hepatitis viruses - 2013 (fn) [compatibility mode]
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Hepatitis Viruses - 2013 (FN)TRANSCRIPT
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Hepatitis A-E VirusesDr F Noordeen
Department of MicrobiologyFaculty of Medicine
PeradeniyaMay 2013
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• Modes of transmission and the pathogenesis of viralhepatitis in humans
• Main clinical features of viral hepatitis
• Principles of diagnosis, management and preventionviral hepatitis in humans
Learning outcomes
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AA“Infectious”
“Serum”
Viral hepatitis
Entericallytransmitted
Parenterallytransmitted
F, G other?
EE
NANB
BB DD CC
Viral Hepatitis - Historical Perspectives
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Source ofvirus
Faeces Blood/blood-derived
body fluids
Blood/blood-derived
body fluids
Blood/blood-derived
body fluids
Faeces
Route oftransmission
Fecal-oral Percutaneouspermucosal
Percutaneouspermucosal
Percutaneouspermucosal
Fecal-oral
Chronicinfection
No Yes Yes Yes No
Prevention Pre/post-exposure
immunization
Pre/post-exposure
immunization
Blood donorscreening;
risk behaviormodification
Pre/post-exposure
immunization;risk behaviormodification
Ensure safedrinking
water
Hepatitis A-E
A B C D E
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Hepatitis A virus
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Hepatitis A virus Non enveloped RNA virus Related to enteroviruses, formerly known as
enterovirus 72, now put in the family: heptovirus Only one stable serotype 4 genotypes exist but in practice most of them
are group 1
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Incubation period: Average 30 daysRange 15-50 days
Jaundice by <6 years, <10%age group: 6-14 years, 40%-50%
>14 years, 70%-80%
Complications: Fulminant hepatitisCholestatic hepatitisRelapsing hepatitis
Chronic sequelae: None
Hepatitis A - Clinical features
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FaecalHAV
Symptoms
0 1 2 3 4 5 6 12
24
Hepatitis A infectionHepatitis A infection
Total anti-HAV
Titre ALT
IgM anti-HAV
Months after exposure
Typical Serological Course
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Close personal contact(Household contact, sexual contact and child care centers)
Contaminated food and water(Infected food handlers & raw shellfish)
Blood exposure (very rare)(Injecting drug use and transfusion)
Transmission of Hepatitis A
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Laboratory diagnosis Acute infection is diagnosed by the detection of
HAV - IgM in serum by ELISA Past Infection i.e. immunity is determined by the
detection of HAV - IgG by ELISA
Direct Detection - EM, RT-PCR of faeces Can detect illness earlier than serology
but rarely performed
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Many cases occur in community-wide outbreaks No risk factor identified for most cases Highest attack rates in 5-14 year olds Children serve as reservoir of infection
Persons at increased risk of infection Travelers Homosexual men Injecting drug users
Hepatitis A Vaccination StrategiesEpidemiologic Considerations
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Pre-exposure Travelers to intermediate and high
HAV-endemic regions
Post-exposure (within 14 days)Routine Household and other intimate contactsSelected situations Institutions (Day care centers) Common source of exposure (Food prepared
by infected food handler)
Prevention – Immunoglobulin
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Hepatitis B Virus Enveloped DNA virus
Core - HBcAg and HBeAg
Coat – HBsAg
HBV - 8 genotypes (A-H)
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Incubation period: Average 60-90 days
Clinical illness (jaundice): <5 years, <10%5 years, 30%-50%
Acute case-fatality rate: 0.5%-1%
Chronic infection: <5 years, 30%-90%5 years, 2%-10%
Premature mortality fromchronic liver disease: 15%-25%
Hepatitis B - Clinical features
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Chronic Hepatitis B 1. Chronic persistent hepatitis -
asymptomatic
2. Chronic active hepatitis -symptomatic exacerbations
3. Cirrhosis
4. Hepatocellular carcinoma (HCC)
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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 RecoveryTypical Serologic Course
Weeks after Exposure
Titre
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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 HBV InfectionTypical Serologic Course
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High ModerateLow/Not
Detectable
Blood Semen UrineSerum Vaginal fluid Faeces
Wound exudates Saliva SweatTears
Breast milk
Concentration of Hepatitis B Virus in Various Body Fluids
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Sexual - Sex workers and homosexuals
Parenteral - IDU and health workers
Perinatal - Mothers who are HBeAg positive are much more likely to transmit to their offspring during deliveryPerinatal transmission is the main means of transmission in high prevalence populations
Hepatitis B Virus Modes of Transmission
