在慢性乙型肝炎治疗过程中HBsAg水平与HBV DNA病毒复制的相关性分析

目的： 病毒载量的测定常被用来诊断和监测慢性乙型肝炎的疗效。文献报道采用全自动微粒子化学发光免疫反应测定HBsAg水平可作为替代标记。本研究旨在进一步分析慢性乙型肝炎治疗过程中血清HBsAg水平和HBV DNA水平的相关性。方法：本研究选取47例慢性乙型肝炎的患者［男性35人,女性12人,平均年龄(35±8)岁］。聚乙二醇化干扰素α-2a单一治疗患者（18例）、聚乙二醇化干扰素α-2a +拉米夫定联合治疗患者（14例）、拉米夫定单一治疗患者（15例）治疗48周并留取0、4、8、24、48、72周的血清。用TaqMan PCR测定HBV DNA水平,全自动微粒子化学发光免疫反应测定HBsAg水平。结果：18例聚乙二醇化干扰素α-2a单一治疗的患者和14例聚乙二醇化干扰素α-2a +拉米夫定联合治疗的患者可观察到HBsAg滴度随HBV DNA复制水平的一致变化,呈显著相关（r=0.83,P<0.01）。而在15例拉米夫定单一治疗的患者则未观察到HBsAg滴度随HBV DNA复制水平一致的变化趋势,但无相关性。聚乙二醇化干扰素α-2a单一治疗、聚乙二醇化干扰素α-2a+拉米夫定联合治疗的患者HBsAg水平中位数下降幅度均明显优于拉米夫定单一治疗的患者（P<0.05）。结论：在以干扰素为基础的慢性乙型肝炎治疗期间,血清HBsAg水平与HBV DNA 水平显著相关,动态HBsAg定量监测对治疗有一定的指导意义,可作为监测HBV疗效的替代标记。     

拉米夫定与阿德福韦酯初始联合治疗HBeAg阳性慢性乙型肝炎96周疗效观察

目的 观察拉米夫定(LAM)和阿德福韦酯(ADV)初始联合治疗HBeAg阳性的慢性乙型肝炎(CHB)的长期疗效与安全性.方法 自首都医科大学附属北京地坛医院肝病中心2009年2月-2009年5月开始初始抗病毒治疗的HBeAg阳性CHB患者中,选择ETV单药治疗患者、LAM和ADV联合治疗患者各25例进行前瞻性观察;比较治疗96周时两组患者在病毒学应答率、生化学应答率及免疫学应答率等方面有无差异.结果 经过96周抗病毒治疗,取得完全病毒学应答的患者在ETV组为19/22例(86.4％),而联合治疗组仅有9/21例(42.9％),二者差异显著(x2=8.953,P=0.003);在肝脏生化学应答方面两组均取得明显改善;两组的HBeAg阴转、HBe血清学转换、HBsAg阴转等免疫控制指标均无明显变化.两组患者在为期96周的治疗随访过程中,均未发生病毒学突破或HBV DNA反跳.两组患者在为期96周的治疗随访过程中,未发现任何不良反应.两组患者的肾功能在基线及96周时均处于正常范围,且治疗前后无显著性差异.结论 在HBeAg阳性CHB初始抗病毒治疗患者中,应用ETV单药治疗组的96周病毒学应答率显著高于LAM和ADV联合治疗组.     

