Hepatitis b,c, &d
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Transcript of Hepatitis b,c, &d
Hepatitis B, C & D Viruses
Dr. Masood Ahmad
Viral hepatitis B
Etiology Hepatitis B virus (HBV) HBV is a kind of hepadnavirus Three particles in serum: spherical particles and tubular particles with a
diameter of 20 nm, composed of HBsAg large particles with a diameter of 42 nm, named Dane
particle. It consists of an outer protein shell (envelope, contain HBsAg) and an inner body ( core, contain HBcAg, HBeAg, HBV-DNA and DNAP )
Hepatitis B Virus
pathology Three antigen-antibody system
HBsAg-- anti-HBs system: HBsAg appears 1-2 weeks (late up to 11-12 weeks) after
exposure, persists for 1-6 weeks( even 5 months) in acute hepatitis B.
In chronic patients or carrier, HBsAg persist many years HBsAg is the marker of infectivity HBsAg can be found in blood and secretions: saliva, urine,
semen, tears, sweat and breast milk Anti-HBs appear after HBsAg disappear several weeks (or
months) anti-HBs is protective antibody, can persist for many years
pathologyHBcAg—anti-HBc system HBcAg can be found in the nuclei of liver cells, no free
HBcAg in serum HBcAg is the marker of replication of HBV The stage called window phase Anti-HBc IgM is a marker of acute infection and acute
attack of chronic infection of HBV. Anti-HBc IgG is the marker of past infection, high titer means low level replication of HBV
pathology
HBeAg—anti-HBe system HBeAg is a soluable antigen HBeAg is a reliable indicator of active replication of
HBV Anti-HBe is a marker of reduced infectivity. If exist
long may be a marker of integration of HBV into liver cell
Pathogenesis Hepatitis B:
HBV invades into the human body by skin and mucosa, Via blood flow enters the liver and other organs such as pancreas, bile ducts, vessels, WBC, bone marrow, glomerular basement membrane
HBcAg,HBsAg,HBeAg and HLA- appear on the Ⅰliver cells infected with are recognized by CTL simultaneously and lead to the cytolysis of liver cells
Pathogenesis
Helper T cell are activated by the receptor of HLA- on its surface combing with HBsAg, HBcAg and HLA- antigen on the B cells promote B cell to release anti-HBs and clear HBV
The representation of HBcAg on the liver cells may cause cytopathy
Incubation period: Average 60-90 daysRange 45-180 days
Clinical illness (jaundice): <5 yrs, <10%5 yrs, 30%-50%
Acute case-fatality rate: 0.5%-1% Chronic infection: <5 yrs, 30%-90%
5 yrs, 2%-10% Premature mortality from
chronic liver disease: 15%-25%
Hepatitis B - Clinical Features
Spectrum of Chronic Hepatitis B Diseases
1.Chronic Persistent Hepatitis - asymptomatic
2.Chronic Active Hepatitis - symptomatic exacerbations of hepatitis
3.Cirrhosis of Liver
4.Hepatocellular Carcinoma
Symptoms
HBeAg anti-HBe
Total anti-HBc
IgM anti-HBc anti-HBsHBsAg
0 4 8 12 16 20 24 28 32 36 52 100
Acute Hepatitis B Virus Infection with Recovery
Typical Serologic Course
Weeks after Exposure
Titre
IgM anti-HBc
Total anti-HBc
HBsAg
Acute(6 months)
HBeAg
Chronic(Years)
anti-HBe
0 4 8 12 16 20 24 28 32 36 52 Years
Weeks after Exposure
Titre
Progression to Chronic Hepatitis B Virus Infection
Typical Serologic Course
Symptomatic Infection
Chronic Infection
Age at Infection
Chronic Infection (%)
Sym
pto
matic In
fection
(%)
Birth 1-6 months 7-12 months 1-4 years Older Childrenand Adults
0
20
40
60
80
100100
80
60
40
20
0
Outcome of Hepatitis B Virus Infection
by Age at Infection
Ch
ron
ic I
nfe
ctio
n
(%)
High (>8%): 45% of global population lifetime risk of infection >60% early childhood infections common
Intermediate (2%-7%): 43% of global population lifetime risk of infection 20%-60% infections occur in all age groups
Low (<2%): 12% of global population lifetime risk of infection <20% most infections occur in adult risk groups
Global Patterns of Chronic HBV Infection
High ModerateLow/Not
Detectable
blood semen urineserum vaginal fluid feces
wound exudates saliva sweat
tearsbreast milk
Concentration of Hepatitis B Virus in Various Body Fluids
Sexual - sex workers and homosexuals are particular at risk.
Parenteral - IVDA, Health Workers are at increased risk.
Perinatal - Mothers who are HBeAg positive are much more likely to transmit to their offspring than those who are not. Perinatal transmission is the main means of transmission in high prevalence populations.
Hepatitis B Virus
Modes of Transmission
Diagnosis. HBsAg - used as a general marker of infection. HBsAb - used to document recovery and/or immunity to HBV
infection. anti-HBc IgM - marker of acute infection. anti-HBcIgG - past or chronic infection. HBeAg - indicates active replication of virus and therefore
infectiveness. Anti-Hbe - virus no longer replicating. However, the patient can
still be positive for HBsAg which is made by integrated HBV. HBV-DNA - indicates active replication of virus, more accurate
than HBeAg especially in cases of escape mutants. Used mainly for monitoring response to therapy.
