慢性乙型肝炎患者血清HBV DNA水平与HBsAg和HBeAg水平的相关性分析

目的探讨慢性乙型肝炎患者血清HBV DNA水平与HBsAg和HBeAg滴度的关系。方法在951例慢性乙型肝炎患者,采用FQ-PCR法和Abbott化学发光微粒子免疫分析技术分别测定血清HBV DNA水平及HBsAg和HBeAg滴度,分析HBV DNA水平与HBsAg和HBeAg滴度的相关性。结果在951例患者中,HBVDNA阳性率为53.83%(512/951);患者血清HBV DNA水平与HBsAg和HBeAg滴度呈正相关(rs=0.45和re=0.49,P<0.05);在HBV DNA水平≥7lg拷贝/毫升患者,血清HBsAg和HBeAg滴度高于HBV DNA为3～7lg拷贝/毫升患者,HBV DNA为3～7lg拷贝/毫升患者血清HBsAg和HBeAg滴度大于HBV DNA<3lg拷贝/毫升患者,差异均有统计学意义(P<0.05);将HBsAg分为<1000 IU/ml、1000～10000 IU/ml和≥10000 IU/ml3组,结果不同HBsAg滴度患者血清HBV DNA水平差异有统计学意义(P<0.05)。结论在血清HBV DNA≥7lg拷贝/毫升和HBsAg滴度≥10000 IU/mL患者,HBV DNA水平与HBsAg滴度呈正相关,在HBV DNA>3 lg拷贝/毫升患者,血清HBV DNA水平与HBeAg滴度呈正相关。     

HBsAg阳性孕妇免疫接种阻断HBV宫内感染疗效的Meta分析

目的 评价HBsAg阳性孕妇产前应用乙肝免疫球蛋白(HBIG)或联用乙肝疫苗阻断胎儿HBV宫内感染的有效性及安全性.方法 计算机检索6个数据库,手检9种期刊,并追查参考文献,纳入国内外符合纳入标准的随机对照试验和半随机对照试验,由两名评价员独立筛查文献,评价质量和提取资料.用Revman 4.2.10软件分析数据.采用χ2检验鉴定研究间异质性,使用固定效应或随机效应模型合并结果.结果 HBsAg阳性/HBsAg和HBeAg均阳性孕妇孕期应用HBIG总剂量600 IU,胎儿HBV宫内感染率＜空白对照组(RR=0.42, 95%CI= 0.21～0.83, P=0.01),新生儿HBV DNA阳性率低于空白对照组(RR=0.30, 95%CI=0.10～0.85, P=0.02),新生儿HBeAg阳性率Anti-HBs阳性率与空白组比较差异无统计学意义;总剂量大于600 IU时,宫内感染率＜空白对照组(RR=0.39, 95%CI=0.26～0.58, P＜0.000 01),新生儿Anti-HBs阳性率与对照组比较差异无统计学意义.HBsAg和HBeAg均阳性孕妇孕期应用HBIG总剂量＞600 IU,胎儿HBV宫内感染率、新生儿HBeAg阳性率、新生儿HBV DNA阳性率、新生儿Anti-HBs阳性率与对照组比较差异均无统计学意义;总剂量600 IU组新生儿HBeAg阳性率和新生儿HBV DNA阳性率与对照组比较差异有统计学意义.结论 HBsAg阳性/HBsAg和HBeAg均阳性孕妇孕期应用HBIG可降低胎儿HBV宫内感染率;HBsAg和HBeAg均阳性孕妇孕期应用HBIG阻断宫内感染的疗效尚不清楚.     

