Wang H, Ryu WS. Hepatitis B virus polymerase blocks pattern recognition receptor signaling via interaction with DDX3: implications for immune evasion. PLoS Pathog 6 7 :e Immunopathogenesis of hepatitis B virus infection. Immunol Cell Biol 85 1 — Intracellular inactivation of the hepatitis B virus by cytotoxic T lymphocytes. Immunity 4 1 — Front Immunol Temporal analysis of early immune responses in patients with acute hepatitis B virus infection.
Gastroenterology 4 — Viral load reduction improves activation and function of natural killer cells in patients with chronic hepatitis B. J Hepatol 54 2 — Hepatitis B virus-induced lipid alterations contribute to natural killer T cell-dependent protective immunity. Nat Med 18 7 —8. Natural killer T cell activation inhibits hepatitis B virus replication in vivo. J Exp Med 7 — Kupffer cells interact with hepatitis B surface antigen in vivo and in vitro, leading to proinflammatory cytokine production and natural killer cell function.
J Infect Dis 8 — Not interferon, but interleukin-6 controls early gene expression in hepatitis B virus infection. Hepatology 50 6 — Hepatitis B virus particles preferably induce Kupffer cells to produce TGF-beta1 over pro-inflammatory cytokines.
Dig Liver Dis 44 4 — PD-1 inhibits antiviral immunity at the effector phase in the liver. J Exp Med 1 — Functional impairment of myeloid and plasmacytoid dendritic cells of patients with chronic hepatitis B.
Hepatology 40 3 — Favorable effect of adefovir on the number and functionality of myeloid dendritic cells of patients with chronic HBV. Hepatology 44 4 — B7-H1 up-regulation on myeloid dendritic cells significantly suppresses T cell immune function in patients with chronic hepatitis B. J Immunol 10 — Cellular immune response to hepatitis B virus-encoded antigens in acute and chronic hepatitis B virus infection.
J Immunol 10 —9. Viral clearance without destruction of infected cells during acute HBV infection. Science —9. The size of the viral inoculum contributes to the outcome of hepatitis B virus infection. J Virol 83 19 — J Virol 77 1 — J Virol 81 8 — Hepatitis B virus-specific and global T-cell dysfunction in chronic hepatitis B. Gastroenterology 3 Bertoletti A, Gehring AJ. The immune response during hepatitis B virus infection.
J Gen Virol 87 Pt 6 — Hepatitis B vaccine: demonstration of efficacy in a controlled clinical trial in a high-risk population in the United States. N Engl J Med 15 — Dienstag JL, Hepatitis B. Virus infection. N Engl J Med 14 — Management of hepatitis B: summary of a clinical research workshop. Hepatology 45 4 — Hadziyannis SJ, Vassilopoulos D.
Hepatitis B e antigen-negative chronic hepatitis B. Hepatology 34 4 Pt 1 — A mechanism to explain the selection of the hepatitis e antigen-negative mutant during chronic hepatitis B virus infection. J Virol 83 3 — Mol Immunol 45 4 — Role of the coinhibitory receptor cytotoxic T lymphocyte antigen-4 on apoptosis-prone CD8 T cells in persistent hepatitis B virus infection. Hepatology 53 5 — PLoS Pathog 9 3 :e Hepatology 52 6 — EMBO J 6 3 — Hepatitis B and D viruses exploit sodium taurocholate co-transporting polypeptide for species-specific entry into hepatocytes.
The human hepatoma HepaRG cells: a highly differentiated model for studies of liver metabolism and toxicity of xenobiotics. Chem Biol Interact 1 — J Gen Virol 90 1 — Inducible expression of human hepatitis B virus HBV in stably transfected hepatoblastoma cells: a novel system for screening potential inhibitors of HBV replication.
Antimicrob Agents Chemother 41 8 — Primary human hepatocytes — a valuable tool for investigation of apoptosis and hepatitis B virus infection. J Hepatol 38 6 — HLA-DP polymorphisms affect the outcomes of chronic hepatitis B virus infections, possibly through interacting with viral mutations. J Virol 87 22 — Wieland SF. The chimpanzee model for hepatitis B virus infection.
