拉米夫定联合苦参素治疗慢性乙型肝炎68例临床观察

目的　探讨拉米夫定(LAM)联合苦参素治疗慢性乙型肝炎(CHB)患者的临床疗效。方法　将慢性乙型肝炎患者13 4例随机分为治疗组(68例)与对照组(66例)。治疗组给予LAM联合苦参素治疗;对照组单用LAM。疗程6个月,随访6个月。观察治疗前后的血生化,HBeAg ,HBVDNA等指标的变化情况。结果　疗程结束后和停药6个月后,治疗组患者血清HBeAg、HBVDNA等指标显著下降,与对照组比较差异有显著性(P <0 .0 5或P <0 .0 1)。结论　LAM联合苦参素治疗CHB疗效优于LAM单一用药。     

无环鸟苷增强干扰素抗乙型肝炎病毒作用

治疗慢性乙型肝炎(CHB)若能使其病毒转变为潜伏状态,其标志为乙型肝炎 e 抗原(HBeAg)消失,便能使症状消退,肝炎的活动性和感染力也得以消除。因此,CHB 伴有活动性病毒复制时,抗病毒药可成为首选疗法。应用单一药物干扰素(IF)或阿糖腺苷     

CYP2R1基因多态性与恩替卡韦抗病毒治疗乙型肝炎病毒e抗原血清学转换的相关性

目的 探讨维生素D代谢酶基因CYP2R1多态性与慢性乙型病毒性肝炎(CHB)患者恩替卡韦治疗后乙型肝炎病毒e抗原(HBeAg)血清学转换的相关性.方法 选择CHB患者65例,使用恩替卡韦治疗48 w,随访至72 w;根据治疗应答效果分为完全应答(CR)组和非完全应答(NCR)组,对两组患者CYP2R1 rs2060793和rs12794714进行基因分型.观察其疗效和血清HBeAg转换的情况.结果 治疗48 w后,30例为CR组,35例为NCR组.CYP2R1 rs12794714 TT基因型(OR=2.019,95%CI:0.982~4.319,P=0.035)可以预测恩替卡韦治疗完成后持续的HBeAg血清学转换.在恩替卡韦治疗48 w后,CYP2R1 rs12794714 TT基因型患者的HBV DNA含量明显低于非TT基因型患者含量(P<0.05).结论 携带T等位基因的CHB患者在恩替卡韦治疗后更容易获得HBeAg血清转换效果.     

2006年沪港国际肝病会议精选（肝炎部分）

一、乙型肝炎e抗原（HBeAg）阴性慢性乙型肝炎的治疗 法国巴黎大学Patrick Marcellin教授对前C区变异、e抗原分泌缺失或减少的HBeAg阴性慢性乙型肝炎（CHB）的治疗进行了回顾与评述。     

乙型肝炎病毒核心启动子缺失突变导致HBeAg表达不能

目前认为10%～30%的慢性乙型肝炎(CHB)患者为乙型肝炎e抗原(HBeAg)阴性CHB,表现为丙氨酸氨基转移酶(ALT)反复波动或持续异常,对干扰素α(IFNα)治疗的疗效差,病情呈持续发展,易进展为肝硬化和(或)原发性肝癌[1].     

HBV DNA水平与HBeAg血清转换后肝炎暴发风险相关

【据J Infect Dis2011年11月报道】题:血清乙型肝炎病毒DNA水平与自发性乙型肝炎e抗原血清转换的远期不良转归相关(作者Tseng TC等)乙型肝炎e抗原(HBeAg)的状态和血清乙型肝炎病毒(HBV)DNA水平是影响成年HBV携带者预后的主要因素。然而,自发性HBeAg血清转换后病毒负荷对远期转归的影响仍未明确。我国台湾地区佛教慈济综合医院台北分行内科     

