｍｇ／ｄ）,１０７例病人服用安慰剂作对照,共治疗１２周,在１２周治疗结束后,拉米夫定组和安慰剂组病人均继续服用拉米夫定１００ｍｇ治疗至５２周。疗效评估包括临床症状和体征,肝功能和ＨＢＶ复制指标。结果治疗１２周,拉米夫定组ＨＢＶ     

拉米夫定治疗其他方法抗病毒治疗失败的慢性乙型肝炎患者的疗效

目的观察拉米夫定对复发性慢性乙型肝炎患者的疗效和安全性。方法选择27例其他方法抗病毒治疗失败的慢性乙型肝炎患者,给予拉米夫定100mg口服,每日一次,连续服用12个月。结果治疗后12个月时ALT和血清总胆红素平均值(分别为52.7±26.5U/L和19.7±21.1μmol/L),与治疗前平均值(211.3±182.4U/L和54.6±28.8μmol/L)相比显著下降(P<0.01);其ALT复常率为88.9%(24/27),HBV DNA阴转率77.8%(21/27),HBeAg阴转率29.6%(8/27),HBeAg/抗-HBe血清转换率18.5%(5/27)。停药后6个月内有7例复发。治疗全程未见严重不良反应。结论拉米夫定治疗其他方法抗病毒治疗失败的慢性乙型肝炎患者也能够迅速抑制病毒的复制,使肝功能复常,而且安全、方便。     

不同联合免疫策略对乙型肝炎病毒高载量孕妇所生婴儿抗-HBs水平的影响

目的 比较HBeAg阳性且HBV DNA高载量孕妇所生婴儿出生后应用不同剂量的乙型肝炎免疫球蛋白(HBIG)及乙型肝炎疫苗(HBVac)联合免疫接种后的母婴阻断效果,新生儿抗-HBs水平的差异. 方法 随机选取2009年至2013年我院产前检查并足月分娩的HBeAg阳性且建卡及临产均HBV DNA＞1×106 IU/ml孕妇所生婴儿118例,婴儿出生后抽血检查HBV标志物和HBVDNA定量,据产妇及家属意愿抽血后按注射HBIG及HBVac剂量的不同分为3组:A组:58例,予HBIG 200 IU及HBVac 20 μ g肌肉注射;B组:35例,予HBIG 200 IU及HBVac 10 μg肌肉注射;C组:25例,予HBIG 100 IU及HBVac 20 μg肌肉注射,随访至7月龄.婴儿出生至7月龄的HBsAg、抗-HBs、HBeAg、HBV DNA变化采用重复测量方差分析;组间比较采用x2检验,P＜ 0.05为差异有统计学意义.结果 除去5例宫内感染婴儿,113例婴儿免疫接种后均产生抗-HBs.完成HBIG注射后,A、B、C三组1月龄婴儿时抗-HBs滴度分别为(263.56±50.98) mIU/ml、(231.06±74.07) mIU/ml和(99.23±29.82) mIU/ml,C组分别与A、B组比较,t值分别为15.01、8.41,P值均＜0.001,差异均有统计学意义.A、B、C三组7月龄时婴儿抗-HBs滴度分别为(788.10±281.96) mIU/ml、(428.39±347.48) mIU/ml和(708.44±315.69) mIU/ml,B组与A、C组比较,t值分别为5.45、3.19,P值均＜0.05,差异均有统计学意义. 结论 HBeAg阳性高病毒载量孕妇所生非宫内感染儿出生后应用HBIG及HBVac免疫接种能获得较好的免疫保护,应用HBIG 200 IU较100 IU,HBVac 20 μg较10 μg更安全可靠.     