脐带血乙肝标志物筛查乙肝病毒宫内感染的探讨

目的探讨脐带血乙肝标志物用于筛查乙肝病毒宫内感染的可能性。方法收集175例HBsAg阳性孕妇新生儿脐带血及24 h外周血,进行乙肝标志物和HBV DNA检测,6月龄时随访查外周血HBsAg。结果脐带血HBsAg阳性的新生儿外周血HBV DNA均为阳性,6月龄随访HBsAg阳性率均为100%。7例出生时注射了HBIG和乙肝疫苗的HBV DNA阳性的新生儿HBsAg随访阴转;8例脐带血HBsAg和HBV DNA均阴性的婴儿因直接母乳喂养HBsAg随访阳转。结论脐带血表面抗原可以作为筛查胎儿乙肝病毒宫内感染的指标。     

HBsAg阳性孕妇免疫接种阻断HBV宫内感染疗效的Meta分析

目的评价HBsAg阳性孕妇产前应用乙肝免疫球蛋白（HBIG）或联用乙肝疫苗阻断胎儿HBV宫内感染的有效性及安全性。方法计算机检索6个数据库,手检9种期刊,并追查参考文献,纳入国内外符合纳入标准的随机对照试验和半随机对照试验,由两名评价员独立筛查文献,评价质量和提取资料。用Revman 4.2.10软件分析数据。采用χ2检验鉴定研究间异质性,使用固定效应或随机效应模型合并结果。结果HBsAg阳性/HBsAg和HBeAg均阳性孕妇孕期应用HBIG总剂量600 IU,胎儿HBV宫内感染率〈空白对照组（RR=0.42,95%CI=0.21-0.83,P=0.01）,新生儿HBV DNA阳性率低于空白对照组（RR=0.30,95%CI=0.10-0.85,P=0.02）,新生儿HBeAg阳性率Anti-HBs阳性率与空白组比较差异无统计学意义;总剂量大于600 IU时,宫内感染率〈空白对照组（RR=0.39,95%CI=0.26-0.58,P〈0.000 01）,新生儿Anti-HBs阳性率与对照组比较差异无统计学意义。HBsAg和HBeAg均阳性孕妇孕期应用HBIG总剂量〉600 IU,胎儿HBV宫内感染率、新生儿HBeAg阳性率、新生儿HBV DNA阳性率、新生儿Anti-HBs阳性率与对照组比较差异均无统计学意义;总剂量600 IU组新生儿HBeAg阳性率和新生儿HBV DNA阳性率与对照组比较差异有统计学意义。结论HBsAg阳性/HBsAg和HBeAg均阳性孕妇孕期应用HBIG可降低胎儿HBV宫内感染率;HBsAg和HBeAg均阳性孕妇孕期应用HBIG阻断宫内感染的疗效尚不清楚。     

富马酸替诺福韦二吡呋酯和恩替卡韦初治慢性HBV感染者的效果比较

目的比较富马酸替诺福韦二吡呋酯(TDF)、恩替卡韦(ETV组)治疗初治慢性HBV感染者的抗病毒疗效。方法收集2014年7月-2015年7月周口市中心医院和南京中医药大学附属八一医院接受TDF或ETV抗病毒治疗且定期随诊的420例初治慢性HBV感染或肝硬化患者,其中接受TDF治疗者184例(TDF组),接受ETV治疗者236例(ETV组)。监测患者的基线值以及治疗后4、8、12、24、48周的实验室指标:肝肾功能指标、血钙、血磷、肌酸激酶、HBV DNA水平、肝炎标志物(HBs Ag、HBeAg、抗-HBe等),以及药物的不良反应。计量资料组间比较采用t检验,计数资料组间比较采用χ2检验或Fisher确切概率法。结果治疗48周时,TDF组与ETV组的HBeAg阳性患者、HBeAg阳性且HBV DNA>6 lg IU/ml患者的HBeAg阴转率比较差异均无统计学意义(P值均>0.05);TDF组与ETV组的HBeAg阴性患者、HBeAg阳性患者、HBeAg阳性且HBV DNA>6 lg IU/ml患者的ALT复常率比较差异均无统计学意义(P值均>0.05)。给予抗病毒治疗后,2组患者HBV DNA水平逐渐下降。治疗48周时,TDF组与ETV组的HBeAg阳性患者中的HBV DNA水平低于检测值下限率分别为75.5%、60.8%,差异有统计学意义(χ2=5.857,P=0.016);TDF组与ETV组HBeAg阳性且HBV DNA>6 lg IU/ml患者中HBV DNA水平低于检测值下限率分别为75.7%、60.5%,差异有统计学意义(χ2=5.722,P=0.017)。96周时,不管是整体还是在亚组(HBeAg阳性、HBeAg阳性且HBV DNA>6 lg IU/ml)间比较,TDF组HBV DNA低于检测值下限率均高于ETV组(93.5%vs 86.9%,χ2=4.921,P=0.027;89.1%vs 76.2%,χ2=6.781,P=0.009;88.3%vs 73.7%,χ2=7.456,P=0.006)。结论在HBeAg阳性慢性HBV感染者中,TDF抑制HBV DNA的能力明显优于ETV,尤其对HBV DNA>6 lg IU/ml的患者。     