恩替卡韦治疗合并非酒精性脂肪肝的慢性乙型肝炎临床疗效观察

[目的]探讨非酒精性脂肪肝(NAFLD)对恩替卡韦(ETV)治疗慢性乙型肝炎(CHB)临床疗效的影响。[方法]纳入乙型肝炎病毒e抗原(HBeAg)阳性CHB患者273例,按是否合并NAFLD分为2组,其中合并NAFLD的CHB患者123例为观察组,单纯CHB患者150例为对照组。2组患者均予ETV抗病毒治疗至少72周,并行定期临床随访。[结果]在ETV治疗12周和24周时观察组患者的HBV-DNA清除率、HBeAg血清阴转率及谷丙转氨酶(ALT)复常率均显著低于对照组(P0.05);在36周和48周时观察组患者的ALT复常率仍显著低于对照组(P0.05),但2组间HBV-DNA清除率和HBeAg血清阴转率差异无统计学意义;在60周和72周时2组间的HBV-DNA清除率、HBeAg血清阴转率及ALT复常率差异均无统计学意义。Kaplan-Meier曲线示,观察组患者的HBV-DNA清除、HBeAg血清阴转及ALT复常均明显晚于对照组(P0.05)。[结论]NAFLD既可影响ETV治疗CHB的病毒学、血清学及生物化学应答,又是ETV抗病毒获得病毒学和血清学应答基础上生物化学应答欠佳的重要原因,而延长ETV治疗疗程则有助于改善合并NAFLD的CHB患者的生物化学应答。     

HBeAg阴性的慢性乙型肝炎113例三年随访观察

了解HBeAg阴性慢性乙型肝炎 (e-CHB)的预后和转归。对 113例HBeAg/HBeAb血清转换后的e-CHB患者随访三年 ,观察其发展变化和预后转归。e-CHB患者的复发率低于e CHB ,干扰素治疗后的e-CHB复发率高而肝硬化的发生率低。干扰素治疗e CHB有较高的远期疗效和抗肝纤维化作用     

拉米夫定联合中药治疗慢性乙型肝炎11O例

[目的]探讨拉米夫定(LAM)联合中药治疗慢性乙型肝炎(CHB)的临床疗效.[方法]将212例CHB患者随机分为治疗组(110例)与对照组(102例).治疗组给予LAM联合中药治疗;对照组单用LAM治疗.LAM100 mg/d,疗程12个月;中医辨证治疗,根据不同证型,辨证施治,每日服中药1剂,疗程＞8个月.随访1 a.[结果]治疗6、12个月及随访1 a时,治疗组的丙氨酸氨基转移酶(ALT)复常率、HBeAg转阴率、HBeAg血清转换率均明显高于对照组(P＜0.01).HBV-DNA转阴率2组在治疗3、6个月时段差异无统计学意义,而在12个月及随访1 a时段,差异有统计学意义(P＜0.01).[结论]LAM联合中药治疗,可提高CHB患者抗病毒治疗的持续应答率,减少停药后的病情复发,提高临床疗效.     

聚乙二醇干扰素(α-2a)治疗e抗原阳性慢性乙型肝炎患者早期应答的影响因素

<正>慢性乙型病毒性肝炎(CHB)是危害公共健康的传染病之一,e抗原(HBeAg)阳性慢性乙型肝炎患者体内普遍存在乙肝病毒(HBV)的复制,如不能在恰当的时机有效控制其肝细胞的坏死和炎症病变,可发展为肝硬化、肝癌等危及生命的严重疾病。本文拟观察影响聚乙二醇干扰素(α-2a)治疗HBeAg阳性CHB患者早期疗效的因素,分析其对抗病毒治疗预后评估的价值。1资料与方法1.1临床资料选择2010年1月至2012年12月在吉林省肝     

