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Hepatitis viruses

Classification
• Classical or Primary:
– HAV, HBV, HCV
– HDV, HEV, HGV
• Secondary or other viruses infecting liver
– Yellow fever virus, CMV, EBV, Herpes
simplex virus, rubella virus, some
enteroviruses
Hepatitis A virus
Hepatitis A virus (HAV)

• Important properties:
– Enterovirus, member of picornavirus
family
– Positive polarity ssRNA, nonenveloped
– Replicates in cytoplasm
– Has one serotype.
– Also known as enterovirus 72.
Hepatitis A Structure
Hepatitis A virus (HAV)

• Transmission:
– Transmitted through fecal oral route
– Human are only reservoir
– Children are most frequently affected
– Outbreaks occur in hostels etc
• Why not transmitted through blood?
- because low level of viraemia
Hepatitis A virus (HAV)…

• Pathogenesis:
– Incubation period 3-4 weeks
– Replicates in GIT, then via blood spread to
hepatoytes
– Liver cells are damaged by CD8 cells.
– No chronicity
– Excreted in feces 2 weeks before jaundice
Hepatitis A virus (HAV)…
• Clinical findings:
– Same for all hepatitis viruse
– Anorexia, nausea, vomiting, jaundice,
dark urine
• Most cases resolve spontaneously in 2-
4 weeks
• Complete recovery 99%
Hepatitis A virus (HAV)…
• Immunity:
– Is life long,
– IgM appears at the time of jaundice
– IgG appears 2-3 weeks later
• Lab diagnosis
– Serological
• IGM antiHAV by ELISA
• A four fold Rise in IgG titre.
• Rise of serum ALT
Hepatitis A virus (HAV)…
• Treatment:
– No antiviral therapy
• Prevention:
– Active immunization by combined ( HAV&
HBV) vaccine
– Passive immunization (Human Ig)
Hepatitis D (Delta) Virus
δ antigen HBsAg

RNA
Hepatitis D Structure
• Defective virus that requires hepatitis B for
replication
• Enveloped with SS RNA genome
• Only antigen encoded is the delta antigen
• Has one serotype
• Modes of Transmission: Same as HBV, ie;
sexual contact, blood transfusion & perinatal
Hepatitis D virus
Pathogenesis:
Immune mediated
Co-infection: infection with B at the same
time
Superinfection: acquisition of Hepatitis D in
chronically Hepatitis B
Hepatitis D
• Prevention:
• Alpha interferon may reduce hepatocellular
damage
• No vaccine
Hepatitis E virus (HEV)
• Important properties
– Member of calicivirus family.
– Nonenveloped, ssRNA.
– Has one serotype.
• Transmission
– Human are only reservoir.
– Transmitted through fecal oral route.
– Mortality rate is 1-2% and in pregnancy
20%.
Hepatitis E virus (HEV)…
• Pathogenesis
– Incubation period is 4-6 weeks
– Replicates in GIT, then via blood spread
to hepatoytes
– Liver cells are damaged by CD8 cells.
– No chronicity, no carrier state
• Lab diagnosis: Not readily available
• Treatment & Prevention:
– No antiviral therapy
– No vaccine
Hepatitis G virus
• RNA virus.
• Member of Flavivirus family.
• Is known to infect humans, but is not known
to cause human disease.
• There have been reports that HIV patients
coinfected with HGV can survive longer
• Transmission: by blood transfusion &
sexual intercourse have been documented.
Hepatitis B virus (HBV)
• Important properties
– a member of hepadnavirus family
– DNA, enveloped (soft)
– Replicates in cytoplasm
– Has one serotype.
– Three different types of particles
• 22nm spherical ( HBsAg)
• 22 nm diameter filamentous (HBsAg)
• 42 nm (Dane particle)
– Three types of antigens
• HBsAg (Surface antigen)
• HBAg ( core antigen)
• HBeAg ( Early appearing core antigen)
– Has reverse transcriptase & DNA polymerase
Hepatitis B virus (HBV)

