This document discusses the prevention of hepatitis B and C. It notes that India has an overall HBsAg positivity rate of 2-4.7% among pregnant women. Hepatitis B can be transmitted through blood or body fluids, from mother to child during birth, or through sexual contact. High-risk groups include those with multiple sexual partners or intravenous drug use. The hepatitis B vaccine is effective at preventing infection and involves a 3-dose series over 6 months. For exposure, hepatitis B immune globulin and vaccination provides good protection if started within 2 weeks. Universal precautions and immunization are key to prevention in healthcare settings.

1. Prevention of Hepatitis B & C
Sqn Ldr Rajneesh Thakur

2. Problem Statement- India
• Overall rate of HBsAg positivity: 2-4.7%
• Pregnant women : 0.9-6.3%
• The common genotypes : A followed by D

3. Modes of transmission

4. High-Risk Populations
• Persons born in countries/regions with a high
(>8%) and intermediate (>2%) prevalence of
HBV infection.
• Household and sexual contacts of persons
with hepatitis B
• Persons who have used injection drugs
• Persons with multiple sexual contacts or a
history of sexually transmitted disease

5. High-Risk Populations
• Men who have sex with men
• Persons with persistent elevated alanine or
aspartate aminotransferase levels
• Persons with HCV or HIV infection
• Hemodialysis patients
• Pregnant women
• Persons who require immunosuppressive or
cytotoxic therapy

6. Risk of transmission (p/c exposure)
• The risk of developing clinical hepatitis :HBsAg
+ and HBeAg + : 22%–31%
• Developing serologic evidence of HBV
infection - 37%–62%.
• If with HBsAg + , HBeAg-: 1%–6%,
• Serologic evidence of HBV infection: 23%–37%
WHO 2015

7. • HBV has been demonstrated to survive in dried
blood at room temperature for at least 1 week.
• HBV infections with no history of
nonoccupational exposure or occupational
percutaneous injury might have resulted from
direct or indirect blood or body fluid exposures
that inoculated HBV into cutaneous scratches,
abrasions, burns, other lesions, or on mucosal
surfaces

8. • HCV is not transmitted efficiently through
occupational exposures to blood
• The average incidence of anti-HCV
seroconversion : 1.8% (range: 0%–7%)
• Transmission rarely occurs from mucous
membrane exposures to blood
• No transmission in HCP has been
documented from intact or nonintact skin
exposures to blood
MMWR 2013,62(RR10);1-19

9. • Average risk of HIV transmission after a
percutaneous exposure : 0.3% (95%
confidence interval [CI] = 0.2%–0.5%) and
• After a mucous membrane exposure,
approximately 0.09% (95% CI = 0.006%–0.5%)

10. • Universal precautions
• Immunisation

11. Health care setting
WHO 2015

12. Sexual transmission

13. Immunization
• Active immunization
• Passive immunization

14. HBIG
• Hyperimmune serum globulin with high anti HBs titre
• Standard dose 0.06 mL/kg
• Temporary protection : 3–6 months
• Deep IM deltoid or gluteal muscle
• Indications:
– for sexual contacts of persons with acute HBV infection
– babies born to mothers infected with hepatitis B
– victims of parenteral exposure (e.g. needle stick) to HBsAg
positive blood
– To prevent HBV reinfection in patients who undergo liver
transplantation for HBV related liver disease.

15. • Each plasma donation used for the HBIG is
tested by FDA licensed Nucleic Acid testing for
HIV-1/2, HCV and HBV
• Plasma also tested by NAT for HAV and
parvovirus B19
• IgG seperated by anion exchange
chromatography and purified by nanofilters
and Solvent and detergent method

16. Adverse events
• Rare
• Local pain and tenderness at the injection site,
urticaria and angioedema might occur;
anaphylactic reactions, although rare,
• Persons with a history of anaphylactic reaction
to IG should not receive HBIG.

