Pregnancy and Hepatitis B

• Pregnancy is well-tolerated by women who are chronic carriers of hepatitis B. Reactivation of the virus and exacerbation of the disease during or after gestation are uncommon [43]. The placenta forms an excellent barrier against transmission of this large virus, and intrauterine infection with hepatitis B is rare. However, transplacental transmission due to leakage can occur, such as during a threatened abortion [43, 44].
• The major problem for women who are chronic carriers of hepatitis B is the risk of maternal to infant (vertical) transmission at delivery due to exposure to maternal blood in the birth canal.
• Routine prenatal screening of all pregnant women for HBsAg is now the standard of care, as is universal hepatitis B vaccination of all newborns at birth [45].
• Transmission at birth is more likely if the mother is hepatitis B e antigen (HBeAg) positive or has high circulating levels of hepatitis B DNA (HBV DNA) [46,47]. Appropriate immunoprophylaxis of the newborn with both hepatitis B hyperimmune globulin (HBIG) and vaccine interrupts transmission in over 90 percent [48]. Performance of a cesarean section to prevent vertical transmission is not warranted [49].
• There is some evidence that treating the mother in the last month of pregnancy with lamivudine may further reduce the transmission rate if she is highly infectious (HBV-DNA >1.2x109 geq/mL), but this needs to be further substantiated [50].
• Infants born to carriers of the hepatitis B precore mutant (which does not produce HBeAg) are at particular risk for fulminant hepatitis B in the first two to four months following birth [51]. Thus, immunoprophylaxis should be given to infants from all mothers who are HBsAg positive, regardless of HBeAg status.
• Infected mothers should continue to breast feed as there is no additional risk of transmission
FOLLOW UP
Acute infection:
• See at 1 or 2 weekly intervals until aminotransferase levels are normal (usually 4-12 weeks) [15]
• In view of the possibility of chronic infection, serology should be repeated after 6 months even if the liver function tests are normal [15]

Chronic Infection [21]
HBeAg-positive patients:
• HBeAg-positive patients with persistently normal ALT should be tested for ALT at 3-6 month intervals.
• ALT along with HBV DNA should be tested more often when ALT levels become elevated. HBeAg status should be checked every 6-12 months.
• Patients who remain HBeAg positive with HBV DNA levels >20,000 IU/ml after a 3-6 month period of elevated ALT levels between 1-2 times ULN, or who remain HBeAg positive with HBV DNA levels >20,000 IU/ml and are>40 years old, should be considered for liver biopsy, and treatment should be considered if biopsy shows moderate/severe inflammation or significant fibrosis.
• Patients who remain HBeAg positive with HBV DNA levels >20,000
IU/ml after a 3-6 month period of elevated ALT levels >2 times ULN should be considered for treatment.
• HBeAg-negative patients:
● HBeAg-negative patients with normal ALT and HBV DNA <2,000 IU/ml should be tested for ALT every 3 months during the first year to verify that they are truly in the “inactive carrier state” and then every
6-12 months.
● Tests for HBV DNA and more frequent monitoring should be performed if ALT or AST increases above the normal limit.

Patient on treatment of chronic Hepatitis B [21]
• Patients receiving IFN-alpha therapy should have blood counts and liver panel monitored every 4 weeks,
• Patients receiving IFN-alpha therapy should have thyroid stimulating hormone (TSH) and HBV DNA levels every 12 weeks,
• If initially HBeAg-positive, HBeAg/anti- HBe every 24 weeks during treatment.
• Blood counts, liver panel, TSH and HBV DNA, and if initially HBeAg positive, HBeAg/anti-HBe should be tested every 12 weeks during the first 24 weeks post-treatment.
• Patients receiving NA therapy should have liver panel monitored every 12 weeks and HBV DNA levels every 12-24 weeks, and, if initially HBeAg-positive HBeAg/anti-HBe every 24 weeks during treatment.
• In addition serum creatinine should be tested every 12 weeks for patients receiving adefovir or tenofovir.
• HBsAg should be tested every 6-12 months in those who are HBeAg negative with persistently undetectable serum HBV DNA by PCR assay.

