Hepatitis B Immunoglobulin

In India, 1-4% of individuals are chronic carriers of Hepatitis B Virus (HBV). Infection with HBV may occur perinatally (vertical transmission), during early childhood (the so-called horizontal spread), through sexual contact or nosocomially. It should be noted that in our country horizontal route (e.g. child to child) route and the vertical route (i.e. mother to child) are the major routes of transmission of hepatitis B. The risk of infection in a child born to a Hepatitis B positive mother ranges from 10-85% depending on the mother's HBeAg status.

Younger the age of acquisition of HBV infection, higher the chances of becoming a chronic carrier. It is believed that as many as 90% of those who are infected at birth go on to become chronic carriers and up to 25% of chronic carriers will die of chronic liver disease as adults. Infection with HBV is one of the most important causes of chronic hepatitis, cirrhosis of liver and hepatocellular carcinoma. These outcomes are all preventable by early childhood immunization. It is for this reason that the World Health Organization has recommended universal Hepatitis Bvaccination.

Vaccine

The plasma derived Hep B vaccine is no longer available. The currently available vaccine containing the surface antigen of Hepatitis B is produced by recombinant technology in yeast and adjuvanted with aluminium salts and preserved with thiomersol (thiomersol free vaccines is also available, Revac-Bmcf). Hep B vaccine is available as single and multidose vials and should be stored at 2 to 8° C. The vaccine should not be frozen; frozen vaccine should be discarded. The dose in children and adolescents (aged less than 18 years) is 0.5 ml/ 10 ug and in those 18 years and older is 1 ml/20 ug. It should be injected intramuscularly in the deltoid/anterolateral thigh. Gluteal injections should be avoided due to low immuno-genicity. The vaccine is extremely safe and well tolerated. The classical schedule is 0, 1 and 6 months. The vaccine is highly immunogenic and seroconversion rates are greater than 90% after a three dose schedule. Seroconversion rates are lower in the elderly, the immunocompromised and those with chronic renal failure. Four doses at 0, 1, 2 and 12 months of double dose may be given in these patients. Routine testing for anti HBsAg levels 1 month after completion of the immunization schedule is recommended in children born to HBsAg positive mothers, health care workers and those with comorbidities. Antibody titers greater than 10 mIU/ml signify a response and are considered protective. Non responders should be tested for Hepatitis B carrier status. If found to be negative the same three dose schedule

should be repeated. 50% of non responders may respond to the second series; the rest are permanently susceptible. Routine boosters are not needed in healthy children and adults. Studies have shown that individuals who had responded to the vaccination series and had levels of 10 mIU/ml after vaccination are protected against hepatitis B disease for life even if the levels drop to below protective levels or are undetectable later. This is due to immune memory. In the immunocompromised and those with co morbidities such as chronic renal disease, levels should be checked periodically and booster vaccination given whenever levels drop to below protective levels.

Hepatitis B Immunoglobulin (HBIG)

HBIG provides passive immunity and is indicated along with Hep B vaccine in management of perinatal/occupational/sexual exposures to Hepatitis B in susceptible individuals. The dose of HBIG in adults is 0.06 ml/kg and in neonates/infants 0.5 ml. HBIG should be stored at 2 to 8° C and should not be frozen. HBIG provides temporary protection lasting 3-6 months. HBIG should never be given intravenously. HBIG is also used alone following exposure to Hepatitis B in patients who are non responders to Hepatitis B vaccination (genetic reasons/ immunocompromised status). In this situation two doses of HBIG 1 month apart are indicated.

Recommendations for Use

The hepatitis B vaccines are of public health importance. The Government of India has initiated hepatitis B vaccination in EPI since June 2002 with expansion in a phased manner.

For office practice, the IAPCOI recommends offering hepatitis B vaccine to all children who can afford the vaccine (Category 2). Hep B vaccine may be given in any of the following schedules:

 a. Birth, 1 and 6 months

 b. Birth, 6 and 14 weeks

 c. 6, 10 and 14 weeks

Immunologically 0-1-6 months schedule of hepatitis B immunization has been most widely used and proven to be ideal with high antibody titers at the end of the vaccination. However Hep B vaccine is a T-cell dependent vaccine and the titers at the end of immunization schedule may not be important so far as it is well above the protective level. There would occur anamnestic response with the titers going up, should there occur contact with the virus again in future. Also now that Hep B vaccination is integrated into the existing immunization program (EPI) in India, due to operational issues at a national level one has to piggy back on the available contacts for routine immunization, i.e. DTP which is given at 6, 10 and 14 weeks of age. At the same time birth dose has to be given to cover for the vertical route. Hence IAPCOI recommends 0-6-14 weeks schedule for public health. In case birth dose has been missed, 6-10-14 weeks schedule can be followed. In office practice, one can still use 0 - 4/6 weeks - 6 months schedule. As of now, from the data available, none of the above schedules needs a booster. Catch up vaccination with Hep B vaccine as a 0,1, 6 schedule should be offered to all children/adolescents who have not been previously vaccinated with Hep B vaccine. This is to address problems related to horizontal mode of transmission of the virus. Prevaccination screening with anti HBsAg antibody is not cost effective and is not recommended. Catch up vaccination is particularly important for contacts of HBsAg positive patient. Prevaccination screening for HBsAg should be done in these contacts.

All available brands of Hepatitis B vaccine are equally safe and effective and any may be used. Interchange of brands is permitted but not routinely recommended. Combination vaccines containing Hep B are discussed separately.