阿德福韦治疗慢性乙型肝炎过程中HBV DNA及丙氨酸氨基转移酶水平的变化

目的 研究新药阿德福韦(ADV)治疗慢性乙型肝炎过程中HBV DNA及丙氨酸氨基转移酶(ALT)水平的变化情况,从而指导临床用药. 方法 采集16例慢性乙型肝炎(CHB)患者用ADV治疗前血清,即基线(BL)血清,以及持续服药12、16、28、40、48、52、68、80、92周共10个时段的系列血清.用荧光定量PCR法检测其HBV DNA的水平.用全自动生化仪检测其ALT的水平. 结果 从BL到48周时段,HBV DNA中位数显著下降;在52周,HBV DNA中位数出现反弹;从52至92周时段,HBVDNA中位数再次下降.16例不同时段血清ALIT中位数的变化与HBV DNA中位数变化一致.ADV治疗12周时,HBV DNA中位数较基线下降了2.34 lg拷贝/ml,无HBV DNA阴转、HBeAg血清学转换;治疗28周时,HBV DNA中位数较基线下降了2.91 lg拷贝/ml,有2例HBV DNA阴转、ALT恢复正常、HBeAg血清学转换;治疗40、48周时,HBV DNA中位数较基线分别显著下降了3.83、3.95 kg拷贝/ml,有4例HBV DNA阴转、ALT恢复正常、HBeAg血清学转换;治疗52周时,HBV DNA中位数较基线下降了2.90 lg拷贝/ml,出现反弹,但仍有4例HBV DNA阴转、ALT恢复正常、HBeAg血清学转换;治疗68、80、92周时,HBV DNA中位数较基线显著下降了3.51、3.81、4.01 lg拷贝/ml,分别有4、6、6例HBV DNA阴转、ALT恢复正常、HBeAg血清学转换.16例患者接受ADV治疗的两年中,有9例患者分别从16、28、40周开始HBV DNA的水平显著下降;7例患者HBV DNA的水平下降但不显著. 结论 阿德福韦治疗慢性乙型肝炎过程中,HBV DNA及ALT中位数的变化情况基本一致.52周时段HBV DNA水平出现反弹,提示52周可能是抗病毒的关键时段.     

血清HBeAg定量变化与慢性乙型肝炎治疗应答的相关性研究

目的 探讨慢性乙型肝炎(CHB)患者抗病毒治疗过程中血清HBeAg定量动态变化对治疗应答的预测价值.方法 对接受α-干扰紊(α-IFN)治疗的53例患者和核苷类似物(NA)治疗的70例患者,采用电化学发光免疫分析法( ECLIA)测定治疗前、治疗后12、24、48周时血清HBeAg定量,并分析血清HBeAg动态定量与治疗应答相关性.结果 干扰素或核苷类似物治疗48周,完全应答者与非完全应答者血清HBeAg基线水平差异无统计学意义(P＞0.05),而治疗12、24周血清HBeAg水平及下降幅度差异有统计学意义(P＜0.05).治疗24周血清HBeAg定量水平＜100U/ml、下降幅度＞90％的患者完全应答率高(P＜0.05).结论 α-干扰素或核苷类似物治疗慢性乙型肝炎过程中,血清HBeAg定量的动态变化对治疗应答有一定的预测价值.     

阿德福韦酯治疗慢性乙型病毒性肝炎96周疗效观察

目的 观察阿德福韦酯治疗慢性乙型病毒性肝炎患者96周的临床疗效.方法 选取慢性乙型病毒性肝炎患者80例,予阿德福韦酯(1mg/d)抗病毒治疗;服药12周时行HBV DNA检测,无早期应答者(病毒载量下降<2 log10拷贝/ml)予改用其他核苷类药物.疗程96周,观察血清转氨酶(ALT)复常率、HBV DNA阴转率、HBeAg消失率和HBeAg血清转换率.结果 61例有早期应答患者在治疗第96周时ALT复常率达85.25%(52/61),HBV DNA阴转率为95.08%(58/61),HBeAg消失率为51.52%(17/33),而HBeA8血清转换率为42.42%(14/33);治疗至96周时有2例发生病毒学反弹.19例于12周时因无早期应答而改用其他核苷类似物患者,96周时的ALT复常率为57.89%(11/19),HBV DNA阴转率为68.42%(13/19),HBeAg消失率及HBeAg血清转换率均为58.33%(7/12).结论 阿德福韦酯对慢性乙型肝炎患者能有效抑制HBV复制,长期服用有较好疗效;对无早期应答病例及早换药有助提高疗效.     