替比夫定治疗HBeAg阳性慢性乙型肝炎患者血清HBV DNA和HBeAg的动态变化及意义

目的:探讨替比夫定治疗HBeAg阳性慢性乙型肝炎患者时血清HBV DNA,HBeAg动态变化及其意义。方法:选择2008年1月至2008年12月在我院门诊或住院的HBeAg阳性慢性乙型肝炎患者56例,所有患者均给予素比夫治疗6个月。治疗过程中分别留取基线、1个月、3个月、6个月的血清,检测HBV DNA载量、HBeAg滴度。结果:HBV DNA在不同时间转阴的3组患者,1个月、3个月、6个月时HBeAg滴度逐渐降低,组内差异有统计学意义。HBeAg转阴和未转阴组HBV DNA均随治疗时间延长而下降。结论:HBeAg转阴的患者,HBV DNA可维持阴性;HBeAg未转阴的患者,应延长疗程,使HBV DNA载量逐渐下降。     

HBeAg阳性和阴性慢性乙型肝炎患者YMDD的变异

目的研究YMDD变异在HBeAg阳性和HBeAg阴性乙型肝炎病毒（HBV）感染者中发生的情况.方法对我科接受拉米夫定治疗的247例慢性乙型肝炎患者进行定期随访,检测肝功能和HBV病毒学指标,利用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）检测YMDD变异,利用实时定量PCR检测HBV DNA定量以及利用Abbott试剂检测HBV标志物,对比分析HBeAg阳性和HBeAg阴性患者中YMDD变异的发生情况.结果247例患者中共有42例出现YMDD变异,YMDD变异的累积发生率随着时间的延长逐年增加.与治疗前HBeAg阴性患者相比,治疗前HBeAg阳性患者YMDD变异的发生率明显高于治疗前HBeAg阴性患者.结论HBeAg阳性患者YMDD变异年累积发生率高于HBeAg阴性患者.     

Virological significance of HBeAg subtypes (HBeAg/1 and HBeAg/2) in patients with type B hepatitis

In order to establish the virological significance of HBeAg subtypes (HBeAg/1 and HBeAg/2) during hepatitis B virus infection, HBsAg, HBeAg and hepatitis B virus DNA in serum and HBcAg in liver were determined quantitatively in relation to the detection of HBeAg subtypes in agar gel diffusion. Thirty-eight chronic HBsAg carriers with HBeAg, including 16 non-specific reactive hepatitis, 8 chronic persistent hepatitis, 11 chronic active hepatitis and 3 liver cirrhosis, who were seen at Tohoku University Hospital from 1983 to 1985, were examined. Significantly larger amounts of HBsAg, HBeAg and hepatitis B virus DNA in serum and HBcAg in liver were found in patients positive for both HBeAg/1 and HBeAg/2 in serum than in those positive for only HBeAg/1 or negative for both subtypes. These results suggest that the presence of HBeAg/2 in serum may reflect the occurrence of active viral replication. When the detection pattern of HBeAg subtypes was examined during serial follow-up for at least 1 year, three groups of patients were classified with respect to the presence of HBeAg/2, i.e., Type I, consistently positive for HBeAg/2; Type II, consistently negative for HBeAg/2, and Type III, intermittently positive for HBeAg/2. More than 80% of Type I patients were histologically diagnosed having as nonspecific reactive hepatitis, while more than 80% of Type II and III patients had more progressive liver diseases such as chronic persistent hepatitis, chronic active hepatitis and liver cirrhosis. These results suggest that the serial examination of HBeAg subtypes in serum may be important for more detailed evaluations of type B hepatitis.     

Patients with interferon-induced HBeAg seroconversion have a higher risk of HBV reactivation and HBeAg seroreversion

Purpose

It remains unclear whether chronic hepatitis B patients who undergo interferon (IFN)-induced hepatitis B e antigen (HBeAg) seroconversion have a higher risk of hepatitis B virus (HBV) reactivation and HBeAg seroreversion than those with spontaneous HBeAg seroconversion.