Treatment In acute hepatitis B the treatment is
basically symptomatic Rest Ant emetics to control vomiting Plenty of fluids and carbohydrates Hepatotropic agents
Treatment Chronic Hepatitis B Interferon - for HBeAg +ve carriers with chronic active
hepatitis. Response rate is 30 to 40%. Lamivudine - a nucleoside analogue reverse
transcriptase inhibitor. Well tolerated, most patients will respond favorably. However, tendency to relapse on cessation of treatment. Another problem is the rapid emergence of drug resistance.
Successful response to treatment will result in the disappearance of HBsAg, HBV-DNA, and seroconversion to HBeAg.
Prevention 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. It is also given routinely to neonates as universal vaccination in many countries.
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.
Hepatitis C Virus
Hepatitis C virus (HCV) HCV is a member of flavivirus family. HCV genome is a single stranded positive-sense RNA and
contains 9.4kb HCV genome may be divided into many types and subtypes. Resistance Antigen-antibody system The concentration of HCV in blood is low, HCV Ag has not
be detected, anti-HCV is the indicator of infection and the marker of infectivity
HCV-RNA HCV-RNA may be detected from blood or liver tissue, it’s
the direct evidence of infectivity
Incubation period: Average 6-7 wks
Range 2-26 wks
Clinical illness (jaundice): 30-40% (20-30%)
Chronic hepatitis: 70%
Persistent infection: 85-100%
Immunity: No protective antibody response
identified
Hepatitis C - Clinical Features
Chronic Hepatitis C Infection
The spectrum of chronic hepatitis C infection is essentially the same as chronic hepatitis B infection.
All the manifestations of chronic hepatitis B infection may be seen, albeit with a lower frequency i.e. chronic persistent hepatitis, chronic active hepatitis, cirrhosis, and hepatocellular carcinoma.
Symptoms
anti-HCV
ALT
Normal
0 1 2 3 4 5 6 1 2 3 4
Hepatitis C Virus InfectionTypical Serologic Course
Titre
Months
Years
Time after Exposure
Transfusion or transplant from infected donor
Injecting drug use
Hemodialysis (yrs on treatment)
Accidental injuries with needles/sharps
Sexual/household exposure to anti-HCV-positive contact
Multiple sex partners
Birth to HCV-infected mother
Risk Factors Associated with Transmission of HCV
Laboratory Diagnosis HCV antibody - generally used to diagnose hepatitis C
infection. Not useful in the acute phase as it takes at least 4 weeks after infection before antibody appears.
HCV-RNA - various techniques are available e.g. PCR and branched DNA. May be used to diagnose HCV infection in the acute phase. However, its main use is in monitoring the response to antiviral therapy.
Treatment
Acute infection
Chronic infection Interferon - may be considered for patients with
chronic active hepatitis. The response rate is around 50% but 50% of responders will relapse upon withdrawal of treatment. However addition of
Ribavirin – Improves the response rate to almost 70%.
Treatment Different genotypes of HCV have been identified and
have been named as genotype 1 to 8 and there are still many which presently are untypeable.
Many different types of interferons are also available including conventional, pegylated, and consensus interferon.
Genotype 2 & 3(common subtypes in Pakistan) respond well to conventional interferon
Screening of blood, organ, tissue donors
High-risk behavior modification
Blood and body fluid precautions
Prevention of Hepatitis C
Hepatitis D (Delta) Virus
Hepatitis D virus (HDV) HDV (Delta hepatitis virus) is a kind of defective virus HDV is found in the nuclei of infected hepatocytes and replicate HDV genome is a circular single strand RNA and contains 1.7kb The replication of HDV depends on HBV or other hepadnavirus,
coated by HBsAg in blood HDV has one antigen-antibody system No free HDAg is detected in blood, it’s in the nuclei of
hepatocytes; anti-HDV can be detected by RIA or ELISA in serum
HBV and HDV co-infection or superinfection may make the disease exacerbation and may lead to fulminant hepatitis
HDV RNA may be detected from liver cells, blood or humor.
HBsAg
RNA
antigen
Hepatitis D (Delta) Virus
Co-infection– severe acute disease.– low risk of chronic infection.
Super-infection– usually develop chronic HBV infection.– high risk of severe chronic liver disease.– may present as an acute hepatitis.
Hepatitis D - Clinical Features
Percutaneous exposures
injecting drug use
Per mucosal exposures sex contact
Hepatitis D Virus Modes of Transmission
anti-HBs
Symptoms
ALT Elevated
Total anti-HDV
IgM anti-HDV
HDV RNA
HBsAg
HBV - HDV CoinfectionTypical Serologic Course
Time after Exposure
Titre
Jaundice
Symptoms
ALTTotal anti-HDV
IgM anti-HDV
HDV RNA
HBsAg
HBV - HDV SuperinfectionTypical Serologic
Course
Time after Exposure
Titre
HBV-HDV Co-infection
Pre or post-exposure prophylaxis to prevent HBV infection.
HBV-HDV Super-infection
Education to reduce risk behaviors among persons with chronic HBV infection.
Hepatitis D - Prevention
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