Hepatitis B prophylaxis and tratment ppt

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 I nfectious 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. S ource 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 P revelance >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 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 P ost exposure prophylaxis warranted 2. HBsAg ( HBV antigen ) Done in Unvaccinated exposed & If response to previous vaccination unknown

14. Post Exposure Mana gement 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 F or 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

22. POP of Vaccinated subjects with Unknown Response

23. POP of Vaccine NON Responders (3 doses)

24. POP of Unvaccinated Subjects

25. POP of Incompletely Vaccinated Subjects Consider as Responder in future Anti- Hbsab < 10 Complete 2 nd course of vaccine

26. Prevention of PERINATAL Transmission Risk of vertical transmission is 5-15%

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 R ecover 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 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 ) + _ + _ + > 10 5 ↑ Distant infection CHB ( HbeAg - ve ) + _ _ _ + > 10 4 ↑ (persistent/intermittent) Distant infection, older age Immune Tolerent + _ + _ + > 10 7 Normal Minimal elevated younger age,Infected 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- 10 4 copies normal Incidentally Detected HbsAg + mostly Resolved infection _ +/- _ +/- +/- Negative Normal Past Exposure Immunized _ + _ _ _ Neg ative 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 infectio n 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 ( I mmunomodulator ) 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)