Hepatitis B immunization in high risk neonates born from HBsAg positive mothers: comparison between plasma derived and recombinant DNA vaccine

A half dose recombinant hepatitis B vaccine (HBVax II, MSD, 5 micrograms) was investigated for efficacy in the prevention of perinatal hepatitis B virus (HBV) transmission in high risk neonates born from e-antigen positive HBsAg carrier mothers as compared to the half-standard dose regimen of plasma derived hepatitis B vaccine (HBVax, MSD, 10 micrograms). Forty infants born to carrier mothers were given hepatitis B immune globulin (HBIG) 100 IU intramuscularly immediately after birth, combined with either the recombinant or plasma derived hepatitis B vaccine. The infants were randomly divided into two groups of 20 infants each. The plasma derived vaccine (10 micrograms) was given to group I, while infants in group II received the recombinant vaccine (5 micrograms) at birth, 1 and 6 months of age. There were no statistically significant differences in the efficacy and the seroconversion rate of these two combined prophylaxis regimens. The protective efficacy rate of both kinds of HBV vaccine was found to be 94.6 and 89.2 percent in group I and group II respectively. At twelve months of age, the anti-HBs seroconversion rates were 95.0 percent in group I and 84.2 percent in group II. However, the geometric mean titres in group I (179.55 mIU/ml) was significantly higher than those in group II (42.2 mIU/ml) but the anti-HBs titre was still above protective level (10 mIU/ml) in most of the infants.(ABSTRACT TRUNCATED AT 250 WORDS)     

Efficacy of hepatitis-B immunoglobulin and hepatitis-B vaccine in prevention of the HBsAg carrier state in newborn infants of mothers who are chronic carriers of HBsAg and HBeAg

Combined prophylaxis of perinatal transmission of hepatitis B virus (HBV) with hepatitis-B immunoglobulin (HBIG) and hepatitis-B vaccine was investigated in 40 infants born to HBeAg positive carrier mothers. The efficacy of two combined prophylaxis schedules was compared to 78 similar infants in the control group receiving no treatment, by following the HBV markers at regular intervals up to one year of age. In both schedules, the HBIG and HBV vaccine were given at birth, followed by HBV vaccine given at 30 days and 60 days (group I) or 180 days (group II) of age. The incidence of persistent HBsAg carrier in infants born to HBeAg positive carrier mothers was significantly reduced from 92.6 percent at one year of age in the control group to zero percent (group I) and 11.5 percent (group II) in the treated groups. There was no statistical significant difference in the efficacy of these two combined prophylaxis schedules. HBIG given at birth did not interfere with infant immune response to the hepatitis B vaccine. At twelve months of age, anti-HBs could be detected in 77.8 percent of infants in group I and 89.5 percent in group II with mean titre of 621.4 and 1148.0 in group I and group II respectively. It was concluded that combined prophylaxis with HBIG and hepatitis-B vaccine immediately after birth is the best method for prevention of HBV perinatal transmission from HBeAg positive carrier mothers to their infants.     

Hepatitis B immunization in high risk neonates born from HBsAg and HBeAg positive mothers: comparison of standard and low dose regimens

A reduced dose of plasma derived hepatitis B vaccine (Hevac B) was tested for efficacy in the prevention of perinatal hepatitis B virus (HBV) transmission in high risk neonates born from e-antigen positive HBsAg carrier mothers. Forty newborn infants born of these mothers were given hepatitis B immune globulin (HBIG) 100 IU intramuscularly immediately after birth, combined with either standard or reduced doses of HBV vaccine. The infants were divided into two groups of 20 infants each. The standard dose of HBV vaccine (5 micrograms) was given to group I, while infants in group II received reduced dose (2 micrograms) at birth and at 1, 2 and 12 months of age. There was no statistically significant difference in the efficacy and antibody responses of these two combined prophylaxis regimens. The protective efficacy rate of HBV vaccine was found to be 94.0 and 93.2 percent in group I and group II, respectively. At twelve months of age, the anti-HBs seroconversion rates were 80.0 percent in group I and 86.7 percent in group II, with geometric mean titres of 84.57 mlU/ml and 78.56 mlU/ml, in group I and group II, respectively. One month after a booster at one year of age, anti-HBs could be detected in 86.7 percent of the infants in both groups. The geometric mean titres were 429.04 and 664.81 mlU/ml, in group I and group II, respectively. Anti-PreS2 antibody was detected in high titre as early as 4 months after the first dose of HBV vaccine, with a geometric mean titre of 116.30 mlU/ml and 107.97 mlU/ml, in group I and group II, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

