Screening of pregnant women and hepatitis B prophylaxis in newborns

Prevention of perinatal hepatitis B includes: (1) screening ol pregnant women for hepatitis B surface antigen, and (2) immunoprophylaxis of babies at risk. HBIG treatment seems to be of some efficacy in preventing the HBsAg carrier state while it permits passive active immunization to occur. The disadvantage of HBIG is that it confers only temporary immunity. Therefore, it infection does not occur, babies will still be susceptible to the virus when passively administered anti-HBs will no longerbe circulating. On the other hand, vaccine provides a long term but not immediate protection. Therefore the ideal approach in post-exposure prophylaxis is a combination of passive plus active immunization. The aim is to provide an immediate protection, with the HBIG, and a long term immunity, with the vaccine, to babies born to HBsAg carrier mothers.     

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.     

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.     

Immunoprophylaxis of perinatal transmission of the hepatitis B virus: efficacy of hepatitis B immune globulin and hepatitis B vaccine in a low-prevalence area

One hundred eleven newborn infants born of Spanish hepatitis B surface antigen (HBsAg) carrier mothers were consecutively assigned to one of three treatment groups. Group A was treated with three or four doses of hepatitis B immune globulin (HBIG) in one of three different schedules. Group B received one dose of hepatitis B vaccine (Hevac-B, Pasteur) at birth and at 1, 2 and 12 months. Group C was treated with the same vaccination schedule as group B and in addition received a single dose of HBIG at birth. Comparisons were made in the 85 babies who had strictly completed the immunization schedule and had been followed for at least 12 months. The three immunization protocols were equally effective, since none of the children became a chronic HBsAg carrier or developed acute symptomatic infection. There were five transient and subclinical infections among children who received only HBIG (group A), one transient infection in group B, and one in group C. There seems to be some correlation between anti-HBs levels and degree of protection, since all transient infections in group A occurred in the subgroups who did not maintain protective antibodies during the first 6 months. Although the percentage of responders in the two vaccinated groups did not differ significantly, children who received only vaccine reached higher antibody levels than those who also received HBIG. Our results suggest that any immunization schedule able to maintain anti-HBs levels during the first 6 months of life would be useful to prevent mother-to-infant transmission of the hepatitis B virus in areas where most of the carrier women are expected to be anti-HBe positive and hence relatively less infectious.     

Successful postexposure vaccination against hepatitis B in chimpanzees

To study the effect of postexposure vaccination, four chimpanzees were vaccinated with hepatitis B (HB) vaccine 4, 8, 48, and 72 hr, respectively, after intravenous injection of an infectious hepatitis B virus (HBV) inoculum. The second and third vaccine inoculations were given 2 and 6 weeks later, i.e., at considerably shorter intervals than recommended either for ordinary prophylactic vaccination or for postexposure vaccination in combination with hepatitis B immune globulin (HBIG). The chimpanzees were followed for 1 year. None showed HBs-antigenemia, liver enzyme elevation (ALT), or histopathological alterations in liver biopsies. Late appearance of anti-HBc was observed only in the serum of the animal whose series of vaccination started 72 hr after HBV inoculation. An unvaccinated control chimpanzee, which received the HBV inoculum only, developed clinical hepatitis B with ALT-elevations and HBs-antigenemia within 2 months of the experimental HBV inoculation. These results indicate that postexposure vaccination against hepatitis B begun within 48 hr after HBV exposure, with short intervals between the vaccine injections, can protect against hepatitis B infection also when concomitant HBIG-prophylaxis is not given.     

Recombinant Hepatitis B Vaccine

Recombinant hepatitis B vaccine Engerix B((R)) [Hep-B(Eng)] is a noninfectious subunit hepatitis B viral vaccine indicated for the active immunisation of adults, children and infants against hepatitis B virus infection. It contains hepatitis B surface antigen (HBsAg) which is produced by the yeast Saccharomyces cerevisiae by use of recombinant DNA technology. In adults and children seroprotection rates [anti-HBsAg antibody (anti-HBs) titres >/=10 IU/L] were 93 to 100% 1 month after completion of the immunisation schedule with Hep-B(Eng) [0, 1, 6-month schedule]. A more rapid immunological response has been reported with accelerated Hep-B(Eng) immunisation schedules, such as the 0, 1, 2, 12-month schedule. Hep-B(Eng) produces seroprotection rates similar to those achieved with the plasma-derived vaccines and the recombinant hepatitis B vaccine, Recombivax-HB((R)) [Hep-B(Rax)] when administered at recommended doses. In studies in Taiwanese and Thai neonates born to hepatitis B carrier mothers, seroprotection rates were >/=94% 12 months after immunisation with Hep-B(Eng) [+/- hepatitis B immunoglobulin (HBIG)] and protective efficacy was high, with 相似文献   

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.     