Cold Spring Harb Perspect Med 5 6. The pathology of viral hepatitis types A and B in chimpanzees. A comparison. Am J Pathol 85 1 — Experimental chronic hepatitis B infection of neonatal tree shrews Tupaia belangeri chinensis : a model to study molecular causes for susceptibility and disease progression to chronic hepatitis in humans.
Virol J Efficient infection of primary tupaia hepatocytes with purified human and woolly monkey hepatitis B virus. J Virol 75 11 —9. Antiviral effects of PNA in duck hepatitis B virus infection model. Acta Pharmacol Sin 28 10 —8. The woodchuck model of hepatitis B virus infection. ILAR J 42 2 — Lack of effect of antiviral therapy in nondividing hepatocyte cultures on the closed circular DNA of woodchuck hepatitis virus. J Virol 71 12 —9. Infection and uptake of duck hepatitis B virus by duck hepatocytes maintained in the presence of dimethyl sulfoxide.
Virology 2 — Virus cccDNA amplification efficiency in natural infection is regulated by virus secretion efficiency. PLoS One 10 12 :e Just because a woman has been vaccinated does not mean she is HBsAg negative.
Since postvaccination testing is not performed for most vaccinated people, she could have been vaccinated even though she was already actively infected. I've identified a patient in my obstetrical practice who is HBsAg positive. Should she be evaluated for liver disease during her pregnancy, or should the evaluation wait until the postpartum period?
What should I recommend for her husband and her children? How urgent is the time frame? The earlier the evaluation is done, the better. Consultation with or referral to a liver disease specialist such as a hepatologist, gastroenterologist, or infectious disease specialist should be done. In addition, the patient's sex partner and children or other household contacts should be tested for HBV infection total anti-HBc and HBsAg as soon as possible.
If any are HBsAg positive, they should be referred to or have consultation with a liver disease specialist. If a mother's HBsAg test result is not available at the time of birth, how should the infant be managed? Only single antigen HepB vaccine should be used for the birth dose. For preterm infants, see the next question. Please review the hepatitis B vaccination recommendations for preterm infants who weigh less than 2, grams 4. Preterm infants weighing less than 2, grams 4. By age 1 month, medically stable preterm infants, regardless of initial birth weight or gestational age, have an immunologic response to HepB vaccination that is comparable to that of full-term infants.
The birth dose the initial HepB dose should not be counted as part of the vaccine series. The final dose should not be administered before 24 weeks of age.
Testing should not be performed before age 9 months anti-HBs resulting from use of HBIG might still be positive and therefore misleading or within 1 month of the most recent HepB dose testing for HBsAg sooner than 1 month of a vaccine dose might produce a transient HBsAg-positivity. The birth dose of vaccine should not be counted as part of the 3 doses required to complete the HepB series.
The final dose in the series should not be administered before 24 weeks of age. Complete the vaccine series per the recommended schedule.
For preterm infants weighing 2, grams or more at birth, follow the recommendations for full-term infants including a HepB dose within 24 hours of birth. What is the recommended time to do hepatitis B testing for evidence of success or failure of immunoprophylaxis given at birth to an infant born to a hepatitis B surface antigen HBsAg -positive mother?
Postvaccination testing HBsAg and hepatitis B surface antibody [anti-HBs] is now recommended 1 to 2 months after completion of at least three doses of the HepB vaccine series, but not before 9 months of age. For a child vaccinated on schedule, testing should be done at age 9 to 12 months.
Testing should not be performed before age 9 months because hepatitis B immune globulin HBIG might still be present at age 6 to 8 months, nor should testing be performed within 1 month of the most recent HepB dose because a transient false positive HBsAg might occur. Antibody to hepatitis B core anti-HBc testing of infants or children is not recommended because passively acquired maternal anti-HBc might be detected up to age 24 months in children of HBV-infected mothers.
Children who are HBsAg positive should receive medical evaluation and ongoing follow-up. For additional information, see www. How should I manage an infant of an HBsAg-positive mother who tests negative for anti-HBs after 3 properly spaced doses of vaccine? What should I do if an infant tests negative for anti-HBs after 2 complete vaccine series? HBsAg-positive infants should be referred for appropriate follow-up with a physician who specializes in evaluating infants with liver disease.