Dynamics and impact of perinatal transmission of hepatitis B virus in North India

The magnitude and significance of perinatal transmission of hepatitis B virus (HBV) were assessed in infants of 8,575 women, of whom 3.7% were seropositive for HBV surface antigen (HBsAg). The e antigen of HBV (HBeAg) was found in 7.8% of these carriers, the antibody to HBeAg (anti-HBe) was found in 30.1% of them, and HBsAg alone was found in 62.1% of them. The estimated incidence of HBsAg positivity by 6 months of age in infants of carrier women was significantly (P less than .001) higher than in controls (18.6% vs 3.0%). Transmission was most frequent (87.5%) if the carrier mother was HBeAg positive and was much less so if she was positive for anti-HBe (17.5%) or for HBsAg alone (9.6%). Toward the end of infancy incidence of HBsAg positivity among offspring of carriers and among controls was not different. Most infants positive for HBsAg and HBeAg continued with the infection beyond 6 months of age. It is estimated that about one-third of the adult asymptomatic HBV carriers in India evolve directly from perinatal infection, while the majority become infected during childhood or early adulthood.     

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.     

Perinatal transmission of hepatitis B virus in Thailand

Perinatal transmission of hepatitis B virus (HBV) from asymptomatic HBsAg carrier mothers to their infants was studied in 78 mother-infant pairs by determination of HBsAg, HBeAg and anti-HBe both in the mothers and in their infants at regular intervals for those children up to the time when they reached at least one year of age. Twenty-five out of the 78 (32.1%) infants born to these mothers were HBsAg-positive 2-6 months after birth and they remained so throughout the observation period of at least one year or more. Perinatal HBV transmission occurred only in infants born to HBsAg carrier mothers who were HBeAg-positive (92.6%) but not in those born to HBsAg carrier mothers who had no detectable HBeAg. This study suggests that preventive measures against HBV transmission during the perinatal period should be taken only for infants born to HBsAg carrier mothers who are HBeAg-positive. In addition, the active immune response to HBV was studied in 75 non-HBsAg carrier infants born to HBsAg carrier mothers by determination of anti-HBs at one year of age or older. Forty-three of these infants were treated with HBIG at birth and 32 infants received no treatment. It was found that infants born to HBsAg carrier mothers who were HBeAg-positive had a better active immune response (84.2% positive for anti-HBs) than infants born to HBsAg carrier mothers who had no detectable HBeAg or anti-HBe (14.3% and 20.4% positive for anti-HBs respectively).     

Prevention of perinatal transmission of hepatitis B virus (HBV): a comparison of two prophylactic schedules

Perinatal transmission of hepatitis B virus (HBV) from HBsAg carrier mothers who were HBeAg+, antiHBe+, or negative for both HBe markers, was interrupted using either 4 doses of vaccine, or one dose of hepatitis B immunoglobulin (HBIG) at birth, combined with 4 doses of vaccine. In those infants who received HBIG at birth, the antiHBs titre was significantly higher at 1 and 2 months old, but at 6, 9, and 18 months old, there was no significant difference. Among the infants of carrier mothers who did not display HBeAg (i.e., were antiHBe+, or negative for both HBe markers), a transient subclinical infection would have been expected in around 10% had there been no intervention. No evidence of such infection was detected, and no difference in outcome was found between the two treatment groups. Amongst infants born to HBeAg+ carrier mothers, infection occurred in 1 out of 8 who had received HBIG and vaccine, and in 3 of 8 who had received vaccine only. The difference in outcome was not statistically significant, but the numbers analysed were small. The infections which occurred in spite of prophylaxis may be attributable to in utero infection, poor response to vaccine by the infant, or to the mother having a particularly high HBV-DNA level. HBIG given at birth to infants of HBeAg+ carrier mothers may enhance the protection of infants who are destined to be poor responders to vaccine.     

