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.     

乙型肝炎免疫球蛋白阴 HBV宫内感染的疗效

已经发生宫内感染的胎儿出生后使用乙型肝炎疫苗 (或和乙型肝炎免疫球蛋白 [ＨＢＩｇ]联用 )预防感染无效 ,这些新生儿极易成为慢性ＨＢＶ携带者。乙型肝炎免疫球蛋白可以和ＨＢｓＡｇ结合形成抗原抗体复合物 ,促使免疫系统清除乙型肝炎病毒 ,我们在妊娠晚期给ＨＢｓＡｇ阳性孕妇肌注ＨＢＩｇ ,观察其阻断宫内感染的疗效 ,同时探讨其使用的指征。材料与方法一、研究对象以我院 1998年 6月～ 1999年 10月产前门诊筛选无症状ＨＢｓＡｇ携带者的孕妇 86例为研究对象 ,排除甲、丙、戊、庚型肝炎病毒感染 ,未进行过抗病毒治疗。年龄 2 2～ 33岁。…     

Diarrhea and acaroid mites： A clinical study

AIM: To explore the characteristics of diarrhea caused by acaroid mites.METHODS: Acaroid mites in fresh stools of 241 patients with diarrhea were separated by flotation in saturated saline.Meanwhile, skin prick test, total IgE and mite-specific IgE were detected in all patients.RESULTS: The total positive rate of mites in stool samples of the patients was 17.01% (41/241), the positive rates of mites in male and female patients were 15.86 % (23/145)and 18.75 % (18/96), respectively, without significant difference (P＞0.05). The percentage of skin prick test as ″+++″″++ ″″+ ″″±″″-″ was″+++, ″++″,″ +″, ″±″ and ″-″was 9.13 % (22/241), 7.47 %(18/241), 5.81% (14/241), 4.98 % (12/241) and 72.61%(175/241), respectively. The serum levels of total IgE, mitespecific IgE in patients with and without mites in stool samples were (165.72±78.55) IU/ml, (132.44±26.80) IU/ml and (145.22±82.47) IU/ml, (67.35±45.28) IU/ml,respectively, with significant difference (P＜0.01). The positive rate of mites in stool samples in staffs working in traditional Chinese medicine storehouses or rice storehouses (experimental group) was 26.74 % (23/86), which was significantly higher than that (11.61%, 18/155) in people engaged in other professions (X2=8.97, P＜0.01).CONCLUSION: Acaroid mites cause diarrhea and increase serum levels of total IgE and mite-specific IgE of patients,and the prevalence of diarrhea caused by acaroid mites is associated with occupations rather than the gender of patients.     

拉米夫定阻断慢性HBV感染孕妇母婴传播的临床效果和安全性

乙型肝炎疫苗联合乙型肝炎免疫球蛋白(HBIG)对新生儿进行双重免疫虽能明显降低乙型肝炎病毒(HBV)感染率,但仍有20%～30%的新生儿免疫失败,这与宫内感染有关[1].我们近年来对部分慢性HBV感染孕妇使用拉米夫定进行阻断,并对在母婴垂直传播阻断中的效果和安全性进行了观察和总结.     

乙肝疫苗联合乙型肝炎免疫球蛋白接种阻断血清HBsAg阳性母亲HBV母婴传播效果分析*

目的 分析乙肝疫苗联合乙型肝炎免疫球蛋白（HBIG）接种阻断血清HBsAg阳性母亲乙型肝炎病毒（HBV）母婴垂直传播的效果。方法 在血清HBsAg阳性母亲所分娩的712例新生儿中,356例接受标准乙肝疫苗,另356例在接种乙肝疫苗的同时,接受 HBIG接种,比较1~10岁儿童接种成功率和HBV母婴垂直传播阻断率。结果 在56例1~2岁、234例3~4岁、249例5~6岁、135例7~8岁和38例9~10岁年龄组儿童,血清抗-HBs阳性率分别为89.3%、87.6%、81.1%、83.7%和76.3%,HBsAg阳性率分别为0.0%、0.4%、0.4%、1.5%和2.6%,各年龄组比较,无显著性统计学差异（P>0.05）;联合接种与乙肝疫苗接种组血清抗-HBs阳性率分别为84.3%和64.3%,血清HBsAg阳性率分别3.1%和15.2%,两组差异显著（P<0.05）;在血清HBsAg/HBeAg双阳性母亲所分娩的儿童,246例联合接种组血清HBsAg阳性率为1.6%,显著低于162例只接种乙肝疫苗组的11.7%（P<0.05）,而在血清HBsAg阳性母亲所分娩的儿童,110例联合接种与194例只接种乙肝疫苗组比,血清HBsAg阳性率无显著性差异（2.7%对6.2%,P>0.05）。结论 对血清HBsAg/HBeAg双阳性母亲所分娩的新生儿,给予乙肝疫苗联合HBIG接种可能更有效地阻断HBV母婴垂直传播。     