17. HBV Vaccine
• Two types- Plasma Derived & Recombinant
• Recombivax & Engerix-B (yeast derived)
• Combination Vaccine
– Hep A (Twinrix)
– Diptheria
– Hib

18. HBV Vaccine
Sherlocks 12 Ed

19. Pathobiology
• HBV vaccine consists of the highly immunogenic HbsAg
protein.
• When administered, it interacts with antigen presenting
cells present in the blood where it is lysed and processed.
• This epitope coupled with MHC -II molecule on the cell
surface is then presented to TH-2 cells.
• The TH-2 cells stimulate the differentiation of B-cells to
plasma cells.
• These cells then release hepatitis B surface antibodies in
large quantities as well as induce development of memory
B and T cells
• These memory cells then play an important role in long-
term protection

20. HBV Vaccine
• Efficacy (Anti HBs antibody titre > 10 mIU/mL)
– In adolescents and healthy adults aged <40 years,
– 30%–55% after the first vaccine dose,
– 75% after the second, and
– >90% after the third.
– Vaccine-induced immune memory has been
demonstrated to persist for at least 20 years**
• Post vaccination testing
– Routine post-vaccination testing for anti-HBs is not
recommended by WHO/CDC #
– High risk population only
– 1 to 2 mo after 3 doses
Sherlocks 12 Ed
# WHO 2015
**CDC 2015

21. Primary series
• Three different 3-dose schedules for
adolescents and adults
• These vaccines can be administered at
0, 1, and 6 months;
0, 1, and 4 months; and
0, 2, and 4 months.
CDC 2015

22. 2016 ACIP Adult Immunization Schedule- Medical/Occupational and Behavior-Based
Recommendations (USA)
Pregn
ancy
Immunoco
mpromisin
g
conditions
excluding
HIV
HIV &
CD4
Count
<200
cell/
µl
>200
cell/
µl
Men
having
sex
with
men
(MSM)
Heart
disease,
chronic
lung
diseases,
chronic
alcoholic
Aspleni
a
includi
ng
elective
Splenec
tomy
Chro
nic
liver
dise
ases
Diabete
Kidney
failure,
ESRD,
on
hemodi
lysis
Health
-Care
perso
nnel
Acknowledgment of a specific risk factor by those who seek protection is not needed.

23. Adverse events
• Pain at the injection site and mild to moderate
fever
• Vaccine Adverse Event Reporting System (VAERS)
of alopecia in children and adults after
administration of plasma-derived and
recombinant hepatitis B vaccine
• No association between hepatitis B vaccine and
the occurrence of serious adverse events,
including Guillain-Barré syndrome, transverse
myelitis, multiple sclerosis, optic neuritis, and
seizures
CDC, unpublished data, 1991)

24. Non responders
• A nonresponder is defined as a person with anti-
HBs <10 mIU/mL after ≥6 doses of HepB vaccine.
• 5-10% of healthy adults do not mount an anti-
HBs response to the primary immunization
schedule
• Repeat vaccination :0, 1 and 2 months with a 6-
month booster with double the standard dosage
of vaccine ( protective antibody levels in 44–80%
of individuals)
CDC 2011

25. Causes of non response
HLA DRB1*0301, HLA-B8, SC01, DR-3, HLAB44,
FC-31, DR-7

26. INTRADERMAL ADMINISTRATION OF THE VACCINE
• Efficacy of high-dose intra-dermal hepatitis B
virus vaccine in previous vaccination non-
responders with chronic liver disease. Dhillon S,
Moore C, Li SD, Aziz A, Kakar A, Dosanjh A, Beesla A, Murphy L, Van Thiel DH
Dig Dis Sci. 2012 Jan; 57(1):215-20
• Intradermal versus intramuscular hepatitis B
vaccination in hemodialysis patients: a
prospective open-label randomized controlled
trial in nonresponders to primary vaccination
.Barraclough KA, Wiggins KJ, Hawley CM, van Eps CL, Mudge DW, Johnson DW,
Whitby M, Carpenter S, Playford EG .Am J Kidney Dis. 2009 Jul; 54(1):95-103

27. IMPROVED IMMUNOGENICITY
• Adding pre-S1, pre-S2 particle or
nucleocapsids containing core antigen (HBcAg)
to the S-protein to enhance efficacy of the
vaccine. Clinical experience with a new recombinant hepatitis-B vaccine in
previous non-responders with chronic renal insufficiency.Haubitz M, Ehlerding G,
Beigel A, Heuer U, Hemmerling AE, Thoma HA. Clin Nephrol. 1996 Mar; 45(3):180-
2.

28. HEPLISAV-B™
• HEPLISAV-B™, a toll like receptor (TLR) agent
in which HbsAg is combined with
immunostimulatory TLR 9 agonist to enhance
response on a 2 dose regimen over 1 mo
compared to the current 6 mo 3 dose
regimen.
• In November 2016, Dynavax Technologies Corporation announced the
receipt of a Complete Response Letter (CRL) from the U.S. Food and
Drug Administration (FDA) regarding its Biologics License Application
(BLA) for Heplisav-B [Hepatitis B Vaccine, Recombinant (Adjuvanted)]
for immunization of adults 18 years and older against hepatitis B
infection.