不同剂量乙型肝炎疫苗对慢性乙型肝炎患者特异性T淋巴细胞应答反应的影响

目的研究接受不同剂量重组酵母乙型肝炎疫苗治疗的慢乙肝患者外周血淋巴细胞对疫苗的特异性细胞免疫反应。方法选择72例6个月内无使用抗病毒治疗的慢性乙型肝炎患者按1：1：1的比例随机分为90tLg组、60tLg组、安慰剂组（0μg）。患者同时联合使用干扰素alb5MIU每周3次共24周。所有患者均停药后观察24周。在不同的时间点检测患者HBVDNA、HBeAg及肝功能，酶联免疫斑点试验（ELISPOT）法检测产生IFN-7的细胞数。结果治疗前三组患者的ELISPOT阳性率的差异无统计学意义。治疗24周时高剂量、低剂量和安慰剂组ELISPOT试验阳性的患者分别有12例、12例和7例。重组酵母乙型肝炎疫苗组（高剂量、低剂量）ELISPOT阳性率比安慰剂组明显升高，差异有统计学意义（P=0．0446）。24例ELISPOT阳性的重组酵母乙型肝炎疫苗组（高剂量、低剂量）患者中有6例产生HBVDNA转阴、7例发生HBeAg消失或转换，而7例ELISPOT阳性的安慰剂组患者均无HBVDNA转阴及HBeAg消失或转换。停药后24周，ELISPOT阳性者中。重组酵母乙型肝炎疫苗组（高剂量、低剂量）共有4例产生HBVDNA转阴、9例发生HBeAg消失或转换，而接受安慰剂治疗组均无HBVDNA转阴、仅有1例发生HBeAg转换。结论重组酵母乙型肝炎疫苗对慢性乙型肝炎患者有提高特异性T淋巴细胞功能的作用。高剂量组和低剂量组ELISPOT阳性率差异无统计学意义。     

Quantitative analysis of HBV DNA level and HBeAg titer in hepatitis B surface antigen positive mothers and their babies: HBeAg passage through the placenta and the rate of decay in babies

It is well documented that perinatal transmission is the major cause of chronic HBV infection in China. However, the mechanisms of HBV perinatal transmission are not defined clearly. It is not known whether hepatitis B e antigen can cross the human placenta, and the rate of HBeAg decay in babies with and without HBV breakthrough has not been studied. In this study, HBV serological markers were investigated in 95 hepatitis B surface antigen positive pregnant women. These markers were also studied in the babies at birth and at the age of 6 months and 12 months. The data show that 7.4% (7/95) children were infected with HBV during the first year after birth despite receiving passive-active immunoprophylaxis with hepatitis B immune globulin and hepatitis B vaccine. The surface gene fragment of HBV DNA was cloned and sequenced following PCR amplification in 7 cases of HBsAg positive babies and their mothers. All babies had the same sequences as their mothers, although two babies also had sequences that would produce an amino acid substitution within the "a" determinant. Furthermore, we measured HBeAg titers and HBV DNA levels by using Abbott AxSYM system and LightCycler-based real-time fluorescence quantitative PCR in 54 mother-infant pairs. Thirty-three mothers were HBeAg positive, and 21 mothers were HBeAg negative. Seventy percent (23/33) of neonates from HBeAg-positive mothers were HBeAg positive at birth compared with 0% (0/21) of neonates from HBeAg negative mothers. HBeAg was present at higher titer in the birth sera of the babies with HBV breakthrough than in babies without breakthrough. HBeAg was cleared from the serum in all 19 babies without breakthrough. In 17 of these 19 babies, the HBeAg was cleared within 6 months, and in two babies clearance took 12 months. The mean serum HBV DNA level in the mothers of the 4 infants with HBV breakthrough was significantly higher than in the mothers of babies who did not become infected. In conclusion, this data suggests that HBeAg can cross the human placenta, and disappears from serum within 6 months in most babies. HBV DNA levels in hepatitis B carrier mothers are associated with the failure of HBIG and vaccine immunization, and the additional influence of transmitted HBeAg cannot be excluded.     