阿德福韦酯治疗慢性乙型病毒性肝炎96周疗效观察

目的 观察阿德福韦酯治疗慢性乙型病毒性肝炎患者96周的临床疗效.方法 选取慢性乙型病毒性肝炎患者80例,予阿德福韦酯(1mg/d)抗病毒治疗;服药12周时行HBV DNA检测,无早期应答者(病毒载量下降<2 log10拷贝/ml)予改用其他核苷类药物.疗程96周,观察血清转氨酶(ALT)复常率、HBV DNA阴转率、HBeAg消失率和HBeAg血清转换率.结果 61例有早期应答患者在治疗第96周时ALT复常率达85.25%(52/61),HBV DNA阴转率为95.08%(58/61),HBeAg消失率为51.52%(17/33),而HBeA8血清转换率为42.42%(14/33);治疗至96周时有2例发生病毒学反弹.19例于12周时因无早期应答而改用其他核苷类似物患者,96周时的ALT复常率为57.89%(11/19),HBV DNA阴转率为68.42%(13/19),HBeAg消失率及HBeAg血清转换率均为58.33%(7/12).结论 阿德福韦酯对慢性乙型肝炎患者能有效抑制HBV复制,长期服用有较好疗效;对无早期应答病例及早换药有助提高疗效.     

HBeAg阴性肝硬化患者抗病毒治疗的护理要点

目的 探讨HBeAg阴性的乙型肝炎肝硬化患者接受核苷(酸)类似物治疗过程的护理要点.方法 将111例患者分为抗病毒组58例和对照组53例,抗病毒组在常规护肝治疗的基础上加用核苷(酸)类似物抗病毒治疗,对照组给予常规护肝治疗,对所有患者进行护理观察,总结护理要点.结果 除死亡8例外其余患者均完成96周治疗和随访,抗病毒组的ALT复常率和HBV DNA下降幅度均高于对照组,抗病毒组及对照组的HBV DNA转阴率(<500拷/m1)分别为88.7%及32.5%,两组差异有统计学意义(x2=31.427,P=0.001).结论 核苷(酸)类似物对HBeag阴性的肝硬化能有效抑制HBV复制,改善肝硬化患者肝功能.在治疗过程中做好疾病及药物知识宣教,建立良好的护患关系,强化患者的遵医行为,及时观察处理并发症,是治疗成功的关键.     

HBeAg阴性肝硬化患者抗病毒治疗的护理要点

目的 探讨HBeAg阴性的乙型肝炎肝硬化患者接受核苷(酸)类似物治疗过程的护理要点.方法 将111例患者分为抗病毒组58例和对照组53例,抗病毒组在常规护肝治疗的基础上加用核苷(酸)类似物抗病毒治疗,对照组给予常规护肝治疗,对所有患者进行护理观察,总结护理要点.结果 除死亡8例外其余患者均完成96周治疗和随访,抗病毒组的ALT复常率和HBV DNA下降幅度均高于对照组,抗病毒组及对照组的HBV DNA转阴率(<500拷/m1)分别为88.7%及32.5%,两组差异有统计学意义(x2=31.427,P=0.001).结论 核苷(酸)类似物对HBeag阴性的肝硬化能有效抑制HBV复制,改善肝硬化患者肝功能.在治疗过程中做好疾病及药物知识宣教,建立良好的护患关系,强化患者的遵医行为,及时观察处理并发症,是治疗成功的关键.     

甘草酸二胺对阿德福韦酯治疗HBeAg阳性慢性乙型肝炎疗效影响的研究

目的评价短期应用甘草酸二胺(甘利欣)对阿德福韦酯(ADV)治疗HBeAg( )慢性乙型肝炎患者抗病毒疗效的影响。方法采用随机、有限的(24周)双盲、安慰剂(PLB)对照、多中心临床研究。HBeAg阳性的慢乙肝患者按照2∶1的比例,随机分为ADV ADV组:ADV10mg/d,治疗48周;PLB ADV组:PLB10mg/d,24周后改用ADV10mg/d,治疗24周,共48周。评价研究过程中使用甘草酸二胺对病毒学应答、血清学应答及生化应答的影响。结果ADV ADV组和PLB ADV组应用甘草酸二胺和未用者间的病毒学、血清学和生化学应答方面无明显差异。在治疗0~24周期间短期应用甘草酸二铵的两组患者,治疗前人口学、既往治疗史、HBV DNA和ALT水平间无差别。治疗12、24周后,ADV ADV组血清中HBV DNA平均水平明显低于PLB ADV组,HBV DNA与基线相比的下降量则明显高于PLB ADV组患者,P<0.05。结论甘草酸二胺单独应用不能替代ADV的抗病毒作用,但与ADV同时应用不影响其抗病毒疗效。     

