Clinical Practice
Prevention of Hepatitis B with the Hepatitis B Vaccine
N Engl J Med 2004; 351:2832-2838December 30, 2004DOI: 10.1056/NEJMcp041507
- Article
This Journal feature begins with a case vignette highlighting a common clinical problem. Evidence supporting various strategies is then presented, followed by a review of formal guidelines, when they exist. The article ends with the authors' clinical recommendations.
A 25-year-old registered nurse comes for a visit to initiate prenatal care after receiving a positive result on a pregnancy test. On review of her vaccination status, she reports that she declined hepatitis B vaccination when it was offered by her current employer, since she does not draw blood and thus does not consider herself at risk for infection. Should she receive the vaccine? What are the current recommendations for hepatitis B vaccination?
The Clinical Problem
Hepatitis B Virus and Infection
The hepatitis B virus (HBV) is an enveloped, double-stranded DNA virus. It is the smallest DNA virus known to infect humans. The virus is very infectious in nonimmune persons. The incubation period for acute infection is 45 to 160 days, with a mean incubation period of 90 days. The primary reservoir is chronically infected people. There are no known animal reservoirs and no clear evidence that insects are responsible for transmission of HBV.
Acute HBV infection can be symptomatic or asymptomatic. The acute phase is followed by either a clearance of the infection or a chronic, indolent infection that can lead to cirrhosis, liver failure, hepatocellular carcinoma, and death. The risk of the development of the chronic carrier state is inversely related to the age at the time of infection. The risk of chronic carriage in infected neonates is as high as 90 percent. Prospective studies of infection in Taiwan demonstrate that 25 percent of persons who have a persistent HBV infection in infancy or early childhood ultimately die from either hepatocellular carcinoma or cirrhosis. The death rate declines to 15 percent for persistent infection that develops in adolescents and young adults.1
Epidemiology
HBV infection occurs throughout the world and is endemic in Africa, Eastern Europe, the Middle East, Central Asia, China, Southeast Asia, the Pacific Islands, and the Amazon basin of South America. In these areas, most persons become infected as infants or young children, and up to 70 percent of the adult population tests positive for prior infection. Among those populations, 8 to 15 percent have chronic HBV infection. Globally, this translates into more than 2 billion people with evidence of previous HBV infection and more than 350 million chronic carriers of the virus, with an estimated 1 million deaths each year due to cirrhosis and hepatocellular carcinoma. Widespread immunization programs against HBV, which have been implemented in more than 100 countries, have dramatically reduced the occurrence of chronic HBV infection and hepatocellular carcinoma, and the vaccine can thus be considered the first anticancer vaccine.2 In the United States, screening of blood and blood products with serologic tests to detect HBV, hepatitis C virus, human immunodeficiency virus, and human T-cell lymphotropic virus have dramatically reduced the transmission of these viruses through transfusions. Improved disposal of needles and other sharp objects and new devices designed to reduce the risk of inadvertent needle sticks have diminished exposures in medical settings. Furthermore, successful vaccination efforts have resulted in high proportions of vaccination and prenatal screening. As a result, reports of acute HBV infection have continued to decrease over the past decade in the United States. In 2002, the last year for which figures are available, the reported incidence of acute HBV infection in the United States was 8064 cases, but the incidence has continued to be higher among men than among women (by a ratio of 1.7 to 1).3
Sources of Infection and Transmission
HBV infection results from percutaneous or mucosal exposure to the blood or bodily fluids of infected persons. Infected persons need not be symptomatic to transmit the virus. Blood contains the highest concentrations of virus. Common sources of exposure include sexual contact, contaminated needles, contaminated blood or blood products, and perinatal exposure to an infected mother. In as many as one third of cases of acute HBV infection, the source of exposure is unknown. Nonsexual transmission has been documented in cases of long-term exposure in household settings. Although the mechanism has not been elucidated, it appears that horizontal transmission of HBV can occur among infants, children, and elementary school students who live with an infected household member. HBV is not transmitted by the fecal–oral route. Young adults (18 to 39 years of age) are at increased risk for HBV infection; this increase is attributed to the greater likelihood of multiple sex partners (defined as four or more sex partners during one's lifetime), illicit injection of drugs, and other high-risk behaviors in this age group than in others.4
In countries where HBV is endemic, most infections result from vertical transmission from mother to child in the peripartum period or from infection in early childhood. There is no evidence of viral transmission through breast milk.5 In countries where the rate of endemic disease is low, transmission is primarily a result of multiple sexual contacts or the illicit injection of drugs. Chronically infected refugees from countries where the disease is endemic also represent sources of possible infection.
Strategies and Evidence
Effective strategies to prevent HBV infection include the avoidance of high-risk behaviors, the prevention of exposure to blood and bodily fluids, the screening of women in late pregnancy for the presence of HBV, active immunization with the hepatitis B vaccine, and passive immunization with hepatitis B immune globulin before or after exposure. Optimal protection is achieved with a completed series of hepatitis B vaccine before exposure occurs.
Hepatitis B Vaccine
Hepatitis B vaccines have been available in the United States since 1981. Multiple formulations (Recombivax HB and Comvax, Merck; Engerix-B, Pediatrix, and Twinrix, GlaxoSmithKline) are now licensed in the United States (Table 1Table 1
Dosing Schedule for Recombivax HB, Engerix-B, and Twinrix Hepatitis B Vaccines.); all are produced with the use of yeast (Saccharomyces cerevisiae) and recombinant techniques to generate the hepatitis B surface antigen (HBsAg) protein.In 1991, the Advisory Committee on Immunization Practices (ACIP) recommended a comprehensive strategy to eliminate HBV transmission in the United States, which included universal vaccination of infants. In 1995, routine immunization of adolescents was added. In 1999, the strategy was further modified to include immunization of all persons up to 18 years of age. This strategy has reduced the overall annual incidence of acute HBV infections in the United States (from 8.5 cases per 100,000 persons in 1990 to 2.8 per 100,000 in 2002, a decrease of 67 percent).
