Hepatitis B prophylaxis and tratment

1. HBV POST EXPOSURE PROPHYLAXIS (pep)
&
APPROACH
TO
HBSAG POSITIVE SUBJECTS
Dr Ravi Prakash
MD Medicine

2. Learning objectives
Assess and manage incidents of exposures to
blood & body fluids capable of transmitting
Hepatitis B.
Approach to an exposed person showing HBSAg
positivity
Approach to an Incidentally detected
Asymptomatic HBSAg positive subjects (IDAHS)

3. Types of Exposure
Exposures may be
 Occupational
Work related exposures
Health care Workers or Emergency service provider
Accidentally sustain injury during job duties
Needle stick injuries or sharp objects
 Non Occupational
Exposures outside the work place
Sexual exposures
Bites
Blood splashes
Needle sharing

4. Assessment of exposure Risk
A SIGNIFICANT Exposure is when a potentially infectious body fluid
comes in contact with the tissues of exposed person by :
 Percutaneous Exposure
Needle stick injury
Sharp object cut or puncture
 Contact with mucus membrane
A splash to eyes/nose/mouth
Sexual contact
 Contact with non intact skin
Disruption of epidermis (abraded/chapped)
Skin injury < 3 days old
Dermatitis/eczema/burn wounds/psoriasis
 Biting or receiving bite with presence of blood

5. Risk of Transmission
 Needle Stick/Sharp exposures : 6 to 30 %
 Bites with break in skin: much lesser risk
( HBV concentration in Saliva is 1000-10000 times lesser than in
blood)
 Unprotected Sex : high risk
HBV carries greatest risk of transmission among all blood borne
pathogens following community acquired injuries
HBV can survive in dried blood for 7 days or more on
envoirmental surfaces

6. Risk of Transmission contd…
A Greater risk of exposure/transmission seen in
 Device visibly contaminated with blood
 Deep injury ( sharp object)
 Needle was directly inside artery or vein
 Neddle stick injury with a large gauze needle
 Larger volume of exposed blood or body fluid

7. Vehicles of Transmission
Potentially infectious body fluids are
 Blood contains highest HBV titres
 Serum, plasma & all biological fluids visibly
contaminated with blood
 Cerebrospinal, Amniotic & Synovial fluids
 Pleural, pericardial & peritoneal fluids
 Semen & Vaginal fluids ( sexual transmission )
 Saliva
 Organs & Tissues
 Lab specimens , samples or cultures containing
concentrated HBV

8. Vehicles of Transmission ctd….
Potentially NON Infectious body fluids are
 Breast milk
 Bile
 Faeces
 Sweat
 Sputum
 Tear
 Urine
 Vomitus
 Nasopharyngeal secretions
But These can be potentially infectious if visibly contaminated
with blood

9. Blood & Body fluid Exposure Management
 FOUR indications for post exposure management are
1. Percutaneous , permucosal , non intact skin exposure
2.Exposure to blood/potentially infectious body fluids/tissue
3. Source is considered potentially infectious
4. Exposed person considered susceptible to HBV
 If 4 indicators are present
Post exposure management required
Assess risk of the source of HBV
Determine status of exposed for HBV
Complete baseline serology of exposed
Determine HBV susceptibility
 IF 4 indicators are not present
Post exposure management not required
Educate , counsel & provide rationale to exposed

10. Source Person
Source of blood/body fluids must be considered
Source may determine the risk of transmission of infection
in significant exposures
Known Source
check h/o HBV/HIV/HCV infection
check evidence of recent testing
check immunization status of HBV/date of last
immunization/immune titres of HBV
h/o injection drug use/needle sharing/multiple
sexual partners
Unknown source
eg a needle found in an area of high injection drug use

11. High Risk Source
 One who Practices high risk sexual Behaviour
1.Without always using protection
2.Homosexual men
3.Has multiple sexual partners
4. Has a sexual partner who is an injection drug user (IDU)
 Has an HBV infected sexual partner with high risk sexual
behaviour
 Has a h/o injection drug use
Has a h/o sharing drug related equipment
Received a Tatto or Piercing with a non sterile equipment
Person from highly endemic regions for HBV
eg sub sahara Africa , East asia ( HbSAg Prevelance >2%)