29. NASVAC
• Nasvac,nasal vaccine, combination of HBV surface and
core antigen has shown good efficacy in healthy as well
as chronic HepB carriers possibly by stimulating naive
human B cells
• In Phase 1 trials of NASVAC, a mixture of 50 mcg of
HBsAg and HBcAg were administered via nasal spray to
healthy adults (age 18-45) in five doses at 0, 7, 15, 30
and 60 d.
• Anti-HBc seroconversion in 100% of patients as early as
day 30 with anti-HBs titers > 10 IU/L in 75% of the
patients at day 90 with no major side effects
• 01 Dec 2016 Abivax completes a phase-II/III trial in Hepatitis B in New Zealand and
Australia (NCT02249988)

30. V-5 Immunitor™
• A once daily oral preparation, has shown
efficacy both in development of protective
antibody as well as normalization of liver
function tests in chronically infected
individuals.
• Batdelger D, Dandii D, Jirathitikal V, Bourinbaia AS. Open label
trial of therapeutic hepatitis B vaccine V-5 Immunitor (V5)
delivered by oral route. Lett Drug Des Discov. 2007;4:540–544
• As of Nov 2016 in phase II.

31. Postexposure Prophylaxis
• Average risk of transmission depends upon HBeAg status of
the patient
• Wash the skin/mucous membrane with soap & water
• No Squeezing
• Test the patient for HBsAg + status
• HBIG
• Vaccine
HBeAg +ve 22.0% - 30.0%
HBeAg -ve 1.0% - 6.0%
HCV 1.8%
HIV 0.03%

32. Postexposure Prophylaxis
• HBIG & Hep B vaccine ideally within 24 hrs;
70% to 90% effective
• HBIG not later than 14 days sexual,>7 days
percutaneous
• Vaccine- 0,1,6 months
• Antibody testing – 1 to 2 mnths after last dose
• Pregnancy- No contraindication
World Gastroenterology Organisation

33. CDC 2013

34. Postexposure Prophylaxis
Vaccination and/or
antibody response status
of exposed person
HBsAg positive HBsAg negative Source unknown or not
available for testing
Unvaccinated/non-immune HBIG ×1; initiate HBV
vaccine series
Initiate HBV vaccine series Initiate HBV vaccine series
Previously
vaccinated,known
responder
No treatment No treatment No treatment
Previously
vaccinated,known non-
responder
HBIG ×1 and initiate
revaccination,
or HBIG ×2
No treatment No treatment unless
known high-risk source; if
high-risk source,then treat
as if source were HBsAg
positive
Previously
vaccinated,antibody
response unknown
Single vaccine booster dose No treatment No treatment unless
known high-risk source; if
high-risk source,then treat
as if source were HBsAg
positive
If still undergoing
vaccination
HBIG ×1; complete series Complete series Complete series
World Gastroenterology Organisation 2009

35. Non occupational exposure
Source Unvaccinated Vaccinated
HbsAg +
Percutaneous /mucosal HBIG x 1 + Vaccine series Single booster
Sex /needle sharing HBIG x 1 + Vaccine series Single booster
Sexual assault HBIG x 1 + Vaccine series Single booster
Unknown Hbs Ag status
Percutaneous /mucosal Vaccine series No Rx
Sex /needle sharing Vaccine series No Rx
Sexual assault Vaccine series No Rx
December 8, 2006 / 55(RR16);30-31

36. Materno fetal transmission
HBIG- newborn infants whose mothers are HBsAg-positive, particularly if they
are also HBeAg-positive.
In HIV-infected pregnant and breastfeeding women (including pregnant
women in the first trimester of pregnancy and women of childbearing age), a
once-daily fixed-dose combination of tenofovir + lamivudine (or emtricitabine)
+ efavirenz is recommended as first-line ART. This recommendation applies
both to lifelong treatment and to ART initiated for PMTCT and then stopped.
(Strong recommendation, low to moderate quality of evidence)
HBIG and initiation of the hepatitis B vaccine series at birth is 85%–95%
effective in preventing HBV infection

37. Hepatitis C
• Universal precautions
• IG not recommended
• Antivirals not recommended

38. Hepatitis C