Management of mother-to-child transmission of hepatitis B virus: Propositions and challenges

Chronic hepatitis B virus (HBV) infection due to mother-to-child transmission (MTCT) during perinatal period remains an important global health problem. Despite standard passive–active immunoprophylaxis with hepatitis B immunoglobulin (HBIG) and hepatitis B vaccine in neonates, up to 9% of newborns still acquire HBV infection, especially these from hepatitis B e antigen (HBeAg) positive mothers. Management of HBV infection in pregnancy still need to draw careful attention because of some controversial aspects, including the failure of passive-active immunoprophylaxis in a fraction of newborns, the effect and necessity of periodical hepatitis B immunoglobulin (HBIG) injection to the mothers, the safety of antiviral prophylaxis with nucleoside/nucleotide analogs, the benefit of different delivery ways, and the safety of breastfeeding. In this review, we highlight these unsettled issues of preventive strategies in perinatal period, and we further aim to provide an optimal approach to the management of preventing MTCT of HBV infection.     

Analysis of a pregnancy-screening and neonatal-immunization program for hepatitis B in Hamilton, Ontario, Canada, 1977-1988

During the 12 years from January, 1977, to December, 1988, the Hamilton Centre of the Canadian Red Cross Society (CRCS) Blood Transfusion Service screened 98,712 pregnant patients for hepatitis B surface antigen (HBsAg) and identified 120 positives (0.12%). The number of positives ranged from six to 16 per year. We were able to trace and enroll 65 mothers (54%) and 96 of their children in the follow-up study. The majority of the women were between 20 and 30 years of age (95.4%) and married (86%), and about one-half were employed outside the home. Sixty-five percent were white and 34% Asian, and 20 countries were listed as their places of origin. Hepatitis B immune globulin (HBIG) was available for neonatal immunization since 1977 and combined with vaccine since 1982. Of the 96 candidates for HBIG, 60 (63%) received HBIG within 24 hr, one after 3 months, four unknown, and 31 did not receive it. Of the 56 candidates for vaccination from 1982 to 1989, 26 (46%) received three doses, seven had two doses, eight had one dose, one was unknown, and 14 had none. HBsAg tests were performed on 69 children (71.8%) and anti-HBs on 61 (63.5%). Four of the children are HBsAg positive, 31 have anti-HBs, and 31 have no detectable antibodies. All four HBsAg positives had not received vaccine, and only one had received HBIG. Of the children positive for hepatitis B surface antibodies, five had received no immunization and therefore had been subclinically infected.(ABSTRACT TRUNCATED AT 250 WORDS)     

Accidental administration of hepatitis B immune globulin to a patient positive for hepatitis B surface antigen

Approximately 24 hours after receiving hepatitis B immune globulin (HBIG), a renal transplant surgeon developed localized urticaria at the site of injection followed by generalized urticaria and angioedema, which resolved after administration of corticosteroids but recurred ten days later. Blood drawn from the surgeon prior to his receiving the HBIG injection was positive for hepatitis B surface antigen (HBsAg). We believe that the adverse reaction may have been caused by HBsAg-HBIG immune complexes. This case illustrates the necessity for knowing the results of hepatitis serology before injection of HBIG is given in high risk individuals. It also re-emphasizes the value of periodic screening for hepatitis B in such persons and the need for hepatitis B vaccine.     

Protective efficacy of hepatitis B vaccines in neonates

A literature search was carried out to investigate the factors that influence the protective efficacy (PE) of hepatitis B vaccines when given to neonates of hepatitis B surface antigen and e antigen positive mothers. Hepatitis B vaccines with either high or low antigen doses are very effective in preventing chronic hepatitis B infection in neonates at risk, but there is evidence that with lower dosages simultaneous use of hepatitis B immune globulin (HBIG) administration is more important than with higher dosages to elicit good protection (PE ≧ 90%). There is also a tendency for lower dosages to confer high PE less consistently, with noticeably greater numbers of chronic surface antigen carriers in neonates who received a complete vaccination course. Furthermore vaccination courses with higher vaccine dosages give high PEs, without concomitant HBIG administration at birth, provided that the first vaccine dose is given at birth and that the second dose follows within 2 months. © 1994 Wiley-Liss, Inc.     