树突状细胞疫苗的制备及治疗慢性乙型肝炎的疗效观察

目的　探讨自体乙肝疫苗致敏的树突状细胞 (DC)的制备方法及其治疗慢性乙型肝炎 (CHB)的疗效。方法　取 CHB患者外周血 2 0 ml分离单个核细胞 ,加入重组人粒细胞—巨噬细胞集落刺激因子 (r GM- CSF)和白细胞介素 4 (IL- 4 )进行 DC体外扩增 ,于培养第 5天加入 5 0 μg/ m l乙型肝炎疫苗 ,7天收获细胞。 34例 CHB患者根据年龄和发病时间分为治疗 1(年龄 11～ 2 0岁 ,发病时间 0 .5～ 8.5年 )、2 (年龄 2 1～ 2 8岁 ,发病时间 3.5～ 18年 )、3(年龄 32～ 6 0岁 ,发病时间 10～ 4 2 .5年 )组 ,皮内回输 DC;对照组 CHB患者 (均为自愿停药者 ,2 0例 )注射等量生理盐水 ,均每周 1次 ,连续 8次。于回输 DC后 2周检测患者血清 HBV- DNA含量。结果　培养后可得到形态及功能典型的 DC,治疗 1、2、3组患者回输 DC后血清 HBV- DNA含量拷贝数均较对照组显著降低 (P<0 .0 1) ,总应答率 5 8.8% (2 0 / 34) ,对照组输注前后无明显变化 (P>0 .0 5 ) ;治疗 1组与 3组相比 HBV- DNA定量拷贝数降低幅度有显著性差异 (P<0 .0 1)。结论　 DC可明显降低CHB患者血清 HBV- DNA含量 ,感染病毒时间短和 /或年龄小者降低幅度大     

慢性乙型肝炎患者肝细胞内乙型肝炎核心抗原阳性的临床意义

目的探讨CHB患者肝组织HBcAg阳性的意义。方法对200例CHB患者应用荧光聚合酶链反应（FQ-PCR）法精确定量检测血清HBV DNA含量。患者均检测血清中HBeAg含量,同时进行肝活组织检查,应用免疫组织化学技术检测HBcAg情况,并进行相关性分析。结果按测定血清HBV DNA水平,分为A组（＜3 log10拷贝/ml）20例,B组（≥3 log10拷贝/ml-＜5 log10拷贝/ml）13例,C组（≥5 log10拷贝/ml～＜6 log10拷贝/ml）24例,D组（≥6 log10拷贝/ml～＜8 log10拷贝/ml）116例,E组（≥8 log10拷贝/ml）27例。肝组织HBcAg阳性者175例,占87．5％,A组HBcAg阳性率55．0％（11/20）,B组53．8％（7/13）,C组75．0％（18/24）,D组96．6％（112/116）,E组100．0％（27/27）,HBcAg阳性率与血清HBV DNA水平之间呈显著正相关（r=0．80,P＜0．01）。血清HBV DNA水平高低与HBeAg阳性率之间呈显著正相关（r=0．47,P＜0．01）。其中20例HBV DNA阴性者中（A组）,HBeAg阳性者5例（25％）,HBcAg阳性者11例（55％）；15例HBV DNA阴性且HBeAg阴性者中有7例HBcAg阳性,占46．7％。结论CHB患者肝组织HBcAg阳性能更可靠地反映肝细胞内HBV复制状态。检测肝组织内HBcAg对CHB患者疗效评价和对治疗反应性的预测更具有临床意义。     