12. Test the Source person
Testing of the source person
 If the source person is known
Check his health status
look for risk factors
Take a blood sample for HBsAg testing
 if source is unknown (eg found needle)
Blood/fluid testing not recommended

13. Test the Exposed Person
Baseline Testing of the Exposed Person
 Should be done at time of exposure or soon after
 Follow up testing again at 2 & 6 months post exposure
Anti HBsAb & HBsAg
1. Anti HBs (HBV surface antibodies)
Titre > 10mIU/ml Person is immune
Immunized (vaccinated)
Infected in Past & non infectious now
Titre < 10mIU/ml Person is susceptible to infection
Post exposure prophylaxis warranted
2. HBsAg ( HBV antigen ) Done in Unvaccinated exposed
&
If response to previous vaccination unknown

14. Post Exposure Management
TREATMENT OF EXPOSURE SITE & FIRST AID
 Remove Contaminated Clothing
 Immediately allow the wound to bleed freely
 Wash wound & injured area well with soap & water
 Apply an anteseptic ( no evidence of reduced transmission)
 Not Recommended is
.Application of caustic agents such as bleach
.Injections of antiseptics / disinfectants into wound
Flush mucus membranes well with water /saline (atleast
1000ml), if eye, nose or mouth involved
Consider the use of tetanus toxoid vaccine /Ig for wound
management based on nature of wound

15. Post Exposure Prophylaxis (PEP) HBV
PEP of an exposed person at risk of HBV depends on
 Person’s susceptibility to HBV infection
 History of prior infection with HBV
 History of prior HBV Vaccination
 HBV Vaccine response status ( anti HBs titres) of
exposed person known or unknown
 Source is High Risk or low Risk
If HBV test results of exposed person & source are not
available within 48 hours Manage as a case of
possible Exposure (HBsAg positive)

16. PEP(Post Exposure Prophylaxis)
Two Types of Products are available for prophylaxis
against HBV infection
 Hepatitis B Vaccine
Pre & post Exposure Prophylaxis
long term protection
 HBIG
Only in post exposure prophylaxis
Temporary protection ( 3to 6 months)

17. Hepatitis B Vaccine
Available As
 Single antigen formulation
Composed of Recombinant HbsAg protein
Recombivax Hb ( Merck)
Engerix -B ( GlaxoSmithline)
 Combined Hepatitis A & Hepatitis B vaccine
For persons > 18 yr
With increased HAV & HBV infection risk
Twinrix ( GlaxoSmithline)
Contains Recombinant HBsAg & inactivated HAV

18. Hepatitis B Vaccination
Primary Hep B vaccination of adults
 3 Doses of 10/20ug of recombinant HbsAG protien
 Intramuscular route into Deltoid muscle
 3 Dose schedule at 0,1,6 months
Alternate 4 dose schedule at 0,1,2,12 months (U.S
approved)
Both schedules have a similar rate of seroprotection
Highly effective in preventing acute infection after exposure
if given within 7 days (Ideally within 48 hours).

19. Hep B vaccine Seroprotection
Vaccine RESPONDERS
 Immunocompetent persons with vaccine induced Anti HBS levels
>10mIu/ml 1-2 months after receiving 3 or more doses of HepB vaccine
 Studies suggest HepB vaccine responders are Seroprotected against acute &
chronic Hepatitis B infection for >20 years due to persistence of AntiHBs
antibody
 Post vaccination seroprotection achieved in
95% healthy infants
92% adults < 40 years
84% adults > 40 years
 Anti Hbs levels decline over time after primary vaccination
Vaccine NON RESPONDERS
 Person with AntiHbs levels < 10mIu/ml after 6 or more doses HepB
vaccine
 Unvaccinated / Incompletely vaccinated /Immunocompromised persons