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.     

阻断乙型肝炎病毒母婴传播方案探讨

目的探讨阻断乙型肝炎病毒母婴传播的有效方法。方法将乙型肝炎病毒携带孕妇,根据她们的不同情况和就诊的不同时期分为6组,Ms组为乙肝表面抗原阳性乙肝e抗原阴性的孕妇,根据就诊的不同时期分为Ms1组、Ms2组、Ms3组。Mse组为乙肝表面抗原和乙肝e抗原双阳性孕妇。MF组为孕妇与配偶均为乙型肝炎病毒携带者。F组为孕妇为非乙型肝炎病毒携带者配偶为乙型肝炎病毒携带者的孕妇。各组采用不同的方法阻断乙型肝炎病毒的垂直传播。结果 Ms1组230例中有22例母亲孕期用过乙肝免疫球蛋白（占本组总数9.6%）。Ms2组：372例中有37例母亲孕期用过乙肝免疫球蛋白（占本组总数9.9%）。Ms3组287例中有4例母亲孕期检测乙型肝炎病毒脱氧核糖核酸阳性用过HBIG（占本组总数1.4%）,与Ms1组和Ms2组母亲用乙肝免疫球蛋白率9.6%和9.9%比较经统计学处理差异都非常显著（χ2=17.850,P=0.000）;（χ2=20.311,P=0.000）。Mse组32例母亲在孕期都用过乙肝免疫球蛋白（占本组总数100%）。MF组72例中有20例母亲在孕期用过乙肝免疫球蛋白（占本组总数27.7%）。F组：48例中3例母亲在孕期用过乙肝免疫球蛋白（占本组总数6.2%）;32例母亲在孕期用过乙肝疫苗接种（占本组总数66.6%）。各组共1041例新生儿生后24h内静脉血乙肝抗原抗体定性检测：乙肝表面抗原和乙肝e抗原均为阴性。生后3个月至1岁随访检测婴儿静脉血1041例乙肝抗原定性乙肝表面抗原和乙肝e抗原仍均为阴性。结论孕妇或配偶为乙型肝炎病毒携带者,如乙肝e抗原阳性或乙型肝炎病毒脱氧核糖核酸阳性孕妇孕期需要注射乙肝免疫球蛋白阻断乙型肝炎病毒传播,否则不需要。父母为乙型肝炎病毒携带者,如新生儿生后检测乙型肝炎病毒抗原检测阳性需要注射乙肝免疫球蛋白,否则不需要。所有新生儿必须接种乙肝疫苗。     

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.     

不同方案阻断乙型肝炎病毒母婴垂直传播的随访观察

目的探讨阻断乙型肝炎病毒母婴垂直传播的方法.方法将488例HBsAg阳性孕妇分成四组,单纯HBVac治疗组116例,单纯HBIG治疗组116例,左旋咪唑涂布剂加两者联合应用120例,未治疗组136例.治疗组均在孕26周起开始注射,孕妇和新生儿血清HBsAg、抗-HBs、HBeAg、抗-HBe、抗-HBc检测采用ELISA法.随访产妇及新生儿的乙肝标志物(HBVM)变化.结果脐血中HBsAg阳性率:HBVaC治疗组为18.10%,HBIG治疗组为9%,联合治疗组为3.33%,未治疗组为24.26%.随访母亲HBVM多数转为HBSAg、抗-HBC、抗-HBc阳性,所生儿童抗-HBs＞70%.结论携带HBV孕妇于孕晚期给予HBVac、HBIG和左旋咪唑涂布剂联合两者治疗后,可有效阻断HBV母婴之间传播.     