新生儿乙型肝炎疫苗普遍接种的长期免疫效果

目的 观察新生儿乙型肝炎(简称乙肝)疫苗普遍接种预防儿童期乙型肝炎病毒(HBV)感染的长期免疫效果和对儿童乙肝发病的影响。 方法 1986年起在乙肝高发区隆安县实施不筛检母亲HBsAg、新生儿普遍接种常规剂量乙肝疫苗的免疫方案。采用出生队列定群随访、横断面调查和监测乙肝发病情况的方法对血源乙肝疫苗和重组酵母乙肝疫苗的保护效果进行观察。 结果 血源乙肝疫苗免疫后1～1 3年HBsAg阳性率为0.7％～2.9％,平均1.7％,保护率为83.5％～96.6％,HBV感染率为1.1％～5.1％,平均2.4％,保护率为93.5％～98.4％。重组酵母乙肝疫苗免疫儿童的HBsAg阳性率为1.8％～2.4％,平均2.0％,保护率为78.4％-85.2％。免疫实施14年后, 1～14岁人群乙肝发病率为1.5/10万,比历史对照同龄者减少了91.8％;未免疫儿童发病率为14.4/1 0万,与历史对照差异无显著性,免疫儿童中无乙肝病例发生,保护率为100％。 结论 新生儿乙肝疫苗免疫后13年内不必加强免疫,重组酵母乙肝疫苗与血源性乙肝疫苗的保护效果相似,乙肝疫苗预防作用已初见成效。     

Persistence of Anti-HBs Among Palestinian Medical Students After 18 - 22 Years of Vaccination: A Cross-Sectional Study

Background:

Hepatitis B infection is a global public health problem affecting various sectors in the society. Vaccination is the first line measure to prevent the disease.

Objectives:

To assess the persistence of anti-HBs marker among medical students after 18 - 22 of vaccination as an indicator for Hepatitis B virus vaccine efficacy.

Patients and Methods:

In this study, 249 Palestinian medical students vaccinated at birth, 1, and 6 months of age using Engerix™-B starting from 1992 were studied. About 58% (144/249) of the students were Palestinians holding Israeli citizenship, while 42% (105/249) were Palestinians from the West Bank. Students were tested serologically for anti-HBs, as a marker for vaccine-induced immunity.

Results:

Over 75% (188/248) of students had levels of anti-HBs greater than 10 mIU/mL indicating immunity and protection. Five cases had positive results for anti-HBc indicating exposure to HBV infection; however, none of these cases showed any sign of HBV-DNA indicating effective clearance of the virus by the vaccine. Around 57% of the study group had anti-HBs level of 100 - 1000 mIU/mL. No significant association was found between anti-HBs level and age, sex, locality and level of anti-HBc (P > 0.05). The students were aware of different aspects of hepatitis B infection regarding the virus, symptoms, prevention and mode of transmission.

Conclusions:

The Palestinian and Israeli official policies to give a booster dose for risk groups like medical students at anti-HBs level below 10 mIU/mL should continue to ensure absolute protection. The currently-used vaccine and its time program cleared virus from students believed to have been exposed to the virus during their lifetime.     

Randomized trial of lamivudine versus hepatitis B immunoglobulin for long-term prophylaxis of hepatitis B recurrence after liver transplantation

BACKGROUND/AIMS: The long-term prophylaxis of hepatitis B after liver transplantation requires further optimization. In a randomized trial we investigated a regimen where the initially given hepatitis B immunoglobulin (HBIg) is replaced by long-term lamivudine treatment. METHODS: Twenty-four liver transplant recipients (all HBsAg-positive/HBV DNA-negative before transplantation), who had received HBIg for at least 6 months without HBV recurrence, were randomized to receive lamivudine (n = 12) or HBIg (n = 12) for 52 weeks. The efficacy criteria involved seronegativity for HBsAg and undetectable HBsAg/ HBcAg in the liver. RESULTS: Twenty-one of 24 patients completed the study without hepatitis B virus (HBV) recurrence (11 on HBIg, ten on lamivudine), while three patients became HBsAg-positive. Amongst those without HBV recurrence HBV DNA was detectable only by polymerase chain reaction, intermittently in serum and lymphocytes, and in liver specimens from six of eight patients receiving HBIg and five of seven receiving lamivudine. YMDD variant was found in four cases with no viral antigen expression. Eight patients continued lamivudine after the study and during an additional 6-22 months remained HBsAg-negative with normal graft function. CONCLUSIONS: Substitution of HBIg with lamivudine is effective for prevention of HBV recurrence in low-risk liver transplant recipients and offers a convenient and cost-effective alternative for long-term HBV prophylaxis.