替比夫定联合HBIG和乙肝疫苗阻断HBV母婴传播临床效果分析*

目的 探讨应用替比夫定联合乙型肝炎高效价免疫球蛋白（HBIG）和乙肝疫苗阻断乙型肝炎病毒（HBV）母婴传播的临床效果。方法 在HBV感染孕妇197例中,92例在孕7月时开始口服替比夫定至分娩后3个月,两组新生儿均接受标准HBIG和乙肝疫苗接种。随访12个月。结果 研究组孕妇分娩时血清HBV DNA水平显著低于对照组（P<0.05）;研究组新生儿出生24 h和出生1个月宫内感染率均为6.7%,显著低于对照组（分别为19.6%和22.8%,P<0.05）;研究组新生儿出生12个月后HBsAg阳性率和HBV DNA阳性率分别为5.7%和0.9%,显著低于对照组（分别为19.6%和9.8%,P<0.05）,血清抗-HBs阳性率为94.3%,显著高于对照组的84.8%（P<0.05）。结论 应用替比夫定联合HBIG和乙肝疫苗能够有效抑制孕妇HBV DNA复制,降低新生儿宫内感染率,提高抗-HBs阳性率,对新生儿有良好的保护效果。     

拉米夫定和小剂量乙型肝炎免疫球蛋白合用可预防肝移植术后HBV反弹

据Medscape．com 4月19日报道（原载Gastroenterology 2007；132：931-937），小剂量的乙型肝炎免疫球蛋白（HBIG）与拉米夫定合用和大剂量的HBIG疗效相同，都可以预防HBV阳性患者肝移植术后疾病的复发。大剂量HBIG（大约10000单位／月）被证明可以有效地防止HBV感染的复发，但是对于许多乙型肝炎流行国家，这种治疗价格非常昂贵。[第一段]     

妊娠后期应用替诺福韦治疗血清HBV高载量孕妇阻断HBV母婴传播的疗效及安全性分析*

目的 探讨在妊娠后期应用替诺福韦抗病毒治疗阻断HBV高载量孕妇HBV母婴传播的效果及安全性。方法 2015年3月~2017年9月我院诊治的HBV高载量孕妇83例,其中56例在妊娠28周接受替诺福韦口服抗病毒药物至分娩结束,另27例未接受抗病毒治疗。两组新生儿在出生后立即注射乙肝免疫球蛋白（HBIG）和乙肝疫苗,在婴儿出生12个月时检测血清HBV DNA、HBeAg和HBsAg水平,判断感染阻断情况。结果 在分娩时,接受抗病毒治疗妇女血清HBV DNA水平为（3.9±0.7） lg IU/ml,显著低于未抗病毒组[（7.6±0.5） lg IU/ml,P小鱼0.05],血清HBsAg水平为（674.3±301.9） IU/ml,显著低于未抗病毒组[（1104.1±401.2） IU/ml,P小鱼0.05],血清HBeAg水平为（2059.8±996.4） s/co,显著低于对照组[（3479.4±1287.6） s/co,P小鱼0.05]; 抗病毒组HBV母婴传播阻断率为100.0%,显著高于未抗病毒组的81.5%（P小鱼0.05）;抗病毒孕妇均未出现因药物治疗而引起的不良反应,两组新生儿出生时各项生长发育指标比较差异无统计学意义（P大鱼0.05）。结论 在妊娠后期应用替诺福韦抗病毒治疗HBV高载量孕妇对阻断HBV母婴传播效果好,安全性高。     