Is it safe for an HBsAg-positive mother to breastfeed her infant? An HBsAg-positive mother who wishes to breastfeed should be encouraged to do so, including immediately following delivery. Although HBsAg can be detected in breast milk, studies done before HepB was available showed that breastfed infants born to HBsAg-positive mothers did not demonstrate an increased rate of perinatal or early childhood HBV infection.
More recent studies have shown that, among infants receiving post-exposure prophylaxis to prevent perinatal HBV infection, there is no increased risk of infection among breastfed infants. Can Pediarix be given at birth? Pediarix should not be given before age 6 weeks of age because it can result in suppression of the immune response to the acellular pertussis component. If I want to use Pediarix is it acceptable to give a 4-dose schedule of hepatitis B vaccine to infants?
The use of a 4-dose HepB schedule is acceptable when giving the monovalent HepB vaccine birth dose followed by the use of Pediarix. The use of a 4-dose HepB schedule, including schedules with a birth dose, has not increased vaccine reactogenicity and results in higher final antibody titers that should correlate with longer duration of detectable antibody. You may still use monovalent HepB in a 3-dose series. We are receiving conflicting information about whether their HepB vaccine dose 4 is a valid final dose because of the shortened interval between dose 3 and 4.
Our electronic health record says dose 4 is valid regardless of the short interval from dose 3 but the health department says it is not.
Which is correct? According to subject matter experts at CDC, your electronic health record is correct. The CDC website states that HepB dose 4, if given, must be at 24 weeks of age or later, at least 16 weeks from dose 1, and at least 8 weeks from dose 2.
There is no minimum interval requirement between dose 4 and the previous dose. An infant was vaccinated with monovalent HepB at birth. Later we gave her monovalent HepB at age 1 month and age 4 months. Did we give her the third dose too early? Poorer immune response rates are seen in infants who complete the vaccination series prior to age 6 months. Do not count dose 3, which you gave at age 4 months. Repeat dose 3 when the infant is at least 6 months of age no earlier than age 24 weeks.
If an infant got a dose of the adult formulation of HepB in error, should the dose be counted? When should the next dose be scheduled for this infant? Do we need to be concerned about a possible adverse event? If an infant received an adult dose of HepB contains twice the antigen in a dose of the pediatric formulation , the dose can be counted as valid and does not need to be repeated.
Hepatitis B vaccines are very safe vaccine and no unusual adverse events would be expected because of this administration error. The next age appropriate dose should be given on the usual schedule. The recommended age for the last dose of HepB in an infant is 6 months. What is the earliest age the last dose can be given to an infant? The minimum age for the last dose of HepB is age 24 weeks the minimum age is the youngest age that is acceptable for giving a vaccine and having it "count" as a valid dose.
This allows healthcare providers more flexibility in administering HepB should a parent bring an infant in for a well-baby check before the infant reaches a full 6 months of age. If the third dose is given prior to age 24 weeks the dose should not be counted. Poorer response rates are seen in infants who complete the vaccination series prior to age 24 weeks. The third dose should be repeated when the infant is at least age 24 weeks.
For Children and Teens Back to top Should all children age 0 through 18 years be vaccinated against hepatitis B? CDC recommends that all children age 0 through 18 years be fully vaccinated against hepatitis B.
Vaccination should be initiated for children and teenagers not previously vaccinated and vaccination completed for all those whose vaccine series is incomplete. All children and adolescents younger than age 19 years including internationally adopted children who were born in Asia, the Pacific Islands, Africa, or other intermediate or high-endemic countries or who have at least one parent who was born in a high-endemic area should be tested for HBsAg and should complete the vaccine series if they were not previously vaccinated or were incompletely vaccinated.
Can adolescents be immunized on a 0-, 2-, 4-month schedule for hepatitis B? There are data that show adequate seroprotection using this schedule in young adults. If this schedule is used, you should be aware that the studies were in young adults and might not translate to older adults age 40 years or older. There are other schedules that offer flexibility in vaccination as well.