Post Vaccination response testing
• Follow-up testing of vaccine responders is recommended annually for chronic hemodialysis patients.


SCREENING AND PRIMARY PREVENTION

• Hepatitis B testing in asymptomatic patients should be considered in [53]
1. Men who have sex with men,
2. Sex workers (of either sex),
3. Intravenous drug users,
4. HIV-positive patients,
5. Sexual assault victims,
6. People from countries where hepatitis B is common (outside of Western Europe, North America, and Australasia),
7. Needle-stick victims
8. Sexual partners of positive or high-risk patients
9. Neonates of HBsAg positive mothers
• If non-immune, consider vaccination
• The simplest initial screening test in someone who is unvaccinated or is of unknown infection status is anti-hepatitis B core antigen (anti-HBc), with the addition of other tests as necessary. Some also screen for hepatitis B surface antigen (HBsAg) initially [15]
• Measure anti-HBs in those who have been vaccinated
• Vaccination should be offered to non-immune patients in most of the above groups . The main exception is people born in countries of high endemicity but not at continuing risk who are being screened primarily to detect chronic carriage [54]
• HIV-positive patients show a reduced response rate to the vaccine (approximately 40%) and become anti-HBs negative more quickly, although double dose vaccine increases the response by 13% . Offer a repeat course of three doses of vaccine, which may be double dose, for HIV-positive vaccine non-responders
• If patient has to be vaccinated against hepatitis B, two recombinant hepatitis B vaccines have been licensed in the United States: Engerix-B and Recombivax HB. Engerix-B is formulated to contain 20 mcg HBsAg/mL while Recombivax HB contains 10 mcg HBsAg/m [55].
• The recommendation for adults is to administer Engerix-B 20 mcg or Recombivax HB 10 mcg in three doses at months 0, 1 to 2, and then 6 to 12 [15].
• In infants, three doses of 0.5 mL vaccine are required to complete the course, the timing of which depends upon the clinical setting [15].
• If patient has to be vaccinated against hepatitis B, longer than recommended intervals between doses do not reduce final antibody concentrations, although protection might not be attained until the recommended number of doses has been administered. Thus, an interruption in the vaccination schedule does not require restarting the entire series of vaccination or adding extra doses [15].
• If the vaccination series is interrupted after the first dose, the second dose should be administered as soon as possible. The second and third doses should be separated by an interval of at least two months. If only the third dose is delayed, it should be administered when convenient.
• If person is to be vaccinated against hapatitis B using monovalent vaccine or combined A+B one of the regeimn is to give injections at 0, 7, 14 days, 12 months which has advantage of inducing Rapid immunity,Short duration and high antibody titres at 12 and 13 months. It has potential for better uptake while it has disadvantages of being not tested in HIV or other immunocompromised patients, having little published data ,low antibody titres in the first year (but current evidence suggests that protection is still adequate in the immunocompetent [15].
• If vaccine is given at 0, 1, 2 and 12 months the advantages include early immunity, shorter time to early immunity than the 0, 1, 6 course and high antibody titres at 12 and 13 months and the disadvantage is antibody titres lower than the 0, 1, 6 in the first year[15].
• If vaccine is given at 0, 1, 6 months the advantages include higher antibody titres at 7 months than other two regimens, although this may not be clinically important, long established regimen and most researched in HIV and the Disadvantages include poor uptake of the 6 month dose in the clinical setting
• If person is to be vaccinated quickly the new ultra-rapid 0, 7, 14 day regimen offers the advantage of potentially higher uptake of the full course [15].
• If person is vaccinated the test for response (anti-HBs >10 IU/l, ideally >100 IU/l) 4-12 weeks after the last dose
• Persons who remain at risk for HBV infection such as infants of HBsAg-positive mothers, health care workers, dialysis patients, and sexual partners of carriers should be tested for response to vaccination. Postvaccination testing should be performed 3 to 9 months after the last dose in infants of carrier mothers and 1 to 2 months after the last dose in other persons.
• If person is a non- or poor responders usually respond to further doses (up to three injections), ideally as a repeat course with response rates up to 100% [15].
• If person is to be vaccinated with new pre S containing vaccine which are effective and may also be used for conventional-vaccine non-responders
• If person is vaccinated with Hepatitis B Vaccine it is probable that booster doses of vaccine are not required for at least fifteen years in immunocompetent children and adults who have responded to an initial vaccine course
• If person vaccinated is HIV-positive or other immunocompromised patients will still need to be monitored and given boosters when antibody to hepatitis B surface antigen (anti-HBs) levels fall below 100 IU./l [15].
• If vaccine courses are not completed in immunocompetent patients, the outstanding doses can be given four or more years later without the need to restart a three dose course. One or two doses of vaccine may provide immunity in 40% and over 90% of immunocompetent patients respectively [15].
• If person is vaccinated with Hepatitis B Vaccine, the most common adverse reaction is soreness over the site of injection, which occurs in fewer than 25 percent of the vaccinees. Other adverse reactions reported by 1 to 3 percent of vaccinees include low grade fever, malaise, headache, joint pain and myalgia. These adverse reactions are usually mild and do not result in any serious clinical sequelae [15].
• If person is vaccinated with Hepatitis B Vaccine , they have no teratogenic effects and can be administered during pregnancy
• If person is vaccinated with Hepatitis B Vaccine, there are three main groups of vaccine nonresponders: Patients with underlying medical conditions such as chronic renal failure and immunosuppressed states. In patients undergoing hemodialysis, response rate to the standard dose of vaccine is between 50 to 60 percent. This can be augmented to above 70 percent by doubling the dose of the vaccine. The response rate can also be augmented by intradermal administration of the vaccine [55]
POST EXPOSURE PROPHYLAXIS [52]
Contamination incidents include needle stick or sharps injuries, bites, scratches or other incidents such as contamination of the mucous membrane or conjunctivae. Most contamination incidents occur as a result of handling used needles or other sharps. Clinical staff is also at risk from blood borne diseases if minor cuts, abrasions and other open skin lesions are contaminated with blood, serum or other body fluids.
In studies of health care workers who sustained injuries from needles contaminated with blood positive for both HBsAg and HBeAg, the risk of developing clinical hepatitis was 22% - 31% and the risk of serologic evidence of HBV infection was 37% - 62%. In comparison, the risk of developing clinical hepatitis from a needle contaminated with HBsAg-positive, HBeAg-negative blood was 1% - 6%, while the risk of developing serologic evidence of HBV infection was 23% - 37%