On the basis of data indicating a decrease in the burden of acute (and hence chronic) HBV infection as a result of immunization programs for infants, children, and adolescents,6 the World Health Organization (WHO) has recommended that all countries provide universal HBV immunization programs for infants and adolescents.7 As of 2003, 79 percent of the 192 WHO member states had adopted policies of universal childhood immunization against HBV.8,9 One compelling example of the associated benefit is the dramatic decline in the incidence of neonatal HBV infections and subsequent sequelae in Taiwan after the introduction and widespread use of hepatitis B vaccine.10-12
Since 1991, the Occupational Safety and Health Administration has mandated that health care workers be educated about the vaccine and that employers offer it free of charge. Except for pregnant women, routine screening for HBsAg or for antibodies to HBsAg (anti-HBs antibodies) is not routinely recommended; whether or not to screen is a clinical decision that should be based on the likelihood of previous exposure to HBV or hepatitis B vaccine. Table 2Table 2
Groups for Whom Hepatitis B Vaccine Is Recommended. lists persons who are at high risk for HBV infection and who should therefore receive the vaccine.Administration of Vaccine
All currently licensed hepatitis B vaccines are given intramuscularly,14-18 in the thigh (for neonates and infants) or the deltoid muscle (for children, adolescents, and adults). The needle should be long enough to achieve deep intramuscular penetration. For many people, a standard 12.7-cm (5/8-in.) needle is insufficient to penetrate the deltoid fat pad and result in intramuscular deposition of vaccine.18 The required needle length increases with increased body weight (Table 1).18
Some researchers have advocated the use of split, smaller doses, to be delivered as repeated intradermal immunization in patients in whom a response has not occurred (i.e., the anti-HBs antibody level is less than 10 mIU per milliliter after the third dose of vaccine).19,20 This option is not recommended, because lower immunogenicity may result. Furthermore, the vaccine is not licensed for use in this manner.
The vaccine is generally administered in three doses, with the second dose given one month after the first dose and the third dose given six months after the first dose (Table 1). Vaccines from the two U.S. manufacturers can be used interchangeably, and it is not necessary to restart the series if there have been prolonged intervals between doses. Twinrix combines the vaccines for hepatitis A and B and is licensed for use in persons 18 years of age or older for whom both vaccines are indicated.21
Vaccine Immunogenicity
The antibody response declines with increasing age. Patients older than 30 years have an increased risk of nonresponse to HBV vaccine, as compared with younger persons.22 Thus, immunization during childhood or adolescence offers the greatest potential for protection22 and provides lifelong immunity.
Ninety percent of healthy adults and 95 percent of infants, children, and adolescents have protective serum anti-HBs antibody concentrations after the vaccine series has been completed.23 Among immunocompetent persons in whom antibody levels of at least 10 mIU per milliliter develop, the efficacy of the vaccine is nearly 100 percent.
Lack of Response
Ideally, the antibody response (the anti-HBs antibody level) is determined within one to three months after the last dose of vaccine in persons with risk factors for a lack of response (including an age greater than 30 years, obesity, or immunodeficiency) or those at high risk for exposure to blood or bodily fluids. Unfortunately, the antibody response is frequently tested years after completion of the vaccination series, in which case a true nonresponse (an antibody level of less than 10 mIU per milliliter after the appropriate vaccine series) must be distinguished from “waning” antibody levels (those that are initially protective but that become undetectable over time). Administration of a single dose of vaccine, followed by measurement of the anti-HBs antibody response 4 to 12 weeks later, will differentiate persons with no response (indicating an absence of protection against disease) from those with waning antibody levels (in whom an anamnestic response will occur, with anti-HBs antibody levels of at least 10 mIU per milliliter). For persons who remain seronegative after this booster dose, a second series, which involves two additional doses of vaccine (i.e., for a total of three doses), will result in seroconversion in 50 to 60 percent of recipients. For those with risk factors for nonresponse, the 40-μg dose should be used. A clinical algorithm for immunizing those in whom a response does not occur has been published.24
Several studies of vaccination in very-high-risk subjects have shown that in a small number of persons (1 to 9 percent) who initially had a protective antibody level after vaccination, this response was lost over time and markers of HBV infection (specifically, antibodies to hepatitis B core antigen [HBc]) developed.25-30 Generally, such infections were asymptomatic, and anti-HBc antibodies were identified by regular blood monitoring. Rare cases of chronic infection have been identified in such persons, generally those who are not immunocompetent.
Safety
Both the currently licensed vaccines and the previous plasma-derived vaccine have been demonstrated to be safe. Concerns about potential disease risks (including vaccine-induced autoimmune diseases, diabetes, chronic fatigue syndrome, demyelinating disorders, optic neuritis, and other syndromes7,31,32) have not been supported by scientific data. Multiple studies have found no evidence of the initiation, relapse, or exacerbation of demyelinating disorders in association with hepatitis B vaccination.9,31-34 Concerns regarding thimerosal and aluminum in vaccines have likewise not been supported by well-conducted studies.7,35 The Institute of Medicine, the WHO's Global Advisory Committee on Vaccine Safety, and a number of independent scientific bodies have not found evidence to support these concerns and have concluded that hepatitis B vaccine is both safe and effective.7,9,31-36
Hepatitis B Immune Globulin
Hepatitis B immune globulin is used to prevent hepatitis B infection in persons without demonstrated immunity to HBV who have been exposed to the virus perinatally (i.e., infants born to HBsAg-positive mothers), by cutaneous or mucosal contact with HBsAg-positive blood or bodily fluids or by sexual contact with a person who is positive for HBsAg, or in the case of infants younger than 12 months, by exposure to a primary caregiver in whom acute hepatitis B infection has been diagnosed.13 Generally, one dose of hepatitis B immune globulin is administered as soon as possible after exposure (within 24 hours after birth for perinatal exposure, within 7 days after needle-stick exposure, and within 14 days after sexual exposure), along with the first dose of the hepatitis B vaccine series (followed by additional doses of vaccine on the usual schedule). The reported efficacy of this approach is 85 to 95 percent for the prevention of newborn infection and approximately 75 percent for the prevention of infection after needle-stick or sexual exposure.13
Maternal Screening for Hepatitis B
To prevent vertical transmission, women should be screened for HBsAg during the first prenatal visit and, if seronegative but at high risk, screened again in late pregnancy.37 Since the administration of hepatitis B vaccine is safe during any stage of pregnancy, nonimmune, uninfected pregnant women with risk factors can be immunized. The recommended management strategies for infants born to HBsAg-positive mothers are summarized in Table 1. All such infants should then undergo testing for anti-HBs antibodies and HBsAg at 9 to 15 months of life.