304例阻断HBV母婴传播效果观察

目的:探讨乙肝疫苗(HepB)和高效价乙肝免疫球蛋白(HBIG)联合(以下称主被动免疫)阻断HBV母婴传播效果.方法:将宁夏平罗县304例血清HBsAg阳性孕妇及其所生婴儿作为研究对象,按孕妇血清HBeAg定性结果分为阳性组、阴性组,并对阻断结果进行分析.结果:经主被动免疫方法阻断HBV母婴传播,孕妇HBeAg阴性组阻断率达100%,HBeAg阳性组阻断率达96.51%(P＜0.05),总体阻断率达98.63%.经主被动免疫后,孕妇HBeAg阳性组婴儿12月龄抗-HBs阳转率为53.85%(56/104),孕妇HBeAg阴性组婴儿12月龄抗-HBs阳转率为58.00%(116/200)(P＞0.05),两组婴儿12月龄抗-HBs总体阳转率为56.57%.分娩方式和喂养方式不同,婴儿12月龄血清HBsAg阳性率无差别(P＞0.05).结论:主被动免疫方法阻断HBV母婴传播效果肯定.HBsAg阳性孕妇所生婴儿12月龄检查HBV-M是必要的.经主被动免疫情况后,HBeAg阳性孕妇自然分娩和母乳喂养没有增加婴儿感染HBV的危险性.     

替诺福韦、替比夫定分别联合双重免疫方案对HBV母婴传播阻断效果的比较

目的比较替诺福韦、替比夫定分别联合双重免疫方案对妊娠HBV母婴传播的阻断效果。方法选取2016年1月至2018年7月首都医科大学附属北京佑安医院妇产科收治的82例HBV感染孕妇,随机分为替诺福韦组与替比夫定组,各41例。2组均于孕28周开始服药,替诺福韦组300 mg/d;替比夫定组600 mg/d。母乳喂养者产后停止服药,不进行母乳喂养者则用药至产后4周。2组胎儿娩出后注射乙型肝炎免疫球蛋白与乙型肝炎疫苗。比较2组服药前1 d、分娩前3 d内孕妇血清ALT和HBV DNA水平,新生儿出生时、出生后1年的HBsAg阳性率、HBeAg阳性率、HBV DNA≥100 IU/mL发生率,妊娠结局与不良反应。结果 2组孕妇分娩前3 d内血清ALT、HBV DNA均较服药前1 d显著降低(P0.05)。替诺福韦组分娩前3 d血清ALT、HBV DNA分别为(32.65±6.91) U/L、(2.89±0.56) lgIU/mL,显著低于替比夫定组的(43.25±7.11) U/L、(3.67±0.67) lgIU/mL (P0.05)。2组出生时与出生后1年的HBsAg阳性率、HBeAg阳性率、HBV DNA≥100 IU/mL发生率的差异均无统计学意义(P0.05)。2组治疗期间均未见流产、产后出血、肝肾功能不全,早产、剖宫产、胎儿畸形、贫血、妊高症、胆汁酸增高发生率的差异无统计学意义(P0.05)。结论替诺福韦与替比夫定联合双重免疫方案均可有效抑制HBV复制,降低血清病毒载量,阻断HBV母婴传播,而前者对HBV抑制作用更强,有利于改善患者肝功能,临床价值更高。     

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.     

