Guideline of Hepatitis B Vaccination
2. Epidemilogy of HBV
3. Risk groups and risk factors for HBV infection
4. Diagnosis and differential diagnosis
5. HBV vaccines and vaccination
6. HBV treatment
Hepatitis B is a viral diseases process caused by the Hepatitis B Virus (HBV). The virus is endemic worldwide. The virus is shed in all body fluids by individuals with acute or Chronic infection and by asymptomatic carriers, and is transmitted primarily by parenteral route such as blood transfusion or sharing needless. Oral transmission has a low efficiency. Sexual contact is a frequent cause. Healthcare workers are a high-risk group because of the risk of needlestick injury.
2. Epidemiology of Hepatitis B
Approximately 30% of the world’s population or about 2 billion people. have serological evidence of hepatitis B virus infection.
Of these, an estimated 400 million have chronic HBV infection and at least one million carriers die from liver cirrhosis and liver cancer each year.
The prevalence and incidence of HBV varies greatly in different areas of the world. The HBV virus is endemic worldwide with the areas of highest endemicity being China, Southeast Asia, sub-Saharan Africa, most Pacific Islands and the Amazon basin. In South America HBV is mstly not endemic. It is rare in children and more frequent in High Risk Groups.
In the developed world it is an illness affecting mostly high-risk adults, in the world’s poorer areas it is highly endemic and widely present in children. Any vaccination programmes in those areas therefore are best focused on immunization in infants and children whereas in the Western world it is better to focus vaccination on adults in high risk groups such as healthcare workers.
HBV infection leads to one of four outcomes :
a) Fulminant hepatitis
b) Recovery after acute infection
c) Chronic carrier state
d) Chronic Hepatitis B
The extent to which the outcome of HBV infections depends on immunological factors or on virus characteristics is uncertain. The age at which the infetion occurs plays a very important role. In infants under 1 yrs old, chronic infection will develop in 80-90% of cases, in children between 1-5 year 30-50% will go on to develop chornic infection. By comparison, 30-50% of adults who become infected HBV are symptomatic but only 2-6% of these adults develop chronic infection.
3. Risk groups and risk factors for HBV infection.
Adult Risk groups for HBV infection
Asylum seekers and refugees
Injecting drug users
HBV tansmission routes :
HBV is transmitted through body fluids such as blood, semen, urine (Breast milk is controversial). The route can be :
Perinatal (From mother to baby at birth)
n From child to child
n From unsafe injections and transfusions.
n Unsterile instruments tatooneedles, dental equipments, other sharp objects.
n Sexual contact
n Unprotected sex (whether heterosexual or homosexual)
n Antibody of HBeAg (anti-HBe) indicating low infectivity and probably recovery
HBV is transmitted through either skin puncture or mucosal with blood or other infectious body fluids. The virus is found in highes concentrations in blood ans serous exudates.
Safe activities would include
Swimming in a pool
There is no evidence of a possible link between HBV vaccination and multiple Sclerosis.
4. Diagnosis and differential diagnosis :
The Most common symptom of hepatitis infection is fatigue or tiredness. Fever, muscle and joint aches as well as nausea may also eccur. Some people will notice that their urine becomes darker and their skin will show a yellowish tint (Jaundice).
Fatigue and tiredness
Muscle & Joint aches
Diacomfort in the abdomen on the right sise
Less common symptoms
HBV is one of 6 viruses know to cause hepatitis in humans and the acute clinical illness caused by there viruses maybe similar, Specific diagnostic tests are required therefore to determine the cause in each case. Differential diagnosis include CMV, EB virus and Herpes virus.
Serological tests are available commercially for a veriety of antigens and antibodies associated with HBV infection. HBeAG negative mutants are important subset of patients.
For antigens :
Hepatitis B Surface (HBsAg) for the presnse of the vireus.
Hepatitis B e antigen (HBeAg) correlates with viral replication and infectivity
For antibodies :
Antibody to HBsAg (anti-HBs)
Antibody to hepatitis B core antigen (anti-HBc) these antibodies to the core can be either IgM (acute) or IgG (chronic)
Other markers would be:
HBV DNA= indicates virus presence
DNA polymerase= determines the presence of HBV DNA
HBsAg in liver cells= Orcein stain=Shakata= HBsAg inside hepatocytes
Serological markers of HBV infection very depending on whether the infection is acute or chronic.
A diagnosis of acute HBV infection can be made on the basis of the detection of IgM class antibody to hepatitis B core antigen (IgM anti HBc) in serum; IgM anti HBc is generally detectable at the time of clinical onset and declines to subdetectable levels within 6 months. IgG anti-Hbc persists indefinitely as one progress to chronic infection. Anti HBs becomes detectable in patients who do not progress to chronic infection. The presence of anti-HBs after actute infection generally indicates recovery and immunity from reinfection.