ACTION TO BE TAKEN BY STAFF FOLLOWING A CONTAMINATION INCIDENT

1 Wash the site of exposure/injury liberally with soap and warm water but without scrubbing. Exposed mucous membrane or conjunctivae should be irrigated copiously with water. If there is a puncture wound free bleeding should be encouraged but the wound should not be sucked.

2 Bleed the source patient (if known) for HBsAg as soon as possible.

3 Bleed the staff member involved in the incident for 1st storage sample
4 Report the incident
5 The following information should be obtained from the injured person and verified from their medical/occupational health record:
• Dates of hepatitis B immunizations,
• Postimmunization titer, if known
• Previous testing (if available) for HIV, HBV, and HCV
• Tetanus immunization status
• Current medications
• Current or underlying medical conditions that might influence drug selection (eg, pregnancy, breast feeding, renal or hepatic disease)

Significant exposure

A significant exposure includes:
• percutaneous exposure (sharps injury)
• mucocutaneous exposure (contamination of broken skin/mucous membrane exposure/bite)

A percutaneous exposure carries a higher risk than a mucocutaneous exposure. The risk is greater the greater the volume of blood involved. A deep sharps injury carries a higher risk than a superficial one
Non-Significant Exposure

• Small splashes of blood onto intact skin and scratches (unless contaminated by the patient’s blood)
• Exposure to saliva, urine, vomit and faeces (unless blood stained).
• Exposure to uncontaminated sharp objects