HBeAg阴性肝硬化患者抗病毒治疗的护理要点

目的 探讨HBeAg阴性的乙型肝炎肝硬化患者接受核苷（酸）类似物治疗过程的护理要点.方法 将111例患者分为抗病毒组58例和对照组53例,抗病毒组在常规护肝治疗的基础上加用核苷（酸）类似物抗病毒治疗,对照组给予常规护肝治疗,对所有患者进行护理观察,总结护理要点.结果 除死亡8例外其余患者均完成96周治疗和随访,抗病毒组的ALT复常率和HBV DNA下降幅度均高于对照组,抗病毒组及对照组的HBV DNA转阴率（〈500拷/m1）分别为88.7%及32.5%,两组差异有统计学意义（x2=31.427,P=0.001）.结论 核苷（酸）类似物对HBeag阴性的肝硬化能有效抑制HBV复制,改善肝硬化患者肝功能.在治疗过程中做好疾病及药物知识宣教,建立良好的护患关系,强化患者的遵医行为,及时观察处理并发症,是治疗成功的关键.     

慢性乙型肝炎患者肝组织中HBV抗原表达特征及其临床意义

目的探讨慢性乙型病毒性肝炎肝活检组织中检测乙肝表面抗原(HBsAg)和乙肝核心抗原(HBcAg)表达强度及表达方式的必要性。方法采用EnVision免疫组织化学法检测196例慢性乙型肝炎患者肝穿组织中HBsAg和HBcAg的表达水平,并用荧光定量PCR检测其血清中的HBV DNA的含量。对肝组织进行炎症活动度分级和纤维化分期。结果肝组织中的HBsAg表达强度和表达方式与炎症分级、纤维化分期和血清乙肝病毒载量均无相关性(P>0.05)。HBcAg表达强度与炎症分级无相关性(r=-0.02,P>0.05);与纤维化分期呈负相关(r=-0.28,P<0.01);与血清乙肝病毒载量呈正相关(r=0.53,P<0.01)。HBcAg表达方式与炎症分级为负相关(r=-0.27,P<0.01),其中浆型组炎症活动度分级高于核型组和混合型组(P<0.01),混合型组高于核型组(P<0.01)。HBcAg表达方式与纤维化分期亦呈较弱的负相关(r=-0.23,P<0.01),其中浆型组纤维化分期高于核型组和混合型组(P<0.05)。HBcAg表达方式与血清乙肝病毒载量呈正相关(r=0.22,P<0.01)。结论区分肝组织中的HBsAg表达强度和表达方式无益于了解慢性乙型肝炎患者肝损害的程度,而检测肝组织中的HBcAg则有助于临床抗病毒治疗。     

聚乙二醇干扰素α-2a联合基因重组酵母乙肝疫苗治疗HBeAg阳性CHB的疗效观察

目的 探讨聚乙二醇干扰素α-2a联合基因重组酵母乙肝疫苗治疗HBeAg阳性的慢性乙型肝炎患者疗效.方法 总75例HBeAg阳性慢性乙型肝炎纳入本研究,其中单用聚乙二醇干扰素α-2a治疗的45例（A组）;聚乙二醇干扰素α-2a联合基因重组酵母乙肝疫苗的HBeAg阳性慢性乙肝患者30例（B组）.对比分析两组在治疗0、24、48和72周时ALT、HBsAg水平、HBeAg血清转换率和HBV DNA阴转率的差异.结果 治疗前（0周）时两组患者的年龄、ALT、HBsAg和HBV DNA水平差异均无统计学意义（P＞0.05）,其中联合治疗组（B组）HBeAg水平明显高于对照组（A组）,差异具有统计学意义（P＜0.05）.第24周和48周时,两组患者的ALT、HBsAg水平、HBeAg血清学转换率和HBV DNA阴转率差异并无统计学意义（P＞0.05）.在治疗结束随访至72周时,A、B两组ALT、HBeAg血清转换率和HBsAg水平差异没有统计学意义（P＞0.05）,但B组HBV DNA阴转率高于A组,差异具有统计学意义（P=0.032）.结论 聚乙二醇干扰素α-2a联合基因重组乙肝疫苗治疗HBeAg阳性的慢性乙型肝炎患者可以提高48周治疗结束后72周时的HBV DNA阴转率,但是与HBeAg血清学转换和HBsAg水平降低无关.     