不同剂量HBIG对母婴乙型肝炎病毒抗原抗体宫内传播的影响

目的探讨不同剂量乙肝免疫球蛋白（HBIG）对乙型肝炎病毒（HBV）抗原抗体宫内传播的影响。方法将母亲乙肝表面抗原（HBsAg）阳性的婴儿作为500例观察对象,根据出生前母亲是否用HBIG分为：观察1组：产前母亲孕末期28w、32w、36w各用200IU（蓉生）HBIG 200例;观察2组：产前母亲孕末期28w、32w、36w各用400IU（蓉生）HBIG 100例;对照1组：产前母亲孕末期不用HBIG 200例。观察生后12h内新生儿静脉血乙肝五项：HBsAg、乙型肝炎表面抗体（HBsAb）、乙型肝炎e抗原（HBeAg）、乙型肝炎e抗体（HBeAb）、乙型肝炎核心抗体（HBcAb）。结果观察1组200例新生儿HBsAg阳性1例,阳性率为0.5%,HBeAg阳性3例,（其中1例HBsAg同时阳性）阳性率为1.5%。对照组HBsAg阳性2例,阳性率为1%,HBeAg阳性8例,（其中2例HBsAg同时阳性）阳性率为4%。经统计学处理（HBsAg）χ2=0.336,P=0.562;（HBeAg）,χ2=2.337,P=0.126。观察1组与对照组生后24h内HBV抗原检测比较无显著差异。观察1组、观察2组与对照组HBsAb检测比较：观察1组新生儿HBsAb阳性率1%,观察2组新生儿HBsAb阳性率2%,对照组HBsAb阳性率1%,各组HBeAb和HBcAb检测比较,结果HBeAb和HBcAb检测母婴符合率均在97%-97.5%之间。结论孕妇HBV携带者产前孕末期用HBIG 200IU隔4w连用3次的方法对阻断乙肝病毒的宫内感染效果不显著。加大HBIG的用量400IU可基本阻断HBV垂直传播胎儿。但鉴于对照组宫内感染率仅4%,加大用量不适用所有HBV携带者孕妇,尤其是HBsAg单阳性孕妇。     

Reduced doses of hepatitis B immune globulin in the prevention of perinatal transmission of hepatitis B

From October 1982 to May 1983, newborn infants of 79 hepatitis B surface antigen (HBsAg)-positive women were enrolled in a study of the efficacy of hepatitis B immune globulin (HBIG) in the prophylaxis of perinatal transmission of hepatitis B virus (HBV) infection. HBIG 0.5 ml or 0.25 ml was given to the newborn within 15 minutes of birth and at 3 and 6 months. The mother-infant pairs were followed-up every 3 months for at least 9 months. Similar observations of untreated infants were used for comparison. Among infants of hepatitis B e antigen (HBeAg)-positive carrier mothers, the HBsAg carrier rates at 3 months were similar in the 0.5-ml and 0.25-ml HBIG dose groups. At 12 months the difference--17.7% of 17, 40% of 15--did not reach statistical significance, but the differences between these rates and that of the untreated control-85.7% of 35--did. Among infants of HBeAg-negative carrier mothers, HBV infection rates in both dose groups were similar to those of untreated infants. In the treated groups at 12 months about 45% of infants of HBeAg-positive mothers and 90% of infants of HBeAg-negative mothers were still negative for HBsAg and anti-HBs. Vaccination to induce active antibody is necessary to prevent postnatal infection and chronic carriage of HBV. To reduce the cost of combined passive and active hepatitis B immunoprophylaxis in children born to HBeAg-positive carrier mothers, 0.25 ml of HBIG could be used instead of the usually recommended 0.5 ml.     