View www. Three years ago at a middle school, my patient received the first dose of the HepB series. Should I give her the second dose now or do I need to start over again with the first dose? There is no need to restart the series. Give the second dose of HepB now and be sure there are at least 8 weeks between that dose and the third dose. Increasing the interval between the first two doses has little effect on immunogenicity or final antibody concentration. The third dose confers the maximum level of seroprotection but acts primarily as a booster and appears to provide optimal long-term protection.
Longer intervals between the last two doses result in higher final antibody levels but might increase the risk for acquisition of HBV infection among people who have a delayed response to vaccination. No differences in immunogenicity have been observed when one or two doses of hepatitis B vaccine produced by one manufacturer are followed by doses from a different manufacturer.
Describe the 2-dose regimen for hepatitis B vaccine for certain young adolescents. For the 2-dose adolescent schedule, the adult dose of Recombivax HB 1. As with other HepB vaccination schedules, if administration of the 2-dose schedule is interrupted, it is not necessary to restart the series.
Children and adolescents who have begun vaccination with a pediatric 0. If it is not clear which dose an adolescent was administered at the start of a series, the series should be completed with the 3-dose schedule. Heplisav-B, the 2-dose HepB vaccine given with a 4-week interval between doses, is licensed only for adolescents and adults beginning at age 18 years. How should we complete the series if a year-old starts the 2-dose Recombivax HB adult formulation series but fails to receive dose 2 before his or her 16th birthday?
The 2-dose Recombivax HB schedule is only approved for use in children age 11 through 15 years. A year-old child would need two additional doses of pediatric HepB to complete a 3-dose series. I am confused about the volume of hepatitis B vaccine dose to give an adolescent. Is it 0. The dosage depends on the schedule and manufacturer of the vaccine that you are using. For children 11 through 15 years of age, the 2-dose Recombivax HB volume is 1. Heplisav-B, the 2-dose HepB vaccine given with a 4-week interval between 0.
IAC offers a handy resource with charts detailing the correct dosages and schedules for monovalent hepatitis B and hepatitis A vaccines and combination products that include hepatitis A and hepatitis B vaccines.
Go to www. I have some Asian and African children and teens in my practice who were born abroad. Should I test them all for hepatitis B, or just make sure they are all vaccinated?
All foreign-born people including immigrants, refugees, asylum seekers, and internationally adopted children born in Asia, the Pacific Islands, Africa, and other regions with high or intermediate endemicity of HBV infection should be tested for HBsAg, regardless of vaccination status. Initiating HepB vaccination of immigrant children should not be delayed while awaiting HBsAg test results: you may draw blood for testing then administer the first dose of vaccine at the same visit.
All people found to be HBsAg-positive should have ongoing medical management by a physician knowledgeable about hepatitis B and its complications. For Adults Back to top Which hepatitis B vaccines can be given to adult patients?
Twinrix combination HepA-HepB, 3-dose series and Heplisav-B 2-dose series are approved for adults age 18 years and older.
Engerix-B and Recombivax HB as a 1. Which adults should receive HepB vaccine? Please provide details about the ACIP recommendation for the use of hepatitis B vaccine in adult diabetic patients. The HepB series is recommended for unvaccinated adults with diabetes age 59 years and younger. Among people in this age group with no other risk factors for hepatitis B, studies have shown that adults with diabetes have twice the odds of developing acute hepatitis B compared to those without diabetes.
Among older age groups the increased risk was not as high but at the discretion of the treating clinician, the vaccine also may be administered to unvaccinated adults with diabetes age 60 years and older.
There have been a number of outbreaks of HBV infection in settings that provide assisted blood glucose monitoring for people with diabetes. Administration of either the 2-dose Heplisav-B or 3-dose Engerix-B, Recombivax HepB series should be completed as soon as feasible after diabetes is diagnosed.
No serologic testing or additional HepB vaccination is recommended for adults who received a complete series of HepB vaccinations at any time in the past. HepB vaccine may be administered during healthcare visits scheduled for other purposes, as long as minimum intervals between doses are observed.
No maximum interval between doses exists that would make the HepB vaccination series ineffective or that would require restarting the series. You can read the details of this recommendation and the rationale behind it in the December 23, issue of MMWR, available at www.