Serum M2BPGi level is a novel predictive biomarker for the responses to pegylated interferon‐α treatment in HBeAg‐positive chronic hepatitis B patients

Serum Mac‐2‐binding protein glycosylation isomer (M2BPGi) level was found to be a useful prognostic marker for hepatitis B e antigen (HBeAg)‐positive chronic hepatitis B (CHB) patients treated with nucleoside/nucleotide analogs (NUCs) therapy, and the aim of our study is to evaluate the clinical implementation of M2BPGi level in the prediction of antiviral responses to pegylated‐interferon‐α (PEG‐IFN‐α) treatment in HBeAg‐positive CHB patients. Ninety‐six CHB patients who received PEG‐IFN‐α treatment for at least 48 weeks were recruited. The serum M2BPGi, alanine aminotransferase (ALT), hepatitis B surface antigen (HBsAg), HBeAg, and HBV DNA levels at baseline, weeks 4, 12, and 24 after PEG‐IFN‐α treatment were determined and their associations with antiviral responses were evaluated and the virological response (VR) rate and serological response (SR) rate after 48 weeks of treatment were 65.6% and 35.4%, respectively. Baseline serum M2BPGi level was significantly different between VR and non‐VR (P = 0.002) or SR and non‐SR groups (P = 0.012). Multivariate analyses suggested that baseline serum M2BPGi level was independently associated with VR and SR of PEG‐IFN‐α treatment at week 48. The area under the ROC curve (AUC) of baseline M2BPGi was 0.682 in predicting VR, which was superior to HBsAg (AUC = 0.566) or HBV DNA (AUC = 0.567). The AUC of baseline M2BPGi in predicting SR was 0.655, which was also higher than that of HBsAg (AUC = 0.548) or HBV DNA (AUC = 0.583). These results suggested that baseline serum M2BPGi level was a novel predictor of VR and SR for PEG‐IFN‐α treatment in HBeAg‐positive CHB patients.     

Application strategies of serum HBV DNA detection in HBV infection patients: A retrospective study of 5611 specimens

The detection of hepatitis B virus (HBV) DNA plays a critical role in determining the level of viral replication in HBV-infected patients. However, how to select appropriate HBV DNA detection method, low-sensitivity (ls) and hypersensitivity (hs) remains unclear. In this study, hepatitis B surface antigen (HBsAg), hepatitis B e-antigen (HBeAg), alanine transaminase (ALT), aspartate transaminase (AST), and hs HBV DNA titers in serum of 5611 cases with suspected HBV infection were reviewed. Besides, the dynamic changes of HBV DNA and HBsAg in 85 chronic hepatitis B (CHB) patients receiving peginterferon α (PegIFNα) or entecavir (ETV) were observed. The results showed the positive rate of HBV DNA was 32.8%, of which low viral load (20 to 500 IU/mL) accounted for 51.8%. In the 5611 cases, when the HBsAg was less than 1000 IU/mL, the proportion of low viral load was 76.3%. Moreover, in patients receiving antiviral treatment, when HBsAg was less than 2000 IU/mL (PegIFNα) or HBsAg was less than 3500 IU/mL (ETV), the proportion of patients with low viral load was 79.5% or 78.0%, respectively. We developed a strategy of serum HBV DNA detection in HBV-infected patients. When HBsAg was negative, HBV DNA detection should be unnecessary. When HBsAg was 0.05 to 1000 IU/mL, hs HBV DNA should be detected in patients with abnormal level of ALT, AST, or HBeAg. While HBsAg was greater than or equal to 1000 IU/mL, ls HBV DNA was recommended. Moreover, the cutoff value of HBsAg increased during antiviral therapy of CHB patients. In conclusion, hs HBV DNA is of great value in HBV-infected patients with low viral load. HBV DNA detection methods should be selected reasonably according to the levels of HBsAg, HBeAg, ALT, and AST.     

HBsAg level and clinical course in patients with chronic hepatitis B treated with nucleoside analogue: five years of follow-up data

Background/Aims

Quantification of the hepatitis B surface antigen (HBsAg) is increasingly used to determine the treatment response in patients with chronic hepatitis B (CHB). However, there are limited data about the clinical implications of Quantification of HBsAg long-term nucleoside analogue treatment for CHB. We investigated the clinical correlation between HBsAg level and clinical course in patients with CHB who are treated long-term with nucleoside analogues.

