Review: hepatitis B immune globulin for prevention of hepatitis B infection

Specific hepatitis B immune globulin (HBIG) contains a high titer of antibody to hepatitis B surface antigens and provides immediate passive protection against infection with hepatitis B virus, after acute exposure to infection. It is now generally combined with active immunization with hepatitis B vaccine. The principal indications for administration of HBIG are: a single acute percutaneous exposure to hepatitis B virus (HBV); mucocutaneous exposure; unprotected sexual exposure; mother-to-infant transmission; prevention of re-infection after liver transplantation; non-responders to hepatitis B vaccine and immunosuppressed patients.     

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.     

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.     

Hepatitis B prophylaxis post liver transplantation with newer nucleos(t)ide analogues after hepatitis B immunoglobulin discontinuation

Newer nucleos(t)ide analogues (NUCs) have better resistance profiles making hepatitis B immunoglobulin (HBIG)-sparing protocol an attractive prophylactic approach against hepatitis B virus (HBV) recurrence after liver transplantation (LT). We evaluated the risk of HBV recurrence after withdrawal of HBIG in patients who had been under HBIG plus NUCs after LT. Stable patients without HBV recurrence after LT while receiving combination of HBIG plus NUCs for at least 12?months were eligible for HBIG discontinuation. The patients were at low risk for HBV recurrence (only 4.5% had detectable HBV DNA at the time of LT, and 32% had HBV/hepatitis D virus co-infection). All patients were followed up with HBV serum markers, HBV-DNA, and evaluation of renal function, including glomerular filtration rate. Forty-seven recipients discontinued HBIG and were maintained on newer NUCs. Median follow-up post-HBIG withdrawal was 24?months (range: 6-40?months). Twenty-eight (60%) patients continued on lamivudine in combination with adefovir dipivoxil (n?=?23, 82%) or tenofovir (n?=?5, 18%); 10 (21%) and 9 (19%) of the 47 patients continued on tenofovir and entecavir monoprophylaxis, respectively. Although 3 (6.3%) patients developed detectable hepatitis B surface antigen, all of them had undetectable HBV DNA and no clinical manifestations of HBV recurrence. Renal function was similar between the different groups of patients. In conclusion, maintenance therapy with newer NUCs after discontinuation of HBIG prophylaxis was effective, but further studies in larger cohorts with longer follow-up are needed.     

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.     

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.     

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.     

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.     

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.     

Cost-effectiveness and long-term outcomes of liver transplantation using hepatitis B core antibody-positive grafts with hepatitis B immunoglobulin prophylaxis in Korea

Background/AimsHepatitis B core antibody (anti-HBc)-positive donors are used as an extended donor pool, and current guidelines recommend the usage of nucleos(t)ide analogues (NAs) as prophylaxis for preventing de novo hepatitis B virus infection (DNH). We analyzed the long-term outcomes of a large cohort of liver transplantation (LT) patients receiving anti-HBc-positive grafts and evaluated the risk of DNH when hepatitis B immunoglobulin (HBIG) monotherapy was used as prophylaxis. We also compared the cost-effectiveness of HBIG and NAs.MethodsWe retrospectively reviewed 457 patients with anti-HBc-positive grafts and 898 patients with anti-HBc-negative grafts who underwent LT between January 2001 and December 2018. We compared recipient characteristics according to the anti-HBc status of the donor, and compared the costs of using NAs for the rest of the patient’s life and using HBIG to maintain hepatitis B surface antibody titers above 200 IU/L.ResultsThe 1-, 5-, and 10-year patient survival rates were 87.7%, 73.5%, and 67.7%, respectively, in patients with anti-HBc-positive grafts, and 88.5%, 77.4%, and 70.3%, respectively, in patients with anti-HBc-negative grafts (P=0.113). Among 457 recipients with anti-HBc-positive grafts, 117 (25.6%) were non-HBV recipients. The overall incidence of DNH was 0.9%. When using HBIG under insurance coverage, the cumulative cost was lower compared with using NA continuously without insurance coverage in Korea.ConclusionsAnti-HBc-positive grafts alone do not affect patient survival or graft survival. HBIG monoprophylaxis has good outcomes for preventing DNH, and the patient’s long-term cost burden is low in Korea because of the national insurance system in this cohort.     

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.     

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.     

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。     

乙肝免疫球蛋白预防乙肝母婴垂直传播随机双盲对照研究

目的 探讨乙肝免疫球蛋白（HBIG）预防乙型肝炎病毒（HBV）母婴传播的效果。方法 将单纯HBsAg阳性及HBsAg、HBeAg双阳性孕妇随机各分两组，其中各一组作试验组，定期注射HBIG，另两组作对照组，不注射HBIG，然后随访并测定婴儿HBsAg。结果 注射HBIG组，对单纯HBsAg阳性孕妇及HBsAg、HBeAg双阳性孕妇，出生婴儿HBsAg感染率均显著低于对照组；HBIG对单纯HBsAg孕妇预防效果优于HBsAg、HBeAg双阳性孕妇。结论 HBIG能有效预防母婴传播。减少HBV感染率。     

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。     

孕期注射乙肝免疫球蛋白对婴儿anti-HBs产生的影响

目的探讨孕期注射乙肝免疫球蛋白的孕妇分娩的婴儿对乙肝疫苗免疫应答情况。方法以HBsAg阳性孕妇及其新生儿为研究对象,孕期母亲注射乙肝免疫球蛋白的300例新生儿为实验组,未使用者80例为对照组,比较两组新生儿出生时及联合免疫后7个月anti-HBs产生情况。结果实验组与对照组婴儿出生时anti-HBs阳性率分别为10.3%（31/300）和1.25%（1/80）,差异有统计学意义;7个月龄实验组anti-HBs产生率为96.1%（124/129）,对照组anti-HBs产生率95.3%（41/43）,差异无统计学意义;出生时anti-HBs阳性的新生儿25例,7个月龄均产生anti-HBs,出生时anti-HBs阴性或弱阳性的147例婴儿中有7例婴儿anti-HBs仍为阴性或弱阳性,差异有统计学意义。结论孕期使用乙肝免疫球蛋白可提高新生儿出生时anti-HBs产生率,但对7个月anti-HBs产生率无影响。     

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)     

Infections by hepatitis B surface antigen gene mutants in Europe and North America

Hepatitis B virus (HBV) mutants have usually been studied in patients in Asia because of the wider use of HBV immunization there and the resultant emergence of viral mutants. Nevertheless, HBV surface antigen (S) gene mutants also are found in Europe and North America. In Europe and North America, HBV with mutations in the portion of the S gene coding the "a" determinant of the hepatitis B surface antigen (HBsAg) have been documented in small numbers of infants born to HBV-infected mothers following post-natal HBV vaccine and hepatitis B immune globulin (HBIG) prophylaxis and in many liver transplant recipients who develop HBV re-infection despite HBIG prophylaxis. In some cases, these mutations have included a glycine to arginine substitution at position 145 (G145R), which results in a conformational change and different reactivity to monoclonal antibody reagents than that of the wild-type virus. Mutations in the a determinant (but not G145R) also have been reported in European patients with chronic HBV infection who have not received HBV vaccine or HBIG. However, it appears that such mutations are only responsible for a small proportion of "occult" or "silent" HBV infections, which are characterized by the presence of HBV DNA in serum in the absence of detectable HBsAg. However, some of these mutant forms of HBV in cases of occult HBV may theoretically escape detection and could present a risk to blood safety.     

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.