乙肝疫苗联合HBIG接种阻断HBsAg/HBeAg双阳性孕妇HBV母婴传播的效果研究

] 目的 比较乙肝疫苗联合乙型肝炎免疫球蛋白（HBIG）与乙肝疫苗接种阻断HBsAg/HBeAg双阳性母亲HBV母婴传播的效果。方法 对血清HBsAg阳性或HBsAg/HBeAg双阳性母亲所生新生儿分别按标准方法接种乙肝疫苗或者乙肝疫苗与HBIG联合接种,比较儿童HBV感染率情况。结果 在110例血清HBsAg阳性母亲所生的110例只接种乙肝疫苗的儿童中,出生和6月龄血清HBsAg阳性率分别为28.2%和10.9%,与240例HBsAg/HBeAg阳性母亲所生的240例只接种乙肝疫苗的新生儿（分别为39.6%和24.2%）比,无显著性相差（P>0.05）;在150例血清HBsAg阳性母亲所生的150例接种乙肝疫苗联合HBIG儿童中,出生和6月龄血清HBsAg阳性率分别为17.3%和3.3%,与100例HBsAg/HBeAg阳性母亲所生的100例新生儿（分别为25.0%和11.0%）比,也无显著性相差（P>0.05）,但无论在血清HBsAg阳性还是血清HBsAg/HBeAg阳性母亲,联合接种儿童HBV感染率均显著低于只接种乙肝疫苗者（P<0.05）。结论 采取乙肝疫苗联合HBIG接种能降低乙型肝炎病毒携带母亲所生儿童的HBV感染率。     

乙肝疫苗联合HBIG接种阻断HBsAg/HBeAg双阳性孕妇HBV母婴传播的效果研究

目的 比较乙肝疫苗联合乙型肝炎免疫球蛋白（HBIG）与乙肝疫苗接种阻断HBsAg/HBeAg双阳性母亲HBV母婴传播的效果。方法 对血清HBsAg阳性或HBsAg/HBeAg双阳性母亲所生新生儿分别按标准方法接种乙肝疫苗或者乙肝疫苗与HBIG联合接种,比较儿童HBV感染率情况。结果 在110例血清HBsAg阳性母亲所生的110例只接种乙肝疫苗的儿童中,出生和6月龄血清HBsAg阳性率分别为28.2%和10.9%,与240例HBsAg/HBeAg阳性母亲所生的240例只接种乙肝疫苗的新生儿（分别为39.6%和24.2%）比,无显著性相差（P>0.05）;在150例血清HBsAg阳性母亲所生的150例接种乙肝疫苗联合HBIG儿童中,出生和6月龄血清HBsAg阳性率分别为17.3%和3.3%,与100例HBsAg/HBeAg阳性母亲所生的100例新生儿（分别为25.0%和11.0%）比,也无显著性相差（P>0.05）,但无论在血清HBsAg阳性还是血清HBsAg/HBeAg阳性母亲,联合接种儿童HBV感染率均显著低于只接种乙肝疫苗者（P<0.05）。结论 采取乙肝疫苗联合HBIG接种能降低乙型肝炎病毒携带母亲所生儿童的HBV感染率。     

Effect of hepatitis B immunoglobulin on interruption of HBV intrauterine infection

AIM: To evaluate the efficacy of hepatitis B immunoglobulin (HBIG) in interrupting hepatitis B virus (HBV) intrauterine infection during late pregnancy.METHODS: We allocated 112 HBsAg positive pregnant women into 2 groups randomly. Fifty seven cases in th HBIG group received 200 IU (unit) HBIG intramuscularly every 4 wk from the 28 wk of gestation to the time of delivery, while 55 cases in the control group received no special treatment. HBsAg, HBeAg, HBcAb, HBeAb, HBsAb and HBV DNA levels were tested in the peripheral blood specimens from all of the mothers at 28 wk of gestation, just before delivery, and in blood from their newborns within 24 h before administration of immune prophylaxis.RESULTS: The intrauterine infection rate in HBIG group and control group were 10.5% and 27.3%, respectively, with significant difference (P&lt;0.05). It showed ascendant trend as HBV DNA levels in the peripheral blood increased before delivery.CONCLUSION: HBIG is potent to cut down HBV intrauterine infection rate significantly when administered to pregnant women regularly during late pregnancy. The possibility of HBV intrauterine infection increases if maternal blood HBV DNA≥10^8 copies/mL.     