Methods

A total of 80 and 251 non-cirrhotic patients with interferon-induced and spontaneous HBeAg seroconversion, respectively, were analyzed.

Results

Compared to spontaneous HBeAg seroconverters, more IFN-induced HBeAg seroconverters were males (p = 0.004). For all patients, the IFN-induced HBeAg seroconverters faced a higher risk of HBV reactivation and HBeAg seroreversion than spontaneous HBeAg seroconverters (p < 0.001). For spontaneous HBeAg seroconverters, age at HBeAg seroconversion, male sex, HBV genotype C, and pre-S deletions were independent predictors of HBV reactivation. For IFN-induced HBeAg seroconverters, older age at baseline and HBV genotype C were independent predictors of HBV reactivation. To determine whether the difference in the rates of HBV reactivation or HBeAg seroreversion between two groups was age-dependent, patients were grouped and analyzed according to their age at HBeAg seroconversion (20–30, 31–39, ≥40 years). IFNs treatment was an independent factor in HBV reactivation and HBeAg seroreversion only in the groups of patients 31–39 and ≥40 years of age, but not in the group of patients 20–30 years of age.

Conclusions

IFN-induced rather than spontaneous HBeAg seroconversion was associated with higher risk of HBV reactivation and HBeAg seroreversion, especially in patients who were older than 30 years at HBeAg seroconversion.     

HBeAg阳性和阴性的慢性乙型肝炎患者组织病理学及免疫组化学研究

目的探讨HBeAg阴性和阳性慢性乙型肝炎（CHB）患者组织病理学及免疫组化学的特点。方法对156例HBeAg阴性和阳性CHB患者肝组织炎症分级（G）及纤维化分期（S）的结果进行对比分析,并分别探讨两组CHB患者HBVDNA与ALT、G及S的关系,检测CHB患者肝组织HBsAg和HBcAg阳性表达率。结果HBeAg阴性CHB患者HBVDNA含量明显低于HBeAg阳性者,肝组织炎症程度高于后者,HBVDNA水平与ALT、G和S呈正相关,HBeAg阳性CHB血清HBVDNA与ALT、G无相关性。CHB患者肝组织HBcAg阳性率随炎症程度升高而升高。结论与HBeAg阳性CHB相比,HBeAg阴性者HBVDNA水平低,炎症程度高,HBVDNA水平与ALT、G、S正相关。CHB患者肝组织HBcAg阳性率随炎症程度增高而升高。     

e抗原阴性的慢性乙型病毒肝炎

在乙型肝炎病毒被发现 30年以来 ,世界上已超过2 0亿人口感染过乙型肝炎病毒 ,每年有 5 0 0 0万新发病例 ,每年大约有 1 5 0万人死于乙肝相关的肝硬化、肝癌[2 2 ] 。乙型病毒性肝炎已成为世界健康中的一大问题。过去人们认为在慢性乙肝病毒感染中 ,HBeAg与抗HBe的血清转换标着     