20. Hepatitis B Immunoglobulin
 Provides Passive Anti HBs antibodies
 Temporary Protection for 3-6 months
 Prepared from human plasma containing high AntiHBs titre
 Used with HepB vaccine for PEP but at different injection site
Only indicated when source is HBsAg
 Primary method of protection in HepB vaccine non responders
 Adult Dose .06 ml/kg by I.M route over an appropriate muscle
mass ( deltoid/gluteal) with an appropriate needle size to
deliever large volume of HBIG
Ideally given within 48 hours
May be given upto 7 days after percutaneous exposure (needle )
upto 14 days after permucosal exposure (sexual assault)

21. POP of Vaccinated Subjects
Documented
RESPONDER
after 3 doses
of vaccine
Source HBsAg +
or Unknown
Documented
NON
RESPONDER
after 6 doses of
Vaccine
NO
ACTION
REQUIRED
Source is
HBsAg -
HBIG * 2 doses
seperated by 1
month
NO ACTION
REQUIRED

22. POP of Vaccinated subjects with Unknown
Response
Anti HBsAb > 10 mIu/ml
3 dose vaccine response unknown
VACCINE RESPONDER
No ACTION
REQUIRED
Measure Anti HBsAb level
Anti HBsAb <10 mIu/ml
Don’t Test source for HbSAg
status
VACCINE NON RESPONDER
Test source for HBsAg status
Baseline tests of exposed

23. POP of Vaccine NON Responders (3 doses)
Source HBsAg +/unknown Source HBsAg -
HBIG * 1 Dose HBIG not given
Revaccinate with second series of
Hepatitis B Vaccine ( 3 doses)
Post Vaccination Serology testing
Anti Hbs ab levels 1-2 months after last dose of vaccine
Anti Hbsab > 10
Anti Hbsab <10
Vaccine Non responder after 6
Doses of HepB vaccineConsider as Vaccine responder in future
NO ACTION REQUIRED NOW Recheck Infection status by Hbsag &
antiHBc level

24. POP of Unvaccinated Subjects
Unvaccinated
Source HbSag +/Unknown Source HbSag -
HBIG * 1
Complete Vaccination
Complete
Vaccination
Post Vaccination serologic testing 1-2 months
after Last vaccine dose

25. POP of Incompletely Vaccinated Subjects
1 Dose of Vaccine 2 Doses of Vaccine
Test Anti-HBs ab levels
HBIG * 1 dose
1 Dose of vaccine
Test for Anti-HBs ab levels
Give 3rd dose of vaccine
< 10 /
unknown
Complete
Vaccination
>10
HBIG * 1
Test Anti-Hbsab
Level at 6 months
Consider as
Responder
in future
Anti-Hbsab < 10
Complete 2nd
course of vaccine

26. Prevention of PERINATAL Transmission
Risk of vertical transmission is 5-15%
Prenatal
ll
• Intrauterine route
• If HBsAg +
• Check HBV DNA
titre & HBeAg
status
• HBV DNA titre
>200000 Iu/ml
• Antiviral drugs are
indicated
• Tedofovir in III TM
upto 12 weeks post
delivery
• Delivery by CS if
HBV DNA is high
Natal
• During Delivery - max %
• Maternal blood &
cervical secretions
contains virus
• Immunoprophylaxis :
New born born to Hbsag
+ mothers
• HBIG & first dose of
HepB vacccine
• Within 12 hr delivery
• Complete Vaccination
• Revaccinate vaccine non
responders at 9 mt
Postnatal
• HBV dNA +
In breast
milk
• No need to
delay BF
• No add. Risk
for HBV
transmission
• Give IPx
• Continue
vaccination
asscheduled

27. Clinical Outcomes Of Hepatitis B
Infections

28. Practical Approach to HBsAg positive Subject
Exposure
HBsAg detectable
after 4-6 weeks
HBsAg +
Acute Hepatitis B Chronic Hepatitis B
HbeAg +
HBsAg disappear within 4-6 mth
AntiHBs ab appear few week later
HBsAg persists beyond 6
mths
HBeAg + in active phase
HBsAg –
AntiHBs ab not appeared yet
Only detectable marker anti-HBcIgM
K/a WINDOW PERIOD