Changes in levels of hepatitis B virus markers in patients positive for low-titer hepatitis B surface antigen

Aim: Recently, patients positive for the low-titer hepatitis B surface antigen (HBsAg) have been found occasionally owing to the increase in the accuracy of detection methods. The aim of this study is to clarify the clinical status of acute hepatitis B virus (HBV) infection in patients positive for low-titer HBsAg. Method: Eight patients, who were positive for HBsAg at low titers and diagnosed as having acute HBV infection, were enrolled in this study. Assays of HBsAg, hepatitis B core antibody (anti-HBc), hepatitis B e-antigen (HBeAg), hepatitis B e-antibody (anti-HBe), hepatitis B surface antibody (anti-HBs) and HBV DNA, and biochemical tests were basically conducted every 4 weeks for at least 24 weeks. Result: The average cut-off index of HBsAg was 8.7 ± 9.6 (range, 1.0–25.7). All the patients were negative for anti-HBc, HBeAg, anti-HBe and HBV DNA on their initial visit. The genotype of HBV could be determined in four patients: two were infected with genotype B/HBV, one was infected with genotype A/HBV, and the remaining patient was infected with genotype C/HBV. Although HBsAg clearance was observed within 4 months in all the patients, none of the other HBV markers seroconverted during the observation period. Conclusion: HBV infection terminating with seronegativity for HBV markers may occur in transient HBV infection.     

A randomized controlled clinical trial： Interruption of intrauterine transmission of hepatitis B virus infection with HBIG

AIM: To evaluate the efficacy of interruption of intrauterine infection of HBV with HBIG in pregnant women with positive HBeAg and HBsAg. METHODS: A prospective randomized controlled trial was adopted. Sixty cases with positive HBeAg and HBsAg were coincident with the criteria of inclusion, and 8 cases were excluded. Fifty-two cases were analyzed (28 cases in trial group and 24 in control group). All cases in trial group received 200 IU HBIG intravenously every 4 wk for 3 times from the 28th wk. The cases of control group received placebo in the same way. All pregnant women were detected for HBeAg and HBV-DNA at the beginning of the trial and end of the trial (delivery). The cord blood of all newborns were collected for detecting HBeAg and HBV-DNA simultaneously. RESULTS: For investigation of HBeAg of newborns in trial group, 6 of 28 cases of newborns had positive HBeAg, the HBeAg positive rate being 21.4%, the total rate of 95% CI being 8%-41%. In control group, 19 of 24 cases of newborns had positive HBeAg, HBeAg positive rate was 79.2%, the rate of 95%CI being 5%-93%. By statistical analysis, x2 = 17.26, P < 0.01, RR = 0.27, 95% CI (6.3×10-6, 8.6×10-5). For investigation of HBV-DNA of newborns in trial group, 7 of 28 cases of newborns had positive HBV-DNA, HBV-DNA positive rate being 25%, the total rate of 95% CI being ll%-45%. In control group, 20 of 24 cases of newborns had positive HBV-DNA, HBV-DNA positive rate was 83.3%, the total rate of 95% CI being 63%-95%. By statistical analysis, x2 = 17.62, P < 0.01, RR = 0.30, 95% CI (1.5×10-5, 1.7×10-4). The results indicated that there was significant difference in HBeAg positive rate and HBV-DNA positive rate of newborns between the two groups. In trial group, 7 of 28 newborns had HBV-DNA positive, but the HBV-DNA load of newborns was lower than that of their mothers. In control group, 20 of 24 newborns still had HBV-DNA positive, and the HBV-DNA load of newborns was close to those of their mothers. Statistical analysis indicated that there was no significant difference in HBV-DNA load between postnatal women without HBIG intervention and their filial generations (T = 81.5, P > 0.1). CONCLUSION: It is effective and safe to prevent in-trauterine infection of HBV with HBIG from the 28th wk in pregnant women with positive HBeAg and HBsAg. In clinical application, those pregnant women with negative HBeAg and positive HBV-DNA also need to be interrupted by HBIG.     