Does the recommendation to administer hepatitis B vaccine to diabetics younger than age 60 extend to women with gestational diabetes? The CDC recommendations for HepB vaccination of people with diabetes pertain to those with type-1 and type-2 diabetes.
They do not apply to women with gestational diabetes. It is worth noting that pregnancy is not a contraindication to HepB vaccination, and that women with gestational diabetes are more likely to develop type-1 or type-2 diabetes later in life. Diabetic women who become pregnant can be vaccinated, if indicated.
At what anatomic site should hepatitis B vaccine be administered to adults? What needle size should be used? The deltoid muscle is recommended for routine intramuscular IM vaccination among adults. The anterolateral thigh also can be used. The gluteus muscle should not be used as a site for administering HepB. Is post-vaccination testing needed for adults who receive hepatitis B vaccine? Serologic testing for immunity after HepB vaccination is recommended only for people whose subsequent clinical management depends on knowledge of their immune status.
Testing is not necessary after routine vaccination of adults. Post-vaccination anti-HBs testing is recommended for the following: healthcare and public safety workers at a reasonable risk of continued exposure to blood on the job; immune compromised people; and sex or needle-sharing partners of HBsAg-positive people. Testing should be performed 1 to 2 months after the last dose of vaccine. Sexually transmitted infections, including hepatitis B, can be transmitted by sexual assault.
Unless the victim has a documented history of completed HepB vaccination, a series of HepB alone 2 or 3 doses depending on brand should be administered with the first dose as soon as possible after the assault.
If a patient receives HepB vaccine while undergoing hemodialysis, will the vaccine be effective? Will the dose need to be repeated? Recommendations for immune compromised people, such as hemodialysis patients, are different than those for immune-competent people.
Hemodialysis patients who do not respond to an initial vaccine series should be revaccinated with two to four additional doses of HepB depending on the brand.
For hemodialysis patients who have responded with adequate anti-HBs postvaccination testing should be done 1 to 2 months after the vaccine series to HepB vaccination, no HBsAg testing is needed but anti-HBs should be done annually. Retesting immediately after the booster dose is not necessary. What is the maximum number of hepatitis B vaccine doses a dialysis patient can receive? There is no maximum number of HepB booster doses a dialysis patient can receive.
Serology is not recommended more frequently than once a year, so boosters wouldn't be given more than once a year. A physician ordered a mcg dose of hepatitis B vaccine for a hemodialysis patient. The clinic does not stock the Recombivax HB mcg dose dialysis formulation Merck and would like to give 2 doses of Engerix-B mcg dose GSK for each dose in the series.
If given on the same day as separate injections in separate sites, two injections of Engerix-B 20 mcg can be counted as the equivalent of one Recombivax HB mcg dose. According to the package insert, Engerix-B is licensed for use in this manner vaccine package inserts for all vaccines are available at www. Note that an all-Engerix-B or mixed-brand dialysis schedule is a 4-dose series doses at 0, 1, 2, and 6 months.
Vaccination using only Recombivax HB dialysis formulation is a 3-dose schedule doses at 0, 1, and 6 months. Vaccination of a hemodialysis patient also may be completed with Heplisav-B using the standard 0. Is this practice advisable? When using Engerix-B or Recombivax HB brands of HepB to vaccinate hemodialysis or other immunocompromised people, a higher dose is recommended, so to the extent these patients are immunocompromised, this is within ACIP recommendations note that "immunocompromised" is not defined in the recommendations.
Regardless, this practice is appropriate for several reasons, including that these patients may be starting hemodialysis soon, and because use of the higher dose is not harmful.
When using Heplisav-B, the standard 0. Can a dialysis or pre-dialysis patient receive Heplisav-B vaccine?
Use the standard dose and dosing interval 1 month. I would like more information about Twinrix, the combination hepatitis A and B vaccine. The vaccine contains EL. In the United States, Twinrix is licensed for use in people who are age 18 years or older. It can be administered to people who are at risk for both hepatitis A and hepatitis B, such as certain international travelers, people with chronic liver disease, men who have sex with men, illegal drug users, or to people who want to be immune to both diseases.