Multicenter trial on the efficacy of HBIG and vaccine in preventing perinatal hepatitis B. Final report

In an attempt to interrupt perinatal transmission of hepatitis B, 92 infants born to HBsAg carrier mothers (49 to HBeAg-positive mothers, 30 to anti-HBe-positive with abnormally elevated ALT levels, and 13 to HBeAg/anti-HBe-negative mothers) received 0.5 ml/kg BW of HBIG at birth and at 1 month of age. Three IM injections of hepatitis B vaccine were given at 3, 4, and 9 months of life. All babies who were given the three doses of vaccine developed an active anti-HBs response: of these, 53 (62.3%) had antibody titers higher than 1,000 mIU/ml, 29 (34.2%) had levels between 100 and 1,000 mIU/ml, and the other three (3.5%) were below 100 mIU/ml. At the end of the 2-year follow-up, these three poor responders became anti-HBs negative, whereas the others still had antibody. All but three babies were protected by HBIG plus vaccine treatment. Two chronic HBV infections occurred within 6 months of life presumably because the babies were already infected when prophylaxis started. The third baby became an HBsAg carrier at 9 months of age in spite of a previous response to the vaccine. Simultaneous presence of HBsAg of y specificity and anti-HBs (anti-a) was still detectable at 24 months of age. The vaccine was well tolerated. Passive plus active immunization is an effective procedure for preventing perinatally transmitted HBV infection.     

Hepatitis B vaccine alone or in combination with anti-HBs immunoglobulin in the perinatal prophylaxis of babies born to HBsAg carrier mothers.

The efficacy of hepatitis B virus (HBV) vaccine alone (group I) or in combination with hepatitis B immunoglobulin (HBIG) (group II) for prevention of perinatal transmission of the virus was assessed in 21 and 24 neonates, respectively. 58 infants who could not be vaccinated constituted the control group. It was observed that in the unvaccinated group approximately 70% of the infants became infected. In both the vaccinated groups, the seroconversion and seroprotection rates (anti-HBs > or = 10 IU/1) were almost similar at 6 months of follow up, but, at 12 months, infants given HBIG and vaccine showed better seroprotection rate (85%) than those given vaccine alone (58.8%). Immune response to the vaccine was also better in both the groups if the mothers were anti-HBe positive. Despite immunization, 14.2% and 25% infants in group I and II, respectively, became chronic carriers if their mothers were HBeAG positive.     

新生儿不同时期静脉血HBsAg含量对HBV母婴传播阻断失败的预测研究

目的探讨HBV慢性感染孕妇新生儿出生后不同时期静脉血HBsAg含量变化对ItBV母婴传播阻断失败的预测价值。方法以HBsAg、HBeAg双阳性、血清HBVDNA含量≥10^5拷贝／ml慢性HBV感染孕妇所娩新生儿150例为研究对象,出生后立即注射乙肝免疫球蛋白200Iu,并按0、1和6个月程序接种乙肝疫苗10～20μg。分别于新生儿出生时、生后1个月、生后7个月采取静脉血检测HBV血清学指标,分析新生儿不同时期静脉血HBsAg含量对HBV母婴传播阻断失败的预测。结果共有11例新生儿发生HBV母婴阻断失败。新生儿出生时、生后1个月、生后7个月HBsAg阳性率分别为41．26％、10．49％、7．69％,HBeAg阳性率分别为97．90％、65．75％、13．29％。以出生时I-IBsAg≥O．05和HBsAg≥1IU／ml预测HBV母婴传播阻断失败,阳性预测价值分别为18．64％和70％;生后1个月HBsAg〉~O．05和HBsAg≥1IU／ml的阳性预测价值分别为73．33％和100％。结论出生时静脉血HBsAg含量≥1IU／ml时应高度怀疑HBV母婴传播的失败。生后1个月HBsAg≥1IU／ml对母婴传播阻断失败有高度的预测价值,如何提高出生时和生后1个月静脉血HBsAg阳性新生儿的HBV感染阻断率是以后研究的重点。     