29. Acute hepatitis B
• > 95% do not require specific treatment
• Recover spontaneously

30. Treatment Indications for Acute Hepatitis B
Severe acute fulminant hepatitis B characterised by
 Coagulopathy (INR > 1.5)
 Protracted course (persistent symptoms or marked
jaundice for > 4 weeks)
 Signs of acute liver failure
Treatment options
 NA antiviral agents (Tenofovir, Entecavir).
 Liver Transplantation

31. Phases of Chronic hepatitis B

32. WORK UP oF HBsAg Positive
LFT’s
• ALT/SGPT
• AST/SGOT
• GGT
• Alkaline Phosphatase
• Bilirubin
• Albumin
• Globulin
VIRAL MARKERS
• Markers of HBV
replication / Disease
Activity
• Hbe Ag
• Anti Hbe ab
• Qunatitative HBV DNA
• Markers of HBV
Infection status
• IgMHBc / Total HBc
• Anti Hbsab level
Disease Stage & Activity
Determination
• USG
• Liver Biopsy
• Fibroscan ( non invasive)
• Elastography
• Degree of inflammation &
fibrosis
• Important factor to decide
antiviral therapy
CBC INR
Family Screening for
HbsAg & Anti HBs ab
levels
INTERPRETATION OF
RESULTS

33. HBeAg - & Hbeab +
Seroconversion is an indication of resolution
Long time reduction viral replication & load
Response Marker to therapy
HBeAg +
Marker of viral load
Elevated in early infectious stage
later converts to antibody

34. Interpretation of serological testing
Disease
phase
HBs Ag Anti
HBs
HbeAg Anti
HBe
Anti
HBc
HBV-
DNA
ALT History
Acute
HBV
+ _ + _ IgM positive ↑ Recent
exposure
CHB
(HBeAg
+ve)
+ _ + _ + >105 ↑ Distant
infection
CHB
(HbeAg
-ve)
+ _ _ _ + >104 ↑
(persiste
nt/inter
mittent)
Distant
infection,
older age
Immune
Tolerent
+ _ + _ + >107 Normal
Minimal
elevated
younger
age,Infec
ted in
infancy

35. Interpretation of serological testing
Disease
phase
HBs Ag Anti
HBs
HbeAg Anti
Hbe
Anti
HBc
HBV-
DNA
ALT History
Inactive
HbsAg
carrier
+ _ _ + + Neg-104
copies
normal Incidentally
Detected
HbsAg +
mostly
Resolved
infection
_ +/- _ +/- +/- Negative Normal Past
Exposure
Immunized _ + _ _ _ Negative Normal History of
vaccination

36. HBsAg +
HBeAg +
No Cirrhosis
No ALF/ACLF
No F/H of HCC
ALT< ULN
(ULN IS 35 U/L-M
25 U/L-F)
HBV DNA > 20000 IU/mL(10 copies/ml)
AntiHBe ab Negative
Immune Tolerant Phase
HBeAg+ Chronic infection
Antiviral treatment not needed
MONITOR ALT & HBV DNA every 3-6 mth
HBsAg every 1 year

37. HBsAg +
HBeAg +
No Cirrhosis
No ALF/ACLF
No F/H of HCC
ALT >ULN & < 2* ULN
ALT < 70 U/L
HBV DNA
Usually > 20000 IU/mL
Exclude other causes of ALT elevation
Assess disease severity with non invasive test /Liver Biopsy
Minimal
Inflammation & Fibrosis
Moderate
NecroInflammation & Fibrosis
Immune tolerant phase
Monitor ALT/HBV DNA 1-3 mthly
Treat if ALT/DNA persistently elevated > 6 mth
Especially if Age > 40 yrs
Immune Active phase
HBeAg+ chronic Hepatitis
HBV DNA m/b < 20000 iu/ml
AntiHBe ab m/b + in 5-10%
AntiViral treatment required
Antiviral treatment not needed

