world hepatitis day 2015: diagnosis and vaccination 2015
TRANSCRIPT
Diagnosis and vaccination
Dr Geethani Galagoda
Consultant Virologist
Medical Research Institute
Symposium on Hepatitis Prevention
Hepatitis Day 2015
Points at which laboratory can contribute
• Screening for infection
• Diagnosis of infection
• Staging of disease severity
• Decision on treatment ▫ Before
▫ During
▫ After
Markers of hepatitis B
• Samples: serum or plasma • Antigens
▫ Hepatitis B surface Antigen ▫ Hepatitis B e antigen ▫ Hepatitis B core antigen – not seen in blood
• Antibody ▫ Hepatitis B surface antibody ▫ Hepatitis B e antibody ▫ Hepatitis B core antibody (IgM and total)
Hepatitis B surface Antigen (HBsAg)
• First serological marker – 3-5 weeks (30 d) after
exposure, before hepatic injury
• Acute infection – cleared in 6 months
• Chronic infection – if persists after 6 months
• Transient positivity seen for 18 days after vaccination
Hepatitis B e Antigen (HBeAg)
• Related to core antigen (soluble nucleo-capsid antigen)
• Indicates active viral replication (HBV DNA > 100,000 –
1 million IU/ml)
• Highly infectious
• Greater risk of progression to liver disease
• Mutant forms do not have HBeAg
• Management depends on the presence of
HBeAg
Hepatitis B core Antibody (HBcAb)
• First antibody to appear, before liver injury • Does not neutralise virus • IgM – recent infection, reactivation of chronic hepatitis • IgG – persists for life
▫ With HBsAb – recovery from natural infection ▫ Alone
Window period False positive Immune with low levels of HBsAb Chronic infection with low levels of HBsAg Reactivation
Hepatitis B e Antibody (HBeAb)
• Appears with clearing of HBeAg
• After a few weeks
• Shows low infectivity
• Good prognosis to disease
Hepatitis B surface Antibody (HBsAb)
• Last antibody to appear
• Alone – after vaccination (protective level ≥ 10 IU/L)
• Indicates immunity to infection with Hepatitis B
• With HBcAb (total) – after recovery from natural
infection
Molecular assays
• Hepatitis B DNA
▫ Qualitative
▫ Quantitative
• Methods
▫ Conventional and Real Time PCR assay
Diagnosis of acute hepatitis B
• Initial testing - HBsAg
• Followed by HB core IgM antibody and HBeAg
• If HBeAg negative – HBeAb
Follow up assay
• Acute infection – repeat HBsAg 6 months after
• To exclude chronic infection
• Persistence of HBsAg after 6 months – chronic
infection
• Chronic infection – HBeAg followed by HBeAb
• DNA viral load assay
DNA viral load assay
• Correlates with circulating viral particles
• Either measured as copies / ml or IU / ml
• Detection limit should be 15 IU / ml
• Treatment recommended if HBV DNA - > 20,000 IU / ml
Follow up
• Patients not on treatment
▫ HBsAg, HBeAg, ALT levels and DNA viral load assay annually
• Patients on treatment
▫ HBsAg, HBeAg, DNA viral load assay every 3 months
• Discontinuation of treatment
▫ HBsAg, HBeAg, DNA viral load assay every 3 months for the
first year
Guidelines for the prevention, care and treatment of patients with chronic hepatitis B infection WHO March 2015
Diagnosis of HCV
• HCV antibody (positive 1-6 months after
infection)
• All anti-HCV positive patients
▫ HCV RNA for confirmation
▫ Viral load assay
▫ Genotyping
Treatment of HCV
• HCV RNA testing at initiation of treatment
• Dual therapy ▫ Baseline, 4, 12, 24 weeks, end of treatment, 12 and 24
weeks after therapy
• Follow up ▫ Annual or more frequent HCV RNA assays for patients
with SVR
EASL Clinical guidelines: Management of hepatitis C virus infection 2014
Hepatitis B - Populations at risk
• Health care workers
• Patients
▫ Multi transfused patients / Chronic haemodialysis / Treatment for
malignancy
• People with high risk sexual behaviour
▫ Commercial sex workers / MSM
• Intravenous drug users
• Inmates of mental health / long term care institutions
• Prisoners
• Family contacts of carriers
• Armed forces / Police
Prophylaxis - (specific prevention)
Vaccine - long term protection
plasma derived / recombinant comparable efficacy & safety
HBIG - short term protection
NBTS 24/05/07
Hepatitis B immunoglobulin
• Human plasma with high titer of Hep B antibody
• Given with hepatitis B vaccine
• Not for treatment of hepatitis B
• Given within 48 hours, (up to a week), Depending on body
weight
• Different site from vaccine – antero-lateral thigh
• Do not give intra-venously
NBTS 24/05/07
Hepatitis B immunoglobulin cntd.
• Indications
▫ Parenteral exposure, before starting vaccination
▫ Neonates whose mothers are HBeAg positive
▫ Known non-responders
• CI - bleeding disorder
• Pregnancy?
• SE – very rare
Pre Exposure Prophylaxis
• Given before exposure to high risk groups
• Pre vaccination screening is not essential
• 3 doses at 0, 1, 6 months
• Check for Anti HBs 1 – 2 months after the 3rd dose
• Routine booster doses & regular testing not recommended
• Transient HBsAg positivity after vaccination
• CI – anaphylaxis to a component
• Safe in pregnancy & breast feeding
• Adverse effects
▫ fever, rash, malaise
▫ GBS
• Response - >100 mIU / ml preferable
▫ >= 10 mIU / ml accepted as adequate
▫ <10 mIU / ml - susceptible
Pre Exposure Prophylaxis contd.
Anti HBs positive - responder (>=10 mIU/ml) Anti HBs negative check for HBsAg
HBsAg positive Carrier - counsel
HBsAg negative Repeat 3 doses of vaccine (1 month apart) Check for Anti HBs
Pre Exposure Prophylaxis contd.
Following two courses of vaccine
Anti HBs positive - responder (45 – 100%)
Anti HBs negative - primary non-responder
• Precautions to avoid exposure • HBIG foll. known exposure to HBsAg + source
NBTS 24/05/07
Primary non-responder
• 10 – 15% do not respond
▫ Over age 40
▫ Obesity
▫ Smoking
▫ Alcoholics
▫ Advanced liver disease
Post Exposure Prophylaxis
• Given within 48 hours, (up to a week)
• Following known / possible exposure
• Vaccine with or without HBIG used
• Depending on
▫ Vaccination & antibody status of the recipient
▫ HBsAg status of the source
• Needs specific advice
Neonatal transmission - prevention
In all other situations -
• HBIG
▫ Within 12 hours after birth, 0.5 ml IM
• Followed by vaccination – 3 doses
▫ Birth – within 12 hours after birth, 1 month, 6 months
▫ With EPI in Sri Lanka - at birth, 1, 2 and 12 months
Management depends on maternal HBsAg and HBeAg status
If mother is HBeAg negative and HBeAb positive •Hepatitis B vaccine - within 12 hours after birth, 1 month, 6 months
Vaccination policy in Sri Lanka
• Childhood vaccination at 2,4,6 months – WHO
recommendation – Birth dose with 2 or 3 follow up doses
• Vaccination of health care workers
• Vaccination of other high risk groups
▫ Multi-transfused patients
▫ Patients undergoing chemotherapy
▫ Patients undergoing haemodialysis
▫ Household contacts of carriers