Mother-to-infant transmission of hepatitis B virus: a Chinese experience

Over 90% of infants infected with hepatitis B virus (HBV) caused by mother-to-infant transmission will evolve to carrier status, and this cannot be prevented until widespread administration of the HB vaccine and hepatitis B immune globulin (HBIG) is implemented. This prospective study of 214 infants born to HBsAg-positive mothers was carried out to determine if either perinatal or intrauterine HBV transmission could be effectively prevented with HBIG and the HB vaccine. Peripheral blood was collected from mothers and from newborns before they received HBIG and the HB vaccine, as well as at 0, 1, 7, 24, and 36 months after birth. Infants born with an ratio of signal to noise(S/N) value of >5 for HBsAg (ABBOTT Diagnostic Kit) were defined as mother-to-infant transmission cases, those with an S/N between 5 and 50 were classified as perinatal transmission cases, and those with an S/N >50 were considered intrauterine transmission cases. Mother-to-infant transmission occurred in approximately 4.7% (10/214) of the infants; the perinatal transmission and intrauterine transmission rates were 3.7% (8/214) and 0.9% (2/214), respectively. The risk of mother-to-infant transmission increased along with maternal HBeAg or HBVDNA levels. After 36 months of follow-up, all perinatal cases became HBsAg-negative, whereas all intrauterine transmission cases evolved into carrier status. These results indicate that infants infected via intrauterine transmission cannot be effectively protected by HBIG and HB vaccine.     

乙肝疫苗联合乙肝免疫球蛋白对阻断母婴垂直传播乙型肝炎病毒的临床分析

目的探讨孕妇产前用乙肝免疫球蛋白（HBIG）与乙型肝炎疫苗联合免疫阻断母婴传播的效果。方法将504例HBsAg（＋）孕妇分为A（预防组）,B（对照组）两组。A组：246名HBsAg阳性孕妇孕晚期每月分别注射基因重组型乙肝疫苗10μg、HBIG200IU（200IU/ml）,新生儿出生后采股静脉血,同时在出生后24h内注射HBIG200IU,然后在0、1、6月龄接种基因重组型乙肝疫苗,每次10μg。B组：258例产前未注射HBIG和基因重组型乙肝疫苗的HBsAg阳性孕妇,其所生新生儿在0、1、6（30μg、30μg、30μg）月龄只用基因重组型乙肝疫苗免疫。A、B两组婴儿都分别在0、3、6、9、12、24月龄静脉采血,用酶联免疫吸附试验（ELISA）检测HBV标志物,同时随访。结果A组的宫内感染率为3.25%,B组为4.16%,差异无统计学意义（χ^2=1.43,P〉0.05）。A组没有发生慢性HBV感染的婴儿,而B组中有7例婴儿发生慢性HBV感染,B组婴儿发生慢性HBV的感染率显著高于A组（χ^2=4.41,P〈0.05）。结论产前用HBIG和新生儿HBIG联合免疫可降低慢性HBV感染率,阻断宫内感染的慢性化,提高产程感染的阻断效果。     

不同剂量乙肝疫苗与HBIG联合免疫阻断HBV母婴传播的效果对比

目的 探讨10 μg和20 μg乙肝疫苗与HBIG联合免疫阻断HBV母婴传播的效果.方法 124例HBsAg阳性孕妇所生的婴儿随机分为两组,即10 μg乙肝疫苗组和20 μg乙肝疫苗组.婴儿于出生6h内及30 d分别注射200 IU HBIG,同时分别于出生24 h内、1个月及6个月注射3次10 μg或20 μg重组酵母乙肝疫苗.检测婴儿出生时以及1岁时血清HBV标志物.结果 两组新生儿血清HBsAg、HBeAg及抗-HBe阳性率与滴度之间差别均无统计学意义（P＞0.05）.所有新生儿血清HBV DNA水平均小于检测下限（500 U/ml）.出生12个月时,所有124例婴儿血清HBsAg和HBeAg检测结果均为阴性;血清HBV DNA水平均在检测下限以下;10 μg和20 μg乙肝疫苗组血清抗-HBs阳性率分别为90.3％和96.8％,差异无统计学意义（P＞0.05）;抗-HBs水平分别为325.5±342.2 mIU/ml和463.7±353.3 mIU/ml,后者显著高于前者（P=0.01）.而且,20 μg乙肝疫苗组产生高应答抗-HBs（＞ 100 mIU/ml）的比例显著高于10μg乙肝疫苗组（P =0.035）.结论 20 μg乙肝疫苗联合HBIG方案阻断HBV母婴传播的效果优于10 μg乙肝疫苗联合HBIG方案.     