38. HBsAg +
HBeAg +
No Cirrhosis
No ALF/ACLF
No F/H of HCC
ALT >2*ULN
ALT >70
HBV DNA > 20000 IU/mL
(Usually)
Immune Active phase
HBeAg+ chronic Hepatitis
AntiViral treatment required
HBV DNA 2000-20000 IU
Immune Active phase
HBeAg+ chronic Hepatitis
AntiHBe ab m/b + in 5-10%
May Indicate Seroconversion
Monitor ALT/HBV DNA 1-3 mthly
Exclude other causes of ALT elevation
Treat if ALT/DNA persistently elevated > 6 mth,
Liver biopsy moderate Inflammation or fibrosis
Especially if Age > 40 yrs

39. HBsAg +
HBeAg -
No Cirrhosis
No ALF/ACLF
No F/H of HCC
ALT< ULN
(ULN IS 35 U/L-M
25 U/L-F)
HBV DNA < 2000 IU/ml HBV DNA > 2000 IU/ml
Antiviral treatment not
needed
Monitor
ALT & HBV DNA every 3-6 mth
HBsAg every 1 year
Monitor ALT & HBV DNA every 3 mth
For 1 yr & then every 6 month
If ALT elevates
Exclude other
causes
Liver biopsy to assess
disease activity
Treat if
Persistent ALT elevation > ULN with
HBV DNA >2000 iU/ml
Moderate inflammatiom & fibrosis

40. HBsAg +
HBeAg -
ALT >ULN & < 2* ULN
ALT < 70 U/L
HBV DNA < 2000 IU/ml
HBVDNA 2000-2000 Iu/ml
HBV DNA > 20000 IU/ml
No Cirrhosis
No ALF/ACLF
No F/H of HCC
Inactive Carrier phase
HBeAg –
AntiHBe ab +
Low HBV DNA levels
Antiviral treatment
not Required
Assessment of fibrosis by
non invasive methods or liver
biopsy
l
Minimal
Inflammation
& Fibrosis
Moderate
Inflammation
& Fibrosis
Inactive carrier
phase
Antiviral
treatment not
needed
Immune
Reactivation
phase
Antiviral
treatment
Required
HBeAg- Immune
Reactivation phase
HBeAg- chronic
hepatitis
Antiviral
treatment
Required
Treat
Persistent ALT raised > ULN
HBV DNA >2000 iU/ml
Moderate inflammatiom &
fibrosis
Especially if Age > 40

41. HBsAg +
HBeAg -
ALT >2* ULN
ALT > 70 U/L
HBV DNA < 2000 Iu/ml HBV DNA > 2000 IU/ml
Immune Reactivation phase
HBeAg- chronic hepatitis
Antiviral treatment Required
Monitor ALT 3 monthly & Assess
disease activity by liver biopsy
Inactive Carrier phase ( mostl likely)
HBeAg – chronic infection
Antiviral treatment not Required
Exclude other causes of raised ALT
Treat if
Persistent ALT raised > ULN
Moderate inflammatiom & fibrosis
Especially if Age > 40
No Cirrhosis
No ALF/ACLF
No F/H of HCC

42. Special populations with HBV infection
Family H/O
Cirrhosis
HCC
• Cirrhosis ( compensated or
Decompensated
• Liver failure ( ALF/ACLF)
• ExtraHepatic manifestation of HBV
Regardless of
ALT levels
HBeAg Status or
HBV DNA levels
AntiViral treatment required
HBV DNA > 2000 IU/ml
Regardless of
ALT levels
HBeAg Status
AntiViral treatment
required

43. DRUGS USED FOR ANTIVIRAL TREATMENT
 Pegylated IFN alpha -2a ( Immunomodulator)
180 mcg once a week by s.c route for 48 weeks
 Entecavir ( nucleoside analogue) Preferred
.5 mg od ( I mg od in lamivudine resistant cases)
 Lamivudine (nucleoside analogue) Not preferred
100 mg od
High risk of resistance , poor Hbsag clearance, pancreatitis risk
 Adefovir ( nucleotide analogue) Not preferred
10 mg od
Ac renal failure, lactic acidosis , fanconi syndrome
 Tenofovir ( nucleotide analogue) Preferred
300 mg od ( c/b given in pregnancy - class ‘B’ )
 Telbivudine (nucleoside analogue) Not preferred
600mg od ( High Risk of resistance)