hepatitis b co-infection & post exposure prophylaxis

8/7/2019 HEPATITIS B CO-INFECTION & POST EXPOSURE PROPHYLAXIS

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PRESENTER

DR R . DEVANATHAN

4/9/09


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INTRODUCTIONy There is an estimated 350 million hepatitis B carriers

worldwide.

y Mono infection with HepB infection in ruralpopulation is estimated to be 10%, and urban 1%.

y The routes of transmission of HepB and HIV is similar,but Hep B is more efficient.

y Co-infection in SA is estimated to be between 4.8%-17% depending on the population group studied.


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HEPATITIS B

BIOLOGY

y Hepatitis B virus is an HEPADNAVIRUS.

y Composed of partially double stranded DNA.

y Virus replicated through an RNA intermediate form byREVERSE TRANSCRIPTASE- Similar to RETROVIRUS.

y Replication takes place in the liver. Virus also spreadsinto the blood circulation. Virus specific proteins and

their corresponding Antibodies are found in infectedpersons.

y Blood tests for proteins and Ab used to diagnose theinfection.


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Micrograph showingofHepatitis B

virus


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Virology-Structurey The virion consists of an outer lipid envelope and an

icosahedral nucleocapsid core composed of protein.

y

The nucleocapsid encloses the viral DNA and a DNApolymerase (this has reverse transcriptase activity)

y The virus has filamentous and spherical bodieswithout a core. These particles are not infectious andcontains a lipid and a protein. This forms part of the

surface of the virion-called the surfaceantigen(HBsAg)

y This is produced in excess during the life cycle of thevirus.


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A simp i ie rawingo t eHBV

particleand surfaceAg


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Thegenome

y Genome of HBV circular DNA-But is unusual becauseit is not fully double stranded.

y The core protein is coded by gene C (HBcAg)y HBeAg is produced by proteolytic processing of the

pre-core protein.

y The surface antigen is coded by gene S.


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ThegenomeorganisationofHBV.

Thegenes overlap.


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Replication

y Hep B is one of the few known non-retroviral viruswhich uses reverse transcriptase as part of itsreplication process.

y DNA virus enters hepatocytes nucleus-theproduction of RNA-this is released into the cytoplasm-with the help of nucleoside reverse transcriptase theRNA gets converted back to DNA strand for viralpackaging - released from the hepatocyte- further

infection.


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Hepatitis B virus replication


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Specialfeatures.

y HBV has 8 genotypes.(A-H)

y Genotypes are represented in different geographicallocations.

y Genotype influences both the prognosis and treatmentresponse rates.

y In SA- common genotypes A1 and E.

y In Asia- B and C

y GenotypeC does not respond well to inteferon therapy asgenotype A and D.

y GenotypeC also associated with increased rates of liverfailure and hepatocellular carcinoma.


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Cirrhosis oftheliverandliver

cancermayensuefromHep B.


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Transmissiony Follows the same blood/body fluid pattern asHIV.y BUT is more EFFICIENT.y Rate of HIV transmission from needle stick injury is 0.03%,

and that of Hep B can be high as 30%.y Serum, semen and saliva are effective infectious agents.y Horizontal spread in young children- major mode of

tranmission of Hep B in Southern africa.y Perinatal spread is very important in Asia-due to delivery

not during breastfeeding.y HIV related immunosuppression increases the viral load of

Hep B. HIV/Hep B coinfection-have higher viral loads.Therefore co-infection would make transmission of HepBmore efficient.


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Cont..y Vertical transmission from mother to child during

child birth.

yThere is a 20% risk of passing to her offspring at thetime of birth if she is HBsAg.

y This risk increases to 90% if mother is HBeAg.

y 30% or reported hep B among adults cannot be

associated with an identifiable risk factor.


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reva enceo ep v rus as o

2005.


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SEROLOGY and DIAGNOSISy HBsAg most frequently used to screen for the presence of

infection. It is the 1st detectable virus Ag to appearfollowing an infection.

y NB! Early in infection it may not be present and may beundetectable later in infection- as it is cleared up by HOST.

y During this window where the individual is infected andthe host is successfully clearing up the virus- the IgM Ab tothe HBcAg may be the only serological evidence of disease.

y The presence of HBeAg indicates higher rates of viralreplication and enhanced infectivity.

y Anti-HBe will rise immediately thereafter.


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Serologyy As the host clears the HBsAg, HBcAg- IgG to the antigens

will appear.(Anti-HBsAg, AntiHBcAg)

y The time of removal of Ag to the detection of Ab is calledthe window period.

y If Negative for HBsAg and positive for Anti-HBs Ag

implies that the patient has cleared an infection ORvaccinated previously.

y If HBs Ag positive for at least 6 months- are HB carriers.

y Carriers may have chronic hepatitis B reflected by

elevated s-alanine aminotransferase levels andinflammation of the LIVER.

y NB! If carriers have a negative HBeAg status- this implieslittle risk of long term complications or transmittinginfection.


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Hep B viralAgandAb detectablein

thebloodffg acuteinfection


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v g

detectableinthebloodofa

chronicallyinfectedperson


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Clinical Complications ofCo-

infectiony HIV increases the risk of an acute hepB infection

progressing to chronic active infection.(pos HBsAg for >6months.

yCo-infected individuals have a higher HBV viral loads.

y HIV infected individuals- have a higher risk of reactivatingthe latent HBV infection.

y Occult HepB infection is commonly seen in HIV infectedpatients. If not treated lead to Hepatocellular carcinoma

and cirrhosis.y Hep B does not interfere with the disease course of HIV

infection.y Co- infected patients may also have increased risk of

Hepatic steatosis and lactic acidosis from ARVs


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JaundiceinamanwithHepatic

Failure.


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Managementy Treatment of HBV not curative-because viral reserves are

not eradicated.y Idea to reduce viral load-thereby reducing liver damage.

y Treatment of HBV mono-infection: interferon alpha,lamivudine,adefovir, tenofovir,emtricitabine,entecavir,telbivudine, and interferon.

y Monotherapy with lamivudine for hepatitis B in co-infected patients will result in resistance in 60-80% of

patients within 12 months.y Tenofovir/lamivudine with stocrin is very effective intreating both HIV and Hepatitis B- should be 1st linetherapy in these patients.

y Problem: Difficult to get authorization for tenofovir.


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Vaccinationy Benjamin Franklins saying, An ounce of prevention is

worth a pound of cure could not be more appropriate inthe situation of HIV/HBV.

y EPI 6,10,14 weeks.y Those already infected with HIV, the vaccine is not as

effective.

y CD4>500 response rate is 87%

y

200-500- 33%y It recommended to vaccinate when CD4 is above 350.

y HB vaccine response rate improves when the HIV VL is

hepatitis b co-infection & post exposure prophylaxis

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