Is the course of perinatal hepatitis B virus infection influenced by genetic heterogeneity of the virus?

We studied the relations between genetic heterogeneity of pre-C region of hepatitis B virus (HBV) DNA and outcome of HBV infection in 5 infants with perinatal infection, 3 born to antihepatitis B e antigen (HBeAg), and 2 to HBeAg positive mothers. HBV infection developed in the babies at 3–4 months of age, but it resolved with seroconversion to anti-HBs in infants born to anti-HBe positive mothers, while the infection became chronic in the 2 babies born to HBeAg positive mothers. HBV-DNA extracted from the first hepatitis B surface antigen (HBsAg) positive serum sample of each baby was amplified and directly sequenced for the pre-core region. HBV-DNA sequences from 3 babies born to anti-HBe positive mothers showed at position 1896 the contemporary presence of 2 nucleotides (G + A), indicating a mixture of wild-type and "e minus"variant HBV. These findings suggest a possible co-transmission of the 2 viruses from anti-HBe positive mothers to newborns. HBV-DNA from babies born to HBeAg positive mothers showed wild-type sequences only. The results of this study suggest that the outcome of HBV infection in newborns depends not only on the host's immunocompetence and on viremia level in maternal blood, but also on heterogeneity of HBV. Transmission of mixed HBV populations appears associated with an early immunoelimination of the virus, while infection with wild-type HBV alone contributes to induction of chronicity. © 1993 Wiley-Liss, Inc.     

Use of hepatitis B virus DNA quantitation to predict hepatitis B e antigen reversion in cases of chronic hepatitis B

Seventy-three chronic hepatitis B patients who had either hepatitis B e antigen (HBeAg) seroconversion (group I) or HBeAg-negative disease (group II) were studied. HBV DNA levels at HBeAg seroconversion (group I) and at initial visits (group II) were significantly lower among patients who were persistently negative for HBeAg than among those who underwent HBeAg reversion.     

Perinatal transmission of the hepatitis b virus and of the hbv-associated delta agent from mothers to offspring in northern italy

We report a prospective study on infants born to hepatitis B surface antigen (HBsAg) carrier mothers to estimate the incidence of perinatal transmission of HBV and HBV-associated delta agent in Northern Italy. The risk of infection to the infant was related to the presence of the HBe antigen-antibody system, HBV-specific DNA polymerase activity and antibody to delta in maternal sera, and to the titer of anti-HBe in babies at birth. The data of this study indicate: 1. Babies born to HBsAg carrier mothers with HBeAg in serum are at extremely high risk of acquiring HBV infection and of developing a chronic carrier state, whereas those born to anti-HBe-positive mothers are at a lower (P <.01) yet consistent risk of infection. 2. HBs antigenernia is usually prolonged and symptomatic in babies born to HBeAg–positive mothers while being self-limited and asymptomatic in babies born to anti-HBe-positive mothers. 3. DNA polymerase activity in maternal serum appears to be the most sensitive marker predicting HBV transmission to the infant since it was detected in all the HBeAg-positive mothers and also in two anti-HBe-positive mothers and in one HBeAg/anti-HBe-negative mother who transmitted infection to their babies. 4. High titers of anti-HBe (up to 1:10³) do not prevent HBV infection. 5. Vertical transmission of delta infection seems to occur only in circumstances that permit perinatal transmission of HBV infection.