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.     

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.     

孕期不同阶段应用HBIG阻断乙肝母婴传播效果初探

目的探讨孕期不同阶段应用HBIG阻断乙肝病毒宫内感染的效果。方法设计自孕20周起,给予乙肝孕妇每四周免疫HBIG一次,共5次。对比常用的孕晚期3次免疫方法及孕期无干预措施的乙肝孕妇,在脐血、新生儿外周血及羊膜、胎盘感染方面进行比较。结果20周免疫组新生儿宫内感染率与28周免疫组相比无明显减少,同时新生儿抗体产生率也无明显增加。但是在胎盘感染的微观方面,20周免疫组明显低于28周免疫组。两个干预组较未干预组相比宫内感染率都有明显降低。结论孕期应用HBIG阻断乙肝母婴传播可有效的减少宫内感染率;20周开始免疫和28周开始免疫相比,在临床上,未见明显的优势,但是胎盘感染的微观方面,有明显低的感染率,新生儿外周血能比脐血更准确的诊断乙肝感染情况;羊膜的感染率与胎盘相同。     

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.     

Epidemiology and prevention of hepatitis B virus infection

Hepatitis B virus (HBV) infection has been a major global cause of morbidity and mortality. The recognition of the problem led to a worldwide effort to reduce transmission of HBV through routine infant vaccination. HBV infection is the most common cause of chronic liver diseases and hepatocellular carcinoma in Korea. After hepatitis B vaccine era, seroprevalence of hepatits B surface antigen is decreasing, particularly in children. Hepatitis B vaccine is remarkably safe and shows high immunogenicity. Universal childhood immunization with three doses of hepatitis B vaccine in the first year of life is a highly effective method for prevention and control of hepatitis B.     

How to: prophylactic interventions for prevention of Clostridioides difficile infection

BackgroundClostridioides difficile infection (CDI) remains the leading cause of healthcare-associated diarrhoea, despite existing guidelines for infection control measures and antimicrobial stewardship. The high associated health and economic burden of CDI calls for novel strategies to prevent the development and spread of CDI in susceptible patients.ObjectivesWe aim to review CDI prophylactic treatment strategies and their implementation in clinical practice.SourcesWe searched PubMed, Embase, Emcare, Web of Science, and the COCHRANE Library databases to identify prophylactic interventions aimed at prevention of CDI. The search was restricted to articles published in English since 2012.ContentA toxin-based vaccine candidate is currently being investigated in a phase III clinical trial. However, a recent attempt to develop a toxin-based vaccine has failed. Conventional probiotics have not yet proved to be an effective strategy for prevention of CDI. New promising microbiota-based interventions that bind and inactivate concomitantly administered antibiotics, such as ribaxamase and DAV-132, have been developed. Prophylaxis of CDI with C. difficile antibiotics should not be performed routinely and should be considered only for secondary prophylaxis in very selected patients who are at the highest imminent risk for recurrent CDI (R-CDI) after a thorough evaluation. Faecal microbiota transplantation (FMT) has proved to be a very effective treatment for patients with multiple recurrences. Bezlotoxumab provides protection against R-CDI, mainly in patients with primary episodes and a high risk of relapse.ImplicationsThere are no proven effective, evidenced-based prophylaxis options for primary CDI. As for secondary prevention, FMT is considered the option of choice in patients with multiple recurrences. Bezlotoxumab can be added to standard treatment for patients at high risk for R-CDI. The most promising strategies are those aimed at reducing changes in intestinal microbiota and development of a new effective non-toxin-based vaccine.     

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.     

Genetic variation of hepatitis B surface antigen coding region among infants with chronic hepatitis B virus infection

Variants in the amino acid composition of the primary antibody-binding site of hepatitis B surface antigen (HBsAg) have been identified in a number of populations with chronic hepatitis B virus (HBV) infection. Direct sequencing of amplified or cloned PCR products, solid phase detection of sequence-specific PCR products (SP-PCR), and limiting dilution cloning PCR (LDC-PCR) were compared to determine their sensitivity in detecting differing concentrations of HBsAg variants. LDC-PCR had the greatest sensitivity and could detect HBsAg variants at a concentration of 0.1% of the total viral population. HBsAg variants were detected in 51% of infants with chronic HBV infection acquired after postexposure prophylaxis, and more than half of the variants were detected only by the most sensitive methods.     