• Epidemiology &Transmission
– Worldwide,
– 50 million carrier
– Human are only reservoir
– All age group are affected
– Transmitted through following route
• Blood
• Sexual
• Perinatal
• Why not transmitted through food ?
Hepatitis B virus (HBV)…
• Pathogenesis
– I.P is 6-8 weeks
– Replicatesin hepatoytes but no cytopathic effect
– Liver cells are damaged by CD8 cells.
– Chronicity occur
• 5% adults
• 95% infants and young children
– Ag –Ab complex responsible for early symptoms
• Immunity
– Is life long mediated by Anti HBsAg
– IgM appears at the time of jaundice
– IgG appears 2-3 weeks later
• Clinical findings
– 65 – 80% are asymtomatic, insidious onset
– Anorexia, nausea, vomiting, jaundice, dark urine
– Fulminant hepatitis can occur
HBV...
HBV...

Outcome of HBV infection in adults


– Recovery and immune to next infection 90 -
95%
– Persistent infection
• Asymptomtic carrier 10 -15%
• Chronic persistent hepatitis
– Clearance
– Chronic active hepatitis
» Cirrhosis of liver
» Hepatocellular carcinoma
– Death due to fulminant hepatitis 1%
HBV ...
Causes of chronicity are
– in infants
• deficiency of interferon gamma
– in adults
• inadequacy of CD8 cell response
High rate of HCC in chronic carrier
– due to persistent cellular regeneration
– integration of HBV genome into the hepatocyte DNA
HBV...
In te r p r ita tio n o f H B V s e r o l o g ic m a r k e r
H B s A g H B s A b H B e A g H B e A bH B c A b
A c u te H B V + - + - IgM
C h .H B V ( h ig h + - + - IgG
in f e c t .)
C h .H B V + - - + IgG
(lo w in f e c t.)
R ecovery - + - - IgG
V a c c in a t io n - + - - -
HBV...

Treatment and prevention:


– Alpha interferon
– Lamivudin (nucleoside analog)
– Active immunization by Component vaccine
(HBsAg)
– passive immunization by hyperimmunoglobulin
– Post exposure vaccine (passive-active immunization)
Serologic and clinical pattern of acute HBV infection
Hepatitis D virus ( HDV )
Important properties
•Defective virus( incomplete virus )
•HDV uses the surface antigen of HBV as its envelop protein
•only one protein, Delta antigen
•causes chronic hepatitis
Transmission and epidemiology
•Like HBV but sexual transmission is less
Pathogenesis and immunity
•cytotoxic T cell damages infected hepatocyte
•uncertain long term immunity
Hepatitis D virus ( HDV )

Clinical findings
•coinfection with HBV- more severe
•superinfection- fulminant hepatic failure
Lab diagnosis:
•IgM Ab to Delta antigen
Prevention & treatment:
•Alfa interferon
Hepatitis C virus ( HCV )

Important properties
•Flavivirus family
•enveloped virus
•six serotype based on envelope glycoprotein
Transmission and epidemiology
•via biood
•iv drug abusers
•sexual and from mother to child is less
•human are the reservoir
HCV...
Pathogenesis and immunity
•no cytopathic effect on hepatocyte
•cytotoxic T cell causes the damage
•strongly predisposes to hepatocellular carcinoma(HCC)
•alcohol greatly enhenence the rate of HCC
•prolonged liver damage and rapid growth rate causes HCC
•causes chronic infection 75%
•chronic active hepatitis and cirrhosis occurs in 10% of these

Clinical findings
•acute infection is milder than HBV
•Many infection ( acute and chronic ) are asymptomatic
•incubation period- 40- 120 days
•HCV cirrhosis is the indication for transplantation
•leads to autoimmune reaction
HCV...

Laboratory diagnosis
•Antibody detection by ELISA
•RIBA ( recombinant immunoblot assay)
•PCR
Treatment and prevention
•alfa interferon and ribavirin
•Pegylated interferon
•no vaccine available