Areas of Uncertainty and Concern
Although some authors have recommended a 5-year or 10-year booster dose, data are lacking to support these recommendations, and neither the ACIP nor any official U.S. or European professional society currently recommends routine booster doses. Nonetheless, it is uncertain whether protective antibody levels are still present three or more decades after immunization, since the vaccine has not been routinely used for that long. Questions remain about the relevance of potential differences in immunogenicity among currently available vaccine formulations38 and about the effects of different dosing regimens and intervals.
The incidence of acute HBV infection actually increased from 1990 to 2002 among men 20 to 39 years of age and among men and women 40 years and older.3 This may indicate the need for a national program of HBV immunization in adults.
An area of particular concern is the identification of HBV “escape mutants,” for which immunity that is induced by the current vaccines may not be protective.39 Although the incidence of these mutants is uncertain, they have only rarely been recognized (and in persons who are from areas in which HBV is endemic or who have received antiviral therapy), are generally confined to one genetic region of the virus, and have led only in rare cases to breakthrough HBV infection (despite apparently protective levels of anti-HBs antibodies). To date, there is no evidence that these viruses are disrupting efforts to control HBV through immunization programs.
The role of new HBV vaccines that are in development remains unclear. So-called mixed-particle vaccines (which contain pre-S1, pre-S2, and S antigens) have been studied and have not been found to be superior to S subunit vaccines that are given in higher doses (40 μg) in persons who do not have a response to a standard series of three doses of 10 or 20 μg.40 Two doses of a novel recombinant vaccine containing pre-S2 and S subunits combined with an MF59 adjuvant resulted in a seroprotection rate of 89 percent and significantly higher antibody titers than after three doses of licensed vaccine.41 DNA vaccines for HBV have also been tested and, in one study, found to elicit antibody responses in persons in whom long-lasting responses did not occur after a standard vaccine series.42 These new candidates for vaccine are not currently approved by the Food and Drug Administration.
Guidelines
Guidelines for the administration of hepatitis vaccine are provided by the ACIP (www.cdc.gov/nip/publications/acip-list.htm) and endorsed by the Centers for Disease Control and Prevention; a list of indications appears in Table 2. Currently, all of the physician-based professional societies endorse the routine use of HBV vaccine in persons 18 years of age and younger and in those at high risk for infection.13
Summary and Recommendations
The use of HBV vaccine has been associated with a dramatic decrease in the incidence of HBV infections, as well as of hepatocellular carcinoma, in countries where it is widely used. Because of the serious nature of HBV infection, clinicians should be vigorous in their attempts to achieve universal vaccination of infants and children through the age of 18 years and to identify and vaccinate persons at risk for infection. For pregnant women, such as the woman described in the vignette, testing for HBsAg is warranted, to reduce the risk of vertical transmission. If the result is positive, the baby will need hepatitis B immune globulin and vaccination at birth; investigation is warranted to determine whether the infant's father (and, potentially, other sexual partners of the mother) could be the source of infection. If she is not at high risk (Table 1), this patient should be tested again in her last trimester of pregnancy. Given the potential for work-related exposure, even if she does not draw blood, we would recommend immunization, since HBV vaccine is not contraindicated during pregnancy.
We are indebted to Gail Sim for assistance in gathering references and to Kim Zabel for editorial assistance.
Source Information
From the Mayo Vaccine Research Group (G.A.P., R.M.J.), the Program in Translational Immunovirology and Biodefense (G.A.P.), the Department of Internal Medicine (G.A.P.), and the Department of Pediatric and Adolescent Medicine (R.M.J.), Mayo Clinic, Rochester, Minn.
Address reprint requests to Dr. Poland at the Mayo Vaccine Research Group, Mayo Clinic and Foundation, 611C Guggenheim Bldg., 200 First St. SW, Rochester, MN 55905, or at poland.gregory@mayo.edu.