Maternal hepatitis B virus (HBV) DNA positivity and sexual intercourse are associated with HBV intrauterine transmission in China: a prospective case-control study

BACKGROUND AND AIM: Hepatitis B virus (HBV) intrauterine transmission from infected mothers contributes significantly to the persistence of the high number of HBV carriers. The aim of this study was to identify potential risk factors for HBV intrauterine transmission. METHODS: A case-control study was performed on pregnant women tested positive for HBsAg at Shaanxi Maternal and Neonatal Health Hospital, Xi'an, China, from September 2002 to October 2004. Serum samples were taken from infected women and their newborn infants and used for the detection of HBsAg. A structured standard questionnaire was used to collect demographic, medical and maternal data, and maternal HBV DNA, HBeAg, anti-hepatitis C virus and anti-hepatitis D virus were also assessed. Ten neonates validated as having HBV intrauterine transmission were selected as cases and others as controls. RESULTS: The univariate analysis indicated that maternal HBeAg positivity (odds ratio [OR] = 5.96, 95% confidence interval [CI]: 1.61-22.12), HBV DNA positivity (OR = 12.09, 95% CI: 2.97-40.17) and sexual intercourse in the second trimester (OR = 9.15, 95% CI: 1.08-202.99) were significantly associated with an increased risk for HBV intrauterine transmission, whereas contraceptive measures before pregnancy (OR = 0.21, 95%CI: 0.04-0.99) were associated with a decreased risk. The multivariate analysis, however, identified maternal HBV DNA positivity (OR = 19.18, 95%: CI: 3.26-118.73) and sexual intercourse in the second trimester (OR = 1.29, 95%: CI: 1.00-1.66) as the only independent risk factors for HBV intrauterine transmission. CONCLUSIONS: The risk of HBV intrauterine transmission increased with increased frequency of sexual intercourse. Therefore, it is concluded that maternal HBV DNA positivity and sexual intercourse in the second trimester are independent risk factors for HBV intrauterine transmission.     

胎盘组织在乙型肝炎病毒宫内传播中的作用及其机制的研究进展

我国是乙型肝炎高发地区,人群中HBsAg阳性率高达10％以上。近年来研究表明：乙型肝炎病毒（HBV）宫内感染是HBV的主要传播途径,是造成我国人群中存在大量乙型肝炎病毒携带者的主要原因。目前针对HBV宫内感染机制的研究有很多,具体机制仍不十分清楚,但大多数研究表明宫内感染与胎盘感染有关,在宫内传播过程中,胎盘组织起重要作用,     

Risk factors of HBV intrauterine transmission among HBsAg‐positive pregnant women

Little is known about the risk factors associated with hepatitis B virus (HBV) intrauterine transmission among HBsAg‐positive mothers. We conducted a study in Taiyuan, China, including 1133 HBsAg‐positive mothers and their babies. A total of 101 neonates had HBsAg and/or HBV DNA positive with an intrauterine transmission rate of 8.9%. Maternal menstrual irregularity (OR = 4.95, 95% CI: 1.71, 14.33) and severe nausea during the first trimester (OR = 1.86, 95% CI: 1.11, 3.09) were associated with an increased risk of intrauterine transmission, while caesarean delivery (OR = 0.32, 95% CI: 0.20, 0.51) was associated with a decreased risk after adjusting for potential confounders. Maternal HBeAg positive was a strong independent predictor for intrauterine transmission (OR = 2.56, 95% CI: 1.54, 4.27). A positive association between maternal HBV DNA levels and intrauterine transmission was suggested. Maternal HBIG administration during pregnancy, family history of HBV infection and premature rupture of membranes was not associated with the risk of intrauterine transmission. The study confirmed that maternal HBeAg positive was a risk factor and caesarean delivery was a protective factor for intrauterine transmission. The new findings associated with menstrual irregularity and severe nausea during the first trimester warrant further investigation.     