Comparison between quantitative hepatitis B surface antigen,hepatitis B e‐antigen and hepatitis B virus DNA levels for predicting virological response to pegylated interferon‐α‐2b therapy in hepatitis B e‐antigen‐positive chronic hepatitis B

Aim: The aim of this study was to compare the clinical applicability of quantitative serum hepatitis B surface antigen (HBsAg), hepatitis B e‐antigen (HBeAg) and hepatitis B virus (HBV) DNA for predicting virological response (VR) to pegylated interferon (PEG‐IFN) therapy. Methods: Thirty HBeAg‐positive chronic hepatitis B patients who received PEG‐IFN‐α‐2b for 48 weeks were enrolled. Quantitative HBsAg, HBeAg and HBV DNA were measured before, during and after the therapy. Paired liver biopsies were performed before and after treatment for covalently closed circular (ccc)DNA and intrahepatic HBV DNA analysis. Results: VR at 48 weeks post‐treatment, defined as HBeAg seroconversion and HBV DNA less than 10 000 copies/mL was achieved in 10 (33.3%) patients. Responders had significantly lower baseline HBsAg, HBeAg, cccDNA and intrahepatic HBV DNA levels than non‐responders. Baseline and reduced levels of log₁₀ HBsAg and log₁₀ HBeAg correlated well with those of log₁₀ cccDNA and log₁₀ total intrahepatic HBV DNA. Responders showed consistent decrease in serum HBsAg, HBeAg and HBV DNA levels during therapy. HBeAg level of 2.0 log₁₀ sample to cut‐off ratio at week 24 on therapy provided the best prediction of sustained virological response, with sensitivity and negative predictive values of 85% and 92%, respectively. One patient (3.3%) who cleared HBsAg at follow up exhibited a more rapid decline in serum HBsAg during therapy than those who developed VR without HBsAg clearance. Conclusion: Quantitative measurement of serum HBeAg during therapy may be superior to serum HBsAg and HBV DNA as a prediction of HBeAg seroconversion. Kinetics of HBsAg levels on therapy may help predict HBsAg clearance after treatment.     

Clearance of hepatitis B surface antigen during long-term nucleot(s)ide analog treatment in chronic hepatitis B: results from a nine-year longitudinal study

Background

Clearance of hepatitis B surface antigen (HBsAg) is considered the ultimate goal in chronic hepatitis B treatment. One treatment option is long-term nucleot(s)ide analog (NA) therapy. We followed a group of long-term NA therapy patients to evaluate the efficacy of this treatment in promoting clearance and longitudinal declines of HBsAg.

Method

The study included 791 NA therapy patients who received lamivudine as their first drug. At the baseline, 442 patients were hepatitis B e antigen (HBeAg)+ and 349 were HBeAg?. All analyses were performed after separating the HBeAg+ and HBeAg? cohorts. Cox proportional hazards models were used to determine which factors were associated with HBsAg clearance.

Results

HBsAg clearance was observed in 18 (4.1 %) of the HBeAg+ patients and 20 (5.7 %) of the HBeAg? patients at baseline, giving seroclearance rates of 6.4 and 6.9 %, respectively, over the nine-year study period. HBsAg clearance was influenced by several independent factors that varied according to HBeAg cohort. For HBeAg+ patients, these included previous interferon therapy, infection with hepatitis B virus (HBV) genotype A, a ≥0.5 log IU/mL decline in HBsAg level within six months, and clearance of HBeAg at six months. For HBeAg? patients, these included infection with HBV genotype A, decline in HBsAg at six months, and a baseline HBsAg level of <730 IU/mL.

Conclusion

This study suggests that both direct antiviral potential and host immune response are needed to achieve HBsAg clearance by NA therapy. Viral genotype strongly influenced HBsAg clearance during NA therapy.     