HBIG联合HBVac阻断HBV宫内感染的研究

目的探讨孕期多次联合注射乙型肝炎免疫球蛋白 (HBIG)和乙型肝炎疫苗(HBVac )阻断乙型肝炎病毒HBV)宫内感染效果.方法对30例HBsAg阳性孕妇从孕20周开始联合注射HBIG和HBVac,另23 例未行注射的HBsAg阳性孕妇作对照.采用敏感特异的套式聚合酶链反应检测孕妇及新生儿血清及外周血单个核细胞(PBMC)中HBV DNA.结果阻断组和对照组新生儿血清HBV DNA检出率分别为10%(3/30)和34.8%(8/23),二组差异显著,而PBMC中HBV DNA检出率二组无显著性差异;阻断组孕妇血清 HBV DNA水平下降率38.5 %(10/26),而对照组10.5%(2/19),差异显著, PBMC中HBV DNA水平二组无显著性差异.结论孕期多次联合注射HBIG 和 HBVac 可有效降低孕妇体内HBV DNA水平,从而降低HBV宫内感染率,但对孕妇PBMC中 HBV 影响不大, 并不降低新生儿 PBMC 中HBV DNA的检出率.     

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.     

Elevation of serum sex hormone-binding globulin in females with fulminant hepatitis B virus infection

Amongst adults exposed to the hepatitis B virus (HBV), the infection pursues a fulminant course more frequently in females, while conversely a chronic carrier state is more frequent in males. Because of these differences in sex ratio, we investigated the relationship between the outcome of HBV infection and serum concentrations of sex hormone-binding globulin (SHBG), a circulating glycoprotein that exerts an important influence on the balance of free sex hormones. SHBG levels were significantly elevated in females with fulminant HBV infection compared to females with either uncomplicated acute or chronic HBV infection (P less than .05 and P less than .001, respectively). That this was not a nonspecific effect of fulminant hepatitis was confirmed by the significantly higher levels in this group than in age-matched females with fulminant hepatitis unrelated to HBV (P less than .05). In contrast, four of 15 female HBsAg carriers had SHBG values in the male range, and these included three of four patients who had acquired HBV as adults. SHBG levels were normal in all male groups. These results suggested that for adults the hormonal environment may be important in determining the course of HBV infection.     

Cellular immune response of ducks to duck hepatitis B virus infection

Duck hepatitis B virus (DHBV) has been a useful model for hepadnavirus infection. There have been few studies on immunity to DHBV and none describing the cell-mediated immune response by acute and chronically infected ducks. A duck hepatitis B antigen-specific blastogenesis assay was used to measure DHBV antigen-specific responses of duck peripheral blood (PBMC) and splenic mononuclear cells (SMCs) from uninfected control ducks, ducks acutely or chronically infected with DHBV, and ducks immune to DHBV. A comparison of the group mean responses by PBMC to DHBV surface antigen (DHBsAg) found that the immune group was significantly different to the other three groups (controls or unexposed, P < 0.0001; acutely infected, P< 0.01; chronically infected, P < 0.01). The responses to DHBsAg by PBMC of the acute group (P< 0.01) were significantly different also to that of the unexposed group. For DHBV core antigen (DHBcAg), significant differences in the responses were found between immune ducks and unexposed (P < 0.0005) and acutely infected (P < 0.05) groups. The SMC showed a significant difference between unexposed ducks and immune ducks (P< 0.05) in the group mean responses to DHBsAg. The responses to DHBcAg were significantly different between the immune group and the acute (P < 0.01) and unexposed (P < 0.01) groups. The group mean of unexposed ducks was also significantly different to that of acutely infected ducks (P < 0.01). This study indicates that the cellular immune response in immune animals differs from acutely and chronically infected ducks. Further studies of these differences may provide some explanations for the differing outcomes of DHBV infection.     

Minimal role of hepatitis C virus infection in childhood liver diseases in an area hyperendemic for hepatitis B infection

To investigate the role of hepatitis C virus (HCV) in childhood liver disease in Taiwan, an area hyperendemic for hepatitis B, we studied antibody to HCV (anti-HCV) with a second generation enzyme immunoassay in 195 infants and children, including 96 hepatitis B surface antigen (HBsAg) positive children (66 with chronic hepatitis B, 23 children with hepatocellular carcinoma, and 7 with fulminant hepatitis B), 6 children with fulminant non-A, non-B hepatitis, 42 infants with neonatal hepatitis, 11 with biliary atresia, and 40 prospectively followed blood recipients. For comparison, another 748 apparently healthy children (from neonates to 12 years) were also screened for anti-HCV. The positive rate of anti-HCV was low in both apparently healthy children (0.13%) and patients with various liver disorders (0 to 4.4%) except fulminant hepatitis. The seropositive rate in 6 cases of non-A, non-B fulminant hepatitis was higher (16.7%) although the case number was too small. We conclude that HCV is generally not a major etiologic factor in the liver diseases of Taiwanese children. © 1993 Wiley-Liss, Inc.