Hepatitis B Virus1

Properties of HBV A member of the hepadnavirus group

They are Circular partially double-stranded DNA viruses

Its Replication involves reverse transcriptase.

Hyper endemic in many parts of the world.

A number of mutant variants

It has not yet been possible to propagate the virus in cell culture

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Source:

Horizontal Transmission(10%)

Injection Drug use

Infected unscreened blood products

Tattoos or Acupuncture needles

Vertical Transmission(90%)

HbsAg positive mother

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HBV : Structure Virion also referred to as Dane particle (ds-tranded DNA)

42nm enveloped virus

Core antigens located in the center (nucleocapsid) * Core antigen (HBcAg)

* e antigen (HBeAg)- an indicator of transmissibility (minor component of

the core- antigenically distinct from HBcAg)

Other forms:

22nm spheres and filaments other forms- no DNA in these forms so they are not infectious (composed of surface antigen)- these forms outnumber the actual Virion

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HBV : Structure

HBV Structure & Antigens

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Dane particle

HBsAg = surface (coat) protein ( 4 phenotypes : adw, adr, ayw and ayr)

HBcAg = inner core protein (a single serotype)

HBeAg = secreted protein; function unknown

GENOME

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4 Overlapping – Open Reading Frames which encode structural and non structural viral proteins.• S gene encodes 3 Surface Proteins

[ Small(S),Middle(M),Large(L) ]• C gene encodes Core Proteins Hepatitis B core

Antigen( HBcAg)

& Hepatitis B e (Hbe) Protein (Non structural protein)• P gene encodes HBV Polymerase (has 2 motifs- Reverse transcriptase motif

RNAse H Motif)

[ Code for 2 enzymes involved in HBV replication ]• X gene encodes X Protein (Transcriptor involved in HBV replication)

HBV Genome

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Replication of HBV

8 Genotypes ( A to H ) are identified which are associated with different clinical outcomes

Predominant in Common in

Genotype A Northern& Western Europe Homosexuals

Genotype D Mediterranean sea & Eastern Europe Intravenous

drug abusers

Genotype B & C In Asia & Asian immigrants

Genotype C Higher incidence of Severe liver disease &

Hepatocellular Carcinoma

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•Incubation period = 30-150 days

•Jaundice in 1/3rd of Adult Patients with Acute hepatitis B

•most cases are unrecognised

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High ModerateLow/Not

Detectable

blood semen urineserum vaginal fluid faeces

wound exudates saliva sweat

tearsBreast milk

Concentration of Hepatitis B Virus in Various Body Fluids

Diagnosis 4 Markers should be sought for Diagnosis

•HBsAg

•Total Anti HBc Antibodies

•Anti HBc IgM Antibodies

•Anti HBs Antibodies

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Acute Hepatitis B characterised - HBsAg & Anti HBc IgM antibody Anti HBs Antibodies are not seen In Convalescence Phase Patient lose HBsAg, before appearance of Anti HBs Antibody Recovery is characterised by appearance of Anti HBs antibodies & Total Anti HBc Antibodies

Anti HBc IgM levels remains at high levels for Patients life time Anti HBs Antibody titres Flucuate and become undectable after several years

Quantitative HBsAg Assessment during the course of Acute hepatitis B may be useful, if the levels doesn’t decrease rapidly the patient is at risk for chronic evolution.

Patients who remain HBV-DNA & HBeAg positive for 6 weeks after the onset of symptoms likely to develop chronic infections

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Current Treatment Options

Interferon Alfa (Response rate is 30 to 40%.)

Lamivudine (relapse ,drug resistance)

Adefovir

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Interferon Alfa:

- Effective in patients with - low viral load

Serum Transaminases twice the upper limit of normal

- Acts by Augmenting native immune response

- Response is lower in HBeAg –ve patients

- Contraindicated in Cirrhosis ( as it increases Serum transaminase levels which may

precipitate liver failure)

Adverse effects:

Fatigue, Depression, irritability, Bone marrow depression, and thyroid disease

Treatment

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Lamivudine:

- It is a nucleoside analogue

- It inhibits DNS polymerase thus supresses HBV DNA levels

- Effective in improving liver function in Decompensated cirrhosis and prevents need for transplantation

- Long term therapy (after 9 months) may lead to HBV DNA polymerase mutants

- These viral mutants are less hepatotoxic than the native virus

- Tendency to relapse on cessation of treatment

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Adefovir:

- It is also a nucleoside analogue

- It inhibits DNA polymerase

- It may be used to treat Lamivudine resistance

- Reduces HBV DNA by 3-4 logs

- Enhances HBeAg seroconvesion and leads to histological improvement

CONTRAINDIACTED IN RENAL FAILURE

Entecavir:

- It is more effective than Adefovir and Lamivudine in reducing the viral load in HBeAg – positive and negative chronic Heaptitis

- Antiviral resistance mutations occur in 1% after 3 years of Drug exposure

Prevention

Vaccination

- highly effective recombinant vaccines

Hepatitis B Immunoglobulin (HBIG)

- exposed within 48 hours of the incident/ neonates whose

mothers are HBsAg and HBeAg positive

Other measures - screening of blood donors, blood and body fluid precautions.

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Vaccination:

• Highly effective recombinant vaccines are now available.

• Vaccine can be given to those who are at increased risk of HBV infection such as health care workers, Dialysis patients, Homosexuals, Pregnant women, sexual partners of HBV carriers.

• Recombinant HBsAg in 3 injections (0,1 and 6 months)

• Lower dose at same time points (0,1 and 6 months)

for – New Borns, Children & adolescents

• Infants

-mother HBsAg Positive: vaccine and Hepatitis B immunoglobulin

within 12 hours of birth and at 1st and 6th months

• Adults on Dialysis

- 4 injections at 0,1,2 and 6 months

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• Hepatitis B Immunoglobulin - HBIG may be used to protect persons who are exposed to hepatitis B. It is particular efficacious within 48 hours of the incident. It may also be given to neonates who are at increased risk of contracting hepatitis B i.e. whose mothers are HBsAg and HBeAg positive.

• Other measures - screening of blood donors, blood and body fluid precautions.

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