聚乙二醇化干扰素治疗乙型肝炎病毒e抗原阳性慢性乙型肝炎患者乙型肝炎病毒表面抗原消失的相关因素

目的 探讨聚乙二醇化干扰素（PEG-IFN α-2a）治疗HBeAg阳性慢性乙型肝炎(CHB)患者过程中预测HBsAg消失的相关因素。方法 对72例HBeAg阳性CHB患者,应用PEG-IFN α-2a 180 μg,每周1次,共48周。每3个月检测ALT、AST及HBV DNA、HBeAg和H BsAg定量,对48周治疗结束时HBsAg消失与基线、12周、24周的HBV DNA、HBeAg和HBsAg定量的相关关系进行分析。计数资料行Fisher精确检验及受试者工作特征(ROC)曲线分析。结果65例HBeAg阳性CHB患者完成本研究,其中7例HBsAg消失。48周时HBsAg的消失与治疗12周时H BeAg水平有关（Fisher确切概率法,P=0.023）,与治疗24周时HBeAg水平高度相关 （Fisher确切概率法,P=0.004）,与12周或24周时HBsAg＜250 IU/mL相关(Fisher确切概率法,P=0.001,P=0.002)。与12周时HBV DNA阴转相关（Fisher确切概率法,P=0.039）,而与24周时HBV DNA是否阴转无关（Fisher确切概率法,P= 0.130）。经ROC曲线分析显示,12周、24周HBsAg及24周HBeAg曲线下面积(AUC)分别为0.8584(P=0.0021)、0.9606(P=0.001)及0.8350(P=0.040)。结论 联合应用24周HBeAg和HBsAg定量水平可能是预测48周疗程结束时是否发生HBsAg消失的有效指标。     

Missed opportunities for prevention of perinatal transmission of hepatitis B: A retrospective cohort study

BACKGROUND:

Perinatal transmission of hepatitis B virus (HBV) can occur despite postexposure prophylaxis (PEP). Recent literature suggests that antiviral treatment during pregnancy when maternal HBV DNA levels are elevated can further decrease vertical transmission. However, HBV DNA screening is not routinely performed antenatally.

OBJECTIVE:

To determine the rates of HBV prevalence and perinatal transmission in an antenatal cohort.

METHODS:

A retrospective review of public health records (December 2008 to December 2010) was performed for both mothers and newborns.

RESULTS:

A total of 725 mother-infant pairs were included. Of these, 574 of 715 (80%) women had antenatal hepatitis B e antigen (HBeAg) testing performed, and 127 of 574 (22%) were HBeAg positive (HBeAg+). Of babies born to hepatitis B surface antigen-positive (HBsAg+) mothers, only 573 of 725 (79%) received complete PEP. In addition, 172 of 725 (24%) infants did not receive post-PEP blood testing or were lost to follow-up. Of the 552 infants with results available, seven cases (1.3%) of mother-to-child HBV transmission were observed, six of which involved infants born to HBeAg+ women.

CONCLUSIONS:

Our findings suggest that routine HBeAg screening could identify a subset of mother-infant pairs among HBsAg+ pregnant women who are at higher risk for vertical HBV transmission. Determination of viral load in expectant HBeAg+ mothers may provide more precise insight into HBV transmission to their infants.     

Switching to peginterferon for chronic hepatitis B patients with hepatitis B e antigen seroconversion on entecavir – A prospective study

Nucleos(t)ide analogues (NA) are effective in suppressing hepatitis B virus (HBV) replication, but most patients require long‐term treatment. This study aimed to investigate switching to peginterferon as a strategy to stop NA. Hepatitis B e antigen (HBeAg)‐positive chronic hepatitis B patients who developed HBeAg seroconversion during NA treatment were studied. All patients received open‐label peginterferon alfa‐2a 180 μg/wk for 48 weeks, and NA was stopped at week 4 of peginterferon treatment. The primary endpoint was sustained response, which was defined as negative HBeAg, positive anti‐HBe and HBV DNA <2000 IU/mL at week 72. Other secondary endpoints including HBsAg loss at week 72 were also studied. Forty‐one patients treated with entecavir for 56 ± 23 months were recruited. Sustained response was achieved in 30 patients (73%, 95% confidence interval 58%‐84%). At week 72, 31 (76%) patients had HBeAg seroconversion, 56 (23%) patients had undetectable HBV DNA, 31 (76%) patients had normal ALT, and 6 patients (15%) had HBsAg loss. Baseline HBsAg level was the best predictor for both sustained response and HBsAg loss; the best HBsAg cut‐off for sustained response was <1500 IU/mL and that for HBsAg loss was <500 IU/mL by receiver operating characteristic curve analysis. Twenty‐two of 25 (88%) patients with baseline HBsAg <1500 IU/mL had sustained response. Five of 10 (50%) patients with baseline HBsAg <500 IU/mL developed HBsAg loss. Switching to peginterferon can be considered as a treatment option in NA‐treated patients with HBeAg seroconversion, particularly among those with lower HBsAg levels.     