A standard Twinrix series consists of 3 doses given intramuscularly on a 0, 1, and 6 month schedule. It consists of 3 doses given within 3 weeks, followed by a booster dose at 12 months 0, 7 days, 21 to 30 days, and 12 months. The 4-dose schedule could benefit individuals needing rapid protection from hepatitis A and hepatitis B, such as some people traveling imminently. Twinrix cannot be used for post-exposure prophylaxis. It is now thought that host immune responses to viral antigens and to viral replication in infected hepatocytes are the main determinants of hepatocellular injury and HBV pathogenesis.
This review will focus on the determinants of innate immunity in controlling viral replication and their contribution to viral pathogenesis, with respect to both acute and chronic infection. In general, innate immunity is important in controlling infection immediately after contact with the pathogen, in order to limit the spread of the infection and to initiate efficient development of an adaptive immune response.
The innate immune system is activated by pathogens by using pattern-recognition receptors PRRs that recognize specific structures on pathogens, such as double-stranded RNA and bacterial wall components. Following recognition of virus associated molecular patterns by cellular PRRs, recruitment of their distinct adaptor proteins will sequentially activate signalling cascades to induce cytokine production in virus-infected cells.
Earlier studies have evaluated whether HBV has the ability to stimulate the interferon pathway of the innate immune response during the early stage of infection. Data from patients and animal models have shown that there is a delay between HBV inoculation and efficient replication. While it is tempting to speculate that this initial lag of replication is a result of efficient control of the virus by the innate immune response, animal studies have indicated that this is not the case, but rather that somehow the virus manages to evade being recognized.
In contrast to the immune response in HCV infection, where expression of a large number of IFN-regulated genes was rapidly induced in the liver of HCV-infected chimpanzees [ 16 ], the same group has shown that HBV did not cause any change in genes associated with innate immune responses during acute HBV infection of chimpanzees [ 17 ]. The authors concluded that HBV did not induce an intrahepatic innate immune response that could be detected in the infected animals because it acts like a stealth virus early in infection, remaining undetected and spreading until the onset of the adaptive immune response several weeks later.
However, the mechanisms by which HBV accomplishes this task are less understood. Interestingly, HBV replication is sensitive to the suppressive effects of interferons in studies using the transgenic mouse model or hepatoma cell lines. The importance of noncytolytic T cell functions was shown in a study where the onset of viral clearance in HBV infected chimpanzees was tightly associated with the appearance of virus-specific T cells and mRNA in the liver, before the onset of hepatocyte destruction and clinical hepatitis [ 21 ].
In a primary human hepatocyte model, Hosel et al. Taken together, these results suggest the existence of a functional innate antiviral mechanism in hepatocytes that is associated with favourable outcome in both acute and chronic infections. Its activation under certain conditions may also be used for therapeutic purposes. DCs are major players in immune responses, due to their ability to process foreign antigens and present them to effector cells.
The presence of HBV or HBsAg during cytokine induced maturation of dendritic cells resulted in a more tolerogenic phenotype, as shown by a decreased T-cell stimulatory capacity [ 29 ]. These studies indicate that the virus exerts an immune regulatory effect that may directly contribute to its persistence during chronic infection. The immuno-modulatory properties of HBV are also reinforced by studies that show changes in the T regulatory cells Tregs population in HBV chronically infected patients.
During chronic HBV infection they seem to have a deleterious effect, because they increase in number compared to acute infection or healthy controls and this increase correlates with the viral load, suggesting a direct effect on viral replication [ 32 , 33 ]. Generation of Tregs is also a mechanism by which pDCs contribute to immunological tolerance in healthy individuals [ 34 ]. This effect also contributes to the immune suppression that characterizes chronic infection, since pDCs from patients with chronic HBV infection were able to generate a higher proportion of Tregs compared to healthy controls [ 35 ].
Other evidence to support active immunosuppressive strategies employed by HBV includes its ability to affect the production of IL, a cytokine with known immunosuppressive effects.
HBcAg was able to induce significantly higher IL levels in peripheral blood mononuclear cells from patients with chronic HBV infection compared to those from healthy controls [ 38 ]. In this setting of decreased activation of cytotoxic T cells, there is a continuous stimulation of other cell types that may explain the persistence of chronic infection and subsequent liver inflammation that characterize chronic HBV infection. Their expression is increased in both the peripheral blood and liver of patients with chronic HBV infection, where they positively correlate with liver inflammatory damage [ 41 , 42 ], suggesting their active role in this process.