In patients with chronic HBV infection, both HBsAg and IgG anti-HBc remain persistently detectable, generally for life. In addition, a negative test for IgM anti HBc together with a positive test for HBsAg in a serum specimen usually indicates that an individual has chronic HBV infection.
5. HBV vaccines and vaccination :
Since the discovery of HBV 25 years ago vaccination continues to be the best way for dealing with the condition, Hepatitis B is preventive and universal vaccination is probably best.
Two types of Hepatitis B vaccine are available :
Recombinant to genetically engineered vaccines are made using HBsAg. synthesized in yeast (Saccharomyces cervisiase) or in a mammalian cells into which the HBsAg gene has been inserted. Both consist of a suspension of HB sufrace antigen. Each country has different preparations.
Human plasma-Dervided Vaccines (PDV) are prepared from purified HBsAg from the plasma of persons with chronic HBV infection. There are more than 15 different PDVs licensed worldwide (not being used in India).
There are no significant differences in safety, immunogenicity or efficacy between these two types of vaccines.
HBV vaccines will generate protective (>10 IU/ML) Levels of antibodies to HBsAg in 95% of children and 90% of adults. Re-vaccination works in 30-50% of persons who did not respond to primary vaccination. Revaccination of non-responders is not recommended after two series of vaccination (6 doses).
A distinction can be made between Pre-Exposure and post-Exposure Vaccination.
Pre-Exposure Vaccination: In a country like India all children upto 10 years of age should be the target group.
However vaccination can be made at any age, High risk groups like Health Care providers, Family member of positive case, frequently blood transfusion receivers shall be vaccinated at the earliest Recombinant vaccine: (Any recombinant vaccine can be interchanged).
Child<10yr>10 yr 20 ug (1 Ml)
Adult 20 ug (1 ml)
Immunosuppressed person 40 ug (2 ml)
Dialysis person 40 ug (2 ml)
Post-exposure Vaccination :
A combination of Hepatitis B immunoglobulin (HBlG–‘‘Hepabig’’) vaccine is recommended.This is of especial relevance in neonates where an immediate start of post exposure immunisation will prevent neonatal infections of HBV infected mothers, It is important to vaccinate within 24 hours. There is no evidence of a protective effect if the vaccine is given after 7 days (0.5 mg)
Direct exposure (Percutaneous inoculation or transmucosal exposure) to HBsAg positive body fluid (eg Needle Stick Injury) :
HBlG single intramuscular dose of 0.06 mg/kg (as soon as possible).
Followed by complete course of HBV vaccination (within 7 days)
Direct Exposure following sexual contact with a patient with HBV
HBlg single intramuscular dose of 0.06 mg/kg (within 14 days)
Followed by complete course of HBV vaccination
Contraindications & Sideeffects :
There are very few contraindications
i) Servere allergic reaction to previous doses
ii) Severe allergic reaction to baker’s yeast (as used in making bread), plasma derived HBV vaccine can be used instead.
The following are not contraindications to administering HBV vaccine :
i) Any minor illness such as respiratory tract infection or diarrhea with a temperature below 38.50C,
ii) Allergy or asthma,
iii) Treatment with antibiotics,
iv) HIV Infection, more informatin is, however, needed on the efficacy of HBV vaccination in neonates or infants that are infected with HIV.
vi) History of seizures.
vii) Chronic illnesses
viii) Stable neurological conditions
ix) Prematurity or low birthweiht
x) History of jaundice at birth
Vaccination dosage Schedule :
Vaccination in infants, adolescents and adults involves a multistep process with the first two injections given one month apart and the 3rd one 6 months leter. (O - I - 6 months).
Drop out: It is to be emphasize that the person receives vaccines in time, however, in case of any delay for second dose it is to be observed that a gap of 4 months is maintained between 2nd and 3rd dose. and in case of 3rd does delay of one month may be allowed. It means a delay of one month can be allowed in either case. In case of further delay re-scheduling of three doses is to be done.
Immunogenecity is 95% in immuocompetent adults but can be reduced be age. It is 85% in those over 40 yrs and 75% in theose over 60 yrs of age. Vaccination in immunosuppressed patients is less effective.
For example in patients with:
n Steriod use
n Chronic renal disease
Vaccination Route & Site
Infants: intramuscular injection in the anterolateral aspect of the thigh
Older children : intramusccular injection in the deltoid muscle.
Adults : intramusccular injection in the deltoid muscle.