定量检测710例肝病患者HBsAg和H BeAg临床意义

目的：了解乙型肝炎与肝硬化患者表面抗原（HBsAg）与e抗原（HBeAg）定量变化规律,探讨分层次联合抗病毒治疗并争取满意效果的可行性。方法采用荧光磁微粒酶免法检测710例 HBV 相关肝病患者 HBsAg 和HBeAg,用SPSS19．0软件包进行统计学处理。结果 HBsAg＜0．2 IU/mL 61例,占8．5％;HBsAg＞0．2 IU/mL～＜100 IU/mL 为低水平 HBsAg组,55例,占7．7％;HBsAg ＞100 IU/mL～＜1000 IU/mL 为中等水平 HBsAg 组,142例,占20％;HBsAg 1000～5000 IU/mL为高水平 HBsAg 组,211例,占29．7％;HBsAg＞5000 IU/mL 为超高水平HBsAg组,241例,占33．9％;各型肝炎随年龄增大,HBsAg 定量值逐步下降,转阴高峰集中在46岁左右;HBeAg 阴性组（＜1．0 CI）453例,占63．8％;低水平 HBeAg阳性组（＞1．0 CI～＜10 CI）96例,占13．5％;中等量水平 HBeAg 阳性组（＞10 CI～＜100 CI）55例,占7．7％;高水平 HBeAg 阳性组（＞100 CI～＜500 CI）23例,占3．2％;超高水平HBeAg阳性组（＞500 CI）83例,占11．6％;从慢性 HBV携带者,慢性乙型肝炎,代偿期肝硬化到失代偿期肝硬化,年龄逐步增大,HBsAg和 HBeAg定量秩均值逐步下降,卡方检验有显著性差异。结论 HBsAg 和 HBeAg 定量随年龄增加与病情发展逐步下降,根据 HBsAg,HBeAg 和 HBV DNA定量进行分层次联合抗病毒治疗可争取较满意效果。     

Transformation of hepatitis B serologic markers in babies born to hepatitis B surface antigen positive mothers

AIM: To better understand the clinical significance of hepatitis B seroiogic markers in babies born to hepatitis B surface antigen (HBsAg) positive mothers, the incidence of maternal seroiogic markers of hepatitis B via placenta and its transformation in these babies were investigated. METHODS: Mothers with positive HBsAg were selected in the third trimester of pregnancy. Their babies received immunoprophylaxis with hepatitis B immunoglobulin and hepatitis B vaccine after birth, and were consecutively followed up for hepatitis B seroiogic markers and HBV DNA at birth, mo 1, 4, 7, 12, and 24. RESULTS: Forty-two babies entered the study, including 16 born to hepatitis B e antigen (HBeAg)-positive HBsAg carrier mothers and 26 to HBeAg-negative HBsAg carrier mothers. Apart from four babies born to HBeAg-positive carrier mothers and demonstrated persistent positive HBeAg eventually became HBV carriers, all other babies developed anti-HBs before 12 mo of age. Among the other 12 babies born to HBeAg-positive carrier mothers, HBeAg was detected in 7 at birth, in 4 at mo 1, and in none of them thereafter. No antibody response to the transplacental HBeAg was detected. Among the babies born to HBeAg-negative carrier mothers, anti-HBe was detected 100% at birth and mo 1, in 88.5% at mo 4, in 46.2% at mo 7, in 4.2% at mo 12 and none in mo 24. Among all the immunoprophylaxis-protected babies born to either HBeAg-positive or HBeAg-negative carrier mothers, anti-HBc was detected in 100% at birth, mo 1 and mo 4, in 78.9% at mo 7, in 36.1% at mo 12 and in none at mo 24. CONCLUSION: HBeAg can pass through human placenta from mother to fetus and become undetectable before 4 mo of age, but no antibodies response to the transplacental HBeAg can be detected till mo 24 in the immunoprophylaxis-protected babies. The sole existence of anti-HBe before 1 year of age or anti-HBc before 2 years of age in babies born to HBsAg carrier mothers may simply represent the transplacental maternal antibodies, instead of indicators of HBV infection status.