血清HBeAg阴性与HBeAg/IC及A1896变异的关系

目的探讨血清ＨＢｅＡｇ阴性（双抗体夹心法）与ＨＢｅＡｇ／ＩＣ形成及ＨＢＶ变异株Ａ１８９６的关系，评价ＨＢｅＡｇ／ＩＣ检测的临床意义．方法单克隆抗ＨＢｅ固相ＥＬＩＳＡ检测血清中ＨＢｅＡｇ／ＩＣ；套式多聚酶链反应检测ＨＢＶＤＮＡ；３＇碱基特异多聚酶链反应判断Ａ１８９６变异；ＥＬＩＳＡ检测ＨＢｅＡｇ、抗ＨＢｅ，研究对象为１１７例慢性ＨＢＶ感染者，２０例健康对照统计处理采用卡方检验．结果ＨＢｅＡｇ／ＩＣ阳性血清中ＨＢＶＤＮＡ检出率明显高于ＨＢｅＡｇ／ＩＣ阴性血清，Ｐ＜０００１（９１３％ｖｓ３６２％）；２９份ＨＢｅＡｇ阴性、ＨＢＶＤＮＡ阳性血清中仅５例（１７２％）检出Ａ１８９６，而且其中２例与野毒株（Ｇ１８９６）混合感染并伴ＨＢｅＡｇ／ＩＣ阳性．２９份中１７份（５８７％）为ＨＢｅＡｇ／ＩＣ阳性的Ｇ１８９６感染；血清抗ＨＢｅ阳性组Ａ１８９６检出率高于抗ＨＢｅ阴性组，Ｐ＜００５（２５％ｖｓ３２％）．结论ＨＢｅＡｇ／ＩＣ为ＨＢＶ活跃复制指标；临床ＨＢｅＡｇ阴性、ＨＢＶＤＮＡ阳性患者仍多数为Ｇ１８９６感染，ＨＢｅＡｇ／ＩＣ形致双抗体夹心法不能检出ＨＢｅＡｇ；抗ＨＢｅ应答可能为促使前Ｃ变异的重要因素     

替比夫定和恩替卡韦治疗HBeAg阳性慢性乙型肝炎的疗效及HBeAg血清学转换的预测因素

目的 观察替比夫定(LDT)与恩替卡韦(ETV)治疗HBeAg阳性慢性乙型肝炎的52周临床疗效.方法采用1∶1随机单盲、对照设计.共人组HBeAg阳性慢性乙型肝炎患者180例,其中LDT组90例,LDT 600mg口服,每天1次; ETV组90例,ETV 0.5 mg口服,每天1次.治疗52周进行疗效评估,并对HBeAg血清学转换相关的因素进行分析.根据资料不同采用t检验、x2检验或Logistic回归分析进行统计学分析.结果 治疗52周时,HBV DNA检测不到率,ETV组为88.9%,LDT组为78.9%,差异无统计学意义.HBeAg阴转率、HBeAg血清转换率和HBeAg较基线下降水平,LDT组分别为28.9%、27.8%和(774.7±542.4)PEIU/ml,ETV组分别为15.6%、14.4%和(603.4±480.5)PEIU/ml,两组比较,x2值分别为4.63和4.80,t值为2.02,P值均＜0.05,差异有统计学意义.治疗52周时,病毒学突破率LDT组为4.4%,ETV组为0%,x2=4.09,P＜0.05.LDT组和ETV组在治疗52周时是否出现HBeAg血清学转换与基线ALT和HBV DNA水平无相关性.多因素逐步Logistic回归分析显示,LDT组有3个因素与治疗52周HBeAg血清学转换相关,依次为:24周时HBeAg下降＞2 log,12周时HBeAg下降＞1log,基线HBeAg水平;ETV组有3个因素与52周HBeAg血清学转换相关,依次为24周时HBeAg下降＞2 log,36周时HBeAg下降＞2 log,12周时HBeAg下降＞2 log.结论 治疗HBeAg阳性慢性乙型肝炎52周,LDT较ETV有更高的HBeAg转换率,ETV组有更低的耐药率.24周时HBeAg下降＞2 log可同时作为两组患者52周HBeAg血清转换的最佳预测因素.