Methods

Patients with CHB who started lamivudine or entecavir monotherapy before June 2007 were enrolled. HBsAg was quantified at baseline, at 6 months, and at 1, 2, 3, 4, and 5 years of treatment. We compared data between the groups according to the presence or absence of a virological response (VR) and resistance.

Results

Forty-eight patients were analyzed. There was no definite reduction in HBsAg level during the early period of treatment; differences in HBsAg levels between baseline and each time point were significant only at 5 years (P=0.028). In a subgroup analysis, this difference was significant only in non-resistant patients at 5 years (P=0.041).

Conclusions

There was no definite decrease in the HBsAg level during the early period of nucleoside analogue treatment, with long-term treatment being required to observe a significant reduction.     

Hepatitis B surface antigen levels at 6 months after treatment can predict the efficacy of lamivudine-adefovir combination therapy in patients with lamivudine-resistant chronic hepatitis B

Background/Aims

Quantitation of hepatitis B surface antigen (HBsAg) is an increasingly popular method to determine the treatment response in chronic hepatitis B (CHB) patients. The clinical value of HBsAg level measurement during rescue therapy for lamivudine (LMV)-resistant CHB patients have not been evaluated to date. Therefore, this study investigated the correlation between HBsAg level and treatment response in LMV-resistant CHB patients treated with adefovir (ADV) add-on therapy.

Methods

LMV-resistant CHB patients treated with LMV-ADV combination therapy for over 2 years were included. HBsAg levels were measured at 6 month intervals until 1 year, and annually thereafter. Treatment response was assessed by determining the virological response (VR, undetectable HBV DNA levels) during treatment.

Results

Fifty patients were included, of which 40 showed a VR. HBsAg levels were not different significantly at baseline (4.0 vs. 3.6 Log10 IU/mL, P=0.072). However, the HBsAg level decreased after 6 months of treatment in patients with a VR and became different significantly between the groups thereafter (3.9 vs. 3.3 at 6 months, P=0.002; 3.8 vs. 3.2 at 1 year, P=0.004; 3.9 vs. 3.2 at 2 years, P=0.008; 3.7 vs. 3.1 at 3 years, P =0.020).

Conclusions

The HBsAg level at 6 months after treatment can help predict treatment response.     

乙肝肝硬化患者血清HBV DNA与透明质酸的关系

目的研究乙肝肝硬化患者血清HBV DNA水平和血清透明质酸的关系。方法临床确诊为乙肝肝硬化的62例患者,采用荧光定量PCR检测血清HBV DNA水平,放射免疫法检测血清透明质酸,对血清HBV DNA水平和透明质酸的关系进行研究分析。结果乙肝肝硬化患者的血清透明质酸水平显著升高,随Child分级的加重血清透明质酸也呈增高趋势(P<0.05),但与血清HBV DNA水平差异无统计学意义(P>0.05)。结论乙肝肝硬化患者的血清HBV DNA和肝硬化的程度及血清透明质酸水平无显著相关性。     

慢性乙型肝炎患者血液流变学的研究

目的　探讨慢性乙型肝炎 (慢性乙肝 )患者血液流变学的改变 ,并分析其与患者HBVDNA、肝功能、氧化损伤各项指标间的关系。方法　检测 5 5例慢性乙肝患者血液流变学指标、氧化损伤指标、肝功能、HBVDNA ,并对此做出相关分析。结果　乙肝组与正常对照组比较 :全血低切粘度、红细胞聚集指数均有明显升高 (P <0.0 5 )。ALT异常组与正常组及正常对照组比较 :红细胞压积、全血低切粘度、红细胞聚集指数均有明显升高 (P <0 .0 5 )。HBVDNA阳性组与阴性组比较差异无统计学意义 (P >0.0 5 )。血液流变学指标和氧化损伤指标间无相关关系 (P >0.0 5 )。结论　慢性乙肝患者体内存在微循环障碍及氧化损伤 ,血液流变学及氧化损伤指标与HBVDNA是慢性乙肝患者检查中相对独立的指标