Injection equipment :
0.5 ml, 1.0 or > 2.0 ml syringe
25 mm, 22 or 23 guage needle
Vaccine Safefy & quality
HBV vaccines should never be frozen. The frezing point of HBV vaccine is 0.50C
HBV vaccine is stable for at least 4 years if stored between 2-80C
HBV vaccines are relatively heat stable and have only a small loss of potency when stored for 2-6 months at a temperature of 370C
The Shake Test
It you see HBV vaccine Frozen then it is damaged. However, a vaccine may also have been frozen earlier and then thawed again. The Shake test can be used to check if the vacure has been damaged by earlier freezing.
n Compare the vaccine that you suspect has been frozen and thawed with vaccine from the same manufacturer that you are sure was never frozen.
n Shake the caccine vials
n Look at the contents carefully
n Leave the vaccines to stand side by side for 15-30 minutes for any sediment to settle
n Do not use it if a sediment settles below an almont-clear liquid.
6. HBV treatment
1. Treatment of acute HBV infection
A spontaneous recovery after acute infection with HBV occurs in 99% of previous healthy adults. Antiviral therapy is not likely therefore to improve the rate of recovery and is not required.
In fulfilment hepatitis meticulous intensive care may improve surviaval. Orthrotropic liver transplantation is the only proven therapy that improves patient outcomes.
2. Treatment of chronic HBV infection
Treatment of chronic HBV infection is difficult and limited in long-term efficacy.
There are three treatment options.
a) Interferon monotherapy
b) Lamivudine or other nuceloside anologue (Adfovir, Teloiyudine, entecavir)
c) Combination therapies of interfeorn with a nucledside analogue
A decision to treat must be based on a combination of
n Serum liver tests (increased serum AST and ALT levels)
n Virologic assays (presence of HVeAg or HBV DNA levels > 105 Copies/ ml
n liver histology (disease activity; fibrosis)
n Virologic tests to exclude HCV, HDV, HIV
If the disease is inactive or mild it is best to do nothing and to monitor ALT levels.
It the disease is moderate to severe, treatment must be recommended.
Initial Approch :
If a at HSsAg positive patient comes to you he should be clinically evacuated and should be observed weather he is having any sign and symptom of chronic liver disease.
Lab Diagnosis :
HBV patient should be admited for SGOT/SGPT and HBeAg and HBV DNA (quasition test) for make-up decision wheather he should be treated on not. Once liver function tests should be performed according to the clinical preservators to the patient.
decision to Treat :
When not to treat :
If a person is HBSeAg positive but ACT (SGPT) is normal and HBeAg is nagetive he should be considerd as inactive HBV infaction (or so called carrier) and should not be treated. But he should be evaluated at 6 monthly interval for stain of ACT.
When to treat :
i) If a human is HBsAg positive, ACT > 2 tinen of uper limit of normal, HBsAg is positive and / or HBV DNA is > 105 copies / ml.
ii) If a person is HBsAg positive ACT raines, HBeAg nagetive, but HBV DNA is > 105 copies / ml and / or an liver Biopcy avidence of fibrosis is injelartive (chronic hepatitis is remain).
What drug to be used :
i) Interferon is still best mode of treatment.
ii) Alternatively, Lamivudine, Telbivudine as entacavir and newer drug can be used.
iii) Combination of both the group of drug are used in mutant cases.
iv) In HBeAg nagetive, HBV DNA positive comes, interferon is only treatment.
v) The patient who are HBsAg positive, very high ACT and HBeAg positive comes oral medicines are effective.
vi) In decampesantal liver diseases, interferon should not be used.
* Inteferon-a-therapy recommended dose :
-5 Million Units (MU) daily or 10 Mu 3 times weekly
* 6 MU/m2 3 times weekly for children, subcutaneously, for 16 weeks (up to 32 weeks may be beneficial)
* Short treatment duration
* No avtiviral resistance (but precore mutants might be induced by previous interferon treatment)
* Excellent duration and quality of response
* Side-effects (interferon treatment may be associated with flares-sometimes severe flares)
* Parentaral route less efficacy
* Decompensated liver disease
psychiatric ilness, in particular depression and sucidal tendency
authoimmune or systemic disease
severe leukopenia or thrombocytopenia
Pequlated Interferon :
New forms of interferon are being developed in which the agent is covelently bound to polythylene glycon (PEG). The interferon is slowly relaesed as these covalent bonds degrade. PEGylated forms of interferon offer some advantage in case of use. They can be administered once a week only and they better meet the need for continous circulating levels of interferon.
Lamivudine therapy :
Long-term therapy with lamivudine is recommended for patients with advanced or decompensated chronic hepatitis B. Transplanation may become necessary because of deterioration in liver function, development of resistance of apearance of Hepatocillular carcinoma (HCC).
100 mg daily/oral
150 mg twice daily in HIV infected patients (and only in combination with other antiretrovirals)
Easy to administrater and monitor
Better response in selected groups (> 30% eAg loss)
Effective in subpopulation not responsive to Interferon.
Long-term durability of response not as for interferon-alpha
Therapy often needs to be long-term (> 12 months)
Dose not produce HBsAg loss
Treatment of hepatitis B is fill developing and in future, less expensive oral therapy of shorter duration may be available.