Abstract：

Objective To investigate the efficacy of Telbivudine and Entecavir for therapy of HBeAg positive chronic hepatitis B for 52 weeks. Methods In this random and control study, the efficacy of Telbivudine and Entecavir treatments were compared in 180 patients with HBeAg positive chronic hepatitis B.The patients were randomly assigned to a daily 600 mg Telbivudine treatment group or daily 0.5 mg Entecavir group for 52 weeks. Results At week 52, HBV DNA undetectable rate was better in the Entecavir-treated group than in the Telbivudine-treated group, but didnt reach statistical signficance. The viral breakthrough rates were significantly lower in the Entecavir-treated group than in the Telbivudine-treated group ( x2 = 4.09, P ＜ 0.05). The clearance and seroconversion of HBeAg and the mean reductions of HBeAg from baseline at week 52 were significantly greater in the telbivudine-treated group than in the entecavirtreated group ( x 2 clearance = 4.63, x2 seroconversion = 4.80, tmean reductions= 2.02; P ＜ 0.05). The HBeAg seroconversion rates were not associated with both baseline ALT and baseline HBV DNA in both groups (P ＞ 0.05). In Telbivudine-treated group, the HBeAg decline＞2 log at week 24, HBeAg decline＞1 log at week 12 and the HBeAg baseline were independent factors correlated to HBeAg seroconversion rates at week 52 by Binary Logistic analysis, and also in entecavir-treated group the HBeAg decline＞2 log at week 24, HBeAg decline ＞2 log at week 36 and the HBeAg decline＞2 log at week 12 were independent factors correlated to HBeAg seroconversion rates at week 52. Conclusion Significant difference of HBeAg seroconversion rates at week 52 existed between Telbivudine-treated group and Entecavir-treated group. Entecavir is significantly superior to Telbivudine with less resistance to nucleosides. HBeAg decline＞2 log at week 24 is the best predicting factor for HBeAg seroconversion at week 52.     

HBeAg阳性慢性乙型肝炎患者血清HBeAg与肝组织病理的相关性研究

目的探讨慢性乙型肝炎（cHB）患者血清HBeAg与肝组织炎症活动度及纤维化程度的关系。方法采用回顾性病例序列研究方法,搜集我院2005年1月至2009年12月行肝组织活检术的137例HBeAg阳性CHB患者的临床资料,血清HBeAg滴度均采用微粒子免疫发光法检测,血清HBVDNA采用荧光定量PCR法检测。结果肝组织炎症分级及纤维化分期与血清HBeAg滴度呈负相关,与ALT水平呈正相关,与HBVDNA水平无相关性;血清HBeAg和ALT水平可独立预测肝组织炎症≥G2和纤维化≥S2,优于血清HBVDNA水平和年龄;且血清HBeAg预测肝组织炎症≥G2的价值优于ALT,而预测纤维化≥S2的价值略低于ALT。肝细胞HBcAg阳性组血清HBeAg、HBVDNA水平均高于肝细胞HBcAg阴性组（均P〈0．01）。血清HBeAg滴度预测肝细胞表达HBcAg的灵敏度、特异度分别为80．02％和65．89％,高于血清HBVDNA（78．89％和43．21％）。血清HBeAg滴度与HBVDNA水平呈正相关（r=0．274,P=0．002）,与ALT水平呈负相关（r=0．212,P=0．013）。结论血清HBeAg与肝组织炎症程度及纤维化分期呈负相关;血清HBeAg滴度预测肝组织炎症程度的价值优于年龄、血清ALT、HBVDNA水平,预测肝纤维化程度的价值低于ALT。血清HBeAg较血清HBVDNA更能反映肝细胞内HBV复制情况。     

应重视HBeAg 阴性慢性乙型肝炎的诊断和治疗

HBeAg是由HBV核心基因(前C区)编码的可溶性蛋白,尽管HBeAg在病毒复制和急性感染中不是必需成分,但其是病毒复制、传染性、病情严重程度以及对治疗应答评价的重要指标。既往认为HBeAg阳性提示HBV复制活跃,传染性强,HBVDNA水平高,当HBeAg阴转同时伴有抗-HBe阳转时,则HBV DNA水平下降或消失,传染性小,同时伴肝脏炎症减轻或消失,表现为转氨酶正常,是病情趋于稳定的状态。但临床观察发现有些患者在HBeAg阴转、出现抗-HBe后仍然有转氨酶升高和肝脏的炎症坏死;随着HBV DNA检测广泛应用,发现这些患者存在明确的病毒复制,因此将慢…