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Diagnosis An array of serological tests are used for the diagnosis of
acute and chronic HBV infection HBsAg - Used as a general marker of infection Anti-HBs - 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/infectiveness Anti-HBe - Virus no longer replicating
The patient can still be positive for HBsAg HBV-DNA - Indicates active replication of virus, more
accurate than HBeAg Used mainly for monitoring response to therapy
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Treatment Interferon alpha Lamivudine Adefovir Entecavir
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Prevention Vaccination - Highly effective recombinant vaccines
Vaccinate those at increased risk of HBV infection (healthcare workers)Given routinely to neonates as universal vaccination
Hepatitis B Immunoglobulin - HBIG may be used toprotect persons who are exposed to hepatitis BIt is particular efficacious within 48 h of the incidentGiven to neonates who are at increased risk ofcontracting hepatitis – mothers HBsAg + HBeAg positive
Other measures - Screening of blood donors, blood andbody fluid precautions (ABC)
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Hepatitis C virus (HCV) A flavivirus of RNA genome
HCV has a total of six genotypes (type 1 to 6)
Genotype 1 and 4 has a poorer prognosis and response to interferon therapy
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Incubation period: Average 6-7 wks
Clinical illness (jaundice): 30-40% (20-30%)
Chronic hepatitis: 70%
Persistent infection: 85-100%
Immunity: No protective antibodyresponse identified
Hepatitis C - Clinical features
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Chronic hepatitis C infection
The spectrum of chronic HCV infection is essentially the same as chronic HBV infection
All the manifestations of chronic HBV infection may be seen, with a lower frequency i.e. chronic persistent hepatitis, chronic active hepatitis, cirrhosis and HCC
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Symptoms
anti-HCV
ALT
Normal
0 1 2 3 4 5 6 1 2 3 4
Hepatitis C Virus InfectionTypical Serologic Course
Titre
Months YearsTime after Exposure
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Transfusion or transplant from infected donor
Injecting drug use (IDU) Hemodialysis (years on treatment) Accidental injuries with needles/sharps Sexual/household exposure to HCV RNA
positive contact Multiple sex partners Birth to HCV-infected mother
Risk factors associated with transmission of HCV
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Laboratory diagnosis HCV antibody - Used to diagnose HCV infection
Not useful in the acute phase as it takes at least 4 weeks for the antibody to appear
HCV RNA - Various techniques are available e.g. PCR and qPCR used to diagnose HCV infection in the acute phase and in monitoring the response to antiviral therapy
HCV antigen - An ELISA for HCV antigen is available It is used in the same capacity as HCV RNA tests but is much easier to carry out
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Treatment Interferon and Ribavirin in combination
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Screening of blood, organ and tissue donors
High-risk behavior modification
Blood and body fluid precautions (ABC)
Prevention of Hepatitis C
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HBsAg
RNA
antigen
Hepatitis D (Delta) Virus
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Hepatitis D virus (HDV) The delta agent is a defective virus
The agent consists of a particle 35 nm in diameter consisting of the delta antigen surrounded by an outer coat of HBsAg
The genome of the virus is very small and consists of RNA
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Co-infection– Severe acute disease– Low risk of chronic infection
Superinfection– Usually develop chronic HDV infection– High risk of severe chronic liver disease– May present as an acute hepatitis
Hepatitis D - Clinical features
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Hepatitis E virus
• Non enveloped RNA virus• Very labile and sensitive
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Incubation period: Average 40 days
Case-fatality rate: Overall, 1%-3%Pregnant women, 15%-25%
Disease severity: Increased with age
Chronic sequelae: None identified
Hepatitis E - Clinical features
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Outbreaks: Faecally contaminated drinking water
Large epidemics have occurred in the Indian subcontinent, China, Africa and Mexico
Hepatitis E -Epidemiologic features
Prevention and Control Avoid drinking water of unknown purity,
uncooked shellfish & uncooked fruits/vegetables Vaccine?
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Following serological data for a 42 year old male that had a history of unprotected sexual encounter during his travel 5 weeks ago to China presented with fever, jaundice and malaise.
Laboratory findings
HBsAg - positive IgG anti-HBc - positive IgM anti-HBc - positive Anti-HBsAg - negative
Your diagnosis based on these findings is?
A. acute HBV infection B. acute HCV infection C. vaccinated against HBV D. super infection with HDVE. chronic HBV infection