HBV宫内感染机制及基因的影响

乙型肝炎是一个世界性公共卫生问题。我国地处乙型肝炎高发区，人群中HBsAg阳性率高达10％以上。近年来的研究表明HBV宫内感染是HBV主要传播途径，亦是造成我国人群中大量乙肝病毒慢性感染者的主要原因，但对宫内感染机制尚无全面系统的研究。现将HBV宫内感染机制及易感因素的近期研究成果综述如下。     

HBV宫内传播的研究进展

HBV宫内感染是乙肝免疫失败的主要原因, HBV宫内传播的途径主要有胎盘途径、PBMCS途径及经生殖细胞的传播. 其中胎盘的渗漏或胎盘细胞的感染是主要的途径. 母亲血清HBV DNA含量、HBV基因型、遗传因素是影响宫内感染的主要因素. 近年来的临床研究显示孕期使用乙肝高效价免疫球蛋白或拉米夫定可以阻断大部分宫内感染, 但目前尚缺乏大样本的随机对照研究, 探索宫内感染的机制和可行的阻断措施是我国控制乙型肝炎流行的关键所在.     

HBIG联合乙肝疫苗阻断乙肝病毒母婴垂直传播的研究

探讨阻断乙肝病毒母婴垂直传播的方法。将166例HBsAg( )孕妇分成三组,第一组婴儿注射乙肝疫苗(HBVac);第二组婴儿肌注乙肝免疫球蛋白(HBIG)加HBVac;第三组母亲于妊娠28、32、36周各肌注HBIG,婴儿用HBIG和HBVac(同第二组),血清检测HBVM采用ELISA法。21个月龄儿HBeAg阳性率分别为29.1％、20％、5.36％。孕晚期给予HBIG和婴儿给予。HBIG和HBVac联合治疗可有效阻断母婴垂直传播。     

Application of hepatitis B virus (HBV) DNA sequence polymorphisms to the study of HBV transmission

Short sequences in hypervariable regions of the hepatitis B virus (HBV) genome can be used to identify different strains, providing a novel approach to the study of HBV transmission. The nucleotide sequence in positions 2551-2650 (1:EcoRI site) was determined for serum HBV DNA from 96 Chinese children living in Hong Kong and from 38 of their parents. HBV DNA was extracted and sequenced after amplification with the polymerase chain reaction, using as primers oligonucleotides corresponding to two conserved sequences. Among 82 unrelated children, 32 HBV DNA variants were present. One sequence was present in 33 children and 31 variants were found among the other 49. Siblings within each of nine families had the same variant; in three families siblings had different variants. Six of the eight fathers and 28 of the 30 mothers had HBV DNA sequences identical to those of their offspring. A total of 34 variants were found among the 134 individuals. The hypothesis of random assortment of sequences in parents and children was rejected (P less than .00005). Thus, this new approach proves the occurrence of intrafamilial transmission of HBV among Chinese.     

乙型肝炎病毒前C区突变株感染的临床和病理

探讨乙型肝炎病毒（ＨＢＶ）前Ｃ区突变株（１８９６位点Ｇ→Ａ点突变）慢性感染患者的临床特点、病理特征及与干扰素疗效的关系。方法采用突变特异性ＰＣＲ检测１０８份慢性ＨＢＶ感染患者血清和／或肝组织中ＨＢＶ前Ｃ区突变株,按Ｋｎｏｄｅｌｌ方法评价肝组织病理损伤。结累ＨＢＶ前Ｃ区突变株在不同ｅ系统均存在,但ＨＢｅＡｂ（＋）组中单纯突变株感染或突变株感染占优势的混台感染（１４．２９％,４６．２３％）显著地高于ＨＢｅＡｇ（＋）组（０％,６．４５％）;突变株感染与肝脏疾病严重程度相关,慢性肝炎重度组检出率（１３．６４％,４０．９１％）极显著地高于慢性无症状携带者（０％,１０．２６％）。５例前Ｃ区突变株感染者应用干扰素治疗可产生应答和无应答２种结果。临床症状较轻的ＨＢＶ前Ｃ区突变株感染者的肝脏病理损伤程度无明显加重。结论前Ｃ区突变株感染普遍存在,但更常见于ＨＢｅＡｂ阳性者。【关键词】##4乙型肝炎病毒;;突变;;病理学;;治疗