hepatitis b co-infection & post exposure prophylaxis
TRANSCRIPT
-
8/7/2019 HEPATITIS B CO-INFECTION & POST EXPOSURE PROPHYLAXIS
1/23
PRESENTER
DR R . DEVANATHAN
4/9/09
-
8/7/2019 HEPATITIS B CO-INFECTION & POST EXPOSURE PROPHYLAXIS
2/23
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.
-
8/7/2019 HEPATITIS B CO-INFECTION & POST EXPOSURE PROPHYLAXIS
3/23
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.
-
8/7/2019 HEPATITIS B CO-INFECTION & POST EXPOSURE PROPHYLAXIS
4/23
Micrograph showingofHepatitis B
virus
-
8/7/2019 HEPATITIS B CO-INFECTION & POST EXPOSURE PROPHYLAXIS
5/23
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.
-
8/7/2019 HEPATITIS B CO-INFECTION & POST EXPOSURE PROPHYLAXIS
6/23
A simp i ie rawingo t eHBV
particleand surfaceAg
-
8/7/2019 HEPATITIS B CO-INFECTION & POST EXPOSURE PROPHYLAXIS
7/23
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.
-
8/7/2019 HEPATITIS B CO-INFECTION & POST EXPOSURE PROPHYLAXIS
8/23
ThegenomeorganisationofHBV.
Thegenes overlap.
-
8/7/2019 HEPATITIS B CO-INFECTION & POST EXPOSURE PROPHYLAXIS
9/23
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.
-
8/7/2019 HEPATITIS B CO-INFECTION & POST EXPOSURE PROPHYLAXIS
10/23
Hepatitis B virus replication
-
8/7/2019 HEPATITIS B CO-INFECTION & POST EXPOSURE PROPHYLAXIS
11/23
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.
-
8/7/2019 HEPATITIS B CO-INFECTION & POST EXPOSURE PROPHYLAXIS
12/23
Cirrhosis oftheliverandliver
cancermayensuefromHep B.
-
8/7/2019 HEPATITIS B CO-INFECTION & POST EXPOSURE PROPHYLAXIS
13/23
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.
-
8/7/2019 HEPATITIS B CO-INFECTION & POST EXPOSURE PROPHYLAXIS
14/23
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.
-
8/7/2019 HEPATITIS B CO-INFECTION & POST EXPOSURE PROPHYLAXIS
15/23
reva enceo ep v rus as o
2005.
-
8/7/2019 HEPATITIS B CO-INFECTION & POST EXPOSURE PROPHYLAXIS
16/23
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.
-
8/7/2019 HEPATITIS B CO-INFECTION & POST EXPOSURE PROPHYLAXIS
17/23
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.
-
8/7/2019 HEPATITIS B CO-INFECTION & POST EXPOSURE PROPHYLAXIS
18/23
Hep B viralAgandAb detectablein
thebloodffg acuteinfection
-
8/7/2019 HEPATITIS B CO-INFECTION & POST EXPOSURE PROPHYLAXIS
19/23
v g
detectableinthebloodofa
chronicallyinfectedperson
-
8/7/2019 HEPATITIS B CO-INFECTION & POST EXPOSURE PROPHYLAXIS
20/23
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
-
8/7/2019 HEPATITIS B CO-INFECTION & POST EXPOSURE PROPHYLAXIS
21/23
JaundiceinamanwithHepatic
Failure.
-
8/7/2019 HEPATITIS B CO-INFECTION & POST EXPOSURE PROPHYLAXIS
22/23
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.
-
8/7/2019 HEPATITIS B CO-INFECTION & POST EXPOSURE PROPHYLAXIS
23/23
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