- References
References
1
Hsieh CC ,Tzonou A ,Zavitsanos X ,Kaklamani E ,Lan SJ ,Trichopoulos D . Age at first establishment of chronic hepatitis B virus infection and hepatocellular carcinoma risk: a birth order study. Am J Epidemiol 1992;136:1115-1121
Web of Science | Medline2
Zuckerman AJ . Prevention of primary liver cancer by immunization. N Engl J Med 1997;336:1906-1907
Full Text | Web of Science | Medline3
Incidence of acute hepatitis B -- United States, 1990-2002. MMWR Morb Mortal Wkly Rep 2004;52:1252-1254
Medline4
Meheus A . Teenagers' lifestyle and the risk of exposure to hepatitis B virus. Vaccine 2000;18:Suppl 1:S26-S29
CrossRef | Web of Science | Medline5
Beasley RP ,Stevens CE ,Shiao IS ,Meng HC . Evidence against breast-feeding as a mechanism for vertical transmission of hepatitis B. Lancet 1975;2:740-741
CrossRef | Web of Science | Medline6
Patrick DM ,Bigham M ,Ng H ,White R ,Tweed A ,Skowronski DM . Elimination of acute hepatitis B among adolescents after one decade of an immunization program targeting Grade 6 students. Pediatr Infect Dis J 2003;22:874-877
CrossRef | Web of Science | Medline7
Duclos P . Safety of immunisation and adverse events following vaccination against hepatitis B. Expert Opin Drug Saf 2003;2:225-231
CrossRef | Medline8
Global progress toward universal childhood hepatitis B vaccination, 2003. MMWR Morb Mortal Wkly Rep 2003;52:868-870
Medline9
Hall A ,Kane M ,Roure C ,Meheus A . Multiple sclerosis and hepatitis B vaccine? Vaccine 1999;17:2473-2475
CrossRef | Medline10
Chang M-H ,Chen C-J ,Lai M-S , et al. Universal hepatitis B vaccination in Taiwan and the incidence of hepatocellular carcinoma in children. N Engl J Med 1997;336:1855-1859
Free Full Text | Web of Science | Medline11
Hsu H-M ,Chen D-S ,Chuang C-H , et al. Efficacy of a mass hepatitis B vaccination program in Taiwan: studies on 3464 infants of hepatitis B surface antigen-carrier mothers. JAMA 1988;260:2231-2235
CrossRef | Web of Science | Medline12
Chen H-L ,Chang M-H ,Ni Y-H , et al. Seroepidemiology of hepatitis B virus infection in children: ten years of mass vaccination in Taiwan. JAMA 1996;276:906-908
CrossRef | Web of Science | Medline13
Hepatitis B virus: a comprehensive strategy for eliminating transmission in the United States through universal childhood vaccination: recommendations of the Immunization Practices Advisory Committee (ACIP). MMWR Recomm Rep 1991;40:1-25
14
Lindsay KL ,Herbert DA ,Gitnick GL . Hepatitis B vaccine: low postvaccination immunity in hospital personnel given gluteal injections. Hepatology 1985;5:1088-1090
CrossRef | Web of Science | Medline15
Suboptimal response to hepatitis B vaccine given by injection into the buttock. MMWR Morb Mortal Wkly Rep 1985;34:105-8, 113
Medline16
Lemon SM ,Weber DJ . Immunogenicity of plasma-derived hepatitis B vaccine: relationship to site of injection and obesity. J Gen Intern Med 1986;11:199-201
CrossRef | Web of Science17
Shaw FE Jr ,Guess HA ,Roets JM , et al. Effect of anatomic injection site, age and smoking on the immune response to hepatitis B vaccination. Vaccine 1989;7:425-430
CrossRef | Web of Science | Medline18
Poland GA ,Borrud A ,Jacobson RM , et al. Determination of deltoid fat pad thickness: implications for needle length in adult immunization. JAMA 1997;277:1709-1711
CrossRef | Web of Science | Medline19
Coleman PJ ,Shaw FE Jr ,Serovich J ,Hadler SC ,Margolis HS . Intradermal hepatitis B vaccination in a large hospital employee population. Vaccine 1991;9:723-727
CrossRef | Web of Science | Medline20
Das HS ,Sawant P ,Shirhatti RG , et al. Efficacy of low dose intradermal hepatitis B vaccine: results of a randomized trial among health care workers. Trop Gastroenterol 2002;23:120-121
Medline21
FDA approval for a combined hepatitis A and B vaccine. MMWR Morb Mortal Wkly Rep 2001;50:806-807
Medline22
Fisman DN ,Agrawal D ,Leder K . The effect of age on immunologic response to recombinant hepatitis B vaccine: a meta-analysis. Clin Infect Dis 2002;35:1368-1375
CrossRef | Web of Science | Medline23
Mast E, Mahoney F, Kane M, Margolis H. Hepatitis B vaccine. In: Plotkin SA, Orenstein WA, eds. Vaccines. Philadelphia: Saunders, 2004:299-337.
24
Poland GA . Hepatitis B immunization in health care workers: dealing with vaccine nonresponse. Am J Prev Med 1998;15:73-77
CrossRef | Web of Science | Medline25
Wainwright RB, McMahon BJ, Bulkow LR, Parkinson AJ, Harpster AP, Hadler SC. Duration of immunogenicity and efficacy of hepatitis B vaccine in a Yupik Eskimo population — preliminary results of an 8-year study. In: Hollinger FB, Lemon SM, Margolis H, eds. Viral hepatitis and liver disease: proceedings of the 1990 International Symposium on Viral Hepatitis and Liver Disease. Baltimore: Williams & Wilkins, 1991:762-6.
26
Hadler SC, Coleman PJ, O'Malley P, Judson FN, Altman N. Evaluation of long-term protection by hepatitis B vaccine for seven to nine years in homosexual men. In: Hollinger FB, Lemon SM, Margolis H, eds. Viral hepatitis and liver disease: proceedings of the 1990 International Symposium on Viral Hepatitis and Liver Disease. Baltimore: Williams & Wilkins, 1991:766-8.
27
McMahnon BJ, Wainwright RB. Protective efficacy of hepatitis B vaccines in infants, children, and adults. In: Ellis RW, ed. Hepatitis B vaccines in clinical practice. New York: Marcel Dekker, 1993:243-61.
28
Wainwright RB ,McMahon BJ ,Bulkow LR , et al. Duration of immunogenicity and efficacy of hepatitis B vaccine in a Yupik Eskimo population. JAMA 1989;261:2362-2366
CrossRef | Web of Science | Medline29
Hadler SC, Judson PM, O'Malley NL, et al. Studies of hepatitis B vaccine in homosexual men. In: Coursaget P, Tong MJ, eds. Progress in hepatitis B immunization. London: Colloque Inserm/John Libbey Eurotext, 1990:165-75.
30
Wainwright RB ,McMahon BJ ,Bulkow LR ,Parkinson AJ ,Harpster AP . Protection provided by hepatitis B vaccine in a Yupik Eskimo population: seven-year results. Arch Intern Med 1991;151:1634-1636
CrossRef | Web of Science | Medline31
DeStefano F ,Verstraeten T ,Jackson LA , et al. Vaccinations and risk of central nervous system demyelinating diseases in adults. Arch Neurol 2003;60:504-509
CrossRef | Web of Science | Medline32
Confavreux C ,Suissa S ,Saddier P , et al. Vaccinations and the risk of relapse in multiple sclerosis. N Engl J Med 2001;344:319-326
Free Full Text | Web of Science | Medline33
Expanded Programme on Immunization (EPI): lack of evidence that hepatitis B vaccine causes multiple sclerosis. Wkly Epidemiol Rec 1997;72:149-152
Medline34
Ascherio A ,Zhang SM ,Hernan MA , et al. Hepatitis B vaccination and the risk of multiple sclerosis. N Engl J Med 2001;344:327-332
Free Full Text | Web of Science | Medline35
Global Advisory Committee on Vaccine Safety, 20-21 June 2002. Wkly Epidemiol Rec 2002;77:389-394
Medline36
Stratton K, Almario DA, McCormick MC, eds. Immunization safety review: hepatitis B vaccine and demyelinating neurological disorders. Washington, D.C.: National Academies Press, 2002.