The lack of type 1 IFN responses in the setting of in vivo infection seems surprising, given the fact that the majority of infected individuals are able to resolve the infection.
This indicates that the viral replication may be controlled by other arms of the innate immune system. Natural killer cells NK cells are the main effector population involved in innate immune responses to viral infections.
Accumulating evidence indicates that NK cells are major determinants of the clinical outcome following HBV infection. A study performed on two seronegative blood donors who became positive for HBsAg and HBV DNA without evidence of liver pathology, indicating successful containment of infection, were monitored throughout early stages of infection. This study suggested that early and efficient induction of innate responses control the infection by non-cytolytic mechanisms rather than by hepatocyte lysis and may also contribute to timely induction of adaptive responses.
These results are in contrast to those observed the chimpanzee model [ 17 ] and may reflect differences between the two hosts. Studies on NK cell function early in natural human infection are rare because the incubation period of HBV infection is always asymptomatic and therefore difficult to study.
These effects were not observed in non-responders to the vaccine, suggesting that the two cell types play an important role in the immune response following hepatitis B vaccination by also contributing to a robust adaptive immune response [ 47 ]. The ability of NKT cells to control viral replication was also confirmed in vivo. However, activation of NK and NKT cells has also been linked to liver injury in HBV transgenic mice, due to their ability to secrete proinflammatory cytokines in the hepatic microenvironment [ 49 ].
The involvement of NK activation in liver injury was not observed in human studies. On the contrary, one study comparing NK cell function in patients with chronic HBV infection with those from chronic HCV infection and healthy controls showed a more pronounced functional defect in chronic HBV infection than in the other two groups [ 50 ]. Overall, these studies indicate that the main function of NK and NKT cells is to limit viral replication via cytokine production rather than direct cytotoxicity and that function is compromised during chronic HBV infection, which may contribute to viral persistence.
Although the exact contribution of NK and NKT cells to chronic inflammation that characterizes chronic hepatitis B is yet to be established, the current literature suggest that strong innate responses are associated with subsequent adaptive immune activation and control of viral replication in the absence of hepatocyte lysis. Inefficient activation of the innate pathways gives rise to a lower, but persistent proinflammatory activity that cannot clear the infection and has deleterious effects on the liver microenvirnment.
Recent developments in our understanding of the HBV infection have shown that the virus is not just a stealth pathogen, but that it employs active mechanisms to avoid recognition by the innate immune system.
This may explain previous observations on its apparent inability to be detected by PRRs. HBV polymerase was reported to impair antiviral innate immune responses by inhibiting IRF activation in response to TLR3- and RIG-I- induced pattern recognition receptor signalling in human hepatoma cell lines [ 53 — 55 ].
Regulatory HBx protein binds to beta interferon promoter stimulator 1 IPS-1 and targets it for inactivation. Human cell lines studies have also indicated that adaptor protein mitochondrial antiviral signalling MAVS is another target for HBx. See Drug Reference for a full list of side effects.
Drug Reference is not available in all systems. If you are exposed to HBV before you have received all three shots in the vaccination series, a dose of hepatitis B immune globulin HBIG usually will prevent infection until the vaccine takes effect.
If you have already had hepatitis B and have developed protective antibodies to the virus, you do not need the vaccine because you have lifetime protection immunity against the infection. If you are not sure whether you have had hepatitis B, you can be tested, or you can be vaccinated without testing. The vaccine is not harmful for you if you are already immune. If you have chronic HBV infection, the vaccine will be ineffective, although it is not harmful.
The vaccine is safe for women who are pregnant or breastfeeding. This information does not replace the advice of a doctor. Healthwise, Incorporated disclaims any warranty or liability for your use of this information.
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Top of the page. How It Works The hepatitis B vaccine is given to protect people from getting the infection. All babies need three doses: The time between the first and second shot should be at least 1 month. The time between the second and third shots should be at least 2 months; ideally, it should be 4 months or more.
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