Post Exposure Prophylaxis is given as
• If person is unvaccinated and patient to whose secretions is exposed is HBsAg +, start HBIG once at a dose of 0.6 ml/kg; initiate HB vaccine series
• If person has significant exposure and is unvaccinated and source is HBsAg -, start HBV vaccination series
• If person has significant exposure and is unvaccinated and source is HBsAg unknown, start accelerated HBV vaccination series (An accelerated course of vaccine consists of doses spaced at 0, 1 and 2 months. A booster dose may be given at 12 months to those at continuing risk of exposure to HBV.)
• If person has Non-significant exposure consider HBV vaccination only if continued exposure is anticipated like health care workers, but if not anticipated like public, reassure only.
• If exposed person has significant exposure and  1 dose HB vaccine pre-exposure (HBV status of person exposed – please wait until result is available providing this will be within 48 hours before vaccinating with HBIG or an accelerated HB vaccine) and source is HBsAg +, recommend accelerated course of HB vaccine and one dose HBIG
• If exposed person has significant exposure and  1 dose HB vaccine pre-exposure (HBV status of person exposed – please wait until result is available providing this will be within 48 hours before vaccinating with HBIG or an accelerated HB vaccine) and source is HBsAg unknown, recommend accelerated course of HB vaccine
• If exposed person has significant exposure and  1 dose HB vaccine pre-exposure (HBV status of person exposed – please wait until result is available providing this will be within 48 hours before vaccinating with HBIG or an accelerated HB vaccine) and source is HBsAg -, initiate course of HB vaccine
• If exposed person has no significant exposure and  1 dose HB vaccine pre-exposure (HBV status of person exposed – please wait until result is available providing this will be within 48 hours before vaccinating with HBIG or an accelerated HB vaccine) consider HBV vaccination only if continued exposure is anticipated like health care workers, but if not anticipated like public, reassure only.
• If exposed person has significant exposure and  2 doses HB vaccine pre-exposure (anti-HBs not known) (HBV status of person exposed – please wait until result is available providing this will be within 48 hours before vaccinating with HBIG or an accelerated HB vaccine) and source is HBsAg +, recommend one dose of HB vaccine followed by second dose one month later
• If exposed person has significant exposure and  2 doses HB vaccine pre-exposure (anti-HBs not known) (HBV status of person exposed – please wait until result is available providing this will be within 48 hours before vaccinating with HBIG or an accelerated HB vaccine) and source is HBsAg – or unknown, recommend one dose of HB vaccine
• If exposed person has no significant exposure and  2 doses HB vaccine pre-exposure (anti-HBs not known) (HBV status of person exposed – please wait until result is available providing this will be within 48 hours before vaccinating with HBIG or an accelerated HB vaccine) recommend to finish vaccination and reassure
• If exposed person has significant exposure and is a known responder to HBV vaccine (anti-HBs  10 miU/ml), and source of any HBsAg status, consider giving a booster dose
• If exposed person has no significant exposure and is a known responder to HBV vaccine (anti-HBs  10 miU/ml), and is a health care worker consider booster and if not at risk of reexposure no prophylaxis is required.
• If exposed person has significant exposure and is a known non-responder to HB vaccine (anti-HBs  10 miU/ml 2-4 months post-vaccination and source is HBsAg + or unknown, give HBIG once and consider booster dose of HB vaccine
• If exposed person has significant exposure and is a known non-responder to HB vaccine (anti-HBs  10 miU/ml 2-4 months post-vaccination and source is HBsAg -, consider booster of HBV vaccine.
• If exposed person has no significant exposure and is a known non-responder to HB vaccine (anti-HBs  10 miU/ml 2-4 months post-vaccination consider booster of HBV vaccine for person with continued risk E.g. healthcare worker and no prophylaxis is required if no continued risk.
• HBIG should be given as soon as possible after exposure but preferably within 48 hours of the incident. It should not be given later than 7 days following exposure
Pregnancy and Lactation

• Because of the potential risks from exposure to Hepatitis B infection pregnancy is not considered to be a contraindication to the use of HBIG when clearly needed. It is not known whether HBIG can cause foetal harm when administered to pregnant women.

• It is not known if transmission of HBIG to a nursing infant presents any unusual risk. HBIG should be administered with caution to nursing women.