37
Gall SA . Maternal immunization. Obstet Gynecol Clin North Am 2003;30:623-636
CrossRef | Web of Science | Medline38
Averhoff F ,Mahoney F ,Coleman P ,Schatz G ,Hurwitz E ,Margolis H . Immunogenicity of hepatitis B vaccines: implications for persons at occupational risk of hepatitis B virus infection. Am J Prev Med 1998;15:1-8
CrossRef | Web of Science | Medline39
Wilson JN ,Nokes DJ ,Carman WF . The predicted pattern of emergence of vaccine-resistant hepatitis B: a cause for concern? Vaccine 1999;17:973-978
CrossRef | Web of Science | Medline40
Bertino JS Jr ,Tirrell P ,Greenberg RN , et al. A comparative trial of standard or high-dose S subunit recombinant hepatitis B vaccine versus a vaccine containing S subunit, pre-S1, and pre-S2 particles for revaccination of healthy adult nonresponders. J Infect Dis 1997;175:678-681
CrossRef | Web of Science | Medline41
Heineman TC ,Clements-Mann ML ,Poland GA , et al. A randomized, controlled study in adults of the immunogenicity of a novel hepatitis B vaccine containing MF59 adjuvant. Vaccine 1999;17:2769-2778
CrossRef | Web of Science | Medline42
Rottinghaus ST ,Poland GA ,Jacobson RM ,Barr LJ ,Roy MJ . Hepatitis B DNA vaccine induces protective antibody responses in human non-responders to conventional vaccination. Vaccine 2003;21:4604-4608
CrossRef | Web of Science | Medline
- Citing Articles (79)
Citing Articles
1
Nicholas A. Meanwell, Stanley V. D'Andrea, Christopher W. Cianci, Ira B. Dicker, Kap-Sun Yeung, Makonen Belema, Mark Krystal. Antiviral Drug Discovery. In: Drug Discovery. John Wiley & Sons, Inc., 2013:439-515.
2
M. J. Lohouès-Kouacou, A. Ouattara, C. Assi, E. Allah-Kouadio, S. B. Gohean, M. Diakité, S. Koné, D. Soro, S. A. Eloumou, B. M. Camara. (2013) Impact positif d’un film éducatif sur la connaissance de l’hépatite virale B par les élèves à Agnibilékro en Côte d’Ivoire. Journal Africain d'Hépato-Gastroentérologie 7:1, 22-26
3
J. Levitsky, K. Doucette, . (2013) Viral Hepatitis in Solid Organ Transplantation. American Journal of Transplantation 13:s4, 147-168
4
H. Jiang, J. Wang, W. Zhao. (2013) Lamivudine versus telbivudine in the treatment of chronic hepatitis B: a systematic review and meta-analysis. European Journal of Clinical Microbiology & Infectious Diseases 32:1, 11-18
5
Nada Kanaan, Benoit Kabamba, Céline Maréchal, Yves Pirson, Claire Beguin, Eric Goffin, Ziad Hassoun. (2012) Significant rate of hepatitis B reactivation following kidney transplantation in patients with resolved infection. Journal of Clinical Virology 55:3, 233-238
6
Ke Ma, Wei Guo, Meifang Han, Guang Chen, Tao Chen, Zenguang Wu, Daofeng Yang, Jiaquan Huang, Yuancheng Huang, Xiping Zhao, Deying Tian, Jianxin Song, Junying Qi, Qin Ning. (2012) Entecavir treatment prevents disease progression in hepatitis B virus-related acute-on-chronic liver failure: establishment of a novel logistical regression model. Hepatology International 6:4, 735-743
7
Edmund J. Bini, Steven Kritz, Lawrence S. Brown, Jim Robinson, Donald Calsyn, Don Alderson, Kathlene Tracy, Patrick McAuliffe, Cheryl Smith, John Rotrosen. (2012) Hepatitis B virus and hepatitis C virus services offered by substance abuse treatment programs in the United States. Journal of Substance Abuse Treatment 42:4, 438-445
8
Mostafa Ragheb, Abeer Elkady, Yasuhito Tanaka, Shuko Murakami, Fadia M. Attia, Adel A. Hassan, Mohamed F. Hassan, Mahmoud M. Shedid, Hassan B. Abdel Reheem, Anis Khan, Masashi Mizokami. (2012) Multiple intra-familial transmission patterns of hepatitis B virus genotype D in north-eastern Egypt. Journal of Medical Virology 84:4, 587-595
9
Wei-Ling Wang, Zhi-Jun Shu, Li-Xia Zhou, Yan-Rong Zhao. (2012) Clinical characteristics of hepatitis B virus infection in middle school students born after the universal infant vaccination program in Shanghai, China. Archives of Virology
10
Vaccine-Preventable Diseases. In: Immunology for Pharmacy. Elsevier, 2012:197-213.
11
Patrick Duff. . 2012:238.