乙肝免疫球蛋白不能阻断乙肝病毒感染人绒毛膜癌细胞

目的: 观察不同浓度乙肝免疫球蛋白(HBIG)在体外对乙肝病毒(HBV)感染人绒毛膜癌细胞系JAR细胞的影响。方法: 实验分为HBIG实验组、空白对照组(胎牛血清)、阴性对照组(健康人血清)。HBIG实验组又分为高浓度HBIG组(HBV+10³IU/L HBIG、HBV+10² IU/L HBIG)、最低保护浓度HBIG组(HBV+10 IU/L HBIG)、低浓度HBIG组(HBV+1IU/L、HBV+0.1 IU/L)和HBV组;采用MTT法检测HBIG对细胞生长的影响;采用实时荧光定量PCR检测细胞内HBV-DNA的表达;采用细胞免疫荧光染色法检测细胞内乙肝表面抗原(HBsAg)的表达变化。结果: (1) 不同浓度的HBIG对JAR细胞生长无影响;(2) 不同浓度HBIG组的细胞内HBsAg的荧光强度无显著差异(P>0.05);(3)不同浓度HBIG组的细胞内HBV-DNA无显著差异(P> 0.05)。结论: HBIG不能阻断HBV感染体外培养的JAR细胞。     

Hepatitis B immunoglobulin for prevention of hepatitis B virus infection and recurrence after liver transplantation

Intravenous hepatitis B immunoglobulin (HBIG) is a human plasma-derived purified gammaglobulin (IgG) that has proven efficacy and dose-dependent response in the prevention of hepatitis B virus (HBV) recurrence after liver transplantation. It is also indicated for postexposure prophylaxis after contact with blood or body fluids of serum hepatitis B surface antigen (HBsAg)-positive carriers and in prevention of mother-to-child (vertical) transmission. The exact mechanism of passive immunization is unknown; HBIG may block HBV entry and binding to hepatocytes, neutralize circulating HBV and target HBV-infected cells through an antibody-mediated immune response. The drug is well tolerated and common side effects include fever, chills and arthralgias that are usually mild and transient. This article summarizes the main indications and the recommendations for use of intravenous HBIG, as well as the usage of intramuscular HBIG in the liver transplant setting.     

Low incidence of acute rejection in hepatitis B virus positive liver transplant recipients and the impact of hepatitis B immunoglobulin

Historically, hepatitis B virus (HBV) liver transplantation (LT) recipients have less acute cellular rejection (ACR) than those without HBV. We questioned whether this has persisted in an era of decreased Hepatitis B immunoglobulin use (HBIG) given its in vitro immunoregulatory effects.We compared the incidence, risk factors and outcomes of ACR among 40,593 primary LT recipients with HBV, hepatitis C, steatohepatitis, and immune liver disease (OPTN 2000-2011). We also assessed the in vitro effect of HBIG on alloimmune lymphoproliferation and regulatory T cell generation using mixed lymphocyte reactions.In multivariate analysis, HBV status remained a strong independent predictor of freedom from ACR (OR 0.58, 95% CI: 1.5–2.1). Patient (67.7% vs 72.3%) and graft (60.8% vs 69.1%) survival were significantly lower in patients with ACR versus no ACR for all causes except HBV. HBIG use had no statistical association with ACR. In vitro, HBIG at concentrations equivalent to clinical dosing did not inhibit lymphoproliferation or promote regulatory T cell development. In summary, the incidence and impact of ACR is lower now for HBV LT and does not appear to be secondary to HBIG by our in vitro and in vivo analyses. Rather, it may be due to the innate immunosuppressive properties of chronic HBV infection.     

Immune-mediated myelitis following hepatitis B vaccination

The hepatitis B virus (HBV) is an important international cause of infectious acute and chronic liver diseases. HBV vaccines were developed to combat the potential life-threatening effects of HBV infection. Published case histories, retrospective reviews and analyses of epidemiological data report on the onset of immune-mediated myelitis after recombinant HBV vaccination, mostly in adults with a presumed genetic/immunologic predisposition. However, HBV vaccination has not borne out to be a significant trigger of serious autoimmune events, including acute myelitis, in populations at large over prolonged observation periods after immunization.Published study methods lack the sensitivity to categorically establish a causal relationship between exposure to HBV vaccine components and immune mediated myelitis, but in practice the faint possibility of such a link should not be totally rejected.     

Failure of preexisting antibody against hepatitis B surface antigen to prevent subsequent hepatitis B infection.

We studied a patient who developed acute hepatitis B virus (HBV) infection despite the presence of preexisting antibody to the surface antigen of HBV (anti-HBs). Anti-HBs has been reported to consist primarily of antibody against the common a determinant of HBV. Antibody directed against this major determinant appears to confer protection against HBV, regardless of the subtype. Our patient was shown to have had preexisting anti-HBs of anti-d but not anti-a specificity. She subsequently developed non-A, non-B viral hepatitis followed by an episode of acute hepatitis B after exposure to HBV of the ayw subtype.