12
Shih-Yi Lin, Jiung-Hsiun Liu, Shu-Ming Wang, I-Kuan Wang, Chen-An Tsai, Yao-lung Liu, Hsin-Hung Lin, Chiz-Chung Chang, Chiu-Ching Huang. (2012) Association of response to hepatitis B vaccination and survival in dialysis patients. BMC Nephrology 13:1, 97
13
Hui-Hui Tan, Paul Martin. (2011) Care of the Liver Transplant Candidate. Clinics in Liver Disease 15:4, 779-806
14
Robert M. Jacobson, Inna G. Ovsyannikova, Robert A. Vierkant, V. Shane Pankratz, Gregory A. Poland. (2011) Human leukocyte antigen associations with humoral and cellular immunity following a second dose of measles-containing vaccine: Persistence, dampening, and extinction of associations found after a first dose. Vaccine 29:45, 7982-7991
15
Usa Thisyakorn, May Montellano, Andrew Lane. (2011) Routine Newborn Hepatitis B Immunization. Infectious Diseases in Clinical Practice 19:5, 326-331
16
L. P. SHEN, Y. ZHANG, F. WANG, S. ZHANG, J. Y. YANG, K. X. FANG, T. YU, X. Y. WANG, W. Y. ZHANG, S. L. BI. (2011) Epidemiological changes in hepatitis B prevalence in an entire population after 20 years of the universal HBV vaccination programme. Epidemiology and Infection 139:08, 1159-1165
17
James Neuberger. (2011) The management of patients awaiting liver transplantation. Indian Journal of Transplantation 5:2, 66-71
18
Stephen E Congly, Kelly W Burak, Carla S Coffin. (2011) Hepatitis B immunoglobulin for prevention of hepatitis B virus infection and recurrence after liver transplantation. Expert Review of Clinical Immunology 7:4, 429-436
19
C. Assi, E. Allah-Kouadio, A. Ouattara, M. Diakité, S. Koné, M. J. Lohoues-Kouacou, B. M. Camara. (2011) Couverture vaccinale contre l’hépatite virale B et prévalence de l’antigène HBs dans une profession à risque: étude transversale portant sur 244 sapeurs-pompiers de la ville d’Abidjan. Journal Africain d'Hépato-Gastroentérologie 5:2, 115-118
20
C. Assi, A. Ouattara, E. Allah Kouadio, M. Diakite, S. Koné, M.J. Lohoues Kouacou, B.M. Camara. (2011) Vaccination coverage against hepatitis B and prevalence of HBsAg: A cross-sectional study involving 592 persons attending public screening in Abidjan. Clinics and Research in Hepatology and Gastroenterology 35:6-7, 506-507
21
Shu-Shan Zhao, Lan-Hua Tang, Xia-Hong Dai, Wei Wang, Rong-Rong Zhou, Li-Zhang Chen, Xue-Gong Fan. (2011) Comparison of the efficacy of tenofovir and adefovir in the treatment of chronic hepatitis B: A Systematic Review. Virology Journal 8:1, 111
22
David T Arnold, Louise M Bentham, Ruth P Jacob, Richard J Lilford, Alan J Girling. (2011) Should patients with abnormal liver function tests in primary care be tested for chronic viral hepatitis: cost minimisation analysis based on a comprehensively tested cohort. BMC Family Practice 12:1, 9
23
Xuejun Chen, Yuefang Shen, Wenqing Xiang. (2011) Distribution Characteristics of Hepatitis B Serological Markers in Hospitalized Children and Adolescents in Zhejiang, China between 2006 and 2010. Gut and Liver 5:2, 210
24
Michael Costello, Linda M. Sabatini, Margaret Yungbluth. Viral Infections. In: Henry's Clinical Diagnosis and Management by Laboratory Methods. Elsevier, 2011:1037-1064.
25
Lei Wang, Hua Liu, Xiaoxiao Ning, Feng Gao. (2010) Sequence analysis of the S gene region in HBV DNA from patients positive for both HBsAg and HBsAb tests. Hepatology Research 40:12, 1212-1218
26
John W. Ayers, Hee-Soon Juon, Sunmin Lee, Eunmi Park. (2010) Hepatitis B Vaccination Prevalence and its Predictors Among Asian, Pacific Islander, Native American, and Multiracial Adults in the National Health and Nutrition Examination Survey. Journal of Immigrant and Minority Health 12:6, 847-852
27
Yao-Li Cui, Fang Yan, Yue-Bin Wang, Xue-Qin Song, Li Liu, Xue-Zhong Lei, Ming-Hua Zheng, Hong Tang, Ping Feng. (2010) Nucleoside Analogue Can Improve the Long-Term Prognosis of Patients with Hepatitis B Virus Infection-Associated Acute on Chronic Liver Failure. Digestive Diseases and Sciences 55:8, 2373-2380
28
K. M. Chow, S. H. K. Lo, C. C. Szeto, S. K. Yuen, K. S. Wong, B. C. H. Kwan, C. B. Leung, P. K.-T. Li. (2010) Extra-high-dose hepatitis B vaccination does not confer longer serological protection in peritoneal dialysis patients: a randomized controlled trial. Nephrology Dialysis Transplantation 25:7, 2303-2309
29
Patrick Duff. Acute and Chronic Hepatitis. In: Protocols for High-Risk Pregnancies. Wiley-Blackwell, 2010:243-249.
30
Khalid Mumtaz, Sarah Haroon Khan, Owais Iqbal Bhatti, Saeed Hamid, Wasim Jafri, Khalid Mumtaz. Interferon alpha for chronic hepatitis B. In: Cochrane Database of Systematic Reviews. John Wiley & Sons, Ltd, 2010.
31
T. Han, H. Liu, Z.L. Yu, J. Li, L. Wang, S.X. Xiao, Y. Li, M.L. Yu. (2010) Serum peptide profiles during progression of chronic hepatitis B virus infection to liver failure. Journal of Viral Hepatitis 17, 18-23
32
J. Levitsky, K. Doucette, . (2009) Viral Hepatitis in Solid Organ Transplant Recipients. American Journal of Transplantation 9, S116-S130
33
Ka-Kit Li, James Neuberger. (2009) The management of patients awaiting liver transplantation. Nature Reviews Gastroenterology & Hepatology 6:11, 648-659
34
Vladimir Gilca, Gaston De Serres, Nicole Boulianne, Philippe De Wals, Donald Murphy, Gisele Trudeau, Richard Massé, Bernard Duval. (2009) Antibody kinetics among 8–10 years old respondents to hepatitis B vaccination in a low endemic country and the effect of a booster dose given 5 or 10 years later. Vaccine 27:43, 6048-6053
35
Erik H C J Buster, Hajo J Flink, Halis Simsek, E Jenny Heathcote, Sachithanandan Sharmila, George E Kitis, Guido Gerken, Maria Buti, Richard A de Vries, Elke Verhey, Bettina E Hansen, Harry L A Janssen. (2009) Early HBeAg Loss During Peginterferon α-2b Therapy Predicts HBsAg Loss: Results of a Long-Term Follow-Up Study in Chronic Hepatitis B Patients. The American Journal of Gastroenterology 104:10, 2449-2457
36
Ji Sun Jang, Hyoung Su Kim, Ha Jung Kim, Woon Geon Shin, Kyung Ho Kim, Jin Heon Lee, Hak Yang Kim, Dong Joon Kim, Myung Seok Lee, Choong Kee Park, Byung-Hoon Jeong, Yong-Sun Kim, Myoung Kuk Jang. (2009) Association of concurrent hepatitis B surface antigen and antibody to hepatitis B surface antigen with hepatocellular carcinoma in chronic hepatitis B virus infection. Journal of Medical Virology 81:9, 1531-1538
37
Tomás de Artaza Varasa, Juan José Sánchez Ruano, Almudena García Vela, Rafael Gómez Rodríguez, Marta Romero Gutiérrez, Gema de la Cruz Pérez, Ana Zaida Gómez Moreno, José María Carrobles Jiménez. (2009) Eficacia y seguridad de la vacunación para la hepatitis A y la hepatitis B en pacientes con hepatopatía crónica. Gastroenterología y Hepatología 32:7, 483-488
38
L. Bracciale, M. Fabbiani, A. Sansoni, L. Luzzi, L. Bernini, G. Zanelli. (2009) Impact of Hepatitis B Vaccination in Children Born to HBsAg-Positive Mothers: a 20-year Retrospective Study. Infection 37:4, 340-343
39
Oidda Museru, Carlos Franco-Paredes. (2009) Epidemiology and clinical outcomes of hepatitis B virus infection among refugees seen at a U.S. travel medicine clinic: 2005–2008. Travel Medicine and Infectious Disease 7:3, 171-174
40
Omphile E. Simani, Geert Leroux-Roels, Guido François, Rosemary J. Burnett, André Meheus, M. Jeffrey Mphahlele. (2009) Reduced detection and levels of protective antibodies to hepatitis B vaccine in under 2-year-old HIV positive South African children at a paediatric outpatient clinic. Vaccine 27:1, 146-151
41
Patrick Duff, Richard L. Sweet, Rodney K. Edwards. Maternal and Fetal Infections. In: Creasy and Resnik's Maternal-Fetal Medicine: Principles and Practice. Elsevier, 2009:739-795.
42
Jia-Horng Kao, Ding-Shinn Chen. (2008) Universal Hepatitis B Vaccination: Killing 2 Birds with 1 Stone. The American Journal of Medicine 121:12, 1029-1031
43
Sinan Akay, Zeki Karasu. (2008) Hepatitis B immune globulin and HBV-related liver transplantation. Expert Opinion on Biological Therapy 8:11, 1815-1822
44
A. Sobrero, M. Di Benedetto. (2008) Current challenges and future perspectives in the medical treatment of solid tumours. European Journal of Cancer Supplements 6:14, 91-93
45
Chris Ugwu, Prathibha Varkey, Stephanie Bagniewski, Timothy Lesnick. (2008) Sero-epidemiology of Hepatitis B Among New Refugees to Minnesota. Journal of Immigrant and Minority Health 10:5, 469-474
46
Daniel Ekra, Karl-Heinz Herbinger, Seydou Konate, Annie Leblond, Catherine Fretz, Vannina Cilote, Caroline Douai, Alfred Da Silva, Bradford D. Gessner, Pierre Chauvin. (2008) A non-randomized vaccine effectiveness trial of accelerated infant hepatitis B immunization schedules with a first dose at birth or age 6 weeks in Côte d’Ivoire. Vaccine 26:22, 2753-2761
47
E Tharavichitkul, S Thongprasert, S Tongsawat. Viral agents: hepatitis B and hepatocellular carcinoma. Informa Healthcare, 2008:53-60.
48
Dildora Avazova, Fuat Kurbanov, Yasuhito Tanaka, Masaya Sugiyama, Ivan Radchenko, Dilmurod Ruziev, Erkin Musabaev, Masashi Mizokami. (2008) Hepatitis B virus transmission pattern and vaccination efficiency in Uzbekistan. Journal of Medical Virology 80:2, 217-224
49
Maya Gambarin-Gelwan. (2007) Hepatitis B in Pregnancy. Clinics in Liver Disease 11:4, 945-963
50
Philippe Colson, Patrick Borentain, Anne Motte, Mireille Henry, Valérie Moal, Danielle Botta-Fridlund, Catherine Tamalet, René Gérolami. (2007) Clinical and virological significance of the co-existence of HBsAg and anti-HBs antibodies in hepatitis B chronic carriers. Virology 367:1, 30-40
51
Seung-Wook Chi, Do-Hyoung Kim, Si-Hyung Lee, Iksoo Chang, Kyou-Hoon Han. (2007) Pre-structured motifs in the natively unstructured preS1 surface antigen of hepatitis B virus. Protein Science 16:10, 2108-2117
52
Stefan Baral, Susan G Sherman, Peggy Millson, Chris Beyrer. (2007) Vaccine immunogenicity in injecting drug users: a systematic review. The Lancet Infectious Diseases 7:10, 667-674
53
Wei Zhang, Xuzhao Zhang, C. Tian, Tao Wang, Phuong Thi Nguyen Sarkis, Yongmin Fang, Shu Zheng, Xiao-Fang Yu, Rongzhen Xu. (2007) Cytidine deaminase APOBEC3B interacts with heterogeneous nuclear ribonucleoprotein K and suppresses hepatitis B virus expression. Cellular Microbiology 0:0, 070801234236001-???
54
Frank Tacke, Samad Amini-Bavil-Olyaee, Albert Heim, Tom Luedde, Michael P. Manns, Christian Trautwein. (2007) Acute hepatitis B virus infection by genotype F despite successful vaccination in an immune-competent German patient. Journal of Clinical Virology 38:4, 353-357
55
Yen–Hsuan Ni, Li–Min Huang, Mei–Hwei Chang, Chung–Jen Yen, Chun–Yi Lu, San–Lin You, Jia–Horng Kao, Yu–Chen Lin, Huey–Ling Chen, Hong–Yuan Hsu, Ding–Shinn Chen. (2007) Two Decades of Universal Hepatitis B Vaccination in Taiwan: Impact and Implication for Future Strategies. Gastroenterology 132:4, 1287-1293
56
Khalid Mumtaz, Saeed Hamid, Wasim Jafri, Khalid Mumtaz. Pegylated interferon for chronic hepatitis B. In: Cochrane Database of Systematic Reviews. John Wiley & Sons, Ltd, 2007.
57
Robyn R. M. Gershon, Martin Sherman, Clifford Mitchell, David Vlahov, Melissa J. Erwin, Mary Kathleen Lears, Sarah Felknor, Rebecca A. Lubelczyk, Miriam J. Alter. (2007) Prevalence and Risk Factors for Bloodborne Exposure and Infection in Correctional Healthcare Workers • . Infection Control and Hospital Epidemiology 28:1, 24-30
58
Vinod K Rustgi, Raymond S Koff. (2007) Future therapy for hepatitis B. Future Virology 2:1, 79-90
59
Miguel Bruguera. (2006) Prevención de las hepatitis virales. Enfermedades Infecciosas y Microbiología Clínica 24:10, 649-656
60
Anne Motte, Philippe Colson, Catherine Tamalet. (2006) Evaluation of the clinical performance of the Beckman Coulter Access® AbHBsII immunoassay for the detection of hepatitis B surface antibodies. Journal of Clinical Virology 37:3, 213-217
61
J. Yuan, J. Lin, A. Xu, H. Li, B. Hu, J. Chen, J. Yao, H. Dong, M. Jiang. (2006) Antepartum immunoprophylaxis of three doses of hepatitis B immunoglobulin is not effective: a single-centre randomized study. Journal of Viral Hepatitis 13:9, 597-604
62
Ian R Schreibman, Eugene R Schiff. (2006) Entecavir: a new treatment for chronic hepatitis B infection. Future Virology 1:5, 541-552
63
Mar??a A. Pando, Christian T. Bautista, Sergio Maulen, Ricardo Duranti, Ruben Marone, Jorge Rey, Moira Vignoles, Maria E. Eirin, Mirna M. Biglione, Gloria Griemberg, Silvia M. Montano, Jean K. Carr, Jos?? L. Sanchez, Mar??a M. ??vila. (2006) Epidemiology of Human Immunodeficiency Virus, Viral Hepatitis (B and C), Treponema pallidum, and Human T-Cell Lymphotropic I/II Virus Among Men Who Have Sex With Men in Buenos Aires, Argentina. Sexually Transmitted Diseases 33:5, 307-313
64
Andrew SH Lai, Kar Neng Lai. (2006) Viral nephropathy. Nature Clinical Practice Nephrology 2:5, 254-262
65
S. James Matthews. (2006) Entecavir for the treatment of chronic hepatitis B virus infection. Clinical Therapeutics 28:2, 184-203
66
Jia-Horng Kao, Ding-Shinn Chen. (2006) HBV genotypes: Epidemiology and implications regarding natural history. Current Hepatitis Reports 5:1, 5-13
67
J BARKIN. (2006) Prevention of Hepatitis B With the Hepatitis B VaccinePoland GA, Jacobson RM (Mayo Clinic, Rochester, Minn) N Engl J Med 351:2832–2838, 2004§. Yearbook of Medicine 2006, 438-440
68
Young Won An, Eun Hee Chung, Insoo Rheem. (2006) A study of the current(2003-2005) prevalence of anti-HBs and immunologic memory of hepatitis B vaccine in children from the central area of Korea. Korean Journal of Pediatrics 49:6, 630
69
Kai Ming Chow, Man Ching Law, Chi Bon Leung, Cheuk Chun Szeto, Philip Kam-Tao Li. (2006) Antibody Response to Hepatitis B Vaccine in End-Stage Renal Disease Patients. Nephron Clinical Practice 103:3, c89-c93
70
References. In: McAlpine's Multiple Sclerosis. Elsevier, 2006:811-946.
71
Gregory A. Poland. (2005) Evaluating existing recommendations for hepatitis A and B vaccination. The American Journal of Medicine 118:10, 16-20
72
Jay S. Keystone. (2005) Travel-related hepatitis B: risk factors and prevention using an accelerated vaccination schedule. The American Journal of Medicine 118:10, 63-68
73
Peter Stärkel, Michel Stoffel, Jan Lerut, Yves Horsmans. (2005) Response to an experimental HBV vaccine permits withdrawal of HBIg prophylaxis in fulminant and selected chronic HBV-infected liver graft recipients. Liver Transplantation 11:10, 1228-1234
74
Jeffrey C. Laurence. (2005) Hepatitis A and B immunizations of individuals infected with human immunodeficiency virus. The American Journal of Medicine 118:10, 75-83
75
Maria H. Sjogren. (2005) Prevention of hepatitis B in nonresponders to initial hepatitis B virus vaccination. The American Journal of Medicine 118:10, 34-39
76
A. Y. HUI, H. L.-Y. CHAN, A. Y.-K. CHEUNG, G. COOKSLEY, J. J.-Y. SUNG. (2005) Systematic review: treatment of chronic hepatitis B virus infection by pegylated interferon. Alimentary Pharmacology and Therapeutics 22:6, 519-528
77
Amanda C. Cohn, Karen R. Broder, Larry K. Pickering. (2005) Immunizations in the United States: A Rite of Passage. Pediatric Clinics of North America 52:3, 669-693
78
Meenakshi Rao, Shanthini Sockanathan. (2005) Molecular mechanisms of RNAi: Implications for development and disease. Birth Defects Research Part C: Embryo Today: Reviews 75:1, 28-42
79
J. J. Goedert. (2005) Preventing Infection-Associated Cancer: From Bench to Hillside. JNCI Journal of the National Cancer Institute 97:4, 245-246
